Pathology: Test 1: 04-05 Cellular and Tissue Accumulations I II Flashcards
1
Q
- What are cellular adaptations and what causes them? <br></br>Give 4 kinds of cellular adaptation and briefly describe what each one does
A
a. Cellular adaptations are reversible functional/structural responses to sever physiological stress/pathological stimuli
<br></br>i. Hypertrophy: increase in size/functional activity of cell
<br></br>ii. hyperplasia: increase in # of cells
<br></br>iii. atrophy: decrease in size/metabolic activity of cells
<br></br>iv. metaplasia: change in cell phenotype
2
Q
- When does cell injury occur? What are the stages of progressive impairment of the cell?
A
When limits of adaptive response to stimulus are exceeded
<br></br>Adaptation, reversible injury, and cell death represent stages of progressive impairment of cell’s normal function/structure
3
Q
- What are the two patterns of cell death and how are they different from each other? Give an example of each
A
Necrosis: cell death after abnormal stresses (i.e. ischemia/chemical injury), always pathological
<br></br>Apoptosis: cell death occurring because of internally controlled suicide pattern (i.e. embryogenesis; withdrawal of hormones.
4
Q
- What kind of cell process does nutrient deprivation trigger?
A
Autophagy (self-eating)
5
Q
- What may cause subcellular alterations in a cell?
A
Cells exposed to sublethal or chronic stimuli.
6
Q
- What are intracellular accumulations due to?
A
Metabolic derangements.
7
Q
- Give and briefly describe two forms of metabolic (subcellular alterations) accumulations/deposits
A
(Intracellular accumulations due to metabolic derangements, depositing of i.e. proteins, lipids, carbohydrates)
<br></br>Pathological calcification: Ca deposits at site of cell death
<br></br>Cell aging: cells show morphological and functional changes
8
Q
- What are physiological adaptations?
A
Responses to normal stimulation by hormones or endogenous chemical mediators (breast, lactation)
9
Q
- How is pathological adaptations different/same than physiological adaptations?
A
Pathological adaptations share the same underlying mechanism, but they allow modulation of environment and ideally escape injury.
10
Q
- What happens to cells in hypertrophy? Is it physiologic or pathologic? Caused by? Can occur in conjunction with? Most common stimulus for hypertrophy is?
A
<br></br>No new cells, just BIGGER cells, happens in non-dividing cells
<br></br>Can be both
<br></br>Caused by increased functional demand or specific hormone
<br></br>Can occur alone or with hyperplasia (increased # cells), if cells are able to divide
<br></br>Most common stimulus is increased workload
11
Q
- What causes the physiological enlargement of the uterus?
A
Both hypertrophy of existing smooth muscle cells and hyperplasia of smooth muscle
12
Q
- Give two examples of pathological hypertrophy occurring in the heart
What enlarges? When does it happen?
A
Cardiac enlargement that occurs with hypertension or aortic valve disease
Enlargement of individual cardiac fibers following an myocardial infarction (MI, heart attack) with death of surrounding myocytes (makes up for dead cells)
13
Q
- How do striated muscle cells divide in the heart and skeletal muscle? Undergo what cellular adaption?
A
Cannot divide and make more cells, thus only hypertrophy
14
Q
- What hypertrophies in the heart?
<br></br> when does this happen after?
A
Enlargement of individual cardiac fibers following an myocardial infarction (MI, heart attack) with death of surrounding myocytes
15
Q
- In chronic cardiac overload, what genes are expressed? What does contractile proteins switch to?
A
Genes normally in neonatal heart reactivate <br></br>
Contractile proteins switch to fetal isoforms (contract slower)
16
Q
- What is hyperplasia and what it result in? What does its occurrence depend on?
A
Hyperplasia: Increase in # of cells, leads to increased organ size and weight.<br></br>
Occurs if cell synthesize/mitosis
17
Q
- What are the two kinds of physiologic hyperplasia?
