Cellular Accumulations

Question 1

Inherited form of AA Amyloidosis

Answer 1

Familial Mediterranean Fever

Can involve transthyretin (TTR) protein

Question 2

Stain for hemosiderin

Answer 2

Prussian Blue

Question 3

Bilirubin Accumulation

Answer 3

Yellow-green pigment that’s a result of heme breakdown

Causes Jaundice in skin and Icterus in Eye

Question 4

Immune disorders and malignancies that cause AA Amyloidosis

Answer 4

1. Rheymatoid arthritis
2. Crohn’s Disease/UC
3. Medullary Carcinoma of the Thyroid and Renal Cell Carcinoma

Question 5

Protein Accumulation in Kidney

Answer 5

In some glomerular disease, large amounts of proteins are lost to “leaky” glomerular basement membrane

Protein accumulates as discrete pink droplets within cytoplasm of proximal tubule cells

Question 6

Alpha-1-Antitrypsin Disease

Answer 6

Abnormally folded Alpha-1-Antitrypsin cannot be exported from endoplasmic reticulum in the liver, where it accumulates

Is required in the lung because it degrades elastase, so lack of this enzyme causes emphysema

Question 7

Accumulation of cholesterol

Answer 7

Cells other than hepatocytes have no way of metabolizing cholesterol, so it is stored within them indefinitely

Macrophages ingeest large amounts of it and become Foamy

Foamy macrophages accumulate and cause atherosclerosis

Question 8

Pathology caused by excess Iron

Answer 8

1. Lipid peroxidation via free radical generation
2. DNA damage from free radicals
3. Stimulation of collagen synthesis

Question 9

Fates of Fatty Acids in liver

Answer 9

1. Be oxidized to ketones
2. Used to synthesize phospholipids
3. Used to create cholesterol esters
4. Be esterified to create triglicerides

Question 10

Metastatic Calcification:

Definition and Examples

Answer 10

High serum levels of calcium cause deposition of calcium salts in viable tissue

Typically accumulates in cells with alkaline environments because they secrete acid (gastric mucosa, kidneys)

Examples:

1. Hypersecretion of PTH
2. Destruction of Bone
3. Vitamin D poisioning

Question 11

Normal Iron Metabolism and Accumulation

Answer 11

Iron is first stored bound to ferritin within phagocytic cells, and later transported via transferrin in the blood to the liver

Digestion of ferritin forms hemosiderin, a brown intracellular pigment

There is no physioloigc way to rid the body of excess iron

Question 12

Pathologic Calcification

Answer 12

Involves necrosis and irriversibly injured mitochondria

Question 13

Accumulation of triglicerides can occur when:

Answer 13

1. Increased delivery of Fatty Acids (Ethalon or Diabetes)
2. Decreased oxidation of Fatty Acids (hypoxia, ethanol, toxins)
3. Reduced apoprotein availability (CCL4, malnutrition)

Question 14

Mechanisms of Amyloid formation

Answer 14

1. Mutation of a gene resulting in abnormally folded protein
2. Normal protein with intrinsic tendency to form amyloids given enough time or high enough concentration
3. Abnormal metabolism of a normal protein

Question 15

Accumulation of exogenous pigments

Answer 15

Carbon accumulation in dust cells

Tattoo ink ingested by macrophages in connective tissue

Question 16

Mallory’s hyalin

Answer 16

Normal protein that’s damaged during injury, resulting in an undigestable accumulation within a cell

Usually Cytokeratin accumulations within liver cells due to ethanol poisioning

Question 17

Lipofuscin Accumulation

Answer 17

Yellow-brown pigment composed of polymers of lipids and protein that is thought to be the final product of peroxidation

Found in aging myocardial cells and hepatocytes

Question 18

AA Amyloidosis

Answer 18

Associated with acute and chronic inflammatory disorders

Characterized by accumulation of serum AA protein that is abnormally processed by macrophages and deposited as amyloid

Question 19

Amyloid and Alzheimer’s

Answer 19

Amyloid deposits in cerebral plaques and blood vessels of Alzheimer’s patients form ß-amyloid protein

Question 20

Diseases that have microvascualr fat deposits

Answer 20

1. Reye’s Syndrome
2. Fatty Liver of Pregnancy

Question 21

Process of Copper metabolism

Answer 21

Excreted through the biliary system

Question 22

Dystrophic Calcification

Definition and examples

Answer 22

Occurs with deposition of calcium in necrotic or chronically traumatized tissue

Associated with normal serum levels of calcium

Examples:

1. Fat necrosis
2. Coagulation, caseous, or liquefactive necrosis
3. Atherosclerosis
4. Aortic Stenosis (damaged heart valves)

Question 23

Dialysis-Associated Amyloidosis

Answer 23

ß2-microglobulin accumulates because it does not pass through dialysis membrane

Results in destructive arthropathy

Question 24

Amyloidosis

Answer 24

Abnormal proteinaceous deposit in extracelular space

Characterized by ß-Pleated sheats

Hyaline (or glassy-pink) stain on H&E

Question 25

Diseases that lead to excess iron

Answer 25

1. Diseases that cause ineffective hematopoesis or that require numerous transfusions (lots of RBC lysis)
2. Genetic hemochromatosis involving too much uptake of iron

Question 26

Mechanisms of how substances accumulate within cells

Answer 26

1. Normal endogenous substance produced at increased rate
2. Abnormal protein does not fold correctly so it accumulates
3. Inactivating enzymes mutated so intermediates in a metabolic pathway accumulate
4. Injury or damage results in alteration of an intracellular constituent that cannot be removed
5. Abnormal exogenous substance is taken up and retained

Question 27

Wilson’s Disease

Answer 27

Autosomal Recessive disorder marked by toxic levels of copper in liver and brain

Involves inability to excrete copper into canniculi resulting in accumulation into hepatocytes and regurgitation into circulation

Question 28

Stain for Amyloid

Answer 28

Congo Red

Question 29

AL Amyloidosis

Answer 29

Amyloid deposits formed by abnormal immunoglobin light chains

Associated with Multiple Myeloma (excess production of parts of antibodies)

Deposit in heart (where they restrict contraction) and glomeruli (where they allow protein leakage)