CELL
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It is a structural & functional unit of body
Cellular physiology characterized by
Closed interdependence of various components &
activities.
Balancing control mechanism aimed at maintaining
constant condition.
Very efficient compensatory & repair mechanisms to
minimize the damage
CELL INJURY
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Etiology
Hypoxia & ischemia- Reduced supply of blood.
Physical agents- Mechanical trauma, thermal trauma.
Chemicals & drugs- Poisons like cyanides, arsenic,
strong acids & alkali's environmental pollutants.
Microbial agents- Fungi, bacteria & protozoa.
Immunological agents- Hypersensitivity reaction,
anaphylactic reaction.
Nutritional agents- Deficiency of nutrients, excess of
nutriets.
PATHOGENESIS
Of reversible cell injury
 If ischemia of short time effects are reversible
 Sequential changes in reversible cell injury
 Decrease cellular ATP.
 Damage to plasma membrane sodium pump.
 Reduced protein synthesis.
 Ultra structural changes1)Endolasmic reticulum-distention of cisternae.
2)Mitochondria- swelling.
3)Plasma membrane- loss of microvilli & focal projection of
cytoplasm.
4)Nucleolus- segregation of granular fibrilar components &
reduced RNA synthesis.
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PATHOGENESIS
Of irreversible injury
 Mitochondrial dysfunction
 Membrane damage1)Accelarated degradation of membrane phospholipids.
2)Cytoskeletal damage.
3)Breakdown of lipid.
4)Reperfusion damage.
 Hydrolytic enzyme-damage to lysosomal membrane followed
by liberation of hydrolytic enzyme which on activation causes
enzymatic digestion of cellular components & induce nuclear
changes & hence cell death.
 Serum estimation of liberated intracellular enzyme.
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CELL DEATH
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Autolysis
Disintegration of cell by its own hydrolytic enzyme
liberated from lysosomes. It can occur in living body
surrounded by inflammatory reaction or postmortem
change where complete absence of inflammatory
response. It is rapid in some tissues e.g. Pancreas,
gastric mucosa. Intermediate in tissues e.g. Heart,
liver & kidney. It is slow in fibrous tissue.
Morphologically it is identified by homogenous &
eosinophilic cytoplasm with loss of cellular details &
remains of cell debris.
APOPTOSIS
Programmed death of cell. In this process normal abnormal or
unwanted cells are eliminated. It is different from necrosis.
 Apoptosis in health1)metamorphosis of tadpole to frog.
2)loss of auto reactive response of T cells in thymus preventing
autoimmune attack.
3)atrophy & involution often in withdrawal of hormones.
 Apoptosis in disease1)Irradiation.
2)virus infection.
3)Action of cytotoxic T cells e.g. in rejection of transplant organ.
4)in tumour apoptosis & proliferation rate control the rata of
tumour growth.
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NECROSIS
It is focal death of cell along with degeneration of
tissue by hydrolytic enzyme liberated by cells.
 There are 5 types of Necrosis1)Coagulative necrosis
2)liquification (colliquative) necrosis.
3)Caseous necrosis.
4)Fat necrosis
5)Fibrinoid necrosis.
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Coagulative Necrosis
It is most common type.
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Causes- mostly due to sudden cessation of blood flow & less
often from bacterial & chemical agents. Organs affected are
heart, kidney & spleen
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Appearance of affected organGrossly-:
In early stage pale firm & slightly swollen with progression
becomes yellowish softer & shrunken.
MicroscopicallyCells swollen more eosinofillic conversion of normal cell to
tombstone i.e. outline retained but the nuclear details are lost.
Those results from
1)
Denaturation of proteins &
2)
2)Enzymatic digestion of cell
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Liquefaction (colliquative) Necrosis
Causes- It occurs due to ischemic & hypoxic injury & bacterial
agents as well as degradation tissue by action of hydrolytic
enzymes.
 Organs affected- infarcts of brain. Abscess cavity.
 AppearanceGrosslyAffected organ is soft with liquefied center containing necrotic
debris.
MicroscopicallyMacrophages filled with phagocytosed material cell wall formed
by proliferating capillaries inflammatory cells & gliosis in case
of brain & proliferating fibroblast in case of abscess cavity.
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Caseous Necrosis
Found in the center of foci of tubercular infection it has
combine features of both above necrosis.
 AppearanceGrosslyDry cheese & soft granular & yellowish appearance partly
attributed to histotoxic effect of lipopolyscchariedes present in
capsule of tubercle bacilli.
MicroscopicallyFoci are eosinophilic structure less & contain granular debris.
Surrounding tissue shows inflammatory reaction consisting of
epitheloid cells with interspersed giant cells of langerhans &
foreign body & peripheral mantle of lymphocytes.
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Fat Necrosis
Occurs in two types1)Accute pancreatic necrosisthere is liberation of pancreatic lipase from injured or inflamed
tissue results in necrosis.
