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181 Cards in this Set
- Front
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DESCRIPTION
8 ELEMENTS |
Location
Distribution Shape and Contour Size / Extent Colour Consistency / Texture Margins Special Features |
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LOCATION
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Indicate name of affected organ(s)
~~ ie lung or bronchioles Use precise anatomical terms ~~ ie subcutis, cranial lung lobe, pars esophagea Include any abnormal positions and or relationships to other organs ~~ ie attachment, rotation, displacement |
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DISTRIBUTION
3 TYPES |
Often the single most useful observation
Single Lesion Multiple Lesions Diffuse Lesions |
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SINGLE LESIONS
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Focal
~~ single lesion representing small portion of the entire organ Locally Extensive ~~ a single LARGE lesion involving a considerable amount of the entire organ Useful Terms ~~ Segmental - for segments of linear organs ~~ Unilateral, bilateral etc |
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MULTIPLE LESIONS
2 TYPES 2 KEY QUALIFIERS 5 USEFUL TERMS |
Multifocal
~~ multiple lesions throughout an organ separated by UNAFFECTED tissue Multifocal to Coalescing ~~ multiple lesions which merge together to create larger lesions Random ~~ scattered without any predictable pattern ~~ ie lesions caused by blood born infectious agents Zonal ~~ distributed throughout the organ according to predictable repetitive pattern ~~ ie bronchioles ~~ ie zones of hepatic lobule Miliary ~~ numerous small focal lesions Disseminated ~~ numerous small lesions evenly distributed throughout the whole organ or tissue Bilateral ~~ lesions in PAIRED organs ~~ lung, kidneys, brain Billaterlly Symetrical Generalized Distribution ~~ indicates all structures of an organ (ie glomeruli) or all organs of a system (ie lymph nodes) are affected Note can also quantify lesions |
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DIFFUSE LESIONS
|
Entire organ, tissue or specified subunit is involved
~~ easy to overlook because no contrast with normal Widespread or Extensive ~~ large portion of specimen , organ, tissue involved Transmural ~~ affecting the entire thickness of the wall of an organ or cavity |
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SHAPES
DIRTY DOZEN |
Spherical
Rectangular Rhomboidal Pyramidal Circular Dilated Wedge-shaped Reniform ~~ yes as in renal Striated Irregular Linear Reticular ~~ net like |
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SURFACE CONTROUR
14 DECORATIVE STYLES |
Bulging or Raised
Depressed Flat or Level Pitted Smooth Rough Corrugated or Rugose Crusted Eroded ~~ NOT through basment membrane ~~ tf no leakage of ISF ~~ tf no exudate or fibrin Ulcerated ~~ through basement membrane Umbilicated Nodular Papillated ~~ nipple shaped projections Villar ~~ numerous short hair like projections on membranes |
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SIZE
|
Metric Measure
% of organ affected |
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COLOUR
10 STANDARDS |
Black
White Grey Green Red Brown Mahogany Tan Yellow Transparent or combinations Avoid ISH !!! Avoid redundancy ~~ ie red in colour |
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CONSISTENCY AND TEXTURES
13 |
Must Touch
~~ tip for 4th yr don't describe texture if you can't touch it Friable ~~ crumbles easily when palpated Turgid ~~ hard due to internal fluid pressure Firm ~~ used as a moderate form of hard Rubbery ~~ slight increase in firmness Spongy Flaccid Hard vs Soft Strong vs Weak Fluid, semi liquid, viscuous, gelatenous pliable pitting elastic Fibrous ~~ strong as in tendon |
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MARGINS
5 |
Well Demarcated
~~ lesion has distinc, clearly defined boundary Poorly Demarcated ~~ boundary between lesion adn adjacent tissue is not sharp Indistinc Infiltrative ~~ invasive Expansile ~~ out of tissue ~~ ie wart |
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SPECIAL FEATURES
7 |
Weight
Odor pH Protein content Specific Gravity Fluorescence etc |
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MORPHOLOGICAL DIAGNOSIS
2 BIGGIES |
Main Disease PROCESSES
~~ inflammation - decribe exudate ~~ necrosis ~~ hemorrhage ~~ neoplasia ~~ hypertrophy ~~ etc Anatomical LOCATION ~~ precise Also Duration ~~ acute ~~ subacute ~~ chronic Severity ~~ mild ~~ mutltifocal ~~ diffuse Distribution |
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DIFFERENTIAL MORPHOLOGICAL DIAGNOSIS
|
Alternative diagnosis, since more than one interpretation may be possible based on gross characteristics of the lesion or set of lesions
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ETIOLOGICAL DIAGNOSIS
|
interpretation based on the cause of the lesions
~~ location ~~ etiologcal name of disease |
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EITIOLOGY
|
Cause
~~ ie name of bacteria |
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DEFINITIVE DIAGNOSIS
|
Name of Disease
|
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PATHOLOGY
DEFINITION |
Study of structural and functional consequences of diseases
|
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FOUR ASPECTS OF DISEASE
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Eitiology
Pathogenesis Morphologic Chandges Clincal Significance |
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LESION
|
A pathologic chane in the tissues
~~ avoid using this term at all costs!!! |
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HYPERPLASIA
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Increase in the NUMBER of cells in an organ or tissue
Usually results in an increased volume of the organ or tissue Only occurs in tissues which have cells capable of MITOTIC division Often occurs in conjuction with hypertrophy ~~ may be trigged by same external stimulus Physiologic or Pathologic |
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HYPERTROPHY
|
Increase in the size of cells through NORMAL METABOLIC processes
~~ synthesis of structural components ~~ increase in cytoplasm NOT due to cellular swelling ~~ ie influx of water Generally restricted to ~~ skeletal muscle ~~ cardiac muscle ~~ smooth muscle ~~ - ~~ often enlargement is due to hyperplasia as in uterus Mechanisms ~~ Pathologic ~~ Physiologice ~~ via increased funtional demand ~~ via specific hormonal stimulation |
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ORGAN HYPERTRPOPY
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Increase in size of organ due to increase in size but NOT number of cells
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CELLULAR ATROPHY
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Shrinkage in SIZE of cell by loss of cell substance
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ORGAN OR TISSUE ATROPHY
|
Decrease in size of an organ or tissue AFTER it has reached NORMAL size
`` caused by LOSS of cells or DECREASED cell size Physiologic ~~ ie early embryonic development ~~ ie female reproductive organs Pathologic ~~ local ~~ generalized |
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METAPLASIA
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Reversibel change in which on ADULT cell type (Epithelial or Mesenchymal) is replaced by another NORMAL adult cell type that does NOT normally belong in that location
May represent an adaptive substitution of cells that are sensitive to stress by cell types better able to withstand the adverse environment Metaplasioa of respiratory columnar sqamnous epi tintrache, bronchi andbronchioles exposed to chronic irritation ~~ ie cigarette smoke ~~ ie lung worms Vit A deficiency ~~ tf Night Blindness aka Nyctolopia ~~ tf induction of squamous metaplasia in Lacrimal duct ~~ tf Xerophthalmia via decreased tears ~~ in birds squamous metaplasia in esophageal glands and respiratory epi Estrogen producing Sertoli Cell tumor ~~ tf squamous metaplasia of prostate epi |
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OSTEOPOROSIS
