GENERAL OUTLINE 0F PATHOPHYSIOLOGY
PREFACE
Aims:
(1) Introduce the Pathophysiology
(2) Introduce the course of Pathophysiology
Main Contents:
Pathophysiology is a special course, which studies the
etiology, pathogenesis and basic principles of treating diseases.
In the course of pathophysiology, only the basic knowledge of etiology,
pathogenesis and treatment principles will be learned.
CHAPTER 1. DISEASE
Aims:
(1) Learning some important concepts
(2) Learning the etiology , course and ending of disease
Main Contents
(1) Basic concepts
The basic concepts are health, disease, symptom, sign, the third state,
pathological process and syndrome.
(2)Etiology
Etiologyis the science to study the causes of the diseases. Etiological
factor determines the characters or nature of the disease. Precipitating
factors promote the development of disease through the enhancing the
etiological factors. Predisposing factors refer to the factors that
influence the susceptibility or resistance of the body to certain disease.
(3) Course of disease
Acute disease has a relatively sudden onset and short time. Chronic
disease lasts for a long time. The course of disease can be divided into
four stages: latent period, prodromal stage, period of manifest illness
and ending stage.There are three endings of diseases: complete
recovery, incomplete recovery and death.
(4) Death
Traditional concept of death regards death as a process. Which is
divided into agonal stage, stage of clinical death and stage of
biological death.
Modern concept of death is brain death. Brain death indicates that all
the activity of all the brain has irreversibly stopped. Criteria of brain
death from WHO are irreversible coma and cerebral irresponsibility,
absence of cephalic (brain stem) reflexes and dilated pupils, absence of
vital functions and absence of any electrical activity of the brain.
Teaching Hours: 2
CHAPTER 2. DISORDERS OF WATER AND ELECTROLYTE
METABOLISM
Aims:
(1) Learning the normal metabolism of water and sodium
(2) Learning the disorders of water, sodium and
potassium
metabolism
Main Contents:
1.Normal metabolism of water and sodium
1)Some basic concepts are body fluid, electrolytes, osmosis and
tonicity. Body fluid accounts for the 60 percent of the body weight in
adult, which can be divided into intracellular fluid (ICF), extracellular
fluid (ECF).
2) The composition and the characteristics of ECF and ICF.
3) Function of water and sodium.
4) Balance of sodium includes content of sodium and balance of intake
and loss.
5) Regulation of water and sodium metabolism consists of thirst,
antidiuretic hormone, aldosterone and atrial natriuretic peptide.
2. Disorders of water and sodium metabolism
There are three kinds of dehydration: hypertonic dehydration,
hypotonic dehydration and isotonic dehydration. The major
overhydrations are hypotonic overhydration and isotonic
overhydration (edema).
1) Hypertonic dehydration: The water loss is excess of salt loss. The
basic reasons of hypertonic dehydration are (a) increased loss of body
fluid via skin, respiration, gastrointestinal tract and kidney;(b)
decreased intake of water. The adaptive responses are thirst and
increased release of ADH. The effects on the body are oliguria, dry
mouth, fever, intracellular dehydration, loss of body weight and blood
concentration. Principle of treatment is to replace firstly with 5%
glucose solution, then add small amount of 0.9% NaCl
2) Hypotonic Dehydration: The salt loss is excess of water loss. The
main reason is replace of water only after the loss of fluid. The
adaptive responses are decreased ADH release, increased secretion and
no thirst. Effects on the body include variable urine volume,
hypotension, reduced skin elasticity, intracellular overhydration, low
salt syndrome and blood concentration. Principle of treatment is the
replacement of isotonic saline.
3) Isotonic dehydration: [Na+] and osmolarity are within normal range.
Adaptive responses are thirst, increased ADH and aldosterone
secretion. Effects on the body are diminished urine volume, poor skin
turgor and blood concentration. Hypotonic or isotonic saline are
needed to replace the fluid deficiency.
4) Water intoxication: Excessive hypotonic fluid in the body is called
overhydration. The main causes are excessive intake, less excretion of
water from kidney. Adaptive responses are inhibition of ADH secretion,
increased aldosterone secretion and no thirst. Effects on the body are
low [Na+] both in ICF and ECF, rapid weight gain, cellular
overhydration of central nervous system and pulmonary edema.
