calcification, pigments & amyloid

Question 1

what is calcification

Answer 1

• abnormal deposition of calcium salts (along with iron, magnesium, and other minerals) in tissues
• seen as dark blue granular material on H&E stained sections

Question 2

what is dystrophic calcification (mineralization)

Answer 2

• calcification of necrotic tissue in an animal with normal serum calcium
• Ca accumulates in the mitochondria, since dead cells cannot regulate influx of calcium into cytosol
• ex: necrotic skeletal muscle, granulomas, dead parasites, necrotic abdominal tissue secondary to pancreatitis

Question 3

what is metastatic calcification (mineralization)

Answer 3

• occurs in living tissues as a result of hypercalcemia
• begins in the interstitium (extracellular space) of organs affected (kidney, lung, blood vessels, stomach)

Question 4

what are causes of hypercalcemia

Answer 4

• hypercalcemia of malignancy (lymphomas, anal sac gland carcinomas, parathyroid-like hormone - PTH-rP- produced by these tumors)
• primary hyperparathyroidism (due to parathyroid adenomas) (VD toxicity - plant-derived, therapeutic overdoses, cholecalciferol rodenticides)
• destruction of bone from primary or metastic neoplasia (rare)

Question 5

metastatic mineralization

what is uremic mineralization

Answer 5

• renal failure
• abnormal Ca:Phos ratio
• hypo-, normo- or hypercalcemic
• tongue, parietal pleura, pulmonary interstitium, left atrium, kidney, gastric mucosa

Question 6

what are pigments

Answer 6

colored substances that can be either exogenous or endogenous

Question 7

what are the 4 major endogenous pigments

Answer 7

1. hemosiderin
2. bilirubin
3. melanin
4. lipofuscin/ceroid

Question 8

what is hemosiderin

Answer 8

• hemoglobin-derived globular golden-yellow to yellow-brown pigment
• found in macrophages at sites of erythrocyte lysis or breakdown
• small amounts normally present in bone marrow, spleen and liver
• following lysis of RBC, iron is sequestered by macrophages and eventually converted to hemosiderin in lysosomes
• hemosiderin is positive with prussian blye staining

Question 9

what is bilirubin

Answer 9

• jaundice (icterus) is the clinical manifestation of hyperbilirubinemia and is the yellowish staining of the integument, sclera, and deeper tissues with bile pigments resulting from increased levels of bilirubin in plasma
• green-brown, amorphous, globular pigment
• major component of bile, waste product
• does NOT contain iron
• RBC breakdown -> heme portion of hemoglobin converted to biliverdin and then bilirubin by chemical rx
• bound to albumin in blood

Question 10

what is pre-hepatic icterus

Answer 10

hemolytic

• due to massive breakdown of erythrocytes; many different causes (immune medated, infectious, metabolic, trauma)
• causes increased unconjugated bilirubin; quickly converted into conjugated

Question 11

what is hepatic icterus

Answer 11

• hapatocellular disease comprises the liver’s ability to uptake unconjugated bilirubin and/or excrete conjugated bilirubin into bile canaliculus
• increase in both unconjugated and conjugated bilirubin

Question 12

what is post-hepatic icterus

Answer 12

• bile duct obstruction
• increase in conjugated bilirubin

Question 13

endogenous hemoglobin derived pigments after a contusion (bruise):

Answer 13

• blunt trauma
• damage to local blood vessels
• extravasation of blood (hemorrhage)
• lysis of erythrocytes
• RBC debris is phagocytized by macrophages
• hemoglobin is degraded by lysosomes
• red-blue (hemoglobin)
• green-blue (biliverdin and bilirubin) and hemosiderin (golden yellow)

Question 14

what is vitiligo

Answer 14

partial or patchy loss of melanin pigment - depigmentation

Question 15

what is albinism

Answer 15

mutation in the tyrosinase gene - too little melanin

Question 16

what is hyperpigmentation

Answer 16

develop secondary to almost any cutaneous insult (damage to melanocytes can also result in this)

Question 17

melanin

what is neoplasia

Answer 17

benign melanocytoma or malignant melanoma

Question 18

what is lipofuscin

Answer 18

• brownish-yellow intracellular pigment
• increases w/ age and atrophy
• “wear and tear” or “aging” pigment
• liver, heart, brain, thyroid gland, adrenal glands, macrophages
• formed in lysosomes
• derived from free radical oxidation of unsaturated lipids, has proteins
• not harmful to cell but marker of past free radical injury

Question 19

what is ceroid

Answer 19

common histologic and histochemical features with lipofuscin; produced by macrophages and accumulates in disease states (VE dificiency)

Question 20

what is amyloid

Answer 20

• diverse group of proteinaceous substances with a similar appearance, depsited in organs
• causes atrophy or impaired function

Question 21

what are characteristics common to all types of amyloid

Answer 21

• smooth fibrillar and eosinophilic using hematoxyin and eosin (H&E) stains
• stains red with congo red stain and has apple-green birefringence when viewed with polarized light
• molecular structure is a beta-pleated sheet

Question 22

what is light chain (AL) amyloid (primary)

Answer 22

• made up of monoclonal immunoglobulin light chains
• seen with plasma cell dyscrasias and plasma cell tumors and equine nodular cutaneous amyloidosis
• NOT related to inflammation

Question 23

what is reactive (AA) amyloid (secondary)

Answer 23

• made up of serum amyloid-associated (SAA) protein (an acute phase protein produced by the liver during inflammation)
• seen after chronic antigenic stimulation and chronic inflammation
• familial in Shar Pei dogs and Abyssinian and some Siamese cats

Question 24

what is islet amyloid (IAPP)

Answer 24

• precursor polypeptide is co-secreted with insulin by the beta cells in the pancreatic islets; deposition in pancreatic islets in aged cats; has been associated with diabetes mellitus; many old cats have islet amyloidois and do NOT have diabetes mellitus