Acid/Base Physiology 1 (Gunn)

Question 1

Normal blood pH is…

Answer 1

Normal blood pH is 7.37-7.42,

extreme pH range is 7.0-7.8 (compatible with long-term survival).

Question 2

How do we deal with axid?

Answer 2

Acids produced by body are very effectively buffered by blood and tissues. However, maintenance of acid base balance relies on:

• Excretion of CO₂ formed as a result of oxidative metabolism by the lungs;
• Removal of acid generated by protein catabolism via the kidney.

Question 3

Describe the 2 ways acid is produced in our body

Answer 3

Oxidative Metabolism

Oxidative metabolism produces 13,000-20,000mmole/day CO₂. This leads to formation of carbonic acid, which is only weakly dissociated. Because carbonic acid is in equilibrium with a dissolved CO₂, it is often referred to as a volatile acid.

CO₂ + H₂O H₂CO₃ H⁺ + HCO₃^- (1)

Protein Catabolism

In meat-rich diets, protein catabolism produces 40-60mmole/day non-carbonic acid.

• This is due to sulphuric acid, produced by oxidation of sulfur-containing amino-acid residues.
• This is also due to phosphoric acid (small contribution), produced by catabolism of phospholipids.

Because non-carbonic acid is not in equilibrium with a volatile component, it is known as non-volatile/fixed acid. Under some circumstances, non-volatile acids may increase markedly:

• In extreme exercise or ischemia, there is lactic acid formation due to anaerobic metabolism.
• In diabetes (insulin deficiency), there is ketoacidosis with production of aceto-acetic acid and b-hydroxybutyric acid.

Question 4

How do you calculate pH? (Henderson Hasselbalch equation)

Answer 4

Question 5

Describe the buffering of non-volatile acid (bicarbonate buffer system)

Answer 5

Bicarbonate Buffer System

In bicarbonate buffer system, buffers are weak acids (e.g. carbonic acid), which only partially dissociated in physiological pH.

• Dissociation constant K_a of this reaction is such that H⁺ addition drives reaction to right. Added protons combine with HCO₃^– (bicarbonate ion) to produce H₂CO₃ (carbonic acid). Thus, pH remains relatively constant, but [HCO₃^–] falls.
• This bicarbonate buffer system is described by Henderson Hasselbalch equation (3).

As indicated above, H₂CO₃ is in equilibrium with dissolved CO₂ in plasma. While [H₂CO₃] <<< [dissolved CO₂], dissolved CO₂ represents total pool of bicarbonate that is available for buffering. Moreover, [dissolved CO₂] in plasma is directly proportional to P_CO2 (partial pressure of CO2).

Therefore, Henderson Hasselbalch equation can be rewritten (4) in physiological and clinical use:

• Firstly, status of buffer system can be readily characterised using standard measurements of blood chemistry. Constant 0.03 converts P_CO2 (mmHg) to [dissolved CO₂] (mmol/L) in plasma at 38°C.
• Secondly, it encapsulates separate contributions of each body components involved with acid-base regulation. Since [HCO₃^–] = 24mmol/L (regulated by kidney) and P_CO2 = 40mmHg (regulated by respiratory), pH is regulated to 7.4.

Buffering Of Non-Volatile Acid with Bicarbonate Buffer System

Henderson Hasselbalch equation can be presented in a [HCO₃^–]-pH plot. Addition of non-volatile acid leads to fall in both pH and [HCO3-]. Acid is buffered in the form of H₂CO₃ and dissolved CO2 (readily removed in lungs).

Bicarbonate system is main buffer of non-volatile acids in extracellular fluid (plasma/blood and interstitial fluid). This is because:

• [HCO₃^–] is much higher in ECF (plasma and interstitial fluid) than either proteins or organic phosphates.
• Bicarbonate system is in equilibrium with volatile CO₂, which is transported in blood and readily eliminated by lungs.

Non-volatile acid added to body is rapidly transferred to ECF, therefore bicarbonate system can provide effective short-term buffering (seconds to minutes).