Principles of treatment are restriction of water intake, diuretics and
hypertonic saline.
3.Potassium Balance
1) Content and distribution: About 98% of potassium is in ICF. About
2% of K+ is in the ECF. [K+]e=3.5～5.5 mmol/L.
2) Function of potassium includes involving metabolism, maintaining
membrane potential and osmotic pressure and regulation of pH.
3) Regulation of K+ balance depend on the balance of intake and
excretion of potassium via kidney and intestinal tract and equilibrium
of potassium in ICF and ECF by Na+ -K+ pump, acid-base balance and
the regulation of hormone (insulin, aldosterone).
4.Hypokalemia
1) Hypokalemia means the [K+] in plasma is < 3.5 mmol/L.
Hypokalemia is not equal to potassium deficiency of the body.
2) The causes of hypokalemia are decreased intake, excessive loss of
K+ from gastrointestinal tract and kidney, more K+ moving into cells
and blood dilution.
3) Effects on the body include effects on neuromuscular irritability,
heart, acid-base balance, kidney and metabolism.
4) Principles of treatment are etiological treatment and replacement
of potassium salts slowly.
5.Hyperkalemia
1) Serum [K+]>5.5mmol/L is defined as hyperkalemia. The
hyperkalemia does not means potassium excess.
2) Causes of hyperkalemia are decrease of renal excretion potassium,
increased potassium intake, increased movement of potassium from
cells to ECF and blood concentration
3) The effects on the body include effects on the neuromuscular
irritability, the heart and the acid-base balance.
4) Principles of treatment include complete restriction of exogenous
potassium intake, etiologic treatment, movement of the serum K+ into
cells and protection of cardiac cells.
Teaching hours: 10
CHAPTER 3. EDEMA
Aims:
(1) Learning the basic mechanism of edema
(2) Learning the mechanisms of cardiac edema, pulmonary edema and
brain edema.
Main Contents:
1. Concept and classification
Edema is the excessive fluid accumulated within the interstitial space.
Edema is a pathologic process, edema is not a disease.
2.Basic mechanisms of edema
1) Imbalance of exchange between intra-vascular and extra-vascular
fluid: The reasons are increased capillary hydrostatic pressure(CHP),
decreased plasma colloidal osmotic pressure(COP), increased
permeability of the capillary wall and obstruction of lymphatic return.
Local factors against edema are increased lymphatic return with more
protein and normal negative interstitial fluid pressure.
2) Imbalance of exchange between intra- and extra- body fluid: The
reasons are (a) decrease of glomerular blood flow; (b) reduction of
permeability of glomerular membrane;(c)decreased filtration area of
glomeruli; (d) increased water and sodium reabsorption in renal
tubules.
3. Mechanism of cardiac edema
Decreased cardiac output reduces the GFR and increase the
reabsorption of water and sodium. Increased venous blood pressure
and vascular permeability lead to the formation of more edematous
fluid.
4. Mechanisms of pulmonary edema are (a)increased pulmonary
capillary blood pressure;(b)increased pulmonary vascular permeability
and (c)decreased plasma COP.
5.Brain edema
1) Concept of brain edema is defined as the increase of brain volume
caused by the increase of brain water content.
2) Brain edema is divided into cellular brain edema, vasogenic brain
edema and interstitial brain edema.
3) Pathogenesis of brain edema.
6.Effects of edema on the body
The beneficial effects are protective effects of inflammatory edema
and as a “safety valve” of circulatory system. The harmful effects are
increasing the distance between capillary and cells and dysfunction of
edematous organs.
7.Priciples of treatment
Teaching hours: 2
CHAPTER 4. ACID-BASE DISTYRBANCE
Aims:
(1) Learning the basic concepts and normal regulation of acid-base
balance.
(2) Learning the laboratory parameters of acid-base balance.
(3)Learning the causes, mechanisms, compensations, manifestations
and treatment principles of metabolic and respiratory acid-base
balances
Main Contents:
1. Some basic concepts and knowledge:
1) The concepts are acid, base, pH, acidosis, academia, alkalosis and
alkalemia. The basic knowledges are sources and classification of acid
and base,
2) Regulation of acid-base balance includes chemical buffers,
respiratory regulation, renal regulation, cellular regulation and bone
salt.
