Bicarbonate Production Research Articles

Cimetidine-induced bicarbonate production in canine gastric pouches

Secretion of HCO 3 − into a mucus-gel “unstirred layer” has been proposed as part of the gastric mucosal defense system. Cimetidine has a cytoprotective effect on salicylate-challenged gastric mucosa independent of its acid-inhibiting property. This study was done to (1) evaluate whether cimetidine increases gastric mucosal HCO 3 and to (2) ascertain if ionic shifts accompany the HCO 3 − to explain the mechanism of its production. Six dogs with Heidenhain gastric pouches were fasted 24 hr prior to testing. Pouch access was provided by a cannula fitted with an airtight apparatus for test solution instillation and removal and transmucosal potential difference (PD) measurement. A test solution composed of 175 m M mannitol, 25 m M NaCl, and 50 m M EPPS buffer was used, its pH adjusted to above 8.0; 14C-labeled polyethylene glycol was added for volumetric determinations. Nine 15-min periods comprised each test: four control periods of iv saline infusion; a fifth period when an iv cimetidine bolus was given; and four test periods when doses of 2.5, 5, or 10 mg/kg/hr cimetidine were infused iv. Test solution (50 ml) was placed in the pouch and an initial sample taken; 15 min later a final sample was taken, the pouch rinsed, and the next period begun. Concentrations of HCO 3 −, Na +, K +, and Cl − were determined for each sample as well as changes in osmolality, pH, volume, and PD. Mean net HCO 3 − increased from 79 μmol/15 min during saline infusions to 109, 124, and 123 μmol/15 min with 2.5, 5, and 10 mg/kg/hr cimetidine iv; all are significantly increased compared to saline controls ( P < 0.01). None of the other measured parameters changed significantly after cimetidine infusion. Cimetidine causes modest but significant increases in gastric mucosal HCO 3 −. The clinical role, if any, of these increases in HCO 3 − in gastric mucosal defense remains to be determined.

The mechanism of hyperchloremic acidosis during the recovery phase of diabetic ketoacidosis.

To determine the mechanism of hyperchloremic acidosis during recovery from diabetic ketoacidosis (DKA), serial measurements were made in eight patients of serum and urinary electrolytes and organic acids, and of urinary net acid. On admission, the average decrease in serum total CO2 was 17.5 mmol/L, corresponding to the excess anion gap, 18.5 meq/L, and the serum organic acids, 17.1 meq/L. With the treatment, the anion gap and organic acids decreased by 16.1 and 14.7 meq/L, respectively, but the serum CO2 increased only by 8.4 mmol/L; serum electrolyte balance was maintained by increase in chloride concentration. Fluid retention was insufficient to explain the disparity between the increase in CO2 and the decrease in organic acids. Renal loss of bicarbonate precursors during treatment was modest and was exceeded by renal bicarbonate production. The disparity between the increase in serum CO2 and the decrease in organic acids during treatment of DKA may be explained to a large extent by a difference in volume of distribution between bicarbonate and organic anions. The renal loss of ketone anions before admission, however, is ultimately responsible for the persistence of substantial metabolic acidosis.

Anion mobility in soils: Relevance to nutrient transport from forest ecosystems

Nutrient transport from forest ecosystems is strongly regulated by the availability of anions in soil solution. Each of the major anions in forest soil solutions has some unique properties which affect its production and mobility. The production of bicarbonate, one of the most common anions, is regulated by soil CO 2 pressure and pH. The mobility of phosphate is most strongly affected by adsorption reactions. The mobility of nitrate is regulated almost solely by biological processes, whereas chloride is relatively uninvolved in either biological or inorganic chemical reactions. Sulfate is intermediate, being involved in both biological and inorganic chemical reactions. Knowing these properties of the major anions, it is possible to assess and to predict the effects of several diverse site manipulations on soil leaching rates. Case studies from a site in Washington State consistently demonstrate the importance of accounting for bicarbonate transformations following site manipulations. Although organic anions are frequently dominant in cold-region soil solutions, very little information on the complex factors affecting their mobilities is available. Further research into organic anion mobility and futher attention to bicarbonate mobility should add greatly to the body of knowledge on nutrient transport processes in forest soils.

