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

[icecreamman]

I have another really broad question related to the alkaline-acidic view of metabolism VS Ray's view of the benefits of CO2 (which seem to me to either elaborate and broaden the former into a more complex view or even contradict to a degree).

I'll go further into what confuses me there once we're finished with the stuff on Na, I don't want to be a menace haha

 

[Amazoniac]

Interesting. So while focusing on these alkaline minerals (Na, K, Mg, Ca) is important, Na isn't as critical enough to be focused on if the others are sufficient in the diet? Will it not pose a problem if the K:Na is somehow disturbed or something? I'm asking because another thread I read emphasized the critical need for Na:

Optimal Sodium Intake Is At Least 230% Higher Than RDA

So if you had to rank all these alkalinizing Na salts by beneficial effect or just preference, bicarbonate, acetate, citrate, malate..etc. what would you say? Btw I thought citrate was under some scrutiny on here for some reason hahah..I remember Ray talking about how it's essentially derived from a mold so the commercial low quality citric acid was deemed to be problematic due to excepients, but I was never sure what the citrate aversion is about (if you can dumb it all down for me :P)

Prevention of overacidification is accomplished through complete cellular respiration:

- Electron transport chain | BrainKart

Spoiler

Whenever possible, it's preferable to rely on food potassium salts for alkalinization and obtain sodium with chloride for being an important counterpart in extracellular compartments.

However, despite both sodium and chloride being known as predominantly extracellular ions, they don't occur in equivalent numbers in the body, sodium is normally found in excess.

- Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation

"A strong ion is defined as one that is almost completely dissociated at physiological pH. As both Na+ and Cl− are the major strong ions in plasma their ratio relative to one another largely determines the SID [strong ion difference]."

"[..]normal saline 0.9% has equimolar concentrations of Na+ and Cl− (153 mmol/l) and therefore has an SID of 0. The administration of large quantities of normal saline will progressively lower the plasma SID, producing a hyperchloraemic metabolic acidosis. A solution of Ringer's lactate, which has an SID of 28 mmol/l, would decrease the pH to a lesser extent."​

People supplement their meals with 99.5% saline, at times in large amounts and an abnormal saline because if table salt is simplified as having equal parts of each (1:1), sea salt can have the sodium-chloride ratio tipped in favor of chloride (1:1.2 for example) as opposed to the extracellular ratio of about 1.4:1 (140:105), only accentuating the imbalance.

Those are concentrations of ions in body compartments, not their actual amounts, but when we consider how fluids are distributed taking into account their concentration, it's possible to confirm that most chloride is indeed found outside the cell.
- Electrolyte Fluid Balance | Austin Community College​

It's not a serious concern because the ocean was here first, we should be adapted to these proportions and capable of normalizing the imbalance relatively fast, 'vegetables, fruits and milk' usually have chloride in excess of sodium, and there are those who supplement HCl directly; but it may be stressful if the person is already trapped in a vicious cycle of 'base deficit'.

Hydrogen and sodium are positively charged ions in plasma, but the source of acidity is not due to hydrogen ions making up for sodium because it would destroy the person; it occurs in tiny amounts relative to sodium. Chloride would be taking up hydrogen carbonate's space to maintain neutrality, therefore buffering is compromised. This probably occurs along with an increase in blood volume since sea salt should attract water to where it accumulates, working through dilution of hydrogen carbonate.
- Why Is Saline So Acidic (and Does It Really Matter?)

If balance was being maintained through dehydration (lower the rest when hydrogen carbonate can't be increased for whatever reason), then such process would make a 'base deficit' evident.

- Chloride: The queen of electrolytes?
- Disorders of Chloride: Hyperchloremia and Hypochloremia


On industrial citrate production:
- Common Food Additive Promotes Colon Cancer In Mice

 

[Amazoniac]

- Acid Value (AV) and the quality of fats and oils | ChemPRIME (or here)

"When an acid is titrated with a base, there is typically a sudden change in the pH of the solution at the equivalence point. If a few drops of indicator solution have been added, this sharp increase in pH causes an abrupt change in color, which is called the endpoint of the indicator (See the animation on the left). The actual magnitude of the jump in pH, and the pH range which it covers depend on the strength of both the acid and the base involved, and so the choice of indicator can vary from one titration to another."

"The pH of the solution in the flask will only change drastically when we reach that point in the titration when only a minute fraction of the hydronium ions remain unconsumed, i.e., as we approach the endpoint."

"The effect of the buffering action of the CH3COOH/CH3COO– conjugate pair is [..] to keep the pH some three units higher than before and hence to cut the jump in pH at the endpoint by approximately this amount."​

- NMR Determination of Free Fatty Acids in Vegetable Oils

- acid value | YouTube

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

 

[icecreamman]

@Amazoniac can you comment on the points made in this thread btw? It's exceptionally interesting to me as it's so similar to Ray's unique perspective on the acidity-alkalinity question (cell normally being acidic on the interior while alkaline on the exterior), along with CO2's importance being highlighted and finally one of the comments to the original article even mentioning Buteyko and his work:

Acids Regulate Metabolism, Not Alkalis

 

[Amazoniac]

@Amazoniac can you comment on the points made in this thread btw? It's exceptionally interesting to me as it's so similar to Ray's unique perspective on the acidity-alkalinity question (cell normally being acidic on the interior while alkaline on the exterior), along with CO2's importance being highlighted and finally one of the comments to the original article even mentioning Buteyko and his work:

Acids Regulate Metabolism, Not Alkalis

I remember, it motivated me to post this:
- Would A Knowledgeable Doctor Be Helpful Around Here?

It's difficult to comment on such rant because many topics were brought up, it's possible to argue on either side of acid-base wars. If it's acknowledged that balance has to be maintained and it's determined by two interdependent components, I don't know how to conclude that either regulates metabolism because changing one will affect the other. Found this:

Spoiler

Plants start from carbon dioxide and water to synthesize glucose and release oxygen. We reverse the process, but before completion, metabolic processes generates acids and the body has to be primed to defend against this if it goes awry. The list of causes of acidosis is extensive in comparison to alkalosis. How many conditions are characterized by defective celullar respiration? When it's incomplete and there's an impairment halfway through, acids build up instead of ending up neutralized as water, but we are clearing these acids, contrary to the pot of yogurt. Just because systems are efficient in removing them, it doesn't mean that they're not a burden. A more realistic scenario for us is to be confronted with disturbing amounts of acids, but too much of either is harmful.

- Terrestrial biological carbon cycle - Wikipedia

Spoiler

That author decided to focus on extracellular compartments because we can't yet track as easily what happens in cells. If we could, both phases (bottom) involve phosphate and the person would have given just as much attention to other buffering systems including this one.

There are limitations for the hydrogen carbonate buffer system in cells because if energy production is high to meet some demand, there will be a lot of carbon dioxide in the overworked tissues, yet this should've been the result of removal of hydrogen ions through the formation of carbonic acid/carbon dioxide; what was supposed to be your end-product is already in excess. This then risks damaging proteins and histidine is often mention as being susceptible to attack, carnosine (alanine+histidine) sometimes is considered a buffer, not sure if it works in sacrifice.

After ATP is formed, utilizing it releases hydrogen ions and (conversely) reforming it consumes them with creatine being involved, it prevents overacidification so that other buffers can catch up.

