cell injury part 3.pdf

Cell Injury Part 3 Types of Cell injury (cont) Dr Prathibha Prasad Assistant Professor College of Dentistry Ajman University  programmed &" - Cell & - Apoptosis, A form of ‘coordina...

Cell Injury Part 3 Types of Cell injury (cont) Dr Prathibha Prasad Assistant Professor College of Dentistry Ajman University  programmed &" - Cell & - Apoptosis, A form of ‘coordinated = - and internally programmed - - & cell death’ having significance in a variety of& - & physiologic and T - - pathologic conditions and is not accompanied by any - --- & inflammation. & Greek- meaning ‘falling off ’ or ‘dropping off ’ Morphology Of Apoptosis pab by phayosites > - - - Morphology of Necrosis  & - - & - - S & & -  Dan Apoptotic cells in oral epithelial dysplasia  Apoptosis in& physiologic situations Apoptosis in & pathological conditions -e During embryogenesis, organogenesis, - Cell death produced by a variety & - of injurious stimuli & metamorphosis e.g. - radiation, hypoxia and -mild thermal injury. Cell death in tumours exposed to = - - chemotherapeutic agents Shedding of the - - - endometrium during & Cell injury in certain viral diseases - breast post-weaning. e.g. Destruction of lymphocytes in& menstruation, Regression of - AIDS & Normal cell destruction followed by& - - - & - atrophy in parenchymal organs after - replacement Pathologic - - - duct obstructions, - such as in & proliferation - intestinal epithelium. such as occurs in- -- pancreas and parotid. Aging In degenerative diseases of& - > CNS e.g. in - - Alzheimer’s disease; & -- e Heart diseases e.g. heart failure, acute myocardial infarction (20% - - necrosis and 80%& & apoptosis). necrosis ↳ appotosis  ask the Dir Mechanism of Apoptosis:- & Tomarrow Initiators of apoptosis: Triggers for & & - signaling -intracellularly or extracellularly. = - - -2n 19 i) Withdrawal of signals required for normal cell survival (e.g. absence of certain - & & - hormones, growth factors, cytokines). - - - & ii) Intracellular stimuli e.g.000 heat, radiation, hypoxia etc. - iii) Extracellular signals triggering of programmed cell death (e.g. activation of - - - - O FAS receptor belonging to- TNF-R family). & -- ⑧ FAS receptor  genes o ↑collSouth - based on what surviving - factor Besides& BCL-2, the 5t well activate - apoptotic pathway - is partly also 8 E governed by p53 molecule. --- Cell death: proteolytic actions on nucleus, chromatin clumping, cytoskeletal damage, disruption of - endoplasmic reticulum, mitochondrial damage, and disturbed cell membrane. - -  then so outof the Insid ofcellMompana urfal Phagocytosis. membrane changes - Phosphatidylserine & - 11 - and thrombospondin - molecules which - - - & are normally present on the& inside of the cell membrane, appear on the& outer surface of the - - & - & & cells in& L - - - - -- apoptosis, which facilitate their identification by adjacent phagocytes and promotes phagocytosis. - - & - - - & - Lamege - - & -- - not released - - - - - - - - - - & - & &59.., 8 E & & & - & & & - - - - - E & & - - - Pathologic calcification: - & Deposition of- - calcium salts in tissues other than & - & is osteoid or enamel -- - called pathologic or heterotopic calcification. Two distinct types of - - & & pathologic calcification are recognised: - D - D 1) - - L e Dystrophic calcification, which is characterised by deposition of - calcium salts in dead or degenerated tissues with normal calcium metabolism and normal serum calcium levels. - -- -normal Tissue 2) Metastatic -calcification, on the other hand, occurs in apparently - - - => normal tissues and is associated with deranged calcium metabolism - T - - - and hypercalcaemia.  DYSTROPHIC CALCIFICATION: Calcification in dead tissue: 1.- Caseous necrosis in tuberculosis is the most common site for - = - dystrophic calcification. 2.