Inflammation

Question 1

Define inflammation

Answer 1

Inflammation is the body’s response to any form of cellular injury eg. infection, heat, trauma, hypoxia, radiation etc.
Inflammation aims to remove injurious agents, clear away any dead tissue and trigger healing of the damaged tissue.

Inflammation is intended to be a protective response

Question 2

Outline the processes involved in acute inflammation

Answer 2

usually a rapid, transient process involving vascular changes and neutrophil accumulation. Acute Inflammation = cell injury + vascular changes + neutrophil leukocytosis

Question 3

Outline the processes involved in chronic inflammation

Answer 3

a more persistent form of inflammation in which there is on-going tissue destruction and attempted repair

Chronic inflammation is said to occur when inflammation persists for weeks, months or longer. It may arise from unresolved acute inflammation or occur from the outset.

Chronic inflammation= persistent cell injury + lymphocytes, macrophages, plasma cells + fibrosis

Question 4

Describe the vascular changes in acute inflammation

Answer 4

There is dilatation of blood vessels resulting in increased blood flow to the area of injury. In addition, endothelial cell activation causes increased permeability of capillaries which results in leaking of fluid and small proteins (eg. fibrinogen) into the area of damage.

Activation of the coagulation cascade (see pg 2 of the Cardiovascular Pathology 1 notes) results in production of thrombin which converts fibrinogen into insoluble fibrin in the area of damage.

Question 5

Define granuloma

Answer 5

A granuloma is an aggregate of activated (epithelioid) macrophages.

Necrosis in the middle

Question 6

Describe the pathophysiology of tuberculosis,

Answer 6

Bacilli inhaled into the terminal airways are engulfed by alveolar macrophages. Alveolar macrophages are unable to destroy the mycobacteria because their thick cell wall resists attack.

Survival of the organism allows it to multiply within macrophages, eventually leading to cell death and release of more microorganisms. Over a period of weeks, mycobacteria spread in macrophages via the blood to the apices of the lungs and multiple other organs such as the kidneys, adrenals, bones and meninges.

• if, however, the T helper cell response is more Th2 driven, an inappropriate repertoire of immune cells are recruited.
→ there is an intense but ineffective immune response to the organism which leads to extensive tissue destruction and survival of the organisms.

Question 7

describe important causes of inflammation in clinical practice

Answer 7

• persistent infection eg. H.pylori, M. tuberculosis, Hepatitis C.
• autoimmune diseases.
• non-living material eg. asbestos → asbestosis; coal dust → pneumoconiosis.

Question 8

explain the pathogenesis of atherosclerosis

Answer 8

The damaged endothelial cells become dysfunctional: Endothelial Injury

• there is increased permeability.
• they produce adhesion molecules and cytokines which attract inflammatory cells and prothrombotic molecules. eg. VCAM-1 (vascular cell adhesion molecule-1) binds monocytes and T cells.

Consequently, there is recruitment of inflammatory cells to the site of injury: monocytes and T cells adhere to the endothelium and migrate into the intima. The monocytes differentiate into macrophages.

The macrophages have a number of effects:
• they produce free radicals that drive LDL oxidation to form oxidised LDL.
[Remember: native LDL is not atherogenic. oxidised LDL is highly atherogenic.]
• they engulf oxidised LDL and cholesterol crystals, becoming foam cells.
[A foam cell is a macrophage containing abundant lipid in its cytoplasm, giving the cytoplasm a ‘foamy’ appearance microscopically - hence the name].

• foam cells produce growth factors what stimulate migration of smooth muscle cells from the media to the intima.

Question 9

name some common causes of granulomatous inflammation

Answer 9

• infections eg. mycobacteria.
• sarcoidosis.
• Crohn’s disease.

Question 10

Protective role of granulomas in TB

Answer 10

Activated macrophages aggregate around mycobacteria to form granulomas. The granulomas wall off viable organisms in an anoxic and acidic environment which does not favour mycobacterial survival. The ultimate result is a calcified scar in the lung parenchyma and the hilar lymph node. Together this is referred to as the Ghon complex.

Question 11

2 steps of scar formation

Answer 11

• organisation – replacement of inflammatory exudate by granulation tissue. Granulation tissue is a fragile complex of proliferating capillaries, macrophages and fibroblasts. Macrophages phagocytose the debris. The capillaries give granulation tissue its distinctive red colour. Granulation tissue: fragile complex of proliferating interconnecting capillaries, fibroblasts and some macrophages
• scar formation – granulation tissue is replaced by a scar. The scar is laid down by fibroblasts. A scar is composed mainly of fibrous tissue. Collagen fibres are the main component of fibrous tissue.

Question 12

What is the difference between empyema and abscess?

Answer 12

Empyemas are accumulations of pus in a pre-existing rather than a newly formed anatomical cavity.

Question 13

3 examples of chronic inflammation

Answer 13

• persistent infection eg. H.pylori, M. tuberculosis, Hepatitis C.
• autoimmune diseases.
• non-living material eg. asbestos → asbestosis; coal dust → pneumoconiosis.

Question 14

5 outcomes of chronic inflammation

Answer 14

• Scarring (= fibrosis)- Healing by scarring may lead to problems. eg. chronic gastric ulcer causing gastric outlet obstruction.
• Tissue Destruction eg. gastric ulcer causing perforation or haemorrhage.
• Development of Cancer eg. H. pylori gastritis predisposes to gastric carcinoma.
• Diversion of nutrients- There is huge demand to maintain inflammatory/immune response and regeneration. In time this leads to weight loss, anaemia of chronic disease, decreased host resistance.
• Amyloidosis- Reactive systemic amyloid (AA amyloid

Question 15

5 people at risk of TB

Answer 15

• immunocompromised individuals, particularly HIV.
• immigrants from countries with high rates of tuberculosis.
• elderly.
• alcoholics.
• diabetes mellitus.

Question 16

5 symptoms of TB

Answer 16

• feeling unwell for weeks or months.
• persistent cough.
• constitutional symptoms eg. fever, night sweats, Loss of appetite and weight

Question 17

Define TB latency

Answer 17

infection with M. tuberculosis where mycobacteria are alive but not currently causing active disease.

Question 18

3 stages of TB diagnosis

Answer 18

• compatible history.
• radiological findings eg. CXR or CT showing infiltrates involving upper lobes +/- cavitation.
• laboratory features (microscopy and culture):
-3 respiratory samples (preferably spontaneously produced, deep cough sputum samples, otherwise induced sputum or bronchoscopy and lavage; preferably 1 early morning sample)
-microscopic examination of samples spread on to a slide (a sputum
smear) and stained with the Ziehl-Neelsen stain. Ziehl-Neelsen stain highlighting
-culture remains the gold standard to confirm the diagnosis of M. the M. tuberculosis bacilli
tuberculosis (since other non-tuberculous bacteria can be found in
sputum and are acid fast) and determine sensitivities.

Question 19

3 aspects of TB management

Answer 19

• Antituberculous therapy should be commenced - often quadruple therapy (rifampicin, isoniazid, pyrazinamide, ethambutol – RIPE) . Patient compliance should be monitored.
• TB is a notifiable disease, and so the diagnosis must be notified.
• Contact tracing should be undertaken for those with active pulmonary disease.

Question 20

4 risk factors for atherosclerosis

Answer 20

• smoking
• hypertension
• diabetes mellitus
• dyslipidaemia

Question 21

Explain why atherosclerosis is a chronic inflammatory process

Answer 21

• persistent injury (endothelial damage due to the previously described risk factors).
• on-going inflammation (macrophages and lymphocytes).
• repair with scarring (the fibrous cap of the plaque).