- Exercise-Induced Metabolic Acidosis: Where do the Protons come from? | Robert A Robergs

"In order to reform the amine terminal of creatine, a proton from solution is consumed in the reaction, thus explaining the alkalinization."

Spoiler

If carbon dioxide by itself was the key to health, we would have developed means to conserve it better. Altitude adaptations are triggered by stress (for example, more mitochondria to get the most out of available oxygen), it's adjusting to different conditions and there should not be anything superfluous in it. Artificial increase of carbon dioxide can mimic some aspects of adequate cellular respiration and be therapeutic, but it's what got you to it that generated the energy. If it wasn't interconvertible with hydrogen carbonate, it would lead to trouble earlier.

It's called acid-base balance for a reason. In terms of blood, hydrogen carbonate is in great excess of carbonic acid/carbon dioxide for transportation but it also puts the person in a state of readiness to control shifts in acidity, same for bones, which act as a base reservoir. But to keep hydrogen ion concentration stable, these proportions have to be maintained whether both are increased or decreased together.

- Acid-Base Lesson: The Henderson-Hasselbalch Equation (H-H) | Lane Community College

"When the HCO3– is 24 mEq/L, and the PaCO2 is 40 mm Hg, the base to acid ratio is 20:1 and the pH is 7.4 (normal).
H-H equation confirms the 20:1 ratio and pH of 7.4 as follows:"

Spoiler

- Acid dissociation constant - Wikipedia (carbonate is ignored because it's outside of physiological range)

K: dissociation constant
Ka: acid-dissociation constant (carbonic acid in this case)
pKa: logarithmic acid-dissociation constant​

- "The Primary Sources Of Acidity In The Diet Are Sulfur-containing AAs, Salt, And Phosphoric Acid" (the manipulation of the equation to isolate hydrogen ion concentration that end up with species 'flipped')

Carbonic acid has a dissociation constant just like the acids from the previous posts here, it's about 6.1 (and increased slightly at body temperature). Carbon dioxide is used a proxy for it and is measured in mm Hg for being a gas. After conversion (to work with concentration per liter), you'll have the relationship between hydrogen carbonate and carbonic acid, making it easy to compare and confirm how there's way more base in circulation.

Open anesthesiology book , it is al dere)))

 

[Amazoniac]

On the metabolism of baking soda:

Fluid distribution in the body (70 kg man):

Spoiler

- Response to 100 mmol of sodium bicarbonate | Deranged Physiology (8.4 grams; 8.4% of the 100 ml solution infused)

Spoiler

After infusion (if it passes through the stomach, it may be an opportunity to ease the imbalance since it will carry some chloride along that could later be redistributed), sodium remains in the extracellular compartment, same for hydrogen carbonate prior to metabolism (as opposed to carbon dioxide that can move freely). Initially then, 100 mmol were expected to be found distributed evenly outside cells. From the image above, once 100 mmol of baking soda is infused, 3/4 would move towards interstitial fluid and 1/4 plasma.

Normal hydrogen carbonate concentration in extracellular fluid is about 24 mmol/L (check out the 20:1 ratio figure from previous post). Since there are 14 liters of fluid outside cells, we combine these values and there were supposed to be 336 mmol in total. After the 100 mmol infusion, the expected should be 436 mmol, or 31.1 mmol/L.

However, this doesn't happened because it starts to be processed right away. Kidneys' recovery of hydrogen carbonate apparently decreases when the concentration is beyond 26 mmol/L, making the person lose it in urine, which contributes to normalization.

The response also depends on the person's hydrogen carbonate level before intervention:

- The concept of bicarbonate distribution space: The crucial role of body buffers

"Applying the pharmacological concept of volume of distribution, a distribution volume for bicarbonate, or apparent bicarbonate space (A.B.S.), is defined as the ratio of administered bicarbonate to the observed change in the plasma bicarbonate concentration. Under normal conditions the A.B.S. is 40% to 50% of total body weight or approximately twice the extracellular fluid volume. Although some early studies had suggested that the A.B.S. is constant in a given animal [1], clinical observations have led to the recognition that the A.B.S. expands in severe metabolic acidosis [2]."​

Therefore, if levels are relatively normal, the dispersion factor can be more than twice as great as we were using, decreasing the prediction to 26.9 mmol/L [24 mmol/L + (100 mmol/35)].

Sodium will attract water to these compartments and dilute the concentration further, but still not compatible with the usual response.

Since balance between 'hydrogen carbonate' and 'carbonic acid' has to be maintained, after an abrupt rise in the former, the body can't rely on the hydrogen ion concentration in circulation because it's tiny, it needs alternative sources and other buffer systems can cooperate in donating hydrogen ions for conversion into carbonic acid, leading to a sharp compensatory rise in carbon dioxide. Given that their normal ratio is 20:1, it takes a little extra carbon dioxide for a significant increase in the ability to tolerate hydrogen carbonate without disturbances until other systems kick in to correct the situation and decrease both proportionally.

- The increase in CO2 production induced by NaHCO3 depends on blood albumin and hemoglobin concentrations

So, the kidneys and the lungs regulate it quite well when these are operating fine. It's then a matter of dealing with sodium and its effects should interest LLight.

 

[Amazoniac]

This is useful for comparison:

Spoiler

Not sure where it originated from.

How extreme the rise of 'measured' ions has to be to compromise the 'unmeasured' ones?

People who benefit from taurine might also be running low on sulfate. Would it be possible for any of the 'measured' anions to drop sulfate to a concerning level? What are the consequences?

Why is Terma so knowledgeable?

 

[Amazoniac]

It's remarkable what this guy did in Excel:
- CurTiPot: pH Calculation and Acid-Base Titration Curves - Freeware for Data Analysis and Simulation

 

[Amazoniac]

- The history of 0.9% saline

Spoiler

"Each year nearly 10 million litres of 0.9% sodium chloride (saline) are infused intravenously in the UK (data from Baxter Healthcare, UK). Despite being one of the most frequently used crystalloids for resuscitation, replacement and maintenance, the origins of 0.9% saline remain obscure."

"The use of saline is believed to have originated during the cholera pandemic that swept across Europe and reached England in 1831.[1-9] However, the solutions used by Latta,[10] Jennings[11] and other pioneers of that era show little similarity to 0.9% saline. How, therefore, did 0.9% saline come into use and when did it become accepted as 'normal' or 'physiological'?"

"To understand how a concentration of 0.9% saline came into general use, a hand-search was undertaken of the literature from the 19th and early 20th centuries. The constituents of the solutions were described in traditional chemical terms (Table 1) and apothecary's measures (Table 2). We have recalculated the composition of the various solutions[3,6,10,20,22,26-41] and have expressed the ionic composition in mmol/l (Table 3)."

Spoiler

"It was Latta in 1832 who, having modified his original solutions, devised one most closely resembling the concentration of electrolytes seen in blood.[31] This solution containing sodium 134 mmol/l Na+, 118 mmol/l Cl− and 16 mmol/l HCO3− was closer to the composition of plasma and, therefore, more 'physiological' than 0.9% saline. Despite this, Latta's solution was not adopted by his contemporaries who made no further reference to it. Indeed, no solution of similarly physiological composition was described until that of Sydney Ringer 50 years later[37,42] (Table 3). A possible explanation for this may be Latta's death from pulmonary tuberculosis in 1833.[1]"

"Having heard of the use of intravenous saline injections by Latta and Lewins, O'Shaughnessy thought the results exceeded his 'most sanguine expectations'.[43] Supporters of this new treatment, however, were few and articles describing the failure of saline injections appeared.[44-46] Latta felt the need to defend his practice against 'members in the profession guilty of scribbling on medical subjects in the newspapers of the day' and felt 'this was a crime for which they have no excuse'.[47] Latta referred to Craigie who had written to a newspaper claiming credit for discovering the new treatment and went on to cite the main reason for any failures of his treatment as the delay in its use until the disease was too far advanced and all other treatments had failed. Even some of his survivors were initially moribund with 'the pulse gone, even in the axilla'."

