Parts of the Nephron E3

Identify

Early proximal tubule cell (PCT)

Key identifier: If you look and see a ton of secondary symporters in the apical membrane and the reabsorption of glucose and amino acids, you definitely have this cell type

Note: Na+, Cl-, and urea will cross paracellularly

There are no transport processes for urea in the PT

Identify.

Late proximal tubule (PST)

Key identifier: Secondary active chloride transport. There are NO chloride transport proteins in the early proximal tubule. If you see formate. Chloride moves passively AND actively

Note: Na+, Cl-, and urea will cross paracellularly

There are no transport processes for urea in the PT

SGLT2 and GLUT2 transporters have low affinity and high capacity. T/F

TRUE

Remember —> in the early PT, glucose concentrations are really high! Affinity isn’t an issue, it is just responsible for rapid movement for reabsorption. Responsible for 90% of the filtered load of glucose by the mid-length of the proximal tubule

Where are SGLT2 and GLUT2 found?

1. Apical membrane of early proximal tubule

2. Basolateral membrane of early proximal tubule

Where are SGLT1 and GLUT1 found?

1. Apical membrane of late proximal tubule

2. Basolateral membrane of late proximal tubule

GLUT1 and SGLT1 are describe as high affinity, low capacity transporters. T/F

TRUE

• This means they can’t move a lot of glucose, but they can pick up small amounts and move them across the membranes

How do SGLT2 inhibitors work?

• They are used in the treatment of type II diabetes mellitus

• Examples: Glifozins, Invokana

MOA: They selectively inhibit SGLT2 because it is a low affinity, high capacity transporter that’s responsible for reabsorbing majority of glucose. So if you inhibit that transporter, you end up not reabsorbing all of the glucose, and the glucose shows up in the urine. So, you end up excreting glucose and that helps lower glucose concentrations in the plasma

—> BUT this isn’t great because glucose in the urine is good incubator for bacteria. Yeast infections and UTIs are super common while on this medication

What is the thin descending limb responsible for?

• Highly permeable to water, no solute permeability

• Contains AQP-1 channels that play a major role in concentrating the urine

• Reabsorption of water

• Urea secreted here via facilitated diffusion

What is the tAL responsible for?

• Impermeable to water

• Does not reabsorb significant amounts of any solutes

• Urea secreted here via facilitated diffusion

—> Does nearly nothing

What is the TAL responsible for?

• Impermeable to water AND urea

• Permeable to solute —> major site of Na+/K+/Cl- reabsorption

• Site of H+ secretion

• By the end of the LOH, more solute is reabsorbed than water = filtrate hyposmotic

• Distal end forms part of the JGA = has macula densa that mediates TGF response

• Reabsorbs 25% of solutes!!

Identify.

TAL cell

Key identifiers: The Na+/K+/2Cl- symporter on the apical membrane. This transport processes senses the sodium/chloride concentration in the filtrate. Secretion of H+ via transporter placed on the apical membrane

What influence does the K+ back leak have in the TAL?

Creates a +8mv and stimulates the movement of Na+, K+, Mg++, and Ca++ into the interstitial fluid through paracellular diffusion = too much positive charge accumulating!

Which segment of the nephron reabsorbs the most water?

Proximal tubule (70%)

—> most water is reabsorbed here!

What is the early distal tubule responsible for?

• SAME AS TAL: permeable to solute, impermeable to water and urea

• Called the “diluting segment” = reabsorbs another 5% of water making the filtrate even more hyposmotic

Identify.

Early distal tubule

Key identifier: it’s ONLY job is to reabsorb Na+ and Cl-. Sodium/ Chloride secondary active symporter

What are the two different cell types found in the late distal tubule and cortical collecting duct?

1. Principal Cells

2. Intercalated Cells

   • Alpha

   • Beta

What are principal cells responsible for?

• The site of ALDOSTERONE and ADH action!

• Reabsorb Na+ and H2O

• Secrete K+

Identify

Principal Cell

Key Identifiers: The Na+/K+ ATPase is on the basolateral membrane that keeps the sodium concentration low and potassium gradient high inside the cell. This promotes the passive movement of Na+ into cell to be actively pumped out. K+ is secreted into the lumen. Processes are regulated by aldosterone

Is the late distal tubule/ cortical collecting duct permeable to urea?

No

What are alpha intercalated cells responsible for?

• Function is important during ACIDOSIS

• Secrete H+ into the lumen, reabsorb K+ and HCO3-

• Excrete acid from the body via urine

• SECRETING ACID, ABSORBING BASE

Identify.

Alpha intercalated cells

Key identifier: Secreting acid H+, and reabsorbing base HCO3- and K+

What are beta intercalated cells responsible for?

• Function important for alkalosis

• Secrete K+ and HCO3-

• Reabsorb H+

• Opposite to alpha intercalated cells

Identify.

Beta intercalated cells

Key identifiers: Primary active H+ transporters in the basolateral membrane, and bicarb secreted on apical membrane. B cells secrete base.

What is the medullary collecting duct responsbile for?

• Contains principal cells and alpha intercalated cells

• Processes less than 10% of Na+ and H20 but still very important

• Site of Aldosterone and ADH action

• Urea is REABSORBED via facilitated diffusion

• Secretes H+ using the same mechanism as the alpha intercalated cells

• Where balance is created