8 - Renal Potassium and Acid-Base Handling Flashcards
Where is the body’s potassium located?
Approximately 98% of body’s potassium is within the cells.
2% is in ECF where the concentration is 4 mEq/L, this is tightly regulated.
What is normal daily potassium intake? What is that per meal and what effect would that have on EC K concentration?
About 100 mEq/day, which is 33 per meal.
An increase in 33 mEq/L in the 14 L ECF would increase EC K from 4 to 6.4 mEq/L which would cause hyperkalemia.
What are the first signs of hyperkalemia in cardiac tissue? What do further increases lead to?
Tall, thin T waves.
Further increases lead to prolonged PR intervals, depressed ST segments, and lengthened QRS interval.
When ECF is ~10 mEq/L K+, ventricles begin to fibrillate.
How does the body prevent hyperkalemia from occuring? What causes this to occur?
By increasing cellular uptake of K.
Insulin, aldosterone, and b-adrenergic stimulation all increase cellular K+ uptake by stimulating Na/K ATPase pump.
What are factors that increase extracellular potassium?
Insulin deficiency, aldosterone deficiency, alpha adrenergic stimulation, acidosis, and increased plasma osmolarity.
How is K+ handled by the kidneys? How much of the filtered K+ from the kidney is excreted under normal to high intake?
It it freely filtered.
15-80% of the filtered load is excreted in urine.
How much K+ is reabsorbed in the PT and loop of henle under normal/high intake?
What happens to K+ in the CD?
60% reabsorbed by paracellular diffusion in the PT
20-30% in the loop of henle by the Na/K/2Cl transporter
Secreted in the principal cells of the CD via BK and ROMK channels.
How does excretion of K+ change during potassium depletion? How does filtration change and how does PT and thick ascending loop handling change?
Final excretion is about 1% of the filtered load.
K+ is still freely filtered and handled the same way in the PT and thick ascending loop of henle.
How does renal potassium handling differ under depleted conditions?
Difference is in the distal tubule and CD.
Instead of net secretion of K+ by principal cells, there is a reabsorption of K+ in the distal segments by the intercalated cells of the CD.
What are factors that increase potassium secretion?
- Increased ECF potassium concentration - stimulated Na/K ATPase in principal cells, increased potassium gradient, increased aldosterone
- Increased aldosterone
- Increased tubular flow rate (increased Na+ delivery)
- Acidosis (acute) - inhibits K+ excretion
- Acidosis (chronic)- stimulates K+ excretion
How is K+ secretion in the late distal tubule and collecting duct regulated?
Feedback loop.
Increase in plasma K+ increases aldosterone, which increases K+ secretion in the cortical CD, which increases K+ excretion.
What are five ways that elevation of aldosterone increase potassium excretion?
- Increasing Na/K ATPase in basal membrane
- Increased expression of ENaC in apical membrane
- Elevating SGK1 which increases ENaC expression
- Stimulating CAP1 which activate ENaC
- Stimulating permeability of apical membrane to K+
What are the two things that control potassium excretion rate?
Aldosterone and ECF potassium.
What is Addison’s disease and what does it cause?
Lack of aldosterone due to adrenal insufficiency.
Loss of sodium, accumulation of potassium.
What is Conn’s syndrome and what does it cause?
Aldosterone excess due to adrenal tumors.
Sodium retention and potassium depletion.
How much acid does a normal individual produce in a day? Where is the majority of this derived from and where does most of it go?
15-20 moles/day.
Derived from CO2 and removed by the lungs.
Where does the rest of the acid made in our body come from (if not CO2)?
Catabolism of sulfur-containing and cationic amino acids such as H2SO4 and HCl.
These would greatly decreased the body’s pH if they weren’t buffered and eliminated.
What are the three ways that the body defends itself against changes in the fluid hydrogen ion concentration? How fast is each?
