PATHOLOGY: (unit 1-5)
Unit 1:
Medical terminology: https://quizlet.com/_d0ie6h?x=1jqt&i=4zagl0
Prefixes: https://quizlet.com/_d0igi8?x=1jqt&i=4zagl0
suffixes: https://quizlet.com/_d0igi8?x=1jqt&i=4zagl0
UNIT 2:
Classification of diseases:
Various ways to classify a disease:
https://www.youtube.com/watch?v=QYWNXp36O48
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ICD - International Classification of diseases
WHO - World Health Organization
Communicable - infectious / transmissible due to pathogens
Non-communicable - cannot be passed on from person to person
Diagnosis and treatment of a disease:
THERAPY:
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The treatment of disease with the aim of:
a.) achieving a cure
b.) reducing the signs and symptoms to a level where normal function can be
restored.
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Different types of therapy (DAVIES 12-16):
Medical treatment:
➢ Mainly treatment by medicines, i.e. by drugs, but includes other nonsurgical measures such as dietetic therapy, rest, reassurance and
often, of the highest importance, medical nursing care.
➢ The term medical is here used in its restricted sense as referring to the
province of the physician, as opposed to that of the surgeon.
➢ Drugs are used extensively in medical treatment and also as adjuvants
in many other types of therapy. Some important types of drugs will be
indicated later.
Palliative treatment:
➢ Treatment to relieve symptoms, but not providing a cure.
Surgical treatment:
➢ Consists in most cases of treatment by surgical operations (i.e.
procedures in which an instrument such as a scalpel or diathermy
needle is used to cut into body tissues for therapeutic purposes), and
any preoperative or postoperative measures necessary in conjunction
with such operations.
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➢ Certain non-operative techniques such as the closed reduction of
fractures and dislocations and techniques using laser beams may also
be regarded as forms of surgical treatment.
➢ The term surgery means work by hand. Surgical operations, other than
certain of those of a minor nature, fall within the province of the
specialist surgeons, aided by other doctors who are specialist
anaesthetists, who maintain the patient in a pain-free and unconscious
state during operations. They also provide all the essential life support,
and supervise the care of the patient in the postoperative recovery
period.
➢ In the operating theatre, surgeons and anaesthetists are helped by
both theatre nursing staff and trained assistants called operating
department assistants.
➢ In the surgical wards, skilled and efficient surgical nursing is of prime
importance in postoperative management of most patients who are
subjected to operation, while in many it is also a leading factor in
preoperative treatment as well.
Intensive care (therapy):
➢ This is provided in a special unit equipped for the concentrated medical
attention and extra nursing facilities needed for gravely ill patients from
any of the clinical departments, particularly immediately after serious
major operations; in cases of severe shock following multiple injuries or
other cause; cerebral compression; cardiac, respiratory, renal and liver
failure; drug overdosage; and near drowning.
Physiotherapy:
➢ This means treatment by physical (i.e. natural) methods, including
measures such as the therapeutic use of exercise, light, heat,
ultrasound and water.
➢ A hospital physiotherapy department is staffed by physiotherapists
usually under the general direction of a medical practitioner who is a
specialist in rheumatology and rehabilitation. Rheumatology is the
branch of medicine concerned with the diagnosis and treatment of
musculoskeletal disorders, particularly joint disease. Rehabilitation is
the process of restoring a disabled person to a condition in which he is
able, as early as possible, to resume a normal life.
➢ Physiotherapy has a wide application in both medical and surgical
conditions, but finds its most extensive use in diseases and injuries of
the locomotor system (i.e. the bones, joints and muscles), in the
rehabilitation of patients with head injuries or cerebrovascular
accidents and in the early mobilization of postoperative patients.
➢ Physiotherapists work closely with occupational therapists and their
combined approach should achieve optimal results. There are many
types of physiotherapy, but they are basically in two separate groups
active and passive procedures.
➢ The passive procedures include the application of heat, usually with
wax baths. Short-wave diathermy and ultrasound both produce deep
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heat within muscles. Conversely, ice is occasionally applied
to acute injuries.
➢ Electrotherapy is employed to maintain active muscle contractions in
enervated muscles. Active procedures occupy about 70% of a
physiotherapist's working time.
Exercise therapy:
➢ consists of assisted movements, free movements, isometric and
isotonic exercises, exercises with apparatus and mobilization
exercises.
➢ Passive movements of joints and muscles help to maintain the mobility
of joints and muscles, particularly in patients with strokes or spinal
injuries.
➢ Breathing exercises are an important part of the postoperative care of
patients and are of great value in assisting patients in the expulsion of
bronchial secretions (sputum). Physiotherapists are particularly
involved in the care of patients in the intensive care unit.
Hydrotherapy:
➢ Hydrotherapy, as the word would suggest, is the treatment of patients
in special swimming pools. The buoyancy provided by the water assists
the movement of weak muscles and damaged joints.
➢ This is particularly usual in the rehabilitation of patients with lower limb
injuries, severe rheumatoid arthritis and patients with poliomyelitis.
Radiotherapy:
➢ consists of treatment by ionizing radiation produced by, for example,
superficial and deep X-ray apparatus, linear accelerators, betatrons,
neutron generators, or ionizing radiations emitted spontaneously by
radium, radiocobalt, radio phosphorus, radioiodine, and other
radionuclides (radioactive isotopes).
➢ This form of therapy is chiefly employed for malignant new growths but
is also used for some non-malignant conditions (e.g. certain types of
skin disease).
➢ A doctor who specializes in radiotherapy is called a radiotherapist and
his technical assistants are called therapeutic radiographers.
➢ An essential adjunct to a radiotherapy department is a department of
medical physics under the direction of a hospital physicist and staffed
also with medical physics technicians. This department is concerned
with the planning of treatments prescribed by radiotherapists, the care
and the calibration of apparatus, the design and construction of
specialized items of equipment, and so on; the care of radionuclides;
and other tasks, among which are important duties relating to the
protection of patients and staff against possible hazards arising from
the diagnostic and therapeutic uses of ionizing radiation.
➢ The treatment of cancer by cytotoxic drugs and hormones also
frequently falls within the province of radiotherapy departments. The
increasing use of such methods either as adjuvants to, or substitutes
for, treatment with ionizing radiation has led to many such departments
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now being called departments of radiotherapy and oncology, such a
designation being more indicative of their role in modern
hospital practice.
Psychiatric treatment:
➢ includes the use, in patients with disorders of the mind, of (a) medical
measures (e.g. sedative drugs, stimulant drugs, antidepressant drugs,
tranquillizers),(b) surgical measures - nowadays performed only to a
very small extent. (c) physical measures (e.g. electroconvulsive
therapy), and (d) psychotherapy, and group therapy forms of treatment
for mental illness which do not include medical surgical or physical
methods.
