Countercurrent Mechanism & Urine Concentration

• The body needs stable electrolyte concentrations in extracellular fluid for cells to function.
• Osmolarity, the total solute concentration in extracellular fluid must also be regulated to prevent cell swelling or shrinking.
• Osmolarity is determined by the amount of solute, mainly sodium chloride, divided by the extracellular fluid's volume.
• Extracellular fluid osmolarity and sodium chloride concentration are controlled by the amount of extracellular water.
• Factors regulating thirst influence fluid intake.
• Factors influencing glomerular filtration and tubular reabsorption regulate the renal water excretion.
• Kidneys eliminate excess water by excreting dilute urine.
• Kidneys conserve water by excreting concentrated urine.
• Renal feedback mechanisms control the extracellular fluid sodium concentration and osmolarity.
• Thirst and salt appetite mechanisms control the intakes of water and salt.
• The kidneys adjust the relative amounts of solutes and water in urine to maintain homeostasis when challenged.
• Kidneys excrete urine with an osmolarity as low as 50 mOsm/L when excess water reduces body fluid osmolarity.
• When the body lacks water and extracellular fluid osmolarity is high, highly concentrated urine with an osmolarity of 1200 to 1400 mOsm/L can be excreted.
• Regulating water excretion independently of solute excretion is essential for survival, especially when fluid intake is limited.

Antidiuretic Hormone Controls Urine Concentration

• Plasma osmolarity and sodium concentration are regulated via a feedback system that adjusts renal water excretion independently of solute excretion rate.
• Antidiuretic hormone (ADH), also called vasopressin, is a primary effector of this feedback.
• The posterior pituitary gland secretes more ADH when body fluid osmolarity increases above normal.
• Increased ADH increases the permeability of the distal tubules and collecting ducts to water.
• Water reabsorption increases and urine volume decreases, but renal solute excretion rate is not markedly altered.
• Reduced extracellular fluid osmolarity triggers decreases ADH secretion by the posterior pituitary.
• Decreased permeability of the distal tubule and water collecting ducts leads to increased amounts of dilute urine.
• ADH secretion rate determines whether the kidney excretes dilute or concentrated urine.

Renal Mechanisms for Excreting Dilute Urine

• Kidneys excrete up to 20 L/day of dilute urine with concentrations as low as 50 mOsm/L when there is a large excess of water.
• The kidney keeps reabsorbing solutes without reabsorbing much water in the distal nephron.

Tubular Fluid Remains Isosmotic in Proximal Tubules

• Fluid flowing through the proximal tubule has little change to its osmolarity as solutes and water are reabsorbed in equal amounts.
• The proximal tubule fluid at 300 mOsm/L will remain isosmotic to the plasma.
• Water is reabsorbed by osmosis as fluid flows down the descending loop of Henle.
• The tubular fluid reaches the renal medulla coming into equilibrium with the osmolarity of the surrounding interstitial fluid.
• Tubular fluid becomes more concentrated as it flows into the inner medulla at about two to four times the osmolarity of the original glomerular filtrate.

Tubular Fluid is Diluted in the Ascending Loop of Henle

• The ascending limb of the loop of Henle avidly reabsorbs sodium, potassium, and chloride, especially in the thick segment.
• This tubular segment is impermeable to water, regardless of ADH presence.
• As tubular fluid flows up the ascending loop of Henle into the early distal tubule, it becomes more dilute.
• Fluid leaving the early distal tubular segment is hypo-osmotic, having an osmolarity of about one-third that of plasma, whether ADH is present or absent.

Tubular Fluid in Distal and Collecting Tubules Is Further Diluted in Absence of ADH

• Additional sodium chloride is reabsorbed as the dilute fluid in the early distal tubule passes into the late distal convoluted tubule, cortical collecting duct, and medullary collecting duct.
• The tubule portion is impermeable to water when ADH is absent
• The tubular fluid becomes more dilute as a result of the additional solute reabsorption, decreasing its osmolarity to as low as 50 mOsm/L.
• The combined failure to reabsorb water and continued reabsorption of solutes leads to a large volume of dilute urine.
• Forming dilute urine involves reabsorbing solutes from the distal tubular system segments while also reducing water reabsorption.
• Fluid leaving the ascending loop of Henle and early distal tubule is always dilute in healthy kidneys, regardless of ADH levels.
• In the absence of ADH, the urine is further diluted in the late distal tubule and collecting ducts, and a large volume of dilute urine is excreted.

