RENAL - Proximal Tubule Function

Question 1

Where does most reabsorption in the nephron occur?

Answer 1

• 65% in the PCT
• 15% in Loop of Henle
• 15% in DCT
• 5% in collecting duct

Question 2

Describe reabsorption in the early PCT. PART 1

Answer 2

• Intracellular sodium concentrations are low - maintained by sodium-potassium ATPase
• Reabsorption mainly via SGLT2 in kidney and transports sodium and glucose in 1:1 ratio
• Glucose secreted from basolateral membrane through various GLUT transporters using facilitated transport
• Sodium absorbed in anti-transporter fashion through exchange with hydrogen

Question 3

Describe reabsorption in the early PCT. PART 2

Answer 3

• Sodium can facilitate amino acid transport. Hydrogen (previously secreted in exchange for sodium) reabsorb amino acids
• Lots of amino acids transporters exist on apical and basolateral membrane using various transport mechanisms depending on amino acid - use sodium and/or hydrogen to facilitate reabsorption
• SGLT2 inhibitors treat T2D - inhibit SGLT2 - prevent glucose reabsorption from lumen

Question 4

Describe bicarbonate reabsorption. PART 1

Answer 4

• Used to buffer hydrogen ions in blood and filtered at glomerulus
• Hydrogen secreted in exchange for sodium combines with bicarbonate in lumen to form carbonic acid (unstable - can break down back into bicarbonate and hydrogen)

Question 5

Describe bicarbonate reabsorption. PART 2

Answer 5

• Carbonic anhydrase on apical membrane of PCT cells - carbonic acid converted into water and carbon dioxide - reabsorbed by PCT cells
• Intracellular carbonic anhydrase converts H2O and CO2 back into carbonic acid - breaks down back into H+ and HCO3-.
• Bicarbonate reabsorbed by specialised transporters on basolateral membrane

Question 6

Describe ammonia reabsorption. PART 1

Answer 6

• Bicarbonate synthesised de novo due to use when buffering acids
• Synthesis of bicarbonate occurs in PCT cells involving glutamine metabolism

Question 7

Describe ammonia reabsorption. PART 2

Answer 7

• Glutamine metabolism into glutamate produces ammonia as by-product - some reabsorbed into circulation, majority secreted into tubule for excretion
• Glutamate further metabolised through TCA cycle - bicarbonate is a by-product - secreted from basolateral membrane into circulation

Question 8

Describe reabsorption in the late PCT. PART 1

Answer 8

• Most reabsorption occurs in first 1/3 of PCT - when filtrate reaches late PCT, certain substances become more concentrated
• Chloride - left behind after sodium reabsorption

Question 9

Describe reabsorption in the late PCT. PART 2

Answer 9

• High sodium concentration in interstitium creates electropositive environment relative to lumen - facilitates paracellular reabsorption of chloride
• Other substances such as glucose and amino acids present in high quantities in interstitium - raises osmolality of interstitium and facilitates water reabsorption via osmosis.

Question 10

Describe reabsorption in the late PCT. PART 3

Answer 10

• As water is reabsorbed, greater concentration of substances in luemn facilitating their reabsorption
• Potassium reabsorption utilises this to increase reabsorption - as water is reabsorbed, relative concentration increases - concentration gradient between lumen and interstitium
• As chloride ions reabsorbed, voltage of lumen more positive - potassium repelled towards interstitium

Question 11

A frequent symptom of diabetes is frequent urination. Suggest why. PART 1

Answer 11

• Blood glucose levels elevated - reabsorption mechanisms in PCT (i.e SGLT2) saturated - cannot reabsorb all filtered glucose passing through glomerulus
• High amount of glucose left in filtrate, osmolarity of lumen higher than that of interstitium - water reabsorption doesn’t occur so water reamins in filtrate

Question 12

A frequent symptom of diabetes is frequent urination. Suggest why. PART 2

Answer 12

• Water can be drawn out of interstitium via osmosis
• Increased water content therefore increased urine volume

Question 13

Describe glycosuria.

Answer 13

• Maximum amount of glucose that can be reabsorbed by kidney around 10 mmol per litre
• If plasma glucose elevated above by ~5mmol/L, glycosuria occurs

Question 14

Describe metabolic intermediaries.

Answer 14

• Important for metabolism - freely filtered at glucose
• 3 types - monocarboxylates (e.g lactate and pyruvate), dicarboxylates and tricarboxylates (labelled on TCA cycle on slide 10)
• Reabsorbed in PCT - important for PAH secretion