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Renal physiology
SESSION OUTCOME
At the end of the lecture, the group should be able to:
1. describe the basic principles of solute transport in a renal tubule
and;
2. understand the concepts on reabsorption and secretion along
different parts of the nephrons.
ESSENTIAL
QUESTIONS:
HOW IS URINE PROCESSED?
HOW SOLUTES ARE
TRANSPORTED ACROSS RENAL
TUBULES?
Nephron:
functional unit of the kidney
 The nephron consists of:
 Vascular components
 Afferent & efferent
arterioles
 Glomerulus
 Peritubular capillaries
 Vasa recta
 Tubular components
 Proximal convoluted
tubule
 Distal convoluted tubule
 Nephron loop (loop of
Henle)
 Collecting duct
 Tubovascular component
 Juxtaglomerular
Concentration and
Dilution of the Urine
• Maximal urine concentration
= 1200 - 1400 mOsm / L
(specific gravity ~ 1.030)
• Minimal urine concentration
= 50 - 70 mOsm / L
(specific gravity ~ 1.003)
FORMS OF MEMBRANE
TRANSPORT
8
CELL MEMBRANE
Polar heads
Hydrophilic
Non-polar tails
hydrophobic.
Membrane
transport
Passive
Simple diffusion
Facilitated
Diffusion
Active
Primary
active
Secondary
active
PASSIVE
TRANSPORT
With concentration
gradient (downhill)
No need for energy
10
11
ACTIVE TRANSPORT
• Against concentration gradient (UP hill)
• need energy (ATP, Creatine
Phosphate)
12
13
14
Tubular reabsorption
Both requires passive and active
transport mechanism
Solute can be transported through
paracellular pathway or transcellular
Water moves through osmosis
Primary Active Transport of Na+
Sodium diffuses across the luminal
membrane into the cell down an
electrochemical gradient
Sodium is transported across the
basolateral membrane against an
electrochemical gradient by the
sodium-potassium ATPase pump.
 Sodium, water, and other substances
are reabsorbed from the interstitial
fluid into the peritubular capillaries
by ultrafiltration
Secondary Active Transport mechanism
No energy required
Includes Sodium glucose
transporter(SGLT2 and SGLT1)
Sodium-hydrogen exchanger(NHE)
Carrier molecule is needed
“PUNONG PUNO NA
AKO SA INYONG
LAHAT!, DI KO NA
KAYA ah!!!”
PETMALU KA
BATO!!!!
GLUCOSE
TUBULAR TRANSPORT
MAXIMUM
It is the maximal amount of a substance (in mg) which
can be transported (reabsorbed or secreted) by tubular
cells/min.
 Carrier proteins have a maximum transport
capacity (Tm) which is due to saturation of the
carriers.
23
Glucose transport maximum
Transport maximum: 375 mg/min
Filtered load : 125 mg/min
Plasma concentration: 100mg/100 ml
Substance Measure Filtered* Excreted Reabsorbed % Filtered Load Reabsorbed
Water L/day 180 1.5 178.5 99.2
Na
+
mEq/day 25,200 150 25,050 99.4
K
+
mEq/day 720 100 620 86.1
Ca
++
mEq/day 540 10 530 98.2
HCO3
-
mEq/day 4320 2 4318 99.9+
Cl
-
mEq/day 18,000 150 17,850 99.2
Glucose mmol/day 800 0 800 100.0
Urea g/day 56 28 28 50.0
Interstitial
Fluid
Tubular
Lumen
Tubular
Cells
Reabsorption of Water and Solutes is Coupled
to Na+ Reabsorption
Na +
K+
ATP
Na +
K+
ATP Na +
- 3 mV
0 mv
H20
Cl-
Urea
Na +
H +
glucose, amino
acids
Na +
- 70 mV
Copyright © 2006 by Elsevier, Inc.
