cell injury by bishnu adhikari

Topics: Cell Injury by Bishnu Adhikari Gmail: [email protected]

Computerized by Bishnu Adhikari.

PATHOPHYSIOLOGY

Rudolf Virchow (1821-1902) the father of modern pathology.

Basic Principles of Cell Injury & Adaptation

Pathos means suffering

Logos means study

Thus “pathology” is derived from two Greek word pathos meaning suffering & logos meaning study.

Pathology is thus scientific study of structure & function of the body in disease. It deals with cause,

effect, mechanism & diseases.

Father of cellular pathology: Rudolf Virchow

Father of medicine: Hippocrates.

Some Termination used in pathology

Patient: patient is the person affected by the diseases.

Diseases: It is the condition of structural & functional abnormalities of the organ system called diseases.

In simple language diseases is opposite of health.

Lesions: lesions are the characteristic change in tissues & cells produced by diseases in an individual or

experimental animal.

Etiology: (why causes of diseases)

The casual factors responsible for lesions or included etiology of diseases. Why of diseases? E.g.:-

intrinsic or genetic & acquired.



Pathogenesis: (How of diseases)

The mechanism by which the lesions are produced is term as pathogenesis of diseases.

Symptoms: The functional implication of the lesions felt by the patient is known as symptoms.

Diagnosis: To know what is wrong by morphological & functional changes together with results of other

investigation.

CELL INJURY

Cell injury is defined as variety of a stresses a cell encounter as a result of changes in its internal and

external environment.

If an injury exceeds the adaptive level of the cell, then only its effect can be seen. This condition is called

cell injury.

Etiology of cell injury :

The causes of cell injury, reversible or irreversible, may be broadly classified in to two main groups.

1) Genetic causes 2) Acquired causes

Genetic causes:

a) Development defects ( errors in morphogenesis)(teratogenesis).

Eg: Thalidomide

b) Cytogenetic (karyotypic) abnormalities

c) Single gene defects

d) Storage diseases

2) Acquired:

These causes are gained during life time. It comprises of vast majority of common diseases afflicting

mankind. The acquired causes of cell injury on the basis of underlying agent are categorized as:

a) Hypoxia and ischemia

b) Physical agent

c) Chemical agent and drugs

d) Microbial agents



e) Immunological agent

f) Nutritional derangement

g) Psychological factors

a) Hypoxia and ischemia:

Reduced supply of oxygen to the cell (i.e. hypoxia) causes difficulty of cell to perform the metabolic

function and the cell cannot generate energy.

So hypoxia is major causes of cell injury, the causes of hypoxia are,

Ischemia (reduced supply of blood to cells) is a major cause of hypoxia.

Other causes like anemia, carbon monoxide poisoning, cardio respiratory insuffiency, increased

demand of tissue, defects in alveolar space of lungs e.t.c.

b) Physical agents: They include:

mechanical trauma (road accidents)

Thermal trauma (by heat and cold)

Radiation (ultra violet and ionizing (α, β, γ)

Rapid change in atmospheric pressure.

c) Chemical agents and drugs:

Chemical poison such as cyanide, arsenic, mercury.

Strong acids and alkali

Environmental pollutant.

Insecticide & pesticides

Oxygen at high concentration.

Hypertonic glucose and salt.

Social agents such as alcohol, narcotics drugs.

Therapeutic administration of drugs.

Endogenous toxins: uremia, jaundice, diabetes, ketosis.

d) Microbial agents:

Infection caused by, Bacteria, viruses, fungi, protozoa, metazoan and other parasites.

e) Immunological agents: They act like a double edge ‘sword’. Sometimes protects the hosts against

various infectious agents but sometime may also turn lethal and causes cell injury. E.g. Hypersensitivity

reaction, Anaphylactic reaction, Autoimmune diseases



f) Nutritional derangement:

Due to deficiency or an access of nutrients

Starvation

(Marasmus, kashwashiwork) deficiency

Anemia

Obesity

Atherosclerosis

Heart diseases

Hypertension

g) Psychological factors:

Common acquired mental diseases like

Mental stress

Mental strain

Anxiety (a feeling of worry, uneasiness)

Over work & frustration. (E.g. depression, schizophrenia)

In this condition there are no specific biochemical or morphological changes.

