Acute and chronic inflammation Flashcards
Define acute inflammation
- A rapid response to deliver leukocytes and plasma proteins to sites of infection or tissue injury; short duration
- Examples are acute appendicitis, acute bronchitis, abscess
Define chronic inflammation
- Inflammation of prolonged duration (weeks or months), in which inflammation, tissue injury and attempts at repair co-exist, in varying combinations
- Examples are tuberculosis, autoimmune diseases
What is the purpose of inflammation broadly?
- Inflammation is a defensive reaction (innate immune response) of a macro-organism against injury caused by trauma, toxic chemical, or an invading pathogen
- Protective response, but can be harmful - components of inflammation capable of destroying microbes can also injure normal surrounding tissue
What is the purpose of acute inflammation?
- Alert body and initiate appropriate immune response
- Limit spread of infection or injury
- Protect injured site from becoming infected
- Eliminate dead cells/tissue
- Create conditions required for healing
What are the factors that cause acute inflammation?
- Infections
- Bacteria
- Viruses
- Parasites
- Fungi
- Toxins
- Tissue damage due to:
- Physical agents - frost bites, burns, radiation (ionising, UV)
- Chemical agents - chemical burns, irritants, bites
- Mechanical injury and ischemia - Trauma, tissue crush, reduced blood flow
- Foreign bodies
- Splinters
- Sutures
- Dirt
What are the factors that cause chronic inflammation?
- Failure to close acute inflammatory reactions - Persistent infections (viruses, mycobacteria, parasites, fungi
- Misdirected inflammatory reaction - harmless environmental substances (allergies), self-antigens (autoimmune disease)
- Chronic inflammation underlyling many disorders - cancer, atherosclerosis, alzheimer, tpye 2 diabetes
Describe the signs acute inflammation
- Heat - Increased blood flow and metabolic activity
- Redness - Increased blood flow (hyperaemia) to injured area
- Swelling - Fluid accumulation due to permeability of vessels
- Pain - Release of pain mediators; pressure on nerve ends
- Loss of function - Damage
Describe the systemic changes that can occur as a result of acute inflammation
- Fever
- Endogenous pyrogens (IL-1, TNF- alpha)
- Exogenous pyrogens (microbial components)
Pyrogens are a group of substances that cause fever and shock. As seen, edogenous pyrogens (such as those listed cytokines) and exogenous pyorogens cause fever
- Neutrophilia
- GM-CSF (cytokine) stimulation of bone marrow to replenish dead neutrophils
- Acute phase reactants - These are molecules that are elevated as a result of acute inflammation
- C-reactive protein (CRP), fibrinogen, complement, serum amyloid A protein (SAP)
- Produced in the liver
- Induced by the cytokines IL-6, IL-1, TNF-alpha
- Increased fibrinogen means RBCs begin stacking = faster sedimentation rate (rate at which RBCs settle)
- Complications - In rare cases causing a severe systemic inflammatory reaction (sepsis) or inflammatory response syndrome (SIRS)
Describe the stages of an acute inflammatory response
- Vascular - Acute changes in local vasculature. Vasodilation, plasma exudation, oedema
- Cellular - Infiltration of inflammatory cells. Cell recruitment, phagocytosis, NETosis (type of cell death)
- Humoral - Release of inflammatory mediators. Complement, plasma factors, clotting cascade, cytokines, chemokine
- Resolution - Inflammation is controlled and self-limiting. Healing, regeneration, repair of tissue
Describe what happens during the vascular events of acute inflammation
What molecules induce these events to happen?
Vasodilation:
- Increase in vascular diameter
- Induced by histamine and serotonin released by injured cells, mast cells, macrophages
- Results in hyperaemia (increase BV to area, leads to redness, heat)
Increased vascular permeability (micro vessels):
- Leads to leakage of fluids into tissues (swelling)
- As exudate accumulates, pressure increases, nerve endings stimulated by excess fluid and inflammatory mediators (pain)
- Endothelial cell activation increasing their expression of adhesion molecules
Leucocytes + plasma proteins exit vessels, enter inflammation site to deal with infection
Endothelial cells constriction- gaps occur due to contraction (e.g myosin and shortening of individual endothelial cells)
- Loss of proteins (especially albumin and fibrinogen) from place into the tissue, increases osmotic pressure, leads to fluid leakage to area, causes oedema
- Cell transmigration - chemotaxis
Inflammatory exudate (due to increased vessel permeability)
- Water. salts, small plasma proteins (fibrinogen), inflammatory cells, red blood cells -> these get out of vessels and enter tissues or serous cavities
Transudate = fluid leaks due to altered osmotic/hydrostatic pressure; vessel permeability normal
Describe the types of inflammatory exudate
- Serous:
- A few cells, no/few microbes
- Fluid derived from plasma, secreted by mesothelial cells
- Serous cavities (pleura, peritoneum, pericardium)
- Skin blisters (burns, viral infections)
- Purulent (fibrino-purulent):
- Pus - many leucocytes (neutrophils), dead cells, microbes
- Pus-producing bacteria (pyogenic) e.g staphylococci, acute appendicitis, abscess (localised collection of purulent inflammation)
- Fibrinous:
- Fibrin deposition (derived from fibrinogen in plasma)
- Large vascular leaks (fibrinogen exits blood and enters tissue)
- Serous cavities (meninges, pleura, pericardium)
- Can lead to scarring if not cleared (fibroblasts → collagen)
- Haemorrhagic:
- Red blood cells predominate
- Blood vessel ruptures, trauma
What cells are mediators of inflammation?
- Macrophages
- Neutrophils
- Mast cells
- Platelets
What are the humoral factors that mediate inflammation?
- Complement
- Plasma factors
- Clotting cascade
- Cytokines
- Chemokines
Describe the role of tissue resident macrophages in inflammation
- Generally first tissue resident cell to recognise an invading pathogen through pattern recognition receptors on their cell surface
- Macrophage becomes activated, engulfs bacterium and then immediately produces mediators of inflammation for example, prostaglandins, leukotrienes and platelet activating factor (PAF)
- Macrophage then secretes inflammatory cytokines and chemokines
Describe the actions of the proinflammatory cytokines
- Activated tissue resident macrophages secrete the inflammatory cytokines:
- IL-1 - Activates vascular endothelium, activates lymphocytes, local tissue destruction, increases access of effector cells, causes a fever and production of IL-6
- IL-6 - Lymphocyte activation, increased antibody production, causes fever, induces acute-phase protein production
- CXCL-8 (IL-8) - Chemotactic factor recruits neutrophils, basophils, and T-cells to site of infection
- IL-12 - Activates NK cells, induces the differentiation of CD4 cells into TH 1 cells
- TNF- alpha - Activates vascular endothelium and increases vascular permeability, which leads to increased entry of IgG, complement, and cells to tissues and increased fluid drainage to lymph nodes. Causes fever, mobilisation of metabolites, shock
- These cytokines act locally + play key role in forming inflammatory response
Describe the role of mast cells in inflammation
- Secrete histamine
- Chemical signals released by activated macrophages + ,mast cells at injury site cause endothelial activation, vasodilation, increased vascular permeability