➢ The study of the mind is called psychology and the branch of medicine
which deals with diseases of the mind is termed psychiatry and is
practised by doctors who are specialist psychiatrists.
➢ In the investigation of some aspects of mental illness, and also in the
giving of some forms of treatment and rehabilitation work, psychiatrists
are assisted by clinical psychologists, whose training includes the
obtaining of a university honours degree in psychology. Also working
within the field of mental illness and concerned with its social aspects
are professional staff termed psychiatric social workers.
➢ While psychiatric outpatient clinics are a common feature of general
hospitals, facilities for the inpatient treatment of mental disorders are,
to a large extent, mainly provided in special hospitals, termed mental
hospitals, which aim at providing a therapeutic community where all
staff of the hospital help with treatment.
➢ Modern thought, however, inclines to the view that such treatment
would be better provided in special wards attached to general
hospitals.
Other methods:
➢ Chiropody - the specialized treatment of foot disorders given by
chiropodists, professional staff who have been trained in podology, i.e.
the branch of medicine concerned with the study of human foot in
health and in medical and surgical disease conditions.
➢ Diet therapy - the word diet means a customary or prescribed form of
feeding and the control of a patient's feeding for therapeutic purposes
is termed diet therapy. Therapeutic diets are planned and their
provision is supervised by hospital dietetic departments in the charge
of professionally trained dietitians. The hospital dietitian is also
concerned with advising outpatients regarding their diets at home.
➢ Occupational therapy - as defined by the Board of Education of the
College of Occupational Therapy - is the treatment of physical and
psychiatric conditions through specific selected activities in order to
help people reach their maximum level of function and independence in
all aspects of daily life.
➢ Orthoptic treatment - is a process of mental training, involving special
eye exercises, employed in the treatment of squint and other disorders
of normal binocular vision. Investigation and treatment of such
conditions are carried out by orthoptists, working under the direction of
ophthalmic surgeons of ophthalmic medical practitioners.
➢ Optical treatment - is the correction of errors or refraction by spectacles
or contact lenses. Sight testing and prescribing of spectacles and
contact lenses may be performed by medical practitioners and also by
qualified ophthalmic opticians, who may also supply visual appliances.
Dispensing opticians supply visual appliances but do not test sight.
➢ Speech therapy - is undertaken by speech therapists and, as described
by Hatfield, as "the scientific treatment of persons suffering from
disorders of speech, language and voice. Suitable cases include
defects of the peripheral speech organs (e g. cleft palate); articulatory
and voice disorders of neuromuscular origin (e.g. cerebral palsy,
Parkinson's discase): delayed or deviant speech in childhood; loss of
spoken and written language due to cortical damage (aphasia, etc.);
functional and organic voice disorders, and stammering”.
Drugs: https://quizlet.com/_d0ikws?x=1jqt&i=4zagl0
Remember, certain drugs may completely destroy infecting organisms, e.g.
Antibiotics, WHILE, certain drugs only relieve the symptoms even though the
underlying cause is not corrected, e.g. Anticonvulsants.
genetic factors
congenital
factors in utero
classification of diseases
combination of genetic &
enviromental factors
TRAUMATIC
INJURIES
MAY BE DUE TO: violence,
mechanical irretation, external
physical and chemical agents
INFECTIVE
caused by invation of
pathogenic organisms, e.g.
malaria, HIV, measles
NEOPLASTIC
due to pathalogical process called
neoplasia, formation of benign and
malignant tumors
CHEMICAL
POISONING
due to entering of chemical
poisons into the body, e.g. lead,
insectisites
ENDOCRINE
defective functioning of the
endocrine glands, e.g. diabetes,
dwarfism
acquired
METABOLIC
due to ack of essential foods,
nutrients or vitamins, e.g.
RICKETS- lack of vitamin D
desturbances in the metabolic process,
e.g. defective removal of uric acid
ALLERGIES
caused by various types of
hypersensitives, e.g. hayfever
PSYCHIATRIC
due to mental status, e.g. depression,
schitzophrenia
IATROGENIC
caused by the side effects of
prescribed medications or other
medications for other diseases,
e.g. sensitive reactions to
penicillin
IDIOPATHIC
of unknown cause, e.g. essential
hypertention
UNIT 3:
Functions of the organelles in a typical animal cell:
https://www.youtube.com/watch?v=JL19uv7NT7s
Two types of energy production in the cell:
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Aerobic (aerobic glycolysis- energy liberated from glucose):
➢ Most complex - Occurs in the mitochondria (with O2)
➢ Supplies 90% of the body’s energy needs
➢ Requires the heart, lungs and all of the circulatory system to work
efficiently
➢ Obtained from using the large stores of glycogen in the body
➢ This is synthesized into ATP
➢ May also be obtained through breakdown of fats, proteins and
carbohydrates (requires more O2)
➢ By products = CO2 and H2O (easily released from the body)
Anaerobic:
➢ Occurs in the cytoplasm (without O2)
➢ Obtained through glycolytic process
➢ NB pathway during periods of ↓ O2 and cells that lack mitochondria
Glucose → Pyruvic acid → ATP from ADP
➢ By products = lactic acid (toxic and thus must be broken down – this is
achieved by the liver)
➢ NB : Lactic acid ↑ with strenuous exercise; heart failure, severe
infection; shock OR when the liver is damaged or diseased
Homeostasis:
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Cells are the fundamental units of the body
Cells operate in a very narrow range of physiologic parameters, thereby
maintaining HOMEOSTASIS.
HOMEOSTASIS: (Maintenance of a constant internal envi-ronment)
➢ equilibrium of the micro-environment of the cell
➢ every cell is involved
➢ change at a cellular level can affect the entire body
➢ any external stressor can disrupt homeostasis, thus leading to illness
➢ The nervous system and the endocrine system are responsible for
maintaining homeostasis
➢ Factors that can influence homeostasis are: 1. Sugar level 2. Osmotic
pressure 3. Respiratory gases 4. Temperature.
If the cell encounters physiological STRESS or pathologic stimuli, it will try to ADAPT
to prevent cell injury.
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STRESS:
➢ Any demand on the cell which requires adaptation
ADAPTATION
➢ Adaptations are reversible changes in size, number, metabolic activity
or functions of cells in response to changes in their environment
NORMAL CELL
(homeostasis)
REVERSIBLE INJURY
Injurious
stimulus
ADAPTION
CELL INJURY
Severe,
progressive
IRREVERSIBLE INJURY
NECROSIS
Cell death
APOPTOSIS
• Cellular
adaptations to stress
can be
PHYSIOLOGICAL or
PATHOLOGICAL:
• Eliminating the
stress can result in
the cell returning to
its original state
WITHOUT harmful
consequences.
