Lec1 Cell Injury Flashcards
1
Q
What is Adaptation? Is it irreversible or reversible? What are the 4 types?
A
- cell avoids injury
- reversible
- can be pathological or physiological
- 4 types
- – hypertrophy
- – hyperplasia
- – atrophy
- – metaplasia
2
Q
What is Hypertrophy? What change in cells
A
- type of adaptation
- bigger cells
- increase in cell size due to increase in number of cell organelles, structural proteins DNA
3
Q
What is hyperplasia? What change in cells?
A
- type of adaptation
- increase in number of cells due to more cell division
- can only occur in dividing cells [not skeletal or cardiac muscle]
4
Q
What is atrophy? What changes in cells?
A
- type of adaptation
- decrease size and function of cell [and sometimes number]
- apoptosis
- may not be reversible
5
Q
What is Metaplasia? What changes in cells?
A
- type of adaptation
- reprogramming of stem cells, replacement of one type of differentiated tissue by another type of differentiated tissue
- no change in size or number of tissues
- pretty much always pathologic
6
Q
physiological causes of hypertrophy
A
- high estrogen in pregnancy
- uterus myometrial hypertrophy
- breast in lactation
- development
- skeleal muscle
7
Q
pathological causes of hypertrophy
A
- hypertension –> left ventricular hypertrophy
- kidney contractile nephritis –> kidney hypertrophy
- increased nutrition [extra calories] –> hypertrophy of adipocytes
8
Q
Physiological causes of hyperplasia
A
- development
- uterus in pregnancy - glandular hyperplasia
- breast in lactation
9
Q
pathological causes of hyperplasia
A
- chronic blood loss –> erythroid hyperplasia
- obesity –> hyperplasia of adipocytes
10
Q
Stresses that cause atrophy
A
physiologic
- menopause [withdraw hormones]
pathoglogic
- immobilization [decreased functional demand]
- starvation [decreased nutrients]
aging
[ex. myocardial atrophy]
11
Q
How do functional demand, endocrine stimulation/withdrawl, and nutrition cause adaptations?
A
increase functional demand = hypertrophy + hyperplasia
endocrine stimulation = hypertophy + hyperplasia
increased nutrition = hypertrophy and hyperplasia
decrease functional demand = atrophy
endocrine withdrawl = atrophy
decreased nutrition = atrophy
12
Q
Stresses that cause metaplasia
A
smoking: pseudostratified –> squamous in trachea
GI acid from stomach to esophagus
13
Q
Types of intracellular storage material
A
- normal endogenous substance accumulates as by-product of normal metabolism
- normal endogenous substance accumulated at increased rate
- Normal or abnormal endogenous substance accumulates due to genetic defect in biochemical pathway [inborn error]
14
Q
What is lipofuscin?
A
- polymer of lipids
- wear and tear pigment
- seen in liver/heart in elderly
- often in atrophic tissue
- usually innocuous
- shows up as brown pigment
15
Q
What are two examples of normal intracellular materials produced at increased rate?
A
Triglycerides in liver in alcohol
= indication of reversible injury
Hemosiderin
- in small amounts post-hemmorage is innocuous
- in large amount in hereditary hemochromatosis may cause irreversible injury
16
Q
What is hemosiderin? What disease associated with it?
A
- in liver
- in small amounts [post hemorrhage] is innocuous
- in large amount [hereditary hemochromatosis] may cause irreversible injury
17
Q
What are different mech by which genetic defect in biochemical pathway may cause increase in intracellular substance?
A
- failure of breakdown of normal or abnormal substance [storage disease] [often cause irreversible injury]
- Error in producing or packaging of normal or abnormal substance
- Exogenous material accumulates and can’t be metabolized
18
Q
What type of disease is niemann-pick?
A
- inborn storage disease
- failure in breakdown of sphingomyelin
19
Q
What type of disease is hurler syndrome?
A
- inborn storage disease
- failure in breakdown of mucopolysaccharides
20
Q
What type of disease is hereditary tyrosinemia?
A
- inborn storage disease
- failure in breakdown of precursor tyrosine metabolites
21
Q
What is alpha-1-antitrypsin? What disease?
