L11: acid base regulation Flashcards
Normal pH range and deviations
Normal: 7.35-7.45
Acidosis: 6.8-7.35
Alkalosis: 7.45-8
Deviations outside of these ranges result in death.
What happens if pH goes outside the normal range?
- proteins are denatured, enzyme function lost, nerves hypersensitive, muscle spasms, heart rate changes etc,
- our daily metabolic processes produce (and consume) substantial volumes of free H+ ions/acids that are effectively removed from the body.
Sources of H+ ions
- ingested protein metabolism
- cell metabolism - produce CO2
- food products - processed foods, sodas, meats etc
- medications - aspirin, warfarin, indomethacin
- metabolic intermediate by-products e.g. exercise produces lattice acid
- disease processes - e.g., diabetes may c improper breakdown of fats and generation of keto-acids
Buffer systems in the body
- Intracellular fluid (in cells): phosphates can collect H+ to become phosphoric acid; amino acids also accept H+
- Interstitial fluid (part of ECF): carbonic acid/bicarbonate buffer system
- Blood (part of ECF): haemoglobin, plasma proteins, carbonic acid/bicarbonate buffer system
Issue with buffering
Buffering is good but it is a temporary short-term fix to the problem. They will bind to H+ when they are in excess and pH is low and release them when there are too few H+ and pH is high. Ultimately excess acids and bases must be eliminated from the body.
The carbonic acid/bicarbonate buffer is a great ECF buffer because both the lungs and kidneys can be used to restore pH.
The carbonic acid / bicarbonate buffer system
CO2 + H2O H2CO3 H+ + HCO3-
Lungs can alter the depth and rate of ventilation to alter arterial PCO2.
Tubular excretion or reabsorption of H+ and HCO3-.
Unique because it works both ways.
What are the 3 defence mechanisms in the body that buffer against or prevent pH changes?
1st defense: chemical buffering - seconds (<1second)
2nd defense: respiratory - minutes
3rd defense: renal days (5-7)
If any one organ is unable to do their job, the other one can compensate for it,
Normal ABG values
CO2 and bicarbonate levels in the blood need to be kept constant for pH to remain unaltered. Arterial blood gases (ABG) can be easily obtained from the radial artery to provide values for:
- pH: 7.4 (7.35-7.45)
- PCO2: 40mmHg (35-40)
- HCO3-: 24mmol/L (22-26)
What are the 4 ways of renal acid-base regulation?
- Reabsorb HCO3- back into the blood when H+ levels are too high and pH is too low.
- Excrete H+ when H+ is too high and pH is too low.
- Generate HCO3- when H+ is too high and pH is too low.
- Excrete HCO3- when HCO3- is too high and pH is too high.
What happens if there is too much H+ in the blood (acidosis)?
If HCO3- has been reabsorbed and it is still too acidic then H+ is excreted. If this keeps happening it will change the pH of the urine and will cause pain and discomfort to urinate due to acidity, and eventually the lining of the bladder and urethra would become damaged. If acidity reaches 4.4-4.5 or below, the renal phosphate or renal ammonia buffer systems are used.
Renal phosphate buffer system
HPO42- + H+ H2PO4-
In the kidney tubules:
- filtered phosphates (HPO42-) can buffer excess H+ in the filtrate
- phosphoric acid is excreted in the urine (called titratable acid)
- limited supply because 75% of phosphates that are filtered are also reabsorbed
- in this process new bicarbonate can be generate by the renal tubules and reabsorbed into the blood
- (this buffer is also an intracellular buffer)
Renal ammonia buffer system
- renal tubular buffer only
- glutamine in PCT cell is converted to ammonia (NH3) which accepts H+ to become ammonium (NH4+)
NH3 + H+ NH4+
In the kidney tubules:
- NH4+ is excreted in the urine
- in this process new bicarbonate can be generated by the renal tubules which is reabsorbed by the blood
- NH3 buffers and excreted 50% of excess H+ in urine and contributes to generation of 50% of the new bicarbonate
- most effective because there are no means of absorbing ammonium once it is made
What are the two types of acid-base imbalance?