HYPERTROPHY:
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Increased cell and, thus, increased organ size
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Often in response to increased workload OR
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Induced by mechanical stress and by growth factors
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Involves an increase in functional components
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Occurs in tissues incapable of cell division(cardiac and muscle tissue)
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Can occur due to normal physiological changes or Pathological changes
HYPERPLASIA:
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Increase in number of cells in a tissue or organ
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Occurs in tissues whose cells are able to divide eg. Epidermis, epithelium of
the intestinal tract and glandular epithelium
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Can involve activation of genes controlling cell proliferation
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Controlled process occurring in response to an appropriate stimulus
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Normal physiologic - Hormonal = uterine / breast enlargement OR
Compensatory = after partial hepatectomy - healing of connective tissue
NB … most pathologic forms of hyperplasia occur as a result of excessive
hormonal OR growth stimulation
ATROPHY:
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Decreased cell and, thus organ size
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Cells have fewer mitochondria, endoplasmic reticulum etc. – decreased
protein synthesis due to ↓ metabolic activity
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Due to a decrease in workload or adverse environmental conditions – O2
consumption and protein synthesis ↓
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Involvement of a sufficient number of cells = tissue atrophy
General causes:
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Disuse
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Denervation
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Loss of endocrine stimulation
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Inadequate nutrition
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Ischemia or decreased blood flow
METAPLASIA:
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Definition: transformation of one type of tissue into another type of the same
differentiation.
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cells sensitive to a particular stress are replaced by other cell types able to
withstand the adverse environment
Mechanism: it seems to be induced by altered differentiation pathway of
tissue stem cells (genetic reprogramming of stem cells rather than trans
differentiation of already differentiated cells)
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Types of metaplasia:
1. Epithelial metaplasia:
• Squamous metaplasia: changes in bronchus, uterine, endocervix,
gallbladder, prostate, renal pelvis and urinary bladder
➢ Vitamin A deficiency: squamous metaplasia in the nose, bronchi,
urinary tract, lacrimal and salvatory glands
• Columnar metaplasia: intestinal metaplasia in healed chronic gastric
ulcer and Barret’s oesophagus
2. Mesenchymal metaplasia:
• Osseous metaplasia
• Cartilaginous metaplasia
If the cell cannot adapt OR The stimulus is strong enough to cause injury like
ischaemia, toxicity and infections = CELL INJURY DEVELOPS
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Cells that are normally columnar or stratified may change to squamous.
Examples:
➢ With continued smoke exposure, ciliated columnar cells are changed to
stratified squamous cells
➢ Cervical cells change when exposed to STD or HPV
✓ Continued exposure may predispose to cancerous
transformations
Causes of cell injury:
1. Toxic
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Endogenous (metabolic errors; gross malformations; hypersensitivity
reactions)
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Exogenous- chemical ( alcohol; lead; carbon monoxide, pesticides and drugs
that alter cellular function
2. Infectious (exogenous)
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Viral; bacterial, fungal, protozoa
3. Physical (exogenous)
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Thermal (radiation; electrical, extreme temperatures)
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Mechanical (trauma or surgery – injured blood vessels, (fractured bones etc.)
4. Deficit injury
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lack of H20
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lack of O2 (hypoxia ; ischaemia)
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lack of nutrients OR excesses in nutrition
5. Immunologic reactions
6. Genetic defects – due to deficiency of functional proteins
7. Aging
Mechanisms of cell injury:
1. Free radical injury – a highly reactive chemical with an unpaired electron
(radiation injury; toxic gases; cellular ageing, microbial infections;
inflammation)
2. Hypoxic cell injury – disrupts oxidative metabolism and generation of ATP –pH
falls – Na/K- adenosine triphosphate pump failure
3. Impaired calcium homeostasis – Ca important for cell responses (ischaemia
and toxins = increase calcium =activation of enzymes which can be damaging
to the cell)
Cell injury varies from cell to cell and is dependent on:
1. Type, duration and severity of the injury
2. Type and adaptation of the affected cell
Therefore cell injury can be REVERSIBLE or IRREVERSIBLE
CASCADE OF EVENTS:
Normal cell (homeostasis maintained) → cell injury e.g. Mitochondrial damage:
hypoxia & cellular ischemia → Ion shift (↑ acid → changes in Na/K pump) →
Cellular swelling occurs and/or fatty changes (REVERSIBLE) → Mitochondrial
swelling → Intracellular disruption occurs → Cellular damage (IRREVERSIBLE CELL DEATH)
Reversible cell injury
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The functional and morphologic changes are reversible if the damaging
stimulus is removed
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The two main morphologic correlates of reversible cell injury are cellular
swelling and fatty changes.
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The injury has typically not progressed to severe membrane damage and
nuclear dissolution
Irreversible injury - Cell death
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With continuing damage, the injury becomes irreversible, at which time the
cell cannot recover and dies.
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There are two types of cell death— necrosis and apoptosis—which differ in
their morphology
APOPTOSIS: (cell suicide)
• Regulated cell death as a result of activation of enzymes called caspases
• Apoptosis can be ÷ into:
1. Initiation phase
➢ caspases become catalytically active
2. Execution phase
➢ caspases trigger the degradation of cellular components
The process:
✓ Production of enzymes known as Dnases brought about, which destroy the
DNA in the nucleus of the cell.
✓ Break down of cellular components needed for survival.
✓ The cell shrinks and sends out distress signals, which are answered by
vacuum cleaners known as macrophages.
✓ The macrophages clean away the shrunken cells, leaving no trace, so these
cells have no chance to cause the damage that necrotic cells do.
APOPTOSIS – highly selective process, can be a physiological or pathological
process.
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Physiological examples include:
➢ During embryogenesis, development of structures
➢ Hormone deprivation as in the menstruation cycle
➢ Regression of the breast after weaning from the breast
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Pathological examples include:
➢ DNA damage due to radiation/chemotherapy, hypoxia
➢ Cell injury in infection eg Hep B and C
➢ Neuro-degenerative disease eg. Alzheimers and Parkinson’s disease
NECROSIS: (cell murder)
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Refers to cell death in an organ or tissue
Occurs as a result of the degradative action of enzymes on lethally injured
cells.
