Tubular Reabsorption & Secretion
A comprehensive guide to transport mechanisms, thresholds, energetics, and clinical syndromes.
Mechanisms & Calculations
Reabsorption is the selective reclamation of substances from the tubular fluid back into the blood. Unlike filtration, which is non-selective based on size, reabsorption is highly selective.
Excretion = Filtration - Reabsorption + Secretion
Selective Handling:
- Complete Reabsorption: Glucose, Amino Acids (100% returned to blood).
- Partial Reabsorption: Ions like Na+, Cl-, HCO3- (regulated by body needs).
- No Reabsorption: Waste products like Creatinine (excreted efficiently).
Calculations
Filtered Load
Load = GFR × Plasma Conc.
Example: GFR 180L/day × Glucose 1g/L = 180g Glucose/day.
Transport Maximum & Thresholds
The Concept of Saturation
Glucose reabsorption relies on carrier proteins (SGLT). Like any enzyme-like system, it can be saturated.
- Transport Maximum (Tm): The maximum rate of reabsorption when all carriers are full. For glucose, Tm ≈ 375 mg/min.
- Renal Threshold: The plasma concentration at which glucose first appears in urine. Theoretically ~300 mg/dL, but actually ~200 mg/dL due to "splay".
- Splay: The gap between the Threshold and Tm. It occurs because not all nephrons have the same length or number of carriers. Some release glucose before the average Tm is reached.
Transport Differences:
High Capacity / Low Affinity. Reabsorbs 90%.
Low Capacity / High Affinity. Sweeps up remaining 10%.
Glucose Titration Curve
Green line flattens at Tm (Transport Max). Blue line rises only after Threshold is passed.
Proximal Tubule Workhorse
Major Reabsorption Statistics
Cellular Adaptations
The proximal tubule cells are highly metabolic with extensive brush borders (microvilli) to maximize surface area. They contain abundant mitochondria to power the Na+/K+ ATPase pumps.
Secondary Active Transport
Sodium-Glucose Co-transport: Sodium moves down its gradient (established by the basal pump), dragging glucose or amino acids with it against their gradients.
Angiotensin II Effect: Stimulates the Na+/H+ Exchanger (NHE) on the luminal membrane, increasing Na+ reabsorption and H+ secretion (linked to Bicarb reabsorption).
Amino Acid Transport
Amino acids are reabsorbed via specific carriers, similar to glucose. They are grouped by chemical nature:
- • Acidic (Aspartate, Glutamate)
- • Basic (Lysine, Arginine)
- • Neutral (Glycine, Proline)
Note: Proteins enter via Pinocytosis (endocytosis) and are digested into amino acids within the cell.
Renal Energetics
The kidney consumes oxygen primarily to support sodium reabsorption. There is a linear relationship between Na+ reabsorbed and O2 consumed.
- • Renal blood flow is high (20-25% of Cardiac Output) not for metabolic need, but for filtration.
- • Basal O2 Consumption: Even with no filtration, kidneys use O2 for basic cell survival (yellow area in graph).
- • Beyond basal, every unit of O2 is spent pumping Na+.
Concentration Changes Along the Tubule
Tubular Fluid / Plasma Ratio (TF/P)
This graph shows how the concentration of solutes changes as fluid moves through the proximal tubule.
- Sodium: Remains at 1.0. Because water is reabsorbed at the exact same rate as sodium (Iso-osmotic reabsorption), the concentration doesn't change, even though the total amount decreases.
- Glucose/AA: Drops rapidly. Reabsorption is faster than water reabsorption. By the end of the proximal tubule, concentration is near zero.
- Creatinine: Rises sharply. It is not reabsorbed at all. As water leaves the tubule, Creatinine gets concentrated.
- Urea: Rises moderately. About 50% is passively reabsorbed, but the rest concentrates as water leaves.
Passive Transport & Pathology
Passive Reabsorption Mechanisms
Reabsorption of Na+ and water creates a concentration gradient for Cl-, and also makes the lumen slightly negative compared to interstitium. Cl- follows passively.
Passive reabsorption. As water leaves, urea concentration rises in the lumen, creating a gradient for it to diffuse back into blood (~50% reabsorbed).
Cell membranes are lipid bilayers. Lipid-soluble drugs or vitamins diffuse freely back into blood and are hard to excrete.
Protein Handling
Proteins like albumin are generally too large (7nm) to filter, but small amounts do pass.
Proteins bind to the brush border, the membrane invaginates forming a vesicle. Inside the cell, enzymes digest the protein into amino acids which are then returned to blood.
Requires energy (ATP). This is an active transport mechanism.
Nephrotic Syndrome
Definition: Increased permeability of glomerular capillaries to proteins, leading to massive proteinuria (>3.5g/day).
- Cause: Damage to podocytes or slit diaphragm proteins (Nephrin, Podocin).
- Consequence: Loss of albumin reduces blood oncotic pressure -> fluid leaks into tissues -> Severe Edema.
Fanconi's Syndrome
Generalized failure of the Proximal Tubule reabsorption.
- Mechanism: Genetic or acquired (toxins/drugs) damage to proximal cells or lack of ATP.
- Result: Loss of EVERYTHING that is normally reabsorbed early:
- - Glucose (Glycosuria)
- - Amino Acids (Aminoaciduria)
- - Bicarbonate (Acidosis)
- - Phosphate (Rickets/Bone issues)