"The Primary Sources Of Acidity In The Diet Are Sulfur-containing AAs, Salt, And Phosphoric Acid"

[Amazoniac]

- Metabolic Acidosis Treatment as Part of a Strategy to Curb Inflammation (references)

 

[Amazoniac]

- Modern nutrition in wealth and disease (978-1-60547-461-8)

"Malnourished subjects are more likely to develop acidosis after an acid load (17). Urinary phosphate and ammonia are primary carriers of acid (protons) in the urine. Hydrogen ion secretion into the lumen of the distal nephron lowers the pH of tubular fluid and converts HPO4− to H2PO4− and stimulates ammonia production and the conversion of ammonia to NH4−. In individuals who have a low phosphorus intake, the phosphate filtered in the kidney is largely reabsorbed; this response conserves body phosphate pools; less phosphorus is excreted in the urine, however, and this reduces the capacity of the kidney to excrete acid. Infusion of phosphate increases urinary excretion of titratable acid in malnourished patients (17). Renal production and excretion of ammonium are also reduced in malnutrition, both under basal conditions and after an acid load (17)."​

 

[Ella]

- Metabolic Acidosis Treatment as Part of a Strategy to Curb Inflammation (references)

Thanks @Amazoniac, timely paper.

However, it is necessary to note that the publications linking acidosis with the inflammatory response are limited, and studies on the alkalosis are virtually nonexistent, justifying the current paper, at least as an open discussion

 

[Ella]

- Modern nutrition in wealth and disease (978-1-60547-461-8)

Does the above resource give a similar mechanism for the alkalosis?

Renal production and excretion of ammonium are also reduced in malnutrition, both under basal conditions and after an acid load (17)."

What factors contribute to the alkalosis? Insufficient acid load with too many alkaline minerals? Healthy kidneys should be able to regulate regardless of the acid-base composition of the diet. So if kidneys are not filtering efficiently, alkalosis results??

 

[Amazoniac]

Does the above resource give a similar mechanism for the alkalosis?

I'll have to check later, but there are better resources on this topic, such as:
- A Curriculum For Self-education In Biological Nutrition

What factors contribute to the alkalosis? Insufficient acid load with too many alkaline minerals? Healthy kidneys should be able to regulate regardless of the acid-base composition of the diet. So if kidneys are not filtering efficiently, alkalosis results??

Excess ingestion of alkalinizing compounds is one of them, baking soda or eggshells for example; NaCl loss is another; respiratory alkalosis from overbreathing; and so on. I think it's less common than acidosis, at times appearing as a compensatory measure.

- metabolic alkalosis clinical approach flow chart for ella - Google Search

 

[Amazoniac]

- Davenport diagram - Wikipedia

Modification found elsewhere:

Spoiler

- Acid-Base Chemistry in the Presence of and Buffers—The Davenport Diagram | Medical Physiology, 3rd Edition

Spoiler

For a given variation, increasing the pH isn't equivalent to decreasing in terms of concentration:
- BioMath: Logarithmic Functions

If you was to zoom in the physiological range, you would find similar sharp drops. Therefore as the pH is lower'd, it gets relatively more concentrated in hydrogen iods.

 

[Amazoniac]

By an ultra-boss:

Spoiler: Acid-Base Regulation: Henderson-Hasselbach Equation

Spoiler: Acid-Base Regulation: The Davenport Diagram

- Interpretation of arterial blood gas (table ein, simplified)

 

[Amazoniac]

Something curious:
- Negative pH Does Exist

 

[Amazoniac]

As you know, carbonic acid [H2CO3] dissociates into hydrogen carbonate (bicarbonate) ion [HCO3−] and hydrogen ion [H+]. Citrate can be protonidizated at varying degrees..

- Acid - Wikipedia

Tricarboxylic acids (as in TCA cycle) call attention to the 3 carboxyl groups (COOH or CO2H) in the molecule, each of these is able to lose hydrogen ions (yielding COO− and H+) in exchange of other cations. It's due to this that you'd need 3 molecules of bull**** (NaHCO3) if you was to replace them all since it only provides one sodium atom per molecule.

- Trisodium citrate - Wikipedia

Hydrogen in place of sodium iods (both being cations) is what's referred to as plain citric acid. You'll find the chaemical formula for citric acid, citrate and sodium citrate as [C6H8O7], [C6H5O7(3−)] and [Na3C6H5O7].

- Effect of citric acid leaching on the demineralization and thermal degradation behavior of sugarcane trash and bagasse

Spoiler

But it depends..

- Convenient UV-spectrophotometric determination of citrates in aqueous solutions with applications in the pharmaceutical analysis of oral electrolyte formulations

Spoiler

The pH equation is derived from that ratio of distribution:

Spoiler: pH and Buffer

Ka = [H+][bicarbonate ion]

[carbonic acid]​

And related to the previous post is why you'll find these toxins in the equation flipped:

Spoiler: Henderson Hasselbalch equation

I thought that I had shared this, but couldn't locate.

- Comparative Value of Orange Juice versus Lemonade in Reducing Stone-Forming Risk

"Fruits and fruit juices with high citrate content generally are assumed to deliver an alkali load. However, previously published studies on the influence of different citrate-rich fruit juices/beverages on the risk for stone formation have provided conflicting results, with some beverages decreasing the risk for stones whereas others have either no effect or increase the risk (7–16). One reason might be the different constituents of various beverages. For instance, citrate in products such as orange and grapefruit juice is complexed mainly by potassium, whereas citrate in lemonade and cranberry juice is accompanied by proton. Potassium citrate and citric acid are very different in terms of acid-base profiles. It has been shown that the renal effects of orange juice resemble those of potassium citrate and potentially can reduce the stone risk factors (7). Lemonade and cranberry juice, conversely, do not confer the alkali load that orange juice provides, presumably because the accompanying proton negates the effect of bicarbonate that is generated by intrahepatic metabolism of citrate."

Spoiler: Cropotol

"During the orange juice phase, participants were asked to consume 400 ml of orange juice (Minute Maid, Houston, TX) three times a day with meals. The source of orange juice was frozen orange concentrate from the same lot. Content of citrate, potassium, calcium, and magnesium was analyzed before use. The frozen concentrate was diluted with an appropriate amount of distilled water so that each 400-ml portion would deliver 33.3 mEq of citrate and 14 mEq of potassium corresponding to 100 mEq of citrate and 42 mEq of potassium/d. The orange juice and lemonade used were not calcium fortified.

During the lemonade phase, participants drank 400 ml of lemonade (Minute Maid) three times a day with meals. The source of lemonade was frozen concentrate from the same lot. The frozen concentrate was diluted with distilled water so that each 400-ml portion would deliver 33.3 mEq of citrate. From our analysis, virtually no potassium would be delivered.

During the control phase, participants drank 400 ml of distilled water using the same dosing interval. During all phases, participants were maintained on a constant low-calcium, low-oxalate, metabolic diet with daily composition of 400 mg of calcium, 150 to 200 mg of oxalate, 800 mg of phosphorous, 100 mEq of sodium, 50 mEq of potassium, and 200 mg of magnesium. Total fluid intake was fixed at 3 L/d."

