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Topic One[Cont'd]
Define of terms used in Anatomy and Physiology
Anatomy:
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Topic 1: Defination of Terms
- Aetiology - Causal factors (“why” of disease – the cause of disease)
- Lesion - Structural alterations in tissues that give rise to functional abnormalities)
- Characteristic changes in tissues and cells produced by a disease
Morphology - structure or shape
- Natural history - Course of disease from the beginning to the end without treatmentOrganic disease - Disease associated with structural changesFunctional disease - Disease with functional abnormalities but no structural abnormalities
- Pathologic anatomy - Study of changes in structure and morphology
- Pathogen - An organism or substance that can cause disease.Disease producing agent (restricted to living agent)
- Pathogenesis - Is the origin and development of disease including factors that influence it.
- Mechanisms by which lesions are produced
- Pathogenesity - The capacity to produce disease
- Pathognomonic - Describes anything that is typical of a particular disease
- Patient - Person affected by disease
- Prognosis - The prediction of outcome of the disease which is based on the Knowledge of natural history and response to treatment
- An opinion concerning the eventual outcome of the disease
Symptoms - Subjective complains (manifestations) from a patientSigns - Physical/objective findings
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Topic 1: Significance of Studying Pathology
The study of pathology forms a vital bridge between the initial learning phases of the basic sciences (anatomy, physiology, microbiology, and parasitology) in the pre-clinical year and the final phase of clinical sciences (internal medicine, surgery, orthopaedics & traumatology, obstetrics/gynaecology, paediatrics and pharmacology) in the clinical years
Divided into two main branches –
i) General Pathology - focuses on the fundamental cellular and tissue responses to pathologic stimuli
ii) Clinical/systemic pathology - examines the particular responses of specialized organs An in-depth of understanding of disease process is essential for clinicians to recognise, diagnose and treat diseases with accuracy and competence
The knowledge of Pathology enables:
1. The learner to explain the signs and symptoms of the various disease conditions exhibiting the understanding of aetiology, pathophysiology and pathology of the disease.
2. One to learn the mechanics by which normal anatomy and physiology is altered by pathological processes.
3. One to develop basic knowledge of disease process and how these relate to the signs and symptoms, how the disease develops in the absence of therapy and how therapy may alter these processes.
4. One to be able to accurately predict complications and prognosis of the disease 5. Investigations and interpretations of results
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Topic 1: The Branches and Subdivisions of Pathology
Branches
There are various disciplines of pathology such as human pathology, animal pathology, plant pathology, veterinary pathology, poultry pathology etc.
Human pathology is the largest branch of pathology and is divided into general pathology (describes general principles of disease) and systemic/clinical pathology (pertaining to specific organs and body systems)
Subdivisions
Diagnosis is the procedure of determining the nature and cause of a patient’s
illness by a clinician. It is based on the clinician’s evaluation of the patient’s
symptoms (subjective manifestations), signs (Objective manifestations detected
by the clinician) and results of various laboratory tests and other appropriate
diagnostic procedures e.g. X-rays, CT scans Symptoms are detected by the process of history taking while the signs are
detected by the process of physical examination which has various components After making a diagnosis, the clinician can determine the prognosis (an opinion
concerning the eventual outcome of the disease) and appropriate institute
treatment. HISTORY
Clinical history is a very import part of patient evaluation and consists of several parts
namely history of patient’s current illness, the past medical history, the family history,
the social history and review of systems (systemic enquiry) PHYSICAL EXAMINATION Physical examination is a systematic examination of the patient. The clinician
should place particular emphasis on the part of the body affected by the illness.
Abnormalities defected are correlated with the clinical history. Consider various
diseases or conditions that would fit the findings (differential diagnosis). Physical examination entails general examination and systemic examination using
the four physical examination techniques are inspection, palpation, percussion
and auscultation. DIAGNOSTIC TESTS AND PROCEDURES There are a wide array of diagnostic tests and procedures available to help the
clinician make a diagnosis and treat the patient properly. Classified into 2 main groups i) Invasive procedures-Involve actual invasion of the body in some way to obtain diagnostic
information e.g. introducing needles, catheters, trochers and other
instruments into the patient’s body. ii) The non-invasive procedures- Do not involve invasion of the body and have no risk or minimal risk or
discomfort to the patient e.g. chest X-Ray (CXR) and urinalysis Classification of diagnostic tests
and procedures clinical laboratory tests Endoscopy Tests
that measure the electrical activity of the body e.g. electrocardiography (ECG) and
electroencephalography (EEG), medical Imaging Tests using radioisotopes
(radionuclides), ultra sound procedures, X-ray examination and magnetic
resonance imaging ( MRI) , position emission tomography(PET scans) b)Inflammatory
diseases;-Inflammatory diseases are those
conditions in which the body reacts to an injurious agent by means of
inflammation. Examples:Pneumonia, Allergic
reactions
A. INFECTIOUS AND PARASITIC
INFECTIONS (A00 – B99) Examples B. NEOPLASMS (C00 – D48) C. DISEASES OF BLOOD AND BLOOD
FORMING ORGANS (D50 – D89) D. ENDOCRINE, NUTRITIONAL AND
METABOLIC DISEASES (E00-E90) E. MENTAL AND BEHAVIOURAL DISORDERS
(F00 – F99) F. DISEASES OF THE NERVOUS SYSTEM
(G00 –G99) G. DISEASES OF THE EYE AND ADNEXA
(H00 – H59 H. DISEASES OF THE EAR AND MASTOID
PROCESS (H60 –H95) 1. Ischaemia (Hypoxia) 2.Physical agents 3.Chemicals and Drugs 4.Microbial agents 5.Immunologic agents 6.Nutritional 7.Metabolic 8.Psychological 9.Genetic Defects 1. Reversible cell injury Pathogenesis -The reversible cell injury that ensues
from ischaemia occurs thorough the following stages: There
is decreased oxygen supply due to failure of aerobic respiration resulting in
decreased ATP,
no
cellular energy Anaerobic
glycolysis generates ATP from glycogen resulting in rapid depletion of
glycogen, accumulation of lactic acid, reduced intracellular pH, damage to cell
membrane thereby
increasing permeability Irreversible cell injury Features of Irreversible Cell
Injury Cellular adaptations 1. Agenesis- Agenesis is complete absence or failure
of development of tissue or organ. Agenesis may also be referred to as
aplasia. It results from teratogenic effects which
cause developmental defects E.g.
Congenital agenesis of: Kidney ,Uterus ,Heart. 2. Hypoplasia- is incomplete development or
underdevelopment of an organ such that the organ does not attain its normal
size resulting in the presence of a rudimentary organ (partial failure of
development).This is because of decreased numbers of
cells. It is a less severe form of agenesis. Hypoplasia can occur as a result of: -Genetics
and mutations, Endocrine
insufficiency, Cell
loss due to infection or poisoning 6. Metaplasia- is a reversible change of one
type of differentiated epithelial or mesenchymal adult cells into another type
usually of the same class but which is less specialized. Also the transition of one type of
differentiated tissue into another one usually in response to abnormal stimuli.