Always a pathological process
Process involves:
✓ Loss of plasma membrane integrity
✓ Leaking out of contents resulting in inflammation in the surrounding tissue
✓ Digestion of the necrotic cell by lysosomes
Damage to the nucleus:
✓ Pyknosis (pyko=dense osis= condition) nucleus shrinks
✓ Karyorrhexis (karyo=nucleus rrhexis=rupture) nucleus fragments/ruptures
✓ Karyolysis (karyo=nucleus lysis=destruction) nuclear membrane disintegration
✓ https://www.youtube.com/watch?v=1vaEVcMfa1E&vl=en
✓ https://www.youtube.com/watch?v=4_0-7UOAgx8
Patterns of necrosis:
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Coagulative necrosis
➢ Most common type of necrosis
➢ Mostly as a result of cessation of blood flow
➢ Acidosis develops –denaturing enzymes and proteins
➢ Cells become dry, hard and appear white
➢ It is characteristic of infarcts (areas of ischaemia) in all solid organs
except the brain
➢ Organs commonly affected are the heart, kidney and spleen
Liquefaction (colliquative) necrosis
➢ Seen in focal bacterial or fungal infections
➢ CELLS DIE BUT CATALYTIC ENZYMES NOT DESTROYED
➢ Liquefaction completely digests the dead cells resulting in
transformation of the tissue into a liquid viscous mass with acute
inflammation, the material is creamy yellow and is referred to as pus.
Caseous necrosis
➢ Encountered most often in foci of tuberculous infection
➢ Cell death due to toxins from TB bacteria
➢ Combines features of coagulative and liquefactive necrosis
Caseous = “soft cheese like debris” – dead cells persist
➢ Derived from the yellow- white appearance of the area of necrosis
➢ Often enclosed within a distinctive inflammatory border - known as a
granuloma
Fat necrosis (enzymatic)
➢ Focal areas of fat destruction
➢ Due to TRAUMA or ENZYMES
➢ Typically arises from the release of activated pancreatic lipases hydrolyses fat into glycerol and fatty acids - generally occurs in acute
pancreatitis
➢ These fatty acids form soaps which appear as white opaque masses or
plaques in the fat
Gangrene
➢ Due to a considerable mass of tissue undergoing necrosis
➢ Can be dry or moist:
Dry
- Area becomes dry and shrinks- slow
spread
- Arterial interference with no venous
interference (Spread is slow)
- Colour change from dark brown to
black
- Usually applies to the extremities,
generally the lower leg, that has lost its
blood supply and has undergone
coagulative necrosis, involving multiple
layers
Moist/wet
-Area is cold, swollen and pulseless –
due to interference with venous return
(skin is moist and black)
-Liquefaction occurs and a foul odour is
caused by the bacterial action
-Can affect any internal organ and
extremities
-Bacterial infection plays an important
role
-Spread of tissue damage is rapid
-can be fatal
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Gas gangrene
➢ Infection of tissue by one of many Clostridium bacteria(anaerobic)
considered to be serious and potentially fatal
➢ Toxins are produced that dissolve membranes causing death of muscle
cells, oedema, haemolysis of RBC and renal failure
➢ Occurs in trauma and compound fractures in which dirt and debris are
embedded - can occur in the stomach, gallbladder, intestine, vagina
and skin
➢ Characteristic of this disorder are bubbles of hydrogen sulfide gas that
form in the muscle
https://www.youtube.com/watch?v=jUydEE4vYAs
Pathological calcification:
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Common process in a wide variety of disease states.
May be defined as:
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The abnormal tissue deposition of calcium salts together with smaller
amounts of iron, magnesium and other mineral salts
Often occur at sites of necrosis
There are two types:
• Dystrophic : occurs in dead or dying tissue
• Metastatic: occurs in normal tissue
Dystrophic(normal calcium metabolism and levels):
✓ Deposition of calcium salts in injured tissue/area of necrosis
✓ Either intracellular or extracellular - end product formation of crystalline
calcium phosphate
✓ Components are derived from the bodies of dead or dying cells as well as
from the circulation and interstitial fluid
✓ Appear as fine white granules or clumps
✓ Always present in atheromas of advanced atherosclerosis (intimal injury in the
aorta and large arteries – accumulation of lipids)
✓ Commonly develops on aging or damaged heart valves
Metastatic:
✓ Occurs in normal tissues whenever there is hypercalcaemia
✓ There are 4 principle causes of hypercalcaemia
1. Increased secretion of the parathyroid hormone
2. Destruction of bone tissue secondary to primary tumours (e.g. multiple
myeloma) or diffuse skeletal metastases (e.g. breast cancer) or accelerated
bone turnover (Pagets disease)
3. Vitamin D related disorders
4. Renal failure (phosphate retention)
Cell aging:
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Result of a progressive decline in the proliferative capacity and life span of
cells and
Continuous exposure to exogenous factors that cause accumulation of
cellular and molecular damage (e.g. by free radicals); reduced capacity to
divide ; reduced ability to repair DNA damage; accumulation of metabolic
damage
Examples of the effects of cell aging:
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Decrease in elasticity of blood vessels; bowel mobility, muscle mass and
subcutaneous fat
UNIT 4:
Infection:
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Definition: Is present when pathogenic micro-organisms have established
themselves in the tissues of some part(s) of the body and are able to survive
and reproduce themselves therein
Micro organisms responsible for causing infections:
➢ Bacteria:
✓ Small unicellular replicating organism that lacks an organized
nucleus(prokaryotes) - contains both DNA and RNA.
✓ Cell wall determines the shape of the bacterium
eg. Spherical = cocci
Helical = spirilla
Elongate = bacilli
✓ Bacteria can be motile (flagella) and can adhere(fimbriae/pili) to
mucous membranes or other bacteria
➢ Viruses:
✓ Smallest intracellular pathogen categorized by various characteristics:
• Acellular (no cytoplasm or organelles).
• They carry out no metabolism on their own.
• Replicate using the host cell's metabolic machinery.
• Viruses don't grow and divide.
• New viral components are synthesized and assembled
within the infected host cell.
✓ Viruses also have the ability to transform normal cells into malignant
cells e.g. Ebstein Barr virus; HPV and Hepatitis B
Fungi:
Free-living eukaryotic saprophytes found in every habitat on earth
Some are present in the normal human microflora
Only a few are capable of causing disease e.g. Infections of the skin
and subcutaneous tissue
✓ Separated into two groups:
• Yeasts (intra/extracellular)
• Molds (extracellular)
✓ E.g. athlete’s foot (fungal skin infection
Caused by dermatophytes)
➢
✓
✓
✓
➢ Prions:
✓ Protein that lacks a demonstrable genome (misfolded proteins) which
causes neurodegenerative diseases
✓ Fatal
✓ E.g. Creutzfeldt-Jakob disease SIMILAR to “Mad cows disease”
✓ How prions kill:
➢ Parasites:
✓ Organisms that infect and cause disease in other animals.
