Chapter 1 Nursing - PDF

INTRODUCTION Pathology: The science which deals with the study of structural and functional changes that occur in body tissues and organs in diseases. Pathology is the scientific study of diseases. Disease: A state of ill-health resulting from structural and functional changes in any organ or tissu...

INTRODUCTION Pathology: The science which deals with the study of structural and functional changes that occur in body tissues and organs in diseases. Pathology is the scientific study of diseases. Disease: A state of ill-health resulting from structural and functional changes in any organ or tissue outside normal range. The study of General Pathology: Deals with the general principles of disease and responses of the living tissue to pathologic stimuli. CAUSES OF DISEASES: (A) Genetic: Mongolism, favism and thalassemia. (B) Acquired: 1- Biological: Bacteria, viruses, parasites, protozoa, fungi. 2- Physical: Heat, cold, trauma, radiation. 3- Chemical: Acids, alkali, toxins, drugs. 4- Immunological: hypersensitivity reactions and autoimmune diseases. 5- Endocrinal: Hypopituitarism, Hyperthyroidism, hyper-adrenalism. 6- Metabolic: Diabetes mellitus. 7- Hemodynamic disorders: Ischemia, hypoxia, cerebral stroke, shock. 8- Nutritional: Marasmus, scurvy, iron-deficiency anemia. 9- Carcinogenic agents. ASPECTS OF DISEASE STUDY: I- Etiology: Means the cause of the disease, it includes: a) Predisposing factors: Help the development of the disease, e.g. immune deficiency, diabetes, old age increases the risk of infections. b) Exciting factors: The actual cause the disease. II- Pathogenesis: It is the mechanism of the disease process, by which the pathological changes of the cells and tissues in response to the etiological agents are produced. III- Morphological (structural) changes: The characteristic structural changes that occur in the organs, tissues and cells. a) Gross changes (Macroscopic, Naked-eye picture): It is the naked eye description of the affected organ or tissue regarding: Size, Weight, Shape, Surface, Color, Capsule, Cut section, Consistency, border. b) Microscopic picture: The structural changes in tissues and organs detected by microscopic examination. Different types of microscopes are used as: * Light microscope: Sections stained by routine, histochemical and immune- histochemical stains. * Special microscopes: Electron microscope (E/M), Flourescent microscope. IV- Clinical Picture (functional changes) of the disease: * Signs: Features of the disease detected by the physician. * Symptoms: Complaints of the patient. * Complications: Additional pathological changes which may occur during or after the usual course of the disease which may affect or modify the disease outcome. N.B: The clinical picture together with the results of the investigations helps in diagnosis of diseases. V- Prognosis (fate of the disease): What is going to happen as regarding the course and termination of disease whether complete recovery, chronicity or fatal outcome. TYPES OF PATHOLOGICAL SPECIMENS: (A) Tissue specimens: 1- Whole organ: nephrectomy and hysterectomy specimens. 2- Biopsy: Tissue sample from the affected organ.  Excisional biopsy: Sampling of the whole diseased tissue.  Incisional biopsy: Sampling of a portion of the diseased tissue. It includes: Punch biopsy: in skin lesions. Endoscopic biopsy: GIT, respiratory tract and urinary tract. Core cut needle biopsy: A wide needle is introduced into a suspected area to obtain a core of tissue from organs e.g. liver or breast. 3- Autopsy: Postmortem specimens taken from organs and tissues to determine the cause of death (Medico-Legal). (B) Fluid specimens (cytology): 1- Exfoliated cells: cells falling off tissues e.g.: - in body fluids: Sputum, urine, C.S.F. - in Effusion fluid: Ascetic fluid, pleural & pericardial effusions. - in Body discharges: Nipple and ear discharge. - Brushing specimens: Cells collected from the lesion by brush as in cervico- vaginal and buccal smears. - Imprint smears. 