What is the total CO2 produced in a day on average?
25mol/day
Name 6 buffering systems in the body?
1) Hb
2) Bicarbonate
3) Phosphate
4) Proteins
5) Ammonia
6) Misc organic acids
What is the reference range for blood pH?
7.45-7.35
What is the reference range for plasma [H+]?
35-45mmol/L
What is the Henderson-Hesselbalch equation and whatr does it show?
pH = pK + log([HCO3]/[pCo2}xa)
Says the pH and thus [H+] is determined by the balance between H+ and HCO3 so [H+] homeostasis requires a balance between H+ production and regeneration of HCO3-
Give 4 sites of acid-base metabolism?
Lungs
Kidneys
GI tract
Liver
Which are the 2 main sources of excretion of acid from the body?
Lungs (as CO2)
Kidneys (H+)
Describe how reactions of CO2 within the RBC cause O2 to be released to tissues in tissue gas exchange?
CO2 is released from the tissues and is non polar so passes straight across the RBC membrane
CO2 reacts within the RBC to become H+ and HCO3-
H+ sticks to the Hb molecule (a protein), this acidifies the protein causing it to change shape and release the O2
Thus O2 is released from the RBC to the tissues
Describe how reactions within the RBC cause O2 to be taken up and CO2 to be released by RBC’s at the lungs?
More O2 outside the RBC enters the RBC
The O2 binds to the Hb molecule causing H+ to be released which binds to HCO3- to form H20 and CO2 which is released into the lungs
Name the 3 things which cause a right shift of the O2-Hb dissociation curve?
You get a right shift (O2 released more readily) with:
1) Increased temp
2) Acidosis
3) Increased 2,3 DPG
Which 2 buffering systems are considered to be most important in the body?
1) Bicarbonate
2) Hb
What role does the kidneys play in acid-base homeostasis (3 mechanisms)?
1) Renal reclamation of bicarbonate
2) Renal generation of bicarbonate
3) Mineralocorticoid action in kidney in excreting H+
What is the mechanism of renal reclamation of bicarbonate?
1) Bicarbonate is a small molecule so is filtered out of the blood into the renal tubule
2) Its combined with H+ pumped into the renal tubule in exchange for Na+ to form CO2 and H2O
3) CO2 is reabsorbed and converted back into bicarbonate
What is the mechanism for renal generation of bicarbonate?
Renal tubular cells produce bicarbonate and in doing so produce H+ which is lost in the urine
How does mineralocorticoid action in the kidney affect acid-base homeostasis?
Occurs in the distal tubules
Under endocrine control via the hormone aldosterone
Either K+ or H+ can be excreted from the kidneys in exchange for Na+
If [H+] is high then H+ is excreted under the control of aldosterone
What role does the GI tract have in acid base homeostasis?
Stomach excretes acid, this needs to be balanced by alkaline excretion
Bicarbonate is excreted in pancreatic juices to neutralise this acid, this has to be balanced to prevent disturbances
What role does the liver have in acid-base homeostasis?
1) Dominant site of lactate metabolism
2) Only sight of urea synthesis
What role does the urea cycle have in acid-base homeostasis?
1) Proteins catabolised to NH4+ and HCO3-
2) The average protein produces an excess of NH4+
3) The role of the urea cycle is to combine NH4+ and CO2 to neutralise HCO3-
HCO3- can be converted to H+ and Urea, this is inhibited by acidosis
NH4+ is converted to NH3 which is excreted in the urine (loses a H+) and this is stimulated by alkalosis
How can severe liver failure lead to metabolic alkalosis and NH4+ toxicity?
Because these 2 reactions do not occur:
1) NH4+ + oxo-glutarate -> glutamine
2) NH4+ + CO2 -> urea + H+
Which are the 2 important reversible reactions involved in acid-base homeostasis?
CO2 HCO3- + H+
2NH4+ + HCO3- (NH2)2CO2 + H+
acidosis alkalosis
What are the 2 kind of acid base states that can occur?
