Haemodynamic disorders thrombosis and shock Flashcards
What are the 5 causes of oedema
- Increased hydrostatic pressure
- Reduced plasma oncotic pressure
- Lymphatic obstruction
- Salt retention
- Leaky endothelium
Give examples of scenarios that result in increased hydrostatic pressure
- Impaired venous return
- CHF
- Constrictive pericarditis
- Ascites (liver cirrhosis)
- Venous obstruction or compression (thrombosis or external pressure e.g mass)
- Lower extremity inactivity with prolonged dependency - Arteriolar dilation
- Heat
- Neurohumoral dysregulation
Give examples of scenarios that reduce plasma oncotic pressure
- malnutrition
- liver cirrhosis (ascites)
- Protein losing glomerulopathies (nephrotic syndrome)
- Protein losing gastroenteropathy
Give examples of clinical scenarios that result in lymphatic obstruction
inflammatory
neoplastic
postsurgical
post-irradiation
Give examples of clinical scenarios that cause salt retention
- Excessive salt intake with renal insufficiency
- Increased tubular reabsorption of Na > renal hypoperfusion, increased renin-angiotensin-aldosterone secretion
Increased endothelial permeability is the pathogenesis of oedema occurring in…
- local anaphylaxis
- adult respiratory distress syndrome
Development of generalised oedema in chronic liver failure involves
- increased renal Na retention
- increased renal renin secretion
- reduced plasma colloid osmotic pressure
Intact endothelium synthesizes and secrete or ‘presents’
- thrombomodulin
- adenosine diphosphatase (ADP-ase)
- prostacyclin (PGI2)
- plasminogen activator
- NO
- Heparin like molecules
What is an exudate
Protein rich fluid that accumulates due to increase in vascular permeability caused by inflammatory mediators.
Protein rich, cloudy due to presence of white cells.
What is a transudate
Non inflammatory and protein poor effusions (e.g heart failure etc)
Normally translucent, straw coloured with the exception of peritoneal effusions caused by lymphatic blockage (chylous effusion), can be milky due to presence of lipid.
Compare and contrast hyperemia and congestion
Both stem from increased blood volumes in tissues.
Hyperemia - active process, active arteriolar dilation (e.g sites of inflammation or muscle during exercise). Leads to increased blood flow and oxygen delivery. RED TISSUE
Congestion - passive process due to reduced venous outflow, can be systemic (CHF) or localised (DVT). CYANOTIC. Can lead to scarring.
Outline the general sequence of events leading to haemostasis at the site of vascular injury
- Arteriolar vasoconstriction
- Occurs immediately, due to neurogenic mechanisms and release of endothelin.
- Transient effect. - Primary haemostasis
- Formation of the platelet plug
- Disrupted endothelium exposes subendothelial vWF and collagen which promotes platelet adherence and activation.
- Activated platelets release secretory granules and change their shape (spiky increasing their surface area)
- Secretion promotes more platelets and aggregation = primary haemostatic plug. - Secondary haemostasis
- Tissue factor is exposed by vasular injury.
- A membrane bound glycoprotein (found in subendothelial cells).
- Tissue factor binds to factor 7, kicks off coagulation cascade. Thrombin cleaves fibrinogen to fibrin = mesh network + potent activator of platelets = more platelets = consolidation of plug. - Clot stabilisation and resorption.
- Fibrin and platelet contract = solid permanent plug.
- Counter-regulatory mechanisms e.g TPA limit clotting to site of injury and eventually lead to clot resorption and repair.
What cells are the central regulators of haemostasis
Endothelial cells, balance between the antithrombic/prothrombotic activites determine if thrombus formation, propogation or dissolution occur.
What shape are platelets are where are they found
- Anucleate disc shaped cell shed from megakaryocytes in bone barrow and float in circulation.
What critical role do platelets play in haemostasis
Formation of primary plug
Provide a surface that binds and concentrates activated coagulation factors.
What two granules do platelets release
- Alpha granules: Have the adhesion molecule P-selectin in their membrane. Contain proteins involved in coagulation (vWF, V, fibrinogen), as well as factors involved in healing like PDGF).
- Dense bodies/delta granules: Contain ADP, ATP, calcium, serotonin, adrenaline.
4 steps involved in formation of primary plug
- Platelet adhesion
- Platelet shape change
- Secretion of granules
- Aggregation
Outline how platelet adhesion works (first step in plug formation)
Mediated by interactions between Gp1b (platelet receptor) and vWF.
Gp1a/IIa also invovled
Outline how platelets change shape (second step in plug formation)
- Go from smooth discs to spiky sea urchins that increase SA.
- Results in a conformational change in cell surface glycoprotein (iib/iiia) which increases affinity for fibrinogen AND translocation of negatively charged phospholipids (bind calcium and acts as sites for assembly of coag complexes)
Outline the secretory step of platelet plug formation
Occurs alongside the change in shape (these two steps are often referred together as platelet activation).
Triggered by multiple factors including thrombin and ADP.
Thrombin activates platelets by GPCR (protease activated receptor).
ADP is a component of dense granules. It acts as mediator for further platelet activation (i.e recruitment).
Activated platelets produce TXA2 which induces platelet aggregation.
Outline the steps in platelet aggregation.
Platelet activation is followed by platelet aggregation.
Conformational change of GPIIa/IIIa allows fibrinogen to bind, which forms a bridge between adjacent platelets.
Initial wave of aggregation is reversible.
Thrombin is then activated, promotes more platelet aggregation + irreversible platelet contraction.
Thrombin also converts fibrinogen into the insoluble fibrin = secondary haemostatic plug.
Following injury to a small artery, the formation of a temporary platelet plug is… (4 things)
- unaffected by therapeutic doses of heparin
- unaffected by therapeutic doses of dicoumarol
- associated with local vasoconstriction
- is not followed by the conversion of insoluble plasma fibrinogen to insoluble fibrin
What does the PT asssess
extrinsic pathway
What does PTT assay scree for
Intrinsic pathway
