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MMMD 1 - QH > Cellular Processes > Flashcards

Cellular Processes Flashcards

1
Q

Steps cells response to stress/injury:

Homeostasis > stress

A

ADAPTATION> Cellular alterations
if can’t adapt>INJURY> (reversible) recover
if can’t recover>death:necrosis/apoptosis

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2
Q

What are cellular adaptations?

A
  • hyperplasia
  • hypertrophy
  • atrophy
  • metaplasia
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3
Q

Hyperplasia

A

More cells! > increase mass of tissue

  • in cells undergoing division
  • reversible
  • growth factors > increase proliferation of mature cellsand production of new cells
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4
Q

Ex of physiologic hyperplasia

A
  • hormonal hyperplasia - breast tissue, endometrium in preg

- compensatory hyperplasia: RBC during trauma and blood loss

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5
Q

Ex of pathologic hyperplasia

A

Too much hormones:

  • endometrial hyperplasia
  • prostatic hyperp
  • ductal hyperp of breast
  • HPV>squamous cell proliferation
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6
Q

Hypertrophy

A
  • BIGGER cells > increae mass
  • NO cell division
  • reversible
  • growth factors > increase production of proteins and cell components
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7
Q

Ex of physiologic hypertrophy

A
  • hormonal: myometrium during preg

- compensatory: skeletal muscles with excercise

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8
Q

Ex of pathologic hypertrophy

A
  • cardiac muscle in trying to pump harder

- bladder muscle in tryign to overcome obstruction

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9
Q

Atrophy

ex:

A

-decrease in size and # of cells > decrease mass
-reversible
-increase protein degrad and decrease production
ex:
-normal embryogenesis processes
-reversal of physiological hyperplasia/hypertrophy
-not using limbs
-loss of innervation, blood supply, nutrition, hormones
-pressure on tissue

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10
Q

metaplasia

A
  • mature cell change to another type in response to stress
  • adaptative and questionable reversible
  • cytokines, growth factors > alter transcription factors > change differentiation of cells
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11
Q

Ex of physiologic metaplasia. describe

A
  • ONLY ONE: squamous metaplasia of cervix (columnar>squamous) due to exposure to vagina at puberty
  • increase risk of infection + cancer (HPV)
  • screening and vaccination impt. if highly dysplastic (HSIL) > remove to prevent cancer
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12
Q

Ex pathologic metaplasia

A
  • squamous metaplasia of bronchus (columnar > squamous)
  • Barrett’s metaplasia of esophagus (squamous > columnar)
  • interstinal metaplasia of stomach (stomach>intestinal)
  • squamous meta of bladder (transitional > squamous)
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13
Q

What is altered cellular constituents?

A
  • not adaptations.
  • sign of damage
  • usually excessive accumulation due to:
    1. increase synthesis/decrease degrad of normal content
    2. abnormal protein production
    3. exogenous material not transported/degraded/metabolism
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14
Q

Ex of pathologic altered cell constituents

4

A
  • steatosis of liver due to alcohol
  • Gaucher’s disease - enzyme failure > lipid
  • Alzheimer’s - folded protein accumulate
  • parkinson’s - abnormally folded proteins accumulate
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15
Q

What are amyloids

A
  • abnormally folded protein > B-sheet
  • resistant to degradation
  • seen in kidney obstruction, inflammation, Alzheimer’s
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16
Q

What are prions?

A
  • PrP protein abnormally foleded into B sheets
  • aggregate and resistant to protease
  • PrPSc protein is infectious, self-replicative > induces others to go into Bsheets. can jump species
    ex: CJD, kuru, mad cow
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17
Q

Dysplasia?

A
  • cellular alterations > disordered growth
  • premalignant but not cancer!
  • maybe reversible
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18
Q

Neoplasia?