Quite often the transition results into a less specialized tissue.The cells revert to normal on removal of
the stimuli but if the stimuli persist for a long period it may transform to
cancer that cannot be reversed to the original tissue. 7. Dysplasia- is a pre-malignant disturbance of cell proliferation and maturation
within
an epithelium such that there is loss of normal architectural pattern of the
epithelium. Dysplasia is a disordered cellular
development often accompanied with metaplasia and hyperplasia. It is characterized by cellular
proliferation and cytologic changes. 8. Neoplasia –tumours Cell death 1. Autolysis: Autolysis is the death of cells and
tissues after the death of the whole organism. It can also be seen when tissues are
removed surgically from the organism. This occurs due to post-mortem release of
digestive enzymes from lysosomes. 2.Apoptosis: Apoptosis is a coordinated and programmed
death of tissues which is a significant active process in health and disease. It is programmed cell death stimulated by
diverse agents and occurs under physiological and genetic control. The process of apoptosis helps to
eliminate unwanted cells by an internally programmed series of events effected
by dedicated gene products. Apoptosis involves cell death of single
cells or small groups of cells where the other cells are functioning well. Apoptosis is an energy-dependent process
needed to maintain membrane pumping systems and synthesis of cellular proteins. It is not associated with inflammation
and once initiated the process is irreversible. Apoptosis can be seen in physiological
and pathological processes. Examples of Physiological Apoptosis
Examples of Pathological Apoptosis Process of apoptosis Stage 1 – Initiation Stage 2 – Execution Stage 3 – Disposal (Elimination): Apoptotic
bodies are disposed through phagocytosis by macrophages and adjacent epithelial
cells Usefulness of apoptosis Structural changes in apoptosis
NECROSIS Introduction Necrosis is the death of a cell or a group of cells in a viable tissue (living tissue) due to lethal injury Not an energy dependent active process but a consequence of sudden changes in the cell
microenvironment which abolishes cell function Results from denaturation of proteins and release of digestive enzymes that destroy the tissues. Aetiology 1) Ischaemia Impaired blood supply, which leads to lack of oxygen and hypoxia. Ischaemia could result from
blockage of blood vessels by thrombus (thrombosis) emboli (embolism) and ligation of vessels. The
death depends on the type of tissue/cell – Examples neurone cell will die after 5 minutes of hypoxia,
myocardial cell will die after 15 – 20 minutes of hypoxia, ischial tuberosity cell will die after 20 minutes
of hypoxia, renal tubule cell will die after 1 – 2 hours of hypoxia and gluteal maximus cell will die after
4 hours of hypoxia 2) Toxins May be produced by bacteria (endotoxins, exotoxins or liberate enzymes), plants, snakes and
scorpions. Clostridium welchii produces toxin lecithinase that digests the lipid of the cell membrane.
The toxins destroy tissue and cause thrombosis. Other toxins/enzymes are Diphtheria, Salmonella,
Staphylococcus, Streptococcus and Shigella
3) Immunological injury - includes the hypersensitivity reactions and autoimmune disease
4) Infection of cells - viral infections e.g. infection of the anterior horn cell in poliomyelitis, bacterial infection
and parasitic 5) Chemicals and poisons - can be endogenous or exogenous which cause necrosis by destruction of
cellular proteins by acids, strong alkali, mercury, cyanide and carbon tetrachloride 6) Genetic disorders - Sickle cell disease 7) Physical agents - physical agents such as extreme heat >45o C, Extreme cold – frost bite, sunburn,
Radiation, Mechanical trauma and electrical injury 8) Nutritional disorder - obesity and malnutrition Pathology Microscopic changes that are seen in the cells include eosinophilia of the cytoplasm, shrinkage of the
nuclear (Pyknosis), disintegration of the nuclei (Karyorrhexis) and complete dissolution of the nuclei
(Karyolysis) Necrotic tissue exhibits opaque appearance, whitish or yellow colour, loss of normal translucence of living
tissues and cellular changes with swelling and loss of the cell details of the cytoplasm and the nuclear Cytoplasm becomes opaque, dense and homogenous with loss of the fine granularity or reticulation
Cellular outline is obliterated and the nucleus is shrunken and condensed into a small mass with loss of
the nuclear details Classification of Necrosis
Two principal types 1) General forms (coagulative and colliquative/liquefactive)
2) Special forms (fat, caseous, infarction, fibrinoid and gangrene). Colliquative Necrosis (Liquefactive Necrosis) Commonly results from ischaemic injury and bacterial infections Tissues containing excess liquid usually exhibit colliquative necrosis. Characterized by release of
powerful hydrolytic enzymes that degrade cellular components and extracellular material to produce a
proteinaceous soup.
Involves two processes of necrosis and liquefaction Commonly encountered in the brain and spinal cord, abscess formation and infections from pus forming
bacteria due to bacterial toxins and proteolytic enzymes. There is release of powerful hydrolytic enzymes that degrade cellular components and extracellular
material Necrotic area undergoes softening and is filled with turbid fluid with complete loss of structure Pathogenesis Liquefactive necrosis is usually caused by focal bacterial or fungal infections, because they can attract
polymorph nuclear leukocytes Enzymes in the polys are released to fight the bacteria, but also dissolve the tissues nearby, causing an
accumulation of pus, effectively liquefying the tissue (hence, the term liquefactive). Example: abscess Pathology Macroscopy - softened cells with large amounts of fluid, centre of the dead tissue contains debris and a
cyst wall is formed
Microscopy - necrotic debris and macrophages and cyst wall formed of proliferating capillaries and
inflammatory cells Coagulative Necrosis
Commonly caused by irreversible focal injury usually ischaemia (from sudden cessation of blood flow)
and less frequently from bacterial & chemical agents Most common form of necrosis occurring mainly in solid organs (heart, spleen and kidney) Characterized by coagulation of the proteins of the dead cells or dying cells by intracellular enzyme
liberated by autolysis and formation of an exudate at the site for example kidney infarct, spleenic infarct
or pulmonary tuberculosis (PTB). There is denaturation of intracellular proteins (analogous to boiling the
white of an egg).
Examples: The Kidney, the spleen and the myocardium Pathogenesis Ischemia rapidly results in decreased ATP increased cytosolic Ca++ and free radical formation, each of
which eventually cause membrane damage Decreased ATP
o Results in increased anaerobic glycolysis, accumulation of lactic acid, and therefore decreased
intracellular pH
o Causes decreased action of Na+
/K+ pumps in the cell membranes, leading to increased Na+ and
water within the cell (cell swelling) Ribosomal detachment from endoplasmic reticulum occurs; blebs on cell membranes, swelling of
endoplasmic reticulum and mitochondria. These changes are reversible, if oxygenation is restored If blood flow stops, necrosis causing the cytoplasm to become eosinophilic, and the nuclei to lyse or
fragment or become pyknotic (hyperchromatic and shrunken) Pathology Basic architecture and cellular outline is preserved because the offending injury does not destroy
structured proteins, cytoplasm and nucleus but only destroys enzymes within the lysosomes Inflammatory cells release enzymes that digest the cellular component The resulting debris are removed by phagocytosis (by macrophages). Macroscopy Tissue appears as an opaque homogenous mass, the necrotic area is swollen, firm and lustreless and
later necrotic tissue becomes yellow (when containing less blood), softer and shrunken. Microscopy Cell outlines are preserved but the cytoplasmic and nuclear details are lost, nucleus shows either
karyolysis or karyorrhexis, cytoplasm is opaque and eosinophilic (affinity for the red dye, eosin), damage
to the plasma membrane, swollen necrotic cells, infiltration by inflammatory cells and dead cells are
phagocytosed leaving debris and fragments of the cells. Focal Necrosis Necrosis of small areas of cells in certain organs like the liver, spleen and lymph nodes in diseases such
as typhoid, diphtheria and eclampsia. Yellow fever and Weil’s disease Results from effects of the toxins of the organisms and endogenous metabolic toxins or may result from
obstruction of blood vessels e.g. in focal nephritis Caseous Necrosis
Special type of coagulative necrosis where cellular structures are lost with the production of a cheesy
mass The stroma is destroyed unlike in the usual coagulative necrosis where the stroma is preserved. For
example, in tuberculosis (TB) cellular destruction occurs with production of dry, cheesy, granular
material, which is amorphous in character There is no chemotaxis hence no polymorph nuclear leucocytes are attracted to the site so there is no
liberation of proteolytic enzymes by the leucocytes. With secondary infection setting in, polymorphs move in with liquefaction of the mass-taking place to
form a cold abscess
Caseous material has high fat content and therefore calcification is noticed. In syphilis, the gummatous
lesion is a caseous necrosis Caseation can be seen in TB and infarcts when the necrotic tissue has the following characteristics a
firm cheese-like appearance, absence amorphous granular oesinophilic material in cell outline with loss
of cell details and presence of fat.
