First MBBS Renal Physiology Lecture

1. Tubular Functions
Renal Physiology 2
Dr Raghuveer Choudhary

2. Q. List different functions of
renal tubules
- Reabsorption: Transport of
substance from lumen of
tubule to blood.
- Secretion: addition of
substance to the glomerular
filtrate coming from blood .
- Synthesis: addition of new
substance to glomerular
filtrate e.g ammonia.

3. 3
TUBULAR FUNCTION
The glomerular filtrate is
formed at a rate of 125
ml/min. or 180 L/day. It
passes to the renal tubules.
In the tubules, the tubular
fluid is subjected to the 2
main tubular functions,
reabsorption & secretion.
It is finally excreted as urine
at a rate of about 1-2 ml/min.
or ca. 1.5 L/day.

4. Reabsorption & Secretion
 Secretion:- refers to the transport of solutes
from pritubular capillaries in to the tubular
lumen,i.e. it is the addition of substance to
the filterate.
 Reabsorption- denotes the active transport
of solutes & passive movement of water
from tubular lumen in to the peritubular
capillaries,,i.e. the removal of a substance
from the filterate

5. Filtered Load
 Filtered load (mg/min) =GFR(ml/min) x
Plasma Conc. of that solute(mg/ml)
 Is the amount of solute transported across
the glomerular membrane per unit time

9. Renal Tubular Transport
Maximum (Tm)
 Tm=it referes to maximum amount of a
given solute that can be transported
(reabsobed or secreted) per minutes by the
renal tubules.
 Tm – pertains to solutes that are actively
transported.
 Substances that are passively transported
(urea) do not exhibit a Transport
Maximum(Tm)

10. Tubular Reabsorption is a Function of the Epithelial
Cells Making up the Tubule
Lumen
Plasma
Cells

11. substance to be reabsorbed must
be transported
 across the tubular
epithelial membranes
into the renal interstitial
fluid
 through the peritubular
capillary membrane
back into the blood

12. The transporting pathways of
substance through the renal tubular
epithelial cells
 Transcellular pathway:
through the cell
membranes
 Paracellular pathway:
through the junctional
spaces

13. Movement of substances in
and out of cell

14. Types of carrier proteins
– A uniport carrier: transport one substance.
– A symport carrier: transport two substances in the same
direction.
– An antiport carrier: transport two substances in the opposite
directions.

15. Mechanisms of Reabsorption
1. Passive transport
1). Down electrochemical gradient;
2). not require energy;
3). Mode:Diffusion,Osmosis,facilitated
diffusion
4). Example:H2O

16. 2. Active transport
1). Against an electrochemical gradient;
2). require energy;
3). Depend on carrier proteins that penetrate
through the membrane
4). divided into two types:
– Primary active transport: coupled directly to an
energy source(hydrolysis of ATP)
– Secondary active transport :coupled indirectly to
an energy source(an ion gradient)

17. Primary active transport is
linked to hydrolysis of ATP
 Importance: move solutes against an
electrochemical gradient
 energy source: hydrolysis of ATP
 Example: sodium-potassium ATPase pump

18. Inside Outside
K+
K+
Na+
Na+
Na+

19. Inside Outside
K+
K+

20. Na+-K+ ATPase hydrolysis ATP  release energy 
Transport Na+ out of the cell into the interstitium
Transport K+ from the interstitium into the cell
The intracellular concentration of sodium is lower
(chemical difference)
The cell interior is electrically negative than the
outside (electrical difference)
Favor Na+ to diffuse from the tubular lumen
into the cell through the brush border




22. Secondary active transport
 Co – transport:
glucose-sodium transport
amino acids -sodium transport
phosphate -sodium transport
 Counter- transport:
H+-Na+ transport

24. Co – transport of
Glucose (or amino
Acids) along with
Sodium ions through
The brush border of
The tubular epithelial
cells

25. Tubular Reabsorption
A) Active transport; against electrochemical gradient.
(1) Primary active transport
Requires energy directly from ATP.
Example; Na+ reabsorption in PCT
(2) Secondary active transport
-It does not require energy direct from ATP.
a) Co-transport
two substances bind to a specific carrier are cotransported in one direction.
b) Counter-transport
two substances bind to a specific carrier are
transported in two directions.
B) Passive reabsorption;
(1) Simple diffusion
Passive reabsorption of chloride & Osmosis of water
(2) Facilitated diffusion
Need carrier.
C) Pinocytosis
It is an active transport mechanism for reabsorption of proteins and
peptides in the proximal convoluted tubules.