✓ Protozoa – infections are passed directly from host to host through
sexual contact OR indirectly through contaminated water or food or by
way of an arthropod vector(malaria being the most common)
✓ Helminths – wormlike parasites – transmission through ingestion or
penetration through the skin; can involve many sites such as the lung,
liver, urinary tract(schistosomiasis)
✓ Arthropods – vectors of infectious diseases eg. ticks, mosquitoes,
biting flies AND ectoparasites eg. Lice, mites and fleas
Relationships that co-exist between micro-organisms and their host:
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Commensal:
✓ micro-organism obtains nutritional support from the host – but host not
adversely affected (neutral- Staphylococcus epidermis)
Mutualistic:
✓ micro-organism and host benefit (positive e.g. Ecoli …. NB Ecoli can
cause harm)
Parasitic:
✓ infecting organism benefits at the expense of the host – can vary from
slight to fatal injury(tapeworm)
Routes of entry of microbes:
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Direct –Inhalation or Ingestion
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Direct contact:
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STD’s ; placental i.e. mother to child
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Penetration due to direct inoculation
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Urinary or genital tract
Body’s mechanisms of defense:
First line defense (physical and chemical barriers):
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The skin
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Sweat & bacteria
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Tears
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The mucous membrane of the upper respiratory tract
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Coughing and sneezing
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Stomach acids
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Vomiting & diarrhea
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Constant flow of urine
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Neutrophils
Second line defense:
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Lymphatic system is activated when 1st line defense fails
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Inflammatory fluid drains predominantly into lymph vessels and from there
into lymph nodes where the bacteria are made inactive
Third line of defense
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Reticulo-endothelial (macrophage-phagocytic) system
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Widely dispersed phagocytic cells which protect individual organs e.g.
Kupffer cells in the liver ; Histiocytes in connective tissue and Glial cells in
nervous connective tissue
Factors influencing the effect of a pathogen on the host:
1. Nature of the organism
•
Toxicity
•
Quantity
•
Portal of entry
•
Virulence
2. Nature of the host
•
General state of health
•
Presence of pre-existing infections
•
Health of the immune system
Spread:
•
•
•
Local- spread i.e. to adjacent structures.
Lymphatic spread:
✓ lymphadenitis (inflamed lymph nodes)
✓ lymphangitis (inflamed lymph vessel)
Systemic - Blood- spread to distant tissues causing secondary infections:
✓ bacteraemia (presence of bacteria in the blood)
✓ septicaemia (a systemic disease with fever and low blood pressure,
due to bacteraemia –which can be fatal)
infection & inflammation:
•
Difference:
Infection
• Is present when pathogenic
micro-organisms have
established themselves in the
tissues of some part(s) of the
body and are able to survive
and reproduce themselves
therein
Inflammation
• Mechanism by which the body
deals with an injury or insult
• Process is characterized by
release of inflammatory
mediators and movement of
fluid and leukocytes from the
vasculature into the
extravascular tissue
The inflammatory response: https://www.youtube.com/watch?v=qCpWXPSMBIY
Clinical features of inflammation:
https://www.youtube.com/watch?v=Kpx56iDvCdU
Causes of inflammation:
•
Infections (bacterial; viral ; fungal and parasitic) and microbial toxins – can
range from mild to severe inflammation
•
Tissue necrosis due to ischemia, trauma, physical and chemical injury (e.g.
burns, frostbite, irradiation and environmental chemicals)
•
Foreign bodies(splinters, dirt, sutures) or endogenous substances( urate
crystals ; cholesterol crystals) and lipids (obesity associated metabolic
syndrome)
•
Immune reactions (allergies or auto-immune diseases)
Without inflammation, infections would go unchecked, wounds would not heal and
injured tissues might remain permanent festering sores:
Cells of inflammation i.e. endothelial cells; platelets, leukocytes:
•
Endothelial cells
✓ Lines the blood vessels and form capillaries
✓ Separates intravascular and extravascular spaces
✓ Produce agents that maintain vessel patency + vasodilators +
vasoconstrictors
✓ In the inflammatory process – provides a selective permeability barrier to
exogenous and endogenous stimuli + regulates leukocyte
extravasation(DIAPEDESIS) + regulation of immune responses +
regulate immune cell proliferation
✓ Part of repair process- produces growth factors
•
Platelets
✓ Plays a role in homeostasis
✓ Release inflammatory mediators that increase vascular permeability ; alters
chemotactic, adhesive and proteolytic properties of endothelial cells
✓ Over 300 proteins can be released when a platelet is activated
•
Leukocytes:
Leukocytes
Nuetrophils
Granuolcytes
Eosinophils
Basophils
Monocytes
Agranulocytes
Lymphocytes
✓ Granulocytes:
Neutrophils:
- Most numerous: first to appear at the site of inflammation.
- Short life span
- Scavenger cells: contain enzymes that degrade and engulf
microbes and dead tissue.
- Contain pathways for H2O2 and NO that aid in the destruction of
pathogens
Eosinophils:
- Accounts for 2-3%: appears much later than neutrophils- slow
mobility
- Longer life span than neutrophils
- It contains a protein that is highly toxic to large parasitic
worms that cannot be phagocytosed
- Important in allergic reactions and collagen diseases: releases
chemical mediators
Basophils:
- Accounts for <1%
- Most prominent in allergic reactions: mediated by IgE
- Prevalent along the mucosal surfaces of the GIT tract; lung and
dermis of the skin
- Rich in histamine(triggers inflammation) and heparin(anticoagulant)
- Stimulate the synthesis of cytokines and chemokines
✓ Agranulocytes:
Monocytes: (Macrophages)
- Constitutes 3-8% of WBC: largest of circulating leukocytes
- Longer life span than granulocytes: assists in destroying
causative agent, resolve inflammatory process, contributes
to healing process
- NB in maintaining chronic inflammation
- Linked to inflammatory conditions such as atherosclerosis
- Produces vasoconstrictive mediators: inflammatory cytokines
and growth factors that promote the regeneration of tissues
- Capable of phagocytosis and bacterial killing
Lymphocytes:
- Smallest of the leukocytes: predominant in the lymphatic system
than in the blood
- Participates in immune and non-immune mediated inflammation
caused by infectious agents
- Production of antibodies directed against persistent antigens
The inflammatory process: (the 5R’s)
•
RECOGNITION :
Offending agent in extravascular tissues is recognized by host cells and
molecules
•
RECRUITMENT:
Leukocytes and plasma proteins located to area of offending agent
•
REMOVAL:
Leukocytes and proteins activated to destroy and eliminate offending agent
•
REGULATION:
Reaction is controlled and terminated
•
REPAIR:
The damaged tissue is repaired
Pathophysiology of the cardinal signs of inflammation:
•
•
•
•
Rubor, Calor: (inflammation and heat)
✓ Increased movement of blood through dilated vessels
✓ Additional number of erythrocytes passing through the area
✓ Mediated by histamine
Tumor: (swelling)
✓ The result of increased passage of fluid from dilated and permeable
blood vessels into the surrounding tissues
✓ Infiltration of cells into the damaged area
✓ Mediated by histamine
Pain:
✓ Due to the direct effect of mediators
✓ Either from initial damage or from the inflammatory response itself, and
the stretching if sensory nerves due to oedema
✓ Mediated by PGE2 & Bradykinin
Functio laesa: (loss of function)
✓ Simple loss of mobility in a joint
✓ Due to oedema and pain, or to the replacement of functional cells with
scar tissue
Acute and chronic inflammation:
•
Differentiate:
Acute
Almost an immediate reaction of
local tissues and blood vessels to
injury aimed primarily at removing
the infectious agent – occurs before
adaptive immune response
Aim: removal of injurious agent and
the limiting of tissue damage
Chronic
Self-perpetuating and lasts for
weeks, months or even years
Result of a recurrent or progressive
acute inflammatory process or from
low grade responses that fail to
produce an acute response
1. https://www.youtube.com/watch?v=suCKm97yvyk
FOR:
1.1. Signs of inflammation
1.2. The stages of acute inflammation…… ensure that you
are able to explain the following for test purposes:
✓ Margination: Margination refers to the process in which white blood cells
(leukocytes) migrate to the periphery of blood vessels during inflammation.