2- Fine needle aspirate (F.N.A): Taken from subcutaneous or deep- seated lesions of different organs for cytological examination e.g. breast, thyroid and lymph nodes. Chapter 1 CELL INJURY AND TISSUE DEPOSITS  The normal cell function requires a balance between physiologic demands and the limitations of cell structure and metabolic capacity. Maintenance of this steady physiological state is termed as homeostasis.  More severe physiologic stress and some pathologic stimuli may lead to cellular adaptation, during which new but altered steady state is achieved. These changes include: hypertrophy, hyperplasia, atrophy and metaplasia.  When the limits of adaptive response to stimuli are exceeded, or when the cell is exposed to more severe injurious agent, a sequence of pathologic events occurs, termed as cell injury.  Cell injury is reversible up to a certain point, but if the stimulus is severe enough and prolonged, the cell suffers irreversible cell injury (cell death).  - Cellular adaptation: New altered steady state in which the cells show increase or decrease in their number, size and function in response to prolonged stimuli. - Reversible cell injury (degeneration): The injury is not severe enough to kill the cell (sub-lethal stimuli). The cytoplasmic organelles are affected without affection of the nucleus. Such changes are reversible after cessation of the stimulus. -Irreversible cell injury (cell death): The injury is severe enough to kill the cell (lethal stimuli). It affects the cell organelles as well as the nucleus and leads finally to cell death. There are two morphologic patterns of cell death: a) Necrosis, and b) Apoptosis A) CELL INJURY Definition: Biochemical, structural and morphological changes occurring in cells due to exposure to an injury. The cell injury may be: 1- Reversible (Degeneration). 2- Irreversible (Cell death). 1) Causes of cell injury: a-Genetic causes: as thalassemia and inborn errors of metabolism. b-Acquired causes:  Hypoxia: Important cause of cell injury and cell death due to reduction of aerobic oxidative respiration.  Ischemia: Produce more rapid and severe injury than hypoxia due to reduction of both oxygen & glucose.  Physical agents: Mechanical trauma, extremes of temperature (burns & deep cold), radiation and electric shock.  Chemical agents: Strong acids & alkalis, glucose or salts in hypertonic concentration, poisons, air pollutants, insecticides, alcohol and drug abuse.  Infectious agents: Viruses, bacteria, fungi and parasites.  Immunological reaction: Hypersensitivity reactions and autoimmune diseases.   Nutritional abnormalities: Both over- and under-nutrition lead to different types of cell injury.  Metabolic diseases: e.g. diabetes mellitus. Mechanism of cell injury: Four cellular systems are mainly affected: mitochondria, cell membrane, DNA and protein synthesis. 1) Mitochondrial damage: Frequently associated with both hypoxic and chemical injury, leads to decrease energy production and defects in all vital cellular processes. 2) ATP depletion: leads to:  Defect in sodium potassium pump causing cellular swelling.  Decrease of all metabolic activities of the cells.  Increase of intracellular calcium (calcium levels are kept in check by ATP–dependent enzymes).  Reduction of protein synthesis. 3) Defects in cell membrane permeability: Damage of plasma membrane lead to:  Osmotic imbalance with influx of fluids & ions.  Loss of cellular proteins and enzymes. 4) Loss of calcium homeostasis: Increase of intracellular calcium above normal level will activate different enzymes as ATPase, phospholipase, proteases and endonucleases which cause cell damage. 5) Accumulation of oxygen free radicals: Free radicals are unstable, highly reactive molecules. They are normally present in small amounts during normal cellular respiration. Its accumulation leads to cell injury. CLINICAL CORRELATE: The loss of membrane integrity (cell death) allows intracellular enzymes to leak out, which can be measured in the blood as clinical markers of cell death and organ injury.  Morphologic alterations in cell injury I- Reversible Injury (degeneration) Definition: Reversible structural and biochemical changes in cells after exposure to an injury not severe enough to kill the cell. Types of reversible cell injury: 1) Disturbance of water metabolism:  Cloudy swelling.  