Buffering Of Non-Volatile Acid with Other Buffer Systems

There are other acid buffer systems with intracellular proteins and organic phosphates in red cells, tissue and bone.

• Capacity of intracellular proteins and organic phosphates to buffer H+ acid is relatively large
• However, utilisation of these buffers involves exchange of extracellular H+ with intracellular Na+ and K+ across cell membrane. This means time-course of this process is relatively long (hours to days).

The Isohydric Principle

For homogeneous solution of multiple buffer systems at equilibrium, isohydric principle applies (following equation). It follows that pH can be determined from status of any buffer systems.

• This is reasonably accurate for extracellular (ECF) (blood and interstitial) phase.
• However, it is less accurate for intracellular (ICF) phase, which is not homogenous with ECF.

Question 6

Describe the buffering of volatile acid (production and transport excess CO2)

Answer 6

Under normal circumstances, CO₂ produced by oxidative metabolism is eliminated in lungs. However, if alveolar ventilation does not match CO₂ production, volatile acid will accumulate.

Therefore, excess CO₂ equilibrates in ECF (interstitial fluid and plasma), and diffuses into blood at arterial end of capillaries, which are readily enters red blood cells (for buffer).

Note that CO₂ hydration is negligible in ECF (interstitial fluid and plasma), most hydration happens in red blood cells.

Under normal circumstances, CO₂ that formed by tissue metabolism is:

• 2/3 carried by red blood cells (in form of HCO₃^-)
• 1/4 bound to haemoglobin (in form of carbamino-haemoglobin).
• The rest is carried in dissolved form.

Non-Buffering of Carbon Dioxide via Bicarbonate Buffer System

CO₂ cannot be buffered by bicarbonate system in ECF, because CO₂ hydration leads to formation of equal amounts of H⁺ + HCO₃^- i.e. it is essentially adding more buffer to the buffer system (cannot buffer a buffer!).

Buffering of Carbon Dioxide via Red Blood Cell (RBC) Buffer System (RBC is 6% Total Buffer but v. Effective Due to Continuous Transport)

Question 7

Describe the Buffering of Carbon Dioxide via Red Blood Cell (RBC) Buffer System

Answer 7

Main Processes

1. In RBC, most CO₂ undergo hydration to form c_arbonic acid (H₂CO₃_), which is catalyzed via carbonic anhydrase (CA). In turn, H₂CO₃ itself can be buffered effectively in blood. As a result:

• HCO₃^- is formed, which is diffused from RBC (ICF) to plasma (ECF). This adds HCO₃^- buffer to plasma.
• H⁺ is formed, but retained within RBC (ICF) because cell membrane is relatively impermeable to cations (charge balance is maintained by Bohr shift via Cl- across membrane).

CO₂ + H₂O -> H₂CO₃ -><-H⁺ + HCO₃^-

1. In RBC, some CO₂ is bound to haemoglobin to form carbamino-haemoglobin. As a result, additional H⁺ is formed and retained within RBC.
   
   • _​​_Carbamino-Hb: 30% of the Co2 eliminated in lung.
     
     • In capillaries: O2 falls…Hb becomes reduced (i.e. deoxyHb)
       
       • It become sless acid/better base
       • It becomes a better buffer

Dissociation of Oxygen

Note that H⁺ formed from these processes above binds to deoxy-haemoglobin facilitating release of O₂ from deoxy-haemoglobin.

1. • • Haldane effect: increased ability of blood to carry Co2 when oxyHb reduced.
       * 70% deoxyHb is 3.5x more effective than oxyHb in forming carbamino acompounds.
       * 30% deoxyHb is a better buffer than oxyHb thus improving Co2 carraige as bicarbonate.

Question 8

Describe the Blood Buffer Line

Answer 8

Performance of blood as a buffer for CO₂ is quantified as blood buffer line. It is an empirical relationship that reflects buffering capacity of whole blood (in a test tube) for CO₂, with [haemoglobin] of 148g/L.

• Whole blood that is fully saturated with O₂ is exposed to CO₂ at P_CO2 of 23-85mmHg.
• Resultant pH and HCO₃^- levels are measured, which shows that pH is linearly related to [HCO₃^-] over P_CO2 range.

