Presentation on theme: "Urinary System L 2, 3 Tubular Reabsorption & secretion"— Presentation transcript:
1Urinary System L 2, 3 Tubular Reabsorption & secretion Prof. Madaya Dr Than Kyaw1, 8 October 2012
2Tubular Reabsorption & secretion For reabsorption a substance- must pass from tubular lumen through tubular epithelial cells- diffuse through interstitial fluid (ISF)- enter the capillarySecretionFor secretion a substance- must leave the capillary- diffuse through ISF- pass thru tubular epithelial cells into the lumen
4Reabsorption of Na+, Cl-, glucose and A/A Substances important for body functions (e.g. glucose, a/a) enter tubular fluid by filtration at the glomerulusDue to their relatively small molecular size - pass easily thru’ glomerular membraneConcentration in the filtrate and plasma the sameIf they are not returned (not reabsorbed) to blood – they are excreted in the urine and lost from the body
5Proximal convoluted tubules - the longest part; make up most of the renal cortex- cuboidal cells with a luminal border modified with microvilli (brush border)providing large surface area- important substances like glucose and amino acids % reabsorptionGlucose orA/A inTubular lumenDiffuse intoperitubular capillaryTransport coupledwith transport of NaActive transport(energy used -Na+ -K + -APTase)Carrier proteinNo additionalenergy neededfor glucose or A/ANa+ + glucoseorNa+ +A/A
6Reabsorption and secretion Once inside the tubular cell – A/A or glucose uncoupled from the carrierDiffuse basal or lateral border to ISF → capillariesNa+ – actively transported from tubular epithelial cells to ISF and then to capillariesThe carrier protein return to its previous conformation to transport more glucose /amino acids/ Na+Unlike other tissues, glucose in the renal tubules and instestine is actively and continually transported even though its concentration in the lumen is minute; thereby loss of glucose from the body is prevented by active transport (uphill)Active transport needs both carrier and energy
7Reabsorption and secretion Transport of Na+ from tubular lumen into the tubular epithelial cell andits co-transport with glucose.Energy requirement is provided by the Na+ -K + -APTase (sodium pump)
8Protein channel (carrier protein): pores; contain a single or a cluster of proteins;specificity for certain substances or restrictive due to the size.Water easily diffuses through protein channel.
9- Transported molecule enters the carrier protein channel and bind with the receptor. After binding the carrier protein undertakes conformational change to open the channel on the opposite side.- Then transported molecule is released and carrier protein returns to original conformation for transport of another molecules.
10Reabsorption and secretion Some low molecular weight substances- bound to plasma proteins- retained in the blood plasmaE.g. - calcium, iron, hormones (e.g. thyroxine)- only a small fraction of them that are unbound passthrough
11Reabsorption of Water and Urea Removal from lumeninto ISF and capillariesNa+, Cl- ,65% water,85 – 90% HCO3100% glucose, amino acidsOther substances Concentration of water in the lumenAbsorption favoured byLow HPColloidal osmotic PressureWater reabsorbed by osmosis into the ISF and capillaries
12Tubular secretion Some substances are removed (secreted) - from blood through the peritubular capillary network- into the distal convoluted tubules or collecting ducts.- These include: H+ ions, K+, NH3 , creatinine, and drugs.- H+ ions – secreted throughout the length of nephron tubule (except thin loop of Henle);- coupled with reabsorption ofK+ - secreted at DCT and CT and CD;- coupled with reabsorption of Na+- NH3 - its secretion rate depends on acid-base equilibrium of body fluid- Urine is a collection of substances that have not been reabsorbed during glomerular filtration or tubular secretion.
13Tubular Transport Maximum (TM) TM = Substances associated with membrane transporters (carrier or active transport) for reabsorption have a maximum rate at which they can be removed– e.g. glucoseRenal threshold = the plasma concentration of a substance when it first appears in the urine- TM for the substance is exceeded its limit.
14Renal threshold of gucose and diabetes mellitus Impaired movement of glucose from plasma into body cells↑plasma concentration of glucose↑ Plasma and tubular load exceeds availability of carrier molecules for glucose transport and reabsorption123Aboverenal thresholdGlucose in the tubules & urine(Glucosurea)Deficient or lack of insulin
15Renal threshold of gucose and diabetes mellitus Glucose contributes effective osmotic pressure of the tubulesWater in the tubules & hence in the urine↑ Volume of water in the tubules & hence in the urineOsmotic diuresisFrequent urinationDrink more waterGlycosuria (glucosuria): presence of glucose in urinePolyuria: frequent urinationPolydipsia : increased thirstPolyphagia : increased hunger
16Renal counter-current mechanisms 1. Countercurrent multiplier system2. Countercurrent exchanger systemCountercurrent multiplier system:It is the process by which a progressively increasing osmotic gradient is formed as a result of countercurrent flow.
