Cell Accumulation and Aging

Question 1

What is characterized by the accumulation of intracellular parenchymal triglycerides and is observed most frequently in the liver, heart, and kidney? What is the cause?

Answer 1

fatty change

imbalance among the uptake, utilization, and secretion of fat

Question 2

What are the pathologic accumulations of cholesterol? (4)

Answer 2

• atherosclerosis
• xanthomas
• foamy macrophages 2º to inflammation and necrosis
• cholesterolosis of the gallbladder

Question 3

What are the classic appearances of accumulated cholesterol?

Answer 3

cholesterol clefts

foam cells

Question 4

____ _____ of proteins leads to reabsorption droplets in proximal renal tubules and Russell Bodies in alcoholic liver disease.

Answer 4

Excess accumulation

Question 5

Disorders of protein folding involve failure of protein structural stabilization or degradation by specialized proteins known as what?

Answer 5

chaperones- important chaperones include heat shock proteins induced by stress (ubiquitin which marks abnormal proteins for degradation)

Question 6

Two kinds of pathogenic mechanisms include what?

Answer 6

1. abnormal protein aggregation (characteristic of amyloidosis and a number of neurodegenerative diseases)
2. abnormal protein transport and secretion (characteristic of cystic fibrosis and alpha1-antitrypsin deficiency)

Question 7

What is caused most often by nonspecific accumulations of proteinaceous material?

Answer 7

hyaline change

Question 8

This group of disorders is characterized by the deposition of amyloid, a proteinaceous material with certain physiochemical features.

Answer 8

amyloidosis- one of a group of disorders characterized by abnormal protein folding, always have Beta-pleated sheet configuration

Question 9

Amyloid is characteristically extracellular in distribution, most often appearing as accumulations proximate to what?

Answer 9

basement membranes

Question 10

What is stained by Congo red dye and demonstrates apple green birefringence when viewed under polarized light?

Answer 10

amyloidosis

Question 11

What is caused by deposition of amyloid fibrils derived from immunoglobulin light chains, referred to as AL protein?

Answer 11

primary amyloidosis (immunocytic dyscrasia amyloidosis)- this is the form frequently associated with plasma cell disorders such as multiple myeloma

Question 12

What is the deposition of fibrils consisting of the amyloid protein called AA protein, which is formed from a precursor, serum amyloid-associated protein (SAA) is characteristic?

Answer 12

secondary amyloidosis (reactive systemic amyloidosis)- chronic tissue destruction leads to SAA

Question 13

What is associated with an amyloid derived from a protein known as transthyretin?

Answer 13

protuguese type of polyneuropathy- characterized by severe peripheral nerve involvement caused by amyloid deposits

Question 14

What is characterized by deposits of an amyloid protein referred to as A4 amyloid, or amyloid b-protein, which differs from AL, AA, and transthyretin-derived amyloid?

Answer 14

Alzheimer disease- the gene that codes for the protein precursors of A4 amyloid has been localized to chromosome 21

Question 15

What is an autosomal recessive disorder occurring in persons of Eastern Mediterranean origin?

Answer 15

Familial Mediterranean fever- characterized by episodic fever and polyserositis

Question 16

What is characterized by prominent amyloid deposits within the tumor and is derived from calcitonin?

Answer 16

Medullary carcinoma of the thyroid

Question 17

What is the insulin-resistant-adult-onset form (type 2) characterized by deposits of amyloid in islet cells?

Answer 17

Diabetes mellitus
- amyloid is derived from either insulin or glucagon

Aylin interferes with insulin sensing beta cells

Question 18

What is characterized by minor deposits of amyloid found at autopsy in the very elderly?

Answer 18

Senile amyloidosis- involves heart, brain, and other organs

In the heart- protein is derived from transthyretin

Question 19

What is characterized by amyloid deposits in the joints of patients who have undergone hemodialysis for several years?

Answer 19

Dialysis-associated amyloidosis

Amyloid is derived from beta-microglobulin, a protein not readily filtered by the dialysis membrane

Question 20

Pulmonary accumulations of carbon (______ pigment), silica, and iron dust

Answer 20

Anthracotic pigment

Accumulation of exogenous pigments

Question 21

Plumbing (____ poisoning), Argyria (_____ poisoning), which may cause a permanent gray discoloration of the skin and conjunctivae.

Answer 21

Lead, silver

Accumulations of exogenous pigments

Question 22

This pigment is formed from tyrosine by the action of throsinase, synthesized in melanosomes of melanocytes within the epidermis, and transferred by melanocytes to adjacent clusters of keratinocytes and also to macrophages in the sub adjacent dermis.

Answer 22

Melanin

• increased melanin pigmentation is associated with sun tanning and disease conditions
• decreased melanin is observed in albinism and vitiligo

Question 23

This pigment is a catabolic product of the heme moiety of hemoglobin and, to a minor extent, myoglobin.

Answer 23

Bilirubin

-accumulates and stains the blood, sclera, mucosal, and internal organs producing a yellow color called jaundice

Question 24

This iron-containing pigment consists of aggregates of ferritin. It appears in tissues as golden brown amorphous aggregates and can be positively identified by its staining reaction with Prussian blue dye.

Answer 24

Hemosiderin

Question 25

What is defined by accumulation of hemosiderin, primarily within tissue macrophages WITHOUT associated tissue or organ damage?

Answer 25

Hemosiderosis

Question 26

What is more extensive accumulation of hemosiderin, often within parenchyma cells, WITH accompanying tissue damage, scarring, and organ dysfunction?

Answer 26

Hemochromatosis- can be hereditary (primary) and secondary forms

Question 27

What is a yellowish, fat-soluble pigment that is an end product of membrane lipid peroxidation?

Answer 27

Lipofuscin- sometimes referred to as “wear-and-tear” pigment

Elderly patients- in hepatocytes and at the poles of nuclei of myocardial cells

Question 28

The combination of lipofuscin accumulation and atrophy of organs is referred to as what?

Answer 28

Brown atrophy

Question 29

The cause of metastatic calcification is _____ most often resulting from what? (4)

Answer 29

Hypercalcemia

1. Hyperparathyroidism
2. Osteolytic tumors with resultant mobilization of calcium and phosphorus
3. Hypervitaminosis D
4. Excess calcium intake, such as in the milk-alkali syndrome

Question 30

What is defined as calcification in previously damaged tissue, such as areas of old trauma, tuberculosis lesions, scarred heart valves, and atherosclerotic lesions?

Answer 30

Dystrophic calcification- typically the serum calcium concentration is normal

Question 31

Cellular aging is the result of a progressive decline in cellular function and viability caused by what?

Answer 31

Genetic abnormalities and the accumulation of cellular and molecular damage due to the effects of exposure to exogenous influences

Question 32

Hematopoietic stem cells suffer ____ new mutations per year, and it is likely that this accumulating damage explains why the most common hematologist ______ are diseases of the aged.

Answer 32

14, malignancies

Question 33

All normal cells have a limited capacity for ____, and after a fixed number of divisions cells become arrested in a terminally no dividing states known as what?

Answer 33

Replication

Replicating senescence

Question 34

As most somatic cells age, their ____ become shorter and they exit the cell cycle, resulting in an inability to generate new cells to replaced damaged ones.

Answer 34

Telomeres

Question 35

In immortalized cancer cells, _____ is usually reactivated and ______ length in stabilized, allowing the cells to proliferate indefinitely.

Answer 35

Telomerase

Telomere