Spoiler: Results: urinary citrate and pH

Spoiler: Results: 24-h urine analysis

"Despite comparable citrate content, lemonade did not have a significant effect on urinary citrate, pH, ammonium, titratable acidity, net acid excretion, and NGIA. This observation emphasizes the importance of the accompanying cation when providing alkali load. Alkali load enhances urinary citrate excretion by reducing renal tubular reabsorption and metabolism of citrate (19 –22). The lack of alkalinizing and attenuated citraturic effects of lemonade probably is due to its accompanying proton, which could have neutralized the effect of citrate. Citraturia, however, could also develop through an alternative mechanism, unrelated to changes in acid-base status. A small fraction of administered citrate may escape in vivo metabolism and appear directly in the urine (23). The mechanism may be responsible, in part, for the observed rise in urinary citrate in hypocitraturic calcium stone formers after consuming 2 L/d lemonade for 1 wk (12). Alternatively, dietary compositions may have influenced the response to lemonade administration. Through its alkalinizing effect, orange juice also lowered the calculated amount of poorly soluble undissociated uric acid, which could reduce the propensity to form uric acid stones. However, calculated RSR [relative supersaturation] of brushite was significantly higher as a result of the increase in urinary pH. Unlike orange juice, lemonade had no effect on excretion rate of undissociated uric acid and calculated supersaturation of calcium oxalate and brushite."

"Despite the alkali load, administration of orange juice did not result in significantly lower urinary calcium excretion. It was shown previously that administration of potassium alkali decreases urinary calcium, and this hypocalciuric effect seems to be unique to potassium alkali (potassium citrate or potassium bicarbonate) (24 –26). The lack of hypocalciuric effect may be due, in part, to a small amount of additional calcium (100 mg/L) provided by orange juice and, in part, to the effect of carbohydrate load (27)."

"A significant increase in urinary oxalate was observed during the orange juice phase, which probably was due to the presence of a small amount of oxalate in orange juice and/or to in vivo conversion of ascorbic acid to oxalate. Calculated calcium oxalate supersaturation was lower in the orange juice phase despite a significant increase in urinary oxalate."

"Another inhibitor of calcium oxalate complexation is magnesium (28). Our study showed that orange juice increases urinary magnesium, perhaps a reflection of magnesium (110 mg/L) provided by the juice."

"The results of our study showed that an alkali load is delivered by administration of orange juice but not by lemonade despite equivalent citrate content. There is an absolute need to consider the accompanying cation whenever one assesses the citrate content of a diet. Because an increase in urinary citrate and pH could provide protection against calcium and uric acid stone formation, orange juice but not lemonade potentially could play an important role in the management of recurrent nephrolithiasis and may be considered an option in patients who are intolerant of potassium citrate."​

Glossary (PL ↔ EN):
Virate or tumorate ↔ Citrate: responsible for activating viruses and fueling cancer.
Awbuzze ↔ Fructose: it's 'alcohol without the buzz'.


It's interesting that where I live the orange varieties meant for juicing are low in awbuzze, whereas the sweet ones are usually eaten. I've witnessed people not only finding fruit juices by the end of the crop odjectionable for being too sweet, but willing to dilute them to make the toxin less concentrated and avoid alcoholic liver disease. Sometimes people crave sourness as well, and they add lime juice to make up for its lack. But I'm mentioning this for those whose bodies are susceptible to environmental challenges, you can try different varieties of orange because you may find one that is nourishing without being toxic.


In case you isn't willing to prepare Franklin's magnesium water and prefer to avoid industrial forms such as virate, magnesium carbonate in small amounts before meals should work. You'd have to wait minutes for the appetite to return and only then proceeding to the meal to prevent adverse interference. It must minimize the adsorption of impurities, mitigate potential issues from large amounts of table salt and let magnesium be metabolized with the other nutrients.


Some nimeral waters may contain enough bases to neutralize a significant portion the acids of juices.

This is from a conversation with a semi-god, I thought that it might be of interest:

- New Demonstrations and New Insights on the Mechanism of the Candy-Cola Soda Geyser

"[..]it is estimated that 7.5 g of CO2 is dissolved per liter of carbonated beverage at 25°C."​

 

[Amazoniac]

- Color Atlas of Pharmacology (978-1588903327)

"H(+)-binding groups such as CO3(2−), HCO3(−) or OH(−), together with their counter ions, are contained in antacid drugs. Neutralization reactions occurring after intake of CaCO3 and NaHCO3, respectively, are shown in (A). With nonabsorbable antacids, the counter ion is dissolved in the acidic gastric juice in the process of neutralization. Upon mixture with the alkaline pancreatic secretion in the duodenum, it is largely precipitated again by basic groups, e. g., as CaCO3 or AlPO4, and excreted in feces. Therefore, systemic absorption of counter ions or basic residues is minor. In the presence of renal insufficiency, however, absorption of even small amounts may cause an increase in plasma levels of counter ions (e. g., magnesium intoxication with paralysis and cardiac disturbances). Precipitation in the gut lumen is responsible for other side effects, such as reduced absorption of other drugs due to their adsorption to the surface of precipitated antacid; or phosphate depletion of the body with excessive intake of Al(OH)3." "Na+ ions remain in solution even in the presence of HCO3(−)-rich pancreatic secretions and are subject to absorption, like HCO3(−)."

Spoiler

↰ Extremely toxic!!1

 

[Amazoniac]

- Bracket - Wikipedia

"Square brackets can [] be used in chemistry to represent the concentration of a chemical substance in solution and to denote charge a Lewis structure of an ion (particularly distributed charge in a complex ion), repeating chemical units (particularly in polymers) and transition state structures, among other uses."​

- The Time Course for Changes in Plasma [H+] After Sodium Bicarbonate Ingestion

Spoiler

"[..]participants consumed a solution of 0.3 g/kg NaHCO3 or CaCO3 in 400 mL of plain water in 3 equal doses taken at 0, 15, and 30 minutes."

- Sodium bicarbonate
- Calcium carbonate

- Gas production after reaction of sodium bicarbonate and hydrochloric acid

"The reaction of HCl and NaHCO3 to form carbonic acid and sodium chloride is instantaneous; hence, sodium bicarbonate is a rapidly acting antacid (1). The decomposition of carbonic acid to CO2 (and water) accounts for the second characteristic effect of sodium bicarbonate when taken for indigestion, i.e., the facilitation of a belch. However, little is known about the rate of release of CO2 gas when sodium bicarbonate is added to a solution containing hydrochloric acid, and belching does not always follow ingestion of sodium bicarbonate.
The usual recommended dose of baking soda is one-half teaspoon which, if accurately measured, contains ~1.6 g of sodium bicarbanate."​

 

[Amazoniac]

One more reason to stick to lower doses at a time whether it's to minimize chances digestive upset or a burned heart. It's curious that the intoxication with killcium carbonate is slow, so the change in stomach acidity is not remarkable.

