Renal Handling of K, Ca, PO4 3- Flashcards
Normal K+ levels
Why is deviation dangerous?
3.6 to 5.2mEq/L– deviaition is cause for alarm because the resting membrane potential of excitibility cells critically dpends on Extracellular K+
Elevated extracellular K+ depolarizes cells while low K+ levels will hyperpolarize cells.
What percent of K+ is outside? WHy? What happens if this inscrease
2%- by the collective operation of the Na-K-ATPase in cells around the body.
vigorous exercise may acutely damage some muscle cells and this may dump extra K+ into the extracelullular compartment. A quick shift of K+ into skeletal muscle (body wide) can and does “buffer” this type of K+ disturbance.
What two hormones regulate K+ shift? And when?
What else regulates K+ movement between intra and extracelluar
INsulin (after meal) and Epi (fast after trauma or exercise). Both of these hormones promote K+ uptake in muscle by stimulating the Na-K-ATPase activity.
Also K+ intra and extracellular movement is controlled by pH. When acidosis K+ moves out of the cell and alklasis does the opposite. — reasons still debated
What is the prodominant means of K+ excretion?
Urine– although a small amount is lost through feces and urine.
Example what happens to buffer K+ rises
1 K+ load causes a sudden rise
- Theres a fast movement of K+ into cells– serves as an immediate storage so ec K+ isn’t too high
- Overtime (8-14 hours later) there is anincrease in excretion of K+
How much of Potassium (k+) is fillered?
Freely Filtered
PT- 80% - paracellular passive through tight junctions
Thick Ascening Loop of Henle- 10%- Na-k-2CL
Distal and CD- VARIES- this is what is important for body’s regulation (although medullary CD is always associated with net K+ reabsoprtion)
What part of the nephron vaires in K+ absorption/Secretion?
What happens when low dietary intake?
High Dietary intake of K+?
When low dietary intake- distal nephron has small K+ reabsoption (2% of the 10% remaining in filtrate) and then 6% at the medullary CD so only 2% is excreted. (Note that the distal nephron does very little to conserve K+ but active in getting rid of it– high dietary intak)
High intake
- 20-160% of the load is secreted (mainly in the cortical CD)! (10-150% of the filtered amoutn can be excreted- because the secretion makes up for all the early reabsoption in the nephron)
2, Medullary CD still reabsorbs even when K+ is high
In the CD there is both absorption and secretio in the CD? How does this happen?
The principle cells mediate K+ secretion. – since secretion can be so large this is the key modulatory in K+ excretion amounts.
The intercalated cells mediate K+ reabsortpion
Explain the process of secretion of K+ at the cortical CD
On the principle cells!!
- Active Na/K at BL membrane (can be inhibited by ouabin)
- Passive diffusion of K+ into lumen at apical– this K+ is bought in by the BL Na/K+ pump
- There is also K+ channels in the BL so K+ can leak back out.– but little does because of the electrical gradient across the epithelium– more negative towards Apical
How can K+ net secretion be altered
remmeber at the COrtical CD on principle cells
- Closig apical K+ channels so then K+ would leave through BL K+ channels– opposite true as well
- Close apical Na channels- this would reduce the Na/K Pump so less K+ avliable to enter the apical K+ channel
- Abnormally low K+ levels would limit K+ avliable for the Na/K pump so less secretion. High plasma would od the oppotiste.
- Higher than normal tubular K+ woudl redue the electrochemical gradient so there would be a reducton in secretion. Remember this graident is what makes K+ go throught he apical channel into lumen and not the BL chanell back to interstitum.
K+ affects which hormone? How
Aldoesterone! High plasma K+ triggers Aldosterone release. which promotes the opening of apical K_ channels allowing for more secretion. Secretion changes proportionally to aldosterone. Aldosterone also increase Na/K ATPase operation.
Explain tubular flow rate affect on K+ secretio
increased tubular flow (or increased urine formation rate) promotes K+ secretion. Consequently, the increased urine flow associated with extracellular volume expansion leads to
increased K+ secretion
When tubular flow rate is low, the K+ moving out of the
principle cell into the tubular lumen has time to accumulate, slowing further K+ movement out of the cell. When tubular flow rate is high, the K+ moving out of the principle cell is swept away, promoting further K+ movement out of the cell.
