Session 5

Question 1

Q. What range must plasma pH must be maintained within?
A. pH 7.35 – 7.45
Q. What is the range of the very low but tightly regulated concentration of H+ ions
A. 44.5 – 35.5 nmol.l-1

Question 2

1. What ion does alkaemia effect?
2. What ion does acideamia effect?
3. What are the symptoms/consequences of alkalaemia
4. pH depends on ratio of ?

Answer 2

1. Calcium -> hypocalcaemia
2. Potassium -> hyperkalaemia
3. paraesthesia and tetany,

Acidaemia lowers free calcium by causing Ca2+ ions to come out of solution (bound to albumin , albumin has carboxyl group loses H+ when high plasma pH negatively charged albumin binds to positive calcium channels) -> Increases neuronal excitability

4. [HCO3-] to pCO2

Question 3

1. pCO2 determined by respiration
   – Controlled by ?
   – Disturbed by ?
2. [HCO3-] determined by the kidneys
   – Controlled by the ?
   – Disturbed by ?
3. How do the kidneys work to control plasma pH?
4. How do the lungs work to control the plasma pH?
5. Where is HCO3- made? What controls its concentration? Give the value of its concentration in arterial blood and the range.

Answer 3

1. chemoreceptors (both peripheral and central)

Respiratory disease

2. kidney, metabolic & renal disease
3. variable recovery of hydrogen carbonate (PCT - Na+/H+) and active secretion of hydrogen ions (
4. diffusion of O2 into the blood and CO2 out of blood – control pO2 and pCO2
5. RBC
   Kidneys
   25 mmol.l-1
   Range 22-26 mmol.l-1
   But can be changed to maintain pH

Question 4

1. How do we normally produce acid?
2. This does not deplete HCO3- because: (4)
3. Explain how the kidneys recover HCO3- (5)
4. Draw a diagram showing how hydrogen bicarbonate is reabsorped in the PCT

Answer 4

1. Metabolism - because of breakdown of proteins
2. • kidneys recover all filtered HCO3-
     - Proximal tubule makes HCO3- from aa, putting NH4+ into urine
     - Distal tubule makes HCO3- from CO2 & H2O; the H+ is buffered by phosphate & ammonia in the urine
3. • HCO3- filtered at the glomerulus
     - Mostly recovered in PCT
     - H+ excretion linked to Na+ entry in the PCT
     - H+ reacts with HCO3- in the lumen to form CO2 which enters cell
     - Converted back to HCO3- which enters ECF
4. Image

Question 5

State how HCO3- is produced in the proximal tubule?

Answer 5

Glutamine -> a – ketoglutarate and NH4+ (AMMONIUM)

HCO3- enters ECF

NH3+ & H+ enters lumen (urine)

ammonium converted to ammonia as it can pass through the membrane

Then reforms ammonium

think about it is should be easy for an acid to pass the membrane - NH3

GLUTAMINE

Question 6

1. State how the distal tubule makes HCO3-

Answer 6

• Distal tubule and collecting ducts also secrete H+ produced from reaction of CO2 with water — H+ ions are ACTIVELY secreted
• H+ buffered by ammonia and phosphate (titratable)
  Produce NH4+ and H2P04- which are excreted
• No CO2 is formed to re-enter the cell
• Allows HCO3- to enter plasma

Question 7

1. Out of the three methods above to maintained HCO3- (when it is being used by the H+ created by metabolism) which method is the most effective?
2. Explain how the ammonia produced from glutamine reduced the pH

Answer 7

1. • Excretion of ammonium (HEALTHY indiv)
   • Ammonium generation from glutamine in proximal tubule can be increased in response to low pH
2. NH4+ -> NH3 + H+
   - NH3 freely moves into lumen and throughout interstitium
   - H+ actively pumped into lumen in DCT & CT
   - H+ combines with NH3 -> NH4+ (trapped in lumen)
   - NH4+ can also be taken up in TAL and transported to interstitium and dissociates to H+ & NH3+ —> lumen of collecting ducts (how does this help?)

Question 8

ACID EXCRETION

1. The minimum pH of the urine is ?
2. How much HCO3- is left in the urine?
3. What is H+ buffered by and what does it react with?
4. How much acid is excreted per day?
5. Why is this acid secretion required?

