renal plasma clearance Flashcards
what is inulin ?
- inert polysaccharide
- filters freely through the glomerular membrane
- not absorbed secreted or metabolised
- used to measure GFR
describe the inulin method
- Preparation and Infusion Initiation:
* Inulin that is freely filtered by the kidneys but neither reabsorbed nor secreted, is administered intravenously at a steady rate.
* The infusion is continued until plasma inulin concentration (𝑃𝑖𝑛 ) reaches a steady-state level. - Monitoring Plasma Inulin Stability:
* The steady-state is achieved when the rate of inulin infusion equals the rate of inulin excretion. - Timed Urine Collection:
* Once plasma inulin concentration is stable, urine is collected over predetermined time intervals.
* The collection period is recorded accurately to measure urine flow rate (𝑉) - Midpoint Blood Sampling:
* A blood sample is obtained at the midpoint of each urine collection period to determine plasma inulin concentration (𝑃𝑖𝑛). - Measurement of Urine and Plasma Inulin Concentration:
* Urine inulin concentration (𝑈𝑖𝑛) and the total volume of urine collected (𝑉) are analyzed. - GFR is calculated
what is the formula for GFR ?
what is renal clearance ?
Renal clearance of a substance is the volume of plasma that is completely cleared (excreted into urine) of the substance by the kidney per unit of time, (expressed in ml/min)
describe the renal clearance of inulin
- Filtration: Inulin is freely filtered by the glomerulus into the filtrate.
- No Reabsorption or Secretion: Inulin is neither reabsorbed nor secreted, meaning it only exits the body through urine.
- Complete Excretion: All filtered inulin is excreted, and none remains in the tubules.
- Clearance Calculation: Since 125 ml of plasma is filtered per minute (GFR), this same volume is cleared of inulin per minute.
- Renal Plasma Flow: Of the 625 ml of plasma reaching the kidneys per minute, only 125 ml is filtered and cleared of inulin; the remaining 500 ml retains its inulin.
- Clinical Use: Inulin clearance directly measures GFR, helping assess kidney function.
what is the formula for renal clearance ?
what are the drawbacks of the inulin method ?
- prolonged infusion
- repeated plasma samples
- difficult routine clinical use
what are the advantages and disadvantages of the creatinine method ?
describe creatine (cr) and creatinine (crn) metabolism
- Muscle Storage: 94% of Cr is in muscles; uptake via Na⁺/Cl⁻-dependent transporter (muscle can’t synthesize Cr).
- Sources: Obtained from diet or biosynthesis.
- Conversion to Crn: ~2% of Cr/PCr converts daily to Crn, which is excreted by kidneys.
Supplementation Benefits:
✅ Increases PCr stores for ATP regeneration
✅ Speeds up PCr resynthesis during recovery
✅ Reduces adenine nucleotide breakdown & lactate buildup
Risks & Safety:
⚠️ No long-term safety studies available
⚠️ Avoid in renal impairment (increases Crn & uremic toxins)
⚠️ Healthy individuals see only a small increase in Crn
what is EGFR ?
- eGFR is estimated Glomerular Filtration Rate:
- An equation using blood tests, age, sex, and other information to estimate GFR
- This isn’t as good as measuring it (i.e. 24h urine collection), but is much simpler as it requires just one blood test.
- Can spot kidney disease earlier than would be possible using just creatinine measurements
Drawbacks:
* It is only an estimate……A significant error is possible.
- eGFR is most likely to be inaccurate in people at extremes of body type, for example malnourished, amputees, etc.
- is not valid in pregnant women or children, poor in patients older than 70yrs
what are the stages of chronic kidney disease ?
describe the clearance of different substances
- Substances with clearance = inulin (= GFR)
~ 125ml/min in adult male and 10% less in females
e.g. antibiotics (streptomycin/gentomycin) - Substances with clearance < inulin (< GFR)
Either not filtered freely
Or reabsorbed from tubule - Substances with clearance > inulin (> GFR)
Secreted into tubule
describe substances that are reabsorbed or not freely filtered
Substances That Are Not Freely Filtered:
* The glomerular filtration barrier prevents large molecules (e.g., proteins) from passing through.
* Example: Albumin
* Albumin is a large protein, so it is not freely filtered at the glomerulus.
* This results in zero clearance (0 ml/min) because it stays in the plasma and does not appear in the urine.
* Some drugs (e.g., digoxin, warfarin) bind to albumin in the blood.
* Since albumin is not filtered, the bound portion of the drug is also not filtered, reducing its clearance.
* Only the unbound (free) drug can be filtered and excreted.
Substances That Are Reabsorbed:
* Some substances do get freely filtered but are completely reabsorbed back into the bloodstream.
* Example: Glucose
* Glucose is freely filtered at the glomerulus.
* Normally, the proximal tubule reabsorbs 100% of filtered glucose.
* Since no glucose remains in the urine, its clearance is 0 ml/min.
* However, in conditions like diabetes mellitus, excess glucose exceeds the kidney’s reabsorption capacity, leading to glucose in the urine (glycosuria).
describe substances that are actively or passively reabsorbed
Actively Reabsorbed (Energy-Dependent):
✅ Fully reabsorbed unless excess is filtered → Clearance = 0 ml/min
✅ Uses ATP-dependent transporters
🔸 Examples:
* Amino acids → Fully reabsorbed unless pathology (e.g., Bence-Jones proteins in multiple myeloma)
* Ions: Ca²⁺, Na⁺, PO₄³⁻, Mg²⁺ (regulated by hormones)
* Water-soluble vitamins (Vitamin C, B-complex)
Passively Reabsorbed (No Energy Required)
✅ Moves by diffusion or osmosis following gradients
✅ Can be influenced by urine pH
🔸 Examples:
* Chloride (Cl⁻) → Follows Na⁺ reabsorption
* Urea → Some reabsorbed to maintain medullary concentration gradient
* Some drugs → Weak acids (e.g., aspirin) reabsorbed in acidic urine, weak bases (e.g., amphetamines) reabsorbed in alkaline urine
How does probenecid affect the excretion and action of penicillin?
Probenecid competes with penicillin for the same transporters in renal tubules, slowing its active secretion into the urine. This reduces penicillin’s excretion rate, prolonging its presence in the bloodstream and extending its therapeutic effects.
describe Renal Plasma Flow (RPF) & Renal Blood Flow (RBF)
- RPF is the rate at which plasma flows through the kidney
- Estimating the RPF through the kidneys allows us to estimate the rate of total blood flow (RBF) through the kidneys
- Blood consists of about 55% plasma and about 45% cellular components (mostly RBCs)
what is Para-aminohippuric Acid ?
- PAH is weak acidic metabolite of glycine, originally found in horse’s urine
- Filtered freely and enters glomerular filtrate, but a large amount still in plasma
- Majority is secreted back into proximal convoluted tubule excreted in urine
- Suitable as a marker to measure renal plasma flow
describe PAH secretion
describe PAH and renal plasma flow
describe renal filtration fraction
give a summary
