Nephron Anatomy and Function Quiz

Proximal Tubule

• Bulk absorber of the nephron
• Concentration of tubular fluid beyond the proximal tubule remains relatively unchanged
• Reabsorption and secretion of various solutes occur in the proximal tubule

Loop of Henle

• Reabsorption of NaCl, K, Ca, and Mg occurs in the loop of Henle
• Tubular fluid becomes dilute (hypotonic) compared to plasma and interstitium
• The interstitial fluid of the medulla is extremely hypertonic, with osmolality reaching up to 1200 mOsm/kg H2O
• Half of the osmolality is due to NaCl and the other half due to urea
• The thin descending limb of the loop of Henle is very permeable to water due to the presence of aquaporin channels

Aquaporin Family

• More than 200 aquaporin (AQP) isoforms have been identified across species
• At least 7 AQP isoforms are known to be present in the human kidney
• AQP1 is a tetrameric complex of 4 identical monomers and is abundant in the proximal tubule and thin descending limb
• AQP2 is abundant in the collecting duct and its expression can be modified by vasopressin
• AQP3 and AQP4 are located on the basolateral membrane in the collecting duct

Thin Descending Limb

• Initially, the fluid in the thin descending limb is isosmotic compared to the interstitium
• An osmotic pressure gradient develops as the fluid moves through the loop, resulting in osmotic water flow from the tubular fluid into the interstitium
• The tubular fluid becomes very concentrated, reaching up to 1200 mOsm/kg H2O

Thin and Thick Ascending Limb

• The ascending portion of Henle's loop is impermeable to H2O but permeable to some solutes (Na, Cl, and K)
• The ascending limb is referred to as the diluting segment
• Fluid entering the ascending limb has a higher NaCl concentration than the interstitium due to the concentrating actions of the descending limb
• Passive diffusion of Na and Cl occurs, and H2O cannot follow
• In the thick ascending limb, Na, Cl, and K are further reabsorbed, and H2O cannot follow

Na/K/2Cl Cotransporter

• Na, Cl, and K are transported into cells by a downhill gradient
• Energy comes from the electrochemical potential gradient generated by NaK ATPase on the basolateral membrane
• 1Na:2Cl:1K = electroneutral
• Cl leaves cells on the basolateral side through Cl channels and KCl co-transporter via electrochemical gradient
• K can leave cells on the basolateral side through the KCl co-transporter
• K can also leak from the cell on the apical side through K channels, resulting in a lumen-positive electrical potential
• Lumen-positive electrical potential drives Mg and Ca across epithelia paracellularly

Distal Tubule

• Na and Cl continue to be reabsorbed in the distal tubule
• Ca is also reabsorbed (transcellular) in the distal tubule
• Like the thick ascending limb, the distal tubule epithelium is relatively impermeable to H2O
• The distal tubule dilutes the urine even more

Collecting Tubule

• The collecting tubule is responsible for the final modification of the urine
• The collecting tubule is responsible for the reabsorption and secretion of various solutes

Nephron

• The nephron is the functional unit of the kidney
• Each kidney has approximately 10^6 nephrons
• The nephron is divided into four sections: proximal tubule, loop of Henle, distal tubule, and collecting tubule
• The nephron begins at the glomerulus and ends at the ureter
• The length of the nephron spans the renal cortex and medulla

Nephron Epithelium

• The nephron is lined with a single layer of epithelial cells
• Epithelial cells have apical (lumen) and basolateral (interstitial) sides
• Different types of epithelial cells line the nephron segments
• Ionic and water flow are dictated by the properties of these epithelial cells

Movement across the Nephron Epithelium

• Na dictates ionic flow, and water follows
• Active Na reabsorption occurs throughout the nephron
• The NaK ATPase is located on the basolateral membrane throughout the nephron
• The NaK ATPase pumps 3 Na ions out to the interstitium for every 2 K ions into the cell
• The NaK ATPase creates an electrochemical potential gradient
• The energy required for transport of most other solutes comes from the ECP gradient generated by the NaK ATPase

