Week 9: Role of Kidney in Acid-Base Balance

Question 1

What are the 3 important mechanisms that regulate the bodies pH? What do they eliminate?

Answer 1

1. Body fluid chemical buffers - These buffers are rapid, but temporary 2. Lungs - Eliminates CO2 (if there is increased hydrogen concentration, there will be increased ventilation which will increase CO2 loss) 3. Kidneys - Slow to react but powerful - Eliminate non-volatile acids

Question 2

What is the essential buffer that the kidneys play a major role in reabsorbing?

Answer 2

Bicarbonate (HCO3-)

Question 3

Summarise the 3 most important functions of the kidney in acid base balance

Answer 3

1. Excretion of non-volatile acids 2. Bicarbonate reabsorption 3. Hydrogen ion secretion

Question 4

What is the type of acid that the kidneys can excrete that the lungs cannot? - This is essential

Answer 4

Non-volatile acids - these are acids you cannot breath out.

Question 5

Which enzyme is responsible for the reabsorption of bicarbonate and secretion of Hydrogen ions as it catalyses reactions?

Answer 5

Carbonic anhydrase

Question 6

Why do carbonic anhydrase inhibitors act as a diuretic?

Answer 6

Carbonic anhydrase inhibitors reduce H+ secretion and thus, reduce Na+ reabsorption - act as diuretic. (Because of the Na+/H+ antiporter)

Question 7

Where does the reabsorption of bicarbonate occur in the nephron?

Answer 7

PCT (85%), thick ascending limb, and then the distal convoluted tubule

Question 8

Where does the secretion of bicarbonate occur in the nephron?

Answer 8

Intercalated cells in the collecting duct

Question 9

Where does the secretion of hydrogen ions occur in the nephron?

Answer 9

in the PCT by NHE pump in the alpha-intercalated cells through hydrogen ATPase and hydrogen potassium ATPase

Question 10

What would happen if you blocked carbonic anhydrase to the complex?

Answer 10

Inhibit H+ secretion Inhibit reabsorption of bicarbonate

Question 11

Describe the secretion of hydrogen ions and reabsorption of bicarbonate process

Answer 11

This H+ will combine with filtered HCO3- to form H2O and CO2 which can easily pass into the tubule cell (lipid soluble) This H2O and CO2 then go back to step 1, combining to form H2CO3 This H2CO3 will then dissociate into H+ and HCO3- This H+ will be secreted into the lumen in exchange for Na+ (by the NHE exchanger) - This is the secretion of H+ This HCO3- will then be reabsorbed into the capillary either by; - Exchange for Cl- antiporter - With Na+ symporter - Either way there is bicarbonate reabsorption at the basolateral membrane

Question 12

Where does the process of the secretion of hydrogen ions and reabsorption of bicarbonate occur?

Answer 12

In the proximal convoluted tubule

Question 13

What is the acid-base equation that faciliates the secretion of hydrogen ions and reabsorption of bicarbonate?

Answer 13

H2O + CO2 <–> H2CO3 <–> HCO3- + H+

Question 14

What do the alpha intercalated cells do and how?

Answer 14

1. Hydrogen excreting
   - Through both Hydrogen-ATPase and Hydrogen-Potassium-ATPase
   - On the luminal side
2. Bicarbonate reabsorbing
3. Potassium Reabsorbing

Respond during acidosis

Question 15

What do the beta intercalated cells do?

Answer 15

1. Hydrogen reabsorbing
   - Through both Hydrogen-ATPase and Hydrogen-Potassium-ATPase
   - On the Basolateral side
2. Bicarbonate excreting
3. Potassium excreting
   - These beta-intercalated cells increase during alkalosis

Question 16

What are the 3 buffers for when tubular hydrogen concentration is high?

Answer 16

1. Bicarbonate buffer
2. Phosphate buffer
3. Ammonia buffer

Question 17

What are the two buffers excreted in urine with hydrogen ions which are used to buffer the increased amount of hydrogen ions in the urine?

Why is bicarbonate not used as a buffer as well?

Answer 17

1. Phosphate Buffer
2. Ammonia buffer

Bicarbonate not used as a buffer as it is reabsorbed.

Question 18

Where is ammonia produced?

Answer 18

Proximal convoluted tubule, thick ascending loop and distal tubules epithelial cells from glutamine, a reaction catalysed by glutaminase (enzyme)

Question 19

How does ammonia reabsorption occur?

Answer 19

Occurs in the thick ascending limb by the sodium-pottassium-2-chloride symporter

It is the reabsorbed at the basolateral membrane by a sodium antiporter

Question 20

What happens to glutamine when its broken down (think of the pathways)

Answer 20

via a sodium transporter which breaks it up into NH3 and H+

These the pass into the lumen

Question 21

What triggers an increase in ammonia synthesis?

