Pigments and tissue deposits Flashcards

1
Q

Haemoglobin

A

Red when bound to oxygen
Red staining of tissues=haemoglobin imbibition
Cherry red when bound to carbon monoxide (carboxyhaemoglobin)
Chocolate brown when haem is oxidized (methaemoglobin)
Anemia (pallor)=lack of hemoglobin or RBCs

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2
Q

Hemoglobin catabolism: normal processing of RBCs

A
  1. Effete RBCs removed from circulation in splenic macrophages
  2. Iron and globin recycled leaving heme moiety
    - iron stored as hemosiderin
    - globin broken down into amino acids
  3. heme is enzymatically converted to bilirubin
    - heme is converted to biliverdin using heme oxygenase, and then to bilirubin using bv reductase
  4. Insoluble bilirubin (unconjugated) bound to albumin transported from spleen to liver through the bloodstream
  5. Liver removes bilirubin from blood stream and adds glucuronic acid (conjugation) to make soluble
  6. conjugated bilirubin secreted into bile
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3
Q

Bilirubin processing

A
Unconjugated bilirubin (insoluble) is carried by Albumin to liver
Hepatocyte conjugates bilirubin (soluble) for secretion  using diglucuronide
This is secreted into the bile

Too much bilirubin in the blood =hyperbilirubinemia
when bilirubinemia&raquo_space; 2 mg/dl you get yellow staining of tissues and fluids= jaundice or icterus

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4
Q

What might measuring conjugated and unconjugated bilirubin in jaundiced animal patients be useful

A

Conjugated indicates damaged RBCs

Unconjugated indicates not damaged RBCs

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5
Q

Jaundice or Icterus

A

Increased bilirubin in tissues
Yellow discoloration of tissue or fluid
Most prominent in mucous membranes, adventitial surfaces
Do not use fat to assess, esp livestock, corn fed chickens, monkeys
Gross only

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6
Q

Bilirubin secretion

A

The liver is central to the processing of bilirubin but jaundice does not only indicate liver disease
Processing of bilirubin can be affected by:
-increased RBC breakdown (hemolysis)
Decreased hepatocyte function/hepatocyte damage
Blockage of bile duct

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7
Q

Clinical classifications of jaundice

A

Prehepatic/hemolytic
Hepatic/hepatocellular
Posthepatic/obstructive

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8
Q

Prehepatic jaunice

A

Bilirubin production from hemolysis RBCs exceeds hepatocellular uptake
Increased RBC break down

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9
Q

Prehepatic jaunice- extravascular lysis

A

Excess RBC phagocytosis in spleen

Splenomegaly

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10
Q

Prehepatic jaunice- intravascular lysis

A
damage to RBC in circulation
Release of free hemoglobin
Hemoglobinemia
Filtered at kidney (toxic nephrosis)
hemoglobinuria
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11
Q

Hemolytic anemia- infectious

A

babesiosis (red water) in cattle: intraerythrocytic parasite causes intravascular lysis and hemolglobinuria
Mycoplasma hemofelis in cats: extraerythrocytic parasite causes extravascular lysis and splenomegaly

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12
Q

Prehepatic jaunice- toxic

A

Oxidative damage to RBC surface by drugs, chemicals, plants)

Copper poisoning in sheep, Brassica poisoning in cattle, nitrate toxicity: can cause intravascular or extravascular

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13
Q

Prehepatic jaunice- immune mediated

A

antibodies target or destroy RBCs: can cause intra or extravascular lysis
Canine autoimmune hemolytic anemia
Neonatal isoerythrolysis
Incompatible blood transfusion

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14
Q

Hemoglobin catabolism- extravascular hemolysis

A

Hb not free in blood to be filtered by the kidney
In the spleen:
-phagocytosis of RBCs -> Anemia and splenomegaly
-> heme -> bilirubin
-> circulation -> jaundice (too much bilirubin and albumin)
-> bilirubin and albumin unconjugated to liver
-> bilirubin and glucoronide (conjugated) -> bile

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15
Q

Hemoglobin catabolism- intravascular hemolysis

A

Excess Hb filtered by kidney
haptoglobin soon saturated so wind up with free hemaglobin
Lysis of RBCs in circulation-> anemia
Free hemaglobin-> hemoglobinemia
Hemoglobin+haptoglobin -> phagocytosis in spleen -> jaundice
Saturation of haptoglobings

Free hemoglobin in renal tubule in kidney -> hemoglobinuria
Toxic nephrosis

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16
Q

Hemoglobin in kidney

A

homogenous red-orange material in renal tubules

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17
Q

Hemoglobinuria

A

Hemoglobin in urine
dark red-brown urine (and kidney)
Pink serum (hemaglobinemia) as hemoglobin complexes with haptoglobins
Only from intravascular lysis

Intravascular damage to RBCs -> release of free hemoglobin

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18
Q

Hematuria

A

Blood in urine from lower urinary tract lesion
dark red brown urine
Normal (straw coloured) serum
RBCs in urine will separate n standing or centrifugation
Hemorrhage in urinary tract (trauma, cystitis, neoplasia)