27. Q. List different Characteristic features of PCT
- PCT is about 15 mm long and 55 μm in diameter.
- PCT wall is lined by single layer of epithelial cells that
are connected by tight junctions at their luminal edges, but
there is a space between the cells along the rest of their
lateral borders (lateral intercellular spaces) which contains
interstitial fluid.
- The luminal borders of cells have brush border due to
presence of large number of microvilli which increase
surface area for reabsorption.
- The PCT cells have large numbers of mitochondria
(energy supply).

28. Proximal Convoluted Tubule
 65% of the nephron
function occurs in PCT.
 The PCT has a single layer
of cuboidal cells with
millions of microvilli.
– Increased surface area for
reabsorption.
 PCT's main function is
reabsorption.
 The PCT is full of
mitochondria

29. Reabsorption in Proximal Tubule
 100% Glucose, protein and Amino Acids
 60% Sodium, Cl, and H2O.
 80% PH, HCO3, K.
 60% Ca.
 50% of Filtered Urea.

30. Reabsorption of glucose:
 Position: proximal tubule.
 All the filtrated glucose is reabsorbed under
normal condition.
 Secondary active transport, accompanied by
the primary active transport of sodium .

32. Renal threshold for glucose:
 the maximal blood sugar concentration
which can not result in glucosuria.
 Reasons: there is a limit to the amount of
transporter proteins and binding site.

33. 33
GLUCOSE:
At normal blood glucose levels (~100 mg%), glucose is freely filtered at a rate of
125 mg/min. (= plasma conc. X GFR = 100 mg% x 125 ml/min.).
The amount filtered is completely reabsorbed from the upper half of PCT by Na+-
glucose cotransport (mechanism: see before).
There is, however, a limited number of Na+-glucose carriers:
a- At a blood glucose level of less than 180 mg%, all the filtered glucose can be
reabsorbed because plenty of carriers are available.
b- At a blood glucose level of 180 mg%, glucose starts to appear in urine.
This level of blood glucose is called the renal threshold for glucose. It
corresponds to a renal tubular load of 220 mg/min.
c- At a renal tubular load of glucose of 320 mg/min, all the carriers are
saturated, i.e., the transport maximum for glucose, TmG, is reached.
Any further  in filtered glucose is not reabsorbed & is excreted in urine.

34. Glucose reabsorption
 The transporter for glucose on the basolateral
membrane has a limited capacity to carry glucose back
into the blood. If blood glucose rises above 180 mg/dl,
some of the glucose fails to be reabsorbed and remains
in the urine  glucosuria.

35. Tubular maximum for glucose (TmG):
 The maximum amount of glucose (in mg ) that can be
reabsorbed per min.
 It equals the sum of TmG of all nephrons.
 Value; 300 mg/min in ♀ , 375 mg/ min in ♂.
Renal Threshold for Glucose
• Is approximately 180 mg/dl
• If plasma glucose is greater than 180 mg/dl:
– Tm of tubular cells is exceeded
– glucose appears in urine

37. Plasma
Glucose
(mg%)
Glucose filtered
(mg/min)
PG x GFR/100
100 125
200 250
300 375
400 500
500 625
600 750

38. 180

40. 180
180

41. GLUCOSE REABSORPTION HAS A
TUBULAR MAXIMUM
Plasma Concentration of Glucose
Glucose
Reabsorbed
mg/min
Filtered Excreted
Reabsorbed

43. 375mg/min

44. Glucose titration curve
Plasma
Glucose
(mg%)
Glucose
filtered
(mg/min)
PG x GFR/100
100 125
200 250
300 375
400 500
500 625
600 750

47. 180

48. Glucosuria
presence of glucose in urine
1. Diabetes mellitus
–blood glucose level > renal threshold.
2. Renal glucosuria
–It is caused by the defect in the glucose
transport mechanism.
3. Phlorhizin
–A plant glucoside which competes with glucose
for the carrier and results in glucosuria
(phloridzin diabetes).