Blood buffer line is overlaid on isobars with bicarbonate buffer system, since both must be in equilibrium. Therefore:

• Exposure of blood to increased CO₂ is associated with increased [HCO₃^-] and [H+] with minimized change in pH (due to blood buffer, not bicarbonate buffer!).
• With reduced [haemoglobin], there is reduced slope steepness of blood buffer line, which means decreased blood buffer effectiveness (reduced [HCO₃^-] at same pH).
• With addition of small amounts of acid or base to whole blood, there is respective downward (acid) and upward (base) translation of blood buffer line.

Question 9

Describe Buffering of Carbon Dioxide via Other Buffer Systems

Answer 9

Excess CO₂ (due to mismatched alveolar ventilation) enters tissue relatively quickly, where it is mostly buffered by RBC, but some buffered by organic phosphates and protein in ECF. As a result of CO₂ hydration in ECF, H⁺ is formed:

• Some H⁺ is buffered in ECF by HCO₃^- formed in RBC.
• Some H⁺ is exchanged with intracellular Na+ and K+, and buffered by lactate ions that move out of cells. These processes take place over hours to days.

Question 10

How are base excess (BE) and base deficit (BD) defined?

Answer 10

Non-carbonic acid (non-volatile acid) removed in metabolic alkalosis and added in metabolic acidosis can be quantified, which are termed base excess and base deficit, respectively.

• Base excess (BE) is measured by titration of a blood sample with strong acid (HCl or its equivalent) to pH 7.40 at P_CO2 of 40mmHg and at 37°C
• Base deficit (BD) (negative base excess) is measured by titration of a blood sample with NaOH to pH 7.40 at a P_CO2 of 40mmHg and at 37°C.

* note, in practice, both are just calculated fromt he Henderson-Hasselbalch equation

Question 11

Describe the Acute responses to acid base disturbance

Answer 11

C) Metabolic Acidosis

Metabolic acidosis is associated with ¯pH and ¯[HCO₃^-] with no change in P_aCO₂

1. Excess production and accumulation of non-volatile acid production (e.g. ketones in diabetic ketoacidosis, lactic acid in circulatory shock)
2. Failure to excrete sufficient acid (e.g. renal failure)
3. Loss of bicarbonate ions (e.g. diarrhoea)

D) Metabolic Alkalosis

Metabolic alkalosis is associated with ­pH and ­[HCO₃^-] with no change in P_aCO₂

1. Addition of non-volatile alkali to body (e.g. through ingestion of antacids)
2. Loss of non-volatile acids (e.g. vomiting or nasogastric suction).

A) Respiratory Acidosis

Respiratory acidosis is associated with ¯pH and ­P_aCO₂ with no change in [HCO₃^-]. This results from inadequate alveolar gas exchange relative to CO₂ production due to:

1. Inadequate ventilation (e.g. drug-induced depression of respiratory centres)
2. Impaired gas diffusion (e.g. asthma, chronic obstructive pulmonary disease (due to bronchitis of emphysema), pulmonary oedema (due to heart failure))

B) Respiratory Alkalosis

Respiratory alkalosis is associated with ­pH and ¯P_aCO₂ and no change in [HCO₃^-]. This results from excessive alveolar gas exchange relative to CO₂ production due to:

1. Hyperventilation (e.g. endogenous/drug-induced stimulation of respiratory centres, anxiety, fear)

Mixed Disorders

Combinations of respiratory and metabolic acid-base disorders can occur at the same time. In heart failure, there is respiratory acidosis combined with metabolic acidosis:

• There is respiratory acidosis due to impaired gas diffusion
• There is metabolic acidosis due to reduced cardiac output leads to reduced systemic O₂ delivery resulting in anaerobic metabolism and lactic acidosis.

Question 12

What responses to acid base disturbances are these?

Answer 12

A = Resp aci

B = Resp alk

C = Met aci

D = Metabolic alk

Question 13

Answer 13

I = C

II = B

III = D

IV= A

Question 14

Diagnose + State the Compensatory mechanism

Answer 14