SBO: PATHOLOGY ~~ CELLULAR INJURY AND CELL DEATH, CELL GROWTH AND DIFFERENTIATION *** 1.

DESCRIBE THE PATHOGENIC MECHANISMS INVOLVED AND THE PROTOTYPE TYPES OF NECROSIS TYPE OF COAGULATION LIQUEFACTION ENZYMATIC FAT NECROSIS NECROSIS NECROSIS NECROSIS DESCRIPTION form of necrosis in digestion of the dead focal areas of fat which the cells destruction architecture of dead tissues is preserved for a span of at least some days CHARACTERI tissues exhibit a firm tissue into a liquid visible chalky-white STIC texture viscous mass; creamy areas (fat yellow because of the saponification) presence of dead Histologic exam: leukocytes (pus) form of foci of shadowy outlines of necrotic fat cells, with basophilic calcium deposits, surrounded by an inflammatory reaction MECHANISM denatures not only microbes stimulate release of activated structural proteins but the accumulation of pancreatic lipases into also enzymes and so leukocytes and the the substance of the blocks the proteolysis liberation of enzymes pancreas and the of the dead cells; as a from these cells peritoneal cavity result, eosinophilic, (acute pancreatitis); anucleate cells may pancreatic enzymes persist leak out of acinar cells and liquefy the membranes of fat cells in the peritoneum. The released lipases split the triglyceride esters contained within fat cells. The fatty acids, so derived, combine with calcium. EXAMPLES OF EACH OF THE FOLLOWING CASEOUS NECROSIS caseous (cheeselike); encountered most often in foci of tuberculous infection friable white appearance Histologic exam: collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border (granuloma) a form of coagulative necrosis, in that no liquefaction has occurred, but microscopically the affected tissue appears completely structureless, under the microscope and exhibits a greater than usual affinity for acidic dyes such as eosin GANGRENOUS NECROSIS serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies affected areas turning black and/or green and/or yellowish brown

reduced blood supply to the affected tissues, which results in cell death

EXAMPLES

COAGULATIVE NECROSIS: Gross: Image of the heart from this case, note the area of fresh myocardial infarction (arrows) in the anterior portion of the left ventricle and extending into the anterior portion of the interventricular septum. Note that the walls of the left and right ventricle are slightly

LIQUEFACTION NECROSIS: Gross: the cerebral infarction at the upper left here demonstrates liquefactive necrosis. Eventually, the removal of the dead tissue leaves behind a cavity. Histology: Liquefactive necrosis (arrow). The necrotic brain tissue is homogeneous and eosinophilic.

ENZYMATIC FAT NECROSIS: Gross: a mesentery that has become gorged with necrotic fat; some relatively normal white fat is visible and necrotic fat in the middle of the mass Histology: As with any necrotic condition, inflammation will occur in fat necrosis, reflected by the large numbers of inflammatory cells around the lesion.

ENZYMATIC FAT NECROSIS: Gross: On closer inspection, the granulomas have areas of caseous necrosis. This is very extensive granulomatous disease. This pattern of multiple caseating granulomas primarily in the upper lobes is most characteristic of secondary (reactivation) tuberculosis. However, fungal granulomas (histoplasmosis, cryptococcosis,

GANGRENOUS NECROSIS: Histology: intestinal gangrene: extensive necrosis of the entire intestinal wall. HE stain. Gross: Seen here is the lower leg from a below the knee amputation. The affected skin is dark red to black and there is a large area of ulceration.

2. GIVE THE 3 GROUPS OF CELLS BASED ON THEIR REGENERATIVE CAPACITY, THE PROTOTYPE OF EACH AND THE CLINICAL SIGNIFICANCE OF EACH CATEGORY a. Labile cells (continuously dividing cells)- continue to multiply throughout life under normal physiologic conditions. Eg: surface epithelial cells of epidermis, alimentary tract, respiratory tract, urinary tract, vagina, cervix, uterine endometrium, hematopoietic cells of bone marrow, cells of lymph nodes and spleen b. Stabile cells (quiescent cells)- decrease/lose their ability to proliferate after adolescence but retain the capacity to multiply in response to stimuli throughout adult life. Eg: parenchymal cells of organs like liver, pancreas, kidneys, adrenal and thyroid; mesenchymal cells like smooth muscle cells, fibroblasts, vascular endothelium, bone and cartilage cells c. Permanent cells- lose their ability to proliferate around the time of birth. Eg: neurons of nervous system, skeletal muscle and cardiac muscle cells 3. DEFINE AND GIVE AT LEAST ONE ILLUSTRATIVE EXAMPLE OF EACH OF THE FOLLOWING TYPES OF CELLULAR ADAPTATIONS OF GROWTH AND DIFFERENTIATION TYPE OF HYPERPLASIA CELLULAR HYPERTROP ATROPHY METAPLASIA ADAPTATIO HY PHYSIOLOGIC PATHOLOGIC N DESCRIPTIO decrease in increase in cell increase in the number of cells when a differentiated cell N cell size size abnormal increase in cell of a certain type is 1. Compensatory replaced by another cell division hyperplasiatype, which may be less Eg: endometriosis permits tissue differentiated and organ regeneration Eg: epithelial cells of the epidermis and intesti ne, liver hepatocytes, bo ne marrow cells, and fibroblasts 2. Hormonal hyperplasiaoccurs mainly in organs that depend on estrogen Eg: estrogen-dependent uterine cells undergo hyperplasia and hypertrophy following pregnancy