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19
Q

Myoglobinuria

A

Myoglobin in urine from rhabdomyolysis
Dark red brown urine
Normal (straw colored) serum (myoglobinanemia does not stain tissues) and is rapidly cleared from blood and does not bind and form a complex with haptoglobin

damage to skeletal damage -> release of myoglobin

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20
Q

etiology of intravascular hemolysis- oxidative damage

A
Acetaminophen
Benzocaine
Nitrite
Brassica spp 
Onions,
red maple
Acute zinc or copper toxicosis
propylene glycol (cat foods, some antifreeze)
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21
Q

etiology of intravascular hemolysis- erythrocyte metabolic deficiency

A

G-6-PD
GSH (sheep)
Phosphofructokinase (dogs)

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22
Q

etiology of intravascular hemolysis-Infectious

A

Intraerythrocytic parasites
Clostridium hemolyticum
E. coli
Lepto

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23
Q

etiology of intravascular hemolysis-Immune mediated

A

IMHA
Neonatal isoerythrolysis
Incompatible transfusions

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24
Q

etiology of intravascular hemolysis-Direct membrane damage

A
Castor beans (contain ricin)
Snake venom
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25
Q

Hepatic jaundice: bilirubin processing reduced

A

Hepatocellular dysfunction or necrosis

  1. decreased bilirubin uptake
  2. Decreased conjugation
  3. decreased secretion in bile
  4. decreased bile flow along canaliculi
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26
Q

Posthepatic jaundice

A

Obstruction of bile duct

  1. bile not secreted into intestine
  2. Bile refluxes into bloodstream
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27
Q

Hemoglobin catabolism: hemosiderin

A

iron from hemoglobin stored as hemosiderin
heme to bilirubin
globin- broken down into amino acids
Hemosiderin accumulation
1. local: chronic congestion, hemorrhage
2. widespread: hemolysis, inherited disorders in Fe storage
Accompanies processes associated with RBC breakdown

28
Q

Hemosiderin

A

Intracellular iron storage esp spleen

Gross- must have a lot to impart gross brown color

29
Q

Hemosiderin- microscopic

A

Dark-yellow-brown, coarse granular cytoplasmic pigment

Stains blue-black with Prussian blue/Perls

30
Q

Hemosiderin photos

A

Mynah bird liver
Generalized hemosiderosis due to hemolysis
Dog heart and lung: mottles brown lungs due to diffuse accumulation of hemosiderin in macrophages- rounded heart
Localized hemosiderosis due to chronic congestion- heart failure cells

31
Q

Erythropoietic porphyria

A

Pink tooth
A developmental anomaly of calves, cats, pigs
Inherited deficiency of uroporphyrinogen III cosynthetase defect in heme (porphyrin ring) synthesis
-defective RBCs- hemolytic anemia
-porphyrins accumulate in:
dentin and bone (pink teeth and brown bones that fluoresce in UV light)
skin (photosensitivity)

32
Q

Melanin-gross

A

Black/brown tissue color

33
Q

Melanin- histo

A

Fine brown/black cytoplasmic granules

34
Q

Melanin synthesis

A
Requires- copper, tyrosine, tyrosinase
tyrosine 
uv light, hormones, inflammation
tyrosinase (Cu)
Dihydroxyphenylalanine
Melanin
packages in melanosomes
transferred to epithelial cells or melanophages
35
Q

Lipofuscin- gross

A

usually nothing

Tissue obtains a brownish color after large amount of accumulation

36
Q

Lipofuscin- histo

A

Golden-brown, fine granular cytoplasmic pigment

37
Q

Lipofuscin

A

Post mitotic or permanently stable cells
Derived from the breakdown of lipids- an un-degradable remnant of breakdown of organelles
Composed of lipid complexed with protein
Commonly found in aged cells and injured cells (wear and tear pigment)
Especially accumulates in post mitotic cells

38
Q

Exogenous pigmentation carbon

A

Pulmonary anthracosis
Carbon build up inhaled- taken up by pulmonary macrophages
pathogenesis: inhaled carbon deposits in peribronchiolar macrophages aggregates
pneumoconiosis=inhaled dust, antrhocosis is a subtype

39
Q

Exogenous pigmentation carotenoids

A

Pony lesser omentum
Carotenoids are found in plants (photosynthesis) and accumulate in adipose of animals
They function as antioxidants in animals

40
Q

Exogenous pigmentation: tetracyclines

A

teeth of dog
Path: mother ingested tetracycline during gestation -> deposited in mineralizing tissue of fetus -> offsprings teeth and bone discolored yellow-brown

41
Q

Exogenous pigmentation- expect the unexpected

A

Wild pig subcutis

Ingestion of certain anticoagulant rodenticides

42
Q

Calcification: gross

A

White gritty granules/plaques

Hard

43
Q

Calcification: histology

A

Basophilic amorphous granules of inconsistent size/shape in H&E
Stain black with vonKossa
A band of calcification is in the middle of the gastric mucosa

