Term
|
Definition
-the reaction of vascularised tissue to injurious agents and tissue damage
-cells and exudate accumulate in irritated tissues, generally to pretect from further damage |
|
|
Term
| Name and describe the cardinal signs of inflam |
|
Definition
-Reddening - caused by hyperaemia due to dilation of cap.
-Swelling - due to exudation of fluid from dilated b.v
-Heat - due to incr. blood flow
-Pain - due to release of chemical mediators of pain by damaged tissues
-Loss of function - due to pain and damage to tissues |
|
|
Term
| What 3 things does inflam consist of? |
|
Definition
-vascular changes
-cellular changes
-systemic reactions |
|
|
Term
|
Definition
| chemical mediators derived from plasma proteins or cells and produced in response to or activated by the inflam stimulus |
|
|
Term
| What is the purpose of inflam? |
|
Definition
-destroy, dilute or wall off the injurious agent
-bring the components of the im. syst. into contact w. the injurious agent or damaged tissues
-start the process of healing and repairing damaged tissues |
|
|
Term
|
Definition
-rapid response to injurious agent
-delivery of WBCs and plasma proteins to the site of injury
-primarily exudative i.e. high protein
-lasts few hours - days
-simultaneous activation of the innate im. system |
|
|
Term
| Describe the basic sequence of events in acute inflam |
|
Definition
-momentary vasoconstriction
-dilation of b.v. - first cap. due to release of chem. mediators, then arterioles under influence of local axon reflex
-exudation of fluid
-margination of leukocytes
-emigration of leukocytes by chemotaxis
-emigration of RBCs
-induction of an incr. in temp |
|
|
Term
| How may T be incr in acute inflam? |
|
Definition
-may be locally or systemically
-incr. BF locally
-pyrogens released from neutrophils, eosinophils, macrophages act on T control centres in hypothalamus
-necrosis of damaged tissues
-cellular coat of gram-ve organisms
-ant-AB complexes
-tumours esp. if metastasised |
|
|
Term
| Briefly describe the vascular changes in inflam |
|
Definition
-structural changes to the microvasculature comprising incr. blood flow (HYPERAEMIA) and INCR PERMEABILITY, with haemostasis
-results in SWELLING and OEDEMA |
|
|
Term
| Why do vascular changes in inflam result in haemostasis? |
|
Definition
| damage / constriction of the endothelium triggers the coagulation cascade (end product fibrin), to prevent further blood loss |
|
|
Term
| What causes incr. vacular permealibilty in inflam? |
|
Definition
-endothelial contraction (most common)
-direct injury
-WBC mediated
-delayed prolonged leakage
-transcytosis
-leakage from new b.v. |
|
|
Term
| Why does endothelial contraction result in incr. vasc. permeability? |
|
Definition
-when the cells contract, gaps form between them
-due to release of vasoactive mediators released in response to aetiological agent |
|
|
Term
| How do WBCs cause an incr. vasc. permeability? |
|
Definition
| activated WBCs release toxic oxygen species and enzymes |
|
|
Term
| Why does delayed prolonged leakage result in incr. vasc. permeability? |
|
Definition
| -may involve direct injury causing apoptosis or cytokine activation of endothelial cells |
|
|
Term
| When is incr. vasc. permeability due to delayed prolonged leakage seen? |
|
Definition
-after 2-12 hours and lasts hours-days
-seen in late appearing sunburn in people and w. some bact. toxins and UV radiation |
|
|
Term
|
Definition
| transport across the endothelial cytoplasm via vesicles |
|
|
Term
| Why do new b.v. result in incr. vasc. permeability? |
|
Definition
-endothelial cells aren't yet mature and lack intercellular junctions
-VEGF may cause an increase in transcytosis |
|
|
Term
| What is the purpose of vascular changes in inflam? |
|
Definition
-prevent further blood loss from damaged b.v. by activation of the coag. cascade
-fill any cavities which may have formed with fibrin
-fibrin clot provides a matrix for repair - "scaffolding"
-oedema - dilute toxins and devliver ABs and enzymes
-activates the endothelium to express adhesion mol. to bind WBCs
-Decr. BF and incr. viscosity allows margination of WBCs |
|
|
Term
| Briefly describe the cellular changes in inflam |
|
Definition
-influx and activation of WBCs to the site of injury, where they attempt to eliminate the injurious agent
-also influx of platelets and involvement of cells resident in the tissue: mast cells, macrophages and LCs |
|
|
Term
| In inflam, how to WBCs attempts to remove the injurious agent? |
|
Definition
-phagocytose the agent
and/or
-release proteolytic enzymes and ROI
The WBC also digest and remove necrotic debris |
|
|
Term
| How are mast cells involved in inflam? |
|
Definition
MCs are resident in injured tissues and release histamine, LTs, enzymes and many cytokines
-major role in initition of vasc. and cell. responses
-like basophils they have IgE-R and involved in HS reactions |
|
|
Term
| How are macrophages involved in inflam? |
|
Definition
Macrophages are resident in tissues (remember monocytes in the blood)
-role in innate im syst - phagocytic and secrete most of the cytokines
-also present antigens amd regulate T-cells in adaptive im. resp i.e. APCs
-important later in inflam, after neutrophils |
|
|
Term
| When are neutophils important? |
|
Definition
-in early inflam
-presence indicates pus - they release their granule contens into the inflam exudate to enhance the acute inlam resp. and cause liquefaction to form pus |
|
|
Term
| When are eosinophils important? |
|
Definition
-in HS / allergic reactions
-in some parasitic inf. |
|
|
Term
| When are basophils important? |
|
Definition
-involved in HS reactions
-v. small numbers!