"Although Latta understood the need for repeated injections guided by the response to treatment,[10] many of his contemporaries did not and therefore under-treated their patients. Other reasons for the failure of saline treatment include the use of hypotonic fluids causing haemolysis, infection due to the lack of sterility of the fluids and equipment then in use, and inadvertent air embolism.[48]"


"Interest in the composition of salt solutions was given further impetus by 19th century studies of isolated frog nerve and muscle. Perhaps the best known of these were performed by Sydney Ringer[33,37,42,49,50] which led to the development and subsequent modification of Ringer's solution, the basis of the modern solutions such as Hartmann's.[37,38,51-53] Ringer set out to 'ascertain the influence each constituent of the blood exercises on the contraction of the ventricle'[37] and, having bathed frog heart muscle preparations in solutions of different constituents, found that a 0.75% saline solution 'makes an excellent circulating fluid in experiments with the detached heart'. He later discovered that the saline solution previously used was made using pipe water supplied by the New River Water Company and not distilled water as intended.[37] On repeating the experiments he found that bathing the heart muscle in saline solution made with distilled water made the ventricle grow 'weaker and weaker' leading to cessation of contractility in about 20 min. He concluded that the effects he had previously obtained were 'due to some of the inorganic constituents of the pipe water'.[37] Ringer's solution (Table 3) was developed as a consequence of these observations and later modified by Alexis Hartmann who added sodium lactate to it with the aim of reducing the acidosis seen in infants suffering from diarrhoea, dehydration and oliguria.[53]"

"Three decades prior to Ringer's experiments, Koelliker had observed that nerve and muscle preserved their irritability and appearance for many hours in solutions of 0.5-1% sodium chloride which he therefore termed 'indifferent' solutions.[54] Nasse later determined the optimal concentration of salt for the preservation of the irritability of tissues was 0.6%. Hermann designated this solution 'physiological water'.[55] The term 'physiological salt solution' appears to have been popularised after observations that transfusions of this solution were capable of saving the lives of animals and humans after profuse haemorrhage.[55]"


"The reassuring terms 'normal' and 'physiological', now commonly applied to 0.9% saline, while having no scientific validity, may have aided its widespread acceptance in practice, despite the fact that it is neither chemically normal, implying a concentration of 58.5 g NaCl/l, nor physiological, i.e. similar to extracellular fluid.[59]"

"None of the intravenous saline solutions described between 1832 and 1895 bear any resemblance to 0.9% saline (Table 3). The first reference to a solution similar to 0.9% saline appeared in 1896.[60] In his article W.S. Lazarus-Barlow cites Hamburger as the main authority for suggesting that a concentration of 0.92% saline was 'normal' for mammalian blood.[60]"

"Hartog Jakob Hamburger was a Dutch physiological chemist, appointed lecturer in physiology and pathology at the Utrecht Veterinary School in 1888.[61] Although remembered for his 'phenomenon' (the chloride shift); his 'interchange' (secondary buffering), and his 'law' (which states that when blood is rendered acid, albumins and phosphates pass from the red blood corpuscles to the serum and the chlorides pass from the serum to the cells) no mention is made in his obituary[61] of his role in the evolution of saline solutions."

"In a lecture delivered at the University of London and published in the Lancet of 19th November 1921, Hamburger[56] refers to his own work which 'alas, has of late been too often overlooked'. He was originally inspired by the work of the botanist Hugo de Vries in 1882 on the force with which plant cells attract water.[62] A year later Hamburger performed experiments on the effect of solutions, with varying concentrations of salt, on the escape of colouring matter from erythrocytes.[63] He found that 'for every salt a concentration could be obtained in which the least resistant blood corpuscles lost their colouring matter' and speculated that 'the salt solutions used caused a swelling which a number of the blood corpuscles could not withstand without losing their colouring matter'."

"It is accepted that the freezing point of human serum is −0.52 degrees C. Hamburger, after comparing the 'freezingpoints' of serum obtained from animals and human subjects, concluded that 'the blood of the majority of warm-blooded animals, including man, was isotonic with a NaCl solution of 0.9 per cent., and not of 0.6 per cent., as was generally thought ... and which had always been called the physiological NaCl solution'.[56] His theory linking the isotonicity of 0.9% saline to human blood, although credibly backed by his experimental evidence, was not universally accepted.[60] The scientific evidence supporting the use of 0.9% saline in clinical practice seems to be based solely on this in vitro study. It remains a mystery how it came into general use as an intravenous fluid in vivo. Perhaps it was due to the ease, convenience and low cost of mixing common salt with water."


"Fluid therapy with saline solutions, in the form of proctoclysis and hypodermoclysis, became routine in the early 20th century. In 1911 Evans[64] stated his intention to 'sound a note of warning against the thoughtless and indiscriminate use of this remedy' and to dispel the erroneous belief that the administration of 'sodium chlorid' solutions was harmless just because the salt was present in all foodstuffs, in body fluids, and incorrectly thought to be readily excreted by the kidneys. Having highlighted the dangers of salt overload and retention he urged restricting its use to 'those conditions in which either quantitative or qualitative changes in the blood-plasma present logical indications for its application' and where 'circulatory or renal contraindications do not exist'. It would appear, from subsequent literature, that Evans' plea for caution fell on deaf ears."

"In 1913 Trout[66] reported a study of postoperative fluid replacement by proctoclysis in some 2000 patients treated at 232 hospitals, who were allocated to receive either tap water or 'normal' saline enemas. Whilst Trout acknowledged some flaws in the experimental design, this was nonetheless the first scientific study of the management of postoperative fluid balance. Trout calculated that, using normal saline, 'we would be forcing into an already weakened patient, in the space of 24 hours, the average amount of salt consumed as a condiment by a normal man in one month'. He also noted transient albuminuria, using saline, which disappeared 24 h after water was substituted, returning again on further use of saline. Trout concluded 'surgeons have simply drifted into employing salt solution by rectum without giving any serious consideration to what they were doing, and such is our excuse for this paper'."

"A decade later Rudolph Matas, regarded as the originator of modern fluid therapy,[2] introduced the concept of 'the continued intravenous drip',[67] but also warned of the potential dangers of saline infusions. He referred to work by Roessle who showed organic changes in human heart muscle after saline infusions, by Hoeszli who noted degenerative changes in the heart and kidneys of guinea-pigs[6-7] h after massive saline infusions, and by Thiess who in 1910 pointed out 'that a healthy man needs 17 gm. of salt per day, but receives 27 gm. when given 3 litres of 0.9 per cent. salt solution ... part of the salt is eliminated by the kidneys, but some is retained in tissues, where it attracts liquids and causes oedema'.[68] Matas concluded for the above reasons that his preferred solution was 5% glucose rather than saline."