3.9 Fat Necrosis
Fatty necrosis occurs when there is damage to adipose tissues Two forms namely: - traumatic fat necrosis and enzymatic fat necrosis Traumatic Fat Necrosis There is release of lipids from fat cells, which provokes a chronic inflammatory process and giant cell
response with proliferation of the connective tissues Cells involved are the giant cells and macrophages Common at injection sites and subcutaneous tissue of the breast where trauma may lead to rupture of
the adipocytes and release of fatty acids which elicit an inflammatory reaction leading to scarring and
formation of a palpable mass. Enzymatic Fat Necrosis Associated with pancreatic diseases Allows lipase in the abdominal cavity, which splits neutral fats in the lipid cells leading to a small, opaque,
soft white areas giving a chalky appearance due to calcium deposits (this is diagnostic of acute
pancreatitis) Can also be seen in the omentum and mesenteries. In pancreatitis there is damage to pancreatic acini
which results in release of proteolytic and lipolytic enzymes which denature fat causing inflammation and
is accompanied by calcium deposition (dystrophic calcification). Infarction
Describes necrosis caused purely by ischaemia Examples – myocardial infarction, renal, cerebral infarcts Fibroid Necrosis
Associated with deposition of fibrin in the necrotic tissue Gangrenous Necrosis (Gangrene) A life threatening conditions which occurs when coagulative necrosis of tissues is associated with
superadded infection by putrefactive/saprophytic bacteria (usually anaerobic Gram-positive Clostridium
spp derived from the gut or soil which thrive in conditions of low oxygen tension) Bacteria produce toxins which destroy collagen and enable the infection to spread rapidly. It can be
systemic (i.e. reach the blood stream – septicaemia). If fermentation occurs, gas gangrene ensues. Breakdown of the tissues leads to production of volatile bodies and gases that result in foul smell. The
gas produced accumulates in tissues resulting in crackling on palpation (crepitations) Colour change is due to altered haemoglobin; most prominent when dead tissue contains a lot of blood.
Colour varies i.e. dark brown, greenish brown or black Gangrene is commonly seen affecting the distal part of a limb, appendix, a loop of small intestine and
organs such as the gall bladder, pancreas or testis. Aetiology 1. Blood vessel obstruction
a. Arterial obstruction by thrombosis, embolism, arteritis e.g. in diabetes mellitus, senile
arteriosclerosis, Raynaud’s disease, ergot poisoning, Buerger’s disease and effects of intra-arterial
injections e.g. cytotoxic substances
b. Venous obstruction 2. Trauma (Traumatic gangrene)
a. Direct injury – crushes, pressure sores e.g. bed sores and severely lacerated injury where the main
artery is damaged
b. Indirect injury – ligation of the main artery 3. Infection (Infective gangrene)
a. Specific – gas gangrene (clostridium bacteria)
b. Non-specific – cancrum oris (nomas) – boils, carbuncles and gangrene of scrotum (Fournier’s
gangrene) 4. Physical agents e.g. excessive heat – burns, scalds, excessive cold – frost bite, chemical injuries,
irradiation, electricity and escharotics Classification 1) Primary gangrene (gas gangrene) 2) Secondary gangrene - wet gangrene and dry gangrene Depends on the blood supply to the part affected and amount of fluid loss from the affected part
through drainage and evaporation Is a combination of coagulative necrosis and liquefactive necrosis When the coagulative pattern dominates the gangrene is described as dry gangrene and when
liquefaction dominates it is wet gangrene. Primary (Gas) Gangrene Tissue death caused by toxins of anaerobic bacteria, which then invade the dead tissues bringing about
the digestive changes Called primary gangrene because tissue death and putrification is by the same agent – the anaerobic
bacteria
Is an inflammatory disease of muscular and fascial layers caused by clostridia bacteria, which secrete
potent exotoxins Aetiology : Anaerobic microorganisms e.g. the gram-positive anaerobic gas-forming clostridia – Clostridium welchii
(perfringes), Clostridium septicum, Clostridium oedimatiens (novyi), Clostridium bifermentans, Clostridium
histolyticum, Clostridium ranosum, and Clostridium sporogenes Pathogenesis 1) Microorganisms gain entry into the tissues through open contaminated wounds in the muscles or
operation sites. 2) Intestinal commensals of man can invade wounds where they produce exotoxins killing adjacent tissues
which they then invade 3) Toxin lecithinase digests the ground substance (lecithin is an important component of cell membrane) of
cells. 4) Toxins produced cause necrosis of the affected tissues. 5) Inflammation occurs with formation of exudate (fluid exudate called oedema and cellular exudate
containing white blood cells exudation 6) Oedema formed oedema locally can be absorbed into the circulatory system giving systemic features of
disease 7) Clostridium welchii ferments sugar leading to carbon dioxide production which collects as bubbles in the
dead tissues producing crepitations on palpation 8) Secondary contamination of the dead tissues occurs with microbes such as staphylococcus,
streptococcus, and Escherichia coli, Proteus that utilize oxygen producing an anaerobic environment
favourable for further proliferation of anaerobic bacteria Pathology Gross appearance - swollen, oedematous, painful affected part, crepitations on palpation and colour
change to black or green Microscopic appearance: - coagulative necrosis with liquefaction, identify the bacteria, leucocytic
infiltration, oedema and congestion Secondary Gangrene Tissue death is due to some other causes e.g. lack of blood supply or chemical injury and then the
saprophytic bacteria invade the dead tissue causing putrification Dry Gangrene
Results from ischaemic necrosis or infarction of a part of the body e.g. toes or feet Putrification is minimal and there is adequate evaporation of fluid leaving the area dry. It is usually a
sequel of coagulative necrosis Spreads proximally reaching a point where blood supply is adequate to keep the tissue viable where a
distinct line forms between the gangrenous part and the viable part (line of demarcation). The line results
from formation of a granulation tissue following the processes of inflammation Haemolysed red blood cells liberate Hb, which releases iron that combines with hydrogen disulphide
(from the bacteria) to form a black substance iron sulphide. Aetiology 1) Vascular occlusion
a. Sudden occlusion – embolism, ligation and mechanical trauma
b. Gradual occlusion - senile arteriosclerosis, arteriosclerosis,
2) Ergot poisoning
3) Extreme cold, frost bite (vasoconstriction, inflammation) Pathology Macroscopy (gross): Dry, shrunken, dark black part (resembles mummification) Microscopy: Features of necrosis, inflammatory cells and granulation tissue Wet (Moist) Gangrene Occurs in naturally moist tissues and organs such as the mouth, bowel, lung, cervix, and vulva when
both venous (major) and arterial blood flow is blocked and the part contains a lot of fluid sufficient for
growth of putrefying bacteria. It is usually associated with colliquative necrosis Can be seen in acute pancreatitis, volvulus, intussusception, strangulated hernia, mesenteric thrombosis,