Kidneys Conserve Water by Excreting Concentrated Urine

• For mammals living on land, the ability of the kidney to form concentrated urine is essential for survival.
• Water is continuously lost through the kidneys.
• The loss of water via urine is minimized by forming a small volume of concentrated urine.
• The body requires fluid intake to match water loss.
• Kidneys continue to excrete solutes while increasing water reabsorption and decreasing urine volume to form concentrated urine when there is a water deficit.
• The human kidney can produce a maximal urine concentration of 1200 to 1400 mOsm/L being four to five times the osmolarity of plasma.
• Some desert animals, like the Australian hopping mouse, can concentrate urine to as high as 10,000 mOsm/L allowing it to survive in the desert.
• Animals adapted to freshwater environments have minimal urine-concentrating ability like Beavers which can concentrate the urine only to about 500 mOsm/L.

Obligatory Urine Volume

• The minimal volume of urine that must be excreted which is dictated via the kidneys maximal concentrating ability, called obligatory urine volume, can be calculated as follows: 600 mOsm/day / 1200 mOsm/L = 0.5 L/day
• This minimal loss of volume in the urine adds to dehydration.
• The limited ability of the kidneys to concentrate the urine to only about 1200 mOsm/L explains why severe dehydration results when drinking seawater.
• Sodium chloride concentration in the ocean is, approximately, 3.0% to 3.5%, with an osmolarity between, approximately, 1000 and 1200 mOsm/L.
• The kidneys are limited to excreting only about 600 mOsm/L of sodium chloride.
• For every liter of seawater that is ingested, 1.5 liters of urine volume is required.
• This volume would result in a net fluid loss of 0.5 liter for every liter of seawater, explaining the rapid dehydration.

Urine Specific Gravity

• Rapidly estimating urine solute concentration in clinical settings is often accomplished via use of specific gravity.
• Higher urine concentrations result in higher specific gravity.
• Urine specific gravity is a weight measure of solutes in a certain volume of urine determined by the number and sizes of solute molecules.
• Osmolarity is determined only by the number of solute molecules.
• Urine specific gravity is generally expressed in grams per milliliter (g/ml).
• In humans, from 1.002 to 1.028 g/ml is the normal range.
• Specific gravity rises by 0.001 for every 35- to 40-mOsm/L increase in urine osmolarity.
• Significant amounts of large molecules in the urine, i.e. glucose, will alter the relationship between specific gravity and osmolarity.
• Urine specific gravity measurements in the presence of significant amounts of large molecules may falsely suggest highly concentrated urine, despite a normal urine osmolarity.
• Most laboratories use a refractometer when measuring specific gravity but dipsticks can measure approximate urine specific gravity.

Excreting Concentrated Urine Requires High ADH Levels and Hyperosmotic Renal Medulla

• Requirements for forming concentrated urine:
• High level of ADH which increases water permeability of the distal tubules and collecting ducts.
• High osmolarity of the renal medullary interstitial fluid which creates an osmotic shift driving water reabsorption.
• Water moves by osmosis into the renal interstitium moving back into the blood via the vasa recta when ADH levels are high, and the renal medullary interstitium surrounding collecting ducts is hyperosmotic.
• Urine-concentrating ability is limited via the level of ADH and hyperosmolarity of the renal medulla.

Countercurrent Multiplier Mechanism

• Process whereby renal medullary interstitial fluid becomes hyperosmotic.
• The nephrons' loops of henle and vasa recta anatomical arrangements.
• Specialized peritubular capillaries of the renal medulla are also dependent on this mechanism.
• Juxtamedullary nephrons which make up about 25% of the nephrons in humans include loops of Henle and vasa recta that go deeply into the medulla before returning to the cortex.
• The vasa recta and collecting ducts, also loop down into the medulla before returning to the renal cortex.
• Collecting ducts carry urine through the hyperosmotic renal medulla prior to excretion.

Countercurrent Multiplier Mechanism Produces Hyperosmotic Renal Medullary Interstitium

• Interstitial fluid osmolarity in the body is similar to plasma osmolarity at approximately 300 mOsm/L.
• In the medulla the interstitial fluid of the kidney is much higher and increases progressively to about 1200 to 1400 mOsm/L at the pelvic tip of the medulla.
• Great excess of water and solutes accumulate in the renal medullary interstitium, which maintains high solute concentration via a balanced inflow and outflow of water and solutes in the medulla.
• Factors contributing to the buildup of the solute concentration into the renal medulla:
• Sodium ions active transport and co-transport of potassium, chloride, and other ions out of the ascending portion of the loop of Henle.
• Active transport of ions from the collecting ducts into the medullary interstitium.
• Facilitated diffusion of urea from the inner medullary collecting ducts into the medullary interstitium.
• Diffusion of only small amounts of water from the medullary tubules into the medullary interstitium, being far less than the reabsorption of solutes into the medullary interstitium

