What is a conjugate base?
What is the acid dissociation constant?
What is pH7 in terms of ions?
When an acid HA dissociates it yields H+ and its conjugate base A-
Ka, measure of an acid in solution: Ka= [H+][A-]/[HA]. Strong acid = high Ka and low pKa (pKa = -log10Ka). And pH = -log10[H+]
Equal numbers of H+ and OH- i.e. a neutral solution
What is the Henderson-Hasselbalch equation?
What is the pH range compatible with life? What happens if you go above/below this?
What pH levels cause death if you go above/below? Why?
pH = pKa + log [A-]/[HA]
7.35 - 7.45, alkalosis (alkalaemia)/acidosis (acidaemia)
8/6.8. Denatures proteins, enzyme systems and ETC disrupted -> organ failure
What are the 2 different classes of acids produced by the body?
1) Respiratory (volatile): H2CO3 (carbonic acid)
2) Metabolic (fixed): lactic acid. Harder to regulate.
Production of Respiratory (volatile) acids
A normal adult metabolism produces how much CO2/day?
What is the equilibrium equation showing how CO2 is carried in the blood?
300L (end product of complete oxidation of carbs and FAs)
H2O + CO2 <=> H2CO3 <=> HCO3- + H+
Carbonic acid dissociates into hydorgen and bicarbonate ions. CO2 must be rapidly excreted.
What are the 3 ways metabolic (fixed) acids are produced?
1) Incomplete oxidation of carbohydrates and fats produces non-volatile acids e.g. actic acid
2) Metabolism (oxidation) of proteins and aas produces strong acids e.g. HCl and H2SO4
3) Incomplete FA oxidation in disease states produces non-volatile acid e.g. diabetes: keto acids
What does a chemical pH buffer solution contain?
What 3 mechanisms does the body have to limit changes in pH?
A weak acid (HA) and its conjugate base (A-)
1) chemical buffer systems (1st line of defence)
2) respiratory control systems (2nd line)
3) renal control of pH (3rd line)
Describe some chemical buffers in intracellular and extracellular fluid.
What is carbonic anhydrase?
What buffer systems contribute most to the buffer?
Intracellular: protein (acidic and basic side chains can give/take up H+), phospate (H+ + HPO42- <=> H2PO4-, buffers H+ in urine with ammonia), bicarbonate/CO2 system (imp in acid-base physiology, controlled by lungs and kidney)
Extracellular: Hb (buffers changes in H+ caused by CO2: H+ + Hb -> HHb in tissues and releases it in lungs to take up O2), phosphate, bicarbonate
Catalyses conversion of CO2 and H2O to carbonic acid and back.
Bicarbonate and Hb
Describe respiratory control of pH.
Any increase in blood H+ driven by changes in CO2 triggers activation of central chemoreceptors -> medullary respiratory neurons -> generates breathing. (H+ can't cross BBB directly so CO2 combines with it to cross.) This blows off CO2 and removes acid. Response = minutes.
Describe renal control of pH.
What are the 2 main sites where H+ excretion can be regulated, and how in each?
Filtered bicarbonate reabsorbed. Titratable acids (e.g. phoshoric, H2SO4) are formed. Ammonia (NH3 and NH4+) added to urine. All involves H+ secretion by tubular epithelium so urine is acidified. The H+ excretion is buffered by phosphate and ammonia.
1) PCT: CO2 diffuses from blood to tubular cell -> carbonic anhydrase converts it to H2CO3 which dissociates to H+ and HCO3- -> H+ transported out of cells into urine via Na+/H+ exchanger -> HCO3- returned to blood
2) CD: H+ secreted via electrogenic H+ ATPase pump and electroneutral H+/K+ ATPase exchanger which can acidfy urine to pH 4.5. Bicarbonate absorption too.
In renal control of pH, how is bicarbonate reabsorbed?
What is the renal response to alkalosis?
Filtered from blood but can't be reabsorbed b/c impermeable renal tubule cells. Reacts with secreted H+ to form H2CO3. Extracellular carbonic anhydrase converts it to H2O and CO2. CO2 diffuses into tubule cells where intracellular CA converts it to H2CO3 -> dissociates to HCO3- and H+. H+ is excreted in urine and HCO3- diffuses into blood.
H+ excretion by Na+/H+ antiport is inhibited, allowing filtered bicarbonate to be lost in urine. If extreme, mechanism can reverse, excreting Na+ and retreiving H+ = alkaline urine.
What is the [HCO3-]:[CO2] ratio in normal pH?
How would respiratory acidosis be caused in COPD?
Why are the measurements of the following important:
20:1 (HCO3- = 24mM, CO2 = 1.2mM), keeps blood at pH7.4 according to henderson hasselbalch equation
CO2 retained = increased [H+] (CO2 = 2.4mM so pH = 7.1)
a) acidosis or alkalosis?
b) respiratory indicator
c) metabolic indicator
List 4 simple acid-base disturbances, the primary cause for them, and compensation type.
1) respiratory acidosis: CO2 retention e.g hypoventilation -> renal compensation (H+ excretion, HCO3- gain)
2) respiratory alkalosis: CO2 loss e.g. hyperventilation -> renal compensation (HCO3- loss, H+ retention)
3) metabolic acidosis: gain of acid, loss of base e.g. diarrhoea, keto(or lacto)-acidosis -> respiratory compensation (CO2 loss, HCO3- falls)
4) metabolic alkalosis: loss of acid, gain of base e.g. vomiting, hypokalaemia, ingestion of HCO3- -> respiratory compensation (CO2 rises, HCO3- rises)
What is a Davenport diagram used for?
What is the anion gap?
To interpret mixed acid-base disturbances
Difference between primary measured cations (Na+) and primary measured anions (Cl- and HCO3-). Useful in determining some conditions. [Na+] - ([Cl-] + [HCO3-]) = [anion gap]. Normally = 8-14mEg/L