1. Describe pathological physiology as fundamental and integrative science and academic discipline. The
subject and objectives of pathophysiology: its place in the system of higher medical education.
Pathophysiology as a theoretical and methodological basis for modern clinical medicine.
PATHOPHYSIOLOGY - SECTION OF MEDICINE AND BIOLOGY,
• studies and describes specific causes, mechanisms and general patterns of occurrence,
development and completion of diseases, pathological processes, conditions and reactions;
• formulates the principles and methods of their identification (diagnosis), treatment and prevention;
• develops the doctrine of the disease and the sick organism, as well as the theoretical provisions
of medicine and biology.
1. Subject (object) of study of pathophysiology is not homogeneous and includes three components:
“Disease”, “typical pathological process” and “typical form of pathology”. All components of the
subject "pathophysiology" (both as a science and as an academic discipline) are studied and
described from the standpoint of the etiology and pathogenesis of diseases or pathological
processes, their manifestations and mechanisms of development, the principles of their diagnosis,
treatment and prevention.
2. Tasks... Pathophysiology develops the problems of the etiology and pathogenesis of diseases,
the mechanisms of their manifestations, formulates the principles of diagnosis, treatment and
prevention of diseases.
3. Etiology.Pathophysiology finds out, describes and explains the causes and conditions of the
onset of diseases, disease states and pathological processes. Knowledge of these factors allows
us to answer the question “why does it arise?” A disease or pathological process.
4. Pathogenesis.Pathophysiology investigates, describes and explains the mechanisms of
development of diseases and pathological processes, the mechanisms of their
manifestations. This makes it possible to answer the question "how is it developing?" disease
or pathological process.
5. Diagnostics.Pathophysiology formulates and substantiates the principles and methods of
identifying (diagnosing) diseases and pathological processes. The solution to this problem is
based on knowledge of the mechanisms of occurrence, development and completion of diseases
and pathological processes. This makes it possible to scientifically substantiate a rational scheme
of diagnostic search for each specific patient, i.e. answer the question "how to identify?" disease or
pathological process.
6. Treatment and prevention.Pathophysiology formulates and argues the principles and methods
of treatment, as well as the prevention of diseases and pathological processes, i.e. answers the
question "how to treat and prevent?" disease.
Ps General concepts that may be asked, but I think it is not necessary !!!
• Typical pathological processes - components of various diseases. So, "inflammation" is a
component of meningitis, pneumonia, gastritis, panaritium, hepatitis, dermatitis, etc. Characteristic
signs of a typical pathological process: polyetiology, monopathogenicity, complexity and standard of
manifestations.
♦ Polyethiological. There are many reasons for a specific typical pathological process. For example,
the causes of inflammation can be microorganisms, mechanical injury, exposure to heat or cold,
various chemicals, and many others.
♦ Monopathogenicity. A typical pathological process has a more or less standard (stereotyped)
mechanism of development. For example, the pathogenesis of inflammation includes components of
alteration (damage), exudation and proliferation.
♦ Complexity. Any typical pathological process is always a complex of adaptive and pathological changes.
♦ The standard of manifestations. A typical pathological process has characteristic (standard)
manifestations. So, any acute inflammation is characterized by both general (leukocytosis, fever,
dysproteinemia) and local (pain, redness, tissue edema, increased temperature and dysfunction) signs.
• Typical forms of pathology. The set of pathological processes characteristic of the pathology of
individual tissues and organs is a typical form of tissue or organ pathology. For example, anemia as a
typical form of pathology of the erythrocyte system can be caused by various reasons, but all anemias are
manifested by a decrease in the hemoglobin (Hb) content per unit of blood volume. Like typical
pathological processes, typical forms of pathology have the same characteristic features (polyetiology,
monopathogenicity, complexity, standard manifestations).
• Syndromes, diseases and painful conditions. The aggregate of typical pathological processes and
typical forms of pathology developing with a specific injury in the body characterize a syndrome, illness
or disease state.
2. Describe the methods of pathophysiology. Modeling as the main and specific method of pathophysiology:
its types, possibilities and limitations. Describe the advantages and disadvantages of various methods of
pathophysiology.
Pathophysiology employs a number of methods: modeling, theoretical analysis, and clinical research.
The main one is modeling.
• Modeling consists in the reproduction of individual diseases, pathological processes or reactions, methods
of diagnosis, treatment and prevention, as well as the patient as a whole on
"Artificial copies" (models) in order to study the mechanisms of occurrence, development and
completion of diseases. Modeling on physical objects and formalized modeling is possible.
Views:
♦ Modeling on physical objects (material), i.e. on animals, their organs, tissues, cells and individual cell
components.At the same time, it is known that the modeling of pathological processes in animals has
drawbacks due to significant species differences in the processes of vital activity in animals and
humans, as well as the very important role of social factors in the occurrence, development and
outcomes of human diseases. Modeling of pathology with the use of artificial physical systems
(artificial heart, kidney, blood, ventilators, artificial circulation, etc.) is also used to address certain
issues of pathophysiology.
♦ Formalized modeling (intangible): logical, intellectual, mathematical and computer.
CLINICAL STUDY METHODS
... The availability of modern devices and the latest technologies allows a targeted study of the
dynamics of the state of various organs and their systems, structural changes in them, biochemical
and electrophysiological indicators of the vital activity of the body as a whole in a sick person. The
prerequisites for performing such studies are their harmlessness to the patient and a reasoned
need for conducting them. Many manipulations in patients are carried out by non-invasive methods.
The data obtained during the direct examination of the patient allow, firstly, to carry out an
accurate diagnosis of the disease; secondly, to evaluate the effectiveness of treatment; third, to
investigate the features and patterns of the onset, development and outcomes of the disease in
humans; fourthly, they provide material for a scientific explanation of the etiology and
pathogenesis of diseases and pathological processes.
METHOD OF THEORETICAL ANALYSIS
Theoretical analysis and development on this basis of scientific concepts, concepts, hypotheses and
theories related to the solution of fundamental and applied problems of medicine and biology is an
important method of pathophysiology. The result of this work is the formulation of a system of
grounded ideas about the causes and mechanisms of the onset, development and completion of
diseases, painful conditions and pathological processes, about the principles and methods of their
detection, treatment and prevention, theoretical provisions of medicine and biology.
Medical thinking. Pathophysiology (along with other fundamental medical specialties) is the
intellectual basis of medicine and the basis for solving its urgent problems. Formation of the
foundations of medical thinking among students is the most important task of pathophysiology. This
task is achieved in the course of pathophysiological analysis of specific experimental or clinical data
when solving professional problems of a doctor in the classroom. This imitates the behavior of a
doctor who simulates the disease and the patient as a whole, formulates methods for diagnosing the
disease and composes the patient's treatment regimen.
3. Expand the basic concepts of general pathophysiology: norm, health,
transitional the state of the body between health and illness (pre-illness).
Health... There is currently no generally accepted concept of "health".
♦ More often, health is defined as a state of optimal adaptation of a person to changing conditions of life.
The definition given by WHO experts: Health - a state of complete physical, spiritual and social well-being, and not
just the absence of diseases or physical defects.
Norm - the state of optimal vital functions of the organism in the specific conditions of its
existence... The concept of "norm" is often used as a synonym for health ("health is normal
state of the body "). However, the concept of "norm" is broader than the concept of "health". So, you can be a
healthy person, but differ from any generally accepted standards of the norm (for example, height, weight or
dimensions of the body, the nature of communication with other people, the level of intelligence).
Pre-illness. The onset of the disease is often preceded by a state of pre-disease (premorbid, the situation:
"neither disease, nor health"). This condition is characterized by overvoltage of adaptive sanogenetic (Greek sanus - healthy) - mechanisms due to the action of damaging factors or the manifestation of
defects in the genetic program. Against the background of this state, the impact of non-pathogenic
other conditions of the agent can cause illness. The state of pre-disease has no specific signs,
but it can be detected by stress tests that allow detecting a critical decrease in the effectiveness of adaptive
mechanisms.
4. Give a definition to the concepts: pathological process, pathological reaction, pathological condition,
typical pathological process, "vicious circle".
Pathological reaction - qualitatively or quantitatively inadequate and biologically inexpedient (inadaptive) response
of an organism or its part (tissue, organ, system) to the action of conventional or pathogenic agents.
As a rule, a pathological reaction is the result of a violation of the reactivity of the body as a whole or
reactive properties of tissues, organs and their systems. An example is allergic reactions, phobias (unmotivated
fear of any object or phenomenon), pathological reflexes (for example, spasm of the coronary arteries with the
development of an attack of angina pectoris when the wall of the gallbladder is irritated
calculus).
pathological process - a natural dynamic set of pathogenic and adaptive changes in tissues, organs
and their systems, arising under the influence of a damaging factor, characterized by a violation of the
vital activity of the organism.
The pathological process (as opposed to the disease) is usually local. In this regard, it may have a less pronounced
effect on the body (for example, soft tissue injury, burns of a relatively small area of the skin, erosion of the
stomach). However, with an increase in the scale and degree of damage, the pathological process can lead to
illness (for example, post-traumatic or burns, gastric ulcer).
PATHOLOGICAL CONDITION - long-term deviation from the norm of the structure, biochemical and /
or functional properties of tissues, organs, their systems, arising under the influence of a pathogenic
agent, characterized, as a rule, by disruption of the vital activity of the organism
A distinctive feature of the pathological condition is a protracted (sometimes throughout life) course.
Examples: deformation of the heart valve openings after endocarditis; conditions after removal of one of the
eyeballs, tooth, kidney, part of the intestine, lung; various deformities and consequences of developmental
abnormalities (for example, a cleft lip or hard palate, clubfoot)
Vicious circle. The pathogenesis of a number of diseases is characterized by the formation of
vicious circles (Latin circulus vitiosus), when one of the links in pathogenesis is the cause of
disorders that support or potentiate the implementation of another link.
For example, with heatstroke, an increase in body temperature increases neuromuscular excitability,
which leads to the development of seizures and an increase in contractile thermogenesis.
The latter potentiates a further increase in temperature and increases the excitability of the nerve centers
and muscles.
5. Describe the concept of a disease, its stages, classification. Describe the role of etiology in the onset of
disease. Describe the role of causes and conditions in the onset of diseases, their relationship. Give concepts
about the external and internal causes of the disease. Describe the types of disease outcomes.
Usually (although not always) in the process of the disease, several periods or stages can be
distinguished: latent, prodromal, severe disease, and outcomes of the disease.
Latent stage of the disease.The stage of latent development of a disease, or incubation, is a
period of latent, clinically not manifesting its development: from the moment the pathogenic
agent affects the body to the first signs of the disease.
At this stage, there are no symptoms of the disease. However, when performing stress tests, signs
of exhaustion and insufficiency of the body's adaptive mechanisms can be revealed.
The stage of harbingersThe stage of precursors (prodrome) of the disease is observed from the
moment of its first manifestations to the development of a typical clinical picture.
At the prodromal stage, the first nonspecific (both subjective and objective) signs of the disease
are revealed: malaise, fatigue, irritability, soreness in muscles and joints, decreased appetite,
headache, discomfort, etc.
Stage of severe manifestations of the diseaseAt the stage of pronounced manifestations
(peak), local and general symptoms typical for a particular disease appear. With an unfavorable
course of the disease, various complications may develop (for example, a hypertensive crisis in
hypertensive disease; collapse in hyperthermia; coma in diabetes mellitus - diabetes mellitus).
Disease Outcome StageThere are several possible outcomes of the disease: recovery (complete
and incomplete), relapse, remission, complication, transition to a chronic form, death.
Complete recovery
the formation of effective adaptive processes and reactions that eliminate the cause of the disease and
its pathogenic consequences, completely restore the body's homeostasis. Such a recovery is called
complete.
Recovery is incomplete.When the so-called residual phenomena of the disease, individual
structural and functional abnormalities remain in the body after its completion, as such, recovery is
called incomplete.
Relapse- re-emergence or re-increase (aggravation) of the symptoms of the disease after their
elimination or weakening.
Remission- temporary weakening (incomplete remission) or elimination (complete remission) of the
disease. Complications - a pathological process, condition or reaction that develops against the
background of the underlying disease, but is not obligatory for it. Complications aggravate the
course of the underlying disease.
With an unfavorable development of the disease, other outcomes are possible: chronic course
and cessation of vital activity, death of the patient.
Death (biological or clinical) - the process of termination of the body. This is preceded by a more or
less long period of dying of the organism. It includes: preagony, terminal pause, agony, clinical death,
biological death. The first four stages of the dying period are reversible, provided that medical
measures are taken to resuscitate the body in a timely and effective manner, biological death is
irreversible.
The key concepts of the doctrine of etiology are the damaging factor, the conditions for the onset
of diseases, the reactivity of the body and etiotropic therapy:
Conditions for the development of the disease - factors that contribute to, prevent or modify the
action of the causative agent and give the disease specific features.
• The conditions for the onset of the disease are divided into external (exogenous) and
internal (endogenous).
♦ The most significant external conditions include: ❖ environmental factors (for example, polluted air,
water, exposure to the body of harmful industrial, agricultural and domestic factors); ❖ quantitative and
qualitative inadequacy of food; ❖ violation of orderliness and the optimal balance of work and rest; ❖
social and psychogenic factors (for example, frequent conflict situations).
♦ Internal conditions play a significant role: ❖ resistance (resistance) of the body; ❖ features of
its constitution;
❖ type of higher nervous activity (VNI); ❖ gender and age;
❖ body reactivity
Reactivity - the property of the whole organism to react differentiatedly with changes in vital activity
to the influence of factors of the external and internal environment
International Classification of Diseases, 10th revision
Class I. Certain infectious and parasitic diseases
Class II. Neoplasms
Class III. Diseases of the blood, hematopoietic organs and certain disorders involving the
immune mechanism
Class IV. Endocrine system diseases, eating disorders and metabolic disorders
Class V. Mental and behavioral disorders
Class VI. Diseases of the nervous system
Class VII. Diseases of the eye and its adnexa
Class VIII. Diseases of the ear and mastoid
Class IX. Diseases of the circulatory system
Class X. Diseases of the respiratory system
Class XI. Diseases of the digestive system
Class XII. Diseases of the skin and subcutaneous tissue
Class XIII. Diseases of the musculoskeletal system and connective tissue
Class XIV. Diseases of the genitourinary system
Class XV. Pregnancy, childbirth and the puerperium
Class XVI. Certain conditions arising in the perinatal period
Class XVII. Congenital anomalies (blood defects), deformities and chromosomal abnormalities
Class XVIII. Symptoms, signs and abnormalities identified in clinical and laboratory studies,
not elsewhere classified
Class XIX. Injury, poisoning and some other consequences of exposure to external causes
Class XX. External causes of morbidity and mortality
Class XXI. Factors affecting the state of health of the population and referrals to health care institutions
6. Name the main groups of environmental factors that affect the body. The pathogenic effect of sound and
noise on the body: mechanisms of specific and nonspecific action on the body.
Noise - an unpleasant or undesirable sound or a combination of sounds that break the silence, have an
irritating effect on the human body and reduce its performance. The high-pressure region and the
following low-pressure region form sound waves. Propagating in the air at a speed of about 340 m / s,
they carry a certain amount of energy. The human ear perceives sound with an oscillation frequency of
16 to 20,000 Hz (1 Hz is one oscillation in 1 s).
Sounds of high frequency (up to 4000 Hz), with their equal intensity, are perceived by a person as
louder. When sound intensity exceeds 3 kW / cm2, disturbances in the general state of the body occur:
convulsions, complete loss of consciousness, paralysis are possible.
There are specific and non-specific effects of noise on the human body.
Specific the effect of noise is associated with a dysfunction of the auditory analyzer, which is based on a
prolonged spasm of the sound-perceiving apparatus, leading to a violation of metabolic processes and, as
a result, to degenerative changes in the endings of the vestibular cochlear nerve and cells of the organ of
Corti. Noises with a level of 80-100 dB and above quickly cause hearing loss and the development of
hearing loss. Severe short-term stunning (concussion) can cause temporary (reversible) hearing loss
Nonspecific the effect of noise on the human body is associated with the flow of excitation into the
cerebral cortex, hypothalamus and spinal cord. At the initial stages, transcendental inhibition of the
central nervous system develops with a violation of the balance and mobility of the processes of
excitation and inhibition. The subsequent depletion of nerve cells underlies increased irritability,
emotional instability, memory impairment, decreased attention and performance.
As a result of prolonged exposure to intense noise, noise sickness develops - a general disease of the
body with a predominant impairment of the hearing organ, the central nervous and cardiovascular
systems, and the organs of the gastrointestinal tract.
Ultrasound - elastic waves inaudible to the human ear, the frequency of which exceeds 20
kHz. The main physical characteristics of ultrasound as acoustic radiation are frequency, intensity (or
specific power - W / cm2) and pressure (Pa).
In recent years, ultrasound has found application in medical practice for therapeutic and
diagnostic purposes.
The biological effect of ultrasound is due to its mechanical, thermal and physicochemical
action.The sound pressure in the ultrasonic wave can vary within ± 303.9 kPa (3 atm). Negative pressure
promotes the formation of microscopic cavities in the cells, followed by their rapid collapse, which is
accompanied by intense hydraulic shocks and ruptures - cavitation. Cavitation leads to depolarization and
destruction of molecules, causes their ionization, which activates chemical reactions, normalizes and
accelerates the processes of tissue metabolism
High-intensity ultrasound (3-10 W / cm2) has a damaging effect on individual cells, tissues and the body
as a whole.
7. Etiology of the pathogenic effect of high barometric pressure on the body: the pathogenesis of
decompression sickness; manifestations and prevention of this condition.
The disease-causing effect of high atmospheric pressure (hyperbaria) is exposed when submerged under
water during diving and caisson work.
With a rapid transition from an environment with normal atmospheric pressure to an environment with
increased pressure (compression), an indentation of the tympanic membrane may occur, which, if the
Eustachian tube is obstructed, causes a sharp pain in the ears, compression of intestinal gases,
increased blood filling of internal organs. With a very fast (sharp) dive to great depths, rupture of blood
vessels and pulmonary alveoli can occur.
The main pathogenic effect of hyperbaria during the compression period is associated with increased
dissolution of gases in the body's liquid media (saturation). There is a direct relationship between the
volume of dissolved gas in the blood and body tissues and its partial pressure in the inhaled air. When
immersed in water, every 10.3 m, the pressure increases by 1 atm, and the amount of dissolved nitrogen
increases accordingly. Fat-rich organs are especially actively saturated with nitrogen (adipose tissue
dissolves 5 times more nitrogen than blood). Due to the high lipid content, the nervous system is primarily
affected, mild excitement ("deep delight") is quickly replaced by a narcotic and then toxic effect weakening of concentration, headaches, dizziness, impaired neuromuscular coordination, possible loss of
consciousness. To prevent these complications in diving operations, it is advisable to use oxygen-helium
mixtures, since helium dissolves worse (than nitrogen) in the nervous tissue and is indifferent to the body.
During the transition from the area of increased barometric pressure to the area of normal
atmospheric pressure (decompression), the main symptoms of caisson (decompression) develop.
onny) disease, due to a decrease in the solubility of gases (desaturation). Nitrogen released in excess
from tissues does not have time to diffuse out of the blood through the lungs and forms gas bubbles. If
the diameter of the bubbles exceeds the lumen of the capillaries (over 8 microns), gas embolism occurs,
causing the main manifestations of decompression sickness - muscular-articular and retrosternal pain,
visual impairment, itching, vegetative-vascular and cerebral disorders, lesions of peripheral nerves.
8. The disease-causing effect of low barometric pressure on the body: etiology and pathogenesis,
manifestations of mountain and altitude diseases.
Low barometric pressure action. Mountain (altitude) sickness
The term "altitude sickness" describes mainly cerebral and pulmonary syndromes that may develop
shortly after ascent to great altitude. A person experiences the effect of low barometric pressure
(hypobaria) when climbing mountains, when climbing to a height in non-pressurized aircraft, in special
pressure chambers. The resulting pathological changes are due to two main factors - a decrease
atmospheric pressure (decompression) and a decrease in the partial pressure of oxygen in the inhaled
air.
At an altitude of 9000 m (225.6 mm Hg) and more, in 10-15% of flights in non-pressurized cabins (but with
oxygen devices), symptoms of decompression occur, which is associated with the transition to a gaseous
state of nitrogen dissolved in tissues and the formation of bubbles free gas.
Bubbles of nitrogen enter the bloodstream and are carried by the blood to various parts of the body,
causing vascular embolism and tissue ischemia. At an altitude of 19,000 m (47 mm Hg) and above,
"Boiling" of body fluids at body temperature, there is a so-called high-altitude tissue emphysema.
Mountain (altitude) sickness caused by a decrease in the partial pressure of oxygen in the
inhaled air when climbing to great heights. Risk Factors for Altitude Sickness
are: high ascent rate, permanent residence at an altitude below 900 m, physical stress, the presence of
concomitant cardiopulmonary diseases, age over 50, genetically mediated individual sensitivity Cold
temperature is an additional risk factor, since cold increases the pressure in the pulmonary artery and
stimulates the sympathetic nerve system, therefore high-altitude pulmonary edema occurs more often in
the winter. Climbers and skiers who already have similar episodes may have a sudden relapse at high
altitude. In this case, high-altitude pulmonary edema
quickly reversible (it is enough to descend to a lower height), which distinguishes it from acute
respiratory distress syndrome.
By pathogenesis, high-altitude pulmonary edema is not cardiogenic, i.e. not associated with heart
weakness, it develops as a result of increased pressure in the pulmonary artery system. Hypoxia
increases the excitability of the sympathetic nervous system, which causes constriction of the pulmonary
veins and an increase in capillary pressure.
High-altitude cerebral edema (the final stage of acute altitude sickness) is manifested by impaired
coordination of movement and impaired consciousness, drowsiness or even stupor, less often convulsions,
may be accompanied by retinal hemorrhage, cranial nerve paralysis due to increased intracranial
pressure. When climbing to a great height, almost all people experience brain swelling to one degree or
another.
... In the pathogenesis of altitude sickness, two stages are distinguished: the stage of adaptation and
the stage of decompensation.
The stage of adaptation. At an altitude of 1000-4000 m, as a result of hypoxemic blood irritation of the
chemoreceptors of the vessels of the carotid sinus and the aortic arch (most sensitive to a lack of oxygen),
reflex stimulation of the respiratory and vasomotor centers and other centers of the autonomic system
occurs. Shortness of breath, tachycardia occur, blood pressure rises (slightly), the number of erythrocytes
in the peripheral blood increases [up to (6-8) -1012 / l] due to their reflex "release" from the spleen and
other depot organs. At an altitude of 4000-5000m, there are signs of disinhibition and excitation of cortical
cells: people become irritable, hidden character traits are exposed (in the mountains it is easier to get to
know each other better). Violation of cortical processes can be detected with the help of a "writing test" handwriting changes, writing skills are lost. As a result of increasing hypoxia in the kidneys, the production
of erythropoietin is turned on, which leads to the activation of the processes of erythropoiesis in the bone
marrow and an increase in the number of reticulocytes and erythrocytes in the peripheral blood.
Stage of decompensation (the actual disease). This stage usually develops at an altitude of 5000 m and
more (see Table 2-2). As a result of hyperventilation of the lungs and a decrease in the formation of CO2 in
tissues (due to tissue hypoxia, the oxidation of carbohydrates and fats does not end with the formation of
carbon dioxide and water) hypocapnia and gas alkalosis develop, which reduce the excitability of the
respiratory and other centers of the central nervous system.
Euphoria and excitement give way to oppression, depression. Fatigue, drowsiness, and inactivity
develop. Inhibition of differentiated reflexes is observed, then disappear
positive food and other reflexes. Breathing becomes more rare and periodic (like Cheyne-Stokes and Biot).
Progressive hypocapnia and alkalosis at altitudes above 6000-8000 m can cause death from paralysis of
the respiratory center
9. The pathogenic effect of low temperatures on the body: compensatory mechanisms, pathological
changes in organs, body systems during decompensation, the cause of death.
As a result of the action of low temperatures in the human body, a number of local and general reactions
occur that can cause colds, a decrease in body temperature, local changes in tissues (frostbite) and end
with the freezing of the body. The occurrence and severity of changes in the body during its cooling depend
on the ambient temperature and the nature of its effect (air, water), the speed of air movement (wind) and
its humidity, insulating
properties of thermal protection of the body and other factors. Distinguish between general and local
cooling of the body.
Total cooling - violation of the heat balance in the body, leading to a decrease in body
temperature (hypothermia). Hypothermia occurs:
1) with increased heat transfer and normal heat production;
2) with a decrease in heat production and normal heat transfer;
3) with a combination of these factors.
Most often in warm-blooded animals, the first variant of the development of hypothermia occurs,
therefore, in the compensation phase, reactions are primarily aimed at limiting
heat transfer: reflexively there is a spasm of blood vessels, sweating decreases, breathing slows down.
Further, the mechanisms of thermoregulation are turned on, aimed at increasing heat production: muscle
tremors (chills) arise, the processes of glycogenolysis in the liver and muscles increase, the content of
glucose in the blood rises, and the basal metabolism increases.
With prolonged exposure to low temperatures, a decompensation phase develops. The body
temperature decreases, muscle tremors cease, oxygen consumption and the intensity of metabolic
processes decrease, peripheral blood vessels expand. As a result of inhibition of the functions of the
cerebral cortex and suppression of the subcortical and bulbar centers, blood pressure decreases, the
rhythm of heart contractions slows down, the frequency of respiratory movements progressively
weakens and becomes less frequent, and a gradual extinction of all vital functions is noted. Death
occurs from paralysis of the respiratory center.
The suppression of the functions of the central nervous system during hypothermia can also have a
protective value, which is associated with a decrease in the sensitivity of nerve cells to a lack of oxygen. A
decrease in tissue metabolism reduces the body's need for oxygen.
It is also known that hypothermia increases the body's resistance to intoxication, infection and some other
adverse environmental influences. An artificial decrease in body temperature (hibernation), achieved
under anesthesia with the help of physical influences, is used in medical practice (in particular, in cardio
and neurosurgery) in order to reduce the body's need for oxygen and prevent temporary cerebral
ischemia.
Low temperature local action can cause frostbite of varying severity, the pathogenesis of which
is associated with changes in the colloidal state of the tissue, disturbances in intracapillary blood
flow and rheological properties of blood.
I degree of frostbite, the mildest, approximately the epidermal layer is affected. A frozen and pale area
causes a burning and tingling sensation, after warming it is hyperemic, burning
hurts, swells. Recovers in 3-7 days.
II the degree of frostbite, approximately corresponds to the 2-3A degree of the burn. The frostbite area loses
sensitivity after paleness and burning. After warming, bubbles are formed.
liquid, after removal, the bottom of the wound is painful, bleeding. The area of damage itches and hurts, sensitivity
is restored. Scars are not formed during wound healing.
III degree - damage leads to skin necrosis. The bubbles formed after warming the frostbite zone contain
hemorrhagic fluid, the sensitivity and color of the damaged zone are not
are restored. After a while, the damaged elements of the skin are rejected, there is a danger of an infectious wound
process, the wound heals with the formation of a scar.
Frostbite IV degree. Damage to all soft tissues including bones and joints. No bubbles form
swelling of the tissues quickly sets in, the surface temperature remains cold.
The pathogenic effect of high temperatures on the body. Describe
compensatory mechanisms, pathological changes in organs and systems of the body, decompensation
phenomena
10.
1 the degree of burn is damage to the epidermis to the papillary layer, i.e. to the basement membrane.
2 the degree of the burn - damage to the epidermis and partially the growth zone, part of the papillae perishes.
Grade 3A - the epidermis, its growth layer and partly the dermis die, the sebaceous and sweat glands, hair
follicles are preserved.
3B burns - death of the entire epidermis and dermis to the subcutaneous tissue.
4 degree - charring of all soft tissues - skin, subcutaneous fat, muscles. Down to the bone
Exposure to high temperatures can cause burns, burns and overheating of the body.
Burn (thermal) - local (local) tissue damage with an increase in their temperature within 45-50 ° C and
higher as a result of the action of flame, hot liquids, steam, heated solids. Depending on the depth of
tissue damage, four degrees of burns are distinguished: 1) skin redness (erythema); 2) the formation of
bubbles; 3A) partial or complete necrosis of the Malpighian (growth) layer of the skin; 3B) complete
necrosis of the skin in its entire thickness; 4) necrosis of the skin and underlying tissues.
The mechanism of occurrence of burns is associated with an inflammatory reaction at the site of action of
a thermal agent and coagulation of proteins, leading to cell death and tissue necrosis.
Burn disease - versatile functional disorders of internal organs and systems of the whole organism,
caused by extensive (more than 10-15% of the body surface) and deep burns. In the development of
burn disease, four periods are distinguished:
1) burn shock (see chapter 4);
2) general toxemia - the result of autointoxication with tissue decay products formed at the site of the burn
(denatured protein, biologically active amines, polypeptides, etc.), and the production of specific burn
autoantibodies. In addition, a burn autoantigen was found in the skin of animals and humans, which is
absent in healthy people and in tissues with a different nature of damage;
3) septicotoxemia (accession of infection);
4) convalescence (recovery).
Overheating (hyperthermia) - a temporary passive increase in body temperature due to the accumulation
of excess heat in the body (with difficulty in heat transfer processes and the action of high ambient
temperatures).
To maintain a normal body temperature at a maximum level of heat production (work) and heat
entering the body of 100-150 kcal / h due to thermal radiation, a total heat transfer to the
environment of about 500-600 kcal / h is required.
When the temperature of the skin and the environment is equalized (on average 33 ° C), the transfer of
heat from the body surface due to convection and thermal radiation stops. At higher ambient
temperatures, heat loss is only possible due to the evaporation of sweat from the skin surface. Stopping
the separation or evaporation of sweat (high air humidity, moisture-proof clothing, etc.) can lead to
overheating already at 33-34 ° C. Overheating is promoted by a lack of water in the body and insufficient
replenishment of its losses with sweat.
An increase in body temperature is accompanied by a sharp increase in respiratory movements caused by
irritation of the respiratory center with heated blood (PN Veselkin), thermal dyspnea develops. Further,
there is an increase in heart rate and an increase in blood pressure. Due to the loss of water through
increased sweating, blood thickens, electrolyte metabolism is disturbed, hemolysis of erythrocytes
increases, and the phenomena of intoxication of the body with the decomposition products of hemoglobin
occur. Damage to various tissues is also accompanied by the accumulation of toxic products of their decay.
Due to the destruction of VII, VIII, X and other plasma factors, blood clotting is impaired.
Overstrain of the mechanisms of thermal regulation leads to their depletion, accompanied by inhibition of
the functions of the central nervous system, depression of respiration, cardiac function, a decrease in
blood pressure and, ultimately, to deep hypoxia.
Acute overheating of the body with a rapid rise in body temperature and prolonged exposure to high
ambient temperatures can cause heatstroke. The main disorders in the body during heatstroke are
shown in Fig. 2-1.
Death from heatstroke occurs from paralysis of the respiratory center.
11. The pathogenic effect of the rays of the solar spectrum, ultraviolet rays on the body: types of
pathogenic effects on the body, their mechanisms. Influence of laser radiation on the body: types of
pathogenic effects on the body, their mechanisms. The use of laser in medicine.
Ultraviolet (UV) radiation penetrates the skin and conjunctiva of the eyes to a depth of tenths of a
millimeter. However, its effect is not limited to local changes, but extends to the entire body.
The biological properties of UV radiation differ depending on the wavelength. In this regard, the entire
range of UV radiation is divided into three regions: region A (long wave) - 400-320 nm; region B
(medium wave) - 320-280 nm; region C (shortwave) - 280-200 nm.
Area A It is also called fluorescent (by the ability to cause the glow of certain substances, for example, in
fluorescent lamps), or tanning due to the pigment-forming effect: Area B (with short exposure to UV
radiation in small doses) is characterized by a strong general stimulating effect. The mechanism of the
general stimulating photochemical action of UV radiation is associated with its ability to excite atoms and
increase their reactivity. In general, this leads to an increase in the activity of chemical reactions in cells,
which has a stimulating effect on metabolic and trophic processes. Ultimately, the growth and regeneration
of tissues are enhanced, the body's resistance to the action of infectious and toxic agents increases, and
physical and mental performance improves.
D3 (cholecalciferol).
Area C has a pronounced bactericidal effect, the maximum of which is at a wavelength of 254 nm.
The pathogenic effect of a one-time excessive UV irradiation (photochemical burn) is associated with the
activation of free radical (peroxide) lipid oxidation, which leads to membrane damage, breakdown of
protein molecules, and cell death in general (see Chapter 3).
Excessive UV radiation can provoke an exacerbation of certain chronic diseases (rheumatism, stomach
ulcer, tuberculosis, etc.). With intense UV irradiation, due to the increased formation of melanin and the
destruction of proteins, the body's need for essential amino acids, vitamins, calcium salts, etc. increases.
Excessive UV irradiation in the wavelength range of 280-200 nm (region C) can lead to inactivation of
cholecalciferol - to the transformation him in
indifferent (suprasterols) and even harmful (toxysterols) substances, which must be taken into
account during prophylactic UV irradiation.
Prolonged excessive UV exposure can promote the formation of mutagenic peroxides and epoxies and
induce basal cell and squamous cell skin cancers, especially in fair-skinned people.
The general effect of UV radiation, together with the thermal effect of the sun's rays (infrared rays heating
deeper tissues), manifests itself in the form of the so-called sunstroke. The effect of UV radiation on the
nervous system is mediated through blood proteins and cholesterol irradiated in the capillaries of the skin.
There is an excitement of the vegetative centers of the hypothalamus and subcortical nodes, an increase
in body temperature, an increase and further drop in blood pressure, drowsiness, collapse and death from
paralysis of the respiratory center (see section 2.5).
Sunstroke often occurs when you are on the beach for a long time.
the disease-causing effect of laser radiation.
Lasers - devices for obtaining narrow monochromatic beams of high-intensity light energy,
successfully used
are used for the treatment of a number of diseases (eye diseases, tumor growths, etc.).
The effect of laser radiation is measured in hundred-thousandths of a second, therefore, despite the
sufficiently deep penetration of the laser beams into the body (up to 20-25 mm), there is no pain
sensation. Pigmented tissues are most sensitive to laser radiation.
The mechanism of the damaging effect of laser radiation is not well understood. The direct damaging
effect of laser radiation on a cell is associated with the excitation of atoms and, ultimately, with damage to
protein molecules. The free radical mechanism plays an important role in the damaging effect of laser
radiation (see Section 3.2.1). The formation of free radicals under the action of laser beams was found in
melanin-containing tissues and skin of black mice, as well as in pigmented areas of the skin of guinea
pigs.
Laser radiation has a thermal and cavitation effect. The thermal effect is associated with the absorption of
the energy of the infrared part of the radiation spectrum by the tissue and the thermal inactivation of the
protein. The cavitation effect is caused by a rapid increase in temperature to a level at which the
evaporation of the liquid part of the cell occurs. An "explosive effect" (cavitation) occurs due to the
instantaneous formation of a microcavity with increased pressure (up to tens and hundreds of
atmospheres) and a shock wave propagating from it, tearing the tissue. This effect is at the heart of the
laser scalpel. One of the mechanisms of the damaging effect of laser radiation can also be the inactivation
of enzymes caused by it or a change in their specific activity.
The severity of the damaging effect of laser radiation depends on the type of optical quantum generator,
radiation density and power, physicochemical and biological characteristics of the irradiated tissues (the
degree of their pigmentation, blood circulation, thermal conductivity).
12. Describe the damaging effect on the body of mechanical influences and electric current: factors on
which the damaging effect depends, the mechanisms of damage.
Mechanical factors can have both local and general damaging effects on the body. The effect of their
pathogenic action is determined by the strength of this action (kg / cm2) (stretching, compression) or in the
form of kinetic energy of a mass moving at a certain speed (mV2 / 2g) (blow, fall, bullet or other gunshot
wound). The damaging effect of mechanical factors also depends on the state of reliability, strength or
resistance of the damaged structures.
Durability biological structures (tendons, bones, blood vessels, muscles, etc.) is called their ability to
resist the deforming effects of mechanical damaging agents. Ultimate strength (e = P / F) is the ratio of
the applied load
(P, kg) to the cross-sectional area of the material (F, cm2). This value characterizes the stress at which the
tissue is destroyed by deformation.
Stretching and tearing. Mechanical forces can stretch living structures. Elongation - the reciprocal of the
elasticity or elasticity of the tissue (resistance to deformation and the ability to restore the original state),
shows how much (DL) of the original length (L) the test object can be stretched.
extensibility is the elongation e = AL / L.
With age, the strength and elasticity of tissues decreases. In this regard, the elderly and the elderly
are more likely to experience fractures, cracks, stretching and deformation of tissues. Various
pathological processes also affect tissue extensibility. For example, inflammation reduces elasticity
and
increase the extensibility and risk of rupture of tendons, ligaments, muscles and other structures. The
result of the action of the tearing force also depends on the initial state of the tissues. So, a muscle at rest
is more extensible than a contracting one.
Compression. The bones and the musculoskeletal system have the greatest resistance to
compression. So, for deformation of the femur by compression, a load of 685 kg / cm2 is required. The
bone tissues of the skull can withstand pressure up to 500 kg / cm2, while their resistance to pressure is
1000 times higher than the impact resistance.
Particularly serious violations occur as a result of prolonged pressure on the body of a person trapped in
rubble during earthquakes, bomb explosions, etc. Shortly after release
from under the blockage (decompression) there are total functional and morphological disorders "prolonged crush syndrome", characterized by shock symptoms, progressive renal failure with
symptoms of oligo- and anuria, the development of edema, increasing general intoxication of the
body.
Hit. This is a set of mechanical phenomena that arise when a moving solid body (or a moving body with
an obstacle) collides, as well as when a solid body interacts with a liquid or gas (a jet hitting a body, a
body hitting a liquid surface, the action of an explosion or shock wave on a body, etc. .). As a result of the
impact, the integrity of the tissue is disrupted: bone fractures, ruptures of the skin, soft tissues, blood
vessels, bleeding, damage to the subcutaneous tissue and internal organs occur.
Electric shock called the ordered motion of charged particles.
A person is exposed to natural (lightning) or technical electricity. Death occurs from heart and / or
respiratory paralysis
The pathogenic effect of technical electricity (electrical injury - damage caused by electric shock or
electric arc). Depending on the type of current (direct or alternating current. Current. At the same strength,
alternating current (periodically changing its direction in the circuit) is more dangerous than direct current
(Table 2-3). A current of 100 mA is
deadly. An alternating current of 50-60 Hz with a force of 12-25 mA induces seizures
("unreleasing"); its main danger lies in "chaining" the affected person to the current-carrying
object captured by him.
Voltage is a value that is numerically equal to the work performed when moving a single positive charge
on a section of an electrical circuit. The voltage of the current source acting on the body up to 40 V does
not cause fatal injuries, at a voltage of 1000 V lethality reaches 50%, at a voltage of 30 000 V - 100%.
The danger of an alternating current at 42.5 V is equal to the danger of direct current at 120 V. However,
direct current is less dangerous than alternating current, only up to a voltage of 450-500 V. At higher
voltages, direct current becomes more dangerous than alternating current
Tissue resistance (a value characterizing the resistance of a part of the human body to electric current) is
due to the conversion of electrical energy into other types of energy. The total (total) resistance of the
human body to variable
This electrical current is called impedance and is the sum of the active (ohmic) and reactive (capacitive)
resistance of tissues. The outer epidermal layer of the skin has the greatest resistance to electric current (up
to 2,000,000 Ohm
Time factor. With an increase in the time of passage through the body, the pathogenic effect of the
action of the electric current increases. So, if the action of a current with a voltage of 1000 V for 0.02 s is
not accompanied by the development of pronounced violations, then with an exposure of 1 s it inevitably
leads to death.
The state of the body's reactivity. Fatigue, weakening of attention, mild and moderate alcohol
intoxication, hypoxia,
overheating, thyrotoxicosis, cardiovascular failure reduce the body's resistance to electrical injury. The
severity of electrical injury is significantly reduced with emotional stress caused by the expectation of the
action of the current, in a state of anesthesia and deep (close to anesthesia) intoxication.
Mechanisms of the damaging effect of electric current. Electrical injury can cause local (current
signs, burns) and general changes in the body.
Local reactions to electrical injury. Signs of current, burns occur mainly at the points of entry and exit of
current as a result of the conversion of electrical energy into heat (heat
Joule Lenz). Signs of current appear on the skin if the temperature at the point of current passage does
not exceed 120 ° C, and are small formations of a grayish-white color ("parchment" skin), of a hard
consistency, bordered by an undulating elevation. In some cases, a branchy pattern of red appears
around the circumference of the damaged tissue, due to paralysis of the blood vessels.
At temperatures at the point where the current passes over 120 ° C, burns occur: contact burns from the
release of heat when the current passes through the tissues that provide resistance, and thermal burns
when exposed to the flame of a volt arc. The latter are the most dangerous.
General reactions of the body to electrical injury. When passing through the body, an electric current
causes excitation of nerve receptors and conductors, skeletal and smooth muscles, glandular tissues. This
leads to tonic spasms of skeletal and smooth muscles, which can be accompanied by avulsion and
dislocation of the limbs, spasm of the vocal cords, respiratory arrest, increased blood pressure, involuntary
urination and defecation. Excitation of the nervous system and organs of internal secretion leads to the
"release" of catecholamines (adrenaline, norepinephrine), changes many somatic and visceral functions of
the body.
Respiratory arrest and cardiac arrest are the immediate causes of death from electrical shock.
The defeat of the respiratory and vasomotor centers is due to depolarization of cell membranes
and coagulation of cytoplasmic proteins.
13. Give the mechanisms of space flight factors damaging the organism: pathogenesis of the effect of
weightlessness, overloads on the organism. Damaging effect of ionizing radiation on the body: pathogenesis
of direct and indirect action of ionizing radiation on the body...
damaging effect of overloads and space flight factors.
The factors that have the most significant impact on the state of the human body in space flights
include:
1) accelerations and overloads caused by them in active flight phases (during takeoff of a spacecraft and
during descent);
2) weightlessness; 3) stressful influences, in particular emotional.
In addition, the state of the astronauts is influenced by changes in the rhythm of the daily period, sensory
isolation to varying degrees, a closed habitat with microclimate features, periodically some dustiness of
the artificial atmosphere of a spacecraft, noise, vibration, etc. The impact of ionizing radiation is taken into
account when providing spacecraft with radiation protection, when planning manned space walks.
Acceleration, overload. Accelerations are expressed at the beginning of the flight during takeoff of the
spacecraft and at the end of the flight during the descent of the spacecraft from orbit (entry into the dense
layers of the atmosphere and landing).
Acceleration is a vector quantity that characterizes the speed of changes in the speed of movement or
direction of movement. The amount of acceleration is expressed in meters per second squared (m /
s2).
"Overload" - this is the force of inertia that occurs when moving with acceleration, acts in the
direction opposite to the movement
According to the ratio of the vector to the longitudinal axis of the human body, there are longitudinal
positive overloads (in the direction from the head to the legs), longitudinal negative (from the legs to
the head), transverse positive (chest-back), transverse negative (back-chest), lateral positive (right left)
and side negative (left to right).
...
Circulatory changes in zero gravity are due to several factors.
This causes an increase in blood volume in the vessels of the head, swelling of the soft tissues of the face,
and
a feeling of fullness of the head, sometimes a headache in the first days of flight (a period of acute
adaptation). In response to these disorders, reflexes arise that change the tone of the vessels of the
brain.
Redistribution of blood in the vascular bed, a change in venous return, the disappearance of such an
essential factor as hydrostatic pressure, a decrease in the total energy consumption of the body - all this
affects the work of the heart. In conditions of weightlessness, the ratio of the load on the left and right parts
of the heart changes. As a result, the phases of the cardiac cycle, the bioelectrical activity of the
myocardium, the diastolic blood filling of the heart cavities, and the tolerance of functional tests change.
Due to the redistribution of blood in the vascular bed, the center of gravity of the body shifts in the cranial
direction. In the early period of being in zero gravity, a significant redistribution of blood in the vascular bed
and a change in the blood filling of the heart cavities are perceived by the afferent systems of the body as
information about an increase in the volume of circulating blood and cause reflexes,
Changes in water and electrolyte metabolism in the early period of weightlessness are explained
mainly by a decrease in the secretion of antidiuretic hormone and renin, and then aldosterone, as well
as an increase in renal blood flow, an increase in glomerular filtration and a decrease in tubular
After space flights, a decrease in erythrocyte mass is noted. Recovery of hematological parameters
occurs within 1.5 months after the end of the flight.
Stressful influences. In space flight, a person is exposed to stresses (see Section 4.1), which are based
on a combination of factors: changes in the influence of gravity, tension of attention, intense loads, etc. The
period of acute adaptation to weightlessness can be characterized as a stress reaction that has arisen in
response to on the action of a complex of specific (zero gravity) and nonspecific factors (emotional and
physical stress, altered circadian rhythms, circulatory disorders).
Cosmic form of motion sickness resembling seasickness, manifests itself during the first days of the
flight. With rapid head movements, dizziness, pallor of the skin, salivation, cold sweat, a change in the
frequency of heart contractions, nausea, vomiting, and a change in the state of the central nervous
system are observed. These disorders are mainly caused by changes in microcirculation in the vessels of
the brain.
Immunological reactivity of the body. After space flights exceeding 30 days, as a rule, there is a
decrease in the functional activity of cell populations belonging to the T-system of immunity, and in some
cases there are signs of sensitization to microbial and chemical allergens. These changes increase the
risk of infectious and allergic diseases and may be a consequence of the restructuring of the immune
system in the process of adaptation to a complex of flight factors.
Re-adaptation. At the end of the flight, the transition from zero gravity to g-forces during descent and the
return to Earth's gravity from the moment of landing are combined with significant emotional stress and
are, in essence, a combined stress that occurs under conditions of tense adaptation reactions. At the
same time, changes in the state of the body reflect the dynamics of adaptive and stress reactions.
During the period of readaptation, the action of the factors that caused dehydration in
weightlessness, redistribution of blood in
vascular bed, etc.
pathogenesis of direct and indirect ionizing radiation
Direct action is the direct effect of ionizing radiation on molecules of various biological structures (primarily
hormones and enzymes). Depending on the dose of absorbed rays, the process b> depolymerization of
colloidal structures or, conversely, their polymerization can take place. Indirect action - due to the harmful
effect of the products of water radiolysis on the biological structures of the body:2O2 , O -, OH-.
Peroxidesubstances have strong oxidizing and toxic properties. Entering into compounds
2
with organic
substances, they cause significant chemical changes in cells and tissues, denaturation of protein and other
organic structures with the formation of toxic histamine-like substances. Radiochemical processes cause
depolymerization of hyaluronic acid, gluco- and lipoproteins, disrupt the permeability of cell membranes,
and cause changes in DNA and RNA.
The damaging effect of radiation on organic molecules (including such vital target molecules as DNA,
proteins, etc.) can be based on two mechanisms (Fig. 1). The first mechanism is caused by damage to the
target molecule as a result of direct interaction of radiation with this molecule, i.e. as a result of the direct
action of radiation. The second mechanism is caused by damage to the target molecule by active products
(for example, radicals) formed from other molecules as a result of their direct interaction with radiation.
Thus, in this case, damage to the target molecule occurs as a result of the indirect (or indirect) action of
radiation.
14. Give the definitions of the concepts: acute and chronic radiation sickness. Describe their stages,
changes in the body.
The first period of acute radiation sickness develops in response to radiation exposure. The time of onset of
individual symptoms, their severity, and the duration of preservation depends on the severity of radiation
injury.
The main manifestations of a common primary reaction:
— dyspeptic syndrome (nausea, vomiting that occurs suddenly);
— changes in the central nervous system (headache, dizziness,
agitation or weakness, drowsiness, loss of consciousness, hyperthermia, hyperhidrosis, impaired coordination
of movements, muscle tremor, general weakness, increased tendon and periosteal reflexes, meningeal
syndrome);
— changes in the cardiovascular system (palpitations, pain in the heart, arterial hypertension, then
hypotension, in severe cases - acute cardiovascular failure, collapse);
— neutrophilic leukocytosis.
Latent period (relative clinical well-being).
The general well-being improves. Symptoms of reflex origin disappear: temperature normalizes, headache,
nausea disappears,
improves appetite. Signs of asthenia and vegetative-vascular dysfunction persist: fatigue, sweating, mood
instability, sleep disturbance, loss of appetite, tachycardia, hypotension.
Signs of damage to the hematopoietic system progress: leukopenia with
lymphopenia, anemia, and thrombocytopenia (pancytopenia). The changes are most pronounced by the end
of the latent period.
At the end of this period, hair loss is noted in areas of the skin that received irradiation with a dose of more
than 3 times
The peak period
The clinical picture of this period is mainly a consequence of the depression of bone marrow
hematopoiesis.
Pancytopenia leads to a sharp decrease in the body's defenses.
As a result, infectious complications develop: necrotizing tonsillitis, stomatitis, pneumonia, enterocolitis
and, in severe cases, sepsis. Hemorrhagic syndrome is a consequence of thrombocytopenia, a
decrease in the resistance of the vascular wall: hemorrhages on the mucous membranes of the oral
cavity, skin, nose, intestinal bleeding, hematuria.
A sharp decrease in appetite, vomiting, diarrhea, fever lead to dehydration, metabolic disorders.
Characterized by severe weakness, weakness, headaches, dizziness.
Neurological examination reveals symptoms of irritation of the meninges. Biochemical blood test:
hypoproteinemia due to hypoalbuminemia.
Recovery period
It begins with signs of hematopoiesis restoration - the appearance of immature cells (myeloblasts,
promyelocytes, myelocytes, reticulocytes) in the peripheral blood. Within a few days, the number of
leukocytes increases.
The clinical picture: a critical drop in body temperature, an improvement in general well-being, the
disappearance of signs of bleeding. Physical activity and appetite are restored.
Asthenization, vegetative-vascular dysfunction, instability of hematological parameters, trophic and
metabolic disorders, vestibular disorders, diencephalic syndrome persist for a long time. The recovery
period lasts from several months to a year.
The period of the disease formation lasts from several months to several years, depending on the intensity
of radiation, the rate of dose accumulation, and the individual reactivity of the organism. May continue after
cessation of exposure. The sequence of the onset of symptoms depends on the unequal sensitivity of
organs to penetrating radiation. The severity of clinical manifestations is determined by the severity of the
lesion.
Symptoms: dysfunction and organic changes in the central nervous system (focal changes,
encephalomyelosis, pyramidal insufficiency), inhibition of hematopoiesis (especially leukopoiesis),
hemorrhagic syndrome. Dysfunctions of the gastrointestinal tract (inhibition of secretion and motility), a
decrease in the function of the endocrine glands (especially the thyroid gland), and skin changes may
develop.
The recovery period begins after the termination of irradiation. During treatment, there is a gradual
disappearance of the symptoms of the disease, the function of internal organs is normalized.
The period of long-term complications and consequences is observed mainly with pronounced forms of
chronic radiation sickness. Mild cases of the disease end in a relatively short period of time with full
recovery.
Chronic radiation sickness of mild (I) degree develops slowly. During the formation period, there are
complaints of headache, which is difficult to eliminate by conventional means (analgesics), rapid fatigue,
general weakness, sleep inversion (sleepiness during the day and sleeplessness at night), impaired
appetite, dyspeptic disorders not associated with errors in nutrition, unpleasant sensations in the area
hearts. General blood test: slight leukopenia, thrombocytopenia, anemia, reticulocytopenia, lymphocytosis
Chronic radiation sickness of moderate degree (II) severity is characterized by functional and organic
changes in internal organs.
Patient complaints: persistent headache, general weakness, fatigue, loss of appetite, weight loss,
bleeding symptoms, hyperthermia, menstrual irregularities. Patients look older than their age,
emotionally labile. General blood test: leukopenia, thrombocytopenia, anemia, reticulocytopenia ...
In the leukocyte formula, lymphocytosis, neutrophilic shift to the left. Hypocoagulation is observed
Chronic severe (III) radiation sickness degree is characterized by pronounced dystrophic
changes in internal organs, early onset of thermoregulation disorders.
Symptoms of organic brain damage are revealed: an increase or decrease in tendon and abdominal
reflexes, impaired muscle tone and statics, optico-vestibular symptoms, nystagmus. General blood
analysis: severe pancytopenia, reticulocytopenia. Reduced osmotic resistance of erythrocytes.
15. Classification of types of reactivity, forms of reactivity. Give clinical examples of different forms
of reactivity
All living organisms have the property of changing their state under the influence of the influences of the external
environment. Moreover, every living object is capable of responding to stimuli with the help of programmed reactions
or acquired ones that arose in the course of its individual experience.
A person's susceptibility to a certain infection or other damaging factor is determined not only by the properties of the
pathogenic agent, but also by the properties of the organism: its reactivity and resistance. The founder of the first
concept of the role of reactivity in pathology is considered to be Claudius Galen, who wrote,
that the causative factor causes disease only in an organism that has a special state of predisposition.
Reactivity (R) - this property of the organism to respond with changes in life activity to the influence of factors of the
internal and external environment. R is characteristic of all living organisms and was formed in the process of
evolution. R can be considered as a special biological form of reflection inherent in all levels of organization of a living,
however, the simpler the organism is, the less developed its nervous system, the simpler it is R. Living beings at a
higher stage of evolution also have more complex responses. The most primitive of the simplest and lower animals,
more complex and diverse
– in warm-blooded animals and humans.
Reactivity classification:
Distinguish between species, group and individual R.
Species (biological)- a complex of responses characteristic of all individuals of a given species, it was formed in
the process of evolution and is determined by the hereditary properties of the organism - this is the so-called
primary R.
Examples of species reactivity: seasonal migration in fish and birds; changes in body temperature when the
environment t0 changes in amphibians (amphibians); hereditary immunity to infection in animals and humans - for
example, human resistance to canine distemper; resistance of dogs to tetanus, chickens - to anthrax (because their
bodies are> optimal for the development of this KSD), immunity of rats to diphtheria toxin (their cells do not have
receptors for it).
Group (typical) –R, characteristic of a group of individuals within the same species. The division into groups can be
based on age, sex, constitutional, racial characteristics, the presence of the Rh factor, blood group, type of higher
nervous activity, etc.
Examples of group reactivity: resistance to the effects of alcohol in representatives of various nations (the Indians of
North America, the indigenous population of Siberia - the Ostyaks, the Tungus quickly acquired alcohol dependence),
different resistance to UV exposure in Negroids and Caucasians. One of the modern classifications of constitutional
types proposed by Chernorutsky: asthenics, hypersthenics and normosthenics - connects the body type with a
predisposition to certain diseases.
It is interesting that already in the most ancient Indian manuscripts - Ayurveda - the following classification of
individuals, depending on their constitution and reactions, is described: gazelle, fallow deer and elephant-like
cow.
Individual - this is R, characteristic of an individual and distinguishing it from other representatives of this species. It
is formed on the basis of species and group, and also depends on the influence of the external environment in which
the organism lives. IndividualRm.b. changed artificially by hardening, training or vaccination, and other influences.
Example: unequal manifestations of the disease, for example, a mild course of influenza in one person and a severe
one in another.
Types of individual reactivity...
R can be physiological and pathological.
Physiological reactivity- it is R of a healthy organism in favorable conditions for life;
Pathological reactivityIs painfully changed R. It is characterized by an inadequate response of a sick organism to a
stimulus.
Examples of physiological and pathological reactivity:
•
•
peaks and normalizes by the end of 2]glucose[this is an experiment with a sugar load (100 g of glucose in
200 ml of water in the morning on an empty stomach): in a healthy person after 30-60 minutes th at all).Ü
within 3-4 hours (or not Ü glucose is observed after 60-150 minutes and ]from[h, and in a patient with
diabetes mellitus the maximum
Changes in responses in shock (phagocytosis is weakened, fever does not develop, the body does not
respond to the release of hormones); for epilepsy (conditioned and unconditioned reflexes are suppressed,
hypo-
or paresthesia, the absence of allergic reactions of anaphylactic type after a seizure), with anesthesia,
the synthesis of AT, phagocytosis is inhibited, inflammation develops more slowly and is accompanied
by¯(> alteration, patients with coronary artery disease - coronary spasm during exercise.
There are also nonspecific and specific reactivity:
Nonspecific reactivity- the response of the body to stimuli of a non-antigenic nature.
Examples of non-specific physiologicalR - lacrimation; sneezing; withdrawal of the hand from a hot object, the stage of
altitude sickness adaptation, etc.;
nonspecific pathological t­R - stage of decompensation of altitude sickness; in a patient with meningitis, even a very
weak light and sound cause sharp pain, in a patient with hypertension, the effect of 0 on the body causes not
expansion, but narrowing of blood vessels.
Specific reactivity- this is the body's response to antigens, this includes all types of immunological R: the
production of antibodies, antitoxins, addiction to poisons, allergic reactions, reactions between the tissues of the
adult body and the embryo, transplant rejection reactions, etc. (see p. 145).
16 Give the violations of the mechanisms of energy supply of the cell: resynthesis of ATP, transport
and energy recovery.
Energy supply of cells is carried out due to ATP, which is formed mainly in the process of oxidative
phosphoridation in mitochondria and, to a lesser extent, in glycolysis reactions in the cytosol.
The energy supply of the cell can be upset at the stages of resynthesis, transport and
utilization of ATP energy. (Figure 4-2).
Fig. 4-2. Mechanisms of energy supply disruption in a damaged cell.
DISORDERS OF ATP RESYNTHESIS
ATP resynthesis is impaired as a result of a deficiency of oxygen and / or metabolic substrates, a
decrease in the activity of enzymes of tissue respiration and glycolysis, damage and destruction of
mitochondria, in which the reactions of the Krebs cycle and the transfer of electrons to molecular
oxygen, coupled with phosphorylation of ADP, take place.
ENERGY TRANSPORT DISORDERS
The energy of ATP contained in high-energy bonds is normally delivered from the sites of resynthesis mitochondria and cytosol - to effector structures (myofibrils, membrane ion pumps, etc.) using
ADPATP translocase (adenine nucleotidyl transferase) and CPK.
Adenine nucleotidyltransferase ensures the transport of energy of the high-energy phosphate bond of
ATP from the mitochondrial matrix through their inner membrane, and CPK transfers it further to creatine
with the formation of creatine phosphate, which enters the cytosol (Fig. 4-3). CPK of effector cell
structures transports the phosphate group of creatine phosphate to ADP with the formation of ATP, which
is used in the processes of cell life.
Fig. 4-3. ATP energy transport mechanism in the cell. AdT - adenine nucleotidyl transferase; Cr - creatine;
Kf - creatine phosphate; SM - substrates of metabolism; FN - inorganic phosphate.
Energy transport systems can be damaged by various pathogenic agents, and therefore (even against the
background of a high total ATP content in the cell), ATP deficiency in energy-consuming structures can
develop.
DISORDER OF ENERGY USE MECHANISMS
Disturbances in the energy supply of cells and disorders of their vital activity can develop as a result of
damage to the mechanisms of energy utilization, mainly due to a decrease in the activity of ATPases
(myosin ATPase, Na +, K + ATPase of plasmolemma, proton and potassium ATPase, Ca2 + ATPase
[Ca2 + pump], etc. ). Consequently, a disorder of the vital functions of cells can develop even under
conditions of normal or increased content of ATP in the cell.
Disruption of energy supply, in turn, can become one of the factors of disorders in the function of the
membrane apparatus of cells, their enzyme systems, the processes of transport of ions and water,
as well as the mechanisms of cell regulation.
17. Describe the typical forms of damage to the membrane apparatus and enzyme systems of cells.
Diaphragm damage
Damage to cell membranes occurs due to the following processes:
• Hydrolase activation. Under the influence of pathogenic factors, the activity of membrane-bound, free (solubilized) and
lysosomal lipases, phospholipases and proteases can significantly increase (for example, with hypoxia and acidosis). As a
result, phospholipids and membrane proteins undergo hydrolysis, which is accompanied by a significant increase in membrane
permeability.
• Membrane repair disorders. When exposed to damaging factors, reparative synthesis of altered or lost membrane
macromolecules (as well as their de novo synthesis) is suppressed, which leads to insufficient membrane restoration.
• Conformational disorders of macromolecules (their spatial structure) leads to changes in the physical and
chemical state of cell membranes and their receptors, which leads to distortions or loss of their functions.
• Rupture of membranes. Overstretching and rupture of membranes of swollen cells and organelles as a result of their overhydration
(a consequence of a significant increase in osmotic and oncotic pressure) is an important mechanism of membrane damage and cell
death.
• Free radical and peroxide reactions - normally it is a necessary link in electron transport, synthesis of PG and leukotrienes,
phagocytosis, metabolism of catecholamines, etc. Proteins are involved in free radical reactions,
nucleic acids and, especially, lipids, given the presence of a large number of them in cell membranes (free radical lipid
peroxidation - SPOL). Under the action of pathogenic factors, the generation of free radicals and SPOL increases significantly,
which increases cell damage.
♦ Stages of the SPOL: formation of reactive oxygen species - generation of free radicals of organic and inorganic substances production of lipid peroxides and hydroperoxides.
Reactive oxygen species - ❖ singlet (Ό2) ❖ superoxide radical (O2-)
❖ hydrogen peroxide (H2O2) ❖ hydroxyl radical (OH-).
♦ Prooxidants and Antioxidants. The intensity of SPOL is regulated by the ratio of its activating (prooxidants) and suppressing
(antioxidants) factors.
❖ Prooxidants - easily oxidizing compounds that neutralize free radicals (naphthoquinones, vitamins A and D, reducing agents NADPH2, OVERH2, lipoic acid, products of the metabolism of PG and catecholamines).
❖ Antioxidants - substances that limit or even stop free radical and peroxide reactions (retinol, carotenoids, riboflavin,
tocopherols, mannitol, superoxide dismutase, catalase).
♦ Detergent effects of amphiphils. As a result of the activation of lipid peroxide reactions and hydrolases, lipid hydroperoxides,
free fatty acids and phospholipids - amphiphils (substances capable of fixing both in the hydrophobic and in the hydrophilic zone
of membranes) are accumulated. This leads to the formation of extensive amphiphilic clusters (the simplest transmembrane
channels), micro-rupture and destruction of membranes.
18. Describe the significance of the imbalance of ions and fluid in the mechanisms of cell damage.
Intracellular fluid contains approximately 65% of all body water and is characterized by low concentrations of Na + (10 mmol / L),
Cl- (5 mmol / L), HCO3- (10 mmol / L), but high concentration of K + (150 mmol / L) and PO43- (150 mmol / L).
Low concentration of Na + and high concentration of K + are due to the work of Na +, K + -ATPase, which pumps out Na+ from cells
in exchange for K+... Cellular imbalance of ions and water develops following disorders of energy supply and
damage to membranes.
The manifestations of ionic and water imbalance include: ❖ change in the ratio of individual ions in the cytosol; ❖ violation of the
transmembrane ion ratio; ❖ cell hyperhydration; ❖ hypohydration of cells; ❖ violations of electrogenesis.
• Changes in ionic composition caused by damage to membrane ATPases and membrane defects. So, due to the disruption of
the work of Na +, K + -ATPase, an excess of Na + accumulates in the cytosol and the cell loses K+...
• Osmotic swelling and osmotic shrinkage of cells. The state of cells with a change in osmosis is considered in Fig. 4-3.
• Hyperhydration. The main reason for the overhydration of damaged cells is an increase in the content of Na+, as well as
organic substances, which is accompanied by an increase in osmotic pressure and swelling of cells. This is combined with
stretching and micro-rupture of the membranes. Such a picture is observed, for example, with osmotic hemolysis of
erythrocytes.
Hypohydration cells are observed, for example, with fever, hyperthermia, polyuria, infectious diseases (cholera, typhoid fever,
dysentery). These conditions lead to the loss of water by the body, which is accompanied by the release of fluid from the cells, as
well as organic and inorganic water-soluble compounds. erythrocytes suspended in NaCl solution. On the abscissa: concentration
(C) NaCl (mmol / l); Y-axis: cell volume (V). At a NaCl concentration of 154 mmol / L, the cell volume is the same as in the blood
plasma (isotonic NaCl solution). With an increase in NaCl concentration (hypertonic NaCl solution), water leaves the erythrocytes,
and they shrink. With a decrease in the concentration of NaCl (hypotonic NaCl solution), water enters the erythrocytes, and they
swell. If the solution is hypotonic, approximately 1.4 times higher than the value of the isotonic solution,
• Electrogenesis disorders (changes in the characteristics of the membrane potential - MP and action potentials - AP) are
essential, since they are often one of the important signs of the presence and nature of cell damage. An example is ECG
changes with damage to myocardial cells, electroencephalograms with pathology of brain neurons, electromyograms with
changes in muscle cells.
19. Give the main types of intracellular disorders
mechanisms regulation of cell function.
Typical forms of cell pathology: dystrophy, dysplasia, metaplasia, hypotrophy (atrophy), hypertrophy, as well as necrosis and
pathological forms of apoptosis.
Hypotrophy and atrophy. Hypotrophy is characterized by a decrease in the size and mass of the cell, the extreme degree of
which is atrophy. Hypotrophy and atrophy are usually combined with a decrease in the number of cells - hypoplasia. This leads
to a decrease in the volume of the organ, thinning of the skin and mucous membranes. Example: a decrease in the mass and
number of cells in an ischemic tissue or organ. Hypertrophy. Hypertrophy is characterized by an increase in the size and mass of
the cell. This is often accompanied by an increase in the number of cells (hyperplasia). Allocate physiological and pathological
hypertrophy.
