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Tubule Reabsorption

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imissyou419's version from 2017-04-07 00:19

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Question Answer
Proximal tubule % volume reabsorbed65% volume reabsorbed (glucose, a.a., H2O, Na+, K+, Cl-)
LoH % volume reabsorbed20% volume reabsorbed (Descending - H2O & minimal Na+; Ascending - Na+, K+, Cl-)
Glucose and a.a. are only reabsorbed where?proximal tubule
Which part of the tubule is impermeable to water?ascending limb of LoH (no water channels), distal convoluted tubule
DCL & Collecting duct % volume reabsorbed14% volume reabsorbed (Distal - Na+, K+, Cl- Ca2+; Collecting duct - Na+, H2O dependent on hydration and Na+ status)
Transcellular reabsorptionlumen -> apical/luminal membrane -> basement/basolateral membrane -> interstitium -> pertibular/vasa erecta capillary
Transcellular secretionperitubular/vasa erecta capillary -> interstitium -> basement/basolateral membrane -> apical/luminal membrane -> lumen
Paracellular reabsorptiontight junctions affect transport by affecting how close epithelial cells are
Sodium reabsorption functiondrives reabsorption, 30x concentration gradient higher from filtrate (outside of cells) to tubule cells
Examples of Na+ reabsorptionENaC (sodium channel), Na+/glucose symporter (SGLT1 & SGLT2), Na+/H+ exchangers (NHE3), Na+/K+ ATPase
What is the major anion reabsorbed?Cl-
Examples of Cl- reabsorptionchloride channels, chloride symporters (NCC - 1 Na+ and 2 Cl-), chloride multiporters (NKCC2 - Na+, K+, 2Cl- in same direction)
Cl- transport challenges1. transport is against an electrical gradient into tubule cells (-);
2. transport out of tubule cell must have a chemical gradient
Water reabsorptionfollow ions via osmosis when water channels available only or paracellularly
Water reabsorption examplesAQ I, II, III, IV - simple diffusion; paracellular water reabsorption only in proximal tubule; AQ channels in proximal tubule or CD (when ADH is there)
Diabetes Mellitusincreased filtered load of glucose saturate the SGLT transport so some glucose is excreted (water follows via osmosis) leading to osmotic diuresis (normally water would follow all glucose paracelluarly or through AQ)
Symptoms: higher than normal level of glucose in blood, urine contain glucose
Hyperuricemiaincreased level of uric acid (urate) in the blood from purines, leading to gout (fingers and toe inflamed by crystals of uric acid like arthritis) and kidney stones b/c excess uric acid is secreted back into tubules after filtered uric acid is reabsorbed in the proximal tubule (antioxidant function)
Causes of hyperuricemiadecreased uric acid secretions (problems with transporters), increased meat and alcohol intake (high purines)
Aldosterone release from the adrenal gland is stimulated byangiotensin II, high K+ levels (too much K+ = cardiac arrest), ACTH (minor effect)
Baroreceptors for low Na+ levelssympathetic innervation from carotid sinus baroreceptors reflex to juxtaglomerular cells (NE); juxtaglomerular cells also intrarenal baroreceptors (distend more or less depending on blood flow through afferent arteriole)
Chemoreceptors for low Na+ levelsmacula densa cells detect FILTRATE Na+ levels and release paracrine factors i.e. adenosine if high, NO & prostagladins if low
Most renin release from juxtaglomerular cells 3 conditions1. low BP from carotid sinus, 2. low intrarenal pressure, 3. low Na+ in filtrate (NO, prostagladins secreted by macula densa)
Macula densa cells detect NaCl how?NKCC multiporter activity (since it is part of ascending limb - if transporter is not working then NaCl is low)
High Na+/High fluid flow locallymacula densa cells release ATP (cleaved to adenosine) -> ↓ GFR and bind to purinergic receptors inhibiting renin release from juxtaglomerular cells
Low Na+/Low fluid flow locallymacula densa cells release NO (↑ GFR) - tubloglomerular feedback and prostagladins which bind to juxtaglomerular cells stimulating renin release (ANG II ↓ GFR globally)
How does macula densa cells respond to filtrate flow?cilia which bend
ANPpeptide hormone produced by atrial cells by stretching of atria detected by stretch receptors when Na+ levels are high (high BP);
↓Na+ reabsorption by 1. inhibiting aldosterone release from adrenal cortex (more important b/c no transporters can't reabsorb Na+), 2. vasodilate afferent arteriole ↑ GFR (↑ filtered load, ↑ fluid flow)
If high Na+ANP released which vasodilate ↑ GFR globally with each nephron slightly ↓ GFR due to local adenosine
If low Na+ANG II (+ aldosterone) released which vasoconstrict ↓ GFR globally with each nephron slightly ↑ GFR due to local NO