- Chemical buffer system of body fluids (bicarb, phosphate, protein), does not remove or add H+ from the body - seconds
- Respiratory system - minutes
- Kidneys - (most powerful), eliminates excess acid or base - hours to days
What is the function of the bicarbonate buffering system? What is the equation?
Most important ECF buffer system, despite pK of 6.1 and modest concentrations of CO2 and HCO3-.
Important due to regulation of CO2 and HCO3 by the lungs and kidneys.
CO2 + H2O H2CO3 H+ + HCO3-
Where does the phosphate buffering system work? What is the equation?
Buffer for renal tubular fluid and intracellular fluid.
Insignificant in ECF due to low concentrations.
HCl + Na2HPO4 NaH2PO4 + NaCl (excess acid)
NaOH + NaH2PO4 Na2HPO4 + H2O (excess base)
Why is the proteins buffering system useful? What is the general equation?
It’s a slow but powerful intracellular buffer because of high concentrations and optimal pH.
H+ + protein H-protein
Non-volatile acids such as H2SO4 and HCl are buffered in the body, leading to consumption of ______? What must be done as a result of this consumption?
HCO3-
To maintain acid-base balance, the kidneys must excrete Na+ salts, excrete excess acid, and replenish HCO3- that was lost.
What are the equations in which H2SO4 and HCl are buffered?
H2SO4 + 2NaHCO3 NaSO4 + 2CO2 + 2H2O
HCl + NaHCO3 NaCl + CO2 + 2H2O
How do the kidneys regulate extracellular fluid pH?
By excreting an acidic or basic urine.
Describe the renal handling of HCO3-?
4320 mEq of HCO3- filtered each day and nearly all is reabsorbed: 85% in PT, 10% in thick ascending limb, 5% in CD.
What needs to occur for reabsorption of HCO3-?
One H+ needs to be secreted into the tubular lumen to reabsorb one HCO3-
HCO3- is impermeable the luminal membrane so it has to bind H+ to become H2CO3 and dissociate into CO2 and H2O via carbonic anhydrase to enter the cell for reabsorption.
What cells are involved in the H+ secretion and HCO3= reabsorption in the late DT and CD?
Intercalated cells.
How is new HCO3- make in the kidney to replace that consumed by nonvolatile acids?
Glutamine is turned into 2HCO3- and 2NH4+.
The HCO3- is reabsorbed and the NH4+ is excreted.
What is the pH minimum in the PT and CD?
PT : pH 6.5
CD : pH 4.5
What are the most important urinary buffers? What are other urinary buffers?
Important urinary buffers: NH3 and Na2PO4-
Other buffers: urate and citrate
What are things that increased tubular H+ secretion?
Increased H+ and decreased HCO3-
Increased PCO2
Increased Aldosterone
Decreased ECF volume (causes increase in ANGII and Na/H exchanger)
Hypokalemia
What is the initiating change in respiratory acidosis?
Alkalosis?
Acidosis: increase in PCO2
Alkalosis: decrease in PCO2
What is the initiating change in metabolic acidosis?
Alkalosis?
Acidosis: decrease in HCO3-
Alkalosis: increase in HCO3-
What equation can be used to calculate plasma pH?
Plasma pH = 6.1 + log (HCO3-)/(0.03 X PCO2)
What equation can be used to calculate plasma pH?
Plasma pH = 6.1 + log (HCO3-/(0.03 X PCO2))
What is Liddle Syndrome?
An autosomal dominant genetic disease that is caused by a mutation in the B or gamma subunit of ENaC.
Leads to increased ENaC in the apical membrane, causing increased Na reabsorption. (gain of function mutation)
Causes hypernatremia and expansion of body fluids. Secreting a lot of K.
What do principal cells have?
Have ENaC channels and vasopressin-sensitive insertion of AQP into apical membrane
What do intercalated cells have?
Na/K ATPase in basolateral membrane, but have H/K ATPase in the apical membrane
Not sensitive to vasopressin