"Fluid retention in postoperative patients, receiving crystalloid infusions, is exacerbated by their diminished ability to excrete an excess sodium and water load.[70-74] This classical feature of the metabolic response to injury is unfortunately sometimes forgotten.[75-77] That such fluid retention is not innocuous is shown by the work of several authors who have described an increase in postoperative complications and adverse outcomes associated with excess sodium and water administration in the perioperative period.[77-87]"

"Even healthy volunteers have difficulty with saline.[88-91] When 2-l infusions administered over 1 h of either 0.9% saline or Hartmann’s solution were compared, at 6 h 56% of the infused saline was retained in contrast to only 30% of the Hartmann’s solution.[91] A marked and sustained hyperchloraemia was also seen following saline infusion. Infusion of large volumes of saline in healthy volunteers have also been shown to produce abdominal discomfort and pain, nausea, drowsiness and decreased mental capacity to perform complex tasks.[92]"

"The persistent hyperchloraemia after saline infusions[91-98] reflects the lower [Na+]:[Cl−] ratio in saline (1:1) than in Hartmann’s solution (1.18:1) or plasma (1.38:1).[93]"

- Balanced crystalloids for septic shock resuscitation

"While infusions of 0.9% saline produce a significant hyperchloraemic acidosis, infusions of Hartmann’s solution do not significantly alter bicarbonate and chloride concentrations or pH.[91,94] The decrease in the anion gap is more pronounced with saline than with Hartmann's solution and reflects the differential fall in serum albumin concentration.[91,94] As the negatively charged albumin molecule accounts for about 75% of the anion gap,[99] the acute dilutional hypoalbuminaemia produced by crystalloid infusions[91,96] can reduce the anion gap by 2.5 mmol/l for every 10 g/l fall in serum albumin concentration in critically ill patients.[100,101]"

"Veech[93] has emphasised that the kidney is slow to excrete an excess chloride load after the infusion of large amounts of saline. Wilcox found, in animal studies, that sustained renal vasoconstriction was related to hyperchloraemia, which was potentiated by previous salt depletion and related to the tubular reabsorption of chloride[106] which appeared to be initiated by an intrarenal mechanism and was accompanied by a reduction in glomerular filtration rate."

"At the cellular level, salt and water overload can result in cytosolic acidification, membrane hyperpolarisation, inactivation of protein kinases and disruption of phosphorylation, leading to cellular dysfunction.[109] In addition, there is increasing evidence that 0.9% sodium chloride solution has adverse effects on immune cells. Although in vitro studies have demonstrated that 0.9% sodium chloride solution causes activation of human neutrophils,[110] an effect on neutrophil function was not demonstrated in a study in which healthy human volunteers were infused with 2 l of 0.9% saline.[111] Recent animal models of haemorrhagic shock that employed 0.9% sodium chloride as a resuscitation fluid found this led to significant pulmonary inflammatory infiltrates and decreased oxygenation.[112] It has been suggested that the use of 0.9% sodium chloride may exacerbate injury-related neutrophil activation, thus predisposing the host to infectious complications.[113]"

"Whilst there is no doubt that saline infusions have saved a number of lives in medical and surgical practice, this could well have been achieved by a balanced crystalloid, with fewer side effects. Evans[64] put this into perspective by commenting that, 'One cannot fail to be impressed with the danger ... (of) the utter recklessness with which salt solution is frequently prescribed, particularly in the postoperative period.' and going on to state that, '... the disastrous role played by the salt solution is often lost in light of the serious conditions that call forth its use.'"

"The attempt to find a truly physiological crystalloid preparation for both scientific and clinical work has been going on for 175 years and the results have inevitably been a compromise. In conditions of peripheral circulatory failure or liver disease, there may be increased endogenous lactate production or decreased capacity to metabolise infused lactate.[93] On the other hand, the unphysiological proportion of chloride in 0.9% saline causes other problems as outlined. There seems to be no historical or scientific basis, except for Hamburger's in vitro studies of red cell lysis,[56] to support the continued use of 0.9% saline in clinical practice save in cases involving large chloride losses, e.g. due to vomiting. It is also extremely doubtful that, if a range of intravenous fluids were being designed today on evidencebased principles, 0.9% saline would figure prominently. A fresh look at crystalloid formulae is overdue. In the meantime there is a strong case for using solutions nearer in composition to Ringer's lactate or Hartmann's solution rather than 0.9% saline, in most patients requiring more than 1000-1500 ml of crystalloid solution per day for resuscitation or replacement."

 

[Amazoniac]

- Respiratory system - Wikipedia

- Spirometry, Lung Volumes & Capacities, Restrictive & Obstructive Diseases | Alila Medical Media

Spoiler

- Pulmonary Function Tests (PFTs) Made Simple - Pulmonology | Medicosis Perfectionalis

- Composition of inspired and expired air | Marion Priscilla Lloyd (check out the 'Breathing' Wikipedia page too)

Spoiler

 

[Amazoniac]

- Effect of Upright and Slouched Sitting Postures on the Respiratory Muscle Strength in Healthy Young Males

- Carbon dioxide - Wikipedia

"At low concentrations the gas is odorless; however, at sufficiently-high concentrations, it has a sharp, acidic odor. At standard temperature and pressure, the density of carbon dioxide is around 1.98 kg/m3, about 1.67 times that of air."​

- Calcium, Carbonic Anhydrase and Gastric Acid Secretion

- A new role for bicarbonate in mucus formation
- The importance of bicarbonate and proteases for mucin secretion and mucus formation
- Pass the bicarb: the importance of HCO3– for mucin release
- Normal mucus formation requires cAMP‐dependent HCO3− secretion and Ca2+‐mediated mucin exocytosis
- Fundamentals of Bicarbonate Secretion in Epithelia

- Dr Thomas Latta: the father of intravenous infusion therapy (⇈)

- Volume expander - Wikipedia
- Colloids vs. crystalloids as resuscitation fluids | Deranged Physiology (@yerrag)

- Chloride-led Disruption of the Intestinal Mucous Layer Impedes Salmonella Invasion: Evidence for an 'Enteric Tear' Mechanism

- The erythrocyte chloride shift (Hamburger effect) | Deranged Physiology

I wonder how exactly anemia affects acid-base balance considering the importance of red bloody cells. Also, how masks have been affecting the blood-forming nutrients and zinc?

 

[tara]

At low concentrations the gas is odorless; however, at sufficiently-high concentrations, it has a sharp, acidic odor.

I've caught a whiff of that. Wouldn't want to be exposed for long at all.

 

[Amazoniac]

- The therapeutic importance of acid-base balance (!)
⬑ [64] Brain pH effects of NaHCO3 and Carbicarb in lactic acidosis

"Carbicarb [], which consists of 1/3 M Na2CO3 and 1/3 M NaHCO3, was formulated to lower CO2 generation and found to raise blood pH without raising PCO2 (23-26). Carbicarb increases pHa more and PaCO2 less than 1 M NaHCO3 (26-28), even though the total alkalinity (29) of these agents is identical. In more convential terms, both agents raise the blood base excess (30) equally, but Carbicarb has greater alkalinizing strength."

