Flashcards in L80 - Biochemical Investigation of Urogenital Diseases I Deck (102):
Give examples of reabsorption in kidney?
Glucose, amino acids, electrolytes, proteins
What are the 2 metabolic functions of the kidney?
Synthetic: glutathione, glyconeogenesis, ammonia
Catabolic: hormones, cytokines
Sequence of intermediates in Vitamin D production? Start from Previtamin D3 in skin.
Previtamin D3 [skin] > Vitamin D3
+ Vitamin D2 and D3 from diet
>> 25-hydroxyvitamin D [liver]
>> 1,25- hydroxyvitamin D [Kidney] (active form)
What are some endocrine functions of kidney?
Erythropoietin synthesis, activation of vitamin D,
What is the urine formation rate?
~ 1.5 L/day
What is the normal GFR?
Equation for filtration fraction?
filtration fraction is the ratio of the glomerular filtration rate (GFR) to the renal plasma flow (RPF)
FF = RPF/ GFR
What is the normal Hematocrit (Hct) level?
Ratio of the volume of red cells to the volume of whole blood
45% to 52% for men and 37% to 48% for women.
What is the normal Renal blood flow rate?
~ 20% Cardiac Output
How much H2O in glomerular ultrafiltrate is reabsorbed by the kidney??
How is Minimal Volume of Urine Water calculated?
= Waste product of metabolism (mOsm/day) / Maximal urinary concentration attainable
What is the minimal vloume of urine water excreted per day?
about 400 mL/day
Lower than ~ 400 mL/day/ minimal volume of urine water excreted leads to what?
Azotaemia is inevitable with daily Urinary Output < 400 mL
Purpose of assessing GFR?
assess the severity and course of renal disease
adjust the dosage of drugs primarily excreted by kidney (or highly nephrotoxic)
Volume of volume of glomerular filtrate produced by BOTH kidneys per unit time
* glomerular filtrate = Volume of fluid filtered from the kidney glomerular capillaries into the Bowman’s capsule*
Define renal clearance?
Clearance of a substance:
The volume of plasma
from which that substance is completely cleared by the kidneys per unit time
What are the ideal parameters of a substance used to measure GFR?
- Freely filtered at the glomerulus
- Not reabsorbed by the renal tubules
- Not secreted by the renal tubules or other
organs of the body
- Not synthesized or metabolized by the renal
What is the formula for GFR?
M = substance filtered freely
GFR = ( UM x V ) / PM
UM = conc of M in Urine
PM = conc. of M in Plasma
V = volume of Urine per unit time
If a substance is ideal for GFR, what is the rate of excretion and filtration of that substance?
Mass excreted / Time = Mass filtered / Time
What is the formula betwen mass, volume and concentration?
Mass = volume x concentration
If a substance is freely filtered, what is the concentration of it in the filtrate vs in plasma?
conc in filtrate identical to the conc in plasma
What does the Maintenance of a normal GFR depend on?
adequate number of nephrons
Intact glomerular function
normal renal perfusion
Fall in GFR is associated with raised plasma levels of what?
retention of metabolic wastes
>> raised Creatinine and Urea levels in plasma
A decreasing GFR precedes __?
Renal failure in all forms of progressive renal disease
Level of GFR is a strong predictor of __?
the time to onset of renal failure
Name 3 substances used for GFR measurement?
Urine collected over 10 hours = 1 Liter
Urine INULIN concentration = 300 mg/L
Concentration of INULIN in Plasma = 4 mg/L
UV/P = GFR
Volume per hour = 1/10 = 0.1
U = 300mg/L
P = 4mg/L
300 x 0.1 / 4 = 7.5L/ hour = 125 mL/min
If inulin was secreted in body, what would the GFR be?
Higher than true GFR
Why is inulin not used clinically?
requires infusion of the polysaccharide at a continuous and constant rate for several hours
>> inconvenient and costly
Why is Creatinine used over inulin? Limitation?
released into the blood at a relatively constant rate
>> endogenous, no need for intravenous
Limitation of using creatinine for GFR?
