Intracellular Accumulations and Pathologic Calcifications Flashcards
Early atherosclerotic lesion: foam cells
Glycogen storages disease AKA
glycogenoses
endogenous pigment melanin
HEPATIC STEATOSIS
Macrovesicular steatosis.
Where can you see steatosis
Liver, heart, muscles, kidney
What type of pigment is melanin
endogenous
Alcholic hyaline (mallory denk body)
eosinophilic inclusion in liver cells
characteristic of alcoholic liver dz but not specific
complsed of keratin intermediate filaments
cholesterol and cholesterol ester accumulation
generally happens without intracellular accumulation(normal)
Intracytoplasmic vacuoles
Defect in protein folding/transport
Accumulation of abmornal endogenous substance due to genetic or acquired defects in its:
folding
packing
Transport
Eg: mutated forms of alpha 1 anti-trypsin
Anthracosis: blackening of the lung parenchyma
Melanin
endogenous brown black pigment
tyrosinase catalizes oxidation of tyrosine to dihydroxyphenylalanine in melanocytes
Arteriolar hyaline
amorphous eosinophilic material in arteriolar wall
Metastatic calcification
deposition may occur in normal tissues whenever ther eis hypercalcemia
Dystrophic calcification
deposits of calcium locally in dying/ abnormal tissue
typically normal serum calcium levels
typically calcium metabolism is normal
Reversability
Accumulation often reversible: if overload can be stopped or controlled
EG early atherosclerosis
In inherited storage disorders where accumulation is progressive: overload may cause cellular injusry, and it may lead to death of cells and tissue, and patient
Where does intracellular accumulation usually occur
Cytoplasm, nucleus, within organelles (usually lysosomes)
Asbestos bodies
depostition of calcium and iron salts on asbestos fibers
beaded dumbbell appearance
Extracellular hyaline
arterioles in HTN, DM
collagenous fibrous tissues in a scar
Renal tubule reabsorption droplets
Psammoma bodies
necrotic cells can seed calcium depsosition
subsequent deposition of additional layers of calcium givecs a lamellated appearance
(seen particularly in tumors with a papillary morphology, in this case a papilary serous ovarian tumor)
Exogenous pigment: carbon
most common exogenous pigment “coal dust”
air pollutant (worse urban)
Inhaled, picked up by alveolar macrophages transported through lymphatic channels to regional (tracheo-bronchial) lymph nodes
blackens lung and node tissue “anthracosis”
may cauze lung dz with hevy exposure
Tattooing of bowel by surgeon
exogenous tattoo pigment injected into colon at site of biopsy (to aid later surgery- reexcision for example)
Pigment is taken up by local macrophages
Glycogen storage dzs (glycogenoses)
Enzymatic defects in the synthesis or breakdown of glycogen
massive accumulatino of glycogen
causes cell injury and cell death
ex pompe dz, von gierke dz
Dystrophic Calcification
may be seen in areas of tissue necrosis
usually present in atheromas of advances atherosclerosis
May be seen in ageing/damaged heart valves (may hamper function)
“Psammoma bodies”
“Asbestos bodies”
Lipofuscin pigment morphology
yellow brown pigment
finely granular
cytoplasmic, often perinuclear
Most common cause of liver steatosis
Alcoholic liver dz
Lipofuscin pigement
Atherosclerosis
Smooth muscle cells and macrophages in surface/wall of arteried filled with lipid vacuoles
mostly cholesterol/cholesterol esters
Aggregated of foam cells in surface/wall of vessel give yellow appearance of atheromas
Some may rupture releasing into extracellular space
Extracellular cholesterol esters may crystalize as long needles: Cholesterol clefts seen on histologic examination
Protein accumulations
Intracellular accumulations usually rounded eosinophilic (pink) droplets, vacuoles, or aggregates in the cytoplasm
Intracellular hyaline
reabsorption droplets, alcoholic hyaline, russel bodies
Neurofibrillary tangle
Eosinophilic clumped material
can be in cytoplasm or extraacellular
silver stain can show tangle in neuron
tangle on tau immunohistochemistry (tau is a complonent of tangles)
