1-Cell Adaptation, cell injury/cell death Flashcards
1
Q
Four major patterns of cellular adaptation
A
- hypertrophy
- hyperplasia
- atrophy
- metaplasia
2
Q
Hypertrophy
A
- increase in SIZE of cell, =increased organ size
- increase in size is due to increased production of CELLULAR PROTEINS
- may be physiologic or pathologic
3
Q
example of physiologic hypertrophy
A
uterus in pregnancy
-heart is another common organ that hypertrophies (myocardial hypertrophy)
4
Q
mechanisms of myocardial hypertrophy
A
-mechanical stretch (increased work load)
-agonistst (alpha adrenegic hormones, angiotensin)
-growth factors (IGF-1)
All these lead to signal transduction pathways
5
Q
Hyperplasia
A
- Increase in NUMBER of cells, which usually increases mass
- may occur with hypertrophy
- may be physiologic or pathologic
6
Q
Types of physiologic hyperplasia
A
- Hormonal (puberty)
- compensatory (regrowth of liver)
7
Q
Pathologic hyperplasia
A
- hormonal/growth factors
- eg endometrial or prostatic hyperplasia
8
Q
mechanisms of hyperplasia
A
- proliferation of mature cells driven by growth factors
- increased production of new cells from stem cells
9
Q
Atrophy
A
- decreased cell size and number, =reduced size of tissue or organ
- may be physiologic or pathologic
- fundamental change is a decrease in cell size and organelles; reduction in metabolic needs may permit survival
10
Q
common causes of pathologic atrophy
A
- decreased workload (disuse atrophy, like with an arm in a cast)
- loss of innervation (denervation atrophy)
- diminished blood supply
- inadequate nutrition
- loss of endocrine stimulation
- pressure (like bed sores)
11
Q
mechanisms of atrophy
A
- decreased protein synthesis due to reduced metabolic activity
- increased protein degradation in cells due to activation of UBIQUITIN LIGASES
- increased autophagy
12
Q
autophagy
A
engulfment and degradation of cell’s own components
13
Q
Metaplasia
A
- replacement of one differentiated cell type by another
- often represents an adaptation to stress by substituting cells better able to withstand stress
- either epithelial or mesenchymal cells may undergo metaplasia
- REVERSIBLE
14
Q
common area of metaplasia
A
lungs, caused by irritation, especially from smoking.
- the cells go from ciliated columnar to squamous cells (squamous metaplasia)
15
Q
potential downside of metaplasia
A
- loss of certain cell functions (like the ciliary activity in the lungs)
- ?? predisposition to development of neoplasia (process of new growth, controversial)
16
Q
mechanisms of metaplasia
A
- re-programming of stem cells to differentiate along a new pathway
- NOT a change in an already differentiated cell
- differentiation is effected by cytokines, growth factors and extracellular matrix components that promote gene expression
17
Q
Types of cellular adaptations:
A
- Hypertrophy-increase in size of cells
- Hyperplasia-increase in number of cells
- Atrophy-decrease in cell size, number
4 Metaplasia-replacement of one differentiated cell type by another
18
Q
chronic irritation leads to what type of cellular adaptation?
A
Metaplasia
19
Q
in there is a decrease in nutrients or stimulation, what will the adaptation be?
A
Atrophy
20
Q
If there is a stimulus that is Physiologic/pathologic (growth factors, hormones, increased demand) the adaptation will be?
A
Hypertrophy or hyperplasia; or both
21
Q
intracellular accumulations
A
- substances may be normal cellular constituents (lipids, carbohydrates, proteins) or abnormal substances (exogenous or endogenous)
- may be transient or permanent
- may be harmless or toxic
22
Q
steatosis
A
fatty change of the liver
-enlarged and yellow
23
Q
anthracosis
A
carbon pigment deposition in lung
24
Q
Hemochromatosis
A
Iron overload, can occur in liver or pancreas
25
Pathologic calcification of tissues
- abnormal deposition of calcium salts (usually with smaller amounts of other mineral salts
- Two forms:
- Dystrophic calcification
- Metastatic calcification
26
Most common type of tissue calcification
Dystrophic calcification
27
dystrophic calcification
- typically found in areas of tissue necrosis
| - initiated by cell membrane damage
28
Steps of dystrophic calcification
- Calcium ion binds to phospholipids
- phosphatases generate phosphate groups
- repeated cycles of calcium-phosphate binding
- structural changes result in microcrystal
- propagation with more calcium deposition
29
Metastatic Calcification
- occurs in normal tissues in setting of hypercalcemia
| - deposition can occur widely throughout the body
30
The causes of Metastatic calcification
1. Increased secretion of PTH
2. destruction of bone
3. vitamin D-related disorders
4. renal failure
31
Causes of cell injury
- Oxygen deprivation (hypoxia and ischemia)
- physical, chemical, and infectious agents
- genetic derangements, immunologic reactions
- nutritional imbalances
32
Hypoxia
- oxygen deficiency
| - interferes with AEROBIC oxidative respiration
33
ischemia
- loss of blood supply, or mismatch of blood supply and tissue demand due to
- impeded arterial flow or
- reduced venous drainage
- the MOST COMMON cause of tissue hypoxia
34
Examples of generalized hypoxia
- pneumonia
- CNS depression
- high altitude
- anemia of blood loss
- CO poisoning
35
examples of Ischemia
- Atherosclerosis
- thromboembolism (blood clot that gets dislodged)
- external compression of artery by tumor
- severe hypotension (poor blood flow)
36
Which injures tissues faster, hypoxia or ischemia?