"NaHCO3 introduced into an acidotic milieu would be expected to generate CO2 which, by establishing an inward PCO2 gradient, could power pHi. In contrast, Carbicarb, which generates HCO3(−) ions not only from the added HCO3(−) but also from the reaction of CO3(2−) with free protons, actually decreases CO2 tension in vitro (25, 26) and appears to result in intracellular brain alkalinization."​

Killcium carbonate. ☠

 

[Amazoniac]

- Acids and Bases | Mr. Birnbaum's Chemistry and AP Computer Science Principles

- Intracellular pH Regulation | Robert W. Putnam

"Cytoplasmic pH is an important aspect of the intracellular milieu and can affect nearly all aspects of cell function. In most cells, pHi is maintained at a value of about 7.0, well alkaline with respect to the equilibrium pHi, calculated on the assumption that H+ ions are at equilibrium across the membrane. The fact that pHi is alkaline to its equilibrium value creates a passive acidifying influx of H+. In fact, most cells face a continuous acid load due not only to this acidifying influx but to metabolic acid production and leakage from internal acidic compartments as well. Such challenges to a stable pHi can be blunted by cellular buffers[.]"

"The pH of certain organellar compartments can differ from the value of pHi and these differences in pH are important for organellar function. For example, mitochondria maintain an internal pH of 7.5, about 0.5 unit more alkaline than pHi. This pH gradient across the mitochondrial membrane is essential for the major function of mitochondria, the production of ATP. Further, several intracellular organelles in the vacuolar system (e.g. endosomes, lysosomes and storage granules) maintain an internal pH of 5-6, well below pHi. These organelles contribute to the movement of membranes, membrane-bound proteins and soluble proteins around the cell and their acidic pH is essential for this function."

"Protons tend to bind to macromolecules and thus are usually present at very low concentrations in biological solutions. This property is the basis for buffering power. A variety of weak acids and bases can bind H+ through reversible equilibrium binding reactions."

"On addition of H+ (or OH−) to a solution, the pH will change. However, if the solution contains weak acids (or bases), many of the added protons (or hydroxyl ions) will be bound up, thus minimizing the change in the concentration of free H+ and thereby minimizing the change in pH. Since these substances minimize the change in pH upon addition of acid or base, weak acids and bases are referred to as buffers."

"An example will indicate the importance of buffering power to maintaining the pH of a solution. If 1mM NaCl is added to a solution, [Na+] and [Cl−] increase by 1mM (for simplicity, the effects of the non-ideal activity coefficients will be ignored). However, the addition of 1mM HCl to a solution that has a pH of 7.0 and a buffering power of 10 mM/pH unit will cause that [Cl−] to increase by 1 mM, but will cause the pH to decrease by only about 0.28 pH unit, to 6.72. Thus, of the added 1mM of H+, only 0.091% remain free, i.e. only 1 out of every 11 000 added H ions remains free. The rest are bound to the weak acid buffers. If the buffers had not been present, the same addition of 1mM HCl would have changed the solution pH by about 4 units to pH 3. This clearly demonstrates that the presence of buffers in a solution markedly blunts the effects of added acid or base."

"Protons are just like any other cation, except for three distinguishing characteristics:

1. H ions are a dissociation product of water molecules (H2O = H+ + OH-) and thus are always present in aqueous solutions;
2. H ions are present at very low concentrations in most solutions; and
3. H ions have much higher mobility than other cations. However, the equilibrium distribution and movement of H+ across biological membranes are governed by the same principles that govern the movement of all other ions across biological membranes."

"Originally, protons were assumed to be at equilibrium across biological membranes because of their very high mobility. Assuming an extracellular pH (pHo) of 7.4, a Vm of −60 mV (inside negative) and assuming that H ions are passively distributed across the membrane (i.e. at equilibrium), pHi would be 6.4 (calculated from the Nernst equation). However, at such an intracellular pH, metabolism and a variety of other cellular functions would be impaired. With the advent of modern reliable techniques for measuring intracellular pH, including pH-sensitive glass microelectrodes and pH-sensitive fluorescent dyes, it was shown that, in the majority of cells, pHi was between 6.8 and 7.2, well above the calculated value for equilibrium pH. It is now clear that for most cells (with the notable exception of red blood cells), pHi is considerably more alkaline than it would be if protons were at passive equilibrium across the cell membrane."

"The extrusion of H+ to establish a proton gradient renders mitochondria alkaline relative to the cytoplasm by about 0.3-0.5 pH unit. Thus, intramitochondrial pH can be between 7.5 and 8.0. In addition, this pH gradient is maintained in the face of considerable acid loads, indicating that mitochondria may well be able to regulate their internal pH independently of cytoplasmic pH."

Spoiler

"Organelles with a markedly acidic interior are those involved in either the endocytic pathway or the secretory pathway. The acidic organelles involved in endocytosis include coated pits, endosomes (i.e. prelysosomal endocytic vesicles) and lysosomes. Acidic vesicles in the secretory pathway include the Golgi apparatus (or at least part of it) and storage granules for amines (e.g. chromaffin granules involved in catecholamine secretion) and peptides (e.g. secretory granules in the endocrine pancreas). The pH is not known for all of these compartments, but can be as low as 4.5-5.0 in lysosomes and 5.0-5.7 in endosomes and secretory granules. The pH in the Golgi apparatus seems to fall the farther the compartment is from the nucleus, with values of 6.2-6.4 in the medial Golgi and values as low as 5.9 in the trans Golgi network (TGN)."

"The acidic internal environment of these various organelles is believed to be necessary for their function. For example, the primary function of lysosomes is the biochemical degradation of macromolecules and these organelles contain a large number of hydrolytic enzymes whose pH optima are about pH 5.0. This serves as protection for the cell. If the lysosomes should leak, the hydrolytic enzymes would be inactivated by the high cytoplasmic pH, thus preventing the indiscriminate degradation of important macromolecules."

"[..]nuclear pH is from 0.1 to 0.5 pH unit more alkaline than cytoplasmic pH."

"[..]under pathological conditions where mitochondria or acidic intracellular compartments are rendered leaky or mitochondria take up cytoplasmic Ca2+ in exchange for H+, these compartments could influence pHi."

"It is clear that, at the very least, cells face a continual acid load from passive H+ influx. In addition, under many conditions of metabolic stress, cells also experience a metabolic acid load. Thus, cells must possess active extrusion mechanisms to maintain a steady-state pHi well above the equilibrium value for pHi."

"[..]because pH will affect the charge on ionizable groups in proteins, it would be anticipated that changes in pHi could change the configuration of proteins and affect their activity. Such an effect of pHi has been well documented for two key metabolic enzymes. Phosphofructokinase, a key glycolytic enzyme that converts fructose 6-phosphate (F6P) to fructose 1,6-diphosphate (FDP), has an exquisite pH sensitivity in the physiological range (6.5-7.5), its activity decreasing with a decrease of pHi. The actual pH sensitivity is dependent on the cellular levels of F6P and 5'-AMP. Similarly, the conversion of phosphorylase (which catalyzes the metabolism of glycogen) from its inactive to active form is inhibited by a decrease in pHi."

"[..]the general reaction of metabolic enzymes to a decrease in pH is a reduction in activity. This suggests that a decrease in pHi could be used to prevent growth or to put a cell in a dormant state, as has been observed for many cells []."

"Changes in cellular pH can also affect the polymerization of cytoskeletal elements, such as tubulin. It has been shown that, in some cells, alkalinization can cause depolymerization of tubulin and disaggregation of microtubules within the cell."