3) Laboratory parameters of acid-base balance include pH, PaCO2,
Standard bicarbonate (SB), actual bicarbonate (AB) and anion gap
(AG).
2.Acidosis
1) Concept and classification: metabolic and respiratory acidosis.
2) The mechanisms of metabolic acidosis characterized by normal
anion gap are(a)increased loss of HCO3- from kidneys; (b)extrarenal
loss of HCO3- and(c) excessive production of Cl-. The mechanisms of
metabolic acidosis characterized by increased anion gap are (a)reduced
GFR;(b)incomplete combustion of carbohydrates and fatty acids and
(c)administration of excessive salicylates.
3)Compensations of metabolic acidosis include buffering systems,
respiratory compensation, renal compensation and compensation by
cells and bone.
4) Pathogenesis of respiratory acidosis : The basic reason of
respiratory acidosis is the decreased ventilation, which leads to the
decreased elimination of CO2 from lung. The common causes of acute
respiratory acidosis are the depression of respiratory center,
neuromuscular disorders and cardiopulmonary arrest. Chronic
pulmonary acidosis are caused by chronic diseases include emphysema,
bronchitis, poliomyelitis.
5) Compensation against respiratory acidosis include (a)H+ moving
into the cell;(b)CO2 moving into the cells and (c)the renal
compensation which is the same as the renal compensation in
metabolic acidosis.
6) Effects of acidosis on the body are (a)depression of mental
activity;(b)impairment of myocardial contraction;(c) arteriole dilation
and (d)arrhthmias due to hyperkalemia,
3.Alkalosis
1) Concepts and classification of alkalosis.
2) Pathogeneses of metabolic alkalosis are (a)loss of H+ and Cl- via
gastrointestinal tract and kidneys;(b) more administration of HCO3- or
precursors of bicarbonate and(c) severe K+ deficiency.
3) The compensation of metabolic alkalosis is the opposite direction of
the compensation in metabolic acidosis.
4) Concept of respiratory alkalosis
5) Cause of respiratory alkalosis is the increased alveolar ventilation.
6) The compensation of respiratory alkalosis is in the opposite
direction of the compensation of respiratory acidosis.
7) Effects of alkalosis on the body include (a)the effects on the central
nervous system;(b)neuromuscular unit;(c) cardiovascular system and
(d) hypokalemia.
4.Mixed Acid-base Disturbances
1) Concept and classification
Teaching hours: 6
CHAPTER 5 HYPOXIA
Aims：
1. Learning the supply and use of oxygen in body
2. Learning the kinds and causes of hypoxia
3. Learning the functional and metabolic changes of the body in
hypoxia
Main Contents：
1.Introduction
(1)The supply and use of oxygen in body
(2) Concept of hypoxia
2.Parameters of blood oxygen
Partial pressure of oxygen（PO2），Oxygen content（Co2），Oxygen
capacity （ Co2 max ）， Oxyhemoglobin saturation （ So2 ） and
Oxyhemoglobin dissociation curve
3.Classification and etiology of hypoxia
(1) Hypotonic hypoxia
The main feature of this type of hypoxia is that oxygen pressure in
arterial blood(PaO2) is lower than normal. The causes include
decreased oxygen pressure in the inspired air, the functional disorders
of respiratory system, and the shunting of blood(vein to artery).
(2) Hemic hypoxia
This type of hypoxia is caused by a reduction in the amount of
available hemoglobin. The oxygen pressure in this type is normal, and
oxygen content is lower. The causes include anemia, carbon monoxide
(CO) poisoning, and methemoglobinemia.
(3) Circulatory hypoxia
This type of hypoxia is caused by abnormalities in circulation. As a
result, blood flowing to the tissues is reduced with respect to oxygen
need. The causes include generalized circulatory deficiency and local
circulatory deficiency.
(4) Histogenous hypoxia
This type of hypoxia results from the inability of the cell to utilize the
oxygen delivered to the cells. The causes include cyanide poisoning,
mitochondria injury, edema, and vitamin deficiency.
