Renal handling of organic substances

[Ref: AV6:Chp5]

Organic nutrients

• Most organic nutrients are completely resorbed.
• Most are Tm-limited system
• Most are via a symporter with Na+
• Specificity

 

Glucose

• Reabsorbed from lumen across the apical lumen
  * via SGLT2 (symporter with Na+)
• Exit the tubular cells across the basolateral membrane
  * via GLUT2 (uniporter)
• Tm-limited

Tm-limited system

Tm = 375 mg/min

Since GFR = 125mL/min

Tm is reached when plasma glucose
= 300 mg/dL

Renal threshold

Renal threshold is the plasma level of glucose at which glucose first appear in the urine in more than the normal minute amount.

• Arteral plasma glucose level
  = 200 mg/dL, OR
• Venous plasma glucose level
  = 180 mg/dL

NB:

• Lower than the theoretical 300mg/dL due to splay
• Reabsorption of glucose still increases when glucose increases above the renal threshold until Tm is reached
• 1 mol of glucose = ??180 gram

 

Proteins and peptides

Large proteins

Albumin concentration in filtrate = 10mg/L
--> 1.8g/day
--> Only 100mg/day excreted

Proteins in filtrates are taken up at the luminal membrane
* via endocytosis
* Including hormones

Protein taken up into tubular cells
--> Degraded into amino acid
--> Transport across basolateral membrane into ISF

Endocytic mechanism easily saturated

Small peptides

Completely filterable at Bowman's capsule

--> Catabolized into amino acids
* Within proximal tubular LUMEN
* By peptidases located on the luminal membrane

--> Transported across basolateral membrane into ISF

 

pH dependence of passive reabsorption or secretion

Neutral forms of organic acids and bases are more permeable in lipid membranes than ionized formed.

Neutral forms can diffuse in or out of lumen down the concentration gradient

Ionized forms, once in the lumen, cannot diffuse out.

Thus,

• Highly acidic urine
  --> Weak acids less ionized
  --> Greater reabsorption of weak acids
  --> Less excretion of weak acids
• Highly alkaline urine
  --> Weak base less ionized
  --> Greater reabsorption of weak bases
  --> Less excretion of weak bases

The reverse is also true, ie.

• Highly acidic urine
  --> Greater excretion of weak base
• Highly alkaline urine
  --> Greater excretion of weak acids