Lecture 18 - Tubular Reabsorption

Question 1

How is the proximal tubule divided?

Answer 1

The early part (60%) is called the proximal convoluted tubule; the rest is the proximal straight tubule.

Question 2

Describe transport in the proximal convoluted tubule?

Answer 2

• The selective distribution of ion channels, exchangers and co-transporters, and pumps on the apical and basolateral membrane is key to directional ion movement.
• There is movement of tones through cells and between cells.
• The movement of Na+ creates an osmotic gradient for the movement of water trans cellular.
• This segment of the tubule is quite water permeable, implying that the filtrate is isotonic with the interstitial space, which in the cortex means that it is isotonic with plasma.
• Uses the movement of Na+ down its electrochemical gradient into the epithelial cellist drive the movement of other substances.
• Uses the Na+/K+ ATPase. to move Na+ out of the cells on the bas lateral membrane.

Question 3

Describe water movement in the proximal tubule?

Answer 3

• Occurs via both the paracellular route and transcellular route through aquaporin 1.
• Water flows through the paracellular route because of the net outward hydrostatic and osmotic forces.

Question 4

Describe glucose in the proximal tubule?

Answer 4

• Under normal conditions 90% of the glucose is transported by the low-affinity/high-capacity sodium glucose co-transporter (SGLT2). The rest is carried by SGLT1 (high affinity/low capacity) transporter.
• Basolateral transport is by GLUT2 (or GLUT1)
• There is a maximal tubular load for glucose (~380mg/min). This is tubular maximum (Tm) transport.

Question 5

Describe SGLT2 inhibition

Answer 5

• Under normal conditions 90% of the glucose is transported by the low-affinity/high-capacity sodium glucose co-transporter 2 (SGLT2).
• SGLT2 inhibitors have been recently used for the treatment of diabetes.

Question 6

How are amino acids present in the proximal tubule?

Answer 6

• The plasma amino acid concentration is 2.5-3.5nM.
• Transport is Tm (tubular maximum) limited.
• Given the diversity of amino acids, it isn’t surprising that many different transporter contribute, but most are co-transporters that use the Na+ gradient.

Question 7

How is HCO3- present in the proximal tubule?

Answer 7

• 25nM HCO3- is present in the filtrate.
• The main mechanism of removal in the proximal tubule is by its reaction with excess H+, entering through a Na+/H+ exchanger.
• The rate at which equilibrium is achieved is increased by carbonic anhydrase
• Basolateral transport uses a Na+/3HCO3- transporter

Question 8

How is acetazolamide present in the proximal tubule?

Answer 8

• Acts mainly in the proximal tubule.
• Blocks carbonic anhydrase.
• Weak diuretic.
• Uses: glaucoma, mountain sickness prophylaxis
• Affects pH due to the fact that urine becomes alkaline (metabolic acidosis)

Question 9

How is Cl- movement present in the proximal tubule?

Answer 9

• both active and passive movement of Cl-
• Mainactive movement of Cl- is through an anti porter for other anions
• Given the absorption fo HCO3-, with the charge difference balanced by Na+ absorption, less Cl- is moved then Na+ in the early proximal tubule. Given that water is reabsorbed with the Na+ and HCO3-, this means that the Cl- concentration modestly increases along the proximal tubule.
• As the Cl- concentration increases (towards the end of the proximal tubules), it drives (passive) paracellular Cl- movement down its concentration gradient.

Question 10

How does active secretion occur in the proximal tubule?

Answer 10

• many organic anions are actively secreted in the proximal tubule. The negative charge often comes from the carboxylates of sulfonates.
• Organic anions complete with one another for excretion,
• Basolateral membranes: organic anion transporters (OAT).
• Luminal membrane: multidrug resistent-associated protein (MRP).

Question 11

What are the two key functional distinct components of the loop of henle?

Answer 11

1. Descending Limb - permeable to water, which leaves the filtrate because of osmotic force.
2. Thick ascending limb - can sustain an osmotic gradient. Key function is to create a hyperosmolar interstitial space in the medulla to drive water loss from the descending limb and cortical collecting duct

Question 12

What role does furosemide play in the loop of henle?

Answer 12

• Acts in the ascending limb of the loop of Henle
• Blocks Na+/K+/2Cl- co-transporter
• Allow unto 20% of filter Na+ to be excreted, causing enormous natriuresis and diuresis.
• Uses: cardiac failure, renal failure
• Side effects: K+ loss leading to cardiac dysrhythmias

Question 13

How do thiazides and thiazide-like drugs affect the distal tubule?

Answer 13

• Acts in the distal tubule
• Blocks Na+/Cl- co-transporter
• Moderately effective diuretics
• Uses: Antihypertensive. As a diuretic in conjunction with furosemide
• Side effects: increased uric acid, hyperglycaemia, hyponatraemia.

Question 14

How does spironolactone affect the tubules?

Answer 14

• Acts in the collecting tubules and ducts.
• Blocks the effect of aldosterone
• Moderately effective diuretics
• Uses: heart failure
• Side effects: gynaecomastia, menstrual disorders, testicular atrophy, hyperkalaemia

Question 15

What is urea countercurrent multiplication?

Answer 15

• In the late distal tubule and cortical collecting duct as water is removed, the urea concentration rises. In the medullary collecting duct the urea diffuses out of this urea-permeable tubule. urea permeability is increased by ADH by increasing the expression of UT-AT.
• the urea, now in the medullary interstitial space, contributes significantly to the high osmotic pressure in the medulla.
• Hence there is a urea countercurrent, out of the collecting duct and into the loop of henle, which further aids water reabsorption in the medulla.