4.Functional and metabolic changes of the body in hypoxia
(1) Compensatory response
1) Respiratory system
The compensatory response of the respiratory system to hypoxia is
hyperventilation. The mechanism is the excitation of respiratory center
by lower oxygen pressure in arterial blood (PaO2 < 60mmHg), and
some acidic metabolites.
2) Circulatory system:
The manifestations of the circulatory system are increase of cardiac
output, blood redistribution in system circulation, pulmonary
vasoconstriction, and capillary proliferation.
3) Hemic system
The compensatory response is increase of red blood cell (RBC) and
rightward shift of oxyhemoglobin dissociation curve.
4) Cellular adaptation
The cellular adaptations include the increase of cellular ability to use
oxygen, the increase of anaerobic glycolysis and the increase of
myoglobin.
(2) Injurious responses
1)Hypoxic cell damage
The damage includes cell membrane injury, mitochondria injury and
lysosome injury.
2)Dysfunction of central nervous system (CNS)
The CNS is the most vulnerable organ in the body to hypoxia. The
manifestations of CNS in hypoxia include lassitude, decreased mental
activity, impaired judgement, and signs of a slowed reaction time.
3)Dysfunction of respiration
Hypoxia that is severe enough to cause unconsciousness may depress
the respiratory center. Consequently breathing may become slow,
irregular and finally stop.
4)Dysfunction of circulation:
① Pulmonary arterial hypertension
② Decrease of myocardial contractility and extensibility
③ Arrhythmia
④ decreased venous return
Teaching hours: 6
CHAPTER 9 DIC
Aims:
1.Learning the concept of DIC
2. Learning the causes and pathogenesis of DIC
3. Learning the consequences of DIC
Main Contents:
1. Introduction:
1) Normal blood coagulation and fibrinolysis
2) Concept of DIC: Disseminated intravascular coagulation (DIC) is a
pathological syndrome that results from the disturbance of kinetic
balance of coagulation and fibrinolytic processes.
3) Causes of DIC
2. Pathogenesis of DIC：
Under certain circumstances, the coagulation system may be triggered
into uncontrolled activity to produce DIC. DIC can be triggered by
extensive damage of vascular endothelial cells by severe tissue injury
or wound, by excessive destruction of the circulating blood cells, and
by other coagulant substances entering the blood.
1) Extensive damage of vascular endothelial cells: Infection, shock,
hypoxia and immune reactions can damage the vascular endothelial
cells so that blood contacts with exposed collagen to trigger intrinsic
clotting cascade through activation of factor Ⅻ and to aggregate
platelets.
2) Severe tissue injury: Normal tissues and malignant tumors contain
a large amount of factor Ⅲ （tissue factor, TF ）. Severe trauma,
wounds, major operation, malignant necrosis can cause TF release to
trigger extrinsic clotting sequences.
3) Excessive destruction of the circulating blood cells: Generation of
procoagulant-active substances within the blood may occur if red cell,
white cell or platelet membranes become damaged and release
thromboplastic substances. It may trigger both intrinsic and extrinsic
clotting sequences.
4) Other thromboplastic materials entering the blood: A certain amount
of internal substances e.g., amniotic fluid, metastatic cancer cells, or
foreign particles (Ag-Ab complex, bacteria, viruses) once enters the
blood , can be responsible for the activation of clotting system through
the contact of blood with an abnormal surface.
3. Predisposing Factors to DIC:
1) Impairment of the Clearance Mechanism
2) Hypercoagulable State
3) Disorder of Microcirculation
4. Types and Stages of DIC
5. Consequences of DIC：DIC may lead to four clinical consequences
as follows:
1) Disturbance of coagulation---bleeding
It is caused by the following conditions: the consumption of clotting
factors and platelets; the activation of fibrinolytic system; the
production of fibrin degradation products (FDPs).
2) Disturbance of circulation---shock
3) Ischemic tissue damage---multiple system organ failure (MSOF)
4) Microangiapathic hemolytic anemia (MHA)
6. Treatment Priciples of DIC
Teaching hours: 4
CHAPTER 10 SHOCK
Aims:
(1) Learning the concept, stages, mechanism and cells metabolism of
shock, and multiple organ dysfunction syndrome.
(2) Learning the progressive procedure, etiology and classification and
pathophysiological base of prevent and treatment in shock.