Hydropic or vacuolar change. 2) Disturbance of lipid metabolism: Fatty change. 3) Disturbance of glycogen metabolism. 4) Disturbance of mucopolysacraides metabolism. 5) Hyaline change. 1- Disturbance of Water Metabolism A) Cloudy Swelling:  Definition: Common type of reversible cell injury characterized by mild intracellular accumulation of water.  Causes: 1) Hypoxia and ischemia. 2) Exogenous toxins (like bacterial and chemical) and Endogenous toxins (like ketone bodies in diabetes mellitus). Usually affects the paranchymatous organs as liver, heart and kidney. These organs normally need high energy production so they will be the first to be affected.  Pathogenesis: Damage of the mitochondria leads to decrease of ATP production. This leads to failure of Na/K pump (with intracellular accumulation of Na and water), and loss of K ions. Also, increase anaerobic metabolism leads to cell swelling. Pathology:  Gross picture: The affected tissue or organ appears swollen, pale in color, soft in consistency with smooth surface and rounded borders.  Microscopic picture: Cells are swollen showing pale eosinophilic granular cytoplasm due to accumulation of water and mitochondrial fragments. The nuclei are normal.  Effects: kidney (Albuminuria), heart (Tachycardia), liver (Mild hepatomegaly). B) Hydropic (Vacuolar) Degeneration:  Definition: Severe form of cloudy swelling with excessive accumulation of water in the cytoplasm and formation of large cytoplasmic vacuoles.  Examples: 1) Epidermal cells in burns. 2) Liver cells in viral hepatitis. 3) Beta cells of islets of Langerhans in early stage of D.M. 2- Disturbance of Lipid Metabolism A) Fatty Change (steatosis):  Definition: Abnormal excessive accumulation of triglycerides in the non-fatty tissue, especially the parenchymatous organs.  Causes:  Hypoxia & ischemia.  Bacterial toxins: e.g. diphtheria.  Chemicals: CCL4, chloroform, Arsenic and alcohol.  Malnutrition: Decrease lipotropic factors as choline and methionine which are essential for normal fat metabolism. 1- Fatty change of liver: The liver is a major organ responsible for fat metabolism, so it is usually the first organ to be affected by fatty change. Pathogenesis of fatty change in the liver: 1) Excessive entry of free fatty acids in the cells. 2) Increased fatty acid synthesis from acetate. 3) Increased esterification of fatty acids to triglycerides due to increased activity of alpha- glycero-phosphate. 4) Decreased fatty acid oxidation. 5) Decreased apo-protein synthesis. 6) Impaired lipoprotein secretion from the liver.  Gross picture: Mild to moderate enlargement with tense capsule, smooth outer surface, round borders, soft, yellow and greasy on touch.  Microscopic picture: Early, hepatocytes are swollen with multiple small fat globules around the nucleus. Later on, the small fat globules fuse together to form one large globule pushing the nucleus to one side against the cell membrane giving the characteristic signet-ring appearance.  Effect: Liver insufficiency which may progress to liver cirrhosis. 2- Kidney:  Gross picture: The kidney is slightly enlarged and soft with pale yellow coloration especially at the cortex.  Microscopic picture: Fat globules are deposited in the cells of the proximal and distal convoluted tubules.  Effect: Albuminuria. 3- Heart:  Gross picture: The heart is soft, flabby and slightly dilated chambers. In early stages, some cardiac muscles bundles are affected by fatty change and appear yellow while other bundles are still normal and appear red in color giving the heart a mottled tigroid or tabby-cat appearance. In late stages (due to severe toxemia) the whole cardiac muscles appear yellow in color.  Microscopic picture: Tiny fat globules are seen inside the sarcoplasm of cardiac muscle fibers.  Effects: Weak contractility, tachycardia and heart failure. 