Chapter 2 part 4

Question 1

3 types of autophagy

Answer 1

1) chaperone-mediated = direct translocation across the lysosomal membrane by chaperone proteins
2) microautophagy = inward invagination of lysosomal membrane for delivery
3) macroautophagy = major form of autophagy involving sequestration and transportation of portions of cytosol in a double-membrane bound authophagic vacuole

Question 2

Steps of autophagy

Answer 2

1) initiation- triggered by formation of invitation complex and nucleation complex
2) elongation- via LC3
3) maturation of autophagosome
4) fusion with lysosome
5) degradation

Question 3

4 main pathways of abnormal intracellular accumulations

Answer 3

1) abnormal metabolism (fatty liver)
2) defect in protein folding/transport ;eating to accumulation of abnormal proteins
3) lack of enzyme leading to accumulation of endogenous material (lysosomal storage disease)
4) ingestion of indigestable materials leading to accumulation of exogenous materials

Question 4

Steatosis

Answer 4

accumulations of triglycerides within parenchymal cells ; often seen in liver, heart, muscle, kidney
Causes: toxin, protein malnutrition, diabetes, obesity, anoxia

Question 5

Atherosclerosis

Answer 5

smooth muscle cells and macrophages within the intimal layers of aorta and large arteries are filled with lipid vacuoles made up of cholesterol (foam cells)

Question 6

Xanthomas

Answer 6

intracellular accumulation of cholesterol within macrophages; clusters of foamy cells found in sub epithelial connective tissue of skin and in tendons

Question 7

Cholesterolosis

Answer 7

focal accumulations of cholesterol-laden macrophages in the lamina propria of the gallbladder

Question 8

Niemann-Pick disease, type C

Answer 8

lysosomal storage disease caused by mutation affecting an enzyme involved in cholesterol trafficking, resulting in cholesterol accumulation in multiple organs

Question 9

How do intracellular accumulations of proteins appear?

Answer 9

rounded, eosinophilic droplets, vacuoles, or aggregates in the cytoplasm

Question 10

What condition are reabsorption droplets in proximal renal tubules seen in?

Answer 10

renal diseases associated with protein loss in the urine

Question 11

When proteins accumulate and the ER becomes largely distended, what does the ER produce?

Answer 11

Russel Bodies = large, homogenous eosinophilic inclusions

Question 12

What condition is associated with defective intracellular transport and secretion of critical proteins?

Answer 12

a1-antitrypsin deficiency; build up of partially folded intermediated that aggregate in the liver ER and deficiency of circulating enzymes leading to emphysema

Question 13

What are some of the. cytoskeletal proteins that can build up?

Answer 13

• microtubules
• thin actin filaments
• thick myosin filaments
• intermediate filaments: keratin, neurofilaments, dessin filaments, vimentin filaments, glial filaments

Question 14

What condition is associated with aggregation of abnormal proteins

Answer 14

amyloidosis

Question 15

Hyaline change

Answer 15

homogenous, glassy, pink appearance

Question 16

Examples of exogenous pigments

Answer 16

• carbon (coal dust): causes anthracosis in the lungs

- tattooing

Question 17

Examples of endogenous pigments

Answer 17

• lipofuscin
• hemosiderin
• melanin

Question 18

Lipofuscin

Answer 18

insoluble pigment composed of polymers of lipids and phospholipids in complex with protein; sign of free radical injury and lipid peroxidation; prominent in liver and heart of aging patients

Question 19

Melanin

Answer 19

endogenous black pigment formed when tyrosinase catalyzes oxidation of tyrosine to dihydroxyphenylalanine in melanocytes (alkaptonuria)

Question 20

Hemosiderin

Answer 20

hemoglobin derived, golden yellow to brown, granular or crystalline pigment that is one of the major storage forms of iron; when body breaks down heme into iron and biliverdin, the body traps the released iron in hemosiderin

Question 21

Hemosiderosis

Answer 21

when there is a systemic overload of iron, hemosiderin deposits in organs and tissues
Causes: increased dietary iron absorption, hemolytic anemias, repeated blood transfusions

Question 22

Pathologic calcification

Answer 22

abnormal tissue deposition of calcium salts with small amounts of iron, magnesium, and other mineral salts

Question 23

Dystrophic calcification

Answer 23

when the deposition occurs locally in dying tissues

Question 24

Metastatic calcification

Answer 24

results from hypercalcemia secondary to some disturbance in calcium metabolism
Causes: increased secretion of PTH (hyperparathyroidism), resorption of bone tissue, abnormal sensitivity to vitamin D, renal failure causing the retention of phosphate leading to secondary hyperparathyroidism

Question 25

Psammoma bodies

Answer 25

single necrotic cells that constitute seed crystals and become encrusted by mineral deposits that form progressive outer layers in lamellate configurations

Question 26

What is cellular aging the result of?

Answer 26

progressive decline in cellular function and viability caused by genetic abnormalities and accumulation of cellular and molecular damage due to effects of exposure to exogenous influences

Question 27

DNA damage in aging

Answer 27

1) carcinogen exposure and sporadic erros
2) production of ROS
3) DNA damage
4) defective DNA repair
5) mutations
6) cellular aging

Question 28

Werner syndrome

Answer 28

defective helices protein that is involved in DNA replication and repair; causes rapid accumulation of chromosomal damage leading to early aging

Question 29

Cellular senescence in aging

Answer 29

1) cellular senescence (cells limited capacity for replication)
2) telomere shortening
3) decreased cellular replication
4) cell loss
5) cellular aging

Question 30

What tumor suppressor proteins does CDKN2A encode?

Answer 30

p16 and INK4al control G1 to S phase progression during cell cycle

Question 31

Defective protein homeostasis in aging

Answer 31

1) defective protein homeostasis
2) decreased proteins, increased damaged proteins
3) decreased cell functions
4) cellular aging

Question 32

Rapamycin

Answer 32

inhibits mTOR pathway, increase life span, induces promotion of autophagy

Question 33

IGF-1 signaling pathway

Answer 33

1) IGF-1 produced in response to growth hormone secretion by pituitary
2) mimics intracellular signaling by insulin and informs cells of the availability of glucose, promoting anabolic state
3) targets AKT and mTOR downstream

Question 34

Sirtuins

Answer 34

NAD-dependents protein deacetylases that promote expression of genes whose products increase longevity (proteins that inhibit metabolic activity, reduce apoptosis, stimulate protein folding, inhibit harmful effects of oxygen free radicals); also increase insulin sensitivity and glucose metabolism

Question 35

Role of caloric restriction on aging

Answer 35

reduces signaling intensity of IGF-1 pathway and increases sirtuins to overall increase longevity