Transcript Biochemical Tests of Renal Function

Renal Functions
• Renal Functions
– Excretion
– Homeostasis
– Endocrine
• Biochemical Tests of Renal Function
– Creatinine
– Urea
– Uric Acid
• Urinanalysis
An Introduction to the Urinary System
1. Excretion &
Elimination:
–
removal of organic
wastes and waste
products from body
fluids
2. Homeostatic
regulation:
–
of blood plasma
volume and solute
concentration
3. Enocrine function:
-
Hormones
Homeostatic Functions of Urinary System
1.
Regulate blood volume and blood pressure:
–
by adjusting volume of water lost in urine
–
releasing erythropoietin and renin
2.
Regulate plasma ion concentrations:
–
sodium, potassium, and chloride ions (by controlling quantities lost in urine).
Potassium and bicarbonate, and about 75% of sodium, is reabsorbed
isotonically here by energy dependent mechanisms after filtration.
–
calcium ion levels
3.
Help stabilize blood pH:
–
by controlling loss of hydrogen ions and bicarbonate ions in urine
4.
Conserve valuable nutrients:
–
by preventing excretion while excreting organic waste products. Under
normal circumstances, all the glucose, amino acids are reabsorbed
5.
Assist liver to detoxify poisons
The excretory function
 Mechanism for excretion of excess electrolytes, nitrogenous wastes
and organic acids are similar.
 The maximal excretory rate is limited or established by their plasma
concentrations and the rate of their filtration through the glomeruli
 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.
 The primary objective in evaluation of renal excretory function is to
detect quantitatively the normal capacities or the improvement of
impaired ones.
The endocrine function
 Kidneys have primary endocrine function since they produce hormones
 In addition, the kidneys are site of degradation for hormones such as insulin and
aldosterone.
 In their primary endocrine function, the kidneys produce erythropoietin, renin and
prostaglandin.
 Erythropoietin is secreted in response to a lowered oxygen content in the blood. It acts on
bone marrow, stimulating the production of red blood cells.
 Renin the primary stimuli for renin release include reduction of renal perfusion pressure
and hyponatremia. Renin release is also influenced by angiotension II and ADH.
 It is a key stimulus of aldosterone release. The effect of aldosterone is predominantly on the
distal tubular network, effecting an increase in sodium reabsorption in exchange for
potassium.
 The kidneys are primarily responsible for producing vitamin D3 from
dihydroxycholecalciferol.
Each kidney consists of one million functional units:
Nephrone
Urine Formation
Glomerular Filtration
The first step in the production of urine is called glomerular
filtration.
Filtration: the forcing of fluids and dissolved substances through
a membrane by pressure occurs in the renal corpuscle of the
kidneys across the endothelial capsular membrane (Bowman's)
capsule.
The resulting fluid is called the filtrate.
Filtration is a passive process. The total filtration rate of the
kidneys is mainly determined by the difference between the blood
pressure in the glomerular capillaries and the hydrostatic pressure
in the lumen of the nephron
The amount of filtrate that flows out of all the renal corpuscles of both kidneys every minute
is called the glomerular filtration rate (GFR).
In the normal adult, this rate is about 125 ml/min; about 180 liters/Day
Filtrate produced at renal corpuscle has the same composition as blood plasma: without
plasma proteins
This is because the endothelium provide a barrier to red and white blood cells and the
basement membrane,
It is permeable to water and low molecular weight substances, and impermeable to
macromolecules.
This impermeability is related to both molecular size and electrical charge. Proteins with
molecular weights lower than that of albumin (68,000 daltons) are filterable;
Negatively charged molecules are less easily filtered than those bearing a positive charge
(Why).
The filtrate consists of all the materials present in the blood except for the formed elements
and most proteins, which are too large to pass through the endothelial-capsular barrier.
Water, glucose, vitamins, amino acids, small proteins, nitrogenous wastes, and ions pass into
the glomerular capsule.
In the tubules, the solute composition of the ultrafiltrate is altered by the processes of
reabsorption and secretion, so that the urine excreted may have a very different composition
from that of the original filtered fluid.
Tubular reabsorption
 As the filtrate passes through the renal tubules, about 99 percent of it is reabsorbed
into the blood.
 Only about 1 percent of the filtrate actually leaves the body (about 1.5 liters a
day).
 Materials that are reabsorbed include water, glucose, amino acids, urea, and ions
such as Na+, K+, Ca2+ , Cl-, HC03 -, and HPO3- .
