Wound Healing & Hemostasis Flashcards

1
Q

Tissues can be divided into 3 types based on their regenerative capacity: labile, **, and **. Labile tissues continuously cycle to regenerate tissue. What are examples of labile tissues?

A

Small and large bowel (stem cells in mucosal crypts)

Skin (stem cells in basal layer)

Bone marrow (hematopoietic stem cells — CD34+)

[note: stem cells of the lung are type II pneumocytes]

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2
Q

Tissues can be divided into 3 types based on their regenerative capacity: labile, stable and permanent. Stable tissues are quiescent, but can re-enter the cell cycle. What is a major example of this?

A

Regeneration of the liver by compensatory hyperplasia after partial resection; each hepatocyte produces additional cells, and then reenters quiescence

[another example is pts with acute tubular necrosis who regenerate proximal tubule over time]

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3
Q

Tissues can be divided into 3 types based on their regenerative capacity: labile, stable and permanent. Permanent tissues lack significant regenerative potential and include myocardium, skeletal muscle, and nerve tissue. Thus, instead of regeneration they undergo repair which replaces damaged tissue with ____ ____

A

Fibrous scar

[Note: tissues capable of regeneration will also undergo repair by fibrous scar in cases where hematopoeitic stem cells are lost]

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4
Q

Granulation tissue is the initial phase of repair. What are the 3 major players in the formation of granulation tissue?

A

Fibroblasts (deposit type III collagen)

Capillaries (provide nutrients)

Myofibroblasts (contract wound)

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5
Q

Granulation tissue eventually results in scar formation. At this point, type III collagen is replaced with ___________.

________ is what removes type III collagen and requires ____ as a cofactor

A

Type I collagen

Collagenase; zinc

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6
Q

Mechanisms of regeneration and repair are mediated by ________ signaling via __________; interaction of factors with receptors results in gene expression and cell growth

A

Paracrine; growth factors

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7
Q

Importance of TGF-alpha, TGF-beta, PDGF, FGF, and VEGF in regeneration and repair

A

TGF-alpha: epithelial and fibroblast growth factor

TGF-beta: important fibroblast growth factor; inhibits inflammation

PDGF: endothelium, smooth muscle, fibroblast growth factor

FGF: angiogenesis, skeletal development

VEGF: angiogenesis

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8
Q

Cutaneous healing occurs via primary or secondary intention — what is the difference between the two?

A

Primary — wound edges brought together; minimal scar formation

Secondary — edges are not approximated; granulation tissue fills in the defects

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9
Q

The most common cause of delayed wound healing is infection. Other causes include foreign body, ischemia, diabetes, and malnutrition. What are 3 nutritional deficiencies associated with delayed wound healing?

A

Vitamin C deficiency (needed for hydroxylation in crosslinking reaction with collagen)

Copper (lysyl oxidase requires copper as cofactor for crosslinking reaction)

Zinc deficiency (zinc needed as cofactor for collagenase)

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10
Q

_____ = Rupture of a wound; most commonly seen after abdominal surgery

A

Dehiscence

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11
Q

______ ____ = excess production of scar tissue that is localized to the wound

A

Hypertrophic scar

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12
Q

_____ = excess production of scar tissue that is out of proportion of the wound; characterized by excess ___________. There is a genetic predisposition in that it is more common in African Americans. Classically affects the earlobes, face, and upper extremities

A

Keloid; type III collagen

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13
Q

Goal of primary vs. secondary hemostasis

A

Goal of primary hemostasis = formation of a weak platelet plug, mediated by interaction between platelets and vessel wall

Goal of secondary hemostasis = stabilize platelet plug, mediated by the coagulation cascade

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14
Q

Damage to vessel walls is repaired by hemostasis, which involves formation of a ______ at the site of vessel injury

A

Thrombus (clot)

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15
Q

Step 1 of primary hemostasis, and the 2 things that mediate it

A

Transient, rapid vasoconstriction

Mediated by:

  1. Reflex neural stimulation
  2. Endothelin from endothelial cell itself
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16
Q

4 overall steps of primary hemostasis

A
  1. Transient constriction of damaged vessel
  2. Platelet adhesion to surface of disrupted vessel
  3. Platelet degranulation
  4. Platelet aggregation
17
Q

Step 2 of primary hemostasis is platelet adhesion to the surface of disrupted vessel. This occurs when ____ binds exposed subendothelial _______

A

vWF; collagen

18
Q

During step 2 of primary hemostasis, platelets bind vWF using the ______ receptor

A

GPIb

19
Q

vWF is derived from what 2 places?

A

Weibel-Palade bodies of endothelial cells

Alpha-granules of platelets

20
Q

Step 3 of primary hemostasis is platelet degranulation. This occurs because adhesion in step 2 induces shape change in the platelets causing the release of multiple mediators. What are the 2 major mediators released during step 3 and what do they do?

A

ADP (dense granules) promotes exposure of GPIIb/IIIa receptor on platelets

TXA2 (derivative of platelet cyclooxygenase) promotes platelet aggregation

21
Q

Step 4 of primary hemostasis is platelet aggregation. Platelets aggregate at the site of injury via ________, using _______ as a linking molecule. This results in formation of the weak platelet plug.

A

GPIIb/IIIa; fibrinogen

22
Q

Secondary hemostasis stabilizes the weak platelet plug, which occurs via the coagulation cascade. The coagulation cascade generates _____, which converts fibrinogen in the platelet plug to fibrin. Fibrin is then cross-linked, yielding a stable ___________

A

Thrombin; platelet-fibrin thrombus

23
Q

Factors of the coagulation cascade are produced by the _____ in an _____ state

A

Liver; inactive

24
Q

What 3 things are required for coagulation factor activation?

A
  1. Exposure to an activating substance
  2. Phospholipid surface (surface of the platelets)
  3. Calcium (derived from dense core granules of platelets)
25
Q

Intrinsic coagulation pathway

A

Subendothelial collagen activates factor 12 —> 11 —> 9 —> 8 —> 10

[Common pathway is 10 —> 5 —> 2 —> 1]

26
Q

Extrinsic coagulation pathway

A

Tissue thromboplastin activates factor 7 —> 10

[common pathway is 10 —> 5 —> 2 —> 1]

27
Q

What lab (PT or PTT) should be measured when pt is on heparin vs. warfarin?

A

Check PTT on heparin

Check PT on warfarin