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

[Amazoniac]

Can't the starting source be the usual suspect - not from pepsinogen, but from vascular carbonic acid? That would act like the spark that initiates a chain reaction in the gut walls where the activation segment is activated , and this perpetuates the acidity needed to enable a chain reaction of producing carbon dioxide and agmatine, and the agmatine would provide the alkaline environment for carbon dioxide to turn into carbonic acid for use as substrate for making HCl?

Possibly (for now I'll have to take their word for it, I don't understand how agmatine works for this purpose yet).

Perhaps sourcing crapon dioxide this way contributes to increase the acidity when large amounts of protein are being digested. The 'patchy distribution' of pepsinogen would require something else in cells without it, explaining the acidity and protecting them against it.

Thanks for insisting on the topic, otherwise I would have dismissed it.

 

[yerrag]

Possibly (for now I'll have to take their word for it, I don't understand how agmatine works for this purpose yet).

Perhaps sourcing crapon dioxide this way contributes to increase the acidity when large amounts of protein are being digested. The 'patchy distribution' of pepsinogen would require something else in cells without it, explaining the acidity and protecting them against it.

Thanks for insisting on the topic, otherwise I would have dismissed it.

Glad your research brought this to light. If this were a way to increase gastric juice production, I wonder if -

- supplemental arginine would result in increased gastric juice production, and be helpful in addressing acid reflux issue; as I wonder if this arginine supplementation would be able to break a vicious cycle involving faulty digestion involving low acidity by providing a boost in stomach acidity to improve digestion and helping in delivery of nutrients to the blood stream. Concurrent with intake of soda water for its carbon dioxide content to provide for vascular availability of carbon dioxide, while simultaneously aiding the kidneys in excreting acidity from the system, to the effect that a more alkaline acid-base balance would allow room for the conversion of CO2 to carbonic acid, as the lower pH would allow this to take place. If say there is high lactate in the system that needs to be excreted by the kidneys, then making it possible for ammonium lactate to be excreted would relieve the system of a lot of acidity that can only be done by the kidneys, as in an extreme case of metabolic acidosis, there isn't any H+ ions to spare for excretion and this makes it impossible to excrete ammonium lactate, and instead potassium phosphate is excreted, which doesn't relieve the system of acidity much (the reason H+ is unavailable is because H+ ions have transferred to cells and K+ ions replacing it in the blood/ecf as the body's way of lowering the ecf acidity). It may be that high thiamine supplementation is needed as thiamine can enable conversion of lactate into pyruvate and into glucose in the Cori cycle. I'm not sure if i'm right about this though, but I'm hoping that tregular hiamine supplementation can slowly remove lactate from the system and eventually the ecf would not be so acidic, and at this point, the K+ ions can fo back to the cel, and the H+ ions back to the ecf, and then the kidneys can go back to excreting ammonium lactate. So if this is correct, we would have a stack that could be used for fixing acid reflux, as a start, on the way to restoring acid-base balance along with fixing hypothyroid, with some additional tweaks.

Does this make sense to you?

 

[yerrag]

In addition, I'm also thinking that if the production of stomach acid involves arginine (and maybe lysine) being used as substrates to make carbon dioxide, would this be an arginine sink that would divert the urea cycle's production of urea, as before arginine is turned into urea, it is diverted to being used in the gastric walls. So, would BUN be increased when the stomach isn't making enough acid?

 

[Amazoniac]

- 2.1 Acid-Base Balance - Acid-Base Physiology | Anesthesia MCQ

Spoiler

"The acid is more correctly carbonic acid (H2CO3) but the term 'respiratory acid' is usually used to mean carbon dioxide. But CO2 itself is not an acid in the Bronsted-Lowry system as it does not contain a hydrogen so cannot be a proton donor. However CO2 can instead be thought of as representing a potential to create an equivalent amount of carbonic acid. Carbon dioxide is the end-product of complete oxidation of carbohydrates and fatty acids. It is called a volatile acid meaning in this context it can be excreted via the lungs. Of necessity, considering the amounts involved there must be an efficient system to rapidly excrete CO2."

"The amount of CO2 produced each day is huge compared to the amount of production of fixed acids. Basal CO2 production is typically quoted at 12,000 to 13,000 mmols/day."

