Lecture 10 - Acid/Base Balance In The Kidney

Question 1

What happens if the plasma pH is not maintained within a tight range?

Answer 1

Proteins/enzymes denature

Question 2

What is the healthy pH range of the blood plasma?

Answer 2

7.35 - 7.45

Question 3

What is the pH range that the urine varies between?

Answer 3

4.5 - 8.5

Question 4

How does Alkalemia affect plasma free calcium levels?

Answer 4

Decreases free levels of calcium

Question 5

Describe the mechanism by which alkalosis causes lower free calcium levels:

Answer 5

When the blood is alkalotic the hydroxyl group of albumin dissociates its H+, this makes more Ca2- bind to albumin

Question 6

What plasma protein is the main plasma protein in the blood?

Answer 6

Albumin

Question 7

Describe the mechanism by which alkalosis causes lower free calcium levels:

Answer 7

When blood is alkalotic the hydroxyl group on the albumin dissociates releasing H+ to try and decrease blood pH

This change on the albumin leads to Ca2+ binding to t he albumin making it no longer free decreasing plasma Ca2+ levels

Question 8

So if alkalosis causes decreased free plasma Ca2+, how does this affect nerves?

Answer 8

Increased neuronal excitability ( so action potentials fired at slightest signal)

Sensory changes like numbness/tingling with muscle twitches

Can lead to sustained contractions/paralysis

Question 9

How does acidosis change free calcium levels in the plasma?

Answer 9

Increases free calcium levels in the plasma

Question 10

Describe the mechanism by which acidosis causes higher free calcium levels:

Answer 10

When the blood is acidotic the H+ binds to the O- of the what once was the hydroxyl group on the albumin

This leads to Ca2+ being released from the album in and less Ca2+ binding to the albumin
So plasma levels of free Ca2+ increases

Question 11

What affect does increased free plasma Ca2+ have on other ion levels and why is this dangerous?

Answer 11

Increases plasma [K+] levels

Leads to cardiac excitability being affect leading to Arrythmias

Question 12

What are the 2 sources of H+ in the body?

Answer 12

Diet

Metabolism

Question 13

What are some examples of how acids can be obtained?

Answer 13

Proteins = amino acids
Lipids = fatty acids
Carbs = lactic acids

Question 14

What are the 3 different buffer systems to buffer the H+ in the body?

Answer 14

HCO3– in blood/ECF

Proteins, Hb and Phosphates in cells

Phosphates and ammonia in urine

Question 15

What are the 2 organs/systems that regulate plasma pH?

Answer 15

Lungs/respiratory

Kidneys/renal system

Question 16

What is the relative speed by which the ventilation system and the renal system can compensate for plasma pH levels?

Answer 16

Lungs/ventilation = rapid response

Kidneys/renal = slower

Question 17

How do the lungs help regulate blood pH?

Answer 17

Changing ventilation rate changes levels of CO2 present in the blood

Question 18

How do the kidneys alter blood pH?

Answer 18

Excreting and reabsorbing H+

Changing rate at which HCO3- is reabsorbed pr excreted in the urine

Question 19

How much of the HCO3- does the body try and reabsorb from the filtrate in the PCT?

Answer 19

All of it

Question 20

What form is HCO3- absorbed from the filtrate into the PCT cell as?

Answer 20

CO2 + H20

HCO3- + H+ = H2CO3
H2CO3 becomes CO2 + H2O with help of Carbonic anhydrase

Question 21

Describe how HCO3- is reabsorbed into the blood from filtrate:

Answer 21

Na+/K+ ATPase on basolateral membrane pumps Na+ into blood establishing Na+ gradient

Carbonic acid broken down to CO2 + H2O by carbonic anhydrase
CO2 and H2O diffuses into the cell

CO2 + H2O remade into H+ + HCO3- in cell with help from C.A

HCO3- symported into blood across basolateral membrane with Na+

H+ in the cell antiported into blood across apical membrane and Na+ brought into cell

Question 22

What are the 2 buffer systems present in the plasma that help prevent blood being too acidic?

Answer 22

Phosphate buffer

Ammonia (NH3) buffer

Question 23

How does the phosphate buffer system in the urine act to prevent blood becoming to acidic?

Answer 23

H+ reacts with HPO4(2-) forming H2PO4(-)

H2PO4(-) can then be excreted in the urine

Question 24

How does the ammonia buffer system in the urine act to prevent plasma pH becoming to acidic?

