Pathophysiology of pH and Ca²⁺ in bloodstream and brain

Abstract

The highlights of the literature and our work on tetany and hyperventilation are reviewed. Our studies concern the following: (1) the changes of [Ca2+] in circulating plasma caused by respiratory and "metabolic" acidosis and alkalosis; (2) critical plasma [Ca2+] levels associated with signs of tetany and neuromuscular blockade; (3) changes in cerebral [Ca2+]o caused by hypo- and hyper-calcaemia, and the changes in cerebral [Ca2+]o and pHo caused by acute systemic acidosis and alkalosis; and (4) effects of changing [Ca2+]o and pHo levels on synaptic transmission in hippocampal formation. Our main conclusions are (1) changes of plasma [Ca2+] caused by "metabolic" pH changes are greater than those associated with varying CO2 concentration; (2) acute systemic [Ca2+] changes are associated with small cerebral [Ca2+]o changes; (3) the decreases in systemic and cerebral [Ca2+]o caused by hyperventilation are too small to account for the signs and symptoms of hypocapnic tetany; (4) moderate decrease of [Ca2+]o depresses and its increase enhances synaptic transmission in hippocampal formation; and (5) H+ ions in extracellular fluid have a weak depressant effect on neuronal excitability. CO2 is a strong depressant, which is only partly explained by the acidity of its solution. CO2 concentration is a significant factor in controlling cerebral function.

Excitability of human motor and visual cortex before, during, and after hyperventilation

“…The evaluation of the CSP and ICI seen with paired-pulse stimulation reflects complementary approaches for the evaluation of inhibitory mechanisms on the cortical level (10,25). It has been argued that HV increases excitability of spinal motoneurons (26) and motor axons (21,23,28). However, the HV-induced changes in CSP and ICI, seen in the present study, provide good evidence that HV has also distinct effects on neuronal excitability at the cortical level.…”

“…HV is known to have various effects on human physiology (for a review, see Ref. 6).For instance, a reduction in Pa CO 2 increases the excitability of sensory and motor axons in the peripheral nervous system (21,23,28).The aim of the present study was to investigate further the neural mechanisms of the HV-induced changes in cortical excitability. As measures of primary motor cortex (M1) excitability, motor threshold (MT), stimulus-response (S-R) curves (i.e., recruitment curves), intracortical inhibition (ICI), and intracortical facilitation (ICF) were determined.…”

“…For instance, a reduction in Pa CO 2 increases the excitability of sensory and motor axons in the peripheral nervous system (21,23,28).…”

Hypocapnia reduces the T wave of the electrocardiogram in normal human subjects

“…Whereas early studies suggested that hypocapnic voluntary hyperventilation might cause hypocalcemia, modern analysis techniques show that such hypocapnia produces either no hypocalcemia (6,32,48) or too small a reduction to explain adequately any ECG changes, paresthesia, or tetany (14,52).…”

Brain fluid calcium concentration and response to acute hypercalcaemia during development in the rat.

“…The NaCl solutions contained 151-136 mM-NaCl and the artificial CSF solutions contained 121-106 mM-NaCl, 22-6 mM-NaHCO3, 3-6 mM-KCl, 1-2 mMMgSO4.7H20, 01 mM-NaH2PO4 and 04 mM-Na2HPO4, pH 7-2-7-4 (Bass & Lundborg, 1973). Calibration in artificial CSF gave a reduction in apparent [Ca2+], presumably the result of calcium ions complexing with bicarbonate and phosphate (Somjen et al 1987 (Fig. 1A).…”