Acute inflammation and outcomes Flashcards
Define inflammation
Rapid response to injury in vascalarised tissue
What are the 2 phases of inflammation?
Vascular phase
Cellular phase
What happens in the vascular phase?
Vasodilation to increase permeability
Increase in blood flow to area of injury
Plasma proteins leave the capillaries and form inflammatory exudate
What happens in the cellular phase?
Cells leave the bloodstream and travel to the site of injury
Cells are recruited and activated
Phagocytosis
What are the 5 cardinal signs of inflammation?
Rubor (Redness) - Vasodilation
Calor (Heat) - increased blood flow
Tumor (Swelling) - Edema
Dolor (Pain) - Physical/chemical factors at nerve endings
Functio Laesa (loss of function) - Pain causing guarding reflex
What is the vascular phase mediated by?
Mast cells (Histamine) Endothelial cells (Nitric oxide)
What is the inflammatory exudate composed of?
Plasma
Proteins - Fibrinogen mainly
Neutrophils, macrophages and lymphocytes
What can the inflammatory exudate be described as?
Serous - watery/plasma
Haemorrhagic - RBCs, damaged vessels
Fibrinous - Fibrinogen, sticky
Purulent - pus
What do the Endothelial cells do?
Secrete Nitric oxide, Cytokines and other mediators
What do Polymorphonuclear leukocytes do?
Eliminate microbes and dead tissue
What do the plasma proteins do?
Mediate inflammation, eliminate microbes, release clotting factors and kininogens
What do the Lymphocytes do?
Mediate immune response
What do the Monocytes do?
Turn into macrophages and phagocytose
What do mast cells do?
Secrete mediators (Histamine)
What do fibroblasts do?
Secrete ECM
How do neutrophils leave the bloodstream?
Selectins are expressed which roll along the endothelium until a neutrophil is bound. Once bound, integrins are expressed which causes adhesion to the endothelium. CD11 and CD18 aggregate and cause a conformational change. PECAM-1 binds and mediates transendothelial emigration.
How does phagocytosis take place?
Foreign body is bound by Phagocyte
Actin-driven pseodopodium further binds the foreign body
Foreign body is engulfed by internalisation
Membrane fusion forms phagosome
Lysosomes fuse with phagosome and release digestive enzymes
Foreign body is broken down
What is opsonisation?
When a complement protein tags a foreign body for recognition by phagocytes
Name the 2 cell-derived preformed mediators and their origins.
Histamine - Mast cells, Basophils and platelets
Serotonin - Platelets
Name the cell-derived newly synthesised mediators and their origins.
Prostaglandins - Leukocytes, Mast cells
Leukotrienes - Leukocytes, Mast cells
Platelet activating factor - Leukocytes, Endothelial cells
Reactive oxygen species - Leukocytes
Nitric oxide - Macrophages, Endothelial cells
Cytokines - Macrophages, leukocytes, Mast cells, Endothelial cells
Neuropeptides - Leukocytes, nerve fibres
Name the plasma-protein derived mediators for complement activation.
C3a, C3b, C5a, C5b-9
Name the plasma protein derived factor XII actvators.
Kinin system
Fibrinolysis system
Which mediators cause vasodilation?
Histamine, Prostaglandin, Nitric oxide, bradykinin, Platelet activating factor
Which mediators cause increased permeability?
Histamine (briefly), C3a, C5a, bradykinin, leukotrienes, Platelet activating factor, nitric oxide
Which mediators cause Neutrophil adhesion?
IL-1, IL-8, TNFa, Platelet activating factors, leukotrieneB4, C5a, Chemokines
Which mediators cause Neutrophil chemotaxis
C5a, LeukotrieneB4, Bacterial components, chemokines, IL-8
Which mediators cause fever?
IL-1, TNF, Prostaglandins
Which mediators cause pain?
Prostaglandins, bradykinin
Which mediators cause tissue necrosis?
Free radicals, lysosomal granule components
Name the source and action of histamine
Mast cells, basophils and platelets
Vasodilation, increased vascular permeability, endothelial activation
Name the source and action of serotonin
Platelets
Vasoconstriction
Name the source and action of prostaglandins
Mast cells, leukocytes
Vasodilation, pain, fever
Name the source and action of leukotrienes
Mast cells, leukocytes
Increased vascular permeability, chemotaxis, leukocyte adhesion and activation
Name the source and action of platelet activating factor
Leukocytes, endothelial cells
Vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidative burst
Name the source and action of reactive oxygen species
Leukocytes
Killing of microbes, tissue damage
Name the source and action of nitric oxide
Endothelium, macrophages
smooth muscle relaxation, killing of microbes
Name the source and action of cytokines
Macrophages, lymphocytes, endothelial cells, mast cells
Local: endothelial activation
Systemic: Acute-phase response, septic shock
Name the source and action of chemokines
Leukocytes, activated macrophages
Chemotaxis, leukocyte activation
What are the 4 enzyme cascades activated by plasma mediators?
Coagulation system
Kinin system
Fibrinolytic system
Complement system
Name the source and action of complement
Liver
Leukocyte chemotaxis and activation, opsonisation, vasodilation
Name the source and action of kinins
Liver
Increased vascular permeability, smooth muscle contraction, vasodilation, pain
Name the source and action of proteases
Liver
Endothelial activation, Leukocyte recruitment
What are the systemic effects of acute inflammation?
Increased [neutrophil] in blood Fever Fatigue Loss of appetite Increased acute phase proteins in blood
What are the acute phase proteins?
Fibrinogen
C reactive protein
Serum amyloid A
Ferritin
What does SEPSIS stand for?
Shivering Extreme pain Pale skin Sleepy I feel like I might die Short of breath
What are the 4 main outcomes of acute inflammation?
Tissue resolution - normal tissue structure and function returned
Repair by fibrosis - Scar formation
Abscess formation
Chronic inflammation
Define parenchyma and stroma
Parenchyma - Function cells
Stroma - support cells
What is the difference between resolution and repair?
Resolution - restore normal function with minimal or no evidence of damage
Repair - remodel for strength, Lacks some function
What factors affect the outcome of acute inflammation?
Severity of damage
Capacity of stem cells in area of damage to divide: Labile, Stable, Permanent
Type of agent which caused damage
What are the stages of healing by fibrosis?
Granulation tissue - Macrophages, fibroblasts and angiogenesis
Fibrosis and scar formation - Fibroblasts generate matrix, scar is formed from collagen
Remodelling - vessels in area are reduced and pale scar remains
What are the stages of wound healing?
Inflammatory phase - Macrophages produce growth factors
Proliferative phase - Building of tissue, Fibroblasts secrete matrix components, angiogenesis, Epithelial cells grow over wounds
Wound contraction and remodelling phase - Collagen breaks down, wound contracts, decreased vacularity
What does Epidermal growth factor do?
Regenerates endothelium
What does Fibroblast growth factor do?
Fibroblast proliferation, angiogenesis, epithelial cell regeneration
What does Platelet derived growth factor do?
Activate fibroblasts to secrete collagen
What does Transforming growth factor a do?
Regeneration of epithelial cells
What does Transforming growth factor b do?
Fibroblast proliferation, collagen synthesis
What does Insulin-like growth factor 1 do?
Synergisitc effects with other growth factors
What does Tumour necrosis factor do?
Stimulates angiogenesis
How are abscesses formed?
Collection of pus due to infection with pyogenic bacteria
What is chronic inflammation?
Inflammation of a prolonged duration
Which cells are involved in chronic inflammation?
Lymphocytes, plasma cells, eosinophils, mast cells