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Reduction in the quantity of bone
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CACHEXIA
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General weight loss and wasting
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AUTOPHAGY
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Segregation and disposal of damaged organelles within a cell
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CARDIAC HYPERTROPHY
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Physiologic
~~ ie increased exercise Pathologic ~~ ie systemic hypertension ~~ ie semilunar stenosis Triggers ~~ Mechanical - ie stretch ~~ Trophic - polypeptide growth factors, vasoactive agents (angiotensin, alpha adrenergic agonists) Significance ~~ eventually linited by blood supply and or nutrient and waste flow ~~ tf increased burden can not be compensated for ~~ tf "heart failure" ~~ degenerative changes ~~ - ~~ lysis ~~ - ~~ loss of myofibrillar contractile elements ~~ - ~~ apoptosis or necrosis |
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HYPERTROPHY
TUNICA MUSCULARIS GASTRIC PYLORUS DOGS |
Postprandial vomiting
|
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HYPERTROPHY
TUNICA MUSCULARIS ILEUM HORSES |
Functional obstruction
Predisposition to fatal intestinal incidents |
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HYPERTRPOPHY
TUNICA MUSCUALRIS ESOPHAGUS DUE TO OBSTRUCTON AT CARDIA DUE TO ULCERATION AT PARS ESOPHOGEA HORSES |
Funtional obstruction
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PHYSIOLOGIC HYPERPLASIA
|
Usually driven by hormones
Hormone induced hyperplasia increases the function capacity of tissue when needed ~~ hyperplasia of endrometrium of uterus ~~ accompanied by hypertophy of smooth muscle of uterus Compensatory Hyperplasia increases tissue mass after damage of partial loss ~~ hepatocellular compensator hyperplasia after loss of hepatic tissue ~~ - ~~ Prometheus ~~ - ~~ rats replace lobes in weeks ~~ unilateral compensatory renal hyperplasia after pephrectomy ~~ bone marrow hyperplasia after loss of blood |
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HYPERPLASIA
MECHANISMS 3 |
Generally
Increased local production of Growth Factors Increased levels of Growth Factor Receptors on responding cells Activation of specific Intracellular signalling pathways All of which lead to production of transcription factors leading to gene expression for ~~ growth factors ~~ receptors for groth factors ~~ cell cycle regulators Resuts in Cellular Proliferation |
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PATHOLOGIC HYPERPLASIA
2 DISTINGUISH FROM NEOPLASIA |
Excessive Hormonal Stimulation
Exessive production of Growth Factors Hyperplastic tissue responds to normal regulatory control mechanisms ~~ tf when stimulus removed hyperplasia STOPS ~~ in Neoplasia proliferative response continues in absence of stimulus However, Pathologic hyperplasia provides opportunity for development of neoplasia |
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CYSTIC ENDOMETRILA HYPERPLASIA
BITCH |
Secondayr to an exaggerated response of estrogen primed endometruum to progesterone.
Also associated with administration of long acting progestational compounds to delay onse of estrus in bitches |
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LASONIA INTRCELLULARIS
PIGS |
Bacteria invading enterocytes causes severe hyperplasia of SI mucosa
|
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PROSTATIC HYPERPLASIA
INTACT DOGS |
Significant interference with defecation
Moderate interference with micturation |
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LYMPHOID HYPERPLASIA
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Activation of lymph nodes due to inflamatory processes in drainage field
Could also be a neoplasia metastisizing along lyphatic system |
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DISUSE ATROPHY
|
Skeletal muscle hypotrophy and Osteoporosis as a result of disuse
~~ ie limb in cast ~~ lack of wieght bearing Initial rapid decrease in cell size is reversable if activity is resumed in short period of time Prolonged disuse results in loss of myoctyes |
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DENERVATION ATROPHY
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Normal function of skeletal muscle requires neuronal stimulation
~~ ie trauma to brachial plexus |
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ATROPHY DUE TO DIMINISHED BLOOD SUPPLY
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Pathological process in kidneys may produce diffuse Fibrosis
Contracting fibrotic tissue interferes with blood supply Partially contributes to decrease in parenchymal mass of kidney |
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PRESSURE ATROPHY
|
Tissue compression for any lenght of time can cause atrophy
In part caused by compromise of blood supply Enlarging benign tumor compresses surrounding tissue Hydronephrosis |
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HYDRONEPHROSIS
|
Loss of medullar tissue as a result of pressure atrophy created by accumulation of urine due to urinary tract blockage
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NUTRITION ATROPHY
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CACHEXIA (aka Muscle Wasting)
~~ prolonged protein / calrie deficits ~~ - ~~tf use of muscle protein for GNG ~~ chronific inflammatory diseases and cancer ~~ - ~~ tf chronic overproduction of Tumor Necrosis Factor ~~ - ~~ tf appetite suppression and muscle atrophy SEROUS ATROPHY OF ADIPOSE TISSUE ~~ prolonged severe negative caloric balance ~~ normal fat replaced by water gelatinous fluid ~~ assumed to be ISF seeping into empty space vacated by triglyceride storage vacuoles ~~ starvation ~~ poor dentition ~~ severe enteric disease ~~ increased energy demands `~ - ~~ pregnancy ~~ - ~~ cold weather |
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JUST TO MIX THINGS UP
WHAT IS THE DIFFERENCE BETWEEN NEOPLASIA AND ADENOMA |
Neoplasia
~~ any unregulated cellular proliferation (ie any tumor) in any tissue Adenoma ~~ BENIGN tumor in a GLAND |
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ENDOCRINE STIMULATION ATROPHY
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Loss of or Exagerated Endocrine Stimulation
Loss ~~ atrophy of mammary glands and reproductive organs after pregnancy Exagerated ~~ long term exogenous adiminstration of corticosteroids ~~ tf decreased ACTH ~~ tf bilateral adrenal cortical atrophy ~~ tf iatrogenic hyperadrenocorticism (aka Cushings Disease) ~~ also dermal adnexal atrophy ~~ Sertoli cell tumor may produce increased estrogen ~~ tf testicular atrophy |
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SENILE ATROPHY
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Aging process is associated with cell loss
tf tissues without mitotic capabilty shrink Senile Brain Atrophy ~~ loss of brain cells |
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MECHANISMS OF ATROPHY
3 |
Atrophic cells have diminshed function due to reduction of structural components but are NOT dead
If blood supply, nutrition and trophic stimulation continue to diminish APOPTOSIS may induced by the same signals that produce atrophy LYSOSOMES ~~ acid hydrolases ie cathepsins ~~ other proteolytic enzymes ~~ tf degrade emdocytosed proteins from ~~ - ~~ extracellular environment ~~ - ~~ cell surface ~~ - ~~ some cellular components UBIQUITIN - PROTEASOME PATHWAY ~~ degratdation of cytosolic and nuclear proteins ~~ conjugated to Ubiquitin ~~ degraded in Proteasome ~~ induced by ~~ - ~~ Tumor Necrosis Facor ~~ - ~~ Glucocorticoids ~~ - ~~ Thyroid Hormone AUTOPHAGY ~~ segregation and disposal of damaged organelles via autophagic vacuoles ~~ large increases in number of autophagic vacuoles are associated with autophagy ~~ lysosomes merge and inject hydrolytic contents ~~ some cell debris resists digestion and remain as membrane bound cytosolic Sarcophagi ~~ - ~~ ie Lipfuscin ~~ - ~~ tf "Brown Atrophy" |
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POST NECROTIC ATROPHY