3- DISTURBANCE OF MUCOPOLYSACCHARIDES (a) MUCOID DEGENERATION: Definition: Excessive accumulation of mucin in epithelial cells. Examples: In respiratory and intestinal mucosa in catarrhal inflammation. In cells of malignant tumors of stomach, colon, breast and ovaries (signet ring carcinoma). Microscopic picture: At first, mucin appears as multiple small vacuoles in the cytoplasm which later on accumulates into one large clear vacuole displacing the nucleus at one side of the cell membrane (signet-ring appearance). N.B: Alcian blue stain differentiates mucin from fat vacuoles. (b) MYXOMATOUS DEGENERATION: Definition: Excessive accumulation of muco-polysaccharides in the connective tissue stroma giving a soft gelatinous consistency. Examples: Skin in hypothyroidism (myxedema), Mesenchymal tumors as leiomyoma, fibroma and chondroma. Gross picture: The affected part is soft, transparent and gelly-like. Microscopic picture: Myxomatous tissue is formed of small oval, triangular, fusiform, elongated or star-shaped or stellate cells with intercommunicating long processes in a homogenous pale basophilic background. 4- HYALINE CHANGE: Definition: Any intracellular or extracellular alteration which gives a homogenous glassy pink appearance when the tissue sections are stained with Eosin. Types: A- Intracellular hyalinosis:  Russel bodies: Degenerated old plasma cells in chronic inflammation as rhinoscleroma.  Corpora amylacia: In senile prostatic hyperplasia, the detached epithelial cells lining undergo hyaline degeneration and form pink structureless bodies in the acinar lumen.  Beta cells of islets of Langerhans in late stages of D.M. B- Extracellular hyalinosis:  Old scars, old thrombi and keloid.  Blood vessels in benign hypertension and atherosclerosis.  Mesenchymal tumors as leiomyoma and fibroma.  II- Irreversible Cell Injury (cell death) Definition: Severe form of cell injury affecting both the nucleus and cytoplasm leading to cell death. Types: a- Necrosis. b- Apoptosis. a- Necrosis  Definition: Morphological changes that follow cell death of a group of cells in the living tissue. Necrosis may occur directly by severe injury or follow degeneration by prolonged moderate injury.  Causes: Ischemia, bacterial toxins, mechanical trauma, hypersensitivity reactions, physical and chemical agents.  Pathogenesis: The morphological changes of necrosis result from tow processes: denaturation of intra-cellular proteins, and enzymatic digestion of the cellular organelles. These enzymes may be derived from the dead cells themselves or from the surrounding leukocytes. Morphological changes in necrosis:  Gross picture: Necrotic area appears opaque, yellow and surrounded by red zone of inflammation.  Microscopic picture: 1- Nuclear changes:  Pyknosis: The DNA condenses and shrinks into small solid dark basophilic mass (nuclear shrinkage).  Karyorrhexis: Fragmentation of the nuclear material (nuclear fragmentation).  Karyolysis: Lysis of the nuclear content by the action of the endonucleases (nuclear lysis).  2- Cytoplasmic changes:  The cells become swollen (cytomegally).  Increased eosinophilia due to binding of eosin to denatured proteins and loss of basophilic RNA.  The cytoplasm becomes vacuolated and appear moth-eaten (due to lysis of the cytoplasmic organelles).  Finally, the cell membrane ruptures. - Fate of necrosis:  Small necrotic areas are removed by macrophages and then replaced by granulation tissue and fibrosis.  Large necrotic areas are surrounded by fibrous capsule and undergo dystrophic calcification.  Gangrene: Necrotic tissue is attacked by putrefactive bacteria.  Types of necrosis: 1. Coagulative necrosis. 2. Liquifactive necrosis. 3. Caseating necrosis. 4. Fat necrosis. 5. Fibrinoid necrosis. 6. Gangerenous necrosis.  1- COAGULATIVE NECROSIS  Definition: The most common type of necrosis mainly caused by sudden cut of blood supply (ischemic necrosis) of all organs except the brain.  In this type of necrosis, the injury causes denaturation in both structural proteins and proteolytic enzymes. This delays cell lysis, so the tissue architecture is preserved and ghosts of cells remain. Finally, lysis occurs and necrotic tissue becomes structureless.  Examples: Infarctions of all tissues except the brain. 