A
  • NEW growth
  • tumour lost normal control
  • benign or malignant
  • irreversible
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19
Q

What is endometrial hyperplasia?
Cause
Clinical
Tx

A 
-increased proliferation of endometrial glands next to stroma
Cause: excess estrogen. (anovulation, PCOS, obesity, tumours, HRT)
Clinical:
-common
-bleeding
-incrase risk of endometrial cancer
Tx:
-treat underlying
-PROGESTERONE to shut down endometrium
-hysterectomy
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20
Q

What is benign prostatic hyperplasia?
Cause
Clinical
Tx

A

-proliferation of epithelium and stromal cells in periurethral area
Cause: increase dihydrotestosterone with age (stromal cells)
Clinical:
-common, asymptomatic, peeing problems, enlarged prostate, infection risk due to bladder obstruction
-NO incraesed risk of cancer
Tx:
-decrease fluid intakes
-meds: 5-alpha reductase inhibitor (decrease DHT); alpha blocker (decrease muscle tone, loosen prostate for urethra opening)
-surgery to open urethra

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21
Q

What is Barrett’s esophagus?

A 
-pathologic metaplasia squamous > columnar due to exposure to gastric acid
CAUSE:
-gerd
CLINICAL:
-red goblet cells in esoph
-gerd symptoms
-risk of dysplasia>adenocarcinoma
Tx:
-treat gerd
-screen for dysplasia
-resection/radiation
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22
Q

What is intestinal metaplasia of stomach?

A

-stomach tissue > intestinal cells b/c of hpylori exposure
(hpylori doesn’t like intestine so stomach adapted to fight back)
-gastritis
-loss of parietal cells > issues
-ulcer risk
-cancer risk: gastric cancer, gastric lymphoma
Tx:
-eradicate hpylori
-screen for dysplasia
-surgical resection

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23
Q

What is cell INJURY?

6 mechanisms?

A
  • can’t adapt to stress; damaging exposure; instrinsic abnormality
  • decrease ATP production, membrane damage, increase cyto Ca, increase reactive O species, DNA damage, protein misfolded
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24
Q

Reversible vs irreversible injury?

A

Reversible:

  • mild/no dna, protein, membrane damage
  • short
  • less specific

Irreversible > death

  • severe damage to dna, protein, membrane
  • can’t produce atp
  • prolonged
  • specific biomolecular pathway damaged
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25
Q

Injury mechanism 1 - ATP depletion

A
  1. metabolite pump issues, anchoring protein issues: influx of water, Ca, efflux K
    - swelling, loss of microvilli, blebs
  2. respiration issues
    - anaerobic > change pH > clumping of chromatin = dense
  3. ribosome detachment > decrease protein syn > lipid deposition
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26
Q

Injury mech 2: Cytosolic calcium

A

> enzyme activation:
-phospholipase breakdown membrane
-lipase > necrosis and saponification
-endonucleases, DNAases > nuclear breakdown
-caspases > apoptosis
mitochondrial more permeable > loss of H potential, ATP production issues, apoptosis

=membrane damage, nuclear damage, decreaase ATP

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27
Q

Injury mech 3: Mitochondria damage

A

-caused by increase Ca or direct damage
-increase mitoc permeabililty
> loss of H potential > no ATP prod > NECROSIS
>leakage of cytochrom c > caspases > APOPTOSIS

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28
Q

Injury mech 4: Free radicals

how do they damage dna, membrane, proteins

A

-react with other compounds > autocatalytic. hard to stop
-many sources: phosphorylation, energy, inflammation, nitric oxide, drugs, metals
-oxidation leads to:
>fatty acids: per oxidation > membrane damage
>proteins: crosslinking, denaturation, enzymes
>DNA: crosslinking, breaks, mutations
-removed by enzymes, antioxidants, sequestrants

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29
Q

Injury mech 5: Membrane permeability

A
  • loss of ATP in mitochon
  • osmotic loss > inflammation
  • lysosome digestion-membrane leakage with inflammation=NECROSIS
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30
Q

