6 - Acid Base Balance And Potassium Control

Question 1

How do the kidneys control plasma volume?

Answer 1

Through filtering and variably recovering salts.

Question 2

How do the kidneys control plasma osmolarity?

Answer 2

Through filtering and variably recovering water.

Question 3

How do the kidneys control pH?

Answer 3

Through filtering and variably recovering hydrogen carbonate and active secretion of protons.

Question 4

What is the normal range of pH?

Answer 4

7.38 - 7.42.

Question 5

What is alkalaemia? How does it affect the body?

Answer 5

pH > 7.42. Lowers free Ca2+, increasing excitability of nerves; if pH > 7.45, parasthesia and tetany are symptoms. N.B. pH of 7.65 = 80% mortality rate.

Question 6

What is acidaemia? How does it affect the body?

Answer 6

pH < 7.38. Increases plasma K+ and denatures many enzymes - reduced cardiac & skeletal muscle contractility, glycolysis, hepatic function. N.B. pH < 7 is very much life-threatening.

Question 7

What is the Henderson-Hasselbalch equation? What is the ratio of HCO3 to dissolved CO2?

Answer 7

pH = pKa + log([HCO3-] / (pCO2 x 0.23)) pH = 6.1 + 1.3 (or log20) = 7.4 Ratio is 20:1 HCO3- to CO2.

Question 8

What is the amount of CO2 determined by?

Answer 8

Ultimately the lungs - controlled by chemoreceptors - disturbed in respiratory disease.

Question 9

What is the amount of HCO3- determined by?

Answer 9

The kidneys - disturbed by metabolic and renal diseases.

Question 10

What is the cause of respiratory acidosis?

Answer 10

Hypoventilation which results in hypercapnia. Rise in pCO2 causes pH to fall.

Question 11

What is the cause of respiratory alkalosis?

Answer 11

Hyperventilation which results in hypocapnia. Fall in pCO2 causes pH to rise.

Question 12

What are chemoreceptors? What do they do?

Answer 12

Central: maintain pCO2 within tight limits. respiratory changes correct respiratory disturbances of pH. Peripheral: enable changes in respiration driven by changes in plasma pH.

Question 13

How can the body compensate for respiratory acidosis?

Answer 13

The kidneys will increase the [HCO3-] restoring the ratio - increasing the pH.

Question 14

How can the body compensate for respiratory alkalosis?

Answer 14

The kidneys will decrease the [HCO3-] restoring the ratio - decreasing the pH.

Question 15

What is a typical cause of metabolic acidosis?

Answer 15

Excess acid production (lactic acid, ketoacidosis, sulphuric acid) - HCO3- neutralises this. The decrease in [HCO3-] results in acidosis.

Question 16

How is metabolic acidosis compensated for?

Answer 16

Peripheral chemoreceptors detect fall in plasma pH, leading to increased ventilation - lowering pCO2 - restoring pH to normal.

Question 17

What is a typical cause of metabolic alkalosis?

Answer 17

Persistent vomiting. Alkali tide is produced by the body in preparation for the acidic content from the stomach. Acid is vomited, meaning alkali (HCO3-) remains in the body.

Question 18

How is metabolic alkalosis compensated for?

Answer 18

It can only be partially compensated through decreasing ventilation - but can normally be corrected easily by the kidneys (rise in tubular cell pH, reducing acid secretion, reducing recovery of HCO3-).

Question 19

What do kidneys need to be able to do in order to regulate [HCO3-]?

Answer 19

4500mmol of HCO3- is filtered in a day - so it is easy to lose HCO3- (compensate for an alkalosis). To increase HCO3- (compensate for acidosis) must be able to recover all filtered HCO3- and make new.

Question 20

How do the kidneys increase [HCO3-]?

Answer 20

From CO2 + H2O HCO3- + H+ And amino acids, producing NH4- to enter urine.

Question 21

How much HCO3- is reabsorbed normally and where?

Answer 21

100%: 80-90% reabsorbed in PCT and the remainder in the Thick Ascending Limb of the LOH.

Question 22

What channels are important in order to reabsorb HCO3- in the PCT? Why are they important?

Answer 22

Apical: NHE Basolateral: Na-K-ATPase, HCO3- channel Na+ gradient from tubule –> tubular cell –> ECF NHE moves H+ the other way - tubular cell –> tubule. Tubule: H+ + HCO3- –> H2O + CO2 (which enter the cell) Tubular cell: CO2 + H2O –> H+ + HCO3- (leaves via basolateral membrane to ECF). … H+ moves with NHE etc.

Question 23

How is HCO3- created in the PCT?