"Changes in pHi can affect the levels of important intracellular signaling molecules, such as Ca2+ and cAMP. There are several possible ways by which pH can affect intracellular Ca2+. An elevation of cytoplasmic H+ can activate mitochondrial Ca2+-H+ exchange, resulting in a sequestering of H+ within the mitochondria and an elevation of cytoplasmic [Ca2+]. A decreased pHi can reduce Ca2+ entry across the plasmalemma [cell membrade]. The most direct interaction between cytoplasmic H+ and Ca2+ ions, however, results from shared buffers. Many molecules that buffer H+ will also bind, and thus buffer, Ca2+. Depending on the relative affinities, an elevation of cytoplasmic [H+] can elevate intracellular [Ca2+] by displacing Ca2+ ions from intracellular buffer sites."

"Some cells in the body function to sense changes in external pH, either in direct response to external acid (acid-sensing taste bud cells) or to elevated external CO2 (glomus cells of the carotid body and central chemosensitive neurons). In these cells, extracellular acidification results in a maintained intracellular acidification, with pH recovery mechanisms being inhibited (most likely by decreased pHo)."

"[..]it has been shown that a number of cells have a higher pHi in the presence of 5% CO2 than in its absence."

"Cell volume can be rapidly changed by exposure to anisosmotic media, with hypertonic media causing cell shrinkage and hypotonic media causing cell swelling. Many cells respond to shrinkage with a regulatory volume increase (RVI) that involves the net uptake of solutes, and therefore water, so that cells swell back toward the initial cell volume (Fig. 17.9)." "In response to swelling, most cells exhibit a regulatory volume decrease (RVD). RVD involves the efflux of solutes accompanied by water and therefore cell shrinkage back toward the initial cell volume (see Fig. 17.9)."

Spoiler

 

[Amazoniac]

Came across this clear representation:

- Ch. 28: Electrolyte and Water Balance | Textbook of Biochemistry for Medical Students

Spoiler

 

[Amazoniac]

- Dietary factors influencing non-heme iron absorption

Spoiler: Table 8 - Common vegetable and fruit sources of citric, malic, tartaric, and lactic acid

It can vary:

- Effect of Processing on the Quality of Pineapple Juice

 

[Amazoniac]

- Citrate modulates lipopolysaccharide‐induced monocyte inflammatory responses

"Outside its use as an anti‐coagulant, high concentrations of citric acid are found in citrus fruits and citrate salts are used to alkalinize the urine in the treatment of kidney stones[48, 49]. It is tempting to speculate if oral and dietary sources of citrate could alter inflammatory responses. Studies of the renal handling of citrate demonstrate that the increase in urinary citrate does not result directly from an increase in plasma citrate levels. Instead, the kidney increases urinary citrate excretion in response to a metabolic alkalosis, which can be induced by bicarbonate infusion or from the metabolism of citrate into bicarbonate[50]. These studies imply that, when taken orally, citrate is subject to extensive metabolism by the liver and that oral intake of citrate does not result in elevated plasma levels of citrate. In contrast, when citrate is used as an anti‐coagulant, it is infused directly into the systemic circulation. Even then, elevated citrate levels are seen typically only in patients who receive massive blood product transfusions, have liver dysfunction or receive continuous citrate infusions with CRRT[46, 51, 52]. As such, we feel it is unlikely that citrate in food or other sources could produce elevated plasma levels of citrate such that it would impact monocyte inflammatory responses."​

 

[Amazoniac]

- Effects of pH on Potassium: New Explanations for Old Observations

Spoiler

"Acute effects of acid-base disturbances on K+ redistribution have long been known.[1,4] In general, metabolic acidosis with acidemia causes a net shift of K+ from the intracellular to the extracellular space. Conversely, net cellular uptake of K+ is observed in metabolic alkalosis with alkalemia. The directional effects of acidemia and alkalemia on K+ redistribution are similar in respiratory acid-base disturbances as in metabolic derangements,[4] but the effects of respiratory disorders on K+ redistribution tend to be smaller than metabolic acid-base disturbances.[4]"

"As illustrated in Figure 3, the multiple acid-base transport pathways mentioned above may give rise to apparent K+-H+ exchange."

"In the case of the predominant pH regulatory pathway, Na+-H+ exchange, Na+ that enters by this route must be extruded by the Na+,K+-ATPase (Figure 3A). Accordingly, K+ uptake by the Na+,K+-ATPase will be greater when Na+-H+ exchange activity is stimulated and will be diminished when the rate of Na+-H+ exchange is reduced. In the case of acidosis with acidemia, the fall in extracellular pH would result in inhibition of the rate of Na+-H+ exchange, leading to the accumulation of intracellular H+ and a decline in intracellular Na+. The latter would result in reduced Na+,K+-ATPase activity, leading to decreased active cellular K+ uptake to counteract passive K+ efflux through K+ channels.[20] The final result would be as if H+ had entered the cell in exchange for K+."

"Similarly, as illustrated in Figure 3B, Na+-HCO3− cotransport operating in parallel with Na+,K+-ATPase may result in K+-HCO3− cotransport, which is equivalent to K+-H+ exchange. For example, in the case of metabolic acidosis with acidemia, the fall in extracellular HCO3− results in inhibition of the inward rate of Na+-bicarbonate cotransport, leading to a fall in intracellular Na+ and reduced Na+,K+-ATPase activity. Lower Na+,K+-ATPase activity would cause a net loss of cellular K+. Again, the result would be as if H+ had entered the cell in exchange for K+."

"Finally, Cl−-HCO3− exchange also may contribute to apparent K+-H+ exchange if operating in parallel with K+-Cl− cotransport, as shown in Figure 3C. Metabolic acidosis with a fall in extracellular HCO3− would increase the inward movement of Cl− by Cl−-HCO3− exchange. The resulting rise in intracellular Cl− would then promote K+ efflux by K+-Cl− cotransport. The net result would be K+ efflux along with HCO3−, which is an equivalent process to exchanging intracellular K+ for extracellular H+."​

"A striking observation has been that metabolic acidosis caused by mineral acid (hyperchloremic, nongap acidosis) causes a much larger shift of K+ into the extracellular fluid than does organic acidosis (lactic acidosis).[21] The effect of hydrochloric acid but not organic acids to release K+ into the extracellular space had been observed using isolated muscle preparations, indicating this phenomenon can occur independently of systemic factors.[22] In the case of acidemia caused by an organic acidosis like lactic acidosis, there would again be the effect of both low extracellular pH and HCO3− tending to inhibit Na+-H+ exchange and Na+-bicarbonate cotransport. This is illustrated for the case of Na+-H+ exchange in Figure 4, but in contrast to the situation with hyperchloremic acidosis, there would also be a strong inward flux of lactate and H+ through the monocarboxylate transporter, resulting in a larger fall in intracellular pH and HCO3−. The decrease in intracellular pH and HCO3− would tend to stimulate Na+ entry by Na+-H+ exchange and Na+-HCO3− cotransport, stimulating Na+,K+-ATPase activity. The net effect would be to drive net cellular uptake of K+."

"Thus, as illustrated in Figure 4, extracellular and intracellular acidosis are predicted to have opposing effects on the distribution of K+ because of their differing effects on cellular Na+ loading."