Drug addiction like alcoholism & smoking causes various organic diseases like

Liver damage

Chronic bronchitis

Lung cancer

Peptic ulcer

Hypertension

Ischemic heart diseases e.t.c

Pathogenesis of Cell Injury

The etiologic factors produce different underlying alteration in biochemical system of cell for reversible

& irreversible cell injury.

It is when environmental changes exceed the capacity of the cell to maintain normal homeostasis.

But in general, the following principles apply in pathogenesis of the most forms of cell injury by various

agents.



1) Type durations & severity of injurious agent.

2) Type status & adaptability of target cells.

3) Underlying intracellular phenomena

1) Type duration and severity of injurious agent:

E.g.:- small dose of chemical or short duration of ischaemia cause reversible cell injury.

While large dose of the some chemical agents, persistent ischemia causes cell death.

2) Type, status & adaptability of target cell:-

The status of cell based on its nutritional & metabolic condition & adaptation of the cell to hostile

environment affects the susceptibility of the cell to injury.

Type of cell influence the with stand capacity in the following way.

e.g. skeletal muscle can with stand hypoxic injury for long time, while cardiac muscle suffers irreversible

cell injury after 30- 60 minutes of persistent ischemia.

3) Underlying intracellular phenomena :-

Irrespective of other factors, two essential biochemical phenomena underlie all forms of cell injury to

distinguish between reversible & irreversible cell injury.

a) Inability to reverse mitochondrial dysfunction by reperfusion or reoxygenation.

b) Disturbance in cell membrane functions in general & in plasma membrane in particular.

Pathogenesis of ischaemia and hypoxia injury:-

Ischemia & hypoxia are common causes of cell injury. The underlying intracellular process &

mechanism involved in reversible & irreversible cell injury by hypoxia and ischemia are as follows,

Types of cell injury :-

1) Reversible cell injury

2) Irreversible cell injury



1) Reversible Cell Injury:-

If the ischaemia or hypoxia is of short duration, the effects are reversible on rapid restoration of

circulation.

E.g. coronary artery occlusion, myocardial contractility, metabolism and ultra structure is quickly

reversed if the circulation is quickly restored.

The sequential changes in reversible cell injury are as under,

1) Decreased ATP synthesis in cell :-

ATP’s which are essentially required for a variety of cellular functions such as,

a) Membrane transport

b) Protein synthesis

c) Lipid synthesis

d) Phospholipids metabolism

A. Fig: Normal Cell



ATP in human cell derived from two sources:-

a) Aerobic respiration (in presence of o2), or (oxidative phosphorylation).

b) Anaerobic respiration (glycoltic pathway)

In ischemia & hypoxia both there is less supply of o2. So aerobic respiration is decreased & thus ATP

decreases.

Ischemia is more severe than hypoxia because here in ischemia along with reduction in o2 supply blood

supply is also reduced. So ATP synthesis is further decreased.

Thus cell injury is more severe than cell injury in hypoxia.

Highly specialized cells like myocardium, proximal tubular cells of the kidney & neurons of the CNS are

dependent only on aerobic respiration for ATP generation & thus those tissues suffer from ill effects of

ischaemia more rapidly and severely.

Fig:-REVERSIBLE CELL INJURY

2) Reduced intracellular PH:- Due to low oxygen supply to cell aerobic respiration by mitochondria

fails first. This is followed by switch on the glycolytic pathway for energy requirement for this result the

rapid depletion of glycogen & accommodation of lactic acid, lower in the intracellular PH. After reduced

intracellular PH (intracellular acidosis) resulting in clumping of nuclear chromatin.

3) Damage to plasma membrane sodium pump:- In plasma membrane ATP dependent on sodium

pump,(i.e. Na+, k+ ATPase) operates. This allows the transport of Na+ out of the cell & diffuse k+ inside

the cell when sufficient amount of ATP is present.