burns, bed sores and malnutrition Pathogenesis 1) Develops rapidly due venous blockage as a result of thrombosis/embolism 2) Affected part is stuffed with blood 3) Putrefying bacteria invade, multiply and the infections spreads rapidly 4) Toxins produced are absorbed causing systemic features such as septicaemia, toxaemia and death 5) There is no clear line of demarcation Pathology Gross (macroscopic) appearance: Soft, swollen, putrid, rotten dark part Microscopy: Coagulative necrosis, leucocyte infiltration (white blood cells) Tissue Response to Necrosis i) Haemorrhage – results from damage of blood vessels ii) Inflammation – tissue response to injury iii) Fever – some dead cells act as pyrogens iv) Healing and Repair – fibrosis e.g. liver cirrhosis and varices v) Calcification Outcome (Squeal) Of Necrosis 1. Autolysis
Process of “self-digestion” that is seen in all forms of necrosis as it begins after the death of the cell
Rate of development is usually dependent on local enzyme content. 2. Phagocytosis - involves phagocytic cells - macrophages and neutrophils, removes the dead cells (small
amounts). 3. Organization
In situations where a large number of cells are dead, organization and repair (with formation a fibrous
scar) of the dead tissues takes place following the inflammatory response that ensues. 4. Fibrosis - occurs due to formation of scar tissue to replace the dead tissue 5. Calcification
Necrotic tissue fails to be completely removed and there occurs deposition of calcium e.g. in
tuberculous caseous necrosis
Dead tissues may undergo calcification due to deposition of calcium in the dead tissue. Calcification
of necrosed tissue is called dystrophic calcification.
Metastatic calcification takes place in normal tissues with the favoured site being soft tissues, blood
vessels, lungs and kidneys due to the fact that there is hypercalcaemia. It is due to an abnormality
of calcium metabolism leading to high levels of serum calcium 6. Gangrene
Necrosed tissue is infected by organisms, which cause putrification (production of foul smelling gas
with a brown, green or black discolouration of tissue due to altered haemoglobin)
Gangrene is seen on the skin and mucous membranes 7. Organ failure
Depend on the organs or tissues affected e.g. the heart (heart failure), kidney (renal failure), liver
(liver failure), pancreases (diabetes mellitus) and brain (death, hemiplegia, and monoplegia). Therapeutic Cell Death and Its Mechanics 1. Alkylating agents (e.g. cyclophosphamide, melphan) causes breaks in DNA and faulty transcription 2. Anti-metabolites (e.g. cytarabine, methotrexate) block enzyme pathways and damage the
macromolecular structure of cells. 3. Antibiotics (e.g. Adriamycin, daunorubicin) produce local distortion of DNA helix hence they interfere with
cell reproduction and growth NOMENCLATURE Inflammation of a tissue is usually denoted by the suffix – itis. For example – inflammation of the
appendix – appendicitis, liver – hepatitis, breast – mastitis, meninges – meningitis, pleura – pleuritis,
bone – osteomyelitis, heart – carditis, pancreas - pancreatitis. However, there are historical exceptions
e.g. inflammation of the lung is pneumonia. CLASSIFICATION OF INFLAMMATION i) Acute inflammation is of short duration
(hours to 2 weeks) and early body response which is followed by repair. Examples - Coryza
– inflammation of the cells of the membranes of upper respiratory passages Viral
infections of the nose and throat,
trachea and bronchus e.g. influenza, INTRODUCTION
NOTE: These
stimuli induce inflammatory reactions with characteristic features but all the
inflammatory reactions share the basic features (the cardinal signs). The five cardinal signs of acute inflammation are Redness (rubor) which is due to dilation of small blood vessels within damaged
tissue as it occurs in cellulitis. Heat (calor) which results from increased blood flow (hyperemia) due to regional
vascular dilation Swelling (tumor) which is due to accumulation of fluid in the extravascular space
which, in turn, is due to increased vascular permeability. Pain (dolor), which partly results from the stretching & destruction of tissues due to
inflammatory edema and in part from pus under pressure in as abscess cavity.
Some chemicals of acute inflammation, including bradykinins, prostaglandins and
serotonin are also known to induce pain. Loss of function: The inflammed area is inhibited by pain while severe swelling
may also physically immobilize the tissue. Events of acute inflammation: Acute inflammation is categorized into an early vascular and a late cellular responses. 1) The Vascular response has the following steps: a) Immediate (momentary) vasoconstriction in seconds due to neurogenic or chemical
stimuli. b) Vasodilatation of arterioles and venules resulting in increased blood flow. c) After the phase of increased blood flow there is a slowing of blood flow & stasis due
to increased vascular permeability that is most remarkably seen in the post-capillary
venules. The increased vascular permeability oozes protein-rich fluid into extravascular tissues. Due to this, the already dilated blood vessels are now packed with
red blood cells resulting in stasis. The protein-rich fluid which is now found in the
extravascular space is called exudate. The presence of the exudates clinically
appears as swelling. Chemical mediators mediate the vascular events of acute
inflammation. 2) Cellular response
The cellular response has the following stages: A. Migration, rolling, pavementing, & adhesion of leukocytes B. Transmigration of leukocytes C. Chemotaxis D. Phagocytosis Normally blood cells particularly erythrocytes in venules are confined to the central
(axial) zone and plasma assumes the peripheral zone. As a result of increased
vascular permeability , more and more neutrophils
accumulate along the endothelial surfaces (peripheral zone). A) Migration, rolling, pavementing, and adhesion of leukocytes B). Transmigration of leukocytes C). Chemotaxis: A unidirectional attraction of leukocytes from vascular channels towards the site of
inflammation within the tissue space guided by chemical gradients (including
bacteria and cellular debris) is called chemotaxis. The most important chemotactic factors for neutrophils are components of the
complement system (C5a), bacterial and mitochondrial products of arachidonic
acid metabolism such as leukotriene B4 and cytokines (IL-8). All granulocytes,
monocytes and to lesser extent lymphocytes respond to chemotactic stimuli. How do leukocytes "see" or "smell" the chemotactic agent? This is because
receptors on cell membrane of the leukocytes react with the chemoattractants
resulting in the activation of phospholipase C that ultimately leads to release of
cytocolic calcium ions and these ions trigger cell movement towards the stimulus. D) Phagocytosis 1). Recognition and attachment of the particle to be ingested by the leukocytes:
Phagocytosis is enhanced if the material to be phagocytosed is coated with certain
plasma proteins called opsonins. These opsonins promote the adhesion between the
particulate material and the phagocyte’s cell membrane. The three major opsonins
are: the Fc fragment of the immunoglobulin, components of the complement system
C3b and C3bi, and the carbohydrate-binding proteins – lectins.