This movement is facilitated by the slowing down and adherence of
leukocytes to the endothelial lining of blood vessels.
✓ Molecules: Adhesion molecules are proteins present on the surface of white
blood cells and endothelial cells. They play a crucial role in the process of
leukocyte migration from the bloodstream to the site of inflammation.
Adhesion molecules enable the interaction and binding between leukocytes
and endothelial cells, allowing leukocytes to firmly attach to the vessel wall.
✓ Tethering: Tethering is an initial step in the adhesion process during leukocyte
migration. It involves the transient attachment of circulating leukocytes to the
endothelium. This attachment is mediated by selectin molecules expressed on
both leukocytes and endothelial cells.
✓ Diapedesis: Diapedesis, also known as extravasation, is the process by which
leukocytes squeeze or migrate through the endothelial lining of blood vessels
and enter the surrounding tissues. It is an essential step in the immune
response, allowing leukocytes to reach the site of infection or tissue injury.
✓ Chemotaxis: Chemotaxis refers to the directed movement of cells, including
leukocytes, in response to chemical signals or gradients. During inflammation,
damaged tissues release chemical signals called chemokines, which attract
leukocytes to the site of injury or infection. Chemotaxis guides leukocytes
towards the source of the chemical signal, facilitating their migration and
accumulation at the site of inflammation.
✓ Opsonization: Opsonization is a process in which pathogens, such as bacteria
or viruses, are marked for destruction by the immune system. It involves the
coating of pathogens with molecules called opsonins, which can be antibodies
or complement proteins. Opsonization enhances the recognition and uptake
of pathogens by phagocytic cells, such as macrophages and neutrophils,
facilitating their efficient elimination by the immune system.
2. https://www.youtube.com/watch?v=16_VbjmXpXs
FOR: Summarizing the differences between acute and chronic inflammation
Stages of Acute Inflammation:
1. Vascular
•
Involves arteriole, capillaries and venules
•
Changes occur immediately
•
Characterized by:
•
Vasodilation:
Induced by several mediators…. more
histamine and nitric oxide
- Change in blood flow
- Vascular permeability: (characteristic
of acute inflammation). Binding of
chemical mediators to endothelial
receptors causing contraction of
endothelial cells – resulting in
endothelial gaps. Separation of
intercellular junctions – most
commonly caused by histamine,
bradykinin, leukotrienes and chemical mediators.
- Leakage of protein rich fluid into the extra-vascular tissue space:
Changes in osmotic pressure results in increase fluid movement from
vascular component into tissue space thus resulting in swelling, pain
and impaired function.
3 patterns of vascular response (depends on severity):
-
IMMIDIATE transient
response
immidiate
PERSISTANT response
DELAYED PERSISTENT
response
• minor injury
• short duration: 1530min reversible
• e.g. insect bites
• more serious
• several days due to
damage to
endothelium
• e.g. burns; products
of bacterial
infections
• most serious
• increase
permeability begins
after a delay of 2-12
hours and lasts for
hours or days
• e.g. sun damage/
radiation
2. Cellular
• Marked by endothelial cell changes and movement of phagocytic
leukocytes into the area of injury or infection
• Recruitment of leukocytes from the blood: mainly neutrophils
• Rapid response of chemical mediators from mast cells and macrophages
• The sequence of events that follows:
- Margination and Tethering (leukocyte accumulation and release of
adhesion molecules)
- Transmigration
- Chemotaxis (process of movement of leukocytes by chemical signals)
- Activation and phagocytosis by neutrophils, monocytes and
macrophages → Opsonization of microbes (pathogen gets tagged for
elimination)
Exudate:
•
•
Definition: A fluid rich in protein
and cellular elements that
oozes out of blood vessels due
to inflammation and is
deposited in nearby tissues.
Transudate: fluids that pass
through a membrane or
squeeze through tissue or into
the EXTRACELLULAR SPACE
of TISSUES. Transudates are
thin and watery and contain few
cells or PROTEINS.
Functions of the exudate:
•
Dilutes toxins
•
Limits the use of the affected
area and prevents further injury
•
Antibodies neutralize the pathogens
•
Macrophages digest micro-organisms and remove debris
•
Fibrin (clot) attempts to seal off the area and prevents spread of the
infection/inflammatory agent
Exudate and inflammation that forms and accumulate within a cavity have a
specific name:
Membrane
Infection/Inflammation
Cavity
Exudate
Peritoneum
Peritonitis
Abdomen
Ascites
Pleura
Pleuritis
Lungs
Pleural effusion
Pericardium
Pericarditis
Heart
Pericardial effusion
Outcomes of acute inflammation:
Sequels of acute inflammation:
NB: Depends on the severity, cause and site of involvement
•
•
•
•
•
•
•
•
•
Resolution (reversible injured cells): tissue returns to normal architecturecause eliminated
Regeneration: re-growth takes place to replace injured tissue- mediated
by cytokines(e.g. VEGF)
Fibrosis (in tissue that does not re-generate): thickening or scarring of
connective tissue usually as a result of injury - can result in loss of tissue
function
Suppuration: formation of pus due to bacterial infection
Ulceration: necrosis and erosion of epithelial surface
Abscess: lesion containing pus - conditions favour bacterial multiplication
and continued inflammatory response (An abscess is a localized area of
suppuration)
Sinus: a track produced by pus when discharging itself from an abscess
cavity.
Fistula: an abnormal (or surgically made) passage between a hollow
organ and the body surface or between two hollow organs(generally
followed by abscess… can be chronic)
Toxaemia: spread of toxins via the blood stream affecting all organs.
