Pathology Intracellular And Extracellular Accumulations And Pigments (Test 1, Lecture 4)

Front 1

3 categories of intracellular accumulations

Back 1

1. A normal cellular constituent accumulated in excess – H2O, lipids, proteins, CHO
2. An abnormal substance – endogenous or exogenous
3. Pigments - endogenous or exogenous

Front 2

3 mechanisms or types of processes of I/C accumulations

Back 2

1. Incr rate of production and/or decr rate of removal – fatty change in the liver, protein droplets in renal prox tubular cells due to increased leakage from glomeruli
2. Defects in the metabolism, packaging, transport or secretion – lysosomal storage diseases
3. Inability to degrade the exogenous substances – carbon, silica

Front 3

prototype of accumulation of lipids

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hepatic lipidosis

Front 4

5 mechanisms of hepatic lipidosis or steatosis

Back 4

1. Excessive delivery of FFAs either from the gut or from adipose tissue
2. Decreased β-oxidation of FAs to ketones and other substances b/c of mitochondrial injury (toxins, hypoxia)
3. Impaired synthesis of apoprotein (CCl4, aflatoxin)
4. Impaired combination of TGs and protein to form lipoprotein (uncommon)
5. Impaired release of LPs from the hepatocyte (uncommon)

Front 5

another term for lipidosis

Back 5

steatosis

Front 6

If severe - enlarged, yellow, soft and friable; rounded edges of lobes; Cut surface – bulge, soft, friable, of greasy texture; If severe, sections float in formalin; Important to distinguish from glucocorticoid hepatopathy (accumulation of glycogen) in dogs

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gross examination of fatty liver in hepatic lipidosis

Front 7

Initially a few small clear vacuoles → eventually coalesce into larger vacuoles; Vacuoles sharply delineated; Nucleus may be displaced; Need to be distinguished from glycogen and water (hydropic degeneration); Special stains – Oil-red-O for fat; PAS for glycogen; water not stained

Back 7

microscopic examination of hepatic lipidosis with varying degrees of cytoplasmic vacuolation

Front 8

3 causes of accumulation of glycogen

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1. DM
2. excess corticosteroids Rx (most common)
3. glycogen storage disease (glycogenesis)

Front 9

5 causes of accumulation of proteins

Back 9

1. Reabsorption droplets in proximal renal tubular cells – in proteinuria
2. Excessive production of normal proteins – Russell bodies (Mott cells-type of plasma cells which are full of Ab’s)
3. Defective I/C transport and secretion of critical proteins
4. Accumulation of cytoskeletal proteins (Alcoholic hyaline – an eosinophilic cytoplasmic inclusion in liver cells composed of keratin IF)
5. Aggregation of abnormal proteins – I/C or E/C deposits of abnormal or misfolded proteins (proteinopathies)

Front 10

an eosinophilic cytoplasmic inclusion in liver cells composed of keratin IF

Back 10

alcoholic hyaline

Front 11

– a descriptive term that refers to an alteration within cells or in the E/C space that gives a homogeneous, glassy, pink appearance in routine histologic sections

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"hyaline"

Front 12

examples include Reabsorption droplets, Russell bodies, alcoholic hyaline

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I/C hyaline

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example of ____ _____ is hyalinized walls of arterioles in the kidney in longstanding hypertension and diabetes mellitus

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E/C hyaline

Front 14

examples include Autophagic vacuoles; Crystalline protein inclusion bodies (Crystalloids) – in hepatocytes and renal tubular cells in old dogs, unknown significance;
Viral inclusion bodies; Lead inclusion bodies

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other I/C inclusions

Front 15

type of plasma cells which are full of Ab’s

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mott cells

Front 16

examples of _____ _____ include Hyaline casts in the lumens of renal tubules (proteinuria), Serum or plasma in blood vessels, Plasma proteins in vessel walls (ex. porcine edema disease), Old scars (collagen), Thickened BM (glomerulonephritis), Hyaline membranes of the alveolar walls (leakage of alveolar capillaries), Hyaline microthrombi (DIC), Amyloid

Back 16

hyaline substances

Front 17

hyaline substances are examples of ______ ______

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extracellular accumulations

Front 18

a pathologic proteinaceous substance deposited in the extracellular space in various tissues and organs of the body