A
- alpha-1 antitrypsin is protease inhibitor of neutrophil elastase
- alpha 1 antitrypsin deficiency: mutation in AA causes slow folding of protein, partially folded precursor stuck in ER of hepatocytes
- – causes irreversible cell [ER] injury and death
22
Q
What are the pathophysiological effects of alpha-1-antitrypsin deficiency?
A
- hepatic injury due to entrapment abnormal a1AT in ER causes hepatic scarring [fibrosis and cirrhosis]
- deficiency a1AT in rest of body causes pulmonary emphysema
23
Q
What are four neurodegenerative diseases associated with abnormal protein folding
A
- alzheimers
- parkinsons
- huntingtons
- prion disease
24
Q
Effect of carbon dust accumulation
A
- can’t be metabolized so accumulates
- often innocuous
- in large amounts can cause pulmonary fibrosis
25
What is pneumoconiosis?
A non-neoplastic disorder of lungs due to toxic inhalants
26
Reversible cell injury
- hydropic change
| - swelling of organelles
27
How can you tell hydropic change? What causes it?
- swollen, clear cytoplasm
| - due to influx of sodium and water into damaged cell
28
Types of Irreversible cell injury
- damage to mitochondrial aerobic respiration
- damage to integrity of plasma membrane
- fragmented organelles
29
2 Causes of irreversible cell injury
- ischemia
| - free radicals
30
What is Ischemia?
decreased blood flow leads to hypoxia and hypoglycemia
| - causes irreversible cell injury
31
What effect do free radicals have on cells [adaptation, reversible or irreversible cell injury]
chemical species with single unpaired electron in outer orbital
- cause irreversible cell injury
32
Effect of intracellular calcification
- due to cellular injury which allows influx Ca ions
- impairs mitochondrial oxidative phosphorylation
- -- less ATP
- activates intracellular enzymes to facilitate cell death
33
Two types of calcification in tissues [different from intracellular]
- dystrophic calcification
| - metastatic calcification
34
Dystrophic calcification
- tissue calcification in injured tissue
- normal serum Ca
- normal Ca metabolism
35
Which type of tissue calcification occurs in injured tissues?
dystrophic calcification
36
4 Examples of dystrophic calcification
- heart valves [old, abnormal, injured]
- atherosclerotic blood vessels
- areas of necrosis
- neoplasms
37
What is basis for diagnostic mammography?
dystrophic calcification
38
Metastatic calcification
- occurs in normal tissues
- Excess Ca salts accumulate
- increased serum Ca due to derangement in Ca metabolism
- -- ex. hyperparathyroidism, destruction bone, Vit D intoxication, chronic renal failure
39
Which type of calcification has abnormal serum Ca level?
Metastatic calcification
40
4 common sites of metastatic calcifiction
- stomach [mucosa]
- kidneys [tubules]
- lungs [alveolar septa]
- blood vessels
41
Necrosis
- morphologic changes that follow cell death in living tissue
- degradative proteins cause enzymatic digestion and/or denaturation
- characterized by pyknosis/karyorrhexis/karolysis
- stimulates acute inflammation
- bigger cells, occurs in multiple cells
- disrupted plasma membrane
- uncontrolled mech, from infection, membrane injury, ATP depletion, ischemia
42
5 Types of Necrosis
- coagulative
- liquefactive
- caseous
- fat
- fibrinoid
43
What is coagulative necrosis? Architecture? Mech? Cells? Location?
- Cause: ISCHEMIA OR HYPOXIA
- architecture preserved
- in heart [after MI] or kidney
- big neutrophils [PMN]
- mech: denaturation of proteins
44
What is pyknosis?
small nuclei, sign of necrosis
45
What is karyorrhexis?
nuclei broken up into small pieces, sign of necrosis
46
What is karyolysis?
lack of nuclei, sign of necrosis
47
What is liquefactive necrosis? Architecture? Mech? Cells? Location?