Loop of Henle Characteristics That Cause Solutes To Be Trapped in the Renal Medulla

• Reason for high medullary osmolarity is active transport of sodium and co-transport of potassium, chloride, and other ions from the thick ascending loop of Henle into the interstitium.
• The pump is capable of establishing a concentration gradient of about 200-mOsm/L between the tubular lumen and interstitial fluid.
• Thick ascending limb is virtually impermeable to water and the solutes pumped out are not followed by osmotic water flow into the interstitium.
• The active transport of sodium and other ions out of the thick ascending loop adds solutes in excess of water to the renal medullary interstitium.
• Passive reabsorption of sodium chloride which is also essentially impermeable to water further increases the high solute concentration of the renal medullary interstitium.
• The descending limb of Henle is highly permeable to water, and the tubular fluid osmolarity quickly equilibrates with the renal medullary osmolarity.
• Water diffuses out of the descending limb of Henle's loop into the interstitium.
• The tubular fluid osmolarity gradually rises as it flows from the loop toward its tip.

Steps Involved in Causing Hyperosmotic Renal Medullary Interstitium

• The loop of Henle is filled with fluid which equals the same concentration as the proximal tubule fluid leaving at 300 mOsm/L.
• A 200-mOsm/L concentration gradient exists across the tubular wall with less solute in the tubule vs. the intersititium caused by active ion pumping of the thick ascending limb on the loop of Henle.
• Due largely to osmosis of water into the interstitium, osmotic equilibrium is achieved when the tubular fluid in the descending limb of the loop of Henle and interstitial fluid quickly meet one another.
• The interstitial osmolarity level of 400 mOsm/L is maintained due to the continued ion transport out of the thick ascending loop of Henle.
• Fluid continues to enter the loop of Henle from the proximal tubule.
• Repetitive reabsorption of more and more solute to the medulla occurs in excess of water.
• Process of gradually trapping solutes in the medulla with sufficient time via the active pumping of ions which multiplies the concentration gradient out of the thick ascending loop of Henle, which eventually raises the interstitial fluid osmolarity to 1200 to 1400 mOsm/L.
• The continuous inflow of new sodium chloride from the proximal tubule into the loop of Henle, coupled with the repetitive reabsorption of sodium chloride by thick ascending loop of Henle creates a countercurrent mutliplier.
• The sodium chloride that is reabsorbed from the ascending loop of Henle keeps adding to the newly arrived sodium chloride thus, "multiplying" the concentration in the medullary interstitium.

Role of Distal Tubule And Collecting Ducts In Excreting Concentrated Urine

• The fluid in the distal convoluted tubule of the renal cortex is dilute after leaving the loop of Henle.

Urea Contributes to Hyperosmotic Renal Medullary Interstitium and Formation of Concentrated Urine.

• In the kidneys, when a concentrated urine excretion is occurring the urea accounts for approximately 40 -50% of the osmolarity
• A passive form of reabsorption is present in Urea reabsorption from the tubule.
• When water deficit is present along with high levels of blood concentration pertaining to ADH, high amounts of urea are passively reabsorbed at the inner medullary collecting ducts within the Interstitium.
• There is an impermeability feature of the segments related to the ascending loop of Henle including their related distal and cortical collecting tubules; which disallows an excess of urea from the reabsorption processes.
• Rapid reabsorption of water occurs when high concentrations of ADH are present which increases the original concentration due specifically to the impermeability of the urea in this segment. Urea will therefore permeate this segment into the medullary Interstitium.
• Medullary collecting ducts contain a very specific set of urea transporters associated with greatly facilitating diffusion UT-A1 and UT-A3.
• These urea transporters function as an activation mechanism for ADH which increases urea transport out of Inner Medullary.
• A critical level of urea levels remains in tubular urea and the fluid in the kidney despite the reabsorption occurring between.
• A high protein diet elevates the level of urea nitrogenous waste products facilitating elevated concentrated urine capabilities.

