VPP 211: General Veterinary Pathology (1+1)

ACUTE INFLAMMATION AND VASCULAR CHANGES

Aetiology (Causes) of inflammation

• Infectious agents – bacteria, fungi, virus etc.
• Chemical agents – acids, alkalies etc.
• Physical agents – burns, electricity, radiation, cold
• Immunological reactions – Ag – Ab reactions
• Nutritional imbalances – vitamins, minerals
• Necrotic tissue

Vascular changes in acute inflammation

Julius conheim(1839 – 1884)

• Changes in blood vessels following injury (tissue damage, microbial virulence factors, etc)
• Momentary vasoconstriction
• Vasodilation (arteriolar dilatation – nerve stimuli from axonal reflex also)
• Increased blood flow
• Opening of new capillary beds
• Brought about by substances - Histamine  − chemical mediators of inflammation

Changes in the rate of flow

• Increased vascular permeability (Vascular leakage)

Leakage of plasma proteins

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↓ Intravascular osmotic pressure

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↑ Osmotic pressure of interstitial fluid

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↑Outflow of fluid into interstitium

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Haemoconcentration

Essential for movement of leucocytes into ECF

• Haemoconcentration
• Endothelium becomes leaky
• Activated endothelial cells release ptostaglandin which causes vascular dilatation, cytokines (IL-1, TNF, TGF-β) which are chemotactic to leucocytes and procoagulants for coagulation. Besides perivascular mast cells degranulate and release histamine which increase post capillary permeability, heparin antagonizes coagulation and angiogenic and leukotrienes which induce pain. Substance P is released by the nerve.
  • By increasing the capillary bed in the area
  • Swelling of endothelial cells
  • Hemoconcentration
  • Margination of leucocytes

Slowing of blood flow – from capillary filing and endothelial swelling

• Margination
• Rolling – selectin – selectin receptors
• Pavementing- as surface ligands increase → Leucocytes
• Adhesion- integrin, ICAM
• Emigration

Diapedesis of erythrocytes

• Movement of erythrocytes outside the blood vessel during iinflammation.

Chemotaxis

• Unidirectional migration of cells towards a chemical attractant
• It is the force that attracts leucocytes into the inflamed tissue

Chemotactic agents

Exogenous	Endogenous
Bacterial products	Chemical mediators like C5a (complement) Leukotriene B4 Cytokines (interleukins)

Phagocytosis

• It is the process of taking particulate matter in the cytoplasm by cells

Pinocytosis

• Taking in fluid particles
• Discovered by ELLIE METCHNIKOFF in 1884

Steps in Phagocytosis

1. Recognition and Attachment
• Micro-orgranisms are not recognized by neutrophils and macrophages until they are coated by naturally occurring serum proteins
2. Engulfment
• Regurgitation during feeding
• During degranulation leakage of hydrolytic enzymes, metabolic products ( H ₂ O ₂ ) and lysozymes from neutrophil into outside medium cause tissue damage. Kinins released cause vascular dilatation and nerve stimulation. Proteases liberated induce tissue damage, platelets aggregate and release PAF4 which is chemotactic to neutrophils and Coagulation factors causing polmerization of fibrin. PDGF stimulates fibrinogenesis andangiogenesis. Monocytes transform into macrophages to release collagenase, antimicrobial proteases, elastases, complements, IL-1 and TNF. Fever, myalgia and endothelial cell activation. Activation of systemic response leads to releaseb of acute phase proteins (complement, fibrinogen, etc) from the liver and leucocytes and increased haematopoiesis in bone marrow and lymphopoiesis in lymph node and spleen.
3. Killing and Degradation
• Brought about by reactive oxygen species like hydrogen peroxide( H ₂ O ₂ )
• Myeloperoxidase enzyme present in lysosome of neutrophils

H ₂ O ₂ → HOCl (hypochlorous radical)

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Active antimicrobial (kills bacteria)

• Myeloperoxidase deficient neutrophils
  • superoxide, hydroxyl radicals → H ₂ O ₂