Ventral medullary extracellular fluid pH and PCO2 during hypoxemia

We designed experiments to study changes in ventral medullary extracellular fluid (ECF) PCO2 and pH during hypoxemia. Measurements were made in chloralose-urethan-anesthetized spontaneously breathing cats (n = 12) with peripherial chemodenervation. Steady-state measurements were made during normoxemia [arterial PO2 (PaO2) = 106 Torr], hypoxemia (PaO2 = 46 Torr), and recovery (PaO2 = 105 Torr), with relatively constant arterial PCO2 (approximately 44 Torr). Mean values of ventilation were 945, 683, and 1,037 ml/min during normoxemia, hypoxemia, and recovery from hypoxemia, respectively. Ventilatory depression occurred in each cat during hypoxemia. Mean values of medullary ECF PCO2 were 57.7 +/- 7.2 (SD), 59.4 +/- 9.7, and 57.4 +/- 7.2 Torr during normoxemia, hypoxemia, and recovery to normoxemia, respectively; respective values for ECF [H+] were 60.9 +/- 8.0, 64.4 +/- 11.6, and 62.9 +/- 9.2 neq/l. Mean values of calculated ECF [HCO3-] were 22.8 +/- 3.0, 21.7 +/- 3.3, and 21.4 +/- 3.1 meq/l during normoxemia, hypoxemia, and recovery, respectively. Changes in medullary ECF PCO2 and [H+] were not statistically significant. Therefore hypoxemia caused ventilatory depression independent of changes in ECF acid-base variables. Furthermore, on return to normoxemia, ventilation rose considerably, still independent of changes in ECF PCO2, [H+], and [HCO3-].     

Evaluation of a dual-function pH and PCO2 in vivo sensor.

A newly developed, dual-function pH and PCO2 sensor was evaluated in this study. The sensors were placed in the femoral arteries of dogs anesthetized with sodium pentobarbital. Comparisons were made between systemic arterial pH and PCO2 measured using the sensor and those measured from blood samples drawn at 15-min intervals over a 7-h period using a bench instrument. The mean pH of the bench instrument measurements was 7.43. The mean difference of the sensor measurements from the bench instrument measurements for 207 comparisons was 0.0003 pH +/- 0.061 SD. The mean PCO2 of the bench instrument measurements was 40 mmHg. The mean difference of the sensor measurements from those of the bench instrument for 212 comparisons was -1.43 mmHg +/- 5.17 SD. The sensors performed equally well in the presence of metabolic or respiratory acidosis and alkalosis. The dual-function sensors evaluated in this study are useful for trend monitoring of pH and PCO2 over at least a 7-h period without recalibration. With improvement in the consistency of sensor construction, these sensors will be reliable in vivo sensing devices for blood pH and PCO2 and thus valuable research and clinical instruments.     

Adenosine and ATP link PCO2 to cortical excitability via pH

In addition to affecting respiration and vascular tone, deviations from normal CO(2) alter pH, consciousness, and seizure propensity. Outside the brainstem, however, the mechanisms by which CO(2) levels modify neuronal function are unknown. In the hippocampal slice preparation, increasing CO(2), and thus decreasing pH, increased the extracellular concentration of the endogenous neuromodulator adenosine and inhibited excitatory synaptic transmission. These effects involve adenosine A(1) and ATP receptors and depend on decreased extracellular pH. In contrast, decreasing CO(2) levels reduced extracellular adenosine concentration and increased neuronal excitability via adenosine A(1) receptors, ATP receptors, and ecto-ATPase. Based on these studies, we propose that CO(2)-induced changes in neuronal function arise from a pH-dependent modulation of adenosine and ATP levels. These findings demonstrate a mechanism for the bidirectional effects of CO(2) on neuronal excitability in the forebrain.     

Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice

Cerebrospinal fluid (CSF) analysis is an important tool in the diagnostic work-up of many neurological disorders, but reference ranges for CSF glucose, CSF/plasma glucose ratio and CSF lactate based on studies with large numbers of CSF samples are not available. Our aim was to define age-specific reference values. In 1993 The Nijmegen Observational CSF Study was started. Results of all CSF samples that were analyzed between 1993 and 2008 at our laboratory were systematically collected and stored in our computerized database. After exclusion of CSF samples with an unknown or elevated erythrocyte count, an elevated leucocyte count, elevated concentrations of bilirubin, free hemoglobin, or total protein 9,036 CSF samples were further studied for CSF glucose (n = 8,871), CSF/plasma glucose ratio (n = 4,516) and CSF lactate values (n = 7,614). CSF glucose, CSF/plasma glucose ratio and CSF lactate were age-, but not sex dependent. Age-specific reference ranges were defined as 5–95^th percentile ranges. CSF glucose 5^th percentile values ranged from 1.8 to 2.9 mmol/L and 95^th percentile values from 3.8 to 5.6 mmol/L. CSF/plasma glucose ratio 5^th percentile values ranged from 0.41 to 0.53 and 95^th percentile values from 0.82 to 1.19. CSF lactate 5^th percentile values ranged from 0.88 to 1.41 mmol/L and 95^th percentile values from 2.00 to 2.71 mmol/L. Reference ranges for all three parameters were widest in neonates and narrowest in toddlers, with lower and upper limits increasing with age. These reference values allow a reliable interpretation of CSF results in everyday clinical practice. Furthermore, hypoglycemia was associated with an increased CSF/plasma glucose ratio, whereas hyperglycemia did not affect the CSF/plasma glucose ratio.     

Temperature-induced changes in blood acid-base status: pH and PCO2 in a binary buffer.

