Download CHAPTER-IX

Kidney Function Testing
CHAPTER-IX
K.ANITA PRIYADHARSHINI
LECTURER
DEPT.OF PHARMACEUTICAL
CHEMISTRY
SRM COLLEGE OF PHARMACY
An Introduction to the Urinary System
Produces urine
Transports urine
towards bladder
Temporarily store
urine
Conducts urine
to exterior
The Function of Urinary System
A) ‰ Excretion & Elimination:
removal of organic wastes products
from body fluids (urea, creatinine,
uric acid)
B) ‰ Homeostatic regulation:
Water -Salt Balance
Acid - base Balance
C) ‰ Enocrine function:
Hormones
A)
The excretory function
ƒ excretion of excess electrolytes, nitrogenous wastes and organic acids
ƒ The maximal excretory rate is limited or established by their plasma
concentrations and the rate of their filtration through the glomeruli
ƒ The maximal amount of substance excreted in urine does not exceed the
amount transferred through the glomeruli by ultrafiltration except in the
case of those substances capable of being secreted by the tubular cells.
Each kidney consists of one million
functional units: Nephrone
Nephron structure
A) Glomerulus
B) Glomerular Capsule
C) Renal Tubule
ƒ proximal convoluted tubule
•
loop of Henle
•
distal convoluted tubule
D) Collecting Duct
Urine Formation
Urine formation requiers :
a) Glomerular Filtration
Due to differences in pressure water, small molecules
move from the glomerulus capillaries into the
glomerular capsule
b) Tubular reabsorption
many molecules are reabsorbed from the nephron
into the capillary (diffusion, facilitated diffusion,
osmosis, and active transport)
i.e. Glucose is actively reabsorbed with transport
carriers.
If the carriers are overwhelmed glucose appears in
the urine indicating diabetes
c) Tubular secretion
Substances are actively removed from blood and
added to tubular fluid (active transport)
ie. H+, creatinine, and some drugs are moved by
active transport from the blood into the distal
convoluted tubule
Biochemical Tests of Renal Function
… Measurement of GFR
† Clearance tests
† Plasma creatinine
† Urea, uric acid and β2‐microglobulin
… Renal tubular function tests
†
†
†
†
Osmolality measurements
Specific proteinurea
Glycouria
Aminoaciduria
… Urinalysis
† Appearance
† Specific gravity and osmolality
† pH
† osmolality
† Glucose
† Protein
† Urinary sediments
When should you assess renal function?
… Older age
… Family history of Chronic Kidney disease (CKD)
… Decreased renal mass
… Low birth weight
… Diabetes Mellitus (DM)
… Hypertension (HTN)
… Autoimmune disease
… Systemic infections
… Urinary tract infections (UTI)
… Nephrolithiasis
… Obstruction to the lower urinary tract
… Drug toxicity
Biochemical Tests of Renal Function
…Measurement of GFR
†Clearance tests
†Plasma creatinine
†Urea, uric acid and β2-microglobulin
Measurement of glomerular filtration
rate
GFR can be estimated by measuring the urinary excretion of a substance that is completely filtered
from the blood by the glomeruli and it is not secreted, reabsorbed or metabolized by the renal
tubules.
¾ Clearance is defined as the (hypothetical) quantity of blood or plasma completely cleared of a
substance per unit of time.
GFR =
(Uinulin × V)
Pinulin
V is not urine volume, it is urine flow rate
¾ Clearance of substances that are filtered exclusively or predominantly by the glomeruli but
neither reabsorbed nor secreted by other regions of the nephron can be used to measure GFR.
¾ Inulin
¾The Volume of blood from which inulin is cleared or completely removed in one minute is
known as the inulin clearance and is equal to the GFR.
¾Measurement of inulin clearance requires the infusion of inulin into the blood and is not
suitable for routine clinical use
Creatinine clearance and clinical
¾The most frequently used
clearance test is based on the
utility
measurement of creatinine.
¾ Small quantity of creatinine is reabsorbed by the tubules and
other quantities are actively secreted by the renal tubules Î So
creatinine clearance is approximately 7% greater than inulin
clearance.
¾The difference is not significant when GFR is normal but when
the GFR is low (less 10 ml/min), tubular secretion makes the
major contribution to creatinine excretion and the creatinine
clearance significantly overestimates the GFR.
Creatinine clearance clinical utility
¾An estimate of the GFR can be calculated from the creatinine content of a 24-hour
urine collection, and the plasma concentration within this period.
¾The volume of urine is measured, urine flow rate is calculated (ml/min) and the
assay for creatinine is performed on plasma and urine to obtain the concentration in
mg per dl or per ml.
Creatinine clearance in adults is normally about of 120 ml/min,
The accurate measurement of creatinine clearance is difficult, especially in outpatients,
since it is necessary to obtain a complete and accurately timed sample of urine
Creatinine clearance and clinical utility
¾The 'clearance' of creatinine from plasma is directly related to the
GFR if:
¾The urine volume is collected accurately
¾There are no ketones or heavy proteinuria present to interfere
with the creatinine determination.
¾It should be noted that the GFR decline with age (to a greater extent
in males than in females) and this must be taken into account when
interpreting results.
Measurement of nonprotein nitrogencontaining compounds
Catabolism of proteins and nucleic acids results in formation of
so called nonprotein nitrogenous compounds.
Protein
↓ Proteolysis, principally enzymatic
Amino acids
↓ Transamination and oxidative deamination
Ammonia
↓ Enzymatic synthesis in the “urea cycle”
Urea
Plasma Urea
Many renal diseases with various glomerular, tubular, interstitial or vascular damage can
cause an increase in plasma urea concentration.