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Degenerative tissue losses without apparent necrosis
Different mechanisms from Atrophy Viral destruction of villus enterocytes ~~ ie carona virus Infectious, chemical or other injury that produce shrunken, scarred end stage of organs |
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CONNECTIVE TISSUE METAPLASIA
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Formation of Mesenchymal Tissues
~~ cartilage ~~ bone ~~ adipose tissue in tissues that normally do not contain these elements Less clearly seen as an adaptive response Myositis Ossificans ~~ bone formation in muscle Ossifying Pachymeningitis ~~ bone formation in the pachymeninx (dura mater) of spinal cord Pulmonry ossification |
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SIGNIFICANCE OF ADAPTATIONS
WORDS OF WISDOM |
Virtually all lesions are significant
Some will cause clincal signs Others may be significant only as pieces of a comlex puzzle Each lesion has a story to tell If we are clever enough to listen |
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PLASMA MEMBRANE
|
Most important structure Pathogenically
Barrier between cell and environment ~~ tf semipermeable membrane ~~ tf diffusion, passive, active transport Plasma membrane proteins important ~~ cellular antigens ~~ receptors for hormones ~~ cell to cell interactions ~~ cell to substrate interactions ~~ recognition by pathogens, neutrophils, macrophages Morphological Specilizations ~~ microvilli ~~ myelin ~~ intracellular attachements |
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NUCLEUS
|
Heterochrmatin
~~ condensed ~~ intensely basophilic Euchromatin ~~ dispersed ie ACTIVE ~~ lightly staining ~~ prominent in cells actively synthesizing protein and RNA ~~ - ~~ tf rapidly dividing cells ~~ - ~~ tf neoplasia or hyperplasia ~~ specific patterns indicate Apoptosis |
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NUCLEOLUS
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Site of synthesis of most components of Ribosomal RNA
~~ tf significant in neoplasms |
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CYTOPLASMIC ORGANELLES
|
High Nucleic Acid Content vs protein produces basophilia
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MITOCHONDRIA
|
Energy Production via oxidative phosphorylation
Cell Death is associated with drastic damage to mitochondria |
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ROUGH ENDOPLASMIC RETICULUM
|
Protein Synthesis via Ribosomes
~~ tf basophillia ~~ mainly secretatory proteins ~~ - ~~ free ribos for intracellular proteins ~~ high protein secretion common in proliferative cells |
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GOLGI APPARATUS
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Packaged produced proteins into Secretatory vesicles
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SMOOTH ENDOPLASMIC RETICULUM
|
No ribos
Membranous carrier for metabolic and biosynthetic enzymes Site of metabolosis of toxins and drugs in hepatocytes |
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HETEROPHAGY
|
Lysosomaldigestion of material ingested from extracellualr environment
Common activity in Professional Phagocytes ~~ neutrophils ~~ macrophages |
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AUTOPHAGY
|
Lysosomal digestion of cell's own components
Removal of organelles damaged in cell injury Cellular remodeling during differntiation Pronounced in cells undergoing atrophy ~~ nutrient deprivation ~~ hormonal involution |
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FILAMENTS
|
Composed of Actin, myosin and associated regulatory proteins
Proper functioning critical for Leukocyte movement and phagocytosis |
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MICROTUBULES
|
Polymerization of Tubulin protein
Rapid assembly and dissasembly Essential for leukocyte migration and phagocytosis Defects can inhibit ~~ sperm motility ~~ immobilize cilia of respiratory epi ~~ tf inabilty to clear inhaled bacteria ~~ tf bronchiectasis ~~ - ~~ aka immotile cilia syndrome ~~ - ~~ aka Kartagener's Syndrome |
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INTERMEDIATE FILAMENTS
5 NAMES 5 CELL TYPES DONT YOU LOVE THAT HISTOLOGICAL MINUTIA NOW BUT WE DO CARE - WHY? |
flexible intracellular scaffold
Keratin filaments - epi cells Neurofilaments - neurons Desmin Filaments - muscle cells Vimentin Filaments - connective tissue cells Glial Fibrillary Acidic Protein (GFAP) Important in the identification of neoplasms ~~ identifies tissue type |
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NECROSIS
|
Death of cells and tissues in the living animal
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DEGENERATION
|
Reversible deteriorating pathologic change in cells or tissues
~~ functions impaired or destroyed |
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REVERSIBLE CELL INJURY
2 HALLMARKS |
Functional and morphological changes
~~ reversible if the damaging stimulus is removed Reduced Oxidative Phosphorylation ~~ tf reduced ATP level Cellular Swelling ~~ loss of ion and fluid homeostasis ~~ changes in ion and protein concentration ~~ - ~~ decrease ATPase activity ~~ - ~~ lactate and ATP and creatine phosphate breakdown products etc ~~ water influx Also Fatty Change ~~ hypoxic injury ~~ - ~~ tf decreas beta oxidation ~~ toxic or metabolic injury ~~ - ~~ tf inability to metabolize fatty acids |
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REVERSIBLE CELL INJURY
GROSS CHANGES 3 |
Mild Enlargement
Turgid Pale ~~ depends on cause of degeneration |
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REVERSIBLE CELL INJURY
LIGHT MICROSCOPE CHANGES 5 |
Cell Swelling
Cloudy Swelling ~~ altered staining characteristics Vacuolar (aka Hydropic)Degeneration ~~ vacuoles in cytoplasm ~~ distended organelles esp ER ~~ lipid droplets Ballooning Degeneration ~~ big vacuole Lipidosis (aka Fatty Change) ~~ accumulation of excessive intracellular lipid ~~ esp hepatocytes - high fat metabolism ~~ lipid filled vacuoles in cytoplasm |
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REVERSIBLE CELL INJURY
6 ULTRASTRUCTURAL CHANGES |
Plasma Membrane
~~ blebbing ~~ blunting of microvilli ~~ myelin figures ~~ loosening of intercellular attachements Mitochondrial Swelling Dilation of ER (aka Vacuolation ~~ detachment and dsaggregation of ribosomes |
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HEPATIC LIPIDOSIS
|
Reversibly injured cells often cannot adequately carry out normal funtions but are able to maintain homeostasis
~~ tf reamain alive Most common in ~~ hepatocytes ~~ renal tubular epithelium Liver ~~ if most hepatocytes are affected ~~ - ~~ diffusely yellow, greasy friable grossly ~~ if hepatocytes affected zonally ~~ - ~~ reticular pattern grossly Mechanisms ~~ lipids enter as Free Fatty Acids ~~ most esterfied to Triglycerides ~~ some utilized for cholesterol esters or phospholipids ~~ some degraded to ketones ~~ for export TGs complexed with Apolipoprotein or liid acceptor protein to form lipoproteins ~~ accumulation of TG via ~~ - ~~ Exessive delivery of FFA via negative caloric balance ~~ - ~~ toxic injury impairs ability to synthesize apolipoprotein ~~ - ~~ Hypoxia interferes with FFA oxidation in ER |
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HYPOXIC DAMAGE
|
Damage due to lack of oxygen delivery
Normal Circulation ~~ tf anemia ~~ tf CO, CN toxicity etc |
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ISCHEMIA DAMAGE
|
Absence of Circulation
Low O2 Low Nutrients High Lactic Acid High Metabolic Waste |
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STEROID HEPATOPATHY
|
Massive Glycogen Accumulation
Induced by high levels of Corticosteroids Enlarged and Bronze coloured grossly Feathery Vaculation of hepatocytes Histologically ~~ intially microvacuolar ~~ chronically macrovacuolar |
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HYPERCORTICOSTEROIDISM
|
Steroid Hepatopathy
Dermal Degeneration Skeletal Muscle Atrophy All lead to pot belly |
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HEPATIC RETICULAR PATTERN
|
Zonal !!!!!
