Hemodynamic Disorders

• Lean body weight


  60% is water
• Distribution of body water

  • 2/3 is intracellular, 5% of which is in blood plasma
  • Remainder is extracellular, mostly in the interstitium
• Major factors that govern movement of fluids

  • Not provided
• Under normal circumstances, the tendency of vascular hydrostatic pressure is to push the water and salts out of the capillaries into the interstitial space
• It is nearly balanced by the tendency of the Plasma Colloid Osmotic Pressure to pull water and salts back into the vessels
• There is usually a small net movement of fluid into the interstitium
• This small fluid is usually drained by the lymphatic system and returned into the circulation via the thoracic duct
• Edema


  Accumulation of fluid in the tissues
• Effusion


  Accumulation of fluid in the body cavities
• An elevated hydrostatic pressure or a diminished colloid osmotic pressure disrupts the balance and results in the increased movement of fluid out of the vessels
• Disorders that perturb cardiovascular, renal, or hepatic circulation are marked by accumulation of fluid in the tissues (edema), or in the body cavities (effusion)
• If the net rate of fluid movement exceeds the lymphatic draining capacity, fluid starts to accumulate and cause edema in tissues, or effusion in body cavities adjacent to serosal surfaces
• Inflammatory-related edema


  Protein-rich exudates, due to increase in vascular permeability caused by inflammatory mediators, usually localized to few tissues but can be widespread in cases of sepsis that cause widespread endothelial injury
• Non-inflammatory-related edema


  Protein-poor transudates, common in many diseases including heart, liver, and renal diseases, as well as nutritional disorders
• Causes of edema


  • Increased hydrostatic pressure
  • Reduced plasma osmotic pressure
  • Salt and water retention
  • Lymphatic obstruction
• Increased hydrostatic pressure


  • Mainly caused by disorders that impair venous return, if the impairment is localized the edema is confined to the affected site, conditions leading to systemic increase in venous pressure can cause widespread edema
• Reduced plasma osmotic pressure

  • Albumin accounts for half of the total plasma protein, decreased synthesis or increased loss of albumin from the circulation are the most common causes, reduced synthesis is commonly seen in severe liver diseases and protein malnutrition, albumin loss is commonly seen in nephrotic syndrome, reduced plasma oncotic pressure leads to reduced intravascular volume, renal hypoperfusion, and secondary hyperaldesteronism
• Salt and water retention

  • Salt retention comes with obligate retention of associated water, causes include increased hydrostatic pressure due to intravascular fluid volume expansion, decreased plasma oncotic pressure due to dilution, salt retention occurs whenever renal function is compromised, congestive heart failure causes the activation of renin-angiotensin-aldosterone system which is beneficial in early CHF but detrimental in late CHF
• Lymphatic obstruction


  • Trauma, fibrosis, invasive tumors, and infectious agents can cause obstruction or disruption of the lymphatic vessels and impair clearance of interstitial fluid resulting in lymphedema, filariasis can cause obstructive fibrosis of lymphatic channels and lymph nodes, edema of the upper extremity can be due to the destruction of axillary and breast lymph nodes during surgical procedures
• Subcutaneous edema


  • More conspicuous in regions with high hydrostatic pressure, distribution is influenced by gravity (dependent edema), usually appears in the legs when standing and sacrum when recumbent, signals potential underlying cardiac or renal disease, can impair wound healing and clearance of infections, pitting edema - finger pressure on edematous subcutaneous tissue displaces the interstitial fluid leaving a depression
• Pulmonary edema


  • A common clinical problem seen in left ventricular failure, can also occur with renal failure, acute respiratory distress syndrome, and pulmonary infection, fluid accumulates in the alveolar septa and impedes oxygen diffusion, the lungs are often 2-3 times normal weight, secretions yield frothy, blood-tinged fluid - a mixture of air, edema, and extravasated red cells
• Brain edema


  • Swollen brain exhibits narrowed sulci and distended gyri, compressed by the unyielding skull, the brain can herniate to the foramen magnum or the blood supply of the brain stem can be compressed, either can cause injury to the medullary centers
• Pulmonary effusion