Thus, IgG binds to receptors for the Fc piece of the immunoglobulin (FcR) whereas
3cb and 3bi are ligands for complement receptors CR1 and CR2 respectively. 2). Engulfment: During engulfment, extension of the cytoplasm (pseudopods) flow around
the object to be engulfed, eventually resulting in complete enclosure of the particle
within the phagosome created by the cytoplasmic membrane of the phagocytic cell.
As a result of fusion between the phagosome and lysosome, a phagolysosome is
formed and the engulfed particle is exposed to the degradative lysosomal enzymes. 3) Killing or degradation
The ultimate step in phagocytosis of bacteria is killing and degradation. There are two
forms of bacterial killing a). Oxygen-independent mechanism: This is mediate by some of the constituents of the primary and secondary
granules of polymorphonuclear leukocytes. These include:
Bactericidal permeability increasing protein (BPI)
Lysozymes
Lactoferrin
Major basic protein
Defenses It is probable that bacterial killing by lysosomal enzymes is inefficient and relatively
unimportant compared with the oxygen dependent mechanisms. The lysosomal
enzymes are, however, essential for the degradation of dead organisms within
phagosomes. b) Oxygen-dependent mechanism:
There are two types of oxygen- dependent killing mechanisms i) Non-myeloperoxidase dependent
¾ The oxygen - dependent killing of microorganisms is due to formation of reactive
oxygen species such as hydrogen peroxide (H2O2), super oxide (O2) and hydroxyl
ion (HO-) and possibly single oxygen (1O2). These species have single unpaired
electrons in their outer orbits that react with molecules in cell membrane or nucleus
to cause damages. The destructive effects of H2O2 in the body are gauged by the
action of the glutathione peroxidase and catalase. ii) Myloperoxidase–dependent
¾ The bactericidal activity of H2O2 involves the lysosomal enzyme
myeloperoxidase, which in the presence of halide ions converts H2O2 to
hypochlorous acid (HOCI). This H2O2 – halide - myecloperoxidease system is
the most efficient bactericidal system in neutrophils. A similar mechanism is also
effective against fungi, viruses, protozoa and helminths.
Like the vascular events, the cellular events (i.e. the adhesion, the transmigration,
the chemotaxis, & the phagocytosis) are initiated or activated by chemical mediators.
Next, we will focus on the sources of these mediators. Chemical mediators of inflammation Chemical mediators account for the events of inflammation. Inflammation has the following
sequence: Cell injury -Chemical mediators-Acute inflammation (i.e. the vascular & cellular events). Sources of mediators: The chemical meditors of inflammation can be derived from plasma or cells. a) Plasma-derived mediators: i) Complement activation-increases vascular permeability (C3a,C5a) ,activates chemotaxis (C5a), opsoninization (C3b,C3bi) ii) Factor XII (Hegman factor) activation
Its activation results in recruitment of four systems: the kinin, the clotting, the
fibrinolytic and the compliment systems. b) Cell-derived chemical mediatos:
Cell-derived chemical mediators include: Cellular mediators Cells of origin Functions Histamine Mast cells basophiles Vascular leakage & platelets Serotonine Platelets Vascular leakage Lysosomal enzymes Neutrophiles Bacterial & tissue destruction
macrophages Prostaglandines All leukocytes Vasodilatation, pain, fever Leukotriens All leukocytes LB4 Chemoattractant LC4, LCD4, & LE4 Broncho and vasoconstriction SYSTEMIC EFFECTS IN ACUTE
INFLAMMATION EFFECTS OF ACUTE INFLAMMATION Metabolic Changes 1) Protein metabolism Is increased – cell destruction, metabolic products lead to increased osmotic pressure in
interstitial space which attracts water and contributes to edema (swelling = tumor); Metabolic changes, including skeletal muscle catabolism, provide amino acids that can be used
in the immune response and for tissue repair; 2) Glucose metabolism - anaerobe utilization of glucose is increased because of hypoxia with
increased formation of lactic and pyruvic acid 3) Lipid metabolism - increased formation of ketones and fatty acids 4) Mineral metabolism - increased extracellular K+ concentration 5) Acid – base balance - metabolic acidosis (ketones, lactic acid) Beneficial Effects Are conferred by flow of exudates through the inflamed tissues and phagocytic and microbiocidal
effects of emigrated leucocytes 1) Dilution of toxins - exudates dilute toxins and carry them away via the lymphatics 2) Entry of antibodies - fluid exudate carries antibodies obtained through immunization and natural
proteins 3) Fibrin formation - fibrinogen in the exudates is converted to solid fibrin forming a mechanical barrier
to movement and spread of bacteria 4) Delivery of nutrients and oxygen - the exudates contain glucose, oxygen and carry away the waste
products 5) Stimulation of immune response Harmful Effects
Impairment of function due to ischaemia and obstruction especially in restricted areas e.g. brain Results from persistent release of cytokines, destruction of normal tissue, inappropriate
inflammatory response and swelling-Examples
a) Meningitis and encephalitis, the swelling causes increased intracranial pressure leading to
coma and death b) Osteomyelitis pressure on the medullary cavity leads to ischaemic necrosis
c) Ochitis ischaemia causes impotence
d) GIT angio-oedema can be encountered Course, outcome and regulation of acute
inflammation Abscess Formation (Suppuration) Outcome The abscess may: - 1. Acute phase proteins (APP) 2. Corticosteroids 3. Free cytokine receptors 4. Suppressor T cells 5. Anti-inflammatory chemical
mediators CHRONIC INFLAMMATION Definition: Chronic inflammation can be defined as a prolonged inflammatory process
(weeks or months) where an active inflammation, tissue destruction and attempts at repair
are proceeding simultaneously. Causes of chronic inflammation:
1. Persistent infections 2. Prolonged exposure to nondegradable but partially toxic substances either
endogenous lipid components which result in atherosclerosis or exogenous substances
such as silica, asbestos. 3. Progression from acute inflammation: Acute inflammation almost always progresses
to chronic inflammation following:
a. Persistent suppuration as a result of uncollapsed abscess cavities, foreign body
materials (dirt, cloth, wool, etc), sequesterum in osteomylitis, or a sinus/fistula from
chronic abscesses. 4. Autoimmuniy. Autoimmune diseases such as rheumatoid arthritis and systemic lupus
erythematosis are chronic inflammations from the outset. PATHOGENESIS OF CHRONIC INFLAMMATION Occurs in three main ways: - a) Progression from acute inflammation (persistence of acute inflammation) Follows persistence of an injuries agent or extensive destruction of tissues e.g.
