CELL INJURY Normal cell acts in a steady state to handle its physiologic demands. When there is stress, the cell responds by Normal cell (hemeostasis) adaptation Cell injury inability to adapt -Exceeded limits of adaptive ability -No adaptive response

Adaptation: -The cell achieves a new steady state with preserved viability and function. - Hyperplasia, hypertrophy, atrophy & metaplasia.

Types (forms) of Cell Injury According to the duration and severity of the injurious agent. Reversible Irreversible Milder form More severe form Biochemical Morphological Death of cells changes changes DEGENERATION NECROSIS

Causes of cell injury Acquired Genetic -Hypoxia chromosomal -Biological abnormalities -Physical -Chemical -Immunological -Nutritional

Pathogenesis of cell injury The cell Na pump K++++ Na++++ & water Ka+++ K+++

-Failure of sodium pump by -Affect mitochondria…….decrease ATP -Damage of Na pumps -Damage of cell membrane Na +++ K +++ Water+++++ The cell is swollen

Morphological changes of reversible cell injury: -Cloudy swelling -Hydropic change Cloudy swelling: -Swelling of cells -Cytoplasm: pale, vacuolated, clear or granular -EM.:Mitochondrial swelling & Dilated endoplasmic reticulum -Occur in highly specialized parenchymatous organs as liver cells & renal tubules.

Hydropic change: -There is excessive accumulation of intracellular water. -Marked swelling of the cells -e.x.: Skin in Chicken & small pox Liver cells in viral hepatitis Islets of langerhans in early diabetes mellitus

Death of group of contiguous cells within a living tissue or organ. Autolysis is dissolution of dead cells by its own digestive enzymes Another form of cell death is Apoptosis: Single cell death during life IRREVERSIBLE CELL INJURY NECROSIS

NECROSIS Morphological changes Nuclear Cytoplasmic -Pyknosis -H omogeneous or granular ( Shrunked & dense) -Karyorrhexis -Eosinophilic (Fragmentation into small particles) - Karyolysis (Disppearance)

EM changes of necrosis: -Clumping & disappearance of chromatin. -Fragmentation & disappearance of organelles. Pathological lesions associating necrosis: -A cute inflammation -Liquefaction -Absorption of liquefied necrotic tissue (b.v& lymphatics). -Healing by organization or regeneration. -Encapsulation by fibrous tissue (incomplete fibrosis) -Pathological calcification. -Gangrene

TYPES OF NECROSIS 1-COAGULATIVE NECROSIS 2-LIQUEFACTIVE NECROSIS 3-CASEOUS NECROSIS 4-FAT NECROSIS

COAGULATIVE NECROSIS e.g:Infarction heart, spleen & kidney Grossly: Area of necrosis is pale yellow, swollen (raised on the surface) firm opaque Microscopic picture: -Architectural necrosis with preserved architecture -Acute inflammation at the surrounding tissue

LIQUEFATIVE NECROSIS e.g.: An abscess Amoebic abscess Infarction of the brain Grossly: -necrotic tissue consists of a turbid fluid -Leaves a cavity after absorption

CASEOUS NECROSIS e.g.: Tuberculosis Grossly: -Partially liquefied necrotic tissue -grayish yellow -creamy like cream cheese or casein of milk Microscopic picture: necrotic tissue is -Structureless -homogeneous or granular -eosinophilic

FAT NECROSIS Traumatic Enzymatic e.g.breast trauma e.g acute hemorrhagic pancreatitis Grossly: Necrotic area is -opaque white -calcification Microscopic picture: -Cloudy fat cells -Cloudy fat cells -Chronic inflammatory cells & FB giant cells -Chronic inflammatory cells & FB giant cells

APOPTOSIS Death of single cells during life (Programmed obsolescence) An active process (needs energy) Not associated by inflammatory reaction Physiological or Pathological -To maintain a steady state number e.g of cells in tissues Tumors e.g. endometrial shedding atrophy irradiation liver cells in viral hepatitis

Plebs Stages of apoptosis Apoptotic bodies engulfed Shed from surface Cell -Condensed & fragmented Chromatin -Fragmented organelles

INTRACELLULAR ACCUMULATIONS Increases amount of abnormally present pigment Normally present substance Substance e.g.lipids, Carbohydrates proteins Accumulated substance may be Harmless harmful & toxic

Intracellular accumulation by lipids Fatty change Abnormal accumulation of triglycerides (neutral fat) within parenchymatous cells.