Injury mech 6: DNA and protein damage

-apoptosis vs necrosis

A
  • if dna/protein damage alone > APOPTOSIS

- irreparable damage + membrane damage > NECROSIS and apoptosis

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31
Q

What is necrosis? what are the cellular features

A
  • pathological
  • irreversible cell injury with membrane leakage + inflammatory response
    1. coagulation of proteins > cyto eosinophilia - swelling of organelles
    2. coagulation of dna > nuclear basophilia
    3. coagulated phospholipis > myelin figures in cytoplasm
    4. activation of endonucleases and dnases > nuclear changes
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32
Q

What is pyknosis
karyorrhexis
karyolysis

A
  • pyknosis: nucear shrikage and basophilia
  • karyorrhexis: fragmentation of dna
  • karyolysis: fading of nucleus

from activation of endonucleases and DNAases

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33
Q

Coagulative vs liquefactive necrosis?

A 
tissue morphology based on hydrolytic enzymes:
Coagulative:
-preserved architecture
-hypereosinophilia
-loss of nuclei
-delayed entry of neutrophils
ex: infarct

Liquefactive:

  • destruction
  • hypereosinophilia
  • loss of nuclei
  • PUS: neutrophils and debris localized
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34
Q

caseous vs fibrinoid necrosis?

A

tissue morph based on etiology of injury:
CASEOUS: cheeselike, amorphous, debris
-granuloma: macrphages with inflammation
-due to indigestible stimulus
ex: TB
FIBRINOID: immune mediated destruction - fibrin deposit
ex: vasulitis

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35
Q

What is fat necrosis?
ex?
what is saponification?

A
  • not really necrosis
  • degrad of fats > free fatty acids deposition
  • ex: acute pancreatitis: lipase released and break down
  • saponification = free fatty acids + calcium
36
Q

What is gangrene? dry vs wet?

A
  • gangrenous necrosis: limb that lost blood supply > necrosis
  • dry: coagulative necrosis. typical
  • wet: b/c of infection > liquefactive because enzymes of bacteria + neutrophils present
37
Q

Apoptosis?
features?
physio vs patho?

A
  • regulated cell death WITHOUT membrane leakage and inflammation
  • reduced cell size, cytoskeletal breakdown, fragmentation of nucleus
  • physio: maintain steady state. eliminate cells we don’t need.
  • patho: eliminate damage beyond repair while limiting collateral damage (no host rxn)
38
Q

Apoptosis: Intrinsic vs extrensic pathway?

A

Intrinsic: mitochondrial

  • damage or loss of survival signal > activation of proteins that block Bcl2 (normally anti-apoptotic protein on mitochond)
  • leaky channels (Bax/Bak) > cytochrome c leakage > CASPASES > endonucleases and proteases > break down DNA and cytoskeleton > membrane bleb off = apoptotic body with receptor for macrophages to rid

Extrensic: Death Receptor
-FasLigand binds Fas death receptor > CASPASES > endonucleases and proteases > break down DNA and cytoskeleton > membrane bleb off = apoptotic body with receptor for macrophages to rid

39
Q

How to see diff bt necrosis and apoptosis on electrophoresis?

A
  • smear pattern - nonspecific = necrosis b/c endonucleases and DNAases
  • ladder pattern - fragments = apoptosis b/c only endonuc
40
Q

Necrosis vs apoptosis? (6)

A
  1. swelling vs shrinking
  2. pyknosis > karyorrhexis > karyolysis vs fragmentations
  3. membrane leakage vs intact
  4. cellular digestion and leaking vs intact/apoptotic bodies
  5. inflammation in necrosis!
  6. always patho vs apoptosis can be physic/patho
41
Q