"[..]bicarbonate can affect K+ redistribution independent of the effect of extracellular pH.[26,27] Na+ entry by Na+-HCO3− cotransport would be enhanced whenever extracellular HCO3− is increased, resulting in increased cell Na+ uptake, stimulation of Na+,K+-ATPase activity, and net cellular K+ uptake (Figure 3B). Conversely, inhibition of Na+-HCO3− cotransport when extracellular HCO3− is reduced leads to a net loss of cell K+. Analogously, the rate of Cl− entry by Cl−-HCO3− exchange would be higher when extracellular HCO3− is reduced, increasing cell Cl− and enhancing the exit of K+ by K+-Cl− cotransport (Figure 3C). Conversely, Cl− entry by Cl−-HCO3− exchange would be lower when extracellular HCO3− is increased, leading to reduced K+ efflux by K+-Cl− cotransport."

"[..]bicarbonate can affect K+ redistribution independent of the effect of extracellular pH.[26,27] Na+ entry by Na+-HCO3− cotransport would be enhanced whenever extracellular HCO3− is increased, resulting in increased cell Na+ uptake, stimulation of Na+,K+-ATPase activity, and net cellular K+ uptake (Figure 3B). Conversely, inhibition of Na+-HCO3− cotransport when extracellular HCO3− is reduced leads to a net loss of cell K+."

"Analogously, the rate of Cl− entry by Cl−-HCO3− exchange would be higher when extracellular HCO3− is reduced, increasing cell Cl− and enhancing the exit of K+ by K+-Cl− cotransport (Figure 3C). Conversely, Cl− entry by Cl−-HCO3− exchange would be lower when extracellular HCO3− is increased, leading to reduced K+ efflux by K+-Cl− cotransport."


"In view of the longstanding observations discussed above on K+ redistribution in acid-base disorders, one would expect alkalinization by HCO3− administration to be an effective modality for acute treatment of hyperkalemia. However, some investigators have failed to find an effect of HCO3− administration to lower plasma K+ in hyperkalemic patients.[28–30] An effect of HCO3− administration to lower plasma K+ has been more striking in patients with more severe degrees of pre-existing acidosis than in those with only minimal reductions of plasma HCO3−.[31]"

"Effects of pH and HCO3− on internal K+ distribution may be modified by hormonal systems that affect cellular K+ uptake and release. For example, net cellular uptake of K+ is strongly stimulated by insulin because of increased Na+,K+-ATPase activity.[3,2]"

"[..]there is no simple relationship between pH and serum potassium because of the multiplicity of factors affecting internal and external K+ balance. For example, consider the patient with diabetic ketoacidosis. Acidemia will tend to shift K+ out of cells and cause hyperkalemia, but this effect is less pronounced in organic acidosis than in mineral acidosis. On the other hand, hypertonicity in the absence of insulin will promote K+ release into the extracellular space. Renal K+ excretion will be acutely inhibited by acidemia but ultimately enhanced by the increased distal Na+ delivery and flow rate caused by metabolic acidosis and osmotic diuresis in the setting of high aldosterone. Indeed, the patient may present with marked K+ depletion if osmotic diuresis has been going on for some time. Renal K+ excretion may later become reduced when GFR falls as volume depletion ensues. Accordingly, there will not be a straightforward relationship between serum potassium and acid-base status in such a patient. The clinician will need to be knowledgeable about the many factors affecting internal and external K+ balance to provide optimal patient care.

- Chloride shift - Wikipedia

- Protein deficiency disorders

Spoiler

"The main blood buffers are represented by bicarbonate, proteins and haemoglobin. In acquired marasmus, the level of circulating haemoglobin is low because the blood tissue wastes away in the same proportion as the active tissue (Keys et al., 1950), but this drop is insufficient to disturb the blood pH. The marasmic child often suffers phases of diarrhoea with an absolute drop in bicarbonate with a consequent compensated or non-compensated hyperchloraemic acidosis (Dubois, Van der Borght & Vis, 1968). In pure kwashiorkor diarrhoea is less frequent, but there is a decrease in haemoglobin and protein buffers in the blood although in most cases the pH is normal.

Since the buffer reserves are low in either case, the pH will fall more easily than under normal condiq tions. Furthermore, the use of the classical nomogram is not possible in cases of undernourishment and it is still difficult to determine the various disturbances exactly (Moon, 1967)."

- Hypophosphatemia - Wikipedia
⬑ Severe Hypophosphatemia in Respiratory Alkalosis

Spoiler

"The most common causes are alcoholism, dietary deficiency, [and] respiratory alkalosis. Causes of hypophosphatemia fall into 4 categories:

1. impaired dietary intake and/or absorption of phosphorus;
2. redistribution;
3. increased urinary losses of phosphorus; and
4. disease states with combined losses (Table 1)."

"With respiratory alkalosis, it is important to understand that severe hypophosphatemia will normalize with treatment of the underlying acid-base disturbance, making phosphate supplementation unnecessary.[5,6]"

"In respiratory alkalosis (Figure 4), as carbon dioxide (CO2) decreases, intracellular CO2, which is readily diffusible across the cell membrane, moves into plasma. The loss of CO2 from the cell causes the intracellular pH to rise. This rise in pH stimulates glycolysis, which requires phosphate ions to make adenosine triphosphate.[7] This phosphate is obtained from circulating inorganic phosphate stores, which are readily diffusible across the cell membrane. The serum phosphate concentration falls as a result of the intracellular phosphate shift."

"In contrast, in metabolic alkalosis (Figure 5), the intracellular pH does not rise because bicarbonate is poorly diffusible across the cell membrane. There is no increase in intracellular glycolysis, no need for influx of phosphate, and the extracellular space maintains its phosphate concentration.[8]"

- Bicarbonate: An Ancient Concept to Defeat Pathogens in Light of Recent Findings Beneficial for COVID-19 Patients?

Spoiler

"Recent data suggest that replication of many viruses, including coronaviruses, requires extracellular Ca2+ influx into the host cells (1, 2)." "Both experimental and clinical data suggest that HCO3− has a remarkable regulatory effect on Ca2+ concentrations and it can be considered as an overlooked component of the innate immune system (4-6). Importantly, intravenous administration and inhalation of NaHCO3 are safe and have been shown to be beneficial in children with life-threatening asthma, in patients with reactive airways dysfunction syndrome due to chlorine inhalation and pulmonary tuberculosis as well as cystic fibrosis (CF) (7, 8)."

"Ca2+ binding to [] negatively charged and hydrophobic amino acid residues seems necessary to promote viral fusion with the host cell membrane (9). If proteases are available at the cell plasma membrane, the fusion results in direct entry of the genetic material into the cytosol (“early pathway”). However, coronaviruses can enter the cells by endocytosis even in the absence of surface proteases (“late pathway”). Extracellular Ca2+ concentration is high ([Ca2+]e ~1.2 mM) while [Ca2+] is normally very low in these newly formed endocytic vesicles due to efflux pumps. During the later stages of maturation, fusion with Ca2+ containing lysosomes may increase endosomal [Ca2+], which is necessary for viral fusion with the endosomal membrane. In fact, SARS-CoV entry is strictly dependent on the [Ca2+]e and is inhibited by calcium chelators such as BAPTA-AM, which act in endosomes (9). Since TMPRSS2 is present in airway epithelial cells, the “early pathway” seems to be the dominant entry route in the lung. These data indicate that high local [Ca2+] is required for passing of SARS-CoV through the membranes."