~~ tf Hypoxia ~~ - ~~ ie right heart failure ~~ tf Ischemia ~~ tf Metabolic Changes ~~ tf Toxic Change Almost NEVER infection ~~ randam via septic shower from blood |
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IRREVERSIBLE CELL INJURY
2 MAJOR SIGNS 2 TYPES OF DEATH |
Depth of injury from which cell cannot recover
Severe Mitchondrial Damage Loss of Membrane Functionality Necrosis ~~ severe membrane damage ~~ - ~~ tf lysosomal enzymes enter cytoplasm ~~ - ~~ acid hydrolases active in high lactic acid low pH environment of injured cell ~~ - ~~ tf leakage of cellular contents Apoptosis ~~ noxious stimuli esp DNA damaging ~~ nuclear dissolution without complete loss of membrane integrity |
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CELLULAR NECROTIC CHANGES
|
Spectrum of morphologic changes that follow cell death in living tissue
Largely result from progressive degraditive action of released enzymes Tissues Fixed immediately are dead but NOT necrotic Necrosis is the gross and histologic correlate of cell death occurring in the setting of irrreversible injury. |
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NECROSIS
CLINICAL IMPORTANCE |
Leakage of intracellular prodteins across degraded cell membrane
~~ tf reliable detection of tissue specific cellular injury ~~ - ~~ skeletal muscle CK ~~ - ~~ Hepatocytes ALT |
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MORPHOLOGY
CELL INJURY AND NECROSIS TIMING |
All stressors and noxious influences produce effects first at molecular or biochemical level
Time lag between stress and morphologic changes Histochemical and Ultrastructural techniques ~~ show changes minutes to hours after ischemic events Gross examination or light microscopy ~~ several hours to show ischemic events ~~ 4 - 12 hrs for myocardial infarction ~~ - ~~ yet irrevesible injury occured 20 - 60 min ~~ - ~~ tf cant see infarcts that kill |
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MORPHOLOGY
CELL INJURY AND NECROSIS CYTOPLASMIC 8 |
Cytoplasm Swollen
Increase cytoplasmic eosinophilia ~~ loss of ribos ~~ increased binding to denatured proteins Hyalinized cytoplasm ~~ glassy appearance Vacuolated cytoplasm Calcification ~~ Sarcoplasmic Reticulum ~~ ISF Overt discontinuities in plasma and organelle membranes Marked dilation of mitochondria ~~ large amorphous densisties Intracytplasmic Myelin Figures |
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MORPHOLOGY
CELL INJURY AND NECROSIS NUCULEAR 3 |
Nonspecific Breakdown of DNA results in in typical chronology:
Pycnosis ~~ nuclear shrinkage ~~ increased basophillia ~~ - ~~ condenstation of DNA Karyolysis ~~ basophilia of chrmatin fades ~~ - ~~ degrading activity of DNase Karyorrhexis ~~ pyknotic or partially pyknotic nucleus undergoes fragmentation |
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COAGULATIVE NECROSIS
|
Preservation of basic outline of cogulated cell
~~ at least some days Affected tissues ~~ pale ~~ swollen ~~ firm ~~ demarcated hyperemic (reaction) zone ~~ - ~~ more friable than surrounding tissue ~~ - ~~ via proteolytic destruction of cytoskeleton ~~ cellular acidosis becomes severe enough to impair proteolytic enzymes ~~ cogulation of cytoplasmic proteins ~~ reduced blood flow via cell swelling in necrotic area Renal INfarct ~~ acidophilic coagulated anucleate cells persist for days Characteristic of Hypoxic death of cells ~~ in all tissues except brain Impaired circulation preventing leuckocyte invasion may result in ~~ coagulative focus persisting for weeks as sequestrum Microscopic `` Eosino;hillic shadow `` Cellular shape & tissue organization still apparent `` Nucleus usually lost ~~ - ~~ |
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LIQUEFACTIVE NECROSIS
|
Characteristic of focal pyogenic bacterial infections
~~ stimulate accumulation of ~~ - ~~ inflammatory cells ~~ - ~~ proteolytic enzymes ~~ tf affected tissue liquefied Malacia `` Hypoxic death of CNS cells also evokes lquefactive necrosis Liquefaction completely digest dead cells ~~ tf liquid viscous mass ~~ if accute inflammation material is creamy yellow ~~ - ~~ via dead leucocytes ~~ - ~~ tf pus |
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CASEOUS NECROSIS
|
Distinctive form of Coagulative necrosis
Foci infected with highly toxigenic bacteria ~~ mycobacterium bovis ~~ Corynebaceruim pseudotuberculossis Cheesy white and dry gross appearance Microscopically ~~ amorphous granular debris ~~ fragmented coagulated cells ~~ enclosed within distinctive granulomatous inflammatory process TISSUE ARCHITECTURE IS COMPLETELY OBLITERATED Not common |
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GANGRENOUS NECROSIS
|
Not a distinctive process of cell death
Blood loss to extremity results in coagulation necrosis `` Dry Gangrene ~~ subsequent bacterial infection modifies coagulative necrosis ~~ - ~~ liquefactive aciton of leukoxytes attracted to bacteria ~~ WET Gangrene |
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FAT NECROSIS
|
Not a specific pattern of necrosis
Focal areas of fat destruction ~~ typically result of release of activated pancreatic lipases ~~ within and around inflamed pancreas ~~ activated pancreatic enzyme escape from acinar cells and ducts ~~ liquify fat cell membranes ~~ activated lipases split the triglyceride esters within ~~ released fatty acids combine with calcium ~~ produce gossly visble chalk white areas (aka Saponification) Histologically ~~ foci of shadowy outlines of necrotic fat cells ~~ basophillic calcium deposits ~~ surrounded by inflammatory reaction If not cleared in liveing patient ~~ calcium salts and other minerals aggregate ~~ tf calcifiation ~~ aka Dystrophic Calcification |
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DISQUISES OF NECROSIS
3 BIG ONES BUT WHAT GIVES US STRENGHT IN THIS PERPLEXITY |
Classic Gross Appearance
~~ swollen demarcated area of pallor ~~ short lived ~~ gives way to many sequels ~~ BUT LOSS OF STRENGH PERSISTS THROUGHOUT Colour ~~ most changes due to influx of red blood cells ~~ - ~~ subsequent breakdown ~~ mineralization ~~ inflammation ~~ loose tissues like lung and subcutis ~~ - ~~ swelling of dying cells does not prevent massive inrush of blood at periphery ~~ - ~~ tf red appearance from start of process ~~ Abundant Dystrophic Calcification ~~ - ~~ white granular gritty appearance Demarcation by inflammatory reaction of leukocytes and erthrocytes ~~ red and white ring ~~ exists only at initial stages ~~ subsequent blood leakage and inflammatroy infiltration Texture ~~ initial texture allways weaker or more friable ~~ coagulation necrosis tissue feels firm via turgidity of cell swelling ~~ - ~~ but is friable and ruptures easily if palpated ~~ will liquify after a few days ~~ healing process ~~ - ~~ proliferation ~~ - ~~ angioblasts ~~ - ~~ fibroblasts (granulation tissue) ~~ deposits collagen (fibrosis) ~~ - ~~ tf tissue becomes firm |
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SIGNIFICANCE OF NECROSIS TO ANIMAL
4 DEPENDS |
Depends on
~~ size ~~ site ~~ speed of progression ~~ sequels Focus of necrosis within brainstem or myocardial conductions system is almost always fatal Organs with large functional reserve such as liver and kidney can sustain large areas of necrosis Rapid loss clinically more significant than slow loss Sequels such as inflammation and scaring may be more important than necrosis ~~ ie esophageal constriction ~~ ie endothelial repair Focal necrosis on a growth plate causes limb deformity ~~ healthy portion continues osteogenisis |
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SIGNIFICANCE OF NECROSIS OF DIAGNOSTICIAN
|
Character and location of necrotic lesion(s)
~~ important clues about the cause and pathogenesis Group of lesions ~~ create pattern typical of specific disease ~~ footprints of disease ~~ even though lesion themselves have no functional significance |
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DRY GANGRENE
|
Ischemic Necrosis of Extremities
`` bacterial infection absent |
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TYPICAL NECROTIC COLOUR PROGRESSION