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amyloid

Front 19

what is the physical nature of amyloid

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beta-pleated sheet conformation

Front 20

what is the chemical nature of amyloid

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95% fibril proteins, 5% P component and other glycoproteins

Front 21

how many biochemically distinct forms of amyloid proteins

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20

Front 22

what are the 3 most common forms of amyloid proteins

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AL, AA, AB (beta)

Front 23

derived from Ig light chains produced in plasma cells

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AL (amyloid light chain)

Front 24

derived from a unique non-Ig protein synthesized by the liver

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AA (amyloid-associated)

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precursor of AA fibrils and found in the serum

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SAA (serum amyloid-associated)

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The production of ___ protein is increased in inflammatory states as part of the “acute phase response”, therefore, is associated with chronic inflammation, and is often called ______ ______.

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SAA; secondary amyloidosis

Front 27

produced from a precursor protein and is found in the cerebral lesions of Alzheimer disease

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AB (beta) amyloid

Front 28

3 other proteins found in amyloid depostis

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transthyretin (TTR), B2-microglobulin, prion proteins

Front 29

a normal serum protein that binds and transports thyroxine and retinol; A mutant form of this is deposited in a group of familial amyloid polyneuropathies.

Back 29

transthyretin (TTR)

Front 30

a component of MHC-I molecules and a normal serum protein, has been identified as the amyloid fibril subunit (Aβ2m) in amyloidosis associated with long-term hemodialysis.

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β2-microglobulin

Front 31

in a minority of cases of ____ disease, the misfolded _____ proteins aggregate in the extracellular space w/n the CNS and acquire the structural and staining characteristics of amyloid protein

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prion (prion proteins)

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3 other minor components in amyloid

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serum amyloid P component, proteoglycans, and highly sulfated GAGs.

Front 33

serum amyloid P component, proteoglycans, and highly sulfated GAGs.

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amyloid

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When the cut surface of an affected kidney is treated with iodine solution, then w/ dilute sulfuric acid, it turns blue – hence the name meaning “starch-like”

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amyloid

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____-____ stains amyloid orange to orange red and imparts apple green fluorescence on histologic sections

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congo-red

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Common tissues affected in animals – kidney, spleen, LN, liver, islets (cats), endocrine tumors, GI; Systemic

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by amyloid

Front 37

an abnormal condition of the blood or bone marrow.

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dyscrasia

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the most common form of amyloidosis in human, not in animals

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plasma cell dyscrasia

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common form of amyloidosis in animals

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Reactive systemic amyloidosis (secondary amyloidosis)

Front 40

4 other E/C accumulations besides amyloidosis

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fibrinoid change, gout, psuedogout, cholesterol crystals

Front 41

a hyaline deposition of Ig, C, &/or plasma proteins including fibrin in the vascular wall, due to injury to the intima and media such as in IM vasculitides

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fibrinoid change

Front 42

deposition of Na urate crystals or urates in tissue in humans, birds and reptiles

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gout

Front 43

deposition of Ca pyrophosphate crystals in humans, nonhuman primates

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psuedogout

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by-products of hemorrhage and necrosis; E/C accumulation

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cholesterol crystals

Front 45

Abnormal tissue deposition of Ca phosphates or carbonates in dead or normal tissues, together with smaller amount of Fe, Mg and other mineral salts

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pathologic calcification

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deposition of Ca in dying tissues despite normal serum levels of Ca and in the absence of derangements in Ca metabolism

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dystrophic calcification

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deposition of Ca salts in otherwise normal tissues - results from hypercalcemia

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metastatic calcification

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deposition of Ca salts in otherwise normal tissues - results from hypercalcemia

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calcification morphology

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Microscopic - Basophilic, granular, sometimes clumped appearance

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calcification morphology

Front 50

Almost always results from hypercalcemia; Common location of Ca deposition - Gastric mucosa, kidneys, lungs, systemic arteries, and pulmonary veins

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metastatic calcification

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4 causes of hypercalcemia

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Renal failure;Vitamin D toxicosis; PTH and PTH-related protein (Primary hyperparathyroidism - rare; Hypercalcemia associated w/ canine lymphomas and apocrine carcinomas of the anal sac); Destruction of bone from primary or metastatic tumors