Creatinine Clearance only gives an approximation of the true GFR
** small amount of
Creatinine is secreted by the renal tubules
** overestimate the true GFR
Why is very accurate GFR not required clinically?
requires blood sampling and timed urine
>> error-prone due to inaccurate timing of urine collection
2 ways to measure GFR?
Creatinine in blood (plasma / serum) or
measurement of Creatinine Clearance (CrCl)
How does creatinine flow to kidneys?
not protein bound, non-polar, small size (113 D)
freely filtered and carried in blood, filtrate
Relationship between Plasma creatinine and GFR?
Plasma CREATININE is inversely related to GFR
Show how Plasma CREATININE is inversely related to GFR?
Creatinine Excretion = Creatinine Filtered (GFR x Plasma Creatinine Conc)
GFR x Plasma Creatinine = Constant
so GFR = Constant / Plasma Creatinine
Why creatinine not perfect for detecting changes in GFR?
Inability to detect mild to moderate reduction in GFR
GFR has to drop by 40-50% before plasma creatinine levels raise
What influences creatinine production?
Difference in Age, gender and ethnic
Rise in GFR by how much warrants an investigation
rise in blood Creatinine of ≥ 20% from previous levels
***even if the Creatinine level still remains within the reference interval***
What is Flag L and Flag H?
H = abnormally high creatinine
L = abnormally low ''
Why is GFR using creatinine not great for giving signs of acute kidney function deterioration?
Early acute kidney injury >> GFR reduced but not enough time for creatinine to accumulate
>> cannot reflect severity of kidney disease
Blood level rise causes what to rise?
Renal tubular and gastrointestinal mucosal secretion
trimethoprim (UTI drug), H2-blocker cimetidine can influence GFR, how?
increase the level of the
serum creatinine by decreasing creatinine secretion
What other biomarkers can interfere with creatinine levels?
very high level of bilirubin and acetoacetate lead to spuriously low and high creatinine results
Describe the relationship between GFR and serum creatinine in acute kidney disease?
GFR may fall considerably before serum creatinine is significantly increased
What changes in muscle mass and kidney status leads to increased plasma creatinine?
Normal muscle mass + diseased kidneys
Increased muscle mass + normal kidneys
Reduced muscle mass + diseased kidneys
What change in muscle mass and kidney status can mask kidney disease and poor function?
Reduced muscle mass + Diseased kidney
The serum creatinine level is low due to low muscle mass, but diseased kidney removes less creatinine >> mask disease
Compare a skinny vs muscular person, at the same rate of decline in GFR, the skinny person's serum creatinine level increases at higher or lower GFR than muscular?
Change in creatinine due to: aging?
Change in creatinine due to: Female Sex
Change in creatinine due to: Muscular body
Change in creatinine due to: Amputation
Change in creatinine due to: Obesity
Change in creatinine due to: Malnutrition, inflammation, deconditioning
Change in creatinine due to: Neuromuscular diseases
Change in creatinine due to: Vegetarian diet
Change in creatinine due to: Ingestion of cooked meat
What is urea made from?
waste product of amino acid metabolism,
synthesized by the liver from ammonia and CO2
Urea clearance depends on what?
Urine Flow Rate
Movement of urea in kidneys?
Filtered freely by the glomeruli
readily diffuses back into the circulation through renal tubular membrane
Plasma urea Excretory load is dependent on?
net body protein metabolism
Name 2 conditions that raises plasma urea levels?
Cushing syndrome, severe burn
raised urea levels due to accelerated
How does kidney disease impact plasma urea level?
Kidney disease > decrease Renal perfusion or nephron no.
> More urea diffuse back to plasma > raise plasma urea level
Why is urea not good as a GFR indicator?
1. Decrease production or low protein intake >> lower plasma urea level to falsely indicate renal insufficiency
2. GFR has to drop 40% before plasma urea rises
3. Increase production or high protein intake rises plasma GFR > mask renal impairment
List factors that raises plasma urea levels?
* High Protein Diet
* Tissue Trauma
* Gastrointestinal Bleeding
List factors that lowers plasma urea levels?