Lowered ATP in the cell causes consequent increases in ATPase activity which interfere the membrane

regulated process. This result in intracellular accumulation of sodium & diffusion of potassium out of

cell. Sodium accumulation inside the cell leads to increase in intracellular water to maintain iso-osmotic

condition (hydropic swelling).

4) Reduced protein synthesis :- Due to hypoxia (prolonged) the ribosome gets detached from granular

endoplasmic reticulum & polysomes are degraded to monosomes, thus protein synthesis is reduced.

5) Functional consequences:- Due to all above causes it may result in the functional disturbance. E.g.

Myocardial contractility ceases within 60 seconds of occlusion but can be reversed if circulation is

restored.

6) Ultra structural changes:- The following ultra structural changes can be seen in reversible cell

injury.

a) Endoplasmic reticulum: - Distension of cisternae by fluid and detachment of membrane bound poly

ribosome from the surface of RER.

b) Mitochondria: - Mitochondrial swelling & phospholipids rich amorphous densities.

c) Plasma membrane: - loss of microvillus & focal projection of cytoplasm (blebs).

d)Myelin figures:- They appear in cytoplasm’s or outside the cell. They are derived from membrane

(plasma or organelles) enclosing water dissociated lipoproteins between the lamellae of injured

membranes.

e) Nucleolus: - there is segregation granular & fibrillar components of nucleus & reduced synthesis of

ribosomal RNA, up to this point, withdrawal of acute stress that resulted in reversible cell injury can

restore the cell to normal state.

Irreversible Cell Injury :-



FIG:- IRREVERSIBLE CELL INJURY

When ischemia or hypoxia is persistent then cell may be irreversibly injured leading it to the death. This

injury is the continuation of sequence events of reversibly injured cell. Two essential phenomena always

distinguish irreversible cell injury from reversible cell injury.

a) Inability of the cell to reverse mitochondrial dysfunction by reperfusion or re-oxygenation.

b) Disturbance in cell membrane functions in general & plasma membrane in particular.

In addition, there is continued depletion of protein, leakage of lysosomal enzymes in to cytoplasm,

reduced intracellular PH & further reduction in ATP.

1) Mitochondrial dysfunction:-

Due to continued hypoxia, a large cytosolic influx of ca++ ion occurs, especially after reperfusion of

irreversibly injured cell, which is taken up by mitochondria & is morphologically the mitochondria gets

vacuoles deposits of amorphous calcium salts in the mitochondrial matrix takes place.

2) Membrane damage:-

Defects in membrane function in general and plasma membrane in particular, is the most important event

in irreversible cell injury in ischemia. The mechanism involved is:-



a) Accelerated degradation of membrane phospholipids:-

Oxygen deprivation shifts calcium from mitochondria & endoplasmic reticulum in to the cytosol.

Increased level of cytosol activates endogenous phospholipases from ischemia tissue which degrade

membrane phospholipids which are the main constituents of the lipid bilayer membrane. An alternative

hypothesis is decreased replacement synthesis of membrane phospholipids due to reduced ATP.

b) Cytoskeleton damage:- cytoskeleton filaments (intermediate) in cell membrane are damaged due to

degradation by activated intracellular protease or physical effect of cell swelling producing irreversible

cell membrane injury.

c) Toxic oxygen radicals :-

Reactive oxygen derived species- superoxide(o2-), hydrogen peroxide (H2O2) & hydroxyl radicals (OHˉ)

are increased in ischaemia during reperfusion by incoming polymorphs.

Free radical injury is also operative in radiation injury, chemical injury, microbial, killing, aging,

atherosclerosis, carcinogenesis.

d) Breakdown products of lipid:-

lipid break down products & catabolic products which accumulates in the injured cell causes further

damage to various cell membrane.

e) Reperfusion damage:-

normal calcium ion concentrated is 10-3min, extracellular fluid & 10-7 in cytosol ( m for millimole).

Upon reperfusion of irreversibility injured cell calcium homeostasis is disturbed & there is large cytosolic

influx of calcium ions. Increased cytosolic calcium concentration may activate membrane phospholipases

leading phospholipid degradation.

