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Kidney Lect 8
Water Homeostasis
| Question | Answer |
|---|---|
| ___% of body weight in normal adult women is water. ___% of body weight in normal adult men is water. What accounts for this difference? | ~50%; ~60; This difference is due to a smaller amount of fat in men. |
| Intracellular fluid (ICF): definition; how much is found of total body water is ICF? | the fluid contained within cells. ~2/3 of total body water is present in the ICF |
| Extracellular fluid (ECF): definition; how much is found of total body water is ECF? | Extracellular fluid (ECF) consists of fluid outside the cell compartment. ~1/3 of total body water is present in the ECF |
| What are the two major compartments of the ECF? | Intravascular (plasma) fluid volume (the fluid within blood vessels) ~1/4 of the ECF volume; Interstitial (extravascular) fluid volume - which bathes the body tissues. ~3/4 of the ECF volume |
| Bone/dense connective tissue water | part of the hydrated crystalline structure of bone and part of tendon and cartilage. Plays a minor role in body water homeostasis. |
| What determines water movement from cellular compartment to cellular compartment? | Water is fairly soluble across membranes (except some apical membranes), so it will be mostly dictated by osmolality differences and hydrostatic pressure |
| What is the definition of osmolality? Why is it preferred over osmolarity? | Osmoles of solute per kg of water; moles per liter of solution varies with temperature and volume occupied by solutes--thus is less optimal |
| Tonicity | measure of effective osmolality. It represents the solutes that have the ability to exert an osmotic force, i.e., are capable of causing water flow across membranes. |
| ineffective osmoles | Urea, ethanol, and methanol are small molecules that increase total osmolality of the blood without real effect on tonicity since they diffuse relatively freely and rapidly across cell membranes-->do not contribue effective osmolality of blood |
| What is the difference between osmolality and tonicity? | Osmolality: total particles / kg H2O, measurable AND caculable. Tonicity: # of particles that can't freely cross cell membrane per unit volume (effective osmolality; reflects osmotically active solutes); not measurable, calculable |
| Describe the concentration of osmotically active particles varies from compartment to compartment | Although the concentration of osmotically active particles is the same in all compartments, the solute composition varies from compartment to compartment |
| The ____ present in a body compartment determines the distribution of fluid between the ICF and ECF. | type and concentration of solute |
| What are the major cations and anions in the ECF? | Sodium (Na + ) is the major cation. Chloride (Cl - ) and bicarbonate (HCO 3 - ) are the principal extracellular anions. |
| What are the major cations and anions in the ICF? | Potassium (K + ) and magnesium (Mg 2+ ) are major cations. Proteins and phosphate (in muscle) are the major intracellular anions. |
| What provides the separation of Na+ and K+? What maintains the various concentration gradients amongst the different compartments? | Requires active cell metabolism that is supplied by the Na + -K + -ATPase. This active transporter, which is described in the Tubular Transport lectures, pumps Na + out of cells and K + into cells. |
| Gibbs-Donnan Effect | Proteins and their bound ions are not necessarily part of the aqueous phase but their charges have an important effect on composition |
| extracellular osmolality is maintained constant by controlling ____ | renal water excretion |
| For renal H 2 O excretion to occur: | 1. Fluid must be filtered at the glomerulus (normally 150-180L/day; reduced/absent in renal failure). 2. Salt must be removed from the ultrafiltrate (thick AL of loop of Henle). 3. The "free" H 2 O must transverse though tubules that are H 2 O tight. |
| For renal H 2 O reabsorption to occur: | 1. An osmotic gradient must exist (so H 2 O reabsorbed) 2. Gradient is established by generating and maintaining a hypertonic medullary interstitium. 3. Vasopressin-->H2O reabsorption in the collecting duct (insertion of aquaporin 2 in apical membrane) |
| Diuresis | increased renal excretion of H 2 O (fluid) |
| Antidiuresis | - increased renal reabsorption of H 2 O (fluid), such that excretion is limited. |
| How is water handled by the glomerulus? | H2O is freely filtered. ~150 liters of H2O are filtered daily (GFR). |
| How is water handled in the proximal tubule? | Solutes and H2O are reabsorbed isotonically by the proximal tubule. ~60% to 70% of the ultrafiltrate is reabsorbed normally. Up to 90% reabsorption of the ultrafiltrate can occur with severe effective circulating volume depletion (depends on AII) |
| The descending limb is H2O ___, and Na+ ___. | permeable; impermeable |
