Abnormal composition of urine

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Abnormal composition of urine

• mirka.rovenska_at_lfmotol.cuni.cz

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Urine examination

• Physical volume, density, colour, odour,
  turbidity
• Chemical
• Examination of urine sediment

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Chemical examination of urine

• Routine
• pH
• proteins
• ketone bodies
• glucose
• blood in the urine
• nitrites
• leukocytes

• Targeted
• bilirubin, urobilinogen
• amino acid metabolites
• hormones (cortisol, sex hormones, somatotropin)

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pH of urine

• Usual range 5,5 7,0 (maximal range 4,5 7,5)
  
• Aciduria pH lt 5,4
• Cause
• diet high in meat products (sulphur and
  phosphorus are metabolized to sulphates and
  phosphates)
• compensation of metabolic / respiratory acidosis
• along with ketonuria can be predictive of
  starving/lack of saccha-rides if glucosuria is
  also present, the combination can indicate
  decompensated DM
• Alkaluria (alkalinuria) pH gt 6,5
• Cause
• lacto vegetarian diet
• urinary tract infection (bacterial urease)
• compensation of respiratory / metabolic alkalosis
  at its onset

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Proteins in urine

• Proteinuria excessive excretion of proteins
  into the urine gt150 mg/d
• Cause
• physiological physical effort
• pathological
• renal disease according to the origin
• glomerular proteinuria
• tubular proteinuria
• glomerular and tubular proteinuria
• post-renal proteinuria either bleeding into the
  urinary tract, or local secretion of
  immunoglobulin
• pre-renal proteinuria due to an increased
  plasma concentration of low-molecular proteins (?
  increased excretion into the urine)

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Ketone bodies

• Acetone, acetoacetate, ?-hydroxybutyrate
• Synthesis from acetyl-CoA, produced by
  ?-oxidation of fatty acids
• Starvation, physical effort, stress ? ? lipolysis
  and ?-oxidation of FA acetyl-CoA is used
  preferentially for the synthesis of ketone bodies

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Ketonuria

• ? level of ketone bodies in the urine (normally
  very low)
• Causes
• severe DM
• long-term starvation, marked reduction of
  saccharides in diet
• tenacious vomiting
• Test strips acetoacetate (not ?-HB!) reacts with
  nitroprusside (in the presence of alkali),
  producing purple-coloured complexes (Legal
  reaction)

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Glucose in urine

• Physiological range 0,1 1,4 mmol/l
• Test strips glucose is oxidized by glucose
  oxidase H2O2 is formed that converts a
  colourless substrate to a coloured complex
• Glucosuria (glycosuria) increased amount of
  glucose in the urine causes
• hyperglycaemia gt 10 mmol/l (DM, acute
  pancreatitis)
• renal glycosuria (glucose is abnormally excreted
  by the kidney)
• increased intestinal reabsorption

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Blood in urine

• A) hematuria (erythrocyturia) causes
• renal disease (glomerulonephritis, tumours)
• other diseases of the urinary tract
• haemorrhagic diathesis (e.g. thrombocytopathy,haem
  ophilia)
• B) hemoglobinuria excessive intravascular
  haemolysis (haemolytic anaemia, e.g. hereditary
  or after non-compatible transfusion)
• Test
• i) test strip detecting hemoglobin Hb catalyzes
  oxidation of the substrate with peroxide to a
  coloured product (pseudoperoxidase activity)
• ii) erythrocytes in the urinary sediment

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Nitrites in urine

• Nitrates in the urine can by reduced by some
  pathogenic bacteria to nitrites that can thus
  serve as indicators of the infection in the
  urinary tract
• These bacteria include E. Coli, Klebsiella,
  Salmonella, Proteus, Aerobacter, Citrobacter,
  some strains of Enterococcus, Staphylococcus,
  Pseudomonas

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Leukocytes in urine

• Increased amount of leukocytes (gt 20/µl) pyuria
  is a sign of inflammation in the urinary tract
• Test granulocyte esterase activity
• Causes
• infection of the urinary tract
• tumours

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Urobilinogen and bilirubin in urine
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Causes of icterus

• Icterus (jaundice) bilirubin in the blood
  exceeds 10 mg/l (hyperbilirubine-mia) ? bilirubin
  diffuses into tissues, which become yellow
• Pre-hepatic ?haemolysis ? overproduction of
  bilirubin that exceeds the liver's capacity for
  handling bilirubin (haemolytic anaemia, neonatal
  jaundice) ? ?unconjugated bilirubin in blood and
  urobilinogen in urine
• Hepatic liver damage (hepatitis, cirrhosis) ? ?
  capacity for handling bilirubin (uptake,
  conjugation, excretion) ? ? conj. as well as
  unconj. bilirubin in blood, urobilinogen in urine
  can ? if microobstruction is present, otherwise
  it rises (impaired enterohepatic cycle)
• Post-hepatic obstructive obstruction of the
  biliary tree (concretions, tumours) ? conj.
  birubin regurgitates into the hepatic veins and
  lymphatics ? ? conj. bilirubin in blood, no
  urobilinogen in urine