(blood poisoning)
Causes of chronic inflammation:
Unlike acute inflammation showing redness, swelling and pain chronic inflammation
can be invisible
•
•
•
•
•
•
•
•
Autoimmune diseases e.g. lupus
Infectious agents e.g. viruses
Atherosclerosis
Environmental e.g. smoking
Allergens
Obesity
Low grade persistent infections
Injured tissue e.g. fractures
Categorisation of chronic inflammation:
1. Infiltration with mononuclear cells, which include macrophages,
lymphocytes and plasma cells
2. Tissue destruction, induced by the persistent offending agent or by
inflammatory cells
3. Attempts at healing by connective tissue replacement of damaged
tissue, accomplished by proliferation of small blood vessels (angiogenesis)
and in particular, fibrosis
Chronic inflammation can lead to:
Chronic inflammation in summary:
•
It occurs when the acute response is unable to neutralize a pathogenic
agent…. Continued tissue destruction
•
Inflammatory and repair processes take place at the same time.
•
This leads to the deterioration of the function of the organ.
•
Immune response is now activated (fever, loss of appetite and weight loss
generally features of chronic illness)
Whether acute or chronic, the inflammatory process may be modified by:
•
Cause of the damage
•
The nutritional status of the patient
•
The competence of the patient’s immune system
•
Intervention with antibiotics, anti-inflammatory drugs or surgery
UNIT 5:
Infections & inflammation OR Injuries such as fractures and wounds
May cause death of cells in localized areas
Resulting in the loss of continuity in tissues
This prompts the body’s natural processes to restore tissue continuity
✓ Hence the development of REPAIR → REGENERATION & HEALING/FIBROSIS
✓
✓
✓
✓
Terminology:
•
Cell proliferation: a process of increasing cell numbers by mitotic division
•
Cell differentiation: a process whereby a cell becomes more specialized in
terms of structure and function
•
Stem cells: undifferentiated cells that have the capacity to generate into
multiple cell types
•
Cell cycle: orderly sequence of events in which the cell duplicates its genetic
contents and divides
The cell cycle:
Tissue Repair : Regeneration, Healing , Fibrosis:
https://www.youtube.com/watch?v=fUkjk24mEPQ
Tissue repair:
•
•
•
•
Repair, sometimes called healing, refers to the restoration of tissue
architecture and function after an injury
The term repair is often used for parenchymal and connective tissue
The term healing is often used for surface epithelia
Critical to the survival of an organism
•
•
•
The inflammatory response to microbes and injured tissues does not only
serve to eliminate these dangers but also sets the process of repair into
motion
Repair of damaged tissues occurs by two types of reactions:
✓ Regeneration by proliferation of residual (injured) cells
✓ Maturation of tissue stem cells
Deposition of connective tissue to form a scar
The 4 step process overview of tissue repair
after injury:
https://www.youtube.com/watch?v=klKMEfXPVcI
Components of the healing process:
•
•
•
•
•
RESOLUTION: takes place when the injured tissue is restored to its pre-injury
state NB: Organs are composed of parenchyma(functional cells) that are
bound together by stroma (supporting connective tissue, blood vessels,
fibroblasts, nerve fibers and extracellular matrix)
Replacement of injured tissue from parenchyma is called REGENERATION
When fibrous scar tissue fills the gap, the process is called HEALING
Newly formed tissue needs a blood supply and therefore
REVASCULARIZATION is an important aspect of healing
Injury often involves internal or external body surfaces and therefore the
protective epithelium needs to be restored. This is referred to as
REEPITHELIALIZATION
1. REGENERATION: the proliferation of parenchymal cells
-
Cells lost through injury may be replaced by cell division (mitosis) of adjacent
healthy parenchymal cells
-
The process continues until the volume of new tissue is more or less the
same as the volume of tissue that was lost through injury
Examples include: the epithelia of the skin and intestine, and in some parenchymal
organs e.g. the liver.
-
Cell capacity for regeneration: The ability of cells to repair themselves is
determined by their intrinsic proliferative capacity.
Cells are divided into 3 groups:
1. Labile cells:
• Labile (continuously dividing) tissues
• Cells of these are continuously being lost and replaced by maturation
from tissue stem cells and by proliferation of mature cells.
• Labile cells include:
✓ Hematopoietic cells in bone marrow
✓ The majority of surface epithelia
✓ Such as the stratified squamous epithelia of the skin, oral cavity,
vagina, and cervix; the cuboidal epithelia of the ducts draining
exocrine organs (e.g. salvatory glands, pancreas, biliary tract);
the columnar epithelium of the gastrointestinal tract, uterus, and
fallopian tubes; and the transitional epithelium of the urinary
tract. These tissues can readily regenerate after injury as long
as the pool of stem cells is preserved.
2. Stable cells:
• Stable tissues
• Cells of these tissues are quiescent (in the G stage of the cell cycle)
and have only minimal proliferative activity in their normal state
• These cells are capable of dividing in response to injury or loss of
tissue mass
•
Stable cells constitute the parenchyma of most solid tissues , such
as liver, kidney, and pancreas
• They also include endothelial cells, fibroblasts, and smooth muscle
cells; the proliferation of these cells is particularly important in
wound healing
• with the exception of the liver, stable tissues have a limited capacity
to regenerate after injury
3. Permanent cells:
• The cells of these tissues are considered to be terminally
differentiated and non-proliferative in postnatal life.
• The majority of neurons and cardiac muscle cells belong to this
category.
• Thus, injury to the brain or heart is irreversible and results in a scar,
because neurons and cardiac myocytes cannot regenerate.
• Limited stem cell replication and differentiation occur in some areas
of the adult brain, and there is some evidence that heart muscle
cells may proliferate after myocardial necrosis.
• Nevertheless, whatever proliferative capacity may exist in these
tissues, it is insufficient to produce tissue regeneration after injury.
• Skeletal muscle is usually classified as a permanent tissue, but
satellite cells attached to the endomysial sheath provide some
regenerative capacity for muscle.
• In permanent tissues, repair is typically dominated
by scar formation.
2. CONNECTIVE TISSUE REPAIR: tissue loss is replaced with granulation tissue,
and fibrous repair takes place
-
-
Phases of repair:
•
Haemostasis, angiogenesis, and ingrowth of granulation tissue.
•
Emigration of fibroblasts and deposition of extracellular matrix.
•
Maturation and reorganization of the fibrous tissue (remodeling).
Process:
• Occurs when injured tissue is incapable of complete restitution
OR supporting structures are severely injured.
• Thus, there is a laying down of fibrous connective tissue to
restore the strength and structure of the tissue.
