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3.3 PATHOPHYSIOLOGY OF PLASMA LEAK

The initial, febrile, phase of the Dengue disease mimics the picture of common acute viral illnesses. Only towards the end of febrile illness, in a small subset of the patients, features of increased capillary permeability and plasma leak are witnessed. Although it might well be speculated that increased plasma permeability is present in all the case of dengue disease plasma leak remains small and clinically compensated in most of the patients. Only in a small percentage of patients does this condition cross the critical threshold of compensatory mechanisms to become clinically significant. This acute increase in vascular permeability beyond the critical limit of compensatory responses - is the primary pathophysiological event that would differentiate DHF and DSS from uncomplicated DF. This leak is responsible for the loss of plasma into the extravascular compartment, giving rise to the hemoconcentration, hypovolemic state and in extreme condition, to shock.8, 9, 19 In common with classical volume depleted state, it leads to reflex tachycardia and generalized vasoconstriction as a result of increased sympathetic activity.20, 21 This compensated stage of shock is characterized by the responses initiated by the patient to overcome the stress of volume depletion. Physiological mechanisms - neural, hormonal and bio-chemical kick in to compensate for the stress of hypovolemia. The baroreceptors in the arteries detect a drop in BP, and cause the release of adrenaline and noradrenaline. These catecholamines cause vasoconstriction and tachycardia bodys attempt to increase the blood pressure. Vasoconstriction results in tissue hypoxemia and anaerobic glycolysis which in turn gives rise to acidosis. Acidosis mediated respiratory center stimulation causes hyperventilation (tachypnea). By hyperventilating and washing out CO2, the body is, indirectly, trying to correct the acidosis. Vasoconstriction can affect the kidneys, stimulating renin-angiotensinaldosterone axis to cause further vasoconstriction and conservation of fluid via increased renal reabsorption. Vasoconstriction which started in the splanchnic circulation can spread to kidneys, gastrointestinal tract, and other organs to divert blood preferentially to the heart, lungs and brain. This reduction in renal circulation (GFR) manifests itself in the form of reduced urine production.22 Severity of shock in the face of plasma leak - due to increased vascular permeability would depend upon:

State of hydration at the time of the onset of the leak Cardiac reserve Severity of the vasculopathy (rate of plasma leak) Any existing co morbidity