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FMS Week 6 > Intracellular Accumulations and Pathologic Calcifications > Flashcards

Intracellular Accumulations and Pathologic Calcifications Flashcards

1
Q
A

Early atherosclerotic lesion: foam cells

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2
Q

Glycogen storages disease AKA

A

glycogenoses

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3
Q
A

endogenous pigment melanin

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4
Q
A

HEPATIC STEATOSIS

Macrovesicular steatosis.

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5
Q

Where can you see steatosis

A

Liver, heart, muscles, kidney

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6
Q

What type of pigment is melanin

A

endogenous

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7
Q

Alcholic hyaline (mallory denk body)

A

eosinophilic inclusion in liver cells

characteristic of alcoholic liver dz but not specific

complsed of keratin intermediate filaments

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8
Q

cholesterol and cholesterol ester accumulation

A

generally happens without intracellular accumulation(normal)

Intracytoplasmic vacuoles

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9
Q

Defect in protein folding/transport

A

Accumulation of abmornal endogenous substance due to genetic or acquired defects in its:

folding

packing

Transport

Eg: mutated forms of alpha 1 anti-trypsin

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10
Q
A

Anthracosis: blackening of the lung parenchyma

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11
Q

Melanin

A

endogenous brown black pigment

tyrosinase catalizes oxidation of tyrosine to dihydroxyphenylalanine in melanocytes

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12
Q
A

Arteriolar hyaline

amorphous eosinophilic material in arteriolar wall

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13
Q

Metastatic calcification

A

deposition may occur in normal tissues whenever ther eis hypercalcemia

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14
Q

Dystrophic calcification

A

deposits of calcium locally in dying/ abnormal tissue

typically normal serum calcium levels

typically calcium metabolism is normal

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15
Q

Reversability

A

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

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16
Q

Where does intracellular accumulation usually occur

A

Cytoplasm, nucleus, within organelles (usually lysosomes)

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17
Q
A

Asbestos bodies

depostition of calcium and iron salts on asbestos fibers

beaded dumbbell appearance

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18
Q

Extracellular hyaline

A

arterioles in HTN, DM

collagenous fibrous tissues in a scar

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19
Q
A

Renal tubule reabsorption droplets

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20
Q
A

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)

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21
Q

Exogenous pigment: carbon

A

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

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22
Q
A

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

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23
Q

Glycogen storage dzs (glycogenoses)

A

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

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24
Q

Dystrophic Calcification

A

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”

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25
Q

Lipofuscin pigment morphology

A

yellow brown pigment

finely granular

cytoplasmic, often perinuclear

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26
Q

Most common cause of liver steatosis

A

Alcoholic liver dz

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27
Q
A

Lipofuscin pigement

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28
Q

Atherosclerosis

A

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

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29
Q

Protein accumulations

A

Intracellular accumulations usually rounded eosinophilic (pink) droplets, vacuoles, or aggregates in the cytoplasm

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30
Q

Intracellular hyaline

A

reabsorption droplets, alcoholic hyaline, russel bodies

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31
Q
A

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)

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32
Q
A

Atherosclerotic plaque

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33
Q

Local excess of iron breakdown

A

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)

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34
Q
A

Anthracosis: black carbon pigment within macrophages in lung parenchyma

35
Q

Endogenous

A

synthesized within the body

36
Q

Where is glycogen found

A

renal tubular cells, liver, heart cells

37
Q

4 pathways of intracellular accumulation

A

Abnormal metabolism

Defect in protein folding/ transport

Lack of enzyme

Ingestion of indigestable materials

38
Q

Metastatic calcification

A

deposits of ca in otherwise normal tissues

usually associated with hypercalcemia, some abnormality in calcium metabolism

39
Q

Exogenous

A

from outside of the body

40
Q
A

Calcification histology

Amorphous granular basolphilic (purplish) clumps and granules in stroma

41
Q
A

Atherosclerotic plaque

42
Q

4 main causes sof metastatic calcification

A

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)

43
Q

Hemosiderosis

A

systematic overload of iron- hemosiderin may be deposited in many tissues

44
Q

what gives yellow appearance of atheromas

A

aggregated of foam cells in surface/ wall vessel

45
Q

Renal tube reabsorption droplets

A

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

46
Q

Why lysosomes? Lysosomal storage dzs?

