Pathology - Fluid/Haemodynamics Flashcards
What is oedema and what are the causes and the difference in composition of fluid?
-increased fluid in the interstitial spaces or body cavity
1) non-inflammatory (low protein transudates)
- increased hydrostatic pressure = chronic heart failure
- decreased plasma osmotic pressure = cirrhosis, nephrotic syndrome
- lymphatic obstruction = neoplastic
- sodium retention = excessive salt
2) inflammatory (high protein exudates)
- increased vascular permeability = acute/chronic inflammation, infection, tissue necrosis, foreign body, immune
What factors govern the movement of fluid between vascular and interstitial spaces
hydrostatic pressure
colloid osmotic pressure
normal capillary walls (most proteins remain intravascular)
What are the clinical features of heart failure
- cardiac: 3rd heart sound, displaced apex beat, AF, murmur, JVP elevation
- lung: dyspnea, orthopnea, APO, pleural effusions
- renal: fluid retention, pedal edema, AKI
- hepatic: congestion, ascites, cirrhosis
What is the pathogenesis of cardiogenic edema
- decreased cardiac output and renal perfusion
- secondary aldosteronism
- increased blood volume/venous pressure
How does increased hydrostatic pressure cause edema
forces fluid out of vessels, mostly due to impaired venous return caused by:
heart = congestive heart failure veins = obstruction or compression (thrombosis, external pressure, inactivity) arteries = arteriolar dilation (heat)
What is the sequence of events that occurs to produce haemostasis after a vascular injury
1) arteriolar vasoconstriction: occurs immediately, reduced blood flow to area, augmented by endothelin
2) primary haemostasis: formation of platelet plug
3) secondary haemostasis: coagulation cascade leading to formation of a thrombus
4) activation of counter-regulatory mechanism: serves to restrict the haemostatic plug
Describe the process of primary haemostasis
- the formation of a platelet plug
1) endothelial injury exposes subendothelial vWF and collagen
2) platelets bind to endothelial wall via vWF and collagen, which activates platelets to release some granules
3) platelets change shape, which causes an increased affinity of glycoprotein to fibrinogen
4) platelets secrete their granule content: alpha (fibrinogen, factor 5, PDGF), delta (ADP, ATP, Ca+2, TXA2)
5) platelets aggregate by fibrinogen forming bridges between adjacent platelets (stimulated by TXA2 and ADP)
What are the 2 main roles of platelets
1) formation of primary haemostatic plug
2) provide surface to recruit and concentrate coagulation factors
How do platelets adhere at the site of vascular injury
vWF forms bridge between exposed collagen on endothelial wall and GP1b on platelet surface
What is the coagulation cascade (provide an overview, how is it activated post injury)
- a series of steps leading to the deposition of fibrin and formation of a thrombus
- involves sequential steps in which pro-enzymes are converted to activated enzymes to form thrombin
- comprises of 2 pathways that converge on a final common pathway where activation of factor X occurs
1) extrinsic: activated by exposed tissue factor activating factor 7, measured by PT
2) intrinsic: activated by exposed collagen activating factor 12, measured by PTT
-common pathway involves the activation of thrombin and its subsequent conversion of fibrinogen to fibrin
In the normal coagulation cascade, what happens after factor X is activated
- prothrombin is converted to thrombin (also requires calcium and activated factor 5a as cofactors)
- thrombin catalyzes conversion of fibrinogen to fibrin (also requires calcium as cofactor)
- fibrin conversion to a fibrin mesh is catalyzed by factor XIII
What laboratory tests are used to assess different parts of the coagulation cascade
- PT: extrinsic and common pathways: factors 2, 5, 7, 10, fibrinogen
- PTT: intrinsic pathway: factors 2, 5, 8, 9, 10, 11, 12, fibrinogen
- vitamin K dependent factors: 2, 7, 9, 10, protein c/s
Describe the normal process of fibrinolysis
- circulating plasminogen is converted to plasmin by factor 12a or by tPA (produced by endothelial cells)
- plasmin breaks down fibrin mesh
What restricts the activity of the coagulation cascade (how is it limited to site of injury)
1) platelet inhibition:
- intact endothelium blocks platelet access to subendothelial matrix
- PGI2 and NO inhibits platelet binding
2) anticoagulation:
- antithrombin III: endogenous anticoagulant that inactivates factors 2a, 9a, 10a, 11a, 12a
- thrombomodulin: produced by endothelium, binds thrombin, activates protein c/s, inactivates factor 5/8
- tissue factor pathway inhibitor: forms a complex with 10a, which inhibits 10a, TF and 7a
3) fibrinolysis:
- tPA: protease found in endothelial cells and converts plasminogen to plasmin
- plasmin: cleaves fibrin mesh and prevents clot propagation
What is DIC, what are the consequences?
-DIC is a complication of diffuse thrombi activation with consequences of:
widespread fibrin microthrombi in circulation leading to ischaemia of vulnerable organs
concurrent consumption of platelets and coagulation factors causing uncontrollable bleeding
Mechanism and lab findings of DIC
Pathogenesis: pathological activation of the extrinsic +/- intrinsic pathway, with widespread activation of coagulation throughout the body, leading to both excessive blood clot formation and simultaneous depletion of clotting factors.
1) release of tissue factor or thromboplastic substances into the circulation (extrinsic path)
2) widespread endothelial injury promotes platelet aggregation and exposes subendothelial collagen (intrinsic path)
=> consumption of coagulating factors and platelets.
With excessive coagulation, there is activation of secondary fibrinolysis -> haemorrhage as clotting factors and platelets are depleted.
Lab: low Hb, low platelets, low fibrinogen, prolonged PT and aPTT, high INR, high d-dimer
Common causes of DIC
causes:
- infection = gram negative sepsis, meningococcaemia, malaria
- obstetric complications = abruption, amniotic fluid embolism
- trauma = burns, extensive surgery
- malignancy = pancreatic cancer, prostate cancer
Describe the pathogenesis of thrombus
Virchow triad
1) endothelial injury: most important, cause exposure of subendothelium ECM
2) alterations in normal blood flow: stasis (thrombosis in veins), turbulence (thrombosis in arteries)
3) hypercoagulable state: any alteration in the coagulation pathway, may be primary or secondary
Show the relationship between blood loss and cardiac output in haemorrhagic shock
- turns down at around 20%
- dead at 45%