* Liver Disease
What does Renal function test profile?
measurement of Creatinine and Urea conc in serum/plasma
(also Na+, K+, Cl-, HCO3-)
Why is RFT convenient but rather insensitive?
significant reduction of GFR but levels still within reference
Subject to various factors independent of renal function
Unit of Creatinine clearance?
Name 1 pro and 2 cons of creatinine clearance as estimation of GFR?
- More reliable than formula-predicted GFR
- 24-hour urine collection is inconvenient and error-prone
- Measurement Uncertainty may be up to 30%
What is Cockroft and Gault formula based on?
plasma / serum Creatinine,
Age, Body Weight, Gender (diff. equations for adults and children)
What is good about the MDRD equations for eGFR?
more sensitive than plasma / serum Creatinine
especially in detecting mildly impaired GFR
GFR estimated by Cockroft and Gault formula tend to ____ GFR in advanced renal failure?
overestimate GFR in advanced renal failure
Cockrodt and Gault formula correlates better with measure GFR provided__?
Renal impairment is not severe and relatively stable
No inhibition of tubular secretion of creatinine by medications
Plasma [creatinine] is not within normal range
Difference in what Cockroft and Gault meansures vs MDRD?
MDRD = eGFR
Cockroft = creatinine clearance
Name 4 pros of the MDRD eGFR formula?
- No need for timed urine collection
- No need for body weight
- Adjusted for body size (to 1.73m^2 standard)
- Evaluated in subjects with varyinging renal insufficiency
Name 1 con of the MDRD eGFR formula?
Not validated in subjects <18 and >70 yrs, pregnant women
What is needed to be applied to the MDRD eGFR formula for Asians?
Asian ethnic co-efficient
What is the advantage of CKD-EPI over MDRD?
much less bias at
eGFR greater than 60ml/min/1.73m2
Name 2 benefits of CKD-EPI?
Minimising the over-diagnosis of CKD with
the MDRD equation
Lower prevalence of
CKD and better risk prediction
Out of all the formulas, which one is now used for eGFR?
Name of formula for eGFR in children?
Schwartz formula for estimation of GFR in Children
What does the Schwartz formula include as metrics?
serum Creatinine (mg/dL), child’s height (cm) and a Constant (k)
k is a constant that depends on muscle mass
abnormalities of kidney
structure or function, present for >3 months,
with implications for health.
How much Albuminuria in CKD?
Albuminuria >30 mg/day
Why is Plasma Creatinine & Formula-predicted GFR not good for acute renal failure?
very rapid deterioration in renal function may be underestimated by the
What is Goulash effect?
80% rise in creatinine after 300g of cooked beef
How to limit Goulash effect?
Less variability in early morning creatinine
How much does Strenuous exercise increase creatinine?
Which patients are harder to measure muscle mass?
severe muscle wasting
extreme body habitus
What diseases can highly affect plasma creatinine?
What drugs can affect creatinine ?
Drugs inhibiting tubular creatinine secretion
(e.g., trimethoprim, cimetidine, probenecid, amiloride)
Factors affecting tubular secretion of creatinine?
Drugs that induce inhibition of secretion
Factors affecting extra-renal elimination of creatinine?
Drugs inhibit gut creatinase in bacteria
Increase by large volume losses of extracellular fluid
Main use for Cockroft & Gault formula?
Widely accepted for drug-dosing
Main use for Creatinine Clearance by timed urine collection?
For extremes of body composition
Gold standard for GFR measurement?
GFR measured by
Cystatin C is made where? Affected (or not) by what?
Cysteine protease inhibitor
Synthesized by all nucleated cells and produced at a constant
Not affected by muscle mass, gender and diet
What increases Cystatin C by a small amount?
modest increase in production is seen in obesity,
hyperthyroidism, and inflammation
Renal circulation of Cystatrin C?
Freely filtered at glomerulus
Reabsorbed and metabolized by proximal tubules
only a minute amount present in urine
What does Cystatin C measure/ mark for?
Increases in urinary excretion= marker for PCT injury or dysfunction