- Respiratory dysfunction - change in PCO2
2. Metabolic dysfunction - change in [HCO3-]
Relationship between pH and bicarbonate and CO2
pH is directly proportional to [HCO3-] / pCO2
So pH is directly proportional to bicarbonate concentration and indirectly proportional to partial pressure of carbon dioxide.
What is respiratory acidosis?
- pH is too low - below 7.35
- pCO2 is too high - above 45mmHg
Causes of respiratory acidosis?
- respiratory patterns that cause hypoventilation
- holding CO2 in the body - most common A-B disorder
- lung problems - emphysema, oedema, obstruction
- trauma to respiratory centre
- dysfunction of respiratory muscles
- overuse of sedatives, barbiturates, or narcotics such as Valium, heroin etc or other drugs which make you sleepy
What does respiratory acidosis mean for the buffer equation?
Accumulation of CO2 in the bloodstream increases H+ and bicarbonate, because reaction is being driven to the right
Renal compensatory mechanism for respiratory acidosis
- peripheral chemoreceptors will sense the change in pH and try to change rate of ventilation
- however the lungs are unresponsive due to the problem causing the respiratory acidosis
- so the kidneys remove excess H+ in an acidic urine and conserve bicarbonate in the ways discussed before
Davenport diagram and explanation at 13:30
What is respiratory alkalosis?
- pH is too high - above 7.45
- pCO2 is too low - below 35mmHg
Causes of respiratory alkalosis?
- respiratory patterns that cause hyperventilation
- removing CO2 from the body too quickly
- anxiety, fear, pain - hysterical over-breathing not just panting
- lung problems, e.g. pneumonia
- aspirin overdose/ toxicity; too much caffeine
- over-ventilation on mechanical respirator
- ascent to high altitude, fever…
Effect of respiratory alkalosis on the buffer equation
Loss of CO2 from the blood stream decreases H+/bicarbonate, driving the reaction to the right
Renal compensation for respiratory alkalosis
Peripheral chemoreceptors will sense the change in oH and try to alter the rate of ventilation, but the lungs are unresponsive as this is where the problem is. So the kidneys retain H+ and excrete bicarbonate.
What is metabolic acidosis?
- pH lower than normal - below 7.35
- bicarbonate levels too low - below 24mEq/L
Causes of metabolic acidosis
- loss of bicarbonate due to severe diarrhoea (most common)
- accumulation of acid e.g., ketone bodies in uncontrolled diabetes mellitus (ketoacidosis) and starvation
- renal dysfunction leading to impaired H+ excretion
- excess protein consumption (broken down to amino acids)
- ingestion of an acid (aspirin, ethanol, or antifreeze)
- exercise - mild, transient acidosis because of lactic acid
How does metabolic acidosis affect the buffer equation?
Addition of H+ or loss of bicarbonate reduces bicarbonate. So pH rises.
Respiratory/pulmonary compensation for metabolic acidosis
Peripheral chemoreceptors sense the change in pH and the lungs hyperventilate to remove CO2 (and thus H+) from the body. This will lower the bicarbonate even more too. Kidneys eventually remove excess H+ in an acidic urine and conserve bicarbonate.
What is metabolic alkalosis?
- pH is higher than normal - above 7.45
- bicarbonate is higher than normal - above 24mEq/L
Causes of metabolic alkalosis?
- loss of acid due to severe vomiting (most common)
- gastric suction
- use of diuretics leading to renal dysfunction
- excessive intake of alkaline drugs - antacids
- excessive intake of fruits (fad-diets rich in fruits)
How does metabolic alkalosis affect the buffer equation?
Bicarbonate levels rise and H+ levels decrease.
Respiratory/pulmonary compensation for metabolic alkalosis?
Peripheral chemoreceptors sense the change in pH and the lungs hypoventilate to retain CO2 (and thus H+) in the body. This will raise the bicarbonate even more too. Kidneys eventually remove excess bicarbonate in the urine and conserve H+.