 Tubular reabsorption allows the body to retain most of its nutrients.
 Wastes such as urea are only partially reabsorbed.
 Reabsorption is carried out through both passive and active transport mechanisms.
 Glucose and amino acids are reabsorbed by an active process co-transpotred with
(Na+) ions.
 Normally, all the glucose filtered by the glomeruli (125 mg/l00 ml of filtrate/min)
is reabsorbed by the tubules.
Water reabsorption is driven by sodium transport.
As Na + ions are transported from the proximal convoluted tubules into the blood, the osmotic
pressure of the blood becomes higher than that of the filtrate. Water follows the Na + ions into the
blood in order to reestablish the osmotic equilibrium  80 percent of the water is reabsorbed by
this method from the proximal convoluted tubule and it is called obligatory water reabsorption.
The descending limb of the loop of the nephron is passively permeable to the passage of water
while ascending part chloride and more sodium without water are reabsorbed, generating a dilute
urine. In the distal tubule secretion is the prominent activity.
Passage of most of the remaining water in the filtrate can be regulated.
The permeability of the cells of the distal and collecting tubules is controlled by the antidiuretic
hormone (ADH), produced by the hypothalamus and released into the blood by the pituitary
gland
When osmotic pressure is increased  osmoreceptors in the hypothalamus detect the stimulus
and secrete more ADH  increases the permeability of the plasma membranes of the distal
tubule and collecting tubule cells  more water molecules pass into the cells and then into
blood.
Tests for renal function
 The kidneys’ excretory, regulatory and endocrine roles show complex interactions.
 The composition of blood and urine reflects not only functional disorders of the
nephron but also various systemic disorders.
To evaluate kidney status in renal disease the following are tested:
1. The nephron functions of glomerular filtration.
2. The secretary capacity for particular endogenous and exogenous compounds.
3. The kidney’s re-absorptive capacity for water and electrolytes as manifested by the
urine-concentrating ability of the kidneys.
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
– Glucose
– Protein
– Urinary sediments
Biochemical Tests of renal function
 Diseases affecting the kidneys can selectively damage glomerular or
tubular function
 In acute and chronic renal failure, there is effectively a loss of
function of whole nephrons
 Filtration is essential to the formation of urine  tests of glomerular
function are almost always required in the investigation and
management of any patient with renal disease.
The most frequently used tests are those that assess either the GFR
or the integrity of the glomerular filtration barrier.
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.
 Clearance is defined as the (hypothetical) quantity of blood or plasma completely cleared of a
substance per unit of time.
 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.
 Inulin (a plant polysaccharide) can be used.
The 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.
Measurement of inulin clearance requires the infusion of inulin into the blood and is not suitable for
routine clinical use
The most frequently used clearance test is based on the measurement of creatinine.
V is not urine volume, it is urine flow rate
(Uinulin  V)
GFR =
Pinulin
Creatine and Creatinine
Creatine is synthesized in the kidneys
and liver
 It is then transported in blood to other
organs such as muscle and brain, where
it is phosphorylated to phosphocreatine,
a high-energy compound.
 Interconversion of phosphocreatine
and creatine is a particular feature of
metabolic processes of muscle
contraction
1 to 2% of muscle creatine spontaneously converts to creatinine daily and released into body
fluids at a constant rate.
Endogenous creatinine produced is proportional to muscle mass, it is a function of total
muscle mass the production varies with age and sex
 Dietary fluctuations of creatinine intake cause only minor variation in daily creatinine
excretion of the same person.
Creatinine clearance and clinical utility
 Creatinine released into body fluids at a constant rate and its plasma levels
maintained within narrow limits  Creatinine clearance may be measured as an
indicator of GFR.
 The most frequently used clearance test is based on the measurement of
creatinine.
 Small quantity of creatinine is reabsorbed by the tubules and other quantities
are actively secreted by the renal tubules  So creatinine clearance is
approximately 7% greater than inulin clearance.
The 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
An estimate of the GFR can be calculated from the creatinine content of a 24-hour
urine collection, and the plasma concentration within this period.
The 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
The 'clearance' of creatinine from plasma is directly related to the
GFR if:
The urine volume is collected accurately
There are no ketones or heavy proteinuria present to interfere
with the creatinine determination.
It 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.