• Physiological hypertrophy is adaptive in nature (for example, skeletal muscle hypertrophy in athletes).
• Pathological hypertrophy has (along with adaptive) pathological significance. Distinguish between working, vicarious and
neurohumoral pathological hypertrophy, combined with remodeling of an organ or tissue.
♦ Working hypertrophy develops with a constantly increased load (for example, pathological hypertrophy
myocardium in hypertension).
♦ Vicarious (replacement) hypertrophy develops in one of the paired organs when the second is removed.
♦ Neurohumoral hypertrophy develops when neurohumoral regulation is impaired (for example, acromegaly, gynecomastia).
Dystrophies
Cellular dystrophies are metabolic disorders accompanied by a disorder of cell function.
Classification. The main criterion for the classification of cellular dystrophies is the predominant violation of the metabolism of certain
classes of substances. In connection with this criterion, dysproteinosis (protein dystrophies), lipidoses (fatty dystrophies),
dyspigmentosis (pigmentary dystrophies), carbohydrate and mineral dystrophies are distinguished. Tezaurismoses (accumulation
diseases) are distinguished into a separate group.
Metaplasia - replacement of cells characteristic of this organ with normal cells of a different type. Examples:
♦ Chronic inflammatory diseases of the lungs, vitamin A deficiency, smoking lead to the appearance of islets of stratified
squamous epithelium among the cells of the ciliated epithelium of the bronchi.
♦ In chronic cervicitis, it is possible to replace a single-layer columnar epithelium with a stratified squamous epithelium. Necrosis
(from the Greek necros - dead) - pathological cell death as a result of the action of damaging factors on them. Apoptosis (from the
Greek apoptosis - leaf fall) - programmed cell death. Examples of apoptosis
♦ Programmed cell death during embryonic development, histogenesis and organ morphogenesis. Example: the death of
neuroblasts (from 25 to 75%) at certain stages of brain development.
♦ Death of cells that have fulfilled their function (eg, immunocompetent cells upon completion of the immune response or
eosinophils after degranulation).
♦ Elimination of autoaggressive T-lymphocytes at certain stages of thymus development or after completion
immune response.
♦ Aging accompanied by hormone-dependent involution and apoptosis of endometrial cells, atresia of ovarian follicles in
menopausal women, as well as prostate and testicular tissue in elderly men.
♦ Transfection - the introduction into the cell of a fragment of the nucleic acid of the virus (for example, in viral hepatitis,
myocarditis, encephalitis, AIDS) often causes its apoptosis.
♦ Tumor growth is naturally accompanied by apoptosis of a large number of transformed cells.
20. Describe the concepts: extreme states - collapse, coma, their types, give a characteristic of the
pathogenesis of these conditions.
PATHOGENESIS
With collapse, shock and coma, a redistribution of blood flow is observed. A large amount of blood accumulates in the dilated
venous and arterial vessels of the abdominal cavity, lungs, and subcutaneous tissue. This significantly reduces the IOC and
therefore blood flow to the heart. The resulting decrease in cardiac blood output leads to an even greater decrease in IOC and
aggravation of the patient's condition.
Collapse - an acute general pathological condition resulting from a significant inconsistency in the BCC capacity of the vascular
bed.
Characterized circulatory failure, low blood pressure, primary circulatory hypoxia, dysfunction of tissues, organs and their systems.
Collapse reasons
The immediate cause of the collapse is the rapidly developing significant excess of the capacity of the vascular bed in comparison
with the BCC. Depending on the reasons that violate this correspondence, several types of collapse are distinguished: cardiogenic,
hypovolemic, vasodilatory, posthemorrhagic, infectious, toxic, orthostatic, etc.
Coma (Greek koma - deep sleep) - an extreme condition characterized by loss of consciousness, failure of the functions of organs
and physiological systems of the body.
Comatose states arising from various pathological processes can be divided into the following groups.
• Caused by primary damage to the central nervous system (neurogenic). This group includes coma that develops with strokes,
traumatic brain injury, epilepsy, inflammation and tumors of the brain or its membranes.
• Developing with violations of gas exchange.
♦ Hypoxic. Associated with insufficient supply of oxygen from the outside (suffocation) or impaired oxygen transport in severe
acute circulatory disorders and anemia.
♦ Respiratory. They are caused by hypoxia, hypercapnia and acidosis due to significant disturbances in pulmonary gas exchange
in respiratory failure.
• Caused by metabolic disorders with insufficient or excessive production of hormones (diabetic, hypothyroid, hypocorticoid,
hypopituitary coma), overdose of hormonal drugs (thyrotoxic, hypoglycemic coma).
• Toxogenic coma associated with endogenous intoxication with toxicoinfections, liver and kidney failure (hepatic, uremic coma),
pancreatitis; as well as with the effects of exogenous poisons (coma in case of poisoning, including alcohol).
• Due to the loss of water and electrolytes (hyponatremic coma in the syndrome of inadequate ADH production;
chlorohydropenic, which develops in patients with persistent vomiting; alimentary dystrophic, or hungry coma.
General pathogenesis and manifestations
The pathogenesis of coma, regardless of the causes that caused them, includes several common key links.
Hypoxia and disturbances in energy supply processes
Disorder of oxygen supply to tissues and organs is the most important pathogenetic link in coma and can serve as its cause.
Intoxication
Coma of any origin is characterized by the accumulation of toxic substances in the body. They enter the body from the outside
(with exogenous coma) and are formed in it (with coma of any genesis).
Imbalance of ions and water
Violation of the content and ratio between individual ions in the cytosol, intercellular and other biological fluids is an important link
in the pathogenesis of coma.
Electrogenesis disorders
Disorders of electrogenesis are characterized by disorders of the formation of MP and PD, excitability and conductivity. This is most
pronounced in the structures of the brain and heart.
Consequences: impaired consciousness, up to its loss, dysfunction of the nerve centers (primarily respiratory and
cardiovasomotor), the development of cardiac arrhythmias, including ventricular fibrillation.
Imbalance of biologically active substances and their effects
• Violation of the synthesis and release of biologically active substances (neurotransmitters, hormones, cytokines, etc.).
• Disruption of the processes of activation, inactivation, delivery of biologically active substances to target cells.
• Violation of the interaction of biologically active substances with their cellular receptors.
• Disorder of the response of target cells is caused by damage to cell membranes and intracellular mediators of the
implementation of the effects of hormones, mediators and cytokines.
• Disintegration of physiological and functional systems.
• Minimization of the functions of organs and tissues, energy consumption and plastic processes.
• Transition to the metabolic level of regulation of the functions of organs and tissues. This usually precedes the development
of the terminal state.
21. Provide information about the stages, main functional and structural changes in shock.
Shock - general, extremely serious extreme condition. It arises under the influence of superstrong, destructive factors and is
characterized by a stage-by-stage progressive disorder of the vital activity of the organism due to a violation of the functions of
vital systems.
Regardless of the cause and severity of clinical manifestations, there are two successive stages of shock.
• First, there is an activation of specific and nonspecific adaptive responses. This stage was previously called the stage of
generalized arousal, or erectile. In recent years, it has been called the stage of adaptation, or compensation.
•
If the adaptation processes are insufficient, the second stage of shock develops. Stage of maladjustment, or decompensation.
ADAPTATION STAGE
The stage of adaptation (compensation, non-progressive, erectile) is characterized by mobilization and maximum tension of the
adaptive mechanisms of the body, redistribution of plastic and energy resources in favor of vital organs, which is accompanied by
significant changes in their functions.
At the stage of compensation, the neuroendocrine, hemodynamic, hypoxic, toxemic and metabolic links of pathogenesis are of
primary importance.
Neuroendocrine link
As a result of hyperaffection, the release of hormones from the sympathetic-adrenal and hypothalamic-pituitary-adrenal systems,
as well as the thyroid, pancreas and other endocrine glands, is significantly increased. Effects:
• Hyperfunction of the CVS and the respiratory system, kidneys, liver, other organs and tissues. This is manifested by hypertensive
reactions, tachycardia, increased frequency and deepening of breathing, redistribution
blood flow in different regions of the vascular bed, the release of blood from the depot.
•
As the degree of damage increases, these reactions become excessive, inadequate, and uncoordinated, which greatly
reduces their effectiveness. This largely determines the severe or even irreversible self-aggravating course of shock states.
• Consciousness is not lost during shock. At this stage, usually there is nervous, mental and motor excitement, manifested by
excessive fussiness, agitated speech, hyperreflexia.
Hemodynamic link
Violation of hemodynamics in shock is the result of disorders of the heart, changes in the tone of resistive and capacitive vessels,
a decrease in the BCC, changes in blood viscosity, as well as the activity of system factors
hemostasis.
Hypoxic link
The hypoxic link is one of the main and natural components of shock pathogenesis.
• The reasons. Initially, hypoxia is usually a consequence of hemodynamic disorders and is of a circulatory nature. As the condition
worsens, hypoxia becomes mixed. This is the result of progressive breathing disorders, changes in the blood system and tissue
metabolism.
• Effects. A decrease in the effectiveness of biological oxidation potentiates the dysfunction of tissues and organs, as well as
metabolism in them. The accumulation of an excess of active forms of oxygen
yes is one of the reasons for the inadequacy of the tissue antioxidant defense system and activation of peroxide reactions.
Toxemic link
• The reasons:
♦ The extreme factor itself can be a toxin (for example, in toxic, toxic-infectious shock).
♦ Damage to cells by an extreme factor and the release from them of an excess of biologically active substances, products of
normal and impaired metabolism, ions, denatured compounds.
♦ Violation of inactivation or excretion of toxic compounds by the liver, kidneys, other organs and tissues.
•
Consequences: an increase in intoxication potentiates hypoxia, hemodynamic disturbances and multiple organ failure.
Metabolic link 266
• Reasons: excessive amplification of nervous and humoral influences on tissues and organs, hemodynamic disorder in tissues
and organs, hypoxia, toxemia.
• Effects. In general, metabolic changes are characterized by the predominance of catabolic processes: proteolysis, lipolysis and
SPOL, glycogenolysis and others. The content of high-energy compounds decreases, while the level of ions and fluid in the tissues
increases.
With the ineffectiveness of the adaptive mechanisms and the aggravation of the complex of disorders described above, the stage
of shock decompensation develops.
DECOMPENSATION STAGE
At the stage of compensation, the same links of pathogenesis are of primary importance, but changes in them are of a nonadaptive, pathogenic nature.
Neuroendocrine link. Consciousness at the stage of decompensation is also not lost, but signs of lethargy and confusion of
consciousness are noted, hyporeflexia develops. The effects of nervous and hormonal influences are progressively reduced to the
point of absence.
Hemodynamic link
♦ Progressive dysfunction of the heart and the development of heart failure.
♦ A total decrease in the tone of resistive and capacitive vessels. This eliminates the adaptive phenomenon of circulatory
centralization. Reduction of systolic blood pressure to 60-40 mm Hg. is fraught with the cessation of the filtration process in the
glomeruli of the kidneys and the development of acute renal failure.
♦ A further decrease in the BCC and an increase in its viscosity due to the release of the liquid part of the blood into the
intercellular space.
• Manifestations: total hypoperfusion of organs and tissues, significant disorder of microcirculation, capillarotrophic insufficiency.
Hemostasis system. Changes in the hemostatic system consist in the development of an imbalance in the concentration or activity
of factors of the coagulation, anticoagulation and fibrinolytic systems. Consequences: the development of disseminated
intravascular coagulation, ischemia and tissue necrosis, hemorrhages in them.
Hypoxic link. Severe hypoxia of a mixed type and uncompensated acidosis develop due to systemic hemodynamic disorders,
hypoventilation of the lungs, a decrease in BCC, renal failure, metabolic disorders.
Toxemic link characterized by an increase in the content of products of normal and impaired metabolism in the blood and other
biological fluids; accumulation in the blood of compounds released from damaged and destroyed cells (enzymes, denatured
proteins, ions, various inclusions); BAS and others. These substances significantly exacerbate organ damage. The metabolic link of
shock at the stage of decompensation is manifested by the dominance of the processes of catabolism of proteins, lipids,
carbohydrates, minimization of plastic processes in cells, overhydration of cells, accumulation of under-oxidized substances in
biological fluids, and an increase in the level of lipid peroxidation products in tissues. The cellular link in the pathogenesis of shock
at the stage of decompensation is characterized by an increasing suppression of the activity of enzymes and vital activity of cells,
22. Give the definition and etiology of allergy. Describe the etiology and pathogenesis of type 1 and
type 2 allergic diseases according to Coombs and Gill, give clinical examples.
Allergy - a typical pathological form of immune reactivity, in which the response to foreign Ag is accompanied by damage to the
body's own structures.
Cause of allergic reactions: Ag, called in this case allergens.
Allergen - a substance of exo or endogenous origin, causing the formation of antibodies, sensitized lymphocytes, as well as allergy
mediators, damaging both the carriers of the allergen and the body's own structures.
Types of allergens
Allergens enter the body from the outside (exogenous) or are formed in it (endogenous).
• Exogenous allergens. These include:
♦ Food.
♦ Many drugs and vaccines.
♦ Pollen of plants, herbs, trees.
♦ Synthetic compounds of various origins.
• Endogenous allergens - protein or protein-containing compounds formed as a result of denaturation of cells and non-cellular
structures, as well as during their modification under the influence of substances of endo or exogenous origin.
In 1964, Jell and Coombs proposed to distinguish four types of hypersensitivity reactions, which are based on differences in the
pathogenetic mechanisms of hypersensitivity reactions. Belonging to one type or another is determined by the localization and
class of AT or lymphocytes interacting with the allergen.
•
The first (I) type - atonic allergic reactions (anaphylactic or reaginic) are mediated mainly by immunoglobulins of the IgE and
G4 classes.
• The second (II) type - cytotoxic damage, is carried out with the participation of IgG or IgM, interacting with allergens located
on the cells of the individual's own tissues.
215
• The third (III) type is immunocomplex, nrecinitine allergic reactions with the development of conditions and diseases of immune
complexes. In this case, complexes of allergens with IgG and IgM are formed. Antigen + antibody complexes that are not removed
from the bloodstream are fixed in the capillaries, where they induce tissue damage.
• The fourth (IV) type is delayed ooze hypersensitivity. Contact of the allergen with Ag-specific receptors on T cells leads to a
clonal increase and activation of this population of lymphocytes.
Allergic reactions of type I
With the development of atopic reactions of an immediate type, there is an interaction of Ag with AT (IgE and IgG4), leading to
the release of biologically active substances - mediators of allergy (mainly histamine) from mast cells and basophils (Fig. 16-1).
Type I allergic reactions are most often caused by exogenous agents.
The stage of sensitization proceeds with the formation of plasma cell clones specific to Ar, synthesizing IgE and IgG4. These
immunoglobulins are fixed mainly on the surface of mast cells and basophils.
The pathobiochemical stage develops when the allergen re-enters the body and interacts with IgE fixed on the surface of target
cells, which is accompanied by the immediate release of the contents of the granules of these cells (allergy mediators) into the
intercellular space. Allergy Mediator Effects:
♦ Increasing the permeability of the vascular walls of the microvasculature and the development of tissue edema.
♦ Circulatory disorders.
♦ Narrowing of the lumen of the bronchioles, intestinal spasm.
♦ Hypersecretion of mucus.
♦ Direct damage to cells and non-cellular structures.
The stage of clinical manifestations is due to the development of the above effects in target organs. Most often, according to the
described mechanism, pollinosis, allergic forms
bronchial asthma, allergic conjunctivitis, dermatitis, gastroenterocolitis, and anaphylactic shock. Pseudo-allergic reactions
Pathobiochemical and clinical changes similar to those described above are observed in so-called pseudo-allergic reactions. The
latter develop soon after enteral or parenteral ingestion of various agents that cause degranulation of mast cells. Most often,
these substances are food (chocolate, citrus fruits, some berries, etc.), drugs, herbicides, pesticides, etc.
An important feature of pseudoallergic reactions is their development without a visible period of sensitization. Manifestations of
pseudo-allergic reactions: urticaria and Quincke's edema, rashes of various types, itching, redness of the skin, diarrhea, asthma
attacks and even conditions resembling anaphylactic shock.
Allergic reactions of type II
In cytotoxic allergic reactions, immunoglobulins (usually IgG or IgM) bind to Ag on the surface of their own cells, which is
accompanied by the destruction of the latter by phagocytes, killer cells or the complement system. Type II allergic reactions are
most often caused by substances with a relatively low molecular weight and high chemical activity (for example, drugs, hydrolytic
enzymes, free radicals, etc.). These agents change the antigenic structure of the protein components of cell membranes and noncellular elements.
The stage of sensitization occurs with the activation of B-lymphocytes and their transformation into plasma cells synthesizing IgG
subclasses 1, 2 and 3, as well as IgM.
The pathobiochemical stage develops when the allergen re-enters the body and changes under its influence the structure of its
own Ar. Immunoglobulins interact with altered antigenic determinants on the surface of cells and non-cellular structures of the
body. In this case, the mechanisms of complement-dependent and antibody-dependent destruction of the carrier of antigenic
information are realized.
The stage of clinical manifestations is caused by damage to altered structures of the body with the formation of a number of
clinical syndromes of an allergic nature: “medicinal” cytopenias (erythro-, leuko-, thrombocytopenias), hemolytic disease of
newborns; allergic or infectious-allergic forms of nephritis, myocarditis, encephalitis, hepatitis, thyroiditis, polyneuritis, etc.
23. Describe the etiology and pathogenesis of type 3 and 4 allergic diseases according to Coombs
and Gill, give clinical examples.
Allergic reactions of type III
Immunocomplex allergic reactions are characterized by damage to the structures of the body through immune complexes.
Allergic reactions of this type are caused by highly soluble exo- and endogenous proteins (for example, during vaccination, bites
of certain insects, infection with microbes or fungi, tumor growth). The sensitization stage proceeds with the activation of B
lymphocytes by allergens, which is accompanied by the production of IgG and IgM, which, upon contact with Ag, form
precipitates. These precipitates are called immune complexes, and diseases in the pathogenesis of which they play an essential
role are called immunocomplexes.
♦ If immune complexes are formed in the blood or lymph, and then are fixed in various tissues and organs, then it develops
Xia systemic (generalized) form of allergy. Serum sickness is an example.♦ In cases where immune complexes are formed outside
the vessels and are fixed in certain tissues, local forms of allergy develop (for example, membranous glomerulonephritis, vasculitis,
periarteritis, alveolitis, Arthus phenomenon). The pathobiochemical stage is caused by the activation of reactions to remove
immune complexes. Allergy mediators appear in tissues and blood, which cause damage to cells and non-cellular formations.
Elimination of immune complexes with the participation of phagocytes potentiates and expands the scale and degree of allergic
alteration. Activation of proaggregants and procoagulants creates conditions for thrombus formation, disorders
microcirculation, tissue ischemia, development of dystrophy and necrosis in them.
The stage of clinical manifestations is a consequence of the direct action of immune complexes on cells and tissues, as well as the
effects of mediators of allergy and phagocytosis. This type of allergic reaction is a key link in the pathogenesis of serum sickness,
membranous glomerulonephritis, alveolitis, vasculitis, nodular periarteritis, Arthus phenomenon, etc.
Allergic reactions of type IV
Slow cell-mediated allergic reactions involve not AT, but T-cells. Sensitized T-lymphocytes (after presentation of Ag) have both a
direct cytotoxic effect on target cells and with the help of lymphokines.
Type IV allergic reactions most often there are components of infectious agents (tuberculosis, leprosy, brucellosis; parasites,
fungi, viruses), as well as some proteins of a non-infectious nature (for example, altered collagen).
The sensitization stage includes the activation and antigen-dependent differentiation of T-lymphocytes into T-helpers (T-effectors
of delayed-type hypersensitivity reactions) and T
killers. Pathobiochemical stage. With repeated contact of immunocompetent cells with the allergen, proliferation and maturation
of a large number of different T-lymphocytes, mainly cytotoxic, occurs. Sensitized killer T cells destroy target cells both directly
and by releasing allergy mediators and inducing granulomatous inflammation. Granulomas consist of lymphocytes, mononuclear
phagocytes, epithelioid and giant cells formed from them, fibroblasts and fibrous structures.
Fig. 16-2. Phases of vascular injury in immunocomplex diseases (type III hypersensitivity according to Jell and Coombs). A - the
formation of the immune complex; B - fixation of immune complexes; B - inflammation mediated by immune complexes. NL neutrophilic leukocyte, [4].
The stage of clinical manifestations. Most often, reactions manifest themselves as infectious-allergic (tuberculin,
brucellin, salmonella), in the form of diffuse glomerulonephritis (infectious-allergic genesis), contact allergies dermatitis, conjunctivitis
24. Describe the etiology and pathogenesis of type 5 allergic reactions according to Coombs and Gill,
give clinical examples. Describe methods of diagnosis, prevention and treatment of allergic diseases.
Type V immune responses have also been identified. They are caused by IgG directed against cell receptors, cause either
stimulation of their function, for example, thyroglobulin, or blocking the formation of insulin, etc.
PRINCIPLES OF THERAPY AND PREVENTION
Treatment and prevention of allergic reactions is based on the implementation of etiotropic, pathogenetic, sanogenetic and
symptomatic principles.
Etiotropic therapy and prevention
Etiotropic therapy is aimed at eliminating the allergen from the body. Measures are taken to remove microbes, parasites, fungi,
protozoa from the body (sanitation) and remove abnormal proteins and other allergic compounds from the body. Prevention
means preventing the body from contacting an allergen: pollen, dust, components of animal hair, organic and inorganic
substances, drugs, etc.
Pathogenetic therapy
Pathogenetic therapy is aimed at breaking the main links of the pathogenesis of allergy, and prevention - at the advanced blockade
of potential mechanisms of its development (immunogenic sensitizing processes, the formation of allergy mediators). FROM
for this purpose, specific or non-specific hyposensitization is carried out.
•
Specific hyposensitization is achieved by parenteral administration of a sensitizing allergen according to certain schemes (the
method is designed to form a complex of the allergen with AT and reduce the content of the corresponding Ig).
• Non-specific hyposensitization is used in cases when specific for some reason is impossible or ineffective, or when it is not
possible to identify the allergen. It can be achieved by using certain drugs (for example, antihistamines and membrane stabilizing
drugs) for immediate allergies; immunosuppressants (including glucocorticoids) and immunomodulators - for delayed-type
allergies, as well as using some types of physiotherapeutic effects.
Sanogenetic therapy is aimed at activating protective, compensatory, reparative and other adaptive processes and reactions in
tissues, organs and the body as a whole. For this purpose, vitamins, adaptogens (ginseng, eleutherococcus) are used,
stone-based measures: hardening, physical activity, therapeutic fasting and others.
Symptomatic principle means the prevention or elimination of symptoms that aggravate the course of allergies:
headache, dizziness, anxiety, tension, depression, etc.
25. Provide data on the etiology, pathogenesis, clinical forms of autoimmune diseases. Describe the
concept of pseudo-allergy: types, clinical manifestations, pathogenetic differences from true allergies.
TYPES OF DISEASES OF IMMUNE AUTOAGRESSION
Numerous variants of human immune autoaggression diseases are combined into several groups, taking into account the main
distinctive features.
• Depending on the initial (starting) link of pathogenesis: diseases of immune autoaggression caused by disorders in the IBN
system and outside the IBN system (see above).
• Depending on the dominant development mechanism.
♦ Diseases of immune autoaggression, developing mainly with the participation of immunoglobulins (humoral, immunoglobulin,
B-cell). Examples: Hashimoto's thyroiditis, hemolytic anemia, thrombocytopenia, leukopenia, SLE.
♦ Diseases of immune autoaggression, developing mainly with the participation of T-killers (T-killer, T-cell). Examples: certain
types of polymyositis and Sjogren's syndrome.
♦ Diseases of immune autoaggression, developing with the participation of both links of the immune response (cooperative).
Examples: Sjogren's syndrome, manifested by damage to the eyes (keratoconjunctivitis dry) and the mucous membrane of the
mouth (xerostomia); scleroderma; dermato- and polymyositis.
• Depending on the number of organs affected.
♦ Mono-organ diseases of immune autoaggression (organ-specific). Examples: Hashimoto's thyroiditis, Addison-Birmer's
anemia.
♦ Multiple organ diseases of immune autoaggression (systemic, generalized). Examples: SLE, scleroderma.
Pseudoallergies develop soon after enteral or parenteral ingestion of various agents that cause degranulation of mast cells. Most
often, these substances are food (chocolate, citrus fruits, some berries, etc.), drugs, herbicides, pesticides, etc.
An important feature of pseudoallergic reactions is their development without a visible period of sensitization. Manifestations of
pseudo-allergic reactions: urticaria and Quincke's edema, rashes of various types, itching, redness of the skin, diarrhea, asthma
attacks and even conditions resembling anaphylactic shock.
26. Give the concept of arterial hyperemia, describe its types, mechanisms, manifestations. Describe the
outcomes and significance of arterial hyperemia.
Arterial hyperemia - an increase in blood filling and the amount of blood flowing through the vessels of organs
and tissues as a result of the expansion of arterioles and arteries.
The reasons . Factors of exo- and endogenous origin and be of a physical, chemical or biological nature. The most
important are physiologically active substances formed in the body: adenosine, acetylcholine, prostacyclin, nitric
oxide, organic acids (lactic, pyruvic,
ketoglutaric).
Mechanisms of occurrence
The expansion of the lumen of small arteries and arterioles is achieved through the implementation
of neurogenic (neurotonic and neuroparalytic) and humoral mechanisms.
• Neurogenic mechanisms:
♦ The neurotonic mechanism consists in the predominance of the effects of parasympathetic nervous influences
(in comparison with sympathetic ones) on the walls of arterial vessels.
♦ The neuroparalytic mechanism is characterized by a decrease in sympathetic nervous influences on the walls
of arteries and arterioles.
• The humoral mechanism is characterized by a local increase in the content or effects of biologically
active substances with a vasodilating effect (adenosine, nitric oxide, PgE, PgI2, kinins).
Types of arterial hyperemia
Distinguish between physiological and pathological types of arterial hyperemia.
Physiological arterial hyperemia is adequate to the effect and has an adaptive value. It can be functional and
protective and adaptive.
• Functional develops in organs and tissues due to an increase in the level of their functioning (for example,
hyperemia in a contracting muscle, in a hard working organ or tissue).
• Protective-adaptive develops during the course of protective reactions and processes in tissues (for
example, in the focus of inflammation, see Chapter 5).
Pathological arterial hyperemia is not adequate to the effect, is not associated with a change in the function
of an organ or tissue and plays a maladaptive - damaging role.
Examples: pathological arterial hyperemia of the brain in hypertensive crisis, abdominal organs after removal
of ascites, in the skin and muscles of the limb after removing the tourniquet; in a place of prolonged exposure
to heat (sun, when using a heating pad, mustard plasters).
Manifestations of arterial hyperemia
♦ Increase in the diameter of arterial vessels.
♦ Redness, fever, an increase in the volume and turgor of an organ or tissue site.
♦ Increase in the number and diameter of functioning arterioles and capillaries, acceleration of blood flow.
♦ Increased lymph formation and lymph drainage.
Consequences of arterial hyperemia
• With physiological varieties of arterial hyperemia, activation of specific and potentiation of nonspecific
functions of an organ or tissue is noted.
Examples: activation of local immunity, acceleration of plastic processes; provision of hyperfunction and
hypertrophy of organs and tissues with metabolic products and oxygen.
• With pathological arterial hyperemia, as a rule, hyperextension and micro-ruptures of the walls of the vessels
of the microvasculature, micro- and macro-hemorrhages in the tissue, bleeding occur.
Elimination or prevention of these negative consequences is the goal of therapy for pathological varieties of
arterial hyperemia.
27. Give a definition to the concept - ischemia. Describe the reasons for the increase in resistance to
blood flow in the arteries. Describe microcirculation disorders during ischemia, symptoms and
consequences of ischemia.
Ischemia - insufficient supply of arterial blood to tissues and organs in comparison with the need for it.
The reasons
• By nature, physical (compression of arterial vessels, narrowing or closing of their lumen from the inside), chemical (for example,
nicotine, some drugs) and biological factors (for example, biologically active substances with vasoconstrictor effects, exo- and
endotoxins) are isolated.
• By origin: endogenous or exogenous effects of an infectious and non-infectious nature.
Mechanisms of ischemia
The mechanisms of ischemia can be divided into 2 groups: leading to an absolute decrease in arterial blood flow and leading to an
increase in the consumption of metabolic substrates and oxygen (i.e., to their relative lack).
A decrease in the flow of arterial blood to tissues and organs is most common and may be due to the following mechanisms:
neurogenic, humoral and physical.
• Neurogenic mechanisms:
♦ The neurotonic mechanism is characterized by the predominance of the effects of the sympathetic nervous system on the walls
of the arterioles in comparison with the parasympathetic one.
♦ The neuroparalytic mechanism is characterized by the elimination or reduction of parasympathetic influences on the walls of
arterioles.
• The humoral mechanism consists in an increase in the content of biologically active substances with a vasoconstrictor effect
in the tissues (catecholamines, thromboxane A2, angiotensin, etc.) or the sensitivity of the receptors of the arteriole walls to them.
• The physical mechanism is characterized by the presence of a mechanical obstacle to the movement of blood through the
arterial vessels. Reasons: compression of the arterial vessel from the outside; reduction (up to complete closure - obturation) of
the lumen of the arteriole (for example, a thrombus, an aggregate of blood cells, an embolus).
The main manifestations of ischemia with a decrease in blood flow through the arteries
♦ Blanching and decreased temperature of a tissue or organ site.
♦ Reducing the pulsation of arterial vessels.
♦ Decrease in the number and diameter of functioning arterioles and capillaries (with a decrease in blood flow to the tissue).
♦ Decreased lymph formation and lymph drainage.
The consequences of ischemia
The main consequences of ischemia that develop as a result of hypoxia and the release of biologically active substances: a decrease
in specific and nonspecific functions, the development of dystrophies, heart attacks, hypotrophy, hypoplasia of a tissue or organ
site.
The nature, severity and scale of the consequences of ischemia depends on many factors: the rate of ischemia, the diameter of
the affected vessel, the sensitivity of the tissue or organ to ischemia, the value of the ischemic organ or tissue, as well as the
degree of development of collateral blood flow.
Collateral blood flow - the circulatory system in the vessels around the ischemic tissue site and in it. The inclusion (or increase) of
collateral circulation is facilitated by: the presence of a blood pressure gradient above and below the narrowed portion of the
vessel; accumulation of biologically active substances with a vasodilating effect in the ischemic zone; a high degree of development
of the vasculature (collaterals) in the affected organ or tissue.
28. Describe the concept of venous hyperemia. Describe its reason,
microcirculation in the area of venous stasis, symptoms and significance, outcomes of venous
hyperemia.
Venous hyperemia - an increase in the blood supply of a tissue or organ, combined with a decrease in the amount of blood flowing
through their vessels.
The main reason venous hyperemia is a mechanical obstruction to the outflow of venous blood from tissues or an organ. This may
be the result of narrowing of the lumen of a venule or vein during its compression (tumor, edematous tissue, scar, tourniquet,
tight bandage) and obstruction (thrombus, embolus, tumor), heart failure, and the presence of varicose veins.
Manifestations
♦ Increase in the number and diameter of functioning venous vessels and capillaries, pendulum movement of blood in them.
♦ Cyanosis, edema and a decrease in the temperature of an organ or tissue site.
♦ Hemorrhage and bleeding.
The pathogenic effects of venous hyperemia are due to local hypoxia and tissue edema, hemorrhages and bleeding. This causes a
decrease in the specific and non-specific functions of organs and tissues; hypotrophy and hypoplasia of structural elements of
tissues and organs; necrosis of parenchymal cells and the development of connective tissue (sclerosis, cirrhosis) in organs.
29. Give the definition of stasis, describe the types, etiology, pathogenesis, manifestations,
consequences and significance of stasis.
Stasis - a significant slowdown or cessation of the flow of blood or lymph in the vessels of an organ or tissue.
Causes of stasis: ischemia, venous hyperemia, aggregation and agglutination of blood corpuscles.
• Pathogenesis... A decrease in the inflow or outflow of blood creates conditions for slowing down its movement in the vessels of
an organ or tissue. At the final stage of stasis, the process of aggregation or agglutination always takes place.
shaped elements of blood, which leads to thickening of the blood and a decrease in its fluidity. This process is activated by
proaggregants, cations and high molecular weight proteins. Types of stasis. There are primary and secondary stasis. Primary (true)
stasis begins with the activation of blood corpuscles and the release by them of a large number of proaggregants or procoagulants.
At the next stage, the shaped elements aggregate, agglutinate and attach to the vascular wall. This causes a slowdown or stoppage
of blood flow in the vessels.
• Secondary stasis (ischemic or venous stasis) is initially caused by a decrease in blood flow or outflow. Subsequently, aggregation
and adhesion of blood cells develops.
Manifestations of stasis:
♦ decrease in the inner diameter of blood vessels during ischemic stasis;
♦ an increase in the lumen of blood vessels with a venous-stagnant variant of stasis;
♦ the formation of a large number of aggregates of blood corpuscles in the lumen of blood vessels and on their walls;
♦ microbleeds (more often with congestive stasis).
It should be remembered that the manifestations of ischemia itself or venous hyperemia may overlap the manifestations of stasis.
Consequences of stasis. With the rapid elimination of the cause of stasis, the blood flow in the vessels of the microvasculature is
restored and no significant changes develop in the tissues. Prolonged stasis leads to the development of degenerative changes in
tissues, often - to infarction of a tissue or organ site.
30. Describe the typical forms of intravascular disorders of blood microcirculation, their causes,
mechanisms, manifestations. Give a concept of the "sludge phenomenon".
Intravascular microcirculation disorders
• Deceleration (up to stasis) of blood or lymph flow (similar to similar disturbances in blood flow in medium-sized vessels during
ischemia or venous hyperemia).
• Excessive acceleration of blood flow (for example, with pathological arterial hypertension, hypervolemia).
• Violation of the laminarity (turbulence) of blood or lymph flow is caused by changes in the viscosity and state of aggregation of
the blood, as well as damage to the walls of the vessels of the microvasculature with a violation of their smoothness (for example,
with vasculitis or parietal microthrombi).
• An increase in extracapillary blood flow occurs due to the opening of arteriovenular shunts and the discharge of blood from
arterioles into venules, bypassing the capillary network. Cause: spasm of the SMC arterioles and
closure of precapillary sphincters with a significant increase in the level of catecholamines in the blood (for example, in
hypertensive crisis).
Sludge
Sludge is a phenomenon characterized by adhesion, aggregation and agglutination of blood corpuscles with its separation into
plasma and conglomerates of erythrocytes, leukocytes, platelets, which causes microcirculation disorders.
• Sludge reasons.
♦ Central hemodynamic disorders.
♦ Increased blood viscosity.
♦ Damage to the walls of microvessels.
• Sludge development mechanisms.
♦ Activation of blood corpuscles, their release of proaggregants.
♦ Reduction of the surface charge of blood cells and their "recharge". 359
♦ Adsorption of protein micelles on blood corpuscles, potentiation of the processes of their sedimentation on the walls of blood
vessels and adhesion to each other.
• The consequences of sludge: microcirculation disorders with the development of capillary-trophic insufficiency.
In general, the sludge phenomenon is either the cause of microcirculation disorders (in those cases when it develops primarily), or
a consequence of intravascular microcirculation disorders (during their primary development).
31. Describe transmural and extravascular disorders of blood microcirculation, their causes,
mechanisms and manifestations.
Transmural microcirculation disorders
Movement through the wall of a microvessel refers both to the liquid part of the blood (in this case, they speak of permeability)
and to the cellular elements (in this case, they speak of emigration and release of blood cells into the tissue, i.e.,
microhemorrhage).
• Permeability disorders. In various pathological conditions, the volume of movement of blood plasma or lymph through the
vessel wall may increase or decrease.
♦ An increase in the permeability of the vascular wall is observed under conditions of acidosis, with the activation of hydrolases,
rounding of endothelial cells and overstretching of the walls of microcirculation vessels. The movement of fluid occurs through
filtration, transcytosis (volatile pinocytosis), diffusion and osmosis.
♦ A decrease in permeability is caused by a thickening or compaction of the walls of blood vessels, as well as a violation of the
energy supply of intracellular processes.
• Violations of emigration and release of blood corpuscles into the tissue. The emigration of leukocytes through the wall of
microvessels is also normal. In pathology, there is an excessive emigration of leukocytes, as well as a passive exit from the blood
of platelets and erythrocytes with the subsequent development of microhemorrhages.
Extravascular microcirculation disorders
Extravascular (extravascular) microcirculation disorders are accompanied by an increase or decrease in the volume of intercellular
fluid. Both of these lead to a slowdown in its outflow into the vessels of the microvasculature. An increase in the content of
metabolic products and biologically active substances in the interstitial fluid causes metabolic disorders and ions in tissues. Cell
damage also occurs due to their compression by excess interstitial fluid.
• An increase in the volume of intercellular fluid is due to local pathological processes (inflammation, allergic reactions, growth
of neoplasms, sclerotic processes, venous hyperemia, stasis).
• A decrease in the volume of intercellular fluid is observed with hypohydration, ischemia, as well as with a decrease in fluid
filtration in the precapillaries or an increase in its reabsorption in the postcapillaries.
Capillary-trophic insufficiency is a condition characterized by impaired blood and lymph circulation in the vessels of the
microvasculature, which is accompanied by metabolic disorders in tissues and organs. Long-term capillary
trophic insufficiency leads to various types of dystrophies, disorders of plastic processes in tissues, disruption of the vital functions
of the affected organs and the body as a whole.
32. Give a description of the etiology, pathogenesis and manifestations of lymph microcirculation
disorders. Give the concept of capillary-trophic insufficiency syndrome.
Microcirculation is an ordered movement of blood and lymph through small vessels, transcapillary transfer of plasma and blood
cells, and movement of fluid in the extravascular space.
General etiology
♦ Central and regional circulatory disorders. The most significant ones include heart failure, arterial and venous hyperemia,
ischemia, stasis.
♦ Changes in the viscosity and volume of blood and lymph. They develop as a result of hemo (lymph) concentration and hemo
(lymph) dilution.
♦ Damage to the walls of the vessels of the microvasculature. It is usually observed with arterial hypertension, inflammation,
cirrhosis, tumors, etc.
Capillary-trophic insufficiency - a condition characterized by impaired blood and lymph circulation in the vessels of the
microcirculatory bed, which is accompanied by metabolic disorders in tissues and organs. Long-term capillary-trophic insufficiency
leads to various types of dystrophies, disorders of plastic processes in tissues, disruption of the vital functions of the affected organs
and the body as a whole.
33. Describe the concept of energy (basic) metabolism, factors that
determine energy metabolism, causes and mechanisms of energy
metabolism disorders
Katabolism (from Greek καταβολή, "dropping, destruction"), or energy exchange, or dissimilation process metabolic decay, decomposition into simpler substances (differentiation) or oxidation of a substance, usually with release
energy in the form of heat and in the form ATF... Catabolic reactions underlie dissimilation: the loss of complex substances of
their specificity for a given organism as a result of decay to simpler ones.
Examples of catabolism are the transformation ethanol through stages acetaldehyde (ethanal) and acetic
acid (ethanic acid) in carbon dioxide and water, or process glycolysis - transformationglucose in dairy acid or pyruvic acid
and then, in the respiratory cycle, again into carbon dioxide and water.
The intensity of catabolic processes and the predominance of certain catabolic processes as energy sources in cells is
regulated hormones... For example, glucocorticoids increase the intensity of catabolism proteins and amino acids,
simultaneously inhibiting glucose catabolism (more precisely, increasing its anabolism, inducing the accumulation of glucose
in the form of glycogen in the liver and muscle tissue, thereby reducing the concentration of glucose in the blood and lymph,
mediating hypoglycemia), and insulin, on the contrary, it accelerates glucose catabolism and inhibits protein catabolism.
Catabolism is the opposite anabolism - process synthesis or resynthesis new, more complex, compounds from simpler, flowing
with the expenditure of energy ATP. The ratio of catabolic and anabolic processes in the cell is again regulated by hormones. For
example,adrenalin or glucocorticoids shift the metabolic balance in the cell towards the predominance of catabolism, and insulin,
somatotropin, testosterone - towards the predominance of anabolism.
34. Give the classification of disorders of carbohydrate metabolism in the body.
Describe the causes and mechanisms of impaired absorption of carbohydrates in
the digestive tract, the processes of synthesis, storage and breakdown of glycogen,
transport and assimilation of carbohydrates in the cell.
Disorders of carbohydrate metabolism are classified according to the stages of the process. There are several such stages:
1 . Entering the gastrointestinal tract with food, splitting into monosaccharides in the duodenum and upper part of the small
intestine and absorbing them into the blood.
2 . Deposition of carbohydrates.
H. Intermediate metabolism of carbohydrates:
- anaerobic and aerobic glucose breakdown;
- interconversion of hexoses;
- the process of gluconeogenesis (synthesis of glucose from non-carbohydrate precursors).
4. Excretion of glucose through the glomerular apparatus of the kidneys with primary (provisional) urine and its complete
reabsorption in the renal tubules.
Violation of the breakdown and absorption of carbohydrates
Violation of the breakdown of carbohydrates. In a healthy body, the hydrolysis of glycogen and food starch begins in the oral
cavity under the influence of salivary α-amylase. Monosaccharides are able to be absorbed already in the oral cavity. There are
no enzymes in the stomach that hydrolyze carbohydrates. In the cavity of the small intestine, under the influence of? -Amylase of
pancreatic juice, they are hydrolyzed to dextrins and maltose (cavity digestion). On the surface of microvilli of enterocytes,
enzymes are localized: sucrase, maltase, lactase, isomaltase and others, which break down dextrins and disaccharides to
monosaccharides (parietal digestion).
The most typical defects include the lack of disaccharidase enzymes: sucrase and isomaltase, which are always manifested in
combination. As a result, the disaccharides sucrose and isomaltose are not broken down or absorbed by the body. Disaccharides
accumulating in the intestinal lumen osmotically bind a significant amount of water, which causes diarrhea (diarrhea). Under
these conditions, it is also possible for the epithelial cells to absorb a certain amount of disaccharides. However, they remain
metabolically inactive and are quickly excreted unchanged in the urine. In case of defects in the activity of disaccharidases,
loading with disaccharides does not cause hyperglycemia in the interval of 30-90 minutes, as is the case in healthy people.
Suction disorders. In healthy people, monosaccharides such as glucose, galactose, fructose and pentose are absorbed by the
microvilli of the epithelial cells of the small intestine. The transition of monosaccharides through the membrane of epithelial cells
occurs by a secondary active transport with the obligatory participation of an ATP-dependent sodium pump and a specific carrier.
With secondary active transport, the energy of an electrochemical gradient created for another substance (sodium ions) is used to
transfer one compound (for example, glucose).
Among the etiological factors of carbohydrate absorption disorders, the following groups are distinguished:
1 ) inflammation of the mucous membrane of the small intestine;
2 ) the action of toxins that block the process of phosphorylation and dephosphorylation (phloridzin, monoiodoacetate); H) lack
of Na + ions, for example, with hypofunction of the adrenal cortex;
4 ) violation of the blood supply to the intestinal wall;
5 ) in newborns and infants, insufficient activity of digestive enzymes and enzymatic systems of phosphorylation and
dephosphorylation of carbohydrates is possible. As an example, we cite the syndrome of lactose intolerance without a
deficiency of the enzyme lactase and the syndrome of congenital lactase deficiency.
The syndrome of lactose intolerance without a deficiency of the enzyme lactase manifests itself malignantly in the first days
after birth in the form of severe diarrhea, vomiting, acidosis, lactosuria, and often proteinuria. Atrophy of the adrenal glands
and liver, degeneration of the renal tubules are also detected.
Congenital lactase deficiency... In healthy people, lactase breaks down lactose to glucose and galactose. Newborn babies usually
get 50-60 g of lactose (with milk) per day. The most common manifestation of lactase deficiency is diarrhea after milk intake.
Unhydrolyzed lactose enters the lower parts of the small intestine, where it is fermented by the intestinal microflora with the
formation of gases (which causes flatulence) and acids. Their osmotic action attracts large amounts of water into the intestinal
cavity, which causes diarrhea. At the same time, feces have an acidic pH value and contain lactose, sometimes lactosuria is
observed. Over time, the child develops malnutrition. This syndrome should be distinguished from acquired lactase deficiency
(with enteritis, inflammatory bowel disease, sprue), as well as from intestinal lactase deficiency, which occurs in adults.
Carbohydrate storage disorders
Normally, carbohydrates are deposited in the form of glycogen. The glycogen molecule can contain up to a million
monosaccharides. In this case, a kind of crystallization of glycogen occurs and it does not have an osmotic effect. This shape is
suitable for storage in a cage. If such a number of glucose molecules were dissolved, the cell would rupture due to osmotic forces.
Glycogen is the deposited form of glucose. It is found in almost all tissues. It is especially abundant in the liver and muscles,
while in the cells of the nervous system the amount of glycogen is minimal. Muscle glycogen is used as an energy source during
intense exercise. Glycogenolysis in the liver is activated in response to a decrease in glucose concentration during breaks in meals
or in response to stress. The main hormones that activate glycogenolysis are glucagon,
Hormonal regulation of glycogenolysis
Hormone Place of education
Initiator
Effect on glycogenolysis
Glucagon ? - cells
pancreas
Adrenalin Adrenal medulla
Cortisol
Adrenal cortex
Insulin
? -cells of the pancreas
Hypoglycemia
Fast activation
Stress, hypoglycemia
Stress
Hyperglycemia
Fast activation
Long-term activation
Suppression
Violations of the storage of carbohydrates, first of all, include a decrease in glycogen synthesis, an increase in the breakdown of
glycogen and pathological storage of glycogen.
Decreased glycogen synthesis. Among the etiological factors, firstly, toxic damage to hepatocytes (bacterial and viral
microflora, poisoning with phosphorus, carbon tetrachloride, etc.) is noted. Secondly, oxygen deficiency and, as a consequence,
a pronounced decrease in the efficiency of ATP formation. Thirdly, a decrease in the tone of the parasympathetic nervous
system. Fourth, hypovitaminosis B and C. The 5th etiological group includes endocrine diseases - diabetes mellitus,
thyrotoxicosis, adrenal insufficiency (Addison's disease).
Strengthening the breakdown of glycogen. Strengthening of glycogenolysis in the liver occurs, firstly, against the background
of increased activity of the sympathetic nervous system; secondly, with increased production of hormones - stimulants of
glycogenolysis (adrenaline, glucagon, thyroxine and growth hormone). An increase in sympathetic influences and an increased
concentration of glycogenolysis stimulating hormones in the blood are observed with intense muscular work, shock, fever, and
emotional stress.
Pathological storage of glycogen. This is a group of hereditary diseases in which, due to genetic defects in some enzymes
of glycogen metabolism, its excessive accumulation occurs in various organs, primarily in the liver and skeletal muscles. In
some types of glycogenosis, glycogen with a disturbed structure is synthesized. 12 forms of glycogenosis are described.
The most common types of glycogenosis are as follows
Glycogenosis
Type 1
2 types
3 types
4 types
(Krefeld-Gierke)
(Corey and Forbes)
(Pompe)
(Andersen)
Etiology
Autosomal
also
also
also
recessive
inheritance
Inherited
glucose-6? -1,4-glucosidase
amylo-1,6-glucosidase
D-1,4-glucanenzyme
phosphatas
6 -? - glucosyl
deficiency
e
transferase
V iolation
Not
Not
The appearance of
Abnormally
long
glycogen
many shortened side
chains, few side
structures
chains
branches
Places of
Liver and kidney
Tissue of the liver, spleen,
Liver tissue, skeletal Liver and muscle tissue,
accumulation
cells
kidneys, muscle, nervous,
muscle tissue, nervous leukocytes
leucocytes, erythrocytes
tissue, leukocytes and
erythrocytes
Main
Severe
Skeletal muscle hypotonia, Hypoglycemia
Hypoglycemia
manifestations
hypoglycemia
cardiomegaly,
cardiac
hepatomegaly cirrhosis
insufficiency
of the liver, hepatic
failure
In addition to the above types, more rare, as well as mixed glycogenoses are described: type V, or McArdle's disease (McArdle
- Schmid - Pearson); VI type, or Hers's disease; Type VII, or Taruya's disease; Type VIII, or Hodgin's disease, and others.
35. Describe hypoglycemic conditions, their types and mechanisms, disorders of
physiological functions in hypoglycemia. Hypoglycemic coma: etiology,
pathogenesis, manifestations.
HYPOGLYCEMIA - conditions characterized by a decrease in blood plasma glucose (HPA) below normal (less than 65 mg%, or
3.58 mmol / l). Normal HPA on an empty stomach ranges from 65-110 mg%, or 3.58-6.05 mmol / L.
Causes of hypoglycemia.
•
Liver pathology... Hereditary and acquired liver disease is one of the most common causes of hypoglycemia. Hypoglycemia
is caused by disturbances in the transport of glucose from the blood to hepatocytes, a decrease in the activity of glycogenesis
in them and the absence (or low content) of deposited glycogen. Hypoglycemia also develops during prolonged fasting,
and can also develop with significant activation of the body's vital activity (for example, during physical exertion or stress).
•
Digestive disorders... Digestive disorders - abdominal digestion of carbohydrates, as well as their parietal cleavage and
absorption - lead to the development of hypoglycemia. Hypoglycemia also develops in chronic enteritis, alcoholic
pancreatitis, pancreatic tumors, and malabsorption syndromes.
• Kidney pathology... Hypoglycemia develops when glucose reabsorption is impaired in the proximal tubules of the renal
nephron.
• Endocrinopathies... The main reasons for the development of hypoglycemia in endocrinopathies are: a lack of
hyperglycemic factors or an excess of insulin.
• Carbohydrate starvation... Carbohydrate starvation occurs as a result of prolonged general starvation, including
carbohydrate starvation. Deficiency of only carbohydrates in food does not lead to hypoglycemia due to the activation of
gluconeogenesis (the formation of carbohydrates from non-carbohydrate substances).
• Long-term significant hyperfunction of the body during physical work... Hypoglycemia develops during prolonged and
significant physical work as a result of depletion of glycogen stores deposited in the liver and skeletal muscles.
Consequences of hypoglycemia: hypoglycemic reaction, syndrome and coma.
•
Hypoglycemic reaction - an acute temporary decrease in HPA to the lower limit of the norm (as a rule, to 80-70 mg%, or
4.0-3.6 mmol / l).
• Hypoglycemic syndrome - a persistent decrease in HPA below normal (up to 60-50 mg%, or 3.3-2.5 mmol / l), combined
with a disorder of the body's vital functions.
• Hypoglycemic coma - a condition characterized by a drop in HPC below normal (usually less than 40-30 mg%, or 2.0-1.5
mmol / l), loss of consciousness, significant disorders of the body's vital functions.
The principles of therapy.
•
•
•
Etiotropic principle is aimed at eliminating hypoglycemia and treating the underlying disease.
Pathogenetic principle therapy is focused on blocking the main pathogenetic links of hypoglycemic coma or hypoglycemic
syndrome (energy supply disorders, damage to membranes and enzymes, disturbances in electrogenesis, ion imbalance,
acid-base balance, fluid, etc.), as well as on the elimination of disorders of the functions of organs and tissues caused by
hypoglycemia and its consequences.
Symptomatic principle treatment is aimed at eliminating symptoms that aggravate the patient's condition (for example,
severe headache, fear of death, sudden fluctuations in blood pressure, tachycardia, etc.).
36. Give the definition of hyperglycemia, name their types, mechanisms.
Describe the manifestations, consequences of hyperglycemia.
Hyperglycemia- conditions characterized by an increase in HPA above normal (more than 120 mg%, or 6.05 mmol / L on an empty
stomach).
Causes of hyperglycemia: endocrinopathies, neurological and psychogenic disorders, overeating, liver pathology.
•
Endocrinopathy. Endocrinopathies are the most common cause of hyperglycemia. The main reasons for the development
of hyperglycemia in endocrinopathies are an excess of hyperglycemic factors and insulin deficiency.
• Neurological and psychogenic disorders...Neuro- and psychogenic disorders are characterized by activation of the
sympathetic-adrenal, hypothalamic-pituitary-adrenal and thyroid systems. The hormones of these systems have a number
of effects that lead to significant hyperglycemia.
• Overeating... Overeating is one of the causes of hyperglycemia. Glucose is rapidly absorbed in the intestines. HPA
increases and exceeds the ability of hepatocytes to include it in the process of glycogenesis. In addition, an excess of
carbohydrate-containing food in the intestine stimulates glycogenolysis in hepatocytes, potentiating hyperglycemia.
• Liver pathology...With liver failure, transient hyperglycemia may develop due to the fact that hepatocytes are not able to
transform glucose into glycogen. This is usually observed after eating.
The consequences of hyperglycemia: hyperglycemic syndrome and hyperglycemic coma.
Hyperglycemic syndrome - a condition characterized by a significant and relatively long-term increase in HPA above the
norm (up to 190-210 mg%, ie 10.5-11.5 mmol / l or more), combined with a disorder of the body's vital functions.
37. Give the classification of diabetes mellitus, describe the disorders of
carbohydrate and other metabolism in this disease. Describe the complications of
diabetes mellitus, their mechanisms. Describe the pathophysiological features of
various types of diabetic coma.
DIABETES - a disease characterized by a violation of all types of metabolism and a disorder of the body's vital functions; develops
as a result of hypoinsulinism (i.e. absolute or relative insulin deficiency).
Primary forms of diabetes mellitus... Primary forms of diabetes are characterized by the absence in the patient of any specific
diseases that secondarily lead to the development of diabetes. There are two types of primary diabetes:
• insulin-dependent diabetes mellitus (IDDM);
• non-insulin dependent diabetes mellitus (NIDDM).
Secondary forms of diabetes mellitus... Secondary forms of diabetes mellitus are characterized by the presence of any underlying
disease or pathological condition in the patient that damages the pancreas, as well as the effect of physical or chemical factors on it.
This leads to the onset of diabetes. Such diseases, pathological conditions and factors include:
• Diseases affecting the tissue of the pancreas (eg, pancreatitis).
• Other diseases of the endocrine system (for example, familial polyendocrine adenomatosis).
• Exposure to the pancreas by chemical or physical agents.
Diabetes mellitus types I and II
In earlier classifications, type I and type II diabetes were distinguished. These designations were initially used as synonyms for
IDDM and NIDDM, respectively. Modern experts believe this approach is not entirely correct. This is because, for example, patients
with NIDDM can also become dependent on insulin. With its lack, they develop ketoacidosis, fraught with a coma (for example,
this is observed in many non-obese patients who have AT in their blood.
• The term "Type I DM" was used to designate those variants, the main pathogenetic link of which was the immune
(immunoaggressive) mechanism.
• The term "Type II DM" was recommended to be used for that form of DM, the pathogenesis of which did not include
the immune mechanism as a causal (!)
ETIOLOGY...
Diabetes mellitus develops due to either an insulin deficiency (IDDM) or a failure of its effects (NIDDM).
• Insulin deficiency can occur under the influence of factors of a biological, chemical, physical nature, as well as in
inflammatory processes of the pancreas
•
Biological factors. Genetic defectsβ-cells of the islets of Langerhans. Immune factors: Ig, cytotoxic T-lymphocytes, as well as
cytokines produced by them, damaging β-cells and realizing immune autoaggression responses. Viruses tropic to β-cells:
Coxsackie Bfour, hepatitis, measles, chickenpox, mumps, rubella, etc. Endogenous toxic substances that damage β-cells, the
most “aggressive” of them is allokean.
• Inflammatory processesarising in the pancreas under the influence of biological factors (mainly microorganisms), chemical
and physical nature. Chronic pancreatitis in about 30% of cases is the cause of insulin deficiency.
• Lack of insulin effects develops under the influence of causes of a neuro- or psychogenic nature, contrainsular factors, as well
as due to defects in insulin receptors and post-receptor disorders in target cells.
PATHOGENESIS...
Insulin deficiency
With insulin deficiency, the following occurs: damage and death of β-cells of the islets of Langerhans, a decrease in the total
mass of β-cells, suppression of the synthesis and release of insulin into the blood from damaged β-cells.
Lack of insulin effects
The implementation of various variants of the pathogenesis of diabetes in case of insufficiency of the effects of insulin occurs with
normal or even increased synthesis and incretion into the blood (in this case, NIDDM develops).
Allot counterinsular factors, elimination or reduction of the effects of insulin on the target tissue, as well as insulin resistance.
Eliminating or reducing the effects of insulin on target tissueis achieved due to the hyperglycemic effect of excess hormones metabolic insulin antagonists. These include catecholamines, glucagon, glucocorticoids, STH, and iodine-containing thyroid
hormones.
Prolonged and significant hyperglycemia stimulates increased production of insulin (by 3 cells. However, this may not be enough
to normalize HPA, since prolonged hyperactivation of the islets of the pancreas leads to damage to β-cells.
Insulin resistance.Disruption of the realization of the effects of insulin at the target cell level is known as insulin resistance. The
receptor and post-receptor mechanisms of this phenomenon are known.
DIABETES MANIFESTATIONS
Diabetes mellitus manifests itself in two groups of interrelated disorders: metabolic disorders and pathology of tissues, organs, and
their systems. This leads to a disorder of the vital functions of the organism as a whole. In patients with diabetes, signs of disorders
of all types of metabolism are revealed, and not just carbohydrate metabolism, as its name suggests.
Metabolic disorders
Pathology of tissues, organs and their systems
With diabetes, all tissues and organs are affected, albeit to varying degrees. The most affected are the heart, blood vessels,
nervous system, kidneys, eye tissues, and the IBN system. This is manifested by cardiopathies, angiopathies, neuro- and
encephalopathies, nephropathies, decreased visual acuity and blindness, coma and other disorders. They are referred to as
complications of diabetes.
Complications of diabetes mellitus
Complications of diabetes are pathological processes and conditions that are not necessary for it, but are caused either by the causes
of diabetes, or by disorders that have developed with diabetes.
Complications of diabetes mellitus are divided into acute and chronic.
Acutely occurring ("acute complications of diabetes"): diabetic keto acidosis, fraught with the development of acidotic coma;
hyperosmolar (non-cytoacidotic) and hypoglycemic coma.
Long-term (chronic) course ("late complications of diabetes"): angiopathy, neuropathy, encephalopathy, nephropathy, decreased
activity of IBN factors, other complications (osteo- and arthropathies, cataracts).
Acute complications... These complications usually arise under the influence of any provoking factors. The most common reasons
are improper insulin therapy (violation of the calculation of the required amount of injected insulin), stress reactions, the
development of other diseases.
Diabetic ketoacidosis... Diabetic ketoacidosis is common in IDDM. Ketoacidosis and ketoacidotic coma are among the leading
causes of death in patients with diabetes.
Hyperosmolar coma... Hyperosmolar non-ketoacidotic (hyperglycemic) coma is most common in elderly patients with NIDDM. A
hyperosmolar coma develops much more slowly than a ketoacidotic one. However, mortality is higher with it.
Late complications... Signs of late complications of diabetes most often appear 15–20 years after hyperglycemia is detected.
However, in some patients, they may either appear earlier, or not at all. The late complications of diabetes are mainly based on
metabolic disorders in the tissues.
Angiopathies... Distinguish between microangiopathies and macroangiopathies.
Microangiopathies - pathological changes in the vessels of the microcirculatory bed.
Macroangiopathy characterized by early and intensive development of sclerotic changes in the walls of medium and large arteries
in patients with diabetes, which is one of the main risk factors for the development of (accelerated!) atherosclerosis.
Neuropathies... Symptoms of diabetic neuropathies can be observed already in the early stages of the disease in any part of the
nervous system. They are one of the most common causes of patient disability. The most pronounced neuropathies in elderly patients
with chronic diabetes and significant hyperglycemia.
Retinopathies... Retinal damage in diabetes is the main cause of decreased visual acuity and blindness. Nephropathy. Renal
dysfunction is one of the most common causes of disability and death in diabetes. The latter is the outcome of renal failure. Diabetic
nephropathy is the second leading cause of death in people with diabetes.
Immunological lesions... The SD is characterized by a decrease in the efficiency of the IBN system. This is evidenced by data on
more frequent development and severe course in patients with diabetes:
Other complications... Many other complications are observed in patients with diabetes (cardiopathy, cataract,
triglyceridemia, ion exchange disorders, osteo- and arthropathy). This is due to the fact that pathological changes in
diabetes develop in all tissues and organs.
38. Give the classification of protein metabolism disorders in the body. List the
causes of impaired assimilation of food proteins, metabolism of amino acids and
amino acid composition of blood, their pathogenesis
NITROGEN BALANCE
Nitrogen balance - daily difference between incoming and outgoing nitrogen.
Views nitrogen balance.
• Null (the amount of incoming and outgoing nitrogen is the same).
• Positive (the amount of nitrogen entering the body is greater than that of the excreted). It is observed both
normally (for example, with tissue regeneration or pregnancy) and under pathological conditions (for example,
with hyperproduction of STH or polycythemia).
• Negative (the amount of nitrogen entering the body is less than that excreted). It is observed, for example,
during fasting, stress, severe diabetes, hypercortisolism.
DISORDERS OF PROTEIN METABOLISM //// Inconsistency of the amount and amino acid composition of protein
entering the body, protein needs
DIGESTIVE DISORDERS IN THE STOMACH AND INTESTINAL
Disorders of digestion, leading to a violation of protein metabolism, include violations of the breakdown of protein in the
stomach and its digestion in the small intestine.
Disorders of protein breakdown in the stomach
The reasons: Hypoacid conditions; Decreased content and / or activity of pepsin; Resection of a part of the stomach.
Consequences and manifestations: Disorders of protein swelling; Inhibition of the digestion of the collagen component of
products; Insufficient breakdown of muscle fiber proteins; Slowing down the evacuation of food into the duodenum.
Disorders of protein digestion in the small intestine
The reasons: factors (including hereditary ones) that cause digestive disorders in the intestine, including malabsorption
syndromes (malabsorption syndromes).
Manifestations: Creatorrhea; Celiac disease gluten - a syndrome characterized by a violation of the cavity and membrane digestion
of proteins, as well as inhibition of the absorption of amino acids;
Lack of enterokinase leads to a significant decrease in the proteolytic activity of intestinal juice.
DISORDERS OF TRANSMEMBRANE TRANSFER OF AMINO ACIDS
The reasons: membranopathies of various origins (primary - monogenic defects and secondary). Membranopathies lead to
disturbances in the transport of amino acids at several stages: from the intestine to the blood, from the blood to hepatocytes, from
the primary urine to the blood, from the blood to the cells of organs and tissues.
DISORDERS OF AMINO ACID METABOLISM
Disorders of amino acid metabolism, as a rule, significantly alter the metabolism of proteins and lead to metabolic disorders of
nucleic acids, lipids, vitamins, carbohydrates, electrolytes and water. Distinguish between primary (hereditary, congenital) and
secondary (acquired, symptomatic) disorders of amino acid metabolism.
IMPAIRMENT OF PROTEIN CONTENT IN BLOOD PLASMA
The level of proteinemia is the result of the ratio of the processes of proteosynthesis and proteolysis in various tissues and organs.
Dysprotheinemia - typical forms of violations of the content of proteins in blood plasma. Allocate hyperproteinemia,
hypoproteinemia and paraproteinemia.
Hyperproteinemia
There are two types of increase in the total protein content in blood plasma:
•
Hypersynthetic (true, proteosynthetic). There is an overproduction of either normal protein (for example, Ig), or
paraproteins (for example, with plasmacytomas, multiple myeloma);
• Hemoconcentration (false). Hypoproteinemia develops as a result of hemoconcentration without increased proteosynthesis
(for example, with burns, diarrhea, repeated vomiting, prolonged increased sweating).
Hypoproteinemia
There are two known options for reducing the total concentration of proteins in blood plasma:
•
Hyposynthetic (true). This variant of hypoproteinemia can be of two types.
o Primary (hereditary or congenital; for example, hypoproteinemia in Bruton's disease).
o Secondary (acquired, symptomatic; for example, with liver failure, protein starvation, renal failure, burn disease).
• Hemodilutionary... This hypoproteinemia is caused by hypervolemia (eg, with hyperaldosteronism or renal failure).
Paraproteinemia observe when:
•
•
multiple myeloma: tumor plasma cells produce abnormal light or heavy chains of Ig molecules;
lymphomas (lymphocytic or plasmacytic). Lymphomas synthesize abnormal IgM with increased aggregation.
39. Give the disorders of the final stage of protein metabolism, urea synthesis.
Hyperazotemia: types and mechanisms of development.
DISORDERS OF FINAL PROCESSES OF PROTEIN CATABOLISM
Disorders of the final stages of protein catabolism are characterized by a violation of the formation and further changes of urea, uric
acid, ammonia, creatinine, indican, as well as their excretion from the body.