Answer 8

1. 4.5
2. No HCO3- (has all been recovered)
3. Some H+ is buffered by phosphate (titratable)

And reacted with ammonia to form ammonium

4. Total acid excretion = 50 – 100mmol H+ per day
5. To keep [HCO3-] normal (producing acid all the time so need to be excreting acid and producing HCO3-)

Question 9

1. Explain how acidosis causes hyperkalaemia
2. Explain how alkalosis causes hypokalaemia
3. What is the name for the processes that causes an exchange in cation movement?

Answer 9

1. • Potassium ions move out of cells
     - decreased potassium excretion in distal nephron
2. – Potassium ions move into cells
   – Enhanced excretion of potassium in distal nephron
3. Reciprocal cation shifts

Question 10

What is the name for the processes that causes an exchange in cation movement?

Explain how hyperkalaemia causes metabolic acidosis and hypokalaemia causes metabolic alkalosis

Answer 10

1. Reciprocal cation shifts - metabolic
2. The collecting duct secretes potassium into the lumen, the collecting duct also secretes protons into the lumen. Both of these processes are coupled to sodium reabsorption (she said there are so many transporters its easy to get mixed up with what’s happening but just simplify it to this). So basically, sodium goes into the tubule cell and either potassium and protons goes out into the lumen. If I had acidosis, loads of protons need to go out for excretion.. so sodium reabsorption is mainly coupled to proton excretion. Thus, because potassium excretion is reduced, potassium is retained so we get hyperkalemia.

PART 2, in terms of the renal system: she told me focus on the collecting duct only bc that is the ultimate decider for acid-base as this where all the intercalated cells are. This is the most simplest way to think about things… The collecting duct secretes potassium into the lumen, the collecting duct also secretes protons into the lumen. Both of these processes are coupled to sodium reabsorption (she said there are so many transporters its easy to get mixed up with what’s happening but just simplify it to this). So basically, sodium goes into the tubule cell and either potassium and protons goes out into the lumen. Makes sense? So… if I had acidosis, loads of protons need to go out for excretion.. so sodium reabsorption is mainly coupled to proton excretion. Thus, because potassium excretion is reduced, potassium is retained so we get hyperkalemia.

Question 11

How long does it take for the kidneys to compensate for resp acidosis/ alkalosis?

1. If the tissues produce acid what happens to the acid?
2. What happens to the pH
3. This is ?
4. Why is there no decrease in pH?

Answer 11

2-3 days

1. Reacts with and removes HCO3-
2. There is a fall in [HCO3-] -> fall in pH
3. metabolic acidosis
4. extra CO2 produced is breathed off at the lungs so there is no increase in arterial pCO2

Question 12

Q. 1.What is the anion gap?
2. What is the equation?
3. What is the normal range of values for the anion gap?
4. Why is there a range of values?
5. This gap is increased if HCO3- is replaced by other anions.
If a metabolic acid (such as lactic acid) reacts with HCO3- the anion of the acid replaces HCO3-
6. In renal causes of acidosis what will happen to the anion gap and why?.

Answer 12

1. Difference between measured cations and anions
2. ([Na+] + [K+]) – ([Cl-) +[HCO3-])
3. Normally 10 – 18 mmol.l-1
4. Due to other anions not being measured
   5.
5. Anion gap will be unchanged – not making enough HCO3- but this is replaced by Cl-

Question 13

Conditions leading to respiratory alkalosis? (2) What is each condition characterised by?

Answer 13

A. – Anxiety / panic attacks – acute setting
Low CO2
Rise in pH

• *Long- term hypoxia – Type 1 respiratory failure**
• Low pCO2 with initial rise in pH
• chronic hyperventilation can be compensated for by fall in [HCO3-]
• Can restore pH to near normal

Question 14

Conditions leading to metabolic acidosis
1. If anion gap is ? – indicates a metabolic production of an acid

2. State conditions that lead to metabolic acidosis (3) and give examples for each type of acidosis

Answer 14

A. 1. Increased

2. Keto-acidosis
   • diabetes

Lactic acidosis
• Exercising to exhaustion
• Poor tissue perfusion (SHOCK decreased peripheral blood supply)

Uraemic acidosis
• Advanced renal failure – reduced acid secretion, build up of phosphate, sulphate, urate in blood

Question 15

Conditions leading to metabolic acidosis with a normal anion gap

1. How is there a normal anion gap?
2. What conditions lead to metabolic acidosis with a normal anion gap? How common are the conditions? Describe the conditions.

