Figure 1
From: Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside
Description of the principal pathophysiological effects of severe metabolic acidosis with pH <7.2 on a muscle cell. Transient calcium amplitude: the increase in Ca2+ transient amplitude is the net consequence of the inhibitory effect of low intracellular pH on RyRs, NCX and ICa, and the stimulatory effects of low intracellular pH on NHE, NBC, TRVP-1 and sarcoplasmic reticulum Ca2. Myofilament Ca2+ sensitivity: due to the low intracellular pH, Ca2+ binding to troponin is altered and myofilament Ca2+ sensitivity decreased. Cellular hyperpolarization: intracellular acidosis also enhances hyperpolarization through K+ extrusion. Apoptosis: intracellular acidosis has stimulatory effects on BNIP3, promoting apoptosis. Adrenoreceptors: extracellular and intracellular acidosis reduces the number of adrenoreceptors on the cell membrane. Ica, L-type Ca2+ channel; IP3-R, inositol-1,4,5-triphosphate receptor; NBC, Na+/HCO3 − co-transport; NCX, Na+/Ca2+ exchange; NHE, Na+/H+ exchange; pHe, extracellular pH; pHi, intracellular pH; PLB, phospholamban; Ry-R, ryanodine receptor; SERCA, sarco/endoplasmic reticulum Ca2+-ATPase; SR, sarcoplasmic reticulum; TRVP-1, transient receptor potential channels-1.