Renal System Physiology

Datu Agasi Bin Mohd Kamal

P92695
 Learning Objective :
• To explain the mechanism of glucose in
kidneys.
• To understand the principle of transport
maximum in glucose.
• To know the renal threshold for glucose.
• To describe how glycosuria occur.
• To explain how the kidneys handle excessive
acid in the body.
 Case
• A 25-year-old man was diagnosed to have
type 1 diabetes mellitus (insulin dependent)
at the age of 10 years old. He was constantly
thirsty and was urinating every 30 minutes.
He went to see a doctor and his urine test
showed: ketone 2+ and glucose 4+. His
arterial blood gases showed metabolic
acidosis.
 Glucose mechanism in kidney
SGLT (sodium and
• Freely filtered at the Glomerulus. glucose cotransporter)
• 100% reabsorbed at proximal tubule by secondary active
reabsorption. GLUT( Glucose
Transporter)

90%

10%
 Transport Maximum (Tm)
• Most substances that are actively reabsorbed , there is a
limit to the rate of its solute can be transported. This is
called Tm.

• The limit is due to saturation of the capacity of the specific

carrier protein.

• Glucose have its own Tm . When the filtered load of glucose

exceed the Tm glucose will be excreted in urine (glycosuria).

• Tm for glucose in adult human is 375 mg/min.

 Renal threshold for substance
• The plasma concentration of a substance at which the Tm is
reached and the substance start appearing in urine.

• At the Tm of 375 mg/min and GFR of 125 mL/min the renal

threshold for glucose is 300mg/100ml.
Metabolic acidosis
 Acid-base balance
• Acid: [H+] releasing substances.
• Base: [H+] combining substances.
• The pH is used to express [H+].
• A high [H+] corresponds to a low pH and vice
versa.
• The pH of the blood is normally 7.35-7.45.
• A pH >7.45 -Alkalosis
• A pH <7.35 -Acidosis
 Acid-base balance

System regulating
acid-base balance

The chemical The respiratory The renal

buffer systems mechanism mechanism
1.HCO3- buffer system 1.Regulate the
2.Protein buffer system removal of CO2 Excreting acidic
or basic urine
3.Phosphate buffer
system
Kidney regulate acid-base balance by:

1. H+ excretion.
2. Reabsorption of filtered HCO3- .
3. Production of new HCO3- to the plasma
 Secretion of H+ and reabsorption of
HCO3-
• For each HCO3- reabsorbed, a H+ must be secreted.
• H+ secretion differ in different tubular segment.
Secretion of H+ in proximal tubule, thick segment
of asc loop of Henle and early distal tubule
• Secondary active
transport through
sodium-hydrogen
counter-transport.

• Energy derived from

Na+ gradient favoring
Na+ movement into the
cell estabilsh by Na+ -
K+ ATPase pump.

• Na+-HCO3- co
transport.
 Mechanism of H+ secretion at late distal
and collecting tubule
• Primary Type A intercalated cell
active H+ • H+ secreting
secretion • HCO3 - reabsorbing
• K+ reabsorbing
H+ potassium
ATPase • More active at
transporter normal condition
• Increases during
H+ acidosis
transporting
ATPase
Type B intercalated cell
Cl- - HCO3- • Opposite action of
exchange type A
transport • More active during
alkalosis
• Although only 5% but
important in forming
maximally acidic urine.
 HCO3- and H+ in the tubules
• Normal condition tubular H+ secretion is 4400
mEq/day and rate of filtration of HCO3- is
4320mEq/day, there is excess H+ after all
HCO3- used.
• Excess of H+ (80mEq/day) excreted in urine in
combination of urinary buffer esp phosphate
and ammonia.
• Lower limit of urine PH is 4.5.
 Phosphate and Ammonia buffer
system generate new HCO3-

• HCO3- that is generated in tubular cell and enter peritubular

blood represent net gain of HCO3- rather than replacement of
filtered HCO3-.
 Metabolic ketoacidosis

• There is excess H+ over HCO3- in tubular fluid

primarily because of decreased in filtration of
HCO3- because HCO3- ECF fall

• The primary compensation is increased

ventilation rate( reduce PCO2 ) and adding new
HCO3- to ECF
Thank you
• Insulin deficiency causes the body to metabolize triglycerides and amino acids
instead of glucose for energy. Serum levels of glycerol and free fatty acids (FFAs)
rise because of unrestrained lipolysis, as does alanine because of muscle
catabolism. Glycerol and alanine provide substrate for hepatic gluconeogenesis,
which is stimulated by the excess of glucagon that accompanies insulin deficiency.
• Glucagon also stimulates mitochondrial conversion of FFAs into
ketones. Insulin normally blocks ketogenesis by inhibiting the transport of FFA
derivatives into the mitochondrial matrix, but ketogenesis proceeds in the absence
of insulin. The major ketoacids produced, acetoacetic acid and beta-hydroxybutyric
acid, are strong organic acids that create metabolic acidosis. Acetone derived from
the metabolism of acetoacetic acid accumulates in serum and is slowly disposed of
by respiration.
• Hyperglycemia due to insulin deficiency causes an osmotic diuresis that leads to
marked urinary losses of water and electrolytes. Urinary excretion of ketones
obligates additional losses of sodium and potassium. Serum sodium may fall due to
natriuresis or rise due to excretion of large volumes of free water. Potassium is also
lost in large quantities, sometimes > 300 mEq/24 h. Despite a significant total body
deficit of potassium, initial serum potassium is typically normal or elevated
because of the extracellular migration of potassium in response to acidosis.
Potassium levels generally fall further during treatment as insulin therapy drives
potassium into cells. If serum potassium is not monitored and replaced as needed,
life-threatening hypokalemia may develop.
• Symptoms and Signs