Acid-base balance Flashcards by Phoebe Mountain

What is normal arterial pH ?

7.4 +/- 0.4

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What is normal arterial [H+]?

40nM/ 10^-7M

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pH is under the dual control of which two organs?

Kidneys and lungs

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What is a buffer?

A substance that prevents a radical change in fluid pH by absorbing excess hydrogen or hydroxyl ions.

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What is the most abundant buffer in the body?

HCO3-

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What is extracellular bicarbonate concentration?

25mmol/l

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What is meant that the buffer is in an open system?

The HA is not confined to the same compartment where the reaction takes place.

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What two things must the kidneys do to maintain pH?

Reabsorb the filtered load of HCO3-

Regenerate plasma HCO3 - used to buffer/eliminate non-volatile acids

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What is the underlying mechanism the kidneys use to regulate pH?

Secrete H+

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Describe the 3 types of defence against acidosis/alkalosis

Buffer

Ventilatory mechanism: excretion of volatile acids e.g. CO2 from metabolism

Renal mechanism: reabsorption and regeneration of HCO3- via H+ secretion

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What are the main intracellular and extracellular buffers?

Intracellular: proteins e.g. Hb, phosphatases

Extracellular: HCO3-

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What is normal intake and loss of water?

Intake 1500-2000ml

Loss 500-800ml

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Describe the average total body water content and how this is divided

Total: 42 L

Intracellular fluid: 25L

Extracellular fluid 17L( Blood plasma: 3L, interstitial fluid: 13L)

Transcellular fluid: exocrine secretions into gut, synovial fluid is variable

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What is an example of a volatile acid?

CO2

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What are Non-volatile acids?

Acid produced in the body from sources other than carbon dioxide, and is not excreted by the lungs.

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How are volatile acids removed (i.e CO2)?

Carried in body fluids as the potential acid H2CO3, and excreted by the lungs.

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What are examples of sources of NVA (3)?

Produced by metabolism of:

Amino acids
Sulphur-containing (e.g. cysteine H2SO4)
Cationic (e.g lysine HCl)

Phosphate (H2PO4)

Non-complete metabolism of carbohydrates, fats, and proteins (e.g. lactic acid or keto-acids).

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How can some NVA production be offset?

HCO3- production from

Anionic amino acids (e.g. aspartate produces HCO3-)

Organic ions (e.g. citrate HCO3-)

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What is the total NV acid production?

70mEq/day

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How is 70mEq of NVA acid handled initially?

Buffered by HCO3-

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What is the ratio of NVA to HCO3- that buffers it? Thus how much HCO3- is depleted each day?

1:1

70mEq/day

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How much HCO3- is filtered from the blood per day hence needs to be recovered?

4320mEq/day

How does the kidneys recover lost HCO3- and create new HCO3- ?

Secrete H+ equivalent to HCO3- lost

What is the total amount of H+ secreted per day by the kidney?

4320+70= 4390 mEq/day

What % of the HCO3- recovery occurs at the PCT?

80%

What % of the HCO3- recovery occurs at the LOH?

15%

What % of the HCO3- recovery occurs at the DCT, CD?

~5%

What is the mechanism for the retrieval of lost HCO3-?

Bicarbonate reabsorption Secreted H+ ions combine with HCO3- in the lumen CA converts H2CO3 into CO2 and H2O. CO2 can diffuse across the membrane into the cells of PCT. Cytoplasmic CA converts the CO2 into H2CO3 that dissociates into H+ and HCO3− HCO3− is facilitated out of the cell's basolateral membrane by a Na+ HCO3- transporter

Where is the majority of bicarbonate reabsorption?

PCT

What drives H+ secretion in the PCT?

Mainly Na+/H+ exchanger (because there is a large Na+ gradient) Also secretion by a H+-ATPase.

What is the stoichiometry of the basolateral Na+/HCO3- transporter and why is it essential?

3bicarb:1Na. High stoichiometry increases (cubes) driving force for movement of bicarbonate to move Na+ against its electrochemical gradient.

What secretes H+ in the type A intercalated cells?

H+ATPase in type A intercalated cells in collecting duct

Where does HCO3- regeneration occur and why?

Collecting duct type A intercalated cells Fine-tuning

Describe the mechanism of replenishing lost bicarbonate

H+ pumped out the type A cells H+ is buffered by urinary buffers (not HCO3-) HCO3- generated by CO2 hydration exits basolaterally if H+ reacts with buffers in lumen Replacing a HCO3- lost in the titration of nonvolatile acids produced in cellular metabolism.

The CO2 used in regenerating bicarbonate is ..

Equivalent to the amount created by original buffering reaction

What are two potential non-bicarbonate buffers?

Phosphate: H+ + PO43- → HPO42- Ammonia: H+ + NH3 → NH4 +

Where is ammonia synthesised, what from?

Synthesised within PCT tubular cells from glutamine.

What are the steps of ammonia synthesis, what do they produce?

Glutamine → glutamic acid (glutaminase) (hydrolytic deamination) Glutamic acid → α-ketoglutaric acid (glutamate dehydrogenase) Both steps yield one molecule of NH4+ (and one HCO3- ion)

What happens to the buffered ammonia/phosphate?

Excreted in the urine

Why is it essential that buffered ammonia doesn't return to the blood?

Converted to urea by the liver, and, in that process, H+ is generated. This H+ is buffered by HCO3- and thus negates the process of renal “new HCO3- ” generation.

What is different about the reabsorption of HCO3- in PCT and HCO3- regeneration in type A intercalated cells?

Compared to PCT: Non Na+ coupled transport H+ doesn't react with HCO3- in lumen

What stimulates acid secretion across apical membrane (4)?

Decreased plasma pH (in PCT, TALH, CD) Increased blood pco2 (in PCT, TALH and CD) Decreased plasma volume/aldosterone in (PCT, CD) Reciprocal relationship between plasma pH and [K+]

What is the mechanism of stimulation for acid secretion?

PCT and TALH: NHE stimulated by PKC (angiotensin) inhibited by PKA (paraythyroid hormone) In CD: insertion of H+ ATPase into apical membrane from subapical vesicles

How does the majority of NH4+ leave cells and gets excreted?

NH4+ is secreted into the tubular fluid by Na+/H+ exchanger, with NH4+ substituting for H+ on the transporter. It will remain trapped in the tubule and is excreted.

What is the benefit in excretion of NH3 binding to H+ in lumen?

When pronated it becomes trapped in lumen of tubule so excreted

What is a complexity with excretion of NH4+?

In TALH NH4+ is reabsorbed. NH4+ accumulates in the renal medullary interstitium. Resecreted into the tubular fluid by the collecting duct

What cells secrete HCO3-?

Type B intercalated cells

How do type B intercalated cells secrete HCO3-?

Have basolateral H+ ATPase and apical HCO3-/Cl- Secrete Hco3- and absorb H+

When do numbers of type B cells change?

Numbers increase in alkalosis (i.e. so more HCO3- secreted)

Describe reciprocal relationship between pH and [K+]

Hyperkalaemia inhibits H+K+ ATPase and ammoniagenesis thus less H+ excreted BUT Acidosis causes hyperkalaemia (reduced K+ secretion in collecting duct. pH inhibits basolateral Na+K+ ATPase and apical K+ permeability)

What is the major site of HCO3- regeneration in the kidney and the membrane transporters involved?

Distal tubule, H+-ATPase, AE

What is the major site of HCO3- reabsorption in the kidney and the membrane transporters involved?

Proximal tubule, NHE, NBC

What is a consequence of acidosis?

Hyperkalaemia