Answer 23

Glutamine –> alpha-ketoglutarate –> HCO3- + NH4+ HCO3- –> ECF; NH4+ –> Lumen

Question 24

How is HCO3- created in the DCT?

Answer 24

In DCT all filtered HCO3- reabsorbed and Na+ gradient insufficient to drive H+ secretion. Within the tubular cell: H2O + CO2 (metabolism) –> H+ + HCO3-. H+ is actively secreted into the lumen (H+ ATPase); HCO3- moves out of the basolateral membrane.

Question 25

What is the minimum pH of urine? How can H+ be buffered in the lumen of the DCT?

Answer 25

4.5 or [H+] = 0.04mmol/L H+ + HPO4 2- –> H2PO4 - (titrable acid) H+ + NH3 –> NH4+

Question 26

What is H+ excretion controlled by?

Answer 26

Changes in intracellular pH of tubular cells. Changes in rate of HCO3- export to ECF (due to changes in ECF [HCO3-])

Question 27

What are the cellular responses to acidosis?

Answer 27

Upregulating NHE (full recovery of all filtered HCO3-) Increased NH4+ production in DCT, Increased activity of H+ ATPase, Increased capacity to export HCO3- from tubular cells to ECF.

Question 28

What happens to [HCO3-] when acids are produced through metabolic processes?

Answer 28

Lactic acid, Ketone acids etc. are an anion (lactate) and a H+. Some of these H+ react with HCO3- forming CO2 … therefore [HCO3-] will decrease.

Question 29

What is the anion gap?

Answer 29

( [Na+] + [K+] ) - ( [Cl-] + [HCO3-] ) = Anion Gap. It is a measure of whether HCO3- has been replaced with any other anions (which are not accounted for).

Question 30

What is the normal anion gap?

Answer 30

10 - 15mmol/L (more cations than anions).

Question 31

When would the anion gap be increased?

Answer 31

If anions from metabolic acid have replaced plasma HCO3-.

Question 32

When might there be reduced [HCO3-] but a normal anion gap?

Answer 32

If all the HCO3- is replaced with Cl- (hyperchloraemic acidosis).

Question 33

How do changes in tubular cell intracellular pH influence acid secretion in the DCT?

Answer 33

Reduced intracellular pH of tubular cells stimulates acid secretion, stimulating HCO3- recovery - increasing plasma [HCO3-].

Question 34

When might metabolic alkalosis be difficult to correct?

Answer 34

Usually due to persistent vomiting - rise in intracellular pH (tubular cells), reduces acid secretion and HCO3- recovery. If there is volume depletion as well it is more complicated, high rates of Na+ reabsorption (to restore ECV) favour HCO3- reabsorption and H+ secretion.

Question 35

How are metabolic acidosis/alkalosis linked with K+ balance?

Answer 35

Metabolic acidosis: hyperkalaemia (K+ moves out of cells; more K+ reabsorption in DCT) Metabolic alkalosis: hypokalaemia (K+ moves into cells, less K+ reabsorption)

Question 36

How does hyper/hypo kalaemia affect intracellular pH of tubule cells?

Answer 36

Hyperkalaemia makes intracellular pH of tubular cells acid: favours H+ excretion and HCO3- recovery –> metabolic alkalosis. Hypokalaemia: makes intracellular pH of tubular cells alkali: reduce H+ secretion and HCO3- recovery –> metabolic acidosis.

Question 37

In our bodies we often produce acid, does this affect [HCO3-]?

Answer 37

Normally, no. All filtered HCO3- is recovered. PCT: HCO3- made; trade-off AAs –> NH4+ (glutamine –> alpha-ketoglutarate –> HCO3- + NH4+) DCT: HCO3- and H+ produced (from H2O and CO2 - metabolism) - HCO3- reabsorbed; H+ buffered with phosphate and ammonia.

Question 38

How is a 70kg man’s body fluid compartments normally divided?

Answer 38

60%… 42L is total body water 2/3… 28L is ICF 1/3… 14L is ECF.

Question 39

What can ECF be divided into?

Answer 39

ECF is 28L 1/4… 3.5L is plasma; 3/4… 10.5L is interstitial fluid.

Question 40

What are the extracellular and intracellular [K+]? Therefore where is the majority of K+ stored in the body?

Answer 40

Extracellular: 4mmol/L Intracellular: 155mmol/L 98% ICF; 2% ECF; Total body K+ = 3500mmol N.B. only small shifts from ICF –> ECF of K+ are required to change ECF dramatically.

Question 41

What maintains the difference between [K+] in the ECF and the ICF?

Answer 41

The activity of the Na-K-ATPase.

Question 42

Where exactly in the body is the bulk of the K+ stored?

