Exam 2: Cell Adaptation and Injury Flashcards
(123 cards)
1
Q
Why do animals become sick or diseased?
A
Sick cells result in sick animals
Cellular dysfucntion— organ dysfunction— animal dysfunction
2
Q
What is the normal cell confined to a fairly narrow range of function and structure by?
A
Genetic programs of metabolism, differentiation, and specialization
Constraints of neighboring cells
Availability of metabolic substrates
3
Q
What are the cellular responses to stress?
A
More severe physiologic stresses and some pathologic stimuli cause physiologic and morphologic cellular adaptations
Achieve new but altered steady states
Preserve the viability of the cell
Modulate function as cell responds to stimuli
4
Q
What happens if the limits of adaptive response to stimulus are exceeded or if a cell is exposed to an injurious agent or stress?
A
Cellular injury results
5
Q
What happens if the stimulus persists or is severe enough from the beginning?
A
The cell reaches “the point of no return” and suffers irreversible cell injury and cell death
6
Q
Describe normal cells and adaptations
A
Cells have specialized functions and specialized structures based on their functions
All cells have certain “standard” organelles
—Synthesis of lipids, proteins, CHOs
—Energy production
—Transport of ions and other molecules
7
Q
What is homeostasis?
A
Tight control of pH, electrolyte concentration, etc
8
Q
What does departure from homeostasis lead to?
A
Cell damage
9
Q
How do cells respond to homeostatic challenges?
A
By adpatation
10
Q
What results if a new level of homeostasis cannot be achieved?
A
Cell death
11
Q
What are examples of cellular adaptations?
A
Increase in muscle mass with exercise
Increase in cytochrome p450 mixed function oxidation expression in hepatocytes
12
Q
How do cells adapt?
A
By either increasing or decreasing content of organelles
Atrophy, hypertrophy, hyperplasia, metaplasia
13
Q
What is atrophy?
A
Reduction in mass of a tissue or organ
14
Q
What is hypertrophy?
A
Increase in the size of cells, resulting in enlargement of organs
15
Q
What is hyperplasia?
A
Increased number of cells in an organ or tissue
16
Q
What is metaplasia?
A
Transformation or replacement of one adult cell type with another
17
Q
What can atrophy be due to?
A
Either loss of cells or reduction in the size of cells within an organ
18
Q
What are the adaptive responses to altered demands with cellular atrophy?
A
Decreased workload Decreased nutrition Loss of hormonal stimulation Decreased blood supply Loss of innervation
19
Q
What occurs with cellular atrophy?
A
Reversible cellular change
Reduced functional capacity
Continue to control internal environment and produce sufficient energy for metabolic state
20
Q
What may prolonged cellular atrophy lead to?
A
Death of some of the cells
Loss of muscle cells with prolonged denervation
Atrophy at the organ level may become irreversible at this point (muscle) or may be reversible by hyperplasia (liver)
21
Q
Describe hypertrophy at the organ level
A
Hypertrophy increases organ size without cellular proliferation
22
Q
Is cell enlargement in hypertrophy that same as cell swelling?
A
No, it is different
23
Q
What are changes in hypertrophic cells?
A
Increased protein content Increased organelle number ---Myofibrils (muscle) ---Mitochondria ---ER
24
Q
Is the anabolic process or catabolic process greater in hypertrophy?
A
Anabolic, breaking down quicker than we are building up
25
Why may hypertrophy not be advantageous to an animal?
Point of diminishing returns
Heart
-Hypertrophy does not change underlying problem and cannot provide adequate energy/contraction
-Conformational changes associated with hypertrophy decrease ejection volume
-May eventually end up with organ failure
26
What is hypertrophy in the liver?
Induction
27
Describe induction
Effect may be helpful or not helpful:
Tolerance to certain drugs/toxins
More rapid removal of certain drugs/toxins
May increase susceptibility to some toxins
--Metabolites may be more toxic than precursors
28
What is cell injury?
