Intracellular Accumulations and Pathologic Calcification Flashcards
what mechanism of intracellular accumulation occurs in fatty liver/steatosis?
abnormal metabolism
what occurs in abnormal metabolism that results in intracellular accumulations?
inadequate removal of a normal substance secondary to defects in mechanisms of packaging and transport
all major lipids can accumulate in cells. what are they and examples
- triglycerides (eg steatosis)
- cholesterol/cholesterol esters (eg atherosclerosis)
- phospholipids (eg myelin figures in necrotic cells)
what is steatosis
accumulation of triglycerides within parenchymal cells (can be liver, heart, muscle, kidneys)
what is the main organ involved in fat metabolism
liver
is steatosis reversible?
up to a point, otherwise irreversible damage (ie cirrhosis of liver)
what is an important use of cholesterol
synthesis of cell membranes
what is atherosclerosis?
a gross manifestation of atherosclerotic plaques -> smooth muscle cells and macrophages in surface/wall of arteries filled with lipid vacuoles (mostly cholesterol and cholesterol esters)
atheromas have a yellow appearance, what causes this?
aggregates of foam cells in surface/wall of vessels
what are foam cells?
macrophages that have ingested cholesterol
what is a “cholesterol cleft”
the histologic appearance of extracellular cholesterol esters that have crystallized as long needles
what mechanism of intracellular accumulation occurs in atherosclerosis?
abnormal metabolism
a xanthoma can occur in a hyperlipidemic or non-hyperlipidemic state. what is a xanthoma
groups of foamy macrophages found in the CT of skin and in tendons
what is cholesterolosis?
focal accumulation of cholesterol containing macrophages in lamina propria. most often affects gallbladder
what mechanism of intracellular accumulation occurs in renal tubule resorption droplets?
abnormal metabolism
when are renal tubule resorption droplets seen?
- in kidney conditions with protein loss in the urine (proteinuria)
- in heavy proteinuria -> increased resorption of proteins into vesicles
what do protein droplets looks like histologically
pink hyaline droplets within cytoplasm of proximal tubular cells
renal tubule resorption droplets reversible or irreversible?
reversible
what is a russell body
a large eosinophilic cytoplasmic protein droplet that can be seen in some plasma cells actively synthesizing immunoglobulins (ie areas of chronic inflammation or plasm cell neoplasms)
excessive deposits of glycogen may be seen with
abnormal glucose or glycogen metabolism
what is the histologic appearance of glycogen deposits?
it dissolves in aqueous fixatives -> appears clear
diabetes is the most important example of a disorders of glucose metabolism. what can be seen here as far as intracellular accumulations?
glycogen deposits in renal tubular cells, liver, and heart cells
glycogen storage diseases (glycogenoses) are enzymatic defects in the synthesis or breakdown of glycogen. (eg pompe disease and von gierke disease) what happens?
massive accumulation of glycogen -> cell injury and cell death
what occurs when there is a defect in protein folding/transport that causes intracellular accumulations?
•accumulation of endogenous substance due to defects in folding, packaging, or transport of proteins (can be genetic or acquired)
mutated forms of alpha 1 anti-trypsin can cause
intracellular accumulations due to defective folding/transport
what happens at the cellular level in mutated alpha 1 anti-trypsin?
mutation slows down the folding -> build up of partially folded intermediates aggregate in ER of liver cells -> not secreted
what happens at the systemic level with mutated alpha 1 anti-trypsin?
- deficiency of circulating enzyme causes emphysema of lung
* may also be damage from ER stress
what occurs when there is lack of an enzyme that causes intracellular accumulations?