Hyperazotemia
Production hyperazotemia- in case of violation of the synthesis of urea, its amount in the blood and urine decreases, and the
content of residual nitrogen increases. Excess ammonia can be eliminated to some extent due to increased formation of glutamine
and addition to α-ketoglutaric acid, which is converted to glutamic acid, and its oxidation in the tricarboxylic acid cycle is sharply
reduced. As a result, the formation of ATP is reduced.
Retention hyperazotemia- in case of impaired renal excretory function or impaired urinary tract patency. At the same time, the
concentration of residual nitrogen in the blood increases to 140-215 mmol / l, and the content of non-protein nitrogenous products
in the urine decreases. Retention hyperazotemia is one of the factors that play a role in the development of uremic coma.
Mixed (combined) hyperazotemia - with a combination of increased protein breakdown in tissues with insufficient excretion of
nitrogenous products in the urine. This combination is possible with acute renal failure, which has developed on the basis of
septic abortion, or extensive tissue compression (crush syndrome). The combined form of hyperazotemia includes hypochloremic
hyperazotemia, which occurs with indomitable vomiting, pyloric stenosis and profuse diarrhea.
40. Give the classification of lipid metabolism disorders in the body. Describe
the violation of lipid breakdown and absorption.
Depending on the stages of lipid metabolism distinguish disorders:
1 ) Digestion and absorption of lipids in the gastrointestinal tract (for example, as a result of a deficiency of pancreatic
lipases, disorders of bile formation and bile secretion, disorders of cavity and "membrane" digestion).
2 ) Transmembrane transfer of lipids from the intestine to the blood and their utilization by cells (for example, with enteritis,
poor circulation in the wall of the small intestine).
3 ) Lipid metabolism in tissues (for example, with a defect or deficiency of lipases, phospholipases, LPLase).
Depending on the clinical manifestations distinguish between obesity, exhaustion, dyslipoproteinemia, lipodystrophy and
lipidosis.
Impaired lipid digestion and absorption
For normal digestion and absorption of lipids in the intestine, the interaction of factors such as:
1)
2)
the production of the lipolytic enzyme lipase by the pancreas;
intake of bile acids with bile, emulsifying fats and their decay products, activating pancreatic lipase and
participating in the absorption of fatty acids (a complex of fatty and bile acids is absorbed);
3 ) capture of lipid digestion products by cells of the mucous membrane of the small intestine;
4 ) transformation in the intestinal wall of the absorbed lipid hydrolysis products into particles (chylomicrons) for their
further transport into the lymphatic vessels and further into the bloodstream.
If any of these processes are disturbed, steatorrhea develops - an excess of fat in the stool. The causes of impaired
digestion and absorption of lipids are:
1.
2.
3.
4.
5.
6.
7.
8.
Deficiency or low activity of pancreatic lipase (damage to the pancreas), which leads to a violation of the breakdown
of fats.
Insufficient intake of bile acids in the intestine (with hepatitis, cirrhosis, cholecystitis, obstructive jaundice, etc.)
causes a violation of emulsification and breakdown of fat, as well as the transfer of products of its hydrolysis to the
absorbing surface of the intestinal epithelium.
Gastrointestinal hormone deficiency (cholecystokinin, gastrin, etc.), regulating the contraction of the walls of the
gallbladder, the processes of emulsification and breakdown of fats, their transport through the intestinal wall.
Damage to the epithelium of the small intestine with various poisons (phloridzin, monoiodoacetic acid) and
infectious agents that inactivate the enzyme systems of resynthesis of triacylglycerols in the epithelium of the small
intestine, as well as the processes of phosphorylation and dephosphorylation in the intestinal wall.
Avitaminosis A, B, C (since these vitamins are coenzymes of the corresponding biochemical reactions).
Excessive intake of Ca and Mg with food, which leads to the formation of water-insoluble salts of fatty acids (soap).
Choline deficiency in food or its insufficient formation from methionine with low-protein nutrition inhibits lipid
reabsorption.
Changes in the activity of the nervous and endocrine systems: cutting the vagus nerve weakens the absorption of fats
from the intestines, anesthesia works similarly; adrenocorticotropic hormone (ACTH) and thyroxine increase fat
absorption. With a lack of adrenal cortex hormones or an excess of adrenaline, fat absorption slows down.
9.
Increased intestinal motility and diarrhea prevent the reabsorption of most of the fat.
1 0 . Violation of lipid metabolism in enterocytes with the formation of abnormal protein-lipid complexes impairs fat
absorption and causes the formation of fatty accumulations in the wall of the small intestine and in small lymphatic
ducts, which blocks the outflow of lymph.
Lipid deficiency in the body can be associated not only with a violation of their absorption in the intestine, but also with an
increase in their excretion. The body can lose lipids in the urine (lipiduria), which is observed with lipoid nephrosis. Loss of
lipids by the sebaceous glands (eczema, acne) and release of lipids from the depot are possible when large areas of adipose tissue
and bone marrow are traumatized.
The consequences of a lack of lipids are:
1)
development of hypovitaminosis (fat-soluble vitamins A, D, E, K);
2)
the emergence of a deficiency of essential polyunsaturated fatty acids, followed by a violation of the synthesis of
biologically active substances (leukotrienes, prostaglandins, etc.). This, as a rule, is accompanied by hair loss,
inflammatory skin lesions, the appearance of necrotic foci and eczematous phenomena, kidney damage, loss of the
ability to reproduce;
3)
development of exhaustion.
Violation of lipid transport
Dyslipoproteinemias occur or worsen with obesity, diabetes mellitus, hypothyroidism, kidney and liver diseases; their course
and prognosis depend on the severity of the underlying disease. There are 5 types of hyperlipoproteinemia:
I. Hyperchylomicronemia - characterized by a high content of chylomicrons in plasma on an empty stomach.
It manifests itself as xanthomatosis - the deposition of cholesterol and its esters in the Kupffer's cells of the liver, histiocytes of
the subcutaneous tissue and tendons, followed by the proliferation of connective tissue in the form of yellowish plaques and
nodes (Fig. 12-31). Patients develop hepatosplenomegaly, thrombosis and micronecrosis of the pancreas, followed by the
formation of chronic pancreatitis, abdominal colic after eating fatty foods. Xanthomas in the form of yellowish papules are
determined on the skin. The disease can be caused by a hereditary autosomal recessive defect in lipoprotein lipase or
autoimmune diseases of the connective tissue (with systemic lupus erythematosus, antibodies against glycosaminoglycans are
formed, which disrupts the process of heparin activation of lipoprotein lipase).
II. Hyper-b-lipoproteinemia is divided into 2 types:
•
11a - an increase in the content of β-LP in the blood at a normal level of pre-β-LP;
•
11b - an increase in the content of β-LP and pre-β-LP.
The disease is characterized by pronounced xanthomatosis of the eyelids, skin, cornea, the development of coronary heart
disease with myocardial infarction at a very early age, atherosclerotic vascular lesions in children. It is assumed that the disease
is based on an autosomal dominant defect in VLDL and LDL receptors (11b) or a change in the activity of blood plasma
lipoprotein lipase (11a).
III. "Floating" hyperlipoproteinemia, or dis- β-lipoproteinemia... The disease is based on a hereditary violation of the synthesis
of apoprotein E (a protein that is part of chylomicrons and VLDL). The disease is characterized by the appearance in the serum of
floating β-LP, which are called intermediate (intermediate density lipoproteins - IDD). They are fortified with cholesterol and
their triglyceride content can be reduced. These particles are formed in violation of the catabolism of VLDL and chylomicrons.
There are also acquired forms of the disease in hypothyroidism, Tangier disease, and some autoimmune gammopathies. This type
of hyperlipoproteinemia is accompanied by early atherosclerotic manifestations (after 20 years), the development of coronary
heart disease, ischemic encephalopathy up to strokes, xanthomatosis, and obesity.
IV . Hyper-pre- β-lipoproteinemia... The disease can be hereditary (autosomal dominant) or acquired (with alcoholism, acute
hepatitis, acromegaly, diabetes, etc.). The pathogenesis is not fully understood. This type of hyperlipoproteinemia is characterized
by an increase in the level of triglycerides and VLDL in the blood. The content of LDL and HDL varies from normal to
significantly reduced. Patients develop obesity and diabetes mellitus 2
type, xanthomas appear, atherosclerotic lesions of the vessels of the lower extremities, retinal lipidosis and visual impairment,
manifestations of coronary heart disease are possible.
V . Hyper-pre- β-lipoproteinemia and chylomicronemia... With this disease, the content of chylomicrons and VLDL in the
blood increases and the level of LDL and HDL decreases. Patients have hepato- and splenomegaly, obesity, decreased
glucose tolerance (with type 2 diabetes mellitus), myocardial damage. After eating fatty foods, sudden attacks of abdominal
colic may occur, xanthomatosis and atherosclerosis are mild. In the pathogenesis of the primary disease, the main role is
played by the hereditary absence of the lipoprotein lipase cofactor - apoprotein CII (autosomal recessive inheritance), as a
result of which the two main substrates of this enzyme accumulate in the blood. Phenocopy of the disease develops with
alcoholism, Gierke's glycogenosis and some other liver diseases.
Hypo- (a) -lipoproteinemia belong to the group of relatively rare anomalies of the lipoprotein spectrum:
1 . A-β-lipoproteinemia... The disease is based on an autosomal dominant defect in the synthesis of apoprotein B, which leads to
an anomaly in the structure of chylomicrons, a decrease in the content or complete absence of VLDL and LDL in plasma.
Clinical manifestations are associated with impaired absorption of fats and carbohydrates in the intestine, hemolytic anemia,
degeneration of the lateral and posterior cords of the spinal cord, pigmentary retinopathy. Impaired absorption of fats manifests
itself immediately after birth with poor appetite, vomiting, profuse bowel movements, steatorrhea, and the development of
malnutrition. Approximately one third of patients develop mental retardation. With age, neurological disorders intensify, skeletal
deformities, cardiac arrhythmias appear, and vision deteriorates. In the pathogenesis of the disease, a decrease in the content of
cholesterol in cell membranes and the loss of fat-soluble vitamins,
2 . Tangier (or Tenjir) disease... The disease is based on an autosomal recessive disorder in the synthesis of apoprotein A,
which, in turn, disrupts the production of HDL. In patients, the transport of cholesterol esters is impaired, as a result of which
the esters are captured by macrophages and deposited in the cells of the reticuloendothelial system of the spleen, liver, and
lymphoid organs. Lymphadenopathy, hepatosplenomegaly, neurological disorders - weakness, paresthesias, decreased tendon
reflexes are revealed. One of the clearest signs of the disease is the orange-yellow color of enlarged tonsils.
There are other forms of hypolipoproteinemia: cerebrotendinous xanthomatosis (hereditary defect in the synthesis of bile acids
from cholesterol), Walman's disease (autosomal recessive cholinesterase deficiency), hypo-a-lipoproteinemia (genetically
determined hereditary disorders in the production of apoprotein A and most of them), etc. pathology of the synthesis of the protein
part of lipoproteins or with impaired cholesterol metabolism.
41. Describe the etiology, pathogenesis and types of hyperlipidemias. Give
clinical examples of these conditions.
Hyperlipoproteinemia caused by disorders of blood lipid metabolism due to defects in enzymes or cell receptors.
Five distinct subtypes of primary hyperlipidemia (I, II, III, IV, and V) have been described.
The most common form of inherited childhood hyperlipidemia is familial hypercholesterolemia. The frequency of its occurrence
is 1 case among 500 healthy people.
With it, an increase in cholesterol is detected with a normal content of triglycerides (the main part of fats). This is the risk of
developing coronary heart disease (myocardial infarction) in the first decade of life and at the age of 30-40 years. Combined
familial hyperlipidemia - increased cholesterol and triglyceride levels. In adulthood, atherosclerosis of the coronary and
peripheral vessels occurs very early.
Familial type I hyperlipidemia characterized by abdominal pain, enlargement of the liver and spleen, the formation of yellow
spots on the skin.
Familial type II hyperlipidemia - there is either early development of atherosclerosis with severe damage to the coronary vessels,
or a moderate change in lipids and the development of atherosclerosis at the age of 30-40 years.
Familial type III hyperlipidemia or hypertriglyceridemia observed with a diet high in carbohydrates. Yellow spots on
the skin, atheromatosis, severe coronary heart disease are detected early.
Familial type IV hyperlipidemia observed also with an increased content of carbohydrates in the diet. Disorders of glucose
tolerance, ischemic disease are clinically detected.
Familial type V hyperlipidemia clinically characterized by bouts of abdominal pain, enlarged liver and spleen, the
development of atherosclerosis and coronary heart disease, impaired glucose tolerance.
The importance of the disease and its forms is determined by the fact that the process of lipid assimilation is closely associated
with the occurrence of atherosclerosis and coronary heart disease.
42. Give the classification, describe the etiology and pathogenesis of general
obesity. Give clinical examples.
Obesity - excessive (pathological) accumulation of fat in the body in the form of triglycerides. In this case, body weight increases
by more than 20-30%.
Obesity types...
Obesity reasons...
The cause of primary obesity is a disruption in the functioning of the "hypothalamus-adipocytes" system. This is a result of a
deficiency of leptin and / or a deficiency in the effects of leptin.
Secondary obesity develops with excess calorie content of food and a low level of energy consumption of the body. Energy costs
depend on the degree of activity (primarily physical) and the person's lifestyle. Lack of physical activity is one of the important
causes of obesity.
Obesity pathogenesis... Allocate neurogenic, endocrine and metabolic mechanisms of obesity.
Neurogenic obesity options
Centrogenic (cortical, psychogenic) mechanism - one of the variants of an eating disorder (two others: neurogenic anorexia and
bulimia).
•
•
Cause: various mental disorders, manifested by a constant, sometimes irresistible desire to eat.
Possible mechanisms:
o activation of serotonergic, opioidergic and other systems involved in the formation of feelings of pleasure
and comfort;
o
perception of food as a strong positive stimulus (doping), which further activates these systems. This completes
the vicious circle of the centrogenic mechanism of obesity development.
Hypothalamic (diencephalic, subcortical) mechanism.
•
•
Cause: damage to the neurons of the hypothalamus (for example, after a concussion, with encephalitis,
craniopharyngioma, tumor metastases in the hypothalamus).
The most important links in pathogenesis:
o Damage or irritation of neurons in the posterolateral ventral nucleus of the hypothalamus stimulates the
synthesis and secretion of neuropeptide Y and decreases sensitivity to leptin, which inhibits the synthesis
of neuropeptide Y. Neuropeptide Y stimulates hunger and increases appetite.
o Violation of the formation of hunger due to excessive production of neurotransmitters that form the feeling of
hunger and increase appetite (GABA, dopamine, β-endorphin, enkephalins). This leads to a decrease in the
synthesis of neurotransmitters that form a feeling of satiety and suppress eating behavior (serotonin,
norepinephrine, cholecystokinin, somatostatin).
Endocrine obesity options
The endocrine mechanisms of obesity are leptin, hypothyroid, adrenal and insulin.
•
Leptin mechanism - leading in the development of primary
obesity.
o Leptin formed in fat cells. It
reduces appetite and increases energy expenditure
by the body. Leptin inhibits the formation and
release of neuropeptide Y by the hypothalamus.
o Neuropeptide Y participates in the formation of
feelings of hunger. It increases appetite and reduces
energy consumption of the body.
o Lipostat. The leptin-neuropeptide Y contour maintains
body fat mass with the participation of insulin,
catecholamines, serotonin, cholecystokinin, and
endorphins. In general, this system of biologically active
substances providing dynamic homeostasis of energy
metabolism and mass of adipose tissue in the body is
called the lipostat system.
•
Hypothyroid mechanism obesity is turned on when the effects of iodine-containing thyroid hormones are
insufficient, which reduces the intensity of lipolysis, the rate of metabolic processes in tissues and the energy
consumption of the body.
Adrenal (glucocorticoid, cortisol) mechanism of obesity is activated due to the hyperproduction of
glucocorticoids in the adrenal cortex (for example, in the disease and Itsenko-Cushing's syndrome), which
promotes lipogenesis due to hyperglycemia and the activation of the insulin mechanism.
Insulin mechanism the development of obesity develops as a result of direct insulin activation of lipogenesis in adipose
tissue.
•
•
Metabolic obesity mechanisms. The body's carbohydrate stores are relatively small. In this regard, a mechanism for saving
carbohydrates has been developed: with an increase in the proportion of fat in the diet, the rate of carbohydrate oxidation
decreases. With a breakdown of the regulatory system, a mechanism is activated that provides an increase in appetite and an
increase in food intake. Under these conditions, fats are not broken down and accumulate in the form of triglycerides.
Obesity metabolic mechanisms.
1.
2.
Carbohydrate storesin the body are relatively small. They are approximately equal to their daily intake with food. In this
regard, a mechanism for saving carbohydrates has been developed.
When increasingin the diet of the proportion of fats, the rate of carbohydrate oxidation decreases. This is evidenced by the
corresponding decrease in the respiratory coefficient (the ratio of the rate of formation of C02 to consumption rate 02).
3.
4.
If this does not happen (when the mechanism of inhibition of glycogenolysis is disturbed under conditions of a high
concentration of fats in the blood), a mechanism is activated that provides an increase in appetite and an increase in food
intake, aimed at providing the required amount of carbohydrates in the body.
Under these conditions, fats accumulate in the form of triglycerides. Obesity develops.
43. Provide data on the causes, pathogenetic features
and the consequences of various types of hypohydration.
Hypohydration characterized by a negative water balance.
Types of hypohydration
Depending on the osmolality of the extracellular fluid, hypoosmolar, hyperosmolar and isoosmolar types of
hypohydration are distinguished.
•
•
•
Hypoosmolar hypohydration due to the predominance of salt removal over water losses.
Hyperosmolar hypohydration develops as a result of excess fluid excretion over salt losses.
Isoosmolar hypohydration is a consequence of an equivalent decrease in water and salt in the body.
Etiology of hypohydration
The reasons hypoosmolar hypohydration:
•
•
•
•
Hypoaldosteronism (for example, in Addison's disease).
Prolonged intense sweating.
Indomitable vomiting, profuse diarrhea and the presence of fistulas in the stomach or intestines (leading to
loss of gastric and intestinal juice).
Improper dialysis with hypo-osmolar dialysis fluids.
Consequences and manifestations
• Decrease in BCC.
• An increase in blood viscosity due to a decrease in its
plasma volume and an increase in hematocrit (Ht).
• Disorders
of
the
central,
organ-tissue
and
microcirculation, which are a direct consequence of a
decrease in the BCC, an increase in blood viscosity, as well
as hypoperfusion of blood vessels and are characterized by: a
decrease in shock and cardiac output, hypoperfusion of
organs and tissues, impaired blood circulation in the vessels
of the microvasculature.
• Disorders of acid-base balance:
• Hypoxia caused by circulatory disorders (circulatory), blood
loss (hemic), pulmonary perfusion disorders (respiratory),
tissue metabolism (tissue).
• Dryness of mucous membranes and skin, decreased
secretion of saliva (hypo-salivation), decreased elasticity and
tension (turgor) of the skin, muscles, retraction and softness
of the eyeballs, decreased volume of daily urine.
The reasons hyperosmolar hypohydration:
•
•
•
•
•
•
Not drinking enough water (for example, with "dry" fasting with refusal to drink fluids, with a lack of drinking
water).
Neuropsychiatric diseases, accompanied by suppression of the feeling of thirst (for example, with damage to the
neurons of the thirst center as a result of hemorrhage, ischemia, tumor growth, with a concussion).
Hyperthermic states(including fever). An increase in body temperature by 1 ° C leads to an additional
release of 400-500 ml of fluid per day with sweat.
Long-term mechanical ventilationinsufficiently moistened gas mixture. ALV = artificial lung ventilation
Drinking sea water in conditions of dehydration.
Parenteral administration of hyperosmolar solutions for hypohydration.
Consequences and manifestations
• Decrease in BCC.
• Increase in Ht and, as a consequence, blood viscosity.
• Systemic circulatory disorders (central, organ-tissue, microcirculatory).
• Abnormalities of acid-base balance (more often acidosis) as a result of hemodynamic, respiratory and metabolic disorders.
• Hypoxia.
The reasons isoosmolar hypohydration:
•
•
•
•
Acute massive blood loss at its initial stage (i.e. before the development of the effects of emergency
compensation mechanisms).
Polyuria (for example, diabetes insipidus and diabetes mellitus).
Large area burns...
Polyuriacaused by high doses of diuretics.
Consequences and manifestations
The consequences and manifestations of iso-osmolar hypohydration are caused by a decrease in the volume of extracellular fluid
and, as a consequence, by circulatory disorders: Decrease in BCC, Increase in blood viscosity; Violation of the central, organ-tissue
and microcirculation; Disorders of acidic balance.
Pathogenesis and manifestations of hypohydration
Different types of hypohydration have similar manifestations, although they may differ in specific symptoms. The prevalence of
individual symptoms and their severity depends on the degree and type of hypohydration. The following are the most common
common signs of hypohydration.
•
•
•
•
•
•
↓ BCC (hypovolemia).
↑ blood viscosity (due to hemoconcentration).
Systemic circulatory disorders (central, organ-tissue, microcirculatory).
Disorders of acidic abnormalities (more often acidosis).
Hypoxiacaused by circulatory disorders (circulatory), decreased blood volume (hemic), pulmonary perfusion disorder
(respiratory), tissue metabolism (tissue).
Dry mucous membranes and skin, decrease in the secretion of saliva (hyposalivation), decrease in elasticity and
tension (turgor) of the skin and muscles, retraction and softness of the eyeballs, decrease in the volume of daily urine.
PRINCIPLES FOR ELIMINATING HYPHYDRATION
Therapy of various types of hypohydration of the organism is based on etiotropic, pathogenetic
and symptomatic principles.
Etiotropic principle provides for the elimination or reduction of the severity and duration of the causal factor. This therapy is
individual for each patient.
Pathogenetic principle implies:
1 . Elimination of water deficiency in the body, which is achieved by the introduction of the missing volume of fluid.
2 . Reducing the degree of ion imbalance.
3 . Elimination of shifts of the KShR
4 . Normalization of central, organ-tissue and microcirculation.
Symptomatic principle aims to eliminate or reduce the severity of symptoms that aggravate the state of hypohydration.
44.
Describe the causes, pathogenetic features
and the consequences of various types of overhydration.
Overhydration develops with a positive water balance.
Types of overhydration
Depending on the osmolality of the extracellular fluid, hypoosmolar, hyperosmolar and isoosmolar hyperhydration are
distinguished.
•
•
•
Hypoosmolar hyperhydration - an increase in the volume of extra- and intracellular fluid with reduced
osmolality.
Hyperosmolar hyperhydration an increase in the volume of extracellular fluid with increased osmolality.
Isoosmolar overhydration - an increase in the volume of extracellular fluid with normal osmolality.
Etiology of overhydration
The reasons hypoosmolar overhydration:
•
•
•
Excessive introduction of fluids into the body with a low content of salts in them or their absence (for example,
"water poisoning" with abundant drinking of fresh water).
Increased the content of ADH in the blood due to its hyperproduction in the hypothalamus (for example, with
Parkhon's syndrome).
Renal failure with the development of oligo- and anuria.
Consequences and manifestations
• Increased BCC (hypervolemia) and hemodilution.
• Polyuria - increased urine output due to an increase in
filtration pressure in the renal corpuscles.
• Hemolysis of erythrocytes.
•
The appearance of plasma and intracellular components.
• Vomiting and diarrhea due to intoxication
• Psycho-neurological disorders: lethargy, apathy, impaired
consciousness, often convulsions.
• Hypo-osmolar syndrome.
The reasons hyperosmolar overhydration:
•
•
•
•
Drinking sea water...
into the body of hyperosmolar solutions without monitoring the osmolality of blood plasma.
Hyperaldosteronismleading to excessive Na + reabsorption in the kidneys.
Kidney diseaseaccompanied by a decrease in salt excretion (for example, tubulo- and fermentopathy).
Consequences and manifestations
• Hypervolemia.
• Increase in BCC.
• An increase in cardiac output, followed by a decrease in the
development of heart failure.
• Increase in blood pressure.
• Increased central venous blood pressure.
• Edema of the brain.
• Pulmonary edema.
•
Hypoxia caused by the development of heart failure,
impaired blood circulation and respiration.
• Neuropsychiatric disorders caused by damage to the brain
due to its edema, increasing hypoxia and intoxication of the
body.
• Intense thirst, which develops due to hyperosmolality of
blood plasma and hypohydration of cells.
• Hyperosmolar Syndrome.
The reasons isoosmolar hyperhydration:
•
•
•
•
•
Infusion of large amounts of isotonic solutions (e.g. sodium chloride, glucose).
Insufficient blood circulation, leading to an increase in the volume of extracellular fluid.
Increasing the permeability of the vessel walls microvasculature, which facilitates the filtration of fluid in the capillaries
(for example, in case of intoxication, some infections, toxicosis of pregnant women).
Hypoproteinemia, in which fluid is retained in the intercellular space (for example, with general or protein starvation,
liver failure, nephrotic syndrome).
Chronic lymphostasis, accompanied by inhibition of the outflow of intercellular fluid into the lymphatic vessels.
Consequences and manifestations
• Increase in blood volume: its total and circulating fractions (oligocythemic hypervolemia).
• Increased blood pressure due to hypervolemia, increased cardiac output and peripheral vascular resistance.
• The development of heart failure, especially with prolonged hypervolemia.
• Edema formation.
Pathogenesis and manifestations of overhydration
Different types of overhydration have similar and specific manifestations. The presence of individual symptoms and their
severity depends on the degree and type of overhydration.
•
•
•
•
•
•
•
↑ BCC (hypervolemia) and ↑ hemodilution.
↑ cardiac output and blood pressure...
Polyuria (due to an increase in filtration pressure in the renal corpuscles).
Vomiting and diarrhea (due to the appearance in blood plasma of intracellular components, for example, enzymes
and other macromolecules due to damage and destruction of cells of various tissues and organs).
Psychoneurological disorders: lethargy, apathy, impaired consciousness, often convulsions.
With decompensation of cardiac activity and the development of heart failure - the development of edema of various
localization.
Hemolysis of erythrocytes (with hypoosmolar hyperhydration).
PRINCIPLES FOR ELIMINATING HYPERHYDRATION
Treatment of various options for overhydration is based on etiotropic, pathogenetic and symptomatic principles.
Etiotropic principle - leading in most cases of overhydration - is to eliminate or reduce the severity and duration of the
causative factor and in many cases eliminates the signs of overhydration of the body.
Pathogenetic principle provides for the rupture of the main links of the pathogenesis of overhydration
Symptomatic treatment is aimed at eliminating changes in the body that cause an increase in the severity of overhydration
45. Classification of edema. Give the concept of "edema", name their etiological
and pathogenetic factors. Describe the etiology and main links in the pathogenesis
of cardiac and renal edema.
EDEMA - a typical form of violation of the body's water balance, characterized by the accumulation of excess fluid in the
intercellular space and / or body cavities.
CLASSIFICATION OF Edema... Edema is classified depending on their location, prevalence, rate of development and the main
pathogenetic factor in the development of edema.
Depending on the location of the edema distinguish between anasarka and dropsy.
Anasarka- edema of the subcutaneous tissue. Dropsy - edema of the body cavity (accumulation of transudate in it). Ascites is the
accumulation of excess transudate in the abdominal cavity. Hydrothorax is the accumulation of transudate in the chest cavity.
Hydropericardium is an excess of fluid in the cavity of the pericardial sac. Hydrocele is the accumulation of transudate between the
sheets of the serous membrane of the testicle. Hydrocephalus is an excess of fluid in the ventricles of the brain (internal dropsy of
the brain) and / or between the brain and the skull - in the subarachnoid or subdural space (external dropsy of the brain).
Depending on the prevalence distinguish between local and general edema.
Local(for example, in a tissue or organ at the site of an inflammation or allergic reaction). General - the accumulation of excess fluid
in all organs and tissues.
Depending on the rate of development of edema speak of a fulminant and acute development or a chronic course of edema.
Lightning edemadevelops within a few seconds after exposure. Acute edema usually develops within an hour after the action of the
causative factor. Chronic edema develops within a few days or weeks.
Depending on the main pathogenetic factor distinguish between hydrodynamic, lymphogenous, oncotic, osmotic and
membranogenic edema.
PRINCIPLES AND METHODS FOR ELIMINATION OF Edema
Hydrodynamic factor (hemodynamic, hydrostatic, mechanical) factor is characterized by an increase in effective
hydrostatic pressure.
Causes Mechanisms
The hydrodynamic (hemodynamic, hydrostatic) factor is characterized by an increase in the effective hydrostatic pressure in the
vessels of the microvasculature.
The reasons hemodynamic edema.
•
↑ venous pressure...
•
↑ Systemic venous pressure with heart failure due to a decrease in its pumping function.
•
↑ Local venous pressure when veins are obstructed (for example, a thrombus or embolus) or when they are
compressed (for example, a tumor, scar, edematous tissue).
•
↑ BCC (for example, due to hypoxia and an increase in the production of ADH in chronic heart failure).
Mechanisms implementation of the hydrodynamic factor.
•
Inhibition of resorption of interstitial fluid in postcapillaries and venulesas a result of an increase in the effective
hydrostatic pressure - the difference between the hydrostatic pressure of the intercellular fluid (on average 7 mm Hg) and
the hydrostatic pressure of blood in the vessels of the microvasculature. Normally, the effective hydrostatic pressure is
36-38 mm Hg in the arterial part of the microvessels, and 14-16 mm Hg in the venous part. This mechanism plays a
major role in increasing venous pressure.
•
↑ filtration of blood in capillariesdue to the increase in effective hydrostatic pressure. As a rule, this mechanism
is activated with a significant increase in the BCC.
Lymphogenic factor... The lymphogenic (lymphatic) factor is characterized by difficulty in the outflow of lymph from tissues due
to either mechanical obstruction or excessive lymph formation.
The reasons
•
Congenital hypoplasia lymphatic vessels and nodes.
•
Compression of lymphatic vessels (eg, tumor, scar, enlarged adjacent organ).
•
Lymphatic embolism (for example, tumor cells, parasites).
•
Lymph node tumor, as well as metastases in the lymph node of tumors of other organs.
•
↑ central venous pressure (for example, with heart failure or increased intrathoracic pressure).
•
Spasm of the walls of the lymphatic vessels (for example, when an excess of catecholamines is released during
pheochromocytoma, under stress).
•
Significant hypoproteinemia(the content of proteins in the blood plasma is less than 35-40 g / l) and the inclusion of an
oncotic factor in the formation of edema. Due to the increase in the flow of fluid from the vessels into the interstitial
space, the formation of lymph in the tissues is significantly increased.
Mechanisms...
•
•
Mechanical outflow obstruction lymph from tissues - mechanical lymphatic insufficiency - Edema
Significant tissues
- Congestion
the lymphatic vessels Deceleration
increased
lymph of
formation
outflow of lymph from tissues - Dynamic lymphatic insufficiency - Edema
Oncotic factor... The oncotic (hypoalbuminemic, hypoproteinemic) factor in the development of edema is characterized by a
decrease in oncotic blood pressure and / or an increase in it in the intercellular fluid.
Causes Mechanisms
The oncotic (hypoalbuminemic, hypoproteinemic) factor in the development of edema is activated when the oncotic blood
pressure decreases and increases in the intercellular fluid.
The reasons development of oncotic edema.
•
Decrease in oncotic blood pressure as a result of hypoproteinemia (mainly due to hypoalbuminemia; albumins are about
2.5 times more hydrophilic than globulins). Most often, the content of albumin decreases with insufficient intake or
excessive loss of proteins, a decrease in the synthesis of albumin in the liver.
•
Increased oncotic pressure of interstitial fluid during cell destruction and hydrolysis of intercellular fluid proteins.
Mechanism the implementation of the oncotic factor consists in increasing the filtration of the liquid part of the blood in the
capillaries and reducing the reabsorption of water in the postcapillaries and venules (as a consequence of hypoproteinemia and
hyperononia of the tissue).
Osmotic factor... The osmotic factor in the development of edema consists either in an increase in the osmolality of the interstitial
fluid, or in a decrease in the osmolality of the blood plasma, or in a combination of both.
Causes Mechanisms
osmotic factor
The osmotic factor in the development of edema is triggered by an increase in the osmolality of the interstitial fluid and a
decrease in the osmolality of the blood plasma.
The reasons
development of
osmotic edema.
• Factors
that reduce the
osmotic pressure
of the blood and
cause the
development of
hypoosmolar
hyperhydration
(see above).
• Factors
that increase the
osmolality of the
interstitial fluid:
o in
exit from
damaged and
destroyed cells of
osmotically
active substances
(ions Na +, K +,
Ca2 +,
glucose, MC,
nitrogenous
compounds);
o P
increased
dissociation in the
interstitial
th liquid salts and organic compounds (for example, under conditions of hypoxia or acidosis);
o decrease in the transport of osmotically active substances (ions, organic and inorganic compounds)
from tissues as a result of slowing down the outflow of blood through the venules;
o transport of Na + from blood plasma into the interstitial fluid (for example, with hyperaldosteronism). The
mechanism of formation of osmotic edema is the excessive transport of water from the blood to the intercellular fluid along the
gradient of osmotic pressure. This mechanism takes place in cardiac, renal (nephritic), hepatic and a number of other edema.
Membranogenic factor... The membrane factor is characterized by a significant increase in the permeability of the vascular walls
of the microvasculature for water, small- and large-molecular substances (proteins are of the greatest importance among the latter).
Edema in case of heart failure
Cause: heart failure (a condition in which the heart does not meet the needs of organs and tissues for blood supply, adequate to
their function and the level of plastic processes). It is characterized by: a lesser (in comparison with the required) value of cardiac
output; primarily circulatory hypoxia.
46. Give the concept of the acid-base state (CBS), the main indicators of CBS,
regulation mechanisms, the role of buffer systems, kidneys, lungs, liver,
gastrointestinal tract in the regulation of CBS.
The acid-base state (CBS) is one of the most important components of the body's homeostasis, an indispensable condition for the
optimal activity of enzymes that catalyze metabolic processes. In the process of metabolism, various acids and bases are formed,
in addition, they are introduced from the outside. Disorders of various organs can lead to a violation of CBS, which in turn causes
various pathological changes in the body. In some cases, CBS indicators are a fairly accurate criterion of IT efficiency. Therefore,
it is necessary to know the mechanisms of physiological regulation and violations of CBS, to be able to assess their condition and
to correctly prevent and correct violations.
Mechanisms of regulation of acid-base balance
Normally, the body produces almost 20 times more acidic foods than alkaline ones. In this regard, the systems that provide
neutralization, excretion and secretion of excess compounds with acidic properties dominate. These systems include chemical
buffer systems and physiological mechanisms for the regulation of acid-base balance.
CHEMICAL BUFFER SYSTEMS
Chemical buffer systems are mainly represented by bicarbonate, phosphate, protein and hemoglobin buffers. Buffer systems
begin to act immediately with an increase or decrease in [H +] and are able to eliminate moderate shifts in the acid-base balance
within 10-40 s. The capacity and efficiency of blood buffer systems is very high (Table 13-2). The principle of action of chemical
buffer systems is to transform strong acids and strong bases into weak ones.
Hydrocarbonate buffer system - the main buffer of blood and intercellular fluid. The extracellular fluid bicarbonate buffer
consists of a mixture of carbonic acid - H2CO3 and sodium bicarbonate - NaHCO3. In cells, the carbonic acid salt contains
potassium and magnesium. The bicarbonate buffer is an open-type system, it is associated with the function of external
respiration and kidney function (Table 13-3).
Table 13-3. Initial shifts and compensatory reactions in case of violations of acid-base balance
Phosphate buffer system plays an essential role in the regulation of acid-base balance within cells, especially in the kidney
tubules. This is due to the higher concentration of phosphates in the cells compared to the extracellular fluid.
Phosphate buffer consists of two components: alkaline - (Na2HPO4) and acidic - (NaH2PO4)...
Protein buffer system - the main intracellular buffer. It accounts for about three quarters of the buffer capacity of the
intracellular fluid. The components of the protein buffer are a weakly dissociating protein with acidic properties (protein-COOH)
and salts of a strong base (protein-COONa).
Hemoglobin buffer system - the most capacious blood buffer. The hemoglobin buffer consists of an acidic component
- oxygenated HbO2 and a basic one - non-oxygenated Hb.
Bone carbonates function as a depot for the buffer systems of the body. Bones contain a large amount of carbonic acid salts:
calcium, sodium, potassium carbonates, etc. With a rapid increase in acid content (for example, in acute heart, respiratory or
renal failure; shock, coma and other conditions) bone tissue can provide up to 30-40 % buffer capacity.
PHYSIOLOGICAL MECHANISMS
Along with powerful and fast-acting chemical systems in the body, organ mechanisms for compensation and elimination of abnormal
acid levels are functioning. To implement them and achieve the desired effect, more is required.
time - from several minutes to several hours. The most effective physiological mechanisms for the regulation of acid-base balance
include the processes occurring in the lungs, kidneys, liver and gastrointestinal tract.
Lungs provide the elimination or reduction of the shifts of the KShR by changing the volume of alveolar ventilation.
Kidney contribute to the elimination of shifts in blood acid-base balance by means of acidogenesis, ammoniogenesis,
secretion of phosphates and K +, Na + -exchangeth mechanism, which are associated with the formation of hydrocarbonate and its entry into the blood plasma.
Liver plays a significant role in compensating for shifts in the acid-frequency ratio. In it, in addition to the general ones for the
whole organism, specific metabolic reactions take place, participating in the regulation of acid-base balance:
•
Protein synthesis blood entering the protein buffer system.
•
Ammonia formation, capable of neutralizing acids both in the hepatocytes themselves and in the blood plasma and in
the intercellular fluid.
•
Synthesis of glucose from "acidic" non-carbohydrate substances - amino acids, glycerin, lactate, pyruvate.
•
Removal from the body of non-volatile acids - glucuronic and sulfuric during detoxification of metabolic products and
xenobiotics.
•
Excretion of acidic and basic compounds with bile into the intestine.
Stomach participates in the correction of shifts in acid-base balance, mainly by changing the secretion of hydrochloric acid:
with alkalization of body fluids, this process is inhibited, and with acidification, it intensifies.
Intestines helps to reduce the shifts of the acid-base balance through several mechanisms.
•
Intestinal juice secretioncontaining a large amount of bicarbonate. In this case, H + enters the blood plasma.
•
Changes in the amount of sucked liquid, which contributes to the normalization of water and electrolyte balance
in cells and biological fluids.
•
Reabsorption of components of buffer systems (Na +, K +, Ca2 +, Cl-, HCO3).
47. Describe the causes, mechanisms of development and compensation, the
main manifestations and changes in the indicators of CBS in acidosis and alkalosis.
ACIDOSIS
The mechanism of spasm of bronchioles (respiratory acidosis): increased cholinergic effects in conditions of significant acidosis.
This is the result:
• Increased release of acetylcholine from nerve terminals.
• Increased sensitivity of cholinergic receptors to acetylcholine. With
metabolic acidosis
•
Accumulation in the blood of so-called non-volatile acids (lactic acid, hydroxybutyric, acetoacetic, etc.) or the loss of
buffer bases by the body.
• the concentration of bicarbonate in plasma decreases, while the concentration of chlorine anions increases. Potassium
cations leave the cell (the concentration of K + in the blood plasma increases), hydrogen and sodium cations are
exchanged (for 3 released potassium cations there are 1 hydrogen cation and 2 sodium cations). With preserved renal
function, an increased amount of potassium is excreted in the urine, as a result, intracellular hypokalemia is formed
against the background of a normal or slightly overestimated level of K + in the blood plasma.
ALKALOSIS
With alkalosis (especially associated with hypocapnia), general and regional hemodynamic disorders occur: cerebral and
coronary blood flow decreases, blood pressure and minute blood volume decrease. The neuromuscular
excitability,there is muscle hypertonia up to the development of seizures and tetany. Often there is a suppression of intestinal
motility and the development of constipation; the activity of the respiratory center decreases. Gas alkalosis is characterized by
decreased mental performance, dizziness, and fainting conditions.
1. Manifestations of acid-base disorders
states.
The clinical picture of acid base balance disorders depends mainly on the direction of changes in [H +] and pH.
Manifestations of acidosis
•
Compensatory increase in alveolar ventilation... In severe acidosis, deep and noisy breathing can be recorded - periodic
breathing of Kussmaul.
• Increasing depression of the nervous system and GNI, which is manifested by drowsiness, lethargy, stupor
or coma (for example, with ketoacidosis in patients with diabetes).
• Decreased blood flow in the brain, myocardium and kidneys... This aggravates the dysfunction of the nervous system,
heart, and also causes oliguria (decreased urine output).
• Imbalance of ions due to activation of compensatory mechanisms: an increase in the content of K + ions in
intercellular fluid, hyperkalemia, hyperphosphatemia, hypochloremia.
• Hyperosmolar and edematous syndromes...
Manifestations of alkalosis
•
•
•
•
•
Lack of central and organ-tissue blood flow...
Violation of microcirculation, up to signs of capillary-trophic insufficiency.
Hypoxia due to circulatory failure and an increase in the affinity of Hb for oxygen.
Hypokalemia due to the transport of K + from the intercellular fluid to the cells in exchange for H +.
Deterioration of neuromuscular excitability, manifested by muscle weakness, impaired peristalsis of the stomach and
intestines... These disorders, as well as cardiac arrhythmias, are mainly the result of hypokalemia.
In the clinic, violations of CBS are detected by determining a number of blood parameters: pCO2, pH, SB (standard bicarbonate,
i.e. the concentration of bicarbonate at full blood saturation with O2 (pCO2 - 40 mm Hg and t = 38 ° C), BB ( Buffer Base buffer
bases, i.e. the sum of all buffer bases), BE (Base Excess, buffer base shift, i.e. the difference between the concentrations of the
buffer bases determined in standard and given specific conditions).
• Respiratory acidosis - pC O2 > 40 mm Hg Art. (> 5.3 kPa; H +> 40 nmol / L or pH <7.40).
• Respiratory alkalosis - pC O2 <40 mm Hg Art. (<5.3 kPa; H + <40 nmol / L or pH> 7.40).
• Metabolic acidosis - BE <0 mmol / L = BD.
• Metabolic alkalosis - BE> 0 mmol / L.
In case of non-gas violations of the CBS, the BB indicator, as a rule, does not go beyond the normal range.
INDICATORS OF THE ACID-BASIC STATE OF BLOOD
The acid-base state of the blood is assessed by a set of indicators.
PH value - the main indicator of CBS. In healthy people, the arterial blood pH is 7.40 (7.35-7.45), that is, the blood has a
slightly alkaline reaction. A decrease in the pH value means a shift towards the acidic side - acidosis (pH <7.35), an increase in
pH - a shift towards the alkaline side - alkalosis (pH> 7.45).
The range of pH fluctuations appears to be small due to the use of a logarithmic scale. However, a difference in pH unit means a
tenfold change in the concentration of hydrogen ions. PH shifts of more than 0.4 (pH less than 7.0 and more than 7.8) are
considered incompatible with life.
Fluctuations in pH in the range of 7.35-7.45 refer to the zone of full compensation. Changes in pH outside this zone are
interpreted as follows:
• subcompensated acidosis (pH 7.25-7.35);
• decompensated acidosis (pH <7.25);
• subcompensated alkalosis (pH 7.45-7.55);
• decompensated alkalosis (pH> 7.55).
PaCO2 (РСО2) - tension of carbon dioxide in arterial blood. Normally, PaCO2 is 40 mm Hg. Art. fromfluctuations from 35 to
45 mm Hg. Art. An increase or decrease in PaCO2 is a sign of respiratory distress.
Alveolar hyperventilation accompanied by a decrease in PaCO2 (arterial hypocapnia) and respiratory alkalosis, alveolar
hypoventilation - by an increase in PaCO2 (arterial hypercapnia) and respiratory acidosis.
Buffer Base (BB) - the total amount of all blood anions. Since the total amount of buffering bases (in contrast to standard and true
bicarbonates) does not depend on the CO2 voltage, the VV value is used to judge metabolic disturbances of CBS. Normally, the
content of buffer bases is 48.0 + 2.0 mmol / l.
Excess or deficiency of buffer bases (Base Excess, BE) - the deviation of the concentration of buffer bases from the normal level.
Normally, the BE indicator is zero, the permissible fluctuation range is +2.3 mmol / l. With an increase in the content of buffer
bases, the BE value becomes positive (excess of bases), with a decrease, it becomes negative (deficiency of bases). The BE value
is the most informative indicator of metabolic disorders in CBS due to the sign (+ or -) in front of the numerical expression. A
deficiency of bases that goes beyond the fluctuations of the norm indicates the presence of metabolic acidosis, an excess indicates
the presence of metabolic alkalosis.
Standard bicarbonate (SB) - the concentration of bicarbonates in the blood under standard conditions (pH = 7.40; PaCO2 = 40
mm Hg; t = 37 ° C; SO2 = 100%).
True (topical) bicarbonates (AB) - the concentration of bicarbonates in the blood under the specific conditions in the
bloodstream. Standard and true bicarbonates characterize the bicarbonate buffering system of the blood. Normally, the values of
SB and AB coincide and amount to 24.0 + 2.0 mmol / l. The amount of standard and true bicarbonates decreases in metabolic
acidosis and increases in metabolic alkalosis.
48. Describe the main forms of sodium metabolic disorders: types, etiology,
disorders of metabolism and biological functions with them.
DISORDERS OF SODIUM EXCHANGE... The pathology of sodium metabolism manifests itself in the form of hypernatremia
and hyponatremia.
HYPERNATRIEMIA - increase in [Na +] in blood serum above normal (more than 145 mmol / l).
The reasons
•
•
•
•
Excess (more than 12 g per day) intake sodium in the body
Reduced excretion
sodium from the body
Hypohydration of the bodycombined with hypovolemia
Hemoconcentration due to the redistribution of fluid from blood vessels to tissues.
• Excess (more than 12 g per day) intake of sodium into the body.
o Consumption with food and liquids (for example, when food is salted, drinking mineral waters).
o Parenteral administration for therapeutic purposes (for example, NaCl solutions).
• Reduced excretion of sodium from the body.
o Renal failure
o Renin hypersecretion.
o Increased formation of angiotensin.
o Aldosteronism.
• Hemoconcentration - a decrease in the water content in the blood.
o Hypohydration of the body.
o Edematous syndrome.
Manifestations: Hyperosmolality of blood and other extracellular fluids, Disorders of higher nervous activity, Hypohydration of
cells, Increased neuromuscular excitability, Edema, Arterial hypertension.
Effects
•
Hyperosmolarity of blood and other biological fluids (due to the high osmotic activity of Na +).
•
Hypohydration of cells, their shrinkage and, often, destruction (as a result of the transport of water from
cells to the interstitium along the gradient of osmotic pressure).
•
Edema (as a result of the inclusion of an osmotic factor).
•
Increased excitability of nervous and muscle tissues (due to an increase in intracellular Na + and a decrease in
the threshold of excitability).
•
Arterial hypertension (due to the accumulation of excess Na + in the endothelium and SMC of the arteriole
wall, which leads to vasoconstriction and an increase in OPSS).
•
Disorders of GNI (feelings of fear, depression often develop).
Methods for eliminating hypernatremia
• Elimination of the causecausing an increase in the level of Na + in the blood.
• Stimulation of Na + excretion from blood with diuretics
• Parenteral administration of fluids
Hyponatremia - decrease in [Na +] in blood serum below normal (less than 13 mmol / l).
Causes of hyponatremia
•
•
•
Insufficient (less than 8-6 g per day) intake sodium in the body
Excessive elimination sodium from the body
Hemodilution - an increase in the water content in the blood
• Insufficient (less than 6 g per day) intake of sodium into the body.
o Complete starvation.
o Partial (sodium) fasting (for example, with a salt-free diet).
• Excessive excretion of sodium from the body.
Increased excretion of sodium by the kidneys (for example, with hypoaldosteronism, diabetes, chronic
nephritis, renal failure, use of diuretics, overproduction of atrial natriuretic factor).
o Prolonged profuse sweating.
o Chronic diarrhea.
o Repeated vomiting.
Hemodilution is an increase in the water content in the blood.
o Increased fluid intake.
o Parenteral administration of solutions that do not contain sodium (for example,
during detoxification therapy).
o Lack of renal excretory function.
o The flow of fluid from the interstitium into the vessels (for example, when
hypoproteinemic edema is eliminated).
o
•
Manifestations: Hypoosmolality of blood and other extracellular fluids, Decreased turgor of the skin and mucous membranes,
Muscular hypotension, Cell hyperhydration, Disorders of higher nervous activity, Decreased neuromuscular excitability, Arterial
hypotension, Dyspeptic disorders.
Effects
• Hypoosmolarity of blood and other body fluids.
•
Cell hyperhydration and swelling (as a result of the flow of fluid in them from the interstitium along the
gradient of osmotic pressure).
•
Decreased turgor, elasticity of the skin and mucous membranes, their dryness (as a consequence of a
decrease in fluid in the interstitial space - extracellular hypohydration).
•
Decrease in excitability of nervous and muscle tissues (as a result of an increase in the threshold of cell excitability
under conditions of low extracellular Na + level).
•
Muscle hypotension (due to a decrease in the excitability of myocytes).
•
Arterial hypotension (as a result of a decrease in the tone of the SMC of the vessel walls, as well as a
decrease in the contractile function of the myocardium and cardiac output).
•
Violation of VNI, up to the development of asthenia and disorders of consciousness (due to overhydration of
neurons and hypoxia of brain tissue).
•
Dyspeptic disorders - decreased appetite, nausea, vomiting (as a result of dysfunctions of the nerve centers of
the hypothalamus).
Methods for eliminating hyponatremia
•
•
•
Elimination of the cause hyponatremia.
1-2% solution of NaCl i / v...
Parenteral infusion of blood plasma, plasma substitutes, protein-containing solutions.
49. Give the main forms of potassium metabolic disorders: types, etiology, metabolic disorders and
biological functions with them.
K + is the main cation of the intracellular body fluid. It contains approximately 90% of these cations. A significant part
of K + is associated with proteins, carbohydrates, phosphates, creatinine. In blood plasma, the concentration of K + is
3.3-5.1 mmol / l, and in cells - about 155 mmol / l. The ratio of intra- and extracellular K + content is the main factor in
the state of electrical activity of excitable structures.
The human body should receive 40-60 mmol (2-4 g) of potassium per day. Approximately the same amount is excreted
from the body, mainly by the kidneys.
HYPERKALIEMIA
Hyperkalemia - an increase in the concentration of K + in the blood plasma above the normal level.
The reasons
• Decreased renal K + excretion.
♦ Renal failure The kidneys are able to excrete up to 1000 mmol / day of potassium, i.e. much bigger,
than it normally enters the body. Damage to the kidney tissue can lead to hyperkalemia.
♦ Hypoaldosteronism (for example, Addison's disease - adrenal insufficiency) or decreased sensitivity of the tubular
epithelium to aldosterone in patients with nephropathies, systemic lupus erythematosus.
• Redistribution of potassium from cells to blood.
♦ Damage and destruction of cells (for example, with hemolysis; with a syndrome of prolonged crushing of tissues,
their burns or crushing).
♦ Hypoinsulinism.
♦ Intracellular acidosis, which stimulates the release of K + from cells and at the same time - the transport of Cl- into
cells.
• The introduction of excess potassium into the body.
The consequences of hyperkalemia are the result of impaired formation of MP and PD and neuromuscular transmission
of excitation.
♦ Muscle hypotension, muscle paralysis and hyporeflexia, intestinal atony and muscle pain.
♦ Bradycardia and cardiac arrhythmias. At a potassium concentration of 8-10 mmol / l, atrioventricular and
intraventricular blockade of excitation is possible, and at 13 mmol / l - cardiac arrest in diastole.
Methods for eliminating hyperkalemia
• Elimination of the cause of hyperkalemia.
• Activation of K + transport from intercellular fluid to cells.
♦ Intravenous administration of calcium chloride solution.
♦ Intravenous infusion of glucose solution in combination with insulin. The transport of glucose into cells under the
influence of insulin stimulates the transfer of K + into them. This relatively quickly reduces the degree of hyperkalemia
and its cardiotoxic effects.
♦ Intravenous infusion of sodium bicarbonate potentiates the transport of K + into cells.
• Stimulation of the mechanisms of excretion of excess K + from the body.
♦ Use of diuretics (eg furosemide).
♦ Administration of aldosterone preparations (for example, in the form of deoxycorticosterone acetate).
♦ Use of cation exchange resins (eg sodium sulfonate). Once in the intestine, the resins are removed up to 60-100
mmol of potassium during the first 4-6 hours. This is due to the fact that the potassium content in the intestinal juice
is 2-4 times higher than in the blood plasma.
♦ Dialysis Hemodialysis allows to reduce the K + content in blood plasma by half within 3-4 hours from its start.
HYPOCALYEMIA
Hypokalemia - a decrease in the concentration of K + in the blood plasma below normal.
The reasons
• Insufficient (less than 10 mmol / day) intake of potassium into the body with food (for example, when fasting or
restricting the intake of foods containing potassium compounds - vegetables, dairy products).
• Excessive excretion of potassium from the body.
♦ Chronic profuse diarrhea. Intestinal secretions contain large amounts of potassium.
♦ Repeated vomiting. The potassium content in gastric juice is low. However, the development of hypovolemia
causes secondary hyperaldosteronism and increased renal K + excretion.
♦ Increased excretion of potassium by the kidneys (with polyuria).
• Redistribution of K + from blood and intercellular fluid to cells.
♦ Increased insulin levels in the blood.
♦ Hypercatecholaminemia (as a result of the use of drugs adrenaline, norepinephrine, dopamine, or
pheochromocytoma).
♦ Overdose of folic acid or vitamin B12 (these substances stimulate cell proliferation and their consumption of K +).
Effects
• Decreased neuromuscular excitability.
♦ Muscle weakness, even paralysis.
♦ Decreased motility (hypokinesia) of the stomach and intestines.
• ECG changes: lengthening of PQ and QT intervals, flattened or negative T wave.
• Drowsiness, apathy, decreased performance, asthenia.
• Intracellular acidosis caused by a decrease in [K +] in cells and the accumulation of excess H + in them.
• Dystrophic changes in organs and tissues. They are most pronounced in the heart, kidneys, liver, intestines.
Methods for eliminating hypokalemia
• Elimination of the cause of hypokalemia.
• The introduction of potassium salts. Potassium salts can contain any anions, but preference should be given to
potassium chloride, since, as a rule, hypochloremia is also detected in patients (it is necessary to periodically monitor
the level of potassium in the blood and evaluate the ECG parameters).
50. Describe the main forms of calcium metabolism disorders: types, etiology, metabolic disorders and
biological functions in them.
Disorders of calcium metabolism
In the body, calcium is found mainly in bones and teeth (in the form
of oxyapatite). In the blood plasma, the total calcium content is
normally 2.15-2.55 mmol / l.
HYPERCALCIEMIA
Hypercalcemia - an increase in the total calcium in the blood
plasma above the norm.
The reasons
• Excessive intake of calcium salts into the body.
♦ Parenteral administration (eg, CaC12 solution).
♦ Increased levels or effects of vitamin D (stimulating the
absorption of calcium in the small intestine).
• Decreased renal Ca2 + excretion.
♦ An increase in the content or effects of PTH (for
example, with hyperplasia or adenoma of the
parathyroid glands).
♦ Hypervitaminosis D.
♦ Decreased content or effects of calcitonin.
• Redistribution of calcium from tissues to blood.
♦ Acidosis, in which Ca2 + is removed from the bone tissue in exchange for H +.
♦ Prolonged limitation of motor activity and the effect of the
weightlessness factor (for example, when flying in space).
• Increased ionization of calcium (for example, under
conditions of acidosis, in which the proportion of Ca2 + in the
blood plasma increases with its normal total content).
• Malignant tumors are one of the most common causes of
hypercalcemia.
Manifestations and consequences
Pathological symptoms appear with hypercalcemia of more than 2.753 mmol / l.
♦ Hypercalciuria (as a consequence of hypercalcemia).
♦ Formation of calculi in the renal parenchyma
(nephrocalcinosis) and urinary tract. It is a direct result of
the excretion of excess Ca2 + by the kidneys.
♦ Osteoporosis - dystrophy of bone tissue with a decrease in its
density - is a consequence of decalcification of bones and their
resorption by osteoclasts. This phenomenon is referred to as
parathyroid osteodystrophy. It is often accompanied by pain in the
bones and their
fractures.
♦ Mental disorders are characterized by a decrease in the
efficiency of intellectual activity, emotional instability
and rapid fatigue.
♦ Muscle dysfunction: muscle hypotonia and decreased
neuromuscular excitability (up to paresis and paralysis).
♦ Gastrointestinal disorders in the form of anorexia, nausea,
vomiting, weakening of the peristalsis of the stomach and
intestines, constipation, abdominal pain, peptic ulcers are often
detected.
Methods for eliminating hypercalcemia
• Elimination of the cause of hypercalcemia.
• Removal of excess calcium from the body by intravenous
infusion of isotonic sodium chloride solution (up to 3-4 liters per
day) in combination with diuretics.
• Inhibition of bone resorption by osteoclasts using calcitonin
and estrogen preparations. These drugs simultaneously promote
bone tissue recalcification.
HYPOCALCIEMIA
Hypocalcemia - a decrease in the concentration of calcium in
the blood plasma below normal.
The reasons
♦ Hypoparathyroidism. With hypoparathyroidism, the release of
calcium from the bones is inhibited and its excretion by the
kidneys is stimulated.
♦ Hypovitaminosis D. At the same time, the absorption of
calcium in the intestine is significantly reduced.
♦ Hypersecretion of PTH antagonist calcitonin.
♦ Intestinal pathology (chronic enteritis, resection of small
intestine fragments, malabsorption syndromes).
♦ Aholia - the absence of bile in the intestines. Bile is
essential for the metabolism of fat-soluble vitamin D.
♦ Chronic uncompensated alkalosis (see chapter 13 "Violations of
acid-base balance").
♦ Hypomagnesemia. A decrease in the blood Mg2 + content inhibits
the secretion of PTH and also reduces the effects of this hormone
and vitamin D in bone tissue.
♦ Hypoalbuminemia. Is accompanied by a decrease in the level of general
blood plasma calcium due to its fraction associated with albumin.
Manifestations and consequences
• An increase in neuromuscular excitability is
characterized by a complex of signs.
♦ Tetanic cramps of various muscle groups. With a mild degree of
hypocalcemia, latent tetany is noted. It is revealed by the
development of muscle cramps in the hand ("obstetrician's hand")
when pressing on the muscles in the shoulder (Trousseau symptom)
or facial muscles with
tapping in the area of the passage of the branch of the facial
nerve (Khvostek's symptom).
♦ Feeling of numbness in certain parts of the body.
• Hypocoagulant and hemorrhagic syndromes. They are caused
by Ca2 + deficiency, which regulates the activity of a
number of hemocoagulation factors, as well as the
permeability of the vessel walls.
• Dystrophic changes in various tissues (derivatives of ectoderm)
are characterized by dental defects as a result of impaired
calcification of dentin and enamel; hypotrophy, unevenness and
brittleness of the nails; dry skin; brittle hair; calcification
of the lens with the development of cataracts.
• Heart failure and arterial hypotension (mainly due to a
decrease in cardiac output).
Methods for eliminating hypocalcemia
• Elimination of the cause of hypocalcemia. The most common cause
is hypoparathyroidism. To eliminate it, PTH replacement therapy is
performed.
• Elimination of acute hypocalcemia and associated tetany
attacks. This is achieved through intravenous administration of
calcium preparations (for example, calcium chloride solution).
• Elimination of chronic hypocalcemia. Provided by oral
administration of calcium preparations (for example, calcium
gluconate) and vitamin D into the body.
51. Describe the main forms of magnesium metabolism disorders: types, etiology, metabolic disorders
and biological functions in them.
Magnesium metabolism disorders
The body contains up to 25-30 g of magnesium. About 67% of it is
contained in bone tissue, about 31% is contained intracellularly (in
mainly in muscle cells). Magnesium is a cofactor in nearly 300 cellular enzymes. In
the blood plasma, the concentration of magnesium is normal
is 0.65-1.1 mmol / l.
HYPERMAGNESIUM
Hypermagnesemia - an increase in the concentration of magnesium in
the blood plasma is more than normal.
The reasons
• Reducing the excretion of magnesium from the body by the kidneys. It is
observed with impaired renal excretory function (with renal
failure).
• Excessive intake of magnesium into the body, for example, when:
♦ Taking high doses of drugs containing magnesium (for example, some
antacids, laxatives).
♦ Intravenous administration of solutions of magnesium salts to
women with pregnancy toxicosis.
• Redistribution of magnesium from cells into the intercellular fluid and
blood during acidosis, hypothyroidism.
The manifestations of hypermagnesemia are caused by inhibition of
neuromuscular transmission, a decrease in nervous and muscle
excitability. It leads to:
♦ Depression of GNI, up to loss of consciousness ("magnesium sleep"). This is
based on a violation of the transmembrane distribution of ions.
♦ Decrease in alveolar ventilation as a result of oppression of the neurons of
the respiratory center.
♦ Muscular hypotension, hypokinesia, sometimes paralysis.
♦ Arterial hypotension.
Methods for eliminating hypermagnesemia
• Elimination of the cause that led to an increase in the level of magnesium in the blood.
• Intravenous administration of isotonic solutions of sodium and calcium
salts (the latter is a functional magnesium antagonist).
• In case of a serious condition of the patient, hemodialysis is performed.
HYPOMAGNEMIA
Hypomagnesemia - a decrease in the concentration of Mg2 + in the blood
plasma below normal.
The reasons
• Insufficient intake of magnesium in the body under conditions:
♦ Magnesium deficiency in food.
♦ Malabsorption of magnesium compounds in the small intestine.
Develops with prolonged diarrhea, abuse
laxatives, malabsorption syndromes, acholia, chronic enteritis.
Increased excretion of magnesium from the body with:
♦ Primary defects of the kidney tubules (reabsorption of ions, including Mg2
+ suffers, the syndrome of renal tubular acidosis develops).
♦ Secondary suppression of the process of reabsorption of Mg2 + in the
tubules of the kidneys (for example, with hyperaldosteronism,
hypoparathyroidism,
excessive intake of loop diuretics, hypercalcemia,
hypophosphatemia).
• Redistribution of magnesium from blood to cells in respiratory alkalosis,
hyperinsulinemia, alcohol withdrawal, conditions after elimination of
hyperparathyroidism.
Manifestations
♦ Increased neuromuscular excitability. It is characterized by tremor,
muscle spasm of the hands and feet, motor excitement.
♦ Tachycardia and cardiac arrhythmias, increased blood pressure.
♦ Hypocalcemia is caused by suppression of PTH secretion in conditions of
low magnesium content in the body.
♦ Hypokalemia develops due to inhibition of K + reabsorption in the
kidneys.
♦ Trophic erosion and skin ulcers are caused by a decrease in the
activity of magnesium-containing enzymes, impaired metabolism of
carbohydrates and
proteins.
♦ Generalized calcification of tissues, especially of the walls of blood
vessels, kidneys and cartilage. This phenomenon is associated with
increased traffic
calcium in tissue in conditions of low concentration of magnesium in the
extracellular fluid.
♦ Impaired digestion of food in the intestines and the resulting
growth retardation and hypothermia, especially in children. Reasons: a decrease in
the activity of magnesium-containing enzymes involved in membrane digestion.
Methods for eliminating hypomagnesemia
• Elimination of the pathological condition that caused a decrease in the
level of magnesium in the blood.
• Introduction into the body of magnesium preparations (for
example, magnesium sulfate solution).
• Increasing the dietary intake of magnesium-rich foods (eg, beans, peas,
millet).
52. Give the definition and classification of fasting, periods, causes of fasting, changes in metabolism and
various physiological functions in different periods of fasting. Conditions affecting the duration of
fasting.
Fasting is a condition that occurs when the body does not receive nutrients at all, or receives them in insufficient quantities, or
does not absorb them due to illness.
Types and periods of fasting
Starvation - This is a condition that occurs in cases when the body does not receive nutrients at all,
receives them in insufficient quantities, or does not assimilate them due to illness.
Fasting in origin can be:
- physiological - it is repeated in some species of animals in connection with the special conditions of
their habitat or development (hibernation in marmots or ground squirrels, fish, reptiles;
- pathological.
Fasting is
distinguished:
a) complete, maybe without limitation of water and with limitation or without water at all absolute;
b) incomplete (quantitative malnutrition), when all nutrients enter the body, but in an
insufficient amount of calories.
c) partial (qualitative) in case of insufficient intake of one or more food components with food with
its normal energy value.
Complete starvation can have two reasons:
- external - lack of food;
- internal - malformations in children, diseases of the gastrointestinal tract, infectious processes,
anorexia.
In the development of fasting, its duration and, consequently, the life expectancy of the organism,
external (low ambient temperature, high humidity and air velocity, active movements) and internal
(gender, age, general condition of the body, the amount and quality of fat and protein reserves,
metabolic rate) conditions.
The maximum period for complete fasting for a person is 65 to 70 days.
By clinical manifestations complete fasting can be divided into 4 periods:
1) indifference;
2) excitement that grows as the feeling of hunger intensifies;
3) oppression (massive long-term);
4) paralysis and death.