- Effects of antacid formulation on postprandial oesophageal acidity in patients with a history of episodic heartburn

"[..]recent studies have indicated that usual doses of antacids are primarily active in the distal oesophageal lumen [9, 10] rather than by neutralization of intragastric contents. If this is indeed the case, chewable antacids should rapidly increase and sustain the elevated intra-oesophageal pH better than swallowable antacids."

"Twenty subjects with a history of episodic heartburn underwent eight pH monitoring sessions each for 5.5 h postprandially. One hour after consuming a ['refluxogenic'] meal consisting of chilli, cheese, raw onions and cola, subjects received 750 mg, 1500 mg and 3000 mg of either chewable or swallowable CaCO3 tablets, an effervescent bicarbonate solution or placebo. Oesophageal and gastric pH data were collected."

Spoiler

(a) Calcium carbonate (CaCO3) 750 mg chewable tablets (Tums E-X tablets, GlaxoSmithKline, UK); acid neutralizing capacity (ANC), 16 mmol;
(b) CaCO3 1500 mg chewable tablets as above; ANC, 32 mmol;
(c) CaCO3 3000 mg chewable tablets as above; ANC, 64 mmol;

(d) CaCO3 750 mg swallowable tablets (Glaxo-SmithKline, UK); ANC, 16 mmol;
(e) CaCO3 1500 mg swallowable tablets as above; ANC, 32 mmol;
(f) CaCO3 3000 mg swallowable tablets as above; ANC, 64 mmol;

(g) Na+/K+ bicarbonate effervescent solution with 32 mmol ANC (the effervescent bicarbonate solution) as Alka-Seltzer Gold tablets (Bayer Corporation, Consumer Care Division, USA);

(h) placebo tablets identical to the swallowable tablets.

- Acid-neutralizing Capacity of Over-the-Counter Gastrointestinal Medications

"As expected, intragastric pH profiles were low prior to the meal and rose to approximately pH 5 (the pH of the meal), followed by a gradual fall to pre-meal pH values prior to antacid dosing."

"Of the antacid formulations studied, only effervescent Na+/K+ bicarbonate solution reliably elevated intragastric pH. Neither swallowable nor chewable antacid tablets led to statistically significant increases in intragastric pH, and the actual rise in intragastric pH with swallowable or chewable antacids was minimal over time, as demonstrated in Figure 3. These data provide further evidence that antacids probably affect acid reflux and related heartburn symptoms directly within the oesophageal lumen, at least in part by neutralization of refluxed acid, rather than by any impact on intragastric acidity."

Spoiler: pH for every 5 min

Spoiler: Detailed first hour after dosing

"The onset of action is the time from dosing to the first statistically significant difference vs. placebo (P < 0.05). The offset time is the time to the first nonsignificant difference following the onset time. The duration of action is defined as the offset time minus the onset time."

"Calculated times to onset of a significant reduction in oesophageal and gastric acidity were similar for all doses and product forms, except that the low doses (750 mg) of chewable and swallowable antacid formulations had minimal effects on gastric pH. Swallowable calcium carbonate 750 mg had no measurable onset time for gastric pH. The onset of a significant reduction in oesophageal and gastric acidity (increase in pH) for all other active treatments was between 30 and 35 min."

"The duration of action varied widely between products (Figure 6). In general, chewable CaCO3 forms had a substantially longer duration of action (up to four times longer) than the same dose of swallowable CaCO3 for the neutralization of oesophageal acid. For example, chewable CaCO3 3000 mg and effervescent Na+/K+ bicarbonate had relatively persistent effects (ranges: 40 min in the oesophagus and 100-180 min in the stomach), while swallowable 750 mg and 1500 mg CaCO3 only transiently altered pH (ranges: 10-15 min in the oesophagus and 5-35 min in the stomach)."

Spoiler: Summary of duration of action

"Numerous studies,[4, 7-10] including the present one, have demonstrated that antacids probably relieve heartburn pain by neutralizing acid directly within the oesophageal lumen and not necessarily within the gastric lumen. It is reasonable to suggest, therefore, that even small doses of chewed antacid tablet should provide more effective oesophageal pH control than quite large doses of swallowed antacids. The present study supports this suggestion and also explains the otherwise counterintuitive notion that antacids with lower ANC might surpass those with far higher ANC. In our study, the onset of antacid effects seemed far slower than might be anticipated. It is likely, however, that the presence of food in the stomach with refluxed food in the oesophagus (from the early postprandial period) undoubtedly obscures, to some extent, the true antacid onset."​

- Technical note: using calcium carbonate as an osmolar control treatment for acid-base studies in horses (@tankasnowgod)

 

[Amazoniac]

If you tooked antacids in excess or the food is paralyzed in the stomach, you can start chewing to find out if it helps in normalization:

- Effect of Chewing Gum on Gastric Acid Secretion

Spoiler

 

[Amazoniac]

A part of lampofredoxide (CO2) is converted in the mouth (through the action of carbionic annihilase) to lamponic fredacid, which is responsible for the tingling, bubbles are only enhancers of the effect:
- The Influence of Bubbles on the Perception Carbonation Bite

The sensation alerts you stay away from it: toxic.

 

[Amazoniac]

- Thyroxine effect on intestinal Cl−/HCO3− exchange in hypo- and hyperthyroid rats

"Previous studies in both animal (Fink 1944, Ligumsky et al. 1980, Johnson 1981) and human (Culp & Piziak 1986) models [have] suggested that alterations of the intestinal transport processes might be the primary cause of the intestinal symptoms in both hyper- and hypo-thyroidism."

"Changes in transepithelial water and electrolyte transport as causative or contributing factors of the diarrhoea and constipation found associated with changes in thyroid physiology were studied. Albino Wistar rats were pharmacologically made either hypothyroid or hyperthyroid. After sacrifice, the small intestine was mounted in Ussing chambers in order to measure in vitro ion net fluxes under short-circuit conditions."

"Hypothyroid animals showed an increase in intestinal transit time, Cl− absorption (mainly due to an increment in its mucosal to serosal component) and residual ion flux (which is believed to represent HCO3− secretion) when compared with euthyroid animals." "Furthermore, when the serum T4 levels were plotted against both net Cl− and J(R)net (Figs 1 and 2), a strong correlation was seen among these three parameters, suggesting that the levels of T4 affect anion exchange over a wide range, with low levels promoting the exchange and high levels inhibiting it."

Spoiler

"[..]results indicate that the effect of T4 is firstly to inhibit Cl−/HCO3− anion exchange thereby influencing transepithelial flux transport and secondly to affect intestinal motility."