"Increased levels of activity will increase oxygen consumption and carbon dioxide production so that actual daily CO2 production is usually significantly more than the oft-quoted basal level. [Different texts quote different figures usually in the range of 12,000 to 24,000 mmoles/day but the actual figure simply depends on the level of metabolic activity and whether you quote basal or typical figures.]

Daily CO2 production can also be calculated from the daily metabolic water production. The complete oxidation of glucose produces equal amounts of CO2 and H20. The complete oxidation of fat produces approximately equal amounts of CO2 and H2O also. These two processes account for all the body's CO2 production. Typically, this metabolic water is about 400 mls per day which is 22.2 moles (ie 400/18) of water. The daily typical CO2 production must also be about 22,200 mmoles."


"[The 'metabolic acids' term] covers all the acids the body produces which are non-volatile. Because they are not excreted by the lungs they are said to be fixed in the body and hence the alternative term 'fixed acids'. All acids other than H2CO3 are fixed acids.

These acids are usually referred to by their anion (eg lactate, phosphate, sulphate, acetoacetate or b-hydroxybutyrate). This seems strange at first because the anion is, after all, the base and not itself the acid. This useage is acceptable in most circumstances because the dissociation of the acid must have produced one hydrogen ion for every anion so the amount of anions present accurately reflects the number of H+ that must have been produced in the original dissociation.

Another potentially confusing aspect is that carbon dioxide is produced as an end-product of metabolism but is not a metabolic acid according to the usual definition. This inconsistency causes some confusion: it is simplest to be aware of this and accept the established convention.

Net production of fixed acids is about 1 to 1.5 mmoles of H+ per kilogram per day: about 70 to 100 mmoles of H+ per day in an adult. This non-volatile acid load is excreted by the kidney. Fixed acids are produced due to incomplete metabolism of carbohydrates (eg lactate), fats (eg ketones) and protein (eg sulphate, phosphate).

The above total for net fixed acid production excludes the lactate produced by the body each day as the majority of the lactate produced is metabolised and is not excreted so there is no net lactate requiring excretion from the body.

The routes of excretion are the lungs (for CO2) and the kidneys (for the fixed acids). Each molecule of CO2 excreted via the lungs results from the reaction of one molecule of bicarbonate with one molecule of H+. The H+ remains in the body as H2O."

Was is complete metabolism, will is functional lung, won't is burden.

 

[Amazoniac]

- Low-grade metabolic acidosis as a driver of insulin resistance

"There is a decreased buffering capacity in the interstitial fluid compared with the intracellular cytosol and blood. This is due to the fact that the interstitium only has relatively weak pH buffers, such as bicarbonate and phosphate, whereas blood also has proteins such as haemoglobin and albumin that can bind to hydrogen ions. Thus, the interstitial pH varies more than the blood."​

 

[Amazoniac]

- Buffering in acute respiratory acid-base disturbances | Deranged Physiology

"Buffering by proteins is performed by amino acid side chains and various other loose groups which hang off the main protein body and don't participate in bonds which are critical to maintaining the protein structure. Generally speaking, all proteins have these sorts of groups hanging off them, but in practice the only amino acid groups worth a damn as buffers at physiological pH are histidine aromatic rings (the imidazole groups). All the others have a pKa which is well outside the normal survivable range."​

- Proteinogenic amino acid - Wikipedia

- The multiple roles of histidine in protein interactions

 

[Amazoniac]

- Dietary Treatment of Metabolic Acidosis in Chronic Kidney Disease

Spoiler

[31] Effect of L-Methionine on the Risk of Phosphate Stone Formation

It's not usual to take 1.5 g of methionine at once and in isolation, making it prone to be degraded instead of incorporated in proteins. However, we do find people taking cysteine in amounts that are better quantified in grams.

- The diurnal variation in urine acidification differs between normal individuals and uric acid stone formers

Spoiler

---

- Histone Acetylation Regulates Intracellular pH

 

[Amazoniac]

Yes yes, but how much of that crapon actually makes it into the body, and in what form? How much of those 2g escape as gas, starting with the initial can-opening explosion: the increase in pressure to reach equilibrium with the local atmospheric pressure will release a good portion of it. What makes it into the mouth and has a chance to interact with saliva is converted to bicraponate by craponic anushydrase IV, how much depends on speed of ingestion (chugging vs. sipping). So it seems to me that by slowly sipping a craponated beverage, most of the (little) crapon is ingested in the form of bicraponate? Not so much when chugging it -- but then I am not paid by the belching contest industry.

