Acid Base and NH4 Balance Flashcards
What is the Isohydric Principle?
- the Isohydric Principle is that one buffer system reflects all buffers in the same fluid
- CO2/HCO3- buffer system is the one we analyze.
- CO2 can readily cross cell membranes, and thus, changes in extracellular pH typically (but not always) parallel those in the ICF.
Explain what the Intracellular buffers are
• HCO3- contributes equally to buffering of ECF and ICF.
• Phosphate
o intracellular pH is close to the first pK value of phosphate.
• Muscle also contains (~30mM) creatine phosphate
Explain how Bone buffers work in acute and chronic acid-base imbalances.
• In an acute setting, bone H+ ions are exchanged for either Na+ or K+ ions. The surface of bone contains a readily exchangeable pool of HCO3- and CO3– ions.
• Chronic acidosis leads to breakdown of bone matrix
o alkaline salts (hydroxyapatite and carbonate).
Explain how urinary buffers work.
• HCO3- is not a relevant buffer in urine, since practically all HCO3- is reabsorbed in the tubules.
• phosphate is a key urinary buffer.
o Since urinary pH can be lowered down to 4.5, most of the filtered HPO4– is converted to H2PO4-.
• Other urinary buffers include urate, creatinine and citrate.
• Some weak acids, like ketoacids, that are present in the urine during periods of starvation or diabetic ketoacidosis, can be also partially titrated.
• NH3/NH4+ is sometimes referred to as a urinary buffer, although strictly speaking, with a pK value of 9.2 it doesn’t behave like one in the normal range of urine pH.
o Nevertheless, excretion of NH4+ is an important means of regulating acid-base balance by the kidneys.
Why is basal respiration driven by dietary metabolism?
• CO2 is produced at such a high rate during the metabolism of carbohydrates, fat, and amino acids that even a temporary disruption of its removal can lead to profound acidosis.
Why is CO2 called a “volatile acid”? What is a fixed acid?
• Since CO2 is eliminated via the lungs, it is referred to as volatile acid to distinguish from other forms of acid/base equivalents, which are referred to as non-volatile or “fixed”.
What fixed acids are produced from incomplete metabolism of carbs and fat?
- lactic acid during exercise (tissue hypoxia)
* ketoacids during starvation (often in type 1 diabetes)
Why are vegetarians more alkaline?
- Catabolism of the carboxyl moiety of organic anions generates equivalent amounts of OH-, i.e. base.
- On a typical diet, approximately 30 mEq/day base is generated this way.
- However, on a vegetarian diet this value may increase up to 300-400 mEq/day
Can organic anions be used to treat acidosis?
- Yes
- e.g., with a lactated Ringer’s IV solution. The lactate is metabolized into bicarbonate by the liver, which can help correct metabolic acidosis.
- Similarly, Na-acetate is routinely added to the dialysis fluid during kidney dialysis to correct the acidosis associated with renal failure.
What is the citrus juice paradox?
• citrus juice contains citric acid but larger amounts of citrates.
• The overall effect is alkalinization of body fluids.
o metabolism of citric acid an equal amount of base is formed that neutralizes the added H+ ions
o metabolism of citrate anions ingested as citrate salts generates additional base
Explain the acid-base effects of protein metabolism
• H+ ions from the amino group are neutralized by metabolites of the carboxyl group.
• Initial catabolism of the amino groups yields NH4+, which is then converted into urea and H+ in the liver.
• basic amino acids generate net acid. acidic amino acids result in net base production.
o they tend to cancel each other.
• Sulfur-containing amino acids produces sulfuric acid, which ends with a net acid load of ~ 45mEq/d.
Explain the effects of phosphates and nucleic acids.
• nucleic acids and phospholipids are converted into phosphoric acid
o daily acid load of ~ 25mEq
• nucleic acids
o daily acid load of ~5mEq uric acid
Explain the effect of divalent cations.
• Divalent cations in the food are typically in a soluble form, however, they are converted into insoluble carbonate salts in the gut thereby trapping alkali
o daily acid load of ~ 20mEq.
• A common feature of transepithelial H+ ion transport is that for every H+ ion secreted, a HCO3- exits on the basolateral side and enters the blood.
• A common feature of transepithelial H+ ion transport is that for every H+ ion secreted, a HCO3- exits on the basolateral side and enters the blood.
On a typical North American diet what is the overall daily fixed acid load? How does that affect bicarbonate production in the KD?
- ~ 65mEq (equal to ~one and a half gallons of pH 2 hydrochloric acid!)
- The KDs must produce an equivalent amount of bicarbonate.
What is the lower and upper limit of urinary pH?
• 4.5 to 8.0
What is the main urinary buffer? What are its limitations?
Phosphate
What eliminates the remaining acid load?
• NH4
Describe HCO3 reabsorption in the KD Proximal Tubule (Note 100% of HCO3 is reabsorbed and does not affect acid secretion).
• In the Proximal Tubule
o Na/H exchanger-mediated HCO3- reabsorption accounts for ~60-70% of HCO3- reabsorption
o a luminal H+-ATPase, which pumps H+ ions into the urine.
o These two mechanisms together reabsorb ~80% of the filtered HCO3-.
Describe HCO3 reabsorption in the KD in the LOH.
o Bicarbonate concentration increases in the tubular fluid as it flows down the descending limb
o Reabsorption of 10-15% of the filtered load by the ascending limb mediated by Na/H exchange, but unlike the proximal tubule, this segment lacks a luminal carbonic anhydrase.