3) Hydrolytic enzymes:-

Damage to lysosomal membrane is followed by liberation of hydrolytic enzymes (RNAase, DNAase,

Proteases, glycosidases,phosphateses & cathepsin), which on activation cause enzymatic digestion of

cellular components and induce the nuclear changes (pyknosis, karyolysis, & karyorrhexis) & hence cell

death.

Masses of phospholipids called myelin figures replace dead cell. These myelin figures are phagocytosed

by macrophages or there may be calcium soaps formulation.



4) Serum estimation of liberated intracellular enzymes:-

The liberated enzymes leaks across the abnormally permeable cell membrane in to the serum, the

estimation of which may be used as clinical parameters for cell death.

e.g In myocardial infraction, estimation of elevated serum glutamic oxaloacetic transaminases (SGOT),

lactic dehydrogenase (LDH), isoenzymes of creatine kinase & cardiactroponins are useful guides for

death of heart muscle.

Free Radical –Mediated Cell Injury

For life oxygen is both a blessing & curse without its life is impossible, but its metabolism can produce

partially reduced oxygen species ( reactive oxygen intermediates) that reacts with virtually any molecule

they reach.

Free radical- mediated cell injury plays an important role in the following situations:

In ischemia reperfusion injury, by incoming inflammatory cells (WBC’s), by adhesion and

activation of neutrophils.

In chemical toxicity.

Hyperoxia (toxicity due to oxygen therapy)

cellular aging

killing of exogenous biologic agent.

inflammatory damage

Destruction of tumor cells.

Chemical carcinogenesis

Atherosclerosis

Generation Of Oxygen Free radicals

Generation of oxygen free radicals begin within mitochondrial inner membrane, when cytochrome

oxidases catalyses the four electron reduction of oxygen (o2) to water(H2O). Intermediate between

reaction of H20 to O2 three partially reduced species of oxygen are generated depending upon the

number of electrons transferred.

These are

Superoxide oxygen (O2) : one electron

Hydrogen peroxide (H2O2) : Two electron

Hydroxyl radical ( OHˉ) : Three electron

A few other oxygen radicals may be generated in reaction other than those during O2 to H2O are,

Hypochlorous acid (HOCL)

Peroxynitrate ion (ONOO)



Nitric oxide (No)

Free radical generation (synthesis):- The three partially reduced oxygen intermediate species formed

during conversion of O2 to H2O are derived from enzymatic reaction as under:-

1) Superoxide (O2) :- superoxide anion(O2) may be generated by direct auto-oxidation of O2 during

mitochondrial electron transport reaction. Also enzymatic action of xanthine oxidase & cytochrome P450

overt O2 in mitochondrial or cytosol produces it. O2 so formed is catabolised to produce H2O2 by

superoxide dismutase (SOD).

2) Hydrogen peroxide (H2O2):

The H2O2 is reduced to water enzymatically by catalase ( in the peroxime) & glutathione peroxide

(GSH) (both in the cytosol & mitochondria).

3) Hydroxy radicals (OHˉ):-

OHˉ radicals is formed by 2 ways in biological process:-

a) By radidolysis of water (Dissociation of water by nuclear radiation)

b) By reaction of H2O2 with ferrous (Fe++) ions (Fenton reaction).

FREE RADICAL REACTIONS:-

FIG:- Mechanism of generation of free radicals by free radicals (SOD =

Superoxide Dismutase ; GSH = Glutathione peroxide



a) Lipid peroxidation:-

poly unsaturated fatty acids (PUFA) of the membrane (phospholipids) are attack repeatedly & severily by

oxygen derived free radicals (O2, H2O2, OHˉ) & abstracts the hydrogen atom to yield highly destructive

PUFA radicals & lipid hydroxyperoxy radicals & lipid hypoperoxide. This reaction is termed as lipid

peroxidation.

The lipid radicals (hydroxyperoxy radicals) now reacts with molecular oxygen (O2) & forms a lipid

peroxide radical.

The peroxide radicals can in turn function as a initiator to remove another hydrogen atom from a second

unsaturated fatty acid. A lipid peroxide attacks another lipid radicals resulting a chain reaction of lipid

breaking finally collapse the membrane. The decomposition of lipid peroxidases is possible by transition

metal such as iron.

b)Oxidation of proteins:-

The OHˉ radicals may also attack the proteins the sulphur containing amino acids

(cistine,methinone,arginine,histidine,protine).

