Acid base regulation Flashcards by Isabel Sadler

What is pH?

pH = -log[H+]

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How is pH regulated?

pH is regulated using buffers, the main one in circulation is:
H+ + HCO3- <—> H2CO3 <—-> H2O + CO2
H2CO3 does not remain long in circulation before being converted again.

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What are the normal pH values?

pH on arterial side is very close to 7.40
On venous side, 7.35, slightly more acidic as tissues produce acid.

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What are normal HCO3- values?

Arterial blood 24mM
Venous blood 25mM, slightly higher as CO2 is converted to HCO3-.

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What are normal PCO2 values?

Arterial 40mmHg
Venous 46mmHg, slightly higher due to CO2 production from cells.

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How is CO2 regulated?

CO2 is mainly modified by the lungs.
Hyperventilate to get rid of CO2.
Decrease ventilation to maintain CO2.
Changing the concentration of CO2 or HCO3- also changes [H+].

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What is the Henderson Hasselbach equation for HCO3-?

pH = pKa + log10 [HCO3-]/[H2CO3]
[H2CO3] can also be PCO2, which is 0.03mmHg.

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How else can [H+] be determined?

Hydrogen ion concentration can be determined by the ratio of HCO3- and CO2.
High CO2, fix pH by also increasing HCO3-

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When is H+ produced as a waste product?

ATP is hydrolysed
During anaerobic respiration, with the production of lactate.
During the production of ketones (which are high in diabetes mellitus.
During ingestion of acids.
Acids are also ingested from citric fruits and fermented products.

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How is excess H+ removed?

H+ is reacted with HCO3- to produce CO2 and H2O, CO2 is then exhaled.
This causes a loss of HCO3-.
The kidney reabsorbs filtered HCO3- and creates new HCO3- to replace this.

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Why is HCO3- reabsorbed?

HCO3- is freely filtered in the glomerulus because it is small, so it needs reabsorbed back into the cortical interstitial space

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How is HCO3- reabsorbed in the proximal tubule?

HCO3- and H+ are in equilibrium with CO2 and H2O, and is sped up by carbonic anhydrase.
CO2 and H2O cross easily into the cell from the filtrate, as the CO2 is small and uncharged.
CO2 and H2O recombine to form HCO3- in the cell.
HCO3- then moves out the cell into the body.

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How is HCO3- reabsorption driven?

The Na+/H+ exchanger on the apical surface uses the electrical gradient of Na+ to drive H+ out of the cell, to combine with HCO3-.
The basolateral cotransporter removes 3 HCO3- from the cell with 1Na+, using the HCO3- gradient to move Na+ out.

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How is the HCO3- reabsorption limited?

There is a transport maximum - the maximum rate at which the cotransporter on the basolateral surface and exchanger on the apical surface can work.
The filtered HCO3- concentration is proportional to the plasma concentration.
So at low HCO3-, HCO3- is reabsorbed, but at high concentration it is not reabsorbed.
So when there is excess HCO3-, the kidneys stop reabsorbing and excess goes into urine.

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When is new HCO3- made?

If the source of CO2- is from the vasa recta (blood vessel), not the filtrate, new HCO3- can be produced.
Luminal H+ is buffered by HPO4 2-.

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How is new HCO3- produced in the proximal tubule?

CO2 enters cell from cortical interstitial space, and combines with water to form HCO3- and H+.
The Na+/H+ exchanger drives H+ into the filtrate and out the body.
3 HCO3- goes out into the body with a Na+.

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How is urine buffered?

The H+ produced from HCO3- production is excreted in urine, but this can be painful.
So HPO4 2- is used to buffer H+ and limit the harm it could cause the epithelial cells of the bladder.
This also removes phosphate that is produced in the body.

How is H+ secreted in the distal tubule?

H+ can be secreted by Na+/H+ exchanger using Na+ gradient.
ATPases (H+/K+) uses ATP to pump H+ into filtrate
Found on specialised epithelium cells, on distal tubule -
a-intercalated cells .

What are the forms of phosphate in the body?

PO4 3- in solution only at very basic pH.
If pH drops below 12.7, mainly have HPO4 2-
pH drops below 6.8, H2PO4- dihydrogen phosphate
pH drops below 2.1, H3PO4 phosphoric acid
Most phosphate will be in HPO4 2- or H2PO4-

What is the normal form of phosphate?

At arterial pH:
In systemic circulation, ratio of base (HPO4 2-) to acid (H2PO4-) is 4:1
So most phosphate is in form of HPO4 2- (hydrogen phosphate).

What is the form of phosphate in the urine?

