02/16d Cell Injury IV - Lysosomes and Intracellular Accumulations

Question 1

What are the two types of digestion carried out by lysosomes?

Answer 1

Heterophagy - digestion of exogenous material

Autophagy - digestion of endogenous material

Question 2

What are the basic steps of heterophagy?

Answer 2

1) Exogenous material is phagocytosed/endocytosed
2) Primary lysosome fuses with the phagosome, forming the secondary lysosome
3) Phagocytosed material is digested and exocytosed, or retained in some cases as a residual body

Question 3

What are the basic steps of autophagy?

Answer 3

1) Endogenous material is engulfed by the smooth ER
2) Primary lysosome fuses with autophagosome
3) Endogenous material is digested and recycled or exocytosed

Question 4

What is anthracotic pigment?

Answer 4

Accumulation of carbon particles and other inhaled particles that are phagocytosed but not expelled

Question 5

What is hemosiderin?

Answer 5

Metabolic product of hemoglobin, produced by macrophages which have phagocytosed red blood cells
Often present in heart failure cells, where red blood cells have leaked into the alveolar space

Question 6

What is Pompe’s Disease?

Answer 6

Lysosomal storage disease caused by a genetic lack of lysosomal glucosidase, resulting in glycogen accumulation
Causes very enlarged organs (heart, liver, etc.) due to the buildup of glycogen

Question 7

What is Gaucher’s Disease?

Answer 7

Lysosomal storage disease caused by a genetic lack of lysosomal glucocerebrosidase, resulting in cerebroside accumulation
Causes enlarged organs such as spleen and liver

Question 8

What is lipofuscin?

Answer 8

Insoluble, brownish-yellow intracellular pigment that accumulates with age, particularly in the brain, liver, and heart
Made up of complexes of lipids and protein derived from peroxidation of lipids from subcellular membranes
Usually harmless

Question 9

What are the four types of molecules that can form intracellular accumulations?

Answer 9

Lipids, including fatty acids and cholesterol
Proteins
Glycogen
Pigments

Question 10

What are six causes of steatosis/fatty liver disease?

Answer 10

Alcoholism - causes increased synthesis and decreased breakdown of lipids
Diabetes and obesity - cause nonalcoholic fatty liver disease
Carbon tetrachloride poisoning - causes reduced synthesis of apoproteins
Protein malnutrition - causes reduced synthesis of proteins
Hypoxia - inhibits fatty acid oxidation
Starvation - increases mobilization of fatty acids from peripheral stores

Question 11

What gross characteristics distinguish a fatty liver from a cirrhotic liver?

Answer 11

Fatty liver has a smooth surface, with the cut surface appearing greasy and yellow
Cirrhosis causes scarring and fibrosis of the liver parenchyma, which causes an uneven surface

Question 12

What are four causes of cholesterol accumulation?

Answer 12

Atherosclerosis
Xanthomas (lipid accumulation in the dermis)
Cholesterolosis (lipid storage disease)
Niemann-Pick disease Type C (lipid storage disease)

Question 13

What are three general causes of intracellular protein accumulation? Give examples of each

Answer 13

Excessive amounts of normal proteins - Russell bodies (immunoglobulin) in multiple myeloma
Defective intracellular transport and secretion - cystic fibrosis (mucous)
Aggregation of abnormal proteins - systemic amyloidosis, alpha-1 antitrypsin deficiency

Question 14

What are the two sources of indigestible pigments that can form accumulations?

Answer 14

Exogenous - carbon/pollutants in the lungs (anthracosis)

Endogenous

Question 15

What are four examples of endogenous pigments?

Answer 15

Hemosiderin (accumulations can occur in patients who undergo multiple blood transfusions)
Lipofuscin
Melanin
Bilirubin

Question 16

What are the two types of pathologic calcification?

Answer 16

Dystrophic - occurs in areas of necrosis and atherosclerosis, and implies there is damage to the underlying organ
Metastatic - occurs in normal tissues when there is hypercalcemia

Question 17

What are four causes of metastatic calcification?

Answer 17

Excess parathyroid hormone (digests bone and increases circulating calcium levels)
Destruction of bone
Vitamin D disorders
Renal failure, which results in inadequate control of parathyroid function