Lecture 10 - Acid Base Balance Flashcards
Why are metabolic reactions very sensitive to the pH of the fluid in which they occur?
Due to high reactivity of H ions with negative proteins –> changes in configuration and function
What is the normal pH of arteralised blood?
7.4
What kind of ions contribute to pH?
Only free H ions
What are the sources of H in the body?
Respiratory acid Metabolic acid
How does respiratory acid form?
CO2 + H2O H2CO3 H + HCO3 But formation of carbonic acid not usually net contributor to increased acid because increase in production leads to increased ventilation
How are metabolic acids formed?
From inorganic ions, e.g. S containing AAs –> H2SO4 and phosphoric acid is produced from phospholipids Organic acids - fatty acids, lactic acid
What is a major source of alkali in the body?
Oxidation of organic anions, e.g. citrate
What are the function of buffers?
Minimise changes in pH when H ions are added/removed
What is the most important extracellular buffer?
Bicarbonate
What is the Henderson-Hasselbalch equation?
pH varies with [HCO3-]/ PCO2
What is the bicarbonate buffer system?
—> incH+ + HCO3- H2CO3 H2O CO2 Increased ECF H+ drives reaction to the right, so additional H ions removed and pH is normalised
Explain why the bicarbonate buffer system is no ordinary buffer system and why when there is increased products, the reaction doesn’t reach a new equilibrium position?
Because CO2 is released by ventilation, so this continues a pull to the right
Elimination of H from the body is done by what organ?
Kidneys
What is H ion elimination coupled with?
Regulation of plasma bicarbonate
pH varies with what?
Bicarbonate/PCO2 (renal/respiratory regulation)
What are 2 other buffers in the ECF?
Plasma proteins - Pr- + H+ HPr Diphasic phosphate (HPO4)2- + H+ H2PO4- monobasic phosphate
What are the primary intracellular buffers?
Proteins, organic and inorganic phosphates
What is the primary buffer in erythrocytes?
Haemoglobin
Why does binding of H ions by ICF buffers cause changes in plasma electrolytes?
Since to maintain electrochemical neurality, movement of H must be accompanied by Cl as in red cells or exchanged for a cation, K
Why can acidosis lead to VF and death?
Movement of K out of cells into plasma can –> hyperkalaemia –> depolarisation of excitable tissues
What additional store of buffer does bone have?
Bone carbonate (important in chronic acid loads e.g. CRF –> wasting of bones)
How does the body form bicarbonate?
Within cells, CO2 –> H2CO3 in the presence of
What organ regulates bicarbonate concentration?
Kidneys
How do the kidneys regulate bicarbonate concentration?
a. Reabsorbing filtered HCO3 b. Generating new HCO3
What is the mechanism by which HCO3 is reabsorbed in the kidneys?
A. Active H secretion from tubule cells B. Coupled to passive Na reabsorption C. Filtered HCO3 reacts with secreted H –> H2CO3, carbonic anhydrase on luminal membrane converts this into H2O and CO2 D. CO2 freely permeable + enters cell E. Within the cell, CO2 –> H2CO3 (in presence of carbonic anhydrase) which dissociates to form H and HCO3 F. Hydrogen ions are source of secreted H G. Bicarbonate passes into peritubular capillaries with the Na
Where does the bulk of the bicarbonate reabsorption occur?
Proximal tubule
Is there a net excretion of H ions during bicarbonate reabsorption?
No!
How much H is usually produced per day by the body?
50-100mmoles
If H was present as free H ions in the urine what would happen?
pH of urine would be very low and it would be very uncomfortable
What is present in the urine to prevent H ions being free?
Weak acids and bases (which act as buffers) Mostly dibasic phosphate, uric acid and creatinine
Describe the process of how H is buffered in the urine
Na2HPO4 is in lumen, one Na reabsorbed in exchange for a secreted H+ Monobasic phosphate removes H from body
What source of new HCO3 comes from the blood?
CO2 from the blood enters tubule cells, combines with H2O to form carbonic acid (carbonic anhydrase), which dissolves to yield H, used for secretion and new HCO3 which passes with Na into the peritubular capillaries
Where does the production of new bicarbonate principally occur?
Distal tubule (as this is where phosphate ions not reabsorbed by the proximal tubule Tm become greatly concentrated)
What is the process of making new HCO3 dependent on?
PCO2 of blood
What is the chemical formula for ammonia?
NH3
What is the chemical formula for ammonium?
NH4
Which of ammonia/ammonium is lipid soluble?
Ammonia
What is ammonia produced by?
Deamination of amino acids, esp. glutamine by the action of renal glutaminase within renal tubule cells
How is excess ammonia removed?
NH3 moves out of tubule lumen, where it is combined with secreted H ions to form NH4+ which combines with Cl ions (from NaCl) to form NH4Cl which is excreted in the distal tubule (Source of H is CO2 in the blood) New HCO3 passes with Na into peritubular capillaries (NB in proximal tubule there is a NH4/Na exchanger so NH4 ions formed within cells passes out of lumen)
What does the activity of renal glutaminase depend on?
pH If intracellular pH falls –> increased RG activity + more NH4+ produced + excreted
What is the main adaptive response of the kidneys to acid loads?