Nature of the intestinal slow wave waxing and waning zone

SUNY, Syracuse, New York. n.s.wong. From the Surgical Service, VA Hospital and Univererty of California, San Francisco. Intestinal slow waves (also called BER or pace-setter potentials) are responsible for the phasic, sometimes rhythmical contractions of the small intestine, and are also involved in peristaltic contractions. I the cat, and perhaps in other species well, the frequency of slow waves recorded in situ decreases ahorally in step-wise fashion, resulting in frequency plateaus which are separated by short zones (l-3 cm) of waxjnq and waning (Diamant and Bortoff, Am. J. Physiol. 216:301, 1969). The purpose of this study as to describe in detail the nature of the axing and waning (W and W) zone. Volume recordings were obtained from isolated segments of cat jejunum, using an array of eight recording electrodes, each separated from the next by 3 mm. It as found that slow waves propagate across the W and W zone during its waxing period, but the propagation velocity gradually diminishes ending in propagation failure. This is followed imediately by qeneration of slow waves at a slightly lower frequency by a pacemaker oscillator located just distal to the point of failure. Toward the end of the waning period one or two slow waves generated by this oscillator sometimes propagate in a retrograde direction; this phenomenon has been recorded both in vitro and in viva. Eventually the mire orad pacemaker again takes over and the W and W zone begins the waning phase of the cycle. The overall result is that there is one slow wave less per W and W cycle in the distal plateau, than in the proximal one. Thus, except for the activation of a more distal pacemaker the process resembles the Wenckebach phenomenon in the heart. The mechanical consequences of W and W zones are that propulsive contractions can cross the zone during its waning period, but are blocked during the waxing period. Thus, the W and W zones serve to regulate intestinal transit. (This work as supported in part by Grant AM 06958 from the Nat. Inst. of Arth. Met. and Diq. Dis.) We investigated pancreatic secretion in Syria” golden hamsters. Male hamsters (100-150 g) were fasted and anesthetized with urethane. The c-o” bile-pancreatic duct was cannulated near the duodenum, and ligated at the liver hilum to exclude bile from the collection. Basal samples of unstimulated juice were collected for up to one hour, and then secretin (GIli) was give” IV a bolus (0.09 to 17.7 U/Kg body weight). These experiments provided information on dose response to secretin, flow rates, and chloride and bicarbonate production. Another group of animals was stimulated by a single maximal dose of secretin (2 U/Kg body weight). These experiments provided information about [HCO -1 and [protein] in juice. Samples were weighed an a analyzed for chloride, bicarbonate and total protein content. Results: A secretin dose of 2 U/Kg body weight produced a maximal secretory response. [HCO -1 varied inversely with [Cl-] and appeared to exchange 2 or chloride with a ratio of 1.15:1 (bicarbonate:chloridel. At high flow rates, maximal [HCO -1 was 117+4.0 mEq/l and minimal [Cl-] was 28.4+2.0 mEq31, but [HC03-I decreased and [CJ-] increased at flow rates greater than 1.5x10 ul/min/g body weight. Pancreatic juice [HC03-] varied inversely with protein concentration. These results suggested that secretin stimulated secretion arises from two independent sources of different composition. One is protein rich with a high [Cl-]; the other is low in chloride and protein and has a high [HC03-1. Admixture of varying amounts of these fluids, well a rate limited exchange diffusion of the major anions both account for the observed characteristics of pancreatic secretion in the hamster.

