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RENAL BIOCHEMISTRY
DR. FARHANA ATIA
ASSOCIATE PROFESSOR
DEPARTMENT OF BIOCHEMISTRY
NILPHAMARI MEDICAL COLLEGE, NILPHAMARI
KIDNEY & NEPHRON
Renal Blood Flow (RBF)
• Total amount of blood
passing through both
kidneys per minute
• 1200 ml/min
Renal Plasma Flow (RPF)
• Total amount of plasma
passing through both
kidneys per minute
• 650 ml/min
• 55% of RBF
GLOMERULAR FILTRATION RATE
• The quantity of filtrate formed in all the
nephrons of both kidneys per minute
• Normal GFR: 20% of RPF
125 ml/min
180 L/day
• 99% of this filtrate is returned to the
circulation through reabsorption
• Only 1–2 liters of urine is formed per
day
PLASMA LOAD
• Plasma load of a substance refers to the total amount
of that substance in the plasma which passes through
the kidney in each minute
• Plasma glucose concentration: 100 mg/100ml
• Plasma flow through kidney: 650 ml/min
• So, plasma load of glucose: 650mg/min
TUBULAR LOAD (TL)
• Amount of a substance that filters
through the glomerular membrane
into the tubule each minute
• Tubular load= GFR X Plasma
concentration of that substance
• TL of glucose: 125 mg/min
TRANSPORT MAXIMUM (TM)
• transport maximum refers to the point at which increases
in concentration of a substance do not result in an
increase in movement of a substance across a cell
membrane
• It is the maximum rate at which substances can be
transported by the tubular system of kidneys per minute
• For most substances actively re-absorbed or secreted in
the kidney, there is a transport maximum
• For any substances
excretion = (filtration + secretion) - reabsorption
• If TL > Tm : Substance appear in urine
• If TL = Tm , or TL < Tm : Substance does not appear in urine
• TL of glucose: 125 mg/min
• Tm of glucose : 375 mg/min, so glucose does not appear in
urine
• If filtered glucose crosses the Tm level it passes into urine
TRANSPORT MAXIMUM (TM)
RENAL THRESHOLD
• The critical concentration of a substance in plasma
below which none of it appears in urine but above
which progressively larger quantity of it appears in
urine is called renal threshold of that substance.
• Renal threshold of glucose: 180 mg/dl
PLASMA CLEARANCE
• Renal clearance
• Plasma clearance of a substance is the virtual volume of
plasma that is completely cleared of that substance by
the kidneys per minute
• Plasma clearance (ml/min), C =
𝑈 𝑋 𝑉
[𝑃]
Here, [U] = Concentration in urine; [P] = Concentration
in plasma; V = Urine flow rate (ml/min)
PLASMA CLEARANCE & IT’S SIGNIFICANCE
• Glucose = 0; Completely reabsorbed
• Urea = 70 ml/min; partially reabsorbed
• Inulin = 125 ml/min; neither reabsorbed, nor secreted
• Creatinine = 140 ml/min; secreted
• Plasma clearance is a marker of renal function
• Assesses severity of renal impairment
• Helps to measure GFR & RPF
OSMOLAR CLEARANCE
• It is the virtual volume of plasma that is cleared of all
osmotically active solutes through urine per minute
• Osmolar clearance (ml/min), Cosm =
Uosm𝑋 𝑉
Posm
Here, Uosm = Urinary osmolarity; Posm = Plasma
osmolarity; V = Urine flow rate (ml/min)
OSMOLAR CLEARANCE
• Example, Cosm =
Uosm𝑋 𝑉
Posm
Cosm =
900 mOsm/L 𝑋 1 𝑚𝑙/𝑚𝑖𝑛
300 mOsm/L
= 3.0 ml/min
It means, amount of that solute excreted through urine in
each minute in fact present in 3 ml of plasma within the
blood vessel
FREE WATER CLEARANCE
• The difference between water excretion (urine flow rate) and
osmolar clearance
CH₂O = V – Cosm
• Represents the rate at which solute free water is excreted by the
kidneys
• A positive CH₂O denotes- excretion of excess free water (urine-
hypotonic & diluted)
• A negative CH₂O indicates reabsorption of excess free water
(urine- hypertonic & concentrated)
FREE WATER CLEARANCE
• In normal adult,
CH₂O = V – Cosm
= (1-3) ml/min = - 2 ml/min
• So, negative CH₂O indicates urine is hypertonic & concentrated
• In isotonic urine CH₂O is zero
ACIDIFICATION OF URINE
• Kidney plays an important role in maintenance of acid-
base balance by excreting H+ ions and retaining
bicarbonate ions
• The two main mechanism of making alkaline filtrate
(pH-7.4) into acidic urine (pH upto 4.5) are:
1. H+ secretion
2. Bicarbonate ions reabsorption.
RENAL H⁺ SECRETION
• Proximal and distal tubular cells secrete hydrogen ions
• Acidification also occurs in collecting ducts
• Na–H antiport is responsible for H⁺ secretion in PCT
• About 4,380 mEq of H⁺ appear in the renal tubules by filtration
and secretion
• About 4,280 - 4,330 mEq of H⁺ is utilized for the reabsorption
of filtered HCO₃⁻
• Only the remaining 50 to 100 mEq is excreted. It results in the
acidification of urine. .
