Theme 4: Disorders of Metabolism - Part 1 Flashcards
In a titration apparatus, what is put in the burette and what is put in the flask?
- burette contains the base
- the flask contains the acid with a suitable indicator
Why is the maintenance of [H+] so important?
- changes in [H+] can affect the surface charge and physical conformation of proteins, changing their function
- the gradient of [H+] between the inner and outer mitochondrial membrane drives oxidative phosphorylation so the body won’t be able to produce ATP
Where do we remove H+ ions?
- Lungs - excretion of CO2 in expired air
2. Kidney - excretion of H+ in urine
What is the concentration of H+ in the plasma?
40 mol/L
-H+ ions are produced in mmol quantities, yet must be kept at nmol concentrations
Where do our H+ ions come from?
- Glucose (incomplete metabolism)
Glucose —> 2 lactate + 2H+ - Triglycerides (incomplete metabolism - ketogenesis)
- Amino acid metabolism (urea genesis)
-metabolism of neutral amino acids results in the generation of H+
What are acid and bases also known as?
Acids - H+ donors
Bases - H+ acceptors
What is pH and how do you calculate it?
Negative logarithm of the hydrogen ion concentration (mol/L)
pH = -log10[H+]
Why is the pH scale used rather than [H+]?
logs make the wide range of H+ concentrations more manageable
If a patient is acidotic, what does this mean?
[H+] > 45nmol/L
pH < 7.35
If a patient is alkalaemic, what does this mean?
[H+] < 35 nmol/L
pH > 7.45
What is Ka and how do you calculate pKa?
Ka - acid dissociation constant
pKa = -log10Ka
What does it mean if there is a high Ka?
high Ka = greater the dissociation = stronger acid
What is the Henderson-hasselbalch equation?
pH = pKa + log10 [[base]/[acid]]
How does CO2 act as an acid?
when dissolved in plasma, CO2 becomes an acid (carbonic acid; H2CO3) which readily dissociates to release H+
how does HCO3- act as a base?
HCO3- accepts a proton to form carbonic acid, which is converted to CO2 for excretion in the lungs
How can you convert partial pressure of CO2 into a concentration?
x by a
alpHa is the solubility constant
What is a buffer?
A buffer is a solution which resists change in pH when an acid or base is added
Buffering ensures H+ ions are transported and excreted safely without affecting physiological processes
Name 5 buffers in the body
- bicarbonate
- haemoglobin
- phosphate
- ammonia
- proteins
Why does equilibrium of CO2 require a non-bicarbonate buffer?
because buffering CO2 by bicarbonate would only result in the production of more CO2
Describe haemoglobin as a buffer
- principle non-bicarbonate buffer - important for buffering CO2
- reduction of CO2
- production of HCO3
Describe phosphate as a buffer
-Monohydrogen phosphate and dihydrogen phosphate from a buffer pair:
HPO42- + H+ —> H2PO4-
-important buffer in urine, where phosphate is present at a much higher concentration
Describe ammonia as a buffer
-Ammonia and ammonium ions form a buffer pair:
NH3+H+ —> NH4+
-Vast majority of ammonia in the body is already in ammonium form, limiting its buffering capacity
-Most important role in urinary ammonium excretion is providing a route for ammonium disposal that does not result in the generation of H+
Describe proteins as a buffer
- Proteins contain weakly acidic and basic groups due to their amino acid composition, and can therefore accept and donate H+ ions to some extent
- Albumin is the predominant plasma protein, and is the main protein buffer in this compartment (it has a net negative charge, so can “mop up” H+ ions)
- bone proteins also play a role in buffering
Describe the relationship between Hb saturation and pO2
- sigmoid relationship
- pO2 can decrease significantly before saturation is affected
When would the curve shift to the right?
- If body temp increases
- If patient is hypoxic or anaemic (increase in 2,3-DPG)
- [H+] increases - Bohr effect
Hb then has a reduced affinity for O2 and O2 is more available to the tissues
Why does an increase in 2,3-DPG shift the curve to the right?
2,3-DPG binds to haemoglobin and rearranges it to the T state, which decreases its affinity for O2
Explain the 3 acid-base processes in the kidney?
Why are they important?
- Excretion of H+ (distal tubule)
- Reabsorption of bicarbonate (proximal tubule)
- Regeneration of bicarbonate (distal tubule)
These functions create acidic urine containing almost no bicarbonate
How do we reabsorb bicarbonate?
-bicarbonate cannot be directly reabsorbed, as luminal membranes are impermeable to it
- so we rely on CO2 to diffuse
see process acid base lecture part 1
What is the function of carbonic anhydrase in renal bicarbonate reabsorption?
H2CO3 generated from CO2 and H2O under action of carbonic anhydrase –> H2CO3 formed dissociates into H+ and HCO3-
How do we maintain buffering capacity in renal tubular cells?
Continued formation of H+ in the renal tubular cells is accompanied by stoichiometric generation of bicarbonate —> excretion of H+ results in bicarbonate generation