2)Tramatic fat necrosisDamage adipose cells assume cloudy appearance when only free
fatty acids complex with Ca+ to form calcium soaps.
 Appearance –
Grossly- Yellowish white & firm deposits. Chalky white
appearance.
Microscopically- Cloudy appearance & surrounded by
inflammatory tissue. Formation of calcium soap as amorphous
granular & basophilic material.
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Fibrinoid Necrosis
Characterised by deposition of fibrinlike material
which has staining properties of fibrin. It occurs in
immunologic tissue injury.
E.g. Immune complex vasculitis.
Autoimmune diseases.
Appearance –
Microscopically –
Identified by brightly eosinophilic hyaline like
deposition in vessel wall or on luminal surface of
peptic ulcer. Local hemorrhage occur due to rupture
of these blood vessels.
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GANGRENE
It is form of necrosis of tissue with superadded putra
function. There are 3 types of gangrene:
 1)Dry gangrene
 2)Wet gangrene
 3)Gas gangrene
1)Dry gangrene-Begins in distal part of limb due to ischemia
occurs in toes & feet of old patient.
Causes -Atherosclerosis, thromboangitis obliterance, rayaund’s
disease, trauma, ergot poisoning. Line of separation present
between gangrenous & viable part.
Pathologic changes-Dry, shrunken & dark black due to liberation
of Hb from hemolysed RBCs acted by H2S produced by
bacteria result in iron sulphied. Histologically- Line of
separation consist of inflammatory tissue.
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Wet Gangrene
Occurs in moist tissues & organs such as mouth, bowel, lungs,
cervix, vulva etc. diabetic foot is an another example of wet
gangrene. It develops rapidly due to the blockage of venous &
less commonly due to arterial flow from thrombosis &
embolism. There is no line of demarcation between the
gangrenous & viable part.
Pathologic changes –
organ becomes soft, swollen, putrid, rotten, dark.
HistologicallyCoagulative necrosis with shifting of affected part is with
blood. There is ulceration of mucosa & intence inflammatory
infiltration.
Gas Gangrene
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It is the special form of gangrene caused by gas
forming clostridia which gain entry in tissues through
open contaminated wound. Clostridia produces
various toxins which produce necrosis & edema
locally & also absorb producing profound systemic
manifestation.
Pathologic changesArea is swollen edematous painful & crepitant due to
accumulation of gas bubbles within the tissues.
Affected tisse become dark, black, & foul smelling.
CELLULAR ADAPTATIONS
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For the sake of survival on exposure to stress the cells make
adjustment with the changes in their environment to the
physiologic needs & nonlethal pathologic injury.
Decreasing or increasing their size i.e. atrophy or hypertrophy.
By changing pathway of phenotypic differentiation of cells i.e.
metaplasia or dysplasia
Various mechanisms in adaptive cellular responses include –
Altered cell surface receptor binding.
Alteration in the signal for protein synthesis.
Synthesis of protein to the target cell such as heat-shock
protein.
Atrophy
Reduction of number & size of cells.
1)Physiologic atrophy-occurs due to loss of endocrine stimulation
or atherosclerosis e.g. appendix & thymus
2)pathologic atrophyCauses
a)
starvation,
b)
ischemic injury e.g. atrophy of brain
c)
Disuse atrophy- diminished function e.g. pancreatic duct
d)
Neuropathic- Interruption in nerve e.g. polio myelitis
e)
Endocrine atrophy- e.g. hypothyroidism
f)
Pressure atrophy- pressure of benign tumour
g)
Ediopathic atrophy – No specific cause e.g .myopathies,
testicular atrophy.
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Hypertrophy
Increase in size of of parenchymal cell result in
enlargement of organ or tissue without change in
number. There are 2 types of hypertrophy1)physiologic hypertrophy
e.g. hypertrophy of uterus in pregnancy.
2)Pathologic hypertrophy
e.g. Cardiac muscle in cardiovascular diseases.
Compensatory hypertrophy when the organ removed.
Pathologic changes –
Affected organ becomes heavy enlarged. Increase
synthesis DNA & RNA. Increase protein synthesis.
Increase number of organelles like mitochondria, ER,
& myofibrils.
Hyperplasia
Increase in no of parenchymal cells resulting in number of tissue.
Causes- Non-neoplastic disorders of growth. It has been divided
as
A. physiologic –
hormonal hyperplasia e.g. female breast at puberty.
Compensatory hyperplasia-regeneration of epidermis of skin
after abrasion.
B. Pathologic hyperplasiaExcessive stimulation of hormones or growth factors.
e.g. formation of warts due to papilloma virus.
Pathologic changes –
Enlargement of organ & increase in number of cells.
Increase in rate of DNA synthesis & hence mitosis increases.
Metaplasia
Reversible change of one type of epithelial or mesenchyamal cell into
another type in response to stimulus & reverts back after removal of
stimulus. Stimulus persist for long time may persist cancer.