Answer 15

1. HCO3- is replaced by Cl-
2. Renal tubular acidosis (this is a rare condition)
   - Problems with transport mechanism in the tubules
   - Type 1 (distal) RTA – inability to pump out H+
   - Type 2 (proximal) RTA (very rare) – problems with HCO3-, reabsorption

Severe persistent diarrhoea

• loss of HCO3-
• Replaced by Cl-
• Therefore anion gap unaltered

Question 16

Metabolic acidosis & potassium

1. How are fatty acids oxidised?
2. Non-renal causes of metabolic acidosis cause?
3. However in diabetic ketoacidosis may be a total body depletion of K+

Answer 16

Question 17

What happens to the acetyl - coA to produce ketones?

Answer 17

You do not produce enough insulin but still produce glacagon

Question 18

• Water soluble molecules
• Permits relatively high plasma concentrations
• Alternative substrate
• Above renal threshold, excreted in urine -> ketonuria
• Acetoacetate and β hydroxybutyrate are relatively strong organic acids -> ketoacidosis
• Volatile acetone may be excreted via the lungs
• N.B. characteristic smell of acetone (nail varnish remover) on breath

Metabolic acidosis & potassium

1. Non-renal causes of metabolic acidosis effect K+ how?
2. However in diabetic ketoacidosis may be a total body depletion of K+

Answer 18

1. Inc reabsorption of K+ by kidneys & movement of K+ out of cells = hyperkalaemia
2. • high blood glucose
     - need to conserve glucose for the brain GLUT1 and GLUT3

(SGLT2 in enterocytes and kidneys

GLUT2 in intestines and kidneys, pancreas

GLUT4 in muscle and adipose)

• fatty acid oxidation (activation by coA, carnitine, acetyl-coA synthase and lyase, make acetoacetate etc)
• B- hydroxybutyrate and acetoacetate are ACIDIC

– K+ moves out of cells (due to acidosis and lack of insulin less Na+/K+ pump)

– But osmotic diuresis means K+ lost in urine Insulin K+ goes back into the cells causing hypokalemia must replace the lost K+ (more glucose in the blood, more glucose filtered and water follows)

• COMA due to ketoacidosis -> acid damaged neurones

Question 19

Conditions leading to metabolic alkalosis? (3)

Answer 19

Severe prolonged vomiting

Potassium depletion/ mineralocorticoid excess

Certain diuretics (loop and thiazide)

Question 20

How does severe prolonged vomiting lead to metabolic alkalosis

Answer 20

Stomach is a major site of HCO3- production

• By product of H+ secretion
• Severe prolonged vomiting – loss of H+
• Or mechanical drainage of stomach

Question 21

In metabolic alkalosis e.g. after persistant vomiting you cannot compensate by hypoventilation. Thus, how do the kidneys compensate?

Answer 21

• Rise in pH of tubular cells leads to fall in H+ excretion & reduction in HCO3- recovery
• Problem if there is also volume depletion because of high rate of Na+ recovery

– Capacity to loose HCO3- impaired

– Recovering Na+ favours H+ excretion and HCO3- recovery

Question 22

2,3,4 aquapoirn some more!

How do we absorb more water when we have a low osmolarity?

Answer 22

No ADH stimulation means no Aquaporin 2 in apical membrane, AQP 3 & 4 on basolateral membrane only of the the latter DCT & Collecting ducts

Question 23

If [HCO3-] is low, pCO2 is low, pH is relatively normal what is this? Which one is it more likely to be?

Answer 23

Could be either compensated respiratory alkalosis or compensated metabolic acidosis

• If no respiratory disease or altitude exposure – unlikely to be respiratory
• Check anion gap – if increased is metabolic acidosis

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Question 25

Answer 25

Creatinine needs to match to CO of 6L