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Urobilinogen in urine

• Abnormal values 10 mg/l
• Causes
• increased degradation of hemoglobin (heavy
  bleeding, haemolytic jaundice)
• liver disease interfering with the enterohepatic
  urobilinogen cycle (hepatitis, tumours)
• Causes of the absence of urobilinogen in the
  urine
• obstruction in the biliary tree
• failure of bile production in the liver
• absence of intestinal flora

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Direct and indirect bilirubin

• Conjugated bilirubin direct bilirubin x
  unconjugated indirect
• Normally, only conjugated bilirubin can appear in
  the urine ? the level is increased when the
  plasma concentration of conjugated bilirubin
  rises
• On the other hand, only unconjugated bilirubin
  can cross BBB (neonatal jaundice ? encephalopathy
  can occur)

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Bilirubin in blood and urine

• ? conj. bilirubin in blood ? bilirubin is in the
  urine
• liver damage, microobstruction (hepatitis,
  cirrhosis)
• Dubin-Johnson Syndrome defect in the hepatic
  secretion of conjugated bilirubin into the bile
• obstructive jaundice

• ? unconj. bilirubin in blood ? bilirubin is NOT
  in the urine
• hemolytic anaemia
• neonatal jaundice accelerated haemolysis and
  immature hepatic system for bilirubin metabolism
  (low activity of UDP-glucuronosyltransferase)
• Crigler-Najjar Syndrome decreased activity of
  bilirubin UDP-glucuronosyltransferase

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Clinical parameters in 3 different causes of
jaundice
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Phenylketonuria

• Defect in phenylalanine hydroxylase ? Phe cannot
  be converted to Tyr, accumulates, and is
  metabolized to phenylacetate, phenyllactate, and
  phenylacetylglutamine. Urinary level of
  phenylpyruvate is elevated.
• If left untreated, it leads to mental retardation
• Prevention low-Phe diet
• Screening plasma Phe ? genetic test

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Urolithiasis

• Urinary calculi (concretions) are formed in the
  urinary tract
• 80-90 renal concretions made of calcium salts
  (oxalate, phosphate)
• Factors that predispose to calculi formation
• highly concentrated urine (e.g. dehydration)
• increased urinary excretion of
• phosphates, calcium (e.g. increased breakdown of
  bones)
• oxalates
• uric acid (hyperuricosuria)
• cystine (cystinuria may be due to impaired
  resorption in the kidney)
• urine alkalization (in case of excretion of Ca2,
  phosphates, oxalates)
• urine acidification (pHlt5,5) in case of excretion
  of uric acid

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Hyperuricosuria

• Excretion of gt700-800 mg of uric acid into the
  urine/24h serum uric acid rises, too
  (hyperuricemia)
• Causes
• gout
• cancer, especially if treated with cytostatic
  drugs or radiation therapy (increased cell death
  and thus also increased NA degradation)
• renal disease
• high intake of purines in the diet
• dehydration

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Revision purinecatabolism
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Gout

• Enzyme defect in PRPP-synthase or HGPRTase ?
  overproduction of purines, and thereby also of
  uric acid ? crystallization of urates in soft
  tissues and joints ? inflammation (arthritis).
• Therapy allopurinol converted by xanthine
  oxidase to alloxanthine that inhibits the enzyme
  ? ? synthesis of uric acid, more soluble xanthine
  and hypoxanthine are excreted

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PRPPS and HGPRT in purine metabolism
(first step)
(salvage pathway)
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Urine sediment

• Urine sediment
• substances discharged from organs
• crystals (oxalates, urates, phosphates)
• Examination detects the presence of
• blood erythrocyturia (gt5 ery/µl) causes
  impaired permeability of glomerular membrane,
  infection, urolithiasis
• leukocytes pyuria (gt10 leuko/µl) causes
  infection of the urinary tract
• casts formed in the kidney (the matrix is made
  of the protein produced by tubules, other
  components plasma proteins, lipid droplets) ?
  casts can indicate a renal disease (different
  types of casts indicate different types of
  damage)
• epithelial cells
• microorganisms

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macrophage
hyaline cast
erythrocytes
agranulocyte bbacteria
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hyaline cast
cuboidal epithelial cell
atubular epithelial cell (inside a cast) b2
cells of a transitional epithelium
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granular cast
waxy cast (with the cells of tubularepithelium
inside)
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fatty cast
granulocyte
yeast
yeast