Plasma creatinine
Plasma creatinine concentration is inversely related to the GFR
 The reference range for plasma creatinine in the adult population is 60-120
μmol/L,
But GFR can decrease by 50% before plasma creatinine concentration rises
beyond the normal range this means that a normal plasma creatinine does
not necessarily imply normal renal function,
A Raised creatinine usually indicates impaired renal function
Changes in plasma creatinine concentration can occur, independently of
renal function, due to changes in muscle mass.
 Decrease can occur as a result of starvation and in wasting diseases,
immediately after surgery.
Serum Creatinine (µmol/L)
Relationship between Serum Creatinine
Concentration and Creatinine Clearance
800
700
600
500
400
300
200
100
0
0
25
50
75
Creatinine Clearance (ml/min)
100
125
Use of Formulae to Predict Clearance
• Formulae have been derived to predict Creatinine
Clearance (CC) from Plasma creatinine.
• Plasma creatinine derived from muscle mass which is
related to body mass, age, sex.
• Cockcroft & Gault Formula
CC = k[(140-Age) x weight(Kg))] / Creatinine (µmol/L)
k = 1.224 for males & 1.04 for females
• Modifications required for children & obese subjects
• Can be modified to use Surface area
Cystatin-C
•
•
•
•
•
Cysteine proteinase inhibitor C (MW13000)
Small size = freely filtered at glomerulus
Constant production rate by all nucleated cells
No known extra-renal excretion routes
Not influenced by muscle mass, diet or subjects sex
Measurement of nonprotein nitrogen-containing 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
 Urea is the major nitrogen-containing metabolic product of protein
catabolism in humans,
 Its elimination in the urine represents the major route for nitrogen
excretion.
 More than 90% of urea is excreted through the kidneys, with losses
through the GIT and skin
 Urea is filtered freely by the glomeruli
 But it is moves passively out of the renal tubule and into the
interstitium, ultimately to re-enter plasma
 Plasma urea concentration is often used as an index of renal glomerular
function
 Urea production is increased by a high protein intake and it is decreased
in patients with a low protein intake or in patients with liver disease.
Plasma Urea
 Many renal diseases with various glomerular, tubular, interstitial or vascular damage can
cause an increase in plasma urea concentration.
Measurement of plasma creatinine provides a more accurate assessment than urea
because there are many factors that affect urea level.
Nonrenal factors can affect the urea level (normal adults is level 5-39 mg/dl) like:
Mild dehydration,
high protein diet,
increased protein catabolism, muscle wasting as in starvation,
reabsorption of blood proteins after a GIT haemorrhage,
treatment with cortisol or its synthetic analogous
decreased perfusion of the kidneys may cause azotemia (increased blood urea) that is
called prerenal azotemia. Impaired perfusion may be due to decreased cardiac output
or shock secondary to blood loss or other causes.
The key to identifying the azotemia as prerenal is the increase of plasma urea
without parallel increase of plasma creatinine.
Postrenal azotemia is caused by conditions that obstruct urinary outflow through the
ureters, bladder or urethra.
 With obstruction, both plasma urea and creatinine increase, but there is greater rise
of urea than of creatinine because the obstruction of urine flow  backpressure on
the tubule and back diffusion of urea into blood from the tubule.
Clinicians frequently calculate a convenient relationship, the urea
nitrogen/creatinine ratio:
Serum urea nitrogen (mg / dl)
Serum creatinine (mg / dl)
For a normal person on a normal diet, the reference interval for the ratio
ranges between 12 and 20.
Factors affecting the ratio of plasma urea to creatinine are:
Causes of abnormal plasma urea to creatinine ratio
Urea tubular reabsorption increases at low rates of urine flow (e.g. in fluid depletion) and this can
cause increased plasma urea concentration even when renal function is normal.
Reference intervals
The 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.
Urea (in mmol/L) = BUN (in mg/dL of nitrogen) / 2.8
Postrenal azotemia is caused by conditions that obstruct urinary outflow through the
ureters, bladder or urethra.
 With obstruction, both plasma urea and creatinine increase, but there is greater rise
of urea than of creatinine because the obstruction of urine flow  backpressure on
the tubule and back diffusion of urea into blood from the tubule.
Urea tubular reabsorption increases at low rates of urine flow (e.g. in fluid
depletion) and this can cause increased plasma urea concentration even when renal
function is normal.
Reference intervals
The 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.
Uric acid
 In human, uric acid is the major product of the catabolism of the purine
nucleosides, adenosine and guanosine.
 Purines are derived from catabolism of dietary nucleic acid (nucleated cells,
like meat) and from degradation of endogenous nucleic acids.
