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140 Cards in this Set
- Front
- Back
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what percent of the body water is intracellular, extracellular and in plasma?
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intracellular - 2/3
extracellular - 1/3 plasma - 5% |
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what controls movement of water and salts generally?
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opposing effects of hydrostatic pressure out & colloid osmotic pressure in
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where does any residual fluid left at the end of inflow at the venular end of the microcirculation go?
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lymphatics
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what conditions lead to increased interstitial fluid?
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increased capillary pressure
decreased colloid osmotic pressure |
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what are the main causes of increased hydrostatic pressure & give at least 2 examples of each?
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impaired venous return
eg CCF, constrictive pericarditis, ascites, venous obstruction/compression (thrombosis, mass) arteriolar dilatation eg heat, neurohumeral dysregulation |
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what are the 5 pathophysiologic categories of oedema?
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increased hydrostatic pressure
reduced plasma osmotic pressure lymphatic obstruction sodium retention inflammation |
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what are the 4 casuses of reduced plasma osmotic pressure?
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nephrotic syndrome (protein losing nephropathies)
ascites (liver cirrhosis) malnutrition protein losing gastroenteropathy |
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what are the 4 causes of lymphatic obstruction?
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inflammatory
neoplastic postsurgical post irradiation |
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what are the 2 causes of sodium retention?
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excessive oral intake + renal insufficiency
increased tubular reabsorption of sodium (renal hypoperfusion or increased renin-angiotensin-aldosterone secretion) |
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what are the 3 inflammatory causes of oedema
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acute inflam
chronic inflam angiogenesis |
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what is anasarca?
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severe & generalised oedema w widespread subcutaneous tissue swelling
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what distinguishes oedema from hydrothorax/ hydropericardium/ hydroperitoneum (ascites)?
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oedema is an abnormal increase in interstitial fluid
others are collections in body cavities |
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what is the difference between transudate & exudate?
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transudate - protein poor oedema caused by increased hydrostatic pressure/decreased colloid pull
exudate - protein rich, caused by inflammation that leads to increased vascular permeability |
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does Na/water retention cause increased hydrostatic pressure or decreased colloid pressure?
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both - intravascular volume expansion causes increased hydrostatic pressure & dilution causes decreased colloid pressure
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draw the pathway leading to oedema from heart failure, liver failure & the decreased protein/protein loss causes?
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robbins fig 4-2
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how does activation of the renin/angiotensin system lead to oedema?
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retains sodium & water -> increased blood volume
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what kind of oedema is SIADH associated with?
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cerebral
not peripheral |
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what parasite can cause oedema & how?
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filiaris
can cause lymphatic fibrosis of inguinal region -> massive oedema of external genitalia & lower limbs (elephantiasis) |
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in what settings can pulmonary oedema be seen?
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LVF
renal failure ARDS pulmonary inflammation/infection |
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when can oedema be immediately life threatening?
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if cerebral - can cone
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what is hyperaemia?
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active process where arteriolar dilatation leads to increased blood flow (eg inflammation, exercising skeletal muscle)
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what is congestion?
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passive process resulting from reduced outflow of blood from a tissue (systemic eg cardiac failure or local eg isolated venous obstruction)
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how does hyperaemic tissue look different to congested tissue?
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hyperaemic - red because tissues congested w oxygenated blood
congested - dusky due to red cell stasis & accumulation of deoxygenated haemoglobin |
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what consequences does chronic passive congestion have?
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hypoxia w potential ischaemic tissue injury & scarring
can have capillary rupture w small haemorrhagic foci & haemosiderin staining of skin w subsequent catabolism of extravasated red cells |
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what is the definition of haemorrhage?
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extravasation of blood into the extravascular space
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what is the containment of haemorrhage in a tissue called?
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haematoma
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what are petechiae usually caused by? (3)
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locally increased intravascular pressure
thrombocytopaenia defective platelet fn eg uraemia |
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what distinguishes petechiae, purpura & eccymoses?
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petechia are minute, purpura >3mm; ecchymoses (bruises) are >1-2cm
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what causes purpura?
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same causes as petechia plus vasculitis, trauma or increased vascular fragility (eg amyloidosis)
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what compounds characterise colour changes in a bruise?
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haemoglobin (red blue)
-> bilirubin (blue green) -> haemosiderin (gold brown) |
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what percent of blood loss can be tolerated without haemodynamic instability by healthy adults?
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20% rapid
larger slowly depending on site |
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what is pathologic counterpart of haemostasis?
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thrombosis
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what are the 3 components of haemostasis & thrombosis?
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vascular endothelium
platelets coagulation cascade |
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what is the normal sequence of events at a site of vascular injury?
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arteriolar vasoconstriction (transient)
primary haemostasis - formation of platelet plug secondary haemostasis consolidates initial platelet plug with fibrin meshwork & recruitment of extra platelets thrombus formation (polymerised fibrin & platelet aggregates) |
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what happens in secondary haemostasis?