• Specialized cells called fibroblasts lay down strong, collagenrich tissue to form a scar or fibrosis …Scar formation is a
response that “patches” rather than restore the tissue..
NB: Fibrous strands can become organized within the peritoneal cavity following
surgery or peritonitis. These strands are called adhesions and can trap loops of
bowel causing obstruction
3. Revascularization (angiogenesis): Newly formed tissue requires a blood supply
and therefore revascularization is an important aspect of repair.
•
•
•
•
Definition: may be defined as restoration of the blood circulation of an organ
or area
This process is controlled by chemical signals in the body and involves the
migration, growth, and differentiation of endothelial cells, which line the inside
wall of blood vessels.
Several growth factors induce angiogenesis BUT the most important growth
factor is VEGF
A lymph drainage is also re-established
4. Re-epithelialization: Injury often involves internal or external body surfaces
therefore the protective epithelium needs to be restored.
•
•
•
Definition: is an essential component of wound healing and thus refers to the
replacement of the lost surface lining by mitosis of epithelial cells.
The formation of granulation tissue into an open wound allows the reepithelialization phase to take place, as epithelial cells migrate across the new
tissue to form a barrier between the wound and the environment.
Epithelial migration continues until cells from opposite edges meet.
Cutaneous wound healing:
•
Addresses healing of skin wounds
•
Involves epithelial cell regeneration and connective scar formation
•
Depending on the severity of tissue loss, healing occurs either by:
✓ First (primary) intention e.g. sutured surgical wound
✓ Second (secondary) intention e.g. Burns, large surface wounds
•
Cutaneous wound healing is divided into three phases:
1. Inflammatory (vascular and cellular stages)
2. Proliferative (2-3 days after injury- new tissue to fill the wound space)
3. Remodeling (3 weeks after injury – remodeling of scar tissue)
NB: Duration of phases depends on extent of the injury
Healing by first intention:
•
Occurs at a site where there is minimal loss of tissue e.g. surgical incision
•
The acute inflammatory response is minimal
•
The edges of a wound are held together by a thin film of clotted blood
•
Proliferation of adjacent epithelial cells restore continuity at an early stage
•
Macrophages remove debris and inactivate disease agents
•
New capillaries form to increase vascularity
•
Fibroblasts migrate to the area and begin to form connective tissue fibres
•
Where possible, healthy cells multiply to restore normal function and
appearance
Healing by second intention:
•
Occurs when tissue loss is greater and the edges of the wound are not close
together e.g. burns, ulcer or abscess cavity
•
The healing process takes longer as more regeneration and repair is needed
•
Infection or trauma has to be overcome by an acute inflammatory response
and all debris removed by macrophages
•
In trauma, the defect is filled by clotted blood
•
Healing starts from the floor of the wound, through the action of
leukocytes(reticuloendothelial or white blood cells), histiocytes(macrophages),
fibroblasts and re-vascularization.
•
New delicate connective tissue is formed, called granulation tissue,
consisting of fibroblasts, collagen & capillaries
•
Granulation tissue matures from the bottom up, until the area is filled with
fibrous or scar tissue
•
Surface epithelial cells at the periphery proliferate and cover the granulation
tissue
•
Contraction of the wound occurs, resulting in a scar that is smaller than the
original defect
•
Initially the scar is red, but turns white as the capillaries die away
Summary of wound healing:
How bones heal after being fractured:
https://www.youtube.com/watch?v=od8oU5OLMGU
Factors that influence tissue repair:
1. Infection/Presence of foreign material (bacterial contamination): Infections can
impair the healing process by introducing harmful microorganisms, leading to
inflammation, delayed wound closure, and increased risk of complications.
2. Diabetes: Diabetes can negatively affect tissue repair due to impaired blood flow,
reduced immune response, and decreased collagen synthesis, leading to delayed
wound healing and an increased risk of infections.
3. Nutritional status (lack of vitamins): Poor nutrition, particularly deficiencies in
vitamins like vitamin C and vitamin A, can impair tissue repair by impacting collagen
synthesis, immune function, and cell proliferation.
4. Corticosteroids: Prolonged or high-dose use of corticosteroids can inhibit the
inflammatory response, impair collagen synthesis, and weaken the immune system,
leading to delayed healing and increased risk of complications.
5. Mechanical factors (increase pressure or torsion): Excessive mechanical forces,
such as increased pressure or torsion on tissues, can disrupt the healing process,
cause tissue damage, and delay wound closure.
6. Poor perfusion (vascularity): Inadequate blood supply to the injured area, often
caused by poor vascularization or compromised circulation, can limit oxygen and
nutrient delivery to tissues, impairing the healing process.
7. The type and extent of injury: The nature and severity of the injury influence tissue
repair. Complex or extensive injuries may take longer to heal and require more
intensive treatment.
8. The location of the injury: The location of the injury can affect the healing process.
Tissues with a rich blood supply, like muscle, tend to heal faster than tissues with a
limited blood supply, such as cartilage or tendons.
9. Age (decline in collagen synthesis and reduced rate of proliferation): Advanced
age is associated with a decline in collagen synthesis, reduced cell proliferation, and
decreased immune function, leading to slower healing and increased susceptibility to
complications.
Factors that can complicate the tissue repair process include:
1. Infection: Infections in the wound can delay healing, cause inflammation, tissue
damage, and increase the risk of complications such as abscess formation or sepsis.
2. Inadequate formation of granulation tissue: Insufficient development of granulation
tissue, which is essential for wound healing, can result in wound dehiscence
(separation of wound edges) and ulceration, hindering the healing process.
3. Excessive contraction of a scar: Excessive scar contraction can lead to functional
and cosmetic issues. In skin wounds, it can result in deformities, restricted
movement, and even contractures. In internal organs, excessive scar contraction can
cause obstruction, such as in the oesophagus, or stenosis, as seen with scarred
heart valves.
4. Hypertrophic scar or Keloid formation: Abnormal scar tissue formation can result in
hypertrophic scars or keloids. Hypertrophic scars are raised, thickened scars, while
keloids are raised scars that extend beyond the boundaries of the original wound.
These can cause cosmetic concerns and may be associated with symptoms such as
itching or pain.
5. Pain (due to formation of a neuroma): Neuroma formation, the abnormal growth of
nerve endings in scar tissue, can lead to chronic pain, discomfort, and
hypersensitivity at the site of injury.
6. Weakness: Fibrous scar tissue is less elastic and has reduced strength compared
to the original healthy tissue. This weakness can result in compromised tissue
function and may predispose the area to further injury or complications.
7. Cancer (developed from a chronic scarred ulcer): Chronic non-healing ulcers or
wounds that fail to heal properly can be associated with an increased risk of
developing certain types of skin cancer, such as squamous cell carcinoma.