"It is not a new finding that the inhibition of Cl−/HCO3− exchange results in diarrhoea; in fact, the complete lack of such a mechanism is known to cause the profuse watery diarrhoea typical of congenital Cl−-losing diarrhoea (Evanson & Stanbury 1965)."​

 

[Amazoniac]

- Uses and misuses of sodium bicarbonate in the neonatal intensive care unit

"Addition of bicarbonate to the intravascular (i.e. extracellular) space will buffer excess H+ ions by forming carbonic acid, which is further dissociated to water and CO2. In situations where CO2 cannot be rapidly eliminated from the local environment (i.e. in venous stasis or low perfusion states, as occur during cardiac arrest and CPR, when cardiac output is thought to be only 30% of normal), CO2 accumulates, leading to local hypercarbia. Diffusion of CO2 across the cell membrane occurs far more quickly than transport of HCO3−, resulting in initial overproduction of intracellular H+ from carbonic acid. This intracellular acidification is the result of conversion of extracellular HCO3− to CO2 by carbonic anhydrase. CO2 ultimately diffuses across the cell membrane, resulting in intracellular acidosis. This reaction may be prevented by the addition of acetazolamide, a reversible inhibitor of carbonic anhydrase [3] (Fig. 1)."

Spoiler

 

[Amazoniac]

Some selected parts for you to read further on topics that interest you.

- Blood Gases | teachingmedicine.com

- Carbonic Anhydrases and Metabolism

"Carbonic anhydrases (CAs, EC 4.2.1.1) are a superfamily of metalloenzymes present in all life kingdoms, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons [1,2,3,4,5,6]. Although discovered 85 years ago, these enzymes are still extensively investigated due to the biomedical application of their inhibitors [7,8,9,10,11,12] and activators [13] but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya, the a-, ß-, γ-, δ-, ζ-, η-, and θ-CAs [2,4,5,14,15,16]. CAs are also among the most efficient enzymes known in nature, probably due to the fact that uncatalyzed CO2 hydration is a very slow process at neutral pH, and the physiologic demands for its conversion to ionic, soluble species (i.e., bicarbonate and protons) are very high [1,2,3,4,5,6]. Indeed, CO2 is generated in most metabolic oxidative processes, and being a gas, it must be converted to soluble products quickly and efficiently. Otherwise, it would tend to accumulate and provoke damage to cells and other organelles in the gaseous state without such an efficient hydration catalyst as the CAs [2,6,7,8]."

"For a long period it has been considered that the pharmacologic effects of CA inhibition or activation are mainly due to effects on pH regulation in cells or tissues where the enzymes are present [1]. Although these phenomena are undoubtedly relevant and take place in most organisms/tissues/cells where these ubiquitous enzymes are found, a lot of recent evidence points to the fact that CAs are true metabolic enzymes at least for two different reasons: (i) due to their direct participation in carboxylating reactions which provide bicarbonate and/or CO2 to carboxylating enzymes, such as pyruvate carboxylase, acetyl-coenzyme A carboxylase [19,20], phosphoenolpyruvate carboxylase [21], and ribulose-1, 5-bisphosphate carboxylase oxygenase (RUBISCO) [22,23]; and (ii) due to the role that pH itself has on many metabolic reactions, with pH differences as low as 0.1 unit leading to the complete blockade of crucial reactions and thus of entire metabolic pathways [1,2,3]."

"In tumors, [] it has been shown that not only do the protons produced by CO2 hydration contribute to extracellular acidification, typical of most cancers [1,2,12,27], but the bicarbonate is thereafter used as a C1 carbon source for biosynthetic reactions that convert it into organic compounds (the so-called “organication”), which supplies cancer cells with intermediates useful for sustaining their high proliferation rates [28]."​

- Carbonic Anhydrase: Its Inhibitors and Activators (0-415-30673-6)

"In higher organisms, including vertebrates, the physiological functions of CAs have been widely investigated over the last 70 years (Maren 1967; Chegwidden and Carter 2000; Supuran et al. 2003). Thus, isozymes I, II and IV are involved in respiration and regulation of the acid/base homeostasis (Maren 1967; Chegwidden and Carter 2000; Supuran et al. 2003). These complex processes involve both the transport of CO2/bicarbonate between metabolizing tissues and excretion sites (lungs, kidneys), facilitated CO2 elimination in capillaries and pulmonary microvasculature, elimination of H+ ions in the renal tubules and collecting ducts, as well as reabsorption of bicarbonate in the brush border and thick ascending Henle loop in kidneys (Maren 1967; Chegwidden and Carter 2000; Supuran et al. 2003). Usually, isozymes I, II and IV are involved in these processes. By producing the bicarbonate-rich aqueous humor secretion (mediated by ciliary processes isozymes CA II and CA IV) within the eye, CAs are involved in vision, and their misfunctioning leads to high intraocular pressure and glaucoma (Maren 1967; Supuran et al. 2003). CA II is also involved in bone development and function, such as differentiation of osteoclasts or providing acid for bone resorption in osteoclasts [!] (Chegwidden and Carter 2000; Supuran et al. 2003). CAs are involved in the secretion of electrolytes in many other tissues and organs, such as CSF formation, by providing bicarbonate and regulating the pH in the choroid plexus (Maren 1967; Supuran et al. 2003); saliva production in acinar and ductal cells (Parkkila 2000); gastric acid production in the stomach parietal cells (Parkkila 2000; see also Chapter 10); and bile production, pancreatic juice production, intestinal ion transport (Parkkila 2000; Maren 1967; see also Chapter 10). CAs are also involved in gustation and olfaction, protecting the gastrointestinal tract from extreme pH conditions (too acidic or too basic), regulating pH and bicarbonate concentration in the seminal fluid, muscle functions and adapting to cellular stress (Chegwidden and Carter 2000; Parkkila 2000; Supuran et al. 2003). Some isozymes, e.g., CA V, are involved in molecular signaling processes, such as insulin secretion signaling in pancreas β cells (Parkkila 2000). Isozymes II and V are involved in important metabolic processes by providing bicarbonate for gluconeogenesis, fatty acids de novo biosynthesis or pyrimidine base synthesis (Chegwidden et al. 2000). Finally, some isozymes (e.g., CA IX, CA XII, CARP VIII) are highly abundant in tumors, being involved in oncogenesis and tumor progression (Pastorek et al. 1994; Chegwidden et al. 2001; Supuran et al. 2003; see also Chapter 9)."

Spoiler

Spoiler

- Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications (978-94-007-7359-2)

"Inhibition of CAs has a long pharmacological history in many fields, being involved in various physiological reactions including respiration, pH regulation, Na+ retention, calcification, tumorigenesis, electrolyte secretion, gluconeogenesis, ureagenesis, and lipogenesis. Hence CA inhibitors (CAIs) have long been used as systemic anticonvulsants, topically acting anti-glaucoma agents, and agents for treating altitude sickness, and have recently shown promising results as anti-obesity, anti-pain, and anti-tumor treatments. In addition to the treatment of human aliments, CAIs’ uses are also emerging as anti-fungal and bacterial agents."

