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Degenerations and Infiltrations
Part 1
35
Veterinary Medicine
Graduate
06/06/2012

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Cards

Term
4 main categories of disease
Definition

congenital

degenerative

inflammatory

neoplastic

Term
cellular injury, effect on cell determined by
Definition

dose of the injurious agent acting upon the cell

duration for which it acts

the vascular flow, nutrient supply

type of cell injured (highly active cells such as hepatocytes, PCT epithelium of the kidneys, cardiac myocyes are most prone to injury)

Term
Cellular Injury Pathways
Definition
  1. depletion of ATP (needed for normal cell function)
  2. accumulation of products normally expelled such as lactate
  3. increased metabolism in the cell
  4. hypoxia of the cell
  5. pressure changes on cellular organelles 
Term
Degenerations VS Infiltration
Definition
  • Degeneration: individual cell shows some observable changes within it
  • Infiltration: something accumulating in the individual cell or SURROUNDING tissue 
Term

Types of degenerations

 

Definition

Cellular Swelling

Hydrophobic degeneration

Cellular Fatty Change

Mucoid (myxoid, myxomatous) degeneration

Hyaline degeration 

Fibrinoid degeneration

Amyloid 

Term
Types of Infiltration
Definition

Gylcogen infiltration

Cellular inclusions

Term
Cellular Swelling
Definition
  • Mildest, earliest detectable change
  • impairment of cell membrane integrity
  • may be momentary phenomenon passing quickly to more serious damage
  • Gross: paler, slight buldge
  • Microscopic: moderate swelling of individual cells
  • CAUSE: influx of water into the cell, anoxia and mild toxins
  • Signifcance: very subtle changes, mimic early post mortem change

 

Term
Hydropic degernation
Definition
  • more severe // advanced cellular swelling
    • cells may swell up like a balloon prior to destruction
    • discrete vacuole of fluid within cytoplasm
    • lose sha
  • can indicate viral infection 
  • common in very metabolically active cells (hepatocyte, renal tubular epith cells, pancreatic acinar cell which have WELL DEVELOPED pumping mechanisms)
Term
Process of Hydropic degeneration
Definition

Injury

Hypoxia

ATP production decreased

Na & H2O movie into cell

K+ moves out of cell

Osmotic pressure increases

More H2O moves into the cell

Cisternae of ER distend, rupture and form vacuoles

Extensive vacuolation

Hydropic degeneration

Rupture of adjacent cells

Formation of vesicles (blisters)

Term
Fatty Change
Definition
  • intracellular abnormality
  • easily recognized post mortem
  • accumulation or increase of fatty substances w/in cytoplasm of specific cells (parenchyma of liver, kidney, heart)
  • NOT NORMAL BODY FAT STORES 
Term
Fatty Change Gross Appearance & Examples
Definition
  • Liver: increased in size, tan-yellowish color, friable, when cut underlying parenchyma bulges outward, very dill in appearnace and greasy
  • Kidney: cortex appears pales (cats have normally fatty kidneys)
  • Heart: flabby with streaks in the papillary muscles 
Term
Fatty Change Microscopic appearance & examples
Definition
  • Liver & Kidney:  globules or vacuoles of varying size in the cytoplasm of the cells, nucleus pushed to periphery but remains normal
  • Heart: tiny groups of vacuoles dispersed along the myofibrils
Term
Causes of Fatty Change
Definition
  • Dietary and Metabolic
    • starvation- increased moblisation of fat in response to body energy needs, liver unable to cope-> stores as neutral fats
    • overeating- obesity, dietary intake > energy expenditure, fat temporarily store prior to movement to body fat stores
    • lipotrope derangement- lipotropes are substances that hasten the removal of fat from the liver cells, can be amino acids that facilitate conjugation of the fat with proteins to form lipoprotein that is exreted from the cells, defiency of these substances cause fatty change

 

Term
Causes of fatty change
Definition
  • Anoxia
    • reduce oxygen supply to the tissues ->fatty change in the liver
    • Anemia: caused by sustained loss of RBC from vessels as in chronic hemorrhage or excessive destruction of RBCs within the vessels (hemolysis)
    • Circulatory disorders: ischemia (reduced BS to a tissue), chronic venous congestion (slowing of BF through the vasculature) due to a failing heart  
Term
Causes of fatty change
Definition
  • toxins
    • large amount cause fatty swelling
      • bacterial and fungi: produced in BS or elswhere and abosorbed into BS
      • chemical toxins: CCl4, phosphorus, arsenic, lead
      • plant toxins: cause fatty change during early stages of poisioning
Term
Distrubution of fatty change
Definition
  • Diffuse (metabolic dz)
  • Zonary (circulatory dz) 
Term
Mucoid degeneration
Definition
  • extracellular phenomeon of specific cells
  • show faint bluish tinge in H&E stain sections
  • changes in matrix (ground substance) produced by fibroblasts in CT or epithelial tissue (excessive secretion of mucin
  • seen in calvielier KC-> heart failure, valves become slimey, weakened and distoreted
Term
Mucous metaplasia of epithelial surfaces
Definition
  • beneficial, NOT REALLY A DEGENERATION
    •  goblet cells of wet MM and mucous glands increase in number, # of simple columnar reduces
    • increase in production of mucin-> important for lubrication and protective substance, from irritants
      • soothes inflamed surfaces
      • traps and dilutes harmful agents
      • carries specific AB against infectious agents
      • means for removal of irritants/infectious agents
    • can return to normal after irritant/infectious agent is removed
    • constantly changing and reproducing
    • example: Lg intestine, Respiratoru tract
Term
Hyaline degeneration
Definition
  • "glassy"
  • applied to several types of degenerations or infilrations
  • Microscopic: frosted appearance, stains pinkish red w/ eosin in H&E
  • Can be intracellular or extracellular 
Term
Intracellular Hyaline degeneration
Definition
  • Intracelullar:
    • degernation of skeletal muscle
      • swollen
      • loss of structure
      • loss of striations
      • appears as a "blob" histologically 
Term
Extracellular Hyaline degeneration
Definition
  • Extracellular
    • hyaline protein casts in urine
      • problems turn to cats based on tubule structure
    •  hyaline membranes in the lung
      • coagulation of proteinaceous effusions at alveoli where gas exchange occurs, prevent gas exhange
      • alveolar damage
      • can be caused by acute toxic or viral insult to lungs
Term
Fibrinoid degernations
Definition
  • fibrin-like red smudging
  • focal death of vessel wall cells
  • consists partly of degenerated muscle and elastic fibers and partly of an increased amount of protein ground substance around the degenerated fibers
  • suggests either..
    • type 3 hypersensitivity: AB-antigen complexes depositing in BV wall
    • hypertension in the BV- chronic, uncompensated -> high blood pressure 
Term