Answer 42

Skeletal muscle cells. Also liver, RBCs, bone.

Question 43

What is it that creates the resting membrane potential?

Answer 43

The K+ gradient from inside the cell to outside. R.M.P in neuron cells is ~-70mV.

Question 44

How will a high ECF [K+] affect the resting membrane potential? What would a low ECF [K+] cause?

Answer 44

Decrease the K+ gradient from inside to outside - depolarising the cell. Opposite in hypokalaemia - hyperpolarisation of cell. Significantly alters electrical excitability of cardiac and neuromuscular tissues.

Question 45

How does the body deal with hyperkalaemia (high ECF [K+])?

Answer 45

Intracellular buffering plays an important role. Kidneys of little immediate help - cannot excrete K+ quickly.

Question 46

How is K+ absorbed?

Answer 46

In the intestines and the colon. It is immediately absorbed into the ECF - with 4/5 ingested K+ moving into cells within minutes; kidneys begin to excrete K+ slightly later - complete after 6-12 hours.

Question 47

How is [K+] regulated?

Answer 47

External balance: Adjusts renal K+ excretion to match intake - slower. Internal balance: Movement of K+ between ICF and ECF - immediate.

Question 48

What is the average K+ intake? Is all of this absorbed?

Answer 48

100mmol/day. No there is a 5-10% loss in the GI.

Question 49

How do the kidneys regulate [K+]?

Answer 49

They adjust K+ excretion to match intake by controlling K+ secretion. Takes 6-12 hours to be complete; responsible for maintenance of total body K+ content over the longer term.

Question 50

How does the ICF regulate ECF [K+]? What channels are involved?

Answer 50

Depending on ECF [K+] - effect is immediate, responsible for moment-to-moment control. Na-K-ATPase - 2 K+ enters; expels 3 Na+. K+ channels (ROMK channels determine K+ permeability) - K+ expelled from cell.

Question 51

With regards to internal balance of K+, what factors promote the uptake of K+ into cells?

Answer 51

Hormones: insulin, aldosterone, catecholamines Increased [K+] in ECF Alkalosis - low ECF [H+] … H+ moves out of cell to correct alkalosis, K+ moves the other way (into cells).

Question 52

How does insulin affect uptake of K+ into cells?

Answer 52

K+ in splanchnic blood stimulates insultin secretion from pancreas. Insulin stimulates K+ uptake by upregulating Na-K-ATPase in muscle cells and hepatocytes. IV Insulin used to treat life-threatening hyperkalaemia.

Question 53

How does aldosterone affect uptake of K+ into cells? What drug opposes aldosterone’s actions?

Answer 53

K+ in blood stimulates aldosterone secretion. Increases K+ reabsorption in late DCT and CD (upregulates ENaC and Na-K-ATPase).

Question 54

How do catecholamines regulate K+?

Answer 54

Act via B2-adrenoceptors - upregulate Na-K-ATPase stimulating cellular uptake of K+.

Question 55

With regards to internal balance of K+, what factors promote the K+ shift out of cells?

Answer 55

Low ECF [K+], Exercise, Cell lysis, Increase in ECF osmolarity, Acidosis - high ECF [H+] - shift of H+ into cells, K+ goes the other way - out of cells.

Question 56

How does exercise affect K+ balance between ICF and ECF?

Answer 56

Skeletal muscle contraction –> net release of K+ during recovery phase of action potential. Skeletal muscle damage –> release of K+ N.B. change in plasma [K+] proportional to level of exercise.

Question 57

How does the body prevent dangerously high K+ levels during exercise?

Answer 57

Non-contracting tissues take K+ up. Exercise increases catecholamine production (B2 - upregulate Na-K-ATPase). Cessation of exercise causes a sharp drop in plasma [K+] - <3mmol/L.

Question 58

How does cell lysis affect K+ balance between ICF and ECF? What are some causes?

Answer 58

Increases K+ in ECF. Rhabdomyolysis - trauma to skeletal muscle causing muscle cell necrosis. Intravascular haemolysis - inappropriate breakdown of RBCs: Incompatible blood transfustion, G6PD deficient patients treated with certain drugs. Chemotherapy - tumour cell necrosis.

Question 59

How do changes in plasma tonicity affect K+ balance between ICF and ECF?

Answer 59

An increase in plasma & ECF tonicity - e.g. diabetic ketoacidosis will lead to water moving from the ICF into the ECF. This increases relative [K+] in ICF - K+ moves from ICF to ECF because of this.

Question 60

How does acid base disturbances affect K+ balance?

Answer 60

Question 61

How does hypo/hyper kalaemia cause acid base disturbances?

Answer 61