NB: similar to MCs in that cytoplasmnic granules contain histamine and heparin - degranulate when IgE-R cross-link |
|
|
Term
| When are lymphocytes (LCs) important? |
|
Definition
| -key role is in adaptive im response |
|
|
Term
| Why must WBC be activated? |
|
Definition
-to move into tissues - involves extravasation from b.v. and emigration through tissues
-to perform their function in host defence |
|
|
Term
| Which cells does WBC activation apply to? |
|
Definition
-neutophils
-monocytes
-eosinophils
-basophils
-lmyphocytes |
|
|
Term
| How does WBC activation occur? |
|
Definition
| Through the leucocyte adhesion cascade |
|
|
Term
| What occurs in the leucosyte adhesion cascade? |
|
Definition
-initiated in vasc. phase of inflam
-occurs when C / microbes / cytokines bind to R on WBC
-triggers signalling pathway in WBCs, resulting in incr Ca++ and activation of enzymes
i.e. WBC is activated |
|
|
Term
| What are the consequences of WBC activation? |
|
Definition
-modulation of the expresion of adhesion molecules
-phagocytosis
-cytokine secretion
-production of microbiocidal substances-
-production of arachidonic acid metabolites (eicosanoids) |
|
|
Term
Describe the consequence of a leukocye adhesion molecule deficiency
e.g. syndromes in Holstein cattle, Red setters |
|
Definition
-diapedesis is not possible
-neutrophilia
-lack of neutrophils out of vasculature
-recurrent necrotising infections which are fatal before adulthood |
|
|
Term
| Following modulation of expression of adhesion molecules, how do WBCs move into tissues? Sequence of events |
|
Definition
-margination
-temporary adhesion (tethering, rolling)
-adhesion (pavementing)
-diapedesis (/emigration/transmigration)
-chemotaxis |
|
|
Term
| How does margination of WBCs occur? |
|
Definition
-due to vascular changes - incr. vasc. permeability and vasodilation causes incr. viscosity of the blood and causes loss of laminar flow
-so WBCs pushed to edge of bv. |
|
|
Term
| Describe rolling and adhesion of WBCs in WBC tissue emigration |
|
Definition
-initially there are transient, weak on/off adhesions between WBCs and endothelium i.e. rolling
-when the adhesions become more permanent, this leads to pavementing of WBCs |
|
|
Term
|
Definition
| when the b.v. wall is lined with WBC following rolling and adhesions and immediately before diapedesis |
|
|
Term
| What must happen to allow adhesins to form between WBCs and the endothelium of b.v.? |
|
Definition
-endothelium must be activated i.e. must express adhesion molecules
-induced by factors secreted by macrop., MCs, endot. cells in response to injury or by thrombin
-adhesion molecules on WBCs must also be activated (by binding of microbes, cytokines, C) |
|
|
Term
| What factors induce the expression of adhesion molecules on b.v. endothelium? |
|
Definition
|
|
Term
|
Definition
-WBC migrate through the endothelium, then BM, then adhere to ECM
-need to move along a surface which is often fibrin (often provided for by coagulation cascade) |
|
|
Term
|
Definition
-WBCs migrate up a conc. grad of a chemoattractant to the inflam focus
-can occur because R binding also leads to cytoskeletal changes which incr. motility |
|
|
Term
| Give examples of chemoattractants |
|
Definition
-exogenous - bacterial products
-endogenous - components of C system e.g. C5a, C3a
-products of lipogenase pathway e.g. LTB4
-chemokines |
|
|
Term
| Which WBC are phagocytic? |
|
Definition
| macrophages and neutrophils |
|
|
Term
| What are the 3 stages of phagocytosis? |
|
Definition
1) recognition and attachment
2) engulfment
3) killing and degradation |
|
|
Term
| Describe the recognition and attachment phase of phagocytosis |
|
Definition
| via R on WBC surface to the particle or preferentially to an opsonin on the particle |
|
|
Term
| How are recognition and attachment in phagocytosis promoted? |
|
Definition
-opsonisation
i.e. particles coated in opsonins which are recognised by FcR on WBCs |
|
|
Term
| What can act as opsonins? |
