Pathoma: Growth adaptations, cell injury and death Flashcards Preview

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Flashcards in Pathoma: Growth adaptations, cell injury and death Deck (57)
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1
Q

Hypertrophy

A

increase in size of the organ

involves gene activation, protein synthesis, and production of organelles

2
Q

Hyperplasia

A

increase in number of cells in the organ

involves the production of new cells from stem cells

3
Q

Permanent Tissues

A

Cardiac muscle
skeletal muscle
nerve

cannot make new cells
undergo hypertrophy only

4
Q

Pathologic hyperplasia progresses to

A

dysplasia and eventually cancer

exception - benign prostatic hyperplasia, does not increase the risk for prostate cancer

5
Q

Atrophy

A

decrease in stress leads to decrease in organ size by a decrease in size and number cells

6
Q

what process decreases the number of cells in atrophy

A

apoptosis

7
Q

what processes decreases the cell size in atrophy

A

ubiquitin-proteasome degradation of cytoskeleton - intermediate filaments of cytoskeleton are tagged with ubiquitin and destroyed by proteasomes
autophagy of cellular components - generation of autophagic vacuoles - fuse with lysosomes whose hydrolytic enzymes breakdown cellular components

8
Q

metaplasia

A

change in stress on an organ leads to a change in cell type - most commonly one epithelium to another better able to handle the new stress

occurs via reprogramming stem cells
may be reversible by treating stressor

persistent stress - can progress to dysplasia and eventually cancer

Barrett’s Esophagus

9
Q

Barrett’s Esophagus

A

esophagus normally lined by nonkeratinizing squamous epithelium - can handle friction of food bolus
acid reflux from the stomach causes metaplasia to nonciliated, mucin-producing columnar cells- better able to handle stress of acid

10
Q

Vitamin deficiency that can lead to metaplasia

A

vitamin A
necessary for differentiation of specialized epithelial surfaces such as the conjunctiva covering the eye
vit A deficiency can cause goblet cell/columnar epithelium of conjunctiva to undergo metaplasia into keratinizing squamous epithelium
dry eyes (xerophtalmia) can lead to destruction of the cornea and blindness

11
Q

What condition occurs in response to healing in trauma that causes mesenschymal tissues to undergo metaplasia

A

myositis ossificans

connective tissue within muscle changes to bone during healing after trauma

12
Q

Dysplasia

A

disordered cellular growth

most often refers to proliferation of precancerous cells

often arises from longstanding pathologic hyperplasia or metaplasia

13
Q

Aplasia

A

failure of cell production during embryogenesis

ex. unilateral renal agenesis

14
Q

hypoplasia

A

decrease in cell production during embryogenesis, resulting in a relatively small organ

ex. streak ovary in Turner syndrome

15
Q

Common causes of cell injury

A
inflammation
nutritional deficiency or excess
hypoxia
trauma
genetic mutations
16
Q

hypoxia

A

low oxygen delivery to tissue
oxygen is the final electron acceptor in the electron transport chain of oxidative phos
decreased oxygen impairs ox phos, resulting in decreased ATP production
lack of ATP leads to cell injury

17
Q

causes of hypoxia

A

ischemia
hypoxemia
decreased oxygen carrying capacity of blood

18
Q

ischemia

A

decreased blood flow through an organ

decreased arterial perfusion - atherosclerosis
decreased venous drainage - Budd-Chiari syndrome
Shock - generalized hypotension -> poor tissue perfusion

19
Q

hypoxemia

A

low partial pressure of oxygen in the blood - PaO2 decreased PaO2
hypoventilation - increased PaCO2 -> decreased PaO2
diffusion defect - PaO2 not able to push as much O2 into the blood due to a thicker diffusion barrier (interstitial pulmonary fibrosis)
V/Q mismatch - blood bypasses oxygenated lung or oxygenated air cannot reach blood

20
Q

decreased O2 carrying capacity

A

hemoglobin loss or dysfunction

anemia - normal PaO2
carbon monoxide poisoning - PaO2 normal - cherry red appearance of skin, early sign is HA
Methemoglobinemia - iron in heme is oxidized to Fe3+ which cannot bind oxygen - PaO2 normal - seen in oxidant stress - cyanosis with chocolate colored blood - Tx is intravenous methylene blue which helps reduce Fe3+ back to Fe2+

21
Q

hallmark of reversible cellular injury

A

cellular swelling - cytosol swelling results in loss of microvilli and membrane blebbing
swelling of the rough ER results in dissociation of ribosomes and decreased protein synth

22
Q

Hallmark of irreversible cellular injury

A

membrane damage - results in cytosolic enzymes leaking into the serum (cardiac troponin), additional calcium entering cell

End result is cell death

23
Q

Mitochondrial Membrane Damage

A

results in loss of the electron transport chain (inner mito membrane), cytochrome c leaking into cytosol (activates apoptosis)

24
Q

lysosomal membrane damage

A

results in hydrolytic enzymes leaking into cytosol, which are activated by the high intracellular calcium

25
Q

Mechanisms of cell death

A

necrosis and apoptosis

26
Q

morphologic hallmark of cell death

A

loss of nucleus

occurs via nuclear condensation (pyknosis)
fragmentation(karyorrhexis)
and dissolution (karyolysis)

27
Q

Necrosis

A

death of large groups of cells followed by acute inflammation
never physiologic

28
Q

Coagulative Necrosis

A

necrotic tissue that remains firm
organ structure is preserved but nucleus disappears
characteristic of ischemic infarction of any organ except the brain
often wedge-shaped and pale
red infarction arises if blood re-enters loosely organized tissue

