Chapter 4: Haemodynamic Disorders, thromboembolic disease and shock Flashcards
Oedema fluids and effusions may be inflammatory or non-inflammatory. Describe the differences.
Inflammatory: protein rich - due to increases in vascular permeability caused by inflammatory mediators.
Non-inflammatory: protein poor fluids (transudates)
What are the 4 contributing causes to oedema?
Increased hydrostatic pressure (e.g. DVT -> impairs venous return; CCF -> increase systemic venous pressure)
Reduced plasma oncotic pressure (e.g. inadequate synthesis or increased loss of albumin e.g. severee liver disease + protein malnutrition, nephrotic syndrome).
Sodium and water retention -> causes obligate retention of water with increases hydrostatic pressure and diminished vascular colloid osmotic pressure (due to dilutuion). E.g. Na retention occurs wheneever renal function is compromise or CVD that leads to renal hypoperfusion. Increased RAAS
Lymphatic obstruction -> impairs the clearance of interstitial fluid.
Describe how the mechanisms between hyperemia and congestion differ?
Hyperemia is an active process in which arteriolar dilation (e.g. at sites of inflammation or in skeletal muscle during exercise) leads to increased blood flow. Affected tissues turn red from increased delivery of oxygenated blood.
Congestion is a passive process resulting from reduced venous outflow of blood from a tissue. Can be localised vs systemic. Have abnormal blue-red color from deoxygenated blood.
Describe the morphological features of chronic pulmonary oedema (often caused by CCF).
septa are thickened and fibrotic and alveoli often contain heart failure cells i.e. macrophages laden with hemosiderin dervied from phagocytosed red cells.
Nutmeg liver is a sign of acute or chronic hepatic congestion?
Chronic
The centrilobar regions are grossly red-brown and slightly depressed (because of cell death) and are accentuated against the surrounding zones of uncongested tan liver.
Microscopically there is centrilobular congestion and hemorrhage, hemosiderin-laden macrophages and variable degress of hepatocyte dropout and necrosis
What three elements are required for normal hemostasis?
platelets
Clotting factors
Endothelium
Briefly, give an overview of the 4 stages of normal haemostasis? (4)
- Arteriolar vasoconstriction - mediated by reflex neurogenic mechanismss e.g. endothelin. Transient effect.
- Primary hemostasis: formation of the platelet plug. Exposed subendothelial vWBF and collagen -> promote plt adhesion + activation (change in shape + granule release) -> recruit additional platelets.
- Secondary hemostasis: deposition of fibrin. Exposed TF (procoagulant glycoprotein) -> binds and activates VII-> thrombin generation -> fibrinogen to fibrin.
- Clot stabilisation + resorption: Clot retraction + counterregulatory mechanisms (e.g. t-PA) mad eby endothelial cells lead to clot resorption + tissue repair.
What are the two types of granules in platelets?
alpha: adhesion molecule P-selectin, fibrinogen, coagulation factor VV, vWF, fibronectin etc.
Dense: ADP, ATP, Ca, serotonin, adrenaline
Which platelet surface receptor binds to vWF in teh subendothelial matrix (during formation of the platelet plug i.e. primary hemostasis)
Glycoprotein Ib
Which platelet receptor binds to exposed collagen?
Glycoprotein 1a/IIa.
Genetic deficiences of Gp1b results in a bleeding disorder by the name of?
Bernard Soulier syndrome
After platelet adhesion (to collagen or vWF) what happens to platelets and what role does this have in the development of secondary hemostasis (2 events)
–> Platelet activation: change in shape and release reaction.
- Platelets rapidly change shape. - > spikey sea urchins. Also results in conformational changes in cell surface glycoprotein IIb/IIIa that increase its affinity for fibrinogen and by the translocation of negatively charged phospholipids to the plt surface. These phospholipids bind calcium and serve as nucleation sites for hte assembly of coagulation factor complexes.
- Secretion of granule contents: Plts activated by thrombin (via PAR-1, G protein-coupled receptor, protease-activated receptor-1) and ADP (ADP acts by binding 2 G-P coupled receptors. P2Y1 and P2Y12.
How does aspirin work to prevent hemostasis?
inhibits plt aggregation by inhibiting COX (enzyme required to produce TxA2 synthesis (= potent inducer of platelet aggregation).
clopidogrel acts on which G-protein coupled receptors?
P2Y12
Describe the overall sequence of steps in platelet in clot formation?
Platelet adhesion Platelet change in shape Platelet release of granules Platelet aggregation. Platelet contraction
When platelets change shape they become spikey urchins and expose a surface receptor. Name this receptor and describe its role in platelet aggregation?
An inherited deficiency of this receptor results in which syndrome?
GpIIb/IIIa
Binds fibrinogen that bridges platelets and allows platelet aggregation.
Glanzmann thrombasthenia
How do the intrinsic and extrinsic pathways differ with respect to initiating events?
Intrinsic: negatively charged surface cause XII > XIIa
Extrinsic: exposure of vascular TF leads to activation of VII > VIIa
Which coagulation factors are vit K dependent?
II (prothrombin), VII, IX, X
Activated Xa converts prothrombin (II) to thrombin using which cofactor?
Va
Assembly of coag factors occurs on the negatively charged phospholipid surface of plts and requires ca2+ binding to which residues on which coag factors?
What else is required?
Assembly requires ca to bind to y-carboxylated glutamic acid residues that are present in factors II, VII, IX and X. the reaction uses Vit K as a cofactor.
What does the PT time assay assess for?
The function of the proteins in the extrinsic pathway (factors VII, I, V, II, and fibrinogen). It involves TF, phospholipids and ca added to plasma and time for a clot to form.
The partial thromboplastin time (PTT) screens the function of which proteins?
proteins in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, and fibrinogen).
negatively charged particles (e.g. ground glass) activate factor XII (Hageman fator) together with phospholipids and ca, time for fibrin clot to form recorded)
Which coagulation factor deficiency is only associated with mild bleeding?
XI
Clotting in vivo is different to clotting in the lab. In vivo, which clotting factor deficiencies are the most important ?
Factor VIIa/TF complex is the most important activator of IX and that factor IXa/factor VIIIa complex is the most important activator of factor X.