|
Definition
| proteins such as IgG and C3 fragments |
|
|
Term
| Describe the engulfment stage of phagocytosis |
|
Definition
-pseudopods (formed by actin polymerisation) flow around the particle to enclose it in a phagosome within the WBC
-phagosome combines w. lysosome to create a phagolysosome |
|
|
Term
| Describe the killing and degradation phase of phagocytosis |
|
Definition
-largely by oxygen-dependent mechanisms
i.e free radicals and others e.g. NO
-degraded by hydrolases |
|
|
Term
| How can phagocytosis result in tissue damage? |
|
Definition
-release of WBC products
-WBC induced injury
e.g. microbiocidal products released into EC space - ROIs, enzymes, eicosanoids
-WBC infiltrate itself can be problem if persistant - cause acute and chronic dz e.g. RA |
|
|
Term
| What happens to neutrophils following phagocytosis? |
|
Definition
| die by apoptosis due to decr. in growth factors |
|
|
Term
|
Definition
-arachidonic acid metabolites from phospholipids in cell memb.
cell memb. phospholipids --> arachidonic acid (AA) --> AA metabolites
-mediators of inflam and short range hormones |
|
|
Term
| Name AA metabolites / eicosanoids with the associated enzymes |
|
Definition
AA --(LOX)--> Leukotrienes (LT), lipoxins
AA --(COX1&2)--> Prostaglandins (PG), thromboxane (TXA) |
|
|
Term
| What are the 4 major enzyme systems involved in regulating inflam? |
|
Definition
-complement cascade
-coagulation cascade / clotting system
-fibrinolytic system
-kinin system |
|
|
Term
| Describe the secretion and activation of proteins in the C cascade |
|
Definition
-secreted by liver as precursors
-activated after tissue injury exposure to other proteins e.g. Igs or endotoxins |
|
|
Term
| What systems are the complement proteins involved in? |
|
Definition
-part of innmate and adaptive immunity
-involved in vasc. changes of inflam i..e. incr. permeability and vasodilation
-also involved in chemotaxis, opsonisation
i.e. important in inflam |
|
|
Term
| Which C proteins are esp. important in inflam? Why? |
|
Definition
C3a and C5a - mediate incr. vasc. permeability and vasodil.
C5a -chemotactic for neutrophils, noncytes and basophils
-also activate the lipoxygenase pathway
Also C3b - opsonin |
|
|
Term
| Name the 3 pathways of the C cacade and what triggers them |
|
Definition
-classical - by ABs
-Alternative ("tick over") - microorganisms, clotting factors, kinins
-Lectin - binding of bact. proteins to lectin |
|
|
Term
| What is the end result of the coagulation cascade? |
|
Definition
| Thrombin activation and so fibrin clot formation |
|
|
Term
| Describe the end pathways in the coagulation cascade |
|
Definition
Thrombin converts fibrinogen -->fibrin
Thrombin also cnverts XIII --> XIIIa
XIIIa then converts fibrin --> cross-linked fibrin i.e. a clot |
|
|
Term
| What is factor XII / XIIa also called? |
|
Definition
XII = Hageman factor
XIIa = activated Hageman factor |
|
|
Term
| What are the 2 ways the coag. cascade is associated w. inflam? |
|
Definition
1) thrombin binds activated R on endothelium, platelets and sm. musc. cells. Leads to:
-activation of endothelial cells
-upregulation of cytokine production (incl. chemokines, PAF), NO, and COX induction (and so production of PG and TXA)
2)inflam induces coagulation by damaging endothelium |
|
|
Term
| Why is the fibrin clot important? |
|
Definition
-prevents further blood loss
-fills any cavities if formed
-provides a matrix for migration of WBCs, fibroblasts and endothelial cells |
|
|
Term
| Why does the fibrinolytic system do? |
|
Definition
-generates plasmin - lyses fibrin clot and so couterbalances the coag. cascade
-also cleaves C3 and activates XII, and so amplifies the cascade
-fibrin lysis leads to release of FDPs which are chemotactic for neutrophils |
|
|
Term
|
Definition
| Fibrin Degradation Proteins - released in the lysis of fibrin and chemotactic for neutrophils |
|
|
Term
| What protein is most associated with the kinin system? |
|
Definition
Bradykinin