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Question Answer
When is ADH released?when ECF volume is decreased/low BP due to a decrease in total body water, high plasma/ECF osmolarity (most important stimulus), ANG II
ADH made by and storedmade by neuroendocrine cells in the hypothalamus, stored in posterior pituitary in axon terminal
What kind of a hormone is ADH?peptide
Baroreceptors for ADHaortic arch and carotid sinus, also volume receptors in atria (when BP and blood volume decreased -> less AP sent to hypothalamus, increase activity of neuroendocrine cells in hypothalamus w/ axon terminal in posterior pituitary, ADH released;
negative feedback b/c as we conserve water, blood volume and MAP increase)
Osmoreceptors for ADHspecialized neurons located in and around hypothalamus (an increase in plasma osmolarity/hypertonic ECF cause osmoreceptors to shrivel, increase activity of neuroendocrine cells in hypothalamus w/ axon terminals in posterior pituitary, ADH released;
negative feedback b/c as we conserve water, osmolarity of ECF declines)
ADH actionincreases water reabsorption in collecting duct (stimulate AQ II to move to LUMINAL membrane from vesicles in cytoplasm to reabsorb water); without ADH collecting duct is impermeable to water
makes you thirsty
Does ADH have an effect on the basolateral AQ channels?No, AQ III and IV do not respond to ADH
What happens if there is a decrease in blood volume and decrease in plasma osmolarity i.e. dehydrated but don't drink as much water as you should?osmoreceptors are more sensitive (body cares more about osmolarity in normal physiological range - peripheral circulation can perfuse you organs) so decrease ADH a bit;
In case of hemorrhaging, blood volume matters more because need blood to perform your organs, baroreceptors override osmoreceptors, high concentration of ADH cause peripheral vasoconstriction to conserve volume)
Osmolarity of proximal tubule300 mOsm (equal solute and equal water reabsorbed so isotonic)
Osmolarity of descending limbwater reabsorbed leaving by osmosis through water channels (first leave basolaterally then luminally until it reaches outside interstitial concentration); osmolarity of filtrate goes from 300 mOsm -> 1400 mOsm
Osmolarity of ascending limbions reabsorbed; 200 mOsm difference between inside of tube and outside i.e. inside is 300mOsm when outside is 500 mOsm b/c there is paracellular transport of Na+ back into body; osmolarity of filtrate goes from 1400 mOsm -> 300 mOsm
Osmolarity of distal convulated tubulereabsorb ions so osmolarity continues to decrease, most dilute is 100 mOsm (difference of 200 mOsm from inside to outside)
Osmolarity of collecting ducthormones regulate permeability of water and Na+ (no ADH -> water not reabsorb so most dilute urine is 100 mOsm and maximal urine; max ADH -> all luminal membranes have AQ II for maximal water reabsorption, water moves by osmosis to match outside interstitial so inside of tube will be 1400 mOsm if outside 1400 mOsm and minimal urine
Average urine osmolarity300 mOsm, 2 L
Osmolarity of LoHcountercurrent, water and ions move into interstitial space deposition
Diuresis def'n and 3 examplesincreased production of urine e.g. ethanol, AVP receptor antagonist, NKCC transporter antagonist
Natriuresisincreased excretion of sodium
What does ethanol do?inhibit release of ADH
What does AVP receptor antagonist (ligand is ADH) do?inhibit receptor so like you don't have ADH; water pills for high blood pressure, congestive heart failure with build up of fluid
What does NKCC transporter antagonist do?if ion multipler cannot reabsorb Na+, K+, 2Cl- then interstitial medullary osmolarity decreases (1400-1100 mOsm) so can't produce as concentrated urine
Diabetes Insipidus caused byfailure to release ADH (neurogenic) or failure of collecting duct to respond to ADH (nephrogenic) so have increased urine output b/c failure to reabsorb water. Treatment: AVP agonist (synthetic ADH)
Decrease in osmolarity, increase in volumedrinking large amount of water, low ADH release
Increase in osmolarity, increase in volumeingestion of hypertonic saline, higher ADH release
Increase in osmolarity, decrease in volumedehydration (i.e. sweat loss or diarrhea) highest ADH