Figure 27-5;
Guyton and Hall
Mechanisms by which Water, Chloride, and Urea
Reabsorption are Coupled with Sodium Reabsorption
TRANSPORT OF SOLUTE ACROSS THE
TUBULES
Cellular Ultrastructure and Primary Transport
Characteristics of Proximal Convoluted Tubule
65-67% filtered load is reabsorb
Contains extensive brush border
structure
Site for the secretion of toxin, organic
acids and bases
Reabsorption is highly passive
TRANSPORT IN EARLY PCT
Na ion uptake primarily coupled by
hydrogen ion(antiporter) ,glucose(co-
transport),amino acid and lactate
Transtubular osmotic gradient drive
water movement across cell
membrane
TRANSPORT IN LATE PCT
Na and Cl is transported through
parallel operation of Na/H exchanger
and Cl/base
Cl is passively reabsorb in the
basolateral membrane
Cellular Ultrastructure and Transport Characteristics of
Thin and Thick Loop of Henle
 not permeable to H2O
 very permeable to H2O)
 No brush border structure (few
mitochondria) and minimal level of
metabolic activity.
 No brush border structure (few
mitochondria) and minimal level of
metabolic activity.
 20% of filtered load of Na, Cl and K are
reabsorbed
TRANSPORT IN THICK
ASCENDING LIMB
 Movement of sodium across the
luminal membrane is mediated primarily
by a 1-sodium, 2-chloride, 1-potassium co-
transporter
 Tubular fluid is very diluted
 Site of action of some diuretics
Cortical and Juxtamedullary nephron segments
Countercurrent Multiplier System
in the Loop of Henle
 Active transport of sodium ions and co-
transport of potassium, chloride, and other
ions.
 Active transport of ions from the
collecting ducts into the medullary
interstitium.
 Facilitated diffusion of large amounts
of urea from the inner medullary collecting
ducts into the medullary interstitium.
Animal Max. Urine Conc. (mOsm /L)
Beaver 500
Pig 1,100
Human 1,400
Dog 2,400
White Rat 3,000
Kangaroo Mouse 6,000
Australian Hopping Mouse 10,000
• The vasa recta
serve as
countercurrent
exchangers
• Vasa recta blood
flow is low
(only 1-2 % of
total renal
blood flow)
Sodium Chloride Transport in Early Distal Tubule
• not permeable to H2O
• not very permeable to urea
• permeability to H2O depends on ADH
• not very permeable to urea
Figure 27-12;
Guyton and Hall
Sodium Chloride Reabsorption and Potassium
Secretion in Collecting Tubule Principal Cells
Cellular Ultrastructure and Transport Characteristics of
Medullary Collecting Tubules
 The permeability of the medullary collecting
duct to water is controlled by the level of
ADH
 Unlike the cortical collecting tubule, the
medullary collecting duct is permeable to
urea,
HORMONES THAT REGULATE TUBULAR SECRETION
EFFECT OF ANG II IN RENAL TUBULES
Late Distal, Cortical and Medullary
Collecting Tubules
Tubular Lumen
Principal Cells
Cl -
H20 (w/o ADH)
Aldosterone
K+
Na +
ATP
K+
ATP
Na +
Copyright © 2006 by Elsevier, Inc.
Summary of Water Reabsorption and
Osmolarity in Different Parts of the Tubule
• Proximal Tubule: 65% reabsorption, isosmotic
• Desc. loop: 15-20% reabsorption, osmolarity increases
• Asc. loop: 0% reabsorption, osmolarity decreases
• Early distal: 0% reabsorption, osmolarity decreases
• Late distal and coll. tubules: ADH dependent
water reabsorption and tubular osmolarity
• Medullary coll. ducts: ADH dependent water
reabsorption and tubular osmolarity
Renal Physiology: Transport and Concentration of Urine
Renal Physiology: Transport and Concentration of Urine

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Renal Physiology: Transport and Concentration of Urine

  • 2. SESSION OUTCOME At the end of the lecture, the group should be able to: 1. describe the basic principles of solute transport in a renal tubule and; 2. understand the concepts on reabsorption and secretion along different parts of the nephrons.
  • 3. ESSENTIAL QUESTIONS: HOW IS URINE PROCESSED? HOW SOLUTES ARE TRANSPORTED ACROSS RENAL TUBULES?
