Lecture 2: Calcification Flashcards by Jessica Buchy

__ is the abnormal Ca deposition in damaged tissues intracellularly or extracellularly which may cause the functional loss of tissue (i.e. elasticity)

dystrophic calcification

intracellular = mitochondrial
extracellular = plasma membrane, elastic tissue, basement membrane

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sequelae of dystrophic calcification: may be reorganized to form __

heterotopic bone

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__ is acute necrosis of skeletal and cardiac m due to vitamin E and selenium deficiency

white muscle dz

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__ is abnormal Ca deposition in tissue secondary to hypercalcemia

metastatic

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Mechanisms that lead to hypercalcemia

hypervitaminosis D
toxic plants 
primary hyperparathyroidism
nutritional secondary hyperparathyroidism
hypercalcemia of malignancy

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What causes hypervitaminosis D (leads to hypercalcemia/dystrophic calcification)

dietary supplementation 
plant toxicity (cestrum diurnum and solanum malacoxylon)

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Mechanism of hypervitaminosis D

stimulates intestinal Ca absorption and renal tubular Ca reabsorption

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Metastatic calcification is located in the

BVs, elastic fibers, basement membranes (lung, kidney, stomach, oral cavity)

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Common BV for metastatic calcification via hypervitaminosis D

aorta

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sequelae of metastatic calcification

renal tubular dysfunction (nephrocalcinosis)
aortic rupture (rare)
lung (hypoxemia, decreased capacity)

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special stain for calcification that stains it black

von kossa stain

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what causes primary hyperparathyroidism

primary parathyroid adenoma produces elevated PTH (stimulates osteoclast activity to increase bone resportion = increased Ca = hypercalcemia)

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what happens with nutritional secondary hyperparathyroidism

inadequate Ca intake = decreased serum Ca = increased PTH = bone resoprtion = hypercalcemia

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what happens with renal secondary hyperparathyroidism (very common!)

renal dz = decreased tubular phosphate excretion = increased phosphate in serum leads to CaP ppt. Also, Renal interference with Vit D metabolism (abnormal absorption) = HYPOcalcemia which stimulates PTH secretion = bone resorption = HYPERcalcemia. Widespread tissue calcification.

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Many neoplasms produce ___ that induces bone resporption and hypercalcemia (anal apocrine gland adenocarcinoma, lymphoma)

PTH related protein (PTHrP)

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__ pigment is a lipid-protein complex made from membrane lipids that is known as the “wear and tear” pigment

lipofuscin/ceroid

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vitamin E deficiency, stress, increased lipid peroxidation product, age, etc will have__ pigment in tissues commonly seen the heart, liver, and brain

lipofuscin/ceroid

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Lipofuscin/ceriod pigment is intralysosomal, it forms lysosomes by __

autophagocytosis

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see an increased amount of lipofuscin pigment in neurons with genetic autosomal recessive dz called __ (abnormal metabolism of phospholipid)

neuronal ceroid lipofuscinosis

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special stains/features for lipofuscin/ceroid (stains brown with H&E)

acid fast stain (blue) and autofluorescence

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__ occurs in vitamin E deficient dogs and is also known as “brown gut dz”

Intestinal lipofuscinosis (lipofuscin/ceriod)

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brown gut dz in dogs is due to increased membrane __ and accumulation of __ in intestinal smooth m.

lipid peroxidation, lipofuscin

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Cats with vitamin E deficency do not get brown gut dz but have

fat necrosis in abdominal cavity

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__ and __ pigments are derived from hemoglobin

hemosiderin and bilirubin

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__ is derived from Hb when RBCs are phagocytosed and degraded intracellularly

hemosiderin

hemosiderin is normal in mononuclear phagocytes in the __, __, __

BM, spleen, liver

There is excess hemosiderin with __, __, __

hemorrhage/congestion, increased diet Fe, Hemolytic anemia

hemosiderin is usually not __ unless there is too much free ferrous iron (not bound) and the fenton rxn occurs making free radicals.

toxic

When Fe is freed from Hb the body binds it to __ protein so it is less reactive and less likely to make free radicals (fenton rxn)

apoferritin/ferritin

__ is a pathologic disorder of Fe metabolism

hemochromatosis

hemosiderosis is seen with __ due to increased hydrostatic pressure in the lungs and RBC leak into alveoli where macs phagocytize them (brown macs)

chronic left heart failure

special stain for hemosiderin that stains Fe dark blue

prussian blue (perls iron stain)

how is hemosiderin made by macrophages phagocytizing RBC

macrophage breaks down RBC and Fe is bound to apoferritin making granular pigment (hemosiderin) in mac