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tissue factor exposed -> combines w factor VII to initialte coag cascade-> thrombin generation -> thrombin cleaves circulating fibrinogen -> fibrin meshwork
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what happens in primary haemostasis?
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subendothelial extracellular matrix exposed (highly thrombogenic) -> platelets adhere -> platelets change from round to flat -> granules released -> more platelets recruited -> haemostatic plug aggregates
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how important is endothelium on regulation of homeostasis?
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key - balance of anti and prothrombotic activities of endothelium determines whether thrombus forms, propagates or dissolves
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what is the normal state of endothelium & how can it become procoagulable?
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usually anti platelent, anticoagulant & fibrinolytic but becomes pro coagulant after injury/activation?
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what apart from trauma can activate endothelium to become prothrombotic? (4)
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infectious agents
haemodynamic forces plasma mediators cytokines |
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what are the normal antiplatelet effects of the endothelium?
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non activated platelets don't adhere to endothelium
endothelium normally produces prostacyclin & NO which impede platelet adhesion |
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what are the fibrinolytic effects of normal endothelium?
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rPA synthesised by endothelium cleaves plasminogen -> plasmin which in turn cleaves fibrin -> degrades thrombin
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what are the anticoagulant effects of normal endothelium?
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heparin like molecules inactivate thrombin, factors Xa & IXa
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what platelet effects result from endothelial injury?
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platelets contact underlying ECM & then subsequent platelet adhesion occurs via von willebrand's factor normally produced by endothlium
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what are the procoagulant effects seen in endothelial injury?
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tissue factor synthesised in response to cytokines (eg TNF, IL1) or bacterial endotoxins -> activates extrinsic clotting cascade
activated endothelium augments factors IXa & Xa |
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what are the antifibrinolytic effects seen in endothelial injury?
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inhibitors of plasminogen activators
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summarise the role of endothelium in haemostasis?
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intact endothelium is inhibitory to platelet formation & clotting but injured or activated endothelial becomes procoagulant
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what is the role of platelets in haemostasis? (2)
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1. haemostatic plug that seals vascular defects
2. surface to recruit/concentrate activated coag factors |
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what are the 3 stages of platelet activity after encountering ECM constitutents like collagen & von willebrand's factor?
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adhesion & flattening
secretion (release reaction) aggregation |
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what kind of platelet secretion is especially important & why?
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releasing contents of dense bodies
- Ca++ important in coag cascade - ADP potent activator of platelet aggregation |
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what does thromboxane A2 do?
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platelet derived stimulus that amplifies platelet aggregation
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summarise the stages of platelet aggregation?
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initially is reversible but then thrombin generated by coag cascade leads to platelet contraction & an irreversibly fused haemostatic plug
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what are the 2 mechanisms by which thrombin stabilises the platelet plug?
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1. binds to platelet membrane -> induces further aggregation -> platelet contraction -> irreversible secondary haemostatic plug
2. converts fibrinogen to fibrin, cementing the platelets in place |
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what does ADP activation of platelets achieve?
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conformational change in GpIIb-IIIa receptor -> binding to fibrinogen
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how does clopidogrel affect platelets?
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binds to ADP
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how does aspirin affect platelets?
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irreversible COX inhibitor
permanent blocks platelet derived prostaglandin TxA2 (which activates platelet aggregation & is a vasoconstrictor) nb aspirin also inhibits endothelial prostaglandin PGI2 but endothelium can resynthesise active COX & overcome blockade |
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what is the most important coagulation factor?
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thrombin
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what are the components of the complex at each step of the coag cascade? (3)
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enzyme
substrate cofactor (reaction accelerator) |
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where are the compoenets of the coag cascade assemebled & what holds them together?
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assembled on phospholipid surface
held together by Ca++ ions |
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what coag factors require vitamin K?
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II, XII, IX, X
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where do the intrinsic & extrinsic pathways converge?
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activation of factor X
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what is the difference between intrinsic & extrinsic pathways?
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an artefact of in vitro testing - the extrinsic pathway required an exogenous trigger but intrinsic only needed exposing factor XII to a surface.
in the body there are several connections between the 2 pathways |
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which pathway is most physiologically relevant for coagulation in the setting of vascular injury?
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extrinsic - activated by tissue factor (factor III) expressed at sites of injury
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what does prothrombin time asses? what about partial thromboplastin time?
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prothrombin - extrinsic pathway (VII, X, II, V)
APPT - intrinsic |
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what restricts coagulation cascade to the site of the injury to prevent runaway clotting of the whole vascular tree?
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anthithrombins
protein C & S TFPI |
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how does heparin mimic anticoagulation cascade?
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antithrombin III activated by binding to heparin like molecules on endothelium
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what limits the size of a thrombus? what is the primary mediator of this?
