tissue repair

Question 1

2 ways of restoration of tissue architecture and function after an injury:

Answer 1

1. Regeneration
   Proliferation of residual (uninjured) cells
   Maturation of tissue stem cells
   Returns to normal state
2. 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

Question 2

Regeneration is:

Answer 2

Replacement of damaged tissue with native tissue
1. Labile tissues

Continuously dividing cells
Small intestine or epithelium
Stable tissues

2. 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

Question 3

permanant:

Answer 3

Permanent tissues
Lack regenerative potential
Repair replaces damaged tissue with fibrous scar
skeletal heart brain

Question 4

Inflammation:

Answer 4

Macrophages play central role in repair

VEG-F promotes angiogenesis

Question 5

Angiogenesis:

Answer 5

New blood vessel development from existing vessels

Question 6

Formation of granulation tissue

Answer 6

Migration and proliferation of fibroblasts, blood vessels and deposition of loose connective tissue (3-5 days)

Question 7

Deposition of connective tissue

Answer 7

Deposition of ECM proteins produced by fibroblasts

Processes orchestrated by locally produced cytokines and growth factors (PDGF, FGF-2, and TGF-β)

Question 8

Remodeling of connective tissue

Answer 8

Myofibroblasts contract scar
dependent on metal ions (zinc) for activity
need Zinc for metalloproteinases to work: otherwise results in weak connective tissue

Question 9

Repair by Scar: Mechanism

Answer 9

1. Injury induces inflammation, which clears dead cells and microbes (if any)
2. Formation of vascularized granulation tissue
   Fibroblasts deposit collagen III
   Capillaries provide nutrients
   Myofibroblasts to help contract wound
3. 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

Question 10

TEST: What is the co-factor for scar deposition of extracellular matrix?

Answer 10

3. Scar deposition of extracellular matrix
   Collagenase replaces collagen III with collagen I
   Requires zinc as a co-factor

Question 11

Healing by First Intention

Answer 11

1. Inflammation
2. Proliferation of epithelial and other cells
3. Maturation of the connective tissue scar

Question 12

Healing by Second Intention

big ulcer

Answer 12

1. larger Inflammatory reaction more intense
2. Development of abundant granulation tissue: big ulcer
3. Accumulation of ECM and formation of a large scar
4. Wound contraction by the action of myofibroblasts

Question 13

Fibrosis =

Answer 13

=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

Question 14

most common cause of delayed healing?

Answer 14

infection

Question 15

other causes of delayed healing?

Answer 15

foreign body/local, suture

systemic: nutrition: lack of zinc

Question 16

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

Answer 16

Dehiscence = rupture of wounds

Ulceration = inadequate vascularization

Question 17

Excessive formation of the components of the repair process

Answer 17

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

Question 18

2 types of fluid accumulation

Answer 18

transudate: few cells, due to increased pressure
exudate: many cells, due to leaky blood vessels, etc

Question 19

for transudate in lung

Answer 19

left side heart build up, congestive heart failure

Question 20

for exudate to build up in lung?

Answer 20

infection

Question 21

2 types of fluid accumulations in the lungs:

Answer 21

transudate (left side congestive heart failure) exudate infection 2 pulmonary edema

Question 22

effusions happen in:

Answer 22

plueral effusion, pericardiacal effusion

Question 23

most important protein in blood regulation of osmotic pressure

Answer 23

albumin

Question 24

lack albumin:

Answer 24

edema

Question 25

three most important organs associated with edema?

Answer 25

heart, liver, kidneys (albumin, sodium)

Question 26

dependent edema?

Answer 26

pitting edema in leg

Question 27

ascites:

Answer 27

cirrhosis of liver

Question 28

elephantiasis

Answer 28

lymphatic liariasis due to w. bancrofti

Question 29

2 types of increased blood flow:

Answer 29

hyperemia (active process, more oxygenated blood) | congestion (passive process, impaired outflow from tissue affected region is cyanotic)

Question 30

wherever you have _____ you have ______

Answer 30

congestion, edema

Question 31

nutmeg liver is caused by:

Answer 31

right side heart failure, backs up into inferior vena cava and cause edema in liver

Question 32

left side of heart failing causes:

Answer 32

pulmonary chronic passive congestion: lung edema

Question 33

4 types of hemorrhages:

Answer 33

(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

Question 34

endothelial cells roll in hemostasis?

Answer 34

turn blood on and off

Question 35

sequence of hemostasis:

Answer 35

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 4. Thrombus Polymerized fibrin forms solid, permanent plug Counter-regulatory process, e.g. t-PA, set in motion t

Question 36

Thrombosis:

Answer 36

Inappropriate activation of normal hemostasis | Formation of blood clot (thrombus) in normal vasculature

Question 37

thrombosis is described with:

Answer 37

virchow triad

Question 38

top of virchow triad is:

Answer 38

endothelial injury, bc artherosclerosis, slowest blood flow in legs, etc

Question 39

important site of thrombosis hyper lamina flow?

Answer 39

bifurcation: Turbulence: arterial thrombosis | Disruption of laminar flow

Question 40

patients that ____ are _____

Answer 40

smoke hypercoagule

Question 41

arterial thrombosis:

Answer 41

Lines of Zahn Alternating pale layers of platelets with dark layers of trapped RBCs Imply thrombosis at site of blood flow, i.e. antemortem

Question 42

what steps happen with thrombus?

Answer 42

Propagation (obstruction) 2. Embolization Thrombi may dislodge and travel to other sites in vasculature 3. Dissolution Thrombi may be removed by fibrinolytic activity 4. Organization and recanalization Thrombi induce inflammation, fibrosis, and re-endothelialization, ultimately re-establish vascular flow

Question 43

Embolization

Answer 43

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

Question 44

pulmonary thromboembolism originates in:

Answer 44

lower leg (usually multiple)

Question 45

systemic thromboembolism originates:

Answer 45

heart: can go anywhere

Question 46

Paradoxical Embolism

Answer 46

Embolus passes through an intraventricular defect to gain access to systemic circulation