There OHˉ groups attack the sulphur (s) & abstract it. Due to this oxidative reaction the progein

undergoes fragmentation, cross linking of liable amino acids. Finally it leads to aggregation, degradation

of cytosolic neutral protease and eventually the cell destruction.

C) DNA damage:-

The nitrogen(N) present is the base of the DNA is an important target for hydroxyl radical. It causes the

breaking in the single strands of the nuclear & mitochondrial DNA.

A variety of structural alteration occurs which includes DNA stand breaking, modified base cross-linking

between strands, it may also cause malignant transformation.

d) Cytoskeletal damage:-

ROS are also known to interact with cytoskeleton elements & interfere in mitochondria aerobic

phosphorylation & thus cause ATP depletion.



Fig:- Mechanism Of Generation of Free Radicals.

(SOD = superoxide dismutase; GSH ; glutathione peroxidase)

MORPHOLOGY OF IRREVERSIBLE CELL INJURY

(Cell death or cell sucide)

Cell death is state of irreversible injury. It may occur in the living body as local or focal changes.

TYPES OF CELL DEATH

1) Autolysis

2) Necrosis

3) Aptosis

4) Gangrene

1) Autolysis:-

Autolysis is disintegration of the cell by its own hydrolytic enzymes liberated from lysosomes. Autolysis

is rapid in some tissues rich in hydrolytic enzymes such as in the pancreases, GIT mucosa, intermediate

in tissue like heart, liver, & low in fibrous tissue.

Autolysis can occur in the living body when it is surrounded by inflammatory reaction.

2) Necrosis:-

It is defined as focal death along with degradation of tissue hydrolytic enzyme liberated by cell. It can be

caused by various agent such as hypoxia, chemical (ROS) physical (ROS) & microbial & immunological

injury. Changes in necrosis cell digestion by lytic enzyme & denaturation protein.



TYPESS OF NECROSIS:- (C3F2)

a) Coagulative necrosis

b) Liquefaction (colliquaqtive) necrosis

c) Caseous necrosis

d) Fat necrosis

e) fibrinoid necrosis

a) Coagulative Necrosis:-

This is the most common types by irreversible cell injury mostly from sudden cessation of blood flow

(ischemia) and less often from bacterial & ischemia agents. The organs commonly affected are the heart,

kidney, and spleen, (pale from slightly swollen lead to yellow soft shrinkage)

b) Colliquative Necrosis:-

This type occurs due to ischemic injury & bacterial or fungal infections. It occurs due to degradation of

tissue by the action of powerful hydrolytic enzymes. E.g. Brain & abscess activity. Grossly the affected

area is soft’s with liquefied center containing necrotic debris & later a crystal wall is formed.

c) Caseous Necrosis:- caseous necrosis is found in centers of foci of tuberculosis infection. It’s is

combines features of both coagulative and liquifactive necrosis.

d) Fat Necrosis :-

Fat necrosis is a special form of cell death occurring at two anatomically different locations but

morphologically similar lesions.

E.g. acute pancreatic necrosis & in breasts.

In the case of pancreas, there is liberation of pancreatic lipases from injured or inflamed tissue that results

fat depots throughout the peritoneal cavity & sometimes, even affecting the extra abdominal adipose

tissue. Fat necrosis in either of the two instance results in hydrolysis of neutral fat present in adipose cells

in to glycerol & free fatty acids.

The damaged adipose cells assume cloudy appearance when only free fatty acids remain behind, after

glycerol leaks out.

e) Fibrinoid Necrosis:-

Fibrinoid necrosis or fibrinoid degeneration is characterized by deposition of fibrin like material which

has the staining properties of fibrin. It is encountered in various examples of immunological tissue injury.

e.g. in many complex vasculities autoimmune diseases e.t.c.



*APOPTOSIS :- (degeneration mechanism)

Apoptosis is a form of “coordinated & internally programmed cell death”. Which is triggered by a variety

of extracellular & intracellular signals.