Pathogenesis: Fatty acids From blood Glycerol Triglycerides Apoprotein Lipoprotein Liver cell Blood Fatty change is not due to unmasking of the normally present fat but due to the presence of excessive amounts of triglycerides emulsification insolublesoluble

Causes of FATTY CHANGE Hypoxia Toxins Alcohol Diabetes Malnutrition mellitus -Anaemia -Bacterial -Hear failure -chemical -Ischemia

Grossly: The organ is enlarged & soft Liver: -size: enlarged -consistency: soft -edge: rounded -cutsurface: bulging, yellow & greasy. Heart: - -size: enlarged -consistency: flappy -Endocardial surface: yellow and brown streaks (tigroid appearance)

Liver: Fat vacuole Signet ring appearance Fat vacuoles Microscopic picture: H&E: Clear vacuoles Special stains: Frozen sections & Sudan III & Oil red stain orange color of fat

Heart: Multiple small vacuoles On either side of the nucleus Cardiac muscle fiber

Other LIPID accumulations Cholesterol Stromal fatty Abnormal lipids Infiltration e.g. e.g. e.g. -Old hemorrhage -obesity -lipid storage disease -Gall bladder (cholesterolosis) -Atherosclerosis (arterial intema)

GLYCOGEN Abnormal glucose Abnormal glycogen metabolism metabolism e.g. Diabetes mellitus e.g. Glycogen storage disease Tissue is preserved in alcohol and stained by PAS stain for glycogen

PROTEINS e.g. - Plasma cells Russel bodies due to increased intracellular immunoglobulins (eosinophilic bodies). -Lining epithelium of renal tubules in heavy proteinuria (eosinophilic droplets). MUCOPOLYSACCHARIDES Rare hereditary diseases

Disturbance of MUCIN SECRETION Epithelial mucin Connective tissue mucin e.g. E.g. -Catarrhal rhinitis - Marfan syndrome (Inflammation) (medionecrosis of aorta) -Tumors: adenocarcinoma -Tumors: myxoma mucoid change myxoid change -Abnormal mucin: -Myxoedema: mucoviscidosis Dermis in hypothyroidism

FIBRINOID CHANGE -Other terms: Fibrinoid necrosis; fibrinoid degeneration -Its nature is unknown but it shows the same staining reaction of fibrin -Microscopically: a granular eosinophilic material -e.g. - Wall of arteries in malignant hypertension - Collagen diseases: Rheumatoid arthritis Rheumatic fever -Type III hypersensitivity reaction

HYALINE CHANGE -Other terms: Hyaline degeneration, hyalinosis & hyalinization. -A descriptive term to homogenous refractile eosinophilic material. e.g. Connective tissue Epithelial -Wall of blood vessels (old age) -lumen of prostatic acini -Collagen as in scars & keloid (corpora amylacea) -Tumors: as leiomyoma -hepatocytes in viral hepatitis -Kidney: glomeruli as end stage -Kidney: cytoplasm and lumen arteries in benign hypertension of tubules in heavy proteinuria

AMYLOIDOSIS -An extracellular deposition of amyloid material in connective tissue and walls of blood vessels. - Amyloid consists of protein with mucopolysaccharide -It causes cell injury as the extracellular deposition of amyloid causes pressure atrophy of the cells -It does not induces inflammatory reaction

CLASSIFICATION OF AMYLOIDOSIS Chemical clinical -AA (amyloid associated) protein -Secondary Not an immunoglobulin amyloidosis -AL (amyloid light chain) protein -Primary An immunoglobulin produced by amyloidosis plasma cells.

1ry amyloidosis 2ry amyloidosis -Heart, tongue, GIT, -liver, spleen, kidney & nerves & skin lymph nodes -Unknown cause -In chronic diseases as -common with multiple suppurative diseases, TB, myeloma leprosy& malaria -Rheumatoid arthritis.

Grossly: The affected organ is enlarged -Consistency firm & elastic -Cut surface flat, translucent and waxy light brown in color -Edge: sharp Microscopically: H&E: refractile eosinophilic substance Congo red stain: Apple green birefringence under polarized light Thioflavin-T: Yellow fluorescence

H&E

Congo red with polarized light

Thioflavin -T

Effect of amyloidosis on organs _Kidney: Nephrotic syndrome - Adrenal gland: Addison’s disease -Small intestine: Malabsorption syndrome -Liver: Fatty change Portal hypertension Pressure atrophy -Spleen: Sago spleen (localized form) Marked splenomegaly(diffuse form)