Loop of Henle, Regulation of Water, Ion and pH Balance Flashcards
What percentage of salt/water in tubule fluid foes the Loop of Henle reabsorb?
20%
(primary func is to determine osmolarity of urine using countercurrent multiplier system)
What does the loop of henle produce in dehydration or excess hydration?
Dehydration: low volume, high conc urine produced
Excess hydration: high volume, dilute urine
While urine conc occurs in collecting duct, osmolarity of interstitial fluid in medulla must be high and osmolarity of tubular fluid must be low - countercurrent multiplier system achieves this
What is the key principle of the countercurrent multiplier system in the loop of henle?
Reaborption of NaCl and water is not coupled
What happens in the ascending loop of henle
(Juxtamedullary nephrons)
-NaCl reabsorbed via a Na+/2Cl-/K+ co-transporter
-No aquaporins are expressed here - no water transport
-Tubular filtrate becomes increasingly dilute, 100mOm (hypotonic)
-Medullary interstitial fluid becomes concentrated with salt (hypertonic)
(Active transport of Na+, Cl- follows passively impermeable to water)
What happens in the descending loop of henle?
-Permeable to water but not salt
-Cells express AQP1 but not Na+ transporters
-Because of high osmolarity of interstitial fluid (created by ascending limb) - osmotic gradient for movement of water out of descending limb through AQP1- tubular fluid becomes more concentrated as ut descends toward tip of loop (1200-1400 mOsm)
(passively permeable to water)
What is crucial for urine conc in the medulla?
-Salty medulla
-Salt extruded by ascending limb must remain in interstitial fluid
-Water extruded by descending limb must be removed by blood
What is vasa recta?
Long blood vessels that parallel the loop of Henle
-Salt and urea move into descending vasa recta
-Salt and urea move out of ascending wasa recta
-Water moves into acsending vaa recta (net effect)
How much is reabsorbed in early nephron vs distal nephron?
85% of glomerular filtrate reabsorbed in early nephron
15% enters distal nephron
What happens in the distal tubule?
-Further NaCl reabsorption occurs via NCC transporter
-No aquaporins are expressed here
-Tubular fluid becomes for hypotonic (100mOsm)
What happens in the collecting duct?
-Further salt and water reabsorption occurs at a rate required to maintain whole body salt and water balance
-Fluid leaving collective duct is urine
Water balance in collecting ducts vs interstitial fluid
-Tubular fluid in collecting ducts is hypotonic
-Medullary interstitial fluid is hypertonic (Countercurrent Multiplier system)
-Strong osmotic force for movement of water out of collecting duct
-Permeability of collecting duct is regulated to control the rate of reabsorption of water and the conc of urine
What is Aquaporin 2? Where is it found and what does it do?
-Water channel expressed in collecting duct epithelial cells
-Increased abundance of AQP2 on apical membrane - increased rate of water reabsorption - urine vol decreases while osmolarity increases
-AQP2 is also stored intracellularly
-Movement into and from apical membrane is regulated
What happens during dehydration - ADH
-During dehydration, osmolarity of blood plasma will increase above 300 mOsm
-Activates osmoreceptors in hypothalamus whihc stimulates release of ADH or vasopressin into circulation
-ADH transported to kidneys and binds to vasopressin receptors on collecting duct epithelial cells
-Triggers insertion of AQP2 into apical membranes
-Permeability of collecting duct to water increases
-Increases reabsorption of water
What happens in excessive hydration?
-Decreased or no ADH secretion, collecting ducts impermeable to water
-Large volumes of dilute (100mOsm) urine produced
Plasma osmolarity in dehydration vs over hydration?
Dehydration - low water intake - high plasma osmolarity - ADH increased - water reabsorbed - little urine volunme
Overhydration - high water intake - decrease plasma osmolarity - decreased ADH - decreased water reabsorption - more water excreted in urine
What ions does the kidneys regulate?
