The disorders of hemodynamics and homeostasis
The hemodynamic and homeostatic disorders specify abnormal changes in the blood component. Here we shall discuss about them.
Edema is an abnormal increase of fluid within the interstitium of tissues. A disbalance between the capillary hydrostatic and colloid osmotic pressure result in a transudative fluid. Edema among different tissues is separately classified as: hydropericardium, hydroperitoneum, & hydrothorax.
Hydropericardium is the excess accumulation of fluid in the heart cavity. Hydroperitoneum (ascites) is the excess accumulation of fluid within the peritoneal cavity. Hydrothorax is the excess accumulation of fluid within the thoracic cavity.
Anasarca is the extensive swelling of the subcutaneous tissues around the body.
The causes of edema include: Congestive heart failure; protein deficiency; nephrotic syndrome; liver failure; irradiation, malignancy; excess antidiuretic hormone; excessive sodium and water retention; deep vein thrombosis; lymphatic obstruction from inflammation and surgery.
Congestive heart failure increases venous pressure, leading to renal hypoperfusion. This event triggers the renin-angiotensin-aldosterone system that causes sodium, water retention and increased vascular tone. Renal hypoperfusion with increased plasma osmolality triggers ADH release from posterior pituitary gland. This causes water reabsorption and sodium excretion from the kidney.
A continuous water retention worsens congestive heart failure leading to anasarca. Edema is common in the skin, lung, & brain. A foamy, blood tallied fluid confirms pulmonary edema. In brain edema, there is brain size increase, sulci are very narrow, with swollen gyri.
Congestion is an increase in volume and pressure of vessels resulting from a reduced blood outflow from a tissue. It causes edema, capillary hemorrhage, necrosis, & fibrosis. Congestion examples include acute & chronic pulmonary congestion; acute and chronic liver congestion. Both conditions occur in total heart failure.
Hemorrhage is the loss of blood into the extravascular space. Patterns of hemorrhage include: petechiae(1-2mm); purpura (≥ 3mm); ecchymosis (>1cm); hemopericardium; hemothorax; hemoperitoneum & hemarthrosis.
The process of hemostasis and the coagulation cascade.
Hemostasis is the maintenance of blood in a fluid state and regulation of coagulation in vascular injury. There is primary & secondary hemostasis. Primary hemostasis is the initial activation and aggregation of platelets to form clot. Secondary hemostasis is the formation of fibrin meshwork around platelet aggregates.
Platelet adhesion follows endothelial injury. Platelet receptor, glycoprotein 1b (Gp1b) connects with the extracellular matrix of injured endothelium through the Von Willbrand Factor (VWF) causing adhesion. Inherited deficiencies of GpIb & VWF lead to Benard-Soulier syndrome & Von Willbrand disease respectively which cause bleeding disorders.
After adhesion, ADP & thromboxane cause vasoconstriction, platelet aggregation & activation. Platelet receptors, glycoprotein IIb, IIIa link with fibrinogen to enhance platelet aggregation. Inherited deficiencies of GpIIb-IIIa lead to Glanzmann thrombasthenia.
On activation of platelets, their membrane phospholipids become negatively charged which bind calcium. These binding sites act as crucial points for the assembly of complexes of coagulation factors on the platelets. The binding of factors-II, VII, IX, X on the platelet depend on vitamin K.
The coagulation cascade & thrombi formation
This is a timeline of blood clot formation which can occur through an intrinsic and extrinsic pathway. Glass and damaged basal membrane activate the intrinsic pathway. Trauma-caused tissue injury activates the extrinsic pathway.
Tissue factor/thromboplastin (factor III) and activated aggregated platelets lay the foundation for the coagulation cascade activities. Sequence for extrinsic pathway include: III-VII-VIIa-X-Xa-II (prothrombin)-IIa(thrombin)-I(fibrinogen)-Ia (fibrin monomer)- (fibrin polymers)//IIa-V-Va-II-IIa-I-Ia-fibrin polymer. Bolded figures indicate the coagulation factors in this pathway.
Sequence for intrinsic pathway include: XII (Hageman factor) -XIIa-XI-XIa-IX-IXa-VIII-VIIIa-X-Xa-II-IIa-I-Ia//IIa-V-Va//IIa-XI-XIa//IIa-VIII-VIIIa.Where Bolded figures indicate coagulation factors, double slashes indicate factors thrombin can multiply activate.
Factor XIII undergoes activation which strongly binds fibrin polymer. Endogenous anticoagulants help to restrict blood clot to injured surface. They include antithrombin; protein C & S; Tissue factor pathway inhibitor (TFPI).
The liver produces antithrombin III. Heparin sulfate activates this protein molecule where it inhibits enzymes, IXa, Xa, XIa, XIIa, IIa.
The liver produces protein C & S which inhibits Va, VIIIa. The endothelium produces TFPI which inhibits factor III & VIIa. Tissue plasminogen activator (t-PA) enzymatically cleaves circulating plasminogen to plasmin. Plasmin breaks down fibrin, in a process known as fibrinolysis.
Thrombus formation and their types
Thrombi represent pale platelet, fibrin deposit with a dark red-cell rich layer. Thrombus is caused by endothelial injury, turbulent blood flow & stasis, & hypercoagulability, in a pattern known as Virchow’s triad.
Causes of endothelial cell injury include: bacterial endotoxins; hypertension, ulcerated atherosclerotic plaques; cigarette smoking; hypercholesterolemia, homocystinemia; irradiation; traumatic injuries; vasculitis & myocardial infarction (on endocardium).
Ruptured atherosclerotic plaque is the cause of turbulent blood flow. Causes of Stasis include: acute myocardial infarction; rheumatic mitral valve stenosis; aortic & arterial aneurysm; hyperviscosity (in polycythemia vera) & sickle cell anemia. Stasis is influential in the development of deep venous thrombi.
Factors responsible for hypercoagulabity include: point mutations in factor V & prothrombin; oral contraceptives; old age; smoking; obesity; procoagulant products of cancers; antiphospholipid antibody syndrome; heparin-induced thrombocytopenia; homocystinemia & deficiencies of antithrombin III, protein C, & S.
Types of thrombi include: mural thrombi in aorta and heart chambers; arterial thrombi in medium sized arteries; venous thrombi in lower limbs; vegetations in heart valves. Venous thrombi contain more red blood cells & fewer platelets. Arterial thrombi contain platelets, fibrin, red cells, dead leukocytes.
Thrombus formation may either progress to the followings: propagation; embolization; dissolution; organization & recanalization.
The clinical implications of thrombosis include: pulmonary embolization; myocardial infarction; ischemic stroke; disseminated intravascular coagulation; mesenteric ischemia; claudication; varicose ulcers.
Laboratory findings in DIC include: low platelet & fibrinogen; increased prothrombin time; elevated activated thromboplastin time; elevated D-dimer.