Front 52

Production of bone at an abnormal site

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heterotopic (ectopic) bone

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foci of cells or tissues, which are microscopically normal but present at an abnormal location

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'heterotopia'

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2 types of ectopic bone

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heterotopic; osseous metaplasia

Front 55

Substances that are inherently colored

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pigments

Front 56

________ is most common pigment along with ______ (________ is not important in pathology except in a few exceptions)

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hemoglobin; melanin; melanin

Front 57

what is the most abundant mesenchymal tissue in our body

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fibrous tissue

Front 58

synthesized within the body: Melanin, lipofuscin, hemoglobin, hemosiderin, bilirubin, etc

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endogenous pigments

Front 59

are formed outside the body: Carbon, soot, coal dust, silica, other environmental dusts, carotenoid, tetracycline, etc

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exogenous pigments

Front 60

the general term used for any organic and inorganic dust inhaled into and retained in the lung

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pneumoconiosis

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inhalation of carbon

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anthracosis

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inhalation of silicon

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silicosis

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cane pulp dust

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bagassosis

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cotten fiber dust

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byssinosis

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iron (as a result of hemorrhage)

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siderosis

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asbestos

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asbestosis

Front 67

most common exogenous pigment

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ubiquitous carbon in the air

Front 68

Yellow to orange yellow, fat-soluble pigments of plant origin, including β–carotene, the precursors of vitamin A

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carotenoid

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Normally occur in plasma and fat of horses, Jersey and Guernsey cattle, and sometimes dogs

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carotenoid pigmentation

Front 70

The pigments are not seen microscopically in routine pathologic sections b/c they are removed by alcohol; may obscure or confuse the dectection of icterus

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carotenoid pigment

Front 71

also called lipochrome pigments

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carotenoid pigments

Front 72

__________-based antibiotics administered during the teeth development will stain the teeth yellow or brown

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tetracycline

Front 73

also stains bone that is being laid down and has been used experimentally as a marker for that new bone

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tetracycline abx

Front 74

5 major endogenous

Back 74

melanin, lipofuscin, hemoglobin, hemosiderin, bilirubin

Front 75

A normal brown-black pigment in melanocytes, in epidermal cells, in pigmented epithelial cells of the eye, and occasionally in other tissues – protective mechanism (especially against UV light); Little pathologic significance other than need for recognition, depigmented skin and hair conditions, and melanoma

Back 75

melanin

Front 76

a circumscribed, nonpalpable spot <1cm in diameter in characterized by a change in color of skin

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macule

Front 77

an acquired skin disease characterized by patches of unpigmented skin (often surrounded by a heavily pigmented border)

Back 77

vitiligo (think mercy's nose)

Front 78

a general lack of melanin due to a lack of tyrosinase. The affected animal is called albino

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albinism

Front 79

Cu deficiency in cattle and sheep can lead to ____ _ ___

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defect in melaninogenesis

Front 80

An insoluble pigment, aka lipochrome, wear-and-tear pigment or aging pigment; Composed of polymers of lipids and phospholipids complexed with protein; Derived through lipid peroxidation of polyunsaturated lipids of subcellular membrane in the lysosome; Not injurious to the cell of its function; Gross – yellow, tan to brown discoloration of affected tissues, particularly intestine

Back 80

lipofuscin

Front 81

The term _____ is sometimes used to designate the wear-and-tear pigments, e.g., lipofuscin, haemofuscin, ceroid.

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lipochrome

Front 82

More precisely, ________ are yellow pigments that seem to be identical to carotene and xanthophyll and are frequently found in the serum, skin, adrenal cortex, corpus luteum, and arteriosclerotic plaques, as well as in the liver, spleen, and adipose tissue

Back 82

lipochromes

Front 83

In tissue sections, a yellow-brown, finely granular intracytoplasmic, often perinuclear pigmen; Seen in cells undergoing slow, regressive changes and is particularly prominent in the myocardial cells and neurons of aging patients or patients with severe malnutrition and cancer cachexia; EM – highly electron dense, membranous structures

