Acute Inflammation and Wound Healing

Question 1

What are the cardinal signs of inflammation

Answer 1

1. Redness
2. Swelling
3. Heat
4. Pain
5. Loss of function

Question 2

Define the triple response

Answer 2

Histamine is injected intradermally into the skin in response to tissue injury or infection. Its effects are classically desribed as the triple response which are:

1. Redness: vasodilation in the dermal layer of the skin
2. Flare: histamine diffuses in the surrounding tissue, producing a flare pattern of the redness
3. Wheel: Exudation of the fluid from post capillary venules

Question 3

What are the 3 things to remember from this slide

Answer 3

In this slide he started with how macrophages encounter an antigen and give off danger singals to recruit neutrophils and other while blood cells at the site of infection.

Also worthwhile to note is that there is vasodilation as part of the acute inflammatory response that leads to edema.

Also he mentioned here that complement proteins by themselves can lead to the lysis of microbes.

Question 4

Vascular permeability

Answer 4

1. Normal: There is a hydrostatic pressure generated by the left ventricle of the heart that is going to force fluid out of the capilaries. This is opposed by the colloidal osmitic pressure due to plasma proteins (mainly albumin) in the capillaries.
2. Exudate: In this condition there is increased interendothelial spaces which leads to fluid leakage out of the capillaries. Vasodilation and stasis (slowing of the blood) aids in this process. This fluid also contains RBCs and WBCs. Leads to edema
3. Transudate: The example he gave here was when a person has left ventricle failure, blood gets backed up in the lungs, causes increased hydrostatic pressure that can cause fluid leaking. In this case it is the hyperfiltered plasma only, no blood cells leak out. Main cause of transudate is increased hydrostatic pressure.

Question 5

What are the types of edema

Answer 5

Non inflammatory edema: can be due to pulmonary edema due to heart failure (in the case of trasudate) or it can be due to nephrotic syndrome which leads to decrease oncotic pressure (less albumins in the blood due to loss of proteins in the kidney)

Inflammatory edema: due to the triple response or due to irreversible injury such as burns (skin is burned, patient cannot regulate their edema well since vessels are damaged)

Question 6

What are the different chemokines (chemicals that lead to chemotaxis to the site of infection or injury)

Answer 6

There are 2 fundamental different categories which the chemokines can be classified into:

1. Exogenous: N-formyl methionine from terminal amino acid of bacteria and lipids from damaged membranes (one example is LPS, lipopolysacchardie)
2. Endogenous: compliment proteins, IL-8 and arachidonic acid products

Question 7

How are microbes and damaged cells recognized

Answer 7

1. PAMPs
2. DAMPs
3. Complement proteins
4. MBLs and Collectins

Question 8

Transcytosis

Answer 8

Several important points to note here:

1. Histamine causes retraction of endothelial cells which allows the WBCs to physcially cross the endothelial surface into the tissue
2. In case of endothelial injury, WBCs can cross the membrane since the membrane itself is damaged
3. In later stages of inflammation there can be lekocyte mediated endothelial injury that can cause proteins and inflammatory cells to cross the endothelial layer
4. There can increased permeability of the endothelial layer due to VEGF

Question 9

Explain the process of diapedesis in detail

Answer 9

Step 1: Margination, neutrophils move along the sides of the capillaries

Step 2: Pavementing, they start sticking to the capillary walls

Step 3: rolling, this is due to selectins, specifically P-selectin that is stimulated by thrombin, histamine and platelet activating factor (PAF). There can also be E-selectin induction which i caused by IL-1 and TNF.

Step 4: Neutrophils eventually bind to integrins, causes a conformational change in the membrane leading to the neutrophils crossing the endothelial layer.

Question 10

What is the one common enzyme in every WBC. What does it do?

Answer 10

Myeloperoxidase, it creates ROS.

Question 11

What happens when WBCs after transcytosis go to the site of infection

Answer 11

They are activated by different receptors

Question 12

What are the different enzymes found in WBCs that help in killing the microbes.

Answer 12

1. ROS
2. Elastase
3. Lysozymes
4. Defensins
5. Cathelicidins
6. Lactoferrins

Also remember Eosinophils have major basic protein

Question 13

What are the key principles involved when there is a site of infection

Answer 13

1. Amplification is necessary for development of inflammation
2. Inflammation persists until the pathogen and the mediators are removed.