Atherosclerotic plaque
Local excess of iron breakdown
Hemorrhade into tissues eg skin bruise
macrophages breakdown of blood
removal of iron -> ferettin -> hemosiderin
parallel breakdown of heme moiety: biliverdin (green bile) to bilirubin (red bile)
gives rise to the mulicolors of resorbin bruise (red blue, green blue, golden yellow)
Anthracosis: black carbon pigment within macrophages in lung parenchyma
Endogenous
synthesized within the body
Where is glycogen found
renal tubular cells, liver, heart cells
4 pathways of intracellular accumulation
Abnormal metabolism
Defect in protein folding/ transport
Lack of enzyme
Ingestion of indigestable materials
Metastatic calcification
deposits of ca in otherwise normal tissues
usually associated with hypercalcemia, some abnormality in calcium metabolism
Exogenous
from outside of the body
Calcification histology
Amorphous granular basolphilic (purplish) clumps and granules in stroma
Atherosclerotic plaque
4 main causes sof metastatic calcification
1) increased secretion of parathyroid hormone (pth) with subsequent bone resorbtion (eg due to parathyroid tumors
2) resorption of bone (tumors: myeloma, leukemia, extensive metastases; accelerated turnover- padgets dz; immobilization
3) vitamin D related disorders (vit D intox, sarcoidosis (macrophages ctivate vit D precursor)
4 ) renal failure (renal failure -> retentin of phosphate -> hyperparathyroidism)
other: mild-alkali syndome (excessive ingestino of ca and absorbable antacids eg mild or calcium phosphate)
Hemosiderosis
systematic overload of iron- hemosiderin may be deposited in many tissues
what gives yellow appearance of atheromas
aggregated of foam cells in surface/ wall vessel
Renal tube reabsorption droplets
seen in kidney conditions that have protein loss in the urine (proteinuria)
Normally small amounts of protein that filter through the glomerulus are reabsorbed by the proximal tubular cells
heavy proteinuria -> increased reabsorption of pink lyline droplets within the cytoplasm of proximal tubular cells
process is reversible
Why lysosomes? Lysosomal storage dzs?
Lysosomes are waste basket of cell
Russell Bodies
Gastric Xanthoma
Foamy macrophages/ histiocytes in the lamina propria beneath epithelial surface of gastric biopsy
Massive intracellular accumulation of cholesterol
Squamous epithelium with (normal) glycogenation
This is a squamous epithelium (cervix)
The glycogen within the cells makes the cytoplasm appear clear
Lipofuscin is what type of pigment
endogenous
Neurofibrillary tangle
found in alzheimers dz
contains neurofilaments and other proteins (eg tau)
Cardiac valves with calcification
Microvesicular steatosis
fine vacuoles. foamy cytoplasm
Alcoholic hyaline (mallory denk body)
clumped amorphous eosinophilic body
cytoplasmic location
tangled keratin fibrils
second pic: immunostain for karatins
Clumped staining in cytoplasm
Causes of steatosis
Toxins, protein malnutrition, DM, obesity, anoxia
Steatosis/ Fatty change
Accumulation in triglycerides within parenchymal calls
Liver: main organ in fat matabolism
Heart, muscle, kidneys
Causes: toxins, protein malnutrition, DM, obesity, anoxis
Most common cause alcoholic liver dz followed by nonalcoholic fatty liver dz (DM and obesity)
What type of pigment is hemosiderin
endogenous
Hemosiderosis in liver
liver parenchyma : special stain for iron (prussian blue stain)
Note the xytoplasmic granular blue staining representing iron
This is a case of hereditary hemochromotosis
Endogenous pigment hemosiderin
hemoglobin derived pigment
one of the major storage forms of iron
golden yellow-brown granular or crystiline
Endogenous pigment: lipfuscin
wear and tear pigment
seen in cells undergoing slow regressive change
prominent in liver and heart of aging people or pts with severe malnutrition cancer cachexia ( wasting)
Insoluable polymers of lipids and phospholipids in complex with proteins ? derived from breakdown of subcellular membranes
not harmful to cells
may indicate cell exposure to free radical injury