Metabollic acidosis/alkalosis
Respiratory acidosis/alkalosis
What are the 3 main compensatory mechanisms for acidosis/alkalosis?
1) Respiratory
2) Renal bicarbonate regeneration
3) Hepatic shift between urea synthesis and ammonia excretion
What are the 5 possible causes of metabolic acidosis?
1) Increased H+ formation
2) Acid ingestion
3) Reduced renal H+ excretion
4) Loss of bicarbonate
5) Inability to excrete H+ through expiration of CO2
What happens to H+ levels, pCO2 and pO2 in metabolic acidosis?
H+ increases (because its acidosis)
pCO2 decreases and pO2 increases (respiratory compensation causes hyperventilation)
Give 3 possible basic reasons for metabolic alkalosis?
1) Generation of bicarbonate by gastric mucosa
2) Renal generation of HCO3- in hypokalaemia
3) Administration of bicarbonate
What happens to H+ levels, pCO2 and pO2 in metabolic alkalosis?
H+ decreases (because its alkalosis)
pCO2 increases and pO2 decreases (breathing rate decreased as respiratory compensation so blow off less CO2)
What are the 3 main consequences of metabolic alkalosis?
1) K+ moves into the cells and urine
2) PO4 moves into cells
3) Respiratory suppression
What acid-base disorder does excessive vomiting lead to?
Metabolic alkalosis
What kind of acid-base disorder to ectopic ACTH lead to and why?
Metabolic alkalosis
Causes body to produce too much cortisol from the adrenals which stimulates the mineralcorticoid receptors which leads to loss of potassium and H+ and absorption of Na+
Give 3 examples of conditions which lead to respiratory acidosis?
CO2 retention due to:
1) inadequate ventilation
2) parenchymal lung disease
3) inadequate perfusion
What happens to the levels of H+ and pCO2 and pO2 in respiratory acidosis?
increased H+ (because its acidosis) increased pCO2 (its Co2 retention which is leading to the acidosis) pO2 decreased because of reduced ventilation
What causes respiratory alkalosis?
Increased CO2 excretion due to excessive ventilation producing alkalosis
What happens to the levels of H+, pCO2 and pO2 in respiratory alkalosis?
H+ decreases because its alkalosis
pCO2 decreases (its the excessive excretion leading to alkalosis)
pO2 increases because of hyperventilation
Give 4 possible basic causes of metabolic acidosis?
1) Increased H+ formation
2) Acid ingestion
3) Reduced renal H+ excretion
4) Loss of bicarbonate
Give 4 possible reasons for increased H+ formation leading to metabolic acidosis?
1) Ketoacidosis, diabetic or alcoholic
2) lactic acidosis
3) poisoning
4) inherited organic acidoses
Give the 4 mechanisms leading to acidosis in diabetic keto-acidosis?
1) Hyperglycaemia
2) osmotic diuresis -> to pre-renal uraemia
3) hyperketonaemia
4) increase FFA
All 4 lead to acidosis
Give the 2 causes of lactic acidosis?
Type a = shock
Type b = metabolic and toxic causes
How does acidosis occur in an alcoholic?
Get NAD+ depletion and thiamine deficiency
Enhanced glycolysis for ATP formation
Keto-acids to counter regulatory hormones
Profuse vomiting
Can high lactate occur in alkalosis?
Yes
Get increased glycolysis
Reduced O2 delivery due to shift in O2 dissociation curve
Lactate induced vasoconstriction
Impaired mitochondrial respiration
Also get a O2 debt leading to further anaerobic lactate production leading to hyperventilation
Give 2 reasons for reduced H+ excretion?
1) Renal tubular acidosis
2) Generalised renal failure
What 4 steps lead to metabolic acidosis in renal failure?
Due to reduced volume of nephrons:
1) Increased bicarbonate loss
2) Reduced NH4+ excretion
3) NH4+ to liver for urea and H+ synthesis
4) Only fraction of NH4+ derived from glutamine (normally approx. 100%)