__ is a porphyrin (heme) ring of hemoglobin and other sources

bilirubin

bilirubin is conjugated in the __ and excreted in the __

liver, bile

clinical __ is seen when plasma bilirubin is >2-3mg/dl

icterus

__ is toxic, cannot be excreted in the urine (bound to Albumin)

unconjugated bilirubin

__ has low toxicity and can be excreted in the urine

conjugated bilirubin

RBC are broken down into __ and __

ferrous iron and unconjugated bilirubin

unconjugated bilirubin is taken up by the __ where it is conjugated and excreted to the bile duct for transportation to the __

hepatocyte, intestine (reabsorption and/or excretion via kidney)

5 things that can cause hyperbilirubinemia/icterus/jaundice

1. increased heme breakdown (anemai, hemorrhage) 2. decreased hepatic uptake (drugs, dz) 3. impaired conjugation (neonate, dz) 4. impaired intra-hepatic excretion (cirrhosis, drugs) 5. bile duct obstruction (inflamm, parasites, neoplasm, fb)

Melanin pigment is formed by oxidation of __

Tyrosine

special stain for melanin that stains it black

fontana masson (argentaffin stain)

some animals have normally occurring __in their lungs, heart, aorta, brain (sheep, pigs, etc)

melanosis

melanosis is common/normal in __

black-faced sheep breeds

__ occurs when liver accumulates excess fat, turns yellow, and has a greasy consistency. When placed in water the liver will float and histologically hepatocytes will have "holes"

lipidosis, fatty change, steatosis

Cats develop __ frequently due to too much FA to liver which is converted into triglycerides. Difficult to manage medically.

sever lipidosis

Normally fat is processed by the liver via __ entering the cell and being converted into ___ by acetate and glycerophosphate. These TG must be bound to apoprotein to make __ that can leave the cell.

Free FA, triglycerides, lipoproteins

if a dz or toxin affects protein synthesis what happens to the fat in the hepatocyte?

Steatitis - lipid gets trapped, TG need to be protein bound to exit the cell.

lipidosis occurs normally during __

late pregnancy, lactation

5 pathologic causes of lipidosis

1. increased synthesis of FA, TG 2. increased lipolysis and uptake of free FA 3. decreased FA oxidation 4. decreased Apoprotein synthesis 5. decreased lipoprotein excretion

___ is the accumulation of abnormal proteinaceous substance from several protein sources iwth eosinophilic staining that accumulates between cells and has beta pleated sheets

amyloidosis

4 characteristics defining amyloid

1. Abnormal proteinaceous substance 2. Deposited extracellularly 3. Results in organ dysfunction 4. Derived from different proteins

__ form crystals in the tissue (seen in renal granular amyloidosis) which can be stained with __

Amyloid Beta pleated sheets, congo red stain and polarized light (birefringence)

2 Special stains for amyloidosis

Microscopically: Congo red - stains amyloid red (and polarized light for birefringence - yellow refraction) Grossly: Lugol's iodine and dilute sulfuric acid treatment (black) - used to see amyloid grossly (i.e. Dots in kidney) H&E stains eosinophilic

Amyloid more common in people/primates, occurs in vet med but it is less important

Primary Amyloid:AL - Ig light chains

Most common form of amylodosis in animals that causes clinical disease

Secondaryr amyolid: AA - chronic inflammation, SAA precursor

Amylodiosis that commonly is seen in cats caused by a partial degradation of protein in the pancreas leads to amyloid deposits in pancreatic islets (beta cell damage = diabetes)

Endocrine Amyloid Islet amyloid polypeptide (IAPP) precursor secreted by beta cells with insulin, abormal synthesis/process/degradation = amylodosis.

Amyloidosis associated with alzheimer's dz in people described in dogs (human models)

Beta amyloid: senile plaques (APP amyloid precursor protein)

Commonly seen in horses is amylodosis of apolipoprotein AI and AII

Aging associated amyloid

How does secondary amyloidosis arise

Chronic inflammation - macrophage activate - IL and TNF secreted - Hepatocytes make SAA protein (serum amyloid A) - LIMITED PROTEOLYSIS occurs = AA

How do you monitor secondary amylodosis

Via the acute phase reactant protein, SAA - serum amyloid A production

Animal that develop dz from secondary amyloidosis is due to

BOTH limited proteolysis AND abundant production of SAA via the liver

Primary amyloidosis is caused by

Ig light chains and limited proteolysis

Consequences of amyloidosis in the kidney

Protein losing nephropathy

Consequences of amyloidosis in the pancrease

Type 2 diabetes mellitus

Consequences of amyloidosis in the GI tract

Impaired absorption

Consequences of amyloidosis in the brain

Reduced cognitive performance/dementia (alzheimer's in people)

What organs are consequences more commonly seen in people

Liver (atropy, failure) Heart (arrhythmia, failure) Brain (dementia)