Lecture 27: Acid-base Homeostasis 1 Flashcards
What are acids?
Acids are H+ donors
Name a strong acid?
HCl
Name a weak acid?
Carbonic acid
What are bases?
Bases are H+ acceptors
Name a base?
Bicarbonate
What is a buffer?
is a chemical (weak acid and its conjugate base) in solution which resists (minimizes) the change in [H+].
What is the chemical buffer system in blood?
In blood, the principle buffer system is the weak acid (H2CO3) and its conjugate base (HCO3-)
What is pH?
Negative logarithm of the hydrogen ion concentration(mol/L)
pH = -log10[H+]
Why do we use pH rather than [H+]?
pH scale was devised to cope with the wide range of H+ concentrations encountered in chemistry (taking logarithms makes it more manageable)
However Use of H+ rather than pH is becoming more prevalent in medicine, as it is a direct reflection of acid-base status
What is the relationship between pH and [H+] ?
- Change inversely.
- Exponential (non-linear) relationship
What are the reference ranges for blood?
pH: 7.35- 7.45
[H+]: 35 - 45 nmol/L
When is blood acidaemic?
If pH <7.35 ([H+] > 45 nmol/L), the patient is acidaemic
When is blood alkalaemic?
If pH >7.45 ([H+] < 35 nmol/L), the patient is alkalaemic
Why are changes in [H+] important within the body?
- Changes in [H+] can affect the surface charge and physical conformation of proteins (e.g. enzymes), changing their function
- The gradient of [H+] between the inner and outer mitochondrial membrane drives oxidative phosphorylation
When is H+ disposed from the body?
24hExcretion by lungs~ 20000 mmol/24h
Gluconeogenesis, Oxidation~ 1300 mmol/24h
Re-esterification,
Oxidation~ 650 mmol/24h
Oxidation~ 500 mmol/24h
Oxidation of amino acids~ 1100 mmol/24h
Excretion by the kidneys(Fixed acid) ~ 50 mmol/24hNote
When is H+ produced within the body?
Tissue respiration (CO2)~ 20000 mmol/24h
Glycolysis (Lactate)~ 1300 mmol/24h
Lipolysis (Free Fatty acids)~ 650 mmol/24h
Ketogenesis (Ketoacids)~ 500 mmol/24h
Ureagenesis (H+)~ 1100 mmol/24h
Sulphur-and Phosphate a.a.Metabolism ~ 50mmol/24h
What is Respiratory acid-base disturbance?
Abnormality affecting lung ability to excreted CO2
What is Non-respiratory (Metabolic) acid-base balance?
Abnormality anywhere else in the body except lungs
What is a strong acid?
an acid that fully dissociates its H+ ions
What is a weak acid?
an acid that partially dissociates its H+ ions
How does changes in pH affect proteins?
changes in H+ concentrations can affect the surface charge and physical conformation of proteins, changing their functions
How can changes in pH affect aerobic respiration?
the gradient of [H+] between the inner and outer mitochondrial membrane drives oxidative phosphorylation and if this balance is interrupted, so is aerobic respiration
How does tissue respiration affect H+ levels in the blood?
respiring tissues produce CO2 which can form H+ ions when transported in red blood cells
How is H+ produced by sulphur and phosphate metabolism controlled?
the H+ is excreted by the kidneys
How is the H+ produced by respiring tissues controlled?
CO2 is excreted by the lungs
How does glycolysis affect blood pH?
it produces lactate, lowering pH
What two metabolic processes remove lactate from the blood, minimising the pH changes caused by glycolysis?
1) gluconeogenesis
2) Oxidation
How does lipolysis affect blood pH?
it produces free fatty acids, lowering pH
What 2 metabolic processes removes free fatty acids from the blood, minimising pH changes caused by lipolysis?