3 STEPS |
Cellullar swelling excludes blood
`` tf pale firm tissue `` 1st 24 hrs Degradation of cells lowers pressure and blood rushes in `` tf red `` next 24 hrs Macrophages remove blood and fibrous tissue forms `` tf pale and contracted |
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FROST BITE AND LOOSE TISSUE
HAVE WHAT IN COMMON |
Initially Red in Colour when necrotic
Loose Tissue `` cellular swelling does not compress blood vessels Frost Bite `` high water content tissue damaged most `` ie blood vessels tf extravasated blood |
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APOPTOSIS
|
Pathway of cell death that is induced by a tightly regulated intracellular energy dependent program
Cells destined to die activate enzymes that degrade the cell's own nulear DNA and cytoplasmic proteins |
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APOPTOSIS
SEVEN SCINTTILATING FACTS |
Cell Shrinks and fragments
Energy Dependent Regulated enzymatic degradation of DNA and cytoplasmic proteins Plasma membrane remains intact `` tf no leakage Avid phagocytosis via surface ligands No or low inflammatory response `` bc no leakage `` bc rapid phagocytosis |
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NECROSIS
AS OPPOSED TO APOPTOSIS |
Cell Swells
Loss of membrane integrity Enzymatic digestive free for all Loss of energy production Often inflammatory reaction |
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APOPTOSIS AND NECROSIS
DO THEY COEXIST |
Sometimes
|
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PHYSIOLOGIC APOPTOSIS
4 EXAMPLES |
Programmed destruction of cells during embryogenesis
`` implantation `` organogenisis `` developmental involution `` metamorphosis Hormone dependent involution in adult `` reproductive cycle endometrial cell breakdown `` development and regression of mammary glands Cell Deletion in proliferating cell populations `` maintaining constant number of intestinal crypt epithelia Death of old cells that have done their duty `` lymphocytes after the storm `` `` an unemployed lymphocyte is a bad thing.. |
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PATHOLOGIC APOPTOSIS
5 EXAMPLES |
DNA Damage via radiation, cytotoxic drugs etc
`` repair mechanisms overwhelmed by injury `` tf apoptoptic pathways initiated `` avoids potential damage of mutant cell / proteins ER stress `` induced by accumulation of unfolded proteins `` triggers apoptotic pathways Pathologic atrophy in parenchymal organs `` ie via duct obtstruction Cell death in tumors `` most frequently during regression `` can also occur in actively growing tumors Cell death induced by Cytotoxic T Cells `` defense mechanism against viruses and tumors `` eliminates virus infected cells `` eliminates neoplastic cells `` responsible for rejection of transplants |
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APOPTOSIS
5 MORPHOLOGIC CHARACTERISTICS IDENTIFIY THE MOSTEST |
Cell Shrinkage
`` smaller in size `` dense cytoplasm `` organelles normal but tightly packed Chromatin Condensation `` most characteristic feature of apoptosis `` peripheral aggregation into dense masses `` nucleus breaks into two or more fragments Cytoplasmic Blebs and Apoptotic bodies `` first shows extensive surface blebbing `` then fragments into membrane bound apoptotic bodies `` `` cytoplasm `` `` tightly packed organelles `` `` with or without nuclear fragments Phagocytosis of Apoptotic Cells or cell bodies `` usually by macrophages `` apoptotic cells express ligands for macrophages `` `` tf early recognition `` `` tf no release of cellular components `` `` tf no inflammation Plasma membrane remains intact during apoptosis |
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APOPTOSIS
HISTOLOGICAL PERSPECTIVES TAKE 5 |
Intensely Eosinophilic cytoplasm
Dense nuclear chromatin fragments Single cells or small clusters of cells Apoptotic cell `` round or oval mass Considerable apoptosis can occur before histologically apparent `` cell shrinkage `` rapid formation of apoptotic bodies `` rapid phagocytosis `` lack of inflammation |
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NECROSIS vs APOPTOSIS
EIGHT HANDY FEATURES TO THINK ABOUT |
Distribution
Cell Size Nucleus Plasma Membrane Cellular Contents Adjacent Inflammation Physiologic vs Pathologic Energy |
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NECROSIS vs APOPTOSIS
DISTRIBUION |
Distribution
`` often contiguous cells vs `` Usually single cells |
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NECROSIS vs APOPTOSIS
CELL SIZE |
Enlarged via swelling
vs Reduced via shrinkage |
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NECROSIS vs APOPTOSIS
NUCLEUS |
Pyknosis
Karyorrhexis Karyolysis vs Fragmentation into nucleosome size |
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NECROSIS vs APOPTOSIS
PLASMA MEMBRANE |
Disrupted
vs Intact `` altered structure `` esp orientation of lipids |
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NECROSIS vs APOPTOSIS
CELLULAR CONTENTS |
Enzymatic Digestion
`` may leak out of cell vs Intact `` may be released in apoptotic bodies |
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NECROSIS vs APOPTOSIS
ADJACENT INFLAMMATION |
Frequent
vs Rare to None |
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NECROSIS vs APOPTOSIS
PHYSIOLOGIC PATHOLOGIC |
Invariable Pathologic
`` ie consequence of irreversible cell injury vs Often Physiologic `` eliminating unwanted cells Can be pathologic `` `` cell injury esp DNA damage |
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NECROSIS vs APOPTOSIS
ENERGY |
Does not require energy
vs Requires energy |
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MECHANISMS OF APOPTOSIS
TWO PHASES TWO PATHWAYS |
Initiation Phase
`` capases become catalytically active Execution Phase `` caspase enzymes act to cause cell death Initiation of apoptosis occurs principally via signals from Extrinsic Pathway `` aka Receptor Initiated `` aka Death Receptor Initiated Intrinsic Pathway `` aka Mitochondrial Both pathways converge to activate caspases |
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EXTRINSIC AKA DEATH RECEPTOR INITIATED PATHWAY
|
Initiated by engagement of cell surface death receptors
`` variety of cells ie Fas (CD95) Protein `` Fas binds ligant `` associated death domain initiates activation of caspase-8 `` `` C protein driven `` `` Cleaves Aspartate `` `` Degrades `` subsequently triggers execution of apoptosis |
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INTRINSIC AKA MITOCHONDRIAL PATHWAY
|
Result of increased mitochondrial permeability
`` release of pro apoptotic molecules into cytoplasm `` `` cytochrome C `` without involvement of death receptors Reduced production of anti apoptotic members `` via lack of trophic hormones or cell damage `` tf anti apoptotic Bcl-2, Bcl-x of Bcl-2 family proteins `` replaced by pro apoptotic Bak, Bax of Bcl-2 family proteins `` tf increased mito membrane permeability `` tf leakage of messangers of death aka Cytochrom C `` tf activation of caspase-9 `` tf subsequent triggering of apoptosis |
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APOPTOSIS
EXECUTION PHASE |
Final phase of apoptosis
Mediated by proteolytic cascade of caspase enzymes `` more than 10 members `` initiators `` `` ie caspase 8 and 9 `` executioners `` `` ie caspase 3 and 6 After initiator caspase is activated `` enzymatic death program set in motion `` rapid sequential activation of executioner caspases `` tf cleavage of `` `` cytoskeleton `` `` nuclear matrix proteins `` tf activation of endonucleases `` `` cellular fragmentation `` `` formation of apoptotic bodies |
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APOPTOSIS
REMOVAL OF DEAD CELLS |
Dying cells secrest soluble factors that recruit phagocytes
Facilitates prompt clearance of apoptocic cells `` tf no secondary necrosis `` tf no release of cellular contents `` tf no inflammation Surface receptors on apoptotic cells and fragments bind phagocytes Efficient process `` tf dead cells disappear without a trace `` tf no inflammation |