| Describe the Na+ and H2O permeability of the ascending limb of the loop of Henle | The ascending limb is H2O impermeable, but actively transports Na+ out of the tubule and can establish a local osmotic gradient of ~200 mOsm across the epithelial layer |
| countercurrent multiplication | Antiparallel (or countercurrent) flow of fluids through neighboring pathways generates a hypertonic interstitium as well as hypotonic tubular fluid at the end of Henle's loop. |
| The interstitial osmolality varies from between 285 mosmoles/kg H2O in the ___ to up to ~1200 mosmoles/kg H2O in the ____ under conditions of maximum antidiuresis | cortex; inner medulla |
| How does H2O flow out of the descending limb? What is the reabsorptive capacity of the descending limb? | Via aquaporins that facilitate water transport; up to 90% of the H2O in the filtrate that reaches the loop of Henle can get reabsorbed in this segment. |
| In the loop of Henle, where is the concentration of solutes maximum? | The concentration of solutes in the tubular fluid progressively increases to a maximum value at the tip of Henle's loop. |
| How does low ECBV alter renal capacity for the excretion of water? | Decreases; enhancing of proximal fluid reabsorption via hemodynamic effects and a direct stimulation of transport in the proximal tubule and enhanced water reabsorption in the descending limb-->LESS ISOTONIC FLUID DELIVERY TO DISTAL DILUTING SITES |
| What substances are permeable in the ascending limb of the loop of Henle? How does this affect water handling? | H2O impermeable; NaCl is transported out the tubular space-->by end of loop of Henle, osmolality of tubular fluid is quite low; Urea diffuses into the tubular lumen from the interstitium (driven by concentration gradient) |
| In the ____, NaCl passively diffuses out of the tubular lumen. | first portion of the ascending limb (the thin ascending limb) |
| How are Na+ and Cl handled in the latter portion of the ascending limb (the thick ascending limb)? | NaCl is transported out of the tubular lumen by crossing the apical membrane via a Na/K/2Cl cotransporter. The Na+, K+-ATPase then extrudes Na+ from the cell and Cl- exits the cell via basolateral Clselective ion channels. |
| ___% of the filtered H2O is reabsorbed in the loop of Henle. | ~ 15% - 20% |
| Distal convoluted tubule: what is it permeable to? What hormone acts on it? What does it do? | Largely H2O impermeable. Vasopressin will increase H2O permeability of the late distal convoluted tubule. As NaCl is transported out the lumen, the osmolality of the tubular fluids may decrease further. |
| The ____ is the final site of H2O reabsorption by the kidney. | collecting duct |
| What is the H2O permeability of the collecting duct? | In the absence of vasopressin, the apical membrane of the collecting tubule is H2O impermeable-->vassopressing promotes urine CONCENTRATION |
| How does vasopressing affect the collecting duct cells? | H2O permeability of the apical membrane is increased:mediated by the movement of water channels from a cytoplasmic pool to the cell surface |
| The cortical collecting duct is ___ to urea. | largely impermeable |
| As the tubular fluid flows through the medullary collecting duct, ___ can be reabsorbed in the presence of vasopressin by passive diffusion | both H2O and urea |
| Describe the urea permeability in the medullary collecting duct | Urea diffuses out of the medullary collecting duct and contributes to the osmolality of the medullary interstitium and during states of active water reabsorption by the kidney, can account for up to 40-50% of the solutes in the medullary interstitium |
| Describe the general purpose of the loop of Henle countercurrent | 1. Descending limb extracts water and concentrates the ultrafiltrate 2. Thick ascending limb extracts NaCl a. Concentrates medullary interstitium b. Dilutes ultrafiltrate |
| Active transport of NaCl in the ____ by Na-K-2Cl cotransporter in apical membrane and Na-K-ATPase in basolateral membrane => removal of salt from lumen leaves tubular fluid hypotonic as it enters the distal nephron. | thick ascending limb |
| If kidney is trying to conserve water (i.e., a significant amount of ADH is present), water reabsorption will occur through... | ADH-regulated water channels in the cortical and medullary collecting duct. |
| The relative impermeability of the ___ to urea allows urea to build up in the tubules until it reaches the ___, where ADH-regulated urea permeability allows urea to exit and contribute to the generation of the hypertonic environment there. | cortical and medullary collecting duct; inner medulla |
| Osmotic water loss throughout the ____ allows the luminal NaCl concentration to get very high by the hairpin turn. | descending limb of the loop of Henle |
| As it enters the ____, NaCl can passively diffuse out into the interstitium down its concentration gradient. | thin ascending limb |
