REGULATION OF EXTRACELLULAR FLUID;
OSMOLARITY AND SODIUM CONCENTRATION
MA. SOCORRO J. MARAVILLA, M.D.
Regulation of Extracellular Fluid Osmolarity and Sodium Concentration:
FLUID INTAKE & RENAL EXCRETION OF WATER
- eliminate excess water
- conserve water
- renal feedback
- thirst & salt appetite
KIDNEY EXCRETES EXCESS WATER BY FORMING DILUTE URINE…
ANTIDIURETIC HORMONE CONTROLS URINE CONCENTRATION
A powerful feedback system for regulating plasma osmolarity and sodium concentration that operates by altering renal excretion of water independently of the rate of solute excretion.
ANTIDIURETIC HORMONE (Vasopressin)
High Osmolarity Low Osmolarity
Posterior Pituitary Gland
(+) ADH (-)
Permeability of the distal tubules & collecting ducts to water
Increased reabsorption Decreased reabsorption
Decreased urine volume Increased urine volume
The presence or absence of ADH determines whether the kidney excretes a dilute of concentrated urine.
Renal Mechanism for Excreting Dilute Urine
Excess of water in the body, the kidney can excrete as much as 20L/day of dilute urine, concentration low as 50mOsm/L.
The kidneys continue to reabsorb solutes while failing to reabsorb large amounts of water in the distal parts of the nephron.
Formation of dilute urine when ADH is low…
- Water & solutes reabsorbed equally
- Isoosmotic to plasma
Descending Loop of Henle:
- Water is reabsorbed by osmosis
- Tubular fluid more concentrated in inner medulla
Ascending Loop of Henle:
- Thick segment, Na,K, Cl avidly reabsorbed
- Impermeable to water even with ADH
Distal and Collecting Tubules:
- additional reabsorption of NaCl
- impermeable to water in the absence of ADH
In summary, the mechanism for forming dilute urine is to continue reabsorbing solutes from the distal segments of the tubular system while failing to reabsorb water.
The fluid leaving the ascending loop of Henle and early dct is always dilute regardless of ADH.
In the absence of ADH further dilute urine leaves the late dct & collecting ducts.
KIDNEY CONSERVES WATER BY EXCRETING CONCENTRATED URINE…
Water is lost continuously from the body…
- Lungs – evaporation – expired air
- Gastrointestinal tract – feces
- Skin – evaporation – perspiration
- Kidneys – excretion – urine
When there is water deficit in the body, the kidney forms concentrated urine by continuing to excrete solutes while increasing water reabsorption and decreasing the volume of urine formed.
OBLIGATORY URINE VOLUME:
- Maximal concentrating ability of the kidney dictates how much urine volume must be excreted each day to rid the body of waste products of metabolism and ions that are ingested.
- Maximal urine concentrating ability of the kidney is 1200 mOsm/L
- Minimal urine volume that must be excreted is obligatory urine volume.
REQUIREMENTS FOR EXCRETING CONCENTRATED URINE:
1. High level of ADH – increases permeability of dct & collecting ducts to water – reabsorb water
2. High osmolarity of the renal medullary interstitial fluid- provides the osmotic gradient necessary for water reabsorption
The process, by which renal medullary intersitial fluid becomes hyperosmotic, depends on the special anatomical arrangement of the loops of Henle and the vasa recta, specialized peritubular capillaries of the renal medulla.
THE COUNTERCURRENT MECHANISM PRODUCES A HYPEROSMOTIC RENAL MEDULLARY INTERSTITIUM:
Osmolarity of intersititial fluid in almost all parts of the body-300mOsm/l. In the medulla it is 1200-1400mOsm/L.
Major factors contributing to solute concentration:
1. Active transport of Na ions & co-transport of K, Cl & other ions out of the thick ascending limb of Loop of Henle into the medullary interstitium.
2. Active transport of ions from the CD to the MI.
3. Passive diffusion of large amounts of urea from inner medullary CD into the MI.
4. Diffusion of only small amounts of water from the medullary tubules into the MI.
STEPS INVOLVED IN CAUSING THE HYPEROSMOTIC RENAL MEDULLARY INTERSTITIUM…
Step 1. The loop of Henle is filled with fluid with a concentration of 300 mOsm/L
Step 2. Active pump of the thick ascending limb is turned on, reducing the conc. Inside the tubule and raising the interstitial conc.
Step 3. Tubular fluid in desc. Loop of Henle and the interstitial fluid reach osmotic equilibrium-osmosis of water out of desc. Limb.
Step 4. Additional flow of fluid into the loop of Henle from PT, cause the hyperosmotic fluid from the desc. Limb to flow into the ascending limb.
Step 5. Additional ions are pumped into the interstitium by the fluid in the ascending limb, with water left behind. Interstitial fluid osmolarity 500 mOsm/L.
Step 6. Fluid in the descending limb reaches equilibrium with the hyperosmotic medullary interstitial fluid
Step 7. Still more solute is continuously pumped out of the tubules and deposited into the medullary interstitium.
The steps are repeated over and over, the the net effect of adding more and more solute to the medulla in excess of water, with sufficient time, this process gradually traps solutes in the medulla and multiplies the concentration gradient established by the active pumping of ions out of the thick ascending limb.
Countercurrent Multiplier – repetitive reabsorption of sodium chloride by the thick ascending loop of Henle and continued inflow of new NaCl from the PT.
ROLE OF THE DISTAL TUBULE AND COLLECTING DUCTS IN EXCRETING CONCENTRATED URINE
- Fluid is dilute in the DCT in the renal cortex.
