7. Cellular Accumulation

Question 1

Intracellular accumulations

Answer 1

Chronic and sub lethal; injurious stimulus that over a long period of time can cause cell death

Question 2

4 main pathways of intracellular accumulations

Answer 2

1. Abnormal metabolism - normal endogenous material not metabolized, accumulation of lipids
2. Mutations causing alternations in protein folding and transport, so defective molecules accumulate intracellular
3. Deficiency in critical enzymes responsible for breaking down certain compounds causing substrates to accumulate in lysosomes as lysosomal storage diseases
4. Inability to degrade phagocyted particles, carbon pigment accumulation, exogenous substances

Question 3

Steatosis

Answer 3

Fatty change

Abnormal accumulation of triglycerides within parenchymal cells (most commonly in liver)

Fatty change is reversible by can lead to inflammation and fibrosis

Most common cause = alcoholic liver disease

Question 4

Cholesterol and cholesterol esters

Answer 4

Responsible for steroid production

Accumulated in pathological states:

Atherosclerosis - deposition of cholesterol in walls of blood vessels
Xanthomas - deposits under skin
Cholesterolsosis - deposits on gallbladders
Neumann -pick disease = genetic disease in which lipid transportation affected, lipid are not degraded

Question 5

Intracellular protein accumulation

Answer 5

Excessive synthesis
Excessive reabsorption
Defects in cellular transport
Aggregation of abnormal proteins

Can see with glycogen deposits- abnormalities In glycogen storage and glucose metabolism (diabetes and glycogen storage diseases)

Question 6

Exogenous pigment deposition

Answer 6

Carbon or coal dust (most common)
Deposits in lungs cause anthracosis
Tattoos

Benign or malignant

Question 7

Endogenous pigment deposition

Answer 7

Melanin or melanocytes
Hemosiderin is hemoglobin derived, aggregated ferritin

Normal or pathological

Question 8

Calcification

Answer 8

Can be physiological or pathological

Accumulation of calcium deposits

Question 9

Dystrophic calcification

Answer 9

Calcium metabolism is normal but calcium deposits in injured or dead tissue such as in areas of necrosis - phospholipids in disintegrated cellular membranes have a high affinity for calcium

Calcium binds to phospholipid and forms dystrophic calcification

Dystrophic calcification of aortic valves is an important Cause of aortic stenosis in elderly persons

Question 10

Metastatic calcification

Answer 10

Occurs in normal tissues with hypercalcemia

Four causes:

Elevated parathyroid hormone - whose job is to increase blood levels of calcium

Bone destruction due to effects of accelerated turnover - Paget’s disease or malignancies (multiple myeloma)

Vitamin D related disorders - calcium is not absorbed properly, not enough calcium so increase expression of parathyroid hormone and take calcium from bone - cause secondary hyperthyroidism

Renal failure, phosphate retention - secondary hyperthyroidism. Calcium bound to phosphate is not recognized by body as calcium so increases expression of parathyroid hormone to increase free floating calcium

Question 11

Causes of Cellular aging

Answer 11

1. Accumulations of mutations in DNA = DNA repair mechanism not as good
2. Decreased cellular replication = ability to undergo cell cycle reduced due to telomere shortening - cancer does not experience this (infinite cell division) because of telomerase protects telomeres
3. Protein homeostasis is reduced