1- Myocardial infarction 2-Splenic infarction 3-Renal infarction 2- LIQUEFACTIVE NECROSIS  Definition: Type of necrosis characterized by softening and liquefaction of the necrotic tissue due to prevalence of enzymatic digestion over proteins denaturation.  Examples:  Brain infarctions: due to high lipid and fluid content.  Pyogenic abscess: due to liquefaction of the necrotic tissue by the proteolytic enzymes from pus cells. 3- CASEATION NECROSIS  Definition: It is a specific type of necrosis characterized by partial coagulative necrosis and liquefaction of the necrotic area. It is typicaly found in caseating tuberculosis.  The tissue architecture is completely lost. The necrotic parts appear as cheesy-white material (casein-like) surrounded by granulomatous reaction. 4- FAT NECROSIS  Definition: necrosis of adipose tissue, it is of two types: A) Traumatic fat necrosis: trauma to adipose tissue resulting in splitting of neutral fat with activation of macrophages that engulf fat and lead to fibrosis. It commonly occurs in female breast --> chronic granulamatous reaction with excessive fibrosis forming firm adherent breast mass misdiagnosed as cancer breast.  B) Enzymatic fat necrosis: Due to release of lipase enzyme in cases of acute hemorrhagic pancreatitis leading to destruction of mesenteric fat. Lipase enzyme splitts triglycerides into fatty acids and glycrol. The glycerol is absorbed while fatty acids cause chronic inflammatory reaction, fibrosis and deposition of calcium salts --> Chalky white areas. 5- FIBRINOID NECROSIS  Definition: It is a specific type of necrosis affecting the small arteries, arterioles in cases of autoimmune disease and malignant hypertension.  Deposits of immune complexes and fibrin result in bright pink and amorphous fibrinoid material. 6- GANGRENOUS NECROSIS (Gangrene)  Definition: Tissue necrosis with superadded putrefaction. The gangrenous tissue appears black due deposition of iron sulphide.  Causes: a. Arterial occlusion. b. Venous occlusion. c. Invasion by saprophytes: Organisms attack the dead tissue liberating hydrogen sulphide (bad odor) which combine with iron liberated from destructed RBC's to form iron-sulphide (black color). Types of gangrene: 1) According to blood supply and amount of tissue fluid: a. Dry gangrene: Scanty amount of tissue fluids e.g. Senile gangrene. b. Moist gangrene: Large amount of tissue fluids. e.g. diabetic gangrene, bed sores & intestinal gangrene. According to the cause of necrosis and putrefaction: a) Primary gangrene: The organism causes both tissue necrosis and putrefaction e.g. infective gangrene. b) Secondary gangrene: Necrosis and putrefaction are produced by two different causes e.g. diabetic gangrene.  DRY GANGRENE Definition: Necrosis and putrefaction in absence of gross edema, usually occurs in exposed parts. Pathogenesis: The arterial supply is occluded while venous and lymphatic drainage remain opened. The affected part is dry due to: 1- Evaporation of fluids from exposed parts. 2- Drainage of fluid by patent veins & lymphatics. Sites: Usually occurs in the limbs especially the lower limbs starting in the big toe due to poor blood supply. Causes: Arterial occlusion. The veins and lymphatics are opened. Pathological features: 1- Discoloration: * In early cases, the affected part is cold and pale in color (due to ischemia), pulseless with loss of sensation and function. * Due to good drainage of the interstitial fluids, the putrefaction is minimal and the spread of gangrene is slow. The gangrenous part is dry. The offensive odor is slight with minimal toxemia. * A series of colors appear in the form of red (due hemorrhage from damaged blood vessels), blue and then black depending on the increasing amount of iron sulphide. 2- Line of demarcation: Because the necrotic tissue induces inflammation in the adjacent healthy tissue an acute inflammatory zone occurs between living and dead parts. So, at the junctional zone between dead and viable tissue, a thin line of hyperemic granulation tissues appears known as "line of demarcation". 