Cell Pathology 51c2j

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. 

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. 

CELL DEATH  

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. 

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. 

Coagulative Necrosis It is most common type.  Causes- mostly due to sudden cessation of blood flow & less often from bacterial & chemical agents. Organs affected are heart, kidney & spleen  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 

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. 

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. 

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. 

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. 

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. 

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. 

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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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 

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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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. 

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. 

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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