Renal Plasma clearance Flashcards
What is the difference between glomerular filtrate and plasma?
What does this mean for urine tests?
What is proteinuria a sign of?
Devoid of cellular elements like RBC
Essentially protein-free
Hence, urine is routinely tested on wards for protein (proteinuria).
Proteinuria is a sign of renal/urinary tract disease (>0.5g/day OR ≥250mg/L on test-strip)
What is GFR?
Glomerular Filtration Rate (GFR) is how much filtrate is removed from blood each minute NOT how much blood passes through glomerulus each minute
How do we know there is a volume of 625ml of fluid is following through the beginning of tubule?
What happens here and describe the volumes
(1) Filtration
(2) Reabsorption
(3) Secretion
(4) Excretion
What is the equation for the urinary excretion rate?
Urinary excretion rate = GFR – reabsorption rate + secretion rate
Why is GFR important?
What factors determine GFR and what can changes in these factors cause?
GFR contributes to rapid removal of waste products
GFR is ~ 180L/day & plasma volume ~ 3L
- entire plasma can be filtered ~ 60x/day
GFR determined by combination of factors:
- hydrostatic* and oncotic pressures across capillary membranes
- permeability of capillary filtration barrier & surface area available
Change in any of these factors will change GFR
Hence GFR important clinical indicator of functioning of nephrons (renal function)
What are the 4 methods of measuring GFR?
- Filtration only Eg. creatinine
- Filtration, partial reabsorption Eg. electrolytes
- Filtration, complete reabsorption Eg. Glucose, AA
- Filtration, secretion Eg. Organic Acids
What is Inulin? - IT DISPLAYS ALL THESE POINTS EXPLAINED ABOVE OF HOW WE MEASURE GFR?
An inert polysaccharide, MW ~5,000
Filters freely through the glomerular membrane
Not absorbed, secreted or metabolised
As inulin is not secreted or reabsorbed what is the rate of filtration through the membrane equal to?
Rate of filtration through glomerular membrane per minute = Rate of entry into bladder per minute
How do we actually carry out the process of using inulin to measure GFR?
Rate of filtration through glomerular membrane per minute
On image - look at the recording
- Set up an IV line and infuse with inulin and reach a steady-state - we do these by taken blood samples and measuring until it teachers a steady-state
- Passes through the filter
- passes through the tubule
- Urine is then collected - measure how much in plasma and urine
Therefore
Rate of entry into bladder per minute
Inulin is not absorbed
Inulin is not secreted
- What is the rate of inulin filtration equal to?
- What is the Equation that calculates GFR of inulin?
- What is the equation for the rate of entry into the bladder Rate of entry into bladder = [Uin] x urine flow rate (V*)
- = [Pin] x GFR
- Pin x GFR = Uin x V*
Where:
GFR = glomerular filtration rate; ml.min-1
Pin = plasma inulin concentration; mg.ml-1
Uin = urine inulin concentration; mg.ml-1
V* = urine flow rate; ml.min-1
- The rate of entry into the bladder Rate of entry into bladder = [Uin] x urine flow rate (V*)
Define renal clearance of s substance?
Renal clearance of a substance is the volume of plasma that is completely cleared of the substance by the kidney per unit of time, (in other words excreted in urine each minute) (expressed in ml/min)
How is inulin cleared? (renal clearance)
On image
What is the equation for renal clearance?
Cs x Ps = Us x V*
Cs = Us x V* / Ps
where: 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?
What other method is better?
Drawbacks inulin method:
prolonged infusion
repeated plasma samples
difficult routine clinical use
Clinically use creatinine for GFR measurement
What are the advantages and disadvantages of measure GFR using creatinine?
What antibiotic is administered to treat urinary tract infections?
Advantages: An intrinsic inert substance Released at ~steady level in plasma from skeletal muscle No infusion needed Freely filtered Not reabsorbed in the tubule
Disadvantages:
On image
Trimethoprim (antiobiotic) – competitive inhibitor of creatinine
How and where is Creatinine produced?