RENAL H⁺ SECRETION
• Excretion of H+ occurs by
three mechanisms:
1. Bicarbonate Mechanism
2. Phosphate Mechanism
3. Ammonia Mechanism
BICARBONATE MECHANISM
• The secreted H⁺ combines with HCO₃⁻
that are already in the tubular fluid. H⁺
and HCO₃⁻ together will form H₂CO₃
• H₂CO₃ dissociates into CO₂ and H₂O in
the presence of carbonic anhydrase
enzyme
• CO₂ moves inside the cell and combines
with the H₂O molecules that are already
present inside. CO₂ and H₂O once again
forms H₂CO₃
BICARBONATE MECHANISM
• H₂CO₃ further breaks down into H⁺ and
HCO₃⁻
• HCO₃⁻ from the tubular cell enters the
interstitium. Simultaneously, Na+ is
reabsorbed from the renal tubule under
the influence of aldosterone.
• Now the H+ is secreted into the tubular
lumen from the cell in exchange for Na+
PHOSPHATE MECHANISM
• [Na⁺] in the lumen of tubule is high
and [H⁺] is low in the tubular cell.
Thus Na⁺ moves inside the cell,
extruding H⁺ ions in the tubular fluid
and this phenomenon is known as
Sodium-hydrogen counter transport
• In DCT & CD where no filtered
HCO₃⁻
• So, generation of HCO₃⁻
AMMONIA MECHANISM
• In tubular cell the amino acid
Glutamine is converted into Glutamic
Acid by the enzyme Glutaminase
• NH₃ is formed & secreted into tubular
lumen
• Here, it combines with H⁺ to form NH₄⁺
• Thus, H⁺ is added to urine in the form
of ammonium compounds resulting in
acidification of urine
AMMONIA MECHANISM
• For each NH₄⁺ excreted one
HCO₃⁻ is added to interstitial fluid
• Thus, by excreting H⁺ and
conserving HCO₃⁻, kidneys
produce acidic urine and help to
maintain the acid-base balance of
body fluids
LIMITING PH
• The maximal H⁺ gradient against which the transport
mechanisms can not secret H⁺ in human correspond
to a urine pH of about 4.5
• This pH 4.5 is the limiting pH
• At this pH, urinary [H⁺] is 1000 times more than in
plasma
Thank You

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Renal biochemistry

  • 1. RENAL BIOCHEMISTRY DR. FARHANA ATIA ASSOCIATE PROFESSOR DEPARTMENT OF BIOCHEMISTRY NILPHAMARI MEDICAL COLLEGE, NILPHAMARI
  • 3. Renal Blood Flow (RBF) • Total amount of blood passing through both kidneys per minute • 1200 ml/min Renal Plasma Flow (RPF) • Total amount of plasma passing through both kidneys per minute • 650 ml/min • 55% of RBF
  • 4. GLOMERULAR FILTRATION RATE • The quantity of filtrate formed in all the nephrons of both kidneys per minute • Normal GFR: 20% of RPF 125 ml/min 180 L/day • 99% of this filtrate is returned to the circulation through reabsorption • Only 1–2 liters of urine is formed per day
  • 5. PLASMA LOAD • Plasma load of a substance refers to the total amount of that substance in the plasma which passes through the kidney in each minute • Plasma glucose concentration: 100 mg/100ml • Plasma flow through kidney: 650 ml/min • So, plasma load of glucose: 650mg/min
  • 6. TUBULAR LOAD (TL) • Amount of a substance that filters through the glomerular membrane into the tubule each minute • Tubular load= GFR X Plasma concentration of that substance • TL of glucose: 125 mg/min
  • 7. TRANSPORT MAXIMUM (TM) • transport maximum refers to the point at which increases in concentration of a substance do not result in an increase in movement of a substance across a cell membrane • It is the maximum rate at which substances can be transported by the tubular system of kidneys per minute • For most substances actively re-absorbed or secreted in the kidney, there is a transport maximum
  • 8. • For any substances excretion = (filtration + secretion) - reabsorption • If TL > Tm : Substance appear in urine • If TL = Tm , or TL < Tm : Substance does not appear in urine • TL of glucose: 125 mg/min • Tm of glucose : 375 mg/min, so glucose does not appear in urine • If filtered glucose crosses the Tm level it passes into urine TRANSPORT MAXIMUM (TM)
  • 9. RENAL THRESHOLD • The critical concentration of a substance in plasma below which none of it appears in urine but above which progressively larger quantity of it appears in urine is called renal threshold of that substance. • Renal threshold of glucose: 180 mg/dl
