5. accumulation Flashcards
Accumulation of abnormal amounts of various substances
Reversible/ irreversible if the derangement controlled
reverse
Substances accumulated fall into 3 categories
Normal cellular constituent such as H2O, lipids, proteins, & carbohydrates
Abnormal exogenous or endogenous substance
Pigment
Mechanisms of intracellular accumulation 3
rate of metabolism is inadequate to remove the substance eg. fatty liver disease
Genetic or acquired defects in metabolism, packaging, transport, or secretion e.g., lysosomal storage disease
The cell lacks enzyme to degrade or transport it e.g., carbon or silica
water accumulation
hydropic change
early signs of cellular injury
lipid accumulation can be
TAG
cholestrol
xanthomas
TAG accumulation
Accumulations of triglycerides within parenchymal cells
Liver but also in the heart, muscle & kidney
TAG 1st accumulates in the ………….=> fat globules without membrane
rough ER (liposomes)
under microscope seen as clear vacuole so stains are
Special stains like Sudan IV or oil red are used to confirm
Fatty change (steatosis) of the liver:mechanisms
Excessive entry of free fatty acids
Increased fatty acid synthesis
Decreased fatty acid oxidation
Excess esterification of fatty acid to triglycerides: alcohol poisoning
Decreased apoprotein synthesis : malnutrition, CCL4, phosphorus
Impaired lipoprotein secretion from the liver
Causes of fatty change of the liver
Alcohol
Non-alcoholic fatty liver disease in metabolic syndrome (obesity, type II DM, dyslipidemia & hypertension)
Nutritional: Kwashiorkor
Drugs & toxins: steroids, ART, mushroom
Metabolic: abetalipoprteinemia
Others: acute fatty liver of pregnancy, Hepatitis C virus
why Alcohol most common hepatotoxin
Alters mitochondrial function
Increases free fatty acid (FFA) synthesis
Diminishes triglycerides utilization
Decreases fatty acid oxidation
Blocks lipoprotein excretion
Enhances lipolysis
Increases delivery and uptake of FFA
causes of Fatty change of the heart
poor oxygenation
diptheria exotoxin
Differential diagnosis of clear space in an H&E-stained tissue in a cell
Special stains:
Periodic acid-Schiff (PAS) for glycogen
Mucicarmine & Alcian blue for mucin
cholestrol accumulation in
tunica intima
athermatious plaque
Cholesterol crystals appear to be………..
Cholesterol crystals appear to be needle-shaped clefts
xanthomas
Intracellular cholesterol accumulation
Deposited in skin & tendons as foam cells
Acquired / hereditary hyperlipedemic states
Tumor like masses ”Xanthomas”
foam cells
protein accumulation causes 3
causes of glycogen accumulation
DM
glycogen storing disease
Insoluble pigments inside cells are typically stored in ………………
phagolysosomes
types of pigments endogenous and exogenous examples
exo
coal/ carbon
tattoo
endo
lipofuscins
The carbon blacken the lungs & nearby lymph nodes and is called “…………..” which is harmless
Anthracosis
coal worker’s pneumoconiosis
a condition in which large areas of lung tissue are replaced by scar tissue.
Heavy exposure in coal miners induce fibroblastic reactions
tatoo
Inoculation of metal salts into the skin
Ink is taken by dermal macrophages, keratinocytes, fibroblasts within a month
endogenous
lipofuscin
Lipofuscin is a yellow-brown pigment that accumulates in the lysosomes of cells as a result of oxidative damage and incomplete degradation of cellular components. It is often referred to as the “wear and tear” pigment because it accumulates with age and is associated with cellular aging and degeneration.
melanin
albinism lack of tyrosine kinase
seen in melanocyte and their tumors (mole/naevus or melanoma)
increased pigmentation in pregnancy and addisons disease
melanosis coli pigment
Melanosis coli is a condition characterized by the abnormal accumulation of a brown-black pigment in the lining of the colon. The pigment is often referred to as “pseudomelanin” or “melanin-like pigment” because it resembles melanin
following cascara laxative intake or inflammatory bowel disease (IBD)
results from apoptosis of the colonic epithelial cells
hemosiderin
Hemoglobin derived golden yellow to brown, granular pigment
Pigments represent aggregates of ferritin micelles
Normally small amounts in mononuclear phagocytes of RES
stain to know hemosiderosis
Prussian blue stains blue
types of hemosiderosis
localized and systemic
local hemosiderin causes
Longstanding congestion (lungs, leg veins) or repeated minor injury (sports, bruise, etc.)
Generalized (systemic) hemosiderosis causes
Causes
Multiple blood transfusions
Increased absorption of dietary iron
Longstanding hemolysis
Impaired use of iron
Hemochromatosis
In Hemochromatosis excess hemosiderin causes ………….by generating free oxygen radicals in liver, heart & pancreas
by reaction called
organ failure
bilirubin
Non-iron containing, yellow-orange pigment that results from breakdown of porphyrin rings (mostly hemoglobin)