 Overproduction of uric acid may result from increased synthesis of purine
precursors.
 In humans, approximately 75% of uric acid excreted is lost in the urine;
most of the reminder is secreted into the GIT
Uric acid
Renal handling of uric acid is complex and involves four sequential steps:
Glomerular filtration of virtually all the uric acid in capillary plasma entering
the glomerulus.
Reabsorption in the proximal convoluted tubule of about 98 to 100% of
filtered uric acid.
Subsequent secretion of uric acid into the lumen of the distal portion of the
proximal tubule.
Further reabsorption in the distal tubule.
 The net urinary excretion of uric acid is 6 to 12% of the amount filtered.
 The pka of uric acid is 5.57; above this pH, uric acid exists mainly as urate ion,
which is more soluble than uric acid. At a urine pH below 5.75, uric acid is the
predominant form.
Clinical Significance of Uric acid
 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.
 Gout occurs when monosodium urate precipitates from supersaturated body fluids;
 Gouty arthritis may be associated with urate crystals in joint fluid as well as with deposits of
crystals (tophi) in tissues surrounding the joint. The deposits may occur in other soft tissues
as well, and wherever they occur they elicit an intense inflammatory response.
Renal disease associated with hyperuricemia may take one or more of several forms:
 Gouty nephropathy with urate deposition in renal parenchyma.
 Acute intratubular deposition of urate crystals.
 The formation of crystal aggregates in the urinary tract results in kidney stones: about 20 %
patients with gout also has urinary tract urate stones.
Plasma β2-microglobulin
β2-microglobulin is a small peptide (molecular weight 11.8 kDa),
It is present on the surface of most cells and in low concentrations in the
plasma.
It is completely filtered by the glomeruli and is reabsorbed and catabolized
by proximal tubular cells.
The plasma concentration of β2-microglobulin is a good index of GFR in
normal people, being unaffected by diet or muscle mass.
It is increased in certain malignancies and inflammatory diseases.
Since it is normally reabsorbed and catabolized in the tubules, measurement
of β2-microglobulin excretion provides a sensitive method of assessing
tubular integrity.
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 proteinuria
– Glycouria
– Aminoaciduria
• Urinalysis
– Appearance
– Specific gravity and osmolality
– pH
– Glucose
– Protein
– Urinary sediments
Renal tubular function tests
•
The glomeruli provide an efficient filtration mechanism for ridding the body of
waste products and toxic substances
•
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
180 liters of fluid pass into the glomerular filtrate each day, and more than 99% of
this is recovered
•
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
 Injury of glomerular integrity results in the filtration of large molecules which are normally
retained and is marked as proteinuria: the appearance of abnormal quantity of protein in the
urine.
Proteinuria 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.
Measurement of individual proteins such as β2-microglobulin have been used in the early
diagnosis of tubular integrity.
With severe glomerular damage, red blood cells are detectable in the urine (haematuria), the red
cells often have an abnormal morphology in glomerular disease.
 Haematuria can occur as a result of lesions anywhere in the urinary tract,
Proteinuria
The glomerular basement membrane does not usually allow passage of
albumin and large proteins. A small amount of albumin, usually less than 25
mg/24 hours, is found in urine.
When larger amounts, in excess of 250 mg/24 hours, are detected,
significant damage to the glomerular membrane has occurred.
Quantitative urine protein measurements should always be made on
complete 24-hour urine collections.
Albumin excretion in the range 25-300 mg/24 hours is termed
microalbuminuria
Proteinuria
– Normal < 200 mg/24h.
– Causes: • overflow (raised plasma Low MW Proteins, Bence Jones, myoglobin)
• glomerular leak
• decreased tubular reabsorption of protein (RBP, Albumin)
• protein renal origin
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 proteinuria
– Glycouria
– Aminoaciduria
• Urinalysis
– Appearance
– Specific gravity and osmolality
– pH
– Glucose
– Protein
– Urinary sediments
Urinalysis
Urinalysis is important in screening for disease is routine test for every patient, and not just
for the investigation of renal diseases
Urinalysis comprises a range of analyses that are usually performed at the point of care rather
than in a central laboratory.
Urinalysis is one of the commonest biochemical tests performed outside the laboratory.
 Examination of a
patient's urine should not
be restricted to
biochemical tests.
