Lec 27-Pharmacology of inflammation Flashcards
5 cardinal signs of inflammation
-Redness (rubor)- due to increased blood flow
-Swelling (Turgor)- oedoma cause by increased blood flow (Vasodilation)
-Heat (Calor)- heat and metabolism
-Pain (Dolor)
-Loss of function
Wheal and flare
Under what conditions does inflammation appear
Inflammation is not a disease but a consequence of injury or infection/disease
- Cut
- Burn
- Infection
- Toxic insult
- Also RA; asthma; allergies
Acute or chronic inflammation
ACUTE -Rapid in onset -Duration: days-weeks -Changes in blood flow -Increased vascular permeability -Accumulation of protein rich oedema fluid, WBC CHRONIC -Present weeks/months after insult -Greater tissue destruction (fibroblasts can't act the same as the tissue) -Cellular infiltrate -More fibrous tissue present
Possible outcomes of acute inflammation
- Resolution
- Suppuration- abscess formation
- Healing-scar
- Chronic inflammation
What is the stereotypical response in acute inflammation
- Local changes to the microcirculation
- Increased blood flow in capillaries
- Increased permeability
- Escape of plasma and plasma proteins to form a serous exudate
- Escape of WBC’s
Changes in vasculature 1) blood flow
- Possible immediate transient venue constriction (smooth muscle response
- Widespread dilation of arterioles and venues- Hyperaemia (X10 more blood flow)
- Constriction of veins, leading to local increase in pressure
- Leakage of plasma leads to slowing of blood flow in vessels (stasis), encouraging cell adhesion and clotting
2) vascular permeability
- Increased pressure causes increased leaking
- Inflammatory exudate proteins at 35-50g/L
- Extravascular contact activates clotting cascade (plasma protein come in contact with collagen)
- Exudate carrying foreign matter carried to lymph glands, where immune response initiated (dilute toxins, wash area, transport microbes)
WBC recruitment
- Expression of adhesion molecules
- Emigration (neutrophils 2-9mins)
- Directed to site of injury/infection by chemotaxis
- Neutrophils predominate in first 24 hours
Role of the Neutrophils (PMN’s)
- Life 3-4 days
- Die at the inflammatory site
- Phagocytose, engulf and remove agent
- Microbial killing is achieved by: lysosomal enzymes; free radicals generated in the respiratory burst (NO, this chemical is incredibly reactive, this therefore reacts with membranes, organelles and DNA)
- If neutrophils engulf a inert object (asbestos) they won’t destroy compound but causes chronic damage to surrounding cells
Morphological factors
- Cardinal signs (triple response, wheal and flare)
- Severe skin injury- blister
- Epithileal injury- ulceration
- Boil- collection of neutrophils and debris= pus. bakes e.g. staph infection
Effects of acute inflammation- should be beneficial
- Dilution of toxins
- Plasma protein release (antibodies)
- Fibrin formation- delays bacterial spread
- Plasma mediator system achieved
- Cell nutrition
- Promotes immunity
Harmful effects
-Swelling- obstruction of breathing
-Interference with blood flow- schema- meningitis
-Inappropriate inflammation
+Type | hypersensitivity- allergy
+Type |V hypersensitivity- Autoimmune disease
Resolution of acute inflammation
-Removal of stimuli
-No permanent loss of function
-associated with healing
OR Incomplete
-Excessive exudate and necrosis lead to scarring
Chronic inflammation
- Main WBC is the macrophage
- Healing and repair co-exists with inflammation
- Fibroblasts important- fibrosis is main cause of loss of function
- E.g. RA; IBS
Chronic inflammation
-Progression form acute \+Chronic abscess e.g. BONE \+Prostheses \+Foreign embedded material- wood -Or chronic from the outset \+Toxic substance- asbestos \+Fungal infections \+Intracellular infection- TB leprosy
