Acid/Base Physiology 3 and Clinical Lectures (Gunn)

Question 1

What must happen for metabolic alkalosis to be present?

Answer 1

If plasma bicarbonate is > 24mmols/l, HCO3 is excreted by the kidney. (rapid correction of circulating alkali)

Thus metabolic alkalosis requires both

1. An initiator
   
   • Gain of alkali in the ECF
   • Loss of H+ from ECF
   • Chloride depletion (common)
   • Potassium Depletion (rare)
2. Impaired renal correction

Steady state reflects

• Reabsorption of all filtered fixed acid/regeneration of plasma HCO3
• Excretion of filtered fixed acid/regeneration of plasma HCO3

Question 2

Describe some initiators of metabolic alkalosis

Answer 2

• Gain of alkali in the ECF
  
  • Exogenous (e.g. IV NaHCCO3 infusion, citrate in transfused blood)
  • Endogenous (e.g. metabolism of ketoanions to produce bicarbonate)
• Loss of H+ from ECF
  
  • Kidneys (e.g. use of diuretics)
  • Gut (vomiting gastric fluid, NG suction)
    
    • e.g. pyloric stenosis in babies
• Chloride depletion (common)
  
  • Lack of Cl- results in increased HCO3- reabsorption/formation
  • Cl- and HCO3- are the only anions present in appreciable quantities in ECF
  • When Na+ and K+ are reabsorbed we need a balancing act to maintain electroneutrality
  • Thus deficiency of one -? increased reabsorption of the other
    
    • e.g. diuretics (e.g. frusemimde): loss of NaCl. Risk if…
      
      • + volume depleted (increasing aldosterone levels)
      • + a low dietary chloride intake (‘salt restricted’ diet)
• Potassium Depletion (rare but impt)
  
  • Hyperaldosteronism: primary: Conn’s; secondary: Bartters
    
    • Increased distal tubular Na+ reabsorption and Increased K+, H+ loss
    • Increased HCO3- reabsorption matches i_ncreased loss of H+_
      
      • Indirect: Increased Na+ reabsorption -? Increased negative cell voltage promoting H+ secretion
      • Direct: stimulates H+ ATPase
      • Upregulates anion exhcnager, facilitating HCO3-/Cl exchange

Question 3

How do you calculate the Anion gap?

Answer 3

Anion Gap: Metabolic Acidosis

Blood electrolyte data can be used to reduce range of possible candidates responsible for metabolic acidosis, using anion gap.

[Na+] - ([Cl-] + [HCO3-]) = 143-(98+22) = 23

This patient has a large anion gap (anion of non-volatile acid is not Cl^-, anion gap will increase). Therefore, lactic acidosis is a possibility, but lactate levels would need to be tested to establish this directly.

Question 4

Describe the Alveolar Gas Equation of this Patient

A 75 year old man with a long history of severe COPD is admitted to hospital with fever, confusion and significant respiratory distress. He lives alone, but his neighbour says he has been unwell for a week and has deteriorated over previous 4 days. There is a long history of heavy smoking. Consider the following arterial blood gases:

Answer 4

Alveolar Gas Equation: Low P_AO₂ (Due to High P_aCO2)

Patient’s P_aO₂ is extremely low, and it is instructive to consider what might be responsible for this.

Alveolar gas equation can be used to provide additional insights here.

Effect of elevated P_aCO₂ on P_AO₂ in this patient is estimated below

P_AO₂ = 150 – 55/0.8 + 2 = 83mmHg

• Increased P_aCO₂ to 55mmHg (from 40mmHg normally) has reduced P_AO₂ by ~20mmHg (from 100mmHg normally) (exchange of O2 with CO2 in lungs before haemoglobin binding).
• This accounts for some, but not all of reduction in P_aO₂.