Theories about aging

A
  • ext changes, alterations in tissues, decrease response ability, increase risk of disease
  • accumulated cell damage due to oxidative stress, dna damage+mutation, mitochon damage, abnormal proteins, cellular senescence +telomeres
42
Q

replicative senescence

A
  • decreased replication until an arrest state = non dividing
  • Hayflick limit: ~50 times of replication for normal somatic cells
  • but role in aging still unclear
  • not seen in germ cells and stem cells
43
Q

telomeres

A

short repeat DNA at ends of chromosomes

  • prevent fusion and ensure complete replication
  • shortened with every replication cycle (5’ end of dna shortened b/c polymerase can’t completely copy the 3’ end). shortened until no more. can’t replicate a normal protein = stop cell.
  • telomerases maintain length > continue replication (seen in cancer)
44
Q

aging and caloric restriction?

sirtuins?

A
  • 1930s, mice on restricted diet lived 40% longer
  • hard to study on humans. side effects: hunger, depression, low energy, libido
  • activated via sirloins: increase expression of gene > resistance to cell stress, increase insulin sensitivity, glucose met
45
Q

where may sirtuin be found?

A

RESVERTATROL - in red wine (need high quantity)

but alcohol has other issues

46
Q

Aging and gene mutations?

A
  • mutations to lower level of GH, IGF1 > resistance to injury in animals
  • in humans not sure…
47
Q

What is acute inflammation?

A
  • rapid, non-specific tissue rxn
  • neutrophil-mediated
  • vasodilation, vascular permeability, leukocytes!
48
Q

Cardinal features of inflammation?

A

“red hot painful bump that can’t do much”

  • red hot painful swelling
  • loss of fnc
49
Q

Stimuli for acute inflammation

A

-infarction, infection, toxin, trauma

  • endothelial retraction due to nitric oxide, histamine
  • direct endothelial damage: burns, toxins
  • leukocyte-induced endothelial injury: inflammation from something else?
  • transcytosis - VEGF induced leaking?
50
Q

Rxns of blood vessels in acute inflamm?

transudate vs exudate?

A

Edema b/c of increase hydrostatic and decrease colloid P

  • Transudate: low protein, low cellularity, low specific gravity. THUS NO underlying inflammation but a P issue
    ex: CHF, liver disease, kidney disease
  • Exudate: high protein, high cellularity, high specific gravity THUS leaky from underlying inflam
51
Q

rxn of leukocytes in acute inflamm

A
  • injury > tissues release:
    1. > cytokines: IL1, TNF > endothelial cells express SELECTINS = low aff adhesion to rolling leukocyte
    2. > chemokines > change configuration of INTEGRINS = high aff adhesion to endothelial
    3. Diapedesis: migration of abc through endothelium
    4. Chemotaxis: wbc follow chemokines to offending agent
    5. Kill via Phagocytosis or Phagolysosome or reactive oxygen species
52
Q

Mediators of inflammation?

A
  1. Preformed: granules, rapid
    - Histamine
    - Serotonin
    - lysomoal contents in leukocytes
  2. Synthesized: delayed
    - Arachodoic acid metabolites: prostaglandins, thromboxane, leukotrienes
    - Nitric Oxide
    - Cytokines: TNF, IL1
  3. Plasma derived
    - complements
    - coag factor XII > coagulation, fribrinolysis
    - kinin system > bradykinin
53
Q

Morphological hallmarks of acute inflamm?

A
  • dilation of vessels
  • engorgemnt of blood
  • exudation of wbc, fluid
54
Q

WBC involved in inflammation?

A
  1. neutrophils - early; more lysosomal enzymatic killing - secrete into tissue - can cause more damage
  2. Macrophages - higher phagocytosis to remove debris and REPAIR
  3. Monocytes
55
Q

Role of histamine in inflammation?

A

-in mast cells
-degranulated when injury, IgE on mast cells, complement activation, cytokines, leukocyte peptide activation
> VASODILATION, ENDO PERM via contraction

56
Q

Role of serotonin in inflamm

A

-in platelets and neuroendocrine cells
-degradunlated when there is platelet aggregation/antigen-ab complex formed
>ENDO PERM

57
Q

Enzymes in inflamm wbc?

