Pathology of inflammatory response Flashcards
What is acute inflammation?
Short lived and neutrophil rich. Consists of inflammatory exudate, oedema and pus.
What is calor?
Heat associated with inflammation
What is dolor?
Pain associated with inflammation
What are the microbial causes of inflammation?
Pathogen associated molecular patterns (PAMPS) such as LPS, peptigoglycan and lipotechoic acid
Virulence factors
How does recognition occur for inflammation?
Damage associated molecular patterns (DAMPS) are found on WBCs which are released when membrane lysis occurs of damaged cells which initiate inflammation.
What is an exudate?
Fluid discharged from blood vessel, typically during inflammation. Inflammatory exudate is rich in protein and leukocytes.
What is a transudate?
Fluid which passes through the membrane/tissue which contain little/no proteins, which develops from imbalance in hydrostatic or oncotic pressure. This can cause oedema.
THis is the fluid in serous inflammation that occurs in skin burns.
What are the microvascular changes in inflammation?
Formation of inflammatory exudate containing fibrinogen. This enters the interstitial space causes oedema and leads to pus
What is the role of fibrinogen in inflammation?
Converted into fibrin to form a mesh scaffold for healing and repair.
What is the process of acute inflammation?
Pathogen binds to C3 for activation of complement cascade. C3b opsonises pathogen while C5a and C3a induce increased vascular permeability and expression of adhesive proteins for attachment and exudation of WBC. Endothelium further drives this with production of NO.
What is an inflammatory exudate?
Fluid which leaks out of blood vessels rich in protein and leukocytes which move to the site of injury.
What is pus?
Purulent (pus) exudate which is full of dead neutrophils and dying cells and bacteria.
What is chronic inflammation?
Long lived, driven by lymphocyte, plasma cells and macrophage rich
What are the cellular mediators of inflammation?
Vasoactive amines, arachidionic acid derivatives, lysosymal enzymes, oxygen radicals and Nitric oxide
What are the vasoactive amines?
Histamine and tyramine
What are the arachidionic acid derivatives?
Leukotrienes, thromboxane and prostacycline and prostaglandins.
What is the kinin system?
Proteins in the blood which cause inflammation such as bradykinin.
What are the plasma derived mediators of inflammation?
Kinin system, complement system and coagulation and fibrinolytic system.
What is Hageman factor?
It is inactive Factor XII/Pro-coagulation factor which initiates the intrinsic pathway.
What is plasmin?
Serine protease which acts to dissolve fibrin blood clots.
What is the effect of acute inflammation on the body?
Increases bone marrow WBC production causing fever, and tachycardia. Vasodilation causes drop in BP, loss of appetite and vomiting. It alters liver metabolism and HPA axis by increasing cortisol production.
What causes fever?
Pyrogens produced by a bacterium. The heat of fever increases the performance of immune cells and resets temperature control of the hypothalamus
What is an exogenous pyrogens?
The bacterial product lipopolysaccharide, peptidoglycans or lipoteichoic acid.
What is endogenous pyrogens?
Cytokines such as IL-1 and IL-6 produced by WBC which induce fever.
Why is altered liver metabolism occur?
Increases production of acute phase inflammatory proteins such as fibrinogen in response to inflammatory cytokines.
How is the HPA axis affected in inflammation?
Increased cortisol production which causes general malaise
Why does congestion occur during infection?
Bacteria cause release of inflammatory exudate with protein rich fluid containing fibrin into alveolus. This accumulates in the alveoli and solidifies, creating pulmonary consolidation.
What is consolidation?
Accumulation of inflammatory exudate on alveoli. Neutrophils and RBC enter alveolus causing fluid to spread to adjacent alveoli and cause solidification
Why does grey hepatisation occur?
Macrophages recruited digest dead neutrophils and fibrin mesh
What is resolution?
End stage of inflammation with the restoration of normal tissue when architecture is intact. If architecutre is not intact, repair stage is initiated instead.
What is abscess?
Accumulation of pus containing dead neutrophils and chronic inflammatory cells such as fibroblasts and macrophages enclosed in fibrin due to a bacterial infection. It occurs in chronic inflmmation because it fails to drain and is poorly vascularised and difficult to treat with antibiotics so may require surgical excision.
What is supparative inflammation?
Inflammatory exudate contains large amounts of pus during due to the chemotaxis of many neutrophils in areas of infection which undergo autolysis. The release of proteases causes tissue destruction and forms an abscess.
What is fibrinous inflammation?
Inflammatory exudate has a high plasma protein content. This typically occurs in membrane lined cavities such as the pleura and pericardium.
What are the features of chronic inflammation?
Failure to resolve inflammation means the continued recruitment of macrophages which proliferate can lead to harm to the body such as formation of an abscess , excess scarring driven by fibroblasts and development of autoimmunity.
How is inflammation resolved?
Marked by the production of the anti-inflammatory mediators lipoxins, resolvins, maresins and protectins to reduce tissue infiltration by WBCs and the cytokines release. This is to prevent excessive tissue injury and chronic inflammation.
What are the types of chronic inflammation?
Non specific, autoimmune, supparative and granulomatous
What is non specific chronic inflammation?
Formation of granulation tissue, a type of connective tissue which plugs a wound formed of lymphocytes, macrophages and plasma cells. This includes abscesses.
What causes non specific chronic inflammation?
Persistent viral infection.
What is a granuloma?
Cluster of WBC
What are the microscopic features of granulomatous inflammation?
Charactersised by lesions or granulomas containing cluster of macrophages surrounded by lymphcytes
What is the cause of granulomatous chronic inflammation?
Formation of granulomas due to chronic persistent infection, commonly tuberculosis or a T cell-mediated response
What is the microbiology of chronic inflammation?
Organ transplant rejections
Mycobacterium tuberculosis
Unregulated immune response
Mycobacterium tuberculosis
Mycobacterium leprae
fungi
Potozoa
What are the macroscopic features of chronic inflammation?
Ulcers, lesions, abcesses, caesating necrosis, fibrosis, stricture (narrowing of lumen)
What is a sacroid granuloma?
Formation of granulomas in the organs due to chronic inflammation
What are the microscopic features of chronic inflammation?
Infiltrstion of macrophages and lymphocyte, with eosinophils if it is a parasitic infection. Tissue necrosis, granulation tissue, fibrous tissue
What are the microscopic features of acute inflammation?
Innate immune defence such as neutrophils, dendritic cells
What is immunostaining?
Identifying cells based on type such as protein rather than morphology
What is Intra-vital fluorescent multi-photon microscopy?
Used to view biological process in living tissue
What is Formalin fixed paraffin-embedded tissue/ FFPE?
Tissues are embedded in paraffin wax for nucleic acid extraction
Difference between flow cytometry and mass cytometry?
Mass cytometry can analyse more molecules in a given sample but does not always leave cells intact
What is digital spatial profiling?
Used to view tissue which is non destructive of the proteins and RNA to view cellular interactions.
Antibody in placental transfer
IgG
Antibody which is membrane bound
IgD- this is co expressed on B cells
What are lipoxins?
Metabolite of arachidionic acid produced in the gut mucosa which promote anti-inflammatory and inflammation resolution along with resolvins, to inhibit neutrophil entry.
