Acid/ Base

Question 1

Acid

Answer 1

Proton donor [HA]

Question 2

Base

Answer 2

Proton acceptor [A-]

Question 3

Buffer

Answer 3

Solution which consists of a weak acid and its conjugate base, which has the ability to minimise changes in [H+] when an acid or base is added to it - physicochemical process

HA (weak acid) + Base <=> A- (conjugate base) + BaseH

Question 4

Efficacy of a buffer system determined by

Answer 4

• pKa of the buffer
• pH of the solution
  => Buffers have greatest buffering capacity when pH = pKA (+/- 1)
• Amount of buffer
• Open vs closed system
  => An open buffer system can have the amount of chemical at one (or both) ends adjusted by physiological means.

Question 5

Acidaemia

Answer 5

Arterial blood pH <7.35

Question 6

Intracellular buffers

Answer 6

• Hb - major buffer for H+ which is produced in the red cell when HCO3- is formed from CO2 + H2O. Deoxyhb is more powerful buffer than oxyHb so O2 unloading assists in increasing the carriage of CO2 (Haldane effect)
• Proteins and phosphates (organic and inorganic)

Question 7

Extracellular buffers

Answer 7

• Bicarb - present in highest concentration, major ECF buffer
• Calcium bicarb in bone
• Plasma proteins
• (Hb)

Question 8

Henderson-Hasselbach equation

Answer 8

pH = pka + log [A-]/[HA]

Question 9

Anion Gap

Answer 9

Gap between measured cations and anions. Used to determine the presence of unmeasured anions. (Albumin often the major unmeasured)

AG = [Na+] - ([Cl-]-[HCO3-])

Normal AG = 8-16mmol/L

Question 10

Causes of increased AG acidosis

Answer 10

MUDPILES
Methanol
Uraemia
DKA
Paraldehyde
Isoniazid
Lactic acid
Ethylene glycol
Salicylates

Question 11

Temperature + Solubility

Answer 11

As temperature falls partial pressure falls.
Decr temp => decr kinetic energy => incr solubility, but total CO2 content remains constant => decr PaCO2

• Left shift of Hb-O2 dissociation curve => incr O2 solubility, decr PaCO2

Question 12

Partial Pressure

Answer 12

Hypothetical pressure exerted by that gas if it alone occupied the entire volume of the original mixture at the same temperature

Total pressure of an ideal gas mixture is the sum of the partial pressures of the gases in the mixture (Dalton)

Question 13

Temperature + pH

Answer 13

As temperature falls, pH rises
- Decr ionic dissociation of H2O => decr H+ activity => incr pH
- Metabolic rate is reduce so CO2 production is reduced
- CO2 solubility is increased as PaCO2 is reduced

Question 14

Role of kidney in excretion of acids

Answer 14

1. Recover filtered HCO3-
   - 4000-5000mmol of HCO3- filtered/day
   - H+ is secreted into tubular lumen and combines with filtered HCO3-
   - HCO3- rendered soluble => reabsorbed
   - No net H+ excretion through this process
2. Excrete fixed acids
   - Kidney is only way to excrete fixed/ non-volatile acids
   - Daily load 50-100mmol
   - Excreted in 2 main ways:
   => Formation of NH4+
   => Buffering via ‘titratable acidity’
   - No net H+ excretion through this process
3. Make extra HCO3- in setting of acidosis
   - via up regulation excretion of fixed acids
   - No net H+ excretion through this process

Question 15

Ammonium and excretion of acids

Answer 15

• Excretes 75% of metabolic acids
• Glutamine is metabolised in tubular cells releasing NH4+ into the lumen and HCO3- into blood
• This is new HCO3-, an important feature
• NH4+ gets reabsorbed by tubular cells then pumped back into the lumen of the CD then excreted

Question 16

What affects the buffering capacity of Hb

Answer 16

1. pH of solution (closed buffers only effective at pKa +/- 1)
2. State of oxygenation of the Hb (deoxyHb better buffer)
3. Hb concentration (high the [Hb], the more buffering capacity per unit volume of blood)

