Acid/ Base Flashcards
Acid
Proton donor [HA]
Base
Proton acceptor [A-]
Buffer
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
Efficacy of a buffer system determined by
- 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.
Acidaemia
Arterial blood pH <7.35
Intracellular buffers
- 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)
Extracellular buffers
- Bicarb - present in highest concentration, major ECF buffer
- Calcium bicarb in bone
- Plasma proteins
- (Hb)
Henderson-Hasselbach equation
pH = pka + log [A-]/[HA]
Anion Gap
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
Causes of increased AG acidosis
MUDPILES
Methanol
Uraemia
DKA
Paraldehyde
Isoniazid
Lactic acid
Ethylene glycol
Salicylates
Temperature + Solubility
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
Partial Pressure
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)
Temperature + pH
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
Role of kidney in excretion of acids
- 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 - 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 - Make extra HCO3- in setting of acidosis
- via up regulation excretion of fixed acids
- No net H+ excretion through this process
Ammonium and excretion of acids
- 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
What affects the buffering capacity of Hb
- pH of solution (closed buffers only effective at pKa +/- 1)
- State of oxygenation of the Hb (deoxyHb better buffer)
- Hb concentration (high the [Hb], the more buffering capacity per unit volume of blood)
Bicarbonate buffer
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
Protein buffer system
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
Hb buffer system
- 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-
Haldane effect
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.
Bohr Effect
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
Metabolic acidosis
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
Metabolic alkalosis
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
Respiratory acidosis
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
Respiratory alkalosis
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
