sbo1- patho

8/6/2019 sbo1- patho

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

***1. DESCRIBE THE PATHOGENIC MECHANISMS INVOLVED AND THE PROTOTYPE EXAMPLES OF EACH OF THE FOLLOWING

TYPES OF NECROSISTYPE OF

NECROSISCOAGULATION

NECROSISLIQUEFACTION

NECROSISENZYMATIC FAT

NECROSISCASEOUS NECROSIS

GANGRENOUSNECROSIS

DESCRIPTION form of necrosis in

which thearchitecture of deadtissues is preservedfor a span of at leastsome days

digestion of the dead

cells

focal areas of fat

destruction

caseous (cheeselike);

encountered most oftenin foci of tuberculousinfection

serious and potentially

life-threateningcondition that ariseswhen a considerablemass of body tissuedies

CHARACTERISTIC

tissues exhibit a firmtexture

tissue into a liquidviscous mass; creamyyellow because of thepresence of deadleukocytes (pus)

visible chalky-whiteareas (fatsaponification)Histologic exam:form of foci of shadowyoutlines of necrotic fatcells, with basophilic

calcium deposits,surrounded by aninflammatory reaction

friable white appearanceHistologic exam:collection of fragmentedor lysed cells andamorphous granulardebris enclosed within adistinctive inflammatory

border (granuloma)

affected areas turningblack and/or greenand/or yellowishbrown

MECHANISM denatures not onlystructural proteins butalso enzymes and soblocks the proteolysisof the dead cells; as aresult, eosinophilic,anucleate cells maypersist

microbes stimulatethe accumulation ofleukocytes and theliberation of enzymesfrom these cells

release of activatedpancreatic lipases intothe substance of thepancreas and theperitoneal cavity(acute pancreatitis);pancreatic enzymesleak out of acinar cellsand liquefy the

membranes of fat cellsin the peritoneum. Thereleased lipases splitthe triglyceride esterscontained within fatcells. The fatty acids,so derived, combinewith calcium.

a form of coagulativenecrosis, in that noliquefaction hasoccurred, butmicroscopically theaffected tissue appearscompletely structureless,under the microscopeand exhibits a greater

than usual affinity foracidic dyes such as eosin

reduced blood supplyto the affected tissues,which resultsin cell death
http://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Cell_(biology)


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EXAMPLES

COAGULATIVE NECROSIS:Gross: Image of the heart fromthis case, note the area of freshmyocardial infarction (arrows)in the anterior portion of theleft ventricle and extending intothe anterior portion of theinterventricular septum. Notethat the walls of the left and

LIQUEFACTION NECROSIS:Gross: the cerebral infarction atthe upper left heredemonstrates liquefactivenecrosis. Eventually, theremoval of the dead tissueleaves behind a cavity.

Histology: Liquefactive necrosis(arrow). The necrotic braintissue is


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ENZYMATIC FAT NECROSIS:Gross: a mesentery that has becomegorged with necrotic fat; some relativelynormal white fat is visible and necrotic fatin the middle of the mass

Histology: As with any necrotic condition,

inflammation will occur in fat necrosis,reflected by the large numbers of

ENZYMATIC FAT NECROSIS:Gross: On closer inspection, thegranulomas have areas of caseousnecrosis. This is very extensivegranulomatous disease. This

pattern of multiple caseatinggranulomas primarily in the upperlobes is most characteristic ofsecondary (reactivation)tuberculosis. However, fungalgranulomas (histoplasmosis,

GANGRENOUS NECROSIS:

Histology: intestinal gangrene:extensive necrosis of the entireintestinal wall. HE stain.