By pathophysiological characteristics the state of metabolism and energy is taken into account:
1) wasteful expenditure of energy (2-4 days for a person);
2) maximum adaptation (40-50 days);
3) tissue decay, intoxication and death (terminal period 3-5 days). With complete
starvation, the following are characteristic:
- reuse of proteins for synthetic processes;
- transition to endogenous nutrition (activation of glycolytic and lipolytic enzymes);
- changes in the primary structure of fermets;
- heat production is maintained during the entire fast at a minimum level and decreases by
the end of the third period;
- heat transfer is somewhat reduced.
In general terms, the first period of fasting is characterized by:
- increased consumption of carbohydrates, in connection with which the respiratory coefficient
increases, approaching 1;
- the glucose level decreases below 3 mmol / l, which leads to a decrease in insulin, an increase
in the activity of a-cells and the release of glucagon, stimulation of the glycocorticoid function of
the adrenal cortex - an increase in protein catabolism and glyconeogenesis;
- decreased basal metabolism (suppression of thyroid function);
- a negative nitrogen balance develops:
- excitement of the nervous system, especially the food center;
- increased function of the thyroid gland, pituitary gland, increased secretion of corticotropin and
thyrotropin - stimulation of the adrenal glands.
In the second, longest period of fasting:
- the respiratory coefficient decreases to 0.7, which reflects the predominant oxidation of fats up
to 80%, proteins - 13% and glucose - 3%;
- activation of metabolism in adipose tissue (low insulin level - glucose delivery to lipocytes decreases
- lack of glycerol for triglycerides; the predominance of the action of glucagon and catecholamines activation of adenylate cyclase and increased lipolysis - free fatty acids enter the blood - lipemia; in
the liver and muscles the level of free fatty acids increases acids; in the liver, the synthesis of fatty
acids and lipogenesis is inhibited, but due to a deficiency
proteins and insufficient formation of lipoproteins, there is a delay of triglycerides in the liver and the
development of fatty infiltration);
- in the kidneys, glyconeogenesis is intensively going on;
- the excretion of ammonium salts in the urine increases - non-gaseous acidosis;
- negative nitrogen balance;
- oppression of the food center, reflexes are reduced;
- decrease in neurosecretion in the nuclei of the hypothalamus - suppression of the
endocrine glands. The third, terminal, fasting period is characterized by:
- a sharp increase in the breakdown of proteins of vital organs, which are consumed as an
energy material;
- the respiratory coefficient is 0.8;
- destructive changes in mitochondria;
- accumulation of chlorides and an increase in tissue osmotic concentration - water retention;
- violation of tissue trophism and a decrease in overall resistance - bedsores and necrosis, keratitis;
- disorder of enzyme systems - the difficulty of restoring enzyme proteins that are
destroyed during starvation.
Incomplete fasting is more common than complete fasting:
1) adaptive mechanisms develop;
2) the basal metabolic rate decreases more significantly by 30-35%;
3) body weight is slowly decreasing;
4) processes of a degenerative nature develop in the tissues;
5) edema develops;
6) bradycardia, hypotension, depression of sexual instinct.
Partial fasting
With a lack of carbohydrates in food, the main disorders are associated with an increase in
ketogenesis in the liver, where fats are transported due to its depletion in glycogen.
Insufficient intake of fats in the body in terms of energy can be replenished with carbohydrates and
proteins. However, to ensure plastic processes, it is necessary to introduce at least a minimum amount
of fat (5-6 g), which contains essential fatty acids - arachidonic, linoleic and linolenic. It should be
borne in mind that fat-soluble vitamins come with fats and therefore fat starvation is inseparable from
vitamin deficiency.
Proteinstarvation occurs in cases where the amount of protein supplied with food. Does not provide
nitrogen balance in the body. Prolonged malnutrition with a predominant lack of protein in food protein-calorie deficiency - can lead to alimentary dystrophy and kwashiocor. The observed violation of
the synthesis of hormones is expressed in various endocrinopathies. Deficiency of essential amino
acids and vitamins leads to the development of pellagra and beriberi. Basal metabolism decreases,
and edema develops.
Mineral starvation can be observed in pure form only under experimental conditions.
With water starvation, animals die faster than with complete starvation.
One of the forms of high-quality fasting is vitamin deficiency (vitamin deficiency and hypovitaminosis),
which can be exogenous or endogenous.
53. Give a description of the concept and describe the etiology of inflammation. Give the types and
mechanisms of alteration as a component of inflammation.
Inflammation - a typical pathological process aimed at
destruction, inactivation or elimination of the damaging agent and
restoration of damaged tissue.
Inflammation is a local process. However, almost all tissues, organs and
systems are involved in its occurrence, development and outcomes.
organism.
Etiology
Inflammation is the body's response to the effect of a cause - a phlogogenic
(from the Greek phlox, phlogos - flame) factor, acting under certain
conditions.
Inflammation causes
• The nature of the phlogogenic factor can be physical, chemical, or
biological.
♦ Physical factors: mechanical tissue injury, excessive
high or low temperature, electric shock or radiant energy.
♦ Chemical factors: organic and inorganic acids, alkalis and salts;
Drugs injected into tissues.
♦ Biological agents: infectious (viruses, rickettsia, bacteria, fungi);
immunoallergic (Ag-AT complexes; denatured proteins and dead tissue
areas; infected with a virus and
tumor cells); toxins of insects, animals, plants.
ALTERATION
Alteration (from Lat.alteratio - change, damage) as a component of the
mechanism of development of inflammation includes changes: cellular
and
extracellular structures, metabolism, physical and chemical properties, as
well as the formation and implementation of the effects of inflammatory
mediators.
At the same time, zones of primary and secondary alteration are distinguished.
• Primary alteration is realized due to the action of the pathogenic
agent in the zone of its introduction, which is accompanied by rough,
often
irreversible changes.
• Secondary the alteration is caused by both the pathogenic agent and, in
mainly products of the primary alteration. Later, the secondary
alteration takes on a relatively independent character.
The volume of the zone of secondary damage is always larger than that of
the primary one, and the duration can vary from several hours to several
years.
• Carbohydrates
♦ Glycogenolysis and glycolysis are activated, providing an increase in the
production of high-energy compounds.
♦ Glycolysis under conditions of hypoxia in the focus of inflammation goes to
anaerobic pathway, resulting in the accumulation of excess lactate and
pyruvate, which form metabolic acidosis.
♦ The resumption of tissue oxygenation, as a rule, is accompanied by
the normalization of the energy supply of cellular processes.
• Lipids
♦ Lipolysis is enhanced (it is accompanied by the accumulation of free
HFA) and lipid destruction due to the intensification of SPOL reactions
(with the formation of lipid peroxides and hydroperoxides, keto acids).
♦ Accumulation of excess keto acids (acetoacetic, β-hydroxybutyric, βketoglutaric, and others) due to impaired oxidation of the IVA
causes acidosis and secondary alteration in the focus of inflammation.
• Protein
♦ Proteolysis is activated, the products of which serve as a substrate
for the synthesis of cellular components instead of damaged ones.
♦ Immune (including immunopathological) reactions develop (in connection
with the denaturation of proteins of both their own dead cells and the
phlogogenic agent). The inclusion of cellular and humoral mechanisms of
immunity ensures the detection, destruction and elimination of antigenically
foreign structures.
• Ions and water
♦ The energy supply of the selective transfer of cations is disturbed and the
activity of cation-dependent membrane ATPases (α +, K + -ATPase, Ca2 +
Mg2 + -ATPase) decreases. It causes a violation
the formation of MP and PD, the development of persistent
depolarization of the membranes of excitable cells (for example,
cardiomyocytes and neurons).
54
♦ The extra- and intracellular relationship between individual ions is
violated. There is a loss of K +, Mg2 + by the cell and their accumulation
in
intercellular fluid. Na + and Ca2 + enter the cell.
♦ An additional amount of cations is released (K +, Na +, Ca2 +
,
iron, zinc) during the hydrolysis of salts and the intake of large amounts of
Ca2 + from damaged intracellular depots (mitochondria and cisterns of the
endoplasmic reticulum).
♦ Osmotic pressure inside cells and their organelles increases significantly,
which is accompanied by overstretching and rupture of them.
membranes.
Physicochemical changes
• Metabolic acidosis at the site of inflammation is due to
accumulation of an excess of various acids: lactic, pyruvic, amino acids, HFA and CT.
♦ Development mechanisms: violation of removal from the focus of inflammation
formed in large quantities of acidic metabolic products. This causes
depletion of the buffer systems (bicarbonate, phosphate, protein) of cells
and extracellular fluid.
♦ Effects:
? Increased permeability of membranes, including lysosomes, which
leads to the release of hydrolases into the cytosol and intercellular substance.
? Increasing the permeability of the walls of blood vessels by strengthening
non-enzymatic and enzymatic hydrolysis of extracellular matrix
components, including basement membranes.
? Formation of a sensation of pain in the focus of inflammation due to
irritation and damage to sensitive nerve endings in conditions of excess H +
...
? Changes in the sensitivity of cell receptors (including the walls of blood
vessels) to regulatory factors (neurotransmitters, hormones,
mediators of inflammation), which is accompanied by a dysregulation
vascular wall tone.
• Hyperosmia - increased osmotic pressure in the region
inflammation. It is caused by the accumulation of a large number of
ions and low molecular weight compounds.
♦ Development mechanisms: increased enzymatic and
non-enzymatic destruction of macromolecules, enhanced hydrolysis of salts
and release of osmotically active compounds from damaged cells under
conditions of acidosis.
♦ Consequences: hyperhydration of the inflammation focus,
stimulation of the emigration of leukocytes, changes in the tone of
the walls of blood vessels, the formation of a feeling of pain.
• Hyperonkia - increased oncotic pressure in the tissue during
inflammation.
♦ Development mechanisms: an increase in the concentration of protein in the focus
inflammation due to increased enzymatic and non-enzymatic hydrolysis of
peptides and the release of proteins (mainly albumin) from the blood into
the inflammation focus due to an increase in the permeability of the
vascular wall.
♦ Consequences: the development of edema in the focus of inflammation.
• Change in the surface charge of cells (usually a decrease).
It is caused by a violation of the water-electrolyte balance in
the inflamed tissue.
♦ Development mechanisms: violation of energy supply of
transmembrane ion transport and the development of electrolyte
imbalance.
♦ Consequences: a change in the threshold of cell excitability,
potentiation of phagocyte migration due to electrokinesis; stimulation of cell
cooperation due to a decrease in the value of negative
their surface charge, neutralizing it or even recharging.
• Changes in the colloidal state of the intercellular substance and
hyaloplasm of cells in the focus of inflammation...
♦ Development mechanisms:
? Enzymatic and non-enzymatic hydrolysis of macromolecules
(glycosaminoglycans, proteins, proteoglycans).
? Phase changes in microfilaments, facilitating the transition of their
state from gel to sol and vice versa.
♦ Consequences (main): increased tissue permeability.
• Reducing the surface tension of cell
membranes. It is caused by changes in the structure of plasmolemma molecules.
♦ Development mechanisms: exposure of cell membranes to a
significant amount of surfactants (phospholipids, IVH, K +
, Ca2 +).
♦ Consequences: facilitating cell motility and potentiating cell
adhesion during phagocytosis.
54. Describe the change in metabolism and physical and chemical properties in the focus of inflammation.
Describe the main cellular mediators of inflammation, the processes of their release and activation,
their origin and significance in the dynamics of the development and completion of inflammation.
Physicochemical changes
• Metabolic acidosis at the site of inflammation is due to
accumulation of an excess of various acids: lactic, pyruvic, amino acids, HFA
and CT.
♦ Mechanisms of development: impaired removal from the focus of
inflammation of the acidic metabolic products formed in large quantities.
This causes depletion of the buffer systems (bicarbonate, phosphate,
protein) of cells and extracellular fluid.
♦ Effects:
? Increased permeability of membranes, including lysosomes, which
leads to the release of hydrolases into the cytosol and intercellular substance.
? Increasing the permeability of the walls of blood vessels by strengthening
non-enzymatic and enzymatic hydrolysis of extracellular matrix
components, including basement membranes.
? Formation of a sensation of pain in the focus of inflammation due to
irritation and damage to sensitive nerve endings in conditions of excess H
+
...
? Changes in the sensitivity of cell receptors (including the walls of blood
vessels) to regulatory factors (neurotransmitters, hormones,
mediators of inflammation), which is accompanied by a disorder in the
regulation of the tone of the vascular wall.
• Hyperosmia - increased osmotic pressure in the region
inflammation. It is caused by the accumulation of a large number of ions
and low molecular weight compounds.
♦ Development mechanisms: increased enzymatic and
non-enzymatic destruction of macromolecules, enhanced hydrolysis of salts
and release of osmotically active compounds from damaged cells under
conditions of acidosis.
♦ Consequences: hyperhydration of the inflammation focus,
stimulation of the emigration of leukocytes, changes in the tone of
the walls of blood vessels, the formation of a feeling of pain.
• Hyperonchia - increased oncotic pressure in the tissue during
inflammation.
♦ Development mechanisms: an increase in the concentration of protein in the focus
inflammation due to increased enzymatic and non-enzymatic hydrolysis of
peptides and the release of proteins (mainly albumin) from the blood into
the inflammation focus due to an increase in the permeability of the vascular
wall.
♦ Consequences: the development of edema in the focus of inflammation.
• Changes in the surface charge of cells (usually a decrease).
It is caused by a violation of the water-electrolyte balance in
the inflamed tissue.
♦ Development mechanisms: violation of energy supply of
transmembrane ion transport and the development of electrolyte
imbalance.
♦ Consequences: a change in the threshold of cell excitability,
potentiation of phagocyte migration due to electrokinesis; stimulation of cell
cooperation due to a decrease in the value of negative
their surface charge, neutralizing it or even recharging.
• Changes in the colloidal state of the intercellular substance and
the hyaloplasm of cells in the focus of inflammation.
♦ Development mechanisms:
? Enzymatic and non-enzymatic hydrolysis of macromolecules
(glycosaminoglycans, proteins, proteoglycans).
? Phase changes in microfilaments, facilitating the transition of their
state from gel to sol and vice versa.
♦ Consequences (main): increased tissue permeability.
• Reducing the surface tension of cell
membranes. It is caused by changes in the structure of plasmolemma molecules.
♦ Development mechanisms: exposure of cell membranes to a
significant amount of surfactants (phospholipids, IVH, K +
, Ca2 +).
♦ Consequences: facilitating cell motility and potentiating cell
adhesion during phagocytosis.
Inflammatory mediators
Inflammation mediators are biologically active substances, under the
influence of which the regular development and outcomes of
inflammation are carried out, its local and general signs are formed.
There are two groups of inflammatory mediators: cellular and
plasma.
Cellular mediators of inflammation
The main groups of cellular mediators of inflammation include:
biogenic amines, peptides and proteins, nitric oxide, derivatives of fatty
acids and lipids, nucleotides and nucleosides. Their sources are mast cells,
neutrophilic and basophilic granulocytes, platelets and a number of other
cells in the focus of inflammation.
• Biogenic amines. The most important representatives are
histamine and serotonin.
♦ Histamine, acting on the H2 receptors of target cells, causes dilatation
of the vessels of the microvasculature and increases
permeability of venules, which promotes exudation. Interacting with H1
receptors, histamine causes: sensations of pain, burning, itching, tension.
♦ Serotonin also increases vascular permeability and activates the
contraction of the SMC venules (which contributes to the development of
venous
hyperemia), leads to the formation of a feeling of pain, stimulates
thrombus formation.
• Peptides and proteins
♦ Neuropeptides. Of the neuropeptides in inflammation, the most
significant role is played by P.
♦ Cytokines regulate proliferative activity,
differentiation and phenotype of target cells. Cytokines include growth
factors, interleukins (IL), tumor necrosis factor
(TNF), colony stimulating factors, interferons (IFN) and chemokines.
The general modern term for the entire class is cytokines, the obsolete
names of the subclasses: lymphokines and monokines.
♦ Leukokines - the general name for various biologically active substances
(BAS) formed by leukocytes, but not related to
immunoglobulins (Ig) and cytokines. The group of leukokines includes
acute phase proteins, cationic proteins, and fibronectin.
♦ Enzymes. In the focus of inflammation, enzymes of all major groups
are found. Their main source is neutrophils and other phagocytes. At
the onset of inflammation, enzymes cause
loosening of the connective tissue couplings around the vessels and
destruction of the intercellular substance of the vascular walls, contributing
to
vasodilation and increased vascular permeability. In later
stages of inflammation thanks to enzymes, the focus of inflammation is
cleared from dead cells and tissues, and is also implemented
proliferative processes.
• Nitric oxide (endothelium-released vasodilation factor) is an important
mediator of inflammation.
• Lipid mediators of inflammation
♦ Derivatives of arachidonic acid are prostaglandins, thromboxanes and
leukotrienes. Arachidonic acid is part of the phospholipids of cell
membranes, from where it is released under the influence of
phospholipases. Further transformations of this acid
occur either by cyclooxygenase (with the formation
prostaglandins and thromboxanes), or via the lipoxygenase pathway (with
the formation of leukotrienes).
? Prostaglandins have a wide spectrum of action, including
damage the walls of the vessels of the microvasculature and increase their
permeability, enhance chemotaxis and promote the proliferation of
fibroblasts. PG reduce the pain threshold and
contribute to the development of fever.
? Thromboxanes cause vasoconstriction, promote blood cell aggregation,
and stimulate thrombus formation.
? Leukotrienes cause spasm of the SMC of the walls of blood vessels,
bronchioles and intestines (the duration of the effect of leukotrienes
is very long),
exhibit a positive chemotactic effect on phagocytes and increase
membrane permeability.
♦ Platelet activating factor is formed from membrane phospholipids
and is the most potent vasoconstrictor.
♦ Lipoperoxides are SPOL products. They destabilize the membranes of
lysosomes, promoting the release of enzymes from them, and determine
the effectiveness of the final stages of phagocytosis.
• Nucleotides and nucleosides
♦ ATP provides energy "support" for cells and plastic processes in them in
the focus of inflammation.
♦ ADP stimulates adhesion, aggregation and agglutination of blood cells.
This causes thrombus formation, sludge formation, disruption of blood and
lymph flow in the vessels of the microvasculature.
♦ Adenosine, released from cells, has a significant vasodilator effect with
the development of arterial hyperemia.
55. Describe the main plasma inflammatory mediators, the processes of their release and activation, their
origin and significance in the dynamics of the development and completion of inflammation.
Plasma mediators of inflammation
Plasma mediators of inflammation, like cellular mediators, are
produced by cells and released by them in an inactive state. They
appear when three blood systems are activated kinin, complement and hemostasis. All components of these systems are
found in the blood as precursors and become active after exposure to
cellular mediators of inflammation.
• Kinin system mediators. Bradykinin and kallikrein are of primary
importance in inflammation.
♦ Bradykinin enhances vascular permeability, causes a feeling of pain,
has a pronounced hypotensive effect.
♦ Kallikrein causes chemotaxis of leukocytes, but its main role is
the activation of the Hageman factor.
• Mediators of the hemostatic system: coagulation factors,
anticoagulant and fibrinolytic systems. The Hageman factor is activated
first. It initiates the coagulation of blood proteins, increases the
permeability of the walls of blood vessels, enhances the migration of
neutrophils and platelet aggregation.
• The complement system consists of a group of specialized proteins in
blood plasma that cause lysis of bacteria and cells. Moreover,
some complement components, most notably C3b and C5b,
increase the permeability of the walls of blood vessels, enhance the
chemotactic activity of neutrophils and macrophages.
Inflammatory anti-mediators. At all stages of the development of
inflammation, substances are formed and act to prevent excessive
accumulation or stop the action of mediators, which together can be
combined into a system of anti-mediators
inflammation. Enzymes are the most important anti-mediators. Thus,
histaminase destroys histamine, carboxypeptidases - kinins, esterases complement fractions, prostaglandine dehydrogenase - Pg.
Humoral influences are of great importance. So, one of the types of
antitrypsin formed in hepatocytes inhibits a number of proteases,
involved in inflammation, which inhibits the formation of kinins.
Glucocorticoids weaken vascular responses by stabilizing
vascular membranes, reduce exudation and emigration of leukocytes, and
also weaken phagocytosis. Due to the presence of anti-mediators,
inflammation stops after elimination or inactivation of the
damaging agent and repair of damaged tissues.
56. Describe vascular reactions at the site of inflammation, their stages and mechanisms.
This component of inflammation includes the following processes:
♦ changes in the tone of the walls and lumen of blood vessels;
♦ violation of hemo- and lymphodynamics;
♦ change in the rheological properties of blood;
♦ increased vascular permeability;
♦ the actual process of fluid exudation from microvessels;
♦ migration to the focus of inflammation of leukocytes and phagocytosis,
release of platelets and erythrocytes into the tissue.
Changes in the tone of the walls and lumen of blood vessels.
Regional hemodynamic disorders
The lumen of blood vessels, blood and lymph circulation in the focus
of inflammation change from the moment of onset and throughout
the entire process
inflammation. Moreover, in different parts of it and at different stages, it
usually has a different character.
♦ Ischemia is the result of muscle spasm of arterioles and
precapillaries due to reflex (in response to pain) discharge
neurotransmitters (norepinephrine). External manifestations: pallor, a
slight decrease in the volume and temperature of tissues.
Duration - from several seconds to several minutes, since norepinephrine is
rapidly broken down by enzymatic systems.
♦ Arterial hyperemia due to a decrease in the tone of the muscles of
the walls and the expansion of arterioles under the influence of
mediators
inflammation. The increase in blood supply is an important defense
mechanism and contributes to the energy supply of inflammation. External
manifestations: redness, increased turgor,
a slight increase in the volume and temperature of tissues.
♦ Venous hyperemia due to a violation of the outflow of blood. This is
facilitated by the compression of the venules and capillaries of the
edematous perivasculary tissue, swelling of the endothelium and changes in the
rheological properties of blood. Venous hyperemia increases
hydrostatic pressure in the vessels of the microvasculature and
filtration of the liquid part of the blood in the tissue, and therefore aggravation of edema.
♦ Stasis - temporary cessation of the flow of blood and lymph in the
vessels of the microvasculature. It develops as a result of significant
compression of venules by edematous tissue and the development of a
sludge phenomenon in them.
♦ The normalization of regional blood flow occurs as the
inflammation ends.
Change in the rheological properties of blood. In the vessels of the
inflamed tissue, blood thickens, the marginal standing of leukocytes,
the formation of sludge and cell aggregates, which reduces blood flow and promotes
thrombosis of small vessels.
Increased vascular and tissue permeability
The determining factor of fluid exudation outside the vessels during
inflammation is an increase in the permeability of the vascular wall, with
what is the reason for the formation of exudate. Inflammatory mediators
have a major influence on the permeability of the vascular wall.
Enhancement
vascular permeability promotes interendothelial and transendothelial
plasma transport and the release of blood cells from the vessels.
♦ Interendothelial fissures are formed due to the reduction of
actomyosin in endothelial cells and changes in the structure of the
cytoskeleton in them.
♦ Transendothelial transport is carried out using vesicles and
microchannels.
The increase in tissue permeability is also due to changes in the colloidal
state of the intercellular substance.
Give the classification of exudates, their properties. Describe the mechanisms of exudation during
inflammation.
57.
Exudation (from lat.exsudatum - to sweat, to sweat) - exit process
plasma and blood cells from the vessels of the microvasculature into the
tissues and body cavities with the formation of exudate.
Exudate is a fluid that forms during inflammation and contains
a large amount of protein and blood cells (mainly leukocytes).
A non-inflammatory transudate fluid can also form in the body. It differs
from the exudate in its low content of protein, leukocytes and other blood
cells.
Causes of exudation
• The main cause of plasmorrhage (passive release of blood plasma into
the interstitium) is an increase in vascular permeability and an increase in
hydrostatic blood pressure in the vessels of the microvasculature.
• The main cause of leukocyte tissue infiltration is chemo- and
electrotaxis of leukocytes.
Types of exudate. There are several types of exudate: serous,
fibrinous, purulent, putrid, hemorrhagic and catarrhal. The type of
exudate determines the name of the form of acute exudative
inflammation.
Exudation value. In the focus of inflammation, the exudation process has
a double biological significance: adaptive and pathogenic.
• The adaptive value lies in fixing the phlogogen in the inflammation
focus and creating optimal conditions for its inactivation and
elimination.
• Pathogenic value:
♦ compression and displacement of organs and tissues by exudate;
♦ the spread of the inflammatory process to neighboring tissues or
biological fluids (into lymph, blood, cerebrospinal fluid, etc.) is possible;
♦ the formation of foci of tissue destruction with purulent inflammation.
The mechanism of exudation includes 3 main factors:
1. increased permeability
vessels
(venul
capillaries)in
the
impactmediators inflammation and in some cases the inflammatory agent itself;
and
result
2. increase blood (filtration) pressure in the vessels of the focus of inflammation due to hyperemia;
3. increase osmotic and oncotic pressure in inflamed tissue as a result alterations and the onset of exudation
and, possibly, a decrease in oncotic blood pressure due to loss proteins with abundant exudation.
The maintained dynamic balance between these mechanisms is ensured by the fact that the suction capacity
pleura in a healthy person, it is almost 3 times higher secreting ability, so in pleural cavity contains only a
small amount of liquid.
The leading factor of exudation is an increase in vascular permeability. It is usually biphasic and includes
immediate and delayed phases. The first occurs following the action of the inflammatory agent, reaches a
maximum within a few minutes and is completed on average within 15-30 minutes. The second phase develops
gradually, reaches a maximum after 4-6 hours and sometimes lasts up to 100 hours, depending on the type and
intensity of inflammation. Consequently, the exudative phase of inflammation begins immediately and lasts
more than 4 days.
58. Describe the mechanisms of leukocyte emigration. Describe phagocytosis, its stages and
mechanisms in inflammation
Emigration of leukocytes
Emigration of leukocytes - active process of their exit from the lumen
vessels of the microvasculature into the intercellular space. 1-2 hours
after the effect of the phlogogenic factor on the tissue, a large number of
emigrants are found in the inflammation focus.
neutrophils and other granulocytes, later - after 15-20 hours or more
- monocytes, and then lymphocytes.
The process of emigration sequentially goes through the stages of rolling
(marginal standing - "rolling") of leukocytes, their adhesion to the
endothelium and penetration through the vascular wall, as well as
directed movement of leukocytes in the focus of inflammation (Fig. 5-1).
Functions of leukocytes in inflammation
• Phagocytosis.
• Synthesis and release of inflammatory mediators.
• Antigen presentation to lymphocytes. This function of phagocytes
is realized through processing (absorption and transformation
antigenic structures) and presentation of Ar to cells of the immune
system (transfer of information about Ar to lymphocytes).
Later, a significant part of the leukocytes that migrated to the focus
inflammation, undergoes dystrophic changes and turns into "purulent
bodies" or undergoes apoptosis. Part of leukocytes,
having fulfilled its functions, it returns to the vascular bed and
circulates in the blood.
With a significant increase in the permeability of the vascular walls of
the microvasculature, erythrocytes and platelets also passively enter
the inflammation focus.
PHAGOCYTOSIS
Phagocytosis (Greek phagein - to eat, devour + Greek kytos - cell +
Greek osis - process, state) is an active biological process, consisting in
recognition, absorption and intracellular
destruction of foreign material by specialized cells - phagocytes:
microphages (polymorphonuclear leukocytes) and
macrophages.
In the course of phagocytosis, several main stages are distinguished (Fig. 5-2). Fig. 5-2. Phagocytosis stages: 1 particle adhesion (e.g. bacteria)
using the Fc receptor of the phagocyte membrane; 2 - immersion of
the adhered particle into a phagocyte and the formation of a
phagosome; 3 approximation and attachment to the phagosome of lysosomes; 4 - fusion of
membranes of phagosome and lysosomes with the formation of
phagolysosome; 5 - destruction
absorbed particle. [by 4].
• The phagocyte's recognition of the absorption object and adhesion
to it occurs in several stages:
♦ Detection of surface determinants of the phagocytosis object.
♦ Opsonization of the phagocytosis object.
♦ Phagocyte adhesion to the phagocytosis object. This process is realized
with the participation of leukocyte receptors FcyR (if the object has
the corresponding ligand) and adhesion molecules (in the absence of a
ligand, for example, in non-cellular particles).
• Absorption of an object by a phagocyte, followed by the formation of a
phagolysosome. The absorbed material is immersed in the cell as part of
the phagosome - a bubble formed by the plasma membrane. Lysosomes,
phagosome and lysosome membranes approach the phagosome
merge, and a phagolysosome is formed.
• Intracellular destruction of the phagocytosis object is realized in
as a result of activation of two complex mechanisms: oxygen-dependent
and oxygen-independent cytotoxicity of phagocytes.
♦ Oxygen-dependent cytotoxicity plays a leading role in
destruction of the object of phagocytosis. It is associated with a
significant increase in the intensity of metabolism with the
participation of oxygen (respiratory burst).
♦ Oxygen-independent mechanisms are due to the action of
lysosomal enzymes of the phagocyte.
Incomplete phagocytosis. With incomplete phagocytosis
microorganisms absorbed by phagocytes are not destroyed. it
promotes the persistence and spread of infection in the body. Causes of
incomplete phagocytosis:
• Membranopathy and fermentopathy of phagocyte lysosomes.
• Increased resistance of microbes to phagocyte enzymes.
• The ability of some microbes to quickly leave phagosomes and
persist in the cytoplasm of a phagocyte (rickettsia, chlamydia).
• Insufficient effect of hormones - regulators of the phagocytosis process.
59. Give the concept of the pathophysiological mechanisms of
PROLIFERATION
Proliferation is an important component of the development mechanism
the inflammatory process and its final stage - characterized by an increase
in the number of stromal and parenchymal cells, as well as
the formation of intercellular substance in the focus of inflammation. These
processes are aimed at regenerating or replacing destroyed tissue
elements.
♦ With a favorable course of inflammation, complete tissue
regeneration is observed - replenishment of its dead and restoration
of reversibly damaged structural elements (restitution).
♦ With significant destruction of a tissue site or organ at the site of a
defect in parenchymal cells, granulation tissue is formed first, and as it
matures, a scar, i.e. incomplete regeneration is observed.
proliferation, its stimulants and inhibitors.
The intensity of proliferation is regulated stimulants and inhibitorsthat can be produced far from
the reacting cells (for example, hormones), and inside them.
Continuous proliferation occurs in the early embryogenesis and as differentiation progresses, the periods
between divisions lengthen.
60.
Describe the pathogenesis of local signs of inflammation, types of inflammation, their classification.
SIGNS OF ACUTE INFLAMMATION
Signs of acute inflammation are divided into local and general
(systemic).
• Local signs of acute inflammation. In the focus of acute inflammation
there are: ❖ redness - rubor; ❖ swelling - tumor;
♦ pain - dolor; ❖ fever (increased temperature at the site of inflammation)
- calor; ❖ dysfunction - functio laesa.
Local
Rubor. Causes of redness (Latin rubor):
1.
2.
arterial hyperemia;
an increase in the number and expansion of arterioles and precapillaries;
3.
4.
an increase in the number of functioning capillaries filled with arterial blood;
"Arterialization" of venous blood due to an increase in the content of HbO2 in the venous blood.
Tumor. Causes of swelling (lat.tumor):
1.
2.
3.
4.
an increase in tissue blood filling as a result of the development of arterial and venous hyperemia;
an increase in lymph formation (due to arterial hyperemia);
development of tissue edema;
proliferation in the focus of inflammation.
General
Dolor. Causes of pain (Latin dolor):
1.
2.
3.
effect on the receptors of inflammatory mediators (histamine, serotonin, kinins, some Pg);
high concentration of H +, metabolites (lactate, pyruvate, etc.);
deformation of the tissue with the accumulation of inflammatory exudate in it.
Calor. The reasons for the rise in temperature (lat.calor) in the inflammation zone:
1.
2.
3.
the development of arterial hyperemia, accompanied by an increase in the flow of warmer blood;
an increase in the intensity of metabolism, which is combined with an increase in the release of thermal
energy;
separation of the processes of oxidation and phosphorylation, due to the accumulation of excess IVF, Ca2 +
and other agents in the focus of inflammation.
Functio laesa. Reasons for dysfunction (lat.functio laesa) of an organ or tissue:
1.
2.
61.
the damaging effect of the phlogogenic factor;
development in response to this of alternative processes, vascular reactions and exudation; often, the
dysfunction is limited only to that organ or tissue where inflammation develops, but the vital activity of the body
as a whole can be disrupted, especially if the inflammatory process affects organs such as the brain, heart,
liver, endocrine glands, kidneys.
Describe the pathogenesis of common signs of inflammation, types of inflammation, their classification.
General manifestations of inflammation are due to influences from the focus of the process, mainly
by inflammatory mediators.
Fever is the result of the effect of endogenous pyrogens, in particular IL-1, released by activated
leukocytes of the inflammatory focus and peripheral blood, on the center of thermoregulation.
Accelerated metabolism is a consequence of increased secretion of catabolic hormones, in particular under
the influence of monokines, and can also be secondary to fever. At the same time, an increased content of
glucose, globulins, and residual nitrogen is noted in the blood.
Increased ESR reflects the absolute or relative predominance in the plasma of globulins over albumin,
which occurs due to increased production by hepatocytes under the influence of monokines "acute phase
proteins" or outstripping the loss of albumin during exudation.
The predominance of coarse proteins in plasma reduces the negative charge of erythrocytes and,
accordingly, their mutual repulsion. This increases the agglutination of red blood cells and, therefore, their
sedimentation.
Changes in immune properties organism, manifested, in particular, by increased resistance to
repeated exposure to phlogogen, especially infectious, due to the formation of cellular and humoral
immunity during inflammation. In this, lymphoid cells of the focus of inflammation play an important role,
for example, B-lymphocytes, which turn into plasma cells - producers of antibodies. Inflammation forms
the body's immunological reactivity (“immunity through disease”).
Blood system reactions in case of inflammation, they include the emigration of leukocytes into the focus
and a number of changes from the hematopoietic tissue and peripheral blood:
1) an initial transient decrease in the number of circulating leukocytes in the blood (transient leukopenia),
due to their margination and emigration;
2) a decrease in the number of mature and immature granulocytes and monocytes in the bone marrow as
a result of their increased leaching into the blood, which is provided by reflex and, possibly, humoral
acceleration of blood flow in the bone marrow. When the number of leukocytes in the blood coming from
the bone marrow,
exceeds the number of those who emigrated to the focus of inflammation, leukocytosis develops;
3) subsequent restoration of the number of immature and mature granulocytes and monocytes in the
bone marrow, indicating the activation of hematopoiesis;
4) an increase (against the initial) in the total number of myelokaryocytes and cells of individual
hematopoietic germs in the bone marrow, which indicates the development of its hyperplasia. All this
ensures the development and long-term maintenance of leukocyte infiltration of the inflammation focus.
Activation of hematopoiesis in inflammation, it is due to the increased production of hematopoietic
substances by stimulated leukocytes of the inflammation focus and blood - colony-stimulating factors,
interleukins, etc., which are the initiating link in the mechanism of self-maintenance of leukocyte infiltration
of the inflammation focus. In the self-regulation of infiltration, lysosomal enzymes, reactive oxygen species,
and eicosanoids are essential.
Acute inflammation is characterized by neutrophilic leukocytosis with a shift to the left (an increase in
the number of younger, stab and juvenile neutrophils as a result of the involvement of the bone marrow
reserve and activation of hematopoiesis), as well as monocytosis, for chronic inflammation
- monocytic leukocytosis and lymphocytosis.
In the occurrence of general phenomena in inflammation, humoral and reflex influences from the focus
are important. This is evidenced, for example, by an increase in the Holtz reflex in a frog (a decrease in
heart rate with light tapping on the abdomen) with inflammation of the abdominal organs.
Describe chronic inflammation and its general patterns of development. Explain the role of reactivity in
the development of inflammation, outcomes, biological significance of inflammation.
62.
Chronic inflammation
Chronic inflammation can be primary or secondary.
• If the inflammation after the acute period becomes protracted, then
it is designated as "secondary chronic".
• If the inflammation initially has a persistent (sluggish and
prolonged) course, it is called "primary chronic".
Chronic inflammation manifestations... Chronic inflammation is
characterized by a number of signs: the development of granulomas, the
formation of capsules, necrosis, tissue infiltration by monocytes and
lymphocytes. Activation of macrophages by immune and non-immune
factors
causes additional tissue damage and the development of fibrosis. In
chronic inflammation, the proliferation process often predominates,
and this inflammation is called
proliferative. The causes of chronic
inflammation are manifold:
• Various forms of phagocytic insufficiency.
• Prolonged stress and other conditions, accompanied by an increased
concentration of catecholamines and glucocorticoids in the blood. These
groups of hormones suppress the processes of proliferation, maturation of
phagocytes, potentiate their destruction.
• Interaction of lymphocytes and macrophages infiltrating tissues in
excess in chronic inflammation, with the release of a large number of
damaging mediators
• Repeated damage to tissue or organ (for example, lungs by dust
components), accompanied by the formation of foreign Ag and the
development of immunopathological reactions.
• Features of microorganisms (resistance to the action of factors of the
system of immunobiological surveillance of the body, mimicry, the
formation of L-forms).
OUTCOMES OF INFLAMMATION
The outcome of inflammation depends on its type and course, localization and prevalence. The
following outcomes of inflammation are possible:
1. Almost complete restoration of structure and function (return to normal
- restitutio ad integrum) It is observed with minor damage, when specific tissue elements are
restored.
2. Scar formation (return to normal with incomplete recovery). It is observed with a significant defect at
the site of inflammation and its replacement with connective tissue. A scar may not affect the functions or
lead to functional dysfunctions as a result of: a) deformation of an organ or tissue (for example, scar
changes in the heart valves); b) displacement of organs (for example, lungs as a result of the formation of
adhesions in the chest cavity in the outcome of pleurisy).
3. Organ death and the whole organism - with necrotic inflammation.
4. The death of an organism with a certain localization of inflammation - for example, from suffocation due
to the formation of diphtheria films on the mucous membrane of the larynx. Localization of inflammation in
vital organs is threatening.
5. Development of complications inflammatory process: a) the flow of exudate into the body cavity with
the development, for example, of peritonitis in inflammatory processes in the abdominal organs; b) the
formation of pus with the development of abscess, phlegmon, empyema, pyemia; c) sclerosis or cirrhosis
of an organ as a result of diffuse proliferation of connective tissue in proliferative inflammation.
6. The transition from acute to chronic inflammation.
In the clinical outcome of inflammation, the underlying disease is of great importance, if the
occurrence of a focus (foci) of inflammation is associated with it.
THE IMPORTANCE OF INFLAMMATION FOR THE BODY
In general biological terms, inflammation is an important protective and adaptive
reaction, formed in the process of evolution as a way to preserve the whole organism at the cost of
damaging its part. This is a way of emergency protection of the body, used in the case when the body could
not cope with a harmful agent by its physiological elimination and damage has occurred. Inflammation is a
kind of biological and mechanical barrier, with the help of which the localization and elimination of
phlogogen and (or) the tissue damaged by it and its restoration or compensation of the tissue defect are
provided. Biological barrier properties are achieved
by adhesion, killing and lysis of bacteria, degradation of damaged tissue. The function of a mechanical
barrier is carried out due to the loss of fibrin, clotting of lymph in the focus, blockade of blood and
lymphatic vessels, proliferation of connective tissue cells at the border of damaged and normal tissue
(demarcation). All this prevents the absorption and spread of microbes, toxins, products of impaired
metabolism and decay.
63. Describe the concept of fever. Give the classification of fever.
Describe pathogenesis of changes in heat balance in fever.
Fever - a typical pathological process characterized by a temporary increase
in body temperature due to the dynamic restructuring of the thermoregulation
system under the influence of pyrogens.
ETIOLOGY
The fever is caused by pyrogen. Primary and secondary pyrogens are isolated
according to the source of occurrence and the mechanism of action.
Primary pyrogens
Primary pyrogens themselves do not affect the thermoregulatory center, but
cause the expression of genes encoding the synthesis of cytokines
(pyrogenic leukokines).
By origin, infectious and non-infectious primary pyrogens are
distinguished.
• Infectious pyrogens are the most common cause of fever. Infectious
pyrogens include lipopolysaccharides, lipoteichoic acid, and
exotoxins acting as superantigens.
♦ Lipopolysaccharides (LPS, endotoxins) have the highest pyrogenicity. LPS is
part of the membranes of microorganisms, mainly gram-negative. The
pyrogenic effect is characteristic of lipid A, which is part of the LPS.
♦ Lipoteichoic acid. Gram-positive microbes contain lipoteichoic acid and
pyrogenic peptidoglycans.
• By structure, pyrogens of non-infectious origin are more often proteins,
fats, less often nucleic acids or nucleoproteins. These substances can
come from the outside (parenteral administration of blood components,
vaccines, fat emulsions into the body) or be formed in the body itself
(with non-infectious inflammation, myocardial infarction, tumor
breakdown, erythrocyte hemolysis, allergic reactions).
Secondary pyrogens. Under the influence of primary pyrogens in
leukocytes form cytokines (leukokines), which have pyrogenic activity in a
negligible dose. Pyrogenic leukokines are called secondary, true, or leukocyte
pyrogens. These substances directly affect the thermoregulatory center,
changing its functional activity. Among the pyrogenic cytokines are IL1
(previously referred to as "endogenous pyrogen"), IL6, TNFα, γ-IFN.
PATHOGENESIS OF FEVER
Fever is a dynamic and staged process. According to the criterion of body
temperature change, three stages of fever are distinguished: I - temperature rise,
II - temperature standing at an elevated level and III - temperature decrease to
the normal range.
Temperature rise stage
Stage of rise in body temperature (stage I, st.
incrementi) is characterized by the accumulation of additional heat in the
body due to the predominance of heat production over heat transfer.
• Pyrogenic leukokines from the blood penetrate the blood-brain barrier
and in the preoptic zone of the anterior hypothalamus interact with the
receptors of the nerve cells of the thermoregulatory center. As a result,
membrane-bound phospholipase A2 is activated and arachidonic acid is
released.
• In the neurons of the thermoregulatory center, the activity of cyclooxygenase
is significantly increased. The result of the metabolism of arachidonic acid by
the cyclooxygenase pathway is an increase in the concentration of PrE2.
• The formation of PgE2 is one of the key development links
fever.
The argument for this is the fact that fever is prevented when
cyclooxygenase activity is suppressed by non-steroidal antiinflammatory drugs (NSAIDs, for example, acetylsalicylic acid or
diclofenac).
• PgE2 activates adenylate cyclase, which catalyzes the formation of cyclic 3
', 5'-adenosine monophosphate (cAMP) in neurons. This, in turn, increases the
activity of cAMP-dependent protein kinases, which leads to a decrease in the
excitability threshold of cold receptors (i.e., an increase in their sensitivity).
• Due to this, the normal blood temperature is perceived as low: the
impulse of cold-sensitive neurons to the effector neurons of the posterior
hypothalamus increases significantly.
In this regard, the so-called "set point" of the heat regulation
center increases.
The changes described above are the central link in the development
mechanism of stage I fever. They trigger peripheral thermoregulation
mechanisms.
• Heat transfer is reduced as a result of the activation of neurons in
the nuclei of the sympathoadrenal system located in the posterior
parts of the hypothalamus.
♦ An increase in sympathoadrenal effects leads to a generalized narrowing of
the lumen of the arterioles of the skin and subcutaneous tissue, a decrease in
their blood supply, which significantly reduces heat transfer.
♦ A decrease in skin temperature causes an increase in impulses from its cold
receptors to the neurons of the thermoregulatory center, as well as to the
reticular formation.
• Activation of heat production mechanisms (contractile and noncontractile thermogenesis).
♦ Activation of the structures of the reticular formation stimulates the
processes of contractile muscle thermogenesis in connection with the
excitation of γand α-motor neurons of the spinal cord. A thermoregulatory myotonic
state develops - tonic tension of skeletal muscles, which is accompanied
by an increase in heat production in the muscles.
♦ The increasing efferent impulses of neurons in the posterior
hypothalamus and the reticular formation of the brainstem causes
synchronization of contractions of individual muscle bundles of skeletal
muscles, which manifests itself as muscle tremors.
♦ Non-contractile (metabolic) thermogenesis is another important
mechanism of heat production in fever. Its reasons: activation of
sympathetic influences on metabolic processes and an increase in the
level of thyroid hormones in the blood.
An increase in temperature is due to a simultaneous increase in heat
production and a limitation of heat transfer, although the significance of each
of these components may be different. In stage I fever, an increase in basal
metabolism increases body temperature by 10-20%, and
the rest is the result of reduced heat transfer from the skin due to
vasoconstriction.
The temperature of the external environment has a relatively small effect on
the development of fever and the dynamics of body temperature.
Consequently, with the development of fever, the thermoregulation system
is not upset, but is dynamically rebuilt and works at a new functional level.
This distinguishes fever from all other hyperthermic conditions.
The stage of standing body temperature at an elevated level
The stage of standing body temperature at an elevated level (stage II, st.
Fastigii) is characterized by a relative balance of heat production and heat
transfer at a level significantly exceeding the pre-febrile stage.
• The heat balance is established through the following mechanisms:
♦ increased activity of heat receptors in the preoptic zone of the anterior
hypothalamus caused by increased blood temperature;
♦ temperature activation of peripheral thermosensors of internal organs helps
to establish a balance between adrenergic influences and increasing
cholinergic effects;
♦ increased heat transfer is achieved due to the expansion of the arterioles of
the skin and subcutaneous tissue and increased sweating;
♦ a decrease in heat production occurs due to a decrease in the
intensity of metabolism.
The combination of diurnal and stage dynamics in fever is designated as a
temperature curve. There are several typical types of the temperature curve.
♦ Constant... With her, the daily range of fluctuations in body temperature
does not exceed 1 ° C. This type of curve is often found in patients with lobar
pneumonia or typhoid fever.
♦ Remitting. It is characterized by daily temperature fluctuations of
more than 1 ° C, but without returning to the normal range (often
observed in viral diseases).
♦ Laxative or intermittent. Fluctuations in body temperature during the
day reach 1-2 ° C, and it can return to normal for several hours, followed by
an increase. This type of temperature curve is often recorded with abscesses
of the lungs, liver, purulent infection, tuberculosis.
♦ Exhausting, or hectic... It is characterized by repeated increases in
temperature during the day by more than 2-3 ° C with its rapid
subsequent drops. This picture is often observed with sepsis.
Several other types of temperature curves are also distinguished.
Considering that the temperature curve in infectious fever depends to a large
extent on the characteristics of the microorganism, determining its type can
be of diagnostic value.
With fever, several degrees of increase in body temperature
are distinguished:
♦ weak, or subfebrile (in the range of 37-38 ° C);
♦ moderate, or febrile (38-39 ° C);
♦ high, or pyretic (39-41 ° C);
♦ excessive, or hyperpyretic (above 41 ° C). Stage of
decrease in body temperature to normal
Stage of decrease in body temperature to values of the normal
range (stage III fever, St. decrementi) is characterized by a gradual
decrease in the production of leukokines.
• Reason: cessation of the action of the primary pyrogen due to the
destruction of microorganisms or non-infectious pyrogenic substances.
• Consequences: The content of leukokines and their influence on
the thermoregulatory center are reduced, as a result of which the
“set point” is reduced.
Varieties of lowering the temperature in stage III fever:
♦ gradual decline, or lytic (more often);
♦ rapid decline, or critical (less often)
64. Describe the concept of fever-like conditions (endogenous hyperthermia). Give their classification,
pathogenesis.
Fever-like conditions (LPS) -a number of endogenous hyperthermia with features similar to
fever, but not associated with the action of pyrogens.
Classification.
1. Neurogenic LPS - which are subdivided into centrogenic,
psychogenic, reflexogenic;
2. Endocrine;
3. Medicinal LPS.
Pathogenesis
Neurogenic LPSs are subdivided into centrogenic, psychogenic, reflesogenic.
Centrogenic LPS
can occur when various parts of the brain are damaged
(hemorrhages, tumors, trauma, edema
brain
The
reason for the development of psychogenic can
be
functional
violation of the highest
nervous
activities
(neurosis, mental
disorders), significant emotional and mental stress,
cases of hyperthermia and the influence of hypnotic suggestion are described.
Reflexogenic can be observed in kidney stones, cholelithiasis, irritation of the
peritoneum, urethral catheterization) In this case, as a rule, there is a pain
syndrome; in some cases, the formation of pyrophilic tissues and leading to
microprocesses. In such cases, along with the reflexogenic mechanism, the usual
mechanism of action of pyrogenic substances will also participate.
Endocrine LPS observed in some endocrinopathies, with particular constancy in
hyperthyroidism.
Medicinal LPS occur with enteral or parenteral administration of certain
pharmacological drugs: caffeine, ephedrine, methylene blue, hyperosmolar solutions,
etc.
65 Describe the concept of pyrogen. List the pyrogenic substances and classify them, describe the
pathophysiological mechanisms of the implementation of the action of pyrogens.
The immediate cause of fever is pyrogenic substances, or pyrogens.
Pyrogens- penetrate into the body and / or are formed in it; stimulate the formation of true-leukocyte pyrogens, which cause a febrile
reaction.
Classification.
By origin criterion distinguish between infectious and non-infectious pyrogens.
Infectious pyrogens:
Infectious pthrogens are the most common cause of fever. It is essential that the fever reaction is triggered not by these pyrogens
(they are primary), but by secondary (true) pyrogens formed in the body under their influence, secreted by various cells (mainly
macrophages and neutrophils). Infectious pyrogens include lipopolysaccharides. , lipoteichoic acids, endo- and exotoxins acting as
superantigens.
Lipopolysaccharides:
Lipopolysaccharides are part of the membranes of microbes, mainly gram-negative. They consist of three main parts - lipid A,
protein, polysaccharide - the pyrogenic effect is characteristic of lipid A. The microbial pyrogen is thermostable, has low toxicity
and does not have group specificity. The pyrogen that causes a febrile reaction does not characterized by toxicity and pathogenicity.
The pyrogenic property of lipid A is used in medicine for therapeutic purposes when using a pharmacological preparation of
pyrogenal obtained from the membranes of individual bacteria.
Superantigens:
Numerous endo- and exotoxins of staphylococci and streptococci act as superantigens - polyclonal activators of T-lymphocyte
receptors with subsequent numerous numerous effects of such activation, including the release of various cytokines from
macrophages and neutrophils.
Non-infectious pyrogens:
By structure, non-infectious progenes are most often proteins, fats, less often nucleic acids or nucleoproteins, steroid substances.
Parenteral administration of sterile protein and / or fat-containing substances into the body is accompanied by the development of
fever.
In addition, a febrile reaction is always observed with aseptic injuries, necrosis of organs and tissues, hemolysis of erythrocytes,
non-infectious inflammation, and allergic reactions.
In addition, primary and secondary pyrogens are isolated.
After ingestion or formation of pyrogenic agents in the body, the content of peptides increases in the blood within 30-70 minutes.
Pyrogenic activity in a small dose. These substances arr. mainly in phagocytic leukocytes (granulo- and agranulocytes,
lymphocytes). , pyrogenic agents indirectly induce the expression of genes encoding the synthesis of cytokines.
Pyrogenic substances that enter the body or are formed are primary pyrogens. The cytokines (leukokines) formed in leukocytes are
called secondary (leukocyte) pyrogens.
Leukocyte pyrogens include: IL-1, IL-6, TNF, IFN. They do not have species specificity and are thermolabile. When re-formed in
the body, they give the same effect as with the first.
66.
Describe the types of febrile reactions, the biological significance of fever, the principles of
antipyretic therapy.
Fever can be divided according to the duration, degree of rise in body temperature and the
characteristics of its fluctuations throughout the day.
Depending on the duration fever can be ephemeral (1-3 days), acute (up to 15 days), subacute (up to
1.5 months) and chronic (more than 1.5 months).
According to the degree of rise Temperatures distinguish between low-grade fever (37.1-37.9 ° C),
moderate (38-39.5 ° C), high (39.6-40.9 ° C) and hyperpyretic (41 ° C and above). The latter type of fever is
observed, in particular, with tetanus and meningitis.
Depending on the size of the daily temperature fluctuations in the second stage of the fever, it is
divided into constant, laxative, intermittent, debilitating, recurrent and atypical. It should be noted that in
most cases, during the development of fever, the normal circadian rhythm of temperature fluctuations
remains, i.e. it is higher in the evening than in the morning (Fig. 11-2).
Persistent fever febris continua) characterized by a high rise in temperature with daily
fluctuations not exceeding 1 ° C (croupous pneumonia, typhus, etc.).
Weakening fever f. remittens)- with it, daily temperature fluctuations exceed 1
° С, but there is no decrease to normal; this type of fever is observed in most viral and many
bacterial infections (exudative pleurisy, tuberculosis, etc.).
Intermittent fever (f. intermittens) characterized by large fluctuations in daily temperature with a drop in
the morning to normal or below (purulent infection, tuberculosis, some types of malaria, rheumatoid
arthritis, lymphomas, etc.).
Wasting fever f. hectica)- daily temperature fluctuations reach 3-4 ° С; observed in purulent
processes, sepsis, tuberculosis and other diseases.
Recurrent fever (f. recurrens) characterized by an alternation of febrile and febrile periods,
the duration of which
which ranges from one to several days (relapsing fever, lymphogranulomatosis, malaria, etc.).
Atypical fever f. athypica)differs in completely irregular temperature fluctuations, and its maximum rise
occurs in the morning (some forms of tuberculosis, sepsis, etc.).
Previously, it was believed that the characteristic features of the temperature curve are of great diagnostic
and prognostic value. However, at present, this indicator is no longer
It is a reliable criterion in this regard, since the natural course of the development of fever and daily
fluctuations in body temperature is often distorted under the influence of treatment. In addition, the
development of fever is influenced by immunological and age-related reactivity. In old and emaciated
people, young children, infectious diseases can occur with little or no fever; the latter may be of poor
prognostic value.
Ichradish fever is considered mainly as a defensive and adaptive reaction of the organism to the action of
various pathogenic factors, formed in the course of evolution. At the same time, like inflammation and
other typical pathological processes, it can have both positive and negative effects on the body.
Biological significance
Protective and adaptive value fever is confirmed by the following observations:
• with fever, the body's immune response is enhanced due to the activation of T- and B-lymphocytes,
accelerating the transformation of the latter into plasma cells, which stimulates the formation of antibodies;
the formation of interferon increases;
• a moderate degree of rise in body temperature can activate the function of phagocytic cells and NK
cells (natural killer cells);
• enzymes that inhibit the reproduction of viruses are activated;
• the reproduction of many bacteria slows down and the resistance of microorganisms to drugs
decreases;
• the barrier and antitoxic functions of the liver increase;
• hepatocytes intensively produce the so-called acute phase proteins; some of these proteins bind
bivalent cations necessary for the reproduction of microorganisms;
• in addition, an increase in body temperature with fever is quite often the first and only sign of any
disease, it is an alarm signal.
Negative impact fever on the body is detected mainly with a pronounced and prolonged increase
changes in body temperature. It is associated with the stimulation of heart function, which can lead to the
development of an overload form of heart failure, especially in elderly and senile people, as well as in
patients who have previously had one or another heart disease. There is a danger of the possibility of
developing a collapse with a critical decrease in body temperature in the final stage of fever. In high-grade
fever, suppression of immune responses may occur. It has been found that moderate fever increases the
survival rate of infected animals, and excessively high fever increases mortality. Children with high fever
may develop seizures, which are not always relieved by taking antipyretic drugs. At temperatures above 41
° C, children may develop cerebral edema or acute circulatory failure due to the lability of water-salt
metabolism. Long-term febrile patients (with tuberculosis, brucellosis, sepsis) are usually in a state of sharp
exhaustion and weakening of vital functions. Of course, in infectious diseases, disturbances are caused not
only by the action of high temperature, but also by microbial toxins.
PRINCIPLES OF ANTI-REDUCING THERAPY
Given the dual nature of the effect of fever on the body, the question of the usefulness of the use of
antipyretic drugs cannot be resolved unambiguously. In addition to the previously mentioned data on the
positive role of fever, one should take into account the fact that its artificial suppression can complicate the
diagnosis and prognosis of the severity of the disease. At the same time, it was found that the positive
effect of fever on the development of the disease is manifested only with its moderate and short course.
High fever causes suffering to the patient, adversely affects the cardiovascular system and the central
nervous system, digestion processes, reduces the manifestation of a number of protective reactions, such
as phagocytosis, the formation of antibodies, etc. As stated by P.N. Veselkin (1981): “The question of the“
benefits ”and“ harms ”of fever for the patient cannot be resolved unequivocally.
The main indications for the use of antipyretic therapy should be considered high and prolonged fever with
a rise in temperature to 39-40 ° C, as well as moderate fever in patients with diseases of the
cardiovascular system and other vital organs, with acute neurological disorders, in the presence of shock,
sepsis, pronounced metabolic disorders. In addition, taking antipyretics should be prescribed to elderly
patients, as well as
the same for children under 5 years old, especially when indicating the development of seizures in the past.
Non-steroidal anti-inflammatory drugs (acetylsalicylic acid, paracetamol, amidopyrine, etc.), quinine,
glucocorticoids and other drugs are used as antipyretics.
Pyrotherapy (from the Greek pyros - fever) is a type of treatment for various diseases through artificially
induced fever or overheating. The reason for the use of pyrotherapy was clinical observations indicating a
more favorable course and outcome of some infectious diseases (for example, sexually transmitted
diseases) against the background of high fever caused by the addition of another type of infection (for
example, with the development of malaria in patients with syphilis).
Later this type of therapy received experimental justification. It has already been mentioned that fever can
reduce the resistance of microorganisms and their ability to reproduce. So, it was found that pneumococci,
gonococci and treponemas die at a temperature of 40-41 ° C. When rabbits were infected with
pneumococci, the disease progressed more severely when the fever was suppressed with antipyretic
drugs.
For the first time this type of therapy began to be used in the middle of the 19th century. for the treatment
of indolent infections and inflammatory processes that are poorly amenable to drug therapy. Plasmodium
malaria, the causative agent of relapsing fever and other microorganisms were used as the causative
agents of fever. In a number of cases, pyrotherapy gave positive results, but sometimes an artificially
induced infectious fever made the patient's condition worse and contributed to the onset of a lethal
outcome. Therefore, in the future, purified non-toxic pyrogenic substances, such as pyrogenal, etc., were
used to artificially induce fever. For this purpose, the recombinant form of IL-1 is also used.
Currently, pyrotherapy is used in combination with drug therapy for joint diseases, flaccid and spastic
paralysis arising in connection with multiple sclerosis and poliomyelitis, neurosyphilis, skin diseases such
as psoriasis, eczema, as well as for the treatment of other lingering chronic inflammatory processes , to
accelerate the resorption of adhesions, etc.
66. Describe the types of febrile reactions, the biological significance of fever, the principles of
antipyretic therapy.
The combination of diurnal and stage dynamics in fever is denoted as a temperature curve
Depending on the course of the temperature curve, the following main types of fever are
distinguished:
Constant- the daily range of fluctuations in body temperature does not exceed 1C. This
type is often detected in patients with lobar pneumonia or typhoid fever.
Remitting - is characterized by daily temperature fluctuations of more than 1C, but
without returning to the normal range. It is often observed in viral diseases.
Laxative or intermittent - fluctuations in body temperature during the day reaches 1-2C,
and it can be normalized for several hours, followed by an increase. Often this type is
recorded with abscesses of the lungs, liver, purulent infection, tuberculosis.
Exhausting, or hectic-characterized by repeated increases in temperature during the day
by more than 2-3C with its rapid subsequent decreases. Observed with sepsis
...
The type of fever is determined by the etiological factor, depending on the
characteristics of the pathogenesis
this disease, immunological restructuring, features of the general reactivity of the
body.
biological significance of fever
Fever appeared and took root in the process of evolution as a protective and adaptive
reaction. However, fever as a pathological process under certain conditions can also have
a pathogenic significance for the body.
Self-heating of an organism with the development of a number of diseases, especially
inf. nature, helps to combat the pathogenic factor and eliminate the consequences of its
impact.
An increase in body temperature prevents the reproduction of most pathogenic
microorganisms. High temperatures can reduce the resistance of some bacteria to drugs.
With fever, metabolic processes in cells are stimulated, their functional efficiency
increases.
The barrier and antitoxic function of the liver increases, diuresis increases, and, as
a result, the release of toxic substances from the body.
The body's immunobiological defense is activated. With an increase in temperature, the
phagocytic activity of leukocytes and fixed macrophages increases, the production of
antibodies, interferon increases; enzymes involved in suppressing the reproduction of
viruses are activated. The negative value of fever is associated with an additional load
on a number of organs and systems, especially on the ccc. In some cases, increased
individual sensitivity of the body to high temperatures is possible. Hyperpyretic fever
can lead to serious functional impairment. A critical drop in temperature in 3 stages of
a febrile reaction leads to the development of a collapse.
The principles of antipyretic therapy.
Antipyretic therapy is aimed at lowering body temperature with fever, accompanied by
negative. the effect of high temperature on the vital functions of the body.
Lowering the temperature can be achieved with medications
acting on the hypothalamic centers of thermoregulation, on the processes of heat
production and heat transfer. Non-narcotic analgesics are widely used as antipyretics:
acetylsalicylic acid, amdopyrine, etc. These substances, acting on thermoregulatory
centers, can increase heat transfer processes due to the vasodilation of the skin and
increased sweating that occurs against the background of their action. One of the
mechanisms of the antipyretic effect of non-narcotic analgesics is the inhibition of the
synthesis of group E prostaglandins.
A decrease in body temperature is also achieved by reducing the processes of heat
production. This effect is given by alkaloids of a number of plants (for example, Kinins),
which have a depressing effect on oxidative processes in tissues.
In principle, it seems possible to lower body temperature by inhibiting the production
of secondary pyrogens. In addition, other medications are used (for example,
sulfonamides).
Pyrotherapy is used - this is a method of treatment using an artificial increase in body
temperature. One of the methods of increasing body temperature is the induction of
artificial fever by pyrogenic substances. For this purpose, highly purified biogenic
preparations are used, for example, pyrogenal, which is a lipopolysaccharide complex
isolated from the cell walls of gram-negative bacteria. It is used to accelerate the
reparative processes after traam, burns, for resorption of nipples, adhesions, etc.
67. Give the definition of hypoxia, characterize the resistance of individual organs and tissues to oxygen
starvation, the principles of classification of hypoxic conditions.
Hypoxia –A typical pathological process that develops as a result of insufficient
biological oxidation, leading to a violation of the energy supply of functions and plastic
processes in the body.
Hypoxia is often combined with hypoxemia.
Criteria for the classification of hypoxic
conditions:
Depending on the causes of the occurrence and developmental mechanisms, hypoxia is
distinguished due to a lack of oxygen in the inhaled air, insufficient intake of it into
the body, insufficient transport of it to the cells and impaired utilization in
mitochondria. In accordance with this, the types of hypoxia are distinguished:
1. Exogenous
a. Hypobaric;
b. Normobaric.
2. Respiratory (respiratory);
3. Circulatory (cardiovascular);
4. Hemic (blood);
5. Tissue (primary tissue);
6. Overload (load hypoxia);
7. Substrate;
8. Mixed.
According to the criterion of the prevalence of a hypoxic state:
a. local hypoxia;
b. General hypoxia.
By the rate of development and duration:
a. Lightning fast;
b. Sharp;
c. I will subacute;
d. Chronic.
By severity:
a.
b.
c.
d.
Lightweight;
Moderate;
Heavy;
Critical (fatal) hypoxia;
Exogenous type of hypoxia occurs due to a decrease in the partial pressure of
oxygen in the inhaled air.
A) Hypobaric hypoxia is caused by a general decrease in barometric pressure and is
observed when climbing mountains or in unpressurized aircraft.
B) Normobaric hypoxia develops at normal general barometric pressure, but reduced
partial pressure of oxygen in the inhaled air, for example. when being in confined
spaces of small volume, working in mines, etc.
The pathological basis of exogenous hypoxia in all cases is arterial hypoxemia,
i.e. a decrease in oxygen tension in the arterial blood plasma, leading to
insufficient saturation of hemoglobin with oxygen and a decrease in its content in
the blood.
Respiratory type hypoxIi occurs as a result of insufficient gas exchange in the
lungs due to alveolar hypoventilation, disturbances in ventilation-perfusion
relations, excessive extra-and intrapulmonary bypass of venous blood, or with
difficulty in diffusion of oxygen in the lungs. The pathogenetic basis is arterial
hypoxemia, combined with hypercapnia.
Circulatory type of hypoxia develops with circulatory disorders, leading to
insufficient blood supply to organs and tissues. It can occur in connection with
microcirculation disorders caused by changes in the walls of blood vessels,
aggregation of blood corpuscles, an increase in its viscosity, and coagulability.
Hemodynamic parameters can vary widely. The gas composition is characterized by
normal tension and oxygen content in arterial blood, their decrease in venous blood
and a high arterial oxygen difference.
Hemic type hypoxia occurs as a result of a decrease in the effective oxygen capacity
of the blood in case of anemia, hydremia, or in violation of the ability of
hemoglobin to bind, transport and give oxygen to tissues.
Tissue type develops as a result of a violation of the ability of cells to absorb
oxygen or in connection with a decrease in the efficiency of biological oxidation
as a result of the uncoupling of oxidation and phosphorylation.
