Human Physiology: Plasma Osmolarity & Sodium Regulation

Urine Concentration and Dilution

• The body's cells function properly in a constant electrolyte concentration and osmolarity in extracellular fluid
• Osmolarity is determined by solute amount/fluid volume
• Extracellular fluid osmolarity, and sodium chloride concentration, is mostly regulated by extracellular water amount.
• Fluid intake is regulated by thirst mechanisms
• Renal water excretion is controlled by factors affecting glomerular filtration and tubular reabsorption.
• Kidneys excrete excess water via dilute urine.
• Kidneys conserve water by excreting concentrated urine
• Extracellular fluid sodium concentration and osmolarity are controlled by feedback systems
• Thirst and salt appetite mechanisms influence water and salt intake, further regulating extra cellular fluid volume, osmolarity, and sodium concentration.

Antidiuretic Hormone (ADH) Controls Urine Concentration

• ADH, also known as vasopressin, is a powerful feedback system for regulating plasma osmolarity and sodium concentration.
• When body fluid osmolarity increases (becoming more concentrated), the posterior pituitary secretes more ADH.
• ADH increases water permeability in distal tubules and collecting ducts for water reabsorption.
• This mechanism decreases urine volume without significantly altering solute excretion rates.
• Excess body water (reduced extracellular osmolarity) decreases ADH secretion from the posterior pituitary.
• This reduction decreases water permeability, resulting in more dilute urine and increased urine volume.
• ADH secretion significantly determines whether the kidney produces dilute or concentrated urine.

Renal Mechanisms for Excreting Dilute Urine

• Highly concentrated urine (up to 20 liters daily) can be excreted when there's excessive body water.
• Solutes are reabsorbed in distal nephron segments without significant water reabsorption.
• This process effectively dilutes urine.

Tubular Fluid in Proximal Tubules

• As fluid flows through proximal tubules, solutes and water are reabsorbed equally.
• Osmolarity remains isosmotic to plasma (about 300 mOsm/L).

Tubular Fluid in Ascending Loop of Henle

• Sodium, potassium, and chloride are actively reabsorbed within the loop of Henle.
• The segment is impermeable to water.
• Tubular fluid becomes more dilute.
• Osmolarity decreases progressively to about 100 mOsm/L by the time it enters the early distal tubule.
• In the absence of ADH, the osmolarity decreases to as low as 50 mOsm/L as it reaches the distal & collecting tubules.

Tubular Fluid in Distal and Collecting Tubules (without ADH)

• Additional reabsorption of sodium chloride occurs.
• Water is not reabsorbed without ADH.
• Tubular fluid becomes even more dilute, decreasing its osmolarity down to 50 mOsm/L.

Kidneys Conserve Water via Concentrated Urine

• The kidneys have the capability to concentrate urine, which is crucial for survival in terrestrial mammals, especially when water is scarce.
• Maximum urine concentration in humans is 1200-1400 mOsm/L (four to five times plasma osmolarity)
• Some desert animals can concentrate urine as high as 10,000 mOsm/L.
• Animals with minimal water scarcity have less concentrating ability (e.g., beavers ~ 500 mOsm/L).
• To excrete solutes and other waste, a minimum urine volume (obligatory urine volume) must be produced daily.

Obligatory Urine Volume

• To remove metabolic waste products and electrolytes from the body, a minimum urine volume (obligatory urine volume), needs to be excreted each day.
• This volume is 0.5 L/day if the maximal urine concentrating ability is 1200 mOsm/L and solute excretion is 600 mOsm/day.
• Severe dehydration occurs if a person drinks seawater.

Urine Specific Gravity

• It's a measure of urine density (g/mL) that correlates with the concentration of solutes in the urine.
• Higher urine osmolarity is associated with higher specific gravity.
• Clinically, specific gravity is used to initially estimate the concentration of solutes in the urine.

Loop of Henle Characteristics

• Crucial for establishing a medullary interstitial concentration gradient
• Active transport of sodium chloride in the thick ascending limb creates this gradient.
• Descending limb of Henle is permeable to water, leading to tubular fluid concentration increase.
• Fluid entering is initially 300 mOsm/L; osmolarity progressively rises to 1200-1400 mOsm/L.
• Medullary interstitial fluid's high concentration is partly due to urea reabsorption.

Countercurrent Multiplier Mechanism & Hyperosmotic Renal Medulla

• A system maintaining high solute concentration within the medulla through the loops of Henle and vasa recta.
• Active sodium chloride transport in the ascending limb generates the solute concentration gradient.
• Water passively moves out of the descending limb, increasing concentration.

Hyperosmotic Renal Medulla's Role

• Crucial for high urine concentration, especially in dry conditions.
• High interstitial solute concentration is required for water reabsorption.
• Helps minimize water intake requirements.

Role of Distal Tubules & Collecting Ducts

• Water permeability depends on ADH levels.
• High ADH leads to high water permeability and urine concentration.
• When ADH levels are low, water permeability is lowered.
• The distal tubule actively transports ions into the medulla, facilitating urine concentration.

Urea's Role in Urine Concentration

• Urea contributes significantly to medullary interstitial osmolarity, especially when urine is concentrated.
• Urea is passively reabsorbed from the inner medullary collecting ducts into the interstitium.
• This process facilitates further urine concentration.

Countercurrent Exchange in Vasa Recta

• Vasa recta maintain a stable medullary solute concentration.
• Specialized capillaries that run alongside loops of Henle, which minimizes solute loss from medulla.

Quantification of Renal Urine Concentration and Dilution

• Osmolar clearance (Cosm) measures the volume of plasma cleared of solutes per minute.
• Calculated using urine osmolarity, urine flow rate, plasma osmolarity.
• Free water clearance (CH2O) measures solute-free water excretion.
• Positive CH2O indicates excess water excretion.
• Negative CH2O indicates water conservation.

Disorders of Urinary Concentrating Ability

• Inappropriate ADH secretion (diabetes insipidus).
• Impairment of the countercurrent mechanism.
• Inability of distal tubules to respond to ADH.
• central diabetes insipidus.
• nephrogenic diabetes insipidus.

Osmoreceptor-ADH and Thirst Feedback Systems

• These mechanisms jointly regulate extracellular fluid osmolarity.
• Osmoreceptor cells in the hypothalamus respond to changes in osmolarity, signaling to the posterior pituitary to release ADH.
• Thirst is regulated based on the need to prevent excessive fluid loss.
• Thirst mechanisms include osmoreceptors, arterial pressure, and blood volume sensors.

Salt Appetite and Sodium Intake Regulation

• A strong desire to consume salt when sodium levels are low.
• Necessary to balance sodium excretion and intake.
• Stimuli for salt appetite may include decreases in blood volume or pressure.