Their ability to augment NH4+ NB this takes 4-5 days to reach maximal effects due to increased protein synthesis + also takes time to switch off
Decreased pH =
Acidosis
Increased pH =
Alkalosis
What do respiratory disorders primarily affect?
PCO2
What do renal disorders primarily affect?
HCO3-
What causes respiratory acidosis?
Reduced ventilation leading to retention of CO2 –> Increased PCO2
What are causes of respiratory acidosis?
Acute: drugs which depress the medullary respiratory centres, e.g. barbiturates, opiates, obstructions of major airways Chronic: lung disease, e.g. COPD, asthma
What happens to bicarbonate in a respiratory acidosis?
It increases to try and protect the pH (Increased production of new HCO3 and increased reabsorption)
Does a rise in bicarbonate in respiratory acidosis correct the original disturbance?
No - only a restoration of normal ventilation would do this So, in chronic respiratory acidosis, ABG values are never normalised
What would a typical ABG of someone with a respiratory acidosis look like?
High PCO2, high bicarbonate
What causes respiratory alkalosis?
Fall in PCO2 due to increased ventilation and CO2 blow off
What are causes of respiratory alkalosis?
Acute - voluntary hyperventilation, aspirin, first ascent to altitude Chronic - living at altitude (decreased PO2 stimulates peripheral chemoreceptors to increase ventilation)
What happens to bicarbonate in respiratory alkalosis?
It decreases to protect pH Less filtered HCO3 is reabsorbed and so is lost in urine
What causes a metabolic acidosis?
Decreased bicarbonate (either due to increased buffering of H or direct loss of HCO3)
What happens to PCO2 in a metabolic acidosis?
It is decreased to try to protect pH
What are the 3 major causes of metabolic acidosis?
Increased H production, e.g. DKA/lactic acidosis Failure to excrete normal dietary load of H (renal failure) Loss of HCO3 in diarrhoea (i.e. failure to reabsorb intestinal HCO3)
What are the two ketones that cause DKA?
Acetacetic acid B-hydroxybutyric acid
What is the increase in ventilation like in metabolic acidosis?
Increase in ventilation depth Kussmaul breathing
How do the kidneys help to correct metabolic acidosis?
Restoring HCO3 and getting rid of H
What is the issue with trying to get rid of H ions but having a lowered CO2 in metabolic acidosis?
Source of H ions is from carbonic acid from CO2 in the blood (So there is less H secreted by renal tubule BUT as plasma HCO3 + therefore filtered HCO3 is reduced, a smaller amount of H is needed for HCO3 reabsorption + so a greater amount is available to be excreted in the form of titratable acid and NH4+)
What are the timings of everything that happens when there is increased metabolic H in the body?
Immediate buffering in ECF and ICF Respiratory comepnsation within minutes Renal correction takes longer as renal glutaminase takes 4-5 days to reach maximum As HCO3 starts to increase, respiratory compensation wears off until get rid of all xs H
What is the cause of a metabolic alkalosis?
Bicarbonate is increased
How does PCO2 compensate in a metabolic alkalosis?
It increases to protect pH
What are the 4 biggest causes of metabolic alkalosis?
- Increased H ion loss, e.g. vomiting 2. Increased renal H loss, e.g. aldosterone excess, excess liquorice ingestion 3. Excess administration of HCO3 in those who have renal impairment 4. Massive blood transfusions (bank blood contains citrate to prevent coagulation which is converted into HCO3)
How many units of blood need to be transfused before there is a risk of a metabolic alkalosis occuring?
8 units
How does the body correct a metabolic alkalosis?
Greatly increased filtered HCO3 load exceeds H secretion able to reabsorb it even in presence of increased PCO2 so excess loss in urine As with a metabolic acidosis the resp compensation delays renal correction but protects pH
What would be the following ABG results: A. H+: B: pH: C. Primary disturbance D. Compensation In a respiratory acidosis?
A. H+: increased B: pH: increased C. Primary disturbance: increased PCO2 D. Compensation: increased bicarbonate
What would be the following ABG results: A. H+: B: pH: C. Primary disturbance D. Compensation In a respiratory alkalosis?
A. H+: decreased B: pH: decreased C. Primary disturbance: decreased PCO2 D. Compensation: decreased bicarbonate
What would be the following ABG results: A. H+: B: pH: C. Primary disturbance D. Compensation In a metabolic acidosis?
A. H+: increased B: pH: increased C. Primary disturbance: decreased bicarbonate D. Compensation: decreased PCO2
What would be the following ABG results: A. H+: B: pH: C. Primary disturbance D. Compensation In a metabolic alkalosis?
A. H+: increased B: pH: increased C. Primary disturbance: increased bicarbonate D. Compensation: increased PCO2
Why for any given increase in PCO2 is there a smaller decrease in pH for chronic respiratory acidosis than for acute respiratory acidosis?
Because - with time can use NH3 production which has a considerable capacity to raise HCO3
What is the anion gap?
The difference between the sum of the principle cations (Na + K) and the principle anions in plasma (Cl and HCO3)
What is the normal anion gap?
14-18mmoles/L
What are the two patterns of metabolic acidosis?
Increased anion gap Normal anion gap
