11/05/1431. Urine Formation by the Kidneys Tubular Processing of the Glomerular Filtrate

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1 Urine Formation by the Kidneys Tubular Processing of the Glomerular Filtrate Chapter 27 pages

2 OBJECTIVES At the end of this lecture you should be able to describe: Absorptive Characteristics of different parts of nephrons Transport Mechanisms operating in nephrons Tubular Reabsoprtion and Secretion 2

3 URINE COMPOSITION ph Colour Specific Gravity Volume freshly voided urine is usually acidic (around ph 6), range=4.8 and 7.5 Bright Yellow & transparent to L per day Albumin 20 µg of albumin per minute (30 mg in 24 hours) Glucose None inulin urea gluc Creat Urinary Excretion Rate = Filtration Rate Reabsorption Rate + Secretion Rate 3

4 Glucose Urea Glucose (g/day) Bicarbonate (meq/day) Sodium (meq/day) Chloride (meq/day) Potassium (meq/day) Urea (g/day) Creatinine (g/day) Amount Filtered Amount Reabsorbed Amount Excreted % of Filtered Load Reabsorbed ,320 4,318 2 > ,560 25, ,440 19, Changes in Average Concentration of Different Substances at Different Points in Tubular System Relative to Glomerular Filtrate 4

5 CLASSIFICATION OF TRANSPORT MECHANISMS SIMPE DIFFUSION FACILITATED DIFFUSION PRIMARY ACTIVE TRANSPORT SECONDARY ACTIVE TRANSPORT PINOCYTOSIS BULK FLOW 5

6 PRIMARY ACTIVE TRANSPORTERS Sodium-potassium ATPpase Hydrogen ATPpase Hydrogen-potassium ATPpase Calcium ATPpase. REABSORTION PATHWAYS PARACELLULAR TRANSCELLULAR 6

7 Ultrafiltration PROXIMAL CONVOLUTED TUBULE many mitochondria brush border multiplies the surface area about 20-fold. tight junctions lateral intercellular spaces. 7

8 PROXIMAL CONVOLUTED TUBULE PCT SGLT 2 Na G H+ Na AA Na Cl- Iso osmotic 65% Na ATP K Org acids & bases bile salts,oxalate urate Ep,NE drugs toxins PAH 8

9 PCT PARACELLULAR PATHWAY Obligatory 80 % Hormonally Regulated 20 % 9

10 10

11 THIN DESCENDING SEGMENT OF LOOP OF HENLE few mitochondria flattened with few microvilli Solutes H 2 O THICK ASCENDING LOOP OF HANLE AND EARLY DCT Many mitochondria and microvilli, but fewer than in the proximal tubule 11

12 THICK ASCENDING LOOP OF HENLE AND EARLY DCT Many mitochondria and microvilli, but fewer than in the proximal tubule Solutes H 2 O 12

13 EARLY DISTAL TUBULE Mechanism of sodium chloride transport in the early distal tubule 13

14 LATE DCT AND CORTICAL COLLECTING DUCT I Cell P Cell Mitochondria and microvilli decrease Principal Cells (Na Abs and ADH related Water abs) Intercalated Cells (Acid Sec and HCO3 Transport) 14

15 Principal Cell intercalated cell 15

16 MEDULLARY COLLECTING DUCT 16

17 High Osmolality Low ECF Volume Osmoreceptors Pressure R ADH P Cell Aquaporins H2O H2O H2O H2O Neelam Valley 17

18 REABSORPTION OF WATER IN DIFFERENT SEGMENTS OF TUBULES PART OF NEPHRON PERCENTAGE REABSORBED Proximal tubules 65 Loop of Henle 15 Distal tubules 10 Collecting ducts 9.3 Passing into urine 0.7 REABSORPTION OF WATER IN DIFFERENT SEGMENTS OF TUBULES PART OF NEPHRON AMOUNT REABSORBED Glomerular Filtrate 125 Flowing into the loops of Henle 45 Flowing into the distal tubules 25 Flowing into the collecting tubules 12 Flowing into the urine 1 18

19 GLUCOSE REABSORPTION IN NEPHRON Lumen Epithelial Cells Peritubular Capillary Early PCT Na G G ATP Na K G SGLT 2 G GLUT 2 BLOOD Tm for Glucose is 375 mg/min GLUCOSE REABSORPTION IN GIT Lumen Epithelial Cells ECF G G Na G SGLT 1 F GLUT 5 G F Na ATP K GLUT 2 BLOOD 19