Amyloidosis (amyloid degeneration)

 

Definition
  • polymerisation of abnormal peptides into fibrilar proteins from a wide variety of cources (albumin, immunoglobulin, acute phase proteins & hormones)
  • not a 'single' dz entity->diverse group of dz processes
  • characterised by deposition in or more organs of heterogeneous group of proteinaceous compounds (protiens fold into fibrils make up 95% beta-pleated folds of amyloids, 5% of amyloids from CT and include serum amyloid P compnent, glycosaminoglycans, proteoglycans)
Term
Causes of Amyloidosis
Definition
  1. chronic inflammatory process elsewhere in the body (most cases) complications
  2. tumors as in plasma cells and thyroid tumors, neoplasia, hepatocytes produce SAA protein-> can't stope or breakdown-> amino acid protein  
  3. prion dz. BSE, small proportion
Term
Pathogenesis of amyloidosis
Definition

Stimulus ->  Soluble precusor: misfolded protein -> insoluble fibrils (how it works)

    • Products of abnormal amounts of protein:
      • stimulus (unknown, carcinogen)-> monoclonal B-lymphocytes proliferation->plasma cells ->immunoglobulin light chains -> limited proteolysis -> AL protien (subtype of immunoglobulin formed)
 
    • Chronic Inflammation ->macrophage activation -> IL 1& 6 -> liver cells -> SAA protein -> limited proteolysis -> AA protein
    • Mutation-> abnormal protein-> abnormal protien
 
Term
Primary Amyloidosis (AL)
Definition
  • AL:Amyloid light chain
    • made up of complete immunoglobulin light chains secreted by plasma cell tumors
    • increase in serum protein-> lose in urine (neoplastic events indicated)
    • affected animals  have monoclonal gammopathyn with abnormal protein in urine (Bence-Jones proteinuria)
    • humans: increased in normal plasma cell bone marrow - dyscrasia  
Term

Secondary Amyloidosis (AA)

 

Definition
  • AA: amyloid associayed protein / reactive systemic amyloidosis
    • 2* to inflammatory rxns, particularly chronic infections, wide variety of infectious agents
    • deposited in renal glomeruli of dog and ox

 

Term
Renal Amyliodosis
Definition
  • AA amyoidosis (secondary)
  • Gross:
    • pale cortex
    •  glomeruli (containing immunoglobulin) appear as white dots
    • stain yellow/brown with iodine
    • subsequent tx with dilute sulphuric acid turns them blue-purple (where almyloid has been deposited)
  • Microscopic:
    • seposition of pink homogenous material in the glmoerulus - replacing the epith and endoth
    • same pink material cuffs around tubules
    • stains pink w/ Congo Red and the amyloid fibrils appear apple-green color in polarized light
Term
Effects of renal amyloidosis
Definition
  • sustained loss of protien (albumin) into urine
  • reduces osmotic potential of blood to attract fluid back into the blood at the venous end of the capillary bed
  • results in edema of subcutis and abdominal cavity
  • 'nephrotic syndrome'
Term
Hepatic amyloidosis
Definition
  • amyloid depostition in liver -> causes hepatomegaly w/ risk of hemorrhage
  • deposited along sinusoids between hepatocytes
  • friable/ vunerable to rupture 
Term
Endocrine associayed amyloidosis
Definition
  • amyloid can deposit in endocrine organs (islets of Langerhans in the pancreas)
  • can cause diabetes mell 
Term
Glycogen Storage
Definition
  • renal tubules (w/ diabetes mell)
  • liver (prolonged corticosteriod therapy)
  • normal present in substantial amounts in liver & muscle where its readily utilisable source of energy
  • moderate amounts of glycogen do not alter gross appearance
  • microscopic: foamy cytoplasmic vacuoles (similar to fat, clear, vacuolated; need to stain to distinguish between the two)
Term
Cellular Inclusions
Definition
  • Viral inclusions
  • Abnormal storage products
Term
Cellular Inclusions; viral inclusion bodies
Definition
  • accumulations of viral nucleic acid or protein
  • nuclear, abnormal cytoplasmic (can be both)
  • subcellular localisation indicated type of virus 
Term
Cellular inclusions; abnormal storage products
Definition
  • hereditary storage diseases in which there is a missing or defective cellular enzyme
  • build up of intermediate metabolites in cytoplasm, unable to be processed in cells
  •  usually affects all tissues
  • CNS is particulary vunerable because it cannot regenerate (ex: Phenylpropanolamine intolerance)
  • (appear solid and without a ' central nucleus')
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