Gastric mucosal defense mechanisms: Effects of salicylate and histamine

Some of the recent concepts about the gastric mucosal defense mechanisms against damage by luminal acid and the effects of histamine and salicylate on these mechanisms are reviewed. The mucosal barrier to acid appears to consist of at least two physiologic components: a permeability mechanism and a metabolic mechanism related to cellular bicarbonate production as a result of acid secretion. In the absence of salicylate, histamine appears to exert some protection by affecting both mechanisms, but in the presence of salicylate, histamine's protective effect is limited to altering mucosal permeability. The actions of salicylate on the gastric mucosa are complex, related in part to the concentration of salicylate and the pH of the luminal fluid. The damaging effects of salicylate appear to be related more to the concentration of acid in the lumen than to the lipid solubility of the drug. Salicylate increases permeability regardless of pH; the increase is initially selective for cations and subsequently becomes nonselective, involving both cations and anions. Although both low and high concentrations of salicylate increase mucosal permeability to hydrogen ions, only high concentrations of salicylate affect cellular bicarbonate production.

The effects of administrations of HCI, NH4CI and NH4HCO3 on the excretion of urea and ammonium in man

In man, HCl acidosis reduces blood and urinary urea with a concomitant rise in ammonium (NH4+) excretion. Significantly less urea is excreted following NH4Cl administration than following equimolar ingestion of NH4 HCO3. The results of these alterations in nitrogen excretion are interpreted in terms of bicarbonate utilization and production.

Plasma secretin and pancreatic bicarbonate response to exogenous secretin in man.

The dose response of duodenal bicarbonate production during synthetic porcine secretin infusions was studied in six healthy volunteers and related to plasma secretin immunoreactivity. Secretin was infused in each individual at four different doses from 0-1 to 2-7 CU/kg/h, each infusion lasting for 60 minutes. Mean maximal bicarbonate secretion was 33 +/- 4 mEq/h. The secretin plasma level for half maximal bicarbonate response was estimated to be 22 pmol/l. As this level is reported to be achieved by intraduodenal acidification in man, it is concluded that secretin may well play a part in the control of duodenal pH.

Intestinal Absorption of Vitamin B12in Patients with Chronic Pancreatic Insufficiency and the Effect of Human duodenal Juice on the Intestinal Uptake of Vitamin B12

The mean absorption of vitamin B12 (Schilling test) was 13.1 +/- 1.0 (% +/- S.E.M.) in 21 patients with chronic pancreatic insufficiency and 17.6 +/- 1.4 in 13 control patients (p less than 0.01). There was no correlation between pancreatic bicarbonate production after secretion stimulation and vitamin B12 absorption in the patient group (r = 0.117). Human duodenal juice reduced the uptake of 57CoB12-rat intrinsic factor (IF) by perfused rat small intestinal segments in vivo (p less than 0.01) as well as the uptake of 57CoB12-human IF by purified guinea-pig intestinal brush borders in vitro (p less than 0.01). The results confirm reduced absorption of vitamin B12 in chronic pancreatic insufficiency, but the mechanism remains uncertain.

Adaptations in urea ammonium excretion in metabolic acidosis in the rat: a reinterpretation.

1. The effects of oral hydrochloric acid, ammonium chloride, sodium bicarbonate and ammonium bicarbonate on urea and ammonium excretion in rats on a constant diet were studied. 2. Hydrochloric acid acidosis significantly reduced urea excretion in the rat, with an equimolar increase in NH+4 excretion and no change in their sum. In ammonium chloride acidosis, most of the additional nitrogen intake is excreted as NH+4 and a small percentage as urea. The converse holds true after administration of ammonium bicarbonate. The physiological significance of this is discussed. 3. The shift in nitrogen excretion from urea to NH+4 in acidosis is interpreted on the basis of bicarbonate production and utilization. Urea formation utilizes HCO-3. For amino acid sources, this utilization is offset by the metabolism of the carbon skeleton, which gives rise to HCO-3. When waste nitrogen is excreted as NH+4, no bicarbonate is utilized and the new HCO-3, generated by the carbon skeleton, hels to maintain hydrogen ion homeostasis.