A
Hormonal hyperplasia (increase function) e.g. lactating breast, pregnant uterus<br> Compensatory hyperplasia e.g. liver grows to make up for lost cells
18
Q
- Pathologic hyperplasia usually results from?
A
Excessive hormones/growth factors
19
Q
- Describe the pathological hyperplasia’s role in menstruation
A
Imbalance between estrogen and progesterone endometrial hyperplasia can occur (abnormal menstrual bleeding)
20
Q
- What induces benign prostatic hyperplasia?
A
Androgens
21
Q
- How are hormonal/growth factor stimulation and cancer different?
A
When hormonal/growth factor ceases, then stimulation ceases.<br></br>
In cancer however, cells continue to grow.
22
Q
- What is responsible for hyperplasia’s healing ability? Give an example
A
Growth factors stimulated by viral infections, warts/papillomaviruses, etc.
23
Q
- What are two stimuli for hyperplasia?
A
Increased growth factor, increased new cells from tissue stem cells
24
Q
- Is atrophy physiological or pathological? Give an example
A
Both, physiological (embryonic structures) or pathological (atherosclerotic brain atrophy)
25
28. Give 6 causes of atrophy
i. decreased workload
ii. loss of innervation
iii. decreased blood supply (senile atrophy)
iv. inadequate nutrition
v. loss of endocrine stimulation
vi. pressure
ii. loss of innervation
iii. decreased blood supply (senile atrophy)
iv. inadequate nutrition
v. loss of endocrine stimulation
vi. pressure
26
29. What does the decrease in cell size and organelles in atrophy reduce? Why?
Metabolic needs; permit survival
27
30. The structural components of the cell reduced in number are because of what two reasos?
The structural components of the cell, are reduced in number due to?
Due to decreased protein synthesis
increase protein degradation
increase protein degradation
28
33. What are autophagic vacuoles?
Accompanies atrophy and are fused lysosomes and intracellular organelles
29
34. What happens to cell debris that resist digestion?
May persist as membrane-bound residual bodies (i.e. lipofuscin)
30
35. What is metaplasia and why does it occur?
Reversible change in cell type to another. Cells stressed are replaced by cells types better able to withstand (columnar -> squamous, as in resp. tract)
31
36. Metaplasia arises by?
Genetic reprogramming of epithelial stem cells or undifferentiated mesenchymal cells
32
37. Most common epithelial metaplasia?
Columnar -> squamous e.g. resp. tract of trachea and bronchi
33
38. In the epithelial metaplasia of the respiratory tract, what happens as an negative side effect?
Important protective mechanisms are lost e.g. mucus secretion and cilliary clearance
34
39. If metaplasia is persistent, what may occur?
metaplastic transformation may induce cancer transformation in the metaplastic epithelium
35
41. Metaplasia in CT causes the formation of what that is usually not found here? Example?
Cartilage, bone, or adipose tissue (mesenchymal tissues)
| e.g. myositis ossificans
36
45. Subcellular responses to injury are associated with alterations only to?
Subcellular organelles and cytosolic proteins
37
46. What lysosomes are involved in lysosomal catabolism?
Primary lysosomes fuse with membrane bound vacuoles containing material for digestion to form secondary lysosomes or phagolysosomes
