Cell Adaptation, Injury, and Death Flashcards
1
Q
What are 3 cellular mechanisms of hypertrophy?
A
- Gene activation
- Protein synthesis
- Production of organelles
2
Q
What is the mechanism for hyperplasia?
A
Production of new cells from stem cells
3
Q
When do hyperplasia and hypertrophy occur together?
A
Uterus - pregnancy
4
Q
Permanent tissue can only undergo _________.
A
Hypertrophy
5
Q
What are 3 main permanent tissue?
A
- Cardiac myocytes
- Skeletal muscle
- Nerves
6
Q
Pathologic hyperplasia can lead to cancer. What is the exception?
A
BPH
7
Q
Atrophy
A
A decrease in size and number of cells
8
Q
By what mechanisms does atrophy occur?
A
- Ubiquitin-proteosome degradation of cytoskeleton
- Autophagy of cellular components -vacuoles/ lysosomes
- Apoptosis
9
Q
Metaplasia
A
Change in cell type to handle stress
10
Q
Barrett Esophagus
A
Change of esophageal squamous epithelium to columnar (non-ciliated, mucinous) epithelium of stomach - acid reflux
11
Q
How does metaplasia occur?
A
Reprogramming stem cells, reversible with removable of driving stressor
12
Q
Metaplasia can progress to dysplasia and cancer except for ____________.
A
Apocrine metaplasia - seen w/ fibrocystic change of breast
13
Q
_________ deficiency can result in metaplasia.
A
Vitamin A - necessary for maintenance of specialized epithelium i.e. conjunctiva (squamous thickening keratomalacia)
Night blindness, immune deficient (maturation), metaplasia
14
Q
Myositis ossificans
A
Mesenchymal tissue metaplasia
Inflammation (trauma) of sk muscle –> Bone
**doesn’t grow off bone
15
Q
Dysplasia
A
Disordered cellular growth - proliferation of precancerous cells (CIN) - from longstanding pathologic hyperplasia or metaplasia
16
Q
Is dysplasia reversible?
A
Yes
17
Q
If stress persists, what does dysplasia proceed to?
A
Carcinoma (irreversible)
18
Q
Aplasia
A
Failure of cell production during embryogenesis - unilateral renal agenesis
19
Q
Hypoplasia
A
Dec. in cell production during embryogenesis - small organ - streak ovary in Turner syndrome
20
Q
Likelihood of injury depends on what 3 things?
A
Stress, severity, and type of cell affected
21
Q
What type of cell is most affected by hypoxia?
A
Nerve cells
22
Q
Hypoxia
A
Low oxygen delivery to tissue - Low ATP - cellular injury
23
Q
What are the 3 major causes of hypoxia?
A
Ischemia, hypoxemia, dec. carrying ability of blood (anemia, CO)
24
Q
What are 3 mechanisms of ischemia?
A
- Block artery
- Block hepatic vein - Budd-Chiari Syndrome
- Shock
25
Hypoxemia
Low partial pressure of oxygen in the blood (PaO2 < 60 mmHg or SaO2 <90%)
26
What are common causes of hypoxemia?
1. High altitude,
2. Inc PACO2 (hypovent, COPD)
3. Interstitial fibrosis
27
Anemia
Dec in RBC mass
| PaO2 normal and SaO2 normal (%)
28
CO poisoning
CO binds Hb more avidly than O2
| PaO2 normal, SaO2 decreased - cherry red skin
29
Methemoglobinemia
Iron in heme is oxidized to Fe3+ - can't bind O2
PaO2 is normal, SaO2 decreased - oxidant stress (sulfa and nitrate drugs) or newborns
Cyanosis w/ chocolate-colored blood - IV methylene blue
30
Hypoxia impairs ___________. which results in decreased ATP.
Oxidative phosphorylation
31
What 3 key things does low ATP disrupt.
1. Na-K pump (Na/H2O builds up)
2. Ca pump (Ca builds up in cytosol)
3. Aerobic glycolysis (lactic acid)
32
What are the findings of reversible injury?
1. Cellular swelling
| 2. Loss of microvilli, membrane blebbing and swelling of RER (dec protein synthesis)
33
What are the findings of irreversible damage?
1. Plasma membrane damage
~Ruptured cell, leaking enzymes, and Inc Ca
2. Mitochondrial membrane damage (Inner membrane) e transport - cytochrome c
3. Lysosome membrane damage - autophagy
34
Morphologic hallmark of cell death is loss of _________.
Nucleus
35
Loss of nucleus can occur via which 3 mechanisms?
Pyknosis, karyorrhexis, and karyolysis
36
Pyknosis
Nucleus shrinks down
37
Karyorrhexis
Nucleus breaks down into pieces
38
Karyolysis
Nucleus breaks down farther into building blocks
39
Necrosis
Death of a large group of cells, followed by acute inflammation
40
Necrosis is always due to underlying _________ process.
Pathologic
41
Coagulative necrosis
Necrotic tissue that remains firm - cell shape/organ structure are preserved, nucleus disappears
42
Ischemic infarction of any solid organ leads to _____________.
Coagulative necrosis - not brain
43
Area of infarcted tissue is often ______-shaped and _____.
Wedge
| Pale
44
Red infarction
Blood re-enters a loosely organized tissue
45
Liquefactive necrosis
Necrotic tissue becomes liquefied - enzymatic lysis of cells and proteins
46
What are the characteristic instances of liquefactive necrosis?
1. Brain infarction (microglial)
2. Abscess (neutrophils)
3. Pancreatitis (pancreatic enzymes)
47
Why does a brain infarction result in liquefactive necrosis?