Recirculation of Urea from Collecting Duct to Loop of Henle Contributes to Hyperosmotic Renal Medulla

• A normal healthy person usually clears 20 to 60% of the filtered urea load, The rate of urea excretion is determined by the following:
• Concentration of urea in the plasma.
• GFR Glomerular Filtration Rate.
• rate of Reabsorption within the Tubular region of the kidneys..
• Compromised GFR results in returning of filtered load, increases in plasma concentrations.
• In the ascending loop of the Henle the distal tubule and cortical segments reduce reabsorbed Urea.
• High concentration of ADH results in permeation from the inner to Outer medullary segments where the urea diffuses across by facilitated diffusion in the urea ( UT-A 1 -3) Transporters.
• Heavy amounts of recycling by the Loops of Henle results back up to the Ascending segments reducing loss factors.
• Hyperosmotic pressure and urea’ function of the renal medulla remains vital to overall kidney functioning.
• Elevated water in the body leads to the urine flow increasing, inner ducts concentration becomes limited or reduced due specifically to transport functions UT-A1 and 3 becoming less available.

Countercurrent Exchange in Vasa Recta Preserves Hyperosmolarity of Renal Medulla

• Kidney cells must derive energy by the blood supply system provided to them by the medulla. Therefore, a special blood flow system in the kidney ensures the solute gradient from the countercurrent system. This system must not dissipate the concentration built up in the tissues.
• Solute concentrations are maintained by medullary blood flow rates and U shaped vascular networks with key points as follows:
• Blood slows across the kidney at <5 %.
• Recta vessels provide countercurrent exchange from vessels entering and exiting the Cortical Medulla.
• Blood enters and exits through the cortices with plasma proteins present.
• Blood then descends into the medulla becoming more concentrated due to fluid loss combined with diffusion into the interstitial regions.
• With a concentration of 1200 Mosm/L the levels return as blood ascends for reabsorption.
• U Vessels are countercurrent in nature with constant exchange into the capillaries. Without U Vessels critical amounts of medullary interstitial fluid would be lost.

Increased Medullary Blood Flow Reduces Concentrating Ability

• Concentrating ability in urine is compromised if medullary blood flood flows are enhanced.
• High ADH levels along with the osmolarity levels in the kidney combined with reductions from hyperosmolarity can lead specifically to reduced medullary flood flow rates.

Summary Of Urine-Concentrating Mechanism And Changes in Osmolarity In Different Tubular Segments

• The changes in osmolarity and volume of tubular fluid as it passes through the different parts of the nephron.
• In the proximal tubule, about 65% of the water is reabsorbed.
• Fluid volumes and osmolarity are elevated or augmented at an equal value where filtration remains about ~> 300 Mosm/L.
• Water volumes are reduced through osmosis and reabsorption channels in the aquaporin area.

Descending Loop of Henle

• Descending segments will have water reabsorbed. The contents possess Aquaporin AQP-1 along with water permeability.
• These segments are less permeable to urea along with sodium chloride but exhibit decreasing filtrates.
• Tubular inter fluids are at 1200 Mosm/L but lower when ADH secretions decrease within the kidney.

Thin Ascending Loop Of Henle

• Thin ascending limbs do not let water through, causing slight reabsorption of sodium chloride increasing fluids moving to the medulla.
• Some medulla is absorbed returning fluid to the tubular segments contributing to the increasing effects of retention.

Thick Ascending Loop of Henle

• The Thick segments possess high water impermeability along with transports of chloride potassium magnesium, leaving the filtrate very thin into concentrations near 140 Mosm/L.

Early Distal Tubule

• Fluids are diluted further with properties similar that are in line with that of the loop of Henle for increasing osmolarity approximately up to 100 Mosm/L with water retained.

Late Distal Tubules and Cortical Collecting Tubules

• Highly permeable to specific concentration levels with great reabsorption qualities based on the ADH concentration. Urea in this are is augmented to where most transports occur.
• Water permeability in the absence of ADH secretions results in low levels,
• Levels are reduced further from active reabsorption sections.

Inner Medullary Collecting Ducts

• Highly dependent on ADH concentrations with diffusion into interstitial fluid and equilibration where fluid remains higher. Tubular segments are near 1200 Mosm/L.
• A decreased secretion of ADH causes sodium excretion and higher degrees of volume.

Quantifying Renal Urine Concentration and Dilution;

Free Water And Osmolar Clearances

• Independent water and solute extretion is required for concentrating or diluting urine.
• Conversely, more solutes are removed when the urine is concentrated.
• Solute clearance in the blood = osmolar clearance (Cosm).
• Volume of solutes cleared each minute.
• Given calculated values of Posm, Uosm one can generate OSMOLAR clearances

Free Water Clearance

• Difference between water excretion and osmolar clearance
• Solute-free water rate excreted by the kidneys = rate of free water
• Indicates conservation versus excretion processes.
• Negative = water is conserved.
• Positive = excess water is excreted by the kidneys.