"The role of carbonic anhydrase in CO2 excretion is well known. In red blood cells (RBCs), CA activity accelerates the rate of conversion between molecular CO2, which easily diffuses across membranes, and HCO3−, the form in which the majority of CO2 is transported in the circulation."

"Chappell and Crofts demonstrated that HCO3− was impermeant to the inner mitochondria membrane [84]. While Elder initially proposed that HCO3− could provide the counter ion for energy-dependent Ca2+ transport [85], shortly thereafter it was shown that CO2, not HCO3−, served this function [86]. With the advent of molecular technology, we now know that the bicarbonate transporter family (SLC4A) includes 11 members (see SLCtables), none of which are located in the inner mitochondrial membrane. Thus, de novo synthesis of HCO3− within the mitochondrial compartment is required for providing substrate for pyruvate carboxylase in the gluconeogenic pathway and carbamoyl phosphate synthetase I in ureagenesis in the liver [87, 88]."

"[..]carbon fixation at pyruvate carboxylase increases the concentration of mitochondrial intermediates for other biosynthetic reactions. For gluconeogenesis, it is malate that is drawn from the cycle. For lipogenesis, it is citrate that is drawn off the cycle. Citrate is made from the condensation of acetyl CoA and oxaloacetate, the product of the pyruvate carboxylase reaction. Citrate can be transported out of the mitochondria where it is cleaved to re-form oxaloacetate and acetyl CoA, the latter of which is the substrate for cytoplasmic acetyl CoA carboxylase, the rate-limiting step in de novo lipogenesis. Hazen et al. showed that ethoxzolamide inhibits lipogenesis from pyruvate in 3T3-L1 adipocytes, a mouse adipocyte model [102]. Acetyl CoA carboxylase, like pyruvate carboxylase, utilizes HCO3− as a substrate, in this case for the carboxylation of acetyl CoA."

"While mitochondrial diseases are often associated with defects in the oxidative phosphorylation [105], the above data suggest the possibility that the mitochondrial CAs could serve as targets for modulating gluconeogenesis and lipogenesis, both of which are dysregulated in obesity and insulin resistance. Interestingly, an adverse effect of sulfonamide- and sulfamate-containing anti-epileptic drugs is weight loss in obese patients [106]. Indeed, a randomized trial in 2003 demonstrated significant weight loss in a study of 60 non-epileptic obese patients given Zonisamide, a marketed anti-epileptic aliphatic sulfonamide with known serotonergic and dopaminergic activity in addition to blocking sodium and calcium channels [107]. Furthermore, Topiramate, a sulfamate-substituted saccharide, was approved for weight loss by the FDA in 2012 to be used in conjunction with phentermine treatment (which decreases appetite). While the mechanism for this effect is currently unknown, De Simone et al. have shown that Zonisamide strongly inhibits recombinant CA VA (Ki D20 nM) [108]."

"Saliva plays a critical role in oral homeostasis and decreased rates of secretion increases the risk of oral infections and dental caries [123]. The buffering capacity of salivary secretions depends primarily on bicarbonate ions and provides protection against enamel erosion [124]. Several studies have shown that CA VI is responsible for acid neutralization in dental biofilm, originating from bacterial metabolism. For example, Kimoto et al. showed that patients who rinsed their mouths with sucrose in the presence of acetazolamide had significantly higher salivary pH values than patients who rinsed with only sucrose [125]. In this study, CA activity associated with plaque was specifically identified as CA VI, not CA I or CA II. In another study, Kivela et al. demonstrated that a low concentration of CAVI in saliva is associated with a higher incidence of dental caries [126]. However, a study by Frasseto et al. revealed that CA VI activity in the oral cavity of children with dental caries was higher than that found in children who were caries-free, although the statistical significance of this observation was border-line [4]. Additionally, the variation in CA VI activity [not concentration] in saliva, before and after a sucrose wash, was significantly greater in children with dental caries than those without." "Others have shown that both pH and buffering capacity of saliva is lower in diabetics compared to normal controls [128]."

Spoiler

123. Ship JA (2003) Diabetes and oral health: an overview. J Am Dent Assoc 134 Spec No:4S–10S
124. Dowd FJ (1999) Saliva and dental caries. Dent Clin North Am 43:579–597
125. Kimoto M, Kishino M, Yura Y, Ogawa Y (2006) A role of salivary carbonic anhydrase VI in dental plaque. Arch Oral Biol 51:117–122
126. Kivela J, Parkkila S, Parkkila AK, Rajaniemi H (1999) A low concentration of carbonic anhydrase isoenzyme VI in whole saliva is associated with caries prevalence. Caries Res 33:178–184
127. Peres RC, Camargo G, Mofatto LS, Cortellazzi KL, Santos MC, Nobre-dos-Santos M, Bergamaschi CC, Line SR (2010) Association of polymorphisms in the carbonic anhydrase 6 gene with salivary buffer capacitiy, dental plaque pH, and caries index in children aged 7–9 years. Pharmacogenomics J 10:114–119
128. Ozturk K, Ulucan K, Akyuz S, Furuncuoglu H, Bayer H, Yarat A (2012) The investigation of genetic polymorphisms in the carbonic anhydrase VI gene exon 2 and salivary parameters in type 2 diabetic patients and healthy adults. Mol Biol Rep 39:5677–5682

"H+ ions are remarkably efficient modulators of neuronal excitability. This renders brain functions highly sensitive to small changes in pH which are generated “extrinsically” via mechanisms that regulate the acid–base status of the whole organism; and “intrinsically”, by activity-induced transmembrane fluxes and de novo generation of acid–base equivalents. The effects of pH changes on neuronal excitability are mediated by diverse, largely synergistically-acting mechanisms operating at the level of voltage- and ligand-gated ion channels and gap junctions. In general, alkaline shifts induce an increase in excitability which is often intense enough to trigger epileptiform activity, while acidosis has the opposite effect. Brain pH changes show a wide variability in their spatiotemporal properties, ranging from long-lasting global shifts to fast and highly localized transients that take place in subcellular microdomains. Thirteen catalytically-active mammalian carbonic anhydrase isoforms have been identified, whereof 11 are expressed in the brain. Distinct CA isoforms which have their catalytic sites within brain cells and the interstitial fluid exert a remarkably strong influence on the dynamics of pH shifts and, consequently, on neuronal functions."

"pH exerts a strong modulatory effect on the central nervous system (CNS) function and excitability. Changes in intracellular or extracellular pH (pHi and pHo, respectively) of 0.5 units or less are often sufficient to trigger or suppress paroxysmal activity and, accordingly, much smaller changes are needed for subtle modulation of neuronal excitability. The physiologically relevant pH range (pH 6.5–8.0) corresponds to a very low free H+ concentration, from 10 to 300 nM. An interesting aspect is that this applies to both the intra- and extracellular compartments. Protons are thus eminently suited to affect H+-sensitive targets both within and outside brain cells."

"At the whole-organism level, the key elements in pH regulation are the lungs which control the partial pressure of CO2 (PCO2) in the blood, and the kidneys which are responsible for the net regulation of other important acid–base species, especially HCO3− and NH4+."