Secretin Snuff: Evaluation of the Action on Pentagastrin-Stimulated Gastric Acid Secretion and on Pancreatic Bicarbonate Production

In an informative qualitative study 75 U (near the range of 1 U/kg) secretin given as a snuff resulted in a weak but significant stimulation of pancreatic bicarbonate output in 8 volunteers studied. The result further indicated that this dose would slightly inhibit pentagastrin-stimulated gastric acid secretion. This was confirmed in a quantitative study at the dose of 150 U (similar to 2 U/kg), and the mean amount of inhibition of MAO was 30% in the 10 subjects studied. A supramaximal dose of 1 mg (approximatively 54 U/kg) of synthetic secretin given to one volunteer resulted in a transient block of near maximally pentagastrin-stimulated gastric acid secretion. The amount of acid inhibition as compared to a control experiment was 45% in the first and 52% in the two post-secretin hours. These results indicate that secretin given as a snuff at dose levels that would induce maximal pancreatic secretion when given as an i.v. injection results only in a weak inhibition of stimulated gastric acid secretion and evokes only a little stimulation of pancreatic bicarbonate secretion. Supramaximal secretin snuff doses have, however, a potent effect on both gastric and pancreatic secretion that is of similar order to that achieved by intravenous secretin. Owing to the obviously incomplete absorption of secretin through the nasal mucosa, secretin snuff is unlikely to solve the therapeutic problem of duodenal ulcer disease. If, however, an active fragment of the peptide could be synthetized at a reasonable price, the greater convenience of pernasal application might compensate for the partial loss of action.

Pulmonary Emphysema and Peptic Ulcer

The theory of gastric CO2 ventilation describes a previously unrecognized reflex mechanism controlled by neurons in the caudal solitary complex (cSC) for non-alveolar elimination of systemic CO2 during respiratory acidosis. Neurons in the cSC, which is a site of CO2 chemosensitivity for cardiorespiratory control, also control various gastroesophageal reflexes that remove CO2 from blood. CO2 is consumed in the production of gastric acid and bicarbonate in the gastric epithelium and then reconstituted as CO2 in the stomach lumen from the reaction between H+ and HCO3−. Respiratory acidosis and gastric CO2 distension induce cSC/vagovagal mediated transient relaxations of the lower esophageal sphincter to vent gastric CO2 upwards by bulk flow along an abdominal-to-esophageal (= intrapleural) pressure gradient the magnitude of which increases during abdominal (gastric) compression caused by increased contractions of respiratory muscles. Esophageal distension induces cSC/nucleus ambiguus/vagovagal reflex relaxation of the upper esophageal sphincter and CO2 is vented into the pharynx and mixed with pulmonary gas during expiration or, alternatively, during eructation. It is proposed that gastric CO2 ventilation provides explanations for (1) the postprandial increase in expired CO2 and (2) the negative P(blood−expired)CO2 difference that occurs with increased inspired CO2. Furthermore, it is postulated that gastric CO2 ventilation and alveolar CO2 ventilation are coordinated under dual control by CO2 chemosensitive neurons in the cSC. This new theory, therefore, presupposes a level of neural control and coordination between two previously presumed dissimilar organ systems and supports the notion that different sites of CO2 chemosensitivity address different aspects of whole body pH regulation. Consequently, not all sites of central chemosensitivity are equal regarding the mechanism(s) activated for CO2 elimination. A distributed CO2 chemosensitive network—at least nine different areas in the CNS, including the cSC, have been reported to date—may reflect the complexity and dynamic nature of the fundamental neural circuitry required to achieve CO2/pH regulation across multiple organ systems under various states of arousal, oxygenation, pH status, and redox state. Moreover, coordination of respiratory and digestive control networks through the cSC could also account for the frequent co-expression of pulmonary diseases that cause chronic respiratory acidosis (and overstimulation of cSC neurons) with peptic ulcer disease or gastroesophageal reflux disease.