A

Lysosomes are waste basket of cell

47
Q
A

Russell Bodies

48
Q
A

Gastric Xanthoma

Foamy macrophages/ histiocytes in the lamina propria beneath epithelial surface of gastric biopsy

Massive intracellular accumulation of cholesterol

49
Q
A

Squamous epithelium with (normal) glycogenation

This is a squamous epithelium (cervix)

The glycogen within the cells makes the cytoplasm appear clear

50
Q

Lipofuscin is what type of pigment

A

endogenous

51
Q

Neurofibrillary tangle

A

found in alzheimers dz

contains neurofilaments and other proteins (eg tau)

52
Q
A

Cardiac valves with calcification

53
Q

Microvesicular steatosis

A

fine vacuoles. foamy cytoplasm

54
Q
A

Alcoholic hyaline (mallory denk body)

clumped amorphous eosinophilic body

cytoplasmic location

tangled keratin fibrils

second pic: immunostain for karatins

Clumped staining in cytoplasm

55
Q

Causes of steatosis

A

Toxins, protein malnutrition, DM, obesity, anoxia

56
Q

Steatosis/ Fatty change

A

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)

57
Q

What type of pigment is hemosiderin

A

endogenous

58
Q
A

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

59
Q

Endogenous pigment hemosiderin

A

hemoglobin derived pigment

one of the major storage forms of iron

golden yellow-brown granular or crystiline

60
Q

Endogenous pigment: lipfuscin

A

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

61
Q

Breif tour of iron metabolism

A

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

62
Q

What causes xanthomas

A

massive intracellular accumulation of cholesterol

63
Q
A

Protein may aggregate leading to ER stress

if unfolded protein response overwhelmed, will lead to apoptosis

64
Q

Amyloidoses

A

Protein accumulations. Usually deposits extracellular

65
Q

Glycogen

A

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

66
Q
A

Lipofuscin pigement

67
Q

Tattoo

A

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

68
Q

Lack of enzyme

A

Failure to degrade metabolite due to inherited enzyme deficiency

Eg: storage disorders

Eg Lysosomal storage dzs

69
Q
A

Cholesterolosis of the gallbladder

focal accumulation of cholesterol containing maccrophages in the lamina propria

70
Q

Neiman Pick Dz Type C

A

Lysosomal storage dz

mutations in enzyme involved in protein trafficking

cholesterol accumulates in multiple organs

71
Q

Abnormal Metabolism

A

Excess sunthesis

Decreased removal

Eg: steatosis/ fatty liver

72
Q

Pathologic calcification

A

abnormal tissue deposition of calcium salts

73
Q

Russell bodies

A

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

74
Q

Hyaline: a morphologic term

A

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

75
Q

Main causes of hemosiderosis

A

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)

76
Q

Ingestion of indigestible materials

A

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

77
Q

Normal iron breakdown

A

may be seen normally in sites where RBCs are broken down (bone marrow, spleen, liver)

78
Q

Metastatic calcification

A

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

79
Q

Cholesterol esters crystalize as long needles called…

A

cholesterol clefts

80
Q
A

Alpha 1 anti trypsin deficciency in liver

aggregates of misfolded A1AT proteins

81
Q

Renal tubule reabsorption droplets

A

proximal tubule cells :abundant eosinophilic cytoplasm

protein reabsorption droplets: small eosinophilic droplets

82
Q

Calcification: microscopic appearance

A

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

83
Q

Macrovascular steatosis

A

cytoplasmic large clear droplets- looks like fat cell/ adipocyte

84
Q

Xanthomas

A

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

FMS Week 6 (12 decks)

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