The microglial cells contain hydrolytic enzymes
48
Gangrenous necrosis - dry
Coagulative necrosis that resembles mummified tissue - Ischemia of lower limb and GI
49
Gangrenous necrosis - wet
Coagulative necrosis w/ superimposed infection - liquefactive
50
Caseous necrosis
Soft, friable necrotic tissue "cottage cheese like" appearance - TB infection or fungal
Characteristic granulomatous inflammation - combo
51
Fat necrosis
Necrotic adipose tissue w/ chalky-white appearance - deposition of calcium -- saponification (FA + Ca)
52
What two types of necrosis are seen with pancreatitis
Fat (peripancreatic fat) and Liquefactive (pancreas)
53
Where is fat necrosis seen?
1. Trauma to fat e.g. breast
| 2. Pancreatitis-mediated damage of peripancreatic fat
54
Saponification
FA released by trauma or lipase join w/ Ca (dystrophic calcification)
55
Dystrophic Calcification
Dead/dying tissue is a deposit site for Ca - serum Ca and PO4 is normal
56
Metastatic Calcification
Serum Ca or serum PO4 is elevated and forces Ca into tissues which then precipitates out
57
Fibrinoid necrosis
Necrotic damage to blood vessel wall - leaking of protein into vessel wall -- bright pink staining
58
What is fibrinoid necrosis characteristic of?
1. Malignant HTN
2. Vasculitis
3. Preeclampsia (30 yo woman)
59
Apoptosis
Energy-dependent, genetically programmed cell death - single cell or small groups of cells
60
What are 3 morphological characteristics of apoptosis?
1. Dying cell shrinks (eosinophilic)
2. Nucleus condenses and fragments
3. Apoptotic bodies fall from cell and are removed by macrophages (no inflammation)
61
Apoptosis is mediated by __________ which activate ___________ and ______________.
1. Caspases
2. Proteases (cytoskeleton)
3. Endonucleases (DNA)
62
What are the 3 pathways that can activate caspases?
1. Intrinsic
2. Extrinsic receptor-ligand
3. CD8+ T cell via perforins and granzymes
63
Intrinsic mitochondrial pathway
Cellular injury, DNA damage, or dec. hormal stim will inactivates Bcl2 -> Cytochrome c leaves from inner mitochondrial matrix into cytoplasm
64
Extrinsic receptor-ligand pathway
FAS ligand binds FAS death receptor on target cell or
| TNF binds TNF receptor
65
How are free radicals generated pathologically?
1. Ionizing radiation (OH*) hydroxyl
2. Inflammation
3. Metals (Cu and Fe)
4. Drugs/chemicals
66
What is the most damaging free radical?
The Hydroxyl radical OH*
67
How does iron generate a free radical, and what is the most common?
1. Fenton reaction
| 2. Hydroxyl
68
How do free radicals cause damage?
1. Peroxidation of lipids
| 2. Oxidation of DNA and proteins
69
What are 3 ways the body can eliminate free radicals?
1. Antioxidants (Vita A, C, E)
2. Metal carrier proteins (transferrin)
3. Enzymes
70
What 3 enzymes are important for the elimination of free radicals?
1. SOD (O2-)
2. Glutathione peroxidase (OH*)
3. Catalase (H2O2)
71
Where is CCl4 commonly seen, and where is it converted to CCl3? What is the classic histologic finding?
1. Dry Cleaning
2. Liver
3. Fatty Liver (RER swelling/no Apolipoprotein)
72
What is the main way a reperfusion injury causes damage?
Return of oxygen and inflammatory cells to dead cells generates free radicals
73
A patient undergoing a myocardial infarction is taken to the cath lab. After the artery is opened up, the cardiac enzymes continue to rise, why?
Reperfusion injury - damage to cardiac myocytes by free radicals
74
Amyloid
Misfolded protein that deposits in extracellular space
75
What are the common characteristics of amyloid
1. Beta-pleated sheet config
2. Congo red staining and apple-green birefringence under polarized light
3. Tends to deposit around blood vessels
76
Primary amyloidosis
Systemic deposition of AL amyloid - derived from Ig light chain
77
What is primary amyloidosis associated with?
Plasma cell dyscrasias (more light than heavy chain)
78
Secondary amyloidosis
Systemic deposition of AA amyloid derived from SAA
79
SAA
Acute phase reactant that is increased in chronic inflammatory states, malignancy and familial mediterranean fever
80
Familial Mediterranean fever
Dysfunction of neutrophils (AR) - fever and acute serosal inflammation --> High SAA during attacks deposits as AA amyloid
81
Classic clinical findings of systemic amyloidosis (3)
1. Nephrotic syndrome (most commonly involved)
2. Restrictive cardiomyopathy or arrhythmia
3. Tongue enlargement, malabsorption, and hepatosplenomegaly
82
Senile cardiac amyloidosis
Non-mutated serum transthyretin deposits in heart - usually asymptomatic
83
Familial amyloid cardiomyopathy
Mutated serum transthyretin deposits in heart - restrictive cardiomyopathy - 5% of AA
84
Type II Diabetes
Amylin deposits in islets of pancreas - derived from insulin
85
Alzheimer Disease
Abeta amyloid deposits in brain forming plaques - derived from beta-amyloid precursor protein (Chrom 21)
86
Dialysis-associated amyloidosis
beta2-microglobulin deposits in joints - not filtered well
87
Medullary carcinoma of thyroid
Calcitonin deposits within tumor - tumor cells w/ an amyloid background