- Cause: Bacterial, fungal infection
- causes abscess in lung/liver
- increased PMNs [neutrophils]
- architecture obliterated because of complete enzymatic digestion
- in lung, liver, or brain
48
What is caseous necrosis? Architecture? Mech? Cells? Location?
- cause: TB
- in lung [or lymph node]
- architecture obliterated
- get walled off area of whatever it is you can't digest
- causes granuloma
- get macrophages, chronic inflammation
49
What is fat necrosis? Architecture? Mech? Cells? Location?
- cause: release of digestive enzymes, commonly follows acute pancreatitis
- preserved architecture
- chronic inflammatory cells present
- mech: autodigestion by lipase
50
What is fibrinoid necrosis? Architecture? Mech? Cells? Location?
- cause: injury to blood vessel in setting of immune-mediated injury or hypertenstion
- in blood vessel
- preserved architecture
- fibrin and PMNs [neutrophils] present
- mech: immune-mediated or hypertension
51
What type of cell death involves inflammation? why?
Necrosis
| - because it involves breakdown of cell peripheral membranes
52
Mech of apoptosis? Cause? Inflammation?
- internal mechanism of programmed cell death via protease and endonuclease cascade
- no inflammation
- phagocytosis
- cell membrane intact
- small eosinophlic cell, fragmented apoptotic bodies
- physiologic: normal develop., immune regulation
- pathologic: virus, transplant rejection, ER stress
- due to transplant rejection, ER cell death,
53
Intrinsic pathways of apoptosis
- cell injury by growth factor withdrawl, DNA damage, or protein misfolding
- causes mitochondria release pro-apoptotic bodies [cytochrome C] --> caspases
54
Extrinsic pathway of apoptosis
- receptory ligated interaction activates capsases
55
Telomerase function
Over time telomeres shorten leading to senescence, telomerase prevents shortening and leads to indefinite replication
56
Hutchinson-gilford progeria
- de novo autosomal dominant
- abnormal intranuclear protein lamin A [progerin]
- normal lamin A protects integrity of nucleus
57
Werner syndrome
- autosomal recessive causes dysfunctional DNA helicase
- normal DNA helicase unwinds DNA during replication
- abnormal causes accumulated DNA damage
58
Genomic instability
idea that lifetime of somatic gene mutations [DNA damage] leads to senescence
59
Superoxide dismutase [SOD]
- SOD converts O2 --> H2O2, decreases ROS
| - knockout of anti-SOD age-1 gene increases lifespan
60
Environmental factors related to aging
- reactive oxygen species
| - diet
61
How does reactive oxygen species [ROS] relate to aging?
- over times ROS damage accumulates
- causes cell breakdown, death
- genomic DNA particularly susceptible
- treat: antioxidants [vit A/D, beta carotene]
62
How does quantity of diet effect aging?
caloric restriction [CR]: decreased intake increases lifespan
--- lower metabolic rate --> decreased generation of ROS
nutrient abundance promotes:
-- insulin/IGF pathway
-- mTOR pathway [regulates cell growth, facilitates replicative senescence]
thus caloric restriction might inhibit these paths
63
Red wine and aging
- contains resveratrol that activates sirtruin [anti-aging protein
- sirtruin may be molecular bases of effectiveness of caloric restriction
- extends life span in mice and high fat, high cal diet
64
What is advanced glycation end products [AGE]?
- source: endogenous in DM, sausage, burger, cookies, occurs in browning meat
- related to arthritis, atherosclerosis
- increases ROS, upregulates inflammation
65
What does sudan IV stain for?
Fat
66
What does PAS stain for?
carbohydrates, glycogen
67
Gangrenous necrosis
- type of caogulative necrosis superimposed with liquifactive necrosis
- usually due to diabetes get necrosis of limbs
68
What does oil red O stain for?
triglycerides
69
Etiologies of hepatic steatosis
- starvation
- obesity
- diabetes mellitus
- alcohol
70
What is etiology of a myocardial infarction?
- infarct = discrete area of coagulative necrosis secondary to occlusion of artery supplying or obstruction of venous outflow from area
71
What is significance of elevated troponin-I or creatine kinase?
- elevation indicates cell membrane breakdown and necrosis
| - sign of MI