The overload type occurs when an overly intense activity of any organ or tissue,
when the functional reserves of the systems of transport and utilization of oxygen
and substrates are insufficient to meet the sharply increased demand.
Substrate type associated with insufficient transport or impaired oxygen
utilization.
68. Describe the etiology and pathogenesis of exogenous types of hypoxia. Describe the indicators of the
gas composition of arterial and venous blood with them.
Exogenous type of hypoxia occurs due to a decrease in the partial pressure of oxygen in inhaled
the air...
Hypobaric hypoxia It is caused by a general decrease in barometric pressure and is observed when climbing mountains
or in unpressurized aircraft without oxygen systems. Noticeable violations are noted at a pressure of about 100 ml Hg. At
a pressure of 50-55 ml Hg, severe disorders arise that are incompatible with life ..
Normobaric hypoxia develops at normal general barometric pressure, but a reduced partial pressure of oxygen in the inhaled
air, for example, when being in closed rooms of a small volume, working in mines, etc.
The pathological basis of exogenous hypoxia in all cases is arterial hypoxemia
,those. a decrease in oxygen tension in the arterial blood plasma, leading to insufficient saturation of hemoglobin with
oxygen and a decrease in its content in the blood.
The respiratory type of hypoxia occurs as a result of insufficient gas exchange in the lungs due to alveolar hypoventilation,
disturbances in ventilation-perfusion relations, excessive extra-and intrapulmonary shunting of venous blood, or with
difficulty in diffusion of oxygen in the lungs. The pathogenetic basis is arterial hypoxemia, combined with hypercapnia.
An additional negative effect is exerted by hypocapnia, which often develops during exogenous hypoxia as a result of compensatory
hyperventilation of the lungs and leads to a deterioration in the blood supply to the brain, heart, electrolyte imbalance, and
69. Describe the etiology and pathogenesis of respiratory and respiratory hypoxia. Describe the indicators
of the gas composition of arterial and venous blood with them.
Respiratory type of hypoxia occurs as a result of insufficient gas exchange in the
lungs in connection with alveolar hypoventilation, disturbances in ventilationperfusion relations, excessive extra-and intrapulmonary shunting of venous blood
or with difficulty in diffusion of oxygen in the lungs.
Pathogenetic basis is arterial hypoxemia, combined with hypercapnia.
Changes in blood gas composition and ph:
Decrease in pao2 andp
(arterial and venous
vo2
hypoxemia). Increase paco2 (hypercapnia).
Acidosis (at an early stage, gas, then non-gas).
Decreased arterial and venous hemoglobin saturation.
70. Describe the etiology and pathogenesis of hemic hypoxia. Describe the indicators of gas
composition of arterial and venous blood with it.
Hemic type of hypoxia arises as a result of a decrease in the effective oxygen
capacity of the blood in case of anemia, hydremia, or in violation of the ability
of hemoglobin to bind, transport and give oxygen to tissues.
Pathogenesis.
The main links in the mechanism of reducing the oxygen capacity of blood is a decrease
in the hemoglobin content in a unit of blood volume and a violation of the transport
properties of hemoglobin. In general, this type of hypoxia is characterized by a decrease
in the ability of erythrocyte hemoglobin to bind oxygen, transport and release its optimal
amount in tissues. In this case, the real oxygen capacity of the blood can be reduced to
5-10%.
A decrease in the hemoglobin content in a unit of blood volume is observed with a
significant decrease in the number of erythrocytes, with severe anemia.
Disturbances in the transport properties of hemoglobin are caused by a change in its
ability to oxygenate in the blood of the capillaries of the alveoli and deoxygenate in
the capillaries of the tissues.
These changes can be inherited or acquired.... Gas
composition changes:
Decrease in volumetric oxygen content in arterial blood; Normal
partial tension of oxygen in arterial blood; Decreased pvo2
(venous hypoxemia);
Decrease pvo2; Nongaseous acidosis;
Decrease in arteriovenous oxygen difference.
71. Describe the etiology and pathogenesis of tissue hypoxia. Describe the indicators of the gas
composition of arterial and venous blood with it.
Causes of tissue hypoxia : factors that reduce the efficiency of oxygen utilization by tissue cells and / or conjugation of oxidation
and phosphorylation...
Pathogenesis...
Decreased efficiency of oxygen uptake by cells is most often the result of inhibition
activity of biological oxidation enzymes, significant changes in physicochemical parameters in tissues,
inhibition of the synthesis of enzymes of biological oxidation and damage to cell membranes.
Suppression of the activity of biological oxidation enzymes is observed when:
-specific inhibition of enzymes (for example, cyanogen ions, which prevent the oxidation of cytochrome). As a result, the reduction
of iron of the respiratory enzyme and oxygen transport to the cytochrome is blocked, hypoxia and disruption of vital activity develop.
-nonspecific inhibition of biological oxidation enzymes by metal ions. In this case, metals reversibly interact with the SH-groups of
the enzyme with the formation of its active mercaptoid form.
-competitive inhibition of biological oxidation enzymes. It consists in blocking the active center of the enzyme with a substance
that has a structural analogy with the natural reaction substrate. This effect can be eliminated with an increase in the content of the
true substrate in the cell. For example, oxalate and malonate
blocking the interaction of succinate with succinate dehydrogenase in the tricarboxylic acid cycle.
Changes in physical and chemical parameters in tissues(temperature, electrolyte composition, pH) reduce the effectiveness of
biological oxidation. Deviation from the norm of these and other parameters is observed in hyperthermia and hypothermia, failure
of various organs, anemia, etc.
Inhibition of the synthesis of biological oxidation enzymes can be observed with general or partial starvation; with most hypo- and
dysvitaminosis; violation of the metabolism of minerals necessary for the synthesis of enzymes.
Diaphragm damage- to the greatest extent this applies to the membranes of mitochondria. Damage and destruction of membranes
are the result of excessive intensification of free radical and lipid peroxide processes, activation of lysosome hydrolases, detergent
action of excess amphiphilic compounds, overstretching and rupture of swollen cells and their mitochondria.
Reducing the degree of sorption of oxidation and phosphorylation of high-energy compounds in the respiratory chain. Under
these conditions, oxygen consumption by tissues and the intensity of the functioning of the components of the respiratory chain
increase. However, most of the energy of electron transport is transformed into heat and is not used for resynthesis of macroergs.
The efficiency of biological oxidation decreases., and cells do not receive energy supply. the processes of oxidation and
phosphorylation are possessed by many endogenous agents (IVC, excess Ca), as well as endogenous substances (dicumarin,
gramicidin).
Gas composition and pH changes:
An increase in the partial tension of oxygen in the venous blood;
Increased saturation of hemoglobin with oxygen in the venous blood;
Increased volumetric oxygen content in venous blood;
Normal range of po2, so2, vo2 in arterial blood (in typical cases); Reduction of arteriovenous
oxygen difference (except for tissue hypoxia); Non-gaseous acidosis.
72. Describe the etiology and pathogenesis of substrate and overload hypoxia. Describe the indicators of
the gas composition of arterial and venous blood with them.
Substrate type of hypoxia
Cause: deficiency of biological oxidation substrates in cells. In clinical practice, we are talking about glucose. At the same
time, oxygen delivery to the cells is not significantly impaired.
Pathogenesis: substrate hypoxia consists in progressive inhibition of biological oxidation. In this regard, the level of ATP and
creatine phosphate in the cells rapidly decreases, the magnitude of MP, various metabolic pathways and plastic processes are
disrupted.
Blood gas changes:
An increase in the partial tension of oxygen in the venous blood. An
increase in the volumetric oxygen content in the venous blood.
Increased oxygen saturation of hemoglobin in erythrocytes of venous blood.
Reduction of arterio-venous oxygen difference.
Normal p valuesao2, SaO2, VaO2.
Acidosis, which develops as a result of metabolic disorders, hemodynamics, external respiration and other changes caused by
a disease or pathological process that caused substrate type hypoxia. For example, with diabetes-glucose deficiency in cells, the
body accumulates CT, lactate, pyruvate, which leads to metabolic acidosis.
Overload type of hypoxia
Cause : significant and / or long-term increase in the function of tissues, organs or their systems. At the same time, the intensification
of the delivery of oxygen and substrates of metabolism, metabolism, conjugation reactions of oxidation and phosphorylation to them
are not able to eliminate the deficiency of high-energy compounds that develops as a result of cell hyperfunction. Most often, we
are talking about situations that cause increased or prolonged functioning of skeletal muscles and myocardium.
Pathogenesis.
Excessive in the level and duration of the load on the muscle (skeletal or heart) causes:
- the relative lack of blood supply to the muscle.
- oxygen deficiency in myocytes, which causes a lack of biological oxidation processes in them. Change in blood gas
composition:
Decrease in the partial tension of oxygen in the venous blood (venous hypoxemia), flowing
from hyperfunctioning muscle.
Decrease in the degree of saturation of hemoglobin of erythrocytes in venous
blood. Increased arteriovenous oxygen difference.
An increase in the partial tension of carbon dioxide (hypercapnia) in the venous blood, which is the result of an activated metabolism
in muscle tissue.
Acidosis in blood samples taken from a vein of a hyperfunctioning muscle.
73. Give a definition of the concept of "tumor". Describe the main types of tumor atypism.
A tumor is an abnormal proliferation of cells characterized by their uncontrolled
division and a number of other biological features called atypism.
anaplasia.
or
Atypism Is an abnormality that distinguishes tumor cells from normal cells.
Anaplasia- changes in the structure and biological properties of tumors, making them look
like undifferentiated tissues.
Tumor cells are fundamentally different from embryonic ones: they do not mature, are
capable of migration and invasive growth into the surrounding adjacent tissues with their
subsequent destruction.
All types of atypism can be divided into 2 types: characteristic of good and malignant
tumors and characteristic only for malignant.
Biological features characteristic of benign and malignant tumors:
1 . Atypism of reproduction - uncontrolled division
tumor
Includes: 1) unregulated cell proliferation. An example is the weakening of the properties
of tumor cells to inhibit the mitotic cycle and to move when in contact with each other.
This property is called contact inhibition. It is inherent in most multiplying normal
cells. Inhibition of cell division during their contact is normally combined with the
cessation of their movements.
2) loss of the upper "limit" of the number of cell divisions. Normal cells divide up to
a certain maximum limit (up to 30-50 divisions), after which they die. Tumor cells acquire
the ability to endlessly divide. This leads to their immortalization.
2 . Differentiation atypism consists in partial or complete inhibition of the process of
cell maturation. It is sharply expressed in malignant tumors and weakly in benign ones.
The causes of this type of atypism are the loss of factors that stimulate the diyerenia
of its cells by the tumor, or decreased sensitivity of cells to them.
3 . Metabolic and energetic atypisms.Include:
1) intensive synthesis of oncoproteins. These proteins cause the appearance of obligate
tumor biological features in cells ... ... ..6 uncontrolled division, loss of the division
limit, immortalization. , protooncogenes are found in all normal cells.
2) a decrease in the synthesis and content of histones. A deficiency of histones promotes
the activation of the synthesis of DNA and RNA templates. This leads to the doubling of
genes, chromosomes, protein mass and to cell division.
3) the formation of embryonic proteins unusual for mature cells, for example, Afetoprotein.
4) A change in the way of ATP resynthesis. It consists in an increase in the proportion
of ATP formed during glycolysis and a decrease, respectively, in the proportion of ATP
resynthesized in the process of tissue respiration. In tumor cells, intense anaerobic
glycolysis does not decrease when anaerobic conditions change to aerobic ones, but
persists. in tumor cells determines their high survival rate under hypoxic conditions.
5) The phenomenon of substrate traps. It consists in enhanced capture and use of substrates
for energy production, for building cytoplasm, cell membranes, for protection against
free radicals and stabilization of membranes.
6) Decrease in the content of cyclic adenosine monophosphate in tumor cells, which has an
inhibitory effect on their division and an increase in cyclic guanosine monophosphate,
which stimulates cell proliferation.
4 . Physicochemical atypism It is manifested by an increase in the content of water,
potassium ions in tumor cells and a decrease in calcium and magnesium in them. An increase
in water content facilitates the diffusion of metabolic substrates into the cells and
its products outward. A decrease in ca decreases intercellular adhesion, and this
facilitates the separation of cells from the tumor tissue. An increase in potassium
prevents the development of intracellular acidosis due to increased glycolysis and the
accumulation of lactic acid.
5 . Functional atypism is manifested by a dysfunction of cells: a) a decrease
; b) inadequate strengthening of functions; c) perversion of functions.
6 . Antigenic atypism consists in multidirectional changes in the antigenic composition of
tumor cells - antigenic simplification or the emergence of new antigens Angenic
simplification - the loss by tumor cells of antigens present in a normal cell (for
example, the loss of organ-specific hepatic h-antigen by cancerous hepatocytes. In tumors,
the appearance of new antigens is possible (for example, A-fetoprotein). The loss of
organ-specific antigen by cells and the appearance of embryonic antigens in them
contributes to
"Masking" tumor cells.
7 . Morphological atypismdivided into tissue and cellular. Tissue is characteristic only
for benign tumors. It consists in a violation of the normal ratio of tissue structures.
Cellular is characteristic of malignant tumors. It is manifested by polymorphism, an
increase in the nuclear-cytoplasmic ratio, hyperchromia of the nuclei, an increased
number and size of chromosomes, etc.
8 . Interaction atypism tumor cells is that, unlike normal cells, tumors do not make a
useful contribution to the integral vital activity of the body, on the contrary, they
cause its disturbances.
Biological features characteristic of malignant tumors.1.Infiltrative
growth concludes. In the penetration of cells into the surrounding tissues.
2.Metastasis- the movement of tumor cells from the primary site of localization to organs
and tissues located at a distance, forming nodes of the same histological structure in
them.
Includes 3 stages: 1) stage of
invasion; 2) the stage of cell
embolism;
3) The stage of penetration of tumor cells from the cellular thromboembolus through the
vessel wall into the surrounding normal tissues, their multiplication with the formation
of new tumor nodes.
4. Recurrence.
4.cahexia- syndrome of exhaustion and general weakness of the organism. Factors
promoting development of
cachexia:
1) violation of the neuro-endocrine regulation of
metabolism; 2) Strengthening the formation of ATP due to
glycolysis;
N) inhibition of lipoprotein
lipase; 4) decrease in RNA
synthesis;
5) the formation of a special protein
"cachectin"; 6) a decrease in the
synthesis of the enzyme catalase; 7)
concomitant tumor complications.
74. Describe anti-carcinogenic, anti-mutagenic, anti-cellulary
mechanisms antitumor resistance of the body.
Antiblastoma resistance is understood as the body's resistance to the emergence and the
development of tumors.
There are 3 main types:
1 . Anticarcinogenic
, addressed to the stage of interaction of the carcinogenic
factor
from cells,
organelles, macromolecules.
2 . Anti-transformational
addressed to the normal cell transformation stage
in tumor and inhibiting it.
3 . Anti-cellulary, addressed to the stage of transformation of the formed individual
tumor cells into a cell colony-tumor.
Anticarcinogenic mechanisms
1 . Anticarcinogenic mechanisms acting against chemical eancinogenic factors. These
include:
1) reactions of inactivation of carcinogens: a) oxidation using nonspecific oxidases of
microsomes; b) reduction using microsome reductases; 3) demethylation - enzymatic nonenzymatic; D) conjugation with glucuronic acid or sulfuric acid using enzymes.
2) elimination of exo- and endogenous carcinogenic agents from the body in the bile
, feces, urine.
3) pinocytosis phagocytosis of carcinogenic agents, accompanied by their
neutralization; 5) the formation of antibodies against carcinogens such as
haptens;
5) inhibition of free radicals by antioxidants.
2 . Anticarcinogenic mechanisms against biological etiological factors
–Oncogenic viruses:
1 ) inhibition of oncogenic viruses by interferons; 2)
neutralization of oncogenic viruses with specific antibodies.
3 . Anticarcinogenic mechanisms acting against physical carcinogenic factors - ionizing
radiation. The main among them are the reactions of inhibition of the formation and
inactivation of free radicals.
Anti-transformation mechanisms
They inhibit the transformation of a normal cell into a tumor one. These include: 1)
anti-uting mechanisms, which are a function of cellular enzyme systems of DNA repair,
eliminating damage, DNA errors.
2 ) anti-oncogenic mechanisms, which are the function of special cellular genes antagonists of oncogenes. Their action is reduced to suppressing cell multiplication and
stimulating their differentiation.
Anticellular mechanisms
These mechanisms are activated from the moment of formation of the first blastoma cells
and are aimed at inhibiting and destroying individual tumor cells and tumors in general.
There are 2 groups of mechanisms:
1) immunogenic functions of the immune system, which carries out immunological supervision
over the constancy of the normal antigenic composition of tissues and organs of the body.
They are divided into specific and nonspecific
-Specific immunogenic mechanisms. These include cytotoxic effects
, growth inhibition and destruction of tumor cells by specific antibodies: immune
T-lymphocytes - killers; k-lymphocytes and macrophages possessing fc-receptors for
immunoglobulins and due to this showing affinity and cytotoxicity for tumor cells coated
with IgG.
-Nonspecific immunogenic mechanisms. These include nonspecific cytotoxic effects, growth
inhibition and lysis of tumor cells.
2 . Non-immunogenic anti-cellulary factors and mechanisms. These include: 1) necrosis
factor of opholes; 2) interleukin-1; 3) allogeneic
braking;
4)
keylon
inhibition; 5) carcinolysis; 6) contact inhibition; 7) mabrocytosis; 8) the regulating
effect of hormones.
75. Provide data on the interaction of tumors and the body (systemic effect of a tumor on the body).
Tumor cachexia.
Kakhekia - a syndrome of exhaustion and general weakness of the body. Cachexia
accompanying the development of malignant tumors is called cancerous.
The development of cancerous cachexia is caused by: 1) violation of the neuro-endocrine
regulation of metabolism;
2) Strengthening the formation of ATP due to glycolysis, which increases the consumption
of energy production substrates;
3) inhibition of lipoprotein lipase, which catalyzes the accumulation of lipids in
the body; 4) a decrease in the synthesis of RNA, providing the synthesis of
proteins and differentiation of adipocytes; 5) the formation of a special protein
"cachectin";
6) a decrease in the synthesis of the enzyme catalase, which contributes to the
accumulation of excess products of free radical peroxidation;
7) concomitant tumor complications: pain, bleeding, impairment
functions gastrointestinal system; the phenomenon of
trapping substrates from the blood by the tumor.
Cachexia can be observed not only in malignant, but also in some benign tumors with their
specific localization: in the gastrointestinal tract, brain, in the region of trophic
nerves.
The emergence and development of a tumor in the body is not a completely autonomous
process. The very fact of transformation of a normal cell into a tumor cell and further
growth is the body's response to the action of various factors.
The interaction of a tumor in the body is carried out with the participation of all
physiological systems
- nervous, endocrine, IBN, blood circulation.
The result of the interaction between the tumor and the body can be different:
- the death of blastoma cells. is observed most often. In the body, in addition to various
mutant cells, tumor cells are also formed, but they are immediately detected and destroyed
with the participation of IBN factors.
There are 2 types of tumor effects on the body: local and general. Local
effects are characterized by:
-Invasive growth, combined with compression and destruction of the surrounding normal
tissue
, violation of microhemo- and lymphocirculation, the development of tissue or organ
failure.
- Formation and release into the intercellular fluid of metabolites with the properties
of biologically active substances, capable of causing organ dysfunction.
-Suppression of the activity of local factors of the system of IBN-phagocytic cells
, lymphocytes, lysozyme, IFN, which contributes to the progression of tumor growth, as
well as the development of inflammation.
Systemic the influence of neoplasms is manifested by the development of a number of
general nonspecific syndromes. They are called paraneoplastic. The most significant
paraneoplastic syndromes include cachexia, immunopathological conditions.
76. Describe the typical forms of neurogenic sensitivity disorders, their types and pathogenesis. Give typical
formsneurogenic movement disorders, their types and pathogenesis. Describe the disturbances in the
formation of pain
Depending on the type of impaired sensitivity and the location of the sensitive
the nerve endings are distinguished:
- contact types (e.g. disorders
tactile, painful,
temperature sensitivity).
- distant types (e.g. disorders of peripheral
department visual, auditory, olfactory analyzers).
Violation of exteroceptive sensitivity (eg, due to damage to sensitive nerve endings of
the skin and mucous membranes).
Interoceptor sensitivity disorder (e.g. due to
defeat visceroceptors, proprioceptors).
Depending on the impairment of perception of the intensity of sensation
highlighted asthesia, hypesthesia,
hypersthesia.
Hypoesthesia - reduction, anesthesia - complete loss of sensitivity or individual
her varieties.
Types of hypesthesia, anesthesia.
Describe the disturbances in the formation of pain
Pain is a special type of sensitivity that forms under the influence of a pathogenic
irritant. It is characterized by subjectively unpleasant sensations, as well as
significant changes in the body, up to disturbances in its vital functions and even
death.
The meaning of pain
Any pain has a signaling and pathogenic meaning.
o
Signal meaning of pain. The sensation of pain is caused by a variety of agents, but
they are united by a common property - a real or potential danger of damaging the body.
In this regard, the pain signal provides mobilization of the body for protection against
the pathogenic agent and protective limitation of the function of the organ affected by
the pain.
o The pathogenic significance of pain. Pain is often the cause or component of the
pathogenesis of various diseases and painful conditions (for example, pain as a result
of trauma can cause shock and potentiate its development; pain with inflammation of the
nerve trunks causes an increase or decrease in blood pressure, impaired heart and kidney
function).
Distinguish between mechanisms of pain formation (nociceptive system) and mechanisms of
pain control (antinociceptive system).
Clinical syndromes
There are several major neuropathic pain syndromes: thalamic pain, phantom pain, and
causalgia. Neuropathic pain should be distinguished from somatic pain arising from damage
to the skin, muscles, internal organs, and joints.
o
Thalamic pain (thalamic syndrome) develops when the nuclei of the thalamus are damaged
or when foci of pathological excitement are formed in them. Manifestations: transient
episodes of severe polytopic pain; pains are accompanied by autonomic, motor and
psychoemotional disorders.
o
Phantom pain develops when the central ends of the nerves cut during amputation are
irritated. Manifestations: pain in a missing part of the body; the intensity of painful
sensations ranges from severe itching and burning to excruciating, intolerable
sensations.
o
Causalgia is caused by a pathological increase in the sensitivity of nociceptors and
the formation of a focus of increased excitation in various areas of the pain impulse.
Manifestations: burning pain in the area of damaged nerve trunks, which is provoked or
intensified by various influences (touch, heat, cold).
77. Describe the main forms of endocrine disorders, their causes and mechanisms.
Endocrine disorders can occur when the function of any link in this system is impaired, from the cerebral
cortex to post-receptor processes in target cells.
There are 3 main pathogenetic variants of endocrinopathies:
1) violations of the central regulation of the functions of peripheral endocrine glands. 2)
primary disorders of hormone formation in the peripheral glands
3) extra-glandular disorders (transport, activity, hormone reception and post-receptor processes).
The etiological factors causing these disorders are very numerous.
and varied.
Central regulation disorders.
Of the pituitary-dependent glands, such regulation includes the cerebral cortex, subcortical structures and
the anterior lobe of the pituitary gland in its part that produces tropic hubbubs.
The pituitary - independent glands lack the tropic hormonal instance.
Violation of the regulatory function of the cerebral cortex, leading to endocrine disorders, can be caused
by mechanical damage, inflammatory processes, circulatory disorders.However, such effects affect not
only the cerebral cortex, but also its other parts. Much more specific to
of cortical genesis of endocrine disorders are functional disorders of higher nervous activity in the form of
psychoses, neuropsychic stress conditions of various kinds. Such conditions often lead to dysfunctions of
the gonads, thyroid gland and other endocrinopathies. In this case, primary cortical disorders are realized
through the involvement of the limbic system and hypothalamic centers.
The causes of such disorders can also be hemorrhages, tumors, infectious processes in the hypothalamus
itself, infectious-toxic damage to it, exo- and endogenous non-infectious intoxication. Violations of
hypothalamic regulation can manifest in offspring in cases where the mother has suffered an infectious
disease or was intoxicated during pregnancy. Hereditary predisposition may be of some importance.
All of the above applies to the pituitary gland as a producer of tropic hormones.
Disorders of neuroendocrine regulation at the level of the hypothalamus and pituitary gland can be
expressed in insufficient or excessive production of liberins, statins, tropic hormones and corresponding
dysfunctions of the peripheral endocrine glands.
2. Primary dysfunctions of peripheral endocrine glands. Various pathological processes can develop in the
gland itself and lead to a violation formation and secretion of the corresponding hormones.
Infections occupy an important place among the causes of damage to the peripheral endocrine glands.
that can be localized in various or specific glands and gradually destroy
Tumors that can develop in any gland are a common cause of glandular damage. The nature of
endocrine disorders in this case depends on the nature of the tumor.
Endocrine disorders can be caused by congenital defects in the development of the glands or their atrophy,
which can be caused by various reasons: sclerotic process, chronic inflammation, age-related involution,
hormone-active tumor of the paired gland, long-term treatment with exogenous hormones. Damage and
atrophy of the gland can be based on autoimmune processes. In some cases, autoimmune processes can
also cause overproduction of hormones.
The formation of hormones can be disrupted due to hereditary defects in enzymes necessary for synthesis,
or inactivation of these enzymes. It is also possible the formation of abnormal forms of hormones in the
gland. Such hormones have inadequate activity or are completely devoid of it. In some cases, the
intraglandular transformation of the prohormone into a hormone is disrupted, and therefore inactive forms
of it enter the bloodstream. The reason for the violation of the biosynthesis of hormones can be a deficiency
of specific substrates that make up their composition.
One of the causes of endocrine disorders may be the depletion of hormone biosynthesis as a result of
prolonged stimulation of the gland and its hyperfunction. Extraglandular forms of endocrine disorders.
The causes of such disorders can be disorders of the binding of hormones to proteins at the stage of their
transport to target cells, inactivation or destruction of the circulating hormone
, disturbances in the reception of hormones, disturbances in the metabolism of hormones, disturbances in
permissive mechanisms.
With a weakening or excessive increase in the ability of plasma proteins to bind hormones, the fraction of
the free, active hormone and its effects in target cells can change accordingly inadequately. In some cases,
liver damage may be the cause of insufficient hormone binding. Inactivation of hormones is associated
with the formation of antibodies to them.
78. Describe the etiology and pathogenesis of gigantism, acromegaly, pituitary dwarfism...
Pituitary gigantism.
Excessive secretion of growth hormone in the early stages of development of the body leads
to pituitary gigantism.
The main manifestation of the disease is increased growth that goes beyond the highest standards for a
given age, gender, race. Along with the rapid elongation of the tubular bones, there is an increased growth
of soft tissues and internal organs. There are no gross imbalances in the physique. However, the forearms
and legs, head relatively small, with an elongated face; the muscular system is well developed at first, but
later muscle weakness occurs
, rapid fatigue, sometimes hypotrophy. In some cases, the size of the internal organs is disproportionately
large, in others they lag behind the growth of the body, and their relative functional failure occurs. In
most cases, hyperglycemia is observed, it may develop. stages of infertility. Often there are various
abnormalities in the mental sphere: decreased intelligence, infantilism, sleep disturbance,
hypochondriacal and depressive syndromes.
The etiology of gigantism is based on tumor processes and hyperplasia of eosinophilic PDH cells associated
with excessive stimulating effects of the hypothalamus. Hereditary predisposition, infectious diseases,
transferred in childhood, are of certain importance.
Acromegaly.
Excessive production of growth hormone in adults leads to the development of this disease.
, which is characterized by the resumption of periosteal bone growth, resulting in their thickening and
deformation. Characterized by: disfiguring enlargement of facial features, enlargement of the dital parts of
the extremities. The bones of the skull thicken, the superciliary and zygomatic arches protrude, the jaws
protrude forward. The nose, lips, ears, tongue are enlarged, the voice coarsens, trophic disorders of the skin
occur. Acromegaly is accompanied by persistent hyperglycemia. characterized by numerous subjective
symptoms: headache, weakness, drowsiness, joint pain, decreased visual acuity, sexual disorders. The
etiology of acromegaly is, in principle, the same as that of gigantism.
Pituitary dwarfism or nanism...
This disease is characterized by a sharp growth retardation, as well as sexual underdevelopment as a
result of insufficient formation of somatotropin and gonadotropins, which occurs already at the stage of
intrauterine development. The body weight of newborns is usually much lower than the lower limit of
the norm; in the future, the lag in growth and weight progresses, and physical development is early
stops.
A dwarf is considered to be below 130 cm.
Dwarfism is usually not accompanied by gross violations of the physique. The predominance of
the length of the body over the length of the limbs is characteristic. Morphinous dico is
characteristic.
There is an underdevelopment of the reproductive system: the genital glands, genitals and secondary sexual
characteristics, leading to infertility. There are no significant disorders in mental development, sometimes
there is some infantile behavior, a decrease in memory and mental performance.
Many pathogenic influences and pathological processes can act as reasons.
79. Describe the etiology, pathogenesis, manifestations of the disease and Itsenko-Cushing's syndrome.
Itsnko-Cushing's disease.
Central hypercortisolism is represented by Itsenko-Cushing's disease.
As the cause of this disease, a hormone-producing tumor of the anterior pituitary gland
- basophilic adenoma was identified. Later it was found that the disease is associated
not only with the tumor but also with the excessive production of corticotropin-activating
factor. An excess of this factor leads to increased formation of ACTH by basophilic cells
of the anterior pituitary gland, excessive stimulation of the fascicular and reticular
zones of PN, and bilateral hyperplasia of these glands. The main manifestations of the
disease are associated with hyperproduction of glucocorticoids, and the excessive
formation of androgens and mineralocorticoids is also important.
Manifestations of the disease.
The disease is most often seen in young and middle-aged women.
Symptoms of the disease are very diverse. Of the nonspecific symptoms, patients are
worried about general malaise, weakness, fatigue, headache, pain in the legs, back,
drowsiness, thirst.
The patient's appearance is very characteristic: a round, moon-shaped face, crimson-red,
moderate hypertrichosis, dysplastic obesity with fat deposition in the face, neck, upper
half of the body with disproportionately thin limbs. Characterized by purple-red, purple
stretching stripes on the skin of the abdomen, shoulders, mammary glands.
Osteoporosis - damage to the protein matrix of bones with secondary demineralization,
leading to fractures of the vertebrae and ribs is often detected.
The sss suffers significantly. Persistent arterial hypertension develops with secondary
disorders: cerebral circulation disorders, retinopathy, wrinkled kidney, overload form
of heart failure. In addition, with I-K disease, there is a decreased glucose tolerance,
hyperglycemia, SD. Often there is a decrease in resistance to infectious diseases,
pustular skin lesions, urinary tract infections. There are disorders of the blood
coagulation system, bleeding, thromboembolism, lymphopenia, eosinopenia, erythrocytosis
are found in the peripheral blood.
Often there are various disorders in the genital area, neurological and neuropsychic
status.
80. Describe the etiology, pathogenesis and manifestation of acute chronic
adrenal failure. Addison's disease.
Acute adrenal insufficiency.
May occur with bilateral coarse injury to the NP cortex as a result of injury
, hemorrhage associated with birth trauma, general capillaropathy or inadequate use of
anticoagulants, with vascular thrombosis, disseminated intravascular coagulation
syndrome, severe infections. Removal of the NP affected by the hormonally active tumor
can also lead to acute insufficiency due to atrophy of the paired NP.
In the absence of effective treatment, progressive muscle weakness, severe arterial
hypotension, dyspeptic symptoms develop rapidly, and death occurs from acute circulatory
failure.
Chronic insufficiency (Addison's disease)...
May be associated with bilateral tuberculous process, tumor metastases
, toxic lesions of the NP, amyloidosis. Idiopathic hypocorticalisms caused by atrophy of
autoimmune NPs are common.
Partial forms of hypocorticism are usually associated with enzyme defects.
Secondary forms of adrenal cortex insufficiency can be caused by ACTH deficiency due to
damage to the adenohypophysis or hypothalamus.
Chronic hypocorticism is manifested by asthenization, apathy, a decrease
performance, muscle weakness, arterial hypotension, anorexia, weight loss. Polyuria is
often observed in combination with renal failure. Peripheral hypocorticism is accompanied
by pigmentation of the skin and mucous membranes associated with an increase in ACTH.
Depending on the treatment and the cause, chronic forms of NP can last for a long time
or turn into an acute form. The manifestations of total hypocorticism are based on the
insufficiency of the effects of all hormones of the NP.
Muscle weakness is associated with electrolyte imbalance and hypoglycemia, as well as
decreased muscle mass. Arterial hypotension is associated with hyponatremia
, loss of the permissive effect of HA and, as a result, a decrease in the reactive
properties of the vascular wall to pressor influences.
The loss of sodium is accompanied by polyuria, hypohydration, and blood clots. Digestive
disorders are associated with insufficient secretion of digestive juices and intense
release of sodium ions by the intestinal mucosa, which leads to profuse diarrhea, promotes
hypohydration.
81.
Give the classification of thyroid dysfunction. Describe the etiology, pathogenesis and manifestations of
congenital myxedema, endemic cretinism, myxedema in adults.
Myxedema - a severe form of hypothyroidism, which usually develops in adults and adolescents. A characteristic feature of
myxedema is mucous edema of the skin and subcutaneous tissue, in which there is no fossa when pressed.
Causes and mechanism of myxedema occurrence:
an increase in the hydrophilicity of connective tissue due to the accumulation of glucuronic and chondroitinsulfuric acids in it, as well as
sodium ions, due to a decrease in the production of atrial sodium uretic factor;
enhancement of the effects of ADH in conditions of a decrease in the concentration of T3 and T4 in blood plasma;
binding of a large amount of fluid to a tissue colloid containing an excess of glycosaminoglycans and sodium ions, with the formation of
mucin.
Manifestations: in adults - Myxedema
Specific edema, which is caused by a violation of the exchange of hyaluronic and chondroitinsulfuric acids, mucin. Characterized by an
increase in body weight, hair loss, brittle nails, dysfunction of the gastrointestinal tract, genital organs, hypothermia, bradycardia,
hypotension, depressive conditions. The face is puffy with poor facial expressions, thickened nose and lips.
- severe bradycardia;
- arterial hypotension, collapse;
- respiratory failure;
- renal failure;
- hypothermia;
- oppression of consciousness;
- atrophic gastritis;
- myxedema;
- myopathy;
- growth retardation.
Cretinism develops with a mild or moderate course of hypothyroidism. Distinguish between sporadic (congenital) and endemic
cretinism (endemic goiter).
In children - Cretinism
Manifestations:
- small growth (dwarfism);
- rough facial features;
- macroglossia;
- wide, flat ("square") nose with a sinking back;
- hypertelorism;
- large belly (development of an umbilical hernia is possible);
- delay in changing teeth;
- prolonged non-closure of fontanelles;
- violation of mental development up to idiocy.
I.
Hypothyroidism - a condition caused by insufficient secretion of thyroid hormones by the thyroid gland.
Primary hypothyroidism (90% of cases of hypothyroidism) develops with damage to the thyroid gland and is accompanied by an increase in TSH levels.
Secondary hypothyroidism develops when the hypothalamic-pituitary system is damaged with insufficient release of thyroliberin and TSH and a subsequent
decrease in the functions of the thyroid gland.
Primary hypothyroidism:
The Wolf-Chaikoff phenomenon - hypothyroidism caused by the introduction of iodine preparations into the body (usually in a large dose). It is observed in
patients with hyperthyroidism (for example, with Hashimoto's thyroiditis, diffuse toxic goiter), as well as in children whose mothers took iodine preparations
during pregnancy.
Development mechanism:
•
•
Suppression of the oxidation of iodides into their more reactive form due to the inhibition of the activity of iodide peroxidase.
Inhibition of the binding of iodide to tyrosyl residues in the thyroglobulin molecule and, as a consequence, the formation of mono- and
diiodotyrosine.
•
Inhibition of oxidative condensation of mono- and diiodotyrosine into tri- and tetraiodothyronine due to inhibition of iodide peroxidase activity.
•
Decrease in the intensity of thyroglobulin hydrolysis in thyrocytes as a result of suppression of the kinetic properties of proteases and peptidases.
Secondary hypothyroidism:
The reasons:
•
•
•
Hypopituitarism of various origins (for the development of hypothyroidism, a decrease in TSH secretion is essential).
Hypothalamic hypothyroidism. The main reason: defects in the synthesis, transport or interaction of thyroliberin with its receptors.
Postglandular hypothyroidism. Main reasons:
o
Inactivation of T circulating in the blood3 and Tfour, TTG
o
Low tissue sensitivity to thyroid hormones
o
Formation of hormone-inactive rТ3
Clinical forms:
Chronic autoimmune thyroiditis (Hashimoto's disease) is the most common clinical form of hypothyroidism. Other forms include cretinism, myxedema,
hypothyroid (myxedema) coma, and manifestations of hypothyroidism in autoimmune polyglandular syndrome.
Cretinism:
1. congenital form
2. endemic goiter.
The reasons: iodine deficiency in water, food, excess TSH production.
Pathogenesis: T3 and T4 deficiency.
Manifestations: goiter, deafness, dumbness, retention of physical development, short stature, large belly, impaired mental development.
Myxedema - a severe form of hypothyroidism, which usually develops in adults and adolescents.
A characteristic feature of myxedema is mucous edema of the skin and subcutaneous tissue, in which there is no fossa when pressed.
Pathogenesis - insufficiency of the effects of thyroid hormones, more often as a result of primary hypothyroidism
Manifestations:
•
Nervous system: Lack of effects of thyroid hormones inhibits the differentiation of nerve structures and GNI, especially in children. In this regard,
develop: Hypothyroid encephalopathy. It is characterized by a decrease in intelligence, mental activity, slowing down of thinking and speech;
Paresthesias.
•
CCC: bradycardia, cardiomegaly, dwarfism, impaired microcirculation in tissues.
•
Gastrointestinal tract: decreased appetite, nausea, indigestion - gastritis, hypotension.
•
Kidney: decreased excretory function, urinary tract infection.
•
Skin: swelling of the face, brittle hair, swelling of the vocal cords.
•
Musculoskeletal system: myopathy, joint damage.
Hypothyroid (myxedema) coma - an extremely severe, often fatal manifestation of hypothyroidism. It is the final stage of any type of hypothyroidism if it is not
treated correctly or not.
Provoking factors: hypothermia, circulatory failure of any genesis, acute infections (flu, pneumonia, meningitis), intoxication, bleeding, respiratory failure, chronic
anemia, heart failure).
Manifestations:
82.
Describe the etiology, pathogenesis and manifestations of diffuse toxic and nodular hyperthyroid
goiter.
Diffuse toxic goiter (DTZ, Graves' disease, Graves' goiter, Graves' disease) is the most common thyroid disease resulting from
increased production of thyroid hormones. In this case, as a rule, there is a diffuse increase in its size.
The disease is more common among the urban population between the ages of 20 and 50, mainly in women.
Etiology and pathogenesis of the disease
Currently, diffuse toxic goiter is considered as a hereditary autoimmune disease that is transmitted by a multifactorial (polygenic)
pathway. Factors provoking the development of the disease: mental trauma, infectious and inflammatory diseases, craniocerebral
trauma, diseases of the nasopharynx.
The pathogenesis of DTG is due to a hereditary defect, apparently, a deficiency of T-lymphocyte suppressors, which leads to
the mutation of prohibited clones of T-lymphocyte helpers. Immunocompetent T-lymphocytes, reacting with thyroid
autoantigens, stimulate the formation of autoantibodies. The peculiarity of immune processes in diffuse
toxic goiter is that autoantibodies have a stimulating effect on cells, lead to hyperfunction and hypertrophy of the gland, while in
other autoimmune diseases autoantibodies have a blocking effect or bind an antigen. Sensitized B-lymphocytes under the action
of the corresponding antigens form
specific immunoglobulins that stimulate the thyroid gland and mimic the action of TSH. They are collectively called TSI. The
suspected cause of the secretion of immunoglobulins is a deficiency or decrease
functional activity of T-suppressors. TSIs are not strictly specific for diffuse toxic goiter. These antibodies were found in patients
with subacute thyroiditis, Hashimoto's thyroiditis. Along with TSI antibodies to the receptor of the cytoplasmic membranes of
thyrocytes (possibly the TSH receptor), antibodies to other thyroid antigens (to thyroglobulin, the second colloidal component,
microsomal fraction, nuclear component). A higher frequency of detecting antibodies to the microsomal fraction is
observed in patients who received iodine preparations. Given the fact that it is they who provide
the damaging effect on the follicular epithelium of the thyroid gland can be explained by the development of the Jod-Basedow
syndrome (iodobazedov) with prolonged use of iodine preparations in patients with diffuse toxic goiter or endemic goiter.
Damage to the follicular epithelium leads to massive flow into the bloodstream
thyroid hormones and the identification of the clinical picture of thyrotoxicosis or its exacerbation after the previous
remission while taking iodine preparations. Based on the clinical picture, iodine Graves 'disease does not differ from the real
Graves' disease. A hallmark of iodine-induced hyperthyroidism is the absence or low uptake of iodine isotopes by the thyroid gland.
Previously, it was believed that hyperthyroidism develops with an increase in the production of thyroid-stimulating hormone. It
turned out that the level of TSH in this disease is not changed or is often reduced due to the suppression of the function of the
pituitary gland by high concentrations of thyroid hormones. In rare cases, there are patients with TSH-producing pituitary
adenoma, while the plasma TSH content is significantly increased, not
there is a reaction of TSH to TRH. In some forms of the disease, an increased content of TSH and thyroid hormones in
the blood is simultaneously detected. It is believed that there is a partial resistance of thyrotrophs to thyroid hormones,
as a result of which the symptoms of thyrotoxicosis develop.
Diffuse toxic goiter is characterized by a triad - hyperthyroidism, goiter and exophthalmos (bulging eyes).
Due to the fact that thyroid hormones have many physiological functions, the disease has a variety of clinical
manifestations, namely:
•
Cardiac: arrhythmia (especially atrial fibrillation), tachycardia (rapid heartbeat), extrasystole, systolic arterial
hypertension, increased pulse pressure (the difference between systolic and diastolic pressure), chronic heart failure
from
peripheral edema, ascites, anasarka...
•
Endocrine: weight loss, weight loss despite increased appetite, heat intolerance, increased BX... In premenopausal
women, there may be a decrease in the number and frequency of menstruation (oligomenorrhea) up to complete
amenorrhea.
•
Dermatological: increased sweating, thyroid acropachia (specific changes
nails), onycholysis(destruction of nails), erythema, edema on the legs (pretibial myxedema in 3-5% of patients with
Graves' disease, should not be confused with myxedema in hypothyroidism).
•
Neurological: tremor (especially noticeable with arms outstretched), weakness, headache, proximalmyopathy
(difficulty getting up from a chair or squatting), restlessness, anxiety, insomnia, overactive tendon reflexes.
•
Gastrointestinal: diarrhea (diarrhea) often, nausea and vomiting (relatively rare).
•
Ophthalmic: the so-called "thyroid eye disease", characteristic of Basedow's disease, includes the following symptoms: lifting
of the upper eyelid, drooping (gaping) of the lower eyelid, incomplete closing of the eyelids (Graefe symptom), exophthalmos
(bulging eyes), periorbital edema and periorbital tissue overgrowth. Defects in visual fields and increased intraocular pressure,
pain in the eyes and even complete blindness can be the result of compression by edematous periorbital tissues of the optic
nerve or eyeball. The patient may also complain of dry and gritty eyes or chronic conjunctivitis due to incomplete eyelid
closure.
•
Dental: plural caries, periodontal disease (seldom).
•
Particular danger to life is thyrotoxic crisis...
Nodular goiter - a collective clinical concept[one], uniting all separate entities in thyroid iron, differing in morphological
characteristics from the rest of the tissue. The term "node" in clinical practice is understood as a neoplasm in the thyroid gland of
any size, which can have a capsule and is determined by palpation or using methods of visual examination. Currently allocated:
endemic nodular
goiter (caused by iodine deficiency); solitary nodular goiter (single node); multinodular goiter (large number
nodes); conglomerate nodular goiter (nodules are interconnected. Thyroid nodules are found in 4% of the US population, while the
identificationthyroid cancer reaches 40: 1,000,000 per year, and mortality - 6: 1,000,000 per year...[2]...
According to autopsy and ultrasonography, up to 50% of the world's population have thyroid nodules. Benign neoplasms are
found 6-8 times more often among women, and malignant (from 5 to 10% of all cases of nodular goiter) are found equally often,
regardless of gender.[3]...
Pathogenesis
With tumors of the thyroid gland, an active proliferation of the pool of tumor cells occurs, gradually forming a node. Follicular
adenoma is a benign tumor from the follicular epithelium, often originating from A-cells. Among follicular adenomas, trabecular
(embryonic), microfollicular (fetal), macrofollicular (simple) are distinguished. Less commonly, an adenoma originates from B cells
(oncocytoma). The pathological significance of follicular adenoma when it reaches a large size is limited by the potential for the
development of compression syndrome. It cannot undergo malignant transformation, but nevertheless the indications for surgical
treatment are determined by the complexity of differential diagnosis with highly differentiated thyroid cancer.
Most nodes over 1 cm in diameter are usually palpable or visible. The knots can be tight, and the large knots sometimes interfere
with swallowing, are squeezed by clothing, they can be soldered to the surrounding tissues, or squeeze the surrounding internal
organs. Usually, the function of the thyroid gland is not impaired, although there are deviations towards hypo- or hyperthyroidism.
Pain is usually associated with rapid enlargement of the node, inflammation, or hemorrhage[3]...
The disease develops more often in women aged 50-60 years, living for a long time in conditions of natural iodine deficiency and
suffering from multinodular euthyroid goiter. The causes of the disease are not fully understood. The clinical symptoms of
multinodular toxic goiter are similar to the symptoms of the above diseases occurring with thyrotoxicosis syndrome.
Ophthalmopathy and pretibial myxedema are absent. On physical examination, several nodes are determined, as a rule, of a
rounded shape, forming a single conglomerate or not connected with each other, with a smooth surface, clear contours, displaced
when swallowing with the thyroid gland. The ultrasound picture is consistent with the physical examination data. Sometimes
ultrasound reveals additional non-palpable nodules. The contours of the nodes are clear, the structure is homogeneous,
echogenicity, generally higher compared to extranodular thyroid tissue. On the basis of radionuclide scanning, three forms of
multinodular lesions of the thyroid gland occurring with thyrotoxicosis syndrome are distinguished: multinodular goiter with
hyperfunctioning nodes and non-functioning extranodular parenchyma (60-80%); multinodular goiter with non-functioning nodes
and hyperfunctioning extranodular parenchyma (10-20%); multinodular goiter, in which both the nodes and the extranodular
parenchyma are simultaneously hyperfunctioning (3-5%). Fine needle aspiration biopsy and cytology should be performed to rule
out thyroid cancer. For this purpose, each node and the extranodular parenchyma of both lobes of the thyroid gland are
punctured. On the basis of radionuclide scanning, three forms of multinodular lesions of the thyroid gland occurring with
thyrotoxicosis syndrome are distinguished: multinodular goiter with hyperfunctioning nodes and non-functioning extranodular
parenchyma (60-80%); multinodular goiter with non-functioning nodes and hyperfunctioning extranodular parenchyma (10-20%);
multinodular goiter, in which both the nodes and the extranodular parenchyma are simultaneously hyperfunctioning (3-5%). Fine
needle aspiration biopsy and cytology should be performed to rule out thyroid cancer. For this purpose, each node and the
extranodular parenchyma of both lobes of the thyroid gland are punctured. On the basis of radionuclide scanning, three forms of
multinodular lesions of the thyroid gland occurring with thyrotoxicosis syndrome are distinguished: multinodular goiter with
hyperfunctioning nodes and non-functioning extranodular parenchyma (60-80%); multinodular goiter with non-functioning nodes
and hyperfunctioning extranodular parenchyma (10-20%); multinodular goiter, in which both the nodes and the extranodular
parenchyma are simultaneously hyperfunctioning (3-5%). Fine needle aspiration biopsy and cytology should be performed to rule
out thyroid cancer. For this purpose, each node and the extranodular parenchyma of both lobes of the thyroid gland are
punctured. multinodular goiter with hyperfunctioning nodes and non-functioning extranodular parenchyma (60-80%); multinodular
goiter with non-functioning nodes and hyperfunctioning extranodular parenchyma (10-20%); multinodular goiter, in which both the
nodes and the extranodular parenchyma are simultaneously hyperfunctioning (3-5%). Fine needle aspiration biopsy and cytology
should be performed to rule out thyroid cancer. For this purpose, each node and the extranodular parenchyma of both lobes of the
thyroid gland are punctured. multinodular goiter with hyperfunctioning nodes and non-functioning extranodular parenchyma (6080%); multinodular goiter with non-functioning nodes and hyperfunctioning extranodular parenchyma (10-20%); multinodular
goiter, in which both the nodes and the extranodular parenchyma are simultaneously hyperfunctioning (3-5%). Fine needle
aspiration biopsy and cytology should be performed to rule out thyroid cancer. For this purpose, each node and the extranodular
parenchyma of both lobes of the thyroid gland are punctured. Fine needle aspiration biopsy and cytology should be performed to
rule out thyroid cancer. For this purpose, each node and the extranodular parenchyma of both lobes of the thyroid gland are
punctured. Fine needle aspiration biopsy and cytology should be performed to rule out thyroid cancer. For this purpose, each
node and the extranodular parenchyma of both lobes of the thyroid gland are punctured.
83.
Provide information about the etiology, pathogenesis and manifestations of hyper- and hypofunction of the
parathyroid glands.
IMPAIRMENT OF THE FUNCTIONS OF THE PARTHYROID GLANDS
The parathyroid glands are located on the back of the thyroid gland under its capsule. Function of the glands - synthesis and secretion
parathyrocrine (PTH). PTH, together with calcitonin and catacalcin, as well as vitamin D, regulates calcium and phosphate metabolism. Various diseases
caused by changes in the level or effects of PTH can be considered as being referred to as hyperparathyroid (hyperparathyroidism) or hypoparathyroid
(hypoparathyroidism) conditions.
Hyperparathyroidism characterized by an increase in serum parathyrocrine (PTH) levels and / or an increase in the effects of PTH. Distinguish between
primary (glandular), secondary (hypercalcemic) and tertiary hyperparathyroidism, as well as pseudohyperparathyroidism.
Primary hyperparathyroidism - pathology of the parathyroid glands themselves.
The reasons: autonomously functioning adenoma, primary glandular hyperplasia, parathyroid carcinoma.
Secondary hyperparathyroidism caused by prolonged hypocalcemia, as a rule, in combination with hyperphosphatemia and the secondary development of
hyperfunction and hyperplasia of the parathyroid glands.
The reasons: kidney pathology (chronic renal failure); intestinal pathology (malabsorption syndrome, steatorrhea); bone pathology (osteomalacia).
Tertiary hyperparathyroidism
Cause: long-term secondary hyperparathyroidism. The latter leads to the development of adenomas (or adenomas), which acquire the property of autonomous
functioning and hyperproduction of PTH. Under these conditions, the inverse relationship between the level of Ca2 + in the blood and the secretion of PTH is
destroyed.
Pseudohyperparathyroidism - overproduction of PTH by ectopic tumors.
It is observed in familial polyendocrine adenomatosis and paraneoplastic syndromes.
Hyperparathyroidism manifestations:
1. Nephropathies (polyuria, secondary polydipsia, nephro- and urolithiasis)
2. Neuromyopathy (myasthenia gravis, myalgia);
3. Gastrointestinal disorders (ulcer, impaired appetite, gastritis)
4. Osteopathies (osteoporosis, bone fractures, deformity)
5. Disorders of higher nervous activity (psychasthenia, depression, sleep disturbance)
6. CV disorders (HF, arterial hypertension, mitral stenosis).
Hypoparathyroid conditions (hypoparathyroidism, hypoparathyroidism, insufficiency of the parathyroid glands) are characterized by a decrease in blood levels and
/ or the severity of the effects of PTH in the body.
Distinguish between glandular and extraglandular hypoparathyroidism (pseudohypoparathyroidism).
Primary (glandular) hypoparathyroidism caused by the absence, damage or removal of the parathyroid glands.
The reasons: 1. congenital absence of glands; 2. immune autoaggression; 3. surgical removal; 4. violation of blood circulation; 5. damage by physical, chemical
factors.
Extraglandular (peripheral) hypoparathyroidism also called pseudohypoparathyroidism. Pseudohypoparathyroidism (eg, Albright's disease)
— an inherited disease characterized by resistance of target organs to PTH.
Manifestations of hypoparathyroidism:
1.
2.
3.
4.
5.
6.
7.
8.
cataract;
hypocalcemia, hyperphosphatemia;
increased neuromuscular excitability;
tetanus;
muscle cramps;
neuropsychiatric disorders;
breathing disorders;
violation of urination;
9. LCD disorders.
Manifestations of
hypoparathyroidism
•
•
•
•
•
•
•
•
•
•
•
84.
Hypocalcemia, usually associated with hyperphosphatemia. Reasons: impaired absorption of Ca2 + in the intestine, inhibition of Ca2 +
mobilization from bones, a decrease in Ca2 + reabsorption in the kidney tubules.
Increased neuromuscular excitability: tetanus and convulsions.
Tetanus is a state of prolonged muscle tension, usually the flexors of the limbs, in severe cases, the muscles of the face.
Convulsions are an involuntary contraction of muscle groups, followed by their relaxation (clonic convulsions), or continuing for a long time
(tonic convulsions). They are accompanied by severe pain.
Disorders of the functions of organs, tissues and their physiological systems.
Neuropsychiatric disorders: increased nervous excitability (manifested by positive symptoms of Chvostek and Trousseau), mental disorders
(insomnia, depression, bouts of melancholy, development of neurotic states).
Circulatory disorders: disturbance of the central, organ-tissue and microcirculation due to changes in cardiac output, fluctuations in the tone of
arterioles, changes in the BCC.
Respiratory disorders: alveolar hypoventilation, sometimes asphyxia (with laryngospasm, bronchospasm).
Digestive disorders: swallowing disorders, pylorospasm, vomiting, abdominal pain, constipation, followed by diarrhea.
Violation of urination. Observed with spasm of the muscles of the bladder.
Cataract. It is caused by calcification of the lens with prolonged course of hypoparathyroidism.
Provide information about the etiology, pathogenesis and manifestations of dysfunctions of the gonads.
Typical forms of pathology caused by disorders of the endocrine function of the gonads are divided into three groups: disorders of sexual differentiation, disorders
of sexual development in girls and sexual function in women, violations of sexual development in boys and sexual function in men.
Disorders of female sexual development:
Premature puberty:
Puberty is considered premature if any of the secondary sexual characteristics appears in girls before 7.5 pet.
Distinguish between central (true puberty), peripheral (false puberty, pseudopubertal) and partial (incomplete) premature puberty.
True premature puberty:
The reasons: premature activation of the synthesis of gonadoliberin (with tumors of the diencephalic region), brain injuries; hyperproduction of gonadotropins by
the adenohypophysis.
Manifestations: Isosexuality of development: the complexity of development (acceleration of body growth, hair growth).
Premature pseudopubertal:
The reasons: autonomous excess synthesis of estrogen by the ovaries or adrenal glands.
Manifestations: 1. bivalence of sexual development - isosexual, heterosexual; violation of the harmony of the development of the body, incompleteness of
sexual development.
Delayed puberty
Delayed puberty is considered to be the absence of secondary sexual characteristics by the age of 14, as well as the absence of menstruation by the age of 16
(primary amenorrhea) in the presence of secondary sexual characteristics.
Views:
•
Primary hypogonadism (ovarian). It is a consequence of inherited, congenital or acquired ovarian failure.
•
Secondary hypogonadism (hypogonadotropic, extra-ovarian)... It is caused by a deficiency of gonadotropic hormones (FSH, LH) of a transient
(transient) or permanent (chronic) nature.
The reasons: 1. transient secondary hypogonadism (stress, chronic debilitating diseases; endocrinopathies) 2. chronic secondary hypogonadism.
Ovarian hypofunction:
•
•
Endocrine ovarian failure is divided into primary and secondary.
Primary ovarian failure (primary hypogonadism) - conditions caused by ovarian pathology and consisting in insufficient production of sex hormones by
them, as well as menstrual irregularities. In this regard, in the blood, as a rule, a compensatory increased level of FSH is found. Causes: the same as
primary hypogonadism, which causes delayed sexual development in girls.
•
Secondary failure (secondary, or extra-ovarian hypogonadism). It is the result of a deficiency of either the gonadoliberins of the hypothalamus or the
gonadotropic hormones of the adenohypophysis. Causes: the same as secondary hypogonadism.
Manifestations: menstrual irregularities, amenorrhea, infertility.
Ovarian hyperfunction:
Disorders of male sexual development:
Premature (primary) puberty - a condition characterized by the appearance of all or some of the secondary sexual characteristics in boys under 9 years of age.
1. True premature development;
2. False premature development.
Manifestations: are the result of an excess of male sex hormones in the body. This causes signs of virilization (the appearance of pubic and axillary hair growth,
coarsening of the voice, enlargement of the testicles and penis; short stature.
Delayed puberty
The absence of signs of puberty in boys by the age of 14 is considered delayed puberty.
The reasons:
1. Deficiency of gonadoliberins of the hypothalamus and / or gonadotropins of adenohypophysis
2. Decreased testosterone production by the testes
3. Reduced sensitivity of target tissues to the action of testosterone.
Manifestations:
Signs of eunuchoidism: decreased testosterone levels in the blood.
Male hypogonadism
The causes of testicular failure.
•
•
- The same as with delayed sexual development in boys.
- Testicular defects. (inherited or congenital (primary) - a decrease in androgen production and impaired spermatogenesis; acquired
(secondary) - with trauma, viral or bacterial inflammation).
DISORDERS OF THE ENDOCRINE
FUNCTION OF THE GENITAL GLAND
Typical forms of pathology caused by disorders of the endocrine function of the gonads are divided into three groups:
•
violations of sexual differentiation;
•
disorders of sexual development in girls and sexual function in women;
•
violations of sexual development in boys and sexual function in men.
Disorders of sexual development and sexual function in genetically female persons
Puberty (puberty) in girls begins between the ages of 8 and 13 and occurs within 3-4 years. The most significant signs of puberty include the growth and
development of mammary glands (thelarche), pubic and
axillary hair growth, the onset of menstruation (menarche) and the formation of a regular menstrual-ovarian cycle.
•
•
The development of the mammary glands (may be asymmetrical), as a rule, precedes the formation of pubic hair.
Menarche (beginning of menstrual function). Menstruation occurs at an average age of 12.5 years, and usually lasts 4-5 days. During the first
two years, your menstrual cycle may be irregular. 20% of girls do not ovulate until the age of 17-18.
The most common forms of puberty and sexual function disorders include premature puberty, delayed puberty, endocrine ovarian hypo- and hyperfunction.
PREMATURE MATURITY
Puberty is considered premature if any of the secondary sexual characteristics appears in girls before 7.5 years of age. Distinguish between central (true),
peripheral (false) and partial (incomplete) premature puberty.
TRUE PREMATURE PUBERTATE
Almost 90% of all cases of premature puberty are true (gonadotropin-dependent) puberty. In girls, it occurs much more often than in boys. This version of
puberty is called true because the body's puberty occurs, albeit prematurely, but according to the usual (as well as normal) scheme: activation of the
hypothalamus and synthesis of gonadoliberins, secretion of gonadotropic hormones, synthesis of sex hormones, the formation of secondary female sexual
characteristics.
The reasons:
•
Premature activation of the synthesis of gonadoliberin. It is observed when the diencephalic region is damaged.
•
Hyperproduction of gonadotropins by the adenohypophysis. It usually occurs with pituitary adenomas.
Manifestations:
•
•
Isosexuality of development of the body (i.e., compliance with the genetic and gonadal female sex).
Complexity ("harmony") of development (including the acceleration of body growth, thelarche, pubic and axillary hair growth, the
formation of other characteristic secondary sexual characteristics).
•
Completeness of development (characterized by menarche and premature onset of ovulation).
PREMATURE PSEUDOPUBERTATE
False premature sexual development is characterized by the acceleration of body growth, as with true premature sexual development. However,
pseudopubertal is always incomplete (no ovulation and menarche).
Cause: autonomous excess synthesis of estrogen in the ovaries or adrenal glands. It is caused, as a rule, by a hormonally active tumor of the ovary.
Manifestations: bivalence of sexual development (the possibility of isosexual or heterosexual development), violation of harmony and incompleteness of the sexual
development of the body.
•
Isosexual (coinciding with the genetic and gonadal female sex) occurs when excess estrogen is synthesized.
•
Heterosexual development (does not match genetic and gonadal sex). Girls develop secondary male sexual characteristics.
PARTIAL PREMATURE SEXUAL DEVELOPMENT
Incomplete premature sexual development is characterized by the early appearance of any one or individual secondary sexual characteristics in the absence of
others.
The reasons:
•
•
•
Premature onset of estrogen synthesis in the ovaries, usually in excess (causes premature thelarche).
Excessive formation of androgens in the adrenal cortex (leading to premature pubic and axillary hair growth).
Increased sensitivity of target cells to estrogens (eg, breast cells). The most common manifestations:
•
Telarhe (usually up to 2-4 years of age, less often after 6 years).
•
Premature growth of pubic and axillary hair.
DELAYED MATURITY
Delayed puberty is considered to be the absence of secondary sexual characteristics in girls by the age of 14, as well as the absence of menstruation by the age
of 16 in the presence of secondary sexual characteristics.
Distinguish between primary and secondary forms of hypogonadism.
Primary hypogonadism (ovarian, hypergonadotropic). It is a consequence of inherited, congenital or acquired ovarian failure.
Secondary hypogonadism (hypogonadotropic, extra-ovarian). It is caused by a deficiency of gonadotropic hormones (FSH, LH) of a transient (transient) or
permanent (chronic) nature.
The most common reasons are:
•
Prolonged states of stress.
•
Chronic debilitating diseases (for example, malabsorption syndrome, chronic myeloid leukemia, osteomyelitis, tuberculosis).
•
Endocrinopathies (eg, diabetes mellitus, Itsenko-Cushing's syndrome, hypothyroid conditions).
•
Hypothalamic pathology (eg, malformations).
•
Pituitary gland pathology (for example, with encephalitis, trauma, hemorrhage, or neoplasms in the Turkish saddle).
IMPAIRMENT OF ENDOCRINE FUNCTION
Ovary
Ovarian hypofunction
Causes and types... Endocrine ovarian failure is divided into primary and secondary.
•
Primary ovarian failure (primary hypogonadism) - conditions caused by ovarian pathology. There is an insufficient production of sex hormones
by them, as well as a compensatory increased level of FSH in the blood.
•
Secondary failure (secondary, or extra-ovarian hypogonadism). It is the result of a deficiency of either the gonadoliberins of the hypothalamus
or the gonadotropic hormones of the adenohypophysis.
Manifestations... Primary and secondary endocrine ovarian failure is characterized by similar symptoms. The main ones include: menstrual irregularities,
amenorrhea, infertility.
•
Menstrual irregularities. Manifested by dysfunctional uterine bleeding.
•
Amenorrhea - the absence of menstruation for more than 6 months in women with their earlier periodic onset (secondary amenorrhea), as
well as the absence of menarche in girls over 16 years of age (primary amenorrhea).
•
Infertility is the absence of pregnancy during one year of regular sexual activity without using methods of contraception. Infertility is registered in
10-15% of married couples.
Ovarian hyperfunction
Endocrine ovarian hyperactivity is characterized by hyperandrogenism or hyperestrogenism.
•
Hyperandrogenism - a condition characterized by increased production or effects of androgen action. It is detected in varying degrees of
severity in 10-15% of women. Manifestations: increased blood levels of androstenedione and testosterone, changes in the LH / FSH ratio in the
blood (usually more than 3), hirsutism, amenorrhea, infertility, obesity.
•
Hyperestrogenism... It is characterized by excess production or effects of estrogen in the body. Manifestations: increased levels of estrogen in the
blood and urine, decreased levels of gonadotropic hormones, premature isosexual puberty, disorders
menstrual cycle (usually in the form of menorrhagias).
Disorders of sexual development and sexual function in genetically males
Puberty in boys begins between the ages of 9.5 and 13.5 and lasts about 3 years. Testicular enlargement is usually the first sign of puberty. Also signs of
puberty are acne, pubertal gynecomastia, pubic and axillary hair, and a number of others.
Endocrinogenic disorders of sexual development and sexual function in males are manifested in the following typical forms: premature sexual
development, delayed sexual development, testicular hypofunction.
Premature sexual development
Premature puberty is a condition characterized by the appearance of all or some of the secondary sexual characteristics in boys under 9 years of age. This is
often combined with emotional and behavioral disorders, as well as impaired social adaptation.
Causes and types... Distinguish between true and false premature development of boys.
•
True (primary) premature development of boys is the result of hyperfunction of the hypothalamic-pituitary system and is characterized by
complete premature sexual development (including activation of spermatogenesis in the testes). Cause:
premature activation of GnRH secretion by hypothalamic neurons.
•
False (secondary) premature development in boys occurs as a result of autonomous hyperproduction of androgens. It is characterized by
incomplete premature sexual development (the appearance of signs of virilization without activation of spermatogenesis). The most common
causes: androgen-producing testicular tumors, hyperplasia of Leydig cells and their synthesis of excess testosterone,
hypersecretion of androgens by the adrenal cortex.
