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Residency > Hemostasis/Coagulation/Inflammatory Response > Flashcards

Hemostasis/Coagulation/Inflammatory Response Flashcards

1
Q

Platelets

A

-derived from karyocytes
-forms initial hemostatic plug that provides a surface for the assembly of activated coagulation factors leading to formation of fibrin stabilized platelet aggregates
-adhere to injured subendothelial tissue to undergo morphological change (aka degranulation)

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2
Q

Platelet alpha granules

A
  • P-selectin
  • fibrogen
  • fibronectin
  • factor V
  • factor VII
  • platelet factor IV
  • Platelet derived growth factor
  • THF- alpha
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3
Q

Platelet delta granules (dense granules)

A
  • ATP
  • ADP
  • Ca2+
  • serotonin
  • histamine
  • epi
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4
Q

Effects of ADP

A

ADP binding causes a confirmational change in GpIIb/IIIa receptors preserve on platelet surface causing deposition of fibrinogen

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5
Q

Initiation phase

A

-injury occurs, blood exposed to tissue factor bearing cells -> FVIIa binds to the exposed tissue factor -> activates more FVII to FVIIa -> activates FIX and FX.

-FXa activates FV

-FXa and FVa combine to form prothrombinase complex -> cleaves prothrombin to thrombin

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6
Q

Which is the only coagulation protein that routinely circulates in blood in its active form?

A

FVIIa

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7
Q

Vasodilation in acute vascular response induced by

A

-NO
-histamine
-leukotrienes
-prostaglandins
-complement factors

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8
Q

Vascular permeability caused by

A

-histamine and serotonin: increase the number and size of intracellular endothelial gaps
-interendothelial gaps formed by endothelial cell retraction caused by hypoxia, endothelial injury, cytokines, and other inflammatory mediators
-Direct trauma
-Leukocyte-mediated endothelial damage

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9
Q

Selectins

A

-Adhesion molecules on endothelial cells

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10
Q

Neutrophil extravasation

A

1) Margination and rolling of leukocytes along the vascular endothelium are mediated through interactions between endothelial selectins with their corresponding leukocyte ligands
2) Chemokines stimulate increased expression and enhanced binding affinity of leukocytes integrins, leading to firm adherence to endothelial cell integrins
3) Leukocyte diapedesis is facilitated by adhesion molecule, platelet-endothelial cell adhesion molecule-1 and leukocytes follow chemokine gradients to the site of injury.

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11
Q

Neutrophils produce which chemokines?

A

-IL-1 alpha
-IL-1
-IL-6
-IL-1 beta
-TNF alpha

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12
Q

Macrophages produce which cytokines?

A

M1:
-INF- gamma
-TNF- alpha
(debride affected site by phagocytosis of foreign material, pathogens, and damaged cells)
-IL-1 beta
-IL- 6
-TNF-alpha
(pro-inflammatory cytokines)

M2:
-IL-4
-IL- 13
-IL-10
(anti-inflammatory cytokines, secrete growth factors to simulate and wound repair and healing)

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13
Q

Mast cells release

A

-Histamine, serotonin, leukotrienes, prostaglandin metabolites, heparin, cytokines
-Mast cell degranulation enhances local inflammatory response

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14
Q

How do endothelial cells become active?

A

Cytokines and bacterial products (endotoxins) activate endothelial cells
-Rapid, transient upregulation of preformed and stored vWF and P-selectin
-This is followed by de novo expression of pro-inflammatory cytokines, chemoattractants, and adhesion molecules.

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15
Q

TLR

A

-pattern recognition receptors
-Type 1 transmembrane proteins that initiate intracellular signaling cascades -> activate NFKB -> leads to altered gene transcription
-Play a role in the release of inflammatory cytokines from the innate immune system

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16
Q

Histamine

A

-Vasoactive amine
-Released in response to physical injury, antibody binding, complement protein binding
-interacts with H1 receptors on endothelial cells during inflammatory response to cause vasodilation and increase endothelial permeability

17
Q

TNF-alpha

A

-Activated M1 macrophages are a major source of TNF-alpha
-Initiates production of proinflammatory cytokines, reactive oxygen intermediates, chemotaxins, and endothelial adhesion molecules, which all facilitate recruitment of cells to the site of inflammation

18
Q

IL-6

A

-Produced by macrophages, T-cells, epithelial cells, enterocytes
-initiates compensatory anti-inflammatory responses and downregulates pro-inflammatory cytokine production
-Considered a prognostic biomarker of inflammation

19
Q

IL-1

A

-Denotes several cytokines produced by macrophages and other cell types
-IL-1beta has pro-inflammatory functions similar to TNF-alpha -> further enhances inflammation

20
Q

IL-10

A

-Anti-inflammatory cytokine produced by CD4+ Th2 T-cells, monocytes, B-cells
-Depresses the production of pro-inflammatory cytokines and chemokines -> inhibits translocation of NFKB

21
Q

Arachidonic acid

A

-Stored in the cell membranes of endothelial cells, leukocytes, and other cells
-Released by activated phospholipase A2
-Inhibited by glucocorticoids because they inhibit phospholipase A2 and upregulate genes encoding antiinflammatory proteins

22
Q

Prostaglandins

A

-Produced by the cyclooxygenase pathway, where arachidonic acid metabolism is catalyzed by enzymes, COX-1 and COX-2.
-Prostaglandins mediate many inflammatory responses primarily through GPCR on a number of cell types.
-They are chemotactic agents that cause
leukocyte recruitment and vasodilation, contributing to the pathogenesis of pain and fever during
inflammation
-COX enzymes are inhibited by aspirin and NSAIDS

23
Q

Platelet activating factor

A

-Metabolized by cell membrane phospholipids by phospholipase A2
-Synthesis modulated by MAPK intracellular signaling pathways
-Platelet activating factor binds to GPCR on various cells where it stimulates arachidonic acid release and increases eicosanoid production
-Proinflammatory
-Platelet aggregation and degranulation

24
Q

Nitric Oxide

A

-Synthesized from amino acid L-arginine by the enzyme nitric oxide synthase
-Causes vasodilation by diffusing into smooth muscle cells and indirectly initiating intracellular signaling events leads to smooth muscle relaxation
-antagonizes the vasoconstrictive effects of angiotensin II, endothelins, and ROS

25
Q

Negative acute phase proteins

A

-Albumin is the main one

26
Q

Positive acute phase proteins

A
  • In response to pro-inflammatory cytokines, peak within 24-48 hours
    -remain elevated while inflammatory persists
    -enhance protective host functions by minimizing tissue damage and enhancing repair
    -C-reactive protein, serum amyloid A, serum amyloid P, complement proteins
27
Q

C-reactive protein

A

-Positive acute phase protein
-Binds to bacteria and promotes activation of complement

28
Q

Bradykinin

A

-endothelial prostacyclin synthesis
-superoxide formation
-tissue plasminogen activator release
-venous dilation through NO release
-increases vascular permeability
-produces associated pain response

29
Q

Substance P

A

-Secreted by inflammatory leukocytes and by neurons in the respiratory tract, GI tract, CNS, skin, and genitourinary system
-Binds to GPCR (NK-Rs) and transmits pain and pro-inflammatory signals on effector cells, including neurons, endothelial cells and leukocytes

30
Q
A
31
Q

Cryoprecipitate involves

A

vWf, factors V and VIII

Residency (13 decks)

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