5.6 Urine Concentration and Dilution.pptx

Urine Concentration and Dilution; Regulation of Extracellular Fluid Osmolarity and Sodium Concentration Lecture Outline I. Kidneys excrete excess water by forming dilute urine II. Kidneys conserve water by excreting concentrated urine III. Countercurrent multiplier mechanism produces hyperosmotic re...

Urine Concentration and Dilution; Regulation of Extracellular Fluid Osmolarity and Sodium Concentration Lecture Outline I. Kidneys excrete excess water by forming dilute urine II. Kidneys conserve water by excreting concentrated urine III. Countercurrent multiplier mechanism produces hyperosmotic renal medullary interstitium IV. Osmoreceptor-ADH feedback system V. Importance of thirst in controlling extracellular fluid osmolarity and sodium concentration 1 Urine Concentration and Dilution; Regulation of Extracellular Fluid Osmolarity and Sodium Concentration Lecture Objectives 1. Identify normal ECF osmolarity and minimum/maximum urine concentration 2. Explain how excess body water is eliminated via a dilute urine 3. List two conditions for excreting concentrated urine 4. Define obligatory urine volume 5. Explain the countercurrent multiplier and identify the major contributors to the development of a hyperosmotic renal medullary intersititium 6. Identify the role of the countercurrent exchanger of the vasa recta 7. List stimuli for ADH secretion 8. Identify the role of thirst in fluid balance 2 References Assigned reading from your text: Hall Chapter 29 3 CF Osmolarity and Urine  ECF osmolarity must be maintained to maintain cell volume • Internal environment • The main osmotically active solute is Na+- largest ion in ECF • Osmolarity is determined by solute/ECF volume • The amount of solute (mainly NaCl) • Amount of ECF water  Total body water is controlled by: • Fluid intake is regulated by factors that determine thirst • Renal water excretion  Kidneys excrete excess water by forming dilute urine  Kidneys conserve water by excreting a concentrated urine Relationship Between Urine Osmolarity and Specific Gravity Osmolarity = ~ 300 mOsm/L mined by number of solute molecules in a volume fic gravity is 1.002-1.028 g/mll asure of weight of solutes in a volume of urine mined by the number and size of solute molecules sed specific gravity and osmolarity indicate higher solute concentration mal urine concentration= 1200 − 1400 mOsm/L (specific gravity ~ 1.03 mal urine concentration = 50 − 70 mOsm/L (specific gravity ~ 1.00 • Influenced by presence of large molecules • Glucose in urine • Protein in urine • Antibiotics • Radiocontrast media Formation of a Dilute Urine  Kidneys excrete excess water by forming a dilute urine (as low as 50 mOsm/L) • Continue normal electrolyte reabsorption • Decrease water reabsorption Mechanism: • Decreased ADH release (Diuresis) • Reduced water permeability in distal and collecting tubules Decreased ADH release produces a dilute urine Diuresis After Ingestion of 1 Liter of Water • Renal response to ingestion of H2O and ECF increase • Urine volume increased 6 times within 45 minutes • Urine dilution occurs in the ascending loop of Henle • With or without ADH- fluid leaving early DT is always hypo-osmotic • In absence of ADH, fluid in distal and collecting tubules is further diluted Formation of a Concentrated Urine When ADH is Elevated  Excreting concentrated urine requires two conditions: • Mechanism: • Increased ADH (Antidiuresis) (Two names- ADH and Vasopressin) • Antidiuresis= decreased water excretion by kidney due to ADH • High osmolarity of renal medulla by establishing the countercurrent multiplier • • Continue normal electrolyte reabsorption Increase water reabsorption bligatory Urine Volume  The minimum urine volume in which the excreted solute can be dissolved and excreted • In OR- we sometimes monitor urine output to assess renal function • It’s not autoregulated • It is a visible sign and useful monitor on long cases • In the OR, 1-ECF changes and 2- medications (eg antibiotics) Example: If the max. urine osmolarity is 1200 mOsm/L, and 600 mOsm of solute must be excreted each day to maintain electrolyte balance, the obligatory urine volume is 600 mOsm/d 1200 mOsm/L = 0.5 L/day.  Australian hopping Urine mouseConcentrating can concentrateAbility urine to 10,000mOsm/L • Doesn’t require water to drink  Humans have a limited urine concentrating ability (~ 600 mOsm/day) • Explains why drinking seawater will result in dehydration • Drinking 1 L of seawater (1200mOsm/L) matches our maximum concentrating ability • The kidney must still excrete other solutes (urea)0 to contribute ~ 600 mOsm/L when urine maximally concentrated- would require 1.5 L H2O • Results in a net fluid loss of 0.5 liters for every liter seawater  In renal disease the obligatory urine volume may be increased due to impaired urine concentrating ability- may increase to 2.0 L/day Factors That Contribute to Buildup of Solute in Renal Medulla  Countercurrent Multiplier- Manipulates solute and water in/around tubule • • • • Active transport of Na+, Cl−, K+, and other ions from thick ascending loop of Henle into medullary interstitium Active transport of ions from medullary collecting ducts into interstitium Passive diffusion of urea from medullary collecting ducts into interstitium Diffusion of only small amounts of water into medullary interstitium Net Effects of Countercurrent Multiplier 1. More solute than water is added to the renal medulla. i.e., solutes are “trapped” in the renal medulla 2. Fluid in the ascending loop is diluted 3. Most of the water reabsorption occurs in the cortex (i.e., in the proximal tubule and in the distal convoluted tubule) rather than in the medulla. 