It seems that Dr. Circus's contention (that was disputed) that "ingesting craponate as bicraponate vvater or craponated vvater has the same end result of passing into the blood as bicraponate" might be true after all?

It's not the same. Carbionic annihilase acting on crapon dioxide won't change the fact that it's the medium that will dictate the dissociation/ionization, obtaining hydrocraponate ions from hydration of CO2 will be matched by an equal amount of hydrogen ions appearing, requiring the body to deal with these. I think that the hydrogen ions can even appear before hydrocraponate because the enzyme attacks crapon dioxide with hydroxide ions that are obtained from water, for this to occur, there will be an hydrogen ion released in the medium while the enzyme is busy with sequestered hydroxide.

Diffusion to tissues can occur before leaving the body and without involving external dissociation:
- Back-diffusion of CO2 and its influence on the intramural pH in gastric mucosa

 

[Jam]

It's not the same. Carbionic annihilase acting on crapon dioxide won't change the fact that it's the medium that will dictate the dissociation/ionization, obtaining hydrocraponate ions from hydration of CO2 will be matched by an equal amount of hydrogen ions appearing, requiring the body to deal with these. I think that the hydrogen ions can even appear before hydrocraponate because the enzyme attacks crapon dioxide with hydroxide ions that are obtained from water, for this to occur, there will be an hydrogen ion released in the medium while the enzyme is busy with sequestered hydroxide.

Diffusion to tissues can occur before leaving the body and without involving external dissociation:
- Back-diffusion of CO2 and its influence on the intramural pH in gastric mucosa

1) Generation of HCl
Parietal cells: CO2 (from blood) + OH- (from H2O) + carbonic anhydrase = H+ (to lumen) & HCO3- (to blood)
Lumen: H+ + Cl- (from parietal cells from blood) = HCL

2) Ingestion of baking soda (NaHCO3)
NaHCO3 + HCl = NaCl + (H20 + CO2 + H2CO3 = carbonated water)

2a) Ingestion of carbonated water (H20 + CO2 + H2CO3)

3) ?

Stimulation by sparkling water of gastroduodenal HCO3- secretion in rats - PubMed

Sparkling water stimulates HCO3- secretion in both the stomach and the duodenum, but the mechanisms involved differ in these two tissues; the response in the former is mainly due to the intracellular supply of HCO3- with the aid of carbonic anhydrase, while in the latter the response is...

pubmed.ncbi.nlm.nih.gov

Conclusions: Sparkling water stimulates HCO3- secretion in both the stomach and the duodenum, but the mechanisms involved differ in these two tissues; the response in the former is mainly due to the intracellular supply of HCO3- with the aid of carbonic anhydrase, while in the latter the response is dependent on the NHE1, AE and NBC, and is mediated by endogenous prostaglandins as well as capsaicin-sensitive afferent neurons, in addition to the intracellular supply of HCO3-.

Major differences between 2 and 2a: 2a requires very little HCl production, so less (or no) HCO3- passes to the blood due to its generation?

What happens next?? Normally, the pancreas would secrete the HCO3- generated in 1) back into the duodenum to neutralize remaining HCl + other acids (including fatty acids).

 

[Amazoniac]

1) Generation of HCl
Parietal cells: CO2 (from blood) + OH- (from H2O) + carbonic anhydrase = H+ (to lumen) & HCO3- (to blood)
Lumen: H+ + Cl- (from parietal cells from blood) = HCL

2) Ingestion of baking soda (NaHCO3)
NaHCO3 + HCl = NaCl + (H20 + CO2 + H2CO3 = carbonated water)

2a) Ingestion of carbonated water (H20 + CO2 + H2CO3)

3) ?

