Acute Inflammation and Wound Healing

Question 1

What are the Cardinal Signs of Inflammation?

Answer 1

Redness (Rubor)

Swelling (Tumor)

Heat (Calor)

Pain (Dolor)

Loss of Function (Functio laesa)

Question 2

What is the triple response?

Answer 2

Redness due to arteriolar and capillary vasodilation

Flare; redness in the surrounding area, due to diffusion of histamine and early stasis

Wheal: due to exudation of fluid from the post capillary venules

Question 3

What physiological change is responsible for both heat and redness of acute inflammation?

Answer 3

Vasodilation (usually we are talking about arterial)

Question 4

What rarely can occcur before vasodilation?

Answer 4

Rarely, there may be an initial transient vasoconstriction

Question 5

What chemical cause vasodilation?

Answer 5

Histamine and NO acting on vascular smooth muscle

Question 6

What is stasis?

Answer 6

The term to desribe vascular congestion of packed red cells moving slowly in dilated small vessels. Stasis leads to neutophils accumulating along the vascular endothelium

-blood vessels dilate to slow down blood blow and by increasing their permeability

Question 7

What are the two possible sources of acute inflammation due to vascular response?

Answer 7

Microbes and Necrotic Tissue

Question 8

How llng will inflammation exist?

Answer 8

Until the inciting stimulkus is removed and the mediators are dissipated or inhibited

Question 9

Edema is the result of what physiological mechanism

Answer 9

Vasodilation that leads to increased vascular permeability and the leakage of fluid out of the blood vessels.

Question 10

Compare exudate to transudate

Answer 10

Exudate is fluid and protein leakage that contain WBCs and cellular debris, and has a high specific gravity (Pus)

-Transudate is a fluid with low protein content, it is essentially an ultra-filtrate of blood plasma that results from osmotic or hydrostatic imbalance across the vesssel wall wihtout an increase is vascular permeability. Can be caused by venous outflow obstruction like congestive heart failure.

Question 11

What are some pathogenesis of non-inflammatory edema?

Answer 11

Pulmonary edema due to Heart Failure

Nephortic syndrome due to renal distrubance (low albumin)

Question 12

What are some pathogenesis of inflammatory edema?

Answer 12

Direct, irreversible injury - all vessels (burns)

or transient increases in vascular permeabiltiy like the triple response

Question 13

What are the sequential step in leukocyte extravasation?

Answer 13

Margination, rolling, and adhesion (pavementing), transmigration or extravasation

-on histo slide margination is the dark stained spots moving out toward the cytosplasm and pavmenting is when they actually begin to stick, the proper adhesion molecules must be present.

Question 14

Why is it important to determine exudate vs. transudate and what is the example?

Answer 14

Transudate you treat with directics, and exudate you treat with antibiotics. example is an exray that shows effsion in the pleural space and infiltrate in teh long. is it pneumonia or heart failure. you have to tap teh effusion with a needle and test the cell count, specific gravity, and protein level. then determine and treat

Question 15

Give examples of both exogenous and endogenous chemo-attractants that result in chemotaxis?

Answer 15

Exogenous: N-formyl methionine terminal amino acids from bacteria, LPS

Endogenous: complement proteins (C5a) chemokines (IL-8), Arachidonic acid products (LTB4)

-chemotaxis is the leukocyte migrating toward the site of injury after extravasation, movement is by extension of filopodia

Question 16

The inflammasome is responsible for the celavage and activation of which chemokine?

Answer 16

IL-1

Question 17

What is transcytosis and what are molecules involved in performing it?

Answer 17

Contraction of endothelial cells resulting in increased inter-endothelial spaces is the most common mechanism of vascular leakage. Usually occurs in post-capillary venules (hallmark of acute inflammation)

-NO, Histamine are important

Question 18

What are the important molecules that mediate the adhesion of leukocytes to the endothelium?

Answer 18

L-selectin is expressed on leukocytes

P-selectin is expressed on platelets

E-selectin is on endothelial cells

the expression of selectins is regulated by cytokines in response to injury including TNF and IL-1

Question 19

What are some mediators of P-selectin and when does it occur?

Answer 19

Thrombin, Platelete-activating factor, and histamine stimulate the redsitribution of p-selectin from the weibel-palade bodies to the cell surface.

Question 20

What molecules induce E-selectin?

Answer 20

TNF-alpha and IL-1

Question 21

When Leukocytes are activated, what is their primary mechanism for killing the microbes that ingest through phagocytosis?

Answer 21

ROS within the lysosome

Question 22

Along with ROS, leukocytes also have granulocytes that contain many enzymes to aid in the killing of microbes. What are some of these enzymes?

Answer 22

Elastase and Lysoszyme, defensins, cathelicidns, lactoferrin

Question 23

What enzyme makes eosinophils particularly effect against parasites?