38
47. Secondary lysosomes/phagolysosomes are involved in?
Breakdown of ingested material in heterophagy or autophagy
39
48. Define heterophagy, phagocytosis, and pinocytosis
Heterophagy: external materials taken up
Phagocytosis: take up of larger materials
Pinocytosis: uptake of smaller soluble material
Phagocytosis: take up of larger materials
Pinocytosis: uptake of smaller soluble material
40
49. How are endocytosed vacuoles degraded?
Comine with lysosomes, insides degraded
41
52. Metabolism of cholesterol and cholesterol esters are tightly regulated for synthesis of cell membrane. Give intracellular accumulation in 3 different processes with specific example for 2 out of 3 of these
```
Atherosclerosis
Xanthomas (acquired & hereditary hyperlipidemic states)
Cholesterolosis (gallbladder) ```
Xanthomas (acquired & hereditary hyperlipidemic states)
Cholesterolosis (gallbladder) ```
42
59. What are mallory bodies composed of? Histologically stains? Give an example of where mallory bodies are found
Eosinophilic intracytoplasmic inclusions composed of cytoskeletal filaments in damaged liver cells
43
60. What are 3 categories of substances that can be intracellular accumulated?
Excessive cell parts
Abnormal substances
Pigments
Abnormal substances
Pigments
44
61. What are four general mechanisms cells get abnormal intracellular accumulations?
i. abnormal metabolism
ii. alterations in protein folding and transport
iii. deficiency of critical enzymes
iv. inability to degrade phagocytosed particles
ii. alterations in protein folding and transport
iii. deficiency of critical enzymes
iv. inability to degrade phagocytosed particles
45
62. What classes of lipids can be accumulated?
All major classes, triglycerides, cholesterol, cholesterol esters, and phospholipids
46
63. What is the term for fatty change and what does it refer to? Is it reversible itself? Often seen? Causes?
Steatosis
Any abnormal accumulation of triglycerides within parenchymal cells
Reversible
Seen around necrotic cells or liver
Causes: toxins, protein malnutrition, diabetes mellitus, obesity, and anoxia. Though alcohol and diabetes most common in industrialized nations
Any abnormal accumulation of triglycerides within parenchymal cells
Reversible
Seen around necrotic cells or liver
Causes: toxins, protein malnutrition, diabetes mellitus, obesity, and anoxia. Though alcohol and diabetes most common in industrialized nations
47
64. What is the significance of fatty change?
```
Mild = no impairment of cellular function
Sever= impair cellular function and cell death ```
Sever= impair cellular function and cell death ```
48
65. What does CCl4 and protein malnutrition do?
Anoxia?
Starvation?
Starvation?
i. Decrease synthesis of protein
ii. Decreased fatty acid oxidation
iii. Increased fatty acid mobilization from stores
ii. Decreased fatty acid oxidation
iii. Increased fatty acid mobilization from stores
49
66. Fatty accumulation appears as what in parenchymal cells? What happens if there is a lot of fat?
Clear vacuoles
| Organ enlarges and yellowed
| Organ enlarges and yellowed
50
67. What are five ways phagocytic cells become overloaded with lipid?
i. Atherosclerosis
ii. Hyperlipidemic syndromes
iii. Inflammation and necrosis
iv. Gallbladder as in cholesterolosis
v. Niemann-Pick disease
ii. Hyperlipidemic syndromes
iii. Inflammation and necrosis
iv. Gallbladder as in cholesterolosis
v. Niemann-Pick disease
51
68. In atherosclerosis, what cells are in plaques, where, and what are they filled with? Appearance? What happens when these rupture?
Smooth cells and macrophages in intimal layer
Filled with lipid vacuoles of cholesterol and cholesterol esters
Foam cells with yellowy appearance
Lipids released then cholesterol esters crystallize into cholesterol clefts
Filled with lipid vacuoles of cholesterol and cholesterol esters
Foam cells with yellowy appearance
Lipids released then cholesterol esters crystallize into cholesterol clefts
52
69. Where does hyperlipidemic syndrome occur? What forms?
```
Foamy macrophages in subepithelial tissues in CT
Forms xanthomas (foam masses) ```
Forms xanthomas (foam masses) ```
53
70. What type of disease is Niemann-Pick disease? What happens in Niemann-Pick disease?
Type C (lysosomal storage disease), cholesterol accumulation
54
71. How do protein accumulations appear?
Pink, hyaline droplets, vacuoles, cytoplasmic aggregates
55
72. Give two examples of protein accumulation
i. Resorption droplets in renal disease
| ii. Synthesis of excess protein such in plasma cells synthesizing immunoglobulins (in eosinophilic Russell bodies)
| ii. Synthesis of excess protein such in plasma cells synthesizing immunoglobulins (in eosinophilic Russell bodies)
56
73. What cell injuries accumulate intracellular proteins?
Alcohol disease may cause mallory body or alcohol hyaline (eosinophilic)
57
74. What proteins in cells are vulnerable to form aggregates/entanglements?
Partially folder chains (intermediates)
58
75. What stabilizes partially folded chains? When are they produced? What other process do chaperones do? Give a heat-shock protein and its role?