  • 10. PLASMA CLEARANCE • Renal clearance • Plasma clearance of a substance is the virtual volume of plasma that is completely cleared of that substance by the kidneys per minute • Plasma clearance (ml/min), C = 𝑈 𝑋 𝑉 [𝑃] Here, [U] = Concentration in urine; [P] = Concentration in plasma; V = Urine flow rate (ml/min)
  • 11. PLASMA CLEARANCE & IT’S SIGNIFICANCE • Glucose = 0; Completely reabsorbed • Urea = 70 ml/min; partially reabsorbed • Inulin = 125 ml/min; neither reabsorbed, nor secreted • Creatinine = 140 ml/min; secreted • Plasma clearance is a marker of renal function • Assesses severity of renal impairment • Helps to measure GFR & RPF
  • 12. OSMOLAR CLEARANCE • It is the virtual volume of plasma that is cleared of all osmotically active solutes through urine per minute • Osmolar clearance (ml/min), Cosm = Uosm𝑋 𝑉 Posm Here, Uosm = Urinary osmolarity; Posm = Plasma osmolarity; V = Urine flow rate (ml/min)
  • 13. OSMOLAR CLEARANCE • Example, Cosm = Uosm𝑋 𝑉 Posm Cosm = 900 mOsm/L 𝑋 1 𝑚𝑙/𝑚𝑖𝑛 300 mOsm/L = 3.0 ml/min It means, amount of that solute excreted through urine in each minute in fact present in 3 ml of plasma within the blood vessel
  • 14. FREE WATER CLEARANCE • The difference between water excretion (urine flow rate) and osmolar clearance CH₂O = V – Cosm • Represents the rate at which solute free water is excreted by the kidneys • A positive CH₂O denotes- excretion of excess free water (urine- hypotonic & diluted) • A negative CH₂O indicates reabsorption of excess free water (urine- hypertonic & concentrated)
  • 15. FREE WATER CLEARANCE • In normal adult, CH₂O = V – Cosm = (1-3) ml/min = - 2 ml/min • So, negative CH₂O indicates urine is hypertonic & concentrated • In isotonic urine CH₂O is zero
  • 16. ACIDIFICATION OF URINE • Kidney plays an important role in maintenance of acid- base balance by excreting H+ ions and retaining bicarbonate ions • The two main mechanism of making alkaline filtrate (pH-7.4) into acidic urine (pH upto 4.5) are: 1. H+ secretion 2. Bicarbonate ions reabsorption.
  • 17. RENAL H⁺ SECRETION • Proximal and distal tubular cells secrete hydrogen ions • Acidification also occurs in collecting ducts • Na–H antiport is responsible for H⁺ secretion in PCT • About 4,380 mEq of H⁺ appear in the renal tubules by filtration and secretion • About 4,280 - 4,330 mEq of H⁺ is utilized for the reabsorption of filtered HCO₃⁻ • Only the remaining 50 to 100 mEq is excreted. It results in the acidification of urine. .
  • 18. RENAL H⁺ SECRETION • Excretion of H+ occurs by three mechanisms: 1. Bicarbonate Mechanism 2. Phosphate Mechanism 3. Ammonia Mechanism
  • 19. BICARBONATE MECHANISM • The secreted H⁺ combines with HCO₃⁻ that are already in the tubular fluid. H⁺ and HCO₃⁻ together will form H₂CO₃ • H₂CO₃ dissociates into CO₂ and H₂O in the presence of carbonic anhydrase enzyme • CO₂ moves inside the cell and combines with the H₂O molecules that are already present inside. CO₂ and H₂O once again forms H₂CO₃
  • 20. BICARBONATE MECHANISM • H₂CO₃ further breaks down into H⁺ and HCO₃⁻ • HCO₃⁻ from the tubular cell enters the interstitium. Simultaneously, Na+ is reabsorbed from the renal tubule under the influence of aldosterone. • Now the H+ is secreted into the tubular lumen from the cell in exchange for Na+
  • 21. PHOSPHATE MECHANISM • [Na⁺] in the lumen of tubule is high and [H⁺] is low in the tubular cell. Thus Na⁺ moves inside the cell, extruding H⁺ ions in the tubular fluid and this phenomenon is known as Sodium-hydrogen counter transport • In DCT & CD where no filtered HCO₃⁻ • So, generation of HCO₃⁻
  • 22. AMMONIA MECHANISM • In tubular cell the amino acid Glutamine is converted into Glutamic Acid by the enzyme Glutaminase • NH₃ is formed & secreted into tubular lumen • Here, it combines with H⁺ to form NH₄⁺ • Thus, H⁺ is added to urine in the form of ammonium compounds resulting in acidification of urine
  • 23. AMMONIA MECHANISM • For each NH₄⁺ excreted one HCO₃⁻ is added to interstitial fluid • Thus, by excreting H⁺ and conserving HCO₃⁻, kidneys produce acidic urine and help to maintain the acid-base balance of body fluids
  • 24. LIMITING PH • The maximal H⁺ gradient against which the transport mechanisms can not secret H⁺ in human correspond to a urine pH of about 4.5 • This pH 4.5 is the limiting pH • At this pH, urinary [H⁺] is 1000 times more than in plasma