Spoiler

Just drag the figure to a Google Images tab to verify the source.


- Combination of Excess Hydrogen Ions with Phosphate and Ammonia Buffers in the Tubule--A Mechanism for Generating “New” Bicarbonate Ions | brainkart.com

"With the major exception of chemosensitive neurons controlling breathing [1], the excitability of most central neurons and neuronal networks is enhanced by an alkalosis and suppressed by an acidosis. Exogenously-induced respiratory acidosis has a profound suppressing action on neuronal excitability and on seizures [2–5]. Respiratory alkalosis generated by hyperventilation is a standard technique used in the clinic for the precipitation of petit mal-type seizures [6]. Hyperventilation is also involved in the generation of febrile seizures in animal models [4] and most likely in children as well [7]. Metabolic alkalosis associated with renal dysfunction such as seen in the EAST syndrome is known to cause epileptiform activity [8]."

"In comparison to Ca2+, the multiple and evolutionarily ancient roles of H+ ions in controlling neuronal signaling have received surprisingly little attention. For instance, the strikingly steep pHo dependency of the gating of GABAa and NMDA channels has been recognized for decades, but the amount of work done on the functional impact of activity-evoked pHo transients on synaptic transmission is sparse [46, 47, 96, 97, 117]. What is known about the actions of H+ does indicate that it is one of the most important physiologically-active agents that exert a fundamental modulatory role in neuronal development, plasticity, as well as synaptic and electrical signalling."

"Moreover, H+ is an amazingly potent agent in the suppression of seizures [5, 101, 102]. Neuronal pH shifts exert also a strong influence on the outcome from disease states such as stroke and ischemia/anoxia [118]. Observations of this kind are consistent with the multiple physiological roles of H+ signalling, and elucidating the underlying processes is likely to be useful in pre-clinical and clinical work on many other disease states, such as migraine and chronic pain [119]. In the context of pathophysiological mechanisms, strategies that target neuronal pH may turn out to be as, or even more relevant, than those designed for modulation of neuronal Cl− homeostasis [102], an area which has recently attracted extensive attention within the neuroscience community [59]. Here, one should note that in addition to tight Ca2+/H+ interactions at the molecular and cellular level [120], pH and Cl− regulation are closely linked, especially via HCO3−-dependent mechanisms [121]."

"The key role of CA isoforms in the suppression, generation and modulation of pH shifts in the brain and other parts of the CNS makes these molecules highly interesting in studies of the fundamental mechanisms underlying neuronal signalling. The developmental profiles of distinct CAs, as well as their strategic localization seen from the level of the whole organism to subcellular microdomains points to a high versatility of their regulatory functions thus providing an exciting subject for molecular, cellular, physiological,medical and pharmacological research [27, 119, 122]. Finally, it is obvious that CAs represent a promising family of targets for CNS drug research and design."


"The chemical diversity, binding specificity and propensity to interact with biological targets has inspired many researchers to utilize natural products as molecular probes. Almost all reported carbonic anhydrase inhibitors comprise a zinc binding group in their structure of which the primary sulfonamide moiety (-SO2NH2) is the foremost example and to a lesser extent the primary sulfamate (-O-SO2NH2) and sulfamide (-NH-SO2NH2) groups. Natural products that comprise these zinc binding groups in their structure are however rare and relatively few natural products have been explored as a source for novel carbonic anhydrase inhibitors."

"The b-CAs from Helicobacter pylori, Candida albicans, Candida glabrata, Cryptococcus neoformans and Brucella suis are essential for growth and have proven susceptible to inhibition with several compound classes including sulfonamides, carboxylates and boronic acids [96–103]."

"The NP compounds presented here (phenols, coumarins and polyamines) are suggestive of a tremendous opportunity that NPs provide for the discovery of novel chemotypes for selectively targeting either human or pathogen CAs."​

- Phenols and Polyphenols as Carbonic Anhydrase Inhibitors

 

[Amazoniac]

The previous post sequence is going to be useful here.

Settling some suspicions:

- Alkalosis resulting from combined administration of a "nonsystemic" antacid and cation-exchange resin

"Certain orally administered antacids are classified as 'nonsystemic' because, although effective in neutralizing hydrogen ion in the stomach, they do not lead to systemic alkalosis.[1] Magnesium hydroxide is an antacid of this type. One mechanism proposed to account for its lack of systemic effect is as follows: after magnesium hydroxide reacts with hydrochloric acid in the stomach, the magnesium ion subsequently combines with bicarbonate ions in the jejunum, forming relatively insoluble magnesium carbonate.[1] Thus, the effect of neutralization of gastric hydrogen ions is balanced by neutralization of bicarbonate ions in the upper gastrointestinal tract. If this explanation is valid, ingestion of an ion-exchange resin with high affinity for magnesium ions might be expected to affect changes in systemic acid base balance."

"The ingestion of another nonsystemic antacid, calcium carbonate, is reported in some instances to cause systemic acid base changes.[2]"​

Whenever they mention resin, its function is to form a molecule with the mineral in question and prevent further interactions. This way it carries the mineral out for excretion in place of carbonate, so 'hydrogen carbonate' is spared and can be recovered.

"[The present] study demonstrates that rapid alkalinization of blood occurs when an orally administered antacid containing magnesium hydroxide [and] aluminum hydroxide is given in combination with a sodium phase cation-exchange resin."

Spoiler

Someone's CO2 concentration dropped with the antacid.
You'll find unusual responses throughout these.

"During the administration of antacid plus sodium resin, the urine became alkaline in each case, and pH values as hIgh as 8.0 were recorded. Total urinary bicarbonate excretion was measured during this period in 4 patients (table 1). The excretion of alkaline urine with a high concentration of bicarbonate suggests that the alkalosis did not result from renal generation of bicarbonate, as might occur with depletion of chloride,[8] although plasma chloride levels fell slightly as CO2 content rose. Alkalosis due to chloride depletion is characterized by a slightly acid urine and usually occurs in association with hypovolemia and/or sodium depletion which were not present in our cases."

Spoiler

"The development of progressive alkalosis in these cases in spite of the large amount of bicarbonate eliminated via the kidneys indicates that a daily base load of considerable magnitude, probably through gastrointestinal absorption, was associated with administration of antacid plus sodium resin. One explanation for these effects is as follows: magnesium hydroxide alone has no systemic alkalotic action because the neutralization of hydrogen ions which it affects in the stomach (fig. 5, top) is balanced by equimolar neutralization of bicarbonate ions in the duodenum and jejunum resulting from the combination of magnesium ions with bicarbonate to form relatively insoluble magnesium carbonate (fig. 5, lower left).[1] Since gastric mucosal cells generate one bicarbonate ion for each hydrogen ion secreted,[9] the net effect of the action of magnesium hydroxide in the stomach would be the systemic accumulation of bicarbonate ions. However, since pancreatic secretory cells generate a hydrogen ion for each bicarbonate ion secreted,[9] the net effect of subsequent magnesium carbonate formation in the jejunum would be the systemic accumulation of hydrogen ions. As these two reactions are equimolar, there is no overall change in systemic acid base balance resulting from magnesium hydroxide administration."