Back 83

lipofuscin

Front 84

a variant of lipofuscin, acid-fast and autofuorescent

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ceroid

Front 85

a group of several genetically distinct disorders in children and animals

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Neuronal ceriod-lipofuscinosis

Front 86

In the dog, vitamin E or Se deficiencies can lead to ________ of the smooth muscle of the intestine; Unsaturated fatty acid-rich diet can increase the amount of ________

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lipofuscinosis; lipofuscin

Front 87

Hemoglobin and Hemoglobin-derived pigments

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hematogenous pigments

Front 88

4 types of hemoglobin

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oxyhemoglobin, unoxygenated Hb, methemoglobin, carboxyhemoglobin

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5 types of hematogenous pigments

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hemoglobin, hemosiderin, bilirubin, hematoidin, hematin

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transports CO2, NO

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globin molecules of Hb

Front 91

transports O2

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heme molecules of Hb

Front 92

a tetrapyrrole porphyrin ring containing ferrous (Fe2+) iron

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heme

Front 93

Hemoglobin with the heme iron changed from the ferrous to the ferric state (Fe3+)

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methemoglobin

Front 94

____________ is often due to nitrates, nitrite, chlorate and acetaminophen toxicities, mostly from fertilizer and drugs. The blood is brown, chocolate color that would stay 4-6 hours after death.

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methemoglobinemia

Front 95

CO attached Hb. Hb has a high affinity for CO. The blood is bright cherry red.

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carboxyhemoglobin/
carboxyhemoglobinemia

Front 96

Also the blood superoxygenated with ______ toxicity is bright cherry red

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cyanide

Front 97

RBC’s die after 120 days and go to spleen to be recycles. _____ is a protein that we want to get back.

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globin

Front 98

O2 carrying pigment of rbc – responsible for the pink appearance of the body

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hemoglobin

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oxygenated arterial blood – bright red is due to what

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oxyhemoglobin

Front 100

the venous blood is bright red as the arterial blood

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cyanide poisoning

Front 101

carboxyHb – cherry red blood

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CO poisoning

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MetHb – reddish-brown (chocolate brown) blood

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nitrite poisoning

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pink plasma, icteric tissue; Hb is excreted by the kidney, staining the kidney dark red to black and the urine red. Similar, but often less severe, change may result from myoglobinuria after the destruction of muscle

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Hb released from severe intravascular hemolysis

Front 104

A Hb-derived, Fe-containing yellow-brown granular pigment; a partially denatured from of ferritin that easily aggregates

Back 104

hemosiderin

Front 105

~ 25% of the body’s total iron content is in an intracellular storage pool composed of _____ (normal) and ______ (abnormal)

Back 105

ferritin; hemosiderin

Front 106

a protein that stores iron and releases it in a controlled fashion

Back 106

ferritin

Front 107

In local and systemic excess of iron, ferritin forms intracytoplasmic _______ granules

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hemosiderin

Front 108

Iron is normally carried by specific transport these glycoproteins in plasma

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transferrins

Front 109

Under normal conditions, small amount of ________ can be seen in macrophages of the bone marrow, spleen and liver, all actively engaged in RBC breakdown; Can be seen in hemorrhagic areas

Back 109

hemosiderin

Front 110

in congestive heart failure, ______ is seen in alveolar macrophages; grossly a yellowish tan to brown color of the lung is seen in pulmonary __________

Back 110

hemosiderin; hemosiderosis

Front 111

Excessive accumulation of iron in parenchymal organs such as the liver and pancreas, either from a genetic defect causing excessive iron absorption (hereditary ________) or as consequence of parenteral administration of iron (secondary ______)

Back 111

hemochromatosis

Front 112

leaking of cells thur capillary

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diapedesis

Front 113

like to accumulate when there is a low oxygen level

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fibroblasts

Front 114

stain specific for iron

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prussian blue reaction

Front 115

Major pigment in bile but is only present in a small about; bile is mostly water and bile acids/salts which don’t contain pigment

Back 115

bilirubin

Front 116

Normal breakdown product of the heme, thus contains no iron (basically take heme, remove iron and then straighten the molecule)

Back 116

bilirubin

Front 117

May accumulate in the blood or in tissues in hemolytic diseases, or in hepatic and cholestatic disease, causing jaundice (icterus)

Back 117

bilirubin

Front 118

A green-brown to yellow-brown pigment in tissue sections

Back 118

bilirubin

Front 119

mixed with bilirubin to make water soluble

Back 119

glucuronic acid

Front 120

before bilirubin, heme is broken down into what

Back 120

biliverdin

Front 121

- Unconjugated hyperbilirubinemia (Crigler–Najjar syndrome type I) results from an autosomal recessive inherited deficiency of hepatic __________.