| Summarize the steps involved in the countercurrent multiplication mechanism | 1) active transport of Na+Cl+K from lumen to interstitium 2) (if ADH) water reabsorption in collecting duct 3) urine concentration in collecting duct via urea and H2O movement 4) osmotic water loss in descending limb 5) TAL: NaCl diffuse into interstitium |
| The ____ provide blood flow to the renal medulla and provide a mechanism for H2O removal from the interstitium. | vasa recta |
| How does the countercurrent exchanger prevent medullary interstitial washout? | Large amount of fluid and solute exchange but little net dilution at each level because of U shape of capillaries |
| Why does the vasa recta blood flow slow down as it progresses towards the deep medulla? | Water (and thus plasma volume) is effectively shunted from the descending to ascending vasa recta at any given level; sluggish flow improves solute trapping to maintain hypertonic medullary interstitium. |
| To maximally dilute the urine (or to rapidly excrete a H2O load)... | the loop of Henle generates a hypertonic interstitium while delivering dilute urine to the distal nephron. The absence of vasopressin will allow the kidney to rapidly excrete the H2O. |
| To maximally concentrate the urine (or to block renal H2O excretion)... | the loop of Henle generates a hypertonic interstitium while delivering dilute urine to the distal nephron. The release of vasopressin will allow the kidney to reabsorb H2O and excrete concentrated urine. |
| Where is ADH made? How is it transported? | In the supraoptic and paraventricular nuclei, transported in granules along their axons, and then secreted from the posterior pituitary, portal capillaries of the median eminence, and the cerebrospinal fluid (CSF) of the third ventricle. |
| Secretion (or release) of vasopressin from the pituitary is regulated by ... | osmolality of the extracellular fluid. Plasma osmolality; it is normally maintained in the range of 280-285 mOsm/kg H2O. |
| What is the setpoint for vasopressin release? | Small increases in osmolality above 280 to 285 mOsm/kg H2O (of only 1 to 2%) will begin to stimulate vasopressin secretion. The rate of vasopressin secretion increases linearly as the osmolality increases |
| What other stimuli besides hyperosmolality can cause ADH release? | Volume depletion or decrease in ECV (modulate osmotic stimulation of ADH release by affecting slope and release set point), drugs, stress, CNS disease |
| What drugs can stimulate ADH release? | barbiturates, narcotics, nicotine |
| Receptors for volume-mediated ADH release appear to be in the... | aortic arch, carotids and left atrium. |
| ADH release is suppressed by ... | hypotonicity, alpha-adrenergic stimulation, ethanol, and volume expansion. |
| What are the receptors for vasopressin? | V1 and V2 |
| Where does vasopressin act? What receptor does it use? What cell signaling method does it use? | specific V2 receptors in the basolateral membrane of collecting tubular cells-->increased cAMP. Movement of H2O channels/aquaporin 2 in membrane vesicles in the cell interior to the apical membrane--> increase apical membrane H2O permeability. |
| What stimulates thirst? | plasma osmolality above 285 mOsm OR decreases in the extracellular fluid volume or "effective" arterial volume will stimulate thirst |
| Its value, relative to plasma osmolality, determines the degree of urinary concentration or dilution. | urine osmolality |
| Free H2O clearance | Clearance of osmotically active particles, or osmolal clearance (Cosm) = (Uosm x V) / Posm Where Uosm = urine osmolality Posm = plasma osmolality And V is the urine volume. |
| During states of water diuresis, the CH2O has a ___ value. During states of antidiuresis, the CH2O has a ___value. | positive; negative |
| electrolytefree water clearance (CeH2O) | CeH2O = V [1 - ((UNa+UK) / PNa)]: useful for estimating ongoing free water losses in the urine when deciding how much to restrict/supplement daily water intake (hypo/hypernatremia) |
| Dehydration: definition and treatment | free water deficit = hypernatremia Treatment: free water repletion (generally slowly) |
| Volume depletion: definition and treatment | Extracellular fluid or effective circulating blood volume depletion Treatment: isotonic fluid replacement (generally more rapidly) |
| Which do you correct first: water imbalances or volume deficits? | Rule of thumb: correct volume deficits first, then correct water imbalances (slowly) |
| Osmoregulation: how is it sensed? How is it clinically assessed? Sensors? Effectors? What is affected? | Plasma osmolality; plasma [Na+], Posm; hypothalamic osmoreceptors; ADH thirst mechanism; water excretion (ADH), water intake (thirst) |
| Volume regulation: how is it sensed? How is it clinically assessed? Sensors? Effectors? What is affected? | Effective circulating volume; history, physical exam, urine [Na+]; carotid sinus, atria, afferent arteriole; SNS, RAAS, natriuretic peptides, ADH; sodium excretion |
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