Bicarbonate

Question 1

EQUATION

Answer 1

CO2 + H2O H2CO3 HCO3- + H+

Question 2

CO2

Answer 2

Regulated by respiratory system

Question 3

H+

Answer 3

Added to body by diet and metabolism

Question 4

HCO3-

Answer 4

• Extracellular anion
• Principal buffer of ECF and blood
• Regulated by kidneys
• Lost in faeces each day

Question 5

What are the 4 actions of the kidney which relate to Bicarbonate?

Answer 5

• Bicarbonate filtration
• Bicarbonate reabsorption
• Titratable acid excretion - regenates bicarbonate
• Ammonium excretion - regenerates bircarbonate

Question 6

Bicarbonate Filtration

Answer 6

• GFR - 180L/day
• Normal plasma bicarbonate - 24mmol/L
• Freely filtered into Bowman’s Capsule
• Filtered Bicarbonate must be returned to the body.

Question 7

Bicarbonate Reabsorption

Answer 7

• 85-90% of filtered bicarbonate is reabsorbed in the Proximal Convoluted Tubule.
• 10-15% of filtered bicarbonate is reabsorbed in the Distal Convoluted Tubule and Collecting Duct.
• Both sites use Carbonic Anhydrase to bring HCO3- back into the blood.
• Proximal Reabsorption also uses co-transport with Na+. The Na+ is brought into the epithelia by a Na+/H+ Exchanger on the apical membrane between the epithelia and the lumen of the tubule. Excess Na+ is reabsorbed via Na+/Ka+ ATPase on basolateral membrane.
• Distal Reabsorption also uses an exchanger to exchange HCO3 out of the epithelia into the blood for a Cl- into the epithelia from the blood. H+ is excreted into lumen of tubule using H+ ATPase.

Question 8

Bicarbonate Regeneration

Answer 8

• Continually produced
• Protons consume bicarbonate - buffering system
• This is why it must be regenerated
• Regeneration raises bicarbonate in renal vein to a level higher than in the artery.
• 2 processes - Titratable Acid Excretion and Ammonium Excretion

Question 9

Titratable Acid Excretion

Answer 9

• Non-bicarbonate buffers enter lumen by filtration
• H+ + HPO4(2-) -> H2PO4-
• At plasma pH of 7.4 - 80% is in monoprotic form (HPO4(2-))
• Other buffers in urine include: Urate, Creatinine and Beta-hydroxybutyrate.
• Regenerates bicarbonate as the H+ ion joins a buffer which is not bicarbonate.
• Relatively constant system.

Question 10

Ammonium Excretion

Answer 10

• Amino acids are metabolised in the liver and form Glutamine.
• In the Proximal Convoluted Tubule, Glutamine is taken up by diffusion down its concentration gradient by Glutaminase. It becomes Glutamate. And then by Glutamic Dehydrogenase, it forms Alpha-ketoglutarate. Each step releases an ammonium ion (NH4+). And further metabolism of alpha-ketoglutarate produces 2HCO3- which get reabsorbed into the blood. The ammonium gets transported out of the cell by exchange with Na+. In the lumen of the tubule, it binds with chloride and becomes Ammonium Chloride (NH4Cl).
• In the Collecting Duct, it is permeable to ammonia (NH3). So ammonia can diffuse into the tubular lumen and bind with H+ to form ammonium. Ammonium gets trapped in the lumen as the collecting duct is impermeable to NH4 (diffusion trapping). So, it binds to chloride and becomes ammonium chloride and gets eliminated. This ammonia buffer system can be upregulated when needed (chronic acidosis).

Question 11

Respiratory Acidaemia

Answer 11

1. Rise in pCO2
2. Parallel change inside the renal tubules cells.
3. intracellular acidaemia
4. increases uptake and use of glutamine, therefore increased ammonium excretion
5. increased bicarbonate regeneration
6. low intracellular pH increases tubular proton secretion and ensures optimal reabsorption of bicarbonate

Question 12

Respiratory Alkalaemia

Answer 12

1. fall in pCO2
2. parallel change instide the renal tubule cells
3. intracellular rise in pH
4. proton secretion falls
5. bicarbonate secretion falls

Question 13

Factors which INCREASE bicarbonate reabsorption and regeneration

Answer 13

• increased pCO2
• increased H+
• decreased ECF volume
• increased angiotensin II
• increased aldosterone
• hypokalaemia

Question 14

Factors which DECREASE reabsorption and regeneration

Answer 14

• decreased pCO2
• decreased H+
• increased ECF volume
• decreased angiotensin II
• decreased aldosterone
• hyperkalaemia

Question 15

Decreasing ECF Volume/ Increasing Angiotensin II causes….

Answer 15

• stimulation of sodium reabsorption
• stimulation of activity of Na+/H+ exchange mechanism
• ratio bicarbonate/H+ in tubular lumen falls
• excess H+ in the tubules
• bicarbonate fully reabsorbed and new bicarbonate is formed

Question 16

What happens when kidney function is impaired?

Answer 16

• AKI and CKI
• Damage to glomerulus and tubule
• Will result in metabolic acidaemia
• Decrease in ammonium secretion by tubule.

Question 17

Type 1 Renal Tubule Acidosis

Answer 17

• AKA Distal Renal Tubule Acidosis
• Lowers capacity to concentrate H+ in distal tubule.
• Urine pH is above 5.5
• Low plasma K+
• Normal GFR
• Plasma bicarbonate is under 10mmol/L
• Rare in both children and adults

Question 18

Type 2 Renal Tubule Acidosis

Answer 18

• AKA Proximal Renal Tubule Acidosis
• Impairs proximal reabsorption of bicarbonate
• Variable urine pH
• Low plasma K+
• Normal GFR
• Plasma bicarbonate between 15 and 20 mmol/L
• Most common RTa in children

Question 19

Type 4 Renal Tubule Acidosis

Answer 19

• AKA Hyperkalaemic Renal Tubule Acidosis
• Caused by reduced aldosterone, inhibits ammonium production.
• Urine pH below 5.5
• High plasma K+
• Slightly impaired GFR
• Plasma bicarbonate is 15-20mmol/L
• Most common RTA in adults.