Breif tour of iron metabolism
in circulation, iron is normally carried by transferrin
in cells, iron is stored with apoferritin to form ferritin miscelles- present in most cells
local or systematic excess of iron -> ferretin forms hemosiderin granules (aggregates of ferritin micelles
these can be seen by microscopy
What causes xanthomas
massive intracellular accumulation of cholesterol
Protein may aggregate leading to ER stress
if unfolded protein response overwhelmed, will lead to apoptosis
Amyloidoses
Protein accumulations. Usually deposits extracellular
Glycogen
Stored in the xytoplasm of cells
excessive deposits may be seen with abnormal glucose or glycogen metabolism
glycogen dissolves in aqueous fixatives -> glycogen accumulation appears clear
DM- the most important example of a disorder of glucose metabolism
glycogen found in renal tubular cells, liver, heart cells
Lipofuscin pigement
Tattoo
exogenous pigment
localized exogenous pigmentation of skin (or bowel)
In skin, pigment is phagocytosed by dermal marcophages
generally inert- not associated with inflammation
May reside locally long term
Lack of enzyme
Failure to degrade metabolite due to inherited enzyme deficiency
Eg: storage disorders
Eg Lysosomal storage dzs
Cholesterolosis of the gallbladder
focal accumulation of cholesterol containing maccrophages in the lamina propria
Neiman Pick Dz Type C
Lysosomal storage dz
mutations in enzyme involved in protein trafficking
cholesterol accumulates in multiple organs
Abnormal Metabolism
Excess sunthesis
Decreased removal
Eg: steatosis/ fatty liver
Pathologic calcification
abnormal tissue deposition of calcium salts
Russell bodies
large cytoplasmic protein droplets (in a plasma cell tumor- myeloma)
Seen in certain plasma cells actively synthesizing immunoglobulins ( area of chronic inflammation, plasma neoplasms)
ER becomes hugely distended
Hyaline: a morphologic term
alteration in cellular or extracellular space that gives hemogenous glassy pink appearance on routine H+E
a variety of pathologies can give rise to hyaline appearance, does not refer to a specific pattern of accumulation
Main causes of hemosiderosis
1) increased absorption of dietary iron (imborn error of metabolism- hemochromatosis)
2) hemolytic anemias (premature lysis of RBCs -> releases abnormal quantities of iron)
3) repeated blood transfusions (equivalent to exogenous administration of iron)
Ingestion of indigestible materials
Deposition and accumulation of abnormal exogenous substance
When cell does not have enzymatic machinery to degrade the substance or the ability to transport to other sited
Eg Carbon or silica accumulation
Normal iron breakdown
may be seen normally in sites where RBCs are broken down (bone marrow, spleen, liver)
Metastatic calcification
may occur throughout the body
particular sites include gastric mucosa, kidneys, kungs- all secrete acid -> have an internal alkaline compartment that predisposed to calcification
microscopically morphologically simiar to dystrophic calcification
usually does not have clinical dysfunction (unless massive deposition in eg lungs, kidneys
Cholesterol esters crystalize as long needles called…
cholesterol clefts
Alpha 1 anti trypsin deficciency in liver
aggregates of misfolded A1AT proteins
Renal tubule reabsorption droplets
proximal tubule cells :abundant eosinophilic cytoplasm
protein reabsorption droplets: small eosinophilic droplets
Calcification: microscopic appearance
Basophilic (purple color on Hand E), amorphous, granular, maybe clumped appearance
Can be extracellular or intracellular or both
heterotopic bone may form in the long-standing areas of calcification
Macrovascular steatosis
cytoplasmic large clear droplets- looks like fat cell/ adipocyte
Xanthomas
Macrophage intracellular accumulation of cholesterol is characteristic of acquired and hereditary lyperlipidemic states
groups of foamy macrophages found in the connective tissue of skin and in tendons formin masses termed xanthomas
May also be seen in non-hyperlipidemic states
