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Design and Function - Kidney (pdf - c)
Biosystems I (PHAR 637)
West Coast University
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Design and Function – Renal
System
Fred Farris, PhD
Anatomical Overview of th
Kidneys
The Nephron: Functional Unit of the Kidney
- Each kidney contains 800,000 to 1,000,000 nephrons
- Each capable of urine formation
- New nephrons cannot be formed
- After age 40, number of nephrons decreases about 10% every 10 years
- Outer portion of nephron located in kidney cortex
- Loop of Henle dips into medulla
Glomerular Filtration
- Glomerular capillaries act as filters
- Filtration is a unidirectional process
- MW cut-off is around 70, Daltons
- Some serum albumin found in urinary filtrate
- Filtration is drive by net difference in three forces - GBHP - BCOP - CHP
Nephron: Glomerulus
GFR = (GBHP – BCOP – CHP)
Renal Active Secretion
- Occurs only for select substances
- Inferred if renal clearance is greater than GFR
- Active carrier-mediated process
- Efficient capacity-limited process
- Continues along length of tubule – exact site depends on substance being secreted
- Different non-specific transporters for weak acids and bases
- Para-amino hippuric acid measures effective renal plasma flow rate (ERPF) = 425 -650 ml/min
Reabsorption
- Must occur is Renal Clearance is less than GFR
- Passive process for most drug and exogenous substances
- Active process for many endogenous substances
- Majority (up to 90%) of reabsorption occurs proximally
- Electrolytes can be actively (or osmotically) reabsorbed
- Water reabsorption is always via Osmosis
- Substances that are filtered but not reabsorbed may concentration 100 fold by time they appear in urine compared to concentration in filtrate
Glomerular Filtration
Unidirectional process Nonselective for small solutes that pass glomerular membrane Proteins (70,000 and bound drugs) not filtered Major driving force: hydrostatic pressure - glomerular capillaries Kidneys receive ≈ 25% of cardiac output via renal artery with little reduction of hydrostatic pressure Of this volume, ≈ 20% of plasma water and solutes traverse glomerulous in single pass Filtrate contains drug in same concentration as free drug in plasma First-order process Glomerular Filtration Rate (GFR): 125 - 130 ml/min Measured by using drug that is excreted only by glomerular filtration - inulin or creatinine
Active Secretion
Inferred when rate of excretion in urine exceeds GFR Active transport process: Highly efficient as long as transport capacity is not saturated Carrier mediated process that requires energy Transport normally against concentration gradient Located along proximal tubule with separate transporters for weak acids and weak bases Dependent on plasma flow-rate but may be so efficient that even protein- bound drugs are completely removed from plasma Para-aminohippuric acid (PAH): Organic acid that is filtered and secreted but not reabsorbed: Essentially all in blood removed in single pass through kidney Measures effective renal plasma flow-rate (ERPFR): 425-650 ml/min
Renal Clearance: Summary I
####### Measured Renal Clearance may be result of any
####### or all of 3 processes:
Glomerular Filtration - Increases clearance Active Secretion - increases clearance Reabsorption - decreases clearance
Renal Clearance: Summary II
ClR = Renal clearance
Clgf = Clearance due to glomerular filtration
Cls = Clearance due to secretion
FR = Fraction of the drug filtered and secreted that
is reabsorbed
Cl
R
= Cl
gf
+ Cl
s
( )
( 1 − FR)
Design and Function - Kidney (pdf - c)
Course: Biosystems I (PHAR 637)
University: West Coast University
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