Acid-Base regulation

Question 1

Give a background to acid-base regulation

Answer 1

13000 mmols/d volatile acid excreted by lungs 99%
100 mmols/d non-volatile acid excreted by kidneys 1%
Plasma [H+]: 40 nmol/L
Normal arterial bicarbonate: 22-26 mEq/L

Question 2

Describe the normal ranges for acid in the body

Answer 2

§ The lungs excrete 99% of the volatile acid in the blood (13,000mmols/d) while the kidneys excrete only 1%.
§ Normal arterial blood ranges in pH from 7.35 à 7.45.
o The minimum and maximum ranges of pH that are compatible with human life are 6.7 à 7.9.
o Plasma [H+] usually sits around: 40nmolL-1.

Question 3

What is the importance of the acid excreted by the kidneys

Answer 3

Small amount of filtrable acid- about 1%

but it is this percentage excreted that allows us to adjust values for pH in the blood

Question 4

Describe the pH of urine

Answer 4

No abnormal pH for urine- it is the regulator
it allows use to accommodate and maintain the regulation- so needs to be taken in context of the patient
pH can vary from lower than 5 to greater than 9

Question 5

Describe the normal ranges for bicarbonate in the body

Answer 5

§ Normal ranges are as follows:
o Arterial: 22-26mEqL-1.
o Venous: 19-25mEqL-1.

Question 6

Summarise the importance of bicarbonate in the body

Answer 6

HCO3- is an important 
HIGH CAPACITY CHEMICAL BUFFER 
that can respond rapidly to changes in
METABOLIC ACID
 and can be produced from 
VOLATILE RESPIRATORY ACID

Question 7

Describe the reabsorption of HCO3-

Answer 7

80% in PCT
10% in ascending limb
6% in DCT
4% in collecting duct

Question 8

Recall the Henderson-Hasselbach equation

Answer 8

pK constant at 6.1- dissociation constant

𝑝𝐻=𝑝𝐾+ 𝐿𝑜𝑔10[𝐻𝐶𝑂3−][𝐶𝑂2] = 𝟔.𝟏+ 𝑳𝒐𝒈𝟏𝟎𝟐𝟒𝒎𝒎𝒐𝒍/𝑳𝟏.𝟐𝒎𝒎𝒐𝒍/𝑳 = 7.4

Question 9

Describe the davenport diagram

Answer 9

A graphical representation of the association between pH, bicarbonate and carbon dioxide in blood.

bottom x-axis =pH
top x-axis = conc H+
left y-axis = plasma bicarb conc
Right y-axis= PCO2 to 6
top x-axis in graph= PCO2 to 16

green lines show normal pH, bicarb and H+ conc

Question 10

Outline how to interpret a davenport diagram

Answer 10

see diagram!

Question 11

Describe bicarbonate reabsorption in the PCT

Answer 11

§ Bicarbonate cannot freely be absorbed, sodium levels maintained by Na+/K+ ATPase.
1. Protons are pumped out and react with bicarbonate in the filtrate.
o H+ ATPase.
o Sodium-proton antiporter.
2. CO2 formed from the breakdown of carbonic acid passes into the cell and reacts with water.
3. Bicarbonate formed in dissociation is pumped out of the cell by transporters labelled.
o Chloride-bicarbonate exchanger. - Cl- moving in comes straight back out to maintain conc gradient
o Sodium-bicarbonate co-transporter (3HCO3- with Na+

Question 12

Describe the carbonic anhydrase inside the cell

Answer 12

Iso-enzyme - performs the reverse reaction to that in the filtrate

Question 13

Describe the acid-secreting alpha cells in the collecting duct and DCT

Answer 13

1. Hydrogen is pumped into the lumen.
   a. H+/K+ ATPase.
   b. H+ ATPase.
   c. sodium proton antiporter
2. This acid can react with bicarbonate which results in carbonic acid formation and resultant breakdown.
3. CO2 passes into the cell and is used to form bicarbonate (re-absorbed) and acid (excreted).
   a. HCO3- reabsorbed via AE1 (chloride that leaks out can co-transport water).