A
  • in neutrophils and macrophages
  • proteases, collagenases, elastases, phospholipase, plasminogen activator
  • leads to C3, C5 complement cascade > further inflamm
58
Q

How do anti-inflammatory drugs work?
steroids
aspirin

A
  • Steroids indhibit PHOSPHOLIPASES that lead to arachidonic acid production. Nonspecific, block early in rxn.
  • Aspirin and other NSAIDS block COX > decrease prostaglandins (vasodilator) adn thromboxane (vasoconstrictor)
59
Q

What do prostaglandins, thromboxane, leukotrienes do in inflamm?

A

PGE>vasodilation
TXA2>vasoconstriction
Leukotrienes > ENDO PERM and vasoconstriction, leukocyte adhesion, chemotaxis

60
Q

Nitric Oxide in inflamm?

A

-synthesized from endothelials and macrophages
>KILLING, VASODILATION, ANTI-INFLAMM (reduces adhesion of platelets and leukocytes)
*enos vs inos
-both pro and anti=inflammatory rxns

61
Q

TNF and IL1 in inflamm?

A
  • activate leukocytes
  • fibroblasts for repair
  • adhesion to endothelium. pro-coag adn anti-coag balnance
  • systemic effects: fever, leukocytosis, more proteins from liver, sleep need
62
Q

Complements in inflamm?

A
  1. Alternative: microbes
  2. Classical: antibody-mediated
  3. lectin: mannose-binding

3 pathways > activation of C3, C5
>recruitment, chemotaxis
>phagocyte binding
>formation of membrane attack complex (C5) to kill
>activate LIPOXYGENASE of arachadonic pathway = anti-inflamm = VASOCON, ENDO PERM, bronchospasm

63
Q

Hageman factor in inflamm?

A

-Factor XII released from liver
-intrinsic clotting pathway
>thrombin: fibrin
>activates COX2 = pro-inflamm = VASODIL, ENDO PERM
>Kinin cascade > BRADYKININ = PAIN

64
Q

What is serous inflammation?

A
  • mild injury
  • minimal vas perm
  • more fluid than leukocytes
65
Q

What is fibrinous inflammation?

A
  • lots of vas perm
  • fibrin (b/c of leakage)
  • local proinfl stimulus
  • common in pleura, pericardium
66
Q

What is supprative inflammation?

A
  • lots of leukocytes
  • pus (neutrophils)
  • pyogenic organisms
67
Q

What are the morphological patterns of acute inflamm?

A
  • serous
  • fibrinous
  • supprative
68
Q

What is chronic inflammation?

A
  • inflammation, tissue damage, and repair co-existing
  • adaptive immunity trying to respond to continuous injury and dysregulated immune response
  • due to viral infections, chronic infections, long injury, autoimmune
69
Q

Macrophages in chronic inflamm?

A
  • in blood and extracellular spaces
  • migration within 48hr of inflame
  • M1: Proinflamm: reactive O2 species, proteases, cytokines, chemokines, coag, AA metabolites
  • M2 REPAIR and anti-inflamm: growth factors, fibrogenic, angiogenic, remodelling collagens
70
Q

IL and TNF in chronic inflamm?

A
  • release by macrophages

- recruit and activate neutrophils > peristant inflammatory response

71
Q

What is a granuloma?

A
  • collection of activated macrophages surrounded by chronic inflammation/fibrosis
  • looks like nodule
  • formed b/c of high INF-gamma in presence of antigen that we can’t eradicate
    ex: TB, leprosy, syphilis, sarcoidosis, crohn’s, parasites, foreign bodies
72
Q

What are giant cells?

foreign body type vs Langhans type?