29
Q

Liquefactive Necrosis

A

necrotic tissue that becomes liquefied
enzymatic lysis of cells and protein results in liquefaction
characteristic of - brain infarction - proteolytic enzymes from microglial cells liquefy the brain
abscess - proteoplytic enzyes from neutrophils liquefy tissue
pancreatitis - proteolytic enzymes from pancreas liquefy parenchyma

30
Q

Gangrenous Necrosis

A

coagulative necrosis that resembles mummified tissue - dry gangrene
characteristic of ischemia of lower limb and GI tract
if superimposed infection of dead tissues occurs then liquefactive necrosis ensues - wet gangrene

31
Q

Caseous Necrosis

A

soft and friable necrotic tissue with cottage cheese-like appearance
combination of coag and liquefactive necrosis
characteristic of granulomatous inflammation due to tuberculous or fungal infection

32
Q

Fat Necrosis

A

necrotic adipose tissue with chalky-white appearance due to deposition of calcium
characteristic of trauma to fat and pancreatitis-mediated damage of peripancreatic fat
FA released by trauma or lipase join with calcium via a saponification

33
Q

Saponification

A

dystrophic calcification in which calcium deposits on dead tissues
necrotic tissue acts as a nidus for calcification in the setting of normal serum calcium and phosphate

34
Q

Metasstatic calcification

A

high serum calcium or phosphate levels lead to calcium deposition in normal tissues

35
Q

Fibrinoid Necrosis

A

necrotic damage to blood vessel wall
leaking proteins into vessel wall results in bright pink staining of the wall microscopically
characteristic of malignant hypertension and vasculitis

36
Q

Apoptosis

A

programmed cell death
ATP (energy) dependent

endometrial shedding during menstrual cycle
removal of cells during embryogenesis
CD8+ T cell-mediated killing of virally infected cells

37
Q

Morphology of Apoptosis

A

dying cell shrinks - cytoplasm becomes more eosinophilic
nucleus condenses and fragments
apoptotic bodies fall from the cell and are removed by macrophages - not followed by inflammation

38
Q

Apoptosis is mediated by

A

caspases - which activate proteases and endonucleases

proteases break down cytoskeleton
endonucleases break down DNA

39
Q

Caspases are activated by

A

intrinsic and extrinsic pathway

40
Q

intrinsic mitochondrial pathway

A

cell injury - DNA damage - or decreased hormonal stimulation leads to inactivation of Bcl2
lack of Bcl2 allow cytochrome c to leak from the inner mitochondrial matrix into the cytoplasm and activate caspases

41
Q

extrinsic receptor - ligand pathway

A

FAS ligand binds FAS death receptor (CD95) on target cell - activates caspases
TNF binds TNF receptor on target cell - activates caspases

42
Q

Cytotoxic CD8+ T cell -mediated apoptotic pathway

A

perforins secreted by CD8+T cell create pores in membrane of target cell
granzyme from CD8+ T cell enters pores and activates caspases
CD8+ T-cell killing of virally infected cells is an example

43
Q

pathologic generation of free radicals occurs with

A

ionizing radiation - water hydrolyzed to hydroxyl free radical
inflammation - NADPH oxidase generates superoxide ions during oxygen dependent killing by neutrophils
metals - copper and iron
drugs and chemicals - p450 system of liver metabolizes drugs, generating free radicals

44
Q

free radicals cause cellular injury via

A

peroxidation of lipids and oxidation of DNA and proteins

DNA damage is implicated in aging and oncogenesis

45
Q

Elimination of Free radicals

A

antioxidants - glutathione and vit A, C, E
Enxymes - superoxide dismutase - mito
- glutathione peroxidase - mito
- catalase - peroxisomes
Metal Carrier Protiens - transferrin and ceruloplasmin

46
Q

Carbon Tetrachloride - CCl4

A

organic solvent used in dry cleaning
converted to CCl3 free radical by p450 system of hepatocytes
causes cell injury with swelling of RER -> ribosomes detach, impairing protein synthesis
decreased apolipoproteins lead to fatty change in the liver

47
Q

reperfusion injury

A

return of blood to ischemic tissue results in production of O2 derived free radicals which further damage tissue
leads to rise in cardiac enzymes (troponin) after reperfusion of infarcted myocardial tissue

48
Q

amyloid

A

misfolded protein that deposits in the extracellular space thereby damaging tissues

multiple proteins can be deposited as amyloid

  • Beta pleated sheets
  • congo red staining and apple - green birefringence
49
Q

Primary systemic amyloidosis

A

systemic deposition of AL amyloid - derived from immunoglobulin light chain
associated with plasma cell dyscrasias (mult. myeloma)

50
Q

Secondary systemic amyloidosis

A

systemic deposition of AA amyloid - derived form serum amyloid-associated protein (SAA) - acute phase reactant that is increased in chronic inflammatory states - malignancy and familial Mediterranean fever

51
Q

Familial Mediterranean Fever

A

AR
episodes of fever and acute serosal inflammation
high SAA during attacks deposits as AA amyloid in tissues

52
Q

Localized Amyloidosis

A

senile cardiac amyloidosis

  • non-mutated serum transthyretin deposits in the heart
  • usually asymptomatic
53
Q

Familial amyloid cardiomyopathy

A

mutated serum transthyretin deposits in the heart leading to restrictive cardiomyopathy

54
Q

Amylin (derived from insulin) deposits where

A

islets of pancreas in DM

55
Q

Alzheimer Amyloid are derived from

A

Beta amyloid precursor protein -> AlphBeta amyloid -> deposits in brainformin amyloid plaques

gene for APP is on chromosome 21

56
Q

Dialysis associated amyloidosis

A

Beta2 - macroglobulin deposits in joints

57
Q

medullary carcinoma of the thyroid

A

calcitonin (produced by tumor cells) deposits within the tumor (tumor cells in an amyloid background)