Lecture 2: Inflammation and Healing

Question 1

What are the 6 stimuli that can trigger acute inflammatory reaction

Answer 1

Infection, Trauma, Physical and chemical agents, Tissue necrosis, foreign bodies, immune reactions (hypersensitivity)

Question 2

What are the substances that activate vessel endothelial cells and resident macrophages

Answer 2

pro inflammatory substances released from necrotic and injured cells.

Question 3

What are the rough 9 main events in acute inflammation

Answer 3

1. Proinflam substances activate endothelial cells and macrophages
2. Activated endothelial cells release substances which cause vasodilation and increased permeability
3. Blood flow to tissue is increased, there is exudate, stasis develops and margination of leukocytes
4. Increased expression of cell adhesion molecules on endothelium luminal surface
5. Neutrophil diapaedesis
6. Neutrophils get activated by signals from the tissue
7. Neutrophils move towards site of injury following chemotactic gradient
8. Neutrophils attack the cause of inflammation and pus starts to form
9. Acute inflammation is terminated

Question 4

What do activated endothelial cells produce to affect the blood vessels in what way, where does this occur especially

Answer 4

They produce inflammatory cytokines, prostoglandins and nitric oxide which cause vasodilation and increased permeability of blood vessels in the injured tissue - especially post capillary venules

Question 5

What are the 3 main effects of this change in blood flow due to activated endothelial cells

Answer 5

1. Increased blood flow to damaged tissue, increasing the flow of protein rich fluid out of vessels into damaged tissue= exudation
2. This loss of fluid eventually increases blood viscosity and slows blood flow= stasis
3. This allows leukocytes to go to the margins of blood flow, neutrophils accumulate along the vascular endothelium.

Question 6

What does exudation in tissues cause

Answer 6

Oedema. The exudate also contains chemical mediators and fibrinogen which is enzymatically converted to fibrin to seal damaged blood vessels and can accumulate on epithelial surfaces as dense fibrinous exudate.

Question 7

How are neutrophils adhered to the endothelial cells of the blood vessels

Answer 7

1. Increased expression of selectin molecules on endothelial cells which bind to neutrophil glycoprotein receptors to make roll very slowly
2. increased expression and avidity of integrin cell adhesion molecules on Neutrophils binds to the addressins on endothelial cells causing firm adherence

Question 8

After adherence, what is diapaedesis

Answer 8

Neutrophils go to the extra vascular space (tissues) by squeezing through the inter-endothelial junctions to get between endothelial cells and basement membrane before crossing the basement membrane

Question 9

What are the signals that activate the neutrophils as they move throughout the tissues and who sends them

Answer 9

Chemokines, endothelial cell surface molecules, IL1 and Tumour necrosis factor alpha (TNFa). They come from damaged tissues, activated endothelial cells and other leukocytes
Bacterial products that bind to toll like receptors on their surface also activate them.

Question 10

How does chemotaxis work

Answer 10

chemotactic factors bind to specific GPCRs on the leukocyte surface which through intermediate steps, leads to actin polymerisation at the leading edge of the cell and cause the extension of filopodia toward the site of injury

Question 11

What are the exogenous and endogenous chemotactic factors which lead neutrophils to the site of injury

Answer 11

Exogenous = bacterial products 
Endogenous= components of complement (C5a), leukotrienes and chemokines (IL8)

Question 12

What leads to pus formation

Answer 12

Necrotic neutrophils release vasoactive, chemotactic and damaging substances which damage adjacent tissues and this killing power is still limited so some of them still die. The pus is made of dead neutrophils mixed with tissue debris and bacteria from the infection

Question 13

What terminates acute inflammation

Answer 13

When the offending agent is eliminated and the secreted mediators of inflammation are broken down.
Excessive damage is prevented by active anti inflammatory mechanisms in place

Question 14

What are the local effects of inflammation

Answer 14

Redness, swelling, heat, pain and loss of function

Question 15

What are these terms : calor, dolor, tumor, rubor, functio laesa

Answer 15

heat, pain, swelling, redness and loss of function

Question 16

What are the 4 systemic effects of inflammation

Answer 16

• Pyrexia (fever): mediated by IL1 and TNF-alpha from endothelial cells and macrophages
• Leukocytosis: increased production and release of leukocytes from the bone marrow
• Acute Phase proteins: increased production of proteins involved with inflammatory response in the liver
• Endocrine changes: increased production of glucocorticoid steroid hormones as a response

Question 17

If the cause of inflammation is prolonged what other cells enter. How long is this after neutrophil response

Answer 17

Other leukocytes like lymphocytes and especially blood monocytes enter the tissues. The monocytes become macrophages once in the tissues, becoming the dominant cell type with greater killing potential. This happens 1 day after neutrophils

Question 18

Describe chronic inflammation- the coordination and simultaneous processes

Answer 18

Inflammatory response is neutrophils, macrophages and lymphocytes signal to one another as well as other cell types such as fibroblasts and endothelial cells to coordinate response which is simultaneous active inflammation, extensive tissue destruction and attempts at repair.

Question 19

What is the granuloma (the focus of chronic inflammation) made of

Answer 19

A core of necrosis with microscopic aggregations of macrophages that are transformed into epithelium like cells- sometimes fused together and multinucleated - surrounded by a collar of lymphocytes.

Question 20

What is the process that happens after inflammation is over and what are the two stages of this

Answer 20

Healing: body’s attempt to restore the original structure and function of an injured tissue.

1. Cleaning up the mess from the original injury and subsequent inflammatory response
2. Rebuilding the structure and function of the tissue that was destroyed by injury and inflammatory response