4. Horizontal gradient of solute concentration established by the active pumping of NaCl is “multiplied” by countercurrent flow of fluid. Recirculation of Urea Absorbed from Medullary Collecting Duct into Interstitial Fluid • Urea is passively reabsorbed in proximal tubule (~ 50% of filtered load is reabsorbed) • In the presence of ADH, water is reabsorbed in distal and collecting tubules, concentrating urea in these parts of the nephron • The inner medullary collecting tubule is highly permeable to urea, which diffuses into the medullary interstitium (UTA-2) • ADH increases urea permeability of medullary collecting tubule by activating urea transporters (UTA1). Vasa Recta Preserve Hyperosmolarity of Renal Medulla  Countercurrent exchanger Vasa recta of long loops Low blood in vasa recta (1-2% of total RBF) Changes in Osmolarity of the Tubular Fluid Figure 29-8 Summary of Water Reabsorption and Osmolarity in Different Parts of the Tubule Proximal tubule: 65% reabsorption, isosmotic Desc. loop: 15% reasorption, osmolarity increases Asc. loop: 0% reabsorption, osmolarity decreases Early distal: 0% reabsorption, osmolarity decreases Late distal and coll. tubules: ADH dependent water reabsorption and tubular osmolarity • Medullary coll. ducts: ADH dependent water reabsorption and tubular osmolarity • • • • • rders of Urine Concentrating Ability • Failure to produce ADH : “central” diabetes insipidus • Failure to respond to ADH: “nephrogenic” diabetes insipidus - Impaired loop NaCl reabs. (loop diuretics) - Drug induced renal damage: lithium, analgesics - Malnutrition (decreased urea concentration) - Kidney disease: pyelonephritis, hydronephrosis, chronic renal failure Total Renal Excretion and Excretion Per Nephron in Renal Failure Normal Number of nephrons 2,000,000 Total GFR (mL/min 125 GFR per nephron (nL/min) 62.5 Total urine flow rate (mL/min) 1.5 Volume excreted 0.75 per nephron (nL/min) 75% loss of nephrons 500,000 40 80 1.5 3.0. Isosthenuria With Nephron Loss in Chronic Renal Failure (Inability to Concentrate or Dilute the Urine) Figure 32-6 Blood pressure regulation by the kidney includes volume regulation:  Mechanisms: • Long term regulation- Thirst mechanism and fluid excretion • Intermediate regulation- Renin-Angiotensin System • Short-term regulation- Baroreceptor reflex Osmoreceptor-Antidiuretic Hormone (ADH) Feedback Mechanism  Homeostatic response to increased osmolarity- Thirst and ADH • Magnocellular neurons synthesize ADH in the supraoptic and paraventricular nuclei of hypothalamus • Increased plasma Na+ causes osmoreceptors in anterior hypothalamus to shrink • Shrinkage causes osmoreceptors to fire APs to posterior pituitary to release ADH (a neuropeptide) which is stored in vesicles ADH enters bloodtransported to kidney where it increases water permeability of late distal tubules, cortical collecting ducts, and medullary 1/6th ADH produced in the nuclei producing oxytocin- will see some effect collecting ducts • + Thirst Regulation of Thirst  Hypertonicity and hypovolemia control thirst  Thirst controls ECF osmolarity and Na+ concentration • CSF and plasma communicate with areas of circumventricular organs (CVO) • Thirst center- wall of 3rd ventricle + preoptic nucleus stimulates thirst • Increased thirst with: • Increased osmolarity dehydrates cells in thirst centers- Osmoreceptors • When Na+ rises ~ 2mEq/L above normal- threshold for drinking • Angiotensin II • Decreased ECF volume and arterial pressure by a separate pathway • Sensed by arterial baroreceptor Ganong FIGURE 17–4 Diagrammatic representation of the way in which changes in plasma osmolality and changes in ECF volume affect thirst by separate pathways. Stimuli for ADH Secretion  ADH release stimulated by: • 1% change in osmolarity • 10% change in ECF volume • Decreased BP • Other stimuli: • Angiotensin II • Nausea • Nicotine • Morphine Figure 29-11 Modified from Dunn FL, Brennan TJ, Nelson AE, et al: The role of blood osmolality and volume in regulating vasopressin secretion in the rat. J Clin Invest 52[12]:3212, 1973. By permission of the American Society of Clinical Investigation. Factors That Decrease ADH Secretion • • • • Decreased osmolarity Increased blood volume (cardiopulmonary reflexes) Increased blood pressure (arterial baroreceptors) Other factors : - Alcohol - Clonidine (antihypertensive drug) - Haloperidol 1. In normal kidneys, which of the followingistrue of the osmolarity of the renal tubular fluid that flowsthrough the early DT in the region of the macula densa? A. B. C. D. Usually isotonic compared with plasma Usually hypotonic compared with plasma Usually hypertonic compared with plasma Hypertonic, compared with plasma, when ADH present 2. A female runner has high circulating ADH and normal renal function. Where is water most reabsorbed in her renal tubules? A. B. C. D. E. Proximal tubule Loop of Henle Distal tubule Cortical collecting tubule Medullary collecting duct 3. Under conditions of normal renal function, what is true of the concentration of urea in tubular fluid at the end of the proximal tubule? A. B. C. D. It is higher than the concentration of urea in tubular fluid at the tip of the loop of Henle It is higher than the concentration of urea in the plasma It is higher than the concentration of urea in the final urine in antidiuresis It is lower than plasma urea concentration because of active urea reabsorption along the proximal tubule 4. Where is ADH synthesized? A. B. C. D. E. In the posterior pituitary In the thalamus In magnocellular neurons of the supraoptic nuclei In the kidney In the adrenal cortex 25