Disorders of Urinary Concentrating Ability

• Issues impairing Kidney's ability to concentrate and or or dilute can have 3 potential abnormalities.
  • Too much or too little ADH which results in impaired water excretion.
  • Hyperosmotic Interstitium of the medulla which limits urinary concentration.
  • Inability to produce ADH or a limited concentration of ADH can cause kidney segments to not respond correctly.
  • Hypothalamus and pituitary are damaged by head trauma Infections this is called central diabetes where without segments of the distal area and their specific concentrations of water cannot be reabsorbed resulting in dilute output levels.
  • If reduced or restricted water levels occur due to injury rapid dehydration can take place.
  • A synthetic analog can be implemented to treat diabetes insipidus in these instances such as Desmopressin reducing urine levels to normal.
• Inability for segments to respond or the kidneys where abnormalities for ADH can arise creating failures in Countercurrent multiplier formations this is NEPHROGENIC diabetes. Increased losses and damages occur with reduced reabsorption rates.
• Renal diseases and renal damage will reduce impairment in urine concentrations.

Control of Extracellular Fluid Osmolarity and Sodium Concentration

• Sodium and osmolarity is balanced and tightly controlled, and regulated.
• Ranges exist between 140 to 145 meq and or volume concentrations.
• Changes in water versus intracellular areas can effect ADH and thirst mechanisms creating and affecting blood pressure and or output levels.

Estimating Plasma Osmolarity from Plasma Sodium Concentration

• Direct measurements are required to track Osmolarity in plasma since it is not routinely measured.
• Sodium is a key point for regulating electrolytes Osmolarity is then calculated given formula:
• Posm = 2.1 X P Na+ (mmol/L).

Osmoreceptor-ADH Feedback System

• This systems purpose focuses on preserving ExtraCellular fluids by detecting osmosis. This process results in detecting neuron shrinkages which release nerve signals for ADH with water volume restored to balance.

Central control

• Impulses affecting membranes can affect and change ADH secretions
• Injury to hypothalamus will negatively compromise ADH electrolyte creation

Renin Angiotensin

• Reduced pressure volume and loss of blood can trigger ADH secretions.
• This has a significant interaction level in fluid output and the balance to ensure normal level retention occurs.

Other

• The increase or reduction of electrolyte secretions or the increase water levels effect ADH and or the central sensory functions resulting in electrolyte and water level changes as well levels within the body.

The importance of Thirst

• Minimizing fluid and losing electrolytes creates an imbalance which the feedback system minimizes. Proper water volume intake becomes very critical for balance within the system. It is dependent on fluid amounts for fluid absorption as there needs to be balance to maintain osmotic stability.

Central Nervous System centers

• Involves ADH sections where small areas regulate stimulation of all of the senses and stimulate the center's area.
• Neural input is from the cardio receptors in systemic areas
• Angiotensin is an important regulatory stimulus

Stimuli Thirst

• Most important function to maintain fluid concentrations to activate thirst.
• Cardio stimulation is dependent on volume.
• Stimuli can be increased with esophogal openings to make absorption possible.
• The body measures fluid to prevent increased intake the processes water for balancing out and not overloading the filtration segments preventing overhydration.

Thresholds for Osmolar Stimulus of Drinking

• Transports is controlled for regulation levels of sodium to be maintained at balance
• The kidneys maintain a balance with losses as well triggering systems and functions responsible for thirst.

Integrated Responses

• Kidney filtration, GFR regulation, water retention ADH balances work very keenly ensure osmotic regulations

Role of Angiotensin 2

• Sodium regulation which helps trigger sodium absorption to regulate kidney filtrations. Fluid is reabsorbed through this process but minimal concentrations do need to occur. There is no impact to volume within the cells themselves.

Salt Appetite Mechanism

• Regulation depends from the balance of sodium intake and excretion levels
• Sodium averages 100mEq with low and high fluctuations but levels balance to the high level

Increased ADH Secretion

• Electrolyte balance is vital with fluid to prevent hyponatremia.
• If extreme conditions trigger ADH, mechanisms maintain correct sodium levels even in extreme cases.
• The bodies mechanism system helps with overall body concentrations due to the sensory mechanisms.

Explore the countercurrent mechanism in the kidneys. Understand how the loop of Henle, vasa recta, and collecting ducts work together to create concentrated urine. Learn about the role of the thick ascending limb and the limitations of the active ion pump.