i. Chaperones
ii. Constitutively or by stress
iii. Facilitation of chaperones successfully folder proteins are degraded
iv. Ubiquitin, marks abnormal protein for degradation by proteasome
ii. Constitutively or by stress
iii. Facilitation of chaperones successfully folder proteins are degraded
iv. Ubiquitin, marks abnormal protein for degradation by proteasome
59
76. What are three mechanisms of protein folding defects that cause intracellular accumulations?
i. Defective intracellular transport
ii. ER stress from unfolded/misfolded proteins
iii. Abnormal protein aggregation
ii. ER stress from unfolded/misfolded proteins
iii. Abnormal protein aggregation
60
77. Give an example of defective intracellular transport and secretion of critical protein
α1-antitrypsin deficiency = buildup of partially folded
intermediates which aggregate and can’t be secreted -> deficiency of enzyme (emphysema)
intermediates which aggregate and can’t be secreted -> deficiency of enzyme (emphysema)
61
78. What do unfolded protein response cause?
i. Decreased unfolded proteins though an
| ii. Increase in chaperones and slowdown of protein translation
| ii. Increase in chaperones and slowdown of protein translation
62
79. What enzyme is concurrently activated and lead to cell death?
Carpases
63
80. Give four diseases that are associated with aggregation of abnormally folded proteins?
Alzheimer’s, Huntington’s, Parkinsons, maybe type II diabetes
64
81. What are disorders of aggregation of abnormal proteins that interfere with normal tissue function called? Example?
Proteinopathies/protein-aggregation disease, i.e. amyloidosis
65
82. Excessive intracellular deposits can be seen in what disorders/cells? (give 5)
i. Diabetes mellitus
ii. Renal tubular epithelium
iii. Cardiac myocytes
iv. β cells of the islets of Langerhans
v. glycogen storage diseases
ii. Renal tubular epithelium
iii. Cardiac myocytes
iv. β cells of the islets of Langerhans
v. glycogen storage diseases
66
83. What is the most common exogenous pigment? How is it processed in body? What is it called when heavily accumulated? Give two examples
Carbon
Inhaled, phagocytosed, transported to tracheobronchial lymph nodes
Anthracosis
Emphysema and coal worker’s pneumoconiosis
Inhaled, phagocytosed, transported to tracheobronchial lymph nodes
Anthracosis
Emphysema and coal worker’s pneumoconiosis
67
84. a. Give an endogenous pigment and describe its appearance.
b. What is it a marker for?
c. What does it consist of and what is this derived from?
d. Seen most often in what kind of patients?
b. What is it a marker for?
c. What does it consist of and what is this derived from?
d. Seen most often in what kind of patients?
a) Lipofuscin (lipochrome) aka wear/tear pigment. Appears yellow-brown intracytoplasmic granules microscopically.
b) Marker for past free radical injury
c) Consist of lipid-protein complexes derived from free radical catalyzed peroxidation of polyunsaturated lipids of subcellular membranes
d) Most often seen in aging patients or ones with malnutrition/cancer cachexia
68
85. a. What kind of pigment is melanin?
b. What is it derived/formed from?
c. What is unique about melanin?
d. Protects against what and accumulates where?
b. What is it derived/formed from?
c. What is unique about melanin?
d. Protects against what and accumulates where?
a. Endogenous
b. non-Hb derived pigment formed from tyrosinase catalyzing oxidation of tyrosine to dihydroxyphenylalanine.