Increased in osmolarity, decrease in volume pathway KNOW THISsweating (removal of hypoosmotic solution) -> decrease in ECF volume (also increase ADH release, carotid sinus baroreceptor reflex onto JG cells which release renin - RAAS activation, intrarenal baroreceptors detect lowered volume of blood in afferent arteriole - renin release, macula densa cells not active, production of ANG II and aldosterone, increased Na+ reabsorption in proximal tubule and collecting duct which improve water reabsorption through osmosis), increase in plasma osmolarity (osmoreceptors detect and ADH released from posterior pituitary), ADH increase water reabsorption in collecting duct; ECF volume normalized and RAAS pathway is turned off; if Na+ levels get too high by initial RAAS activation, macula densa cells detect Na+ and inhibit RAAS pathway
3 Mechanisms to perform acid/base balance by the kidney1. excrete excess H+, reabsorb filtered HCO3-, create new HCO3-
Source of acidsfood - acidic fruit, a.a., fatty acids; metabolic intermediates - pyruvate, components of citric acid cycle; lactic acid by anaerobic metabolism; production of CO2 by aerobic respiration
Source of basesfood - citric fruit
Carbonic anhydrasefound both extracellularly and intracellular, catalyzes CO2 + H2O <-> H2CO3 <-> H+ + HCO3-
Bicarb in proximal tubuleNHE3 (Na+/H+ exchanger) secrete H+, HCO3- combines with secreted H+ to form CO2 through luminal membrane CA, CO2 diffuse into cells, CO2 combines with H2O in tubule cells to form H+ and HCO3- by cytoplasmic CA, H+ is secreted again, HCO3- is reabsorbed by Na+/HCO3- symporter (bicarb drives this b/c concentration and electrical favourable)
Collecting duct: Type A intercalated cells - response to acidosisblood [H+] high, interstital [H+] high, combine with HCO3- to CO2 catalyzed by interstitial/blood CA, CO2 diffuse into type A intercalated cells and CO2 interact with H2O to becomes H+ and HCO3- catalyzed by cytoplasmic CA, H+ secreted through H+/K+ exchanger and H+ ATPase (both use ATP); consequence of acidification results in hyperkalemic; HCO3-/Cl- antiporter reabsorb HCO3- which acts as a buffer to lower [H+], K+ reabsorbed by basolateral K+ leak channel
Collecting duct: Type B intercalated cells - response to alkalosisblood [H+] low, interstitial [H+] low, H2O and CO2 combine by cytoplasmic CA to form H+ and HCO3-, HCO3-/Cl- exchanger on luminal membrane secrete HCO3-; H+ moves across basolateral by H+/K+ ATPase and H+ ATPase so increase H+ in interstitial space; alkalosis result in hypokalemic (K+ leak channel in luminal membrane secreting K+ that moved in from H+/K+ exchanger)
How does body know if type A or type B activated?pH receptor GPCR on basolateral membrane (when pH of type B becomes basic, activated by their receptor and bicarb/Cl- exchanger in luminal membrane, K+ channel (they are normally in vesicles) (when pH of type A cells become acidic, activated, insert ATPases into luminal membrane)
Metabolic acidosis causesexcessive breakdown of fats/a.a, ingestion of aspirin, methanol and antifreeze
Respiratory acidosis causeshypoventilation, drug induced respiratory depression, airway resistance due to asthma, fibrosis, muscle weakness from muscular dystrophy
Metabolic alkalosis causesexcessive loss of H+ due to vomiting, excessive ingestion of antacids
Respiratory alkalosis causeshyperventilation
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Question Answer
Bicarb proximal tubule bicarb transporterNa+/HCO3- symporter (driven by HCO3-)
type A response to acidosis transporterCl-HCO3- antiporter
type A acidosis result inhyperkalemia
type B alkalosis (base) result inhypokalemia
Angiotensin IIincreases Na+ reabsorption in proximal tubule by binding on luminal and basolateral membrane; ↑ activity of Na+/H+ exchanger, Na+/K+ ATPase; potent vasoconstrictor
Aldosteroneincreases Na+ reabsorption in collecting duct bind on intracellular receptor; ↑ # Na+ & K+ channels on luminal membrane, ↑ activity of Na+/K+ ATPase, ↑ expression of Na+ channels and Na+/K+ ATPase
RAAS pathwayangiotensinogen (constitutively expressed by liver), cleaved by enzyme renin (JG) when Na+ levels are low to ANG I, cleaved by ACE to ANG II (ACE highest in pulmonary lung capillaries plasma membrane of endothelial cells), goes to adrenal cortex to release aldosterone
Proximal tubule channelsSGLT2 more common (1 Na+, 1 glucose); ANG II ↑ activity of Na+/H+ exchanger of luminal, ↑ activity of Na+/K+ exchanger of basolateral; AQ I luminal and basolateral; H2O, Cl-, K+ paracellular
Descending limb channelsNa+ channel luminally, AQ I
Ascending limb channelsLuminally: ENAC, NKCC, K+ leak channel to supply NKCC; Basolaterally: K+/Cl- symporter, Cl- channel; Na+ paracellular transport
Distal convoluted tubule channelsLuminally: ENAC, Na+/Cl- symporter, Ca2+ channel (PTH); Basolaterally: K+/Cl- symporter, Na+/Ca2+ exchanger
Collecting duct channelsAldosterone ↑ # ENAC, # K+ channels (secretion), ↑ activity of Na+/K+ ATPase; AQ II by ADH
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