RENAL: Control of Acid/Base and Potassium Balance

Question 1

Why is acid/base balance important?

Answer 1

Body functioning is pH sensitive (e.g. cellular metabolism, muscle functioning)

Rise in [H+] inhibits Ca binding to Trop-C, leads to skeletal + cardiac muscle dysfunction

Plasma pH is maintained via use of H+/HCO3= buffer system extracellularly and intracellularly, buffering is carried out by phosphate system and proteins

Can occur when total Na increased, but total water increased more:

CO2 + H2O ↔️ H2CO3 ↔️ H+ + HCO3-

(Carbonic anhydrase mediates conversion of CO2 into H2CO3)

pH proportional to HCO3- / PCO2

­ HCO3- = ­ pH

­ PCO2 = ¯ pH

Question 2

How does the PCT control acid/base balance?

Answer 2

90% HCO3- reabsorbed at PCT

• Recycling H+ controls HCO3- reabsorption
  
  • CO2 and H2O converted into H2CO3- (Via carbonic anhydrase)
  • H2CO3- dissociates into HCO3- and H+
  • H+ is able to move out of the tubule via Na/H+ or H+ ATPase channels (through apical membrane)
• H+ is secreted into lumen, combines with filtered HCO3 to form CO2 + water, diffuses back into tubule cell where it used to form HCO3-
• Na/H exchanger (NHE) can also excrete NH4+ instead of H+
• HCO3- can move out of tubule with Na through basolateral membrane into interstitial fluid

Question 3

How does the collecting duct control acid/base balance?

Answer 3

Intercalated type A cells: Secrete H+ (acid)

• H2O + CO2 form H2CO3 (via carbonic anhydrase)
• H2CO3 dissociates into H+ and HCO3-
• H+ moves through apical membrane via H+ ATPase channel
• HCO3- can move out cell via anion exchanger, exchanged for Cl- influx, through basolateral membrane

Intercalated type B cells: Secrete HCO3-

• H2O + CO2 form H2CO3 (via carbonic anhydrase)
• H2CO3 dissociates into H+ and HCO3-
• HCO3- moves out of tubule into lumen through apical membrane via anion exchanger, in exchange for Cl-
• H+ can move through basolateral membra

Principle cells of CD reabsorb Na via ENaC. Facilitates H+ excretion by increasing electrical gradient in favour of +ve exit

Question 4

Describe respiratory acidosis and the kidneys role in this

Answer 4

• Decrease in ventilation e.g. COPD
• Increased PCO2 (decreased PO2)
• Increased PCO2 leads to increased free H+ and decreased pH

Can cause muscle cell dysfunction (e.g. cardiac, smooth), decreased BP by reduction of SV and vasodilation

Ventilation needs to be improved

Question 5

Describe respiratory alkalosis and the kidneys role in this

Answer 5

• Increase in ventilation e.g. panic attack, fever
• Decreased PCO2 with decreased HCO3-, less reabsorbed in kidney

Relaxation techniques, e.g. breathing into bag

Question 6

Describe metabolic acidosis and the kidneys role in this

Answer 6

• Increased HCO3- loss e.g. diarrhoea
• Increased compensatory uptake - electroneutrality
• No anion gap difference
• Increased H+ production e.g. lactate production, sepsis
• Extra H+ binds to HCO3-
• Increases anion gap (reduction in free HCO3-)

Issues - Increased ventilation, decrease BP, cardiac arrest

Treatment with bicarbonate

Question 7

Describe metabolic alkalosis and the kidneys role in this

Answer 7

• Loss of H+ (and Cl-) from stomach, e.g. vomiting
• Excessive RAAS - Ang II - Increased H+ excretion, no Cl- loss

Issues - Need to remove HCO3-, need Cl- to do this

Treatment - Cl- dependent fluid treatment

Question 8

Why is potassium balance important?

Answer 8

K+ is the main intracellular cation, it’s controlled by Na+/K+ ATPase

Cells permeable to K at rest, RMP close to Ek of about -90mV

e.g., Nernst equation = EK = 61 log [K]out / [K]in = about -95 mV

­ [K+]o from 3.5 to 7mM = about -80 mV (depolarisation)

¯ [K+]o from 3.5 to 1.5mM = about -120 mV (hyperpolarisation)

Changes in [K+]o balance has profound actions on

resting membrane potential and excitability of cells,

e.g. muscles, nerves

Almost all K+ must be reabsorbed in renal filtrate

Question 9

What are the causes and consequences of hypkalaemia and hyperkalaemia?

Answer 9

Hypokalemia: <3.5m

• E.g. Excessive insulin (More Na/K ATPase activity, more K into cells)
• Diuretics - Loops and thiazides (more K excreted by renal system)
• Hyperpolarisation of excitable cells
• Less stimulation of muscles, cardiac arrhythmias
• Treated by KCl administration

Hyperkalemia: >5.5mM

• E.g. ACEi/AT1 blockers/hypoaldosterone (Principal cells, less K excretion), decrease insulin (DKA), tissue destruction (shift K out of cells)
• Depolarisation of excitable cells, hyperexcitable
• Can cause cardiac arrest, arrhythmias
• Treated using: Insulin, B2 agonists (get K back into cells)

Question 10

How do renal tubules control potassium balance?

Answer 10

PCT: 65% reabsorbed

• Paracellular movement - lots Na/H2O reabsorption, high K+ in lumen, concentration gradient b/w Na and K will drive Na into interstitial space

Thick loop of Henle - 30% reabsorbed, NKCC

CD:

• Regulation by aldosterone - Principal cells, increase K secretion
• Principle cells are regulated by aldosterone
  Loop/thiazide diuretics, Aldo/ENaC blockers - Decrease K reabsorption, hyperkalaemia