-released due to activation of XII |
|
|
Term
|
Definition
-bradykinin is a vasoactive peptide
-bv. dilation and incr. permeability
-incr sensitivity to pain
-incr. AA metabolism |
|
|
Term
| Of the plasma protein systems, which plasma proteins are considered most important? |
|
Definition
-bradykinin
-C3a, C5a
-thrombin |
|
|
Term
| What other chemical mediators are involved in inflam, excluding the 4 main plasma protein systems? |
|
Definition
1)vasoactive amines
2)Platelet Activating Factor (PAF)
3)Cytokines
4)AA metabolites / eicosanoids
5)Nitric oxide (NO)
6)Lysosomal enzymes
7)Oxygen derived free radicals
8)Hypoxia induced factors |
|
|
Term
| Name vasoactive amines. What releases them and what is their role in inflam? |
|
Definition
-histamine / serotonin
-from MCs, basophils, platelets
-generally cause vaodil, incr. vasc. perm, smooth musc. contraction |
|
|
Term
| What releases PAF and what is its role in inflam? |
|
Definition
-from MCs, neutro., macrop., LCs, platelets
- similar role to histamine at low conc., with vasocon. at high conc.
-plus pro-inflam effects e.g. chemotaxin, stimulates WBCs |
|
|
Term
| Within AA metabolism, what does the cycloxygenase pathway result in? role? |
|
Definition
Prostaglandins and thrombaoxane
-vasoconstriction e.g. TXA2
-vasodil e.g. PGI2, PGE1, PGE2
-hyperalgesia (skin) PGE2
-Fever PGE1, PGE2
-Thrombosis TXA2 |
|
|
Term
| Within AA metabolism, what does the lipoxygenase pathway result in? role? |
|
Definition
Leukotrienes:
-incr. vasc. perm.
-chemotaxis
-vasocon
Lipoxins
-secreted mainly by platelets
-pro and anti-inflam |
|
|
Term
| What releases NO and what is its role in inflam? |
|
Definition
-from endothelium, macro.
-vasodil
-some anti-inflam and anti-microbial effects |
|
|
Term
| What is the role of lysosomal enzymes in inflam? |
|
Definition
| degrade bact and the EC matrix |
|
|
Term
| What is the role of oxygen derived free radicals in inflam? |
|
Definition
| EC release can cause incr. expression of cytokines, chemokines, endothelial adhesion mol., and damage or activate the endothelium |
|
|
Term
| What is hypoxia induced factor? |
|
Definition
-a pro-inflam mediator
-produced by cells deprived of oxygen
-activates many genes associated w. inflam e.g. VEGF to incr. vasc. perm. |
|
|
Term
| How is acute inflam terminated? |
|
Definition
-decr. in level of mediators (have a short half life)
-decr. in growth factors (leads to apoptosis e.g. of neutrophils)
Also stop signals:
-switcg from LT to anti-inflam lipoxins
-release of antiinflam TGF-beta from macrophages
-inhin of macrophages and production of TNF ny neural impulses |
|
|
Term
| What are the systemic effects of acute inflam called? |
|
Definition
-Acute Phase Response
-Systemic Inflammatroy Resp. Syndrome (SIRS) when severe |
|
|
Term
| What are the systemic effects of acute inflam? |
|
Definition
-pyrexia
-incr. (or decr) blood levels of APP
-leukocytosis
-decr. plasma Fe and Zn conc
-incr. plasma Cu conc
-incr HR and BP
-Decr. sweating
-shivering
-anorexia
-somnolence
-malaise |
|
|
Term
| What causes pyrexia in inflam? |
|
Definition
-pyrexia is in reponse to pyrogens which stimulate PG synthesis in the hypothalamus
-exogenous pyrogens eg. LPS/endotoxin, stimulate the release of endogenous pyrogens IL1, TNF from macrophagesHow |
|
|
Term
|
Definition
Acute Phase Proteins - plasma proteins which are mediators or inhibitors of inflam
Common examples - C reactive protein (CRP), fibrinogen, SAA (serum amyloid A protein) |
|
|
Term
| What triggers the release of APPs? |
|
Definition
| -released in resp. to cytokines IL6, IL1, TNF |
|
|
Term
|
Definition
| elevated WBCs in peripheral blood |
|
|
Term
| Why is there a decr in plasma Fe and Zn in inflam? |
|
Definition
| Microbes and host compete for these |
|
|
Term
| Why is there an increase in plasma Cu conc. in inflam? |
|
Definition
|
|
Term
|
Definition
| when the systemic response associated with inflam is inappropriately and/or dysregulated |
|
|
Term