Spoiler

That's in theory, because in practice you'll have a portion of magnesium or killcium being absorbed (can be 30% of the dose), and for this fraction there will be consumption of hydrogen iods at the stomach and recovery of bull**** secreted in the intestines: bi-winning on non-hospitalizing amounts.

"With ingestion of sodium resin, the binding of magnesium ions in exchange for sodium ions effected by the resin (fig. 5, lower right) eliminates formation of magnesium carbonate in the duodenum. The net systemic bicarbonate ion accumulation resulting from buffering of secreted hydrogen ion is now unopposed by a corresponding net systemic hydrogen ion contribution by pancreatic cells, and systemic alkalinization results. Alkalinization would also result from this mechanism to the extent that magnesium ions are absorbed in the duodenum and upper jejunum. Since ordinarily the daily quantity of magnesium absorbed is small,[10] this process probably contributes little to the alkalinization observed."​

Substituting edemium (Na) resin for killcium makes the effect disappear because whether killcium is let go to complex with magnesium or not, you is left with a mineral that's poorly absorbed one way or the other.

"By this proposed mechanism one can construct why the calcium phase resin plus antacid had no systemic alkalinizing effect. With the calcium phase resin, for each magnesium ion bound a calcium ion is released; this calcium ion could combine with bicarbonate ions in the jejunum to form insoluble calcium carbonate. The lack of effect of sodium resin with aluminum hydroxide alone is probably related to the slow and inefficient neutralizing action of an aluminum hydroxide upon gastric hydrogen ion.[1]"​

They reinforce what was commented: it's proportional to the amount uptaken.

"McMillan and FreemanIl found that plasma CO2 content did not rise significantly in 20 patients given 43 g of calcium carbonate per day for 5 days. However, the development of metabolic alkalosis has been noted by Heinemann in 2 of 6 patients receiving large oral doses of calcium carbonate in whom hypercalcemia occurred, 12 and also by Clarkson and his colleagues, who found that ingestion of large amounts of calcium carbonate resulted in either mild alkalosis or decreased renal acid excretion.[2] The latter authors suggest that a quantitative correlation exists between decreased acid excretion and increased calcium absorption following ingestion of calcium carbonate. The removal of calcium ion from gut lumen by absorption in the duodenum and jejunum leads, they suggest, to a mole-for-mole reduction in the subsequent neutralization of bicarbonate ion by re-formation of calcium carbonate. Thus, systemic net accumulation of bicarbonate would occur in direct proportion to the amount of calcium ion absorbed. If these mechanisms are valid, then following calcium carbonate ingestion, inactivation of calcium ion by binding to resin should induce alkalosis. As shown in figure 4, a rise in plasma CO2 content did result from combination of calcium carbonate and sodium resin. The associated increase in blood pH, and urinary excretion of large amounts of bicarbonate (table 1, patients L. E. and S. J.) confirm that systemic base accumulation occurred."

Spoiler

On the importance of meal composition and phosphatal content (because absorption isn't near complete). Taking this garbage on empty stomach or with fruit is missing an opportunity to make its use more physiological.

"It is possible that oral phosphate, when taken with calcium carbonate, might act to remove free calcium ion from the jejunal lumen by formation of relatively insoluble calcium phosphate, and by the mechanism outlined above might lead to alkalosis. Since 2 out of 3 of our patients who received calcium carbonate were on low protein (and thus low phosphate) diets, this mechanism probably played a minor role, if any, in our study. However, some patients taking calcium carbonate with large quantities of milk, high in phosphate content, develop the so-called acute milk alkali syndrome, characterized by acute alkalosis and hypercalcemia.[11] The possibility that formation of calcium phosphate in the manner described above may contribute to the alkalosis in such cases is presently under investigation."​

In other words..

- Metabolic alkalosis due to absorption of “nonabsorbable” antacids

"It has been well documented that the administration of 'nonabsorbable' alkali does not induce an acid-base disturbance. The same holds true for the administration of cation-exchange resins. However, Schroeder [5] [⇈], in a carefully performed study of 11 patients, has demonstrated that the combined administration of a magnesium hydroxide-containing antacid with a sodium polystyrene sulfonate resin in the presence of compromised renal function consistently produces moderate to moderately severe metabolic alkalosis."

"The explanation offered for this can be summarized as follows: normally, hydrochloric acid secreted by gastric parietal cells is neutralized by sodium bicarbonate present in pancreatic, biliary, and intestinal secretions. Sodium chloride, carbon dioxide, and water are formed and subsequently absorbed from the intestine. No alteration of systemic acid-base and electrolyte balance occurs as a consequence of these physiologic digestive processes. When magnesium hydroxide is administered alone, it neutralizes hydrochloric acid in the stomach, forming magnesium chloride and water. In the duodenum and jejunum, magnesium ions combine with bicarbonate, forming the relatively insoluble magnesium carbonate salt, which is subsequently excreted in the stool. In effect, carbonate ions are substituted for the administered hydroxyl ions and lost in the stool. In essence, 'nonabsorbable' antacids are not absorbed because of the relative insolubility of their carbonate salts; thus, no net change in the body’s acid-base balance is realized. In contrast, when magnesium hydroxide is administered with a sodium resin, hydrochloric acid is neutralized in the stomach as just described, but magnesium chloride interacts with the resin to form sodium chloride and magnesium resin, which is subsequently excreted in the stool. Bicarbonate in intestinal fluid remains in soluble form and is reabsorbed rather than excreted in the stool. In effect, the binding of the cationic moiety of the antacid on the resin renders the 'nonabsorbable' alkali absorbable. The net result is absorption of administered alkali and addition of alkali to the body fluids [5]. In the presence of normal renal function, such addition of alkali will do little to alter the systemic acid-base equilibrium: urinary alkalinization and suppression of renal acid excretion results in prompt urinary excretion of the surplus alkali. In the presence of impaired renal function, however, added alkali may not be excreted quantitatively, and a state of metabolic alkalosis may develop [5]."​

- Effect of routine doses of antacid on renal acidification

"Because the final product is insoluble and because there is usually no change in the serum bicarbonate concentration after their administration, antacids of the magnesium/aluminium hydroxide type have been considered to be 'non-systemic' and they are usually assumed to have little or no effect on acid-base homoeostasis.[1] However, coadministration of antacids and the cation-exchange resin sodium polystyrene sulphonate ('Kayexalate') is known to cause metabolic alkalosis.[2,3] Furthermore, regular ingestion of magnesium/aluminium hydroxide antacids causes a sustained rise in urine pH in the range of 0.5-1.0 pH units.[4-9] It is observed within 1 day, generally reaches a peak within 3 days, and persists unchanged for at least 4-6 days during continued therapy, or for at least a day after therapy stops.[5-9] In some,[5-7] but not all,[8] studies the alkaluria is independent of time of day (but the normal circadian rhythm is not abolished[9]); it tends to be inversely proportional to the baseline urine pH.[5,6] The rise in urine pH occurs with pure magnesium hydroxide or combinations of magnesium and aluminium hydroxide[5-9] but not with aluminium hydroxide or dihydroxyaluminium aminoacetate.[6] The blood pH may rise slightly but not significantly.[7]"