Answer 21

Acidosis

Question 22

What will an increase in ECF pH, potassium concentration, PCO2, influence?

Answer 22

renal glutamine metabolism, which forms bicarbonate and ammonia/ammonium in PCT

Question 23

Which is the dominant buffer that deals with chronic acidosis?

Answer 23

ammonia - which also generates new bicarbonate ions

Question 24

What are the 4 factors regulating renal regulation of acid-base balance

Answer 24

1. Salt depletion
   - This stimulates the apical sodium-hydrogen antiporter
   - This will stimulate all sodium reabsorption, which will increase NHE, increase hydrogen secretion, increasing bicarbonate reabsorption
2. Aldosterone
   - Stimulates Hydrogen ion secretion through stimulating Hydrogen-ATPase pump in the DCT and collecting ducts
   - Aldosterone will increase during metabolic acidosis and will facilitate Hydrogen secretion in the collecting ducts
   - Hyperaldosteronism will cause acidic urine (as increased Hydrogen-ATPase)
3. Potassium depletion
   - Stimulates hydrogen ion secretion and ammonia production
   - If there is low potassium, there is increased potassium reabsorption in the alpha intercalated cells via the hydrogen-potassium exchanger
   - Hypokalaemia will thus cause metabolic alkalosis – increases urinary excretion of H+ and increased ammonia
   - The body responds to potassium depletion by increasing ammonia production in the PCT to increase hydrogen secretion
   - Hyperkalaemia will cause metabolic acidosis
4. Glucocorticoids
   - Stimulates hydrogen secretion through enhancing the activity of the Sodium-Hydrogen exchanger
   - This causes hydrogen secretion, bicarbonate reabsorption

Question 25

How can increased aldosterone induce alkalosis?

Answer 25

• Increased aldosterone will act to increase the ENaCs in the principal cells of the collecting duct
• This will increase potassium secretion
• There will thus be potassium depletion
• This increases H+ secretion
• Hydrogen secretion will cause bicarbonate reabsorption and production
• Metabolic alkalosis will therefore be caused (as we are losing hydrogen ions and gaining bicarbonate)

Question 26

How can overuse of diuretics induce alkalosis?

Answer 26

• There will then be increased sodium reabsorption (by ENaCs) causing increased potassium secretion
• This will cause potassium depletion in the cell, causing hydrogen excretion
• This will increase bicarbonate production and reabsorption
• This will then cause metabolic alkalosis

Question 27

What is the renal compensation for respiratory alkalosis

Answer 27

• Plasma hydrogen ion concentration is low
• There will be renal compensation leads to reduction in plasma bicarbonate
• As there is less hydrogen ion secretion, there is more bicarbonate lost in urine

Question 28

What is the renal compensation for metabolic alkalosis

Answer 28

• Plasma bicarbonate is high
• Renal excretion of bicarbonate increases
• It does this by decreases the transport of bicarbonate from cell to the ECF, increasing the proportion of beta-intercalated cells compared to alpha

Question 29

What is the renal compensation for respiratory acidosis

Answer 29

• Increased plasma hydrogen ion concentration
• The kidney will secrete more hydrogen ions, increasing bicarbonate reabsorption and formation
• Acute stimulates PCT to secrete hydrogen ions
• Chronic acidosis upregulates NHE antiporter and basolateral sodium-bicarbonate transporters

Question 30

What is the renal compensation for metabolic acidosis

Answer 30

• Reduction in bicarbonate, causing increase in hydrogen ions
• The first compensatory response will be increased alveolar ventilation
• This will also be supplemented by addition of new bicarbonate in non-renal failure patients
• Increased PCT hydrogen secretion, addition of new bicarbonates, apical NHE transporters and basolateral sodium-bicarbonate transporters, enhances ammonia production

Question 31

What is renal tubular acidosis 1 or distal renal tubular acidosis

Answer 31

• If there is an abnormal mechanism of secretion or reabsorption in collecting duct
• Inability to secrete enough hydrogen ions to match normal input
• A defect in acid secretion by alpha-intercalated cells in the distal nephron (Hydrogen-ATPase) causing acidosis in the ECF
• There is difficulty excreting normal net acid loads and is often accompanied by hypokalaemia

Question 32

What is renal tubular acidosis 2 or proximal renal tubular acidosis

Answer 32

• Abnormal secretion reabsorption of bicarbonate in proximal convoluted tubule
• Large amounts of bicarbonate flows into the distal nephron
• Urine is acidic due to distal hydrogen ion secretion
• Large load of unabsorbed solute reaching the distal nephron stimulates potassium secretion – hypokalaemia (due to sodium reabsorption causing loss of sodium)

