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Ch 2: Cellular responses to stress etc > Intracellular Accumulations and Pathologic Calcification > Flashcards

Intracellular Accumulations and Pathologic Calcification Flashcards

(54 cards)

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1
Q

What are the 4 main pathways of abnormal intracellular accumulations? Give examples

A
  1. Inadequate removal of a normal substance due to defects in packaging/transport mechs
    eg fatty liver
  2. Accumulation of an abnormal endogenous substance due to defects in folding/packaging/transport/secretion
    eg alpha1-antitrypsin
  3. Failure to degrade a metabolite due to inherited enzyme deficiencies
    eg storage diseases
  4. Deposition and accumulation of an abnormal exogenous substance when the cell has neither the enzymatic machiner to degrade the substance nor the ability to transport it to other sites
    eg silicosis and other pneumoconioses
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2
Q

T or F: Only some classes of lipids can accumulate in cells.

A

False.
All classes of lipids can accumulate in cells: triglycerides, cholesterol/esters, phospholipids.
Additionally, abnormal complexes of lipids and CHOs accumulate in lysosomal storage diseases.

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3
Q

What is steatosis?

A

Abnormal accumulations of triglycerides within parenchymal cells.

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4
Q

Where is steatosis most commonly seen?

A

Fatty liver

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5
Q

What other organs can steatosis be seen in?

A

Heart, muscle, kidney

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6
Q

What are the causes of steatosis?

A 
Toxins
Protein malnutrition
Anoxia
Diabetes mellitus
Obesity
Alcohol abuse
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7
Q

What are 4 pathologic processes involving cholesterol/ester accumulation?

A
  1. Atherosclerosis
  2. Xanthomas
  3. Cholesterolosis
  4. Niemann-Pick disease type C
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8
Q

Describe atherosclerosis.

A

Smooth muscle cells and macrophages within the intimal layer of the aorta and large arteries are filled with lipid vacuoles.

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9
Q

Smooth muscle cells and macrophges filled with lipid vacuoles are called? Why?

A

Foam cells, because they have a foamy appearance.

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10
Q

Define atheroma.

A

Aggregates of foam cells in the intima

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11
Q

Describe xanthomas.

A

Clusters of foam cells in subepithelial connective tissue of the skin and in tendons forming tumourous masses. Characteristic of acquired and hereditary hyperlipidaemic states.

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12
Q

Describe cholesterolosis.

A

Focal accumulations of cholesterol-laden macrophges in the lamina propria of the gallbladder.

Mechanism unknown

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13
Q

Describe Niemann-Pick disease type C

A

Lysosomal storage disease caused by mutations affecting an enzyme involved in cholesterol trafficking. Cholesterol accumulates in multiple organs.

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14
Q

What kinds of substances can accumulate in cells?

A

Lipids, proteins, glycogen, pigments

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15
Q

Accumulations of protein usually appear as…

A

Eosinophilic droplets, vacuoles or aggregates in the cytoplasm.

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16
Q

Example of a disease where proteins deposit abnormally extracellularly?

A

Amyloidosis

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17
Q

Causes of excessive protein accumulation

A
  1. Reabsorption droplets in proximal renal tubules
  2. Accumulation of excessive amounts of normal secreted proteins eg Russell bodies - eosinophilic immunoglobulin accumulations within plasma cells
  3. Defective intracellular transport and secretion of critical proteins eg alpha1-antitrypsin deficiency
  4. Accumulation of cytoskeletal proteins eg keratin filament accumulation causing alcoholic hyaline in alcoholic liver disease and eg 2 accumulation of neurofilaments into neurofibrillary tangles in Alzheimer’s disease
  5. Aggregation of abnormal/misfolded proteins either intra- or extracellularly eg amyloidosis or other “proteinopathies”.
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18
Q

4 types of cytoskeletal filament

A
  1. Microtubules 20-25nm
  2. Actin filaments (6-8nm)
  3. Myosin filaments (15 nm)
  4. Intermediate filaments (10 nm)
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19
Q

5 types of intermediate filament

A
  1. Keratin (epithelial cells)
  2. Neurofilaments (neurons)
  3. Desmin filaments (muscle)
  4. Vimentin filaments (connective tissue)
  5. Glial filaments (astrocytes)
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20
Q

Glycogen accumulation occurs in disorders of glucose and glycogen metabolism. Describe 2 such disorders.

A
  1. Diabetes mellitus - glycogen accumulates in liver, renal tubular epithelium, beta cells of the islets of Langerhans and heart muscle
  2. Glycogen storage disorders - defective enzymes in the synthesis or breakdown of glycogen
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21
Q

T or F: Pigments may be normal or abnormal, endogenous or exogenous.