Question 5

Describe the Alveolar-Arterial PO2 Gradient:

Answer 5

Aveolar gas equation enables the alveolar partial pressure of O2 PaO2 to be estimated from PaCo2 (PaCo2= PACo2)

• PaO2 is the residual partial pressure left after the effects of moistening of air in the airways and exhcnage of O2 for Co2 in the lungs is accounted for. Normal values are given below.
• Typically, there is a smallg radient in partial pressure between alveoli and pulmonary capillaries and a normal value of PaO2 might be 100mmHg
  
  • Normal PIO2 = 150
  • Normal PAO2 = ~100mmHg

E.g. Alveolar-Arterial PO2 Gradient: Low P_aO₂ (Due to COPD Diffusion Defects)

• A-a P_O2 gradient = PAO2 - PaO2 = 83-45=38mmHg
• Pronounced A-a gradient in this patient is making a major contribution to patient’s severe hypoxaemia. COPD is commonly associated diffusion defects which give rise to such gradients.
  • Our patient Gradient = 38mmHg
    
    • An A-a Po2 gradient of >12 mmHg in young adults breathing air at sea level of > ~25mmHg in an eldery person indicates impaired O2 diffusion in the lung.
    • Tells us that the gas exchange is crap.

Question 6

A 75 year old man with a long history of severe COPD is admitted to hospital with fever, confusion and significant respiratory distress. He lives alone, but his neighbour says he has been unwell for a week and has deteriorated over previous 4 days. There is a long history of heavy smoking. Consider the following arterial blood gases:

What is the intitial hypothesis?

Why might this be suspicious?

How can we confirm this?

Answer 6

Initial Hypothesis

In absence of clinical history or electrolyte data, arterial blood gas results suggest acute (uncompensated) respiratory acidosis.

The clinical hsitory is not consistent with the intial hypothesis!!

• Modest hypercapnic (much more hypoxic)- suspicious

Arterial Blood Gas: Chronic Respiratory Acidosis (and Possible Metabolic Acidosis?)

For a patient with chronic obstructive pulmonary disease (COPD), compensation is metabolic alkalosis.

• With a P_aCO₂ of 55mmHg, we would expect HCO₃^- to be elevated to >30mmol/L and pH to be closer to 7.4.

However, these arterial blood gases suggest that there is an ongoing metabolic acidosis, in addition to chronic respiratory acidosis.

• P_aO₂ is extremely low in this patient, which is likely limiting oxygen delivery to tissues, therefore may cause lactic acidosis.

Anion Gap: Metabolic Acidosis

• Blood electrolyte data can be used to reduce range of possible candidates responsible for metabolic acidosis, using anion gap.

[Na+] - ([Cl-] + [HCO3-]) = 143-(98+22) = 23

• This patient has a large anion gap (anion of non-volatile acid is not Cl^-, anion gap will increase). Therefore, lactic acidosis is a possibility, but lactate levels would need to be tested to establish this directly.

Alveolar Gas Equation: Low P_AO₂ (Due to High P_aCO2)

• Patient’s P_aO₂ is extremely low, and it is instructive to consider what might be responsible for this.
• Alveolar gas equation can be used to provide additional insights here.
• Effect of elevated P_aCO₂ on P_AO₂ in this patient is estimated below

P_AO₂ = 150 – 55/0.8 + 2 = 83mmHg

• Increased P_aCO₂ to 55mmHg (from 40mmHg normally) has reduced P_AO₂ by ~20mmHg (from 100mmHg normally) (exchange of O2 with CO2 in lungs before haemoglobin binding). This accounts for some, but not all of reduction in P_aO₂.

Alveolar-Arterial PO2 Gradient: Low P_aO₂ (Due to COPD Diffusion Defects)

A-a P_O2 gradient = PAO2 - PaO2 = 83-45=38mmHg

• Pronounced A-a gradient in this patient is making a major contribution to patient’s s_evere hypoxaemia_. COPD is commonly associated d_iffusion defects_ which give rise to such gradients.
  
  • Tells us that the gas exchange is crap.
• An A-a Po2 gradient of >12 mmHg in young adults breathing air at sea level of > ~25mmHg in an eldery person indicates impaired O2 diffusion in the lung.

Question 7

What are the steps of analysis and interpretation of arterial blood gases?

Answer 7

• pH
  
  • Normal, acidaemic or alkalaemic
• P_CO2, [HCO₃^-], BE
  
  • Acidosis or alkalosis; respiratory or metabolic (in conjunction with clinical data)
• P_CO2, [HCO₃^-], BE
  
  • Compensated or uncompensated; simple or mixed
• Anion gap
  
  • Normal or increased
• P_O2
  
  • Normal, low or high (relative to F_IO2, and therefore alveolar P_O2)

Question 8

What are the expected responses to simple acid base disorders?