Main Contents:
(1) Etiology and classification of shock
①
Classification of shock by causes
This classification system encompasses three general types of shock: a)
hypovolemic shock, in which blood or plasma has been lost from the
circulation to the exterior of the body or into the tissue; b)cardiogenic
shock, in which the pumping action of the heart is inadequate;
c)vasogenic shock, in which widespread vasodilation increases the
capacity of the circulation so the existing blood volume, even if it is
normal, becomes inadequate.
②
Classification of shock by hemodynamic
There are two kinds of shock in the system which include
hypodynamic shock, in which the peripheral vascular resistance is
increased and cardiac output decreased and hyperdynamic, in which
the peripheral vascular resistance is decreased and cardiac output
increased.
③
The start tach of shock
a)Reduction of blood volume
Approximately 10% of the normal blood volume can be lost without
significant effects. The degree of shock produced is determined not
only by the amount of blood lost, but also by the rate at which it is lost.
Rapid loss of the blood volume may produce more serious shock than
slow loss of the same amount of blood .
b)Decrease in myocardial contractility
The output can be decreased by damage of contractility of the heart.
c)Increased vascular-bed volume
With the extending of blood vessel, relative decreases in blood volume
does not fill the circulatory system.
(2) Periods and pathogenesis
① Stage1-early reversible shock(compensatory shock, stage of
ischemic anoxia)
a)Microcirculation
In this stage, the sympathetic effects are augmented by an increased
release of epinephrine and norepinephrine from the adrenal medulla.
So the blood vessels were contracted.
b)Compensatory meaning:
The heart rate and cardiac contractility increase and vasocontriction
becomes more intense. Blood is shunted to the brain and the heart in
order to protect these vital organ, at the expense of other parts of the
body such as the skin, skeletal muscles, kidney, and so on. Angiotensin
causes increased peripheral resistance, which raises systemic arterial
pressure, and venous constriction, which promotes venous return.
② Stage2-late reversible shock(decompensatory shock, stage of
stagnant anoxia)
a)Microcirculation
With prolonged severe shock ,the blood vessel are unable to remain
constricted, vasodilation occur, peripherial resistance decreases.
b)Effects on body:
In this stage, blood flow to the brain ,heart and kidney is further
reduced and severe hypoxia of these vital organs leads to impaired
function and metabolic disorder.
Stage3-refractory shock (stage of DIC or perfusion failure)
This is the terminal stage of shock. The vasomotor center is depressed
by lack of oxygen and decrease in pH, the vessel dilate, cardiac output
further diminishes, and arterial pressure further diminishes. Excessive
and prolonged reduction of tissue perfusion leads to alteration in
cellular membrane function, aggregation of blood cells, and
“sludging”in the capillaries. These reasons can cause disseminated
intravascular coagulation (DIC).
(2) Humoral factors related with shock
① Noradrenaline and adrenaline
② Renin and angiotensin
③ Vasopressin
④ Histamine
⑤ Kinins
⑥ Prostaglandins (PGs) and leukotrienes (LTs)
⑦ Neuropeptides
⑧ Activated complement
⑨ Tumor necrosis factor (TNF)
⑩ Oxygen free radical
(4)General effects of shock
1)
Disturbance of cell metabolism
2)
Effects on the kidney
3)
Effects on the lungs
4)
Effects on the heart
5)
Effects on the liver
6)
Effects on gastrointestinal tract
7)
Effects on the brain
8)
Mutiple organ failure (MOF) and Mutiple organ disfunction
syndrome (MODS)
(5) Characteristic of various types of shock
1)
Septic shock
Septic shock always has been recognized as a consequence of
gram-negative bacteremia, LPS
(liposaccharide)from the cell wall of gram-negative bacteria play an
important role. Monocytes are stimulated and generate cytokines such
as TNF , while, endotoxin has the effect of pseudosympathetic and
make the sympathetic to be active condition.Cardiogenic shock
Cardiogenic shock occur because of myocardial infarction and various
patterns of arrhythmia,which result in significant reduction in cardiac
output so shock develops.
3)Anaphylactic shock
This kind of shock is due to hypersensitivity reaction. Exposure of
sensitized individuals to certain antigens results in massive release of
mediators such as histamine and so on in to blood. These substances
cause dilation of microcirculation. Blood begins to pool peripherally,
there is precipitous drop in blood pressure. Death may occur in short
time.