  • 4. Nephron: functional unit of the kidney  The nephron consists of:  Vascular components  Afferent & efferent arterioles  Glomerulus  Peritubular capillaries  Vasa recta  Tubular components  Proximal convoluted tubule  Distal convoluted tubule  Nephron loop (loop of Henle)  Collecting duct  Tubovascular component  Juxtaglomerular
  • 5.
  • 6. Concentration and Dilution of the Urine • Maximal urine concentration = 1200 - 1400 mOsm / L (specific gravity ~ 1.030) • Minimal urine concentration = 50 - 70 mOsm / L (specific gravity ~ 1.003)
  • 11. 11
  • 12. ACTIVE TRANSPORT • Against concentration gradient (UP hill) • need energy (ATP, Creatine Phosphate) 12
  • 13. 13
  • 14. 14
  • 15. Tubular reabsorption Both requires passive and active transport mechanism Solute can be transported through paracellular pathway or transcellular Water moves through osmosis
  • 16. Primary Active Transport of Na+ Sodium diffuses across the luminal membrane into the cell down an electrochemical gradient Sodium is transported across the basolateral membrane against an electrochemical gradient by the sodium-potassium ATPase pump.  Sodium, water, and other substances are reabsorbed from the interstitial fluid into the peritubular capillaries by ultrafiltration
  • 17.
  • 18. Secondary Active Transport mechanism No energy required Includes Sodium glucose transporter(SGLT2 and SGLT1) Sodium-hydrogen exchanger(NHE) Carrier molecule is needed
  • 19. “PUNONG PUNO NA AKO SA INYONG LAHAT!, DI KO NA KAYA ah!!!” PETMALU KA BATO!!!! GLUCOSE
  • 20. TUBULAR TRANSPORT MAXIMUM It is the maximal amount of a substance (in mg) which can be transported (reabsorbed or secreted) by tubular cells/min.  Carrier proteins have a maximum transport capacity (Tm) which is due to saturation of the carriers.
  • 21.
  • 22.
  • 23. 23
  • 24. Glucose transport maximum Transport maximum: 375 mg/min Filtered load : 125 mg/min Plasma concentration: 100mg/100 ml
  • 25. Substance Measure Filtered* Excreted Reabsorbed % Filtered Load Reabsorbed Water L/day 180 1.5 178.5 99.2 Na + mEq/day 25,200 150 25,050 99.4 K + mEq/day 720 100 620 86.1 Ca ++ mEq/day 540 10 530 98.2 HCO3 - mEq/day 4320 2 4318 99.9+ Cl - mEq/day 18,000 150 17,850 99.2 Glucose mmol/day 800 0 800 100.0 Urea g/day 56 28 28 50.0
  • 26. Interstitial Fluid Tubular Lumen Tubular Cells Reabsorption of Water and Solutes is Coupled to Na+ Reabsorption Na + K+ ATP Na + K+ ATP Na + - 3 mV 0 mv H20 Cl- Urea Na + H + glucose, amino acids Na + - 70 mV Copyright © 2006 by Elsevier, Inc.
  • 27. Figure 27-5; Guyton and Hall Mechanisms by which Water, Chloride, and Urea Reabsorption are Coupled with Sodium Reabsorption
  • 28. TRANSPORT OF SOLUTE ACROSS THE TUBULES
  • 29. Cellular Ultrastructure and Primary Transport Characteristics of Proximal Convoluted Tubule 65-67% filtered load is reabsorb Contains extensive brush border structure Site for the secretion of toxin, organic acids and bases Reabsorption is highly passive
  • 30. TRANSPORT IN EARLY PCT Na ion uptake primarily coupled by hydrogen ion(antiporter) ,glucose(co- transport),amino acid and lactate Transtubular osmotic gradient drive water movement across cell membrane
  • 31. TRANSPORT IN LATE PCT Na and Cl is transported through parallel operation of Na/H exchanger and Cl/base Cl is passively reabsorb in the basolateral membrane
  • 32. Cellular Ultrastructure and Transport Characteristics of Thin and Thick Loop of Henle  not permeable to H2O  very permeable to H2O)  No brush border structure (few mitochondria) and minimal level of metabolic activity.  No brush border structure (few mitochondria) and minimal level of metabolic activity.  20% of filtered load of Na, Cl and K are reabsorbed
  • 33. TRANSPORT IN THICK ASCENDING LIMB  Movement of sodium across the luminal membrane is mediated primarily by a 1-sodium, 2-chloride, 1-potassium co- transporter  Tubular fluid is very diluted  Site of action of some diuretics
  • 34. Cortical and Juxtamedullary nephron segments
  • 35. Countercurrent Multiplier System in the Loop of Henle  Active transport of sodium ions and co- transport of potassium, chloride, and other ions.  Active transport of ions from the collecting ducts into the medullary interstitium.  Facilitated diffusion of large amounts of urea from the inner medullary collecting ducts into the medullary interstitium.
