Kidney Function and GFR Factors

Kidney Function

• The kidneys receive about 1/4 of the cardiac output
• Approximately 1.5 liters of urine are excreted every day
• The kidneys perform glomerular filtration, tubular reabsorption, and tubular secretion.
• The glomerular filtrate is identical in composition with plasma, but without proteins.

Factors Affecting Glomerular Filtration Rate (GFR)

• Increased intra-glomerular hydrostatic pressure increases GFR.
  • This can be caused by:
    • Dilation of the afferent arteriole
    • Increased arterial blood pressure
    • Constriction of the efferent arteriole
• Increased intra-glomerular osmotic pressure decreases GFR.
  • Caused by increased plasma protein concentration.
• Increased intra-capsular hydrostatic pressure decreases GFR.
  • This may be caused by:
    • Tubular obstruction
    • Renal edema

Tubular Reabsorption & Secretion

• The efferent arteriole subdivides to form peritubular capillaries, where reabsorption and secretion take place.
• The luminal surface of the tubular cell is the apical membrane.
• The basolateral membrane is on the other side of the tubular cell.
• The apex of each tubule cell is surrounded by a tight junction.

Movement Pathway of Ions & Water

• Trancellular pathway: Across the tubular cells.
• Paracellular pathway: Across the tight junctions between cells.

Sodium Reabsorption

• Approximately 67% of sodium is reabsorbed in the proximal convoluted tubule (PCT).
• Sodium is reabsorbed in exchange for hydrogen ions via the Na+/H+ antiporter.
• Intracellular carbonic anhydrase is essential for producing H+ for secretion into the lumen.
• Sodium is transported into blood via the Na+/K+ ATPase in the basolateral membrane.
• The transport of sodium via the Na+/H+ antiport is driven by the Na+/K+ ATPase.

Bicarbonate Reabsorption

• Bicarbonate is normally completely reabsorbed in the PCT.
• Bicarbonate combines with H+ to form H2CO3, which is catalyzed by brush border carbonic anhydrase.
• H2CO3 dissociates to form CO2 and water.
• CO2 is passively reabsorbed in the lumen.

Water Reabsorption

• Water is passively reabsorbed through the paracellular pathway.
• Water reabsorption is secondary to sodium reabsorption.
• Sodium secreted by Na+/K+ ATPase into the lateral intercellular space slightly raises the osmolality, driving water reabsorption by convection.

Chloride Reabsorption

• Chloride is transported into blood by passive reabsorption through the paracellular pathway down its concentration gradient.
• It is also reabsorbed in exchange for anions, such as formate and oxalate.

Nephron Segments: Proximal Convoluted Tubule (PCT)

• Fluid leaving the PCT remains isosmotic to the filtrate that enters Bowman's capsule.

Nephron Segments: Descending Limb

• The interstitial fluid of the medulla is hypertonic.
• The filtrate becomes more concentrated (hyperosmotic) as it passes down the descending limb.

Nephron Segments: Ascending Limb

• Approximately 20% of filtered sodium is reabsorbed in the ascending limb.
• Ions (Na+, K+, Cl-) move into the cell across the apical membrane via a Na+/K+/2Cl- symporter.
• Sodium is transported into blood via Na+/K+ ATPase.
• Chloride is transported into blood by diffusion through Cl- channels and by the K+/Cl- symporter.
• Most of the potassium taken by the Na+/K+/2Cl- symporter returns to the lumen through apical K+ channels.

Nephron Segments: Thick Ascending Limb

• The thick ascending limb is relatively impermeable to water.
• Reabsorption of salt is not accompanied by water reabsorption.
• This makes the filtrate more diluted (hyposmotic) as it passes upward.
• The thick ascending limb is known as the diluting segment.
• The process of concentration and then dilution of filtrate in the loop of Henle is known as the "counter-current multiplier theory".

Nephron Segments: Distal Convoluted Tubule (DCT)

• Approximately 7% of filtered sodium is reabsorbed.
• NaCl is reabsorbed without water, further diluting the filtrate.
• NaCl is reabsorbed via the Na+/Cl- symporter.
• This transport is driven by the Na+/K+ ATPase.

