Lecture 4: Calcification & Amyloidosis

Question 1

2 forms of pathologic calcification***

Answer 1

dystrophic and metastatic

Question 2

dystrophic calcification***

Answer 2

abnormal calcium deposition in damaged tissue (response to local injury)

Question 3

location, functional significance, and sequelae of dystrophic calcification***

Answer 3

1) location: intracellular: mitochondria; extracellular: phosphate-rich plasma membrane, elastic tissue, basement membrane
2) fx sig: loss of tissue function/elasticity
3) sequelae: can serve as focus for heterotopic bone form.

Question 4

how can Vit. E/selenium deficiency lead to calcification?*

Answer 4

can cause necrosis of muscle, followed by dystrophic calcification

Question 5

Von Kossa stain and calcium*

Answer 5

stains Ca black

Question 6

metastatic calcification is caused by***

Answer 6

Abnormal Ca deposition in “normal tissues” secondary to hypercalcemia

Question 7

6 mechanisms of metastatic calcification**

Answer 7

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

Question 8

primary locations where metastatic calcification is found**

Answer 8

• blood vessels/elastic fibers/basement membranes of lung, kidney, stomach, oral cavity
• aorta (ruminants)

Question 9

fx. significance of metastatic calcification**

Answer 9

loss of tissue fx (elasticity)

Question 10

sequelae of metastatic calcification**

Answer 10

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

Question 11

Hypervitaminosis D cause and action*

Answer 11

• dietary supplementation or plant toxicity

- action: stimulates intestinal Ca absorption, renal tubular Ca reabsorption

Question 12

Primary Hyperparathyroidism mech.*

Answer 12

parathyroid adenoma produces excess PTH –> increased osteoclast activity –> increased bone resorption –> Ca released from bone resorption causes hypercalcemia

Question 13

Nutritional Secondary Hyperparathyroidism mech.*

Answer 13

Low Ca intake –> low serum Ca –> elevation of PTH –> increased bone resorption and hypercalcemia

Question 14

Renal secondary hyperparathyroidism mechs.* (complex!)

Answer 14

renal dz –> decreased tubular phosphate excretion –> elevated phosphate complexes serum Ca –> renal interference with Vit. D metabolism –> hypocalcemia –> PTH stimulated –> increased bone resorption and hypercalcemia

Question 15

Mech. of Hypercalcemia of Malignancy*

Answer 15

many neoplasms produce PTH related protein that induces bone resorption and hypercalcemia

Question 16

Amyloidosis*

Answer 16

accum. of abnormal proteinaceous substance from several protein sources with eosinophilic staining properties that accumulates between cells and has beta-pleated sheet conformation

Question 17

Clicker: Calcification in a renal infarct is most likely due to which mech? (dystrophic or metastatic)**

Answer 17

dystrophic

Question 18

Clicker: Which of the following are mechs. of metastatic calcification? CCl4 toxicity, primary parathyroid tumor, and/or hypervitaminosis D**

Answer 18

primary PT tumor, Hypervitaminosis D

Question 19

What does amyloid look like on H&E stain? Congo red stain?*

Answer 19

homogenously pink on H&E. Red on Congo red. Side note: Can also use polarized light to create birefringence

Question 20

most common form of amyloidosis in animals***

Answer 20

secondary amyloidosis (primary in humans)

Question 21

What is primary amyloidosis composed of?*

Answer 21

amyloid AL (immunoglobulin light chains)

Question 22

What is secondary amyloidosis composed of?***

Answer 22

Amyloid AA (amyloid-associatied), aka serum amyloid A protein

Question 23

What is endocrine amyloidosis composed of?*

Answer 23

(derived from hormones) CGRP and IAPP

Question 24

Clicker: The most common form of amyloidosis in animals is derived from:**

Answer 24

Serum Amyloid A protein

Question 25

what is the precursor to AA protein?*

Answer 25

SAA (serum amyloid A) protein

Question 26

Serum Amyloid A protein is produced in response to what type of stimuli?*

Answer 26

chronic inflammation

Question 27

TNF --> liver*

Answer 27

upregulates SAA protein production in liver cells --> AA protein formation

Question 28

consequences of amyloidosis on kidney*

Answer 28

protein-losing nephropathy

Question 29

consequences of amyloidosis on pancreas*

Answer 29

Type 2 diabetes mellitus

Question 30

consequences of amyloidosis on liver*

Answer 30

atrophy, failure

Question 31

consequences of amyloidosis on heart*

Answer 31

arrhythmias, failure

Question 32

consequences of amyloidosis on GI tract*

Answer 32

impairs absorption

Question 33

consequences of amyloidosis on Brain*

Answer 33

reduced cog. performance, dementia

Question 34

Hemosiderin is derived from:*

Answer 34

Hb (when RBCs are broken down)

Question 35

melanin is derived from:*

Answer 35

oxidation of tyrosine

Question 36

What is bilirubin composed of?*

Answer 36

porphyrin ring of Hb

Question 37

What is lipofuscin/ceroid composed of?*

Answer 37

lipid-protein complexes (a product of lipid peroxidation)

Question 38

What stain detects lipofuscin/ceroid?*

Answer 38

blue in acid fast stain, or brownish in H&E. It will also fluoresce under fluorescent light

Question 39

Lipofuscin accumulation increases with what deficiency?*

Answer 39

Vit. E

Question 40

Where does lipofuscin accumulate?*

Answer 40

in lysosomes. Common in heart, liver, brain, intestines

Question 41

Hemosiderin is normally bound to:*

Answer 41

apoferritin/ferritin

Question 42

Where is hemosiderin normally found?*

Answer 42

bone marrow, spleen, liver (within macrophages)

Question 43

What causes hemosiderin excess?*

Answer 43

hemorrhage/congestion, increased dietary iron, hemolytic anemia, etc.

Question 44

T or F: hemosiderin is usually not toxic*

Answer 44

T

Question 45

Hemochromatosis*

Answer 45

too much iron in the body

Question 46

Prussian blue stains iron what color?*

Answer 46

blue

Question 47

Bilirubin is conjugated in the ____ and excreted in the ___*

Answer 47

liver; bile

Question 48

bilirubin has what color discoloration assoc. with it?***

Answer 48

yellow (causes icterus/jaundice)

Question 49

Possible Causes of Hyperbilirubinemia (5)*

Answer 49

- increased heme breakdown - decreased hepatic uptake - impaired conjugation - impaired intra-hepatic excretion - bile duct obstruction

Question 50

Fontana Masson stains what black?*

Answer 50

melanin

Question 51

lipidosis is aka:*

Answer 51

fatty change, steatosis

Question 52

Clicker: Vit. E deficiency and lipid peroxidation contributes to formation of which pigment?**

Answer 52

Lipofuscin

Question 53

Clicker: Which pigments can result in brown pigmentation of organs and cytoplasm?**

Answer 53

melanin, hemosiderin, lipofuscin

Question 54

Steps of free fatty acids entering liver --> lipoproteins exiting liver*

Answer 54

1) free fatty acids transported into liver, bind with glycophosphate to form triglycerides 2) triglycerides form lipoproteins under influence of apoprotein and exit liver

Question 55

How does protein metabolism related to lipidosis?*

Answer 55

need to have functional protein metabolism for triglycerides to form lipoproteins and exit the liver. Anything that depresses hepatic protein synthesis will usually result in increased lipid in the hepatocytes