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fibrinolysis
largely mediated through the enzyme plasmin which breaks down fibrin & interferes w its polymerisation |
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what is tPA? where is it normally made & why is it usefully therapeutically?
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tissue plaminogen activator - synthesised by endothelium & most active when bound to fibrin - useful therapeutically as confines fibrinolytic activity to sites of recent thrombus
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what is virchow's triad?
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endothelial injury
stasis/turbulent blood flow hypercoagulability of blood |
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what does virchow's triad signify?
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three primary abnormalities that lead to thrombus formation
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where is endothelial injury particularly important?
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thrombus formation in the heart/arterial circulation (normally high flow rates might otherwise impede clotting by platelet flow speed & wash out of coagulants)
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what kind of endothelial damage needs to occur for thrombus to form?
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doesn't need to be physically disrupted for a clot to occur - just need to disturb the balance of coagulants/anticoagulants ie dysfunctional cells can clot with intact endothelium
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what is laminar blood flow?
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blood cellular components flow centrally, separated from endothelium by slower moving plasma
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what are the 3 mechanisms by which stasis/turbulence leads to clotting?
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- promotes endothelial activation via flow induced changes in endothelial gene expression
- disrupts laminar flow, bringing platelets into contact w endothelium - prevents washout of activated clotting factors & inflow of clotting factor inhibitors |
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when is turbulence/stasis clinically relevant? (6)
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stasis in aneurysms/dilatations
turbulence in ulcerated atherosclerotic plaques non contractile myocardium in MI rheumatic mitral valve stenosis -> L atrial dilatation -> increased clotting risk (esp w AF) hyperviscosity (eg polycythemia vera) -> small vessel stasis sickle cells -> obstructions |
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what is hypercoagulability?
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any alteration of coag pathways which predisposes to thrombosis
primary (genetic) vs secondary (acquired) |
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what percent of caucasians have factor V leiden?
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2-15%
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what is factor V leiden?
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a mutation that makes factor V resistant to cleavage by protein C
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what is the second most common hypercoagulable mutation?
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prothrombin mutation -> elevated prothrombin levels
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what are the secondary risks for thrombophilia?
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prolonged rest
MI AF tissue injury cancer prosthetic valves DIC HITTS APLAS |
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what causes HITS?
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after unfractionated heparin, antibodies recognising heparin/platelet factor 4 complexes on surface of platelets as well as these complexes on endothelial cells -> activation, aggreation & consumption of platelets -> platelet activation & endothelial damage -> prothrombotic state (despite heparin & low platelet counts)
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what is thought to be the prothrombotic mechanism in APLAS?
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antibody binds to binding sites on plasma proteins like prothrombin which are unveiled by phospholipids -> mlti effect where endothelium is injured + platelets & complement activated
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what is secondary APLAS?
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APLAS if they already have an autoimmune disease eg lupus
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where do thrombi develop?
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anywhere in the cardiovascular system - usually at sites of turbulence in cardiac/arterial & sites of stasis in venous
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where do thrombi extend?
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towards the heart - arterial thrombi tend to grow retrograde whereas venous thrombi grow in direction of flow
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what are mural thrombi?
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thrombi in heart chambers or aortic lumen
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what are the most common sites of occlusive arterial thrombi
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in order:
coronary, cerebral & femoral |
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what four events occur to a thrombus after it has formed?
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propagation
embolisation dissoution organization/recanalization |
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what is propagation of thrombi?
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accumulation of additional platelets & fibrin
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what is embolisation?
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dislodging of thrombus which then travels to other sites
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what is dissolution of thrombus?
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result of fibrinolysis (older thrombi are more resistant as have extensive fibrin deposition & crosslinking - why tPA is only effective in first few hours)
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what happens when a thrombus is organised?
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ingrowth of endothelium, smooth muscle & fibrobasts with capillary channels re-establishing continuity of original lumen
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what is the fate of a thrombus that is continuously recanalized?
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may turn into connective tissue which is incorporated into vessel wall
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where are most superficial venous thrombi in the leg?
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saphenous veins in the setting of varicosities
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what is the embolisation risk of superficial leg thrombi? what are the other risks?
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low risk of embolus
predispose to overlying varicose ulcers |
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in what percentage of individuals are DVTs asymptomatic & why
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50% because venous obstructions can be offset by collateral channels
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what factors in trauma/surgery/burns lead to hypercoagulability?
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immobilisation
plus vascular insult procoagulant release from injured tissue increased hepatic synthesis of coag factors altered tPA production |
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what is migratory thrombophlebitis/Trousseau syndrome?
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increased risk of thromboembolism in disseminated cancers: inflamm & coag factors (tissue factor & factor VIII) released from tumour cells
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what is a major cause of arterial thrombosis?