Manifestations premature puberty.
•
Signs of virilization (the appearance of pubic and axillary hair growth, coarsening of the voice, enlargement of the testicles and penis).
•
Low growth (due to premature termination of epiphyseal bone growth).
Delayed puberty and hypogonadism
The absence of signs of puberty in boys by the age of 14 is considered delayed puberty.
The reasons delayed puberty in boys and hypogonadism in men:
•
•
•
•
•
Deficiency of hypothalamic gonadotropins or adenohypophysis gonadotropins.
Decreased production of testosterone by the testes (as a result of their injury, growth of neoplasms, developmental disorders, orchitis, etc.).
Reduced sensitivity of target tissues to the action of testosterone.
Manifestations of delayed puberty:
Eunuchoidism (underdeveloped testicles and penis, absence or poorly expressed secondary sexual characteristics, effeminate (girlish) voice,
obesity, skeletal imbalance).
•
Decreased blood testosterone levels.
Manifestations male hypogonadism:
•
•
•
Sexual development in men is not impaired. In this regard, the physique and timbre of their voice are in the normal range.
Decreased sex drive.
Impotence.
•
Infertility.
Part 3
85.
Give the definition and classification of heart failure. Describe the myocardial form of heart failure, its etiology and
pathogenesis. Describe the etiology and pathogenesis of absolute and relative coronary insufficiency.
Heart failure - a condition in which the heart cannot provide organs and tissues with a sufficient amount of arterial blood.
Views
By origin
1. Myocardial - due to the action of damaging factors on the myocardium.
The reasons
•
Physical - mechanical injury, electric current
•
Chemical - high concentrations of biologically active substances, ethyl alcohol
•
Biological - streptococci, staphylococci and their toxins
Direct myocardial damage can be caused by infection, intoxication, hypoxia, avitominosis, impaired coronary circulation and other factors. In this case, the
formation of macroergs in cardiomyocytes or the use of their energy is disrupted. This leads to a decrease in the contractile ability of the heart, and therefore to
a decrease in the stroke and minute volume of the heart, which entails an increase in EDV (end diastolic volume) and EDV (end diastolic pressure) in the ventricles
of the heart, and then an increase in venous pressure.
Thus, any SN leads to a decrease in MOC and an increase in VD. These are the two main signs and consequences of heart failure.
Extracardiac compensation mechanisms are also superimposed on intracardiac compensation mechanisms; they are also aimed at restoring MOS. So, circulatory
insufficiency of the cardiac type begins with a decrease in MOC, which entails a decrease in blood pressure in the aorta - this is captured by the baroreceptors of
the aortic arch and the carotid sinus zone and a decrease in impulses from the baroreceptors occurs, this leads to an increase in the tone of the sympathetic nerves
and determines the completeness of the clinical manifestations of HF ( tachycardia, shortness of breath, edema, cyanosis). As a result of the excitement of the
sympathetic researcher the frequency and strength of heart contractions increases. This determines the essential sign of HF - the development of tachycardia. In
addition, under the influence of sympathetic impulses, veins contract, which normally contain up to 50% of all circulating blood. This leads to an increase in venous
pressure,
The main mechanisms of development of myocardial insufficiency
HF is mainly caused by two groups of causes:
having a direct damaging effect on the myocardium, causing functional overload of the heart. Numerous factors of the 1st group
of causes of heart failure can be conditionally divided into 3 subgroups, depending on their nature:
physical nature - myocardial injury, compression of the heart by exudate, tumor, the action of electric current, radiant energy, etc.; chemical (including biochemical)
nature - high concentrations of biologically active substances: adrenaline, thyroxine, angiotensin; large doses of medicinal and non-medicinal substances uncouplers of the process of oxidative phosphorylation, blockers of calcium ion transport, inhibitors of electron transport in the chain of respiratory enzymes of
mitochondria, etc .; biological origin - toxins, microbes, parasites, viruses.
The same group of causes of HF should also include the lack (or absence) in the body of factors necessary for the adequate functioning of the heart: vitamins,
metabolic substrates, oxygen, enzymes, compounds with antioxidant activity. Most often, this situation is a consequence of coronary insufficiency.
Factors causing heart failure due to myocardial overload include:
an excessive increase in the amount of blood flowing to the heart (increased "preload"); a significant increase in resistance, which appears during its expulsion
from the cardiac cavities into the aorta and pulmonary artery (increased "afterload"); changes in various organs and systems: in the heart (valve defects, a decrease
in the mass of the contractile myocardium as a result of its ischemia, heart attack or cardiosclerosis), in the vascular bed (arterial hypertension, arteriovenous
bypass grafting), in the blood system (hypervolemia, polycythemia); neurohumoral dysregulation of cardiac activity (excessive activation of sympathetic influences
on the myocardium, thyrotoxicosis, etc.).
As a rule, HF is the result of the action of pathogenic factors of both groups - damaging the myocardium and causing its overload. However, even taking this
condition into account in the development of HF, it is always possible to determine the leading mechanism.
In this regard, the majority of modern researchers [Meerson FZ 1965; Mukharlyamov N.M. 1978; Fledkenstein A. et al. 1967] distinguish two main
pathophysiological variants of HF:
as a result of myocardial damage ("myocardial" form); due to functional overload of the heart ("overload" form). In most cases, HF develops as a result
of a combination of direct myocardial injury and its overload - a mixed form of HF.
In addition to these forms (they can be conventionally called primary, or "cardiogenic"), there are also those that are mainly due to a primary decrease in blood
flow to the heart with normal contractility. They can be the result of a significant decrease in the mass of circulating blood, a violation of diastolic relaxation of the
heart when it is compressed by fluid accumulating in the pericardial cavity (exudate, blood), and other similar conditions. These varieties of HF are referred to as
secondary, or "noncardiogenic".
In conditions of coronary insufficiency in the experiment or with CHD in the clinic, heart failure often occurs when the heart is damaged due to its transient
ischemia, since any attack of angina pectoris leads to a transient decrease in myocardial contractility, and frequent and constant attacks of angina pectoris fix this
effect [Komarov F. I. Olbinskaya L. I. 1978].
Thus, regardless of the "triggering" mechanism of heart failure (angina attacks, focal changes in the myocardium after acute heart attacks), its development,
severity, among other factors (nature of work, lifestyle, concomitant diseases, etc.), largely depend on the state of the coronary circulation. In this regard, the
optimization of coronary blood flow is one of the important factors in the complex of therapeutic measures for heart failure.
"Coronary and myocardial insufficiency",
The mechanisms of emergency compensation for the reduced contractile function of the heart are shown in the figure.
• Increased contractility of the myocardium when it is stretched by the flowing blood (Frank-Starling mechanism). Provides an increase in the tension
developed by the myocardium and the rate of contraction and relaxation.
— Increased stress. developed by the heart, is carried out in response to the increasing stretching of the myocardium. In this regard, the Frank-Starling mechanism
is called heterometric, i.e. associated with an increase in the length of the muscle fiber.
— An increase in the rate of contraction and relaxation of cardiomyocytes develops in connection with a more rapid release of Ca 2+ from calcium stores
(sarcoplasmic reticulum) and subsequent accelerated pumping of Ca2 + (Ca2 + -ATPase) into the cisterns of the sarcoplasmic reticulum.
Emergency mechanisms of compensation for the reduced contractile function of the heart
An increase in the strength of myocardial contractions in response to increased load. Occurs when the length of the myocytes remains unchanged. Such a
mechanism is called homeometric, since it is realized without a significant change in the length of the muscle fibers.
An increase in the contractility of the heart with an increase in heart rate.
Increased contractility of the heart as a result of increased sympathetic-adrenal influences. It is characterized by an increase in the frequency and strength of
contractions.
— Sympathetic innervation of the myocardium is carried out by the endings of the axons of adrenergic neurons of the cervical superior, cervical middle and stellate
(cervicothoracic) ganglia.
— The activation of the sympathetic nerves produces a positive inotropic effect. The frequency of spontaneous depolarization of pacemaker membranes
increases, impulse conduction in Purkinje fibers is facilitated, the frequency and strength of contraction of typical cardiomyocytes increases.
— The action of catecholamines on cardiomyocytes via beta1-adrenergic receptors is due to a number of subsequent events: stimulation of the beta-adrenergic
receptor with an adrenergic agonist (for example, norepinephrine) -> adenylate cyclase is activated via the G-protein with the formation of cAMP -> activation of
cAMP-dependent protein kinase -> phosphorylation of protein p27 with phosphorylation > calcium entry into the sarcoplasm increases through open voltagedependent Ca2 + channels -> calcium-induced Ca2 + mobilization into the cytosol through activated ryanodine receptors increases -> Ca2 + concentration
significantly increases in the sarcoplasm -> Ca2 + binding with troponin C removes the inhibitory effect of tropomyosin on the interaction of actin with myosin ->
more actomyosin bonds are formed -> the force of contraction increases.
Compensatory hyperfunction of the heart
The functioning of the above mechanisms provides emergency compensation for the contractile function of an overloaded or damaged myocardium. This is
accompanied by a significant and more or less prolonged increase in the intensity of the functioning of the heart.
— its compensatory hyperfunction.
Compensatory hypertrophy of the heart
Myocardial hyperfunction determines the expression of certain genes of cardiomyocytes. It is manifested by an increase in the intensity of the synthesis of nucleic
acids and proteins. Acceleration of the synthesis of nucleic acids and myocardial proteins leads to an increase in its mass - hypertrophy. The biological significance
of compensatory heart hypertrophy lies in the fact that the increased function of the organ is performed by its increased mass.
2. Transshipment - due to overload of the heart.
The reasons
•
•
3. Mixed
Volume overload - excessive ↑ of the volume of blood flowing to the heart (with ↑ BCC, deformation of the heart valves)
Pressure overload - resistance, the cut appears when ejection of blood (with narrowing of the aorta, pulmonary artery overload).
According to the primary impairment of myocardial contractile function
1) primary (cardiogenic) - ↓ will shorten. the ability of the myocardium when it is damaged
2) secondary (noncardiogenic) - ↓ BCC
By localization
1.Levoventricular; 2. Right ventricular; 3.Total
By the speed of development
1.Acute; 2. Chronic.
Mechanism
Etiological factors → disturbances in energy supply to / m, damage to membranes and enzymes to / m, imbalance of ions and liquid to / m. disorders of
myocardial regulation → strength and speed of contraction and relaxation of the myocardium → HF.
Compensation mechanisms
1. ↑ myocardial contractility with ↑ its extensibility; 2. myocardial contractility with increasing load on it; 3. cardiac contractility at ↑ heart rate;
4. contractility of the heart with ↑ sympathoadrenal influences on it.
Decompensation mechanisms
1.C / m growth occurs faster than the formation of capillaries; 2. Growth k / m faster than nerve fibers; 3. Inconsistency between growth of c / m and formation of
mitochondria.
Manifestations
Stagnation of blood in those parts from which blood flows to the heart.
Manifestations of l / f HF - stagnation of blood in the ICC
-dyspnea; -cough (with sputum and blood); - signs of cardiac asthma, asthma attack; - pulmonary edema
Manifestations of p / f HF - stagnation of blood in the CCB
- ↑ liver in size (pain in the right hypochondrium); - ↑ spleen in size (pain in the left hypochondrium); - ↑ jugular veins (in the neck); - ascites (accumulation of
blood in the abdominal cavity); -hydrothorax (accumulation of fluid in the pleural cavity); -hydropericardium (fluid accumulates in the pericardial region); -cyanosis
(cyanosis of the skin); - ↑ t-ra;
In severe cases, cardiac cachexia
Coronary insufficiency is a discrepancy between the coronary circulation and the energy requirements of the myocardium,
manifested by myocardial ischemia.
THE MAIN CAUSES OF CORONARY INSUFFICIENCY: 1) a decrease in blood flow in the vessels with unchanged
metabolic demands of the myocardium; 2) strengthening the work of the heart with an increase in the metabolic needs of the
myocardium
with the inability of the coronary vessels to increase blood flow; 3) a combination of vascular and metabolic factors.
FORMS OF CORONARY INSUFFICIENCY
Distinguish between acute and chronic forms of failure.
Acute coronary insufficiency is characterized by an acute inadequacy of blood flow to metabolic demands
myocardium, more often with altered than with unchanged coronary arteries of the heart, which is manifested by attacks
angina pectoris, often severe heart rhythm and conduction disorders, ECG changes. Acute coronary
failure can lead to the development of myocardial infarction. Chronic coronary insufficiency
characterized by a constant inadequacy of blood supply to the metabolic needs of the myocardium. The prerequisite
for its development are structural changes in the coronary arteries of the heart (narrowing of the coronary bed). The reasons
development of coronary insufficiency, etiology and pathogenesis. Coronary insufficiency occurs at the most
various pathological processes: atherosclerosis of the coronary arteries of the heart (the most common cause), vasculitis
(coronary), infiltration of coronary vessels by tumor cells, vascular injury, acquired and congenital
defects of the heart and great vessels (aortic heart defects, stenosis of the pulmonary trunk, coronary anomalies
vessels), septic endocarditis, cardiomyopathies, some forms of myocarditis (for example, Abramov's type Fiedler), syphilitic aortitis, dissecting aortic aneurysm, shock and collaptoid conditions, anemias and
other heart diseases. The development of acute coronary insufficiency is associated with a sudden violation
patency of the coronary arteries due to their spasm, thrombosis or embolism. Metabolic queries are not
ischemic areas of the heart muscle at the same time increase, which is accompanied by an increase in blood flow in
unchanged adjacent coronary vessels. In this case, a redistribution of blood is possible in favor of non-ischemic
areas and increased ischemia in the area of the affected artery ("the phenomenon of stealing"). In the origin of non-coronary
Ph.D. pathological processes accompanied by a decrease in the minute volume of the heart and
perfusion pressure in the coronary artery system (severe arterial hypotension, significant bradycardia,
hypovolemia), as well as anemia, arterial hypoxia and impaired dissociation of oxyhemoglobin during respiratory
insufficiency, poisoning with carbon monoxide, benzene nitro compounds, etc. Even maximum vasodilation
perfectly normal coronary arteries of the heart cannot meet metabolic needs in these conditions
myocardium. Depending on the time and intensity of action of this or that factor, an acute or
chronic coronary insufficiency. In the origin of the candidate of n. metabolic (non-coronary or more common
mixed) genesis, the increased release of catecholamines when the sympathetic department is excited
autonomic nervous system (acute and chronic stressful situations, accompanied by psycho-emotional
stress) or their excess production by the adrenal glands. Under the influence of catecholamines, it significantly increases
myocardial oxygen demand for their oxidation. The coronary vessels altered by the atherosclerotic process (and
even unchanged), often with inadequate spasms, unable to provide sufficient
blood supply, which leads to ischemia and even necrosis of certain areas of the myocardium (theory of origin
coronary insufficiency, angina pectoris and myocardial infarction - W. Raab, 1963). Pathogenetic significance in
the emergence of c. n. also has tachycardia, especially in combination with arrhythmias (paroxysmal tachycardia,
tachyarrhythmia, frequent group extrasystoles). In these cases, the coronary circulation is impaired due to
decrease in coronary perfusion (shortening of diastole and decrease in minute blood volume) and increase
metabolic requirements of the myocardium. If this occurs against a background of even moderate atherosclerosis
coronary arteries of the heart, pathogenetic factors of coronary insufficiency are summed up. Chronic coronary
failure develops with damage to the coronary arteries of the heart, narrowing them or reducing the ability to
expansion. In most cases, it is due to atherosclerosis of the coronary arteries of the heart, but may be associated with
inflammatory changes, cicatricial deformity, infiltration (rheumatism, systemic diseases
connective tissue, syphilitic arteritis, etc.). There are known cases of the development of acute and chronic coronary
failure after non-penetrating trauma to the organs of the chest cavity (upon impact, compression, action of an explosive
waves falling from a height). In case of injuries, embolism of the coronary arteries of the heart from the pulmonary veins, rupture of
the coronary
vessels, hemorrhage, the formation of an aneurysm of the heart, blood vessels. Direct and strict relationship between the degree
there is no narrowing of the coronary vessels of the heart and no manifestations of chronic coronary insufficiency. It is developmental
collateral circulation, in some cases functionally and organically complete, in others defective.
86. Describe
pathogenesis of the main clinical syndromes, complications and outcomes of angina pectoris and
myocardial infarction.
Angina pectoris - a disease caused by coronary insufficiency and characterized by reversible myocardial ischemia.
Complications of angina pectoris:
1. transition from stable to unstable angina.
Stable exertional angina. It is usually a consequence of a decrease in coronary blood flow to a critical level, a significant increase in the
work of the heart, and more often a combination of both.
Unstable exertional angina. It is characterized by angina attacks increasing in frequency, duration and severity. These episodes are usually
the result of a progressive decrease in coronary blood flow.
2. acute myocardial infarction.
The most common cause of myocardial infarction is coronary artery thrombosis, which developed against the background of atherosclerotic
changes (up to 90% of all cases).
3. violation of the rhythm of the heart (arrhythmia).
Arrhythmias are the result of a violation of automatism, conduction or excitability, as well as their combinations. Contractility disorders underlie the
development of heart (myocardial) failure, and are not the cause of cardiac arrhythmias.
4. heart failure.
Myocardial infarction - focal necrosis of the heart muscle as a result of an acute and significant discrepancy between myocardial oxygen
demand and its delivery.
With myocardial infarction, life-threatening complications are possible:
♦ acute heart failure (cardiogenic shock, pulmonary edema);
♦ rupture or aneurysm of the heart;
♦ insufficiency of valves;
♦ heart rhythm disturbances;
♦ thromboembolism.
87.
Give the classification of heart rhythm disturbances. Give the types, causes, mechanisms and manifestations
of cardiac arrhythmias in violation of automatism.
Arrhythmia - a typical form of heart pathology - characterized by a violation of the frequency and frequency of generation of excitation and / or the sequence
of excitation of the atria and ventricles.
Views
Depending on the place (topography) of the generation of an abnormal excitation pulse, nomotopic and heterotopic arrhythmias are distinguished.
Nomotopic arrhythmias. They arise in the sinus-atrial node. These include sinus tachycardia, sinus bradycardia, and sinus arrhythmia.
Heterotopic arrhythmias. They arise outside the sinus-atrial node and are caused by a decrease in the automatism of the overlying centers of rhythmogenesis.
Manifestations: atrial, atrioventricular, idioventricular (ventricular) rhythms; migration of the supraventricular pacemaker; atrioventricular dissociation (complete
transverse block).
Cardiac arrhythmias as a result of a violation of automatism
Automatism is the ability of the heart tissue to spontaneously generate electrical impulses.
Nomotropic - impulses are generated by the sinus-atrial node.
1) Sinus tachycardia - ↑ HR is higher than normal when the s / p node generates impulses with equal intervals between them.
2) Sinus bradycardia - ↓ HR is below normal when the s / p node generates impulses with equal intervals between them.
3) Sinus arrhythmia - uneven alternation of electrical impulses emanating from the s / n node.
Heterotropic
1) Atrial slow rhythm - rare contractions of the heart.
2) Atrioventicular rhythm - impulses in the s / n node are generated at a lower frequency than in the cells of the atrioventricular node.
3) Ventricular rhythm...
4) Dissociation with interference...
5) Pop-up cuts...
6) Pacemaker migration
NOMOTOPIC ARRHYTHMIAS
Sinus tachycardia - an increase in the resting frequency of generation of excitation pulses in the sinus-atrial node more than 80 per minute with
at regular intervals between them.
Electrophysiological mechanism: acceleration of spontaneous diastolic depolarization of the plasmolemma of the cells of the sinus-atrial node.
The reasons:
1)
Activationinfluence on the heart of the sympathoadrenal system. This situation most often occurs during stress, physical exertion, acute arterial
hypotension, heart failure, hyperthermia, and fever.
2) Decreaseeffects on the heart of the parasympathetic nervous system. This may be due to damage to parasympathetic nerve formations or
myocardial cholinergic receptors.
3) Direct action of damaging factorsof various nature on the cells of the sinus-atrial node. It occurs with myocarditis, pericarditis, etc.
Sinus bradycardia - a decrease in the resting frequency of generation of excitation impulses by the sinus-atrial node below 60 per minute with
at regular intervals between them.
Leading electrophysiological mechanism: slowing down the process of spontaneous diastolic depolarization of the membranes of the sinus-atrial
node cells.
The reasons:
1)
Dominationthe effects of the parasympathetic nervous system on the heart. It occurs when the nuclei of the vagus nerve or its endings are irritated,
intraventricular pressure and myocardial tone increase, pressure on the eyeballs (Aschner-Dagnini reflex), as well as in the projection zone of the
carotid artery bifurcation (Hering's reflex) and in the solar plexus region.
2) Decreased sympathoadrenaleffects on the heart. It is observed with damage to sympathetic structures or a decrease in the adrenergic
properties of the heart.
3) Direct impactdamaging factors on the cells of the sinus-atrial node. Such factors can be mechanical injury, hemorrhage or heart attack in the
sinus-atrial node area, toxins and drugs, metabolites (indirect bilirubin, bile acids).
Sinus arrhythmia - a violation of the heart rhythm, characterized by uneven intervals between individual excitation impulses emanating from the sinus-atrial
node.
Electrophysiological mechanism: fluctuations in the rate (increase, decrease) of slow spontaneous diastolic depolarization of pacemaker cells.
Most common reasons: fluctuation or violation of the ratio of sympathoadrenal and parasympathetic effects on the heart.
Sick sinus syndrome (bradycardia-tachycardia syndrome) - the inability of the sinus-atrial node to provide a heart rate adequate to the level of vital activity
of the body.
Electrophysiological mechanisms: violation of the automatism of the sinus-atrial node, especially the phases of repolarization and spontaneous diastolic
depolarization and the emergence against this background of heterotopic (ectopic) foci of rhythmic activity.
The reasons:
•
Disorder of the balance of sympathoadrenal and parasympathetic influences on the heart, with a predominance of the latter.
•
Death or dystrophy of the cells of the sinus-atrial node (for example, with a heart attack, hemorrhage, tumor, trauma, inflammation).
The main ECG manifestations: periodic or persistent sinus bradycardia, alternating with sinus tachycardia, atrial flutter or atrial fibrillation, slow restoration of
sinus rhythm after cessation of sinus tachycardia, episodes of stopping the sinus-atrial node.
Ectopic arrhythmias
Decreased activity or cessation of activity of the sinus-atrial node creates conditions for the inclusion of automatic centers of the second and third orders. The
ectopic (in relation to the sinus-atrial node) focus with its more rare rhythm takes on the function
pacemaker.
Atrial slow rhythm... The ectopic pacemaker is usually located in the left atrium. The ECG reveals rare (less than 70 per minute) excitation impulses.
Atrioventricular rhythm (junctional rhythm) occurs when impulses in the sinus-atrial node or do not occur at all or
are generated at a lower frequency than in the cells of the atrioventricular (AV) node... The source of excitation pulses can be the upper, middle or lower part
of the AV node. The higher the localization of the pacemaker, the more pronounced its influence and the greater the frequency of the impulses generated by
it.
Migration of the supraventricular pacemaker... It is characterized by the movement of the pacemaker from the sinus-atrial node to the underlying sections (mainly
to the AV node) and back. This usually occurs when the automatism of the sinus-atrial node is suppressed as a result of
transient increase in the effects of the vagus nerve... In this case, the heart rhythm depends on a new source of impulses and therefore becomes incorrect.
Idioventricular ventricular rhythm develops as a substitute when the activity of centers of the first and second order is suppressed. Pulses are generated, usually in
the bundle of His, in one of its legs and, less often, in the Purkinje fibers.
Atrioventricular dissociation - complete cessation of the conduction of excitation from the atria to the ventricles. In this case, the atria and ventricles
contract independently of each other (complete transverse block).
88.
Describe the etiology, pathogenesis and manifestations of cardiac arrhythmias in conduction disturbances.
Arrhythmias due to conduction disturbances
Deceleration and blockade of conduction
The reasons: •
•
increase parasympathetic influences on the heart;
damage to the cells of the conducting system
physical.,
chemical., biological. nature.
heart factors
Violation of sinoauricular conduction - inhibition or blockade of the transmission of the excitation impulse from the
sinus-atrial node to the atria.
Intra-atrial conduction disorder - in connection with the asymmetric arrangement of the sinus-atrial node in relation to
the atria, their excitation normally occurs at different times.
Violation of atrioventricular conduction - slowing down or blockade of conduction of excitation impulses from the
atria to the ventricles.
Intraventricular conduction disorders
excitation pulse
- braking or
blockade propagation of an electric pulse along the legs of the His bundle, its branches
and Purkinje fibers.
89.
Describe the causes and mechanisms, manifestations of cardiac arrhythmias in violation of automatism, excitability
and conductivity of the myocardium.
Arrhythmias due to conduction disturbances
Deceleration and blockade of conduction
The reasons: •
•
increase parasympathetic influences on the heart;
damage to cells of the conducting systemheart factors physical., chemical., biological. nature.
Violation of sinoauricular conduction - inhibition or blockade of the transmission of the excitation impulse from the sinus-atrial node to the atria.
Intra-atrial conduction disorder - due to the asymmetric location of the sinus-atrial node in relation to the atria, their excitation normally occurs at different times.
Violation of atrioventricular conduction - slowing down or blockade of conduction of excitation impulses from the atria to the ventricles.
Intraventricular impulse conduction disorders - inhibition or blockade of the propagation of an electrical impulse along the legs of the His bundle, its branches
and Purkinje fibers.
Acceleration of arousal - Wolff-Parkinson-White syndrome (tachycardia, atrial fibrillation or flutter).
Acceleration of arousal
Cause: the existence of additional ways of conducting excitation. In additional beams, excitation spreads faster and reaches the ventricles before the
impulse passing through the AV node.
Hemodynamic disorders: a decrease in shock and cardiac emissions (due to a reduced filling of the heart chambers with blood in conditions of tachycardia,
atrial fibrillation or atrial flutter), a drop in blood pressure, the development of circulatory failure and coronary insufficiency.
90.
Give the classification of arterial hypertension. Describe the etiology, pathogenesis and stages of essential
arterial hypertension (hypertension), the factors of stabilization of high blood pressure.
Classification of arterial hypertension Stages
of hypertension:
•
•
•
Hypertensive heart disease (HD) stage I suggests the absence of changes in the "target organs".
Hypertension (HD) stage II is established in the presence of changes in one or more "target organs".
Hypertension (HD) stage III is established in the presence of associated clinical conditions.
Risk factors: heredity obesity, diabetes mellitus, negative emotions, physical inactivity, smoking.
Pathogenesis of GB.
During GB, three stages are distinguished:
1) Transient stage, when, against the background of normal blood pressure, episodes of increased blood pressure periodically occur.
2) Stage of blood pressure stabilization at a high level...
3) Organ changes stage - damage to the heart, brain, kidneys.
The value of blood pressure depends on cardiac output and total peripheral vascular resistance(arterioles). There are several
theories explaining the pathogenesis of the first stage of hypertension:
1.
The initial pathogenetic factor is persistent hyperexcitability and reactivity (hyperergia) of the higher sympathetic nerve centers located in the hypothalamus.
The hyperergic state of these centers leads to an increase in the production of catecholamines, vasopressin, ACTH and corticosteroids and renin
hypersecretion. All these factors cause spasm of arterioles, sodium and water retention, increase cardiac output and increase blood pressure.
2. The initial factors in the development of hypertension are genetically determined sodium and water retention by the kidneys. Retention of sodium and water
leads to hypervolemia, increased cardiac output, spasm of arterioles, and increased blood pressure.
3. The initial factor is a generalized hereditary defect in membrane ion pumps. The defect leads to the accumulation of calcium and sodium ions inside the
smooth muscle cells of the vascular stack, which leads to prolonged spasm of arterioles, an increase in total vascular resistance and an increase in blood
pressure.
A prolonged increase in blood pressure disrupts the functioning of the kidneys, causes hypertrophy of the muscular wall of the arterioles, leads to
persistent excitation of the vasomotor center of the hypothalamus and causes the transition of the transient stage of GB to a stable stage and to
changes on the part of various organs and systems.
Hypertension (essential) - a symptomatic disease characterized by ↑ blood pressure, not associated with damage to any organ.
Etiology: Repeated, prolonged psycho-emotional stress.
Major risk factors: an excess of Na - causes an increase in the transport of fluid into the cells and their swelling, further thickening, narrowing of the lumen;
increased sensitivity of myocytes of the walls of blood vessels and the heart to vasoconstrictor factors; violation of the expression of genes that control the
synthesis of vasodilating agents by endothelial cells (nitric oxide, prostacyclin).
The reasons
•
•
•
•
•
•
•
•
•
-hereditary predisposition;
-psycho-emotional overvoltage;
-elderly age;
-atherosclerosis;
-diabetes;
-obesity; -hypodynamics;
-smoking;
-selected consumption of table salt;
-alcohol.
Classification of hypertension:
1. BP is higher than 160/95, no morphological and functional. violations
2. + there are morphological disorders: - left ventricular hypertrophy; - retinal angiopathy; -nephrosclerosis; - atherosclerosis.
3. + functional impairment: -deterioration of vision; -heart failure; - renal failure; - head stroke
brain.
Stages:
Stage I of hypertension:
The initial factor in the pathogenesis of hypertension is the development of a neurotic state. Characterized by activation
centrogenic neurogenic linkpathogenesis of hypertension. The centrogenic neurogenic
mechanism includes:
•
•
•
Formation of the cortical-subcortical complex of stable excitation. It includes the sympathetic nuclei of the posterior hypothalamus.
Strengthening pressor (hypertensive) effects on CVS. It is realized through two interdependent - nervous and humoral - channels.
Realization of the action of the above humoral agents. This, in parallel with the activation of the sympathetic nervous system,
provides an increase in venoconstriction, an increase in the return of venous blood to the heart, and an increase in the BCC.
Stage II of hypertension:
Stabilization of blood pressure at an increased level... Stabilization of blood pressure at an elevated level is provided by reflexogenic endocrine,
hemic mechanisms...
At this stage, stably elevated (hypertensive) blood pressure is recorded, as well as signs of tissue and internal organ damage (heart
hypertrophy, pronounced athero- and arteriosclerosis, nephrosclerosis).
Stage III hypertension:
It is manifested by organic changes and is characterized by damage to structural elements, gross disorders of the functions of tissues and
organs with the development of multiple organ failure. The most commonly observed:
•
•
Severe athero- and arteriosclerosisleading to heart attacks in various organs (most often - myocardium) and strokes.
Cardiomyopathies... One of the reasons is the imbalance in the growth of myocardial structures - the wear complex of the
hypertrophied heart.
•
Sclerotic kidney disease(primary contracted kidney). This name indicates the primary hypertensive genesis of kidney pathology in
hypertension.
•
Dystrophic and sclerotic changes in other organs (brain, endocrine glands, retina, heart).
Treatment: control of blood pressure, risk factors, lifestyle changes, drug therapy.
Non-drug treatment: diet, physical activity, psychological methods, water procedures.
Drug therapy: blockers of slow calcium channels, diuretics, β-blockers., ACE inhibitors, angiotensin II antagonists, α-blockers.
91.
Provide information about the types, causes and mechanisms of development of
secondary renal, endocrine, neurogenic arterial hypertension.
Normal blood pressure for a person between the ages of 20 and 60 ranges from 100/60 to 139/89 mm Hg. pillar. The borderline between normal
and high blood pressure is 140/90 - 159/94 (borderline hypertension) and 160/95 - certainly indicates hypertension.
By origin arterial hypertension is divided into primary essential hypertension, or hypertension and
secondary, symptomatic hypertension.
Secondary hypertension occurs with primary damage to organs or systems involved in maintaining the systemic level
blood pressure (BP) and is a symptom of this lesion.
The most common symptomatic arterial hypertension (AH) in humans is renal and endocrine.
Renal arterial hypertension...
There are two types of renal hypertension: vasorenal (renovascular, renal ischemic) and renoprivative.
Renovascular hypertension.
The reasonrenal vasorenal hypertension is a decrease in perfusion pressure in the vessels of the kidneys. This could be a consequence
crushing, (tumor, scar) narrowing (thrombus, embolus) of the renal arteries or inflammation of the kidneys (glomerulonephritis).
Pathogenesis vasorenal hypertension: a decrease in perfusion pressure in the vessels of the kidneys (renal ischemia) increases the production
of renin by the juxtaglomerular apparatus of the kidney (JHA) нrenin converts angiotensinogen to angiotensin-1 angiotensin-1 under the
influence of a converting enzyme Ten-2 AT-2 causes spasm of arterioles, increases concentration
catecholamines in the blood and increases the production of aldosterone by the adrenal cortex secondary aldosteronism delays
sodium in the body hypernatremia and hyperosmia through irritation of osmoreceptors increase the production of
antidiuretic hormone (ADH) in the hypothalamus ADH retains water in the body and increases the mass of circulating blood, and all this
increases blood pressure.
Renoprivnaya AG (from Latin ren + privo - to deprive, to reduce).
The reason Renoprivial hypertension is a decrease in the mass of the renal parenchyma, which produces compounds with a hypotensive effect prostaglandins (A and E) and kinins (bradykinin and calidin). A decrease in the mass of the kidneys may be a consequence of the removal of one
or both kidneys, nephrosclerosis, hydronephrosis and other processes. Prostaglandins and kinins produced by the medulla of the kidneys dilate
arterioles, increase the excretion of sodium and water from the body, and lower blood pressure. The defeat of this system leads to
the predominance of the renin-angiotensin-aldosterone-ADH system and an increase in blood pressure...
Endocrine arterial hypertension.
I.
Hypertension with adrenal gland damage...
1. Mineralocorticoid hypertension... With hyperplasia or tumor of the adrenal cortex, primary aldosteronism occurs
leads to sodium and water
retention in the body hypervolemia and an increase in cardiac output AH.
2. Glucocorticoid hypertension... With hyperplasia of the fascicular zone of the adrenal cortex, the production of glucocorticoids increases and the
development of Itsenko-Cushing's syndrome with an increase in blood pressure is observed. Glucocorticoids increase the sensitivity of arterioles
to catecholamines, increase the synthesis of angiotensinogen in the liver, have a weak mineralocorticoid effect (retain sodium and water in the
body) and increase blood pressure.
II.
AH in disorders of the hypothalamic-pituitary system.
With an increase in the secretion of supraoptic and paraventricular nuclei of the hypothalamus by neurons of ADH (vasopressin), the mass of
circulating blood increases, which contributes to an increase in blood pressure.
With an increase in the production of adrenocorticotropic hormone (ACTH) (Itsenko-Cushing's disease), the function of the cortex is stimulated
adrenal glands with an increase in the production of gluco and mineralocorticoids and an increase in blood pressure.
92.
Describe the types, causes and mechanisms of the development of arterial hypotension.
Arterial hypotension - decrease in blood pressure below 100/60 mm Hg. Art. in men and 95/60 mm Hg. Art. among women.
Views:
Physiological:
1) Individual version of the norm.
2) Arterial hypotension of high fitness.
3) Adaptive (compensatory) arterial hypotension.
Pathological:
1)
Acute (collapse (due to an acute decrease in heart function), a prolonged decrease in blood pressure, accompanied by anuria,
impaired peripheral circulation and consciousness, for example, with shock).
2) Chronic (Primary - neurocirculatory and idiopathic, Secondary).
Etiology and pathogenesis. According to the initial link of the developmental mechanism, neurogenic, endocrine and metabolic AHs are isolated.
Neurogenic...
1) Centrogenic (repeated stress -> neurosis -> activation of neurons -> increased f / s effects on the c-c system -> decrease in total peripheral
vascular resistance and cardiac output -> AH)
2) Reflex (decrease or cessation of the tonic effects of sympathetic ns on the walls of blood vessels and heart -> decrease in total peripheral
vascular resistance and blood pressure -> AH.
Endocrine...
1) Adrenal (Deficiency of catecholamines, mineral and glucocorticoids -> decreased tone of arteriole walls and total peripheral vascular resistance
-> AH).
2) Pituitary (Insufficient effect of vasopressin, adrenocorticotropic, thyroid-stimulating and somatotropic hormones -> decrease in arteriole tone
and total peripheral vascular resistance, cardiac output -> decrease in blood pressure -> AH).
3) Thyroid (Bradycardia develops due to a decrease or absence of a positive chronotropic effect of thyroid hormones due to their deficiency, a
decrease in the activity of the sympathetic-adrenal system. A decrease in cardiac output, vascular wall tone, and total peripheral vascular
resistance).
Metabolic... The reasons:dystrophic changes in organs and tissues, hypohydration of the body. Pathogenesis: a decrease in the tone of the walls
of blood vessels -> a drop in the total peripheral vascular resistance, cardiac contractility -> a decrease in cardiac output of blood, water in the
body -> a decrease in blood pressure -> AH.
93.
Describe the types, etiology, pathogenesis, clinical manifestations, consequences of
erythrocytosis.
Erythrocytosis - an increase in the content of hemoglobin and the number of erythrocytes; are not caused by diseases of the blood system.
Distinguish
1.
2.
absolute (primary and secondary) erythrocytosis. caused by reactive enhancement of normal erythrocytopoiesis, and
relative hemoconcentration erythrocytosis, characterized by a decrease in the volume of circulating plasma
and the relative predominance of cellular elements of the blood...
With absoluteerythrocytosis, the mass of circulating erythrocytes is increased, with relative erythrocytes, it is not changed. Depending on the
pathogenesis, among the absolute erythrocytosis, there are
•
erythrocytosis due to generalized tissue hypoxia (arterial hypoxemia and isolated tissue hypoxia with normal arterial oxygen
saturation),
•
erythrocytosis caused by local renal ischemia (renal erythrocytosis) and
•
paraneoplastic erythrocytosis...
With hypoxic and renal erythrocytosis, the source of increased production of erythropoietins is the kidneys, with
paraneoplastic- tumors. Hypoxic erythrocytosis are compensatory, renal and paraneoplastic dysregulatorythat do not perform useful functions.
The most common in clinical practice are hypoxic erythrocytosis caused by arterial hypoxemia. Mountain sickness, chronic obstructive pulmonary
diseases, lesions of the blood vessels of the lungs, incl. proceeding with arteriovenous shunts and alveolar-capillary blocks, as well as
carboxyhemoglobinemia, the cause of which is mainly the malignant smoking of tobacco. Isolated tissue hypoxia is observed in hereditary
hemoglobinopathies with an increased affinity of hemoglobin for oxygen and a deficiency of 2,3-diphosphoglycerate in erythrocytes. Congenital
"Blue" heart defects cause hemic hypoxia. The combination of lung diseases, obesity and tobacco smoking contributes to the development of
hypoxia and erythrocytosis.
Renal erythrocytosis observed in polycystic kidney disease, hydronephrosis, occasionally nephrocalcinosis, as well as in renal artery stenosis as a
result of local renal ischemia. Paraneoplastic erythrocytosis is observed in renal adenocarcinoma, cerebellar hemangioblastoma, Hippel-Lindau
syndrome, hepatoma, uterine myoma, atrial myxoma, as well as in tumor diseases of the endocrine glands, when mechanisms that stimulate
erythrocytopoiesis are turned on.
Primary erythrocytosis - a group of various hereditary diseases characterized by increased production
erythropoietin or decreased oxygen sensitivity of the kidney oxygen receptors... The proliferative activity of erythron is increased with it, and
information on the content of erythropoietins is contradictory. Characterized by a significant increase in the number of erythrocytes, pronounced
erythrocyanotic color of the skin and vascular thrombophilic complications.
Relative erythrocytosis can be observed in practically healthy people, in patients with arterial hypertension, heavy smokers and persons who
have been under stress for a long time. It increases the tendency to myocardial infarction and strokes, without significantly affecting the external
status of patients.
When making a diagnosis, you should first exclude the true polycythemia (erythremia), determine the belonging of E. to absolute or relative by
measuring the mass of circulating erythrocytes by the radiological method.
Diagnostic value have the following clinical data: with absolute E. the color of the skin is plethoric, with
relativeit is normal, and a transient red complexion is associated with increased vascular reactivity. In both types of E. the spleen is not enlarged.
The next step is to establish the cause of absolute E. In hypoxic E., cyanosis of the skin is noted, which increases in the patient in the supine
position. Revealing a decrease in the saturation of arterial blood with oxygen verifies the diagnosis of hypoxic E. on the basis of arterial hypoxemia,
and the cause of hypoxia is determined by the clinical picture and data from instrumental examination of the lungs and heart.
Hemoglobinopathies with an increased affinity of hemoglobin for oxygen and congenital 2,3-diphosphoglycerate deficiency are suggested in
children suffering from E., as well as in adults with a clinical picture of hypoxia, but in the absence of arterial hypoxemia.2, Rfifty, oxyhemoglobin
dissociation curve.
Carboxyhemoglobinemiasuspected of heavy smokers, diagnosed by examining the content of carbon monoxide in the blood during the day.
Arteriovenous shunts in the lungs should be assumed in the presence of shortness of breath, cyanosis and E., but in the absence of diseases of
the lungs and heart, especially in patients with hereditary telangiomatosis.
For most renal E. arterial hypertension is characteristic. In all cases, with the exclusion of hypoxic E., the detection of kidney diseases is shown.
Suspicion of the paraneo-lastic nature of E. arises in the presence of the corresponding tumor diseases. The connection with the tumor proves
the disappearance of E. with an adequate operation.
Treatmentis aimed at the underlying disease. With hypoxic E. oxygen therapy is necessary. Bloodletting is shown (hematocrit up to 52-55%), since
high blood viscosity with a hematocrit of over 60% makes it difficult to return
oxygen to tissues. They are also recommended for non-hypoxic E. The prognosis depends on the underlying disease. Excessive blood mass
can lead to thrombotic complications.
21.1. ERYTHROCYTOSIS
Erythrocytosis (from the Greek erithros - red, Greek cytos - cell + oz - pathological process, disease) - conditions characterized by an
increase in the number of red blood cells per unit of blood volume above the norm (more than 4.7x1012 / l in women and 5.0x1012 / l
in men). There are several types of erythrocytosis.
Types of erythrocytosis
A. Primary (independent forms of the disease):
1) erythremia (polycythemia vera, Vakez disease),
2) "Family" (inherited) erythrocytosis.
B. Secondary (symptoms of other diseases, pathological conditions or processes):
1)
2)
absolute (due to increased erythropoiesis and (or) elimination of erythrocytes into the vascular bed from the bone marrow),
relative:
a.
hemoconcentration (hypovolemic),
b. redistributive.
21.1.1 Primary erythrocytosis
Primary erythrocytosisare independent nosological units - Drakes. The most common disease is Vakez (synonyms: erythremia, "true"
polycythemia). The incidence of Vakez disease ranges from 0.6 to 1.6 per 100,000 population. Cases of the disease in relatives are described,
which indicates the possibility of hereditary
predisposition to it.
Etiology and pathogenesis of erythremia...
Erythremias are among the leukemias.
The reasons erythremia, as well as other tumors, can be carcinogenic agents of various
character: physical (neutron flux, X-ray radiation, particles formed during the decay of radioactive substances); chemical (polycyclic
hydrocarbons, aromatic amines, aminoazo compounds, etc.); biological (oncogenic viruses).
An important condition for the implementation of the action of blastomogenic agents is a decrease in the activity of anticarcinogenic and (or)
anti-mutation mechanisms of the body's antitumor defense, inactivating and (or) eliminating these agents, or
the consequences of their actions - mutated genes or activated "oncogenes".
The mechanism of development of erythrocytosis in Vakez disease is based on an increase in the number and unlimited proliferation
cells- precursors of myelopoiesis. In this regard, along with an increase in the number of erythrocytes,
granulocytosis, monocytosis and thrombocytosis (polycythemia). Strengthening of the myeloproliferative process is often noted not only in
the bone marrow, but also in the spleen and other organs containing cells of the hematopoietic system.
The monoclonal nature of myeloproliferation in Vakez's disease is evidenced by the facts of detection in erythrokaryokites, granulocytes
and megakaryocytes of the same chromosome defect (structural aberration, aneuplondia, etc.) or enzymes of the same type.
These defects are absent in lymphocytes.
Manifestations... Erythremia is accompanied by significant changes in the bone marrow, peripheral blood, dysfunctions of the
cardiovascular and other systems.
In the bone marrow, there are signs of neoplastic proliferation of myeloid cells in the proximal and often in the distal parts of the
tubular bones. This process is also detected in flat bones, liver, spleen.
At the same time, signs of acceleration of iron metabolism are noted: the introduction into the body of preparations containing 59Fe and 52Fe is
accompanied by an acceleration of the processes of utilization of iron by the bone marrow tissue and its subsequent excretion. The increase in grip is
not
accompanied by a parallel increase in the radioactivity of erythrocytes circulating in the peripheral blood. The latter testifies to the low
resistance of erythroid cells and their hemolysis even at the "nuclear" stages of differentiation.
Unlike secondary erythrocytosis, Vakez's disease is characterized by a decrease in the level of erythropoietin in the blood plasma. In the late
stages of erythremia, the so-called posterythremic myelofibrosis often develops, leading to a decrease in the "bridgehead" of erythropoiesis,
combined with anemia and often with thrombocytopenia.
In peripheral blood, an increase in the number of erythrocytes, reticulocytes and, as a rule, thrombocytosis, neutrophilia (with a nuclear shift to
the left to metamyelocytes), basophilia and monocytosis, combined with hypervolemia, are detected. Absolute content
hemoglobin in the blood is increased (up to 180-200 g / l), and the color index is below normal. The latter is the result of the lag of hemoglobin
synthesis from the process of cellular differentiation of erythrocytes. At the final stages of the disease, erythropenia, thrombocytopenia and
even pancytopenia develop (a decrease in the number of all or many cells of the myeloid series due to myelofibrosis).
Disorders of the cardiovascular system are manifested by the development of arterial hypertension, violation of organ-tissue and
micro-hemocirculation, overflow of organs and tissues with blood (pletora). Arterial hypertension,
observed in almost half of patients, is the result, as a rule, of a combined increase in peripheral vascular resistance and cardiac output. A
significant pathogenetic factor of hypertension is the activation of the renin system
- angiotensin - aldosterone - an antidiuretic hormone caused by impaired blood circulation in the kidneys, thrombosis and (or) sclerosis of the
renal arteries.
Disorders of organ-tissue blood flow (ischemia, venous hyperemia, stasis), as well as intravascular microcirculation disorders (slowing blood
flow in the vessels of the microvasculature, stasis, blood flow turbulence) are the result of
microthrombus formation in arteries, veins, microvessels. This explains the high frequency of circulatory disorders in the vessels of the brain,
heart, kidneys and other organs. Thrombus formation in Vakez disease is caused by polycythemia, an increase
blood viscosity and in connection with this - a decrease in the speed of its current through the vessels.
In addition, thrombocytosis and often observed thrombocytopathies, which are accompanied by aggregation,
agglutination of blood cellsand the release of hemocoagulation factors from them. Along with thrombosis, bleeding tendencies are often observed
in patients with erythremia. This is associated with a dysfunction of the changed as a result
tumor process of erythrocytes and platelets, as well as the consumption ("consumption") of hemocoagulation factors in conditions of
diffuse thrombus formation.
In addition to Vakez's disease, primary erythrocytosis includes a number of familial inherited nonmyeloproliferative (i.e., not caused by tumor
transformation of myeloid cells, including the erythroid series) diseases with currently poorly understood etiology and pathogenesis. All these
diseases are characterized by an increase in the number of red blood cells per unit of blood volume, hypervolemia and other symptoms
described above for polycythemia. Their difference from Vakez's disease is the non-tumor nature of the activation of the proliferation of
erythroid cells in the bone marrow.
21.1.2. Secondary erythrocytosis
These types of erythrocytosis are symptoms of other conditions, pathological processes or diseases. The elimination of these conditions or
the cure of diseases also causes the disappearance of erythrocytosis without any special therapy.
Depending on the mechanism of development of these erythrocytosis associated with increased erythropoiesis and the release of excess
erythrocytes from the bone marrow into the vascular bed or redistribution of existing erythrocytes (without enhancing the proliferation of
erythron cells) in different regions of the vascular bed, respectively, absolute and relative erythrocytosis are isolated.
Secondary absolute erythrocytosis... The immediate cause of secondary absolute erythrocytosis is an increase in the formation of
erythropoietin.
Most often it is caused by the following conditions.
1. General, as a rule, chronic hypoxia of any genesis. It has been shown that hypoxia is the most important factor stimulating
erythropoietin production... In this regard, erythrocytosis is a mandatory symptom as an exogenous hypoxic state
(normobaric and hypobaric) and endogenous (respiratory hypoxia - with a decrease in the volume of alveolar ventilation; circulatory - due to
insufficient blood supply to organs and tissues; hemic - as a result of a decrease in the oxygen capacity of the blood; tissue - due to a decrease
in the effectiveness of biological oxidation). Erythrocytosis during hypoxia is adaptive, compensatory.
2. Local ischemia of the kidney or both kidneys, less often of the liver, spleen (with cysts in them, edema, stenosis of the arteries, inflammation).
3. Tumor growth, accompanied by the production of erythropoietin (neoplasms of the kidney, liver, spleen).
Manifestations secondary absolute erythrocytosis are signs of diffuse activation of the process of cell proliferation
erythron in a brain suit, which is combined with an increase in the concentration of erythropoietin in the blood plasma. In peripheral
blood, there is an increase in the number of erythrocytes and their precursors - reticulocytes - above normal (the latter are more than 2-10
° o). Unlike erythremia, erythrocytosis is usually not accompanied by thrombocytosis and leukocytosis. Moderate polycythemic
hypervolemia, increased blood viscosity and hematocrit are observed. In this regard, blood pressure and the load on the heart often
increase, which can cause myocardial hypertrophy with prolonged erythrocytosis with subsequent
violation of the rhythm and contractile function of the heart. In the vessels of the microvasculature, there are aggregates of erythrocytes
and microthrombi.
Secondary relative erythrocytosis... Characterized by an increase in the number of red blood cells per unit volume of blood without
activation of their products in the bone marrow and without increasing their absolute number in
the blood. The most common causes of the development of relative erythrocytosis are:
1. decrease in blood plasma volume (hemoconcentration) in case of loss of fluid by the body (diarrhea, vomiting, plasmorrhage in case of burn
disease, lymphorrhagia), which causes the development of polycythemic hypovolemia;
2. release of erythrocytes into the circulating blood from organs and tissues that deposit blood (during stress reactions, acute hypoxia,
hypercatecholaminemia) with the development of polycythemic hypervolemia.
Manifestationssecondary relative erythrocytosis is mainly due to hemoconcentration with the development of normal or hypovolemic
polycythemia and an increase in hematocrit. In this regard, a transient increase in blood viscosity and moderate hypertensive reactions can
be observed.
94.
Give the classification of anemias, data on the etiology, pathogenesis of clinical and
hematological manifestations of B12-, folate deficiency anemias.
B12-deficiency and folate deficiency anemia are anemias associated with impaired synthesis of nucleic acids and replacement of the normoblastic
type of hematopoiesis with megaloblastic due to a lack of vitamin B in the body12 and folic acid.
Cause:
1)
2)
Lack of vitamin in food...
Indigestion of vitamin B12 in the stomach, which may be due to dysfunction of the fundus of the stomach, which produces
gastromucoprotein (vitamin B12 assimilated in combination with gastromucoprotein). Dysfunction
lining cellscaused by exposure to autoantibodies (pernicious or Addison-Birmer or pernicious anemia). In addition, a similar condition
can occur after gastric resection.
3) Indigestion of vitamin B12 in the intestines (with resection of the small intestine, tumor, sprue, diphyllobothriasis, alcoholism).
4) Increased consumption of vitamins during pregnancy...
5) Violation of the deposition of vitamins in the liver with its diffuse lesion.
Pathogenesis... Vitamin B deficiency12 and folic acid, involved in the formation of thymine, which is part of DNA, reduces the rate her education.
Slow down DNA replication in tissues where normal cell division occurs most intensively (in hematopoietic tissue) leads to the formation
of large blood cells: megalocytes, megaloblasts, giant megakaryocytes.
The maturation of megaloblasts to megalocytes is accompanied by impaired enucleation (this is evidenced by the appearance in
megalocytes of Jolly's bodies (remnants of the nucleus) and Kebot's rings (remnants of the nuclear envelope)). The presence of a large
number of megaloblasts and megalocytes saturated with hemoglobin causes hyperchromia (CP> 1.0). There are many degenerative
occurrences in the blood
altered erythrocytes (: poikilocytosis, anisocytosis with microcytosis, hyperchromia, megalocytes with pathological inclusions). The number of
cells of physiological regeneration (reticulocytes, polychromatophiles) decreases, because in the bone marrow, irritation of the erythrocyte
germ is observed with a predominance of the megaloblastic type of hematopoiesis over the normoblastic one.
There is thrombotic and leukocytopenia with atypical cells.
As a result of a lack of vitamin B12 the body accumulates methylmalonic acid, which is toxic to nerve cells. In addition, with vitamin B
deficiency12 fatty acids with altered structure are synthesized in nerve fibers, which is reflected on the formation of myelin and leads to
damage to the axon. Degeneration of the posterior and lateral columns of the spinal cord (funicular myelosis) develops, the cranial and
peripheral nerves are affected.
Vitamin B12 (cyancobolamine) deficiency leads to:
1.
Violation of the transition: folic acid → tetrahydrofolic acid → thymine → DNA ,. in which actively multiplying cells of the
hematopoietic tissue (anemia); gastrointestinal tract (inflammatory and atrophic processes in the mucous membrane).
2. Disruption of the transition of methylmalonic acid to succinic acid (accumulation of methylmalonic acid) has a toxic
effect on the nervous system.
3. Disruption of myelin formation as a result of the synthesis of altered fatty acids.
IN12- deficitnye, folate-independent; As a result of a violation of heme synthesis: iron deficiency, porphyrin deficiency(iron refractory); Due to a
violation of the synthesis of globins: thalassemias and caused by a violation of the primary structure of globin chains; As a result of dysregulation
of the division and maturation of erythroid cells.
Etiology... The main causes are malabsorption or increased consumption of vitamin B12 and folic acid.
acid, less often their insufficient intake with food. Impaired absorption of vitamin B12 is most pronounced in malignant (pernicious) AddisonBirmer anemia, the development of which is due to the absence of Castle's intrinsic factor (gastromucoprotein) in the gastric juice of patients.
The cause of this disease has not been clarified. Vitamin B12 and folic acid are poorly absorbed in various lesions of the small intestine (bowel
resection, parasitism of the broad tapeworm, enteritis.
Megaloblastic anemia is sometimes observed in pregnant women. The reason is the intensive consumption of vitamin B12 and folic acid by the
fetus, when the embryonic type of hematopoiesis in the fetus is replaced by normoblastic (at the 4th-5th month of development).
Pathogenesis... Vitamin B12 and folic acid are essential for normal erythropoiesis. With a lack of vitamin B12 is at a loss
folic acid transition in its metabolically active form — tetrahydrofolic acid. As a result, synthesis is disrupted
DNAin hematopoietic cells, in particular erythro- and normoblasts. Their division and maturation are delayed, which determines the transition
of normoblastic erythropoiesis to megaloblastic.
The cells of pathological regeneration predominate in the bone marrow. A characteristic feature of megaloblastic erythropoiesis is its
ineffectiveness: the percentage of immature cells destroyed in the bone marrow sharply increases (up to 50%). Due to the suppression of mitotic
activity and ineffective erythropoiesis, the number of erythrocytes entering the blood is significantly reduced (hyporegenerative type anemia).
Blood picture... In the peripheral blood appear "giant" cells with a diameter of up to 12-15 microns - megalocytes and single megaloblasts
containing a nucleus. These cells are less resistant than normal erythrocytes, and they easily undergo hemolysis, which aggravates anemia.
Erythrocytes with pathologic inclusions in the form of Joldi bodies (remnants of the nucleus), Kebot's rings (remnants of the nucleus
membrane) and erythrocytes with basophilic granularity can be found in the blood. There is a pronounced anisocytosis with a predominance
macrocytes, there are neutrophils with a hypersegmented nucleus. Anemia is accompanied by leukopenia and thrombocytopenia.
Megaloblastic anemias refer to hyperchromic anemias with a color index above one (1.3-1.5). Hyperchromia is due to the large size of the
"cells". The total hemoglobin content in the blood drops significantly, and the number of erythrocytes decreases even more sharply.
95.
Provide data on the etiology, pathogenesis, clinical and hematological
manifestations, principles of diagnosis of iron deficiency anemia.
Iron deficiency anemia (IDA) - hypochromic microcytic hyporegenerative anemia,
resulting from an absolute decrease in iron resources in the body (as a rule, with chronic blood loss or insufficient
supply of iron from the outside), as a result of which hemoglobin (Hb) deficiency and trophic disorders develop. When
formulating a diagnosis, it is imperative
indicate the etiology of IDA.
Usually, in women, IDA occurs much more often than in men. According to various estimates, up to 20% of
women suffer from IDA.
Etiology (causes) of IDA
Chronic blood loss is the main cause of IDA.
● Uterine: pregnancy, menorrhagia, fibroids, the latter, even in the absence of menstrual bleeding, can lead to
iron deficiency.
● Gastrointestinal: gastroduodenal erosions and ulcers, hiatal hernia, portal hypertension with varicose veins of the
esophagus and rectum, ulcerative colitis, tumors, diverticula of the esophagus, stomach and intestines, Menetrie's
disease (the mucous membrane is easily vulnerable and often
bleeds).
● Pulmonary bleeding is a rare cause of iron deficiency.
● Bleeding from the kidneys and urinary tract, especially with hypernephroma, bladder cancer.
● Helminthic invasion.
● Hematological diseases: coagulopathy, thrombocytopenia, thrombocytopathy, Randu-Weber-Osler
disease.
● Vasculitis and collagenosis.
● Alimentary factors: vegetarianism, starvation, malnutrition, monotonous food.
● Impaired absorption of iron in the gastrointestinal tract: complete gastrectomy, resection of the stomach and /
or intestines, atrophic gastritis, malabsorption syndrome (celiac disease, sprue).
● Increase in the body's need for iron: in infants, in adolescence (all types of milk contain very little iron), during
pregnancy.
● Other causes: paroxysmal nocturnal hemoglobinuria, pulmonary hemosiderosis.
Pathogenesis (development of the process) IDA
Normally, about 15 mg of iron is supplied with food, from which only 1 mg (10-15%) is absorbed.
Obligatory losses of iron are also approximately 1 mg: through latent bleeding in the intestine (0.4-0.5 mg),
desquamation (sloughing) of the skin and intestinal epithelium (0.2-0.3 mg). Iron balance remains stable
throughout adulthood and iron loss is balanced by increased delivery
iron during absorption. The transport and deposition of iron is carried out by special proteins
- transferrin, transferrin receptor and ferritin.
The process of iron absorption occurs in the small intestine, and most intensively in the duodenal enterocytes. Iron
absorption is regulated in several ways: 1) the amount of iron supplied with food (alimentary regulator); 2) total iron
content in the body (depot-regulator or regulator of iron stores); 3) the activity of erythropoiesis (synthesis of
erythrocytes) in the bone marrow (erythroid regulator).
The causes of iron deficiency initially cause a gradual decrease in iron stores from the cells of the spleen, liver
and bone marrow. After iron stores are used up, the concentration of iron in
blood decreases, stimulating at the same time the absorption of iron, which increases 3 times. However, in most
cases, a negative iron balance develops, the most pronounced manifestation
which is the IDA.
Severity of anemia (by Hb level, g / l):
- light - 120-100;
- medium severity - 100-80;
- severe - less than 80.
Clinical picture (symptoms) IDA
With a lack of iron in the body, anemia does not appear immediately. It is preceded by a long period of latent
iron deficiency in the body without obvious symptoms of anemia.
Iron deficiency, even in the absence of anemia, is characterized by the so-called sideropenic symptoms: pronounced
changes in the skin, mucous membranes, nails, hair, which are not found in other types of anemia; muscle
weakness, perversion of taste (patophagia - addiction to chalk, clay, coal, toothpaste, ice) and smell (pathoosmia like the smell of gasoline, kerosene, paints, shoe polish, exhaust gases).
On examination, attention is drawn to the pallor of the skin, sometimes with a slight greenish tint (hence the
name "chlorosis") and with an easily arising blush on the cheeks, the latter is explained
thinness of the skin and pronounced vasomotor reactions. The skin becomes dry, flabby, flakes, cracks easily
form on the arms and legs. No tanning pigmentation. Hair loses its shine
thinner, split, gray, easily break, thin and turn gray early.
Changes in nails are specific: they become thin, dull, flattened, easily exfoliate and break, and transverse striation
appears. With pronounced changes, the nails acquire a concave, spoon-shaped shape (koilonychia - gnarled nails).
Changes in the tongue and mouth are characteristic. In patients, taste sensations decrease; appear
tingling, burning and bloating in the tongue, especially at the tip. Examination reveals atrophic changes in the mucous
membrane of the tongue, sometimes cracks at the tip and along the edges, in more severe cases - areas of
hyperemia ("geographical tongue") and aphthous changes. There are cracks in the lips and seizures in the corners of
the mouth (cheilosis), changes in tooth enamel. Teeth lose their shine, quickly deteriorate, despite the most careful
care of them. With prolonged use of iron preparations, teeth can turn black, so
how iron reacts with hydrogen sulfide released in carious cavities due to decay, with the formation of black
sulfite.
Sideropenic dysphagia syndrome (Plummer-Vinson syndrome) is often observed, manifested by difficulty in
swallowing dry and solid food and even saliva, which is accompanied by excruciating spasms, especially at night.
Patients are forced to chew solid food thoroughly.
Due to frequent choking, they prefer to eat slowly and alone. Esophagoscopy and X-ray examination reveal
spastic narrowing of the initial part of the esophagus. The onset of dysphagia is explained by atrophic processes
in the mucous membrane of the esophagus and the development in its proximal part of cracks, delicate
connecting membranes and bridges, as well as loss of secretion of the mucous membrane of the pharynx and
esophagus, facilitating the sliding of the food bolus. The association of dysphagia with sideropenia is confirmed
by a positive result of treatment of patients with iron preparations: dysphagia disappears along with an increase
in Hb and a return of plasma iron to normal levels.
In patients with IDA, muscle weakness occurs, which is not observed in other types of anemia. Muscle weakness is a
consequence not only of anemic hypoxia, but also the expression of a deficiency of the enzyme αglycerophosphate oxidase, which contains iron. Imperative urge to urinate and bedwetting are associated with
muscle weakness.
Common symptoms for patients with IDA may be shortness of breath, palpitations, chest pain, edema, fatigue,
weakness, irritability, apathy, headache, dizziness, arterial hypotension. Determined by tachycardia, expansion
of the boundaries of the relative dullness of the heart to the left, anemic systolic murmur at the apex and
pulmonary artery. On the jugular and femoral veins
the noise of the top is heard, which is explained by hydremia and increased blood flow velocity. The murmurs are of
a functional nature and disappear along with the elimination of the anemia. With severe IDA, elderly patients may
develop cardiovascular failure (2, 4).
A manifestation of IDA is sometimes fever, the body temperature usually does not exceed 37.5 ° C and disappears
after treatment with iron-containing drugs.
96.
Describe the etiology, pathogenesis, clinical and hematological manifestations of posthemorrhagic anemias.
Post-hemorrhagic anemia (PGA) develop as a result of the loss of a significant amount of blood.
Acute post-hemorrhagic anemia - normochromic normocytic hyperregenerative anemia resulting from acute
blood losswithin a short period of time. The minimum blood loss that poses a danger to the health of an adult is 500 ml. The severity of the clinical
picture is determined by the amount of blood lost, the rate and source of bleeding.
Cause: massive bleeding from damaged large vessels or heart cavities (trauma and surgical interventions, ectopic pregnancy, hemostasis
disorders, various diseases of internal organs, accompanied by acute bleeding).
Manifestations
2)
Common signs of anemia (tachycardia, shortness of breath, drop in blood pressure and venous pressure, pallor of the skin and mucous
membranes). The severity of these changes may not correspond to the severity of the anemia, since they often appear in response to
the cause of the bleeding (for example, pain or injury).
3) Increasing dry mouth feeling Is an important sign of acute bleeding.
4) Peripheral blood... The changes are staged and depend on the time elapsed after bleeding.
- The first hours and days...
•
Normocythemic hypovolemia (an equivalent decrease in the total content of corpuscular elements and blood plasma).
•
Decrease in the index of the volume of circulating red blood cells...
•
Ht, erythrocyte count, Hb level in a unit of blood volume within normal limits.
- 2-3 days after blood loss.
•
•
•
Decrease in Нb level below normal.
Decrease in the number of red blood cells per unit volume of blood and the drop in Ht.
Preservation within the normal range of the color index (due to the fact that mature erythrocytes circulating in the blood, which
were in the vascular bed, including in the depot, before blood loss).
•
Thrombocytopenia (as a result of consumption of platelets in the process of thrombus formation, hemodilution, as well as their loss
during blood loss).
•
Leukopenia (due to the loss of leukocytes during bleeding and subsequent hemodilution).
- 4-5th day after blood loss.
•
•
Decreased Hb content, erythropenia, decreased Ht... All
Erythrocyte hypochromia(color index below 0.85). It is caused by the lag of the rate of Hb synthesis from the rate of proliferation of
erythroid cells.
