Haemodynamic Disorders Flashcards
Oedema / Effusion
- Accumulation of fluid in tissues (oedema) or body cavity (effusion).
- Due to imbalance between vascular hydrostatic and osmotic pressure.
- Microscopically: clearing and separation of extracellular matrix, subtle cell swelling.
Oedema Clinical Features
- Subcutaneous oedema (Pitting oedema)
- Pulmonary oedema.
- Peritoneal effusions (ascites).
- Brain oedema.
Oedema Clinical Features:
Subcutaneous oedema:
-Disease examples and implications
- Cardiac disease.
- Renal disease.
Implications:
- Impairs wound healing.
- Impairs infection clearance.
Oedema Clinical Features:
Pulmonary oedema:
-Disease examples, Morphology and Implications
- Left ventricular failure.
- Renal failure.
- Acute respiratory distress syndrome.
- Pulmonary inflammation / infection.
Macroscopic Morphology:
- 2 -3 x normal weight.
- Frothy, blood-tinged fluid on sectioning (mixture of air, oedema and extravasated red cells.)
Implications:
- Hypoxaemia (impedes gas exchange).
- Creates favourable microbe environment.
- Exacerbated by pleural effusions.
Oedema Clinical Features:
Peritoneal Effusions:
-Disease examples and Implications
- Portal hypertension.
Implications:
- Bacterial seeding.
Oedema Clinical Features:
Brain oedema:
-Morphology and Implications
Morphology:
- Narrowed sulci.
- Distended gyri.
Implications:
- Brain herniation.
- Compression of vascular supply.
- Death.
Oedema Causes
- Increased hydrostatic pressure.
- Decreased plasma osmotic pressure.
- Sodium and water retention.
- Lymphatic obstruction.
- Increased vascular permeabilty (inflammation).
Oedema Causes:
Increased Hydrostatic Pressure:
-Why and How
Due to impaired venous return or arteriolar dilation.
Impaired venous return –> accumulation of fluid in vasculature –> increased hydrostatic pressure –> fluid forced into interstitial space.
Oedema Causes:
Increased Hydrostatic Pressure:
-Disease examples
Impaired venous return:
- Congestive heart failure.
- Constrictive pericarditis.
- Liver cirrhosis (ascites).
- Venous obstruction or compression e.g. DVT, external pressure (e.g. mass).
- Lower extremity inactivity with prolonged dependency.
Arteriolar dilatation:
- Heat.
- Neurohumeral dysregulation.
Oedema Causes:
Decreased Plasma Osmotic Pressure:
-How
Low albumin from decreased production or increased loss.
Low albumin –> low osmotic pressure –> fluid retained in tissues instead of going back to vessel –> oedema –> reduced intravascular volume –> renal hypoperfusion –> secondary hyperaldosteronism –> salt and water retention –> exacerbates low albumin (from dilution) and lowers osmotic pressure further.
Oedema Causes:
Decreased Plasma Osmotic Pressure:
-Disease examples
Decreased albumin production:
- Liver failure.
- Protein malnutrition.
Increaed albumin loss:
- Protein-losing glomerulonephropathies (e.g. Nephrotic syndrome).
- Protein-losing gastroenteropathy.
Oedema Causes:
Salt and Water Retention:
-How
- Increased salt retention.
- Associated water retention (where salt goes, water follows).
- Increased hydrostatic pressure (intravascular volume increase from increased water).
- Decreased osmotic pressure (increased intravascular volume dilutes albumin).
- Fluid moves to insterstitial space.
Oedema Causes:
Salt and Water Retention:
-Disease Examples
Compromised renal function:
- Primary kidney disorders.
- Congestive heart failure (renal hypoperfusion).
Excessive salt intake with renal insufficiency.
Increased renin-angiotensin-aldosterone secretion.
Oedema Causes:
Lymphatic Obstruction:
-How
- Blockage of lymphatics.
- Clearance of interstitial fluid impaired.
- Build up of fluid in interstitium.
- Lymphoedema in affected part of body.
Oedema Causes:
Lymphatic Obstruction:
-Disease examples
- Inflammatory.
- Infectious (e.g. filariasis –> lower limb / genital lymphoedema [elephantiasis]).
- Trauma.
- Fibrosis.
- Neoplastic.
- Post-surgical.
- Post-irradiation.
What are the factors involved in Activated partial thromboplastin time (aPTT) and what is aPTT used to monitor clinically?
Factors:
- ‘Intrinsic Pathway’ - F VIII, vWF, IX, (XI, XII).
- Common Pathway - F II, V, X.
Clinical monitoring:
- Unfractionated heparin therapy.
NB. Patients with vWD may have normal aPTT.
What is the laboratory test used to assess platelet aggregation?
PFA-100 assay (Gold standard test for platelet function).
Inherited Clotting Disorders:
Haemophilia A:
- What is the factor deficiency
- How is it inherited
- What is the distribution between sexes
- What are common symptoms
- What are the laboratory tests
- What is the treatment
Factor deficiency:
- F VIII
Inheritance:
- X-linked recessive.
- Spontaneous mutation.
Sex distribution:
- Males»_space;> Females.
Common symptoms:
- Spontaneous bleeding into joints.
- Arthritis / joint destruction if chronic / recurrent bleeding.