4)Neurogenic shock
Neurogenic shock is caused by a lack of vasomotor tone.
5) Trauma
6) Blood loss and body fluid loss
Blood loss and body fluid loss lead to hypovolemia.
Hypovolemia means diminished blood volume .
Hemorrhage and fluid loss decreases the filling pressure of the
circulation.
(6)Treatment of shock
1)Restore blood volume
A large of blood or fluid need to be perfused.
2)Application of vasoactive drugs
Pressors drugs were applicated in stage 2. Vasocontraction
drugs and vasodialation are applied according to different
stage.
3)Protection of cells:
Glucocorticoid may keep stability of cell membrane.
Teaching hours: 6
CHAPTER 13
HEART FAILURE
Aims:
1. Learning the concept and classifications of heart failure
2 .Learning the causes and pathogenesis of heart failure
3. Learning the compensatory mechanisms in heart failure
4. Learning the function and metabolic alterations in heart failure
5. Learning the treatment principles of heart failure
Main Contents:
1.Concept of Heart Failure: Heart failure may be defined as the
condition in which the heart is no longer able to pump an adequate
supply of blood for the metabolic needs of the body, provided there is
adequate venous return to the heart.
2.Classifications of Heart Failure
3.Basic Causes of Heart Failure:
1)Dysfunction of Myocardium: the dysfunction of myocardium can be
caused by diffuse myocardial damage and myocardial ischemia and
hypoxia
2)Overload for myocardium: including pressure overload and volume
overload
4.Precipitating Causes of Heart Failure: including infection,
arrhythmias, pregnancy and delivery
5. Pathogenesis of Heart Failure:
1)Depressed myocardial contractility:
It is considered that most of myocardial failure has depressed
myocardial contractility. The pathogenesis of depressed myocardial
contractility includes myocardial cellular injuries, myocardial
metabolic dysfunction, dysfunction 0f excitation-contraction coupling
and alterations of the adrenergic nervous system in the failing
myocardium.
2)Altered diastolic properties of ventricles: 30% of the sum of the
heart failure have altered diastolic properties of ventricles. The
mechanisms of altered diastolic properties of ventricles include
dysfunction of ventricular relaxation, reduced ventricular compliance
and asymmetry and asynchronism in ventricular contraction and
relaxation.
6. Compensatory Mechanisms in Heart Failure:
1)The Frank-Starling mechanism
2)Increased release of catecholamines by adrenergic cardiac nerves
and the adrenal medulla
3)Myocardial hypertrophy---long-term adaptation to increased
myocardial work
4)Increase of blood volume and redistribution of blood flow
7. Function and Metabolic Alterations in Heart Failure
1)Alteration in cardiac function: including decreased CO, CI and EF,
increased intracardiac pressure and alterations in myocardial
contractility and its diastolic properties.
2)Blood Pressure
3)Respiratory distress: including dyspnea, orthopnea, paroxysmal
nocturnal dyspnea
4)Congestive hepatomegaly
5)Other symptoms
6)Alterations in serum electrolytes
8. Treatment Principles of Heart Failure: including correcting the cause,
improving cardiac function and maitaining normal fluid volume.
Teaching hours: 6
CHAPTER 14 RESPIRATORY FAILURE
Aims:
1.Learning the concept, diagnosis standards and classifications of
respiratory failure
2. Learning the causes and pathogenesis of respiratory failure
3. Learning the function and metabolic alterations in respiratory failure
4. Learning the treatment principles of respiratory failure
Main contents:
1.Concept and Diagnosis Standards of Respiratory Failure: Respiratory
failure is a syndrome in which the respiratory system fails to
adequately oxygenate the blood with /without retention of carbon
dioxide, it is generally defined as a PaO2 of 8kPa (60mmHg) or less
with/without PaCO2 of 6.67kPa( 50mmHg) or more, and the presence
of hypoxia with or without hypercapnia.
2.Classsifications of Respiratory Failure.
(1)According to duration: acute respiratory failure and chronic
respiratory failure;
(2)According to primary site: central respiratory failure and peripheral
respiratory failure;
(3)According to pathogenesis: hypoxemic (Group I ) respiratory
failure and Ventilatory (Group II) respiratory failure.