•
Increase in the number of young erythroid cells: reticulocytes, sometimes polychromatophilic and oxyphilic erythroblasts (as a result
of the high regenerative capacity of the bone marrow).
•
Thrombocytopenia and leukopenia...
Therapy. It is necessary to restore the BCC (surgical stopping of bleeding, blood transfusion, colloidal solutions).
Chronic post-hemorrhagic anemias
The reasons: prolonged, repeated bleeding as a result of violation of the integrity of the walls of blood vessels (for example, with infiltration of
tumor cells in them, extramedullary hematopoiesis, severe venous hyperemia, ulcerative processes in the gastrointestinal tract, skin, mucous
membranes), endocrinopathies (for example, with dyshormonal amenorrhea) and hemostasis disorders (for example, in violation vascular,
platelet or coagulation mechanisms in patients with hemorrhagic diathesis).
Pathogenesis and manifestationsassociated mainly with the growing iron deficiency in the body. They are a common variant of iron deficiency
anemias.
97.
Provide data on the etiology, pathogenesis, clinical and hematological manifestations of
hemolytic anemias.
21.3.2. Hemolytic anemias
Hemolytic anemias (HA) are the result of the predominance of the intensity of the process of hemolysis of erythrocytes over their production.
Life span of erythrocytes in this regard, it is reduced and does not exceed 90-100 days
By origin, GA is divided into secondary (acquired) and primary (hereditary or congenital).
Types of hemolytic anemias
I. Acquired (secondary)
II. Hereditary or congenital (primary):
1) caused by membranopathies:
a) protein-dependent: - microspherocytosis, - elliptocytosis (ovalocytosis), - stomatocytosis, - pyropoikilocytosis, - Rh-zero disease;
b) lipid-dependent: - acanthocytosis;
2) caused by fermentopathies:
a) glycolysis,
b) pentose-phosphate shunt, c) glutathione system;
3) caused by hemoglobinopathies:
a) with thalassemia,
b) with anemia with a violation of the primary structure of globin chains (sickle cell, etc.).
The main pathogenetic factor is the shortening of the life of erythrocytes and the predominance of the destruction process
erythrocytes over their production... Hemolytic anemias are accompanied by jaundice due to excess in the blood and deposition of bilirubin
pigment in the tissues. Its source is the hemoglobin of destroyed erythrocytes. According to the color index, hemolytic anemias are hypo- or
normochromic, less often - hyperchromic. They belong to regenerative anemias with normoblastic type of erythropoiesis. Due to the occurrence,
they distinguish between acquired and hereditary hemolytic anemias, by the nature of the disease, acute and chronic.
Acquired hemolytic anemias caused mainly by intravascular hemolysis of erythrocytes due to
damage to their membrane by various agents... Acutely developing hemolysis is characterized by the appearance of hemoglobin in the urine
(hemoglobinuria).
The reason are:
1) poisoning with hemolytic poisons (phenylhydrazine, aniline dyes);
2) some infectious and parasitic diseases (anaerobic sepsis, malaria);
3) transfusion of incompatible blood or Rh incompatibility between the fetus and the mother;
4) education in the body of autoantibodies against its own erythrocytes.
Rhesus-incompatibility can occur if the fetus inherits Rh-factor erythrocytes from the father, and the mother is Rh-negative; in the mother's body
against the Rh antigen, antibodies begin to be produced, which cause hemolysis of fetal erythrocytes (hemolytic disease of the newborn). Anemias
resulting from the destruction of red blood cells by anti-erythrocyte autoantibodies are called autoimmune hemolytic anemias. Anti-erythrocyte
autoantibodies can be formed: 1) in the case of changes in the antigenic structure of erythrocytes under the influence of various damaging factors
and 2) in the case of defects in the immunological system itself, as a result of which abnormal mutant clones of lymphoid cells synthesize
antibodies against erythrocytes of their own body.
Hereditary hemolytic anemias: arise as a result of inheritance of pathological types of hemoglobins (hemoglobinopathy), pathological forms of
erythrocytes (erythrocytopathy) and erythrocytes with a deficiency of enzymes (enzymopathy).
Hemoglobinopathies - these are genetically determined disorders of the structure of hemoglobin, differ from normal ones in that they have
altered amino acid composition of globin polypeptide chains... (sickle cell anemia and thalassemia).
Sickle cell anemia arises from the inheritance of pathological HbS. It is different from normalHbA the fact that in the p-chain
glutamic acid is replaced by valine.Erythrocytes take the form of a sickle when the partial pressure of oxygen in the blood decreases (hemoglobin
is precipitated and constricts the erythrocyte membrane). This type of anemia occurs in the population of tropical Africa and some regions of
India and is inherited in a recessive manner. Severe anemia appears only in subjects homozygous for HbS.
Thalassemia (Mediterranean anemia) is caused by a violation of the synthesis of a- or p-chains of normal HbAi and, accordingly, is called
thalassemia or p-thalassemia. With p-thalassemia, the formation of HbAi (a2p2) is inhibited and there is an excessive synthesis of HbAz and HbF
- fetal hemoglobin. For this disease, erythrocytes are typical in the form of a "target", strongly stained along the periphery and in the center.
Erythrocytopathy. Erythrocytopathies include hemolytic anemias caused by a genetic defect in protein or
erythrocyte membrane lipid structure... In these cases, the shape of erythrocytes changes (spherical, oval) and contracts
their lifespan... For example, with hereditary spherocytic anemia, membrane permeability is increased
erythrocytes to sodium... Together with sodium, water penetrates into the cell, the volume of erythrocytes increases, they acquire the shape of
a ball, their mechanical and osmotic stability decreases sharply. Globular erythrocytes (spherocytes) circulate in the bloodstream for no more
than 12-14 days. In hemoglobinopathies and erythrocytopathies, extravascular, intracellular hemolysis prevails. Deformed erythrocytes become
rigid, little elastic. Therefore, passing with difficulty through the smallest vessels, they
are damaged, captured by macrophages of the spleen and liver, and there they undergo premature hemolysis. The liver and spleen are
enlarged in patients.
Enzymopathies caused by a defect in a number of enzyme systems in erythrocytes. For example, with a lack of enzyme in red blood cells
glucose-6-phosphate dehydrogenase the first stage of glucose-6-phosphate metabolism in the pentose cycle is blocked. As a result, the
formation of the reduced form of glutathione decreases (reduced glutathione protects the SH-groups of globin and erythrocyte membranes
from oxidation). Erythrocytes with a reduced glutathione content are easily exposed to various oxidizing substances and hemolyzed. With a
deficiency of glycolytic enzymes (pyruvate kinase, hexokinase)
disrupts glycolysis and energy metabolism in erythrocytes, which contributes to their premature hemolysis.
98 Describe the causes, mechanisms, manifestations and
significance for the body of leukocytosis.
Leukocytosis
-states characterized by an increase
the numbers leukocytes per unit of blood volume above normal.
Causes of leukocytosis:
• The causes of leukocytosis are endogenous and exogenous factors (both can
be infectious and non-infectious).
• The nature of the causative factor of leukocytosis can be physical (for
example, periodic exposure of the body to ionizing
radiation in small doses); chemical (for example, alcohol,
moderate oxygen deficiency in the inhaled air, drugs that stimulate cell
proliferation); biological (usually - microbes, immune
complexes Ag-AT; an excess of biologically active substances that stimulate
leukopoiesis).
Mechanisms for the development of leukocytosis
The development of leukocytosis is a consequence of the stimulation of
leukopoiesis and the release of leukocytes from the hematopoietic tissue
into the peripheral blood,
redistribution of leukocytes in the vascular bed, tumor activation of
leukopoiesis in leukemia and hematosarcomas, hemoconcentration.
• Strengthening normal leukopoiesis. The reasons:
♦ An increase in the level or activity of humoral stimulants of leukopoiesis (for
example, colony-stimulating factors).
♦ Decrease in the content or activity of inhibitors of proliferation of
leukopoietic cells. As a result, the number
proliferating cells of leukopoietic tissue, combined, as a rule, with their
differentiation into mature leukocytes.
• The redistribution of leukocytes in the vascular bed is temporary and is not
accompanied by an increase in the number of young forms of leukocytes.
There is an accumulation of excess mature leukocytes in any region of the
body under the influence of biologically active substances. Leukocytosis with
such
the mechanism of development is called relative. Redistributive leukocytosis is
most often observed after significant physical exertion ("myogenic
leukocytosis"), in shock conditions (in shock
the number of leukocytes in the blood of the vessels of the lungs, liver,
intestinal walls increases, but decreases in other regions of the body).
• Overproduction of tumor leukocytes in hemoblastosis. The reasons:
♦ Activation of proliferation of hemoblastosis cells (as a manifestation
of tumor atypism of their division).
♦ Stimulation of the division of normal leukocytes due to the appearance in
the body of foreign (tumor) Ag, leukopoietins, and other growth factors.
• Hemoconcentration leukocytosis occurs with hypohydration
organism of various origins with the development of hypovolemia. With a total
normal number of leukocytes, their content per unit of blood volume
increased. At the same time, the amount of other blood corpuscles is
increased in the blood.
Manifestations of leukocytosis. The increase in the number of all forms of
leukocytes or their individual types is largely determined by the nature
causal factor.
• With allergic reactions, as a rule, there is a predominant increase in the
number of eosinophils in the blood.
• In bacterial infections, as a rule, myelopoiesis and the release of granulocytes,
mainly neutrophils, into the blood are stimulated.
• When many viruses (for example, pathogens of whooping cough,
hepatitis) and some microbes (for example, pathogens of tuberculosis,
syphilis, brucellosis) are introduced into the body, a predominant
stimulation of lymphopoiesis and an increase in the number of lymphocytes in
the peripheral blood.
• Some viruses, bacteria and protozoa (for example, causing
infectious mononucleosis, rubella, brucellosis, malaria) activate
monocytopoiesis and mobilization of monocytes from the bone marrow into
the blood with the development of monocytosis.
Changes in the leukocyte formula with leukocytosis
True (regenerative, absolute) leukocytosis, developing due to increased
proliferation of myelocytic cells, are accompanied by
changes in the leukocyte formula. Changes in the leukocyte formula are caused by
an increase or decrease in the number of young forms of myelocytic cells in the
peripheral blood and the appearance of forms that are normally absent in it. In
this case, they talk about a change in the ratio of mature and immature forms of
leukocytes - about a nuclear shift of granulocytes (usually neutrophils) to the left
or to the right. The use of these terms is associated with
the location of young forms of neutrophils (stab,
metamyelocytes, myelocytes, promyelocytes) on the left side of the laboratory
blank, and mature ones - on the right side of it.
• The shift to the left is characterized by an increase in the number of young and
immature forms of neutrophils.
• The shift to the right is manifested by an increase in the number of
segmented forms of neutrophils.
Since microscopy of a blood smear is the main criterion for
identification of different forms of maturity of granular leukocytes is
the nature of the nucleus (shape, size, color intensity), changes in
the leukocyte formula are designated as "nuclear".
• The shift to the right is often combined with an increase in signs of leukocyte
degeneration and a decrease in the number of stab neutrophils.
• Shift to the left. Shifts of the leukocyte formula of neutrophils to the left are
determined by the appearance of immature forms of neutrophils. Distinguish
between hyporegenerative, regenerative, hyperregenerative and regenerativedegenerative types of left shift.
• Hyporegenerative. They talk about it with an increase in the content of stab
neutrophils above the norm (more than 6%) and moderate leukocytosis (usually up
to 10-11x109 / l).
♦ Regenerative. It is characterized by an increase above the norm in the
percentage of stab neutrophils, the appearance of metamyelocytes in the
peripheral blood and leukocytosis up to 13-18x109 / l.
♦ Hyper-regenerative (it is sometimes also referred to as regenerative). It is
manifested by a significant increase in the content of stab neutrophils, the presence
of a large number of metamyelocytes in the peripheral blood and the appearance
of myelocytes, an increase in the total number of leukocytes to 20-25x109 / l.
♦ Regenerative-degenerative. It is observed with some infections, chronic
purulent processes, proceeding with significant intoxication. It is characterized by
a more or less pronounced increase in the number of stab neutrophils,
metamyelocytes and myelocytes, a decrease in the number of segmented
neutrophils (as a rule), signs of degenerative changes in the cytolemma, cytoplasm
and nucleus, an increase in the total number of leukocytes.
• Nuclear shift index of neutrophils.
These The above changes
in the ratio of mature and immature forms of neutrophils can be quantified by
calculating the nuclear shift index. It reflects the ratio of the amount of interest
content of all
young
forms neutrophils (stab,
metamyelocytes,
myelocytes, promyelocytes) to their
mature forms. In healthy adults, the nuclear shift index ranges from 0.05 to 0.10.
An increase in it indicates a nuclear shift of neutrophils to the left (i.e., activation
of leukopoiesis), a decrease, about a shift to the right (i.e., inhibition of
leukopoiesis). Types and significance of leukocytosis
• Physiological leukocytosis. These include most of the leukocytosis. They are
characterized by an adaptive nature and adequacy to the factors that cause them.
Among physiological leukocytosis, functional and protective-adaptive ones are
distinguished.
♦ Functional leukocytosis. It is caused by the performance of a certain function by
the body (for example, leukocytosis during pregnancy,
an increase in the number of leukocytes in the blood of intestinal vessels after
eating or muscle after prolonged physical work).
♦ Protective and adaptive. It develops in inflammatory processes, damage to cells
and tissues (for example, after heart attacks or strokes, soft tissue injury), stress. In
these and other similar cases, leukocytosis is accompanied by the activation of
leukocyte functions, including phagocytic.
• Pathological leukocytosis. It is observed with hemoblastosis, most often with
leukemia. Leukemic (i.e., tumor) leukocytes are characterized by a violation of their
functional activity: a decrease in their ability to synthesize and release cytokines,
to realize phagocytosis. In this regard, in patients with leukemia, the effectiveness
of immunity reactions is reduced, allergic reactions and diseases of immune
autoaggression often develop.
TYPICAL CHANGES IN THE LEUKOCYTE FORMULA
Leukocyte formula - a numerical description of the ratio of various types of
leukocytes circulating in the peripheral blood.
Changes in the leukocyte formula are the result of an increase or decrease in the
content of certain types of leukocytes and, in this regard, a change in the ratio
between them.
• Magnification in excess of the norm, the number of certain types of leukocytes
is designated by the appropriate terms: neutrophilia, basophilia, eosinophilia,
lymphocytosis, monocytosis.
• A decrease below the normal range of certain types of leukocytes is also referred
to as neutropenia, eosinopenia, lymphopenia (lymphocytopenia), monocytopenia.
♦ Agranulocytosis is the absence or significant decrease in the absolute number of
all types of granular leukocytes (neutrophils, eosinophils and basophils). This
condition is usually associated with leukopenia.
♦ Term "Basopenia" is not used, as in the norm basophils may be absent in the
peripheral blood.
Relative and absolute changes in the leukocyte formula
• Relative indicators characterize changes in the content of one or another type of
leukocytes in the leukocyte formula (relative to 100% leukocytes).
• Real (absolute) indicators reflect changes in the content of leukocyte pools per
unit volume.
When characterizing changes in the composition of leukocytes, it is necessary to
assess their absolute content. To determine the absolute number of a particular
type of leukocytes in the blood, this value is calculated taking into account the total
number of leukocytes and the percentage of the corresponding cells. For example,
the content of neutrophils in the leukocyte formula
is 80% (relative neutrophilia, normally up to 68%), and the total leukocyte count is
1.0x109 / l (leukopenia). Then the absolute concentration of neutrophils will be
0.8x109 / l (absolute neutropenia). This is more than two times less than 2.0x109 /
l - the lower limit of the normal absolute content of neutrophils.
Value. Analysis of the leukocyte formula allows you to determine the type of
leukocytosis or leukopenia by the cellular composition, the degree of shifts in the
content and ratio of individual forms of leukocytes, the possible mechanism of their
occurrence. Thus, an increase in the total number of leukocytes in combination
with absolute neutrophilia indicates regenerative (true) neutrophilic leukocytosis.
If an increase in the total number of leukocytes is accompanied by absolute neutroand eosinophilia, there is a regenerative mixed - neutrophil-eosinophilic
leukocytosis. The presence of a pronounced nuclear shift of neutrophils to the left
with neutrophilic leukocytosis usually indicates the true (regenerative) nature of
this leukocytosis, and the absence of such a shift is more often observed with the
redistribution mechanism of development of neutrophilic leukocytosis or with
neutrophilic leukopenia.
99 Describe the etiology, pathogenesis, manifestations and
significance for the body of leukopenia.
Leukopenia - conditions characterized by a decrease in the number
of leukocytes per unit of blood volume below normal.
Distinguish between primary (congenital or hereditary) and
secondary (acquired) leukopenias.
• Primary leukopenias include congenital aleukia, familial
neutropenia, intermittent hereditary neutropenia, Kostmann's
disease, and some others.
• Causes of secondary (acquired) leukopenia:
♦ Physical and chemical agents: ionizing radiation; benzene,
insecticides,
drugs
(NSAIDs,
antimetabolites,
sulfonamides,
barbiturates, alkylating agents, antitumor antibiotics, etc. can
lead to neutropenia and even agranulocytosis).
♦ Biological factors: autoaggressive Ig and immunocytes (for
example,
with
systemic
lupus
erythematosus);
generalized
infectious
processes
(typhoid
fever,
influenza,
measles,
rickettsioses, hepatitis).
Mechanisms of development of leukopenia
The development of leukopenia is the result of impairment or
oppression
processes of leukopoiesis, excessive destruction of leukocytes in
the vascular bed and organs of hematopoiesis, redistribution of
leukocytes in the vascular bed, loss of leukocytes by the body,
hemodilution.
• Violation or suppression of leukopoiesis is realized due to:
♦ A genetic defect in leukopoiesis cells (for example,
abnormalities in the genes that control the maturation of
leukocytes).
♦ Disorders of the mechanisms of neurohumoral regulation of
leukopoiesis (in particular, in hypothyroid states, hypocorticism,
a decrease in the level of leukotrienes or the sensitivity of cells
of the leukocyte lineage of hematopoiesis to them).
♦ Lack of components necessary for leukopoiesis (for example,
proteins, phospholipids, amino acids, folic acid, cyanocobalamin).
• Excessive destruction of leukocytes in the vascular bed or
organs of hematopoiesis is associated with the action:
♦ Penetrating radiation.
♦ Antileukocyte antibodies.
♦
Drugs acting as haptens (sulfonamides, barbiturates). Haptens
cause the formation of antibodies, which cause agglutination and
destruction of leukocytes.
•
The redistribution of leukocytes (is temporary) develops under
the influence of biologically active substances (chemotaxins,
activators of adhesion, aggregation, agglutination, etc.), causing
the accumulation or adhesion of leukocytes in certain regions of
the body and a picture of leukopenia (false) in others.
• An increased loss of leukocytes by the body is the result of:
acute and chronic blood loss, plasma and lymphorrhagia (for
example, with extensive burns, chronic purulent processes osteomyelitis, endometritis, peritonitis).
• Hemodilutional leukopenia (occurs relatively rarely) and is
formed due to:
♦ Hypervolemia (with transfusion of a large volume of blood plasma
or plasma substitutes).
♦ The flow of fluid from tissues into the vascular bed along the
gradient of osmotic or oncotic pressure (for example, with
hyperaldosteronism, hyperglycemia, hyperalbuminemia).
Manifestations of leukopenia
• Decrease in the content of leukocytes in a unit of blood volume
of all directions of differentiation (leukopenia) or mainly one of
them:
lymphocytes,
monocytes,
neutrophils,
basophils
or
eosinophils
(lymphocyto-,
monocyto-,
neutro-,
basoor
eosinopenia, respectively).
• Signs of leukocyte degeneration. They are more often detected
in neutrophils and monocytes.
♦ Degenerative changes are manifested by changes in the contour
of leukocytes (poikilocytosis), the presence of cells of different
sizes (anisocytosis), wrinkling or swelling of cells, the
appearance of vacuoles, toxogenic granularity and inclusions in
the cytoplasm, hypersegmentation or pycnosis of nuclei and their
destruction.
♦ A large number of degenerative forms of leukocytes in leukopenia
is often combined with a decrease in the number of segmented
leukocytes and a moderate increase in the content of stab and
even metamyelocytes (this blood picture is designated as a
degenerative nuclear shift to the left).
♦
If the number of segmented leukocytes with signs of
degenerative changes in them increases without an increase in the
number of stab cells, then they speak of a degenerative nuclear
shift to the right.
The meaning of leukopenia.
With severe leukopenia, there is a decrease in the body's
resistance
(mainly
anti-infectious,
as
well
as
antitumor).
100 Provide information about the types, causes, mechanisms of
development, changes in the leukocyte formula.
TYPICAL CHANGES IN THE LEUKOCYTE FORMULA
Leukocyte formula - a numerical description of the ratio of various types
of leukocytes circulating in the peripheral blood.
Changes in the leukocyte formula are the result of an increase or
decrease in the content of certain types of leukocytes and, in this regard,
a change in the ratio between them.
• An increase in excess of the norm in the number of certain types of
leukocytes is indicated by the corresponding terms: neutrophilia,
basophilia, eosinophilia, lymphocytosis, monocytosis.
• A decrease below the normal range of certain types of leukocytes is
also referred to as neutropenia, eosinopenia, lymphopenia
(lymphocytopenia), monocytopenia.
♦ Agranulocytosis is the absence or significant decrease in the absolute
number of all types of granular leukocytes (neutrophils, eosinophils and
basophils). This condition is usually associated with leukopenia.
♦ Term "Basopenia" is not used, as it is normal
basophils may be absent in peripheral blood.
Relative and absolute changes in the leukocyte formula
• Relative indicators characterize changes in the content of one or
another type of leukocytes in the leukocyte formula (relative to 100%
leukocytes).
• Real (absolute) indicators reflect changes in the content of leukocyte
pools per unit volume.
When characterizing changes in the composition of leukocytes, it is
necessary to assess their absolute content. To determine the absolute
number of a particular type of leukocytes in the blood, this value is
calculated taking into account the total number of leukocytes and the
percentage of the corresponding cells.
For example, the content of neutrophils in the leukocyte formula is 80%
(relative neutrophilia, normally up to 68%), and the total content of
leukocytes is 1.0x109 / l (leukopenia). Then the absolute concentration
of neutrophils will be
0.8x109 / l (absolute neutropenia). This is more than two times less
than 2.0x109 / l - the lower limit of the normal absolute content of
neutrophils.
Changes in the leukocyte formula with leukocytosis
True (regenerative, absolute) leukocytosis, developing due to increased
proliferation of myelocytic cells, are accompanied by
changes in the leukocyte formula. Changes in the leukocyte formula are caused by
an increase or decrease in the number of young forms of myelocytic cells in the
peripheral blood and the appearance of forms that are normally absent in it. In
this case, they talk about a change in the ratio of mature and immature forms of
leukocytes - about a nuclear shift of granulocytes (usually neutrophils) to the left
or to the right. The use of these terms is associated with
the location of young forms of neutrophils (stab,
metamyelocytes, myelocytes, promyelocytes) on the left side of the laboratory
blank, and mature ones - on the right side of it.
• The shift to the left is characterized by an increase in the number of young and
immature forms of neutrophils.
• The shift to the right is manifested by an increase in the number of
segmented forms of neutrophils.
Since microscopy of a blood smear is the main criterion for
identification of different forms of maturity of granular leukocytes is
the nature of the nucleus (shape, size, color intensity), changes in
the leukocyte formula are designated as "nuclear".
• The shift to the right is often combined with an increase in signs of leukocyte
degeneration and a decrease in the number of stab neutrophils.
• Shift to the left. Shifts of the leukocyte formula of neutrophils to the left are
determined by the appearance of immature forms of neutrophils. Distinguish
between hyporegenerative, regenerative, hyperregenerative and regenerativedegenerative types of left shift.
• Hyporegenerative. They talk about it with an increase in the content of stab
neutrophils above the norm (more than 6%) and moderate leukocytosis (usually up
to 10-11x109 / l).
♦ Regenerative. It is characterized by an increase above the norm in the
percentage of stab neutrophils, the appearance of metamyelocytes in the
peripheral blood and leukocytosis up to 13-18x109 / l.
♦ Hyper-regenerative (it is sometimes also referred to as regenerative). It is
manifested by a significant increase in the content of stab neutrophils, the presence
of a large number of metamyelocytes in the peripheral blood and the appearance
of myelocytes, an increase in the total number of leukocytes to 20-25x109 / l.
♦ Regenerative-degenerative. It is observed with some infections, chronic
purulent processes, proceeding with significant intoxication. It is characterized by
a more or less pronounced increase in the number of stab neutrophils,
metamyelocytes and myelocytes, a decrease in the number of segmented
neutrophils (as a rule), signs of degenerative changes in the cytolemma, cytoplasm
and nucleus, an increase in the total number of leukocytes.
• Nuclear shift index of neutrophils. The above changes in the ratio of mature and
immature forms of neutrophils can be quantified by calculating the nuclear shift
index. It reflects the ratio of the sum of the percentage of all young forms of
neutrophils (stab, metamyelocytes, myelocytes, promyelocytes) to their mature
forms. In healthy adults, the nuclear shift index ranges from 0.05 to 0.10. An
increase in it indicates a nuclear shift of neutrophils to the left (i.e., activation of
leukopoiesis), a decrease, about a shift to the right (i.e., inhibition of leukopoiesis).
Value. Analysis of the leukocyte formula allows you to determine the
type of leukocytosis or leukopenia by the cellular composition, the
degree of shifts in the content and ratio of individual forms of leukocytes,
the possible mechanism of their occurrence. Thus, an increase in the
total number of leukocytes in combination with absolute neutrophilia
indicates regenerative (true) neutrophilic leukocytosis. If an increase in
the total number of leukocytes is accompanied by absolute neutro- and
eosinophilia, there is a regenerative mixed - neutrophilic-eosinophilic
leukocytosis. The presence of a pronounced nuclear shift of neutrophils
to the left with neutrophilic leukocytosis usually indicates the true
(regenerative) nature of this leukocytosis, and the absence of such a shift
is more often observed with the redistribution mechanism of
development of neutrophilic leukocytosis or with neutrophilic
leukopenia.
101. Describe the types, etiology, pathogenesis, changes in peripheral blood in leukemoid
reactions. Their differences from leukemia, their importance for the body.
Leukemoid reactions
They refer to the number of typical pathological processes in the system of leukocytes, characterized by a
significant increase in the number of their various immature forms of flesh to blast cells and, as a rule, by an
increase in the total number of leukocytes in the peripheral blood. Term
"Leukemoid" indicates that changes in hematopoietic tissue and in peripheral blood resemble those in
leukemia, or leukemia.
However, leukemoid
reactions do not transform into the leukemia that they resemble, and go away after
completion of the main pathological process.
There are two large groups of leukemoid reactions: myeloid and lymphatic (monocyticlymphatic) types (table 4 in the appendix).
Etiology. The most common cause of leukemoid reactions are viruses, microbes, rickettsia, parasites, as
well as biologically active substances released during immune and allergic processes, tissue and tumor
breakdown, erythrocyte hemolysis. Thus, leukemoid reactions are one of the symptoms of other diseases
in most cases of an infectious (chickenpox, infectious mononucleosis, adenoviruses) and allergic nature
(HRT), as well as tumor growth.
The mechanism of development of leukemoid reactions associated with reactive focal hyperplasia of
various germs of leukopoietic tissue, which is accompanied by stimulation of leukopoiesis and the
elimination of significant masses of leukocytes from hematopoietic tissue into the circulatory bed.
Thus, the activity and content of leukopoietins increases and the content decreases.
agents that inhibit cell division, in particular, keylons.
The significance of leukemoid reactions is that they increase the body's resistance by increasing the
total number of mature functionally complete leukocytes.
102 Describe the definition of "leukemia", provide classifications, data on
etiology. Explain the features of hematopoiesis and blood cell composition in
different types of leukemia.
Leukemia - systemic tumor lesion of hematopoietic cells of the bone marrow.
All leukemias (leukemias) are divided into two types - acute and chronic. This division is
due to the different ability of leukemias to grow and develop growing cells.
In acute leukemia, cell development is practically absent; a large number of immature cells
accumulate in the blood at an early stage of development. This leads to inhibition of the normal
hematopoiesis of all sprouts. Such signs are detected in the blood in more than 80% of cases.
Chronic leukemia produces a population of growing granulocytic cells that gradually
replace normal peripheral blood cells.
It should be noted that acute leukemia will never turn into chronic and vice versa.
Acute leukemia
The initial stage of acute leukemia... Usually, it can be assessed only retrospectively, that is,
already when it is over. Blood biochemical parameters can be both normal and slightly
increased or decreased. Mild weakness may also be noted, previously existing chronic diseases
are exacerbated, the herpes virus, other bacterial and viral infections are activated. An extended
period of acute leukemia with pronounced clinical and hematological manifestations, which
consists of exacerbations and remissions and ends with either complete remission (cure) or
transition to the terminal stage. The main criterion for establishing remission is the absence of
blast cells in the peripheral blood.
A complete clinical and hematological remission within 5 or more years can be considered a
cure.
Terminal stage of acute leukemia... It is characterized by the lack of action used in the
treatment of cytostatics, complete inhibition of the hematopoietic system. Some clinics even at
this stage undertake bone marrow transplant operations, but still the mortality rate at this stage
is extremely high.
Chronic leukemia
Unlike acute leukemia, in chronic leukemia, blood cells have time to "mature", but the
overwhelming majority of the resulting blood cells are not able to perform their direct
function. Therefore, in laboratory tests, you can see a fairly high number of leukocytes,
although they are not able to protect the body from infection. In cases where the number of
granulocyte cells is so large that it interferes with normal blood flow, patients are given
leukoparesis - removal of excess leukocytes, including tumor cells. The effect of such a
procedure is quite quick, albeit temporary.
Chronic leukemia may not have any initial phase at all, 50% of patients with chronic leukemia
did not have complaints about their own health, leukemia was diagnosed in them according to
a blood test performed for another reason. Even after diagnosis, chronic leukemia can continue
for years, relatively benign. This phase is called monoclonal and is characterized by the
presence of one clone of tumor cells. The next stage is due to the appearance of secondary
tumor clones, is characterized by a rapid course with the appearance of many blasts and is
called the polyclonal stage, or the stage of the blast crisis. 80% of patients with chronic
leukemia die in the blast crisis stage.
As a result of damage by tumor cells, patients with chronic leukemia develop spleno- and
hepatomegaly (an increase in the size of the spleen and liver), general chronic anemia, and
lymph nodes are generally affected.
Blood picture
The morphological substrate of acute leukemia is formed by young cells (blast forms of the 2nd
or 3rd class of progenitors or cells of the 4th class), the bulk of the tumor in chronic leukemia is
represented by mature and maturing cells. The different forms of acute leukemia are named
according to the normal homologous bone marrow progenitors (lymphoblasts, myeloblasts, etc.).
Chronic leukemia is designated by the name of those mature and maturing cells that characterize
tumor proliferation. The morphological classifications of extra-cerebral tumors divide them into
2 groups: lymphorgranulomatosis (Hodgkin's disease) and non-Hodgkin's lymphomas.
Leukemic cells differ from normal homologous cells in a number of
morphological, chemical, cytogenetic features.
Blast cells can be significantly increased in size (2-3 times) or reduced to the size of a
lymphocyte; anisocytosis is characteristic. The contours of the nucleus are often deformed,
the amount of chromatin is increased and unevenly distributed. Vacuolization of the
nucleus, its segmentation, multinucleation are noted. In the bone marrow, the number of
cells in the mitotic stage is increased. The number of nucleoli is often increased (up to 8 or
more), their size can reach 1 / 3-1 / 2 of the diameter of the nucleus. There is an increased
basophilia of the cytoplasm, its vacuolization. Often, pronounced azurophilic granularity
and Auer's little bodies are found.
103 Describe the types, causes, mechanisms of development,
consequences
thrombocytopenia.
Thrombocytopenia - conditions characterized by a decrease in the
number of platelets per unit of blood volume below normal (less than
180x109 / l).
Types of thrombocytopenia
The International Classification of Diseases (ICD-10) includes thrombocytopenia
in bleeding disorders and class D69 immune disorders.
As an independent disease, it can have an acute (lasting up to six months) and
chronic (more than six months) course. By origin, the disease is divided into:
•
•
primary thrombocytopenia - depends on violations of the process of
hematopoiesis, the production of antibodies to their own platelets;
secondary - develops as a symptom of other diseases (X-ray radiation, severe
poisoning, alcoholism).
D69.5 - a separate code has secondary thrombocytopenia
(symptomatic).
The degrees of thrombocytopenia are characterized by clinical
manifestations of different severity and the level of platelet reduction:
•
•
•
Mild degree - 30-50 x109 / l, the disease is detected by chance, has no
manifestations, sometimes there is a tendency to nosebleeds.
Moderate - 20-50 x109 / l, characterized by the occurrence of small rashes all
over the body (purpura) on the skin and mucous membranes.
Heavy - less than 20 x 109/ l, multiple rashes, gastrointestinal bleeding.
The reasons. Thrombocytopenia can be caused by various factors of
a physical, chemical and biological nature. The mechanism of
thrombocytopenia development is the implementation of one or more
of the following processes:
♦ Suppression of the platelet lineage of hematopoiesis.
♦ Increased destruction of platelets.
♦ Involvement of platelets in the process of generalized
thrombus formation.
♦ Increased deposition of platelets in the spleen.
Thrombocytopenia manifestations
• Bone marrow:
♦ Bone marrow hyperplasia. It is manifested by an
increase
in
the
number
of
megakaryoblasts
and
megakaryocytes in it. It is observed with increased
destruction of platelets or thrombus formation.
♦ Bone marrow hypoplasia. It is detected in patients with
hemoblastosis (leukemia), radiation sickness, tumor metastases
in the bone marrow.
♦ Decreased glycogen and enzyme activity (eg, lactate dehydrogenase,
glucose-6-phosphate dehydrogenase) in megakaryoblasts and
megakaryocytes, which reduces platelet lifespan.
• Peripheral blood: a decrease in the number of platelets, an increase in
their size with a usually normal number of erythrocytes, Hb, leukocytes;
with severe hemorrhagic syndrome, anemia may develop.
• Hemostasis system.
♦ Decrease in the concentration of platelet clotting factors.
♦ Increased duration of bleeding.
♦ Decrease in the degree of retraction of the blood clot.
♦ Development of hemorrhagic syndrome.
Thrombocytopenia therapy
• Etiotropic principle provides for the termination (decrease in the degree)
of the pathogenic action of factors causing thrombocytopenia. For this,
splenectomy is performed and hemangiomas are removed; protection
against ionizing radiation; replacement of drugs causing thrombocytopenia;
prevent the ingestion of substances that cause thrombocytopenia (ethanol,
gold compounds, etc.) into the body.
• Pathogenetic principle. In order to reduce the consumption or
destruction of platelets, to activate thrombocytopoiesis, normalize the
content and activity of pro- and antiplatelet agents in the blood, platelets
are transfused, bone marrow transplanted, lymphoid or plasmapheresis is
used (removal of antiplatelet antibodies and lymphocytes from the blood),
as well as immunosuppressants, antiplatelet agents, anticoagulants ...
• Symptomatic principle. To normalize the functions of
organs
and
their
systems,
impaired
due
to
thrombocytopenia, infusion of components and blood
products is performed, as well as treatment of posthemorrhagic conditions.
104 Provide data on the types, causes, mechanisms of development,
consequences of thrombocytopathies.
Thrombocytopathies - conditions characterized by a violation of the properties of
platelets (adhesive, aggregation, coagulation) and, as a rule, by disorders of the
hemostasis system.
Thrombocytopathies (in contrast to thrombocytopenia), stable, long-lasting
functional, biochemical and morphological changes in platelets are characteristic.
VIEWS
Thrombocytopathies are divided into primary (hereditary and congenital) and
secondary (acquired).
• Primary thrombocytopathies develop with gene defects. Examples: von
Willebrand disease, Glanzmann thrombasthenia, thromboxane A synthetase
deficiency.
• Secondary thrombocytopathies develop under the influence of various factors.
♦ Chemical factors: excess of toxic metabolic products, some drugs,
hypovitaminosis (deficiency of ascorbic acid, cyanocobalamin).
♦ Biological factors: substances formed in tumor cells (they disrupt the division
and maturation of megakaryocytes), degradation products of fibrinogen and fibrin
(with disseminated intravascular coagulation syndrome), increased plasma levels
of normal and abnormal proteins in Waldenstrom's disease and myeloma, high
plasma concentration blood clotting system factors (for example, when transfusing
large doses of blood plasma, procoagulant concentrates).
PATHOGENESIS OF THROMBOCYTOPATHIES
The development of both primary and secondary thrombocytopathies is based on
a disorder of one or several processes: impairment of synthesis and accumulation
of biologically active substances in platelet granules; disorders of the processes of
degranulation and release of platelet factors into the blood plasma; violation of the
structure and properties of platelet membranes (membranopathy).
Partial or combined implementation of these mechanisms determines either a
predominant violation of the contact activity of platelets (their aggregation or
adhesion), or predominant disorders of their procoagulant properties.
MANIFESTATIONS OF THROMBOCYTOPATHIES
• Hemorrhagic syndrome.
• Disorders of microcirculation: changes in the volume and velocity of blood flow
in the vessels of the microcirculatory bed, its turbulent nature
and etc.
• Significant changes in functional properties
platelets (adhesive, aggregation, procoagulation).
• Defects of platelet granules: absence or decrease in their number, impaired
release of their contents.
• Abnormalities in the size and shape of megakaryocytes and platelets.
TREATMENT OF THROMBOCYTOPATHIES
Treatment of thrombocytopathies is a difficult task, and in many patients
(especially with hereditary and congenital forms) it is carried out throughout life.
Etiotropic principle. Aimed at stopping the action of factors of a physical, chemical,
biological nature; treatment of diseases, pathological processes and conditions that
cause thrombocytopathy.
Pathogenetic principle. To prevent (reduce the degree) of violations of adhesive,
aggregation and procoagulant activity of platelets, it is necessary to administer
proaggregants, procoagulants or antifibrinolytic drugs; the use of substances that
stimulate
"Release reaction" (ATP, magnesium sulfate, magnesium thiosulfate), as well as
transfusion of platelet mass, protein blood preparations (fibrinogen, thrombin,
etc.).
Symptomatic principle. To normalize the functions of organs and tissues impaired
as a result of microcirculation disorders, bleeding and hemorrhage in
thrombocytopathy, it is necessary to inject solutions that normalize the rheological
properties of blood (plasma substitutes, plasma), stop bleeding, and treat posthemorrhagic conditions.
105 Provide information about the etiology and pathogenesis of obstructive
ventilation disorders, give examples of diseases.
Chronic nonspecific lung disease
HNZL -a group of lung diseases of various etiology, pathogenesis and morphology, which are
characterized by the development of chronic cough with sputum production and shortness of
breath, which is associated with specific diseases, primarily pulmonary tuberculosis.
The HNZL group includes:
chronic bronchitis, bronchial asthma, bronchiectasis, chronic obstructive pulmonary
emphysema, chronic abscess, chronic pneumonia.
COPD lead to the development of pneumosclerosis, secondary hypertension, right ventricular
hypertrophy, heart failure.
COPD are the underlying diseases for the development of lung cancer.
Chronical bronchitis.
The disease is characterized by excessive production of mucus by the bronchial glands, which
leads to the appearance of a productive cough lasting at least 3 months annually for 2 years.
The reasons:
Causative agents of infections, prolonged irritation of the bronchi by physical and chemical
substances.
Pathogenesis and morphogenesischronic bronchitis is based on a violation of the drainage
function, primarily of the small bronchi, as a result of prolonged exposure to various etiological
factors, while in the bronchial wall in response to damage to the bronchial epithelium, chronic
inflammation, metaplasia, and mucus hyperproduction develop. Chronic catarrhal inflammation
develops in the bronchi.
· The classification of chronic bronchitis is based on 3 criteria:
1) the presence of bronchial obstruction;
2) type of catarrhal inflammation;
3) the prevalence of the process.
· By the presence of bronchial obstruction and the type of catarrhal
inflammation, they are distinguished:
1) chronic obstructive simple catarrhal bronchitis;
2) chronic obstructive mucopurulent bronchitis;
3) chronic non-obstructive simple catarrhal bronchitis;
4) chronic non-obstructive mucopurulent bronchitis.
· In terms of prevalence, chronic bronchitis is divided into:
Local (local);
diffuse. Pathological
anatomy:
In chronic bronchitis, the walls of the bronchi are thickened, surrounded by layers of
connective tissue, sometimes deformation of the bronchi is noted, saccular and
cylindrical bronchiectasis (expansion of the bronchial lumen) may occur.
In the bronchi, chronic mucous or catarrhal inflammation develops with metaplasia of the
epithelium and hyperplasia of the mucous glands. In the wall of the bronchus, cellular
inflammatory infiltration is noted, the proliferation of granulation tissue, which can lead to the
formation of inflammatory polyps of the bronchial mucosa. Sclerosis and atrophy of the muscle
layer are also noted. The most pronounced changes are observed at the level of small bronchi.
Complications:
Bronchopneumonia, the formation of foci of atelectasis (collapse of the lung tissue),
obstructive pulmonary emphysema, pneumofibrosis.
Bronchiectasis.
The term bronchiectasis is adopted to denote persistent pathological expansion of one or more
bronchi, with the destruction of the elastic and muscular layers of the bronchial wall.
Bronchiectasis is a disease characterized by a certain complex of pulmonary and
extrapulmonary changes, in the presence of bronchiectasis in the bronchi.
Pathogenesis:
In the development of bronchiectasis, the mechanism of bronchial obstruction in combination
with a secondary bacterial infection is of great importance. In the cavity of bronchiectasis,
purulent exudate, the content of the microbial body and desquamated epithelium are found. In
the adjacent lung tissue, there are fields of fibrosis, foci of pulmonary emphysema.
The extrapulmonary symptom complex in bronchiectasis is caused by severe respiratory hypoxia
and the development of hypertension in the pulmonary circulation. Patients have fingers in the
form of drumsticks, nails in the form of watch glasses, cyanosis; hypertension in the pulmonary
circulation, leads to hypertrophy of the right ventricle and the development of cor pulmonale.
Complications:
Associated with the possibility of developing pulmonary hemorrhage, lung abscesses, pleural
empyema, chronic pulmonary heart failure. Metaplasia of the epithelium of the bronchi and
bronchiectasis can give rise to the development of bronchial cancer. Against the background of
prolonged ongoing purulent inflammation in the lungs and bronchi, secondary amyloidosis of
internal organs can develop.
Emphysema of the lungs.
Emphysema of the lungsa syndromic concept denoting a persistent expansion of the air spaces
below the terminal bronchioles, accompanied by a violation of the integrity of the alveolar
septa.
The reasons:
The causes of chronic obstructive emphysema are the same as for chronic bronchitis, which
often precedes it (pathogens, prolonged irritation of the bronchi by physical and chemical
substances).
Emphysema of the lungs grows simultaneously with the progression of sclerosis
and is characterized by an increase in the alveoli and the content of air in them.
loading...
The lungs are enlarged, swollen, pale, do not collapse, are cut with a crunch, a mucopurulent
exudate is squeezed out of the lumens of the bronchi. Lung tissue in the foci of emphysema
loses its elastic properties, the interalveolar septa are ruptured or hardened. Pneumosclerosis
develops. There is an increased blood pressure in the pulmonary circulation, cor pulmonale
develops.
Complication is progressive pulmonary heart disease.
Bronchial asthma.
Bronchial asthma chronic lung disease, characterized by paroxysmal disorders of bronchial
patency, the clinical expression of which is attacks of expiratory suffocation caused by
bronchial spasm, hypersecretion of mucus by the bronchial glands, changes in the
composition of mucus, edema of the bronchial mucosa.
Distinguish: atopic, non-infectious-allergic bronchial asthma and infectious-allergic
bronchial asthma.
106. Describe the etiology and pathogenesis of restrictive ventilation
disorders, give examples
diseases.
Restrictive respiratory failure can be caused by: 1. pleural diseases that limit the excursion
of the lung (exudative pleurisy, hydrothorax, pneumothorax, fibrothorax, etc.);
2. a decrease in the volume of the functioning lung parenchyma (atelectasis, pneumonia, lung
resection, etc.);
3. inflammatory or hemodynamically caused infiltration of lung tissue, leading to an increase in
the "stiffness" of the pulmonary parenchyma (pneumonia, interstitial or alveolar pulmonary
edema with left ventricular heart failure, etc.);
4. pneumosclerosis of various etiologies;
5. lesions of the chest (deformity, kyphoscoliosis) and respiratory muscles (myositis).
It should be noted that in many diseases of the respiratory system, there is a combination of
restrictive and obstructive disorders, as well as a violation of the processes of lung perfusion
and diffusion of gases through the alveolar-capillary membrane. Nevertheless, it is always
important to assess the prevailing mechanisms of impaired pulmonary ventilation, having
obtained objective justifications for the appointment of one or another pathogenetic therapy.
Thus, the following tasks arise:
1. Diagnosis of dysfunctions of external respiration and an objective assessment of the
severity of respiratory failure.
2. Differential diagnosis of obstructive and restrictive pulmonary ventilation disorders.
3. Substantiation of pathogenetic therapy of respiratory failure.
4. Evaluation of the effectiveness of the treatment.
107 Give the classification, etiology and pathogenesis of respiratory
regulation disorders. Pathological types of breathing.
Breathing is regulated by the respiratory center located in the reticular formation of the
medulla oblongata. Distinguish between the center of inhalation and the center of exhalation.
The activity of the respiratory center is regulated by the overlying parts of the brain.
The cerebral cortex has a great influence on the activity of the respiratory center, which is
manifested in the voluntary regulation of respiratory movements, the capabilities of which are
limited. A person at rest breathes without any visible effort, most often without noticing this
process. This state is called breathing comfort, and breathing
- eupnea, with a frequency of respiratory movements from 12 to 20 per minute. In pathology,
under the influence of reflex, humoral or other influences on the respiratory center, the rhythm of
breathing, its depth and frequency can change. These changes can be a manifestation of both
compensatory reactions of the body, aimed at maintaining the constancy of the gas composition
of the blood, and a manifestation of disturbances in the normal regulation of respiration, leading
to the development of respiratory failure.
Respiratory dysregulation manifestations are:
bradypnea - rare, less than 12 respiratory movements per minute, breathing. A reflex decrease
in the respiratory rate is observed with an increase in blood pressure (reflex from the
baroreceptors of the aortic arch), with hyperoxia as a result of turning off the chemoreceptors
that are sensitive to a decrease in paO2. When large airways are stenosed, infrequent and deep
breathing occurs, called stenotic. In this case, reflexes come only from the intercostal muscles,
and the action of the Hering-Breuer reflex is delayed (it ensures the switching of respiratory
phases when the stretch receptors are excited in the trachea, bronchi, bronchioles, alveoli,
intercostal muscles). Bradypnea occurs when hypocapnia develops when climbing to a great
height (mountain sickness). Depression of the respiratory center and the development of
bradypnea can occur with prolonged hypoxia (stay in conditions
rarefied atmosphere, circulatory failure, etc.), the action of narcotic substances,
organic lesions of the brain;
polypnoea (tachypnea) - frequent, more than 24 respiratory movements per minute, shallow
breathing. This type of breathing is observed with fever, functional disorders of the central
nervous system (for example, hysteria), lung damage (pneumonia, pulmonary congestion,
atelectasis), pain in the chest, abdominal wall (pain leads to a limitation of the depth of
breathing and an increase in its frequency, gentle breathing develops). In the origin of
tachypnea, greater than normal stimulation of the respiratory center is important. With a
decrease in lung compliance, impulses from the proprioceptors of the respiratory muscles
increase. With atelectasis, impulses from the pulmonary alveoli, which are in a collapsed state,
are amplified, and the inspiratory center is excited. But during inhalation, the unaffected alveoli
are stretched to a greater extent than usual, which causes a strong flow of impulses from the
receptors inhibiting inhalation, which cut off the inhalation ahead of time. Tachypnea
contributes to the development of alveolar hypoventilation as a result of preferential ventilation
of the anatomically dead space;
hyperpnea - deep and rapid breathing. It is noted with an increase in basal metabolism: with
physical and emotional stress, thyrotoxicosis, fever. If the hyperpnea is caused by reflex and is
not associated with increased oxygen consumption
and removal of CO2, then hyperventilation leads to hypocapnia, gas alkalosis. This is due to
intense reflex or humoral stimulation of the respiratory center in case of anemia, acidosis,
and a decrease in the oxygen content in the inhaled air. The extreme degree of excitation of
the respiratory center is manifested in the form of Kussmaul breathing;
apnea - lack of breathing, but usually a temporary cessation of breathing is implied. It can occur
reflexively with a rapid rise in blood pressure (reflex from baroreceptors), after passive
hyperventilation of the patient under anesthesia (decrease in pCO2). Apnea can be associated
with a decrease in the excitability of the respiratory center (with hypoxia, intoxication, etc.).
Inhibition of the respiratory center until it stops can occur under the action of narcotic drugs
(ether, chloroform, barbiturates, etc.), with a decrease in the oxygen content in the inhaled air.
Types of periodic breathing. Periodic breathing is called such a violation. breathing rhythm, in
which periods of breathing alternate with periods of apnea. This includes Cheyne-Stokes
respiration and Biot respiration. During Cheyne-Stokes breathing, pauses (apnea - up to 5-10 s)
alternate with respiratory movements, which first increase in depth, then decrease. When Biota
breathes, pauses alternate with breathing movements of normal frequency and depth. The
pathogenesis of periodic respiration is based on a decrease in the excitability of the respiratory
center. It can occur with organic brain lesions - injuries, strokes, tumors, inflammatory
processes, with acidosis, diabetic and uremic coma, with endogenous and exogenous
intoxications. Transition to terminal types of respiration is possible. Sometimes periodic
breathing is observed in children and elderly people during sleep.
Pathological types of breathing
CHAYNE STOKES BREATH
Named after the doctors who first described this type of pathological breathing - (J. Cheyne,
1777-1836, Scottish doctor; W. Stokes, 1804-1878, Irish doctor).
Cheyne-Stokes breathing is characterized by the frequency of respiratory movements, between
which there are pauses. First, a short-term respiratory pause occurs, and then in the dyspnea
phase (from several seconds to one minute), first, silent shallow breathing appears, which rapidly
increases in depth, becomes noisy and reaches a maximum on the fifth - seventh breath, and then
decreases in the same sequence and ends with the next short respiratory pause.
In sick animals, a gradual increase in the amplitude of respiratory movements (up to
pronounced hyperpnea) is noted, followed by their extinction to a complete stop (apnea),
after which a cycle of respiratory movements begins again, ending also with apnea. Apnea
lasts 30 to 45 seconds, after which the cycle repeats.
This type of periodic respiration is usually recorded in animals with diseases such as petechial
fever, hemorrhage in the medulla oblongata, with uremia, and poisoning of various origins.
During a pause, patients are poorly oriented in the environment or completely lose consciousness,
which is restored with the resumption of respiratory movements. A variety of pathological
breathing is also known, which is manifested only by deep intercalated breaths - `` peaks ''.
Cheyne-Stokes breath, in which interstitial breaths appear regularly between two normal phases of
dyspnea, is called Cheyne-Stokes alternating breath.
Known alternating pathological respiration, in which every second wave is more superficial, that
is, there is an analogy with an alternating violation of cardiac activity. Mutual transitions of
Cheyne-Stokes respiration and paroxysmal, recurrent dyspnea are described.
It is believed that in most cases, Cheyne-Stokes breathing is a sign of cerebral hypoxia. It can
occur with heart failure, diseases of the brain and its membranes, uremia. The pathogenesis of
Cheyne-Stokes respiration is not entirely clear. Some researchers explain its mechanism as
follows. The cells of the cerebral cortex and subcortical formations are inhibited due to
hypoxia - breathing stops, consciousness disappears, the activity of the vasomotor center is
inhibited. However, chemoreceptors are still capable of responding to changes in blood gas
levels. A sharp increase in impulses from chemoreceptors, along with a direct effect on the
centers of high concentration of carbon dioxide and stimuli from baroreceptors due to a
decrease in blood pressure, is sufficient to excite the respiratory center
- breathing resumes. Respiration restoration leads to blood oxygenation, which reduces brain
hypoxia and improves the function of neurons in the vasomotor center. Breathing becomes
deeper, consciousness becomes clearer, blood pressure rises, filling of the heart improves.
Increasing ventilation leads to an increase in oxygen tension and a decrease in carbon dioxide
tension in arterial blood. This, in turn, leads to a weakening of the reflex and chemical
stimulation of the respiratory center, the activity of which begins to fade away - apnea sets in.
BREATH OF BIOTA
Breathing Biota is a form of periodic breathing, characterized by alternation of uniform
rhythmic respiratory movements, characterized by constant amplitude, frequency and depth,
and long (up to half a minute or more) pauses.
It is observed with organic brain lesions, circulatory disorders, intoxication, shock. It can also
develop with primary
the defeat of the respiratory center by a viral infection (encephalomyelitis of the stem
localization) and other diseases accompanied by damage to the central nervous system,
especially the medulla oblongata. Often, the breath of Biota is noted in tuberculous
meningitis.
It is characteristic of terminal states, often preceding respiratory arrest and cardiac arrest. It is
an unfavorable prognostic sign.
BREATH OF GROCK
"Wavelike breathing" or Grokk's breathing is somewhat reminiscent of Cheyne-Stokes
breathing with the only difference that instead of a respiratory pause, weak shallow breathing is
noted, followed by an increase in the depth of respiratory movements, and then its decrease.
This type of arrhythmic dyspnea, apparently, can be considered as stages of the same
pathological processes that cause Cheyne-Stokes respiration. Cheyne-Stokes breathing and
“wavelike breathing” are interconnected and can transform into each other; the transitional
form is called `` incomplete Cheyne-Stokes rhythm ''.
BREATH OF KUSSMAUL
Named after Adolf Kussmaul, the German scientist who first described it in the 19th
century.
Kussmaul's pathological breathing ("big breathing") is a pathological form of breathing that
occurs in severe pathological processes (pre-terminal stages of life). Periods of cessation of
respiratory movements alternate with rare, deep, convulsive, noisy breaths.
Refers to terminal types of breathing, is an extremely unfavorable prognostic sign.
Kussmaul's breathing is peculiar, noisy, quickened without a subjective feeling of
suffocation, in which deep bone-abdominal inspirations alternate with large expirations in
the form of `` extra-expirations '' or active expiratory end. It is observed in extremely serious
conditions (hepatic, uremic,
diabetic coma), with methyl alcohol poisoning or other diseases leading to acidosis. As a rule,
patients with Kussmaul breathing are in a coma. In diabetic coma, Kussmaul's breathing appears
against the background of exsicosis, the skin of sick animals is dry; gathered in a fold, it
straightens with difficulty. There may be trophic changes on the limbs, scratching, hypotonia of
the eyeballs, the smell of acetone from the mouth. Temperature
subnormal, low blood pressure, no consciousness. With uremic coma, Kussmaul breathing
is less common, and Cheyne-Stokes breathing is more common.
108 Describe the general etiology and pathogenesis, manifestations and
consequences of disorders of the digestive system.
The causes of gastrointestinal disorders are quite diverse, which allows them to be
combined into several groups:
1. eating disorders, i.e. malnutrition, overeating, or changes in food quality (imbalance in
proteins, carbohydrates, and fats). In a number of cases, eating disorders are caused by the
psychosocial environment in which people live: for example, the standard of beauty in different
countries is defined diametrically opposite. If in the tribes of East Africa, girls were prepared for
marriage by means of enhanced feeding, and the thicker they are, the more desirable for grooms,
then in Europe and America, many are deliberately limiting their diet, just to stay at the level of
widely advertised beauty standards such as Sharon Stone, Kim Bassinger or Timothy Dalton;
2. violations associated with the pathological effects of microbial flora or helminths;
3. radiation damage and damage to OM;
4. alcohol and nicotine abuse;
5. psycho-emotional trauma and stress;
6. professional harm;
7. endocrine disorders, including age-related.
Under the influence of etiological factors, the following, rather unified, violations in the
activity of various parts of the gastrointestinal tract arise:
1. motor skills and food evacuation;
2. secretion of digestive juices;
3. suction and
4. excretion of food.
Like any other functional system in the body, the gastrointestinal tract is under the control of
neurogenic and humoral signals, which we will talk about in detail when analyzing specific
pathological conditions of the gastrointestinal tract.
It should be remembered that all parts of the digestive system are interconnected, and in some
cases this connection is due to embryogenesis: for example, the intestines, pancreas and liver.
Upon completion of development, the gut maintains contact with its "embryonic partners"
through the bile and pancreatic ducts. In healthy people, these connections persist throughout
life, being broken only under the action of pathogenic factors, which we will talk about later.
Obviously, gastrointestinal and digestive disorders are accompanied by metabolic disorders,
which are caused by the pathology of chemical (enzymatic) processing of food and the digestion
of proteins, fats and carbohydrates.
Dysfunction of the gastrointestinal tract is manifested mainly by five clinical symptoms that
require a brief discussion. These symptoms are pain, bloating, diarrhea, malabsorption, and
vomiting. There are other symptoms that accompany gastrointestinal disorders (heartburn,
constipation, nausea), but we will focus on those mentioned above.
1. Bloating - it can be acute and chronic, mechanical or biochemical in etiology. In young
children, the reason for this is more often an excess of air in the stomach. The most typical
among other mechanical causes are the accumulation of fluid in the abdominal cavity (ascites),
diseases accompanied by severe pain and secondary paralytic ileus (peritonitis, renal colic, etc.).
At the same time, most of the biochemical causes of bloating are mediated by the influence of
acidosis and electrolyte imbalance in the intestine (adrenal insufficiency, cystic fibrosis,
galactosemia, etc.).
2. Abdominal pain is mainly of three types: visceral, peritoneal, and radiating. In general, the
abdominal organs are poorly innervated by the fibers of pain sensitivity, therefore, visceral pain
is usually not very specific in nature, it is poorly localized. The sensation of pain emanating
from the internal organs is a consequence of stretching the bed of the organs, and quite fast.
Peritoneal pain often the result of an inflammatory process, for example, with appendicitis, etc.
Radiating pain appears as a result of irritation of nerve endings in one of the many
branches of the nerve trunk and is felt in one of several areas of distribution of other
branches (for example, in liver diseases, pain can "give" to the region of the kidneys,
stomach, which made it possible to combine these pain sensations as an integral part of the
viscero -visceral reflexes). The causes of abdominal pain can be grouped into three broad
groups:
- gastrointestinal (acute abdomen and therapeutic pathology (hepatitis,
cholecystitis, ulcer, etc.);
- infectious (pneumonia and pleural effusion, parasites, urinary tract infection);
- metabolic (acidosis of any etiology, diabetes, hypoglycemia, hyperlipidemia, etc.,
intoxication (lead, irritating poisons)).
The molecular mechanism of abdominal pain in acidosis is unknown, but ischemia is thought to
increase the concentration of tissue metabolites around nerve endings and thus induce pain.
Diarrhea - Every year, a huge number of people around the world have diarrhea, in the
overwhelming majority of cases of secondary or infectious origin. The intestine is primarily
an absorbing and transporting organ that ensures the transfer of substances from the
environment to the body. In light of this fact, most of the causes of diarrhea are based on one
of the following four mechanisms:
1) osmotic - i.e. due to the presence in the lumen of a clinically unusual amount of poorly
absorbed, osmotically active substances, for example, deficiency of disaccharidases;
2) violation of the processes of active transport (absorption) - chloride diarrhea,
impaired absorption of glucose and galactose;
3) secretory - i.e. increased intestinal secretion (infectious enteritis, accumulation of
secretory substances - bile salts of fatty acids);
4) violation of intestinal motility - hypocalcemia, hypothyroidism, adrenal insufficiency,
cholinergic drugs.
Intestinal malabsorption - is manifested primarily by impaired absorption of fat
(steatorrhea.). Since lipids provide about 50% of the calorie requirement, disruption of this
process can have serious consequences for growth and general well-being. Penetrating with the
help of bile acids into the cells of the intestinal mucosa, fatty acids bind with glycerol, forming
esterified fatty acids. They are surrounded by a thin layer of proteins, forming a transport form chylomicron. The absorption of lipids and fat-soluble vitamins depends on the following
factors:
1) emulsification of lipids, determined by the presence of bile salts;
2) digestion of triglycerides catalyzed by pancreatic lipase;
3) the suction surface of the intestinal mucosa, which is necessary for the formation
of chylomicrons.
Young children are especially sensitive in this regard, in whom the total pool of microvilli of
the jejunum is less than that of adults. For the normal absorption of fat, the action of pancreatic
lipase and cholesterol esterase is of great importance. The causes of intestinal fat absorption
disorders can be divided into three groups:
- associated with the pathology of the pancreas:. cystic fibrosis, Schwachman's syndrome,
lipase deficiency;
- associated with the pathology of the liver and bile ducts: cirrhosis, atresia or
obstruction of the bile duct, impaired synthesis of bile acids;
- associated with bowel pathology: blind loop syndrome, chronic infection, parasites,
radiation damage to celiac disease, etc.
Vomiting - a complex reflex act, as a result of which the contents of the stomach (and
intestines) are spewed out through the mouth. Vomiting is usually preceded by nausea,
hypersalivation, tachypnea, and tachycardia. The vomiting center is located in the medulla
oblongata, near the sensory nucleus of the vagus nerve. From a biochemical point of view, the
metabolic consequences of vomiting are much more important than the act of vomiting as such,
diagnostically relatively insignificant. The consequences of vomiting include dehydration,
alkalosis, hypokalemia, hyponatremia. Vomiting can be caused by:
I - metabolic disorders of amino acids: phenylketonuria, tyrosinemia, etc.
II - organic acidemia: lactic acidosis, methylmalonic aciduria, etc .;
III - disturbances in the urea cycle: hyperornithinemia, arginine-succinic aciduria, etc.;
IV - others .: galactosemia, adrenogenital syndrome, metabolic acidosis, uremia, cystic
fibrosis, porphyria, renal tubular acidosis.
In addition, direct mechanical irritation of the vomiting center is possible (increased
intracranial pressure, so-called "cerebral vomiting").
Vomiting often has a protective effect, freeing the stomach of poor quality food or toxic
substances (similar to gastric lavage).
Having outlined the main clinical symptoms of digestive disorders, we turn to the analysis of
the pathogenetic mechanisms of disorders of individual parts of the gastrointestinal tract.
109 Provide data on ethics and
pathogenesis, manifestations and consequences of appetite
disorders.
Let's immediately define a number of concepts in order to avoid semantic confusion in
the future.
Hunger - This is a feeling of the need to eat, which can be accompanied by a complex complex
of manifestations, including hunger pangs, premature salivation and activation of behavioral
responses to seeking food. In general, this is a painful condition, which, as it intensifies, acquires
a psychopathological character.
Appetite is the desire for food. Unlike hunger, which occurs when the body's supply of
nutrients is depleted below a certain level, appetite can persist even after the hunger is
satisfied. Appetite is influenced by emotions, the presence or absence of attractive or
distracting stimuli.
Satiety means not wanting to eat.
Based on Cannon's data, who revealed a connection between hunger and the appearance of
strong rhythmic stomach contractions, Carlson suggested that the stomach is the organ that sends
the necessary information about hunger or satiety to the central nervous system. Carlson
anticipated the currently widespread view that blood glucose concentration is directly related to
hunger and satiety. Despite the attractiveness of this point of view, there are facts that contradict
it.
On the basis of numerous experimental studies, a working hypothesis has been proposed about
the role of certain regions of the hypothalamus in the regulation of food intake. Ventromedial
nuclei serve as a relay (relay) point that unites the flow of information about saturation.
Destruction of this area interferes with the perception of satiety cues, leading to hyperphagia
(i.e. overeating) and ultimately obesity. In the lateral region of the hypothalamus there is a
"facilitating food center" that functions as an integrating link of all complex visual, auditory,
olfactory, tactile and other reflexes associated with eating behavior.
According to the "classical" theory, information about satiety enters the ventromedial part of the
regulatory mechanism, and signals that inhibit the lateral food centers emanate from the
ventromedial nuclei. Nevertheless, it is assumed that extrahypothalamic mechanisms are more
responsible for feeding behavior than hypothalamic ones. For example, general depletion of the
body during tumor processes develops independently of hypothalamic mechanisms. The
hypothesis of the setting point, or appestat - barostat, is formulated on the basis of the lipostatic
theory of regulation of food intake. According to this theory, the regulation of the amount of
food consumed is associated with a mechanism for controlling lipid stores in adipose tissue. It is
not clear whether the barostat registers constantly changing physical activity or a decrease in fat
stores due to this activity. The physiological state of hunger affects the regulator of food
consumption, as well as a complex of sensory signals that can have a positive effect, enhancing
eating behavior, or, conversely, suppress the corresponding reflexes. It should be noted that a
number of neurotransmitters are also involved in the regulation of food consumption processes:
for example, intracranial administration of norepinephrine activates the food reflex in animals,
but at the same time, sympathomimetics of the anfetamine group inhibit food consumption (for
which they are called anorectics).
The most obvious activators of eating behavior are alpha-adrenergic agonists and opioid peptides
(such as beta-endorphins). The inhibitors include - beta-adrenergic agonists, serotonin,
cholecystokinin, insulin. and some other hormones.
