Tubular reabsorption & secretion

By

Dr. Isam Eldin Mohamed Abd Alla

Tubular reabsorption:
Is the transport of molecules from the
tubular lumen (filtrate) to the tubular cells,
then to the ISF & the blood of peritubular
capillaries & vasa recta.
Tubular secretion: Is the transport of
molecules in opposite direction to
reabsorption.
Sodium reabsorption:
 The source of Sodium is table salt (NaCl).
 Daily requirement of Na+ is 60 mmol.
 The plasma level of Sodium is 135– 145
mmol/L.
 In the kidneys Na+ is freely filtered.
 99.4% of filtered Na+ is reabsorbed from
renal tubules to the blood as follow:
From the lumen proximal tubules to
the tubular cells Na is transported by:
+

Na+-Glucose co-transporters (SGLT1,

SGLT2).
 Na+-Amino acids co-transporters.
Na+-Lactate co-transporter.
Na+-Phosphate co-transporter.
Na+-H+ antiporter
o From the lumen of Loop of Henle to the
tubular cells Na+ is transported by:
Na+-K+-2Cl- cotransporter.
Na+-H+ antiporter.
o From the lumen of Distal tubules to the
tubular cells Na+ is transported by:
Na+- Cl- cotransporter.
o From the lumen of Collecting duct to the
tubular cells Na+ is transported by:
Epithelial Na+ channels ENaC.
Then from the tubular cells in all tubulles
Na+ is transported by Na+ - K+pump to the
ISF to the blood
 Hormone AngiotensinII stimulates Na+
reabsorption from the proximal tubules &
stimulates Aldosterone secretions.
Hormone Aldosterone stimulates Na+
reabsorption from the collecting duct &
distal tubules.
 Na reabsorption → water reabsorption
by osmosis.
Na+ reabsorption is inhibited by:
Dopamine,.
Atrial natriuretic poly peptide ANP,
& Brain- type natriuretic poly peptide BNP.
Prostaglandins.
Na-K pump inhibitors
Functions of Sodium:
 Maintenance of ISF & plasma osmolality
(Sensor of thirst mechanism).
 Important for intestinal absorption & renal
reabsorption of nutrients & water.
 Maintains the blood volume & pressure.
 Generation of electrical activity ( Action
potential) in nerves & muscles.
 Help in regulation of PH by facilitating
renal H+ secretion & HCO3- reabsption.
Glucose reabsorption:
 The fasting plasma level of glucose is 80
mg/dL.
 Amount of glucose filtered = GFR x PGl=
125 ml/min x 80 mg/dL = 100 mg/min.
• Normally all filtered glucose is reabsrbed
from the PCT.
• Reabsorption occurs by SGLT from the
lumen to the tubular cells & then by
GLUT to the ISF to the blood.
Renal threshold for glucose is the plasma
level at which the glucose first appears in the
urine in more than the normal minute amount
(Glycosuria).
= about 200 mg/dL of arterial plasma, (180
mg/dL of venous plasma).
Potassium metabolism:
 Dietary sources: Fruits, honey, milk.meat
 The daily required potassium in the diet
is 1 mmol per Kg of body weight with
average of 60 mmol.
 After ingestion K+ is absorbed from the
lumen of small intestine to the blood.
 K+ is secreted from ISF into the lumen of
the colon, thus diarrhoea leads to
hypokalaemia.
 When the dietary intake of K+ is high for
long period aldosterone secretion
increases stimulating secretion of K+ into
the colonic lumen to be lost with stools 
 Plasma level = 3.5—5,5 mmol/L
(4mmol/L ).
 This level is regulated by short and long
terms mechanisms after intestinal
absorption
1. Short term regulation:
K+ is pumped from ECF to the cells mainly
Red blood cells (RBCs),
hepatocytes,
muscular cells.
Pumping via Na+-K+ pump, stimulated by:
 Aldosterone,
Insulin,
Adrenaline via β2 receptor.
2. Long term regulation:
By the renal system .
K+ is freely filtered in the glomeruli.
90% of the filtered is reabsorbed from the
PCT and ascending limb of Henle loop
Then K+ is secreted into the lumen of
DCT and CD in exchange with sodium
reabsorption.
Aldosterone stimulates this exchange
(K+ secretion with Na+ reabsorption).
NOTE:
H+ ions compete with K+ ions secretion in
exchange with Na+ Thus Acidosis decreases
secretion of K+ causing hyperkalaemia While
alkalosis causes hypokalaemia.
Hyperkalaemia is more serious because it
relaxes the cardiac muscles that can leads
to cardiac arrest.
Causes of hyperkalaemia:
Chronic Renal failure.
Digitalis toxicity.
Aldosterone antagonists (Spironolactone).
Adrenal insufficiency (Addison`s disease)
Excessive use of β blockers.
Excessive Haemolysis (haemolytic anaemia).
Muscular diseases.
Hepatic failure.
Acidosis.
Excessive infusion or ingestion of potassium
Causes of Hypokalaemia:
potassium restricted diet
Diarrheoa.(Acidosis)
Diabetic polyuria.
Alkalosis .
 Loop diuretics,
 Primary Hyperaldosteronism (Con`s
syndrome) & alkalosis
Others
 :Water balance (metabolism)
Water balance occurs by matching the
water input (gain) with water output (Loss)
The body water input results from:
1. Ingestion (Drinking & eating)= 2100 mL
.Metabolism = 200 mL .2
At comfortable temperature water is lost by
Insensible H2O loss from skin Prespiration
from respiratory tract (Expiration), & &
