tissue repair Flashcards
2 ways of restoration of tissue architecture and function after an injury:
- Regeneration
Proliferation of residual (uninjured) cells
Maturation of tissue stem cells
Returns to normal state - Repair
When injured tissues incapable of complete restitution, or supporting structures severely damaged
Laying down connective fibrous tissue
May result in scar formation
Although the fibrous scar is not normal, it provides enough structural stability that the injured tissue is usually able to function
Regeneration is:
Replacement of damaged tissue with native tissue
1. Labile tissues
Continuously dividing cells
Small intestine or epithelium
Stable tissues
- Quiescent cells (G0), but can re-enter cell cycle to regenerate cells when necessary
slower, but still regenerating
paechymal cells of solid organs: liver!!! regeneration, kidney, etc
permanant:
Permanent tissues
Lack regenerative potential
Repair replaces damaged tissue with fibrous scar
skeletal heart brain
Inflammation:
Macrophages play central role in repair
VEG-F promotes angiogenesis
Angiogenesis:
New blood vessel development from existing vessels
Formation of granulation tissue
Migration and proliferation of fibroblasts, blood vessels and deposition of loose connective tissue (3-5 days)
Deposition of connective tissue
Deposition of ECM proteins produced by fibroblasts
Processes orchestrated by locally produced cytokines and growth factors (PDGF, FGF-2, and TGF-β)
Remodeling of connective tissue
Myofibroblasts contract scar
dependent on metal ions (zinc) for activity
need Zinc for metalloproteinases to work: otherwise results in weak connective tissue
Repair by Scar: Mechanism
- Injury induces inflammation, which clears dead cells and microbes (if any)
- Formation of vascularized granulation tissue
Fibroblasts deposit collagen III
Capillaries provide nutrients
Myofibroblasts to help contract wound - Scar deposition of extracellular matrix
Collagenase replaces collagen III with collagen I
Requires zinc as a co-factor
Type I collagen has high tensile strength and is present in skin, bone, tendons, and most organs
TEST: What is the co-factor for scar deposition of extracellular matrix?
- Scar deposition of extracellular matrix
Collagenase replaces collagen III with collagen I
Requires zinc as a co-factor
Healing by First Intention
- Inflammation
- Proliferation of epithelial and other cells
- Maturation of the connective tissue scar
Healing by Second Intention
big ulcer
- larger Inflammatory reaction more intense
- Development of abundant granulation tissue: big ulcer
- Accumulation of ECM and formation of a large scar
- Wound contraction by the action of myofibroblasts
Fibrosis =
=excessive deposition of collagen in internal organs
Heart: fibrosis compromises function
Pathologic process induced by persistent injurious stimuli such as chronic infections and immunologic reactions
Typically associated with loss of tissue
May be responsible for substantial organ dysfunction and even organ failure
most common cause of delayed healing?
infection
other causes of delayed healing?
foreign body/local, suture
systemic: nutrition: lack of zinc
excessive deposition of collagen in internal organs
Pathologic process induced by persistent injurious stimuli such as chronic infections and immunologic reactions
Typically associated with loss of tissue
May be responsible for substantial organ dysfunction and even organ failure
Dehiscence = rupture of wounds
Ulceration = inadequate vascularization
Excessive formation of the components of the repair process
Accumulation of excessive amounts of collagen
Hypertrophic scar = excessive collagen confined to wound → localized raised scar
Keloid = scar tissue grows beyond original wound boundary and does not regress
Characterized by collagen type III
Genetic pre-disposition – more common in African Americans
Classically affects earlobes, face, upper extremities
Exuberant granulation tissue
AKA “Proud Flesh”
Protrudes above the level of the surrounding skin and blocks reepithelialization
Must be removed surgical excision to permit restoration of the continuity of the epithelium
2 types of fluid accumulation
transudate: few cells, due to increased pressure
exudate: many cells, due to leaky blood vessels, etc
for transudate in lung
left side heart build up, congestive heart failure
for exudate to build up in lung?
infection
2 types of fluid accumulations in the lungs:
transudate (left side congestive heart failure) exudate infection 2 pulmonary edema
effusions happen in:
plueral effusion, pericardiacal effusion
most important protein in blood regulation of osmotic pressure
albumin
lack albumin:
edema
three most important organs associated with edema?
heart, liver, kidneys (albumin, sodium)
dependent edema?
pitting edema in leg
ascites:
cirrhosis of liver
elephantiasis
lymphatic liariasis due to w. bancrofti
2 types of increased blood flow:
hyperemia (active process, more oxygenated blood)
congestion (passive process, impaired outflow from tissue affected region is cyanotic)
wherever you have _____ you have ______
congestion, edema
nutmeg liver is caused by:
right side heart failure, backs up into inferior vena cava and cause edema in liver
left side of heart failing causes:
pulmonary chronic passive congestion: lung edema
4 types of hemorrhages:
(filling body cavity): hemothorax, hemopericardium, etc
Ecchymoses (bruise) >1-2 cm
Trauma (degradation of hemoglobin: color changes)
Purpura >3 mm hemorrhages
Vasculitides, thrombocytopenias, platelet/clotting coag defects, infections
Petechiae 1-2 Massivemm hemorrhages
skin, mucous membranes, serosal surfaces
endothelial cells roll in hemostasis?
turn blood on and off
sequence of hemostasis:
Vasoconstriction: slow down blood
Localized secretion of endothelin (potent vasoconstrictor)
Primary hemostasis
Platelets adhere and become activated
Exposure of highly thrombogenic extracellular matrix
Secondary hemostasis: make fibrin from fibrogen
Activation of coagulation cascade
Exposure of tissue factor, procoagulant factor
- Thrombus
Polymerized fibrin forms solid, permanent plug
Counter-regulatory process, e.g. t-PA, set in motion t
Thrombosis:
Inappropriate activation of normal hemostasis
Formation of blood clot (thrombus) in normal vasculature
thrombosis is described with:
virchow triad
top of virchow triad is:
endothelial injury, bc artherosclerosis, slowest blood flow in legs, etc
important site of thrombosis hyper lamina flow?
bifurcation: Turbulence: arterial thrombosis
Disruption of laminar flow
patients that ____ are _____
smoke hypercoagule
arterial thrombosis:
Lines of Zahn
Alternating pale layers of platelets with dark layers of trapped RBCs
Imply thrombosis at site of blood flow, i.e. antemortem
what steps happen with thrombus?
Propagation (obstruction)
- Embolization
Thrombi may dislodge and travel to other sites in vasculature - Dissolution
Thrombi may be removed by fibrinolytic activity - Organization and recanalization
Thrombi induce inflammation, fibrosis, and re-endothelialization, ultimately re-establish vascular flow
Embolization
Detached intravascular solid, liquid, or gas carried by blood to distant site from point of origin
Dislodged thrombi represent 99% of all emboli
I.e. thromboembolism
downstream eschemic necrosis
pulmonary thromboembolism originates in:
lower leg (usually multiple)
systemic thromboembolism originates:
heart: can go anywhere
Paradoxical Embolism
Embolus passes through an intraventricular defect to gain access to systemic circulation
