Which of the following statement(s) is/are true concerning the microvascular and cellular response to shock?

c. The accumulation of anaerobic metabolites override normal homeostatic vasomotor tone and contribute to the maladaptive vasodilatation

d. Abnormal intracellular calcium homeostasis may contribute to the cellular dysfunction of shock

Moderate hypovolemia results in a relatively rapid spontaneous restitution of intravascular volume through expansion of the plasma space. This plasma expansion by erythrocyte free fluid occurs within one hour as a result of alterations in pressure and osmolarity and produces an associated hemodilution. Sympathetic discharge, associated arteriolar constriction, and induced metabolic changes in osmolarity initiate the compensatory events at the microcirculatory level. The initial pressurerelated phase of restitution of blood volume in shock is overlapped by a second phase involving osmotically induced mobilization of intracellular fluid. Osmotic mechanisms contributing to the restitution of blood volume after moderate hemorrhage are not adequate in hemorrhage of greater magnitude. In larger hemorrhages (over 25% blood volume), there is also deterioration of the normal cellular transmembrane potential, an increase in intracellular sodium and water, and a concomitant decrease in extracellular fluid volume. Tissue hypoxia results, anaerobic metabolites accumulate, and the cell cannot maintain the normal cell membrane potential. Accumulation of hydrogen ion, lactate, and other products of anaerobic metabolism override homeostatic vasomotor tone and contribute to a maladaptive vasodilatation, further augmenting hypotension and hypoperfusion. The uptake of fluid by the “failing” cell is a major source of food sequestration following shock. Loss of membrane function is proportional to both the extent and duration of shock or degrees of sepsis. The etiology of membrane failure is unclear but appears multifactorial. Loss of intracellular ATP energy stores during hypoperfusion or direct toxicity during sepsis may inhibit the membrane sodium-potassium pump. Cellular dysfunction also appears to be related to abnormal intracellular calcium homeostasis.