Acid-Base regulation Flashcards
What blood pHs would result in death?
pH <6.8
pH >8
Describe the pathological formation of acid.
- Methanol poisoning - forms formic acid
- Ethylene glycol poisoning - forms glycolic acid, glyoxylic acid, oxalic acid
- Drugs/toxins:
- inhibition of oxidative phosphorylation –> anaerobic metabolism –> lactic acid
- Liver disease –> impaired lactate clearance –> lactic acid - CO:
- inhibition of oxidative phosphorylation –> anaerobic metabolism –> lactic acid
- impaired O2 delivery –> anaerobic metabolism –> lactic acid - Hypotension/hypoxia:
- impaired O2 delivery –> anaerobic metabolism –> lactic acid - uncontrolled diabetes/starvation - forms acetoacetate and beta-hydroxybutyrate
What are the different mechanisms that limit changes in pH? How long does each one take?
- chemical buffer systems in blood (immediate)
- respiratory centre in brainstem (1-3 minutes)
- renal mechanisms (hours to days)
What are the 3 chemical buffers in the body?
- bicarbonate
- proteins (haemoglobin, albumin)
- phosphate
What % of body weight is made up by:
- Plasma (ECF)
- Interstitial fluid (ECF)
- Intracellular fluid (ICF)
- Plasma (ECF): 5%
- Interstitial fluid (ECF): 15%
- Intracellular fluid (ICF):40%
What effect does acid-base disturbance have on blood [K+]?
Acidaemia = HYPERkalaemia Alkalaemia = HYPOkalaemia
What are the main cations and anions forming the plasma?
Cations:
- Na+
- K+
Anions:
- HCO3-
- Cl-
- Protein anions
What are the main cations and anions forming the interstitial fluid?
Cations:
- Na+
- K+
Anions:
- HCO3-
- Cl-
What are the main cations and anions forming the intracellular fluid?
Cations:
- K+
- Na+
Anions:
- PO4 3-
- Protein anions
What ions usually make up the unmeasured cations and anions in the ECF and ICF?
Cations:
- calcium
- magnesium
- proteins (unless plasma)
Anions:
- phosphates (unless ICF)
- sulfates
- proteins
How can the anion gap be calculated? what is the normal range?
([Na+] + [K+]) - ([Cl-] + [HCO3-]) = 12-16 mEq/L
([Na+] + [K+]) - ([Cl-] + [HCO3-]) = 8-12 mEq/L
What are the causes of loss of bicarbonate? What acid-base change does this lead to?
- severe diarrhoea
- chronic laxative abuse
- villous adenoma
- external drainage of pancreatic/biliary secretions (fistulas)
- loss via NG tube
- urinary diversions
- administration of acidifying salts
Causes NORMAL GAP ACIDOSIS
What other situations (apart from loss of bicarbonate) can cause normal gap acidosis?
Reduced kidney excretion of H+
- more bicarbonate is needed to help buffer excess H+ = reduced HCO3-
(no compensation from Cl-)
What can cause reduced kidney H+ excretion (resulting in normal gap acidosis)?
- ketoacidosis
- lactic acidosis
- renal failure
- toxic ingestions
What acid-base change does hypoalbuminaemia result in? What are the potential causes?
Low gap acidosis
(reduced albumin = increased bicarbonate and Cl-)
Causes:
- haemorrhage
- nephrotic syndrome
- intestinal obstruction
- liver cirrhosis
By how much does the anion gap change in metabolic alkalosis?
Small increase of ~4-6 mEq/L
In the kidneys, where is most of the bicarbonate reabsorbed?
Proximal convoluted tubule (70-90%)
DCT (10-30%)
What is secreted and reabsorbed by the alpha-intercalated cells? What channels are used to secrete/reabsorb?
secreted:
- acid (via H+ ATPase and H+/K+ exchanger), in the form of H+
reabsorbed:
- bicarbonate (via basolateral Cl-/HCO3- exchanger)
What is secreted and reabsorbed by the beta-intercalated cells? What channels are used to secrete/reabsorb?
Secreted:
- bicarbonate (via pendrin - specialised apical Cl-/HCO3-)
Reabsorbed:
- acid (via basal H+ - ATPase)
How do renal tubular cells control pH in acidosis?
- Kidney wants to excrete H+
- -> upregulation of Na+/H+ transporter on luminal surface of cells
- -> glutamine anf glutamate are deaminated to excrete ammonia (NH3) into the urine – neutralises the urine
- -> phosphate is also present to reduce the acidity of the urine - Kidney wants to secrete bicarbonate into the blood
- -> will help reduce the acidity of the blood
How do renal tubular cells control pH in alkalosis?
- H2CO3 dissociates into HCO3- and H+
- HCO3- is excreted via the urine by upregulation of a HCO3-/Cl- exchanger (pendrin)
- H+ is secreted/reabsorbed into the blood via H+-ATPase
What is the main reason behind respiratory acidosis occurring? Give examples of situations in which it occurs. What is the compensation for this acid-base change?
Reason: CO2 retention
Situation: hypoventilation (COPD)
Compensation: Renal –> H+ excretion and HCO3- gain
What is the main reason behind respiratory alkalosis occurring? Give examples of situations in which it occurs. What is the compensation for this acid-base change?
Reason: CO2 loss
Situation: hyperventilation (anxiety or altitude)
Compensation: Renal –> H+ retention and HCO3- loss
What is the main reason behind metabolic acidosis occurring? Give examples of situations in which it occurs. What is the compensation for this acid-base change?
Reason: gain of acid, loss of base
Situation: diarrhoea, keto-acidosis, lactic acidosis
Compensation: Respiratory –> CO2 loss and HCO3- falls
What is the main reason behind metabolic alkalosis occurring? Give examples of situations in which it occurs. What is the compensation for this acid-base change?
Reason: loss of acid, gain of base
Situation: vomiting, hypokalaemia, ingestion of HCO3-
Compensation: Respiratory –> CO2 and HCO3- rise