Apotosis is part of the balance between life and death of the cells and determines that a cell dies when it

is no longer useful or when it may be harmful to the organism. It is also a self defence mechanism.

(Apoptosis is a greek word meaning “falling off “ or “dropping off”. The term was first coined in 1972 as

distinct from necrosis.

*GANGRENE:-

Gangrene is a greek word. This name was came from the American football team in 1791. In that team

one player is suffer from the gangrene diseases.

Gang means group

Grene means green (so this diseases is look like as a green.)

Gangrene is a form of necrosis of a tissue superadded puterification due to bacteria and viral infection.

Here superadded means increasing. Puterification means degranulation of protein.

ETIOLOGY OF GANGRENE:-

The bacteria caused gangrene is costeridium perfingus.

Gangrene is caused by a viral attack, bacteria.

It is a maximum caused by Diabeties patient.

Due to the ischaemia condition also.

Due to some chemical also.

TYPES OF GANGRENE:-

1) Dry gangrene

2) Wet gangrene

3) Gas gangrene

1) DRY GANGRENE:-

It is in the external part of the body, where it is less supply of blood.

e.g. in toes, leg e.t.c



2) WET GANGRENE:-

It is in the internal part of the body where bacteria growth easily. Fig: wet gangrene

e.g. in mouth

3) GAS GANGRENE:-

It caused in the muscle of the body due to the increase of bacteria and release of gas.

5.9% of hydrogen, 3.4% of carbon dioxide, 74.5% of nitrogen, 16.2% of oxygen.

Very bad smell comes from the gas gangrene due to the more nitrogen present.

CELLULAR ADAPTATION

Cellular Adaptation:-

For the sake of survival on expose to stress, the cells make adjustment with the changes in this

environment (i.e. adapt) to the physiologic needs (physiologic adaptation) & to non lethal pathologic

injury (pathologic adaptation). The common forms of cellular adaptive process are:-

1) Atrophy 2) Hyper atrophy 3) Hyperplasia 4) Metaplasia 5) Dysplasia

1) Atrophy :- Reduction of the number and size of parenchymal cells of an organ or it’s parts which was

once normal is called atrophy.

Here, aplasia means extreme failuire of development.

Causes:- Atrophy may occur from physiologic or pathologic causes.

A. Physiologic atrophy:- Atrophy is a normal process of aging in some tissues which could be due to

loss of endocrine stimulation or arteriosclerosis.

e.g. Atrophy of breast after menopause, Atrophy of brain.

B. Pathologic Atrophy:- The causes are as under:-

a) Starvation atrophy:- In starvation, there is first depletion of carbohydrates & fat stores followed by

protein catabolism.

e.g. weakness, anaemia



b) Ischaemic atrophy:- Gradual diminution of blood supply due to atherosclerosis may result in shrinkage

of affected organ.

e.g. Atrophy of brain in cerebral atherosclerosis.

c) Disuse atrophy :- prolonged diminished functional activity is associated with disuse atrophy of the

organ.

e.g. wasting of muscle of limb immoblised in cast.

d) Neuropathic atrophy:- interruption in nerve supply leads to wasting of muscles.

e.g. poliomyelitis, nerve section, motor neuron ddiseases.

2) Hypertrophy :- It is an increase in size of parenchymal cells resulting in enlargement of the organ or

tissue, without any change in the number of cells.

CAUSES:- It may be physiologic and pathologic. In both case, it is caused either by increased functional

demand or by hormonal situation. [ in non dividing cells too, only hypertrophy occurs.

A) physiologic hypertrophy:- Enlarged size of thr ulcers in pregnancy is an excellent example of

physiologic hypertrophy as well as hyperplasia. Greater muscle size and strength following repeated

exercise.

B) Pathologic hypertrophy:- Example of certain diseases associated with hypertrophy are as under.