Na+, K+, Cl-, HCO3-, H+
-Urinary excretion of ions is matched to the amounts ingested or produced in the body
-regulating their rates of reabsorption achives this
What is the normal plasma sodium conc and where is Na+ reasborbed?
-135-145 mOsm
-90% of filtered Na+ reabsorbed in the early nephron
-Reabsorption of 10% is in collecting duct and regulated by steroid hormone aldosterone
What is aldosterone?
-Secreted by adrenal gland by low bp and / or low plasma Na+ conc
-Stimulates increased Na+ reabsorption in collecting duct
What triggers the Renin-Angiotensin-Aldosterone System?
-Reduction in blood volume/ pressure (also activates baroreceptors)
-Low Na+ intake (also reduces ECF volume, lower osmolarity inhibits ADH, less H2O reabsorption)
-Reduction in renal afferent arteriolar pressure
-Reduced Na+ conc in tubular filtrate
-Renal sympathetic nerves activated by baroreceptors
(These 3 stimulate granular cells in juxtaglomerular apparatus in nephron to release enzyme renin into circulation)
How does the RAAS work?
-Renin converts a plasma protein, angiotensinogen to angiotensin 1
-In lung capillaries, angiotensin 1 is converted to angiotensin II
-Angiotensin II stimulates the adrenal cortex to release aldosterone
-Aldosterone activates the sodium channel ENaC in collecting duct
-Increased Na+ reabsorption
Look at diagram on slide 19
How is atrial natriuretic peptide (ANP) triggered and how does it work?
-Increased blood volume/blood pressure stimulates atrial stretch receptors which triggers release of ANP into circulation
-ANP acts on kidney to increase GFR and inhibit Na+ and water reabsorption in collecting duct
-Secretion of renein is also inhibited
-Increased water and salt excretion
-Blood volume and blood pressure is reduced
What is natriuesis?
Increased excretion of Na+ into urine
What maintains plasma K+ conc and how
-Aldosterone maintains plasma K+ conc at 3.5-5 meq/L.K+ excretion
-Hyperkalaemia directly stimulates aldosterone release from adrenal gland
In collecting duct aldosterone:
-Activates the basolateral Na+/K+/ATPase
-Activates an apical K+ channel, ROMK
-Increases secretion of K+ into collecting duct
What can abnormal K+ levels cazse?
-Changes in K+ conc alters membrane potentials of cells affecting generation of action potentials
-Hyperkalemia will cause cardiacx arrhythmias
-Hypokalemia causes muscle weaknesses
Where are ions reabsorbed in the kidney for pH balance?
pH 7.4
-Regulate excretion of H+ (acid) into nephron and reabsorption of HCO3- (base) mainly in proximal tubule
-H+ is secreted into lumen in exchange for Na+ (Na+/H+ exchanger)
How does HCO3- reabsorption occur?
-Carbonic anhydrase converts HCO3- to CO2 and water
-CO2 and water diffuse into PT epithelial cells
-Carbonic anhydrase converts CO2 and water to HCO3-
How does bicarbonate reabsorption take place?
Proximal tubule reaborbs abt 80% HCO3-
-Na+/H+ exchanger couples Na+ reabsorption and H+ secretion
-Secreted H+ combines with HCO3- to form CO2 and H2O via carbonic acid catalysed by carbonic anhydrase
-CO2 and H2O absorbed and reverse reaction forms H+ and HCO3-
-HCO3- transported into ECF while H+ re-secreted into tubular fluid
(Increased recycling of H+ increases reabsorption of HCO3-)
How does proximal tubule correct pH imbalances?
Acidosis -PT cells increase secretion of H+ this also increases reabsorption of filtered HCO3- (conserve base)
Alkalosis - PT cells reduce secretion of H+ (conserve acid) this reduces reabsorption of filtered HCO3-
What happens glucose transporters in Diabetes Mellitus?
-Saturated
-Renal plas,a threshold is exceeded
-Transporters have a transport max of 200mg/100ml