20 GLUCOSE REABSORPTION Tmax 375 mg/min FBG= FBG= mg/dl RBG= RBG= mg/dl Filtered Load 125 mg/min (GFRxPlasmaGlu) Renal Threshold 200mg/dl GLUCOSE REABSORPTION 20

21 AMINO ACIDS REABSORPTION IN NEPHRON Lumen Na aa Prot. Sodium Pinocytosis Epithelial Cells Early PCT aa Na ATP Peritubular Capillary K BLOOD Facilitated Diffusion Albumin Excretion in health and disease 21

22 TUBULAR TRANSPORT MAXIMUM The Maximum limit/rate at which a solute can be transported across the tubular cells of kidneys is called TUBULAR TRANSPORT MAXIMUM Tm for Glucose is 375 mg/min TUBULAR TRANSPORT MAXIMUM FOR DIFFERENT SUBSTANCES SUBSTANCE Glucose Phosphate Sulfate Amino Acids Urate Plasma Protein Hemoglobin Lactate Acetoacetate Tm 375 mg/min 0.1 mm/min 0.06 mm/min 1.5 mm/min 15 mg/min 30 mg/min 1 mg/min 75 mg/min variable 22

23 Transport Maximums for Substances That Are Actively Secreted Substance Creatinine Para-aminohippuric acid Transport Maximum 16 mg/min 80 mg/min GRADIENT-TIME TRANSPORT (1) the electrochemical gradient for diffusion of the substance across the membrane (2) the permeability of the membrane for the substance (3) the time that the fluid containing the substance remains within the tubule. 23

24 Sodium Reabsorption from tubular lumen into blood involves 3 steps: 1. Sodium diffuses across the luminal membrane into the cell down an electrochemical gradient established by the sodium-potassium ATPase pump on the basolateral side of the membrane. 2. Sodium is transported across the basolateral membrane against an electrochemical gradient by the sodium-potassium ATPase pump. 3. Sodium, water, and other substances are reabsorbed from the interstitial fluid into the peritubular capillaries by ultrafiltration, a passive process driven by the hydrostatic and colloid osmotic pressure gradients. SODIUM HANDLING Na+ moves by co transport or exchange from the tubular lumen into tubular epithelial cells downhill. From cells into interstitium it moves by primary active transport (Except thin portions of loop of Henle). In DCT and CT it is under hormonal control 24

25 SODIUM HANDLING SITE Proximal Tubule Thick Ascending Limb EarlyDCT Late DCTCollecting Duct APICAL TRANSPORTER Na/Gluc CT Na/Pi CT Na/Amino Acid Na/Lactate Na/H Exchanger Cl/Base Exchanger Na, 2 Cl,, K CT Na/H Exchanger K K Channels NaCl CT Na Channel (ENaC) FUNCTION Na & Gluc Uptake Na & Pi Uptake Na & AA Uptake Na & Lactate Uptake Na Uptake and H Extrusion Cl Uptake Na, 2 Cl,, K Uptake Na Uptake and H Extrusion K K Extrusion Na & Cl Uptake Na Uptake 25

26 Active reabsorption of sodium coupled to the passive reabsorption of chloride Na-H COUNTER TRANSPORT 26

27 HYDROGEN Na-H COUNTER TRANSPORT Luminal Membrane Secreted in Proximal Tubule and Thick ascending LOH by Counter Transport with Na Secreted in DCT by H ATP ase PCT & LOH I Cell intercalated cell 27

28 Effect Of Aldosterone On Cortical Collecting Duct Na Channel (ENaC) UREA Plasma concentration is mmol/l 50 % is reabsorbed in PCT passively with water It is the only waste to be reabsorbed Creatinine and Phenol are not reabsorbed. 28

29 POTASSIUM It is both reabasorbed and secreted 67% of filtered load is reabsorbed by PCT solvent drag secreted by Thick Asc LOH, early distal tubule / collecting duct correlated with dietary intake 80% of filtered load appears in urine if dietary content high 1% if dietary content low CALCIUM Ionized Calcium is freely filtered and reabsorbed in PCT It moves into tubular cells passively (downhill) It moves out of the cell by Ca/Na Counter Transport or Actively by Ca ATP ase Mechanism Its reabsorption is Hormonally controlled 29

30 PHOSPHATE It is reabsorbed by cotransport with Na in PCT in luminal border Its reabsorption is Hormonally controlled It is increased by Vit D and decreased by Parathyroid Hormone SULPHATE Like PHOSPHATE reabsorbed with Na PERITUBULAR CAPILLARY AND RENAL INTERSTITIAL FLUID PHYSICAL FORCES 30

31 31

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