  • Often accompany edema in the lungs, can further compromise gas exchange and compress the lung parenchyma
• Peritoneal effusion


  • Ascites, results more commonly from portal hypertension, prone to seeding by bacteria leading to infections
• Hyperemia


  An active process in which arteriolar dilation leads to increased blood flow, tissues turn red (erythema) due to increased delivery of oxygenated blood
• Congestion


  A passive process resulting from reduced blood outflow, can be localized (isolated venous obstruction) or systemic (cardiac failure), commonly leads to edema due to increased hydrostatic pressure, in chronic passive congestion, the associated hypoxia may result to ischemic tissue injury and scarring, capillary rupture can produce small hemorrhagic foci, there is catabolism of extravasated RBC in the form of hemosiderin-laden macrophages
• Acute pulmonary congestion


  • Engorged alveolar capillaries, alveolar septal edema, focal intraalveolar hemorrhage
• Chronic pulmonary congestion


  • Often caused by congestive heart failure, septa are thickened and fibrotic, the alveoli contain hemosiderin-laden macrophages (heart failure cells)
• Acute hepatic congestion


  • Central vein and sinusoids are distended, centrilobular hepatocytes undergo necrosis, perilobular hepatocytes have better oxygenation
• Chronic hepatic congestion


  • Centrilobular regions are grossly red-brown and slightly depressed due to necrosis, accentuated against surrounding zones of uncongested liver or nutmeg liver
• Hemostasis


  Maintains blood in a fluid, clot-free stage, induces a rapid and localized hemostatic plug at a site of vascular injury, involves platelets, clotting factors, and endothelium, hemorrhagic disorders have excessive bleeding, thrombotic disorders have blood clots forming within intact blood vessels or heart chambers
• Sequence of events leading to hemostasis

  1. Arterial vasoconstriction

  2. Primary hemostasis (formation of platelet plug)

  3. Secondary hemostasis (deposition of fibrin)

  4. Clot stabilization and resorption
• Arterial vasoconstriction


  • Occurs immediately and markedly reduces blood flow, mediated by reflex neurogenic mechanisms and augmented by local secretion of factors such as endothelin, the effect is transient but bleeding will continue without the activation of platelets
• Primary hemostasis


  • Formation of the platelet plug, disruption of the endothelium exposes sub-endothelial von Willebrand Factor (vWF) and collagen which promote platelet adherence and activation, activated platelets change shape and release secretory granules that recruit additional platelets to undergo aggregation and form the primary plug
• Secondary hemostasis


  • Deposition of fibrin, tissue factor is exposed at the site of injury and binds and activates Factor VII, cascades of reactions culminate in thrombin generation which cleaves fibrinogen into insoluble fibrin, the fibrin meshwork is also a potent activator of platelets leading to additional aggregation, secondary hemostasis consolidates the initial platelet plug
• Clot stabilization and resorption

  • Polymerized fibrin and platelet aggregates contract and form a solid permanent plug to prevent further hemorrhage, counter regulatory mechanisms (e.g. Tissue Plasminogen Activator or t-PA) are also activated to limit the clot and lead to clot resorption and tissue repair
• Platelets


  • Critical role by forming primary plugs that form initial seals, disc-shaped anucleated cells from megakaryocytes, have two types of cytoplasmic granules (alpha and dense granules) that contain various proteins and factors involved in coagulation and wound healing, after vascular injury they undergo a sequence of adhesion, shape change, secretion of granule contents, and aggregation to form the primary platelet plug
• After vascular injury, sub-endothelial factors (vWF and collagen) come in contact with the platelet and culminate sequence of reactions
• Platelet adhesion


  • Interaction with vWF, acts as a bridge between the platelet surface receptor glycoprotein Ib (GpIb), vWF disease and Bernard Soulier syndrome can result in bleeding disorders
• Platelet shape change


  • From smooth to spiky "sea urchin" shape, alterations in Glycoprotein IIb/IIIa increases its affinity to fibrinogen, translocation of negatively charged phospholipids to the platelet surface that binds to calcium and serves as nucleation sites for assembly of coagulation factor complexes