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Flashcards in Lec1 Cell Injury Deck (71):
1

What is Adaptation? Is it irreversible or reversible? What are the 4 types?

- cell avoids injury
- reversible
- can be pathological or physiological
- 4 types
--- hypertrophy
--- hyperplasia
--- atrophy
--- metaplasia

2

What is Hypertrophy? What change in cells

- type of adaptation
- bigger cells
- increase in cell size due to increase in number of cell organelles, structural proteins DNA

3

What is hyperplasia? What change in cells?

- 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

What is atrophy? What changes in cells?

- type of adaptation
- decrease size and function of cell [and sometimes number]
- apoptosis
- may not be reversible

5

What is Metaplasia? What changes in cells?

- 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

physiological causes of hypertrophy

- high estrogen in pregnancy
- uterus myometrial hypertrophy
- breast in lactation
- development
- skeleal muscle

7

pathological causes of hypertrophy

- hypertension --> left ventricular hypertrophy
- kidney contractile nephritis --> kidney hypertrophy
- increased nutrition [extra calories] --> hypertrophy of adipocytes

8

Physiological causes of hyperplasia

- development
- uterus in pregnancy - glandular hyperplasia
- breast in lactation

9

pathological causes of hyperplasia

- chronic blood loss --> erythroid hyperplasia
- obesity --> hyperplasia of adipocytes

10

Stresses that cause atrophy

physiologic
- menopause [withdraw hormones]

pathoglogic
-immobilization [decreased functional demand]
- starvation [decreased nutrients]

aging
[ex. myocardial atrophy]

11

How do functional demand, endocrine stimulation/withdrawl, and nutrition cause adaptations?

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

Stresses that cause metaplasia

smoking: pseudostratified --> squamous in trachea
GI acid from stomach to esophagus

13

Types of intracellular storage material

1. normal endogenous substance accumulates as by-product of normal metabolism

2. normal endogenous substance accumulated at increased rate

3. Normal or abnormal endogenous substance accumulates due to genetic defect in biochemical pathway [inborn error]

14

What is lipofuscin?

- 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

What are two examples of normal intracellular materials produced at increased rate?

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

What is hemosiderin? What disease associated with it?

- in liver
- in small amounts [post hemorrhage] is innocuous
- in large amount [hereditary hemochromatosis] may cause irreversible injury

17

What are different mech by which genetic defect in biochemical pathway may cause increase in intracellular substance?

1. failure of breakdown of normal or abnormal substance [storage disease] [often cause irreversible injury]

2. Error in producing or packaging of normal or abnormal substance

3. Exogenous material accumulates and can't be metabolized

18

What type of disease is niemann-pick?

- inborn storage disease
- failure in breakdown of sphingomyelin

19

What type of disease is hurler syndrome?

- inborn storage disease
- failure in breakdown of mucopolysaccharides

20

What type of disease is hereditary tyrosinemia?

- inborn storage disease
- failure in breakdown of precursor tyrosine metabolites

21

What is alpha-1-antitrypsin? What disease?

- 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

What are the pathophysiological effects of alpha-1-antitrypsin deficiency?

- 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

What are four neurodegenerative diseases associated with abnormal protein folding

- alzheimers
- parkinsons
- huntingtons
- prion disease

24

Effect of carbon dust accumulation

- 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