A
  • aggragation of macrophages around something we can’t rid.
    a) around a foreign body
    b) immune type: around fibrotic tissue/area of inflamm
73
Q

Outcomes of acute inflammation?

A
  1. Resolution: fnc restored.
    - not too serious damage, and too much damage, cells can be regenerated (N/A for heart, CNS…)
  2. Healing via Fibrosis: collagen deposit, fnc loss
  3. Abscess: pus formation > fibrosis
  4. Progress to Chronic Inflammation
74
Q

Cardinal features of chronic inflamm?

A
  1. Non-neutrophilic inflammation
  2. architectural destruction
  3. fibrosis
75
Q

What are immune-mediated causes of chronic inflammation?

ex?

A
  1. autoimmunity: excessive immune response > tissue damage > release of self-antigen
    ex: lupus, rheumatoid arth
  2. unregulated immune response
    ex: IBD
  3. hypersenstivity reactions
    ex: asthma
76
Q

What is primary vs secondary nutrition?

A

1: missing 1/more of the necc comp of diet

2. adequate but not getting benefits (insuff, malabsorp, use, loss…)

77
Q

hormones in appetite and weight:
Leptin
Adipoleptin
Ghrelin

A

Leptin:

  • from adipocytes
  • binds hypothalamus > stimulate POMC/CART neurons&raquo_space; REDUCE appetite, INCREASE expenditure
  • loss of leptin fnc&raquo_space;early onset obesity
Adipoleptin: angel against obesity
-from adipocytes
>fatty acids from muscle for oxidation
>less fatty acids to liver
>decrease glucose from liver

Ghrelin:
-gut hormone&raquo_space; INCREASE food intake via hypothalamus

Insulin

78
Q

Kwashiorkor vs Marasmus?

A

Protein-energy malnutrition: affects developing countries
Kwashiorkor: protein def in visceral comparment
-intake is not an issue: eat lots of carb but low protein
-more severe!
-hypoalbuminemia, edema, flaky paint skin lesions, hair loss
-liver steatosis, anoerexia, vitamin def, immune issues

Marasmus: protein and caloric def in somatic comparment

  • starvation > body conservation
  • thin!, anemia, vitamin def, immune def, poor wound healing
79
Q

What is cachexia?

A
  • AIDS, cancer pts
  • loss of fat and muscle
  • increase E expenditures
  • due to TNF, IL, PIF cytokines from tumour
  • death
80
Q

Other malnutrition diseases?

A
  • anorexia nervosa - starvation

- bulimia - binge then self-induce vomitting

81
Q

Vit D deficiency

A
  • maintain Ca and phosporus levels
  • due to diet, sunlight, absorp, renal/hepatic issues
  • def > HYPOCALCEMIA
    ex: Rickets, osteomalacia>osteporosis
82
Q

Vitamin B1 def

A
  • thiamine in grains
  • fnc: ATP synthesis, cofactor for other pathways, neural membrane and nerve conduction
  • due to diet insuff, alcoholism, excess loss (v/diar)

ex:
Dry Beriberi: polyneruopathy, myelin degen
Wet Beriberi: heart issues
Wernicke-Korsakoff Syndrome: CNS lesions

83
Q

Vit B12 def

A

-from: animal proteins, meat, eggs
-IF binds VitB12 > transport of Vit B12
»Megaloblastic anemia, neurological complications

84
Q

What is hemochromatosis?

A
  • iron excess&raquo_space; hepatomegaly, iron deposits in organs, DM, pigmentation of skin, arrthymias, heart failure, testicular atrophy
    tx: phlebotomy, treat damaged organs
    1ary: inherited
  • more in men
  • 2ary: overload, transfusion, intake, liver disease
85
Q

Diet and chemoprevention?

A

unconclusive!

ex: Vit A - lung; Lycopene (tomatoes) - prostate; Vit D (lung, endometrium, breast, colon)

MMMD 1 - QH (7 decks)

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