Stimulation by sparkling water of gastroduodenal HCO3- secretion in rats - PubMed

Sparkling water stimulates HCO3- secretion in both the stomach and the duodenum, but the mechanisms involved differ in these two tissues; the response in the former is mainly due to the intracellular supply of HCO3- with the aid of carbonic anhydrase, while in the latter the response is...

pubmed.ncbi.nlm.nih.gov

Conclusions: Sparkling water stimulates HCO3- secretion in both the stomach and the duodenum, but the mechanisms involved differ in these two tissues; the response in the former is mainly due to the intracellular supply of HCO3- with the aid of carbonic anhydrase, while in the latter the response is dependent on the NHE1, AE and NBC, and is mediated by endogenous prostaglandins as well as capsaicin-sensitive afferent neurons, in addition to the intracellular supply of HCO3-.

Major differences between 2 and 2a: 2a requires very little HCl production, so less (or no) HCO3- passes to the blood due to its generation?

What happens next?? Normally, the pancreas would secrete the HCO3- generated in 1) back into the duodenum to neutralize remaining HCl + other acids (including fatty acids).

The first instance is equilibrated, you start with CO2 and H2O and end with them.

Spoiler

You're then comparing the ingestion of crapon dioxide (from a craponated beverage) and bull****.

Regarding crapon dioxide, most of this CO2 should reach the stomach, some will be lost through burping, the other part will diffuse through tissues and it can be treated as H2CO3 (that can dissociate into H+ and HCO3−); it's acidifying.

H2CO3​

Regarding bull****, it results in immediate consumption of H+ in the stomach, yielding NaCl and H2CO3 (that can be dehydrated to CO2 and behave as the previous case).

NaHCO3 + HCl → Na+ + Cl− + H+ + HCO3− → NaCl + H2CO3​

​

- Cl− can be ignored because the secretion to the stomach matches the recovery at the intestine.​

- H+ will depend on how much reenters the body from diffusion in the form of CO2, we can expect a partial loss as happens in the case of plain CO2. Unlike Cl−, balance is likely not neutral because loss must exceed gain of acid.​

- The reliable component is edemium: it's added to the system and can't be lost. It's going to be absorbed as NaCl without needing extra pancreatic output.​

Therefore, the major difference is the addition of edemium (without new chlorroride), which should result in alkalinization. Buffers that are usually present in beverages (phosphate or citrate) weren't considered.

 

[Jam]

The first instance is equilibrated, you start with CO2 and H2O and end with them.

Spoiler

View attachment 29539

You're then comparing the ingestion of crapon dioxide (from a craponated beverage) and bull****.

Regarding crapon dioxide, most of this CO2 should reach the stomach, some will be lost through burping, the other part will diffuse through tissues and it can be treated as H2CO3 (that can dissociate into H+ and HCO3−); it's acidifying.

H2CO3​

Regarding bull****, it results in immediate consumption of H+ in the stomach, yielding NaCl and H2CO3 (that can be dehydrated to CO2 and behave as the previous case).

NaHCO3 + HCl → Na+ + Cl− + H+ + HCO3− → NaCl + H2CO3​

​

- Cl− can be ignored because the secretion to the stomach matches the recovery at the intestine.​

- H+ will depend on how much reenters the body from diffusion in the form of CO2, we can expect a partial loss as happens in the case of plain CO2. Unlike Cl−, balance is likely not neutral because loss must exceed gain of acid.​

- The reliable component is edemium: it's added to the system and can't be lost. It's going to be absorbed as NaCl without needing extra pancreatic output.​

Therefore, the major difference is the addition of edemium (without new chlorroride), which should result in alkalinization. Buffers that are usually present in beverages (phosphate or citrate) weren't considered.

Thank you for that.

The primary sources of acidity in the diet are sulfur-containing amino acids, salt [Cl], and phosphoric acid in soft drinks (For a more complete discussion of the adverse effects of phosphates, see Lara Pizzorno’s article in IMCJ 13.6).3 You will likely immediately scoff that salt is neutral in pH and is not metabolized to anything that is acid—and you would be right. Nonetheless, research has clearly shown that—happily reversibly—NaCl accounts for 50% of the net acidity of the average American diet.4 The mechanism is not definitively known, it is currently thought to be impairment of the kidney’s ability to excrete acid compounds. Figure 1 shows the sources of salt in the typical Western diet. If you look closely, you will see that wheat products are the primary source of salt—which may account for the common belief that wheat products are acid forming (wheat itself is only slightly acid forming)."