Equations for proton equilibria of a single-phase binary buffer system have been applied to temperature-induced changes in pH and PCO2 of separated dog plasma at constant carbon dioxide content. Predicted behaviour, measured as deltapH/deltaT and deltalog PCO2 /deltaT, and pH and PCO2 as a function of temperature (range 8-45 degrees C), are in reasonable agreement with theory. Theory predicts and data confirm that deltapH/delta T and deltalog PCO2/deltaT functions of temperature; no single "temperature correction factor" is applicable. Comparison of whole blood with binary buffer equations also shows acceptable agreement between theory and experiment. Blood and separated plasma show similar responses in deltapH/deltaT and deltalog PCO2/delta T when compared over identical temperature intervals. For blood or plasma with initial pH (AT 37.5 DEGREES C) values in the range 7.53-7.45 deltapH/delta T (u/ degrees C) values are -0.0139 (37.5-27.5 degrees C) and -0.0192 (19-7 degrees C); comparable deltalog PCO2/deltaT values are 0.0195 (37.5-27.5 degrees C) and 0.0240 (19-7 degrees C). The charge state of protein components in this system remains nearly constant as temperature varies.     

Digital Computer Simulation of Respiratory Response to Cerebrospinal Fluid PCO2 in the Cat

The respiratory control system is treated as linear with a transmission delay between ventilation and sensing points (chemoreceptors). To the accepted variables involving body gas stores, ventilatory effects, transmission effects, and steady state pH, P(CO2), P(O2) chemoreceptor response, certain detailed analysis of the central receptors have been added. By construction of a model for medullary CO(2) receptor utilizing expected values of CNS (central nervous system) circulation, CO(2) production, and tissue-buffering effects, results of experimental observation of the effects of alteration of CSF were simulated. The inclusion of CSF effects also allowed simulation of the response to alteration in inspired CO(2), hyperventilation, and the periodic breathing with prolongation of circulation time.     

A technique for serial sampling of cerebrospinal fluid from conscious swine and sheep.

We devised a method for the atraumatic repeated collection of cerebrospinal fluid samples from conscious swine and sheep. Indwelling needles, with injection caps, were secured intracisternally and protected with plastic "crowns" attached to their skulls. The crowns permitted the animals freer movement with minimal risk of damage to the needles. With sheep, cerebrospinal fluid was withdrawn directly by puncturing the self-sealing injection caps attached to the hubs of the fixed needles. With the pigs, which are less amenable to handling, lengths of sterile polyethylene tubing inserted into the fixed needles enable collection without continuously disturbing the pigs. Serial samples were withdrawn from sheep (.10 to .30 ml) for up to 3 weeks with no problems, and from pigs (.05 to .15 ml) for 8 to 12 days, until the cannulae failed.     

On calculating concentrations of "HCO3" from pH and PCO2

1. As used in the Henderson-Hasselbalch equation, [HCO3], [CO2] and pH may all be variously defined; values of pK'1 must be chosen accordingly. 2. In common usage, "HCO3" may include CO3, carbamate, various ion pairs and possibly other bound CO2, as well as free HCO3 ions. 3. pH measurements may be systematically affected by the choice of standard buffers and by proteins and blood cells, and the errors in pH may be pH-dependent. 4. According to how it is expressed, the solubility coefficient for CO2 (S) may be influenced by sample water content, proteins and lipids. However, it need not feature in the calculation. 5. pK'1 is often found to decrease with increasing pH. This may be partly due to inclusion of CO3 and carbamate, but not of H2CO3.HCO3-, in "HCO3" and partly, perhaps, to errors in pH measurement. 6. To the extent that pH measurements are reliable, concentrations or activities of true HCO3 are calculable from pH and PCO2, but, if pH measurements are likely to be systematically erroneous, it may be preferable to define "HCO3" as "total bound CO2" and to base pK'1 on gasometric or titrimetric determinations of that.     

Cerebrospinal fluid cell preparation methods. An evaluation.

Although the cells from cerebrospinal fluid are widely used for diagnostic purposes, the cell yield on the microscopic slide is only rarely considered and mostly unsatisfactory. A reevaluation of several preparatory methods showed a very low yield with the Sayk-type chamber, a modest yield with the cytocentrifuge and the best yield with a simple, self-adhering chamber on slides coated with a polycation.     

Cerebrospinal fluid and plasma corticotropin-releasing hormone in senile dementia.

Cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) and ACTH, and plasma levels of CRH, ACTH and cortisol were determined in samples taken simultaneously from 28 patients with dementia including senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID), dementia following a cerebrovascular accident (CVD), and the borderline-to-normal state. CRH levels in CSF were significantly reduced in patients with SDAT and CVD, but not in those with MID, as compared with the borderline cases. ACTH levels in CSF were significantly reduced in the patients with SDAT compared to those with MID. Reduced CRH levels in CSF were found in the patients who showed severe dementia and poor activities of daily living (ADL). Plasma levels of CRH, ACTH and cortisol were normal and were not significantly different among the four groups of patients. CRH levels in CSF were positively correlated with ACTH levels in CSF, but not with the levels of plasma CRH, ACTH or cortisol. Plasma CRH levels were positively correlated with plasma ACTH levels. These results suggest that: 1) abnormalities in the extrahypothalamic CRH system play a role in the pathophysiology of senile dementia, which may not be specific to SDAT; 2) CSF CRH is correlated with the severity of dementia and ADL; 3) the levels of CRH in CSF and plasma are independent, and 4) the plasma CRH reflects, at least in part, the activity of the hypothalamic CRH regulating the secretion of pituitary ACTH.