A

True

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22
Q

The most common exogenous pigment is?

23
Q

Coal dust causes…(2)

Study These Flashcards
A
  1. Anthracosis (black deposits in lymph nodes where macrophages take phagocytosed dust)
  2. Coal worker’s pneumoconiosis (inflammatory reaction causes fibroblastic reaction or emphysema)
24
Q

Name 4 types of endogenous pigment

Study These Flashcards
A
  1. Lipofuscin
  2. Melanin
  3. Homogentisic acid
  4. Haemosiderin
25
What is lipofuscin?
Polymers of lipids and phospholipids in complex with protein
26
What is the clinical significance of lipofuscin?
Not inherently injurious to cells, but a marker of free radical injury and lipid peroxidation
27
How is lipofuscin derived?
Probably from lipid peroxidation of polyunsaturated lipids of subcellular membranes.
28
Where in the cell is lipofuscin found?
Perinuclear cytoplasm
29
In what kind of cells is lipofuscin seen?
Cells undergoing slow, regressive change - aging liver and heart, severe malnutrition and cancer cachexia
30
Homogentisic acid is characteristic of which disease?
Alkaptonuria
31
When deposited in skin, connective tissue and cartilage, homogentisic acid causes a black pigmentation known as?
Ochronosis
32
How is iron stored in cells?
In association with the protein apoferritin, to form ferritin micelles
33
What is haemosiderin?
Accumulations of ferritin micelles when there is local or systemic excess of iron
34
Under normal conditions, where is haemosiderin seen?
In macrophages of the liver, spleen and bone marrow which are actively involved in red cell breakdown.
35
What is an example of a local excess of iron causing haemosiderin accumulation?
Bruise
36
When there is ________ overload of iron, haemosiderin may be deposited in many organs and tissues, a condition called ___________
Systemic | Haemosiderosis
37
3 causes of haemosiderosis?
1. Haemochromatosis (inborn error of metabolism) 2. Haemolytic anaemias 3. Repeated blood transfusions
38
Pathologic calcification is...
the abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium and other mineral salts
39
2 forms of pathologic calcification
1. Dystrophic calcification | 2. Metastatic calcification
40
What is dystrophic calcification?
When deposition of calcium occurs locally in dying tissues - it occurs despite normal serum levels of calcification and in the absence of derangements in calcium metabolism.
41
What is metastatic calcification?
When deposition of calcium occurs in otherwise normal tissues, almost always secondary to hypercalcaemia. Can accentuate dystrophic calcification.
42
Dystrophic calcification is often a cause of organ dysfunction. Give 2 examples.
1. Atherosclerosis | 2. Calcific valvular heart disease
43
4 common and 2 rarer causes of hypercalcaemia
1. Increased secretion of PTH with subsequent bone resorption 2. Resorption of bone tissue 3. Vitamin D excess 4. Renal failure 5. Aluminium intoxication 6. Milk-alkali syndrome
44
Causes of bone resorption
1. Primary tumours of bone marrow 2. Diffuse skeletal mets 3. Accelerated bone turnover 4. Immobilisation
45
3 vitamin D related disorders
1. Intoxication 2. Sarcoidosis - macrophages activate vit D precursor 3. Idiopathic hypercalcaemia of infancy (William's syndrome) - abnormal sensitivity to vitamin D
46
How does renal failure lead to hypercalcaemia?
Retention of phosphate results in secondary and then tertiary hyperparathyroidism.
47
Which organs/tissues are principally affected by metastatic calcification?
Interstitium of the gastric mucosa, kidneys, lungs, systemic arteries and pulmonary veins
48
What predisposes these tissues to calcification?
All excrete acid and therefore have an internal alkaline compartment.
49
In pathologic calcifications, calcium salts exist as... (2)
1. Non-crystalline amorphous deposits | 2. Hydroxyapatite crystals
50
Usually metastatic calcification causes no clinical dysfunction except on a massive scale in which 2 organs?
1. Lungs | 2. Kidneys
51
Occasionally over time, _________ ____ may form in the focus of calcification.
Heterotopic bone
52
Describe the formation of psmammoma bodies.
Single necrotic cell becomes the seed crystal that is encrusted by mineral deposits in layers.
53
What types of cancers are apt to develop psammoma bodies?
Papillary ca eg thyroid
54
Calcium and iron depositis gathering about the slender spicules of asbestos form what characteristic shape?
Beaded dumbells

Ch 2: Cellular responses to stress etc (3 decks)

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