1) Hypertrophy of cardiac muscle may occurring number of cardiovascular diseases. A few examples

producing left ventricular hypertrophy are:-

a) systemic hypertension

b) Aortic valve diseases

c) Mitral insuffiency

2) Hypertrophy of smooth muscle:- Examples :

a) cardiac achalasia ( in oesophagus)

b) Pyloric stenosis ( in stomach)

c) Muscular arteries ( in hypertension)

3) Hypertrophy of skeletal muscle:-

e.g. Hypertrophied muscles in athelets and manual labourers.



3) Hyperplasia:- it is an increase in the number of parenchymal cells resulting in enlargement of the

organ or tissue. Quite of an, both hyperplasia and hypertrophy occur together. It occurs due to increased

recruitment of cells from G. (resting) phase of the cycle to undergo mitosis, when stimulated.

e.g. Increased estrogen level at puberty and during the early stage of menstrual cycle leads to an

increased number of both endometrial and uterine stromal cells.

Causes:- As with other non- neoplastic disorders of growth, hyperplasia as also being divided in to

physiologic and pathologic.

A) physiologic hyperplasia :- The two most common types are as follows:

a) Hormonal hyperplasia :- I.e hyperplasia occurring under the influence of hormonal stimulation. E.g.

hyperplasia of female breast at puberty during pregnancy and lactation.

b) hyperplasia of pregnant uterus .

c) Prostatic hyperplasia in old age.

B) compensatory hyperplasia :- I.e. Hyperplasia occurring following removal of part of an organ , or a

contralateral organ in paired organ.

e.g. a) Regeneration of the liver following partial hepatectomy.

b) Regeneration of epiderm is after skin abrasion.

B) Pathologic Hyperplasia :- Most example of pathologic hyperplasia are due to excessive stimulation

of hormons or growth factor.

e.g. a) endometrial hyperplasia following estrogen excess.

b) In wound healing, there is a formation of granulation tissue due to proliferation of fibroblast and

endometrial cells.

c) pseudocarcinimateous hyperplasia of the skin.

4) Metaplasia:-

Meta means transformation

Plasia means growth

It is defined as a reversible change of one type of epithelial or mesenchymal cells, usually in response to

abnormal stimuli, & often reverts back to normal on removal of stimulus. Metaplasia is broadly divided

in to 2 types:-



A) Epithelial metaplasia:- This is the more common type. The metaplasia change may be patchy or

diffuse and usually results in replacement by stronger but less well specialized epithelial. How ever, the

metaplastic epithelial being less well specialized such as squamous type, results in deprivation of

protective mucus secretion and hence more prone to infection

1) Squamous metaplasia :- various type of epithelial are capable of undergoing squamous metaplastic

changes due to chronic irritation that may be mechanical, chemical or infective in origin. E.g. In

bronchous (normally) lined by pseudo stratified columnar ciliated epithelial in chronic smokers.

2) columnar metaplasia :- There are some condition in which there is transformamtion to columnar

epithelium. E.g.

a) Intestinal metaplasia in healed chronic gastric ulcer.

b) Conversion of pseudostartified columnar epithelium in chronic bronchitis & bronchiectasis to

columnar type.

B) Mesenchymal metaplasia:- Less often, there is a conformation of one adult type of mesencdhymal

tissue to another. E.g.

a) Osseous metaplasia:- osseous metaplasia is a formation of bone in fibrous tissue, cartilage and myxoid

tussue. E.g.

In arterial wall in old age

In soft tissue in myositis ossificans.

In cartilage of larynx and bronchi in a elderly people.

2) Cartilaginous metaplasia:- In healing of fracture cartilaginous metaplasia may occur where there is un

due mobility.

5) Dysplasia:- ( disordered of growth)

The cells that compose an epithelium normally exihibit uniformity of size, shape and nucleus or

organized.

More over they are arranged in a regular fashion. Dysplasia mean disordered cellular development,

variation in the size & shape of the cell enlarged.

Disorderly arrangement of the cell within the epithelium, increase nucleo-cytoplasmic ratio (1:4),

increased mitotic activity.

Dysplasia occurs most often in an epithelial cell. It occurs due to chronic irritation or prolonged

inflammation. Some time dysplasia progresses in to carcinoma (cancer). The two most common

examples of dysplastic changes are the uterine cervix and respiratory tract.

cell injury by bishnu adhikari

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