At first glance, one might ask, how can NaCl be alkalinizing in the first (bull**** consumption), while being acidifying in the second (pure NaCl), if it is the Na that makes the first result in alkalinization.

 

[Jam]

Deleted.

 

[Amazoniac]

Both NaHCO3 and NaCl that are ingested should reach the intestine as NaCl. Since the stomach is acidic, HCO3− will protonate to H2CO3, which can be lost as CO2. So, in the case of NaHCO3, it represents a certain gain of Na+ and a potential loss of H+, whereas with NaCl, it's straightforward. This must be a way of preventing abrupt imbalances in the extracellular compartment since Na+ and Cl− are the predominant ions.

- 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."​

- Does Aerobic Respiration Produce Carbon Dioxide or Hydrogen Ion and Bicarbonate?

"While the left-hand side of the following reaction is virtually instantaneous, the right-hand side is very slow in physiologic terms (half time of roughly 7 s at 37°C) without catalysis. However, it is accelerated to completion within milliseconds by carbonic anhydrase (CA).​

​

H+ + HCO3− ←→ H2CO3 ←CA→ CO2 + H2O"​

- Is Bypassing the Stomach a Means to Optimize Sodium Bicarbonate Supplementation? A Case Study With a Postbariatric Surgery Individual

[..]large doses of sodium bicarbonate (i.e., 0.2 - 0.3 g/kg BM) are necessary since, upon ingestion, it is dissociated in the stomach acid to form sodium (Na+) and bicarbonate (HCO3-); substantial amounts of the latter are swiftly neutralised by hydrogen ions (H+), producing carbon dioxide [CO2] (Turnberg, Fordtran, Carter, & Rector, 1970). The production of CO2 in the stomach may cause gastric discomfort with symptoms including bloating and abdominal pain; nausea and vomiting are other commonly reported side effects (Carr, Slater, et al., 2011). Typically, a dose of 0.3 g/kg BM (or 21 g for a 70-kg individual) increases blood HCO3− by ~6 mmol/L (McNaughton, 1992); this represents only ~15% of the expected increase in blood HCO3− if the entire dose were to be absorbed into the bloodstream (considering ~180 mmol of HCO3− from 21 g NaHCO3− should increase HCO3− by ~36 mmol/L in a 5-L bloodstream). This estimation illustrates that the majority of the ingested HCO3− is likely neutralised in the stomach acids or, likely to a lesser extent, eliminated in faeces. Therefore, avoiding losses of bicarbonate due to neutralisation in the stomach could result in less gastric discomfort and larger increases in blood bicarbonate.​

The effect of CaCO3 on the extracellular compartment is weaker than NaHCO3 despite that CO32− and HCO3− yield H2CO3 at the stomach, with the former being more alkalinizing. The incomplete absorption of killcium makes it a possible base robber at the intestine and can be a confounding factor, yet cardiarrestium absorbs similarly well when compared to edemium and doesn't lead to the same extracellular changes. Therefore, the rôle of edemium is not to be ignored.

 

[Jam]

Mechanism of Bicarbonate Absorption and Its Relationship to Sodium Transport in the Human Jejunum

In summary, these studies on pernicious anemia patients suggest that acid secretion mediates bicarbonate absorption in the human jejunum. If so, it would be anticipated that development of hydrogen ion concentration gradients would be the major factor which limits the rate of bicarbonate absorption. Acid secretion lowers the pH of jejunal contents by consuming HC03-, and this effect is accentuated by the acid disequilibrium pH. High luminal bicarbonate concentrations would mitigate this effect considerably and should be associated with higher rates of H' secretion and HC03- absorption. As shown in Fig. 3, the rate of bicarbonate absorption was in fact markedly dependent on bicarbonate concentration in the range of 2-40 mEq/liter, but raising the luminal bicarbonate concentration to 93 mEq/liter had relatively little additional effect. These findings suggest that secretion of acid in the jejunum is limited by pH gradients only when luminal bicarbonate falls below approximately 40 mEq/liter; above this level the pH of jejunal contents is sufficiently alkaline to insure near maximum rates of acid secretion.