Describe HCO3 reabsorption in the KD in the CD.
o The remaining 5-10% of the filtered load is reabsorbed the “α-intercalated cell.”
o This cell secretes H+ ions via H pump (electrogenic) and H/K exchanger (electroneutral)
o Both pumps are driven by ATP hydrolysis and thus can generate a H+ gradient of ~1000:1.
o HCO3- exits this cell via a basolateral Cl-/HCO3- exchanger.
Describe HCO3 reabsorption in the KD (Note 100% of HCO3 is reabsorbed and does not affect acid secretion). All of them
• In the Proximal Tubule
o Na/H exchanger-mediated HCO3- reabsorption accounts for ~60-70% of HCO3- reabsorption
o a luminal H+-ATPase, which pumps H+ ions into the urine.
o These two mechanisms together reabsorb ~80% of the filtered HCO3-.
• In the LOH
o Bicarbonate concentration increases in the tubular fluid as it flows down the descending limb
o Reabsorption of 10-15% of the filtered load by the ascending limb mediated by Na/H exchange, but unlike the proximal tubule, this segment lacks a luminal carbonic anhydrase.
• In the Collecting Duct
o The remaining 5-10% of the filtered load is reabsorbed the “α-intercalated cell.”
o This cell secretes H+ ions via H pump (electrogenic) and H/K exchanger (electroneutral)
o Both pumps are driven by ATP hydrolysis and thus can generate a H+ gradient of ~1000:1.
o HCO3- exits this cell via a basolateral Cl-/HCO3- exchanger.
In conditions of HCO3- excess, the kidney also excrete HCO3-. What are the two mechanisms?
• 1) Reduced fractional reabsorption of HCO3- in the proximal tubule
o when the filtered HCO3- load exceeds proximal tubule Tm
• 2) active HCO3- secretion in the collecting duct
o through β-cell, which is a mirror image of the α-cell, with a luminal Cl-/HCO3- exchanger and a basolateral H+-pump. β-intercalated cells secrete HCO3-.
The pK value of the NH3+H+⇔NH4+ reaction is 9.2. This means that in the physiological pH range (both in the blood and the urine) the reaction is shifted to NH4+
The pK value of the NH3+H+⇔NH4+ reaction is 9.2. This means that in the physiological pH range (both in the blood and the urine) the reaction is shifted to NH4+
Why is excretion of NH4+ the equivalent of excreting H+?
- NH4+ is an acid precursor during urea synthesis.
- If NH4+ remains in the blood, it is converted into urea and H+ in the liver.
- Excreting NH4+ means there is less H+ production in the Liver.
NH4 is toxic. How does the body covertly transport it through the blood to the KD?
- The liver converts NH4+ into glutamine.
- Glutamine is then turned back into two NH4+ ions and α-ketoglutarate in the kidney.
- Metabolism of the two carboxyl groups of α-ketoglutarate in turn generates HCO3- ions, “new bicarbonate”
Explain the excretion of NH4+ (all of it)
• In the proximal tubule,
o the uptake of glutamine via a Na-glutamine cotransporter in both the apical and basolateral membranes.
o NH4+ ions produced intracellularly from glutamine are then secreted
• 1) Na+/NH4+ exchange using the Na+/H+-exchanger residing in the apical membrane, on which NH4+ can substitute for H+ ions.
• 2) NH4+ ions dissociate into NH3 and H+ inside the cell.
• NH3 is a gas and thus is highly diffusible.
• In the tubular fluid NH3 is converted back into NH4+ by secreted H+ ions.
• In the Loop of Henle
o In the descending limb of the Henle’s loop,
• the concentration of HCO3 and the pH of the tubular fluid increases.
• This alkalinization favors the dissociation of NH4+ into NH3 and H+, and some NH3 may diffuse out into the medullary interstitium.
o The ascending limb
• Impermeable to NH3 and actively reabsorbs NH4+.
• Reabsorption by Na/K/2Cl cotransporter, where this time NH4+ is masquerading as a K+ ion.
• NH4+ is reabsorbed paracellularly and through apical K channels
o The result is the accumulation of NH4+ in the medullary interstitium and the development of a corticopapillary gradient.
o All of the NH4+ secreted by the proximal tubule is reabsorbed in the loop.
• The Collecting Duct
o The NH4+ in the medullary interstitium is converted to NH3, depending on HCO3 levels the medulla
o The collecting duct is permeable to NH3, but is impermeable to NH4+.
• As NH3 diffuses into the tubular fluid, it is converted to NH4+ and excreted
o In the inner medullary collecting duct, some NH4 passes through the K part of the Na/K-ATPase
Explain the excretion of NH4+ in the proximal tubule,
• In the proximal tubule,
o the uptake of glutamine via a Na-glutamine cotransporter in both the apical and basolateral membranes.
o NH4+ ions produced intracellularly from glutamine are then secreted
• 1) Na+/NH4+ exchange using the Na+/H+-exchanger residing in the apical membrane, on which NH4+ can substitute for H+ ions.
• 2) NH4+ ions dissociate into NH3 and H+ inside the cell.
• NH3 is a gas and thus is highly diffusible.
• In the tubular fluid NH3 is converted back into NH4+ by secreted H+ ions.