Back 121

UDP-glucuronosyltransferase (UGT) 1A1 activity

Front 122

6 mechanisms leading to icterus

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Excess production of bilirubin (hemolysis); Reduced uptake of bilirubin from the plasma by hepatocytes; Impaired or absent conjugation in hepatocytes, often a inherited abnormality as in Gunn rat; Hepatic necrosis disrupting the wall of the bile canaliculus; Decreased excretion of conjugated bilirubin by the hepatocytes into the bile canaliculus;
Reduced flow of bile from liver to the intestine

Front 123

icterus that is usually associated with intravascular hemolysis

Back 123

hemolytic or prehepatic

Front 124

3 types of icterus

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Hemolytic (Prehepatic); hepatic; Posthepatic (Obstructive, cholestatic)

Front 125

5 steps in the mechanism of bilirubin metabolism and elimination

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Bilirubin production from heme; Unconj bilirubin is bound to serum albumin and delivered to the liver; Hepatocellular uptake;
Glucuronidation in the ER;
Gut bacteria degrade it to colorless urobilinogens. The urobilinogens (stercobilin) and the residue of intact pigments are excreted in the feces, with some reabsorption and excretion into urine (urobilin).

Front 126

Hepatocellular uptake of bilirubin. _________ in the endoplasmic reticulum generate bilirubin __________ and ____________, which are water soluble and readily excreted into bile.

Back 126

glucuronidation; monoglucuronides; diglucuronides

Front 127

Gut bacteria ________ the bilirubin and degrade it to colorless ________. The _________ (stercobilin) and the residue of intact pigments are excreted in the feces, with some reabsorption and excretion into urine (urobilin).

Back 127

deconjugate; urobilinogens; urobilinogens

Front 128

Bilirubin is usually only toxic to the kidney under _______ conditions.

Back 128

hypoxic

Front 129

erythrocyte parasite

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babesiosis

Front 130

a yellow-brown pigment seen occasionally at sites of previous hemorrhage, and is believed to be locally precipitated bilirubin

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hematoidin

Front 131

a derivative of hemoglobin produced in tissues fixed in improperly buffered formalin (referred to as formalin pigment). It resembles hemosiderin but usually can be seen to overlie cells instead of being in them

Back 131

acid hematin

Front 132

category of acid hematin also include _______ hematin

Back 132

parasite

Front 133

Pink teeth and red-brown urine. Their teeth exhibit a red purple fluorescence b/c of the deposition of porphyrins in the dentin. The urine is red-brown b/c of the excretion of large amounts of uroporphyrin I; animals may also have photosensitivity

Back 133

Inherited congenital porphyria

Front 134

Porphyria occurs in cattle and cats as an inherited defect in the synthesis of the normal heme pigment, _______, leading to an accumulation of photodynamic _________.

Back 134

ferroprotoporphyrin; porphyrins

Front 135

3 types of photosensitization

Back 135

primary, secondary (hepatogenous), congenital (enzyme deficiency)

Front 136

the color of bilirubin, hemoglobin

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Icterus

Front 137

the color of MetHb

Back 137

chocolate brown blood

Front 138

color of hemosiderin

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tan to brown

Front 139

color of porphyria

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pink to red-brown

Front 140

excess or lack of blood

Back 140

congestion, hemorrhage, ischemia, anemia

Front 141

color of accumulation of WBCs

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white (abcess, lymphoma)

Front 142

examples of mesenchymal tissues

Back 142

DWCT, fibrosarcoma, fat, bone,

Front 143

examples of deposits

Back 143

Ca, urates

Front 144

pigments produced by organisms

Back 144

pseudomonas, corynebacterium, phaeohyphomyces, etc.