1)Epithelial metaplasiaa) squamous metaplasia-due to chronic irritation that may be mechanical,
chemical, & infective in origin.
e.g. in uterine cervix prolapse of uterus.
In renal pelvis & urinary bladder renal in chronic infection & stone.
b) Columnar metaplasia- Interstitial metaplasia e.g. chronic gastric ulcer.
2)Mesenchymal metaplasiaa) osseous metaplasia- Formation of bone in fibrous tissue cartilage &
myxoid tissue
e.g. arterial wall in old age.
b) Cartilagenous metaplsia- in healing of fractures. It may occur where
there is unique mobility.
Dysplasia
Dissordered cellular death which accompanied with
metaplasia & hyperplasia occurs most oftenly in epithelial
cells. It occurs at cellular proliferation & cytologic change.
These changes include1)Hyperplasia of epithelial cells
2) Dissorderly arrangement of cellfrom basal to surface layer.
3) Cellular & nuclear pleomorphism.
4) Increase cellular pleomorphism.
5) Nuclear hyperchromatism
6) Increase mitotic activities.
Dysplastic changes occurs commonly in uterine cervix &
respiratory tract. Dysplasia occurs due to chronic irritation &
prolong inflammation . On removal of stimulus changes may
disappear. It may progress into carcinoma.
DEGENERATION
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4)
It is the term use to denote morphology of
irreversible cell injury.
There are following types of degeneration:
Cellular degeneration.
Hyline degeneration
Mucoid degeneration.
Fatty degeneration.
Cellular degeneration
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Causes – Bacterial toxins, burns, chemicals, high fever etc. it
results from impaired cellular volume- operative at 3 levels1)Plasma membrane
2)Sodium pump on plasma membrane
3)Supply of ATP. Grossly – organ such as kidney, liver &
heart, muscle enlarge due to swelling, cut surface bulges
outward & slightly opaque. Microscopically –
1. Cells are swollen & microvasculature compressed.
2. Small clear vacuoles are seen those represent distended
cisternae of ER.
3. Ultra structural changesa) Dialatation of ER
b) Detachment of polysoms from the surface of RER
c) Mitochondrial swelling.
Hyline Degeneration
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A.
B.
Descriptive histologic term for glassy homogenous
eosinofilic appearance of material under
hematoxyline & eosin stained section & does not
refer to any specific substance.
Intracellular hyline- mainly seen in epithelial cells
e.g. Hyline drpoplets in proximal epithelium cells in
case of exessive reabsorption of plasma protein.
Nuclear or cytoplasmic hyaline inclusions seen in
viral infection.
Extra cellular hyline- seen in connective tissue
e.g. Hyaline degeneration seen in leiomyomas of
uterus.
Hylinised old scar of fibrocollagenous tissue.
Mucoid Degeneration
Mucine is normally produced by epithelial cells of
mucus membrane & mucous glands as well as by
some connective tissues like umbilical cord.
1) Disturbances in epithelial mucin
e.g. catarrhal inflammation of mucous membrane.
Cystic fibrosis of pancreas.
2) Connective tissue mucin disturbances
e.g. Myxomatous change in dermis in myoedema.
Myxoid change in synovium of ganglion on the wrist.
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Fatty Degeneration
Intracellular accumulation of neutral fat within parechymal
cells. It occurs especially in liver but may occur in nonfatty
tissue like heart, skeletal muscles, kidneys & other.
 Fatty liver – Accumulation of fat in liver.
Etilogy –
1)Alcohol consumption
2)Starvatoin
3)Malnutrition etc.
Pathologic changesEnlarge with tense glistering capsule & rounded margines cut
surface is pale yellow to yellow &greesy to touch.
Microscopically –
Vacuoles are initially small & present around nucleus. But with
progression becomes layer pushing the nucleus to periphery.
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HEALING
It is final stage of tresponse to tissue injury. The capacity of tissue of
regeneration depends upon its proliferative ability, on the type & on the
sevearity of damage.
3 broad groups of cell are considered in the cell cycle.
1)Labile cells- Normally continues turnover
e.g. covering epithelium & bone marrow.
Changes of regeneration are excellent.
2)permanent cells- Not capable to proliferation
e.g. neuron in adult.
Healing by scaring (no regeneration).
3)Stable cells- Normally little little proliferation but remain capable of more
rapid cell division of following injury
e.g. liver, renal tubular epithelium.
Changes of regeneration are good. Regeneration involves 2 processes
a)proliferation of surviving cells to replace the lost tissue.
b)migration of surviving cells into the vacant space.
The factors which control the healing & repair are complex. They include
variety of growth factors.
e.g. epidermal growth factor in case of speciallised cell regeneration.
Transforming GFbeta incase of fibroblast. Vascular GF in case of new
capillary formation.
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THE END