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APOPTOSIS
NAME 4 EXAMPLES |
Growth Factor Deprivation
DNA Damage Mediated Cytotoxic T-Lymphocyte Mediated Dysregulated |
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APOPTOSIS
GROWTH FACTOR DEPRIVATION |
Hormone sensititive cells
Lymphoctes `` not situmlated by anitgens and cytokines apoptosis triggered by intrinsic pathway `` excess of pro apotototic members of Bcl family relative to anti apotototic |
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APOPTOSIS
DNA DAMAGE |
aka Genotoxic Stress
`` radiation `` chemotherapeutic agents Initiates mechanism involving tummor suppressor gene P53 `` aka Correct or Die `` `` best said in heavy Transalvanian accent P53 accumulates when DNA is damaged `` arrests cell cycle `` `` allows time fro repair `` if DNA repair process fails `` `` p53 stimulates production of pro apoptotic members of Bcl Family `` `` tf leakage of mitochondrial membrane `` `` tf cytochrome c leakage `` `` tf activation of caspases Note - when p53 mutated or absent `` cell incapable of inducing apoptosis `` survival favored `` favorite of certain cancers |
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APOPTOSIS
CYTOTOXIC T LYMPHOCYTE |
Bypasses upstream signalling events
Recognizes foreign antigens on infected cells Secretes Perforin `` transmembrane pore forming molecule `` allows entry of Granzyme B Granzyme B cleaves aspartate residues `` tf activates cellular caspases `` tf directly induces Execution Phase of apoptosis Cytotoxic T Lymphocytes also express FasL `` tf bind Fas receptors `` tf induce Extrinsic Pathway |
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APOPTOSIS
DYSREGULATED |
Too Little or Too Much
Inappropriately low rate of apoptosis `` prolong cell survival `` reduce turnover of abnormal cells `` accumlated cells can give rise to `` `` neoplasia `` `` autoimmune disorders `` `` `` non elimination of auto reactive lymphocytes after self antigen encounter Increase apoptosis `` excessive cell death `` diseases characterized by marke loss of normal cells `` `` ie death of virus infected cells `` `` `` feline panleukopenia virus |
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HYPOXIA
4 KEY POINTS |
Deficiency of Oxygen
Creates Cell Injury `` via reducing aerobic oxidative respiration Important and Common cause of cell injury and death Glycolytic Energy production continues `` ie nutrients delivered `` ie waste products removed |
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HYPOXIA
CONSEQUENCES |
Adapt
Sustain Injury Die |
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ISCHEMIA
4 KEY POINTS |
Loss of Blood Supply
`` impeded arterial flow `` reduced venous drainage Reduced aerobic oxidative respiration Inhibited Glycolytic Function `` lack of substrates `` accumulation of waste metabolites `` `` ie lactic acid Injury compared to hypoxia `` more rapid `` more severe |
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HYPOXIA
3 EXAMPLES |
Inadequeate oxygentation of Blood
`` cardiorespiratory failure Loss of Oxygen carrying capacity `` Anemia `` CO poisoning |
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ISCHEMIA
3 EXAMPLES |
Embolism
Heart Failure Shock |
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CELL INJURY
4 PHYSICAL AGENTS |
Mechanical Trauma
Extremes of Temperature Radiation Electric Shock |
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CELL INJURY
INFECTIOUS AGENTS |
Viruses, Bacteria, Fungi, Parasites
`` tf diverse range of mechanisms Viruses `` alter metabolism of host cells Bacteria `` secrete toxins `` tf direct damage to tissue `` ie proteolytic enzymes `` `` Fusobacterium necrophorum `` ie coagulation necrosis `` `` Clostridial sp |
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CELL INJURY
IMMUNOLIGIC REACTIONS |
Anaphylatic reactions to foreign proteins
Autoimmune Disease `` reaction ot endogenous self antigens |
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CELL INJURY
GENETIC DERANGEMENTS |
Genetic Defects can result in cell injury
Enzymatic Defects `` storage diseases `` Bovine Familial Convulsion and Ataxia `` `` swollen axons |
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CELL INJURY
NUTRITIONAL IMBALANCES |
Prolonged and Severe protein-caloric deficiencies can be fatal
Vitamin and Mineral Deficiencies `` Vit E / Se `` `` White muscle disease `` `` reduced scavenging of free oxygen radicals |
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CELL INJURY
CHEMICAL AGENTS |
Many
Trace Amounts can destroy enough cells to cause death within minutes to hours `` arsenic `` cyanide `` mecuric salts Environmental pollutants Insecticides Herbicides Therapeutic and Recreational Drugs |
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3 ELEMENTS OF CELL INJURY
THAT DETERMINE CELLS RESPONSE |
Type of Injury
Duration of Injury Severity of Injury |
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3 CELLULAR CHARACTERISTICS
THAT DETERMINE CONSEQUENCE OF INJURY |
Type of Cell
State of Cell Adaptability of cell ie skeletal striated myocytes `` resistent to intermitant decrease in blood supply ie cardiac striated myocytes `` susceptable to intermitant decrease in blood supply |
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4 SITES OF INJUROUS STIMULUS
|
ATP
`` loss of energy dependent cellular functions `` `` swelling of ER `` `` cell swelling `` `` loss of microvilli `` `` blebing `` `` decreased pH `` `` decreased proteins `` `` increased lipids Membrane Damage `` mitochondria `` `` cell death `` lysosome `` `` enzymatic digestion of cellular components `` plasma membrane `` `` loss of cellular contents Intracellular Ca `` protein break down `` DNA damage Reactive Oxygen Species `` protein break down `` DNA damage |
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DEPLETION OF ATP
HOW MUCH IS TOO LITTLE 4 WAYS TO CELLULAR PAIN |
< 5% - 10% of Normal
`` widespread effects on many critical cellular systems Reduction in activity of plasma membrane energy dependent Na transporters `` intracellular Na accummulation `` loss of intracellular K via diffusion `` net gain of solute `` `` osmotic inflow `` `` `` cellular swelling `` `` `` dilation of ER Switch to anaerobic metabolism ie via ischemia `` glycogen stores rapidly deplete `` accumulation `` `` inorganic phosphates `` `` lactic acid `` tf decrease cellular pH `` `` decreased cellular enzymes Failure of Ca pump `` influx of Ca `` damages numerous cellular components `` activates enzymes that destroy cellular structures Disruption of protein syntetic apparatus `` via prolonged ATP depletion `` detachement of ribosomes from RER `` decreased protein synthesis `` irreversible damage to mito and lysosome membranes `` `` tf cellular necrosis |
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MITOCHONDRIAL DAMAGE
3 WAYS TO GET IT 2 DEADLY CONSEQUENCES |
Decreased ATP results in morphologic changes
`` swelling `` large amourphous densities Increased cytosolic Ca Oxidative Stress Phospholipid Breakdown `` phospholipase A2 `` lipid peroxidation products Formation of high conductance channels (aka pores)on inner membrane `` prevent maintenance of proton motive force `` tf no mito oxidative phosphorylation Leakage of cytochrome C into cytosol `` triggers apoptotoic death pathways |
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LOSS OF CALCIUM HOMEOSTASIS
NORMALS MECHANISM CONSEQUENCES |
Normal Levels
`` Intracellular <0.1 micromol `` Extracellular 1.3 mmol `` most intracellular Ca sequestered `` `` mitos `` `` ER `` Gradients modulated by energy dependent Ca Mg ATPases (calcium pumps) Ischemia and specific Toxins generate early increase in cytosolic [Ca] `` via net inward flux across plasma membrane `` via release from ER `` Subseqent increases via `` `` nonspecific increases in membrane permeability Increased Ca activates many enzymes `` ATPases speed ATP depletion `` phospholipase damage membranes `` proteases breakdown `` `` membrane proteins `` `` cytoskeletal proteins `` endomuclease fragment DNA and chromatin Increase Ca results in mito membrane leakage `` releas of pro apoptotic messangers |