Essential factors governing the acid-base balance of saliva. I. Studies on the acid-base balance of saliva.

Examining chemical and physiological factors governing the acid-base balance of human saliva (mixed and parotid), the following results were obtained.1) A correlation between salivary pH and content of alkali reserve in bloodcan be found in some cases, but not always.2) It was demonstrated by ingestion of abundant alkali that changes of bicarbonate content in blood cannot directly influence the salivary pH, probably because bicarbonate ion do not readily diffuse out across the glandular membrane.3) In respiratory acidosis, the partial pressure of CO2, PCO2 in blood serum can influence that in saliva, probably because the free CO2 diffuses easily across the membrane. But, as PCO2, in blood is maintained approximately constant in physiological conditions, the salivary PCO2, shows also an almost constant value near that of blood PCO2. Thus it cannot be an usual factor which causes the physiological change of salivary pH.4) Determining the main inorganic and inorganic constituents in saliva and comparing their concentrations with one another, it was found that the total mol concentration in saliva, calculated from its freezing point depression is mainly composed of Na+, K+, Cl- and HCO3-. As the bicarbonate ion is the only one of these four which acts as a strong buffer, and as the salivary pH (5.8-7.8) is near its dissociation exponent (6.2 at 37°C), it is concluded that the bicarbonate is the main constituent which determines the salivary pH. It was ascertained that the salivary pH always changed in parallel to changes of total CO2, content i.e. bicarbonate concentration, in physiological conditions.5) The concentration of bicarbonate in saliva and therefore its pH were found to increase with the rise of the rate of salivary flow, and vice versa. Similar relations could be found generally in the extra-cellular salts in saliva, such asNa+, Cl-, Ca++, etc. Their concentrations were all lower than those of blood serum, and they approached the latter when the rate of salivary flow becamecopious. From the facts, it is presumed that these extra-cellular salts are secretedby permeation through the glandular membrane, of which the permeability may be increased by excitation of gland cells. The concentrations of intra-cellular salts, such as K, phosphate, etc. in saliva were always higher than those in blood serum. They remained nearly constant or decreased when the rate of salivary flow became high.6) Since the salivary bicarbonate concentration sometimes surpassed the serum concentration during increased flow, it was presumed that a part of bicarbonate was produced in the excited gland and discharged into saliva in addition to the permeated bicarbonate.7) The mechanism of bicarbonate production was discussed, and it was concluded that it consisted of two reactions, namely the production of K-bicarbonate by the neutralization of metabolic carbonic acid with cell buffer, and that of Na-bicarbonate by cation exchange between NaCl and H2CO3 across the glandular membrane. Possible processes concerning the latter mechanism were discussedin some details.8) It is concluded that the excretion of bicarbonate in saliva refers closely to the excitatory state of gland cells, so that the salivary pH can reflect the glandular activity.

Studies of the Egg of Bacillus libanicus (Orthoptera, Phasmidae) : II. Moisture, Dry Material, and Minerals in the Developing Egg

ABSTRACT 1. Weight, moisture content, and mineral content of freshly laid and of fully developed eggs of Bacillus libanicus (Uv.) were studied. During development of the embryo the egg-shell loses 19 per cent, of its initial mineral content, while the weight of mineral materials in the embryo increases correspondingly. 2. These changes can be explained only as resulting from transfer of minerals from the shell to the embryo. The mineral materials are derived from the calcium carbonate layer of the shell, which, owing to this loss, becomes thinner during embryonic development. 3. It is suggested that the mechanism of this transfer is based on the production of bicarbonate by the reaction of water and carbon dioxide, given off by the embryo, with the calcium carbonate of the shell. 4. Experimental calcium deficiency in the egg-shells results in a marked lowering of the viability of the embryos; although embryogenesis may sometimes proceed till the hatching stage, the few emerging nymphs survive only for a short time. 5. The possible occurrence of mineral transfer in other phasmid eggs is indicated.