Aldosterone has impacts on wht two ions? Why doesn’t that cause probelsm
Na (reabsorption) and K+ (secretion)
High NaCL would lead to high BP so we would reduce aldosterone circulating. Aldosterone promotes Na+ reabsotpin and K+ secretion. so reudcing aldosterone alsosterone will increase Na+ excretion and K+ retention. However, the increased GFR and tubular flow rate (associated with increased blood volume and BP) will promote K+ secretion. The net result is that K+ remains relatively unchanged while the excess Na+ is excreted.
What is a diuretic
An agent that increase urin volume and reduces EC fluid volume. This is usually accomplished by promoting Na+ and H2O excretion. However, the tubular flow dependence of K+ secretion can generate an unwanted side effect of diuretic use. The unwanted side effect is increased K+ excretion.
K+ excretind diuretics- normally act upstream of CD
K sparing- act on CD
When does GI Ca/phophate absorption exceed excretion
When is there a net loss in Ca2+
Growth and pregnancy
In osteoporosis patients, urinary loss of Ca2+ and phosphate can
exceed their gain.
What happens in hypocalcemia
Hypocalcemia increases the excitability of nerves and muscles
which may lead to muscle spasms and/or hypocalcemic tetany. – think— more caclium inside the cytoplasm more liekly to contract
Conversely, hypercalcemia
reduces excitability leading to lethargy and even cardiac arrhythmias.
What two factors control Ca2+ balance and what are the hormones that relate to them
INtake (Vitamin D promotes Ca2+ intake in the GI tract) and output by the kidney
Bone and extracellular
What are the roles of PTH
1) promoting active vitamin D formation,
2) moving Ca2+ from bone to blood and
3) promoting renal Ca2+ reabsorption (i.e. less Ca2+ excretion in urine)
What are the high respostitories of Ca2+ and K+ used for? Where are they
Ca2+ in bones
K+ in cells
these high capacity repositories are used to buffer
sudden changes in plasma Ca2+ or K+ level. Also in both cases, overall long-term balance is
ultimately achieved by balancing renal output with ingested input.
Explain how much Ca2+ is filtered and wher it is reabsorobed
Filtered
50% bound to protein so not filtered
50% free and frelely filtered
Reabsorbed
- 60% at Proximal tubule - passive paracellular– indirectly dependent on Na and H20 because they are the driving force for passive paracellular
- Distal- transcellular
Where is Ca2+ handling paracellular where is it transcellular?
Explain the transcellular
Paracellular in the proximal tubule where 60% of the filtrate Ca2+ is reabsorbed
Transceullar
- Apical has Ca2+ channels
- BL either the Ca2+ atpase of the Ca/Na exchnager=- there is a Na/K BL pump as well
Vitamin Sources? Where can it be activated? Function
Source- body’s cholestrol, sunlight, tablets
Activated through hydroxylation in the kidney or liver
Active form is Calcitriol that promotes uptake of Ca2+ in the GI tract. Acts on bone and kidneys too but those actions are far less important.
Vitamin D deficiency can decrease gut Ca2+ uptake to the
extent that bone formation/reformation is impaired. In children, this can lead to a disease called
rickets.
Where is PTH released from and in response to what? Function
Parathyroid gland in response to low Ca2+
- PTH promotes kindye hydroylation of Vitamin D activating it to calcotriol.
- PTH increases movement of Ca2+ from bone to blood– this is a fast process to help maintain plasma levels
- PTH increases renal-tubular Ca2+ reabsorption mainly by acting on the distal convoluted tubule.
- this PTH action of inhibiting proximal phosphate reabsorption
Amount of phosphate filtered
Where is it reasborobed
90% is freely filtered
10% of phosphate is bound to protein
Reabsorption
- Proximal Tubule- 75%- transcellular by apical Na-Phosphate symporter.– requires an Na+ gradient
Is Tm important for phosphate? why or why not
Yes! Normally we filter just above the Tranport Max so most is reabsorbed. Working so close to the TM means that any increase in filtered phosphate simply adds to the amount excreted in the urine.
Explain what happens with phosphate in tubular fluid at the CD
Phosphate in the tubular fluid of the collecting duct
complexes with hydrogen ions and is the primary titratable pH buffer present in urine (as we will learn later). Interestingly, systemic acidosis promotes phosphate release from bone into the
plasma. This phosphate is filtered and provides more titratable pH buffer in the collecting tubule to help remove excess hydrogen ion from the body.
Does PTH relate to parathyroid. Is yes how
Yes! Rise in phosphate stimulates release of PTH (although low Ca2+ plasma is the main trigger) and acts on proximal tube to reduce reabsoprtion of phosphate— THIS IS THE ONLY HORMONE THAT ACTS ON THE PROXIMAL TUBULE.
