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