"Calcium is not only necessary for virus entry into the eukaryotic cells but for intracellular replication as well. Indeed, porcine deltacoronavirus (PDCoV) stimulates Ca2+ influx from the extracellular space into porcine renal epithelial cells used for virus inoculation. Ca2+ entry to elevate [Ca2+]i was required for viral replication. Either chelating extracellular and intracellular Ca2+ with EGTA and BAPTA-AM or inhibiting voltage-dependent Ca2+ channels by diltiazem hydrochloride inhibited the replication step of PDCoV infection. Furthermore, 2-APB, a transient receptor potential (TRP) channel inhibitor and IP3 receptor antagonist, inhibited viral replication, suggesting that voltage-independent extracellular Ca2+ entry and/or Ca2+ release from internal stores are involved in this process. These data show that regardless of the Ca2+ source, PDCoV increases intracellular calcium concentrations to activate Ca2+ dependent/sensitive enzymes and transcriptional factors to promote virus replication (2)."

"[..]inhibition of extracellular calcium entry suppresses, or at least impedes viral replication."

"Hence, we hypothesize that calcium-chelating agents are potentially beneficial for patients with viral lung infections. Since the airways are continuous with the ambient environment, aerosol drug delivery may be a reasonable therapeutic approach. Although EDTA, a calcium chelator agent has antimicrobial and antibiofilm abilities in wound care, Na2EDTA can significantly increase airway responsiveness and localized calcium deficits may contribute to hyperresponsive airway disease. Among biological ions, HCO3− is ideally suited to support Ca2+ removal because CaCO3 has poor solubility indicating strong binding between Ca2+ and CO32−. Thus, we propose that HCO3− may serve to reduce extracellular Ca2+ concentrations to inhibit viral entry and replication in airway epithelial cells (Fig. 1)."

Spoiler

"Since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, CF became a model disease revealing the key role of HCO3− in a number of physiological processes. CF is a genetic disease caused by mutations in the gene encoding the CFTR protein, which is a cAMP/PKA-regulated epithelial anion channel. Paul Quinton was the first to point out the possible role of HCO3− in CF pathogenesis and noted that the specific role of HCO3− in mucin and fluid secretion had been neglected (13). Recent studies indicate that impaired transepithelial HCO3− transport underlies CF-related pathological alterations in organs such as: lung, pancreas and intestine. Indeed, bicarbonate increases the pH of airway surface liquid (ASL), reduces mucin viscosity, and exerts antibacterial and antibiofilm effects (4, 14). Bicarbonate is critical for proper unfolding of mucins in general and Muc2 more specifically by chelating extracellular Ca2+. These data are in agreement with previous observations demonstrating that high concentrations of Ca2+ in the condensed mucin of exocytosed granules are chelated by HCO3(−)/CO3(2−) in the media (5). Thus, in CF, inhalation of HCO3−-containing aerosols could improve rheological properties of the viscous mucus and suppress bacterial growth and biofilm formation. It has been recently demonstrated that inhalation of nebulized hypertonic NaHCO3 is a safe and well-tolerated therapeutic agent in the management of CF patients (8). Based on the observations reviewed above, we hypothesize that impaired HCO3- secretion plays an important role in early disturbances in the lung microbiome."

[13] The neglected ion: HCO3−​

"A recent systematic meta-analysis has shown that CF patients are more susceptible to influenza virus infections. Regardless of whether impaired HCO3− secretion is acquired (inhibition by viruses and/or inflammation) or due to hereditary CFTR deficiency, the airway pH becomes acidic and lung damage may occur."

"In a correspondence letter to the editor in 1918, Thomas Ely reported the use of sodium bicarbonate during the Spanish flu pandemic (18). He claimed that applying the alkali by mouth, bowel and skin rendered good results and referred to the therapy as “an important new medical fact, or one apparently forgotten or generally overlooked”. Since then inhalation of nebulized spring water aerosols containing high concentrations of HCO3− (1-1.5%) were used in common cold and flu. In addition, we observed that extracellular alkalization and NaHCO3 have beneficial effects on human CF bronchial epithelial cells in vitro (19) (Gróf et al., manuscript in preparation). Although the mechanisms of action are not well understood, clinical studies show that inhalation of aerosolized NaHCO3 has therapeutic effects in lung diseases of various origin (7, 8). Moreover, bronchoalveolar lavage with NaHCO3 is safe and inhibits bacterial and fungal growth in patient with lower respiratory tract infections."

"Although clinical proof of the antiviral properties of bicarbonate are missing, virucidal effects of NaHCO3 have already been demonstrated in the food industry (21). The effects of NaHCO3 alone or in combination with aldehydes and hydrogen peroxide against feline calicivirus (FCV) were investigated. Exposure to NaHCO3 caused a concentration- and time-dependent inactivation of FCV. Exposure to 1% to 20% sodium bicarbonate for 1 min inactivated from 97.22% to 99.99% of the virus. Even more interestingly, 1% and 2% sodium bicarbonate, applied for 10 min, inactivated 98.6% and 99.6% FCV, respectively. Combining NaHCO3 with either glutaraldehyde or hydrogen peroxide further increased the virucidal efficacy."

"Acute inflammation induced by viral infections can lead to lung tissue damage. Therefore, it is of note that orally ingested NaHCO3 reduces inflammation in both rats and humans. This anti-inflammatory effect is probably due to M2 macrophage polarization, which prevents excessive cytokine production (22). In addition, alkaline environmental pH and/or HCO3− activate neutrophils that are more susceptible to neutrophil extracellular trap (NET) formation (23). Although NETosis can be regarded as a double-edged sword, in acute inflammation NETs likely have a protective role as demonstrated recently in Chikungunya virus infection (24). HCO3− is also a potent antibiotic adjuvant, as bicarbonate-rich conditions increase the activity of cationic antibiotics such as aminoglycosides and macrolides (25). Taken together, these data suggest that HCO3− modulates activity of both natural and synthetic antibiotics. Thus, we believe that the likelihood that HCO3− potentiates host immunological defense against bacteria and viruses has been largely overlooked (Fig. 1)."

 

[Amazoniac]

- Nutrition For Women

"Because of their stress-like effects, coffee and tobacco should be avoided in glaucoma. The nutrients that are especially involved in the adrenal stress reaction should be used: ascorbic acid, pantothenic acid, riboflavin, 'vitamin' A, magnesium, and vitamin E.

Progesterone (natural form) is a diuretic and also is a precursor for the anti-stress hormones, and sometimes helps glaucoma. The nutrients mentioned above promote it s synthesis. Estrogen blocks its actions, so it would seem desirable to avoid estrogen, and to use the nutrients which oppose estrogen.

The eye itself has especially high requirements for vitamins A, B2, and niacin, and coenzyme Q.

Salt and water metabolism involve vitamins B6, pantothenic acid, A, C, E, and niacin (see R.J. Kutsky, Handbook of Vitamins and Hormones, p. 263), and various minerals (other than sodium) including magnesium, potassium and zinc.

Because of the role of carbon dioxide in circulation, vitamins B1, B6, and biotin, and zinc, should also be considered. Choline is now known to stimulate acetylcholine synthesis, and so might help to promote a normal parasympathetic innervation."​

 

[Amazoniac]

- Parathyroid hormone and the regulation of acid-base balance
- Metabolic Acidosis of Hyperparathyroidism
- PTH and Acid-Base Regulation

- Bone buffering of acid and base in humans
- Mechanism of acid-induced bone resorption

- The negative effect of unloading exceeds the bone-sparing effect of alkaline supplementation: a bed rest study

- Metabolic acidosis and respiratory acidosis impair gastro-pyloric motility in anesthetized pigs