- Muscle bleeds.
- Major bleeding with dental / surgical procedures (unless FVIII given preOT).
Laboratory tests:
- aPTT.
- FVIII levels.
NB. The lower the level, more severe phenotype (severe = < 1% FVIII).
Treatment:
- FVIII concentrates (Biostate).
- Recombinant product (Xyntha, emicizimab).
- +/- analgesia +/- joint replacements +/- treatments of other complications.
Functions of vWF
- Mediates platelet adhesion at site of injury.
- Stabilises FVIII.
Inherited Clotting Disorders:
von Willebrand’s Disease:
- What Chromosome is vWF encoded
- What are the types
- How is it inherited
- What are common symptoms
- What are the laboratory tests
- What is the treatment
Encoded on:
- Chromosome 12.
Types:
- Type 1 (classical) - quantitative defect of vWF (70% cases).
- Type 2 - qualitative defect.
- Type 3 - quantitative defect.
Inheritance:
- Autosomal dominant.
Common symptoms:
- Mild bleeding - easy bruising, spontaneous mucocutaneous bleeding (e.g. epistaxis), petechiae, menorrhagia, prolonged / delayed bleeding post procedures / surgery.
NB. Type 1 and 3 patients have dual coagulation and platelet function defects.
Laboratory tests:
- aPTT (In type 1 and 3 usually prolonged as reduced / no vWF decreases stability of FVIII).
- F VIII (low in type 3 - severe vWD)
- von Willebrand antigen (low)
- Platelets (normal).
- Platelet function (abnormal).
Treatment:
Type 1 and 2 undergoing procedure / surgery:
- DDAVP (desmopressin) - stimulates vWF release.
- Plasma concentrates of FVIII and vWF
- Recombinant vWF.
Type 3 or longer procedures / surgery:
- Cryoprecipitate.
- FVIII infusions (Biostate).
NB. Recombinant FVIII does not have vWF in it so CANNOT use for these patients.
Thrombocytopaenia:
-What are the two broad categories of causes?
- Defective production.
- Diminished platelet survival.
Thrombocytopaenia:
Diminished Platelet Survival:
-Causes
Usually immune mediated:
- Viral e.g. CMV, EBV, HIV.
- Drugs (must be given 10-14 days prior) e.g. quinine.
- Auto-immune disorders (e.g. SLE).
- Idiopathic (ITP).
- Sepsis / DIC.
- Lymphoproliferative disorders.
- Post transfusional purpura.
Non-immune mediated:
- DIC.
- Microangiopathic disorders (e.g. TTP, HELLP syndrome, HUS, prosthetic valves).
- Giant haemangiomata.
- Extracorporeal circulations.
What is Bernard-Soulier syndrome and what is the deficiency present?
What it is:
- Inherited disorder of platelet function.
- Defect in platelet membrane.
Deficiency:
* Glycoprotein 1b protein (platelet receptor which binds to vWF on damaged endothelial cells –> adhesion of plt to injured area).
What is Glanzmann’s thrombasthenia and what is the deficiency present?
What it is:
- Inherited disorder of platelet function.
- Defect in platelet membrane.
Deficiency:
- Glycoprotein IIb / IIIa (platelet cell surface glycoprotein which binds fibrinogen –> platelet aggregation).
What are some drugs which cause acquired disorders of platelet function?
- Aspirin.
- Clopidogrel.
- NSAIDS.
- Penicillins.
- Cephalosporins.
- Heparin.
- Ethanol.
Treatment of thrombocytopaenia
Immune cause: steroids.
Non-immune cause: platelets.
Clots:
Arterial vs Venous
Venous:
- Low flow.
- Platelet-poor.
- Fibrin-rich.
- More entrapped red cells.
- Red clot.
- Treat with anticoagulants.
Arterial:
- High flow (assembly of clotting cascade on activated platelet surface only).
- Platelet-rich.
- Fibrin-poor.
- White clot.
- Treat with anti-platelet agents.
What is D-dimer and how is it used clinically?
What it is:
- Fibrin degradation product.
- Cleaved from cross-linked fibrin clot by plasmin (active form of plasminogen).
Clinical use:
- D-dimer test (ELISA assay).
- Measure of recent coagulation and fibrinolysis.
- ~95% sensitive for excluding DVT / PE in pateints with low - intermediate clinical suspicion of this.
Thrombophilia:
-Who should be investigated
- Young (< 45 yo).
- Recurrent events.
- Spontaneous DVT.
- Proven FHx.
- Thrombosis in unusaul site.
- Life threatening / catastrophic thrombosis.
What are some antiphospholipid antibodies
- Lupus inhibitors (lupus anticoagulants)
- Anti-cardiolipin abs
- Anti-beta-2 glycoprotein-1 abs
Antiphospholipid Syndrome:
-Indicative Features
- Recurrent venous or arterial thrombosis.
- Early foetal loss.
- Livedo reticularis.
Warfarin:
-Factors affected, how they are affected, and how is this reflected in the laboratory
Factors affected:
- Vitamin K-dependent factors (F II, VII, IX, X)^.
How affected:
- Warfarin blocks post-ribosomal carboxylation of these clotting factors.
Laboratory:
- Elevated INR.
^ TV channels - 2, 7, 9, 10.