- Actively transports NaCl out of the tubule but is relatively impermeable to water.
- Fluid flows into the cortical CD, the water reabsorbed is critically dependent on the plasma concentration of ADH.
- Large amounts of water are reabsorbed into the cortex, rather than into the renal medulla, helps to preserve the high medullary interstitial fluid osmolarity.
- When high levels of ADH are present, the CD become permeable to water, so that the fluid at the end of the CD has the same osmolarity as the interstitial fluid of the renal medulla.
UREA CONTRIBUTES TO HYPEROSMOTIC RENAL MEDULLARY INTERSTITIUM AND TO CONCENTRATED URINE…
- Contributes about 40% of the osmolarity of the renal medullary interstitium.
- Passively reabsorbed from the tubule.
- Ascending limb & DCT – impermeable to urea.
- Inner Medullary CD- further water reabsorption, urea diffuses out of the tubule into the renal interstitium-highly permeable to urea & ADH increases permeability.
RECIRCULATION OF UREA
- A person excretes about 40-60% of the filtered load of urea
- Rate of Urea excretion is determined by 2 factors:
§ Concentration of urea in the plasma
§ Glomerular filtration rate
- Recirculation of urea absorbed from the medullary CD into the interstitial fluid. Then passes into the loop of Henle, through the distal tubules, and finally back into the collecting duct.
- The recirculation of urea helps to trap urea in the renal medulla and contributes to the hyperosmolarity of the renal medulla.
COUNTERCURRENT EXCHANGE IN THE VASA RECTA
- Blood flow must be provided to the renal medulla to supply the metabolic needs of the cells in this part of the kidney
- Two special features of the renal medullary blood flow that contribute to the preservation of the high solute concentrations:
§ Medullary blood flow is low. Sluggish blood flow is sufficient supply metabolic needs of the tissues but helps to minimize solute loss from the medullary interstitium.
§ The vasa recta serve as countercurrent exchangers, minimizing washout of solutes from the medullary interstitium.
- Highly permeable to solutes in the blood, except for the plasma proteins
- Large amounts of solutes would be lost from the renal medulla without the U shape of the vasa recta capillaries
SUMMARY OF URINE CONCENTRATING MECHANISM AND CHANGES IN OSMOLARITY IN DIFFERENT SEGMENTS OF THE TUBULES
o 65% of filtered electrolytes are reabsorbed
o highly permeable to water
o osmolarity - 300mOsm/l
Descending Loop of Henle:
o water is absorbed in the medulla
o highly permeable to water
o less permeable to NaCl & Urea
o osmolarity -1200mOsm/l if ADH is high
Thin Ascending Loop of Henle:
o impermeable to water
o reabsorbs some NaCl
o urea recycling
Thick Ascending Loop Of Henle:
o impermeable to water
o active transport of Na, Cl, K & other ions
o fluid very dilute - 100mOsm/l
Early Distal Tubule:
o further reabsorption of solutes while water remains
Late Distal Tubule & Cortical Collecting Tubule
o fluid osmolarity depends on the presence & absence of ADH
o urea not permeant
Inner Medullary Collecting Ducts:
o Osmolarity of the medullary interstitium
o permeant to urea
Important Points to consider:
o The kidney can, when needed, excrete a highly concentrated urine that contains little sodium chloride.
o other ions like urea & creatinine also excreted
o Large quantities of dilute urine can be excreted without increasing the excretion of sodium.
DISORDERS OF URINARY CONCENTRATING ABILITY
Impairment in the ability of the kidneys to concentrate or dilute the urine appropriately can occur with one or more of the ff. Abnormalities.
1. Inappropriate secretion of ADH
o Central Diabetes Insipidus-inability to produce or release ADH from the posterior pituitary caused by head injuries, infections, congenital. Large volume of urine >15L/d.
o Nephrogenic DI-inability of the kidney to respond to ADH, due to either failure of countercurrent mechanism or failure of the distal & collecting tubules & ducts to respond to ADH
2. Impairment of the countercurrent mechanism
3. Inability of the distal tubule, collecting tubule and collecting ducts to respond to ADH
CONTROL OF EXTRACELLULAR FLUID OSMOLARITY AND SODIUM CONCENTRATION
Plasma sodium concentration & osmolarity must be precisely controlled because they determine the distribution of fluid between the intracellular and extracellular compartments.
2 Primary systems that regulate concentration of sodium & osmolarity of the extracellular fluid:
1. Osmoreceptor - ADH Feedback System
2. Thirst Mechanism
OSMORECEPTOR-ADH FEEDBACK SYSTEM:
ADH release is also controlled by cardiovascular reflexes:
1. Arterial baroreceptor
2. Cardiopulmonary reflexes
ADH secretion is increased:
1. Decreased arterial pressure
2. Dec. blood volume
ADH is more sensitive to small changes in osmolarity than to similar changes in blood volume.
ADH levels do not change appreciably until blood volume is reduced by about 10%
REGULATION OF ADH SECRETION:
Increase ADH Decrease ADH
↑ Plasma osmolarity ↓ Plasma osmolarity
↓ Blood volume ↑ Blood volume
↓ Blood pressure ↑ Blood pressure
ROLE OF THIRST IN CONTROLLING EXTRACELLULAR FLUID OSMOLARITY AND SODIUM CONCENTRATION:
Increased extracellular fluid osmolarity, which causes intracellular dehydration in the thirst centers, is known to stimulate thirst.
↓ Blood volume
↑ Blood volume
↓ Blood Pressure
↑ Blood Pressure
↑ Angiotensin II
↓ Angiotensin II
Dryness of Mouth