| Give an example of septic shock / SIRS |
|
Definition
Overwhelming bact. infection - large doses of LPS causes release of excessive amounts of mediators of inflam esp TNF and IL1
-mediators then present in circulation rather than located at site of infection |
|
|
Term
| What is DIC and what causes it? |
|
Definition
DIC (disseminated intravascular coagulation) - due to high levels of TNF e.g. in septic shock
results in thrombosis from 2 simultaneous reactions
1)LPS and TNF induce tissue factor (TF) expression on endothelial cells
-TF initiated coagulation via the extrinsic pathway
2)LPS and TNF also inhibit natural anti-coag. mechanisms - decr. the expression of TR pathway inhibitor (TFPI) and endothelial cell thrombomodulin |
|
|
Term
|
Definition
-excessive amounts of mediators of inflam esp. TNF and IL1
-high levels of TNF cause DIC and thrombosis
-cytokines at high levels cause liver injury and impaired function and so failure to maintain normal glucose levels
-overproduction of NO leads to systemic vasodilation which causes heart failure and lack of perfusion pressure
-neutrophils activated by TNF BEFORE leaving b.v. so cause damage within the vasculature resulting in oedema
-ultimately there is ischemia due to DIC and decr. perfusion leading to anaerobic metabolism
-depletion of glucose/glycogen stores, accumulation of lactate and decr. ATP
-ion pumps fail, loss of membr. integrity, influx of ions and loss of protein grad., losse oxidatie phophorylation
-mutliple organ failure and death |
|
|
Term
| How is acute inflam classified? |
|
Definition
-According to the character of the fluid that leaks out through the gaps in the endothelium
-no. and type of WBCs that migrate out through the b.v. |
|
|
Term
|
Definition
-rel. mild
-thin, low protein fluid
-tissue contains clear/sl. yellow watery fluid or forms raised, fluid filled vesicles on skin or m. memb |
|
|
Term
| Serous inflam possible aetiologies |
|
Definition
Heat, allergic reactions
e.g. early pneumonia, blisters, pitting oedema |
|
|
Term
| Describe catarrhal inflam |
|
Definition
-involves mucus produced normally by epi. cells which are forming glands or by goblet cells,
-grossly see yellow/grey/green, viscous, mucoid discharge |
|
|
Term
| Catarrhal inflam possible aetiologies |
|
Definition
| low virulence microbes e.g. human common cold, mucous colitis |
|
|
Term
| Describe fibrinous inflam |
|
Definition
-involved in more severe endothelial damage and so incr. vasc. permeability and loss of larger proteins e.g. fibrinogen
-fibrinogen polymerises and forms HIGH PROTEIN, fibrinous exudate
-characteristic of mucous and serous membranes |
|
|
Term
| Fibrinous inflam possible aetiologies |
|
Definition
| bact infection esp in body cavities, joints, lung, meninges |
|
|
Term
| Describe suppurative / purulent inflam |
|
Definition
-pus is present i.e. exudate i.e. high protein
-accumulation of HIGH PROTEIN fluid (oedema) which incl. large numbers of WBCs (mostly neutophils), necrotic cells and bact
-may be present focally w. chronic inflam and within abscesses |
|
|
Term
| Describe haemorrhagic inflam |
|
Definition
| Includes haemorrhagic exudate which includes other components such as serum, WBCs, fibrin |
|
|
Term
| Haemorrhagic inflam possible aetiologies |
|
Definition
Virulent organisms and some toxins which damage vasc. endothelium
e.g. anthrax, pasteurellosis |
|
|
Term
| What is the difference between a transudate and exudate? |
|
Definition
Transudate is low protein
Exudate is high protein |
|
|
Term
| Which morphological type of inflam is characterised by transudate? |
|
Definition
|
|
Term
|
Definition
local defect / excavation on surface of organ or tissue
-breaches musc. mucosa/ BM (which erosion does not) |
|
|
Term
|
Definition
-loss of epithelial layers
-muscularis mucosa and BM remain intact |
|
|
Term
| Potential consequence of acute inflam |
|
Definition
-fatality
-resolution by regeneration in association w. defence mechanisms (may be assisted by therapy)