Answer 23

Major basic protein, which is toxic to many parasites. they may also contain histaminase

Question 24

What are two important molecules in the termination of inflammation?

Answer 24

TGF-beta (transforming growth factor) - anti-inflammatory cytokine from macrophages

IL-10

Question 25

What is the enzyme that makes Arachidonic acid?

Answer 25

Phospholipase A2 turns cell membrane phospholipids into arachidonic acid

Question 26

What inhibits phospholipases?

Answer 26

Corticosteroids!

Question 27

What must occur for healing to occur?

Answer 27

INFLAMMATION

Question 28

What are the two ways an organ can heal?

Answer 28

Regeneration (liver) or collagenous scarring (result of ECM damage),

-regeneration is optimal!

Question 29

What is fibrosis?

Answer 29

A type of repair that results in a collagen scar. Functional tissue replaced by collagenous scar, which is laid down by fibroblasts

Question 30

What are some influences a growth factor can have on healing?

Answer 30

Rate of healing, type of ECM depositied, and cell types present

Question 31

What is the first structural glycoprotein laid down during wound healing?

Answer 31

Firbonectin

Question 32

What allows integrins to be able to influence diapedesis?

Answer 32

The direct connection to actin

Question 33

What are the steps in wound healing?

Answer 33

1. Induction of acute inflammatory response
2. regeneration of parenchymal cells
3. synthesis of extracellular matrix proteins
4. migration and proliferation of both parenchymal and connective tissue cells
5. remodeling
6. collagenization and maturation of wound

Question 34

What is granulation tissue?

Answer 34

initial event in the repair of injury, and consists of richly vascular connective tissue which contians capillaries, young fibroblasts, and a variable infiltrate of inflammatory cells

-do not confuse this with granulomatous inflammation (a form of chronic inflammation)

Question 35

Describe primary intention wound healing?

Answer 35

Clean wound with well-apposed edges and minimal clot formation

Question 36

Describe the wound and its cellular composition at these time intervals: Less than 24 hours, day 3, day 5, 2nd week, and end of 1st month.

Answer 36

Healing by Primary Intention:

• Within 24 hours, neutrophils appear at the margins of the incision, moving toward the fibrin clot. In 24 to 48 hours, spurs of epithelial cells move from the wound edges (with little cell proliferation) along the cut margins of the dermis, depositing basement membrane components as they move. They fuse in the midline beneath the surface scab, producing a continuous but thin epithelial layer that closes the wound.
• By day 3, the neutrophils have been largely replaced by macrophages. Granulation tissue progressively invades the incision space. Collagen fibers are now present in the margins of the incision, but at first these are vertically oriented and do not bridge the incision. Epithelial cell proliferation thickens the epidermal layer.
• By day 5, the incisional space is filled with granulation tissue. Neovascularization is maximal. Collagen fibrils become more abundant and begin to bridge the incision. The epidermis recovers its normal thickness, and differentiation of surface cells yields a mature epidermal architecture with surface keratinization.
• During the second week, there is continued accumulation of collagen and proliferation of fibroblasts. The leukocytic infiltrate, edema, and increased vascularity have largely disappeared. At this time, the long process of blanching begins, accomplished by the increased accumulation of collagen within the incisional scar, accompanied by regression of vascular channels.
• By the end of the first month, the scar is made up of a cellular connective tissue (“cellular cicatrix”) devoid of inflammatory infiltrate, covered now by intact epidermis. The dermal appendages that have been destroyed in the line of the incision are permanently lost. Tensile strength of the wound increases thereafter, but it may take months for the wounded area to obtain its maximal strength.

Question 37

Describe healing by secondary intention?

Answer 37

Wound edges are not apposed (wound infection). Wound fills with granulation tissue from the bottom up. results in a large scar

Question 38

What is wound contration?

Answer 38

occurs in secondary intention usually of large surface wonds. involves the reduction in size of teh defect by the action of myofibroblasts which represent an intermediate type of cell. Process produces faster healing, since a smaller portion must be repaired. But too much contration can create clinical problems.

Question 39

What is the most common cuase of wound dehiscence or ulceration? What are some other potential causes?

Answer 39

Wound infection, hpoxia, malnutirtion (scurvy)

Question 40

What are some clinical examples of contracttion?

Answer 40

Compartment syndromes (circumferential burns), Dupuytren contracture, peyronie’s disease

Question 41

What is dehiscence vs. ulceration

Answer 41

Dehiscence is rupture of a wound usually like an abdominal surgery wound that ruptures due to pressure or vomiting.coughing.

Ulceration is due to inadequat vascularaization during healing.

Question 42

What is responsible for directing the cellular ballet of wound healing?

Answer 42

ECM

Question 43

What is contracture?

Answer 43

Excessive contration of a wound. probelm with extensive circumferential like third degree burns