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atherosclerosis
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what is DIC?
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sudden or insiious onset of widespread fibrin thrombi in the microcirculation
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why is DIC aka consumption coagulopathy?
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platelets & coag proteins are consumed
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is DIC a primary disease?
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no, it's a potential complication of any condition associated with widespread activation of thrombin
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what is an embolus?
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detached intravascular solid, liquid or gaseous mass carried by the blood to a site distant from its point of origin
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what percentage of PEs originate from DVTs? how much more common are DVTs than PEs?
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95% PEs have DVT origin
but DVTs occur 2-3x more commonly than PEs |
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what is paradoxical embolism?
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an embolus passes through an interatrial/interventricular defect & gains access to systemic circulation
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what percentage of PEs are clinically silent & why?
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60-80%
because they are small |
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in what kind of pulmonary vascular does PE usually cause haemorrhage or infarct?
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small end arteriolar pulmonary branches
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what is the possible end point of multiple emboli over time? (2)
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pulmonary HT
R ventricular failure |
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in what kind of pulmonary vascular does PE usually cause haemorrhage or infarct?
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small end arteriolar pulmonary branches
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what is the possible end point of multiple emboli over time? (2)
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pulmonary HT
R ventricular failure |
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what percentage of arterial emboli come from the heart?
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80% from intracardiac mural thrombi
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what conditions are intracardiac mural thrombi associated with?
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2/3 w L ventricular wall infarcts
1/4 w L atrial dilatation & fibrillation the rest from aortic aneurysms, thrombi on ulcerated atherosclerosis or valvular vegetation |
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what percentage of systemic emboli are of unknown origin?
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10-15%
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what are the two major sites of arteriolar embolisation?
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lower extremities 75%
brain 10% |
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what percentage of those w severe skeletal injuries have fat embolism? what percentage of those have clinical finding?
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90%
but 10% have findings |
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what characterises fat embolism (4)
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pulmonary insufficiency
neurological symptoms anaemia thrombocytopaenia |
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what is the typical onset of fat embolism?
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sudden onset 1-3 days post injury of tachypnoea, dyspnoea, tachycardia
irritability/restlessness -> delirium/coma |
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where does the thrombocytopaenia in fat embolism come from?
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platelet adhesion to fat globules & subsequent aggregation/splenic sequestration
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where does the anaemia in fat embolism come from?
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similar to thrombocytopaenia - red cell aggregation/haemolysis
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what effect do free fatty acids released from fat globules have on endothelium?
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toxic
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what volume of air is required to have occlusive effect in the pulmonary circulation? what cardiac/neuro?
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about 100cc of air for pulmonary affect
only need a very small volume trapped in cardiac/neurosurgery for effect |
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what is decompression sickness?
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gas embolism occuring when there is a sudden decrease in atmospheric pressure -> nitrogen comes out of solution in blood/tissues
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what are the complications of chronic gas embolism?
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persistent gas emboli in skeletal system -> multiple ischaemic foci esp at femoral heads, tibia & humeri
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what is the bends?
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rapid formation of gas bubbles in skeletal muscle & joint tissues
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what is the chokes
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gas bubbles in the pulmonary vasculature -> oedema, haemorrhage, focal atelectasis or emphysema
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how common is amniotic fluid embolism?
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rare - 1 in 40000
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what is the mortality of amniotic fluid embolism?
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80%
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what happens if the patient survives the initial amniotic fluid embolism crisis?
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pulmonary oedema
plus DIC in 50% (amniotic fluid is thrombogenic) |
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what is an infarct?
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an area of ischaemic necrosis caused by occlusion of arterial supply or venous drainage
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what conditions are required for venous thrombosis to cause infarct?
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in organs with a single efferent vein eg testis/ovary
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how do we classify infarcts?
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red (haemorrhagic) vx white (anaemic)
septic vs bland (infection vs none) |
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when do white infarcts occur?
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with end arterial occlusion where adjacent capillary beds can't seep into adjoining area
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when do red infarcts occur?
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in venous or dual circulations or loose tissues (eg lung) where blood can collect into infarcted zone
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when are the margins of infarcts well defined?
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after enough time has passed to allow a narrow ring of inflammation to form
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when are haemorrhagic infarcts the rule?
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in the lung
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what is the dominant histologic characteristic of infarction?
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ischaemic coagulative necrosis
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what ultimately replaces most infarcts? what is the exception
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a scar
except in brain -> liquefactive necrosis |
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what determines the eventual outcome of infarcts? (4)
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1. nature of vascular supply
2. rate at which occlusion develops 3. vulnerability to hypoxia 4. oxygen content of blood |
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after what time do neurons undergo irreversible damage when deprived of their blood supply?
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4 min
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how long do myocardium have to survive total ischaemia?
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20-30 min
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what is the definition of oedema?
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abnormal increase in interstitial fluid
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