How is it excreted?
How does Trimethoprim work?
On image
Trimethoprim competes with Crn for same transporters that secrete Crn from tubular blood into urine» increase in serum levels of Crn
How is Creatinine cleared (graphically)
On slides - watch the recording
GFR decreases as we age
Why is there a difference between men and women in GFR?
On slides
Muscle mass and surface area
What does eGFR stand for?
eGFR is estimated Glomerular Filtration Rate
What does eGFR take into account?
What is the equation for this?
What has this been superseded by and why?
Using blood tests, age, sex, and sometimes other information to estimate the GFR from the MDRD equation*
186 x (Creat/88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black) *MDRD equation improvement on original Cockcroft-Gault equation
This has been superseded by:
Superseded by CKD-EPI Adults (Chronic Kidney Disease Epidemiology Collaboration)
This isn’t as good as measuring it (i.e. 24h urine collection), but is much simpler as it requires just one blood test.
It is being used increasingly to spot kidney disease earlier than would be possible using just creatinine measurements
http://www.nephron.com/MDRD_GFR.cgi
The stages of CKD are based on measured GDR values, look at these stages
On table
What are the implications that eGFR being an estimate?
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.
It is not valid in pregnant women, patients older than 70yrs or in children
Race: Some racial groups may not fit the MDRD equation well. It was originally validated for US white and black patients. For Afro Caribbean black patients, eGFR was 21% higher for any given creatinine in the MDRD study.
Compare the clearance of inulin, with the GFR
Substance with clearance = inulin (= GFR)
e.g. antibiotics (streptomycin/gentomycin)
Substance with clearance < inulin (< GFR)
Not filtered freely
Or reabsorbed from tubule
Substance has clearance > inulin (>GFR)
Secreted into tubule
What substances has a clearance less than GFR?
Albumin
Not freely filtered
- E.g. Albumin clearance = 0ml/min
- Similarly for drugs bound to albumin e.g. digoxin, warfarin
Substance that is re-absorbed
Filters freely but is usually absent from urine completely reabsorbed
e.g. Glucose clearance = 0ml/min
How is glucose handled by the kidney?
- Glucose is infused with inulin - inulin is needed to calculate GFR
- As glucose is infused the glucose conc in the blood increases and so does the filtration of glucose.
- Initially, no glucose is seen in the urine, after certain value glucose appears in the urine (15mM - renal threshold) - so, therefore, increase excretion of glucose
- For reabsorption initially, all glucose is reabsorbed - this hits a max value of - the transport maximum (20mM)
- Some glucose appears in the urine before this - each nephron varies
Why does glucose clearance never reach the inulin clearance?
Glucose clearance never reaches inulin clearance because transporters are always working
Describe another substance that has a clearance of other substances < GFR
Actively Reabsorbed
- All amino acids
- clearance = 0ml.min-1 unless excess filtered
- pathological conditions (e.g. myeloma)
- production of Bence-Jones protein in plasma
- Ca2+, Na+, PO42-, Mg2+
- Water-soluble vitamins
Passively Reabsorbed:
Cl–, urea, some imp. drugs
Describe a substance that has a clearance GREATER than GFR
Substance that is secreted
- 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) & Renal Blood Flow (RBF)?
What is the composition of blood?
RPF is the rate at which plasma flows through the kidney
Blood consists of about 55% plasma and about 45% cellular components (mostly RBCs)
Estimating the RPF through the kidneys estimate the rate of total blood flow through the kidneys.
What is Paramminohippuric Acid?
Does it filter?
Where does it enter and leave?
PAH is weak acid metabolite found in horse’s urine
Filtered freely & enters glomerular filtrate
But large amount still in plasma
The majority is secreted back into proximal convoluted tubule excreted in urine
Suitable as a marker to measure renal plasma flow
How is PAH secreted?
Active transport occurs in basolateral membrane
Passive transport across luminal membrane into tubule
What is the equation for PAH clearance?
What is the equation for filtration fraction?
SAME AS BEFORE
gfr/rbf x 100
