ICS Flashcards
Steps of acute inflammation
Increased vessel calibre - inflammation cytokines (bradykinin, prostacyclin, NO) mediate vasodilation - Fluid exudate - vessels become leaky, Fluid forced out of vessel - Cellular exudate - abundant in neutrophils
5 cardinal signs of acute inflammation
Rubor (redness due to dilation of small vessels) - Dolor (pain) - Calor (heat) - Tumor (swelling from oedema or a physical mass) - Loss of function
Causes of acute inflammation
Microbial infections - Hypersensitivity reactions - physical agents - Chemicals - Bacterial toxins - Tissue necrosis
Neutrophil action in acute inflammation
Margination - migrate to edge of blood vessel (plasmatic zone) due to increase in plasma viscocity and slow flow - Adhesion - selectins bind to neutrophil, cause rolling along the blood vessel margin - Emigration + diapedesis - movement out of blood vessel through or inbetween endothelium onto basal lamina and then vessel wall - Chemotaxis - site of inflammation
Neutrophil action at the site of inflammation
Phagocytosis - Phagolysosome + Bacterial killing - Macrophages clear debris
Outcomes of acute inflammation
- Resolution - normal - Supporation - pus formation - Organisation - granulation tissue + fibrosis - Progression - excessive recurrent inflammation -> becomes chronic and fibrotic tissue
Chronic inflammation
Subsequent and prolonged response to Tissue injury - Lymphocytes, Macrophages and plasma cells - Longer onset, long lasting effects - Autoimmune diseases
Causes of chronic inflammation
Resistance of infective agent - Endogenous + materials - Autoimmune conditions - Primary granulomatous diseases - Transplant rejection
Macroscopic appearance of chronic inflammation
Chronic ulcer - Chronic abscess cavity - granulomatous inflammation - fibrosis
Microscopic appearance of chronic inflammation
Lymphocytes, plasma cells and Macrophages - exudate is not a common feature - Evidence of continuing destruction - Possible Tissue necrosis
Cellular cooperation in chronic inflammation
- B lymphocytes - transform into plasma cells and produce antibodies - T lymphocytes - responsible for cell-mediated immunity - Macrophages - respond to chemotactic stimuli, produce cytokines (interferon alpha and beta, IL1, IL6, IL8, TNF-alpha)
What are granulomas?
- An aggregate of epithelioid histocytes (macrophages) - Granuloma + eosinophil -> parasite - Secrete ACE as a blood marker
Types of granulomas
- Central necrosis - TB (identified by Ziel-Neelsen stain) - No central necrosis - sarcoidosis, leprosy, vasculitis, Crohn’s disease
What is thrombosis?
Solidification of blood constituents (mostly platelets) forming in vessels
Platelets
NO nucleus, arise from megakaryocytes - Contain alpha granules (Adhesion) and dense granules (aggregation) - Contain lysosomes - Activated, releasing their granules when they come into contact with collagen - Activation forms thrombus in intact vessels
Thrombosis formation (primary platelet plug)
Platelet aggregation, starts the coagulation cascade - Positive feedback loops
Causes of thrombosis (Virchow’s triangle, typically 2 out of these 3)
Endothelial injury (trauma, surgery, MI, smoking) - Hypercoagulability (sepsis, atherosclerosis, COCP, preggomalignancy) - Decreased blood flow (AF, immobility)
Arterial thrombosis
by atherogenesis and plaque rupture - High pressure, low pulse - Thin cool skin, intermittent claudication - Mainly made of platelets - so treat with antiplatelet (aspirin)
Venous thrombosis
Caused by venous stasis - low pressure, High pulse - Rubor, tumour and pain - Mainly fibrin - so treated by anticoagulants (DOACs, warfarin)
Fate of thrombi
- Resolution (dissolves and clears, normal/best case scenario) - Organisation (leaves scar tissue, slight narrowing of vessel lumen) - Recanalisation (intimal cells may proliferate, capillaries may grow into the thrombus and fuse to form larger vessels) - Embolism (fragments of the thrombus break off into circulation)
Formation of the secondary platelet plug (coagulation cascade)
Prothrombin -> thrombin Fibrinogen -> fibrin
What is an embolism
A mass of material in the vascular system able to block in a vessel and block its lumen
Arterial vs venous embolism
Arterial - Lodges in systemic circulation (from left heart) - eg: AF thrombus lodges in carotid artery -> ischaemic stroke Venous - Lodges in pulmonary circulation (from right heart) - eg: DVT thrombus embolises and lodges in pulmonary artery -> pulmonary embolism
Ischaemia
the reduction in blood flow to a Tissue or part of the body Caused by constriction or blockage of the blood vessels supplying it - effects can be reversible - Brief attack - Cardiomyocytes and cerebral neurons are most vulnerable