49. Glucose
 filtration rate = 100 mg/min (Pc x GFR)
 reabsorption rate = 100 mg/min
– site = early portion of the proximal tubule
 secretion rate = 0 mg/min
 excretion rate = 0 mg / min
 Tm = 375 mg/min
 ideal renal threshold = 300 mg/dL
 actual renal threshold = 200 mg /dL (arterial)
180 mg/dL (venous)
– “splay”

50. SGLT 2
PHLORHIZIN

51. GLUCOSE
100 % REABSORBED

52. Amino Acids
 filtration rate --- small amount
 reabsorption ---- 100 %
– site -- early portion of the proximal tubule
 secretion ---- 0
 excretion ----- 0

53. amino acids
amino acids
amino acids
SIMPLE OR FACILITATED DIFFUSION

54. AMINO ACIDS
100 % REABSORBED

55. Proteins
 peptide hormones, small proteins and
small amount of albumin
 filtration rate = 7.2 g/day (GFR x protein
in the ultrafiltrate)
 reabsorption rate = 7.2 g/day
– site --- early portion of the proximal tubule
 secretion rate = 0
 excretion rate = 0

56. PROTEINS

57. Endocytosis of Proteins
 mediated by apical membrane proteins
that specifically bind with luminal
proteins and peptides.
 they are multiligand endocytic receptors.
– Megalin
– Cubilin

58. PROTEINS
100 % REABSORBED

63. Sodium
 filtration rate = 25,560 mEq/day (575-
580mg/day)
 reabsorption rate = 25,410 mEq/day
(98%)
– site -- proximal tubule, loop of Henle, distal
tubules and collecting duct.
 secretion rate = 0 mEq/day
 excretion rate = 150 mEq/ day

64. 67%
Sodium
25%
5%
1 %
3%

67. Na reabsorption
 At basolateral side of the tubular epithelial cell there is an
extensive Na+-K+ ATPase system (= Na+-K+ pump).
 It pumps 3 Na+ actively out of the cell into the interstitium, and
at the same time carries 2 K+ into the cell.
 But K+ will diffuse immediately back into the interstitium due
to:
(1) high concentration gradient &
(2) high permeability of epithelial cells to K+.
 As a result of this there is:
-  intracellular Na+ concentration
 At luminal membrane there will therefore be passive diffusion of
Na+ into the cell along concentration gradient created by the Na+-
K+ pump. This diffusion is facilitated by a protein carrier.

75. In the early distal
tubule, NaCl reabsorption is coupled via a Na-
Cl cotransporter
. Na+ exit at the basolateral membrane is via
the Na/K-ATPase, and Cl− exit is via the Cl−
channel.

76. Late DCT & Cortical CD:
(1) Principal Cells:
a. They actively reabsorb Na+ in exchange for K+
secretion. This action is increased by aldosterone.
b. Antidiuretic hormone (ADH) causes 
reabsorption of H2O. In the absence of ADH, the
principal cells are impermeable to H2O.
(2) -Intercalated Cells:
- These cells secrete H+ .This action is
increased by aldosterone.

81. DISTAL TUBULE AND CORTICAL COLLECTING DUCT
The distal tubule and the cortical collecting duct are
important areas for fi ne regulation of Na+
excretion.
The hormone aldosterone
increases the activity of the Na+ transport proteins
throughout this area to promote renal Na+
conservation and maintain the extracellular fl uid
volume.

82. DIURETICS
Diuresis is defined as an increase in
the urine flow rate;
diuretics = agents that induce
diuresis.

85. Regulation of sodium
excretion
Glomerulotubular balance in PT

92. Effect of ECF volume on PT
Reabsorption
 ECFV contraction-increased absorption
 ECFV expansion-decreased absorption

93. Factors affecting Na reabsoption
Na reabsorption increased by Na reabsorption decreased by
Peritubular Hydrostatic pressure Peritubular Hydrostatic pressure
Peritubular Colloidal
osmotic pressure
Peritubular Colloidal
osmotic pressure
ECFV contraction ECFV expansion
Aldosterone Glucocorticoids
GFR decreased GFR

