CR15: Tubular Absorption and Secretion

What is the equation describing renal excretion?

Excreted = Filtered + Secreted − Reabsorbed

How may substances in plasma be handled by the kidney?

• May or may not be freely filtered

• May be filtered and partially or totally reabsorbed

• May be filtered and secreted

Give examples of plasma substances handled by the kidney

• Creatinine: filtered only

• Electrolytes: filtered and then partially reabsorbed

• Glucose/amino acids: filtered and reabsorbed completely

• Organic acids: filtered and secreted

In the nephron, secretion always refers to what process?

Transport of solute into the lumen of the tubule

How does reabsorption differ from filtration?

Reabsorption is selective

What are the passive mechanisms of reabsorption?

• Osmosis

• Solvent drag (paracellular movement of solute with water)

• Simple diffusion

• Facilitated diffusion

How do tight junctions vary along the nephron?

Tight junctions become tighter (less leaky) along the length of the tubule

What are the active mechanisms of reabsorption?

• Primary active transport (Na⁺/K⁺-ATPase)

• Secondary active transport (usually Na⁺-coupled)

  • Cotransport

  • Counter-transport

• Pinocytosis (small proteins)

Where is the Na⁺/K⁺ pump always located?

On the basolateral membrane

How is glucose handled by the kidney?

180 g/day filtered, 180 g/day reabsorbed, 0 excreted (100% reabsorbed)

How is sodium handled by the kidney?

25,560 mEq/day filtered, 25,410 mEq/day reabsorbed, 150 mEq/day excreted (99.4% reabsorbed)

Where does the majority of reabsorption occur?

Proximal tubule and thick ascending loop

Where does fine-tuning and regulation of reabsorption occur?

Distal tubule and collecting tubules

Why is Na⁺ reabsorption critical?

• It drives reabsorption of many other solutes

• Some solutes are actively coupled to Na⁺ reabsorption

• Passive reabsorption of water follows Na⁺ movement

• Passive movement of Cl⁻ and urea depends on concentration gradients created by Na⁺ and water reabsorption

How is water reabsorbed in the nephron?

Passively

What does “water follows salt” mean?

Water reabsorption is secondary to solute transport

What is meant by isosmotic reabsorption in the proximal tubule?

Luminal osmolarity does not appreciably change along the proximal tubule

What causes osmotic diuresis?

Presence of poorly reabsorbed solutes

Give examples of substances causing osmotic diuresis.

Sucrose, mannitol (used to treat elevated ICP), untreated diabetes mellitus

What structural features support reabsorption in the proximal tubule?

• High expression of transport proteins

• High mitochondrial density

• Extensive brush border (microvilli)

• High water permeability

How much glucose is reabsorbed in the proximal tubule?

100%

How much amino acid is reabsorbed in the proximal tubule?

100%

Where does most glucose and amino acid reabsorption occur?

First 25% of the proximal tubule

How much sodium is reabsorbed in the proximal tubule?

Approximately 67%

Does sodium concentration change in the proximal tubule?

No, because water is also reabsorbed.

How does creatinine behave in the proximal tubule?

It is not reabsorbed and becomes concentrated

What determines fluid osmolarity in the body?

Sodium concentration

Why is sodium tightly regulated?

To control fluid shifts

How is sodium filtered and reabsorbed?

• Sodium is freely filtered

• Filtered load is ~10x the amount in plasma

• 99% is reabsorbed

Where is Na+ reabsorbed along the tubule?

• 67% in the proximal tubule

• 25% in the thick ascending limb

• 4% in the distal tubule

• 3% in the cortical collecting duct

(1% excreted)

How is sodium reabsorbed in the proximal tubule?

• Cotransport with glucose (SGLT) and amino acids

• Na⁺/H⁺ exchanger (counter-transport) coupled with HCO₃⁻ reabsorption

• Driven by chloride gradient in late proximal tubule

Which transporters mediate glucose reabsorption?

SGLT1 and SGLT2

How do SGLT1 and SGLT2 differ?

They differ in the number of Na⁺ molecules coupled to glucose reabsorption

• SGLT1 transports 2 Na+ molecules

• SGLT2 transports 1 Na+ molecule

If creatinine clearance is 120 mL/min, plasma glucose is 2 mg/mL, and glucose Tm is 340 mg/min, what is glucose excretion?

0 mg/min (glucose excretion should aways be 0!)