3- Line of separation: A groove distal to line of demarcation produced by healthy tissue in which the granulation tissue is transformed into fibrous tissue. The groove slowly deepens until the gangrenous part separates spontaneously. The remaining proximal viable part is called the stump and appears conical in shape because gangrene spreads up higher in the skin than bone and muscles with more rich blood supply.  MOIST GANGRENE Definition: Necrosis and putrefaction in presence of gross edema. Causes: Sudden complete arterial and venous occlusion of the affected part with accumulation of excess tissue fluids. Examples: - Diabetic gangrene starts as dry, but soon becomes moist. - Internal organs as the intestine and lung. - Severe crush injuries. 1- DIABETIC GANGRENE - Predisposing factors: Premature atherosclerosis, elevated tissue sugar level (good media for bacterial growth), decreased immunity and sensory loss due to peripheral neuropathy. - At first, the gangrenous part is dry but soon becomes moist. - Gangrene spreads rapidly with poor line of demarcation. - The color changes are well apparent like that of dry gangrene. - Putrefaction is maximum with severe toxemia and offensive odor. 2- INTESTINAL GANGRENE Gangrene rapidly extends because the affected part is edematous and contains numerous saprophytes. Causes: - Intestinal obstruction: Volvulus, Intussusception, Strangulation. - Mesenteric arterial occlusion. Pathogenesis: * In cases of volvulus, intussusception and strangulation, there is early obstruction of the venous drainage due to mechanical compression. This leads to accumulation of excess tissue fluids with increasing pressure until the arterial supply is also occluded. The affected intestinal loop undergoes ischemic necrosis and invaded by putrefactive bacteria normally present in the lumen. The color rapidly turns black due to iron sulphide. Intestinal gangrene  Table (1-1): Differences between dry and moist gangrene. Item Dry gangrene Moist gangrene Onset Gradual Sudden Site Limbs Limbs and internal organs Causes Arterial occlusion Arterial and venous occlusion Shrunken, Affected part Swollen mummified Edema Absent Marked Slow due to very Putrefaction Rapid due to presence of blood little blood supply Mild as bacteria fail Severe as numerous bacteria Toxemia to survive present Well formed at the Line of junction between Poorly formed demarcation healthy and gangrenous part Line of separation Present Absent Spontaneous Frequent Rare separation Course Slow Rapid and fatal INFECTIVE GANGRENE  Definition: It is a form of primary moist gangrene where the infective organism produces both necrosis and putrefaction. Types of Infective Gangrene: 1) Gas Gangrene:  Definition: A type of infective gangrene characterized by production of gasses as carbon dioxide and hydrogen sulphide.  Sites: Occurs in deep penetrating wounds, and compound bone fractures contaminated by soil containing spores of Gram–ve Closteridia: Saccharolytic and Proteolytic groups. Gross picture: The affected areas are swollen, edematous with foul smelling odor and sero-sangenous discharge. The color changes are evident. Palpation of the wound leads to crepitation in the subcutaneous tissue. Microscopic picture: Necrosis and edema in muscles and C.T with gas formation, inflammation, thrombosis and damaged blood vessels. Gram -ve Clostridia can be demonstrated in the lesion. Effects: Toxemia and spread of infection. 2) Lung Gangrene: It is a rare type of moist gangrene that predisposed by severe lung infections as lung abscess and pneumonia especially in cases of immunosuppression. Gross picture: The affected lung appears soft, friable with black color and offensive odor. It is rapidly fatal. 3) Bed sores: Common complication of prolonged recumbency due to paralysis, operations or bone fracture. Occurs usually in the sacrum and buttocks due to vascular occlusion resulting from pressure over the bony prominences --> tissue necrosis. The necrotic tissue is then superadded by putrefactive bacteria and casts off leaving an ulcer with exposure of the underlying muscles and bone.  