6 - Acid Base Balance And Potassium Control Flashcards
How do the kidneys control plasma volume?
Through filtering and variably recovering salts.
How do the kidneys control plasma osmolarity?
Through filtering and variably recovering water.
How do the kidneys control pH?
Through filtering and variably recovering hydrogen carbonate and active secretion of protons.
What is the normal range of pH?
7.38 - 7.42.
What is alkalaemia? How does it affect the body?
pH > 7.42. Lowers free Ca2+, increasing excitability of nerves; if pH > 7.45, parasthesia and tetany are symptoms. N.B. pH of 7.65 = 80% mortality rate.
What is acidaemia? How does it affect the body?
pH < 7.38. Increases plasma K+ and denatures many enzymes - reduced cardiac & skeletal muscle contractility, glycolysis, hepatic function. N.B. pH < 7 is very much life-threatening.
What is the Henderson-Hasselbalch equation? What is the ratio of HCO3 to dissolved CO2?
pH = pKa + log([HCO3-] / (pCO2 x 0.23)) pH = 6.1 + 1.3 (or log20) = 7.4 Ratio is 20:1 HCO3- to CO2.
What is the amount of CO2 determined by?
Ultimately the lungs - controlled by chemoreceptors - disturbed in respiratory disease.
What is the amount of HCO3- determined by?
The kidneys - disturbed by metabolic and renal diseases.
What is the cause of respiratory acidosis?
Hypoventilation which results in hypercapnia. Rise in pCO2 causes pH to fall.
What is the cause of respiratory alkalosis?
Hyperventilation which results in hypocapnia. Fall in pCO2 causes pH to rise.
What are chemoreceptors? What do they do?
Central: maintain pCO2 within tight limits. respiratory changes correct respiratory disturbances of pH. Peripheral: enable changes in respiration driven by changes in plasma pH.
How can the body compensate for respiratory acidosis?
The kidneys will increase the [HCO3-] restoring the ratio - increasing the pH.
How can the body compensate for respiratory alkalosis?
The kidneys will decrease the [HCO3-] restoring the ratio - decreasing the pH.
What is a typical cause of metabolic acidosis?
Excess acid production (lactic acid, ketoacidosis, sulphuric acid) - HCO3- neutralises this. The decrease in [HCO3-] results in acidosis.
How is metabolic acidosis compensated for?
Peripheral chemoreceptors detect fall in plasma pH, leading to increased ventilation - lowering pCO2 - restoring pH to normal.
What is a typical cause of metabolic alkalosis?
Persistent vomiting. Alkali tide is produced by the body in preparation for the acidic content from the stomach. Acid is vomited, meaning alkali (HCO3-) remains in the body.
How is metabolic alkalosis compensated for?
It can only be partially compensated through decreasing ventilation - but can normally be corrected easily by the kidneys (rise in tubular cell pH, reducing acid secretion, reducing recovery of HCO3-).
What do kidneys need to be able to do in order to regulate [HCO3-]?
4500mmol of HCO3- is filtered in a day - so it is easy to lose HCO3- (compensate for an alkalosis). To increase HCO3- (compensate for acidosis) must be able to recover all filtered HCO3- and make new.
How do the kidneys increase [HCO3-]?
From CO2 + H2O HCO3- + H+ And amino acids, producing NH4- to enter urine.
How much HCO3- is reabsorbed normally and where?
100%: 80-90% reabsorbed in PCT and the remainder in the Thick Ascending Limb of the LOH.
What channels are important in order to reabsorb HCO3- in the PCT? Why are they important?
Apical: NHE Basolateral: Na-K-ATPase, HCO3- channel Na+ gradient from tubule –> tubular cell –> ECF NHE moves H+ the other way - tubular cell –> tubule. Tubule: H+ + HCO3- –> H2O + CO2 (which enter the cell) Tubular cell: CO2 + H2O –> H+ + HCO3- (leaves via basolateral membrane to ECF). … H+ moves with NHE etc.
How is HCO3- created in the PCT?
Glutamine –> alpha-ketoglutarate –> HCO3- + NH4+ HCO3- –> ECF; NH4+ –> Lumen
How is HCO3- created in the DCT?