DYSPLASIA abnormal changes in cellular shape, size, and/or organization

EXAMPLES

ATROPHY: The atrophic glands have scant cytoplasm and hyperchromatic nuclei with occasional punctate nucleoli. The basal cell layer is fragmented but still present as confirmed by high molecular weight

HYPERTROPHY: Myocardial Cell Hypertrophy Compare the nuclei of these huge myocardial cells to the little endothelial cell nuclei that lie between them. Obviously these have more than 92 chromosomes (normal for a sedentary person's heart). Athletic hypertrophy is good, but hypertrophy due to high blood

PHYSIOLOGIC HYPERPLASIA: Endometrial mucosa: normal endometrial gland in the proliferative phase of the menstrual cycle Recall that the proliferative phase of the cycle is an estrogen primed event. Estrogen is a growth promoter and causes the endometrial glandular cells to mitose and undergo mitotic divisions

PATHOLOGIC HYPERPLASIA: Endometrial mucosa: pathologic endometrial hyperplasia due to unopposed estrogen stimulation When comparing this slide above, it is apparent that far more glands are present and they are crowded together. This occurs when a woman has too much estrogen and not enough progesterone, the latter a hormone that causes endometrial glands to undergo atrophy. Examples of unopposed estrogen include a postmenopausal woman who is taking estrogen without progesterone to prevent osteoporosis or an obese woman, who has increased aromatization of androgens into estrogens in the

METAPLASIA: Squamous Metaplasia The physiologic, normal process whereby columnar epithelium matures into squamous epithelium. Squamous metaplasia typically occupies part of the transformation zone. At the squamocolumnar junction it appears as a "ghost white" or white-blue film with the application of acetic acid. It is usually sharply demarcated toward the cervical os and has very diffuse

DYSPLASIA: Immunohistochemical localization of phospho-Akt in human bronchial biopsies Sections from human bronchial biopsies were incubated with antibodies specific for the phosphorylated form (ser473) of Akt, color developed with nickel-DAB (black) and counterstained with nuclear fast red. Representative stains of normal (A), mild dysplasia (B),

** 1. ENUMERATE THE COMMON CAUSES OF CELL INJURY AND THE MECHANISMS INVOLVED IN EACH a. Depletion of ATP -> Na pump failure -> water enters cell -> cells swell b. Mitochondrial damage -> can cause apoptosis c. Influx of calcium and loss of calcium homeostasis d. Accumulation of oxygen-derived free radicals (oxidative stress) e. Defects in membrane permeability -> water enters cell -> cell swells and even death f. Damage to DNA -> DNA and RNA changes (inherited/ acquired) -> if enzymes deficient -> substrate accumulates -> cells swell Damage to proteins -> enzymatic and structural proteins are not synthesized -> cells swell

2. GIVE THE MOLECULAR MECHANISMS RESPONSIBLE FOR CELL INJURY LEADING TO NECROSIS

INITIAL STIMULUS: Interference with energy metabolism Glycolysis modification of the function of the plasma membrane SIGNALLING PATHWAYS: mitochondrial respiration and oxidative phosphorylation are rapidly affected (stimulates anaerobic glycolysis) lack of ATP rapid increase of Ca (activation of other signalling mechanisms including kinases: early gene transcription; modify cytoskeletal function: bleb formation)

3. DEFINITION OF TERMS: a. NECROSIS- (from the Greek , "dead", , "death, the stage of dying, the act of killing") is the premature death of cells and living tissue. b. AUTOLYSIS- The term derives from the Greek words ("self") and ("splitting"). More commonly known as self-digestion, refers to the destruction of a cell through the action of its own enzymes. It may also refer to the digestion of an enzyme by another molecule of the same enzyme. c. HETEROLYSIS- If enzymatic digestion is accomplished by enzymes derived from cells other than the dead or dying ones; may occur as a result of endocytosis, in the course of which phagocytes ingest portions of dead or dying cells and segregate them into phagocytic vacuoles (phagosomes). d. KARYOLYSISdissolution of the cell nucleus with loss of its affinity for basicstains sometimes occurring normally but usually in necrosis e. PYKNOSISa degenerative condition of a cell nucleus marked by clumping ofthe chromosomes, hyperchromatism, and shrinking of the nucleus f. KARYORRHEXISa degenerative cellular process involving fragmentation of thenucleus and the breakup of the chromatin into unstructured granules