Answer 24

NH3 + H+ forming NH4+

This is now charged (ammonium) preventing it entering into any cells which constricts it to the lumen ensuring it is excreted

Question 25

What is the process by which the PCT cells can produce HCO3- to prevent blood becoming too acidic?

Answer 25

Cell makes glutamine Glutamine converted to alpha ketoglutarate and 2NH4+ Alpha ketoglutarate converted to 2HCO3- to be reabsorbed into blood Ammonium (2NH4+) broken down into ammonia (2NH3) and 2H+ 2NH3 then diffuses back into lumen to join monitor buffer system H+ then removed back into lumen

Question 26

What are the cells that deal with acidosis in the DCT/CD?

Answer 26

Alpha intercalated disc cells

Question 27

What are the cells that deal with alkalosis in the DCT/CD?

Answer 27

B intercalated cells

Question 28

What ion can be heavily influenced by the pH/ being acidotic or alkalotic? Why is this dangerous?

Answer 28

Potassium levels Hyperkalaemia and hypokalaemia Can lead to cardiac arrhythmias

Question 29

How can acidosis affect potassium levels in the blood and explain why?

Answer 29

Hyperkalaemia High H+ in plasma exchanged with K+, H+ moved into cell and K+ into the blood from the cell

Question 30

How can alkalosis affect potassium levels in the blood and explain why?

Answer 30

Hypokalaemia Since H+ levels in blood low H+ moved from inside of cells into blood and therefore K+ moved from blood into cells

Question 31

What is the main cause of respiratory alkalosis?

Answer 31

Hyperventilation Lots of CO2 breathed out (hypocapnic) so less carbonic acid

Question 32

What is the form of compensation that occurs with respiratory alkalosis?

Answer 32

Renal/metabolic compensation Less HCO3- reabsorbed in PCT HCO3- secreted in DCT/CD H+ reabsorbed with K+

Question 33

What is the most common cause of Respiratory acidosis?

Answer 33

Hypoventilation More CO2 retained so (Hypercapnic) so higher levels of Carbonic acid

Question 34

What is the form of compensation that occurs with respiratory acidosis?

Answer 34

Renal/metabolic compensation More HCO3- reabsorbed in kidneys and H+ secreted

Question 35

What can cause Metabolic alkalosis?

Answer 35

Excess vomiting of acidic stomach contents Ingesting excess HCO3- like through antacids

Question 36

What are the compensatory mechanisms for a Metabolic Alkalosis?

Answer 36

Resp compensation = Hypoventilation (more CO2 retained to make more acidic blood) The hypoventilation leads to more HCO3- being made from the extra CO2 so some RENAL compensation occurs so less HCO3- reabsorbed in PCT

Question 37

What can cause metabolic acidosis?

Answer 37

Dietary and metabolic input of H+ exceeds excretion Or losing to much HCO3- (diarrhoea) E.g: Lactic acidosis Ketoacidosis

Question 38

What compensation occurs with metabolic acidosis?

Answer 38

Respiratory compensation = hyperventilation to increase removal of CO2 Renal compensation = inc reabsorption of HCO3- and DCT/CD secretion of H+

Question 39

Look at the last slide, look at 1. Investigations and describe what type of acid base disturbance has occured:

Answer 39

Metabolic acidosis with respiratory compensation (partial) PH low PCO2 low so not the cause of the acidosis but HCO3- is low so its the cause

Question 40

Look at the last slide, look at 1. Investigations and describe what type of acid base disturbance has occured:

Answer 40

Metabolic acidosis with respiratory compensation (partial) PH low PCO2 low so not the cause of the acidosis but HCO3- is low so its the cause

Question 41

What is the anion gap?

Answer 41

The difference between measured cations and anions

Question 42

How do you determine the anion gap?

Answer 42

([Na+] + [K+]) - ([Cl- + [HCO3-]) Basically sum of major cations - sum of major anions

Question 43

What form of acidosis is the anion gap remaining unchanged? Why?

Answer 43

Metabolic acidosis Not enough HCO3- but is replaced by Cl-

Question 44

What are some of the common causes of hypokalaemia?

Answer 44

Alkalosis GI loses Renal loses

Question 45

What are some examples of renal loses that can cause hypokalaemia?

Answer 45

Diuretics like furosemide Too much aldosterone production/over activation of RAAS Renal tubular acidosis