•failure to degrade a metabolite due to inherited enzyme deficiency
what is niemann-pick disease (type c)
a lysosomal storage disease with a mutation affecting the enzyme involved in trafficking cholesterol -> accumulation of cholesterol in multiple organs
what is the mechanism involved in intracellular accumulations found in niemann-pick disease type c
lack of an enzyme
what occurs with ingestion of indigestible materials that results in intracellular accumulations
- deposition and accumulation of abnormal substance
* occurs when cell does not have enzymatic machinery to degrade the substance or ability to transport it to other sites
what is the mechanism of carbon or silica accumulation?
ingestion of indigestible materials
what is anthracosis
the blackening of lung parenchyma and node tissues caused by accumulation of inhaled carbon
what is the most common exogenous pigment that can be accumulated in the body
coal dust
how does carbon accumulation occur in lungs
inhalation -> alveolar macorphages -> transported through lymphatic channels to regional (tracheo-bronchial) lymph nodes
lipofuscin or lipochrome is sometimes called the “wear and tear” pigment and has a brown-yellow appearance. where can it accumulate
- cells undergoing slow regressive change
* prominent in liver and heart of aging people or patients with severe malnutrition/cachexia
lipofuscin is considered an endogenous pigment and is not harmful to cells, but its accumulation might indicate that a cell has been exposed to
free radical injury
what does lipofuscin pigment look like histologically
- yellow brown
- finely granular
- cytoplasmic, often perinuclear
how is melanin formed
when tyrosinase catalyzed the oxidation of tyrosine to dihydroxyphenylalanine in melanocytes
hemosiderin is an endogenous hemoglobin derived pigment. what causes it to form
condensation of excess ferritin deposition
when can hemosiderin deposition be seen with normal iron breakdown
in sites where there is red blood cell breakdown (bone marrow, spleen, liver)
in local excess of iron breakdown (ie hemorrhage into tissues -> bruise) macrophages break down blood. what causes the multicolors or resorbing bruise?
- removal of iron -> ferritin -> hemosiderin
* also parallel breakdown of heme moiety (biliverdin=”green bile”, bilirubin=”red bile”)
what is hemosiderosis
in systemic overload of iron -> hemosiderin can be deposited in many tissues
what are the 3 main causes of hemosiderosis?
hemachromatosis, hemolytic anemias, and repeated blood transfusions
what happens in hemachromatosis?
an inborn error of metabolism -> excessive absorption of dietary iron -> excessive deposition of hemosiderin
what happens in hemolytic anemias
premature lysis of red blood cells -> release of abnormal quantities of iron -> excessive hemosiderin deposition
accumulation is reversible in many cases if the overload can be stopped or controlled (eg early atherosclerosis or steatosis). in what cases are accumulations often not reversible?
- inherited storage disorders where accumulation is progressive
- overload -> cell injury -> may lead to death of cells, tissue, and patient
what is dystrophic calcification
- pathologic deposition of calcium locally in dying/abnormal tissue
- typically calcium metabolism is normal
what is metastatic calcification
- pathologic deposits of calcium in otherwise normal tissues
* usually associated with hypercalcemia, some abnormality in calcium metabolism
what is the gross appearance of calcification?
fine white granules that may be clumped and gritty to touch or cut
histologic appearance of calcification
- basophilic
- amorphous granular
- may be clumped
- can be extracellular/intracellular/both
what are psammoma bodies
- can be seen with necrotic cells that cause calcium deposition
- subsequent deposition of additional layers -> lamellated appearance
where are psammoma bodies often seen
in tumors with a papillary morphology (ie serous ovarian tumor)
what are asbestos bodies
- found in lung
- deposition of calcium and iron salts
- beaded dumbbell appearance
increased secretion of parathyroid hormone (PTH), which
can be due to parathyroid tumors, can cause
bone resorption -> hypercalcemia -> metastatic calcification
resorption of bone (ie myeloma, leukemia, extensive skeletal metastases, paget’s disease, immobilization) can cause
hypercalcemia -> metastatic calcification
vitamin d related disorders such as vitamin d intoxication or sarcoidosis can cause
hypercalcemia -> metastatic calcification
renal failure can lead to retention of phosphate -> hyperparathyroidism ->
hypercalcemia -> metastatic calcification
metastatic calcification can occur throughout the body, but some sites are predisposed to calcification. what are they and why
- gastric mucosa, kidneys, lungs
* because they secrete acid -> have an internal alkaline compartment that is predisposed