Calcium Reabsorption

• Calcium is transported through channels in the apical membrane and then transported into blood via the Na+/Ca2+ antiporter.
• Parathyroid hormone (PTH) and calcitriol increase calcium reabsorption.
• Calcium is also reabsorbed via the paracellular pathway in the ascending limb of the loop of Henle.

Hydrogen Ion Secretion

• When all filtered bicarbonate has been reabsorbed in the PCT, the Na+/H+ exchange in the apical membrane continues in the DCT.
• Hydrogen ions are added to Na2HPO4 to give NaH2PO4 and to NH3 to give NH4+.
• Intracellular carbonic anhydrase is essential for producing H+ for secretion into the lumen.

Nephron Segments: Collecting Tubules

• Approximately 5% of filtered sodium is reabsorbed.
• Most of K+ and H+ are secreted.
• The collecting tubule has two types of cells:
  • Principal cells: Where sodium reabsorption and potassium secretion occur.
  • Intercalated cells: Where hydrogen secretion takes place.
• The collecting tubule is under hormonal control:
  • Aldosterone: Controls sodium reabsorption and potassium secretion.
  • Antidiuretic hormone (ADH; vasopressin): Controls water absorption according to the body's water needs.

Aldosterone

• Aldosterone enhances sodium reabsorption and potassium excretion by:
  • Stimulating Na+/H+ exchange by acting on membrane aldosterone receptors (rapid effect).
  • Activating sodium channels in the apical membrane by directing the synthesis of a protein mediator (delayed effect).
  • Increasing the number of basolateral Na+/K+ ATPase.

Antidiuretic Hormone (ADH)

• ADH is secreted by the posterior pituitary.
  • Increased blood osmolality stimulates osmoreceptors in the hypothalamus, which stimulates ADH secretion.
  • Increased blood volume or blood pressure stimulates baroreceptors, which inhibits ADH secretion.
• ADH binds to V2 receptors in the basolateral membranes, increasing water channels in the apical membranes.
• This renders the collecting duct permeable to water, allowing passive reabsorption of water as the collecting duct passes through the medulla.
• The filtrate is concentrated, and the body excretes concentrated urine.

Diabetes Insipidus

• Neurogenic diabetes insipidus: May be caused by a deficiency of ADH secretion.
• Nephrogenic diabetes insipidus: May be caused by insensitivity of the kidney to ADH due to:
  • Congenital mutations in the V2 receptor or water channels.
  • Acquired causes, such as certain drugs.
• In these cases, the collecting duct cells are impermeable to water, leading to excretion of dilute urine, polyuria, nocturia, and polydipsia.
• Daily urine output may reach 10-15 liters.

Other ADH Actions

• At high concentrations, ADH acts on the V1 receptor subtype in smooth musculature, including blood vessels, causing vasoconstriction, increasing blood pressure.
• ADH derivatives: Lypressin, Desmopressin, Felypressin, ornipressin (used for various medical conditions).

Organic Acid & Base Secretion

• Organic molecules enter the renal tubules by glomerular filtration or active secretion.
• Organic anions are exchanged with α-ketoglutarate by an antiport in the basolateral membrane called organic anion transporters (OATs).
• Organic cations diffuse into the cell from blood and are actively transported into the tubular lumen in exchange for H+.
• These systems are powered by the energy derived from Na+/K+ ATPase in the basolateral membrane.

Ammonia Secretion

• Ammonia is formed in the DCT by deamination of glutamine by glutaminase.
• Ammonia diffuses into the lumen and combines with H+, forming NH4+.
• This prevents undue accumulation of H+ in the filtrate and permits continued exchange of H+ for Na+.

Explore the essential functions of the kidneys, focusing on glomerular filtration, tubular reabsorption, and tubular secretion. Understand the factors influencing the glomerular filtration rate (GFR) and how various pressures affect kidney performance. Test your knowledge on these crucial physiological processes.