Table (1-2): Types of necrosis Type Seen in Due to Histology Coagulative Ischemia / infarcts in Ischemia denatures Preserved cellular most tissues (except enzymes leading to architecture (cell outlines brain) blocked proteolysis seen), but nuclei disappear; increase cytoplasmic binding of eosin stain (eosinophilia; red/pink color) Liquefactive Bacterial abscesses and Neutrophils release Early: cellular debris and brain infarcts. lysosomal enzymes macrophages. that digest the tissue Late: cystic spaces and cavitation (brain) or Neutrophils and cell debris with bacterial infection Caseous TB and systemic fungi. Macrophages wall off Fragmented cells and the infecting debris surrounded by microorganism leading lymphocytes & to granular debris macrophages (granuloma) Fat Enzymatic: acute Damaged cells release Outlines of dead fat cells pancreatitis lipase, which breaks without peripheral (saponification of down triglycerides nuclei; saponification of peripancreatic fat) liberated fatty fat (combined with Ca) Nonenzymatic: acids bind Ca leading traumatic (eg, injury to to saponification breast tissue) Fibrinoid Immune reactions in Immune complexes Vessel walls are thick and vessels (eg polyarteritis combine with fibrin pink nodosa), hypertensive leading to vessel wall emergency damage (type III hypersensitivity reaction) Gangrenous Distal extremity and Dry: ischemia Wet: Dry: Coagulative GIT, after chronic superinfection ischemia Wet: Liquefactive superimposed on coagulative  b- Apoptosis  Definition: Programmed cell death to eliminate unwanted cells in the living tissues through activation of intracellular suicidal program. This pathway of cell death is induced by specific death genes and enzymes. It is an active process which needs energy.  Types: Apoptosis may be physiological or pathological. 1- Physiological apoptosis: This serves to remove cells that are no longer needed and to maintain normal number of cells in the tissue: a. During embryogenesis. b. Hormone dependent involution as endometrial breakdown during menstruation, prostatic atrophy after castration and regression of lactating breast after weaning. c. Death of the host cells after performing their useful functions as neutrophils in acute inflammation and lymphocytes at the end of immune response. d. Elimination of self-reactive T-lymphocytes. 2- Pathological apoptosis: a. When the cells are exposed to injurious stimuli as radiation and hypoxia, several DNA mutation occurs. Apoptosis is better for the body because DNA mutations may lead to malignant transformation. b. Cell injury in certain viral disease as in viral hepatitis. c. Pathologic atrophy states. d. Cell death in tumors after chemotherapy and radiotherapy. Morphological changes in apoptotic cells: 1) Nuclear changes:  Start before cell membrane damage.  Chromatic condensation: The chromatin aggregates under the nuclear membrane (pyknosis), then undergo fragmentation (karyorrhexis).  2) Cytoplasmic changes:  Cell shrinkage: The cytoplasm becomes dense and eosinophilic with closely packed organelles.  Fragmentation of the cell membrane: The cells membrane remains intact and form surface blebs. This is followed by fragmentation of the apoptotic cells into apoptotic bodies. Apoptotic bodies: Cell fragments formed of part of cell membrane enclosing part of the cytoplasm, organelles and nuclear chromatin. 3) Phagocytosis of apoptotic bodies: By macrophages that engulf the apoptotic bodies and degrade them rapidly by the lysosomal enzymes.  Table (1-3): Differences between necrosis and apoptosis. NECROSIS APOPTOSIS Definition Death of a group of Programmed cell cells in the living tissue death Stimulus Pathologic only Both physiologic & Pathologic Associated Present Absent Inflammation Cell size Cytomegaly Cell shrinkage Fragmentation Early Late of cell membrane Nuclear changes Pyknosis, karyorrhexis, Nuclear condensation Karyolysis and Fragmentation Energy demand Does not need energy Needs energy B) TISSUE DEPOSITS Nature of tissue deposits: 1. Accumulation of normal cell components (Revisable cell injury): Water, fat, mucin. 