g. APOPTOSIS- also known as programmed cell death; the elimination of unwanted cells with minimum disruption of the surrounding
tissue. HYPOPLASIA- the failure of development of an organ to its full mature size APLASIA- the complete failure of development of an organ, commonly seen in paired organs e.g. kidney, adrenal, gonads. AGENESIS- lack or failure of development ATRESIA- absence or closure of a normal body orifice or tubular passage * 1. GIVE THE 3 BASIC MECHANISMS INVOLVED IN THE PATHOGENESIS OF INTRACELLULAR ACCUMULATION OF THE 3 CATEGORIES OF STOCKPILED SUBSTANCES AND EXAMPLES OF EACH 3 CATEGORIES OF (1) a normal cellular constituent (2) an abnormal substance, (3) a pigment, such as melanin, STOCKPILED SUBSTANCES accumulated in excess, such either exogenous, such as a hemosiderin, lipofuscin, as water, lipids, proteins, mineral or products ofinfectious bilirubin and carbohydrates agents, or endogenous, such as a product of abnormal synthesis or metabolism GENERAL MECHANISMS disordered homeostasis: uptake from exogenous source, endogenous synthesis, or breakdown or transport from cell insolubility of accumulated material in water

h. i. j. k.

2. DESCRIBE THE MECHANISMS INVOLVED IN THE FOLLOWING SUBCELLULAR ALTERATIONS a. LYSOSOMAL HETEROPHAGY AND AUTOPHAGY i. Lysosomal heterophagy

1. The cell takes up particles or molecules by the process of endocytosis, engulfing them in membrane-bounded vesicles or vacuoles that are 2. The endocytosed material enters lysosomes via intermediate membrane-bounded compartments known as endosomes. 3. In higher animals, heterophagy is most prominently used by leukocytes and macrophages. These specialized cells endocytose ii. Lysosomal autophagy 1. Cells segregate regions of their own cytoplasm within compartments that come to be bounded by single membranes and to receive lysosomal 2. Autophagic lysosomes take part in the remodeling of cells as part of the processes of development and during stressful circumstances. 3. They also participate, along with nonlysosomal enzymes and heterophagic lysosomes, in normal turnover of the body's constituentsthe
balanced synthesis and destruction through which most molecules of most cells are replaced by new molecules. enzymes. invasive microorganisms and use endocytosis in clearing debris and disposing of dead or senescent cells. formed at the cell surface.

b. HYPERTROPHY OF SMOOTH ENDOPLASMIC RETICULUM i. Eg: an exogenous metabolic demand on the liver cell by administering drugs that must be detoxified by the mixedfunction oxidase system. 1. Cytochrome P450 and other enzymes of this drug-metabolizing system reside in the smooth endoplasmic reticulum. The liver cell responds to the metabolic demand of detoxification by increasing the amount of smooth endoplasmic reticulum, with consequent hypertrophy of the cell. c. MITOCHONDRIAL ALTERATIONS i. Causes: 1. increases of cytosolic Ca2+ 2. reactive oxygen species

3. oxygen deprivation 4. injurious stimuli, including hypoxia and toxins 5. mutation in mitochondrial genes ii. Mechanisms: 1. formation of a high-conductance channel in the mitochondrial membrane, called the mitochondrial permeability transition pore a. leads to the loss of mitochondrial membrane potential, resulting in failure of oxidative phosphorylation and progressive depletion of ATP, culminating in necrosis of the cell. 2. sequester between their outer and inner membranes several proteins that are capable of activating apoptotic pathways a. these include cytochrome c and proteins that indirectly activate apoptosis inducing enzymes called caspases (leads to apoptosis ~~ remember embryology?? Hehehe ^_^ ). 3. GIVE EXAMPLES OF ABNORMALITIES OF CYTOSKELETON AND MEMBRANE SKELETON a. Plasma membrane alterations: blebbing, blunting, loss of microvilli b. Mitochondrial changes: swelling , appearance of small amorphous densities c. Endoplasmic reticulum: dilation, detachment of polysomes, intracytoplasmic myelin figures d. Nucleus: disaggregation of granular and fibrillar elements katemendoza2014 summarized this from robbins and cotran 8th ed + internet sources read your books for more info yr....happy studying! Sorry kng kulang ah, d ko kasi alam sagot dun..haha!! kinig nlng tau lec nila doc tpos sulat nyo nlng s free space ung tamang sagot.... ^_^

~1st tranx for 2nd