Question 17

Bicarbonate buffer

Answer 17

Most important ECF buffer system
- Bicarb formed in the erythrocyte and then secreted into plasma
- Diffuses into the interstitial and is also the dominant fluid buffer in the interstitial space
- A buffer pair consisting of bicarbonate and carbonic acid
H2O + CO2 <=> H2CO3 <=> HCO3- + H+

Effective:
- Present in large amounts
- Open at both ends
=> CO2 can be adjusted by changing ventilation
=> Bicarb can be adjusted by changing renal elimination
=> Prevents buffer systems from equilibrating and allows it to resist large changes in pH despite its low pKa

Question 18

Protein buffer system

Answer 18

Useful ones at physiological pH = imidazole groups of the histamine residues

• Extracellularly, protein have a small contribution which is due to their low pKa
• Intracellularly, proteins have a much greater contribution
  => Intracellular protein concentration is much greater than extracellular concentration
  => Intracellular pH is much lower (~6.8) and closer to their pKa

Question 19

Hb buffer system

Answer 19

• A protein buffer system
• Most important non-bicarb buffer system
  => Exists in greater amounts than plasma proteins
  => Each molecule contains 38 histidine residues (~3x the buffering capacity of 1g of plasma protein)
• In the cell, Hb exists as a weak acid

pKa of Hb is variable depending on binding to O2
- DeoxyHb pKa = 8.2
=> Because of higher pKa, will more readily accept H+ ions which makes it a better buffer of acidic solutions
- OxyHb pKa = 6.6
=> DeoxyHb is a ‘better’ buffer than OxyHb because Oxyhb histidine residues are near the surface of the protein, whereas DeoxyHb histidine residues are internalised and bind the H+ molecule more strongly

Effective buffer:
- Large amounts in RBC (270 million Hb molecules/ RBC)
- Lots of binding sites (38 histidine residues/Hb molecule)
- Histidine residues have pKa of 6.8 (close to intracellular pH)
- CO2 solubility
- Carbonic anhydrase - catalyses the formation of carbonic acid and thus H+ and HCO3-

Question 20

Haldane effect

Answer 20

Oxygenation of blood in the lungs displaces CO2 from Hb which increases the removal of CO2. Conversely, oxygenated blood has a reduced affinity for CO2.

Question 21

Bohr Effect

Answer 21

Hb’s O2 binding affinity is inversely related both to acidity and to the concentration of CO2. Thus in more acidic/ hypercapnia blood, Hb’s O2 affinity is reduced favouring O2 release for utilisation in tissues. The fall in O2 affinity is due to H+ binding

Question 22

Metabolic acidosis

Answer 22

Compensation - expect pCO2 reduced 1.25 mmHg for each mmol/L HCO3- that is reduced
- Lower than expected = superimposed respiratory alkalosis
- Higher than expected = superimposed respiratory acidosis

Divided into high anion gap and normal anion gap acidosis
- High is new acid in blood - lactate, ketones, poisoning
- Normal is bicarbonate loss (GI or renal) or impaired renal acid excretion

Complete respiratory compensation of metabolic acidosis does not occur

Question 23

Metabolic alkalosis

Answer 23

Compensation - expect pCO2 increased 0.75mmHg for each mmol/L HCO3- that is increased up to a max of 60mmHg
- Lower than expected = superimposed resp alkalosis
- Higher than expected = superimposed resp acidosis

Increased loss of acid from gut or kidney

Question 24

Respiratory acidosis

Answer 24

Compensation

Acute - HCO3 increase by 1mmol/L for every 10mmHg pCO2 increase (up to 30mmol/L)

Chronic - HCO3 increase by 4mmol/L for every 10mmHg pCO2 increased (up to 36mmol/L)
- Lower than expected = superimposed metabolic alkalosis
- Higher than expected = superimposed metabolic acidosis

Question 25

Respiratory alkalosis

Answer 25

Compensation

Acute - HCO3 decreased by 2mmol/L for every 10mmHg pCO2 decreased (down to 18mmol/L)

Chronic - HCO3 decreased by 5mmol/L for every 10mmHg pCO2 decreased (down to 18mmol/L)
- Lower than expected = superimposed metabolic alkalosis
- Higher than expected = superimposed metabolic acidosis