Any change that results in loss of the ability to maintain the normal or adapted homeostatic state
29
What happens when cells become unable to balance the processes that regulate internal environment?
We see morphologic changes that we recognize as cell injury or degeneration
30
What does the extent of cell injury depend on?
Severity of stimulus
Type of cell involved
Metabolic state at the time of injury
31
What is reversible cell injury?
Degeneration
32
What are hallmarks of cell degeneration?
```
Cell swelling
Fatty change
Lipofuscin and ceroid
Hyaline changes
Amyloid
Mucinous change
Calcification
Gout
Cholesterol crystals
Inclusions
```
33
What is an early, almost universal sign of cell injury?
Cell swelling
34
Describe cell swelling
Cells enlarged
Compress adjacent structures (loss of sinusoids in liver)
Altered staining characteristics (pale, cloudy appearance, cytoplasmic vacuoles caused by distended organelles, lipid droplets)
Loss of energy control/production
Not incompatible with life of the cell and is often mild and rapidly reversible
Also occurs in lethal injury
35
What does cell swelling result from?
Loss of control of ions/water with net uptake of water
36
What is the gross appearance of cell swelling?
Organ is often pale
Enlarged, swollen (rounded margins, heavy, wet)
Bulges on cut surface
37
What is the effect of cell swelling in the brain?
Severe effects due to pressure necrosis
38
What is the effect of cell swelling in the liver?
Decreased blood flow, decreased function
39
What is the effect of cell swelling in the pharynx?
Airway obstruction
40
What is fatty change?
Accumulation of neutral fats (TG) in a cell
| Nothing to do with adipose tissue
41
What is fatty change common in?
Injured cells, especially cells that metabolize lots of lipids
42
What do sick cells tend to accumulate?
Triglycerides
43
What is the gross appearance of fatty change?
```
Yellow discoloration (kidney/liver)
Enlarged (liver)
```
44
What is the pathogenesis of fatty change?
Overload (increased mobilization of fats; diabetes mellitus)
Injury to cells (toxins, anoxia)
Deficiencies (methionine, choline)
45
When is lipidosis normal?
In young animals (milk diet)
| Following fatty meals
46
What is seen grossly with glycogen accumulation?
Swollen organ
Rounded margins
Increased pallor
47
What is seen microscopically with glycogen accumulation?
Enlarged cells
Increased pallor
No nuclear displacement
48
What is the pathogenesis of glycogen accumulation?
```
Prolonged, severe hyperglycemia (diabetes mellitus)
Increased corticosteroids (Cushing's, iatragenic)
Enzyme deficiencies (glycogen storage diseases, defects in a step of glycogen breakdown)
```
49
What is lipofuscin?
Pigment that collects in cells
50
What is seen grossly with lipofuscin?
Brown discoloration of affected organs
51
What is seen microscopically with lipofuscin?
Membrane bound brown pigment
52
What is hyaline?
Catch-all phrase for solid, glossy, semi-transparent material
53
What are hyaline droplets?
Cytoplasm contains rounded, eosinophilic droplets, vacuoles, or aggregates
54
What are hyaline casts?
Protein casts within renal tubules (unabsorbed protein)
55
What is connective tissue hyaline?
Compacted collagen, scar tissue
56
What is amyloid?
Homogenous, amorphic, eosinophilic matrix/substance deposited along basement membranes and between cells
Accumulation of serum protein amyloid-A that forms beta-pleated sheets that stick together
57
What is seen grossly with amyloid?
Enlarged, pale, waxy, translucent organ
58
What is calcification?
Abnormal deposition of calcium salts in soft tissues
59
What is seen grossly with calcification?
Chalky, white tissue
| Hard, gritty on cut surface
60
What is seen microscopically with calcification?
Dark blue staining material
Along BM
Stippled throughout cell
Large clumps
61
What is widespread excessive calcification calleD?
Calcinosis
62
What is the term used when there is calcification in the cavities or lumina?