osteomyelitis, lung abscess resulting from pneumonia There is: -
i) Cellular and fluid exudates formation
ii) Mobilization of macrophages (cells of demolition)
iii) Organization
iv) Formation of new blood vessels
v) Deposition of collagen and granulation tissue formation
vi) Regeneration of tissues
vii) Recruitment of Presence of such as lymphocytes, plasma cells and eosinophils Chronic Suppurative Is characterized by formation of an abscess cavity containing pus and this situation
persists
o Attempted organization occurs in the walls of abscess cavity while the exudative
suppuration is still occurring o Results from delay in evacuation of the abscess, presence of necrotic and extraneous
material or defective leucocyte function Delay in Evacuation
o The abscess cavity is avascular and structureless and this prevents: -
i) Establishment of chemotaxis gradients that allow cell movement
ii) Fast movement of polymorphs because they have a long distance to travel from the
vessels to reach the organisms
iii) Formation of a solid stratum over which polymorphs can migrate Causes of delayed evacuation
i) Inadequate drainage
ii) Multiplication of residual bacteria
iii) Foreign material - dirt, wood, clothing, surgical material, plastics, metals)
iv) Indigestible, dead or damaged tissues
v) Piece of dead bone (sequestrum) b) Recurrent episodes of acute inflammation
Results from repeated bouts of acute inflammation e.g. chronic cholecystitis (gall bladder
inflammation) c) Primary chronic inflammation (chronic inflammation starting de novo)
Arises from a process that is distinct from the onset
There is an absence of or only an insignificant phase of acute inflammation
Cellular infiltration is predominantly mononuclear (mononuclear phagocytes and
lymphocytes) with few or no polymorphs
Causes
i) Persistent infections e.g. tuberculosis, leprosy
ii) Foreign material
iii) Auto-immune diseases (think of examples)
iv) Conditions of unknown aetiology e.g. Sarcoidosis, Crohn’s disease COMPONENTS OF CHRONIC INFLAMMATION Include cells (lymphocyte, plasma cell, macrophage/mononuclear, fibroblasts, tissue destruction by
inflammatory cells, repair with fibrosis and angiogenesis (new vessel formation) CELLS 1) Monocytes phagocytes/Macrophages The macrophage is the dominant cell in chronic inflammation Component of the mononuclear phagocyte system (reticuloendothelial system) which consists
of closely related cells of bone marrow origin – blood monocytes and tissue macrophages.
Mononuclear phagocytes arise from a common precursor in the bone marrow giving rise to
blood monocytes which migrate into various tissues and differentiate into macrophages
Tissue macrophages are diffusely scattered in the connective tissue or located in organs - liver
(Kupffer cells), spleen, lymph nodes (sinus histiocytes) and lungs (alveolar macrophages
In chronic inflammation, macrophage accumulation persists due to recruitment of monocytes
(from the circulation), local proliferation of macrophages (after emigration from the bloodstream)
and immobilisation of macrophages within the site of inflammation 2) Lymphocytes Mobilized in both antibody-mediated and cell mediated immune reactions
Are dominant and local tissue cells show degeneration
There is attempted healing with regeneration and fibrosis e.g. HBV (alter liver cell membrane
which is degenerated by CMI causing liver cell death). Immune response is directed against
self-antigens e.g. Hashimotos, thyroiditis, Grave’s disease, GPS and type 2 diabetes. Antigen
stimulated (effector and memory) T and B lymphocytes migrate into inflammatory sites under
the influence of adhesion molecules and chemokines.
Cytokines (from activated macrophages) and chemokines promote recruitment of leucocytes. 3) Plasma cells
Develop from activated B lymphocytes and produce antibody directed either against persistent
antigen in the inflammatory site or against altered tissue components 4) Oesinophils
Abundant in immune reactions mediated by IgE and in parasitic infections
Recruitment involves extravasation from blood and their migration into tissue by processes
similar to other leucocytes. 5) Mast cells
Widely distributed in connective tissues and participate in both acute and persistent
inflammatory reactions.
6) Giant cells
There are three main types of giant cells seen in chronic inflammation
a) Langharn's cell - the giant cell has a peripheral ring (horseshoe) of nuclei in the cytoplasm
b) Foreign body giant cell - the nuclei are centrally placed and overlap each other
c) Touton's cells - there is a ring of nuclei separating a peripheral clear cytoplasma from an
eosinophilic central cytoplasm. 7) Acute Inflammatory Cells
Neutrophils are characteristically involved in acute inflammation, but may also be present during
chronic inflammation, if there is ongoing infection and tissue damage
Eosinophils are particularly prominent in allergic-type reactions and parasitic infestations. 8) Fibroblasts Fibroblasts serve roles in inflammation and immune cell recruitment to sites of tissue injury.
Assist in the activation and migration of resident immune cells such as macrophages
Influence the pathogenesis of fibrosis TYPES OF CHRONIC INFLAMMATION 1)Non-Specific There is non-specific inflammatory cell infiltration e.g. chronic osteomyelitis, lung abscess, and
chronic ulcer 2. Specific (Granulomatous) There is characteristic tissue response with formation of granulomas e.g. tuberculosis, leprosy,
syphilis, sarcoidosis, actinomycosis A unique chronic inflammatory reaction characterized by focal accumulation of activated
macrophages which often an epithelial-like (epithelioid) cells that accumulate in small clusters
(follicles) surrounded by lymphocytes (clusters are called granulomas). A granuloma = a circumscribed, tinny lesion about 1 mm in diameter composed of a collection of
modified macrophages (epithelioid cells) and rimmed by lymphoid cells. It is a focus of chronic
inflammation consisting of a microscopic aggregation of macrophages that are transformed into
epithelium-like cells surrounded by a collar of mononuclear cells. Granulomas have giant cells (fusion of adjacent epithelioid cells), necrosis (e.g. central caseation
necrosis of TB) and fibrosis
Granuloma formation occurs due to presence of poorly indigestible irritants e.g. Mycobacterium
tuberculosis, Mycobacterium leprae, silica, talc and effects of cell-mediated immunity to the irritants. There are two types of granulomas General (morphologic) features 1. Mononuclear cell infiltration INTRODUCTION AND DEFINITIONS
1.1. Regeneration Regenerate – to be formed or created again. Regeneration is the growth of cells and tissues to
replace lost cells by cells of the same type (epithelial cells) through proliferation of surviving cells
Different tissue cells possess varying capabilities of regeneration
Capacity of cells to regenerate can be influenced by the type & severity of damage
Cells regenerate completely restoring normal architecture e.g. the epithelial cells of the skin
Specialized cells cannot regenerate and their healing is dominated by connective tissue response
with formation of a scar (fibrosis) leading to restoration of the structure but with impaired function Involves 2 main processes - proliferation & migration of surviving cells. i) Proliferation of Cells
In adult tissues, the size of cell populations is determined by the rates of cell proliferation,
differentiation and death by apoptosis (physiologic process needed for tissue homeostasis)
Proliferation of parenchymal cells and its capacity varies with different tissues Somatic cells are of 3 types called – labile, stable and permanent cells a) Labile Cells (Continually dividing cells)
Have a substantial regeneration capacity and regenerate throughout life
Examples: Epidermis, gastrointestinal epithelia, respiratory tract, urinary tract,
endometrium, haemopoetic cells (Bone marrow), lymphoid cells. b) Stable (Quiescent) Cells
Exhibit low rate of cell proliferation but can be conditioned (response to stimuli) to
proliferate rapidly because they possess the potential but chances for regeneration are
good
Examples: - Liver, pancreas, renal tubular epithelium, thyroid, adrenal cortex, many
types of mesenchymal cells (fibroblasts, osteoblasts, osteocytes, chondrocytes),
prostate, vascular endothelial cells, smooth muscle cells (blood vessels, visceral walls),
skeletal muscles. c) Permanent Cells (Non-dividing Cells)
Do not show cell proliferation in adult life and healing occurs by the process of
organization (connective tissue replaces dead tissues that cannot be reconstituted by
proliferation)
Restoration of normal structure and function in a damaged organ depends on
replicative capabilities of the surviving cells and preservation of supporting stroma to
allow orderly replacement
Examples: - the nervous system and the cardiac muscles. Control of normal cell proliferation and tissue growth a) Physiologic conditions. e.g. proliferation of the endometrial cells under oestrogen
stimulation during the menstrual cycle and thyroid cells by TSH during pregnancy are
physiological. Excessive physiological stimulation may create pathological condition e.g.BPH from dihydrostestosterone stimulation Many pathologic conditions such as injury, cell
death and mechanical alteration of tissues also stimulate cell proliferation b) Stem cells and growth factors are essential in control of proliferation
Two types of stem cells – embryogenic stem cells and adult stem cells
Embryos - pluripotent embryogenic stems which give rise to all the tissues of the
human body
Many tissues in adults contain reservoirs adult stem cells which have a more restricted
differentiation capacity and are a lineage specific compared to embryogenic stem cells.