Ischemia
37
infarction
irreversible injury/cell death
38
What ceases during ischemia?
Delivery of both oxygenated blood and substrates for glycolysis
39
Mechanisms of cell injury
- depletion of ATP (eg ischemia)
- damage to mitochondria
- influx of clacium
- accumulation of oxygen-derived free radicals (oxidative stress)
- defects in membrane permeability
- damage to DNA and proteins
40
reversible injury
Changes related to reduced oxidative phosphorylation with depleted ATP
-swelling of ER and mitochondria; membrane blebs; clumping of nuclear chromatin
41
two main morphologic correlates of reversible injury:
- Cellular swelling due to failure of ion pumps, water influx (hydropic change, vacuolar degeneration)
- fatty change, (usually live and myocardium)
42
Is necrosis physiologic, pathologic, or both?
ALWAYS PATHOLOGIC
43
Is apotosis physiologic, pathologic, or both?
-frequently physiologic, but may be pathologic
| necrosis and apoptosis may occur in response to the same injury
44
Necrosis: cytoplasmic changes
- sever damage to cell membrane with loss of integrity
- leakage of contents
- digestion of cell by enzymes from cell's lysosomes or leukocytes
- phospholipids phagocytosed or degraded to fatty acids; calcification results in calcium soaps; sometimes necrotic cells/tissue become calcified
45
necrosis: three patterns of nuclear changes
- due to breakdown of DNA and chromatin
1. Karyolysis
2. pyknosis
3. Karyorrhexis
46
Karyolysis
fading of nucleus due to deoxyribonuclease activity
47
Pyknosis
nuclear shrinkage and increased basophilia due to DNA condensation
48
Karyorrhexis
fragmentation and eventual disappearance of pyknotic nucleus
49
Types of tissue necrosis
- coagulative
- liquefactive
- caseous
- fat
- fibrinoid
- (gangrene)
50
coagulative necrosis
"cells are mummified"
- basic tissue architecture is preserved
- injury denatured not only structural proteins but also enzymes; proteolysis is blocked
- eventually necrotic cells are phagocytosed/digested by leukocytes
- typical of ischemic infarcts (except in brain)
51
Liquefactive necrosis
- usually in setting of microbial infections
- inflammatory cells release enzymes that digest (liquefy) fissue
- associated with the formation of PUSS
- typical of cerebral infarcts
- "Wet gangrene"
52
Gangrene
- usually refers to ischemic necrosis (typically of a limb)
- coagulative necrosis (dry gangrene)
- if complicated by bacterial infection, also undergoes liquefactive necrosis (wet gangrene)
53
Caseous necrosis
- most often associated with tuberculous infection
- cheese-like appearance
- cells fragmented, lysed; tissue architecture not identifiable
- usually surrounded by granuloma (special form of inflammatory response)
54
Fat necrosis
- focal areas of fat destruction
- associated with acute pancreatitis, with release of lipases into pancreas and peritoneal cavity;
- adipocyte membranes liquefied; release fatty acids which combine with calcium=fat saponification
55
fibrinoid necrosis
- usually seen in immune reactions involving blood vessels
- deposition of antigen-antibody complexes in vessel wall
- fibrin leaks out of vessel
- BRIGHT PINK amorphous appearance
56
apoptosis
- cell membrane integrity is largely maintained
- active, energy-dependent process; not associated with ATP depletion
- characterized by nuclear dissolution, fragmentation of the cell, followed by removal of cell debris
- irreparable damage to DNA or proteins, or with deprivation of growth factors
57
causes of apoptosis
- programmed cell destruction in embryogenesis
- involution of hormone-dependent tissues
- cell loss in proliferating cell populations
- senescent cell loss
- elimination of self-reactive lymphocytes
- cell death induced by cytotoxic T lymphocytes
- DNA damage (ie radiation)
- accumulation of misfolded proteins
- some infections
- pathologic atrophy after duct obstruction
58
Necrosis summary
- always pathological
- ATP depletion
- membrane injury
- many cells
- cell swelling; disrupted organelles
- inflammation
59
Apoptosis summary
- pathological or physiological
- gene activation; proteolytic enzymes
- single cells
- intact organelles; apoptotic bodies
- no inflammation; phagocytosis or apototic bodies