17Parts involved in countercurrent multiplier system Descending limb of loop of HenleThin segment of ascending limbThick segment of ascending limbCortical collecting ductOuter medullary collecting ductInner medullary collecting duct
18Countercurrent multiplier system 1Impermeable to solutes but permeable to waterWater diffuses by osmosis to the higher osmotic pressure of ISFSolute conc. (mainly NaCl) increasing while approaching hair-pin turn of loop of Henle2Thin segment of ascending limb – permeabe for NaCl but impermeable to waterWater remains in the tubule and NaCl difuses (due to concentration gradient) to ISF
19Countercurrent multiplier system 3Thick segment of ascending limb – active transport of NaCl to the ISFWater continues to be retainedOsmolality of tubular fluid entering descending limb is 300 mOsm/kg H2OTubular fluid leaving ascending limb and entering distal tubule – diluted (osmolality 185 mOsm/kg H2O
20Countercurrent multiplier system Vertical osmotic gradient in ISFIs lower in outer medulla and higher in inner medulla and at hair-pin turn; established and maintained bya) continued active transport of NaCl by thick segment of ascending imbb) conc of tubular fluid in the descending limbc) passive diffusion of NaCl from the lumen of thin segment of ascending limb into the inner medullary ISF
21Countercurrent exchanger system It is a countercurrent system in which transport between inflow and outflow is entirely passive.Vasa recta- is a countercurrent exchanger- Permeable to water and solutes throughout their length
22Countercurrent exchange in vasa recta Blood enter with300 mOsm/kg waterDescends through increasinglyhypertonic peritubular fluidin medulla.3. Water diffuses out.Solutes diffuses in untilhair-pin turn is reached.Blood then ascents throughdecreasing hypertonicity andwater diffuses in and solutediffuses out.Blood returns to the cortex.Milliosmolality is only slightlyhigher than when it enteredVasa recta.
23Countercurrent exchanger system In descending limb – water drawn by osmosis from vasa recta to ISF (hyperosmotic created by countercurrent multiplier)Solutes diffuse from ISF to vasa rectaIn ascending limb – solutes diffuse back into ISFWater is drawn by osmosis back into vasa rectaThe function of countercurrent exchange- to retaine solutes in the ISF of medullaIncrease rate of blood flow in vasa recta – reduce time for diffusion of solute from ascending limb back to ISF – gradual loss of solute from medulla – medullary washoutThis is prevented by low blood flow- 10 to 20% of kidney blood flow
24Role of urea Urea - Contributes high solute concentration in ISF Recirculation of urea assists countercurrent multiplier system and osmotic gradientUrea excretion is maintained almost at the same level whether the urine is dilute or concentrated.
25Concentration of Urine ADH and Osmoregualtion- Epithelial cells of CT, CD – variable permeability depending on ADH amount (Post Pit)- ADH - permeability of these cells for waterADH secretion - significant in 2% changes in plasma osmolalityDegree of ECF dehydration – Osmoreceptor cells in hypothalmusHyperosmolality - secretion of ADH- ADH acts on cortical and medullary CDs- water reabsorptionThirst center in hypothalamus - also stimulated by hyperosmolality
26Relationship among hypothalamus, posterior pituitary and kidney in the regulation of extracellular dehydration
27Thirst – predominant factor for correction of hyperosmolality Control of hyperosmolalityHypothalamus regulatedThirst – predominant factor for correction of hyperosmolality
28Diabetes insipidus- Water is not reabsorbed in the CTs and CDs – excreted as urineHypotonic tubular condition – absence or severely decreased amount of ADHk/s diabetes insipidusAnimal with this condition- polyuria ( excess amount of water in urine)- polydipsia (excessive thirst and excessive water intake)- urine formed - dilute, lower than normal specific gravityWhat are the differences between diabetes melitus and diabetes insipidus
29Diabetes insipidus and diabetes mellitus What are the differences and similarities between diabetes mellitus and diabetes insipidusParticularDiabetes insipidusDiabetes mellituscauseLack or deficient ADH+ce of glucose in urineOsmotic diuresis-ce+cePolyuria+PolydipsiaThirstSpecificiific gravityowHighUrine contentNo glucoseglucose
30Urine concentration Normally - Urine concentration may vary depending on multiple factorsIn extreme cases in domestic animals– urine-to-plasma osmolal ratio may approach (2400:300);the urine concentration is 8 times that of plasmaIn desert rodents – urine-to-plasma ratio (16:1)-- extreme adaption for body water conservation-- water - not available; mostly gained water – metabolic-- water loss minimized for survival
31Renal failure and reduced urine concentration Acute renal failureNormal : high O2 supply and high O2 use in renal tissuePersistently low renal perfusion (low renal blood supply as in shock or renal damage) = decrease in GFR over hours or days = causes acute renal failureChronic renal failure- If renal failure (impaired GFR) remains for months
32Renal failure and reduced urine concentration Concentration failureMostly found in chronic renal diseases - ↓ concentrating abilityMore solute remained in functional nephrons- contribute osmotic diuresisHypertonicity in medullary ISF not maintained due to- loss of medullary t/s or ↓ blood flow in the vasa recta- ↓Na and Cl transport from the thick segament of ascending limb of loop of HenlenDamage to cells in CTs and CDs – making less responsive to ADH