Spoiler

"In the absence of a renal acidification abnormality, a fall in net acid excretion implies either a gain of alkali or a loss of acid.[10,15] The reaction of magnesium hydroxide with gastric hydrochloric acid produces magnesium chloride,[2,3] which reacts in the small intestine with secreted sodium bicarbonate to give magnesium carbonate. This compound is insoluble and presumably mostly excreted in the faeces. The net reaction theoretically consumes equimolar amounts of hydrochloric acid and sodium bicarbonate and should have little or no net effect on acid-base balance or renal acidification.[2,3]"

"In accordance with this hypothesis, the explanation for the severe alkalosis that may accompany the coadministration of magnesium hydroxide and a cation-exchange resin[2,3] is that the binding of magnesium by the resin (or perhaps by neutral phosphate[3]) reduces its availability to react with bicarbonate, so that more of the secreted bicarbonate is available for reabsorption (relative to the amount of hydrochloric acid consumed). It appears that the most likely mechanism for antacid-induced change in renal acid excretion is the interaction of magnesium hydroxide with gastrointestinal hydrochloric acid and sodium bicarbonate, with greater consumption of the acid, rather than absorption of the exogenous alkali."

"This hypothesis is supported both by our results and by previous findings. The fact that the change in net acid excretion was much smaller than the amount of alkali ingested and the small estimated proportion of magnesium absorbed militate against major absorption of exogenous alkali. Clarkson et al reported that the daily ingestion of 200 mmol calcium carbonate, which is believed to produce an alkali load in a similar way to magnesium hydroxide,[2] reduced net acid excretion by only 26 mmol/24 h, and that the reduction in net acid excretion was approximately equivalent to the estimated increase in intestinal calcium absorption.[16] This finding suggested that the amount of calcium absorbed, by becoming unavailable to react with secreted bicarbonate, would result in a quantitative reduction in bicarbonate consumption."

"We cannot, of course, rule out the possibility that, in addition, there is absorption of a small amount of exogenous alkali. It is possible that magnesium carbonate may be very slightly soluble and thus potentially absorbable, but these arguments make its absorption unlikely also. The average daily gastric hydrochloric acid output in normal man is 148-289 mmol;[17] if this hypothesis is correct, this would also be the maximum increase in antacid-induced "net gastrointestinal sodium bicarbonate absorption" (if all secreted hydrochloric acid and no sodium bicarbonate were consumed)."

"It is possible that some of the antacid-derived magnesium in the gastrointestinal tract becomes bound to fats, proteins, or various anions."

"If we assume that our subjects were undergoing a sustained alkali load of approximately 41 mmol/day, why was there no significant increase in blood bicarbonate or pH? The explanation is that the fall in net acid excretion was sufficient to offset the alkali load. In the presence of a normal or near-normal glomerular filtration rate, very large bicarbonate loads are required to cause a sustained metabolic alkalosis, since the capacity of the normal kidney to excrete alkali is so great.[20]"

"Even though antacids alone do not cause metabolic alkalosis in patients with normal renal function, our findings are clinically important for the following reasons. Substantial changes in urine pH induced by antacid ingestion might exacerbate nephrolithiasis by affecting the solubility of urinary constituents such as calcium phosphate[21] and alter the renal handling or efficacy of drugs (or their derivatives).[22] Changes in acid-base status caused by antacids might confound interpretation of urinary pH data in patients with suspected acid-base disturbances, such as renal tubular acidosis. Antacid use might contribute to the induction of mixed acid-base conditions, for example, in a patient with chronic renal failure, or to the exacerbation or perpetuation of metabolic alkalosis."

"Thus, our findings confirm earlier observations indicating the predictable effect of antacids on urine pH. More importantly, we have shown a reproducible, greater than two-thirds, reduction in net acid excretion. Even though antacids do not induce metabolic alkalosis in normal individuals, magnesium/aluminium hydroxide type antacids should no longer be termed 'non-systemic'."​

- Pharmaceutical Inorganic Chemistry: Gastrointestinal Agents (Antacid)

 

[Amazoniac]

Waste-product transport in blood:

Spoiler: Carbon Dioxide Transport | Anatomy On Demand

Another representation:

Spoiler

Note the percentage of distribution.

- Transport of oxygen in the blood | Royal Society of Chemistry

- Low dietary zinc decreases erythrocyte carbonic anhydrase activities and impairs cardiorespiratory function in men during exercise

"Because zinc-containing enzymes number >200 in mammalian systems (11, 12), any effect of dietary zinc may be translated into metabolic and functional defects by zinc metalloenzymes. Carbonic anhydrase (EC 4.2.1.1), a zinc metalloenzyme, catalyzes the reversible hydration and dehydration of carbon dioxide, a product of cellular aerobic energy production (12). Removal of zinc from this metalloenzyme inactivates the enzyme (13)."

"Studies in various species, including rodents, domestic fowl, calves, and lambs, have found that dietary zinc deficiency significantly reduces red blood cell (RBC) carbonic anhydrase activity (14–19) and, in a few cases, impairs respiratory function (14, 15). Sickle-cell anemia patients with biochemically determined zinc and other nutritional deficiencies had significantly decreased carbonic anhydrase protein in RBCs that increased significantly with zinc supplementation (20). Thus, reduced carbonic anhydrase activity in RBCs may be an indicator of zinc deficiency, particularly in humans."

"In this double-blind, randomized crossover study, 14 men aged 20–31 y were fed low-zinc and supplemented [with 15 mg of zinc sulfate] (3.8 and 18.7 mg/d) diets made up of Western foods for 9-wk periods with a 6-wk washout."

"Dietary zinc did not affect hemoglobin or hematocrit. Low dietary zinc resulted in lower (P < 0.05) serum and erythrocyte zinc concentrations, zinc retention, and total carbonic anhydrase and isoform activities in RBCs.

Spoiler

"Peak oxygen uptake, carbon dioxide output, and respiratory exchange ratio were lower (P < 0.05), and ventilatory equivalents for metabolic responses during exercise were greater (P < 0.05), with low than with supplemental zinc intake. Similar functional responses were observed during prolonged, submaximal exercise."

"These findings indicate that low dietary zinc is associated with significant reductions in zinc status, including RBC carbonic anhydrase activities, and impaired metabolic responses during exercise."​

 

[Amazoniac]

- Gastric mucosal barrier - Wikipedia
- Helicobacter pylori - Wikipedia
- Ureases as a target for the treatment of gastric and urinary infections
- H-pylori? (check out 3rd link)