Inflammation Flashcards
Define inflammation
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
Outline the processes involved in acute inflammation
usually a rapid, transient process involving vascular changes and neutrophil accumulation. Acute Inflammation = cell injury + vascular changes + neutrophil leukocytosis
Outline the processes involved in chronic inflammation
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
Describe the vascular changes in acute inflammation
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.
Define granuloma
A granuloma is an aggregate of activated (epithelioid) macrophages.
Necrosis in the middle
Describe the pathophysiology of tuberculosis,
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.
describe important causes of inflammation in clinical practice
- persistent infection eg. H.pylori, M. tuberculosis, Hepatitis C.
- autoimmune diseases.
- non-living material eg. asbestos → asbestosis; coal dust → pneumoconiosis.
explain the pathogenesis of atherosclerosis
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.
name some common causes of granulomatous inflammation
- infections eg. mycobacteria.
- sarcoidosis.
- Crohn’s disease.
Protective role of granulomas in TB
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.
2 steps of scar formation
- 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.
What is the difference between empyema and abscess?
Empyemas are accumulations of pus in a pre-existing rather than a newly formed anatomical cavity.
3 examples of chronic inflammation
- persistent infection eg. H.pylori, M. tuberculosis, Hepatitis C.
- autoimmune diseases.
- non-living material eg. asbestos → asbestosis; coal dust → pneumoconiosis.
5 outcomes of chronic inflammation
- 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
5 people at risk of TB
- immunocompromised individuals, particularly HIV.
- immigrants from countries with high rates of tuberculosis.
- elderly.
- alcoholics.
- diabetes mellitus.