Reabsorption of Organic Substrates

• Na is more abundant outside of the cell (interstitium and lumen)

• The ECP favors Na entry from the lumen into the cell

• It is inefficient to waste energy from the ECP

• Therefore, active transport of organics is coupled to Na reabsorption; NaS cotransporters

• Almost all organic substrates are reabsorbed in the proximal tubule

• However, there are a finite number of transporters in each cell

• Transport maximum is attained when all nephrons are reabsorbing at maximum rate### Proximal Tubule

• Proximal tubule is a bulk absorber

• Concentration of tubular fluid beyond proximal tubule remains relatively unchanged

• Nephron beyond the proximal tubule is specialized to develop urine with variable osmolality and solute composition

Reabsorption and Secretion in the Loop of Henle

• Net effect: reabsorption of NaCl, K reabsorption, Ca and Mg reabsorption (paracellular)
• Tubular fluid becomes dilute (hypotonic compared to plasma and interstitium)

Transport in the Thin Descending Limb

• Interstitial fluid of the medulla is extremely hypertonic in comparison to plasma
• Osmolality can rise to as high as 1200 mOsm/kg H2O
• ½ of osmolality is due to NaCl and ½ due to urea
• Epithelial cells of thin descending limb are very thin (hence the name) and lack significant amounts of mitochondria (no energy source)
• No active transport processes for solutes
• However, they are very permeable to water due to specialized channels called aquaporins

The Aquaporin Family of H2O Channels

• More than 200 aquaporin (AQP) isoforms identified across species
• At least 7 are known to be present in human kidney
• AQP monomers consist of 6 transmembrane domains
• AQP1 is a tetrameric complex of 4 identical monomers
• AQP1 is abundant in the proximal tubule and thin descending limb, its expression is relatively consistent
• AQP2 is abundant in collecting duct, its expression can be modified; the principal target of vasopressin

Transport in the Thin and Thick Ascending Limb

• Initially, the fluid in the thin descending limb is isosmotic (equal) compared to the interstitium
• However, an osmotic pressure gradient develops as fluid moves through the loop
• Results in osmotic water flow from tubular fluid into the interstitium (H2O gets reabsorbed)
• Tubular fluid becomes very concentrated (1200 mOsm/kg H2O)
• At the loop’s bend, the tubular fluid enters the thin ascending limb
• The ascending portion of Henle’s loop is impermeable to H2O but permeable to some solutes: primarily Na, Cl, and K
• Ascending limb is referred to as diluting segment
• Fluid entering the ascending limb has higher (NaCl) than interstitium from concentrating actions of descending limb
• Passive diffusion of Na and Cl (paracellular)
• H2O cannot follow
• Fluid then enters the thick portion of the ascending limb
• Epithelial cells are thicker in this region and contain numerous mitochondria
• Na, Cl, and K are further reabsorbed in the thick ascending limb
• H2O cannot follow

The Na/K/2Cl Cotransporter of the Thick Ascending Limb

• Na, Cl, and K are transported into cells by a downhill gradient
• Energy comes from ECP generated by NaK ATPase on the basolateral membrane
• 1Na:2Cl:1K = electroneutral
• Cl leaves cells on the basolateral side through Cl channels and KCl cotransporter via electrochemical gradient
• Likewise, K can leave cells on the basolateral side through the K-Cl cotransporter
• K can also leak from the cell on the apical side through K channels; resulting in lumen-positive electrical potential
• Lumen-positive electrical potential drives Mg and Ca across epithelia paracellularly

Distal Tubule and Collecting Tubule

• Na and Cl continue to be reabsorbed in the distal tubule
• Ca is also reabsorbed (transcellular)
• Like the thick ascending limb, distal tubule epithelium is relatively impermeable to H2O
• Dilutes urine even more
• Na and Cl transported into cells by Na/Cl cotransporter
• Energy comes from the ECP gradient from basolateral NaK ATPase
• Ca actively transported into the cell by the Ca channel and across the basolateral membrane by the Na/Ca exchanger
• Ca reabsorption can be modified by parathyroid hormone (PTH) at this point