In most H+ secretory systems, the enzyme carbonic anhydrase is thought to provide a plentiful supply of H+ at the H+ secretory site by catalyzing the hydration of C02 to H2CO3. Inhibition of this enzyme might thus be expected to inhibit the rate of jejunal H+ secretion and HC03- absorption. As shown in Fig. 4, acetazolamide did inhibit HCO3- absorption by approximately 50%. However, two facts make interpretation of this effect of acetazolamide difficult. First, carbonic anhydrase is present in only very small and perhaps insignificant amounts in the small intestinal mucosa of animals (10). Second, acetazolamide has been shown to exert effects other than on carbonic anhydrase (11). Thus, acetazolamide may inhibit acid secretion and bicarbonate absorption through mechanisms not involving carbonic anhydrase.

Finally, in what form is the hydrogen secreted? Three possibilities are a neutral HCl pump, an electrogenic hydrogen pump (chloride secretion or sodium absorption would follow passively), and a sodium hydrogen exchange process. Whatever the mechanism of hydrogen secretion, it is clear that it somehow enhances sodium absorption as well as mediates bicarbonate absorption. A neutral HCl pump would not enhance sodium absorption, so this form of acid secretion seems unlikely. The two remaining possibilities cannot be definitely distinguished from the data on hand. The fact that PD does not change with increasing rates of Ho secretion (as bicarbonate concentration rises) favors an electrically neutral sodium-hydrogen exchange. On the other hand, a slight change in PD, perhaps undetectable by our method, might enhance sodium absorption in a tissue which is so highly permeable to sodium ions. Thus, electrogenic He secretion cannot be entirely excluded.

 

[Jam]

 

[Jam]

Not sure if this was posted already in here:

Effects of dietary protein-load and alkaline supplementation on acid–base balance and glucose metabolism in healthy elderly​

Conclusions​

Four weeks of protein-rich diet did not significantly influence acid–base balance. However, alkaline supplementation improved systemic and tissue acid–base parameters and oxidative glucose metabolism.

 

[Amazoniac]

- Factors influencing the concentration of ionised calcium | Deranged Physiology

"First of all, let us address the misnomer of "ionised" calcium. It's all ionised, people. Unless it is in a covalent bond with something, it is present as an ion. To be sure, it might be clinging to the side of an albumin molecule, or it might be complexed with a chelator like citrate, but it is still an ion, and not a member of a molecule per se. However, the trend of calling unbound calcium "ionised calcium" persists, and is prevalent at all levels of academic medicine. It is only this fraction which actually does anything useful, and is also the fraction which enjoys tight regulation by PTH and venom D; whereas the bound fraction is physiologically useless. Respecting tradition and eschewing pedantry, hereafter "ionised calcium" will be used to in reference to the free fraction."​

​

"Generally speaking, when one reads a textbook on this topic, one typically encounters a figure of 45-55% for the amount of calcium which is present in the serum in its free unbound state. The Lancet article [referenced] reports that each 10 g/L of albumin bind about 0.2 mmol/L of calcium. This means the totally deconditioned ICU patient with 10 g/L of albumin will have an ionised calcium which is about 0.6 mmol/L higher than the patient with a normal albumin, if the total serum calcium level is the same for both. Not all protein-bound calcium is bound purely to albumin - some (about 10%) is complexed with globulins."​

​

"The influence of pH on ionised calcium is discussed in slightly greater detail elsewhere."​

↳ Correction of ionised calcium for pH | Deranged Physiology

"[Killcium] binds reversibly to twelve of the sixteen exposed [histidine] imidazole binding sites on the albumin molecule."​

​

"Of these available cation-binding sites, only 10-15% are occupied (i.e. only one or two sites). This means there are plenty of available sites to bind other cations (eg. magnesium) and the divalent cation species rarely enter into binding site competition with one another, particularly as there are so few of them (1-2 mmol/L). On the other hand, the hydrogen (or hydronium) cation is a constant source of competition. The positively charged water molecule species work to displace calcium from its binding sites."​

​

"For each 0.1 decrease in pH, ionised calcium rises by about 0.05 mmol/L."​

- pH-adjusted ionized calcium | Acute Care Testing

"Thus, pH change is inversely proportional to the concentration of iCa2+ (Fig. 1)."​