3.Causes and Pathogenesis of Respiratory Failure：
(1)Ventilatory Disorders: including Restrictive ventilatory disorders
and Obstructive ventilatory disorders. And the blood gases will be
changed.
1)Restrictive ventilatory disorders : Restrictive ventilatory disorders.
Restrictive ventilatory disorders are a characteristic pattern of changes
in lung volume that may be produced by diseases that affect either the
distensibility characteristics of the lungs or chest wall.
2)Obstructive ventilatory disorders:
(i)Central airway obstruction: The central airway obstruction is
defined as the airway obstruction between the glottis and the carina.
(ii)Peripheral airway obstruction: The peripheral airway obstruction is
defined as the airway obstruction in the smaller airways less than 2
mm in diameter
(2) Gas Exchange Disorders
1)Diffusion disorders: Diffusion disorders are generally characterized
by a disruption in the exchange of O2 or CO2 or both across the
respiratory membrane. And the blood gases will be changed.
2)Ventilation-Perfusion
mismatching:
Ventilation-Perfusion
mismatching usually denotes a serious disorder, involving the airways
in such a manner that the distribution of inspired air to the affected
regions is decreased, or the perfusion that the distribution of blood
flow to the affected region is decreased. And the blood gases will be
changed.
3)Right-to-left shunts: In some instances, an abnormal anatomic
pathway does exist, for example, intracardiac communications,
pulmonary arterio-venous fistulas, but in most other instances shunts
occur through normal vessels perfusing regions of lung that are not
ventilated at all because the alveoli are filled or closed, for example,
pulmonary edema, atelectasis, pneumonia.
4.Manifestations of Respiratory Failure
(1) The alteration of blood gas:
①Low PaO2 and high PaCO2. This pattern occurs in depression of
respiratory center, obstruction of central way, and some chronic
obstructive lung disease;
② Low PaO2 and normal PaCO2. This pattern may be seen in
ventilation-Perfusion mismatching, and in diffusion disorder.
③Low PaO2 and low PaCO2.It can occur when the patient suffers from
lung interstitial disease and adult respiratory distress syndrome.
(2)Acid-base disturbances and disorders of electrolyte metabolism:
Many patients with respiratory failure have mixed respiratory and
metabolic acid-base disturbances.
(3) Alterations of the vital systems(respiratory system, cardiovascular
system, hematopoietic system and nervous system);
(4)Basic mechanism of manifestations.
1)Hypoxia: The signs and symptoms of acute hypoxia are chiefly
caused by abnormalities in central nervous system and cardiovascular
function.
2)Hypercapnia: Carbon dioxide has a direct vasodilatory effect on
many blood vessels and a sedative effect on the central nervous
system.
5. Treatment Principles of Respiratory Failure。
Teaching hours: 6
CHAPTER 15 Hepatic Encephalopathy
Aims：
1.Learning the concepts and classification of hepatic encephalopathy;
2. Learning the pathogenesis of hepatic encephalopathy;
3. Learning the precipitating factors of hepatic encephalopathy .
Main Contents：
1. Introduction
(1) Concept of hepatic encephalopathy;
(2) Etiology and classification of hepatic encephalopathy;
(3) Clinical features of hepatic encephalopathy.
2.Pathogenesis of hepatic encephalopathy
(1)Ammonia intoxication hypothesis: The gastrointestinal tract is a
major site of ammonia production. It is formed in the wall of the
intestine and by enteric bacteria from the degradation of amines,
amino acids, and purines. It is also formed by the action on urea of
urea-splitting organisms and intestinal urease. The mechanisms by
which ammonia interferes with CNS function:
Ammonia
intoxication could interfere with cerebral metabolism; Ammonia
intoxication could change the concentrations of neurotransmitter;
Ammonia intoxication could inhibit nerve cell membrane.
(2)Amino acid imbalance and false neurotransmission hypothesis: The
aromatic amino acids(AAA) are increased and the branched chain
amino acids(BCAA) are decreased in liver disease. Thus, the influx of
AAA into the brain increase. By these mechanisms, an increase in the
brain content of precursors of false neurotransmitters is postulated to
occur in chronic liver failure.