Answer 8

Respiratory Acidosis

Acute

For each 10mmHg rise in P_aCO₂, plasma [HCO₃^-] increases by 1mmol/L

Chronic

For each 10mmHg rise in P_aCO₂, plasma [HCO₃^-] and BE_ECF increases by 3-4mmol/L (compensated)

Respiratory Alkalosis

Acute

For each 10mmHg fall in P_aCO₂, plasma [HCO₃^-] decreases by 2mmol/L

Chronic

For each 10mmHg fall in P_aCO₂, plasma [HCO₃^-] and BE_ECF decrease by 5mmol/L (compensated)

Metabolic Acidosis

For each 10mmol/L decrease in plasma [HCO₃^-] or BE_ECF, P_aCO₂ falls 10-13mmHg

Metabolic Alkalosis

For each 10mmol/L increase in plasma [HCO₃^-] or BE_ECF, P_aCO₂ rises 2-9mmHg

Question 9

How do you read the Sigaard Anderson Nomogram?

Answer 9

Question 10

Answer 10

Answer (A)

Hypovolemia (lost both Na and H20) (not just dehydration). less CO and lower blood pressure.

• Cardiac output is low giving rise to relatively low arterial pressure when supine.
• This is exacerbated with postural change, because increased hydrostatic pressures in lower extremities leads to sequestration blood in superficial veins in this region further reducing venous return.

Answer (B)

The patient is acidotic.

1. Primary cause is likely to be diarrhoea and loss of bicarbonate.
2. Secondary factors that might also be ischaemia (lactic acidosis) or i_mpaired renal function_, both associated with hypotension.

Answer (C)

• Low bicarbonate since patient is excreting bicarbonate caused by diarrhoea.
• Low PCO2 is result of respiratory compensation to metabolic acidosis. Hyperventilation will lower PCO2. It also exacerbates reduction in bicarbonate.

Answer (D)

The anion gap increases during metabolic acidosis when the counter ion is not Cl-, which is case with lactic acidoisis or diabetic ketoacidosis.

For this woman, the anion gap is 11mmol/l, which is normal. This indicates that Cl- is the counter ion in her metabolic acidosis. = (Loss of Bicarbonate is causing the Metabolic Acidosis)

Answer (E)

The patient is hypokalaemic. Note that this is not a direct result of acidosis. Buffering of fixed acid in cells over a period of hours to days is associated with an increase in extracellular [K+], as a result of exchange of H+ (enter cell) for K+ (leave cell). - expect hyperkalaemia

• In this case, hypovolemia activated renin-angiotensin-aldosterone system, so aldosterone increased renal K+ excretion and Na+ retention.
• Diarrhea may also contribute to K+ loss.

Question 11

Answer 11

Answer (A)

Hypoxic

Patient’s hyperventilation is not a compensation to acid base disturbance (The patient is in metabolic alkalosis- opposite would be expected with metabolic alkalosis).

It is associated with pneumonia, and perhaps exacerbated by other factors.

Answer (B)

This is a mixed acid-base disturbance with metabolic alkalosis (vomiting) and respiratory alkalosis (hyperventilation).

Elevated pH (alkalotic), PCO2 and HCO3- reflect this.

Answer (C)

The anion gap increases during metabolic acidosis when the counter ion is not Cl-, which is case with lactic acidoisis or diabetic ketoacidosis.

The anion gap is 11mM/L (within the normal range). This indicates that there i_s no evidence of lactic acidosis in this patient._

Answer (D)

The patient’s PCO2 is marginally below normal range and does not contribute to low PO2 on admission.

This is likely due to increased diffusion distance between air in alveoli and pulmonary capillaries, as a result of pneumonia (protein-rich pulmonary oedema).

Answer (E)

As a result of vomiting and hypovolemia (dehydration), alkalosis and RAAS activation both contribute to hypokalaemia.

• Aldosterone- Na/K exchange

Note that hypokalaemia and hyperkalaemia increase risk of life threatening heart rhythm disturbance!

Answer (E)

Impaired respiratory motor activity as a result of hypokalaemia. (due to weakness because of hypokaelamia)

*Alveolar arterial gradient

Question 12

Increased anion gap indicates……

Answer 12

The anion gap increases during metabolic acidosis when the counter ion is not Cl-, which is case with lactic acidoisis or diabetic ketoacidosis.

Question 13

Explain why the anion gap increases during metabolic acidosis

Answer 13

Increases when the counter ion is not Cl-

This is the case with lactic acidosis or diabetic ketoacidosis