Tubular Reabsorption and Filtration

Tubular Reabsorption Overview

• Tubular reabsorption is selective, unlike glomerular filtration which is non-selective (except for proteins and blood cells).
• Substances such as glucose and amino acids can be fully reabsorbed.
• Urea and creatinine are waste products that the body typically excretes.

Filtration Rate

• Filtration is equal to the product of the Glomerular Filtration Rate (GFR) and plasma concentration.
• Glomerular filtration and tubular reabsorption have significant volume.

Reabsorption Mechanisms

• For reabsorption, a substance crosses tubular epithelial membranes into the renal interstitial fluid, then the peritubular membrane and back into the blood flow.
• Peritubular capillaries function similarly to venous capillary ends.
• Water and solutes transport through cell membranes (transcellular) or between cells (paracellular).

Overview of primary active transport

• Na-K-ATPase, H-ATPase, H-K-ATPase, and Ca-ATPase facilitate primary active transport.

Overview of Secondary Active Transport

• Secondary active transport can either be:
  • Co-transport (symport).
  • Counter-transport (antiport).

Pinocytosis Details

• Pinocytosis is a process where some parts of the tubule, mainly the proximal tubule, reabsorb proteins.
• Protein attaches to the luminal membrane's brush border, then invaginates, and a vesicle forms with the protein inside.
• The protein is digested into amino acids, then reabsorbed into the interstitial fluid via the basolateral membrane.
• Pinocytosis requires energy, therefore it is a form of active transport.

Water Reabsorption

• Passive water reabsorption via osmosis links principally to sodium reabsorption.
• Aquaporins facilitate water reabsorption.
  • AQP1, AQP7, and AQP8 are present in the proximal tubule.
  • AQP1 is present in the descending thin-limb epithelium.
  • AQP2, AQP3, and AQP4 are present in the collecting-duct epithelium's principal cells.
  • AQP6 is present in the collecting-duct epithelium's intercalated cell.

Chloride, Urea, And Creatinine Waste

• Chloride passively diffuses through the paracellular pathway.
• Urea is passively reabsorbed from the tubule, but to a lesser extent.
• Creatinine is not typically reabsorbed, and is excreted as waste.

Proximal Tubule Functions

• Proximal tubule typically reabsorbs about 65% of the filtered sodium and water.
• The proximal tubule has a high capacity for active and passive reabsorption.
• Proximal tubule epithelial cells are highly metabolic and have many mitochondria.

Sodium Symport

• Na+ is pumped into the interstitial space by the Na+-K+ ATPase on the basolateral membrane.
• Active Na+ transport creates concentration gradients that drive "downhill" Na+ into the apical membrane.
• Organic nutrients and certain ions are then reabsorbed by cotransport at the apical membrane.
• Water is reabsorbed via osmosis through aquaporins
• Lipid-soluble substances diffuse via the transcellular route
• Various ions and urea diffuse by the paracellular route.

Loop of Henle Details

• Consists of the descending thin segment, ascending thin segment, and ascending thick segment.
• The descending segment is highly permeable to water.
• Ascending segments are virtually impermeable to water.
• The thin ascending segment has much lower absorption capacity.
• The descending part of the thin segment is highly permeable to water and moderately permeable to urea and sodium.
• The nephron segment allows simple substance diffusion through its walls.
• 20% of filtered water typically reabsorbed, mostly in the thin descending limb.
• Filtrate becomes more concentrated as it loses water:
• Juxtamedullary nephrons: 1200 mosm/L
• Cortical nephrons: 600 mosm/L
• The ascending limb (thin and thick portions) is virtually impermeable to water, which concentrates the urine.
• The thick segment has high metabolic activity epithelial cells to reabsorb Na, Cl, and K.
• The thick ascending limb reabsorbs ~25% filtered Na, Cl, and K, including Ca, HCO3, and Mg.
• This segment also secretes hydrogen ions into the tubular lumen

Ascending Loop Transporters

• Movement of sodium across the luminal membrane is mediated by an 1-sodium, 2-chloride, 1-potassium co-transporter.
• This protein uses the potential energy from downhill sodium diffusion into the cell to drive potassium reabsorption against its concentration gradient.

Site of Action

• Furosemide inhibits the Na, 2 Cl, K co-transporter mechanism.
• Significant paracellular reabsorption of cations (Mg, Ca, Na, K) occurs in the thick ascending limb due to the slight positive charge in the tubular lumen relative to the interstitial fluid.
• A Na-H counter-transport mechanism also exists.
• The segment is impermeable to water.
• Tubular fluid becomes very dilute as it flows toward the distal tubule.

