Resp8&9 - Chemical Control of Breathing & Control of Acid-Base Balance

Question 1

What is hyperventilation and hypoventilation?

What is the significance of a fall in pO2 and fall in pCO2

Answer 1

1. ) Hyperventilation - ventilation increase w/out change in metabolism
   - pO2 rises due to breathing in more oxygen
   - pCO2 falls due breathing out more CO2 and no increase metabolic activity
2. ) Hypoventilation - ventilation decrease w/out change in metabolism
   - pO2 falls due to breathing in less O2
   - PCO2 rises due to breathing out less CO2
3. ) Hypoxia - fall in pO2
   - pO2 can fall considerably before oxygen saturation is noticeably affected because the sigmoid graph plateaus by 8 kPa but alveolar pO2 is 13.3 kPa
4. ) Hypocapnia - fall in CO2
   - fairly linear relationship between pCO2 and CO2 content so small changes in pCO2 can cause large changes in CO2 content
   - this means CO2 levels needs tighter control

Question 2

2 ways ventilation can influence plasma pH

Answer 2

1. ) Respiratory Acidosis - caused by hypoventilation
   - fall in pH due to hypercapnia (increase in CO2)
   - compensated by kidneys retaining more HCO3-
   - kidney compensation can take 2-3 days
2. ) Respiratory Alkalosis - caused by hyperventilation
   - rise in pH due to hypocapnia (decrease in CO2)
   - compensated by kidneys secreting more HCO3-
   - kidney compensation can take 2-3 days

Question 3

2 ways metabolism can influence plasma pH

Answer 3

1. ) Metabolic Acidosis - tissues produce acid which reacts with HCO3-
   - fall in HCO3- favours increase in H+ –> fall in pH
   - compensated by increased ventilation which lowers pCO2 to restore pH back to normal
2. ) Metabolic Alkalosis - rise in HCO3- e.g. after vomiting
   - rise in HCO3- favours decrease in H+ –> rise in pH
   - not fully compensated by decreased ventilation (raise CO2) because that will lead to hypoxia which the body really doesn’t want

Question 4

2 respiratory control pathways

Answer 4

1. ) Peripheral Chemoreceptors - found in the carotid and aortic bodies, changes in pO2 lead to:
   - changes in ventilation, HR and blood flow distribution
   - however, they are relatively insensitive to pCO2
2. ) Central Chemoreceptors - found in the medulla that responds to changes in the pH of CSF
   - can detect small changes in arterial pCO2 to change ventilation
   - can reset what pCO2 is considered normal to maintain pH

Question 5

2 features of the control of pH by central chemoreceptors

Short Term
Long Term

Answer 5

1. ) Short Term CSF pH - determined by pCO2
   - blood brain barrier (BBB) is impermeable to HCO3- so the [HCO3-] is fixed in the short term
   - CO2 can freely diffuses across the BBB so CSF pH depends on the pCO2
2. ) Long Term CSF pH - determined by ratio of HCO3- and pCO2
   - choroid plexus cells can change [HCO3-] to correct persistent changes in pH
   - it is a self regulated autonomous system

Question 6

4 features of the response of respiratory control pathway to persisting hypercapnia

CSF pH
New Normal

Answer 6

1. ) Decrease in CSF pH - central chemoreceptors detect rise in pCO2 so they try and stimulate ventilation but this is ineffective
2. ) Acidic pH - this is undesirable for neurones so choroid plexus cells adds HCO3 to return the pH back to normal
3. ) New Normal - central chemoreceptors accept the high pCO2 and raised HCO3 as normal because the pH is normal again
4. ) No Longer Drive Ventilation - central chemoreceptors no longer sensitive to the high pCO2 so will not stimulate ventilation
   - the peripheral chemoreceptors are now responsible for driving ventilation by detecting changes in pO2

Question 7

features of the response of respiratory control pathway to persisting hypoxia

Answer 7

Find out

See Resp8

Question 8

2 causes of hypercapnia due to oxygen therapy

Controlled oxygen therapy

Answer 8

1. ) Reduced Stimulus - improved pO2 removes stimulus for the hypoxic respiratory drive –> hypoventilation
   - hypoventilation leads to hypercapnia
2. ) Reduced Pulmonary Hypoxic Vasoconstriction
   - increased perfusion of poorly ventilated alveoli, diverting blood away from better ventilated alveoli
   - V:Q mismatch
3. ) Controlled Oxygen Therapy - given to patients with coexisting chronic hypercapnia
   - only giving 24-28% of inhaled oxygen to aim for 88-92% oxygen saturation and careful monitoring of pCO2
   - if this doesn’t work, they need ventilatory support

Question 11

4 effects of alkalosis/alkalaemia

Answer 11

1. ) Hypokalaemia - K+ swapped for H+ ions in cells
   - increased excretion of K+ ions in distal nephron due to increased intracellular K+

2.) Increased Neuronal Excitability - alkalosis lowers free calcium by causing Ca2+ to come out of solution

3. ) Paraesthesia and Tetany - occurs when pH > 7.45
   - dangerous when it affects respiratory muscles