95. 95
Hormones acting on the kidney
1. Aldosterone:
 Stimulus for its secretion:
 Blood volume (via renin-angiotentin system).
 Actions & their site:
It stimulates Na+ reabsorption in DCT & cortical CD through:
1) In principal cells:  Na+ reabsorption in exchange with K+.
2) In -intercalated cells:  Na+ reabsorption in exchange with H+.
2. Angiotensin II: It is the most powerful Na+ retaining hormone.
 Stimulus for its secretion:
 arterial bl. pressure & blood volume, e.g., hemorrhage (via renin).
 Actions & their site:
1. It  Na+ reabsorption by several mechanisms:
a. By stimulating aldosterone secretion.
b. In PCT: - By directly stimulating Na+-K+ ATPase at basolateral border.
- By directly stimulating Na+-H+ countertransp. at luminal border.
2. It constricts efferent arterioles.

96. Hormones affecting Na
Reabsorption
 Nacl & water reabsorption by
Aldosteron,Angiotensin II
 water reabsorption- Antidiuretic Hormone
ADH
 Nacl & water reabsorption-
ANP,Dopamine,Urodilatin

97. Hormones that influence sodium
reabsorption in renal tubules
 Angiotensin II
– stimulates sodium reabsorption in the
proximal tubule, thick ascending limb, distal
tubule and collecting duct.
 Aldosterone
– increases sodium reabsorption and
potassium secretion in the distal tubule and
collecting duct
– increases sodium reabsorption in the thick
ascending limb

98. Hormones that influence sodium
reabsorption in renal tubules
 Atrial Natriuretic Peptide and Brain
Natriuretic Peptide
– inhibits sodium chloride reabsorption in the
medullary collecting duct
– inhibits ADH secretion in the posterior
pituitary gland
 Catecholamines
– stimulates sodium chloride reabsorption in
the PT, thick ascending, DT and CD

99. Hormones that influence sodium
reabsorption in renal tubules
 Dopamine
– inhibits reabsorption of sodium chloride in
the proximal tubule
 Adrenomedullin, Urodilatin, Uroguanylin
and guanylin
– increases sodium chloride excretion

100. Potassium
 ECF K+ concentration (N = 3.5 - 5.5 meq/L)
 ICF - 98%, ECF - 2%
 excretion
– kidneys - 90 - 95%
– feces - 5 - 10%

101. ICF K+ concentration
140 mEq/L X 28 L
3920 mEq
ECF K+
concentration
4.2 mEq/L
X 14 L
59 mEq
K+ intake
100 mEq/day
K+ output
Urine = 92 mEq/day
Feces = 8 mEq/day
NORMAL K+ INTAKE, DISTRIBUTION OF K+ IN THE BODY FLUIDS AND OUTPUT FROM THE BODY
Guyton, Medical Physiology, 2006

102.  filtration rate = 756 mEq/day
 reabsorption rate = 644 mEq/day (87.8%)
– site -- proximal tubule and ascendong loop of
Henle
 secretion rate = 31 mEq/day
 excretion rate = 92 mEq/ day

113. 67%
POTASSIUM
20 -25%
4%
12%
Increased ECF potassium concentration
Increased aldosterone
Increased tubular flow rate

118. K+ and acid base disorders

127. Bicarbonate Reabsorption
 Recovery of filtered HCO3− and net acid
excretion is usually required to maintain
acid-base balance—almost all the filtered
HCO3− must be recovered. Most HCO3−
reabsorption occurs in the early proximal
tubule via the mechanism shown in Figure

136. Mechanisms of H+ excretion and HCO3− generation.
B. Titratable acid excretion as H2PO4 − occurs when secreted H+ combines with fi ltered
HPO42−. CA, carbonic anhydrase.

143. Mechanisms of H+ excretion and HCO3− generation.
A. Renal ammoniagenesis results in the formation of NH4+ within cells because NH3
readily combines with H+ at physiologic pH. NH4 +is secreted via the Na/H exchangers

148. Reabsorption of water:
 1. Quantity of reasorption:99%
 2. Passive reabsorption: osmotic pressure
 3. Position and siginificance:
 Proximal tubule:
 65-70%;
 Accompanied by the reabsorption of NaCl
 Has nothing to do with whether the body lack
water or not.
 Not regulated by hormones;

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