We can save more HCO3- to allow more buffer- to help get rid of acid- as well as secreting it in tubular fluid

Question 14

Describe the bicarbonate beta intercalated cells of the DCT and collecting duct

Answer 14

1. CO2 and H2O combine into carbonic acid and dissociate into bicarbonate and acid.
2. Bicarbonate is secreted while acid is reabsorbed.
   a. HCO3- - Chloride-bicarbonate exchanger.
   b. H+ - H+ATPase, sodium proton antiporter, hydrogen potassium ATPase

H+ into interstitial fluid
HCO3- into tubular fluid for excretion

Question 15

Describe HCO3- generation in the PCT via the excretion of ammonium salts

Answer 15

§ Glutamine (an amino-acid) can split into bicarbonate and ammonium salts. (2NH4+ and 2HCO3-)
§ The ammonium salts are excreted with sodium-ammonium antiports.
§ The bicarbonate is absorbed using AE1 (the Na+/K+ ATPase maintains cytosolic concentration

Question 16

Describe the generation of HCO3- in the PCT via the excretion of acid-phosphate

Answer 16

§ The cell creates bicarbonate but maintains the pH in the urine as the proton generated binds to phosphate to create Acid Phosphate.
o H+ATPase is used to secrete the proton while the bicarbonate is absorbed using AE1.

Question 17

Summarise the different types of bicarbonate buffering

Answer 17

In total there are 3 buffering mechanisms (already talked about):
o Phosphate buffer – predominates in the intracellular fluid buffering.
o Protein buffer.
o Bicarbonate buffer – predominates in the extracellular fluid buffering.

Question 18

Describe compensation in respiratory acidosis

Answer 18

1. There is an initial accumulation of CO2 in arterial blood and thus a fall of pH.
2. PCO2 levels stimulate the kidneys to increase HCO3- retention/production, and H+ secretion.
   a. Shown as a rise in BE (more base made).
3. pH begins to normalise.
4. Full compensation.

Question 19

Describe compensation in respiratory alkalosis

Answer 19

1. There is an initial reduction of CO2 in arterial blood and thus an increase of pH.
2. PCO2 levels stimulate the kidneys to decrease HCO3- retention/production, and H+ secretion.
   a. Appears as a low BE (less base made).
3. pH begins to normalise.
4. Full compensation.

Question 20

Describe compensation in metabolic acidosis

Answer 20

1. There is an initial reduction of base created or reabsorbed – low BE – and thus a drop in pH.
2. Low pH stimulates hyperventilation and thus retention of CO2 and base- PCO2 decreases
3. pH begins to normalise.
4. Full compensation.

Question 21

Describe compensation in metabolic alkalosis

Answer 21

There is an initial increase of base created or reabsorbed – high BE – and thus a rise in pH
Hypoventilation to reduce CO2 excretion- increasing PaCO2
3. pH begins to normalise.
4. Full compensation.

Question 22

Your patient has been unwell and has been passing offensive smelling urine. She brings you a sample and you analyse it using a dipstick in your office. The pH comes back as 8. What have you learnt about your patient? (4 marks)

Answer 22

High urine pH means that free proton concentration is low (1 mark) suggesting that bicarbonate is being secreted into the nephron lumen (1 mark). Patient has probably experienced either a metabolic acidosis (if bicarbonate loss is the primary disturbance) (1 mark) or a respiratory alkalosis (if bicarbonate loss is a compensatory mechanism) (1 mark)

Question 23

Is neutral pH normal for urine

Answer 23

FALSE – it is ‘a’ normal pH but not ‘the’ normal pH. pH varies across a wide range.

Question 24

Does darker urine usually have a lower pH

Answer 24

FALSE – no reliable link between colour and pH

Question 25

What can urine proton conc vary by

Answer 25

FALSE - it can vary more than 10,000x!

Question 26

Can respiratory alkalosis and acidosis co-exist

Answer 26

FALSE – the lungs cannot retain and clear carbon dioxide simultaneously

Question 27

Can metabolic alkalosis and acidosis co-exist

Answer 27

TRUE – HCl can be vomited and lactic acid accumulated

Question 28

Identify & explain the probable acid base disturbance expected in a 45- year-old female with renal failure who has missed her dialysis due to a COPD exacerbation (3 marks)

Answer 28

The patient likely has a mixed acidosis – their underlying renal failure and acute worsening of COPD would both cause the accumulation of protons in the blood. Renal failure promotes acidosis due to reduced GFR and damage to significant numbers of nephrons, reducing the acid-secreting potential. COPD promotes acidosis by obstruction-related hypoventilation, causing alveolar PCO2 to rise, reducing the diffusion gradient for pulmonary blood

Question 29

Phosphate, ammonium and protons: explain the mechanisms involved in the excretion of phosphate, ammonium salts and hydrogen ions

Answer 29

Phosphate is freely filtered and 90% reabsorbed. Remaining may bind protons, which makes them unavailable for reabsorption. Glutamine deamination produces ammonium and bicarbonate which enter the filtrate and blood respectively. Several proton pumps which utilise energy to pump protons into filtrate or blood as required.

Question 30

Describe the relationship between alpha cells and beta cells

Answer 30

an alpha cell can become a beta cell and vice versa