Calculi/calculus
63
What does the effect of calcification depend on?
Location
64
What is gout?
Accumulation of urate crystals (tophus/tophi)
65
What is seen grossly with gout?
White, firm, crystal deposites
66
What is seen microscopically with gout?
Granulomas with radiating crystalline material
67
What is the pathogenesis of gout?
Disturbance of purine metabolism
Vitamin A deficiency
Kidney failure
68
What are the 2 forms of gout?
Visceral
| Articular
69
Describe nuclear change in cell injury
Chromatin clumping
Condensation (pyknosis)
Dramatic nuclear change is usually indicative of necrosis
70
Describe plasma membrane changes in cell injury
Loss of surface features
Desmosome breakdown
Bleb formation
71
Describe mitochondria changes in cell injury
Swelling
Loss of dense granules
Calcium deposits
72
Describe ER chanes in cell injury
Dilation
| Dissociation of ribosomes
73
What happens to phospholipids from damaged organelle membranes?
Accumulate to form myelin figures
74
Describe lysosome changes in cell injury
Dilation and rupture
| Usually a late event/terminal event in cell injury
75
Once death occurs, what begins?
Degradation
76
What are characteristics of degradation seen microscopically?
Increased eosinophilia
Loss of cellular detail
Nuclear changes (pyknosis, karyorhexis, karyolysis)
77
What are the 6 causes of cell injury?
```
Oxygen deprivation
Physical agents
Chemical agents
Infectious agents
Nutritional imbalances
Genetic defects
```
78
What are methods of oxygen deprivation?
Hypoxia
| Ischemia
79
Describe hypoxia
Decreased blood oxygen supply
| Decreased blood flow
80
Describe ischemia
Infarction
| Complete or almost complete loss of blood flow
81
What are physical agents that can cause cell injury?
Trauma
Radiation
Burns
82
Describe how chemical agents can cause cell injury
Concentration, dose, length of exposure
Variety of actions:
Injure cell membranes
Interfere with metabolism
83
What are infectious agents that can cause cell injury?
Viruses, bacteria, protozoa, fungi
Elaborate toxins
Host inflammatory responses
84
How does nutritional imbalances cause cell injury?
Deficiencies or excess fats, proteins, CHOs, vitamins
85
What does cell response depend on?
Type of injury
Duration of injury
Cell state at the time of injury
Adaptability of the injured cell
86
What 4 intracellular systems are particularly vulnerable with cell injury?
```
Cell membrane
Aerobic respiration (mitochondria)
Protein synthesis (rough ER, ribosomes)
Preservation of genetic integrity (nucleus)
```
87
What does cell injury interfere with?
Substrates or enzymes
88
What are the most vulnerable systems in cell injury when substrates and enzymes are interfered with?
Energy production:
Glycolysis
Citric acid cycle
Oxidative phosphorylation
89
What is the most vulnerable component in cell injury when enzymes or molecules that degrade cell components are produced?
Membrane
90
What are the common pathways for cell injury?
```
ATP depletion
Oxygen and oxygen derived free radicals
Intracellular calcium/loss of calcium homeostasis
Defects in membrane permeability
Irreversible mitochondrial damages
```
91
What are mechanisms of ATP depletion?
Oxidative phosphorylation of ADP to ATP
Glycolytic pathway
Tissues vary greatly in their ability to utilize pathways
Frequent pathway in ischemic and toxic injuries
92
What are oxygen and oxygen derived free radicals?
Partially reduced reactive oxygen species
93
What are oxygen and oxygen derived free radicals kept under control by?
Scavenging systems
94
Describe free radicals
Auto-catalytic, especially in membranes
95
What happens with intra-cellular calcium/loss of calcium homeostasis?
Normal cytosolic Ca maintained at low concentrations
| Increased calcium
96
What can cause calcium to increase?