​

Spoiler

​

"Unfortunately, there are some sample collection practices that can artificially change the pH and cause an inaccurate iCa2+ result. Prolonged use of a tourniquet or the practice of having the patient clench or pump their fist can increase lactate production, thereby lowering the pH and falsely increasing the amount of iCa2+."​

​

"In addition, iCa2+ specimens must be collected under anaerobic conditions to avoid loss of CO2 and pH increase. Finally, any significant time delay between collection and iCa2+ measurement can cause an apparent hypercalcemia due to metabolic activity (in vitro pH decrease)."​

​

"It can be inferred from Fig. 1 that iCa2+ levels are often increased in patients with metabolic or respiratory acidosis, whereas in metabolic or respiratory alkalosis iCa2+ is decreased."​

- Alkalosis | Wikipedia

"[Alkalosis] may [..] cause low blood calcium concentration. As the blood pH increases, blood transport proteins, such as albumin, become more ionized into anions. This causes the free calcium present in blood to bind more strongly with albumin. If severe, it may cause tetany."​

 

[Amazoniac]

There's a cool (and hopefully traumatizing) way to represent that for every HCO3− derived from H2CO3 (or CO2 + H2O), a H+ will be appearing along and acidifying a system. After all, it's the concentration of free H+ that's isolated in equations.

Spoiler

We know that just like other acids, craponic acid has its dissociation constant, where the unionized and ionized forms in question are in equal parts, it's a small number: 4.4 × 10^−7. However, everything in the familiar equation below (including the dissociation constant) is log-transformed and signs are inverted to deal with more practical values. The following numbers are approximated.

−log([H+]) = −log(Ka) − log([H2CO3]/[HCO3−])
pH = pKa + log([HCO3−]/[H2CO3])

Craponic acid:
Ka: 4.4 × 10^−7
log(Ka): −6.35
−log(Ka) or pKa: 6.35
pKa (physiological): 6.1

- The impact of temperature changes on biological buffers' pKa | Hopax FC

pH = 6.1 + log([HCO3−]/[H2CO3])

If HCO3− and H2CO3 are in equal parts, log(1) = 0. Therefore, pH = 6.1.

If the ratio was 10:1, log(10) = 1. pH would be 7.1 from 6.1 + 1.

To have a pH of 7.4, we arrive at the standard ratio of 20:1, from:

24 mmol/L HCO3−
1.2 mmol/L H2CO3 (obtained from the concentration of CO2 multiplied by a solubility factor of 0.03)

24/1.2 = 20​

pH = 6.1 + log(20) = 6.1 + 1.3 = 7.4

Note that there's a positive sign before log when everything else is supposed to be negative, it's because they inverted the forms:

−log(1/20) = log(20/1)

Spoiler

Source: the internet.

To respect this ratio, we would have something like this:

Spoiler

Yet, the hydrogen ion concentration is kept extremely low relative to other ions. Perhaps such disappearance is what blurs the picture, so to do a speak.

For the great portion of CO2 that's hydrated, like craponic annihilase that sequesters OH− temporarily, hemoglobids (and other proteins) do the same with H+, they take it up and hold on to it until H2CO3 is recomposed to leave in the form of CO2 through the lungs. This way, hydrocraponate appears in plasma alone, making it seem that there was no addition of acid.

Spoiler

Human Physiology: Gas Exchange and Transport | Nathan Staples - Cañada College

In exchange with chlorroride, it's possible to maintain ion balance pairing edemium.

What we get to see:

Spoiler

 

[Amazoniac]

The topic of factors that affect the oxygen-hemoglobin association and dissociation was discussed previously, but here's more on it with details that might have been left out:

- Red blood cells in sports: Effects of exercise and training on oxygen supply by red blood cells

Spoiler

- The oxyhaemoglobin dissociation curve | Deranged Physiology

"Haemoglobin is a heterotetramer protein. It is composed of two α-haemoglobin and two β-haemoglobin subunits. Each subunit binds oxygen independently. Then, once an oxygen molecule is bound to it, the oxygenated subunit increases the oxygen affinity of the three remaining subunits. This is positive cooperativity: the subunits "cooperate" to enhance each other's binding of oxygen."