In DCT all filtered HCO3- reabsorbed and Na+ gradient insufficient to drive H+ secretion. Within the tubular cell: H2O + CO2 (metabolism) –> H+ + HCO3-. H+ is actively secreted into the lumen (H+ ATPase); HCO3- moves out of the basolateral membrane.
What is the minimum pH of urine? How can H+ be buffered in the lumen of the DCT?
4.5 or [H+] = 0.04mmol/L H+ + HPO4 2- –> H2PO4 - (titrable acid) H+ + NH3 –> NH4+
What is H+ excretion controlled by?
Changes in intracellular pH of tubular cells. Changes in rate of HCO3- export to ECF (due to changes in ECF [HCO3-])
What are the cellular responses to acidosis?
Upregulating NHE (full recovery of all filtered HCO3-) Increased NH4+ production in DCT, Increased activity of H+ ATPase, Increased capacity to export HCO3- from tubular cells to ECF.
What happens to [HCO3-] when acids are produced through metabolic processes?
Lactic acid, Ketone acids etc. are an anion (lactate) and a H+. Some of these H+ react with HCO3- forming CO2 … therefore [HCO3-] will decrease.
What is the anion gap?
( [Na+] + [K+] ) - ( [Cl-] + [HCO3-] ) = Anion Gap. It is a measure of whether HCO3- has been replaced with any other anions (which are not accounted for).
What is the normal anion gap?
10 - 15mmol/L (more cations than anions).
When would the anion gap be increased?
If anions from metabolic acid have replaced plasma HCO3-.
When might there be reduced [HCO3-] but a normal anion gap?
If all the HCO3- is replaced with Cl- (hyperchloraemic acidosis).
How do changes in tubular cell intracellular pH influence acid secretion in the DCT?
Reduced intracellular pH of tubular cells stimulates acid secretion, stimulating HCO3- recovery - increasing plasma [HCO3-].
When might metabolic alkalosis be difficult to correct?
Usually due to persistent vomiting - rise in intracellular pH (tubular cells), reduces acid secretion and HCO3- recovery. If there is volume depletion as well it is more complicated, high rates of Na+ reabsorption (to restore ECV) favour HCO3- reabsorption and H+ secretion.
How are metabolic acidosis/alkalosis linked with K+ balance?
Metabolic acidosis: hyperkalaemia (K+ moves out of cells; more K+ reabsorption in DCT) Metabolic alkalosis: hypokalaemia (K+ moves into cells, less K+ reabsorption)
How does hyper/hypo kalaemia affect intracellular pH of tubule cells?
Hyperkalaemia makes intracellular pH of tubular cells acid: favours H+ excretion and HCO3- recovery –> metabolic alkalosis. Hypokalaemia: makes intracellular pH of tubular cells alkali: reduce H+ secretion and HCO3- recovery –> metabolic acidosis.
In our bodies we often produce acid, does this affect [HCO3-]?
Normally, no. All filtered HCO3- is recovered. PCT: HCO3- made; trade-off AAs –> NH4+ (glutamine –> alpha-ketoglutarate –> HCO3- + NH4+) DCT: HCO3- and H+ produced (from H2O and CO2 - metabolism) - HCO3- reabsorbed; H+ buffered with phosphate and ammonia.
How is a 70kg man’s body fluid compartments normally divided?
60%… 42L is total body water 2/3… 28L is ICF 1/3… 14L is ECF.
What can ECF be divided into?
ECF is 28L 1/4… 3.5L is plasma; 3/4… 10.5L is interstitial fluid.
What are the extracellular and intracellular [K+]? Therefore where is the majority of K+ stored in the body?
Extracellular: 4mmol/L Intracellular: 155mmol/L 98% ICF; 2% ECF; Total body K+ = 3500mmol N.B. only small shifts from ICF –> ECF of K+ are required to change ECF dramatically.
What maintains the difference between [K+] in the ECF and the ICF?
The activity of the Na-K-ATPase.
Where exactly in the body is the bulk of the K+ stored?