.with Sweat, Stools & Urine
Water balance
Thirst center in the hypothalamus is
:stimulated by
.Hyperosmolality of the plasma .1
Decrease ECF volume (hyopvolaemia) .2
after polyuria, diarrhoea, sweating, burn,
.vomiting or haemorrhage
.Hypotension -3
.AngiotensinII -4
After water intake, intestinal absorption
occurs by osmosis after the solutes
renal reabsorption of water occurs after &
solutes by osmosis, thus defective
absorption or reabsorption of solutes leads
.to Diarrhoea or Polyuria
About 99.7% of the filtered water is
:reabsorbed from renal tubules
.from lumen of PCT 60-70% )1
from lumen of Loop of Henle 20% -15 )2
.(Descending limb)
.from lumen of DCT 5% )3
14.7% from lumen of Collecting duct
stimulated by Vasopressin (ADH),
o Vasopressin binds to V2 receptors causing
production of cyclic AMP → activation of
protein kinase A → translocation of water
channels aquaporin-2 from the tubular cells
endosomes to their luminal membrane → water
reabsorption.
o Vasopressin deficiency or resistance leads to
Diabetes insipidus with polyuria & polydipsia,
 :Causes of additional water loss
.Diarrhoea
.Vomiting
.Polyuria
.Sweating
.bleeding
.Burns
Additional loss requires additional intake
Functions of water:
Maintenance of blood volume & pressure
Transport of molecules intra &
extracellularly.
 regulation of body temperature by
distribution of body heat.
Acts as a medium for chemical &
biological processes.
Diuretics:
 Are agents that ↑ the rate of urination.
Are used to ↓ water over load, as in
treatment of oedma.
Most of the diuretic act by inhibiting
renal Na+ reabsorption that ↓ water
reabsorption & ↑ the urine flow.
Include:
Carbonic anhydrase (CA) inhibitors eg:
Acetazolamide (Diamox).
CA normally catalyze the reaction of water with
CO2 to form carbonic acid which give H+ to be
secreted in exchange with Na+ reabsorption in
PCT & Loop of Henle. CA inhibitors ↓ Na+ &
H2O reabsorption. Can cause acidosis
Loop diuretics eg: Furosemide (Lasix), Inhibit
the Na–K–2Cl cotransporter in the ascending
limb of loop of Henle. Can cause hypokalaemia
Inhibitors of Na–Cl cotransporter in the
distal tubules eg: thiazides diuretics.
Aldosterone antagonists (spironolactone)
inhibits Na+ reabsortion & K+ secretion
(Poatassium sparing diuretic)
Inhibitors of the ENaCs (amiloride)
NOTE:
Water, Sugar, Alcohol, Caffeine, extreme
increase in ABPr all are diuretics
Urea & Uric acid reabsorption &
secretion:
Urea is a product of proteins
metabolism.
Its plasma level is maintained at 8—25
mg/dL by the renal system as follow:
Urea if freely filtered by the glomeruli,
when the filtrate flows to the proximal
convoluted tubules PCT most of water,
Na+ are reabsorbed, urea concentration in
the tubular fluid increases → Reabsorption
of 50% of urea by passive diffusion from
PCT lumen,
Urea is secreted from the highly
concentrated medullary ISF to the lumen
of Loop of Henle,
In the collecting duct Vasopressin (ADH)
stimulates water & urea reabsorption,
causing 40—60% of urea reabsorption.
From the filtered uric acid up to 90% is
reabsorbed, but there is active secretion of
uric acid into the tubular lumen leading to
higher clearance rate of uric acid exceeding
Inulin clearance.
the serum level of uric acid is 3.0 – 7.0
mg/dL
Creatinine:
Creatinine is a product of metabolism in
the muscles & renal tubular cells.
It is freely filtered .
 not reabsorbed from the tubular lumen,
but it is secreted from the tubular cells
into the lumen.
The serum creatinine level = 0.6—
1.5ᶙg/dL
Other substances:
Calcium reabsorption is stimulated by
Parathyroid hormone PTH & facilitated
by Calcitriol.
Phosphate reabsorption is facilitated by
Calcitriol & inhibited by PTH.
 Penicillin & Para-aminohippuric acid
PAH are secreted into the tubular lumen.
 PAH clearance is used for measurement of
renal blood flow.
The counter-current system:
A system in which the inflow runs parallel,
counter (opposite), and proximal to the
outflow.
In the kidney is represented by:
Ascending & descending limbs of loop
of Henle
 Ascending & descending vessels of Vasa
recta.
 Important for urine concentration by
concentrating the ISF of the medulla as
follw
Loop of Henle acts as a counter-current
multiplier by reabsorption of:
o water from the lumen of descending limb
as it passes to the medulla.
o Solutes (Na+, Cl+,K+ ) from the lumen of
thick ascending limb as it passes to the
cortx,
Thus solutes are multiplied in medulla,
Counter-current
multiplier
Vasa recta acts as a counter-current
exchanger where solutes enter the Vasa
recta vessels descending to the medulla
while water enter the Vasa recta vessels
ascending to the cortex.
Finally solutes circulates in the medullary
ISF causing hyperosmolality of 120 0
mosm/L that facilitates water reabsorption
from collecting duct by osmosis & the
urine becomes concentrated.
Vasa recta