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OXIDATIVE STRESS
NAME EM MECHANISM SELF ABUSE 3 MAJOR HARMFUL EFFECTS |
via Oxygen Derived Free Radicals
`` `` O2- `` `` H2O2 `` `` OH- `` `` NO3- `` single unpaired electron in outer orbit `` energy released via reactions with adjacent molecules `` `` membrane proteins `` `` membrane lipids `` `` membrane carbohydrates `` `` nucleic acids `` tf cellular damage Initiate Autocatalytic Reactions `` molecules react with selves `` tf converted to free radicals `` tf propagation of damage Lipid Peroxidation of Membranes Oxidative Modification of Proteins DNA Damage |
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OXIDATIVE STRESS
LIPID PEROXIDATION OF MEMEBRANES LOCATION MECHANISM PROTECTION |
Plasma and Oranelle Membranes
Oxygen derived free radicals (esp OH) attack membrane Unsaturated Fatty Acids `` produce Peroxides `` induce autocatalytic chain reaction `` tf extensive organelle and cell damage Scavenger required to to terminate autocatylitic chain reaction `` Vit E embeded in membrane on good days |
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OXIDATIVE STRESS
OXIDATIVE MODIFICATION OF PROTEINS MECHANISMS 3 PROTECTION |
Oxidation of amino acid residue sidechains
Formation of protein-protein cross linkages `` ie disulphide bonds Oxidation fo protein backbone `` tf protein fragmentation Damaged cellular proteins conjugated with ubiquitin `` tf degrade by proteasome complex |
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OXIDATIVE DAMAGE
DNA |
Reactions with thymine produce single stranded breaks
`` nuclear `` mito implicated in `` cell aging `` malignant transformation |
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FREE RADICAL GENERATION
6 PROCESSES |
Mito respirtation
`` generation of energy `` via sequential reduction of molecular oxygen to water Activated polymorphonuclear leukocytes `` during inflammation `` rapid burst of superoxide production Transition Metals accept and Donate free electrons `` Cu, Fe `` during intracellular reactions `` Catalyze formation of Free Radicals `` ie Fenton Reaction `` `` H2O2 + Fe2+ > Fe3+ + OH + OH- NO (Nitric Oxide) `` produced by endothelial cells and macrophages `` can act as free radical `` can be converted to highly reactive peroxynitrite anion `` ONOO- Radiant Energy `` uv light, x rays `` hydrolyzes water into free radicals `` `` OH and H Enzymatic metabolism of Exogenous chemicals or drugs |
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OXIDATIVE STRESS
3 DEFENSES |
Antioxidants
`` block initiation of free radical fromation `` inactivate free radicals `` `` ie scavenge `` Vit E,A,C and Glutathione Metal Binding Proteins `` bind Cu and Fe `` tf reduced catalysis of ractive oxygen species `` transferrin `` lactoferrin `` ceruloplasmin Free Radial Scavenging Enzymes `` Superoxide Dismutase `` `` converts superoxide (2O2-) to H2O2 `` Catalase decomposes H2O2 to H2O and O2 `` `` present in peroxisomes |
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DEFECTS IN MEMBRANE PERMEABILITY
5 BIOCHEMICAL MECHANISMS NAME EM EXPLAIN EM |
Mitochondrial Dysfunction
`` results in decreased ATP `` tf decreased phosopholipid synthesis and reacylation `` tf degradation of all cellular membranes Loss of Membrane Phospholipids `` increased intracellur Ca activates endogenous phospholipases `` initiates degradation of phospholipids `` increased acuumulation `` `` free fatty acids `` `` other lipid metabolites `` `` `` ie detergents Cytoskeletal Abnormalities `` increased intracellular Ca activates proteases `` tf damage to cytoskeleton `` tf detachment from cell membrane `` tf susceptability to stretching and rupture Reactive Oxygen Species `` damage to membranes, lipids, proteins, DNA Breakdown Product Accumlation `` unesterfied free fatty acids `` catabolic products resulting from phospholipid degradation `` detergent effect on cell membranes `` `` changes in permeability |
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REVERSIBLE ISCHEMIC CELL INJURY
TELL THE STORY OF ESCALLATION |
ATP depletion via loss of oxidative phosphorylation
Failure of Sodium Pump `` intracellular accumulation of Na `` loss of K `` influx of water `` cellular swelling Morphologic Deterioration `` dispersion of cytoskeleton `` loss of ultrastructure `` `` microvilli disappear `` `` formation of blebs `` Myelin Figures form from membranes `` mitos swell `` ER dilated `` cell markedly swollen |
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IRREVERSIBLE ISCHEMIC CELL INJURY
TELL THE STORY |
Morphology
`` mitos `` `` severe swelling `` `` large amorphous densities `` extensive membrane damage `` lysosomal swelling Massive influx of calcium `` especially during reprofusion `` activation of catabolic enzyemes and apoptosis Cell Death `` cell components progressively degraded `` widespread leakage of cellular enzymes into extracellular space `` influx of macromolecules `` inflammation, disintigration phagocytosis `` |
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REPROFUSION INJURY
2 OUTCOMES 3 MECHANISMS |
Reversible Injury
`` Depending on intensity and duration `` `` Recovery `` `` Death via new and damaging processes Irreversible injury `` Death `` `` via necrosis `` `` via apoptosis Increased Generation of Oxygen Free Radicals `` antioxidants decreased during ischemia `` initiated during reoxygenation `` from `` `` affected tissue `` `` infiltrated neutrophils `` antioxidnt defense mechanisms compromised `` `` tf free radical scavanger therapy may benefit Inflammation `` hypoxic parenchymal and endothelial cells `` `` cytokine production `` `` adhesion molecule expression increased `` tf reprerfusion results in increased inflammation Complement Pathway Activation `` IgM ABs deposited in ischemic tissues `` `` from residual blood during isxhemia `` upon reperfusion `` `` complement binds ABs `` `` activates complement pathway `` `` direct cell injury via attack complexes `` `` inflammation |
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PATHOLOGIC CALCIFICATION
WHAT IS IT WHAT ARE THE FORMS |
Abnormal Tissue Deposition of calcium salts
`` toegether with smaller amounts of `` `` Fe, Mg and other mineral salts Dystrophic Calcification Metastatic Calcification |
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DYSTORPHIC CALCIFICATION
WHAT IS IT PHASES |
Occurs locally in necrotic or degenerative tissues
`` without highserum levels `` without derangements in calcium metabolism Associated with Necrosis of any type `` coagulation `` caseous `` liquefactive `` fat Initiation (aka Nucleation) `` Intracellular `` `` mitos of dead or dying cells that accumulate Ca `` Extracellular `` `` phospholipids in membrane bound vesicles from degenerating cells `` `` phosphatases generate phosphate `` `` Ca binds phosphate and generates a microcrystal Propagation `` microcystal propogates and penetrates membrane `` propagation dependent on `` `` [Ca], [PO4] `` `` inhibitors and other proteins in extra cellular space `` `` `` CT, matrix proteins Accentuated by hypercalcemia |
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METASTATIC CALCIFICATION
MECHANISM 4 CAUSES |
May occur in normal tissues in presence of hypercalcemia
Principally affects tissues which lose acid creating a alkalotic micro environment `` gastric mucosa `` kidneys `` lungs Increased secretion of Parathyroid hormone (PTH) `` subsequent bone resorption `` parathyroid tumor `` paraneoplastic syndrome `` `` secretion of PTH related proteins by other tumors Destruction of Bone Tissue `` primary or metastatic tumors Vitamin D Toxicity Renal Failure `` retention of phosphate `` secondary hyperparathyroidism `` `` inorder to maintain plasma Ca:P ration |
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PATHOLOGIC CALCIFICATION
MORPHOLOGY |
Similar for dystrophic and metastatic
Gross `` Fine white granules or clumps `` `` often with gritty texture Histologically `` Basophilic amorphous granular `` `` sometimes clumped `` intracellular extracellular or both |