- Liquefaction necrosis in chronic abscesses may get calcified. - 3. Infarcts may sometimes undergo- = dystrophic calcification. - 4. In foci of enzymatic necrosis of fat. -- - Eg., Damaged heart valves, Atherosclerotic plaques cholistral ↳ ↑ level  Dystrophic Calcification Pathologic calcification Also occurs in aging -- & Rarely seen in head and neck area & o e.g. mucosal calcified nodule - & - pulp stones ---  Dystrophic Calcification Dystrophic calcification in wall Dystrophic calcification in of blood vessel and stomach a tumor devi MORPHOLOGY: Micro: Deeply basophilic on H&E stain; glassy, amorphous appearance; may be either crystalline or noncrystalline  Normal Tissue > Metastatic Calcification - ↳ Hyper Calcimia May occur - in normal, viable tissues in the setting of cakume - > hypercalcemia due to, - - (1)Increased secretion of - = parathyroid hormone (PTH) - T (2)Destruction of bone tissue - (3)Vitamin D-‐related disorders - (4)renal failure - Metastatic calcification may occur widely throughout the body but & principally % - - - >5 - affects the interstitial - = tissues of the gastric - mucosa, kidneys, lungs, systemic arteries, and - pulmonary veins. - Although quite - different in location, all- & of these tissues lose acid and therefore - have an internal & -- alkaline compartment that predisposes them to metastatic - - calcification. - - -INTRACELLULAR ACCUMULATION Accumulation of normal cellular constituents due to --- the inadequate rate of metabolism - Taking many A normal & endogenous z Accumulation dung > - In substance is produced at a of fats liver - - - normal or - &- - - increased rate, but - the rate of metabolism is & & - - - ↳ inadequate to remove it. - ↑ of remove the & - gol blad er Example: fatty change in the > & liver because of intracellular - accumulation of - triglycerides. & &  Intracellular Accumulation of & - Lipids - & to related -em Steatosis -f (fatty change) liver Cells i - – Accumulation of lipids withinT - - hepatocytes. – Causes include & - ethanol, &drugs and & toxins. – Accumulation can occur at any & - step in the epathway – from - entrance of & fatty acids into cell to packaging and transport of - - - - triglycerides out of cell. - - Cholesterol - accumulations, usually seen in -- –- Atherosclerotic plaque - in arteries  - Accumulation of normal cellular constituents -steatosis Liver in -e - & fatty change is enlarged with not aploty East rounded - margins. Cut surface is&pale- - - yellow to yellow and is -greasy to- Cholesterol laden macrophages (foam cells) touch - - from a focus of -- gall bladder cholesterolosis & & ↳ Cur the fats ↑ ↓ a - rondd Intracellular accumulations & due to & - deficiency & of - -- enzymes required for metabolism of these substances A group of conditions caused by - - genetic defects of - - -a specific enzymes involved in the metabolism of lipid & carbohydrates result in & and E intracellular deposition of & - these substances, largely in& lysosomes. - These are also called& lysosomal storage diseases e.g. > - cerebro site accumulatohom Glucocerebrosides 1( accumulate in- splenic macrophages > - in - Gaucher’s disease due to lack of enzyme & glucocerebrosidase. Important Intracellular Accumulations of non-‐degradable substances - The most common exogenous => > coal dust↑ - pigment is & - carbon or & & & common ↳ most source Phagocytosed & by & alveolar -macrophages and regional lymph nodes but cannot be degraded or - - - - digested & In tattoos the inoculated - pigments are also - - - phagocytosed by --- & dermal macrophages and remain there for life. - & AMYLOIDOSIS Parising microscopy extracellular deposition of proteinaceous substance called & --- amyloid H&E staining under- By O & light microscopy, amyloid appears as & --- extracellular, --- - homogeneous, structureless and eosinophilic hyaline - material; it stains positive with Congo ---- red staining and shows& apple -- green birefringence on polarising microscopy. - Amyloid is composed of= 2 main types of complex proteins: - - I. -- Fibril proteins 95% - II. Non-fibrillar - Chemically i) AL (amyloid light chain) protein & > ii) AA (amyloid associated) protein --  Amyloidosis of Spleen. May have one of the following ⑤ - & - two patterns: onlarsmoon 1.