Renal Plasma Clearance Flashcards
What is GFR?
how much filtrate is removed from blood each minute
What is the first step of urine formation?
1st step in urine formation begins with glomerular filtration
How does GF composition differ from plasma?
same composition as plasma except:
Devoid of cellular elements like RBC
Essentially protein-free
What does the presence of protein in urine suggest?
Urine routinely tested on wards for protein - proteinuria; sign of renal/urinary tract disease
(>0.5g/day OR ≥250mg/L on test-strip)
How is filtration rate regulated?
Filtration across the capillaries is determined by opposing forces (PGC and PBS)
Which force favours filtration?
Favouring filtration:
Glomerular capillary pressure (PGC) = 60mmHg
Which force opposes filtration?
Hydrostatic pressure in Bowman’s space (PBS) = 15mmHg
What is the osmotic force of plasma proteins?
Osmotic force of plasma proteins (ΠGC) = 29mmHg
How do we determine the net filtration pressure?
PGC – PBS – ΠGC = 16mmHg (net filtration pressure)
How do we determine the urinary excretion rate?
Urinary excretion rate = GFR – reabsorption rate + secretion rate
What factors determine GFR?
- hydrostatic* and oncotic pressures across capillary
membranes - permeability of capillary filtration barrier & surface area
available
What is the significance of GFR?
GFR important clinical indicator of functioning of nephrons (renal function)
contributes to rapid removal of waste products
When do the renal processes (e.g GF, Tubular reabsorption etc.) occur?
Each of the processes i.e. GFR, tubular reabsorption and tubular secretion regulated according to needs of the body
Explain how the kidneys respond to excess Na in body
excess Na in body:
Na filtering rate increased
Na reabsorption rate is decreased
=> resulting in increased urinary excretion of Na
What is the effect of a high GFR?
High GFR allows kidneys to rapidly remove waste products that depend primarily on glomerular filtration for their excretion
Kidney can precisely & rapidly control volume and composition of body fluids
How do we measure GFR?
GFR is not measured directly but by measurement of the excretion of a marker substance
Explain how creatinine passes through the kidneys
- Filtration onky
Freely filtered but neither reabsorbed or secreted. Hence it’s excretion rate is = to rate at which filtered
How are electrolytes processed through the kidneys?
- Filtration + Partial Reabsorption
freely filtered but partly reabsorbed from tubules back into blood. Hence rate of urinary excretion is less than rate of filtration at glomerular capillaries (eg. Many electrolytes in body)
Explain the passage of glucose and amino acids through the kidneys
- Filtration + Complete Reabsorption
Freely filtered but NOT excreted into urine as all filtered substance reabsorbed from tubule back into blood
Explain the fate of organic acids as they pass through the nephrons of the kidneys
- Filtration + Secretion
Freely filtered but NOT reabsorbed and additional quantities secreted from peritubular capillaries into renal tubules (eg organic acids & bases)
What is the gold standard method for measuring GFR?
Inulin method
NOT used clinically
Describe the Inulin method of measuring GFR
An inert polysaccharide, MW ~5,000
Filters freely through the glomerular membrane
Not absorbed, secreted or metabolised
How is urine flow rate calculated?
V = urine volume collected / collection period
How do we calculate amount of inulin filtered out per min?
So the load of inulin filtering from the plasma into BC over 1 min is Pin x GFR
How do we calculate the rate at which inulin enters the bladder?
Rate at which inulin enters the bladder is:
Uin x urine flow(V)
What is renal clearance?
The volume of plasma that is completely cleared of the substance by the kidney per unit of time, (ml/min)
How can we calculate the clearance rate of a substance?
Cs x Ps = Us x V*
Cs = clearance rate of substance (s) Ps = plasma concentration of s Us = urinary concentration of s V* = urine flow rate
What are the drawbacks of the inulin method?
prolonged infusion
repeated plasma samples
difficult routine clinical use
Clinically use creatinine for GFR measurement
What are the advantages of measuring GFR using creatine?
Advantages: An intrinsic inert substance Released at ~steady level in plasma from skeletal muscle No infusion needed Freely filtered Not reabsorbed in the tubule
What are the disadvantages of using creatine?
Some secreted into the tubule
What is trimethoprim?
*Trimethoprim (antibiotic) – competitive inhibitor of creatinine
What is the role of Trimethoprim?
Trimethoprim competes with Crn for same transporters that secrete Crn from tubular blood into urine » increase in serum levels of Crn
Where is creatine found in the body?
Cr (94%) found in muscular tissues.
Where is creatine formed?
Muscle virtually has no Cr-synthesizing capacity, so Cr has to be taken up from blood against [large] gradient by Na+ / Cl- dependent transporter
What is the rate of creatine clearance?