¾The reference interval for serum urea of healthy adults is 5-39 mg/dl. Plasma
concentrations also tend to be slightly higher in males than females. High protein diet causes
significant increases in plasma urea concentrations and urinary excretion.
¾Measurement of plasma creatinine provides a more accurate assessment than urea
because there are many factors that affect urea level.
¾Nonrenal factors can affect the urea level (normal adults is level 5-39 mg/dl) like:
9Mild dehydration,
9high protein diet,
9increased protein catabolism, muscle wasting as in starvation,
9reabsorption of blood proteins after a GIT haemorrhage,
9treatment with cortisol or its synthetic analogous
Clinical Significance
• States associated with elevated levels of urea
in blood are referred to as uremia or azotemia.
• Causes of urea plasma elevations:
¾Prerenal: renal hypoperfusion
¾Renal: acute tubular necrosis
¾Postrenal: obstruction of urinary flow
Uric acid
¾Renal handling of uric acid is complex and involves four sequential steps:
¾Glomerular filtration of virtually all the uric acid in capillary plasma
entering the glomerulus.
¾Reabsorption in the proximal convoluted tubule of about 98 to 100%
of filtered uric acid.
¾Subsequent secretion of uric acid into the lumen of the distal portion
of the proximal tubule.
¾Further reabsorption in the distal tubule.
¾ Hyperuricemia is defined by serum or plasma uric acid concentrations higher
than 7.0 mg/dl (0.42mmol/L) in men or greater than 6.0 mg/dl (0.36mmol/L)
in women
Plasma β2-microglobulin
¾β2-microglobulin is a small peptide (molecular weight 11.8 kDa),
¾It is present on the surface of most cells and in low concentrations in the
plasma.
¾It is completely filtered by the glomeruli and is reabsorbed and catabolized
by proximal tubular cells.
¾The plasma concentration of β2-microglobulin is a good index of GFR in
normal people, being unaffected by diet or muscle mass.
¾It is increased in certain malignancies and inflammatory diseases.
¾Since it is normally reabsorbed and catabolized in the tubules, measurement
of β2-microglobulin excretion provides a sensitive method of assessing
tubular integrity.
Renal tubular function tests
•
To ensure that important constituents such as water, sodium, glucose and
a.a. are not lost from the body, tubular reabsorption must be equally
efficient
•
Compared with the GFR as an assessment of glomerualr function, there are
no easily performed tests which measure tubular function in quantitative
manner
•
Investigation of tubular function:
1. Osmolality measurements in plasma and urine; normal urine: plasma
osmolality ratio is usually between 1.0-3.0
2. Specific proteinuria
3. Glycosuria
4. Aminoaciduria
Assessment of glomerular integrity
¾Proteinuria may be due to:
1. An abnormality of the glomerular basement membrane.
2. Decreased tubular reabsorption of normal amounts of filtered proteins.
3. Increased plasma concentrations of free filtered proteins.
4. Decreased reabsorption and entry of protein into the tubules consequent to tubular epithelial
cell damage.
¾Measurement of individual proteins such as β2-microglobulin have been used in the early
diagnosis of tubular integrity.
¾With severe glomerular damage, red blood cells are detectable in the urine (haematuria), the red
cells often have an abnormal morphology in glomerular disease.
¾ Haematuria can occur as a result of lesions anywhere in the urinary tract,
Urinalysis
¾Urinalysis is important in screening for diseaseÎ is routine test for every patient, and not just
for the investigation of renal diseases
¾Urinalysis comprises a range of analyses that are usually performed at the point of care rather
than in a central laboratory.
¾Urinalysis is one of the commonest biochemical tests performed outside the laboratory.
¾ Examination of a
patient's urine should not
be restricted to
biochemical tests.
Urinalysis: Specific gravity
– This is a semi-quantitative measure of concentration.
– A higher specific gravity indicates a more concentrated urine.
– Assessment of urinary specific gravity usually just confirms the impression gained
by visually inspecting the colour of the urine. When urine concentration needs to be
quantitated,
Urinalysis: Osmolality measurements in
plasma and urine
– Osmolality serves as general marker of tubular function. Because the
ability to concentrate the urine is highly affected by renal diseases.
– This is conveniently done by determining the osmolality, and then
comparing this to the plasma.
– If the urine osmolality is 600mosm/kg or more, tubular function is usually
regarded as intact
– When the urine osmolality does not differ greatly from plasma (urine:
plasma osmolality ratio=1), the renal tubules are not reabsorbing water
Urinalysis
…pH
- Urine is usually acidic
- Measurement of urine pH is useful in suspected drug toxicity, abuse.., or where there
is an unexplained metabolic acidosis (low serum bicarbonate or other causes…).
…Urine sediments
- Microscopic examination of sediment from freshly passed urine involves looking for
cells, casts, fat droplets
- Blood: haematuria is consistent with various possibilities ranging from malignancy
through urinary tract infection to contamination from menstruation.
- Red Cell casts could indicate glomerular disease
- Crystals
- Leucocytes in the urine suggests acute inflammation and the presence of a urinary
tract infection.
Urine volume
¾To maintain water homeostasis, the kidneys must produce urine in a volume
precisely balances water intake and production to equal water loss through extra
renal routes.
¾ Minimum urine volume is determined by the solute load to be excreted whereas
maximum urine volume is determined by the amount of excess water that must be
excreted