- > - SAGO SPLEEN. The splenomegaly shows characteristic - -- - translucent pale and waxy nodules resembling - - sago grains and hence the name. - - 2.-- LARDACEOUS SPLEEN. Cut surface of the spleen - shows-- map-like areas of amyloid (lardaceous-lard-like;& lard - -- means fat of pigs). Special stain - Congo Red staining and demonstration of = - apple-green birefringence under & polarizing microscopy. - - generally poor prognosis.  GLYCOGEN STORAGE DISEASES: - - defective glucose metabolism resulting in excessive intracellular accumulation of - = - glycogen in various tissues due to - specific enzyme deficiencies. asked & a - > - livers ↳ -- 1. Hepatic forms. inherited deficiency of hepatic enzymes required for synthesis of - - - glucose. S glycogen for storage (e.g. von Gierke’s disease) or for breakdown of glycogen into - alway asked - - -muscle - asked Q = - 2. Myopathic forms. Genetic deficiency of glycolysis to - form lactate in the striated - muscle resulting in accumulation of glycogen in the muscles (e.g. McArdle’s disease). - x - & T  Pigmentations Pigments are colored substances, some of which are& normal constituents of cells (e.g., melanin), whereas Others are & abnormal and collect in cells only under special circumstances. Exogenous pigments: Endogenous pigments: come from outside the body are synthesized within the body – Carbon pigment in the& - lungs itself - leading to Coal workers - – Melanin- pneumoconiosis I & – Hemosiderin- – Tattoos -  Melanin Pigment The only endogenous - brown- black pigment. - - It is produced by & - & melanocytes. It is seen in large E quantities in dark colored - skin. exesive Melanin T - The dark colored skin & lesion is a-melanoma, a malignant tumor arising from & melanocytes. & - & - - - E.g. Melanotic - macules are the most common - - oral mucosal lesions (hyperpigmentation) of melanocytic origin. Caused due to the & - functional hyperactivity of the regional - & - melanocytes. - - & i) Generalised E hyperpigmentation: sland greval a)- Addison’s disease - women Hamb b) # - Chloasma observed during pregnancy is the hyperpigmentation - -- on the skin of face and e genitalia and occurs under the influence of - - & A similar appearance may be observed in women taking oestrogen. - - - oral - contraceptives.  aspen one In - ii)0 Focal hyperpigmentation: =v a) Cäfe-au-lait spots are pigmented patches seen in - - neurofibromatosis & Albright’s syndrome. - - syndrome is characterised by focal b) Peutz-Jeghers - & peri-oral pigmentation. - c) Melanotic tumours, both benign such as pigmented -- - naevi and malignant such as melanoma. --  - every thiren popole iii) Generalised& Eis an extreme hypopigmentation: Albinism & - degree of generalised hypopigmentation in which & - - - tyrosinase - activity of the melanocytes is genetically e - - - defective and no melanin is formed. They are highly sensitive toS - & - - - sunlight. Chronic sun exposure may lead to precancerous lesions and & => > - squamous and - basal cell cancers of & skin. & -  iv) Localised - & hypopigmentation a) & ---- Leukoderma is a form of partial albinism and is an inherited disorder. - b) & Vitiligo is local hypopigmentation of the& skin and is - more common - - - c) Acquired focal hypopigmentation can result from - various causes such as leprosy, healing of wounds, & - = DLE, radiation dermatitis etc. - -  -Indogenous Hemosiderin pigment - - Iron containing pigment - - Derived from breakdown of - - - hemoglobin - During disturbances in iron - -- - - metabolism Often seen in macrophages in bone, marrow, - & C - spleen and& & liver (lots of red cells and RBC Granular or crystalline yellow --- - - - breakdown); also in macrophages in areas of & - - - brown pigment- recent hemorrhage - -  - Hemosiderin granules in liver cells in Hemochromatosis. H&E section showing - - - golden-‐brown, finely - granular pigment - - in& hepatocytes. - & Hemochromatosis: increased iron build up in the body also called as iron overload