0416 - Inflammation - RM

Question 1

What is Inflammation?

Answer 1

Essential protective part of the non-specific (but not innate) immune response, to limit damage and lay the foundation for repair.
Characterised by redness, swelling, heat, pain, and loss of function of the affected area.

Question 2

What is the difference between acute and chronic inflammation?

Answer 2

Acute – ‘normal’ inflammation. Short time course (up to days). Contains leucocytes (primarily neutrophils), and exudate of fluid and plasma.
Chronic – ‘abnormal’ inflammation. Longer time course (weeks-years). Contains lymphocytes and macrophages, and characterised by proliferation of blood vessels, and tissue fibrosis and necrosis.

Question 3

What are the components of inflammation? (4)

Answer 3

Microvasculature changes (size, blood flow, and ‘leakiness’)
Circulating blood cells (Red and White both leave microvasculature)
Tissue cells (damaged cells secrete/release inflammatory mediators)
Inflammatory mediators (numerous types and roles)

Question 4

Briefly describe the changes in microvasculature in the initial part of the inflammatory response.

Answer 4

1. Arterioles briefly constrict.
2. All vessels vasodilate to increase blood flow.
3. Vasodilation leads to permeability of microvasculature – exudate leaks out.
4. Blood flow slows down (stasis)
5. Leucocytes become ‘marginated’ and migrate into extravascular space.
6. The site becomes red, swollen and hot.

Question 5

What is the difference between exudate and transudate?

Answer 5

Transudate – fluid normally found inside vessels in tissues, very little in ECF. Low protein content.
Exudate – Significantly more protein (reflects plasma protein contents) and cell debris, leaks into the ECF.

Question 6

What are inflammatory mediators? What is their purpose?

Answer 6

Products of blood cells, damaged tissue, and plasma proteins that serve as a signal to attract leukocytes to the site of injury to facilitate phagocytosis of the injurious agent, or otherwise affect the immune response.

Question 7

What characterises the plasma protein-derived inflammatory mediators?

Answer 7

Complement, coagulation, fibrinolytic and kinin systems.

They are all cascade processes – with each step deactivating the previous enzyme. This represents very tight control.

Question 8

What are the cell and tissue-derived inflammatory mediators?

Answer 8

Cytokines (signalling peptides or glycoproteins) that can be autocrine (act on releasing cell), or paracrine (act on nearby cells). Can be classified by family (interferons, interleukins etc), or Function (proinflammatory, anti-inflammatory).
Arachadonic acid metabolites – prostaglandins and leukotrienes – serve to mediate or enhance immune response
Histamine and other amines – case ‘wheal and flare’ tissue response.

Question 9

What are the cellular contributions to inflammation? (6)

Answer 9

Polymorphs – first to arrive, engulf, kill, and digest microbes.
Mast cells – stimulated by complement and release mediators (including histamine).
Monocytes/macrophages – Late arrivals, secrete cytokines and chemokines, and engulf microbes and cell debris.
Platelets – pro-inflammatory, assist in clotting
Vascular Endothelium – contract/relax (vasoconstriction/vasodilation), and assist in angiogenesis.
Neurons – release compounds including substance P (transmits pain).

Question 10

What are the systemic sequelae of inflammation?

Answer 10

Increased temperature
Increased leukocytes (and later lymphocytes)
Stimulated synthesis of plasma proteins.

Question 11

Which cellular membrane components take part in ‘margination’ of white cells?

Answer 11

Selectins, Integrins, and Cytokines

Question 12

In the cascades of coagulation and complement activation, what underlying principle controls each step?

Answer 12

Negative feedback – activation of each step deactivates the previous step.

Question 13

Is there a purpose behind a fever?

Answer 13

Yes. The higher temperature inhibits bacterial growth, while enhancing cell metabolism (increased mobility, enhanced phagocytosis, minimising endotoxin effects, and increasing T-cell proliferation).

Question 14

What different types of fever patterns are described? Are they useful diagnostically?

Answer 14

Countinuous – Steady temperature above normal.
Intermittent – Temperature cycles between normal and high at regular intervals.
Remittent – Temperature fluctuates, while remaining above normal.

The character of fever can give you an indication of what infection or other cause of inflammation may be present.

Question 15

If drugs aimed to minimise inflammation or its consequences, what sites could they target?

Answer 15

Inhibiting the COX enzymes can prevent formation of prostaglandins. Current NSAIDs do this.
Could also target other particular inflammatory mediators, such as histamine.

Question 16

Which inflammatory compounds cause pain? Do they act directly on receptors or via other mechanisms?

Answer 16

Bradykinin – Acts directly on Receptors.
Prostaglandins – Sensitise neurons to pain.
Substance P – Exacerbates pain response in nociceptors.

Question 17

What cellular membrane components take part in margination of white cells?

Answer 17

Cellular adhesion molecules (selectins) exist on the endothelial cells. Carbohydrate ligands on the leukocytes bind to them with marginal affinity.
Leukocyte integrins are also activated by cytokines, and bind to the endothelial cells, immobilising the leukocyte when appropriate.

Question 18

In the cascades of coagulation and complement activation, what underlying principle controls each step?

Answer 18

Negative feedback.