One of the most common appetite disorders is its lack - anorexia. More often we are talking
about the so-called anorexia nervosa, which occurs mainly in girls of puberty and young women
(very rarely in boys). This is a serious condition that, if not interrupted, can result in death.
Usually anorexia nervosa. accompanied by weight loss, amenorrhea, constipation, bradycardia,
decreased body temperature, low blood pressure. The very term "anorexia" in this case is not
entirely accurate, because these people constantly think about food, create complex fantastic
rituals around it, limiting their diet to certain foods. Most of the manifestations of this
condition are associated with the hypothalamus.
Anorexia itself can be caused by excess protein and imbalanced mixtures of amino acids. The
mechanism of this phenomenon is not exactly known, but its implementation does not depend
on the hypothalamus. Anorexia often occurs with liver disease (hepatitis), but
the mechanism of this phenomenon is also unknown, vitamin deficiencies, dehydration,
infectious diseases.
Increased appetite (hyperphagia, bulimia). - a kind of painful condition accompanying
diabetes mellitus, some metabolic diseases. In the United States, where the standard of
Hollywood movie stars is widely adopted, obese people are trying to combat bulimia
deliberately caused by vomiting in combination with diuretics and laxatives.
Hyperphagia can be induced in animals by systematic injections of insulin or
glucocorticoids. It should be noted that increased appetite without adequate feedback results
in obesity, with all the negative consequences.
If everything is in order with appetite, then the next link in the digestive system, where
disturbances are possible, is the oral cavity, where, first of all, mechanical processing of food
takes place. Its violations are possible with the pathology of the dentoalveolar apparatus,
violation of the acts of chewing and swallowing.
Chewing is a function of the mouth, in which all its parts are involved: lips, tongue, teeth, jaw
joints, salivary glands, all kinds of mucosal receptors and chewing muscles. Violation of this
function occurs with damage or absence of teeth, pathology of the chewing muscles, damage to
the temporomandibular joints.
If the supporting state of the teeth is insufficient against the chewing load, then they speak of
traumatic occlusion and a violation of articulatory balance. In this case, the balance between the
chewing load and the resistance of the periodontal tissue is disturbed. Under the influence of the
chewing load, the periodontal death occurs. In the gums, as a result of increased pressure, there is
a disorder of blood circulation, stagnation. Over time, as a result of chronic inflammation, the
connective tissue of the gums proliferates, the gums swell, and a picture of hyperplastic
gingivitis develops. Prolonged and significant overloading causes partial bone death. As a result
of periodontal compression, bleeding, thrombosis, inflammation, and then necrosis and hyaline
degeneration occur. All this affects the development of periodontal disease.
It should be noted that a large number of microorganisms, including pathogenic ones, are
present in the oral cavity. Their rapid growth against the background of a weakened immune
system can lead to oral sepsis. At the same time, there are protective factors in the oral cavity,
for example, lysozyme, an enzyme contained in saliva. It is capable of destroying the
membranes of microbial cells. In addition, up to 250 thousand leukocytes, mainly neutrophils,
migrate into the oral cavity every minute. Salivary immunoglobulins play a protective role.
110 Provide data on the etiology and pathogenesis, manifestations
and consequences of impaired salivation.
So we come close to the pathology of the salivary glands, which perform secretory and
endocrine functions. Saliva moistens food, forms a food lump and ferments carbohydrates
(the action of alpha-amylase, which in large
the amount secreted by the parotid gland). Saliva also contains alpha-glucosidase, proteases
(kallikrein-salivain), nucleases (RNA and DNase), phosphatase, peroxidase, carbonic anhydrase.
Saliva is hypotonic in relation to blood. Washing the teeth and the mucous membrane of the
mouth, saliva has a protective and trophic effect. Salivary enzymes can cause both physiological
(regulating microcirculation in the oral cavity) and pathological reactions (inflammation under
the action of kinins, and an excess of nucleases leads to the development of dystrophy).
Normally, 0.5-2 liters of saliva is secreted.
For ped. f-that.: In newborns, there is a relative immaturity of the salivary glands. little saliva
is released. Although its secretion increases from the first days of life, up to 2-3 months. it is
still not enough. Small amounts of amylase are present in saliva, which limits its role in milk
digestion. The amylolytic activity of saliva continues to increase in children from 1 to 4 years
of age. The pH of saliva in children is 7.32, its bactericidal properties are weaker than in adults.
Hypersalivation, i.e. increased salivation, observed with inflammation of the oral mucosa,
pulpitis, periodontitis, in contact with a drill, with diseases of the digestive system, pregnancy,
the use of parasympathomimetics. At the same time, the total molar concentration of saliva
increases (Gendengain's law). Hypersalivation can lead to the neutralization of gastric juice and,
accordingly, upset stomach. In addition, the loss of a large amount of saliva leads to severe
disturbances in the water-salt balance.
Hyposalivation, i.e. a decrease in salivary secretion, is noted in infectious and febrile
processes, with dehydration, with the action of atropine-like substances, as well as when an
inflammatory process occurs in the salivary glands (sialodenitis, parotitis, submaxillitis).
Known severe systemic damage to the salivary and lacrimal glands (Sjogren's syndrome),
which is characterized by dryness of the mucous membranes of the mouth, eyes and upper
respiratory tract. Hyposalivation is sometimes observed with cystic fibrosis and calculous
sialoadenitis, inflammation of the ducts (sialodochitis). At the same time, the act of chewing
and swallowing becomes difficult, the development of infectious inflammatory diseases of the
oral cavity is initiated.
Salivary hormones include: 1) parotin, which lowers the level of Ca in the blood and promotes
the growth and calcification of teeth and skeleton, urogastron (nerve and epidermal growth
factor), granulocytosis factor, insulin-like substance, glucagon, etc., which proves an important
role salivary glands in many vital processes of the body.
Processing food in the mouth ends with the act of swallowing. ensuring the ingestion of food
into the stomach. Its violation (dysphagia) may be associated with a disorder of the functions of
the trigeminal, hypoglossal, vagus, glossopharyngeal and other nerves, disruption of the
swallowing muscles, congenital and acquired defects of the hard and soft palate, with damage to
the arches of the soft palate and tonsils. Swallowing is impaired in rabies, tetanus and hysteria
(spastic muscle paralysis). The final act of swallowing is the movement of food masses along the
esophagus under the influence of its peristalsis. This process can be disrupted with spasm or
paralysis of the muscular membrane of the esophagus or with its narrowing (burn, diverticulum,
etc.).
From the esophagus, food enters the stomach for further chemical and physical
processing and subsequent transportation to the intestine.
111 Describe the etiology and pathogenesis, manifestations
and consequences of violations of the secretory and motor
functions of the stomach.
Exogenous (more often primary) functional stomach disorders occur with nutritional
disorders: irregular food intake, rapid change of regimen
food, fast food and dry food, overeating, abuse of carbohydrates, pork and lamb fat, coarse
vegetable fiber, mushrooms, smoked meats, spices, insufficient amount of protein, vitamins,
mineral salts, trace elements.
The pathogenesis of functional stomach disorders associated with alimentary errors and toxic
effects is due to disturbances in its periodic activity due to irritation of the baro- and
chemoreceptors of the pyloric region of the stomach with coarse, poorly crushed food, extractive
and toxic substances.
A number of exogenous factors - high air temperature, heavy muscle work, high barometric
pressure, vibration, noise, ionizing radiation, injury, burns, medications (acetylsalicylic acid,
indomethacin, corticosteroids, etc.) can lead to functional stomach disorders - short-term
hyperchlorhydria with the subsequent development of secretory insufficiency. In these cases,
the occurrence of functional stomach disorders is associated with the direct effect of damaging
agents on the gastric mucosa or with their effect on regulatory systems (cerebral cortex,
hypothalamus, pituitary gland, autonomic centers, endocrine organs). The release of an excess
amount of gastrin leads first to gastric hypersecretion and hyperchlorhydria, and over time,
The coordinated activity of the sphincters of the stomach is impaired, which promotes
mixing of food and contact digestion.
Endogenous (usually secondary) functional stomach disorders occur in diseases of other
organs and systems: nervous, endocrine, digestive, cardiovascular, respiratory, urinary,
hematopoietic.
Especially often the cause of endogenous functional disorders of the stomach are diseases of the
digestive system. It is noted that in case of intestinal diseases (chronic enterocolitis, dysentery),
gastric secretion first increases, and then sharply decreases, accompanied by inhibition of the
motor function of the stomach. In chronic cholecystitis, both secretory and motor functions of
the stomach decrease, up to achlorhydria and hypotension. Multidirectional changes in the
secretory activity of the stomach are observed in acute viral hepatitis.
Diseases of the cardiovascular system, in particular myocardial infarction, are often
accompanied by functional stomach disorders. Described cardiospasm, gastric paresis,
vomiting in myocardial infarction, hypertensive crisis, which are often harbingers of an
unfavorable prognosis of the underlying disease. Decrease
of all indicators of gastric secretion (volume of secretion, release of hydrochloric acid and
pepsin) is observed in rheumatism, hypertension.
Chronic infectious processes (tuberculosis, suppurative lung diseases, etc.), accompanied by
intoxication and hypoxia, often lead to functional disorders of the stomach, characterized by
inhibition of gastric secretion and motility and changes in the structure of the gastric mucosa.
Quite often, gastric dysfunction occurs in chronic nephritis, even without uremia, manifested by
gastric dyspepsia and pain in the epigastric region, increasing in chronic renal failure.
A decrease in the secretory and motor function of the stomach is often found with anemia, iron
deficiency.
Diseases of the endocrine organs can also cause functional stomach upset. In particular, in
diseases that occur with an increase in the function of the pituitary gland, adrenal cortex, thyroid
gland, there is an increase in acid-forming function and stomach tone; in diseases With a
decrease in the function of the endocrine glands (for example, Addison's disease,
hypothyroidism) - a decrease in the secretory and motor functions of the stomach.
Hyperchlorhydria was diagnosed in Zollinger-Ellison syndrome (hormone-active pancreatic
adenoma), hypoglycemia, menopause; hypochlorhydria - with hyperglycemia and pregnancy.
During endoscopic and often histological examination of the gastric mucosa in patients with
functional stomach disorders, its normal structure is noted. However, histochemical examination
and electron microscopy reveal changes reflecting the different functional activity of the cellular
elements of the mucous membrane. These changes are especially pronounced in the cells of the
integumentary fossa epithelium of the stomach and in the goblet cells of the villi of the
duodenum, with hyperchlorhydria they are enlarged, contain a large amount of mucin, which
fills the cell and pushes the nucleus towards its base. The PIC reaction, which makes it possible
to detect neutral glycose-aminoglycans, which are an integral part of epithelial mucin, is sharply
positive. Along with signs of hyperfunction of the epithelium, its hyperplasia is observed; this
leads to the deepening and formation of new gastric pits, which gives them a corkscrew-like
appearance. Similar changes occur in the duodenum, as a result of which the villi become
elongated and branched.
In the pyloric and Brunner glands, the size and number of secretory cells, containing a large
amount of mucin rich in glycosaminoglycans, increase.
Histochemical and electron microscopic examination of the main and parietal cells in
hyperchlorhydria showed an increase in their size, the appearance of giant main and parietal
cells. At the same time, an increase in the content of protein-lipoid complexes in the cytoplasm
of parietal cells was noted; RNA, DNA and pepsinogen granules are in the main cells. The
number of over-functioning main and parietal cells in the fundic glands significantly increases
during gastric hypersecretion; they are found in more than 80% of patients with functional
gastric disorders of this type. Less often, with increased secretion of hydrochloric acid and
pepsin, an increase in the number of main and parietal cells or an expansion of the secretory
zone due to the antrum of the stomach is observed. However, morphological and ultrastructural
study of parietal cells
indicates their high functional activity and shows that the hypersecretion of hydrochloric acid
can only be partially explained by an increase in their number.
The combination of parietal cell hyperplasia with their accelerated differentiation
constitutes the morphological substrate of the hypersecretory syndrome.
In hypochlorhydria, histochemical changes of the opposite nature were revealed: the content of
neutral glycosaminoglycans was unevenly reduced both in the integumentary fossa epithelium
and in the goblet cells; most cells are small and optically empty. The functional activity of the
glands, according to the PIC response, is significantly reduced.
Thus, functional indigestion has its own morphological expression. With an increased
secretory function of the stomach, hyperplastic processes of the mucous membrane,
hypertrophy of parietal cells, an increase in the activity of mucoid cells, an increase in the
content of ribonucleoproteins in the main cells and the activity of redox enzymes in the
cytoplasm of parietal cells are often detected. At the same time, the ultrastructural
characteristics of parietal cells also change: the number of secretory granules increases, the
number and size of mitochondria, intracellular tubules expand, and the profile of the
endoplasmic reticulum deepens.
With a reduced secretory function of the stomach, the content of glycosaminoglycans and
the activity of redox enzymes decrease, which has its own ultrastructural expression.
Violation of the motor function of the stomach
Normally, gastric movements are expressed in the form of peristalsis - a wave-like contraction
of the stomach wall, which propels food from the cardiac to the pyloric section, and peristoli tonic muscle tension, which contributes to crushing food.
In pathological conditions, gastric motility can be increased
(hypertonicity) or weakened (hypotonia, atony).
The occurrence of disturbances from the motor activity of the stomach is mainly associated
with the direct response of smooth muscles to the influence of a number of neurotransmitters
and hormones with the participation of receptors. Possible pathology of smooth muscles and
gastric pacemaker (for example, with surgical transection of the vagus nerve). Stem vagotomy
leads to an increase in the tone of the proximal stomach with a simultaneous decrease in the
phase activity of its distal sections. At the same time, the evacuation of fluid from the stomach
is accelerated and the evacuation of solid chyme slows down. With an increase in tone n.
Vagus increases the rhythm and strength of stomach contractions, and accelerates the
evacuation of its contents into the duodenum. On the contrary, activation of sympathetic nerves
decreases the rhythm, the strength of stomach contractions and the speed of propagation of the
peristaltic wave.
The motor activity of the stomach is influenced by gastrointestinal hormones and hormones of
general action. Secretin, cholecystokinin-pancreosimin, enterogastron,
glucagon inhibits gastric motility and the rate of evacuation of food from it. Strengthening
the motility of the gastrointestinal tract occurs under the influence of gastrin, motilin,
histamine, serotonin, insulin.
Gastric motility is inhibited by hyposecretion of gastric juice (hypo- and achlorhydria),
bulbogastron, glucagon, fever, starvation.
Among other causes of disorders of gastric motility, the action of a number of drugs is often
noted, in particular antihypertensive drugs, especially calcium antagonists, to a greater extent
long-acting (prolonged), rauwolfia group, α-methyldopa derivatives, psychotropic,
anticholinergic drugs, nitrates, antispasmodics.
Violation of the motor activity of the stomach is also noted in diseases of the endocrine
(hypothyroidism, hyperparathyroidism, diabetes mellitus), nervous (meningitis, encephalitis,
brain tumor) systems, a number of infectious diseases (Botkin's disease, intestinal infections),
metabolic disorders, electrolyte disorders, and often mental illness (neurogenic anorexia,
indomitable vomiting). In each of the listed diseases, the presence of disorders of the motor
activity of the stomach can be associated with a complex mechanism, including disorders of the
nervous, hormonal regulation, electrical rhythm and functions of the smooth muscles of the
stomach. So, for example, a violation of gastric emptying can develop with a prolonged course of
diabetes mellitus, complicated by visceral neuropathy, which is manifested by a disorder of
autonomic functions not only of the stomach, but also the gallbladder, bladder, intestines.
Gastroparesis in patients with diabetes mellitus is most often caused by visceral neuropathy, but
the influence of drugs that reduce sugar content and psychogenic factors is not excluded.
The primary change in the muscles of the stomach can occur with a number of collagenoses, in
particular with scleroderma and dermatomyositis. Significant violations of the motor activity of the stomach are noted during
surgical operations.
Disorders of the motor function of the stomach are manifested by symptoms such as heartburn,
belching, hiccups, nausea and vomiting.
Heartburn (pyrosis) - a feeling of warmth or burning in the lower esophagus (can be localized
behind the sternum or in the upper part of the epigastric region), spreading from the bottom up from the epigastric region to the neck. Heartburn, as a rule, is the result of the throwing of acidic
(pH <4.0) stomach contents or bile into the esophagus with an antiperistaltic wave with an open
cardiac sphincter (i.e., associated with gastroesophageal reflux). At the level of contact with
gastric contents, a spasm of the esophagus occurs, above - its antiperistalsis. The intensity of this
manifestation depends on the concentration of acid in the gastric contents, the frequency and
duration of its contact with the esophageal mucosa. Heartburn worsens after eating, especially
plentiful, with bending of the torso, in the supine position, with pathology of the abdominal
muscles.
"Sour belching") or bitter, yellow or green (bile).
Heartburn can occur after eating a number of foods: fats, sour fruit juices, tomatoes, garlic,
onions, peppers, etc. or drugs that reduce the tone of the lower esophageal sphincter theophylline, progesterone, antidepressants, nitrates, calcium antagonists, etc. Heartburn is
usually relieved by swallowing saliva, drinking water, and most clearly when taking antacids.
Belching (eructatio) - sudden ingestion of a small portion of the contents of the stomach or
esophagus into the oral cavity. Usually the stomach contains a small amount of gases (gas
bubble), which stimulate its motor and secretory functions. A small amount of air is swallowed
during meals. From 20 to 60% of the gas in the intestine is the share of the swallowed air
(evidence of this is the presence of nitrogen and oxygen, which are present in the atmosphere
and are not produced in the digestive tract). The accumulation of air in the stomach can cause a
feeling of fullness, overstretching it after eating, which is proved by X-ray examination
abdominal cavity. Acute distension of the stomach by swallowed air more often occurs after
an abundant meal and is accompanied by a pronounced pain syndrome resembling angina
pectoris. In the supine position, gastric bladder syndrome can develop, when the air in the
stomach is trapped (below the junction of the esophagus with the stomach) by the pressure of
the liquid located above it, so that this air cannot be belched out.
Aerophagia (swallowing air outside the meal) is more often observed in neurogenic conditions.
Distinguish between belching with air and belching with food. Belching food can be sour or
bitter (admixture of bile), as well as putrefactive (with stagnation of food in the stomach).
Persistent belching of food is a characteristic symptom of cardiac sphincter insufficiency and a
number of diseases of the abdominal organs: gastric ulcer and duodenal ulcer, active
gastroduodenitis, gastroesophageal reflux disease, stomach cancer, esophagus. In atrophic
gastritis, when the gatekeeper gapes, increased gas production in the stomach is often associated
with gas formation in the intestine, while the gas freely enters the stomach. Belching, especially
bitter, often occurs with the pathology of the hepatobiliary system. In addition, belching can
occur reflexively, for example, in diseases of the cardiovascular system.
Some of the swallowed air travels further through the pylorus into the intestines, causing it to
bloat. Air can become trapped in the splenic flexure of the colon (this is left colon flexure
syndrome) when there is a feeling of fullness in the left upper quadrant of the abdomen,
possibly radiating to the left side of the chest. Pain relief often occurs after a bowel movement
or flatulence.
Hiccups (singultus) occurs as a result of a combination of a rapid spasm of the diaphragm,
convulsive contraction of the stomach and a sudden strong inhalation with a narrowing of the
glottis. Hiccups can be observed in diseases of the gastrointestinal tract and other organs of the
abdominal cavity, while more often it occurs reflexively when the center of the phrenic nerve is
excited. Hiccups are observed in diseases of the mediastinum,
pleura, peritoneum, when there is direct irritation of the diaphragm or phrenic nerve.
Nausea (nausea) - this is an unpleasant painless subjective sensation of an impending desire to
perform an emetic act. Nausea often precedes than accompanies vomiting. However, nausea and
vomiting can occur independently of each other. Various physiological reactions occur with
nausea. Due to the proximity to the center of vomiting of the nuclei of the glossopharyngeal and
facial nerves (which innervate the salivary glands), hypersalivation is often observed. With
nausea, tachycardia often develops, probably as a result of a stress reaction to possible vomiting.
Weakness, increased sweating, pallor of the skin, cold extremities, a drop in blood pressure due
to excitation of the parasympathetic and then sympathetic parts of the autonomic nervous system.
Hypotension with bradycardia (vasovagal syndrome) is possible. With nausea, the motility of
the gastrointestinal tract is disturbed and the secretory function of the stomach decreases. The
feeling of nausea is associated with antiperistaltic stomach movements. Nausea is often
accompanied by anorexia, i.e. loss of desire to eat or refusal to eat. Following the ongoing
nausea for some time and short periods of urge to vomit, a sequence of involuntary visceral and
somatic motor acts develops, leading to the onset of vomiting.
Vomiting (vomitus) - a complex reflex act, as a result of which the contents of the stomach are
ejected outward. In the process of vomiting, the stomach plays a relatively passive role.
The expulsion of its contents is provided by the abdominal muscles. When the fundus of the
stomach and gastroesophageal sphincter relax, an increase in intra-abdominal pressure occurs
due to an involuntary contraction of the diaphragm and abdominal wall (external oblique
muscles of the abdomen). This contraction, together with the ongoing contraction of the
pylorus, leads to the expulsion of the contents of the stomach into the esophagus. The increase
in intra-abdominal pressure contributes to the further movement of the contents through the
esophagus into the oral cavity. Reflex rise of the soft palate during vomiting prevents stomach
contents from entering the nasal part of the pharynx, and reflex closure of the glottis and
respiratory depression prevent the aspiration of stomach contents into the airways.
Vomiting causes disturbances in the motility of the gastrointestinal tract. The tone of the
fundus of the stomach and peristalsis of the stomach is usually
decrease, the tone of the duodenum and the proximal jejunum increases, and peristalsis can take
the opposite direction (antiperistalsis). In the latter case, duodenogastric reflux occurs, and this
explains the admixture of bile in the vomit from the duodenum. The role of antiperistalsis in
vomiting is well shown in experiments on animals (cats, dogs), which were injected into the
cavity of the ventricles of the brain with substances that stimulate vomiting. It was found that
before the act of vomiting, there is a change in the electrical activity of the intestine with an
increase in electrical potentials in the proximal direction. Clinically, intestinal antiperistalsis is
manifested by the frequent presence of intestinal contents in vomit. With intestinal obstruction,
vomiting with an admixture of feces is possible.
The emetic act is under the control of two functionally different centers located in the medulla
oblongata: the vomiting center and the chemoreceptor trigger zone. These centers are located
next to other centers of the brain stem that regulate autonomic functions. The afferent
pathway of the gag reflex goes along the sensitive fibers of the vagus nerve to the center of
vomiting, which is located in the lower part of the bottom of the IV ventricle, next to the
respiratory and cough centers.
Centrifugal impulses to the effectors propagate along the motor fibers of the vagus nerve,
along the phrenic, spinal and splanchnic nerves (Fig. 17-2).
The emetic center controls and integrates the emetic act into a single whole. It receives
afferent signals from the intestine, from other parts of the body, from the superior cortical
centers, especially from the inner ear apparatus and the trigger chemoreceptor zone.
Important efferent pathways for vomiting are phrenic nerves (to the diaphragm), spinal
nerves (to the muscles of the abdominal wall), and visceral efferent nerves (to the stomach
and esophagus).
112 Give modern views on the etiology, pathogenesis, manifestations and
consequences of gastric ulcer and duodenal ulcer.
Morphological manifestation- the development of a violation of the integrity of the wall of
the stomach and duodenum 12 and inflammatory changes. The main clinical signs are pain,
vomiting, bleeding.
Peptic ulcer causes:
1. Mechanical theory - mechanical damage to the gastric mucosa (coarse, unchewed,
poor quality food).
2. Inflammatory theory - chronic inflammation in the wall of the stomach - violation of
trophism - ulcer (hyperacid gastritis - ulcer).
3. The peptic theory is an increase in acidity and an increase in the volume of gastric juice.
4. Virchow's vascular theory - a violation of the blood supply to the area of the stomach
wall - atrophic changes - self-digestion of this area.
5. Endocrine theory - changes in hormonal status (in stressful situations, adrenaline and
glucocorticoids - constriction of the vessels of the stomach and violation of trophism).
Contemporary views:
1. Strengthening the acid-peptic properties of gastric juice.
2. Violation of the regeneration of the gastric mucosa
3. Bykov's cortico-visceral theory.
Factors of etiopathogenesis:
1. Alimentary factor (coarse food; coffee - enhances secretion, milk and meat, on the
contrary, bind hydrochloric acid (antacid effect).
2. Bad habits - smoking, nicotine, promote the production of hydrochloric acid and inhibit the
secretion of bicarbonates, reduce mucus formation. Alcohol: high concentrations - inhibit
gastric secretion, low concentrations - stimulate gastric secretion and inhibit the regeneration
of the gastric wall.
3. Medicines: Aspirin, indomethacin, glucocorticoids - ulcerogenic action, by inhibiting the
synthesis of prostaglandins, hyperplasia of cells that produce gastran ..
4. Neuropsychic factors.
5. Hereditary constitutional factors.
6. Microbial factor: Helicobacter pyloris - a microorganism in the stomach and duodenum 12
leads to chronic inflammation leading to an ulcer. Medicines that inhibit the growth of
Helicobacter pylori are antiulcer drugs. In 82-85% of cases of peptic ulcer disease, the
etiological role is played by Helicobacter pylori (adapted to exist in the stomach).
Manifestations:
Stomach ulcer: epigastric pain, dyspeptic symptoms (belching, heartburn, nausea), vegetative
manifestations (decreased performance, weakness, tachycardia).
Duodenal ulcer: pain, vomiting, dyspepsia, seasonality of the disease.
113 Describe the etiology, pathogenesis, manifestations and
consequences of disorders in pancreatic achilia...
Pancreatic achilia is a pathological condition in which there are no pancreatic
juice enzymes in the duodenal contents.
Pancreatic A. is functional or organic. Organic pancreatic A., caused by
atrophy of acinous cells of the pancreas, which produce digestive enzymes, is
more common (eg, in severe forms of hron. Pancreatitis); violation of the
outflow of pancreatic juice (eg. when the pancreatic duct is compressed by a
stone, tumor) or the absence of the pancreas (eg. due to pancreatectomy).
Wedge, symptomatology of organic pancreatic A. is characterized by decreased
appetite, belching, nausea, flatulence, diarrhea with abundant liquid shiny
("fatty stools") and fetid feces. Violation of intestinal digestion leads to
rapid weight loss of the patient and is accompanied by
severe general weakness.
Functional pancreatic A. is caused by a violation of the exocrine function of
the pancreas in certain endocrine diseases (diabetes mellitus, diffuse toxic
goiter, Addison's disease), hypovitaminosis. diseases of the liver and
biliary tract, inf. diseases. Objective signs of damage to the pancreas in
functional pancreatic A. are absent; achilia is usually short-lived. A
moderate degree of functional impairment may not be clinically apparent due
to a compensatory increase in intestinal digestion (including the enzymatic
activity of microorganisms).
The diagnosis is established on the basis of a wedge, a picture, laboratory
determination of pancreatic enzymes (trypsin, lipase, amylase) in the
duodenal contents obtained with duodenal intubation. To clarify the cause
of achilia, the content of pancreatic enzymes in urine and blood is
determined.
Since the absence or a sharp decrease in the content of pancreatic enzymes in
the pancreatic juice leads to impaired cleavage. the presence of these
enzymes can be indirectly judged by the degree of digestion of proteins, fats
and carbohydrates. The most accessible is scatological research (see.
Feces): with pancreatic A., a significant amount of neutral fat
(steatorrhea) and preserved transverse striation of muscle fibers of meat
eaten (creatorrhea) are found in the feces.
In addition, rentgenol provides significant assistance in the diagnosis of
diseases of the pancreas, which can be the cause of pancreatic A. study of
the duodenum in conditions of its artificial hypotension (see relaxation
duodenography), echography of the pancreas
(cm. Ultrasound diagnostics) and etc.
Treatment with pancreatic A. should be directed to the underlying
disease. Prescribe a diet number 5 or 5P with restriction of fats, the
introduction of fats, proteins and carbohydrates in an easily digestible
form. Alcohol consumption is prohibited. For the purpose of replacement
therapy, pancreatin, panzinorm, festal and other drugs containing
pancreatic enzymes are prescribed.
Forecast with functional and organic pancreatic A. is determined by the
underlying disease.
114 Liver failure is characterized by a persistent decrease or complete loss of
one, several or all liver functions, which
leads to disruption of the vital functions of the organism.
VIEWS
Origin.
Hepatocellular (hepatic)... It is the result of primary damage to hepatocytes and their failure to
function.
Shunt (bypass)... It is caused by a violation of the blood flow in the liver and, in this regard, its
discharge (bypassing the liver) through anastomoses (portocaval and cavocaval) into the general
bloodstream.
The rate of emergence and development.
•
•
•
Lightning fast, or fulminant. It develops within a few hours.
Sharp. It develops within a few days.
Chronic... It forms over weeks, months, or years.
Reversibility of damage to hepatocytes.
Reversible... It is observed when the effect of the pathogenic agent is stopped and the
consequences of this effect are eliminated.
Irreversible (progressive). Develops as a result of continuing influence
a causal factor and / or the inability to eliminate pathogenic changes caused by it. Often leads to
the death of the patient
... PATHOGENESIS
Exposure to a factor damaging hepatocytes forms an extensive network
interdependent and mutually potentiating changes. The leading links in the pathogenesis of liver
failure are as follows:
• modification and destruction of hepatocyte membranes;
• activation of immunopathological processes;
• the development of inflammation;
• activation of free radical reactions;
• activation of hydrolases.
The listed factors cause massive destruction of liver cells, which leads to additional potentiation of
inflammatory, immunopathological and
free radical reactions. All this leads to a decrease in the mass of the functioning hepatic
parenchyma and the development of liver failure.
THE REASONS
The reasons for the development of liver failure can be actually hepatic (hepatogenic
— pathological processes and / or effects directly damaging liver cells) and
extrahepatic (non-hepathogenic - pathological processes occurring outside
liver, but secondarily damaging it). The causes of both categories of deficiency are shown in Fig. 25-3.
DYSTROPHIES
Dystrophies and degenerative changes in the liver most often develop under the influence of chemicals
(for example, antibiotics, sulfonamides, drugs; industrial poisons - benzene, carbon tetrachloride,
methanol, nitro paints, household poisons, ethanol and other alcohols, mushroom poisoning).
HEPATITIS
Hepatitis - inflammation of the liver - usually results from a viral infection or intoxication.
Transfer mechanisms.
Parenteral mechanism transmission is typical for viral hepatitis B, C, D, G. The situations,
circumstances and risk groups of infection are listed below.
•
•
•
•
Transfusions of blood and blood products, hemodialysis, injections, surgical
and dental treatment during the previous 6 months
Sexual contact with a person infected with hepatitis B, C, D.
Children born to mothers infected with hepatitis B, C, D, G.
Close household contact with a family member infected with hepatitis B, C, D, G.
Enteral (fecal-oral) transmission mechanism (viral hepatitis A and E).
•
•
•
Contact with the patient 15-60 days before the onset of the disease.
Living in an epidemiologically unfavorable area.
Group morbidity with the formation of epidemic foci in children's and youth groups.
LIVER CIRROSIS
Liver cirrhosis - chronic pathological processes in the liver,
characterized by progressive damage and death of hepatocytes, the development of excess connective
tissue (fibrosis), replacing the parenchyma. Manifested by failure
liver functions and impaired blood flow in it.
DISORDERS OF BLOOD CIRCULATION
Of the circulatory disorders, the greatest clinical significance is the development of portal
hypertension of various origins - a persistent increase in pressure in the vessels of the portal vein
system above the norm (above 6 mm Hg).
Long-term portal hypertension often leads to liver dystrophy and liver failure.
Circulatory disorders of the central, organ-tissue, in the vessels of the microcirculatory bed are most
often observed in collapse, shock, coma, sepsis, and extensive burns.
OTHER REASONS
There are many other reasons for the development of liver failure.
•
•
•
•
•
Parasitic (for example, schistosomiasis, clonorchiasis, opisthorchiasis, fascioliasis), neoplastic
and inherited liver damage (for example, type IV glycogenesis or hemochromatosis), as well as
cholestasis.
Hypoxia of various origins (for example, circulatory - with heart failure, tissue - with intoxication,
substrate - with diabetes).
Chronic renal failure.
Hypo-, dysvitaminosis (for example, hypovitaminosis E, D, A).
Endocrinopathies (for example, hypocorticism, pathology of the parathyroid glands).
115 Obstructive jaundice: the etiology of the pathogenesis of
cholemic and acholic syndromes.
MECHANICAL Jaundice
Etiology
Obstructive jaundice develops with persistent impairment of the excretion of bile through the
bile capillaries (which leads to intrahepatic cholestasis), along the bile ducts and from the
gallbladder (with the development of extrahepatic cholestasis). Causal factors:
•
•
Blocking the biliary tract from the inside (eg calculi, tumors, parasites).
Compressive bile ducts outside (for example, head neoplasms
pancreas or large duodenal papilla; cicatricial changes in the tissue around the biliary tract;
enlarged lymph nodes).
• Violating the tone and reducing the motility of the walls of the biliary tract (dyskinesia).
Pathogenesis... These factors cause an increase in pressure in the bile capillaries, hyperextension
(up to micro-ruptures) and an increase in the permeability of the walls.
bile ducts, diffusion of bile components into the blood. In this case, biliary hepatitis develops.
Manifestations obstructive jaundice
For mechanical (subhepatic, congestive, obstructive) jaundice, the development of cholemia and
acholia is characteristic.
•
•
Cholemic syndrome (bile blood) - a complex of disorders caused by the appearance of bile
components in the blood, mainly bile acids (glycocholic, taurocholic, etc.), direct bilirubin
and cholesterol. Signs of cholemia:
High concentration of conjugated bilirubin in the blood (with the development of jaundice)
and, as a result, in the urine (gives the urine a dark color).
•
•
•
•
•
•
Excess cholesterol is absorbed by macrophages and accumulates as xanthomas (in the skin of
the hands, forearms, feet) and xanthelasm (in the skin around the eyes).
Itchy skin due to irritation of nerve endings with bile acids.
Arterial hypotension due to a decrease in the basal tone of the SMC of arterioles, a decrease in
the adrenoreactive properties of receptors of blood vessels and the heart, an increase in the
tone of the vagus nerve under the influence of bile acids.
Bradycardia due to the direct inhibitory effect of bile acids on the cells of the sinus-atrial node.
Increased irritability and irritability of patients as a result of the decline
activity of inhibitory neurons of the cerebral cortex under the influence of bile components.
Depression, disturbed sleep and wakefulness, increased fatigue (develops in chronic cholemia).
116 Parenchymal jaundice
Etiology
•
•
Infectious causes: viruses, bacteria, plasmodia.
Non-infectious causes: organic and inorganic hepatotoxic substances (for example, carbon
tetrachloride, ethanol, paracetamol, etc.), hepatotropic antibodies and cytotoxic lymphocytes,
neoplasms.
Stages of parenchymal jaundice
First stage (preicteric)
The reasons: in hepatocytes, the activity of enzymes that destroy urobilinogen decreases;
damage to the membranes of hepatocytes, a decrease in the activity of glucuronyl
transferase.
Manifestations: urobilinogenaemia and urobilinogenuria, an increase in the content of "liver"
enzymes in the blood.
Second stage (icteric)
The reasons... The icteric stage is characterized by a further aggravation of the alteration of
hepatocytes and their enzymes. This leads to disruption of the "bilirubin conveyor". Disorder
This mechanism, in combination with damage to cell membranes, causes disruption of
unidirectional bilirubin transport.
Manifestations: release of direct bilirubin into the blood and the development of bilirubinemia, filtration
of direct bilirubin by the kidneys and its excretion in the urine, the ingress of bile components into the
blood and the development of cholemia.
Third stage
The reasons: progressive decrease in hepatocyte glucuronyltransferase activity
leads to disruption of the transmembrane transfer of conjugated bilirubin into hepatocytes and
inhibition of the process of bilirubin glucuronization.
Manifestations
•
•
Increase in the level of indirect bilirubin in the blood...
Decreased blood levels of direct bilirubin (as a result of suppression of the glucuronidation
reaction).
•
•
Decreased concentration of stercobilinogen in blood, urine and faeces.
Decrease in urobilinogen contentin the blood and, as a result, in the urine. It is the result
of a small intake of direct bilirubin in the biliary tract and intestines.
Aggravation of damage to structures and enzymes of hepatocytes with an increase in
cholemia, preservation of enzymemia and hyperkalemia, progression of hepatic
failure, which is fraught with the development of a coma.
•
117 Hemolytic jaundice - a serious illness characterized by increased breakdown of erythrocytes,
edema, anemia, the appearance of an icteric color of the skin and mucous membranes. More often found
as a form of hemolytic disease of newborns, it can be a sign of acute or chronic poisoning with substances
that destroy red blood cells.
The reasons: intra-, extravascular hemolysis of erythrocytes; hemolysis of erythrocytes and their
precursors in the bone marrow, synthesis of unconjugated bilirubin from non-hemoglobin heme in the
liver; excess formation
Etiology and pathogenesis... Suprahepatic jaundice is a congenital or acquired independent disease
(microspherocytic hereditary anemia, hemoglobinopathy, primary shunt hyperbilirubinemia, neonatal
erythroblastosis, acute post-transfusion anemia, etc.) or a symptom of a number of diseases (croupous
pneumonia, subacute, some septic endocardial lesions) as well as the consequence of toxic and medicinal
damage (arsenic, hydrogen sulfide, phosphorus). The pathogenesis of a large group of hemolytic anemias
is associated with a biochemical enzymatic defect in erythrocytes or autoimmune disorders. Distinguish
between idiopathic and symptomatic forms of autoimmune hemolytic jaundice, the latter are observed
in chronic lymphocytic leukemia, lymphosarcoma, systemic connective tissue diseases, and some viral
infections.
Manifestations: 1.signs of erythrocyte hemolysis: anemia, hemic hypoxia, hemoglobinuria, an increase in
the level of unconjugated bilirubin in the blood, an increase in the level of stercobilin to blood, urine,
feces.
Treatmentdifferent depending on the form of anemia: with corpuscular forms caused by a biochemical
defect in erythrocytes, splenectomy is indicated. In autoimmune forms, glucocorticoid hormones have
the most beneficial effect.
The prognosis depends on the form of hemolytic anemia: very serious, especially in the acute
course of idiopathic autoimmune anemia, hemoglobinopathies, favorable - in
primary shunt hyperbilirubinemia.
118 Metabolic disorders in liver failure
Violation of the participation of the liver in carbohydrate metabolism... It consists in a decrease in the
ability
hepatocytes, on the one hand, convert glucose into glycogen, and on the other, break down glycogen
into glucose. This causes a characteristic sign of liver failure (PN) unstable blood glucose levels. After a meal, hyperglycemia develops, and on an empty stomach
— hypoglycemia.
Violation of the participation of the liver in lipid metabolism. It is characterized by a decrease in the
ability of hepatocytes:
a) convert the more atherogenic form of cholesterol (free cholesterol) into less atherogenic
cholesterol-ester and
b) form lipoproteins with antiatherogenic action.
Both of these changes lead to an increase in the level of free cholesterol in the blood and to a decrease
in antiatherogenic phospholipids, which contributes to the deposition of cholesterol in the creiiKax
vessels and the development of atherosclerosis.
Violation of the participation of the liver in protein metabolism... Includes three types of changes:
a) a decrease in the synthesis of albumin by hepatocytes, which leads to hypoalbuminemia and
hypotension of blood, and at the stage of development of portal hypertension contributes to
the development of ascites;
b) a decrease in the biosynthesis of enzymes and proteins - procoagulants
(prothrombin, proaccelerin, proconvertin), which causes the development of
coagulopathies, characterized by a tendency to bleeding. This is also facilitated by
a decrease in the absorption of fat-soluble vitamin K in the intestine, since PN
combined with a violation of the bile-forming and biliary function of the liver;
c) a decrease in the activity of the process of deamination of amino acids and the synthesis of
urea from amino groups and ammonia, which leads to a decrease in the urea content in the
blood.
Violation of the biosynthesis of enzymes by hepatocytes. Is to reduce secretion
hepatocytes into the blood of the enzymes they form (cholinesterase, insulinase, etc.). In addition,
damage to hepatocytes is accompanied by an increase in the release of intracellular enzymes from them
into the blood: alanine transaminase and glutamate transaminase.
Disorder of vitamin metabolism. Consists of:
a) decrease in intestinal absorption of fat-soluble vitamins A, D, E, K;
b) a decrease in the ability of hepatocytes to convert provitamins into active vitamins (for
example, carotene into vitamin A),
c) inhibition of the formation of coenzymes from vitamins (for example, from pantothenic acid acetyl coenzyme A, from vitamin B1 - pyruvate cocarboxylase). All listed
changes lead to the development of endogenous (hepatic) pyuvitaminosis.
Violation of the antitoxic function of the liver... It is characterized by a decrease in liver clearance:
a) intestinal poisons - phenolic aromatic compounds (phenol, indole, skatole), biogenic amines
(cadaverine, putrescine, tyramine), ammonia;
b) toxic metabolites: low molecular weight fatty acids (valeric, nylon), methylated and amic derivatives
of sulfur-containing amino acids (tauric, cystine, methionine), toxic pyruvate derivative - acetoin; c)
exogenous "poisons (fungal, microbial, parasitic origin, pesticides, etc.). Inactivation by Kupffer cells
(stellate reticuloendotheliocytes) of colloidal particles and
microorganisms.
Violation of abrasion and secretion of bile by the liver. This leads to the development of
jaundice (see the appropriate section).
The end of the growing liver failure is a hepatic coma.
119 LIVER COMA
Hepatic coma develops as the final stage of the total
liver failure. Its cause is intoxication of the body, damage to organs and tissues (primarily the
central nervous system) by metabolic products, the transformation, detoxification and excretion
of which with the participation of the liver is grossly disturbed.
Hepatic coma is characterized by complete loss of consciousness, suppression of all reflexes (including
tendon, corneal and pupillary). signs of damage to the brain tissue, resulting in the development of
respiratory and circulatory systems.
Usually, these disorders are preceded by a precomatose state, which can have a different duration.
Uto state is characterized by nausea, vomiting, loss of appetite, headache, signs of disorders of the
central nervous system (drowsiness, alternating
insomnia, increased excitability, impaired consciousness).
There are two variants of the mechanism of development of hepatic coma: shunt and
hepatocellular.
Shunt hepatic coma
This type of coma occurs as a result of severe liver damage from sclerotic
(cirrhotic) character... Liver cirrhosis can be an outcome
1) acute or chronic hepatitis
2) chronic venous-congestive hypoxia
3) lesions of the liver parenchyma (biliary cirrhosis) and is accompanied by the development of
portal hypertension.
Persistent long-term portal hypertension leads to the development of portocaval anastomoses
(through hemorrhoidal, esophageal, umbilical veins), through which part of the blood, sometimes
significant, "dumped", bypassing the liver, into the general bloodstream.
Considering that this blood contains a large number of metabolites that are not rendered harmless in the
liver,
the state of intoxication of the body with metabolic products develops... Normally inactivated
in the liver. This type of hepatic coma has a number of features.
Firstly, it can occur with a relatively minor disorder
biliary and biliary function of the liver... In this regard, with her, jaundice is quite often absent or poorly
expressed.
Secondly, its occurrence is largely associated with the state of intestinal digestion, as well as the nature of the food consumed... So, food rich in protein increases the likelihood of coma due to
the absorption of toxic breakdown products of proteins that enter the general bloodstream. Medium
- ammonia, ammonium carbamate, putrescine, cadaverine, methionine, etc.
Hepatocellular coma
Hepatic cell coma occurs with massive necrosis of the liver parenchyma, when its
homeostatic and barrier functions are significantly reduced.
The development of coma is based on several interrelated: pathogenetic mechanisms.
One of them is hypoglycemia. The experiment has shown that extirpation of the liver in animals
leads to their death in 5-8 hours from acute hypoglycemia. Artificial maintenance
normal blood glucose levels extend their lifespan to 20-40 hours.
Another significant mechanism for the development of coma is severe acidosis. It has been shown
that the correction of the acid-base state makes it possible to prolong the life of animals up to 2-3
days.
An important pathogenetic link in coma is intoxication of the body. It is due
the appearance and increase in the blood level of substances that have a general toxic and, especially,
cerebrotoxic effect.
A significant role in the mechanism of coma development is a violation of amino acid and
protein metabolism. The affected liver is unable to maintain the absolute
the amount and ratio of individual amino acids and protein fractions in the blood. An excess of some
and a deficiency of other amino acids makes it impossible for the normal exchange of proteins in
tissues
organism.
A manifestation of this is an increase in the content of amino acids in the blood (with a decrease in the
level of plasma proteins) and their appearance in the urine. The level of free ammonia in the blood
increases. This is due to a violation of its conversion to urea in the ornithine cycle of hepatocytes.
In addition, part of the urea excreted by the intestinal mucosa is broken down into
it is produced by bacteria ureases with the formation of ammonia, which is absorbed into the blood. Excess
ammonia
damages the cells of organs and tissues, inhibits enzymatic reactions in them and, which is especially
important,
disorganizes the work of enzymes of the tricarboxylic acid cycle... In this case, most of αketoglutaric acid is used to bind excess ammonia to form
glutamic acid. The resulting deficiency of α-ketoglutarate sharply reduces
the intensity of oxidation processes, conjugation of oxidation and phosphorylation, which leads to a
deficiency of ATP.
Many damaged hepatocytes undergo destruction. The substances contained in them enter the
bloodstream and have a pathogenic effect on the cells of organs and tissues, including nervous system. Bile pigments also make their "contribution" to the intoxication of the body: the
content of free bilirubin not captured by the liver increases in the blood, toxic
acting on cell membranes.
The entry into the blood of highly toxic decomposition products of aromatic amino acids (indole, scatal,
phenol), as well as the putrefactive decomposition of proteins (putrescine, cadaverine), increases.
In connection with the general intoxication of the body, systemic hemodynamics is disturbed:
cardiac output, arterial hypotension develops, the volume of circulating blood decreases. Disturbances
in the blood coagulation system (deficiency of prothrombin, fibrinogenesis and other factors, a change
in its rheological properties) create conditions for the development of bleeding, cropping,
sludge of blood in microvessels of organ IIOB and tissues. There is a progressive general hypoxia of
a mixed nature.
120 CAUSES OF KIDNEY PATHOLOGY
Nature causal factor
The nature of the causative factors of renal disease can be infectious (for example,
bacteria, viruses, rickettsia) and non-infectious. Non-infectious causes include chemical, physical,
and biological factors.
•
•
Chemical (for example, compounds of lead, mercury, arsenic, some antibiotics,
diuretics).
Physical (for example, penetrating radiation, radioactive decay products, low
temperature, kidney injury).
•
Biological (for example, antirenal antibodies, NK lymphocytes, macrophages; immune
complexes; allergens; excess or deficiency of catecholamines, endoperoxides, PG, PTH and
other biologically active substances).
Origin reasons
By origin, there are primary (hereditary and congenital) and secondary (acquired) factors.
•
Primary... They are diseases caused by mutations in genes that provide kidney function, and
numerous defects in kidney morphogenesis.
Diseases of this group include fermentopathies, membranopathies, polycystic,
dysplasia, renal diabetes insipidus, pseudohypoaldosteronism, aminoaciduria, phosphaturia,
etc.
• Secondary... Acquired diseases make up the majority of kidney disease.
The level of preferential implementation of the action causal factor
According to the level of pre-renal effects of the causative factor, prerenal, renal and
postrenal causes are distinguished.
•
Prerenal the reasons.
o Neuropsychiatric disorders: prolonged stress, mental trauma,
conditions combined with severe pain (in particular, reflex painful anuria).
o Endocrinopathies (for example, excess or lack of ADH, aldosterone, thyroid
hormones, insulin, catecholamines).
o
•
•
Circulatory disorders in the form of hypotensive and hypertensive
conditions. + organ disorders of blood circulation (ischemia of the kidney, venous
hyperemia, stasis)
Renal the reasons.
o Direct damage to the parenchyma, blood vessels, components of the extracellular
matrix of the kidneys by factors of an infectious or non-infectious nature.
o Disorders of blood circulation in the kidneys in the form of ischemia, venous hyperemia,
stasis.
o Mutations in genes that provide kidney function.
Post-renal the reasons. Violate the outflow of urine through the urinary tract. it
accompanied by an increase in intrarenal pressure (with stones and tumors of the
urinary tract, their edema, prostate adenoma, ureteral kinks, etc.).
121 Pathogenesis of glomerular decrease filtration.
Change in glomerular filtration:
1. Decreased filtration volume of blood plasma as a result:
•
a) lowering the effective filtration pressure at:
o - hypotensive conditions (arterial hypotension, collapse, etc.);
o - ischemia of the kidney (kidney);
o - hypovolemic conditions;
o - urine retention, etc.;
• b) reducing the area of the glomerular filter when:
o - necrosis of the kidney (kidneys) or part of it;
o - multiple myeloma;
o - chronic glomerulonephritis and other conditions;
• c) a decrease in the permeability of the glomerular membranes due to their thickening
and (or) compaction (in chronic glomerulonephritis, diabetes mellitus, amyloidosis and
other diseases).
2. Increased filtration volume of blood plasma as a result:
•
a) increasing the effective filtration pressure at:
o - an increase in the muscle tone of the walls of the efferent arterioles of the glomeruli
(under the influence of catecholamines, prostaglandins, angiotensin, vasopressin);
o - a decrease in the muscle tone of the walls of the arterioles bringing in (under
the influence of kinins, prostaglandins A, E, etc.);
- hypotension of blood (for example, with liver failure, starvation, prolonged
proteinuria) and other conditions;
b) an increase in the permeability of the glomerular filter membranes (for example, due to
"Loosening" of the basement membrane of the glomerular capillaries under the influence of
biologically active substances - mediators of inflammation or allergy: histamine, kinins,
hydrolytic enzymes, etc.)
o
•
122 Pathogenesis of a decrease in the volume of tubular reabsorption,
excretion and secretion.
5561. Absence, decreased activity or suppression of the activity of "transport" enzymes of
the epithelium, deficiency or abnormalities of other carriers (phospholipids, proteins),
disorder of the mechanism of reabsorption of ions, liquids and substances
(amino acids, albumins, glucose, lactate, bicarbonates).
Absence or depression of "transport" enzymes, proteins, membrane phospholipids,
tubular epithelium are often caused by genetic single or
multiple enzymopathies... Examples of the former include cystinuria, indoleaceturia,
the latter, aminoaciduria, phosphaturia, renal diabetes,
bicarbonaturia, renal acidosis. "Passive" mechanisms of reabsorption (diffusion, osmosis)
can be disrupted due to damage to the membranes of the epithelium of the tubules and
the basement membranes of the latter (with inflammation, allergic reactions, dystrophic
processes, etc.).
With the predominant damage to the proximal tubules, the reabsorption of organic
compounds (glucose, amino acids, protein, urea, lactate), as well as inorganic agents bicarbonates, phosphorus, chlorine, potassium, etc. is impaired. reabsorption in them is
mainly sodium, potassium, magnesium, calcium, water.
2. Violation of the processes of excretion and secretion of the epithelium of the tubules
of ions (potassium, hydrogen), "acidic" and "alkaline" metabolites, exogenous
substances.
With predominant damage to the epithelium of the proximal tubules
the energy-dependent process of excretion of organic compounds with "acidic" and "alkaline"
properties, end products of metabolism, foreign
compounds (in particular those used for diagnostic or therapeutic purposes:
para-amino hippuric acid, hippuran, dioderast). In cases with predominant damage to the
distal tubules, the secretion of potassium, hydrogen, and ammonia ions is impaired.
Secretion disorders develop mainly with gene defects and lead to cystinuria, aminoaciduria,
phosphaturia, renal diabetes, bicarbonaturia,
renal acidosis.
123 Changes in urine and urinary rhythm
Diuresis changes (the amount of urine excreted).
•
•
Polyuria - excretion of more than 2000-2500 ml of urine per day . Causes: an
increase in glomerular filtration or, more often, a decrease in tubular reabsorption.
Oliguria - excretion of less than 500-300 ml of urine during the day. Usually results
from decreased filtration or increased reabsorption.
•
Anuria - cessation of urine excretion. Typically, this is the result of a significant
decrease in filtration, which can be combined with an increase in reabsorption.
Changes in the relative density and composition of urine.
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Hypersthenuria - an increase in urine density above normal (more than 1.029-1.030 g / l).
As a rule, it is a consequence of increased reabsorption.
Hypostenuria - decrease in urine density below normal (less than 1.009 g / l). It occurs when
the concentration function of the kidneys is impaired.
•
Isostenuria - excretion of urine, the density of which corresponds to the density of blood
plasma (1.009-1.012 g / l). At the same time, the density of urine changes little during the day.
Indicates a decrease in tubular reabsorption (a decrease in the concentration of the kidneys).
• Fluctuations (outside the normal range) of the content of normal urine components:
glucose, ions, water, nitrogenous compounds.
• The appearance in the urine of normally absent components: erythrocytes (hematuria),
leukocytes (leukocyturia), protein (proteinuria), amino acids (aminoaciduria), salt sediment,
cylinders (tubular casts consisting of protein, blood cells, tubular epithelium, cellular debris).
Changes in the rhythm of urination:
•
Pollakiuria - frequent urination. Causes: Polyuria or irritation
urinary tract (with inflammation, passage of small stones, etc.).
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Olakizuria - rare urination. Is a consequence of oliguria
Nocturia - the predominance of nocturnal diuresis over daytime. Reasons: violation
blood supply to the kidneys, the development of prostate adenoma, kidney damage
(amyloidosis) or urinary tract (urethritis, cystitis).
124 Changes in blood volume and composition
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Hypervolemia (renal genesis). Causes: decreased glomerular filtration, increased
tubular reabsorption.
Hypovolemia (renal origin). Reasons: increased filtration, decreased reabsorption.
Azotemia (an increase in the level of non-protein nitrogen in the blood). Reason: violation
excretory renal function (with glomerulonephritis, pyelonephritis, amyloidosis).
Hypoproteinemia (decrease in the level of protein in the blood). Reason: violation of tubular
reabsorption of proteins, mainly albumin.
Dysproteinemia (violation of the normal ratio of individual protein fractions in the blood globulins, albumin). Cause: albuminuria.
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Hyperlipoproteinemia... One of the most common causes is nephrotic syndrome.
Acidosis, as well as a decrease or increase in the content of phosphorus, potassium, sodium,
calcium, magnesium.
The nature of the abnormalities is determined by the specific kidney disease.
General nephrogenic syndromes: renal arterial hypertension, thrombohemorrhagic syndrome, edema
syndrome, anemic syndrome.
125 Pyelonephritis - a group of syndromes (diseases) caused by microbes and characterized by
the development of an inflammatory process in the renal pelvis and interstitium of the kidney.
Etiology:
Cause: viruses and microbes (in most cases - Escherichia coli, Klebsiella, enterococci, Proteus) both from
endogenous sources and from the external environment.
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•
Exogenous... Germs enter the kidney through the urethra
Endogenous... Microbes enter the kidneys from foci of infection in the body (for example, in the
tonsils, carious teeth, bones with osteomyelitis).
Risk factors:
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Closing (obstruction) and / or compression (compression) of the urinary tract and the kidneys
themselves (for example, a stone, a blood clot formed as a result of damage to the walls of the
urinary tract, tumors of the abdominal organs).
Slow outflow of urine from the kidneys through the urinary tract (for example, with hypotension
of their muscle wall, narrowing of the ureters by a tumor or scar, during pregnancy).
The first two factors also cause compression of the kidneys, a decrease in blood flow in them, their
ischemia and, as a consequence, a decrease in the influx of Ig and a decrease in the migration of leukocytes
into the kidney tissue. In general, this reduces the efficiency of IBN reactions and contributes to kidney
infection.
•
Vesicoureteral reflux (promotes infection of the mucous membrane of the pelvis and calyces, as
well as the interstitial tissue of the kidney as a result of the ascending spread of microbes from
the bladder).
• Immunodeficiencies (promote the introduction and reproduction of microorganisms).
Routes of infection in the kidneys...
•
Hematogenous and lymphogenous... These paths are referred to as “downstream”. Microbes
enter the microvessels of the kidney, glomeruli, tubules and then “descend” into the calyx and
pelvis.
• Urogenic("Ascending" path). Microbes "ascend" to the kidney along the urinary tract.
Development mechanism:
•
•
•
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Microorganisms trapped in the kidney cause inflammation of the mucous membranes of the
calyces, pelvis and / or interstitium.
Generalization of infection is accompanied by the penetration of microbes into the tubules and
glomeruli - glomerulonephritis develops.
As a result of infection, areas of necrosis of the mucous membrane and kidney abscesses are
often formed.
The tubular epithelium can undergo destruction. The rejection of dead epithelial cells
causes obstruction of the lumen of the tubules with cellular detritus.
violation of the processes of filtration, reabsorption and secretion.
The acute course of the process is fraught with the development of acute renal failure,
chronic - chronic renal failure, nephrosclerosis, arterial hypertension.
126 Acute glomerulonephritis - a disease, as a rule, of infectious-allergic and / or immunoautoaggressive genesis.
Etiology
The causes of acute glomerulonephritis can be infectious and non-infectious factors.
Infectious agentsby themselves do not cause glomerulonephritis, however, they provoke the
development of immunopathological processes with kidney damage. Most often these are streptococci
(β-hemolytic group A streptococcus is the most frequent triggering agent of acute
glomerulonephritis), viruses (eg, hepatitis), toxoplasma.
Non-infectious factors: autoaggressive or cross-linked antibodies, immune complexes circulating
in the blood.
Pathogenesis
The main links in the pathogenesis of acute post-streptococcal glomerulonephritis.
•
The ingestion of streptococci causes the formation of antibodies to them
(antistreptokinase, antihyaluronidase, antistreptolysin O).
•
The effect of antibodies on the Ag of streptococci leads to the formation of immune
complexes that circulate in the blood and settle on the basement membrane of the
glomeruli.
Simultaneous action of AT on the structures of the renal corpuscles (especially their membranes),
having similar to streptococcal Ag, leads to additional formation of immune complexes.
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Immune complexes cause the death of kidney cells and the development of diffuse
inflammation of the renal tissue.
Chronic diffuse glomerulonephritis
Chronic diffuse glomerulonephritis in 10-20% of patients is the outcome of acute
glomerulonephritis, and in 80-90% it is a primary chronic disease.
Etiology
In contrast to acute glomerulonephritis, the triggering factors of chronic
glomerulonephritis are mainly non-infectious factors:
•
•
endogenous (for example, Ag of tumors, Ag formed as a result of massive tissue damage);
exogenous (for example, drugs containing lithium or gold, some antibiotics, nonnarcotic analgesics, vaccines, blood serum, alcohol, organic solvents).
Pathogenesis
•
•
•
•
The ingestion of streptococci leads to the formation of antibodies to their Ar.
The impact of AT on streptococci leads to their destruction. Simultaneous
the effect of AT and on the structures of the renal corpuscles (especially their membranes), which
have
similar to streptococcal Ag, cause the death of kidney cells and the development of
inflammation of the renal tissue.
Damage to nephron structures accompanies the formation of autoantigens, which triggers
immune autoaggression reactions (production of nephrocytotoxic autoantibodies and
lymphocytes).
The resulting immune complexes on the basement membrane of the glomeruli and blood
vessels of the microvasculature of the kidneys potentiate and expand the scale
damage to the renal tissue, making it diffuse (hence the name - diffuse
glomerulonephritis).
127 Renal failure
- a syndrome that develops as a result of a significant decrease or cessation of
excretory function, as well as disruption of other processes in the kidneys.
Renal failure is characterized by a progressive increase in the content of nitrogen metabolism products in
the blood (azotemia) and increasing disorders of the body's vital functions.
Acute renal failure occurs "suddenly" and progresses rapidly.
The reasons:
Prerenal... They cause a significant decrease in blood flow in the kidneys: massive blood loss, collapse,
shock, acute heart failure, renal artery thrombosis.
The functions of the kidneys themselves under the action of these reasons at the initial stages of acute renal
failure are preserved.
Renal - have a direct damaging effect on kidney tissue: (necronephrosis, acute significant local or total renal
ischemia, nephrotoxic agents).
Post-renal... - violation (up to cessation) of the outflow of urine along the urinary tract: obstruction of the
urinary tract (kidney stones, tumor, compression of the urinary tract, ureteral kink).
Pathogenesis:
1. Significant and rapidly increasing decrease in glomerular filtration volume.
- renal hypoperfusion as a result of ischemia
- vasoconstriction of renal arterioles
2. Narrowing or obstruction of a large number of renal tubules.
3. Suppression of the processes of excretion and secretion in the epithelium of the tubules under
the influence of nephrotoxic factors
4. Additional (to the action of the above mechanisms) damage to the glomeruli, tubules, interstitial
tissue due to the development of inflammatory and immunoallergic reactions in response to
direct damage to these structures.
Chronic renal failure - a condition (syndrome) that develops as a result of increasing death and a
significant decrease in the number of functioning nephrons and is characterized by a significant,
progressive (often irreversible) decrease in kidney function.
The reasons:
1. Prerenal: chronic arterial hypertension, slowly progressive renal artery stenosis, bilateral renal artery
embolism.
2. Renal: chronic pathological processes in the kidneys.
3. Post-renal... Factors causing long-term impairment of the outflow of urine.
Pathogenesis:
Progressive decrease in glomerular filtration, tubular secretion and reabsorption. At the heart of these
processes is the progressive death of nephrons, their replacement by connective tissue (i.e. the
development of nephrosclerosis). This leads to the growing failure of all kidney functions. The final stage
of chronic renal failure is uremia.
Uremia - a syndrome consisting in the body's autointoxication with metabolic products (normal and
disturbed), "uremic toxins" and exogenous compounds normally excreted by the kidneys.
The immediate cause of uremia is renal failure (acute or chronic).
Pathogenesis
•
Intoxication of the body with an excess of ammonium compounds (ammonia, ammonium
derivatives) formed during the transformation of urea in the intestine.
•
Toxic effect on organs and tissues of metabolic products of aromatic amino acids:
phenols, indoles, skatoles.
• Damage by these and other agents of cell membranes and enzymes is accompanied
by a violation of the energy supply of cells.
• Increasing acidosis is the result of inhibition of acido- and ammoniogenesis, excretion
"Acidic" compounds by the kidneys, hemodynamic disorders (metabolic acidosis) and gas
exchange in the lungs (respiratory acidosis).
• Imbalance of ions and fluid in cells.
• Disorders of electrogenesis in excitable cells, including the brain and heart. This underlies the
loss of consciousness in uremic coma, aggravation of functional disorders
cardiovascular, respiratory and other physiological systems.
"Uremic toxins."
Urea and its metabolic products, guanidine, aliphatic amines (for example,
dimethylamine).
In chronic renal failure, there is an excess of PTH, which leads to
accumulation of Ca2 + ions in cells. And this, in turn, leads to uncoupling of oxidation and
phosphorylation, ATP deficiency and disruption of energy-dependent processes.
Inadequate concentration in blood, interstitial fluid and cells of microelements (Mg2 +, Zn2 +, Cu2 +,
Cr2 + and others).
Uremia often ends in a renal coma. Like any other kidney coma
characterized by suppression of the function of the nervous system and is manifested by loss of
consciousness, hypo or areflexia, significant disorders of the functions of organs and physiological
systems
organism.
128 Nephrolithiasis and urolithiasis
Nephrolithiasis - a condition characterized by the formation of dense calculi (stones)
from inorganic and organic components of urine in the kidney tissue.
The formation of calculi in the pelvis, calyx and ureters is referred to as urolithiasis.
Etiology
The reasons subdivided into endogenous and exogenous.
Exogenous: "Hard" drinking water, monotonous hypovitaminized food (vitamin A deficiency is
important).
Endogenous: infections (urinary tract, gastrointestinal tract, reproductive system, etc.), metabolic
disorders (gout, myeloma, etc.), endocrinopathy (mainly hyperparathyroidism).
Development conditions
Decrease in urine content of solubilizers (agents that maintain salts in a dissolved state: urea,
creatinine, xanthine, citrates, etc.), inhibitors
crystallization of salts (inorganic pyrophosphate), complexing agents (Mg2 +, citrates).
An increase in the level of agents in the urine that trigger the salt crystallization process (mucoproteins,
pyruvic acid salts, collagen, elastin, sulfonamides).
Change in urine pH (at pH below 5 urates precipitate, at pH above 7 - phosphates).
Increased urine content of stone-forming salts (mainly calcium).
Urine outflow disorders...
Mechanisms... Calculus usually contains organic and mineral substances. In this regard, there are two
points of view on the mechanism of stone formation. They are formulated in the form of
crystallization and colloidal theories.
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•
According to the crystallization theory, the beginning of the formation of a stone is given by the
process
crystallization of salts. At the same time, organic components (fibrin, collagen, cell detritus
and others) are included in the composition of the stone (by chance).
The authors of the colloidal theory believe that an organic matrix is formed first, on which
salts crystallize.
Effects... The most significant consequences of nephrolithiasis: hydronephrosis with kidney (kidney)
atrophy, pyelonephritis, nephrosclerosis, kidney abscesses, renal colic.