The serum creatinine concentration is inversely proportional to the creatinine clearance. GFR declines with age
What is eGFR?
eGFR is estimated Glomerular Filtration Rate
How is eGFR found?
Using blood tests, age, sex, and sometimes other information to estimate the GFR from the MDRD equation*
How are the stages of Chronic Kidney Disease (CKD) defined?
The stages of CKD (Chronic Kidney Disease) are mainly based on measured or estimated GFR
How many stages are there of CKD?
There are five stages but kidney function is normal in Stage 1, and minimally reduced in Stage 2
What factors should be taken into consideration when using eGFR?
- Only an estimate; significant error possible
- eGFR most likely inaccurate for extreme body types
- Not valid in pregnant women, patients <70yrs or children
- Race: Some racial groups don’t fit MDRD equation well
- was originally validated for US white & black patients.
Why does inulin clearance in men and women differ?
Because of the difference in body weight & body surface area between men & women the inulin GFR/clearance is different
Which substances are cleared equal to GFR?
Substance with clearance = inulin (= GFR)
e.g. antibiotics (streptomycin/gentomycin)
What is the difference in clearance between men and women?
Clearance of Inulin (GFR) ~ 125ml/min in adult male and 10% less in females
Which substances are cleared < inulin?
Substance with clearance < inulin (< GFR)
Not filtered freely
Or reabsorbed from tubule
What substances have a clearance > inulin?
Substance has clearance > inulin (>GFR)
Secreted into tubule
When might Clearance < GFR?
Not freely filtered
E.g. Albumin clearance = 0 ml/min
Similarly for drugs bound to albumin e.g. digoxin, warfarin
OR
Substance that is reabsorbed
Filters freely but usually absent from urine ⇒ completely reabsorbed
e.g. Glucose clearance = 0 ml/min
Describe the rate of glucose filtration
Rate of glucose filtration increases with plasma [glucose]
until a plasma [gluc] of ~15mM is reached (renal threshold - no glucose in the urine)
Why is there no glucose present in urine?
PCT has reabsorbed the entire load (via carrier mechanism with Na)
What happens if plasma [gluc] exceeds threshold?
Above threshold glucose starts to appear in the urine and then the reabsorption falls short of the filtration
What is the Transport maximum?
Rate at which glucose carrier mechanism is fully saturated
Why does glucose appear in urine before Transport maximum is reached?
Different nephrons have different Tm so some start excreting glucose in urine before others
Describe the rate of glucose clearance at low Pgluc
At low values of Pgluc:
glucose clearance = 0 but above the renal threshold it climbs rapidly at first then more slowly
Why does glucose never reach inulin clearance?
some glucose is always reabsorbed by glucose carrier mechanism
When may active reabsorption cause clearance of substances < GFR ?
All amino acids
clearance = 0 ml.min-1 unless excess filtered
pathological conditions (e.g. myeloma)
production of Bence-Jones protein in plasma
Ca2+, Na+, PO42-, Mg2+
Water-soluble vitamins
Which substaces are passively reabsorbed giving clearance < GFR?
Cl–, urea, some imp. drugs
Why do some drugs have a clearance < GFR?
As GF flows down tubule & more water is reabsorbed, solutes are concentrated providing conc gradient down which they diffuse
But only lipid soluble substances can cross tubular wall, so lipophilic drugs tend to return to blood stream whilst hydrophilic drugs lost in urine
What type of substances are secreted into urine by tubular cells?
Filters freely
Secreted actively against electrochemical gradient
Endogenous substances
- e.g. weak organic acids/bases, adrenaline, dopamine,
steroids
Exogenous substances
- e.g. penicillin, probenecid, para-amino hippuric acid (PAH)
What is renal plasma flow (RPF?)
RPF is the rate at which plasma flows through the kidney
Describe the plasma & composition of blood
Blood consists of about 55% plasma and about 45% cellular components (mostly RBCs)
What is PAH?
Weak acid metabolite found in horse urine
Filtered freely & enters GF
Large amount still in plasma
Majority secreted back into PCT ⇒ excreted in urine
Suitable as a marker to measure RPF
What is the significance of PAH secretion?
> can be given to determine renal blood flow
Active transport occurs in basolateral membrane
Passive transport across luminal membrane into tubule
How does PAH relate to renal plasma flow?
PAH Clearance - RPF
If plasma [PAH] low enough <0.12mg/ml (
What is the filtration fraction?
fraction of plasma that is filtered through the glomeruli
How can we calculate the filtration fraction?
GFR & RPF can be used to calculate the filtration fraction
Filtration Fraction = GFR / RPF = 125 / 660 (x100) =19%
How do we determine GFR?
GFR determined from Inulin clearance
How do we determine RPF?
RPF determined from PAH clearance
What is the clearance of urea?
Urea has a clearance of 65 ml.min-1