Urinalysis using disposable strips
Biochemical testing of urine involves the use of commercially available disposable strips
When the strip is manually immersed in the urine specimen, the reagents react with a
specific component of urine in such a way that to form color
 Colour change produced is proportional to the concentration of the component being tested
for.
To test a urine sample:
fresh urine is collected into a clean dry container
the sample is not centrifuged
 the disposable strip is briefly immersed in the urine specimen;
The colour of the test areas are compared with those provided on a colour chart
Urinalysis
•
•
Fresh sample = Valid sample.
 fresh urine is collected into a clean dry container
 the sample is not centrifuged
Appearance: – Blood
– Colour (haemoglobin, myoglobin,)
– Turbidity (infection, nephrotic syndrome)
Causes of colouration in
urine
Blue Green
Pink-OrangeRed
Red-brown-black
Methylene Blue Haemoglobin
Haemoglobin
Pseudomonas Myoglobin
Myoglobin
Riboflavin
Phenolpthalein
Red blood cells
Porphyrins
Homogentisic Acid
Rifampicin
L -DOPA
Melanin
Methyldopa
•
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 600mmol/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…).
– Many tightly regulated mechanisms affect the blood hydrogen ion
concentration normal H+ excretion via renal tubules by
– Distribution of one of these mechanisms  an acidosis (so-called renal tubular
acidosis or RTA).
– Measurement of urine pH is used to screen for RTA in unexplained metabolic
acidosis.
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.
Proteinuria
The glomerular basement membrane does not usually allow passage of albumin and
large proteins. A small amount of albumin, usually less than 25 mg/24 hours, is found
in urine.
When larger amounts, in excess of 250 mg/24 hours, are detected, significant
damage to the glomerular membrane has occurred.
Red blood cell cast in urine
White blood cell cast in urine
Urinary casts. (A)
Hyaline cast (200 X);
(B) erythrocyte cast (100
X); (C) leukocyte cast
(100 X); (D) granular
cast (100 X)
Urinary crystals. (A) Calcium oxalate crystals (arrows; 100
X); (B) uric acid crystals (100 X); (C) triple phosphate
crystals with amorphous phosphates (400 X); (D) cystine
crystals (100 X)
Urine volume
-
Water homeostasis is determined by several interrelated processes:
1. Water intake and water formed through oxidation of food stuffs.
2. Extra-renal water loss: insensible water loss the via faeces, and sweating.
3. A solute load to be excreted that is derived from ingested minerals and
nitrogenous substances.
4. The ability of the kidneys to produce concentrated or dilute urine.
5. Other factors such as vomiting and diarrhoea become important in various
disease states;
loss of ability to produce concentrated urine is a feature of virtually all types of
chronic renal diseases.
Urine volume
To 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.
 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
Causes of polyurea
Increased osmotic load, e.g due to glucose
Increased water ingestion
Diabetes insipidus: - Failure of ADH production results in marked polyuria (diabetes
insipidus), which stimulates thirst and greatly increases water intake
Nephrogenic diabetes insipidus: The kidneys’ lack of response to ADH has similar
effect ( failure of the tubules to respond to Vassopressin (ADH))
Bilirubin
•
Bilirubin exists in the blood in two forms, conjugated water soluble and unconjugated.
•
Bilirubinuria indictaes the presence of conjugated bilirubin in urine.
•
This is always pathological.
•
Conjugated bilirubin is normally excreted through the biliary tree into the gut mechanical
obstruction  results in high levels of conjugated bilirubin in the systemic circulation
excreted into the urine.
Urobilinogen
• In the gut, conjugated bilirubin is broken down by bacteria to urobilinogen, or
stercobilinogen.
• Urobilinogen is found in the systemic circulation and is often detectable in the urine
of normal subjects. Thus the finding of urobilinogen in urine is of less diagnostic
significance than bilirubin.
• High levels are found in any condition where bilirubin turnover is increased, e.g.
haemolysis, or where its enterohepatic circulation is interrupted by, e.g. liver
damage.
Ketones
• Ketones are the products of fatty acid breakdown.
• Their presence usually indicates that the body is using fat to provide energy rather
than storing it for later use.
• This can occur in uncontrolled diabetes, where glucose is unable to enter cells
(diabetic ketoacidosis), in alcoholism (alcoholic ketoacidosis), or in association with
prolonged fasting or vomiting.
Nitrite
• This test depends on the conversion of nitrate (from the diet) to nitrite by the
action in the urine of bacteria that contain the necessary reductase
• A positive result points towards a urinary tract infection.