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Kidney physiology > Acid-base balance > Flashcards

Acid-base balance Flashcards

1
Q

What is normal arterial pH ?

A

7.4 +/- 0.4

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2
Q

What is normal arterial [H+]?

A

40nM/ 10^-7M

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3
Q

pH is under the dual control of which two organs?

A

Kidneys and lungs

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4
Q

What is a buffer?

A

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

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5
Q

What is the most abundant buffer in the body?

A

HCO3-

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6
Q

What is extracellular bicarbonate concentration?

A

25mmol/l

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7
Q

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

A

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

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8
Q

What two things must the kidneys do to maintain pH?

A

Reabsorb the filtered load of HCO3-

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

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9
Q

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

A

Secrete H+

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10
Q

Describe the 3 types of defence against acidosis/alkalosis

A

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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11
Q

What are the main intracellular and extracellular buffers?

A

Intracellular: proteins e.g. Hb, phosphatases

Extracellular: HCO3-

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12
Q

What is normal intake and loss of water?

A

Intake 1500-2000ml

Loss 500-800ml

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13
Q

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

A

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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14
Q

What is an example of a volatile acid?

A

CO2

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15
Q

What are Non-volatile acids?

A

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

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16
Q

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

A

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

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17
Q

What are examples of sources of NVA (3)?

A

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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18
Q

How can some NVA production be offset?

A

HCO3- production from

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

Organic ions (e.g. citrate HCO3-)

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19
Q

What is the total NV acid production?

A

70mEq/day

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20
Q

How is 70mEq of NVA acid handled initially?

A

Buffered by HCO3-

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21
Q

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

A

1:1

70mEq/day

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22
Q

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

A

4320mEq/day

23
Q

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

A

Secrete H+ equivalent to HCO3- lost

24
Q

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

A

4320+70= 4390 mEq/day

25
Q

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

A

80%

26
Q

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

A

15%

27
Q

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

A

~5%

28
Q

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

A

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

29
Q

Where is the majority of bicarbonate reabsorption?

A

PCT

30
Q

What drives H+ secretion in the PCT?

A

Mainly Na+/H+ exchanger (because there is a large Na+ gradient)

Also secretion by a H+-ATPase.

31
Q

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

A

3bicarb:1Na.

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

32
Q

What secretes H+ in the type A intercalated cells?

A

H+ATPase in type A intercalated cells in collecting duct

33
Q

Where does HCO3- regeneration occur and why?

A

Collecting duct type A intercalated cells

Fine-tuning

34
Q

Describe the mechanism of replenishing lost bicarbonate

A

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.

35
Q

The CO2 used in regenerating bicarbonate is ..

A

Equivalent to the amount created by original buffering reaction

36
Q

What are two potential non-bicarbonate buffers?

A

Phosphate:
H+ + PO43- → HPO42-

Ammonia:
H+ + NH3 → NH4 +

37
Q

Where is ammonia synthesised, what from?

A

Synthesised within PCT tubular cells from glutamine.

38
Q

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

A

Glutamine → glutamic acid (glutaminase) (hydrolytic deamination)

Glutamic acid → α-ketoglutaric acid (glutamate dehydrogenase)

Both steps yield one molecule of NH4+ (and one HCO3- ion)

39
Q

What happens to the buffered ammonia/phosphate?

A

Excreted in the urine

40
Q

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

A

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.

41
Q

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

A

Compared to PCT:

Non Na+ coupled transport

H+ doesn’t react with HCO3- in lumen

42
Q

What stimulates acid secretion across apical membrane (4)?

A

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+]

43
Q

What is the mechanism of stimulation for acid secretion?

A

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

44
Q

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

A

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.

45
Q

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

A

When pronated it becomes trapped in lumen of tubule so excreted

46
Q

What is a complexity with excretion of NH4+?

A

In TALH NH4+ is reabsorbed.

NH4+ accumulates in the renal medullary interstitium.

Resecreted into the tubular fluid by the collecting duct

47
Q

What cells secrete HCO3-?

A

Type B intercalated cells

48
Q

How do type B intercalated cells secrete HCO3-?

A

Have basolateral H+ ATPase and apical HCO3-/Cl-

Secrete Hco3- and absorb H+

49
Q

When do numbers of type B cells change?

A

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

50
Q

Describe reciprocal relationship between pH and [K+]

A

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)

51
Q

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

A

Distal tubule, H+-ATPase, AE

52
Q

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

A

Proximal tubule, NHE, NBC

53
Q

What is a consequence of acidosis?

A

Hyperkalaemia

Kidney physiology (7 decks)

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