2. Abnormal metabolism of certain substances: Calcium, uric acid. 3. Deposition of endogenous pigment: Hemosedirin, melanin, lipofuscin. 4. Deposition of exogenous substance: carbon particles in alveoli, tattooing. Tissue deposits may be: I- Extra-cellular (inter-cellular): calcium, urates. II- Intra-cellular: melanin, hemosiderin, lipofuscin.  I- Extracellular Deposits a- Pathological Calcification: Definition: Abnormal deposition of Ca salts in tissues other than bone and teeth. Types of pathological calcification: 1- Dystrophic calcification, 2- Metastatic calcification. 1-Dystrophic Calcification: Definition: Deposition of Ca salts in necrotic and degenerated tissues. The serum Ca level is normal. The damaged tissues have alkaline pH favoring Ca deposition. A) Necrotic tissue: 1. Caseation necrosis, fat necrosis and old infarcts. 2. Dead parasites as hydatid cysts and bilharzial ova. B) Degenerating tissue: 1. Old scar. 2. Chronic inflammatory lesions as wall of chronic abscess. 3. Atheroma of aorta &coronary arteries. 2-Metastatic Calcification: Definition: Deposition of calcium salts in normal tissue due to high serum calcium level (Hypercalcemia). Causes of hypercalcemia: 1) Hyperparathyroidism: due to parathyroid hyperplasia & tumours. 2) Destruction of bone tissue: as in multiple myeloma, bone metastasis, Paget disease and prolonged immobilization. 3) Vitamine D related disorders: as vitamin-D intoxication and sarcoidosis (the macrophage produce vitamin D precursor). 4) Renal failure due to retention of phosphate leading to secondary hyperparathyroidism.  Sites: May occur in any tissue, but the most affected sites are: Stomach, Lung, Arteries, Kidney. Table (1-4): Differences between dystrophic and metastatic calcification Item Dystrophic Metastatic Incidence Most common Less common Blood Ca level Normal Increased Sites of calcification Dead or degenerated tissue Normal tissue Cause & Related to tissue alkalinity Due to hypercalcemia Pathogenesis Examples Atheroma, fibroid, old scar. Kidney (nephrocalcin osis). b-Uric acid and urate deposition (gout): - Uric acid and urates are end products of purine metabolism - Causes of increased serum uric acid (hyperurecemia): * Increased intake: meat, beans * Increased production: in tissue breakdown states as leukemia * Decreased excretion: In renal tubular disorders - Effects: * Urates stones in urinary tract * Gout: Deposition of urate crystals in small joints especially big toe -- > arthritis - Dietary Advice: Avoid high-purine diet as red-meat, beans. c- Jaundice Definition: Yellow coloration of all tissues due to increased bilirubin levels in the blood. The yellow color is manifested more in the skin and sclera. Types of jaundice: 1) Hemolytic jaundice: Increased hemolysis leads to excess production of bilirubin with increased indirect bilirubin in blood. 2) Hepatocellular jaundice: The diseased liver has low ability to uptake, conjugate and excretes bilirubin. This leads to increased both direct & indirect bilirubin in blood. 3) Obstructive jaundice: Extra-hepatic biliary obstruction leads to increased direct bilirubin in blood.  II- Intra-Cellular Deposits 1- Disturbance in melanin pigmentation: i- Excessive pigmentation: a. Addison’s disease: due to increase in the melanocyte stimulating hormones (MSH) of the anterior pituitary. b. Prolonged exposure to sunlight. c. Nevi and malignant melanoma. ii- Hypopigmentation: a. Albinism: inherited as autosomal recessive trait. The number of melanocytes in the skin is normal but there is absence or inactivation of the tyrosinase enzyme. b. Vitiligo: Focal depigmentation of the skin due to absence of melanocytes. The cause is not known but antibodies to melanocytes have been described (auto-immune basis). 2- Lipofuscin pigment (fuscus=brown): Also called aging, wear and tears pigments. It represents the indigestible residues of the autophagic vacuoles formed during aging or atrophy. It is especially prominent in the liver and heart in aging severe malnutrition. Mechanism: It results from intra-cellular peroxidation of lipids, and indicating free radical injury, e.g. brown atrophy of the heart.