CELL INJURY 4: apoptosis, extra/cellular accumulations, and metabolic derangements Flashcards
(33 cards)
apoptosis
programmed cell death via highly coordinated, energy dependent sequence of events
- active process due to energy dependence
apoptosis cellular features
cell size:
- decreased
nucleus:
- fragmentation into nucleosome-size fragments
plasma membrane:
- intact; altered structure, esp. orientation of lipids
cellular contents:
- intact; may be released in apoptotic bodies
adjacent inflammation:
- NO
- only macrophages clearing apoptotic debris
physiologic or pathologic role and significance:
- physiologic
- pathologic (DNA damage, cell mediated cytotoxicity)
necrosis cellular features
cell size:
- increased
nucleus:
- pyknosis
- karyorrhexis
- karyolysis
plasma membrane:
- disrupted
cellular contents:
- enzymatic digestion may leak out of cell
adjacent inflammation:
- frequent
- including neutrophils and macrophages
physiologic or pathologic role and significance:
- pathologic (culmination of irreversible cell injury)
physiological apoptosis
- involution of tissues during embryonic development
- involution of tissues related to functional phases (mammary gland, postpartum uterus)
- age related involution/atrophy of the thymus
pathological apoptosis
irreversible cell injury with different underlying causes
- infectious agents
- ionizing radiation
- chemicals
- growth factor withdrawal
action of specific enzymes
- caspases
- nucleases
apoptosis pathways
- mitochondrial (intrinsic) pathway
- death receptor (extrinsic) pathway
mitochondrial (intrinsic) apoptosis pathway
cell injury occurs inside the cell and the resulting stress activates the apoptotic pathway
- growth factor withdrawal
- DNA damage - radiation, free radicals, toxins
- protein misfolding
death receptor (extrinsic) apoptosis pathway
pathway begins outside the cell when extracellular conditions determine the cell needs to die
receptor-ligand interactions:
- Fas
- TNF receptor
intracellular accumulations
degenerative changes due to metabolic alterations
excessive accumulation of:
1. normal cellular components:
- water
- lipids
- proteins
- carbohydrates
- abnormal exogenous or endogenous substances:
- mineral or product of infectious agent
- product of abnormal synthesis or metabolism - pigments
extracellular accumulations
- amyloid
- calcification
- urates (gout)
causes of intracellular accumulations
manifestations of metabolic derangement in cells
decreased rate of metabolism
- build up of a normal endogenous substance
- e.g. triglycerides causing fatty change in the liver
genetic or acquired defects in metabolism, packaging, transport, or secretion
- e.g. lysosomal storage diseases
failure of enzymatic machinery to degrade or transport an abnormal exogenous substance
- e.g. carbon particles, silica
intracellular accumulations:
hyaline proteins
caused by a defect in the protein folding transport
protein resorption droplets
- e.g. proximal renal tubule epithelium
Russell bodies in plasma cells
defective protein folding
- some forms of amyloidosis
- more often extracellular in veterinary medicine
intracellular accumulations:
lysosomal storage diseases
in a normal cell:
- complex substrate uses an enzyme to create soluble products
in a diseased cell:
- lack of enzyme so complex substrate cannot be converted into soluble products
Periodic acid-Schiff positive (PAS +) materials are substances that produce red color when reacting with PAS stain
- found in neurons
ex. Suffolk sheep GM1 gangliosidosis
- beta-1 galactidase and alpha-neuraminidase deficiency
- defect in catabolism of glycosphingolipids (normal component of cell membranes)
- leads to intracellular accumulation, particularly in neurons
intracellular accumulations:
lipofuscin
pigment accumualtes in post-mitotic (permanent) cells and stable (slowly-dividing cells)
- neurons, cardiomyocytes
- hepatocytes
final undegradable residual product of autophagocytosis
- composed of proteins & lipids & carbohydrates
indigestible
- accumulates in lysosomes
lipofuscinosis in bovine heart:
- diffuse, brown discoloration
intracellular accumulations:
exogenous materials
cell ingests indigestible materials
- carbon pigment (anthracosis)
intracellular accumulations:
hemosiderin
golden yellow or brown granular pigment
contains iron
- histological confirmation with Perls blue special stain (differentiate from lipofuscin)
organs involved in red cell breakdown (spleen, liver)
- brownish color
hemosiderosis = old bruising with hemorrhage being reabsorbed
local hemosiderosis
- bruising
generalized hemosiderosis
- hemolytic anemia
- hemochromatosis
fixation artefact - formalin pigment
commonly observed in H&E stained sections
“formalin pigment”
acid formalin hematin
- brown to black fine granular spicules of hematin lie between and on the red cells
- worse if fixation of blood-rich tissues in unbuffered (acid) 10% formalin
intracellular accumulations:
glycogen
normally in hepatocytes and myocytes
- hepatocyte level dependent on feeding to sampling interval
- none if starved
increased with corticosteroids
- endogenous steroids (Cushing’s disease)
- exogenous steroids (therapeutic administration of corticosteroids as NSAIDs)
diabetes mellitus
extracellular accumulations:
amyloid
extracellular proteinaceous material
diverse group of glycoproteins
- B pleated sheet configuration
- stains apple green double refraction with Congo red (some amyloids do not respond well to Congo red)
histologically:
- eosinophilic
- amorphous hyaline substance
resistant to normal proteolytic mechanisms
compresses tissue cells (to an extent)
- causing atrophy or even cell death and loss
primary amyloidosis
plasma cell tumors (AL amyloid form Ig light cahins)
important in humans but RARE in domestic animals
pancreatic islets of cats with non-insulin dependent diabetes mellitus (Islet amyloid peptide [IAPP]-derived)
familial AA amyloidosis:
- dogs: beagle, sharpei, gray collie, english foxhound
- cats: abyssinian, siamese, and oriental
secondary (reactive systemic) amyloidosis
most common in veterinary medicine
serum amyloid A (SAA)
- produced by the liver
secondary to chronic inflammation/neoplasia
- sustained production of acute phase lipoprotein by the liver (stimulated by IL-1 and IL-6)
deposits in:
- kidney, affect glomerulus, causes proteinuria
- liver
- spleen
- lymph nodes
cattle:
- chronic supperative pneumonia
- hoof abscesses
- traumatic reticulopericarditis
- visceral abscesses
horses:
- visceral abscesses
renal amyloidosis
- glomerular capillary basement membrane
- glomerular mesangium
- interstitium of medulla and/or cortex
all expanded by amorphous eosinophilic material
gross findings:
- large, pale, waxy kidneys with swoleen cortex
functional implications:
- protein-losing nephropathy (nephrotic syndrome)
- subcutaneous edema, brisket edema, “bottle jaw” as a result of decreased oncotic pressure in the blood
clinical correlates:
- anasarca = generalized edema
- ascites = serous fluid in peritoneal cavity
extracellular accumulations:
pathologic calcification
- calcium salts deposited in tissues (necrotic or normal)
- indicator of previous injury
- affected areas are white and gritty
- calcium salts stain blue (basophilic) with H&E
2 types:
- Dystrophic calcification
- Metastatic calcification
dystrophic calcification
associated with necrosis
most prominent in coagulative and caseous necrosis and fat necrosis
dead/dying cells cannot regulate cytoplasmic Ca influx causing
- calcium accumulation in the mitochondria
Note: Ca accumulates/is released into extracellular space after final dissolution of cells
lamb heart from vit. E and Selenium deficiency:
- irregular whitish, gritty areas of dystrophic calcificaiton associated with myocardial degeneration and necrosis - due to oxidative damage
