Acute inflammation

Question 1

Describe the process of leukocyte emigration into the ECM

Answer 1

1. Endothelial cells are stimulated by inflammatory mediators to express P- selectin and PAF (platelet activating factor)
2. On their surface, leukocytes have oligosaccharides. These oligosaccharides bind to the P- selectin molecule
3. This adhesion is rather weak, so it causes the leukocyte to roll along the p- selectin receptors of the endothelium
4. The leukocyte also has PAF receptors and ICAM receptors
5. The leukocyte will bind to PAF, which stimulates their consequent binding to ICAM- 1
6. Binding to ICAM- 1 causes adhesion of the leukocyte to the endothelium
7. The leukocyte then begins its migration between adjacent endothelial cells and movement into adjacent tissue

Question 2

Discuss the anti-microbial activity of PMNs

Answer 2

• PMNS are short lived suicide cells. Because, when they encounter a microbe, they degranulate and release antimicrobial compounds
• Kill by producing oxygen reactive species: NADPH oxidase enzyme on membrane: forms hydrogen peroxide. Donating electrons changes structure of ions. Bleach In our system kills bacteria by changing their structure
• Phagocytose and kill bacteria
• They contain enzymes like lysozymes and acid proteinases that kill/ digest cells
• When PMN die they accumulate at site of injury, site becomes necrotic
• By- stander effect: scorch earth strategy, kills good and bad cells

Question 3

Identify the outcomes of acute inflammation

Answer 3

• Recovery/ resolution: dilution or neutralisation of toxins by exudate
○ Phagocytosis and destruction of organism
• Abscess: necrosis followed by healing
• Ulceration: with or without pus formation
• Progression to chronic inflammation if no recovery

Question 4

How do pathologists assess whether an inflammatory response is ooccuring in a patient?

Answer 4

• When blood is drawn from the body, the erythrocyte sedimentation rate ESR is measured
• This measured how quickly the red blood cells settle to the bottom
• If it settles very quickly to the bottom, it is an indication that there is high protein content in the blood
• This can only happen if swelling is present because recall that swelling is caused by high hydrostatic pressure and thus leakage of fluids, thus increasing the solute concentration of plasma proteins in the blood

Question 5

What do acute phase proteins and cytokines do during systemic inflammation?

Answer 5

• Leucocytosis: high level of WBC as the bone marrow produces many leukocytes
• Elevates levels of acute phase proteins
• Fever: Large microbial loading, causes many TNF to come, high TNF = activates hypothalamus and thus fever
• Malaise: feelings of unwellness due to IL-1, IL-6 and TNF