-repair by fibrosis
-abscess formation
-development to chronic inflam - depends of persistence of agent and amount of damage caused |
|
|
Term
|
Definition
-a focal collection of purulent inflam tissue
-central necrotic area containing pus, surrounded by rim of neutrophils, then fibrous tissue capsule |
|
|
Term
| When do abscesses develop? |
|
Definition
| when the acute inflam resp. fails to eliminate the inciting agent |
|
|
Term
| Briefly describe chronic inflam |
|
Definition
-gen. prolonged inflam
-characterised by cellular proliferation and active inflam w. tissue destrucution and repair (fibrosis) occuring simultaneously |
|
|
Term
| When does chronic inflam occur? |
|
Definition
-following acute inflam
e.g. failure to eliminate injurious agent - microbe isolated from im. response or resistant to degradation
-result from recurrent episodes of acute inflam e.g. pyoderma
-may be chronic from outset w. an exuberant or long-lasting im. resp e.g. AI dz
-may be associated w. R microbes which have unique biochem. characteristics e.g. Mycobacterium in TB
-occasionally idiopathic |
|
|
Term
| Describe the cellular infiltration associated w. chronic inflam |
|
Definition
| Mononuclear cells - predominately macrophages, also LCs and PCs |
|
|
Term
| Describe the healing associated w. chronic inflam |
|
Definition
| Proliferation of fibroblasts and angiogenesis to form GRANULATION TISSUE, which ultimately matures to FIBROUS TISSUE |
|
|
Term
| Describe the general gross appearance of chronic inflam |
|
Definition
-lesions often grey/cream
-firm due to fibrosis
-may present as nodules (e.g. granulomas, abscesses) or an organ may have a pitted surface (due to contraction of fibrous tissue) |
|
|
Term
| What are chemotactic stimuli for monocytes? |
|
Definition
-chemokines released from other activated macrophages/LCs/other cells
-C5a
-growth factors (GF) e.g. platelet derived GF (PDGF), transforming GF-alpha (TGF-alpha)
-fragments of collagen and fibronectin |
|
|
Term
| What are enlarged / multinucleated macrophages called? |
|
Definition
-incr size = epitheliod
-fused/multinucleated = multinucleated / giant cells |
|
|
Term
| When do multinucleated cells arise? |
|
Definition
-due to fusion of several macrophages
-in response to FB or persistent IC pathogens |
|
|
Term
| What are epitheliod cells adapted for? How? |
|
Definition
-adapted for biosynthesis and protein secretion
-incr. lysosomal enzyme content
-secrete biochemically active substances e.g. cytokines, GFs, enzymes, ROIs
-leads to tissue injury and so give them an incr. ability to phagocytose and kill microbes |
|
|
Term
| How are macrophages activated? |
|
Definition
-cytokines e.g. IFN from sensitized LCs
-NK cells
-LPS/endotoxin - cause innate im. activation which leads to release of ROIs, NO, IFNs
-other chem. mediators |
|
|
Term
| Summarise the function of macrophages |
|
Definition
-eliminate injurious agent
-initiate repair via fibrosis and angiogenesis
-cause influx of other cells
-process ant. for presentation to effector cells of adaptive im. resp.
-release a no. of chemical mediators / factors |
|
|
Term
| What can activated macroophages produce? |
|
Definition
-ROIs
-nitrogen intermediates e.g. NO
-cytokines
-chemoattractants
-GFs |
|
|
Term
| What causes the release of GF from macrophages? |
|
Definition
| hypoxia, low pH, high lactate conc |
|
|
Term
| What do GFs released from macrophages stimulate? |
|
Definition
|
|
Term
| What is the name of chronic inflam in which macrophages predominate? |
|
Definition
| granulomatous inflammation |
|
|
Term
| Including macrophages, what cells are involved in chronic inflam? |
|
Definition
-LCs
-PCs
-eosinophils
-MCs
-platelets
-fibroblasts
-endothelial cells
-neutrophils |
|
|
Term
| How do macrophages and LCs interact birectionally in chronic inflam? |
|
Definition
-macrophages present antigens to Tcells and produce cytokines (e.g. IL-12) to stimulate Tcells