An example is the bone marrow stem cell and tissue stem cells (outside bone marrow). c) Growth factors
Several growth factors act on many cell types where they stimulate proliferation
Have effects on cell locomotion, contractility, differentiation and angiogenesis ii) Migration of Cells
Central process in the development and maintenance of multicellular organisms
Tissue formation during embryonic development, wound healing and immune responses all
require the arranged movement of cells in particular directions to specific locations
The ability of cells to migrate is essential for physiological functions such as
immunosurveillance, wound healing, and tissue morphogenesis WOUND HEALING 2.1. Introduction Wound healing is a natural body function by which the body repairs itself after injury through a
complex and dynamic process Surgical wounds closed by sutures require very little remodelling whereas larger wounds such as
pressure ulcers require considerable tissue reconstruction. Generally, from injury to resolution, wounds go through three phases that involve coordinated cell
activation, cell division and migration of many different cell types Duration of each phase is determined by factors including the size of the wound, the degree of
bacterial infection, the presence of debris from the injury. To balance degradative and regenerative processes the events are finely tuned control of various
biochemical, cellular, and immunological reaction cascades mediated by locally released growth
factors and cytokines 2.2. Types of Wounds Open wounds – the skin or mucous membrane is broken Closed wounds – tissues are injured but the skin is not broken Intentional – for therapy Non-intentional – from trauma Types of Wounds Type Description 1. Abrasion Scraping or rubbing away of skin. Wound caused by superficial damage
to the skin no deeper than the epidermis 2. Contusion Closed wound caused by blow to the body 3. Incision Open, clean with straight edges 4. Laceration Open, torn with jagged edges 5. Penetrating wound Open, skin is pierced 6. Puncture wound Open, made by sharp object penetrating the skin and often the underlying tissues 7. Stab wound Open wound, penetration of the skin and the underlying tissues, usually
unintentional Stages of Healing Haemorrhage Blood Clot Formation: Blood clot occurs as a result of bleeding
after severing of blood vessels.A blood clot is formed by the clotting
system. The fibrin deposited forms a provisional
mechanical stabilization of the wound and dehydration of the clot forms a
protective scab. Acute Inflammation: Acute inflammation occurs as the tissues
respond to the injury. It is a mild reaction at the wound edges
that occurs within 24 hours resulting in further deposition of fibrin and
migration of white blood cells – neutrophils polymorphs, monocytes and
lymphocytes. Gap closure (epithelial changes):Takes place after 18 – 24 hours and
involves the regeneration of the epithelium. Cells from the deeper part of the
epithelium migrate giving a continuous advancing sheet until the cell – cell
signal facilitates contact inhibition to the migration. Stem cells in the basal layer of the
epidermis proliferate to replace lost cells. Demolition:In demolition, the enzymes liberated from
disintegrated neutrophils
polymorphs remove the blood clot. By the 3rd day,
neutrophils have
been replaced by phagocytic
macrophages which digest fibrin, damaged extracellular matrix, red blood cells
and cellular debris. The macrophages produce mediators of
inflammation and repair. Granulation Tissue
Formation/Organization :The dermis and subcutaneous tissues are
replaced by granulation tissue formation. By the 3rd day,
the new capillaries that have been formed are delicate, leak protein rich
fluids and allow emigration of neutrophils. The fibroblasts proliferate and migrate
into the wound and produce extracellular matrix protein and collagen that
reaches maximum at 3 weeks. Remodelling. There is progressive increase in collage
fibrin that takes months. The process of remodelling involves
remodelling of the anatomical configuration of the collagen in response to the
mechanical stress. ii) Secondary (Second) Intention Seen in excised with extensive loss of cells and tissue with ulceration, abscess formation and infarction, dirty, infected wounds, Wounds tend to be less regular and the edges of the wound are further apart Epithelialization and contraction take much longer There is greater risk of infection during the healing process a) Clean Open Wounds: b)Infected wounds
FACTORS INFLUENCING REPAIR PROCESS i) Local Factors ii)Systemic Factors: SKIN GRAFTING 1. Inadequate formation of granulation
tissue or assembly of a scar 2. Excessive repair tissue formation 3. Contracture leading to deformity 4. Infection 5. Painful scars 6. Pigmentary changes 7. Neoplasia - rare HEALING IN SPECIAL AREAS INTERNAL SURFACES; Healing of internal surfaces for example
in the alimentary tract involves regeneration of the epithelial covering is
similar to that of skin. SOLID EPITHELIAL ORGANS; The healing of solid organs e.g. the
kidney, liver following gross tissue damage and loss of supporting tissue
occurs with progressive removal of dead tissue with organization and coarse
scar formation. This results in contraction of the organ
for example in liver cirrhosis and pyelonephritis. When the damage spares the supporting
tissues there occurs regeneration of the epithelial cells with restoration of
the normal structure MUSCLE; There are three types of muscle fibres
namely – skeletal, cardiac and visceral which all have very limited
regeneration capacity. Repair
of a damaged muscle mass is by scar formation (scarring) for example in
myocardial infarction HEALING OF FRACTURES; Definition: A fracture is a break in
continuity of a bone Causes Types of Fractures Main Shapes/Patterns Events in fracture Causation and
Healing COMPLICATIONS OF FRACTURE HEALING
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Topic Two: Principles of Diagnosis
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Topic Three: Classification of Diseases
Diseases fall into several large categories according to lesions produced by the various diseases.
There are two ways of classification: -
1. Based on morphology and pathogenesis2. International statistical classification of Diseases (ICD 10)
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Topic 1: Cell Injury- aetiology of cell injury
Cell injury
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Topic 2: Outcome of Cell Injury
¨The eventual outcome of cell injury could
be reversible cell injury ,
irreversible cell injury or adaptation changes as influenced by cell vulnerability and
dose intensity.Click here to access Unit Two Content..