Skeletal muscle cells. Also liver, RBCs, bone.
What is it that creates the resting membrane potential?
The K+ gradient from inside the cell to outside. R.M.P in neuron cells is ~-70mV.
How will a high ECF [K+] affect the resting membrane potential? What would a low ECF [K+] cause?
Decrease the K+ gradient from inside to outside - depolarising the cell. Opposite in hypokalaemia - hyperpolarisation of cell. Significantly alters electrical excitability of cardiac and neuromuscular tissues.
How does the body deal with hyperkalaemia (high ECF [K+])?
Intracellular buffering plays an important role. Kidneys of little immediate help - cannot excrete K+ quickly.
How is K+ absorbed?
In the intestines and the colon. It is immediately absorbed into the ECF - with 4/5 ingested K+ moving into cells within minutes; kidneys begin to excrete K+ slightly later - complete after 6-12 hours.
How is [K+] regulated?
External balance: Adjusts renal K+ excretion to match intake - slower. Internal balance: Movement of K+ between ICF and ECF - immediate.
What is the average K+ intake? Is all of this absorbed?
100mmol/day. No there is a 5-10% loss in the GI.
How do the kidneys regulate [K+]?
They adjust K+ excretion to match intake by controlling K+ secretion. Takes 6-12 hours to be complete; responsible for maintenance of total body K+ content over the longer term.
How does the ICF regulate ECF [K+]? What channels are involved?
Depending on ECF [K+] - effect is immediate, responsible for moment-to-moment control. Na-K-ATPase - 2 K+ enters; expels 3 Na+. K+ channels (ROMK channels determine K+ permeability) - K+ expelled from cell.
With regards to internal balance of K+, what factors promote the uptake of K+ into cells?
Hormones: insulin, aldosterone, catecholamines Increased [K+] in ECF Alkalosis - low ECF [H+] … H+ moves out of cell to correct alkalosis, K+ moves the other way (into cells).
How does insulin affect uptake of K+ into cells?
K+ in splanchnic blood stimulates insultin secretion from pancreas. Insulin stimulates K+ uptake by upregulating Na-K-ATPase in muscle cells and hepatocytes. IV Insulin used to treat life-threatening hyperkalaemia.
How does aldosterone affect uptake of K+ into cells? What drug opposes aldosterone’s actions?
K+ in blood stimulates aldosterone secretion. Increases K+ reabsorption in late DCT and CD (upregulates ENaC and Na-K-ATPase).
How do catecholamines regulate K+?
Act via B2-adrenoceptors - upregulate Na-K-ATPase stimulating cellular uptake of K+.
With regards to internal balance of K+, what factors promote the K+ shift out of cells?
Low ECF [K+], Exercise, Cell lysis, Increase in ECF osmolarity, Acidosis - high ECF [H+] - shift of H+ into cells, K+ goes the other way - out of cells.
How does exercise affect K+ balance between ICF and ECF?
Skeletal muscle contraction –> net release of K+ during recovery phase of action potential. Skeletal muscle damage –> release of K+ N.B. change in plasma [K+] proportional to level of exercise.
How does the body prevent dangerously high K+ levels during exercise?
Non-contracting tissues take K+ up. Exercise increases catecholamine production (B2 - upregulate Na-K-ATPase). Cessation of exercise causes a sharp drop in plasma [K+] - <3mmol/L.
How does cell lysis affect K+ balance between ICF and ECF? What are some causes?
Increases K+ in ECF. Rhabdomyolysis - trauma to skeletal muscle causing muscle cell necrosis. Intravascular haemolysis - inappropriate breakdown of RBCs: Incompatible blood transfustion, G6PD deficient patients treated with certain drugs. Chemotherapy - tumour cell necrosis.
How do changes in plasma tonicity affect K+ balance between ICF and ECF?
An increase in plasma & ECF tonicity - e.g. diabetic ketoacidosis will lead to water moving from the ICF into the ECF. This increases relative [K+] in ICF - K+ moves from ICF to ECF because of this.
How does acid base disturbances affect K+ balance?
How does hypo/hyper kalaemia cause acid base disturbances?