Gross: Seen here is the lower legfrom a below the knee amputation.The affected skin is dark red toblack and there is a large area of


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2. GIVE THE 3 GROUPS OF CELLS BASED ON THEIR REGENERATIVE CAPACITY, THE PROTOTYPE OF EACH AND THE CLINICALSIGNIFICANCE 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 inresponse 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 cellsc. 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 CELLULARADAPTATIONS OF GROWTH AND DIFFERENTIATION

TYPE OFCELLULAR

ADAPTATION

ATROPHYHYPERTROP

HY

HYPERPLASIA

METAPLASIA DYSPLASIAPHYSIOLOGIC PATHOLOGIC

DESCRIPTION

decrease incell size

increase in cellsize

increase in the number of cells when a differentiated cellof a certain type is

replaced by another celltype, which may be lessdifferentiated

abnormalchanges in

cellularshape, size,and/ororganization

1. Compensatory

hyperplasia-permits tissueand organregeneration

Eg: epithelial cells ofthe epidermis and intestine, liver hepatocytes, bone marrow cells,and fibroblasts

2. Hormonalhyperplasia-occurs mainly in

organs thatdependon estrogen

Eg: estrogen-dependentuterine cells undergohyperplasia andhypertrophy followingpregnancy

abnormal increase in cell

divisionEg: endometriosis
http://en.wikipedia.org/wiki/Cellular_differentiationhttp://en.wikipedia.org/wiki/Cellular_differentiation


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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

HYPERTROPHY: Myocardial CellHypertrophyCompare the nuclei of these hugemyocardial cells to the little endothelialcell nuclei that lie between them.Obviously these have more than 92chromosomes (normal for a sedentaryperson's heart).Athletic hypertrophy is good, but


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PHYSIOLOGIC HYPERPLASIA:Endometrial mucosa: normalendometrial gland in theproliferative phase of themenstrual cycleRecall that the proliferative phase ofthe cycle is an estrogen primed event.

Estrogen is a growth promoter andcauses the endometrial glandular cells

PATHOLOGIC HYPERPLASIA: Endometrial mucosa:pathologic endometrial hyperplasia due to unopposedestrogen stimulationWhen comparing this slide above, it is apparent that far moreglands are present and they are crowded together. This occurs

when a woman has too much estrogen and not enoughprogesterone, the latter a hormone that causes endometrialglands to undergo atrophy. Examples of unopposed estrogeninclude a postmenopausal woman who is taking estrogen withoutprogesterone to prevent osteoporosis or an obese woman, who

METAPLASIA: SquamousMetaplasia

The physiologic, normal processwhereby columnar epithelium maturesinto squamous epithelium. Squamousmetaplasia typically occupies part ofthe transformation zone. At thesquamocolumnar junction it appears asa "ghost white" or white-blue film withthe application of acetic acid. It isusually sharply demarcated toward the


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**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 swellb. Mitochondrial damage -> can cause apoptosisc. 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 deathf. Damage to DNA -> DNA and RNA changes (inherited/ acquired) -> if enzymes deficient -> substrate accumulates -> cells

swellDamage to proteins -> enzymatic and structural proteins are not synthesized -> cells swell

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

DYSPLASIA: Immunohistochemicallocalization of phospho-Akt inhuman bronchial biopsiesSections from human bronchialbiopsies were incubated withantibodies specific for thephosphorylated form (ser473) of Akt,color developed with nickel-DAB(black) and counterstained withnuclear fast red. Representative stains


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3. DEFINITION OF TERMS:

a. NECROSIS- (from the Greek , "dead", , "death, the stage of dying, the act of killing") is thepremature 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 anothermolecule of the same enzyme.

c. HETEROLYSIS- If enzymatic digestion is accomplished by enzymes derived from cells other than the dead or dying ones; mayoccur as a result of endocytosis, in the course of which phagocytes ingest portions of dead or dying cells and segregate them intophagocytic vacuoles (phagosomes).

d. KARYOLYSIS-dissolution of the cell nucleus with loss of its affinity for basicstains sometimes occurring normally but usually in necrosis

e. PYKNOSIS-a degenerative condition of a cell nucleus marked by clumping ofthe chromosomes, hyperchromatism, and shrinking of the nucleus

f. KARYORRHEXIS-a degenerative cellular process involving fragmentation of thenucleus and the breakup of the chromatin into unstructured granules