Urinary pH is more acidic, around 5 or 6, depending on what’s consumed.
So the ratio of HPO4 2- to H2PO4- is very low, so most phosphate is in the form of H2PO4- in the urine.

What is ammonia secretion?

Ammonia can be used to remove H+ by forming ammonium ions, and so regulates pH.
When pH is very low, this system of ammonia is activated.

How is ammonia secreted in the proximal tubule?

Glutamine from liver enters cells of proximal tubule and converted to glutamate, then to a-ketoglutarate, ammonia produced at each step, as enzymes cleave off the amine groups.
Ammonia enters filtrate, and is converted to ammonium ion, which carries H+ out of cell and into the body.

How is ammonia secretion driven?

Driven by Na+/H+ exchanger (SLC9A3 gene), to move H+ across, as charged.
Ammonia can travel by other things e.g. aquaporins as not charged.

How can ammonium be produced by the proximal tubule?

NH4+pumped out by thick ascending limb using NKCC2, when ammonium replaces K+. Pumped into medulla, then pumped into the collecting duct and back into the body.

How does pH change along the nephron?

When filtrate initially forms in glomerulus, pH is equal to plasma As filtrate moves along tubular system, have H+ secretion by exchanger and ATPases. When filtrate reaches end of proximal tubule, 6.9 When reaches renal pelvis and into bladder, then 6.2, or lower.

How do the concentrations of HCO3- change from metabolic changes?

When acid is added, it causes pH to decrease, and HCO3- is used up to form CO2, the curve shifts left. When acid is removed, pH increases, HCO3- is made, and less CO2. Curve shifts right. See picture

How do the concentrations of HCO3- change when there are buffers?

See picture. There are other buffering systems. e.g. proteins have lots of side chains in amino acids, which can accept H+ as pH falls. So effect of adding or removing CO2 is shown by brown and orange line.

How do the concentrations of HCO3- change from respiratory change?

When CO2 is added, CO2 reacts with water to form HCO3- and H+, pH lower. When CO2 is removed, HCO3- and H+ react to form CO2, pH is higher.

What is the Davenport diagram?

Combines the effects of metabolic and respiratory changes. This can be used to analyse acid base disorders. See picture.

What are the types of acid base disorders?

Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis

What is respiratory acidosis?

Caused by hypoventilation (not breathing enough), CO2 is not removed, so its concentration increases. Equilibrium shifts left, increases H+ concentration - acidosis. To compensate, the kidney increases the production of HCO3- to shift equilibrium right, and returns pH towards normal.

What does the Davenport diagram look like for respiratory acidosis?

More HCO3- is produced, due to higher CO2 concentration. pH decreases. See picture.

What is respiratory alkalosis?

Caused by hyperventilation (too much breathing), high altitude. CO2 decrease, so H+ goes down, and pH increases. To compensate, the kidney decreases the production or reabsorption of HCO3- and returns the pH to normal.

What does the Davenport diagram look like for respiratory alkalosis?

Less HCO3- is produced, due to less CO2. pH increases. See picture.

What is metabolic acidosis?

Caused by renal failure, lactic acidosis, ketoacidosis - too many ketone bodies produced from the liver usually in diabetes, or poisoning - by aspirin. Increased H+, so pH decreases, equilibrium shifts right and HCO3- decreases. To compensate, CNS increases ventilation rate to decrease CO2 and return pH to normal.

What does the Davenport diagram look like for metabolic acidosis?

HCO3- falls, as more H+, and pH decreases. See picture.

What is metabolic alkalosis caused by?

Vomiting - acid lost so alkaline tide not balanced out. Taking alkaline as treatment for peptic ulcers. Excess antacid. Contraction alkalosis - losing fluid from vomiting, diarrhoea, diuretics.

What is metabolic acidosis?

H+ decreases, pH increases, so HCO3- increases, or vice versa. To compensate, the CNS decreases ventilation rate to increase CO2, and return pH to normal.

What is the Davenport diagram for metabolic alkalosis?

pH increases, HCO3- increases. See picture.

What is the anion gap?

Used to measure metabolic acidosis and its causes. Usually measured as [Na+]-[Cl-]-[HCO3-]. Balance of cations and anions should be equal, but other cations not measured cause a difference. The difference between cations and anions is measured.

What are the results of the anion gap?

An increase in anion gap suggest there is a high concentration of anions not counted, caused by: Lactate, from anaerobic metabolism. Ketones, from diabetes or alcohol toxicity. Sulphates, phosphates, urate and Hippurate, from renal failure. Aspirin overdose.