Topic 2: Outcome of cell injury-Reversible cell injury
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Topic 2: Outcome of cell injury- Irreversible cell Injury
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Topic 3:Cellular adaptations
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Topic 4: Cell Death ; Autolysis and Aptoptosis
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Topic 4: Cell death: Necrosis
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Topic 1: Inflammation Introduction
This is a normal response of living tissues to injury and it prepares the tissue for healing and repair
The term inflammation originates from a Latin word “inflammare” or inflammatio” meaning to burn.
It is a dynamic process that lasts from a few minutes to a few years depending on the extent and type of
injury and the vascularity of the tissue
Can be defined as ;
The response of living tissue to injury
A defensive process that a living body initiates against local tissue damage
The body’s response to injury of vascularized tissue with a series of events, collectively called
inflammation and repair
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Topic 2: Acute Inflammation
Acute inflammation is the early (almost immediate) response of a tissue to injury
It is nonspecific and may be evoked by any injury short of one that is immediately lethal
Regarded as the first line of defence aimed primarily at removing the injurious agent
Typically, of short duration, occurring before the immune response becomes established
The escape of fluid, proteins and blood cells from the vascular system into the interstitial tissue or
body cavities is called exudation. An exudate is an inflammatory extravascular fluid with high protein
concentration, cellular debris and a specific gravity of 1.020.
Platlete activating factor All leukocytes Bronchoconstriction and WBC priming
Activated oxygen species All leukocytes Endothelial and tissue damage
Nitric oxide Macrophages Leukocyte activation
Cytokines Lymphocytes, macrophages Leukocyte activationClick here to access Unit Three Content..
Topic 2: Cont......Morphological features
Morphologic patterns of acute
inflammation
Varies depending on magnitude of fluid formed and cellular response, nature and texture of affected
organ and degree of tissue damage
1) The Skin
a) Mild inflammation - basis of the cardinal signs (all the cardinal signs of inflammation are
exhibited)
b) Severe inflammation
i) Blisters - there is increased accumulation of exudate locally (Blisters)
ii) Ulcers
Causes loss of a patch of epidermis (Acute inflammatory ulcer)
An ulcer is a local or excavation of the surface of an organ or tissue that is produced by
the sloughing (shedding) of inflammatory necrotic tissue
Common in inflammatory necrosis of the mucosa of the mouth, stomach, intestines or
genitourinary tract as well as subcutaneous inflammation of the lower extremities in
older persons with circulatory disturbances e.g. peptic ulcer (duodenal and gastric)
2)Serous Membranes
Include – the pleura, pericardium and peritoneum.
Normally the membranes are thin, shinny and transparent
Changes during inflammation
i) Increased vasodilatation and increased number of visible blood vessels in the injured tissue
causing injected appearance
ii) Loss of normal sheen due to deposition of fibrin makes the membranes dull and opaque
iii) Excessive deposition of fibrin leads to an opaque creamy layer obscuring underlying tissues
iv) Accumulation of serous exudate in the cavities (pleural effusion, pericardial effusion and ascites)
v) Seropurulent exudate (increased volume of exudate, fibrin and polymorphs)
vi) “Bread and butter” as seen on the pericardium where the fibrin coatings are kept apart by the
exudate. If the exudate is removed by lymphatics the visceral and parietal layers stick together
due to fibrin.
vii) Purulent exudate (pus) - pus is a creamy, yellow, viscid fluid occasionally blood stained. It is
seen in pyogenic bacterial infections where there is massive emigration of polymorphs.
3) Mucous Membranes
Mucous membranes are found in the respiratory tract and gastro-intestinal tract
a) Mild Inflammation – Catarrhal Inflammation
Examples: - coryza, acute enteritis, bacillary dysentery, mild infective food poisoning
Changes:
i) Reddening due to vasodilatation
ii) Swelling due to exudate accumulation causing nasal obstruction
b) Severe Inflammation leads to formation of shallow layer ulcers e.g. ulcerative colitis
c) Pseudomembranous inflammation
Can be due to diphtheria inflammation of the larynx and pharynx, ulcerative colitis and
infection of the bowel by Staph. aureaus.
There is extensive confluent necrosis of the surface epithelium with severe acute
inflammation of the underlying tissue. Fibrin in the exudate coagulates with the necrotic
epithelia trapping in polymorphs, RBCs, bacteria and dead debris giving a false membrane,
which appears as a white, or cream coloured layer over the inflammed mucosa.
The false membrane can be removed by enzymatic action of polymorph-derived enzymes
and heals by formation of a scar
4) Solid Organs
Includes the liver, kidney and the spleen. In the solid organs, it is difficult to detect vasodilatation
as they contain a lot of blood and have a compact structure. The texture and capsule of solid
organs limits oedema formation due to increased pressure. There is necrosis that leads to pus
formation
5) Lungs
Lungs are a collection of interconnecting air-filled spaces and easily allow accumulation of
exudate without much increase in pressure. For example, in lobar pneumonia spreading
inflammatory oedema is limited by visceral pleura
Fluid is reabsorbed by lymphatics leaving a pale solid dry area with a granular surface.
Histology shows alveoli filled with fibrin and polymorphs (grey hepatisation). Hepatisation
means that the lung tissue acquires the texture as that of the liver
Microscopic Features
Features evident when the inflamed tissues are observed under a microscope
Include cellular infiltrates of neutrophils, monocytes and macrophages, fibrin deposits, fluid exudate
and destruction of cell structure. (Think of the features of cell injury/death)Click here to access Unit Three Content..
Topic 2: Outcome of Acute Inflammation
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Topic 3: Chronic Inflammation
Causes of tissue damage in chronic InflammationClick here to access Unit Three Content..
Topic 3: Outcome of Chronic Inflammation
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Topic 1: Introduction and Definations
Repair is the replacement of injured tissues by a fibrous tissue which involves proliferation and
migration of connective tissue cells leading to fibrosis and scar tissue formation
Involves formation of a granulation tissue in a process comprises of two overlapping processes of
granulation tissue formation (organization and progressive fibrosis) and wound contraction.
Repair processes are critical for maintenance of normal structure and function and survival of the
organism
Cells involved in repair include mesangial cells, endothelial cells, macrophages, platelets and
parenchymal cells of injured tissues
1.3. Healing
A natural process of cure or replacement of dead cells or repair of tissues which is the final stage of
the process of tissue response to injury
Comprises of two main processes namely regeneration and repair
Rate at which healing proceeds will vary in different tissues depending on the ability of surviving
cells to divide, the type/nature, duration & severity of the injuryClick here to access Unit Four Content..
Topic 2: Wound Healing
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Topic 2: Wound Healing Continuation
Extent of the processes in the proliferative phase to a large extent depends on whether the wound
is healing by primary or secondary intention.
i) Primary (First) Intention
Seen in incised wounds, clean surgical incisions, wounds with minimal or no tissue loss
with no bacterial contamination (infection)
Edges of the wound are brought into close proximity e.g. when a surgical wound is sutured
Re-epithelialisation is swift and takes place within a few days
Wounds should heal relatively quickly with minimal loss of function provided that no
bacteria entered the wound during incision.
iii) Tertiary (Third) Intention Occurs in wounds that are left open for some time to form granulation tissues and then sutured closed if found to be clean It is also called delayed primary closure
Extent
of tissue damage
Intensity
and duration of the stimulus
Blood
supply
Presence
of foreign bodies
Diseases
e.g. diabetes
Drugs
e.g. treatment with steroidsFactors influencing wound healing
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Topic 3: Healing in special Areas