1) re-esterification
2) oxidation
How does ketogenesis affect blood pH?
it produces keto acid, lowering pH
Which metabolic process removes keto acids from the blood, minimising the pH change causes by ketogenesis?
oxidation of keto acids
What metabolic process helps minimise the pH decrease caused by ureagenesis?
oxidation of amino acids
Give the general equation for anaerobic glycolysis:
glucose -> 2 lactate + 2H+
How does the body respond to increasing lactate (decrease in pH) production during exercise?
more lactate is oxidised
(lactate + H+ + 3O2 -> 3CO2 + 3H2O)
How does the body remove lactate in a diseased state (e.g hypovolaemia)?
bicarbonate production
Give the equation of bicarbonate removing lactate from the blood in a diseased state:
2 lactate + 2H+ + 2HCO3- -> 2CO2 + 2H2O
How does the body respond to diabetic ketoacidosis?
increased bicarbonate regeneration to remove the H+
What is ketoacidosis?
excessive ketogenesis
Give the full 3 part bicarbonate buffering system equation:
H+ + HCO3- <=> H2CO3 <=> CO2 + H2O
What acid does CO2 form when dissolved in plasma or water?
H2CO3 (carbonic acid)
Give the Henderson equation:
[H+] (proportional to) pCO2/ [HCO3-]
Give the Henderson- Hasselbalch Equation:
pH (proportional to) [HCO3-]/ pCO2
Describe how haemoglobin acts as a buffer in red blood cells:
respiring tissues release CO2 into blood cells, forming carbonic acid which partially disociates an H+ ion which is buffered by haemoglobin
What happens to the HCO3- in red blood cells following carbonic acid dissociation?
it passively diffuses out the cell and a Cl- ion enters to maintain electroneutrality (chloride shift)
Why is it that many proteins can act as buffers?
they contain weak acidic and basic groups due to their amino acid composition
Describe how albumin (plasma protein) acts as a buffer:
it has net negative charge so can mop up H+ ions
What protein plays a key role in buffering during chronic acidosis?
Bone protein
What two ions make up the phosphate buffer:
HPO42- (monohydrogen phosphate) and H2PO4 (dihydrogen phosphate)
Give the equation for the phosphate buffer:
HPO42- + H+ <=> H2PO4-
Give the equation for the ammonia buffer system:
NH3 + H+ <=> NH4+
Why is the significance of the ammonia buffer system debated?
the vast majority of ammonia in the body is already in the NH4+ form
Describe the role of the lungs in acid-base homeostasis:
they remove CO2 from the blood into expired gas and respond to stimulation from CO2 sensitive respiratory control mechanisms
Give the three crucial physiological pathways the kidney facilitates in acid-base homeostasis:
1) reabsorption of bicarbonate in the proximal tubule
2) excretion of H+ in the distal tubule
3) regeneration of bicarbonate in the distal tubule
Why can HCO3- not be directly reabsorbed in the kidney?
the luminal membranes are impermeable to HCO3-
Describe the process of reabsorption of bicarbonate in the proximal tubule: (4)
1) H2CO3 is generated is tubular cells from CO2 and H2O aided by carbonic anhydrase
2) this dissociates into H+ and HCO3- with the HCO3- being pumped into the plasma with Na+ for charge balance and the H+ secreted into the glomerular filtrate in exchange for Na+ also
3) the secreted H+ ion combines with HCO3- ions in the filtrate to from H2CO3 and then CO2 and H2O by breakdown
4) the CO2 diffuses into the tubular cells, providing a substrate for continued formation of H2CO3
Where in the kidney does reabsorption of bicarbonate take place?
Proximal tubule
Where in the kidney does excretion of H+ and regeneration of HCO3- take place?
distal tubule
Describe the process of excretion of H+ and regeneration of HCO3- in the distal tubule:
1) H2CO3 is generated from CO2 and H2O under the action of carbonic anhydrase in the tubular cell
2) this dissociates into H+ and HCO3- with the H+ being actively secreted into the glomerular filtrate in exchange for Na+
3) this H+ ion is buffered by HPO42- and excreted as dihydrogen phosphate H2PO4-
4) meanwhile, HCO3- is pumped into the plasma in exchange for Na+
How does the action of aldosterone affect H+ excretion and bicarbonate reabsorption?
it leads to increased potassium and hydrogen ion secretion and sodium reabsorption (Na+ is involved in H+ excretion and bicarbonate reabsorption)
Give 4 ways in which the liver contributes to acid-base homeostasis:
1) it produces buffers such as plasma proteins
2) it produces CO2 from the complete oxidation of carbohydrates and fats
3) it consumes H+ during the metabolism of lactate, ketones and amino acids
4) it produces H+ during the metabolism of NH4+ to urea via the urea cycle
How does liver failure and subsequent ammonia build up manifest?
the respiratory is stimulated, causing the patient to hyperventilate and blow of CO2, leading to increased pH and respiratory alkalosis