44
Q

Calcification- dystrophic

A

Local deposition of calcium in areas of injury
Especially necrotic fat- calcium ions interact with fatty acids, producing insoluble calcium soaps (saponificiation)
Also muscle, granulomas, dead parasites
Lipases released and produced fatty acids that react with Ca

45
Q

Normocalcaemic

A

Basophilic amorphous granules of inconsistent size/shape

46
Q

Calcification-metastatic

A

Widespread deposition of calcium in otherwise normal tissues in association
Caused by imbalance of calcium and phosphate
Hypercalcemia
Deposition of calcium mineral in predilection sites can cause dysfunction of organ/tissue
Dry white streaks

47
Q

Calcification-metastatic- predilection sites

A
Lungs
Pleura
Endocardium
Kidneys
Stomach
Tunica intima and media of vessels
48
Q

Diseases commonly associated with calcification of tissues

A

Hyperadrenocorticism (cushing’s disease)- skin
Chronic renal failure
Johne’s disease (granulomatous inflammation)
Vitamin D intoxication
-rodenticides in small animals
-Vitamin D analogues in plants for herbivores (Cestrum)
Neoplasia (production of PTHrP or severe osteolysis)

49
Q

Calcification-heterotopic ossification

A

Formation of bone at extra-skeletal site (including dystrophic areas)
Common in old dog lungs and dura mater
-palpable at autopsy
-visible on radiographs (small irregular)
Do not mistake for metastasis

50
Q

Calcification of skin- calcinosis cutis

A

not really metastatic or dystrophic
Dogs with hyperadrenocorticism or long term corticosteroid treatment
Pathogenesis not understood
Widespread mineralization of the dermal collagen and epidermal basement membranes

51
Q

Calcification of skin- calcinosis circumscripta

A

Local deposit of calcium in dermis (occasionally tongue)
Especially over bony prominence of large breed dogs (and horses)- can be difficult to heal
Probably form of dystrophic calcification due to trauma
Common and often refractory to treatment

52
Q

Amyloid

A

Misfolded proteins/peptides that aggregate into self-propagating fibrils and B pleated sheets
Deposited and accumulates in extracellular space-compression atrophy of adjacent tissues and organ dysfunction

53
Q

Amyloid light chain (AL)

A

derived from immunoglobulin light chain (k or L)

Deposition in tumors of monoclonal B-lymphocyte proliferation

54
Q

Amyloid A

A

Made from SSA protein synthesized by liver in response to inflammation
Deposited in reactive systemic amyloidosis; associated with chronic inflammatory conditions; certain breed predisposed

55
Q

Endocrine amyloid

A

Derived from islet amyloid polypeptide produced by islet cells
Deposition in islet associated with diabetes

56
Q

AB amyloid

A

In cerebral lesion of alzheimers disease

57
Q

Amyloid-gross

A

Enlarged, firm organs with waxy appearance

Stains blue violet when treated with iodine and sulfuric acid

58
Q

Amyloid- predilection sites

A
Kidney, liver and spleen
Nose, skin, conjunctiva in horses
Dog cerebral cortex (AB)
Cat pancreatic islets 
Shar-pei dogs and abysinnian cats
59
Q

Amyloid-histo

A

Amorphous homogenous eosinophilic extracellular material (hyaline)
Stains pink and has green birefringence with polarized light when stained with congo red

60
Q

Amyloid AA- path

A

Most common in animals
Made from SAA protein synthesized by liver in response to chronic inflammation (cattle with chronic abscess-> renal failure)
Reactive (secondary) systemic amyloidosis
Deposition in kidney, liver, spleen, shar-pei-dogs, abyssinian cats

61
Q

Amyloid light chain- path

A

Derived from immunoglobulin light chain from neoplastic plasma cells (myeloma)
Usually systemic deposits anywhere but can get local deposition in some tumors
e.g plasmacytomas and nasal amyloidosis of horses

62
Q

Endocrine amyloid-path

A

Derived from islet amyloid polypeptide produced by pancreatic islet cells
Local deposition in islets associated with diabetes

63
Q

AB amyloid- path

A

Local deposition in cerebral lesion of Alzheimer disease and dogs with canine cognitive dysfunction

64
Q

Uric acid- gout

A

Accumulation of uric acid crystals in tissues particularly birds and reptiles (and primates)
No uricase; uric acid is end product
Get gout from decreased renal function, dehydration

65
Q

Uric acid- mammals

A

Urea is end product
Get gout from diet, genetic disorders, chemotherapy
Dalmations have slow conversion of uric acid to urea- often have urate cystalluria

66
Q

Uric acid- gross

A

Chalky white foci on surface of visceral organs and serous membranes (liver, myocardium, spleen, pleura, air sacs, etc)
May involve soft tissues around joints

67
Q

Uric acid- histo

A

Needle-like clear spaces (crystals dissolve out in processing)
Tophi- granulomatous inflammation surrounding deposit