The neuronal content of true neurotransmitters, such as noradrenalin
and dopamine, becomes depleted, and the contents of serotonin and
false neurotransmitters, such as octopamine and phenylethanolamine,
increase in liver failure. The net neurophysiologic result of such
changes is presumed to be reduced neural excitation and hence
increased neural inhibition.
(3) GABA hypothesis: GABA is a neuroinhibitory substance produced
in the gastrointestinal tract. When GABA crosses the extrapermeable
blood-brain barrier of patients with cirrhosis, it interacts with
supersensitive postsynaptic GABA receptors. The GABA receptor, in
conjunction with receptors for benzodiazepines and barbiturates,
regulates a chloride ionophore. Binding of GABA to its receptor
permits an influx of chloride ions into the postsynaptic neuron, leading
to the generation of an inhibitory postsynaptic potential.
Administration of benzodiazepines and barbiturates to patients with
cirrhosis increases GABAergic tone and predisposes to depressed
consciousness.
3.Precipitating factors of hepatic encephalopathy
1)Nitrogenous overload: azotemia, constipation, potassium deficiency,
gastrointestinal hemorrhage, dietary protein;
2)Sedatives, tranquilizers, and narcotic analgesics;
3)Fluid and electrolyte abnormalities: paracentesis, hyponatremia,
hypokalemia;
Infections: Infection may predispose to impaired renal function and to
increased tissue catabolism, both of which increase blood ammonia
levels.
4. Principles of treatment
Teaching hours: 4
CHAPTER 16 PATHOPHYSIOLOGY OF KIDNEY
Aims:
(1) To master the causes and pathogenesis of acute and chronic renal
failure.
(2) To master the characteristics and clinical course of acute and
chronic renal failure.
(3) To understand the treatment principles of acute renal failure.
Main contents:
1. Acute renal failure (ARF)
(1) Causes of ARF
1) Prerenal causes
Prerenal disease is caused by any disorder external to the kidneys that
decreases the flow of blood to the nephron.
2) Intrarenal causes
Intrarenal disease is characterized by disease of the renal tissue itself.
It includes:
① Diseases of glomerulus, tubule-interstitial tissue and vessels.
② Acute tubular necrosis(ATN), that is the most important cause
of ARF. Usually it results from renal ischemia and renal poisoning.
3) Postrenal causes
(2) Pathogenesis of ARF
1) Renal hemodynamics
2) Nephronal factors
①
Passive backflow
②
Tubule obstruction
3) Cellular and metabolic mechanisms
(3) Characteristics and clinical course of ARF
The renal response to an acute renal injury is an acute decrease in
GFR and paralysis of tubular function, both characteristic features of
ARF. Clinically this is reflected by a progressive increase in the blood
urea nitrogen (BUN) and serum creatinine concentration, azotemia,
metabolic acidosis and hyperkalemia.
1) Oliguric acute tubular necrosis
It usually develops in four stages, progressing from initial phase,
oliguria phase, diuresis phase to recovery phase.
2) Nonoliguric acute renal failure
(4) Treatment principles of ARF
2. Chronic renal failure (CRF)
1) Causes of CRF
A wide variety of renal disorders can cause chronic renal failure. The
diseases leading to CRF can generally be classified into two major
groups: glomerular disease and tubular-interstitial disease.
2) Clinical course of CRF
① Decreased renal reserve
② Renal insufficiency
③ Renal failure
④ End-stage renal failure or uremia
3) General pathophysiology of CRF
Three theoretical approaches are generally offered to account for
the impaired function of the kidneys in CRF:
① Intact nephron hypothesis
② Trade-off hypothesis
③Glomerular hyperfiltration hypothesis
4) Manifestations of CRF
①
Characteristics of urine
②
Water and sodium imbalance
③
Potassium imbalance
④
Metabolic acidosis
⑤
Renal azotemia
⑥
Cardiovascular abnormalities
⑦
Anemia and bleeding
⑧
Renal osteodystrophy
It consists of four lesions: renal rickets, osteomalacia, osteitis fibrosa,
osteoporosis and osteosclerosis. They are caused by: a).
Calcium-phosphate imbalance and secondary hyperparathyroidism. b)
Hypocalcemia. c. Acidosis.
Teaching hours: 8