Distal Tubule Details

• Consists of a connecting tubule, cortical collecting duct, and medullary collecting duct.
• The initial portion forms part of the juxtaglomerular apparatus, providing GFR and blood flow feedback.
• Hormones control water and ion reabsorption in the distal tubules.
• Next part of the distal tubule is highly convoluted and has the same reabsorptive characteristics, most importantly, the absorption of sodium, potassium and chloride, and the impermeability of water.
• Due to impermeability of water, the segment is referred to as the diluting segment.
• The tubular fluid is diluted to 100 mosm/L.
• ~5% of sodium chloride is reabsorbed in the early distal tubule.
• The Na-Cl co-transporter moves Na and Cl from the tubular lumen into the cell, while the Na-K ATPase pump moves Na out of the cell across the basolateral membrane.
• Cl diffuses into the renal interstitial fluid through Cl channels in the membrane.
• Thiazide diuretics, used for hypertension and heart failure, inhibit the Na-Cl co-transporter.

Late Distal Tubule and Cortical Collecting Tubule

• Has similar functional characteristics to the second half of the distal tubule.
• Anatomically composed of principal and intercalated cells.
• Principal cells reabsorb Na and water and secrete K into the lumen.
• Intercalated cells reabsorb K and HCO3 ions and secrete H ions into the tubular lumen.
• Water reabsorption is controlled by antidiuretic hormone (ADH) concentration.
• Tubular membranes are impermeable to urea.
• Tubule segments reabsorb Na, which secretion can be controlled by Aldosterone and K.
• Intercalated cells secrete H ions via an active H-ATPase mechanism.
• Tubule permeability to water is controlled by ADH.

Medullary Collecting Duct (MCD) Functions

• MCD reabsorbs less than 10% of filtered water and Na, but is the final site for processing urine output.
• The permeability to water is controlled by ADH.
• Unlike the cortical collecting tubule, MCD is permeable to urea, therefore forming a concentrated urine.
• Capable of secreting H ions against a concentration gradient and plays a role in acid-base balance.

Hormonal Control of Tubular Reabsorption Overview

• The kidneys excrete different solutes and water at variable rates, sometimes independently, to regulate body fluid volumes and solute concentrations.
• Principal cells of the cortical collecting tubule: Aldosterone increases NaCl and H2O reabsorption, and increases K+ secretion.
• Proximal tubule, thick ascending loop of Henle/distal tubule, collecting tubule: Angiotensin II increases NaCl and H₂O reabsorption.
• Distal tubule/collecting tubule and duct: Antidiuretic hormone increases H₂O reabsorption, and Atrial natriuretic peptide (ANP) decreases NaCl reabsorption.
• Proximal tubule, thick ascending loop of Henle/distal tubule: Parathyroid hormone decreases 4 reabsorption, and increases Ca++ reabsorption.

Hormonal Control Details

• Aldosterone increases Na reabsorption and K secretion, primarily on principal cells of the distal collecting tubule.
• Angiotensin II increases Na and water reabsorption, stimulates aldosterone secretion, constricts efferent arterioles and directly stimulates Na reabsorption.
• ADH (Vasopressin) increases water reabsorption.
• ANP decreases Na and water reabsorption.
• Parathyroid hormone increases Ca reabsorption.
• Sympathetic activation increases Na reabsorption.

Glucose Reabsorption Specifics

• Plasma and ultrafiltrate glucose concentration: 80-120 mg/dL.
• Reabsorption occurs only in the proximal tubules.
• Secondary active transport mechanisms on the apical side of the proximal tubules and facilitated diffusion occurs at the basolateral portion.
• Excess glucose can be detected in the urine (glucosuria).
• SGLT-2 is a high capacity, low affinity transporter reabsorbing one sodium to one glucose in the initial segments
• SGLT-1 is a low capacity, high affinity transporter, transporting two sodium to one glucose in the final segments.

Transepithelial Glucose Transport

• Primary active transport of Na+ is required, because it is pumped out of the cell on the basolateral side, to maintain a low concentration inside the cell.
• Secondary active transport moves glucose uphill into the cell along with Na+.
• Glucose is transported into the peritubular capillary by facilitated diffusion

Transport Maximum Overview

• Most substances actively reabsorbed or secreted have a transport maximum, which is the limit to the rate at which the solute can be transported.
• The limit occurs due to saturation of the involved transport systems when the amount exceeds the carrier proteins and specific enzymes capacity.

Tubuloglomerular Feedback and Balance

• Intrinsic ability of the tubules to increase their absorption rate in response to increased tubular load, referring to increased tubular inflow.
• Tubuloglomerular feedback helps prevent changes in GFR as a first defense.
• Glomerulotubular balance acts as a second line of defense to buffer GFR changes on urine output.
• Glomerulotubular balance the total reabsorption rate increases as the load increases, even though the percentage of GFR reabsorbed in the proximal tubule averages ~65%.