-activated Tcells produce cytokines (e.g. TNF, IFN-alpha) which activate macrophages |
|
|
Term
| What is granulomatous inflam? |
|
Definition
| -a pattern of chronic inflam in which monocytes/macrophages predominate |
|
|
Term
| When is granulomatous inflam seen? |
|
Definition
-often in immunologically mediated infections e.g. TB
-often in non-infectious conditions e.g. in repsonse to FB |
|
|
Term
| What are the 2 main types of granulomatous inflam? |
|
Definition
-diffuse granulomatous inflam
-nodular i.e. granuloma |
|
|
Term
| Describe a nodular granuloma |
|
Definition
| -high turnover of macrophages, w. high macrop. death and replacement |
|
|
Term
| When are nodular granulomas seen? |
|
Definition
| Most commonly associated w. TB and some fungal inf. |
|
|
Term
| Describe the microscopic structure of a granuloma |
|
Definition
centrally the agent +/- necrosis +/-neurophils/pus
-surrounded by macrophages (activated, epitheliod and giant)
-surrounded by LCs +/- PCs and further macrophages
-older granulomas are enclosed by fibroblasts/fibrous tissue
-in caseous necrosis there may also be central mineralisation |
|
|
Term
| Describe foreign body granulomas |
|
Definition
| -LOW turnover of macrophages w. little macrophage death (c.f. nodular granuloma in resp to TB) |
|
|
Term
| When do granulomas cause a cell mediated im. resp? |
|
Definition
| when granulomas form in resp. to insoluble particles, usually microbes, IC microorganisms and fungi |
|
|
Term
| When may an eosinophilic granuloma form? |
|
Definition
e.g. parasites
or idiopathic |
|
|
Term
|
Definition
| the growth of cells/tissues to replace lost structures |
|
|
Term
| What does regeneration require? |
|
Definition
| an intact c.t. scaffold / EC matrix |
|
|
Term
| How does the regenerative capacity of tissue vary? |
|
Definition
-some tissues have great regenerative capacity e.g. c.t., b.v., fat, surface epi, liver (although this is compensatory growth - incr. size of existing lobes rather than replacing damaged ones)
-some tissues have ltd regeneration e.g. ligaments, tendons, cartilage
-so tissues are unable to regenerate e.g. neurons, cardiac muscle (except in birds, some neonates) |
|
|
Term
|
Definition
| a combination of regeneration and fibrosis |
|
|
Term
|
Definition
| when there is damage to the c.t. scaffold (ECM) and so the damaged is "patched up" |
|
|
Term
|
Definition
-skin wound - epithelial regeneration and dermal fibrosis
-substantial tissue damage / necrosis in tissues which can regenerate
-after abundant fibrin exudation - cannot be cleared and so becomes organised |
|
|
Term
|
Definition
| the formation of granulation tissue w. prolif of fibroblasts and angiogensis/neovascularisation |
|
|
Term
| What is tissue remodelling? |
|
Definition
| the replacement of GT with fibrous tissue |
|
|
Term
|
Definition
-surface is roughened / granular, pink and moist
-builds up to the level of adjacent skin and above ("proud flesh")
-capillary loops are perendiular to the surface and so it bleeds easily but no nn. endings |
|
|
Term
| Describe GT microscopically |
|
Definition
| basketweave pattern - capillaries perpendicular to surface, fibroblasts parallel to the surface |
|
|
Term
| What are the 2 main ways angiogenesis occurs? |
|
Definition
-from pre-existing vessels
-from mobilisation of endothelial precursor cells (EPCs) from bone marrow |
|
|
Term
| Describe angiogenesis from pre-existing vessels |
|
Definition
-vasodil and incr. perm. (vasc. responses of acute inflam)
-degradation of ECM surrounding the b.v. and BM of the b.v. by proteases
-migration of endothelial cells across a protein scaffold (e.g. fibrinogen/fibrin) to an angiogenic stiumulus (e.g. VEGF from mesenchymal cells)
-proliferation of endo. cells
-maturation of endo. cells
-remodelling of capilliary tubes
-recruitment of support cells e.g. pericytes, sm. muscle |
|
|
Term
| Describe fibroblast proliferation / migration |
|
Definition
-deposition of plasma proteins (e.g. fibrinogen) due to inc. permeability of b.v.