Question 33

What is renal tubular acidosis 4

Answer 33

• If there is aldosterone abnormality (accumulation of hydrogen)

Question 34

What is renal tubular acidosis 3

Answer 34

• is a combination of type 1 and 2 renal tubular acidosis

(problem with excretion of hydrogen ions and bicarbonate reabsorption

Question 35

Briefly describe 2 processess by which tubular epithelial cells generate new bicarbonate and add it to the plasma

Answer 35

1. glutmaine breaks down forms 2HCO3 and 2NH4+
2. CO2 + H2O to form H2CO3 which breaks into H+ + HCO3-

Question 36

what is the role of carbonic anhydrase in renal regulation of acid-base balance

Answer 36

1. used to form h2CO3 from HCO + H+
2. dissociates H2CO3

Question 37

NH3 is ___ and NH4 is ____

Answer 37

ammonia and ammonium (combined with H+)

Question 38

what is renal tubular acidosis

Answer 38

abnormal reabsoprtion or secretion mechanism in the kidneys (impaired renal H+ secretion, impaired bicarb reabsoprtion)

Question 39

Why would a patient get hypokalemia (think in terms of renal dysfunction)

Answer 39

Defect in NHE in PCT which will increase sodium reabsorption into the principle cell for reabsoprtion–> increase potassium loss. Also a decrease in H+ secretion of the intercalated cells mean decrease K+ reabsorbed through H+/K ATPase –> potassium loss

This occurs as basically as because the NHE isnt working, sodium is left in tubule. Thus it eventually travels down to ENaCs where it is reabsorbed in distal tubule by Na+/K pump. This pump is also more active as the NHE is not workikng. Therefore, you get increased Na+ reabsorbed and increased K+ excreted.

Question 40

explain the effect of acidosis on ammonia synthesis

Answer 40

increased glutamine metabolism –> incrase glutamine breakdown –> incrase ammonia. also get increase bicarb

Question 41

Why does overuse of diuretics cause acid-base disturbances?

Answer 41

diuretics decrease h2O in body. THis stimulates angiotensin 2 –> stimulates aldosterone –> stimulates H+ secretion and also sodium reabsorption by ENaCs

secretion of potassium via the Sodium potassium exchanger. –> increasing reabsorption of sodium

Because you are losing potassium you then try and reabsorb some possatium via the hydrogen potassium exchanger. This causes secretion of hydrogen. –> increasing potassium reabsorption but this still isnt enough to bring potassium levels up

also sodium hydrogen exchanger. Increase sodium reabsorption and increasing hyrodgen secretion

summarised here:

1. Hypokalaemia
   - As sodium escapes thick ascending limb and has to be exchanged at the principal cell to be reabsorbed, meaning more potassium is secreted out
2. Metabolic alkalosis
   - There is increased potassium in lumen, so there will be increased exchange with hydrogen in alpha-intercalated cell (in collecting duct)
   - When potassium is reabsorbed, hydrogen goes out causing alkalosis
3. Hyperaldosteronism –> because of decrease blood pressure. aldosterone stimulated by increase angiotensin from decrease ECf
   - As you are leaving more sodium in the DCT, there is increased fluid loss
   - This decreases blood volume, causing ischemia
   - Ischemia causes activation of the renin-angiotensin-aldosterone axis
   - This causes aldosterone to be secreted to increase sodium reabsorption

Question 42

why can diabetes can metabolic acidosis?

Answer 42

diabetes –> increase lipolysis , decrease lipogenesis –> increases free fatty acids –> these are converted to ketobone bodies which are acidic.

Question 43

why in diabetes you can get hyperkalemia?

Answer 43

in a normal person increased insulin will increase K+ reaabsorption into cells. Therefore, decrease insulin will mean there is more K+ that remains in the blood.

Question 44

Explain the acid-base abnormalities of ionised calcium

Answer 44

• Acid base abnormalities alter the concentration of calcium by changing the fraction of calcium bound to albumin
• Albumin has negatively charged sites which can bind either to hydrogen ions or calcium ions, thus in acidemia where there is an excess of Hydrogen in blood, more hydrogen binds to albumin leaving fewer sites for calcium (they compete for binding sites)
• Thus, in acidemia, free ionized calcium concentration increases
• In alkalemia there is a deficit of hydrogen ions in the blood, and therefore less hydrogen bound to albumin, leaving more sites for calcium to bind
• In alkalemia the free ionized calcium concentration decreases

Question 45

why does hyperkalaemia cause acidosis

Answer 45

because you have so much potassium therfore you upregulate the potassium hydrogen exchanger. You are trying to excrete more potassium and therefore you reabsorn more hydrogen which causes acidosis