Clinical Biochemistry 2

Clinical Biochemistry 2

1. Urea

   • Excretion and reabsorption is affected by the glomerular filtration/urine flow
   • Derived from ammonia
   • Excreted via glomeruli and intestines
   • Is reabsorbed in the tubules
   • Excretion and reabsorption are affected by urine flow
   • BUN vs urea
     • BUN = blood urea nitrogen
     • Concentration of the nitrogen component of urea
     • BUN + urea won’t have the same reference intervals
       • BUN value is lower than urea value
       • Factor x2.14 for conversion is available
     • UK – urea usually measured rather than BUN
       • BUN is rarely used
   • Uraemia
     • In response to increased urea
     • Specific clinical syndrome (vomiting, anorexia, ulceration)
     • Develops when high levels of toxic substances (ie urea, creatinine) are present in the blood
     • Reduced renal excretion
   • Causes of low serum urea
     • Decreased Liver Function
       • Portosystemic shunts
       • Severe Hepatic Insufficiency
     • Increased Excretion
       • •Extreme PU/PD
       • Overhydration
     • Low protein diet
     • Young animals
       • Increased fluid intake, increased urine output, high anabolic state

2. Creatinine

   • Excretion and reabsorption is not affected by the glomerular filtration rate/urine flow
   • Muscle mass will affect the creatinine value
   • Horses
     • ↓ creatinine = ↓ BCS
     • Normal creatinine = normal BCS
     • Creatinine ∝ BCS ∝ Muscle mass
   • Derived from creatinine (energy store in muscle)
   • Excreted via glomeruli
   • Not reabsorbed in the tubules
   • Azotaemia
     • Increased serum urea concentration – varies based on urine flow, so tend to use ratio
     • Increased serum urea and creatinine concentration – gives a better picture
   • Causes of low serum creatinine
     • Not clinically significant
     • Most commonly seen in animals with little muscle mass

3. Urinalysis

   • Lab evaluation of renal function
     • Urinalysis
     • Serum biochemistry
       • Evaluation of glomerular function: crude assessment
         • Urea
         • Creatinine
         • Phosphate
         • (+ calcium)
   • Normal renal function
     • 30% of plasma is freely filtered in the glomerulus – specific gravity here is 1.010
     • H+ is secreted depending on pH balance in the proximal tubule – specific gravity here is 1.050
     • By distal tubule – urine specific gravity is 1.007
     • Rate of flow affects the rate of urea absorption
   • Measurement of GFR
     • Gold standard for testing of kidney function
       • Significantly more expensive, not always feasible as can be lengthy
     • Methods vary
       • Iohexol with blood sampling at three time points more practical than many previous methods
         • Inject, then take serial blood samples to determine filtration rate
         • ~ £150 to measure 3 tests
         • Add in the cost of the drug, the vet’s time – is a very expensive procedure, and inaccessible for many owners as such
         • Costs may drop with time, resulting in the test becoming more accessible
       • Historically, radioisotopes have been used (not ideal)
   • Dogs / Cats
     • Serum Urea & Creatinine have poor sensitivity for the diagnosis of renal disease
       • Azotaemia develops only when > 65-70% of renal function is lost
       • Early in the course of renal failure, substantial loss of renal function cause mild increase in azotaemia
       • Later in the course of disease, large increases in azotaemia are caused only by a small deterioration of renal function
   • Horses/ruminants
     • Severe renal disease can have normal serum urea concentration because they excrete most of urea via the gut (very little via kidneys)
     • Urea may also vary with diet
     • Serum Creatinine more sensitive indicator than urea
   • SDMA-symmetric dimethylarginine
     • Currently being trialed as a marker
     • Released into circulation following protein degradation
     • Excreted by the kidneys
     • May begin to increase following 40% loss of renal function
     • Less influenced by muscle mass and detects loss of renal function sooner
     • Need to wait before an idea of usefulness in day to day clinical cases is determined
   • Effects on other tests
     • Enzymes amylase and lipase are excreted via the kidney
       • Pancreatic damage, GI disease will also cause an increase in these enzymes
       • Decreased GFR causes increases in the enzymes 2-3x
       • Not really used any more – have other, better markers to use
   • Urine biochemistry
     • Ratios
       • Urine may be variably diluted
       • Materials excreted need to be ‘normalised’
       • Creatinine is freely filtered and minimally absorbed
         • Therefore should be relatively constant in terms of how much has come through – look at this ratio
         • Many test values are compared to creatinine in a ratio
           • Other tests may be compared to concurrent blood levels
     • ‘Numbers’ and absolute values cannot be taken into comparison, as you need to take into account how concentrated the urine is
       • Protein: creatinine ratio is often used to determine loss of kidney function
     • Urine protein: creatinine ratio UPCr
     • GGT: creatinine
     • Fractional electrolyte excretion – not used too much

4. Azotaemia

   • Pre-renal
     • Decreased renal perfusion
       • Hypovolaemia, dehydration, cardiovascular dz
       • Serum urea is increased
       • Serum creatinine is not increased OR slightly increased
       • Urine specific gravity is high (>1.050)
     • High protein diet
       • Only serum urea is increased
       • Serum creatinine is normal
     • Haemorrhage into GI tract
       • Serum creatinine is normal
       • Only serum urea is increased
     • Usually get mild azotaemia, don’t expect SG to get too big
       • >1.030 in dog – working kidney, need more fluid volume into patient
   • Renal
     • Renal disease - 1° kidney disease
     • ONLY evident when more than 60-75% of nephrons are destroyed
     • BOTH serum urea and serum creatinine are increased
       • Urine specific gravity is Low or normal
       • Most species <1.025
       • Cats <1.035
     • Isosthenuria – kidney cannot concentrate urine
     • Acute/chronic – can have kidney disease before azotaemia is seen – quite extensive damage to the kidney before clinical signs are observed
     • Will depend on hydration status of the animal when you look at it
   • Post-renal
     • Urinary tract obstruction
       • Urethra
     • Urinary tract rupture
       • Urethra
       • Bladder
     • BOTH serum urea and creatinine are increased
     • Urine SG : variable – depending on mechanism
       • May not be able to get any urine at all – in the instance of a ruptured bladder, the urine would be going straight into the abdominal cavity
   • Always interpret with urine specific gravity
     • Level of solutes – how concentrated is the urine?
     • Urine SG
       • Isosthenuria: 1.007 – 1.015
         • Neither concentrated nor diluted urine as it passed through kidney
       • Hyposthenuria: < 1.007
         • Excess glucose, hypocalcaemia = dilution of urine
       • Hypersthenuria: usually 1.015/ 1.020 – 1.060 (1.025+ in farm animals)
         • Urine of normal/healthy animals
         • Water has been removed from the urine – normal function

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