Mechanisms of regulation of tubular reabsorption

- Glomerulotubular balance
 Intrinsic mechanism
 Ability of PCT to increase reabsorption capacity due to increased tubular load
 Prevent overloading of the distal tubular segments when GFR ↑

- Peritubular capillaries and Renal ISF physical forces

 Reabsorption = Kf x Net reabsorptive force
 Kf: reabsorption coefficient = 12.4 ml/min/mm Hg
 Net reabsorptive force = 10 mmHg
 Capillary hydrostatic pressure = 13 mmHg
 Results from blood flow in peritubular capillaries
 Opposes the reabsorption
 Depends on two main factors
 Systemic BP: ↑BP = ↑ Hydrostatic P. = ↓
reabsorption
 Resistance of arterioles: constriction ↑ resistance = ↓
Hydrostatic P. = ↑ reabsorption
 Plasma colloid osmotic pressure in peritubular capillaries = 32 mmHg
 Facilitates reabsorption
 Depends on
 Systemic plasma colloid pressure: if increases it will
increase colloid pressure in peritubular capillaries & ↑
reabsorption
 Filtration fraction: if increases it will ↑ protein
concentration and thus ↑ reabsorption
 Interstitial fluid hydrostatic pressure = 6 mmHg: facilitates
reabsorption
 Interstitial fluid colloid osmotic pressure = 15 mmHg : opposes
reabsorption

 Reabsorption = Kf x Net reabsorptive force = 124 ml/min

 When reabsorption decreases
 Due to increases peritubular capillary hydrostatic pressure
 The filtrate will remain in the ISF
 ↓ the net reabsorption
 ↑the back leak & urine formation
 And vice versa
- Hormonal control
 Aldosterone:
 Sodium retaining hormone
 ↑ Na/K pumps of principle cells in DCT and collecting tubules
 Addison's disease: aldosterone deficiency
 Loss of Na+ and water
 Accumulation of K+ (hyperkalemia)
 Conn's syndrome: aldosterone excess
 Na+, water retention
 K+ depletion which causes hypokalemia

 ADH:
 Acts also on distal and collecting duct
 Increase ↑H2O reabsorption
 Production of more concentrated urine

 Angiotensin II:
 Secreted in response to fall in BP
 Responsible for the reabsorption of Na+
 Acts on almost all segment of the nephron
 Activate the secretion of aldosterone
 Constrict the efferent arteriole
 Decreases peritubular hydrostatic pressure
 Increases the filtration fraction
 Increases plasma colloid osmotic pressure
 Increases the tubular reabsorption
 Receptors (AT1) are found on basolateral &
luminal surfaces
 Activates multiple transporters that reabsorbs Na+
 Na-K pump on basolateral membrane
 Na-HCO3 cotransporter on basolateral membrane
 Na-H counter-transporter on luminal membrane
 Acidifies urine and plays a role in acid-base balance

 Vasopressin
 Also known as anti-diuretic hormone (ADH)
 Secreted from the posterior pituitary gland
 The major stimulus for secretion is ↑ plasma
osmolality
 Acts primarily on DCT and collecting tubules
  Increases water reabsorption
 Its receptors (V2) are GPCR & found on basolateral membrane
 Binding to receptors increases c-AMP that stimulates PKA
 PKA causes phosphorylation and activation of aquaporins (AQP2)
 Causes translocation of AQP2 channels to luminal membrane

 Atrial natriuretic peptide

 Secreted from the atrium in the heart
 Works on the distal tubule, collecting tubule and collecting duct
 Reduces sodium reabsorption
 Secreted when there’s an expansion in plasma volume

 Parathyroid hormone
 Works on PCT, thick ascending loop of Henle and distal tubule
 Decreases phosphate reabsorption
 Increase calcium reabsorption

- Sympathetic control of the tubular reabsorption

 Constricting the afferent arteriole primarily
 Constricting the efferent arteriole minimally
 Reduces the filtration of the nephron
 Increases the process of reabsorption
 Increases the filtration fraction
 Increases renin secretion to activate RAAS

Regulation of Potassium (K+) Excretion

- 98% of the body's K+ is found in the intracellular compartment
- 2% is in the extracellular fluid
- It is necessary to keep those percentages fixed
- Hyperkalemia
 Activation of the excitable tissue
 Partial depolarization of cell membranes
 Cardiac toxicity: arrhythmias, fibrillation, asystole and arrest

- Hypokalemia
 Weakening in the excitable tissue
 Reduction in the depolarization
  Hyperpolarization of cell membranes
 Fatigue, muscle weakness
 Hypoventilation
 Delayed ventricular repolarization

- Factors that shift K into the cells:

 Insulin
 Aldosterone
 Beta-adrenergic stimulation
 Alkalosis

- Factors that shift K out of the cells:

 Insulin deficiency
 Aldosterone deficiency
 Beta-adrenergic blockade
 Acidosis
 Damage of body cells: cell lysis and strenuous exercise
 Dehydration and increased osmolality

- Potassium absorption and excretion

 65% of excess K+ is reabsorbed in the proximal tubular segment
 27-30% reabsorbed in the ascending limb of loop of Henle
 The major sites of secretion are the DCT and collecting tubules
 Acidosis decreases K+ secretion
 Alkalosis increases K+ secretion
 Principal cells
 The major cells responsible for K+ secretion
 Contain important K+ channels on their luminal membrane
 Present in distal tubule and collecting ducts
 Channels for K+ secretion are:
 BK channels "Big Potassium channels"
 ROMK "Renal Outer Medullary
potassium channels"
 ENaC channels "Epithelial Na+ Channels"
 Found in the luminal membrane
 Responsible for Na+ reabsorption
 Aldosterone stimulates all of these channels
The effect of increasing the intake of K+ on the levels of K+ excretion
- Increase K+ intake increases plasma K+ concentration
- Increased plasma K+ concentration is the major stimulus of aldosterone release
- Aldosterone increases K+ secretion in collecting tubules thus increasing excretion
- Ingestion of large amounts of potassium doesn’t increases the plasma K+ levels
significantly due to the effect of aldosterone
- Block of aldosterone effect will cause hyperkalemia to dangerous levels

The effect of increase Na+ intake on K+ secretion and excretion:

- Secretion of K+ is not affected much by an increase in Na+ intake
- Increase of Na+ intake increases BP & GFR
- Increased GFR increases the distal tubular flow rate
- Increase tubular flow in DCT will directly enhance K+ secretion
- Na+ intake reduces aldosterone release
- Reduced aldosterone release reduces K+ secretion
- The first effect will cancel the second one