INITIAL STIMULUS:

Interference with energy metabolism Glycolysis

modification of the function of the plasma membraneSIGNALLING PATHWAYS:

mitochondrial respiration and oxidative phosphorylation are rapidlyaffected (stimulates anaerobic glycolysis)

lack of ATP

rapid increase of Ca (activation of other signalling mechanismsincluding kinases: early gene transcription; modify cytoskeletal


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g. APOPTOSIS- also known as programmed cell death; the elimination of unwanted cells with minimum disruption of the surroundingtissue.

h. HYPOPLASIA- the failure of development of an organ to its full mature sizei. APLASIA- the complete failure of development of an organ, commonly seen in paired organs e.g. kidney, adrenal, gonads.

j. AGENESIS- lack or failure of developmentk. 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 EACH3 CATEGORIES OFSTOCKPILED SUBSTANCES

(1) a normal cellular constituentaccumulated in excess, suchas water, lipids, proteins,and carbohydrates

(2) an abnormal substance,either exogenous, such as amineral or products ofinfectiousagents, or endogenous, such asa product of abnormal synthesisor metabolism

(3) a pigment, such as melanin,hemosiderin, lipofuscin,bilirubin

GENERAL MECHANISMS disordered homeostasis: uptake from exogenous source, endogenous synthesis,or breakdown or transport from cell

insolubility of accumulated material in water

2. DESCRIBE THE MECHANISMS INVOLVED IN THE FOLLOWING SUBCELLULAR ALTERATIONSa. LYSOSOMAL HETEROPHAGY AND AUTOPHAGY

i. Lysosomal heterophagy1. The cell takes up particles or molecules by the process of endocytosis, engulfing them in membrane-bounded vesicles or vacuoles that are

formed at the cell surface.

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

invasive microorganisms and use endocytosis in clearing debris and disposing of dead or senescent cells.

ii. Lysosomal autophagy1. Cells segregate regions of their own cytoplasm within compartments that come to be bounded by single membranes and to receive lysosomal

enzymes.

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 constituentsthebalanced synthesis and destruction through which most molecules of most cells are replaced by new molecules.

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 mixed-function oxidase system.

1. Cytochrome P450 and other enzymes of this drug-metabolizing system reside in the smooth endoplasmicreticulum. The liver cell responds to the metabolic demand of detoxification by increasing the amount of smoothendoplasmic reticulum, with consequent hypertrophy of the cell.

c. MITOCHONDRIAL ALTERATIONSi. Causes:

1. increases of cytosolic Ca2+

2. reactive oxygen species
http://humpath.com/spip.php?article10268http://humpath.com/spip.php?article15000http://humpath.com/spip.php?article8585http://humpath.com/spip.php?article8585http://humpath.com/spip.php?article10268http://humpath.com/spip.php?article15000http://humpath.com/spip.php?article8585http://humpath.com/spip.php?article8585


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3. oxygen deprivation4. injurious stimuli, including hypoxia and toxins5. mutation in mitochondrial genes

ii. Mechanisms:

1. formation of a high-conductance channel in the mitochondrial membrane, called the mitochondrial permeabilitytransition pore

a. leads to the loss of mitochondrial membrane potential, resulting in failure of oxidative phosphorylation andprogressive depletion of ATP, culminating in necrosis of the cell.

2. sequester between their outer and inner membranes several proteins that are capable of activating apoptoticpathwaysa. 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 microvillib. Mitochondrial changes: swelling , appearance of small amorphous densitiesc. Endoplasmic reticulum: dilation, detachment of polysomes, intracytoplasmic myelin figuresd. Nucleus: disaggregation of granular and fibrillar elements

katemendoza2014summarized this from robbins and cotran 8th ed + internet sources

read your books for more info ~1st tranx for 2nd 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.... ^_^

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