  • 36.
  • 37.
  • 38. Animal Max. Urine Conc. (mOsm /L) Beaver 500 Pig 1,100 Human 1,400 Dog 2,400 White Rat 3,000 Kangaroo Mouse 6,000 Australian Hopping Mouse 10,000
  • 39. • The vasa recta serve as countercurrent exchangers • Vasa recta blood flow is low (only 1-2 % of total renal blood flow)
  • 40. Sodium Chloride Transport in Early Distal Tubule
  • 41. • not permeable to H2O • not very permeable to urea • permeability to H2O depends on ADH • not very permeable to urea
  • 42. Figure 27-12; Guyton and Hall Sodium Chloride Reabsorption and Potassium Secretion in Collecting Tubule Principal Cells
  • 43.
  • 44. Cellular Ultrastructure and Transport Characteristics of Medullary Collecting Tubules  The permeability of the medullary collecting duct to water is controlled by the level of ADH  Unlike the cortical collecting tubule, the medullary collecting duct is permeable to urea,
  • 45.
  • 46. HORMONES THAT REGULATE TUBULAR SECRETION
  • 47. EFFECT OF ANG II IN RENAL TUBULES
  • 48. Late Distal, Cortical and Medullary Collecting Tubules Tubular Lumen Principal Cells Cl - H20 (w/o ADH) Aldosterone K+ Na + ATP K+ ATP Na + Copyright © 2006 by Elsevier, Inc.
  • 49. Summary of Water Reabsorption and Osmolarity in Different Parts of the Tubule • Proximal Tubule: 65% reabsorption, isosmotic • Desc. loop: 15-20% reabsorption, osmolarity increases • Asc. loop: 0% reabsorption, osmolarity decreases • Early distal: 0% reabsorption, osmolarity decreases • Late distal and coll. tubules: ADH dependent water reabsorption and tubular osmolarity • Medullary coll. ducts: ADH dependent water reabsorption and tubular osmolarity

Editor's Notes

  1. Paracellular transport refers to the transfer of substances across an epithelium by passing through the intercellular space between the cells. It is in contrast to transcellular transport, where the substances travel through the cell, passing through both the apical membrane and basolateral membrane.
  2. An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and the electrical gradient, or difference in charge across a membrane. When there are unequal concentrations of an ion across a permeable membrane, the ion will move across the membrane from the area of higher concentration to the area of lower concentration through simple diffusion. Ions also carry an electric charge that forms an electric potential across a membrane. If there is an unequal distribution of charges across the membrane, then the difference in electric potential generates a force that drives ion diffusion until the charges are balanced on both sides of the membrane.
  3. In secondary active transport, two or more substances interact with a specific membrane protein (a carrier molecule) and are transported together across the membrane. As one of the substances (for instance, sodium) diffuses down its electrochemical gradient, the energy released is used to drive another substance (for instance, glucose) against its electrochemical gradient.
  4. If Tm is exceeded, then the excess substrate enters the urine. Many substances are reabsorbed by carrier mediated transport systems e.g. glucose, amino acids, organic acids, sulphate and phosphate ions.
  5. The technical definition of an equivalent is the amount of substance it takes to combine with 1 mole of hydrogen ions.
  6. The threshold for glucose refers to the filtered load of glucose at which glucose first begins to be excreted in the urine.  The technical definition of an equivalent is the amount of substance it takes to combine with 1 mole of hydrogen ions.