Cell Accumulation and Aging Flashcards
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?
fatty change
imbalance among the uptake, utilization, and secretion of fat
What are the pathologic accumulations of cholesterol? (4)
- atherosclerosis
- xanthomas
- foamy macrophages 2º to inflammation and necrosis
- cholesterolosis of the gallbladder
What are the classic appearances of accumulated cholesterol?
cholesterol clefts
foam cells
____ _____ of proteins leads to reabsorption droplets in proximal renal tubules and Russell Bodies in alcoholic liver disease.
Excess accumulation
Disorders of protein folding involve failure of protein structural stabilization or degradation by specialized proteins known as what?
chaperones- important chaperones include heat shock proteins induced by stress (ubiquitin which marks abnormal proteins for degradation)
Two kinds of pathogenic mechanisms include what?
- abnormal protein aggregation (characteristic of amyloidosis and a number of neurodegenerative diseases)
- abnormal protein transport and secretion (characteristic of cystic fibrosis and alpha1-antitrypsin deficiency)
What is caused most often by nonspecific accumulations of proteinaceous material?
hyaline change
This group of disorders is characterized by the deposition of amyloid, a proteinaceous material with certain physiochemical features.
amyloidosis- one of a group of disorders characterized by abnormal protein folding, always have Beta-pleated sheet configuration
Amyloid is characteristically extracellular in distribution, most often appearing as accumulations proximate to what?
basement membranes
What is stained by Congo red dye and demonstrates apple green birefringence when viewed under polarized light?
amyloidosis
What is caused by deposition of amyloid fibrils derived from immunoglobulin light chains, referred to as AL protein?
primary amyloidosis (immunocytic dyscrasia amyloidosis)- this is the form frequently associated with plasma cell disorders such as multiple myeloma
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?
secondary amyloidosis (reactive systemic amyloidosis)- chronic tissue destruction leads to SAA
What is associated with an amyloid derived from a protein known as transthyretin?
protuguese type of polyneuropathy- characterized by severe peripheral nerve involvement caused by amyloid deposits
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?
Alzheimer disease- the gene that codes for the protein precursors of A4 amyloid has been localized to chromosome 21
What is an autosomal recessive disorder occurring in persons of Eastern Mediterranean origin?
Familial Mediterranean fever- characterized by episodic fever and polyserositis
What is characterized by prominent amyloid deposits within the tumor and is derived from calcitonin?
Medullary carcinoma of the thyroid
What is the insulin-resistant-adult-onset form (type 2) characterized by deposits of amyloid in islet cells?
Diabetes mellitus
- amyloid is derived from either insulin or glucagon
Aylin interferes with insulin sensing beta cells
What is characterized by minor deposits of amyloid found at autopsy in the very elderly?
Senile amyloidosis- involves heart, brain, and other organs
In the heart- protein is derived from transthyretin
What is characterized by amyloid deposits in the joints of patients who have undergone hemodialysis for several years?
Dialysis-associated amyloidosis
Amyloid is derived from beta-microglobulin, a protein not readily filtered by the dialysis membrane
Pulmonary accumulations of carbon (______ pigment), silica, and iron dust
Anthracotic pigment
Accumulation of exogenous pigments
Plumbing (____ poisoning), Argyria (_____ poisoning), which may cause a permanent gray discoloration of the skin and conjunctivae.
Lead, silver
Accumulations of exogenous pigments
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.
Melanin
- increased melanin pigmentation is associated with sun tanning and disease conditions
- decreased melanin is observed in albinism and vitiligo
This pigment is a catabolic product of the heme moiety of hemoglobin and, to a minor extent, myoglobin.
Bilirubin
-accumulates and stains the blood, sclera, mucosal, and internal organs producing a yellow color called jaundice
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.
Hemosiderin
What is defined by accumulation of hemosiderin, primarily within tissue macrophages WITHOUT associated tissue or organ damage?
Hemosiderosis
What is more extensive accumulation of hemosiderin, often within parenchyma cells, WITH accompanying tissue damage, scarring, and organ dysfunction?
Hemochromatosis- can be hereditary (primary) and secondary forms
What is a yellowish, fat-soluble pigment that is an end product of membrane lipid peroxidation?
Lipofuscin- sometimes referred to as “wear-and-tear” pigment
Elderly patients- in hepatocytes and at the poles of nuclei of myocardial cells
The combination of lipofuscin accumulation and atrophy of organs is referred to as what?
Brown atrophy
The cause of metastatic calcification is _____ most often resulting from what? (4)
Hypercalcemia
- Hyperparathyroidism
- Osteolytic tumors with resultant mobilization of calcium and phosphorus
- Hypervitaminosis D
- Excess calcium intake, such as in the milk-alkali syndrome
What is defined as calcification in previously damaged tissue, such as areas of old trauma, tuberculosis lesions, scarred heart valves, and atherosclerotic lesions?
Dystrophic calcification- typically the serum calcium concentration is normal
Cellular aging is the result of a progressive decline in cellular function and viability caused by what?
Genetic abnormalities and the accumulation of cellular and molecular damage due to the effects of exposure to exogenous influences
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.
14, malignancies
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?
Replication
Replicating senescence
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.
Telomeres
In immortalized cancer cells, _____ is usually reactivated and ______ length in stabilized, allowing the cells to proliferate indefinitely.
Telomerase
Telomere