c. Only normal endogenous brown-black pigment
d. UV radiation and can accumulate in basal keratinocytes in skin or dermal macrophages
69
86. a. Hemosiderin is an endogenous pigment derived from?
b. Appearance?
c. Occurs when?
d. Hemosiderin pigments are aggregates of?
e. ID with?
b. Appearance?
c. Occurs when?
d. Hemosiderin pigments are aggregates of?
e. ID with?
a) yellow-to-brown granular pigment
b) Occurs when excess of iron, ferritin forms hemosiderin granules
c) Hemosiderin pigment represent aggregates of ferritin micelles
d) ID’ed with Prussian blue iron stain
70
87. a. Local hemosiderin can result from?
|
b. What do macrophages produce when they take up Hb?
b. What do macrophages produce when they take up Hb?
a. Hb-derived golden, yellow-to-brown granular pigment
|
b. lysosomal enzymes convert Hb and convert to hemosiderin, a ferritin containing pigment
b. lysosomal enzymes convert Hb and convert to hemosiderin, a ferritin containing pigment
71
88. When does hemosiderosis occur?
i. systemic overload of iron occurs in setting of increased absorption of dietary iron
ii. impaired use of iron
iii. hemolytic anemias (excess RBC breakdown)
iv. Transfusions (increase exogenous load of iron)
ii. impaired use of iron
iii. hemolytic anemias (excess RBC breakdown)
iv. Transfusions (increase exogenous load of iron)
72
89. a. What is progressive accumulation also known as and what does it injure?
b. What else can occur and what can it injure?
b. What else can occur and what can it injure?
. Hemochromatosis can injure liver, pancreas, heart, and endocrine organs
b. Liver fibrosis, heart failure, diabetes mellitus
73
90. a. Bilirubin is the major pigment found in?
b. What is jaundice caused by?
c. Bilirubin is derived from? Without what element?
b. What is jaundice caused by?
c. Bilirubin is derived from? Without what element?
a. bile
b. excess bilirubin pigment
c. Hb-derived, contains no iron
b. excess bilirubin pigment
c. Hb-derived, contains no iron
74
91. a. What is pathologic calcification?
b. What does it contain?
c. Two main types?
b. What does it contain?
c. Two main types?
a. Abnormal deposition of Ca salts
b. Calcium salts with smaller amounts of iron, magnesium, and other mineral salts
c. Dystrophic and metastatic
b. Calcium salts with smaller amounts of iron, magnesium, and other mineral salts
c. Dystrophic and metastatic
75
92. Dystrophic calcification is seen in?
Commonly seen on?
Grossly appears?
Histologically calcium salts appear?
Commonly seen on?
Grossly appears?
Histologically calcium salts appear?
a. Areas of injury & necrosis, atheromas of atherosclerosis
b. Damaged heart valves
c. Fine, white granules/clumps
d. Basophilic (blue/purple)
b. Damaged heart valves
c. Fine, white granules/clumps
d. Basophilic (blue/purple)
76
93. Metastatic calcification occurs when?
What are the four main causes of hypercalcemia?
Primarily affects?
What organ dysfunction is caused by metastatic calcification?
What are the four main causes of hypercalcemia?
Primarily affects?
What organ dysfunction is caused by metastatic calcification?
a. Normal tissues with hypercalcemia
b. Four main causes:
i. Increased secretion of PTH
ii. Destruction of bone
iii. Vitamin D disorders
iv. Renal failure
c. Primarily affects interstitial tissues of the gastric mucosa, kidneys, lungs, systemic arteries, and pulmonary veins
d. Usually none, occasionally lung and renal
b. Four main causes:
i. Increased secretion of PTH
ii. Destruction of bone
iii. Vitamin D disorders
iv. Renal failure
c. Primarily affects interstitial tissues of the gastric mucosa, kidneys, lungs, systemic arteries, and pulmonary veins
d. Usually none, occasionally lung and renal
