Renal 4 Flashcards
Where is 98% of our body’s potassium found?
In cells
What happens if potassium homeostasis gets screwed up?
Nerve misfiring, cardiac arrhythmias
In the depleted state, what portions of the nephron reabsorb potassium?
67% is reabsorbed in the PCT, 20% in the thick ascending loop of Henle, and 12% in the distal tubule and CD.
Potassium reabsorption in the PCT is done completely via __________ transport.
paracellular
How do thick ascending Henle cells reabsorb potassium? How does the potassium get into the interstitium? Does solvent drag happen here?
Into cells:
- Paracellular transport
- Na+/2Cl-/K+ cotransporter
Basolateral exit via diffusion
No solvent drag!
____% of the reabsorbed potassium happens in the late distal tubule and collecting duct using the…? In which cell type does this occur?
12% - using the H+/K+ ATPase (2K+ are brought into the cell, 2H+ are pumped into the tubule lumen).
Intercalated cells do this.
How do the kidneys change how much K+ they reabsorb?
By altering secretion in the late distal tubule and CD; K+ is always reabsorbed in the PCT and TAL (not regulated)
What are the three mechanisms by which late distal tubule and CD cells increase K+ secretion?
- Increase the activity of the apical K+ channel - allows more facilitated diffusion of K+ from the cell into the tubule lumen.
- Increase the activity of the apical Na+ channel - allows more Na+ to be reabsorbed from the tubule lumen into the cell, pushing K+ out of the cell (both are pos. charged).
- Increase Na+/K+ ATPase (basolateral) - gets more K+ into the cell so it can diffuse out through the apical K+ channel.
Which cell type is responsible for K+ secretion in the late DCT and CD?
Principal cells
Name the five main factors that affect K+ secretion by principal cells in the late DCT and CD.
- [K+]plasma
- Aldosterone
- K+ channel activity
- Na+ channel activity
- Na+ delivery to principal cells (reabsorption)
Some duretics decrease sodium ________ upstream of DCT and CD principal cells, which ________ (increases or decreases) potassium secretion.
Some diuretics decrease sodium reabsorption upstream, making the lumen in the DCT and CD less negatively charged, increasing potassium secretion.
How does furosemide affect potassium reabsorption and secretion? Explain the two ways these are affected.
Furosemide inhibits potassium reabsorption via (1) inhibiting the Na+/2Cl-/K+ cotransporter in the thick ascending loop of Henle and (2) that inhibition puts more Na+ in the lumen so DCT and CD principal cells have more Na+ reabsorption –> more K+ secretion.
Therefore, Furosemide is a K+ wasting diuretic
How does Bartter’s syndrome affect potassium reabsorption and secretion in the kidneys?
For the same reasons furosemide wastes K+: inhibition of potassium reabsorption via (1) inhibiting the Na+/2Cl-/K+ cotransporter in the thick ascending loop of Henle and (2) that inhibition puts more Na+ in the lumen so DCT and CD principal cells have more Na+ reabsorption –> more K+ secretion.
How do Thiazide diuretics affect K+ secretion?
Thiazide diuretics inhibit the Na+/Cl- cotransporter in the early DCT (which normally reabsorb both ions). This makes the lumen have more Na+ –> more K+ secretion by DCT and CD principal cells. It is therefore a K+ wasting diuretic.
How does Gitelman’s syndrome affect K+ secretion?
The same way Thiazide diuretics do: inhibition of the Na+/Cl- cotransporter in the early DCT (which normally reabsorb both ions). This makes the lumen have more Na+ –> more K+ secretion by DCT and CD principal cells.
What are the two clinical features of Gitelman’s syndrome?
- Hypotension
2. Hypokalemia
What does Amiloride do? Does it waste K+?
It decreases the activity of the Na+ channel in late DCT and CD cells. This spares K+
How does Liddle’s syndrome affect K+ reabsorption/secretion?
Liddle’s increases the activity of the apical Na+ channel in late DCT and CD cells –> increased Na+ reabsorption –> increased K+ secretion –> hypokalemia
Where is most of a person’s calcium?
In bones
Where does calcium reabsorption happen in a nephron?
70% in the PCT, 20% in the thick ascending loop of Henle, 7% in the DCT
What are the two mechanisms of Ca2+ reabsorption in the PCT and what are their relative proportions? How is calcium transported in the thick ascending loop of Henle? What about in the DCT and CD?
Of the 70% of the Ca2+ reabsorption by the PCT, 80% of that occurs via paracellular transport, and 20% occurs transcellularly through apical Ca2+ channels.
Mechanisms are the same in the TAL except there is no solvent drag.
DCT and CD - transcellular transport only via Ca2+ channels.
How do PCT cells get rid of Ca2+ on the basolateral side?
- Ca2+ ATPase - it burns ATP to move the calcium across
2. Na+/Ca2+ antiporter - exchanges 3Na+ for one Ca2+
What two hormones are released in the setting of hypocalcemia and how do they affect the kidneys?
Calcitriol –> increased calcium reabsorption in the DCT
PTH –> increased calcium reabsorption in the loop of Henle and in the DCT
What does calcitonin do?
Released in response to hypercalcemia, it increases bone formation.
Where is most of a person’s phosphate found?
86% in bones, 14% is intracellular, a tiny bit is extracellular
How much phosphate is protein-bound (and not filtered by the kidneys)?
10%
Where along the nephron is phosphate reabsorbed?
80% in the PCT, 10% in the DCT, 10% is excreted
How is phosphate reabsorbed in the PCT? How does it exit cells on the other side?
Entry via 2Na+/PO43- cotransporter, exits via PO43-/anion antiporter
What effect does calcitriol have on phosphate reabsorption? What about calcitonin?
Calcitriol increases reabsorption in the PCT.
Calcitonin decreases phosphate reabsorption in the PCT.
What effect does PTH have on phosphate homeostasis?
PTH increases osteoclast activity - phosphate is released from bones, BUT this is canceled out because there is a decrease in phosphate reabsorption in the PCT. The net result is a loss of phosphate.
Where in the nephron are organic anions and cations secreted? Are there a bunch of different transporters?
In the PCT. All anions compete for the same transporter, and all cations compete for the same transporter.
How are anions secreted in the PCT?
They are brought into the cell with the anion/a-KG antiporter. They are secreted into the lumen with a Cl-/anion exchanger
How does PAH increase the effectiveness of penicillin?
It competes for the same anion transporters in PCT cells so the penicillin isn’t cleared as quickly
How are organic cations secreted in the PCT?
They enter cells via a passive transporter, and exit into the tubule in two ways:
- cation/H+ antiporter
- MDR-related transporter
MDR-related transporters belong to the _____ family of transporters and these are responsible for multidrug resistance of _______ cells.
ABC family
cancer cells
How are peptides and small proteins reabsorbed?
In the PCT via endocytosis with megalin and cubulin receptors, which is then delivered to lysosomes for degradation to AAs.
What is Fanconi’s syndrome?
Defect in the megalin or cubulin receptors (for endocytosing peptides and small proteins in the PCT) or in the V-ATPase –> proteinuria.