Question 14

Expalin ther termination pathway of inflammation

Answer 14

Once inflammation development starts, there are signals sent to actively termiante the inflammatory response at the same time. This involves the production of anti inflammatory lipoxins from arachidonic acid, liberation of anti inflammatory cytokines and release of TGF beta (transforming growth factor beta). There are also neural impusles (cholinergic discharge) that inhibits the products of TNF in macrophages.

Question 15

Need to look more into it. All that I remember is him saying that steroids inhibit arachidonic acid pathway by inhibiting Phospholipase C which is at the very begining

Question 16

What is necessary for healing

Answer 16

Inflammation

Question 17

What is an optimal type of repair and what is a good example of it

Answer 17

An optimal repair is regeneration and liver is a good example of it. If we cut out one lobe of the liver it will regenerate in a matter of days

Question 18

What is the most common form of repair in most of the organs and what is an exception to it

Answer 18

Fibrosis or scarring is the most common way to heal for most of the organs. Even liver undergoes scarring due to alcohol damage.

Once exception to this is the brain which doesnt heal by scarring but it heals by glial scarring.

Question 19

How do organs heal

Answer 19

By turning on growth factors

Question 20

Name the common growth factors

Answer 20

1. Epidermal growth factor (EGF)
2. Fibroblast growth factor (FGF), also causes angiogenesis
3. Insulin like growth factor 1 (IGF1)
4. Platelet derived growth factor (PDGF)
5. TGF alpha
6. TGF beta
7. VEGF

Question 21

Name the components of the ECM

Answer 21

1. Collagens
2. Basement membranes
3. Elastic fibers
4. Fibronectins
5. Proteoglycans

Question 22

What part of the ECM is laid down first

Answer 22

Fibronectin

Question 23

How is ECM associated with granulomas

Answer 23

ECM helps direct the cells to form structures, this is best seen in granulomas.

Question 24

How does ECM directly influence the behavior of cells

Answer 24

ECM have integrins which can bind to the receptors in the cells and diectly cause a change in their behavior

Question 25

What did he mean by ECM as the "force"

Answer 25

Throught the integrins, ECM tells the cells what to do. Like a puppet master

Question 26

What are the different steps involved in healing

Answer 26

1. Induction of acute inflammatory response 2. Regeneration of parenchymal cells 3. Synthesis of ECM 4. Migration and proliferation of parenchymal cells and the stromal cells 5. Remodeling 6. Collagenization and maturation of wound (remember his 6 weeks example of a surgeon)

Question 27

What is granulation tissue

Answer 27

It is the inital event in healing, it is associated with fromation of richly vascular tissue and infliteration of fibroblast and inflammatory cells. This is different from granulomatous inflammation, which is a form of chronic inflammation

Question 28

Differentiate between wound healing by primary intention and secondary intention

Answer 28

Primary intention are the nice neatly cut skin which has its sides opposed to each other, this is done in surgery whereas healing by second intention is when wound edges cannot be opposed, like in stab wounds. Secondary intention wound healing usually results in scar formation

Question 29

Explain the contraction phase of wound healing

Answer 29

Contraction is an important part of wound healing, this is especially important in secondary wound healing when cells calle myofibroblasts causes contraction which results in faster healing. Too much contraction is bad as it associated with clinically significant pathology.

Question 30

What are the different factors that affect wound healing

Answer 30

1. Type, size and location of the wound (if the wound is in a moving body part it will be slow to heal) 2. Vascular supply, diabetics heal poorly 3. Infections can delay wound healing and it can also cause to have more granulation tissue and scarring 4. Ionizing radiation is bad for wound healing, UV is good. 5. Nutrition like vitamin C 6. Steroids, since they reduce inflammation and slow down wound healing 7. Age, younger is better

Question 31

What are some of the complications of wound healing

Answer 31

1. Defective scar formation such as in ulcers and dehiscence The reasons of defective scar formation are wound infection, malnutrition and hypoxia 2. Excessive scar formation like in keloids 3. Contraction - excessive

Question 32

What is compartment syndrome

Answer 32

He talked about compartment syndrome that how circumferential burns can lead to excessive scar formation which can cut off blood supply.