-provides a scaffold for fibroblast migration
-migration and proliferation of fibroblasts
-fibroblasts deposit collagen |
|
|
Term
| What stimulates migration and prolif of fibroblasts? |
|
Definition
| GFs, IL-1, TNF from platelets, macrophages and endothelium |
|
|
Term
| What are the 3 overlapping phases of healing? |
|
Definition
1. Inflam, incl. haemostasis
2. Proliferation - GT formation and re-epithelisation
3. Remodelling - wound maturation and contraction |
|
|
Term
| When does healing by 1st intention occur? |
|
Definition
| w. clean, uninfected, surgical incisions which have been closed e.g. w. sutures |
|
|
Term
| Briefly describe what happens in 1s intention healing |
|
Definition
-narrow incision fills w. clotted blood
-fibrin plug surface dehydrates to form a scab
-replaced by collagen scar following GT deposition |
|
|
Term
| Describe the stages of healing by 1st intention |
|
Definition
-hameostasis and brief acute inflam phase
-healing phase
-epithelisation
-granulation tissue formation |
|
|
Term
| Describe the haemostasis and acute inflam phase of 1st intention healing |
|
Definition
-vasospasm so platelets aggregate and adhere to exposed collagen
-narrow incision fills w. blood, which clots to form a FIBRIN PLUG (hameostasis)
-neutophils arrive and phagocytose debris
-macrophage follow and replace neutrophils by day 3, perform the same function and secrete cytokine |
|
|
Term
| Describe the healing phase of 1st intention healing |
|
Definition
-this is the proliferative phase
-re-epithelisation
-GT laid down |
|
|
Term
| Describe the epithelisation phase of 1st intention healing |
|
Definition
-begins in acute inflam phase
-at margins of the wound, desmosomes between viable epi. cells dissolve and actin is produced (so the cell can flatten, spead out and move/migrate)
-epithelial cells fuse in midline |
|
|
Term
| What affects the speed of epithelisation in 1st intention healing? |
|
Definition
-most rapid if surface is moist and well oxygenated
-slowed by scab presence |
|
|
Term
| Describe the formation of GT in 1st intention healing |
|
Definition
-by day 5 the space is filled by GT
-there is collagen deposition w. some bridging |
|
|
Term
| What is the situation in 1st intention healing by the 2nd week? |
|
Definition
-still some collagen being laid down
-inflam has gone
-vessels are regressing |
|
|
Term
| In 1st intention healing, will the tensile strength of the wound return to normal? |
|
Definition
| No, but nearly (to 70-80%) |
|
|
Term
| When does 2 intention healing occur? |
|
Definition
| skin w. more extensive loss of cells and tissue / wound w. separated edges |
|
|
Term
| Describe 2nd intention healing |
|
Definition
Same events occur as in 1st intention healing, plus:
-larger fibrin clot
-more pronounced inflam reaction
-more GT production
-epithelium has larger area to cover so takes longer
-also wound contraction due to formation of myofibroblasts (to decr. gap between dermal edges) |
|
|
Term
| What can impair wound healing? |
|
Definition
-nutrition e.g. protein, Vit C deficiency which are required for collagen synthesis (guinea pigs require dietary source of vitC)
-other concurrent dz.
-GCC inhibit collagen synthesis e.g. therapeutically or endogenously raised (Cushings)
-wound infection, necrosis, haematomas, FBs
-mechanical factors - excessive mvmt/ lack of immobilisation
-size of wound
-site - well vascularised heal well |
|
|
Term
| What are the potential consequences of impaired wound healing? |
|
Definition
-inadequate GT/scar formation which can lead to wound breakdown or ulceration
e.g. when inadequate vascularisation
-contracture i.e. excessive contraction of the wound. Can cause deformity and loss of function
e.g. esp. w. burns
-healing w. excessive fibrosis and angiogenesis when there is inadequate control of repair - can lead to exuberant c.t. scar formation w. excessive collagen |
|
|
Term
| Name the different types of bone formed in the healing of fractured bones |
|
Definition
-Pro-callus - the formation of GT in the first 24hours - due to penetration of mesenchymal cells and new bv. to the clot
-woven bone - the initial, immature bone formed (not structurally useful, too brittle)
-primary callus - initial disorganised meshwork of woven bone trabeculae which bridges the gap between the bone ends
-secondary callus - mature lamellar bone - replaces woven bone following remodelling and mineralisation |
|
|
Term
| Briefly describe healing of fractures bone |
|
Definition
-haemorrhage and clot formation
-inflam and necrosis of any tissue which has lost its blood supply
-cytokines/GF stimulate repair
-pro-callus / GT within first 24 hours
-# end remodel, necrotic cells absorbed by osteoclasts
-immature woven bone present at ~36hrs
-cartilage may form and may undergo endochondral ossifcation to form trabeculae bone
-primary callus bridges gap between bone ends
-secondary callus forms |
|
|
Term
| Why is GT in bone slightly different to that in the skin? |
|
Definition
Mesenchymal cells in bone are able to differentiate to form bone and cartilage
-because cytokines leads to development and activation of osteoprogenitor cells which can differentiate to osteoblasts (and fibroblasts and chondroblasts, depending on environment) |
|
|
Term
| What removes necrotic bone in bone healing? |
|
Definition
| Osteoclasts absorb necrotic bone |
|
|
Term
| What is the consequence of a bone fracture being inadequately immobilised? |
|
Definition
-lead to formation of an abnormal callus made of mostly fibrous tissue and cartilage
-may lead to a delayed, non-union or false joint formation |
|
|