```
Increased membrane permeability
Increased phospholipase activity
Increased protease activity
Increased ATPase activity
Increased endonuclease activity
Self destruction (activation of apoptotic pathways)
```
97
Describe defects in membrane permeability
Plasma membrane
Mitochondrial membrane
Direct damage: perforin, complement, inflammation
Indirect damage: calcium levels, ATP depletion
98
What happens with irreversible mitochondrial damage?
Direct or indirect targets of virtually all cell injuries
Damaged by everything from toxins to hypoxia
Damage expressed as high conductance channel formation
99
What are results of hypoxia?
Respiratory efficiency
Cardiac function
Tissue demand
Blood flow remains
100
What are results of ischemia?
```
Hypovolemia
Infarction
Vasoconstriction
Shock
Loss of oxygen and loss of substrates
Reversible to a point
```
101
What is reperfusion injury?
Paradoxical increase in death of cells after blood flow is restored
102
What are results of reperfusion injury?
GDV
Stroke
Myocardial infarction
103
What happens with decreased oxidative phosphorylation in the mitochondria?
It leads to ATP depletion, which leads to widespread cellular effects
Na/K ATPase: Na accumulates in cell, water follows Na, cell swelling
ADP, phosphates, lactate: further cell swelling
104
What happens from structural disruption of protein synthesis due to hypoxia/ischemia?
Detachment of ribosomes from RER
| Dissociation of polysomes into monosomes
105
What are the function consequences of hypoxia/ischemia?
Heart muscle ceases to contract within 60 seconds
| Neurons cease to fire or fire erratically
106
What happens with continuing ATP depletion due to hypoxia and ischemia?
Cytoskeleton dispersal
Swelling of mitochondria
ER dilation
More cell swelling
107
What are contributing factors of membrane damage?
```
Mitochondria dysfunction
Loss pf membrane phospholipids
Reactive oxygen species
Lipid breakdown products
Loss of intracellular amino acids
```
108
What is the bottom line regarding hypoxia/ischemia?
They affect oxidative phosphorylation and cause decreased ATP
Membrane damage is a critical step in the movement of a cell from reversible to irreversible damage
Ca is an important mediator of biochemical and morphologic alterations leading to cell death
109
What are free radicals?
Chemical species with an unpaired electron in their outer orbit
110
What is involved in the formation of free radicals?
```
Absorption of radiant energy
Metabolism of chemicals
Byproduct of normal metabolism
Transition metals
Nitric oxide
```
111
What are the injurious effects of free radicals?
Lipid peroxidation of membranes
Oxidation modification of proteins
DNA lesions
112
When is the lipid peroxidation of membranes initiated?
When double bonds of unsaturated fatty acids are attacked
113
What is protection?
Enzymatic and non-enzymatic systems to inactivate free radicals
114
What are non-enzymatic systems that inactivate free radicals?
Anti-oxidants
| Metal transport/storage proteins
115
What are enzymatic systems that inactivate free radicals?
Catalase
Superoxide dismutases
Glutathione peroxidase
116
What are the final effects induced by free radicals dependent on?
The balance between free radical formation and the cells defense systems that scavenge or terminate free radicals
117
What are directly toxic compounds capable of?
Interacting with critical molecular components or cellular organisms
118
Describe indirectly toxic compounds
Vast majority of toxins
| Converted to reactive toxic metabolites by mixed function oxidases
119
What is the bottom line of chemical injury?
Can be due to direct interactions of injurious chemical with cells, but is usually due to interaction of free radical metabolites with membranes and proteins
120
What is the most common mechanisms of toxins?
Free radicals
121
Describe irreversible cell injury
Transition state between living and dead cell
Exact "point of no return" is not possible to identify
Exact point of death is not possible to identify
122
What are the morphologic hallmarks of irreversible cell injury and death?
Severe mitochondrial swelling
Large flocculent densities in mitochondrial matrix
Increased loss of proteins, enzymes, co-enzymes
Greatly increased membrane permeability
123
What is the central factor in irreversible cell injury?
Membrane damage