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PATHOLOGIC CALCIFICATION
SIGNIFICANCE |
Usually mineral salts caus no dysfunction to affected tissues
Important indicators of Pathological Processes |
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CELLULAR AGING
5 PROCESSES |
Reduced Mitochondrial Oxidative Phosphorylation
Reduced Synthesis Reduced Nutrient Uptake Reduced DNA Repair Accumulation |
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CELLULAR AGING
REDUCED SYNTHESIS 5 |
Nuleic Acids
Structural Proteins Enzymatic Proteins Cell Receptors Transcription Factors |
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ACCUMULATION
3 JUNK PILES |
Lipofuscin Pigment
`` product of lipid peroxidation Glycation End porducts `` ie age related glcosylation of lens proteins `` senile cataracts Abnormally folded proteins |
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REPLICATIVE SENESCENCE
WHO HOW |
Somatic cells have limited capacity for replication
Arrest in terminally non dividing state `` after fixed number of replications `` aka cellular senescence `` regulated by telomeres |
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TELOMERES
WHAT ARE THEY SIGNIFICANCE |
aka Genetic Clock
Short repeated sequences of DNA at linear ends of chromosomes `` ensure complete replication `` protect chromasomal ends DNA replication enzymes in somatic cells stop at end of DNA `` tf can not repicate final bit of telomere `` tf telomere gradully lost over multiple replications `` eventually end of chromosome is exposed and damaged `` `` signals arrest of cell cycle `` `` `` tf cell cannot be replaced |
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IMMORTALITY
WHAT DO YOU NEED TO BE WHAT DO YOU NEED |
Germinal or Stem Cells
Express telomerase RNA-Protein Complex `` uses own RNA as template for adding nucleotides to end of chromosome `` tf unlimited life of chromosome |
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IMMORTAL CANCER CELLS
DO WHAT |
Express Telomerase
`` tf telomere elongation important in tumor formation |
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EVEN IF YOU HAD THE ENERGIZER BUNNIE IN YOUR SOMATIC GENETIC CLOCKS WHAT ELSE WOULD LIMIT CELLULAR LIFE
|
Accumulation of
`` Metabolic Damage `` Genetic Damage |
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CELLULAR LIFE
METABOLIC DAMAGE WHAT DOES IT WHAT IS THE EVIDENCE |
Free Radical Damage of Oxidative Phosphorylation
`` covalent modifications of `` `` proteins `` `` lipids `` `` nucleic acids Accumulation of toxic products is implicated in aging because `` overexpression of Superoxide Dismutase (SOD) and Catalase extends life span `` increased generation of mitochndrial superoxde anion radical reduces lifespan `` smaller animals with higher metabolic rates `` tf more metabolic products have shorter livespans |
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CELLULAR LIFE
DNA DAMAGE WHAT IS THE KEY COMPONENT |
DNA repair enzymes fix most DNA damage
`` ie DNA Helicase `` defects result in rapid accumulation of chromosomal damage `` similar to cellular aging injuries |
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PIGMENTS
WHAT ARE THEY WHERE DO THEY COME FROM |
Coloured Substances
Endogenous `` normal cell constituents `` `` ie melanin `` abnormal cell constituents `` `` accumulate when problems Exogenous |
|
PIGMENTS
EXOGENOUS |
Coal Dust
`` most common `` ubiquitous urban air pollutant `` picked up by alveolar macrophages `` transported to lymphnodes in tracheal bronchal regions |
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ANTHROCOSIS
|
Accumulations of coal dust pigment in lungs and lymph nodes
|
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ENDOGENOUS PIGMENTS
NAME 4 |
Lipofuscin
Melanin Hemosiderin Bilirubin |
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LIPOFUSCIN
WHERE DOES IT COME FROM WHY DO WE CARE |
aka Wear and Tear pigment
Histologically `` yello brown `` finely granular `` intracytoplasmic `` often perinuclear Insoluble Derived via lipid peroxidation of `` polyunsaturated lipid membranes Not injurious to cell or functions Telltale sign of `` Free Radical injury `` lipid peroxidation |
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HEMOSIDERIN
|
Endogenous Pigment of Intracellar Iron
`` Hemoglobin derived `` Golden yellow brown `` granular Iron `` normally carried by specific transport proteins `` `` transferrins `` stored intracellularly in association with `` `` apoferritin `` `` forms ferritin micelles `` excess iron causes hemodiderin to accumulate in cells `` `` localized ie hemorrhage `` `` systemic ie brown lymph nodes |
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BRUISE
|
Best example of localized hemossiderosis
Local Hemorrhage `` are first red - blue `` erytrocytes lyse `` macrophages phagocytize red cell debris `` lysosomal enzymes sequentually converts hemoglobin to `` `` biliverdin (green) `` `` blirubin (red) `` `` hemosiderin (yellow) |
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HEMOSIDEROSIS
|
Consequence of systemic iron overload
`` inherited `` `` ie genetic defect in iron metabolism `` aquired `` `` hemolytic anemia `` `` blood transfusion Hemosiderin deposited in many organs `` spleen `` liver |
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BILIRUBIN
|
Normal major pigment of bile
Derived from hemoglobin `` contains no iron `` normal formation and excretion vital to health |
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ICTERUS
WHAT IS IT 4 PLACES TO FIND IT WHAT ARE THE TYPES AND MECHANISMS |
aka Jaundice
Excess of bilirubin within cells and tissues `` yellow discolouration of white or pale tissues `` `` aorta `` `` fat `` `` sclera `` `` mucous membranes Prehepatic `` hemolytic anemia `` high amount of bilirubin in circulation `` hepatic capacity overwhelmed Hepatic `` normal level of circulating bilirubin `` reduced hepatic capacity due to disease Post Hepatic `` bilirubin processed machinery in liver normal `` but bile duct obstruction prevents secretion `` tf hepatic levels rise `` tf circulatory levels rise |
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HEMOGLOBIN
|
Red erythrocytic pigment
|
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HEMOGLOBINURIA
|
Presence of hemoglobin in plasma
|
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MYOGLOBIN
|
Red muscle pigment
|
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MYOGLOBINURIA
|
Myoglobin in Plasma
Indicates massive damage to muscle `` capture myopathy `` exertional rhabdomyolysis |
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INTRACELLULAR INCLUSIONS
4 NAME EM DESCRIBE EM |
Viral Inclusions
`` important diagnostically `` Intranuclear `` `` adenovirus `` `` herpesvirus `` `` parvovirus `` Intracytoplasmic `` `` rabies virus `` `` distemper virus `` `` pox virus Intracellular Non Viral Pahtogens `` coccidia `` Mycobacteria sp Storage Diseases `` usually hereditary `` defects in lysomal enzymes `` `` tf impaired degradation of macromolecules `` `` tf accumulation in lysosomes `` neurons particularly affected `` manosidosis `` locoweed toxicity Prion Diseases `` Transmisssible Spongiform Encephalopathies TSE `` characterized by intrneuronal vacuoles `` BSE `` Scrapie `` Chronic Wasting Disease CWD |
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INTRACELLULAR INCLUSIONS
4 NAME EM DESCRIBE EM |
Viral Inclusions
`` important diagnostically `` Intranuclear `` `` adenovirus `` `` herpesvirus `` `` parvovirus `` Intracytoplasmic `` `` rabies virus `` `` distemper virus `` `` pox virus Intracellular Non Viral Pahtogens `` coccidia `` Mycobacteria sp Storage Diseases `` usually hereditary `` defects in lysomal enzymes `` `` tf impaired degradation of macromolecules `` `` tf accumulation in lysosomes `` neurons particularly affected `` manosidosis `` locoweed toxicity Prion Diseases `` Transmisssible Spongiform Encephalopathies TSE `` characterized by intrneuronal vacuoles `` BSE `` Scrapie `` Chronic Wasting Disease CWD |