How are amino acids reabsorbed?

• Via sodium-coupled secondary active transport

• 99% is reabsorbed in the proximal tubule

How are peptides handled in the proximal tubule?

• Hydrolyzed by brush border peptidases

• Absorbed as individual amino acids and short peptides via secondary active transport (PepT1)

Which proteins are filtered at the glomerulus?

Small proteins and peptides

How much albumin is filtered?

0.01–0.05% of plasma concentration

What peptide hormones are filtered?

Insulin, glucagon, PTH, ADH

How are filtered proteins reabsorbed in the proximal tubule?

By endocytosis

What are the transport characteristics of the thin limbs of the loop of Henle?

Few mitochondria, little transport protein production, mainly passive paracellular reabsorption

What are the properties of the thin descending limb?

High water permeability, no solute reabsorption

(Only water is reabsorbed)

What are the properties of the thin ascending limb?

Very low water permeability

What is the water permeability of the thick ascending limb?

Very low water permeability, active Na+ reabsorption.

How is sodium reabsorbed in the thick ascending limb?

Active Na+ reabsorption via Na⁺-K⁺-Cl⁻ cotransporter (NKCC). Target of loop diuretics.

Also reabsorbed via electrogenic transport.

What is electrogenic reabsorption?

The high positive charge in the lumen drives paracellular cation reabsorption in the thick ascending limb.

What are the characteristics of the early distal tubule?

Low water permeability and Na⁺-Cl⁻ cotransport (absorption of Na+ and Cl-)

• Na/Cl cotransport is inhibited by thiazide diuretics

What are the characteristics of the late distal tubule?

Water permeability dependent on ADH, principal cells mediate Na+ reabsorption.

What transport processes occur in principal cells?

Na⁺ reabsorption via epithelium sodium channels (ENaC) and K⁺ secretion

• Aldosterone acts on principal cells

How does aldosterone affect principal cells?

Increases transcription of basolateral Na⁺/K⁺-ATPase, apical ENaC, and apical K⁺ channels.

• This increases Na+ reabsorption and K+ excretion.

What is the function of type A intercalated cells in the distal tubule?

Secrete H⁺, reabsorb K⁺ and HCO₃⁻, important during acidosis

• More type A cells are expressed during acidosis to eliminate H+

What is the function of type B intercalated cells in the distal tubule?

Secrete HCO₃⁻, reabsorb H⁺, important during alkalosis

• More type B cells are expressed during alkalosis to eliminate HCO3-

What controls water permeability in the medullary collecting duct?

ADH

What happens in the medullary collecting duct?

• Water permeability/reabsorption is controlled by ADH

• Urea transporters maintain high osmolarity in the medulla

• Active secretion of H+ against its gradient

How does aldosterone affect sodium?

Increases Na⁺ reabsorption in principal cells (late distal tubule)

How does atrial natriuretic peptide (ANP) affect sodium and water?

Inhibits Na⁺ and H₂O reabsorption in collecting ducts and inhibits renin secretion

How does norepinephrine (sympathetic) affect renal function?

Decreases RBF, stimulates renin secretion, stimulates Na⁺/H⁺ exchanger and Na⁺/K⁺-ATPase in proximal tubules

(Overall increases Na+ reabsorption)

Where is most potassium located in the body?

98% in intracellular fluid (~3 mol)

How much potassium is in the extracellular fluid?

~2% (~65 mmol)

Why is potassium tightly regulated?

Critical for resting membrane potential and excitability of muscle and nerve cells

Is potassium freely filtered?

Yes

Where is potassium reabsorbed?

80% in proximal tubule, 10% in thick ascending limb

What determines potassium reabsorption and secretion in the distal tubule?

It is highly regulated depending on dietary potassium intake

What happens when there is low K+ intake?

There is high reabsorption and no secretion of K+ in the distal tubules.

What happens when there is normal to high K+ intake?

There are high levels of secretion of K+ in the distal tubules to maintain proper levels.

(20-180% secreted)

What are the key transport features of the proximal tubule?

SGLT, amino acid cotransport, 100% glucose reabsorption; flow-dependent regulation

What are the key transport features of the thick ascending limb?

Na⁺-K⁺-Cl⁻ cotransporter, water impermeable; regulated by loop diuretics

What are the key transport features of the distal tubule and collecting duct?

ENaC channels and aquaporins; regulated by aldosterone and ADH