"Though in a totally deoxygenated state it exhibits a certain aloof disinterest in oxygen, haemoglobin becomes more and more interested the more oxygen it binds. The heterotetrameric form of haemoglobin is therefore an ideal molecule for oxygen transport, exhibiting a low oxygen affinity in the hypoxic environment of the capillaries, and a high oxygen affinity in the well-oxygenated pulmonary circulation."

"Much of positive cooperativity and the resulting sigmoid shape of the dissociation curve is owed to the influence of allosteric effectors such as pH, pCO2, 2,3-BPG and so forth. The shape of the curve in the absence of all allosteric effectors is actually a rather boring hyperbolic one."

"I was able to produce a series of curves to reflect four of the major influences on the shape of the dissociation curve:

Spoiler

"

- Factors which influence the affinity of haemoglobin for oxygen | Deranged Physiology

"2,3-bisphosphoglycerate is a byproduct of the pathway of glycolysis."

"[..]the pathway of glycolysis would normally take a step from 1,3-BPG to 3-phosphoglycerate, producing a molecule of ATP; or it could bypass that ATP-generating step and produce 2,3-BPG instead. An acidic environment inhibits the activity of bisphosphoglycerate mutase and promotes a more "normal" glycolytic pathway, thus inhibiting the production of 2,3-BPG and favouring the production of ATP; this is exploited as a homeostatic mechanism which is discussed later."

"The effect of 2,3-BPG on haemoglobin is profound. It is probably the most important allosteric effector of positive cooperativity."

"In the human erythrocyte, 2,3-BPG normally exists in a 5 mmol/L concentration, which is approximately the same as the intracellular conceration of haemoglobin. Thus, one 2,3-BPG molecule is all that is required to change the affinity of an entire haemoglobin tetramer. It binds to the central cavity of deoxyhaemoglobin, in a space between the H-helices of the beta-chains."

"The absence of one of the histidines (replaced with serine) in the foetal haemoglobin molecule results in a decreased affinity for 2,3-BPG (the cavity is slightly less cozy). The result is an increased affinity for oxygen, and this accounts for the different shape of the oxygen-HbF dissociation curve[.]"

"The effect of decreasing pH (more hydrogen ion activity) on haemoglobin is to stabilise the deoxygenated form, decreasing its affinity for oxygen."

"The chemical basis for the effect of pH on the oxygen affinity of haemoglobin lies in the amino termini and side chains of two histidine molecules, histidine 146 on the β-subunit and histidine 122 on the α-subunit."

"[..]you will never see a patient with a pH of 6.0. But if you did, their p50 would be around 67 mmHg. By comparison, changes in PaCO2 (within a sensible, survivable range) produce relatively minor changes in oxygen-haemoglobin binding."

"Most of the time, lecturers will at this stage produce a slide demonstrating the changes in the dissociation curve which occur with "normal" acid-base derangement, in the range of 7.6-7.2. This is sensible, because most people never see a pH outside of this range. However, in the ICU, all sorts of bizarre acid-base disturbances crop up."

"So, a low pH by itself decreases the affinity of haemoglobin for oxygen. However, by inhibiting the production of 2,3-BPG, low pH increases the affinity of haemoglobin for oxygen. The interaction of these two competing actions results in a useful homeostatic mechanism."

"In essence, 2,3-BPG opposes the Bohr effect. If acidosis shifts the curve to the right, decreasing the oxygen affinity of haemoglobin, the resulting decrease in 2,3-BPG synthesis shifts the curve to the left again, compensating for the change and maintaining the normal position of the curve."

"It is known that extreme hypothermia increase the affinity of haemoglobin for oxygen by a massive amount -- at 0°C, the affinity is 22 times greater than at 37°C." "In most [..] situations, over a "normal" physiological range of temperatures, one only encounters trivial fluctuations in p50 due to temperature."​

- Effect of Sodium Bicarbonate on [HCO3-], pH, and Gastrointestinal Symptoms

- Altitude and Mortality | Ray Peat
- Adapting to High Altitude | Palomar College
- ABC of oxygen: Oxygen at high altitude
- Humans In Hypoxia: A Conspiracy Of Maladaptation?!

 

[Amazoniac]

In theory, it doesn't take extra H+ to recover HCO3−.

Spoiler: Blood filtration

Source: the internet.

- Renal acid-base regulation: new insights from animal models

Spoiler