Wound Healing & Hemostasis Flashcards
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?
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]
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?
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]
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 ____ ____
Fibrous scar
[Note: tissues capable of regeneration will also undergo repair by fibrous scar in cases where hematopoeitic stem cells are lost]
Granulation tissue is the initial phase of repair. What are the 3 major players in the formation of granulation tissue?
Fibroblasts (deposit type III collagen)
Capillaries (provide nutrients)
Myofibroblasts (contract wound)
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
Type I collagen
Collagenase; zinc
Mechanisms of regeneration and repair are mediated by ________ signaling via __________; interaction of factors with receptors results in gene expression and cell growth
Paracrine; growth factors
Importance of TGF-alpha, TGF-beta, PDGF, FGF, and VEGF in regeneration and repair
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
Cutaneous healing occurs via primary or secondary intention — what is the difference between the two?
Primary — wound edges brought together; minimal scar formation
Secondary — edges are not approximated; granulation tissue fills in the defects
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?
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)
_____ = Rupture of a wound; most commonly seen after abdominal surgery
Dehiscence
______ ____ = excess production of scar tissue that is localized to the wound
Hypertrophic scar
_____ = 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
Keloid; type III collagen
Goal of primary vs. secondary hemostasis
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
Damage to vessel walls is repaired by hemostasis, which involves formation of a ______ at the site of vessel injury
Thrombus (clot)
Step 1 of primary hemostasis, and the 2 things that mediate it
Transient, rapid vasoconstriction
Mediated by:
- Reflex neural stimulation
- Endothelin from endothelial cell itself
4 overall steps of primary hemostasis
- Transient constriction of damaged vessel
- Platelet adhesion to surface of disrupted vessel
- Platelet degranulation
- Platelet aggregation
Step 2 of primary hemostasis is platelet adhesion to the surface of disrupted vessel. This occurs when ____ binds exposed subendothelial _______
vWF; collagen
During step 2 of primary hemostasis, platelets bind vWF using the ______ receptor
GPIb
vWF is derived from what 2 places?
Weibel-Palade bodies of endothelial cells
Alpha-granules of platelets
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?
ADP (dense granules) promotes exposure of GPIIb/IIIa receptor on platelets
TXA2 (derivative of platelet cyclooxygenase) promotes platelet aggregation
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.
GPIIb/IIIa; fibrinogen
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 ___________
Thrombin; platelet-fibrin thrombus
Factors of the coagulation cascade are produced by the _____ in an _____ state
Liver; inactive
What 3 things are required for coagulation factor activation?
- Exposure to an activating substance
- Phospholipid surface (surface of the platelets)
- Calcium (derived from dense core granules of platelets)
Intrinsic coagulation pathway
Subendothelial collagen activates factor 12 —> 11 —> 9 —> 8 —> 10
[Common pathway is 10 —> 5 —> 2 —> 1]
Extrinsic coagulation pathway
Tissue thromboplastin activates factor 7 —> 10
[common pathway is 10 —> 5 —> 2 —> 1]
What lab (PT or PTT) should be measured when pt is on heparin vs. warfarin?
Check PTT on heparin
Check PT on warfarin