4.) Mortality - 45% death if pH rises to 7.55, 80% mortality if pH reaches 7.65

Question 12

3 effects of acidosis/acidaemia

Answer 12

1. ) Hyperkalaemia - H+ swapped for K+ ions in cells
   - decreased excretion of K+ ions in kidneys due to low intracellular K+
   - causes excitability esp in cardiac muscle –> arrhythmia
2. ) Denatures Proteins - increasing [H+] affects enzymes
   - affects muscle contractility, glycolysis, hepatic function
3. ) Severity - effects become severe below pH 7.1
   - effects become life threatening below pH 7.0

Question 13

4 features of maintaining HCO3- concentration

Reason For Maintenance
Reabsorption
2 Synthesis

Answer 13

Acid Production - acids are produced during metabolism but are buffered by HCO3- ions
- this doesn’t deplete HCO3 due to 3 mechanisms:

1.) PCT Reabsorption - recover all filtered HCO3-

2. ) PCT Synthesis - HCO3- made from glutamine
   - ammonium ions excreted in urine
   - this can be increased in response to low pH
3. ) DCT and CD Synthesis - occurs in intercalated cells
   - HCO3- made from CO2 and H2O
   - H2PO4- and ammonium ions excreted in urine

Question 14

4 steps in the production of HCO3- ions in the PCT

Answer 14

1. ) Glutamine –> a-Ketoglutarate + NH4(+)
   - this occurs in the cell
2. ) a-Ketoglutarate –> 2HCO3- which enters the ECF via the Na-HCO3- symporter on the basolateral membrane
3. ) NH4 –> NH3 + H+, NH3 diffuses back into the lumen whilst H+ uses NHE (uses Na pump gradient)
4. ) NH3 + H+ –> NH4+ (ammonium ions)
   - occurs in the lumen so NH4+ ions excreted in urine

Question 15

3 features of the anion gap

Definition
Normal Values
Increasing Anion Gap
Diagnostic

Answer 15

1. ) Definition - difference between measured cations and measured anions: (Na+ + K+) - (Cl- + HCO3-)
   - It is normally 10-18 mmol due to the presence of anions that are not measured (protiens)

2.) Increasing Anion Gap - occurs if HCO3- is replaced by other anions. e.g. if a lactic acid reacts with HCO3-, lactate replaces HCO3-

3. ) Diagnostic - help determine the cause of acidosis
   - metabolic acidosis leads to an increased anion gap if HCO3- is replaced by another organic anion
   - in renal causes, anion gap is unchanged because the lack of HCO3- is replaced with Cl- (which is measured)

Question 16

4 steps in the production of HCO3- in the DCT and collecting duct

Answer 16

1. ) CO2 + H2O –> HCO3- + H+
   - this occurs in the cell
2. ) HCO3- enters ECF via HCO3-Cl antiporter on the basolateral membrane
3. ) H+ move into the lumen via proton ATPase (active)
4. ) H(+) + HPO4(2-) –> H2PO4 (-) and H(+) + NH3 –> NH4+
   - H2PO4(-) and NH4(+) are excreted in urine

Question 17

3 features of ammonium in renal control of HCO3-

Adaptive Response
Free Movement
Buffer

Answer 17

1.) Adaptive Respone - excretion of ammonium is the major adaptive response to an increased acid load

2. ) Free Movement - can freely move into lumen and throughout interstitium
   - NH3 in the PCT can move to the DCT and pick up H+
3. ) Buffer - minimum pH of urine is 4.5 to prevent damage to the urinary tract
   - H+ ions are buffered by NH3 and some by phosphate
   - 50-100 mmol of H+ are excreted per day which is needed to keep the conc of HCO3- normal

Question 18

Conditions leading to respiratory alkalosis and acidosis

Acute Alkalosis
Chronic Alkalosis
Acidosis (4 sub causes)

Answer 18

1. ) Acute Respiratory Alkalosis - hyperventilation due to anxiety/panic attacks
2. ) Chronic Respiratory Alkalosis - caused by type 1 respiratory failure which is hyperventilation in response to long-term hypoxia
3. ) Respiratory Acidosis - caused by type 2 respiratory failure which is where the alveoli not properly ventilated
   - caused by severe COPD, severe asthma, drug OD, neuromuscluar disease

Question 19

Conditions leading to metabolic acidosis

Increased Anion Gap (3 causes)
Normal Anion Gap (2 causes)

Answer 19

1. ) Increased Anion Gap - metabolic production of a acid
   - ketoacidosis (DKA), lactic acidosis (extreme exercise)
   - uraemic acidosis (advanced renal failure (AKI/CKD)–> reduced acid secretion and build up of urate in blood)
2. ) Normal Anion Gap - HCO3- replaced by Cl-
   - severe diarrhoea causes loss of HCO3- which are replaced by Cl-
   - renal tubular acidosis: type 1 is inability to pump out H+, type 2 is problems with HCO3 reabsorption

Question 20

4 conditions leading to metabolic alkalosis

Compensation During Reduced Blood Volume

Answer 20

1. ) Severe Vomiting - loss of H+ ions
   - compensated by excretion of HCO3- ions
   - problem is if there is also volume depletion, ability to excrete HCO3- ions is reduced due to high rate of Na+ recovery (volume is more important than pH)
2. ) Mechanical Drainage of Stomach - loss of H+ ions
3. ) Potassium Depletion/Mineralocorticoid Excess - hypokalaemia
4. ) Certain Diuretics - loop and thiazide diuretics