L13: urine as an indicator of disease

Question 1

Advantages of urinalysis

Answer 1

• non-invasive diagnosis
• easily obtained - feasible in local GP practice
• normal composition is mostly known
• for prerenal or renal diseases
• changes in levels of what should be present including material that normally occurs only at low basal levels.

Question 2

Normal levels of urinary excretion

Answer 2

95% water

4:21 for rest of compounds

Question 3

How are urine samples collected?

Answer 3

• in clean/sterile containers
• sometimes preservatives need to be used but this can affect analysis
• random samples - clean catch midstream specimen timing of sampling depends on test required
• test as soon as possible since bacteria will multiply, glucose levels drop, pH drops, crystals may form or disperse
• 24h specimen - empty bladder first

Question 4

Volume of urine in 24hrs

Answer 4

Depends on body size, diet, and fluid intake

Normally 0.8-2.0L

Question 5

Appearance of urine when things go wrong

Answer 5

• normal urine: pale yellow and clear
• concentrated urine (e.g. dehydration): dark
• frothy/foamy urine - proteinuria, conjugated bilirubin
• fat globules floating around
• cloudy urine - due to excess cellular material, elevated protein output, high lipids, WBCs, high milk intake due to high phosphates
• red urine: blood. Blood in urethra (early), throughout (bladder), end (prostrate)
• red urine: pseudohematuria: free Hb, myoglobin, porphyria’s, drugs (laxatives, desferrioxamine, rifampicin, anti-inflammatories).
• red/brown: conjugated bilirubin
• black: melanin (disseminated melanoma)
• other hues: foods, drugs, supplements
• if urine darks on standing, e.g. caused by alkaptonuria and porphyria

Question 6

Microscopic examination of urine

Answer 6

Centrifuge a mixed sample of urine and examine the sediment

Question 7

What is the sediment in urine examined for?

Answer 7

1. Bacteria - confirm dipstick tests for nitrite production then couture to quantitate
2. Cells - more than 10 white cells per ml can indicate kidney damage, red cell can indicate kidney damage
3. Casts (cylindrical bodies) - e.g., hyaline or fine granular. Normal finding especially post exercise and is not proteinuria. 1 red cell cast is always pathological.
4. Crystals - problem is they aggregate to form stones. Most common is oxalate crystals. Cystine, amorphous crystals, triple phosphate etc. Limited clinical value.

Question 8

What is the pH range for urine?

Answer 8

4.5-8

Question 9

What can too much meat in the diet do to the urine?

Answer 9

Make it more acidic

Question 10

What can too much citrus fruit and veg in the diet do to the urine?

Answer 10

Make it more alkaline

Question 11

What diseases can cause pH extremes - acidic?

Answer 11

Uncontrolled diabetes, starvation, respiratory disorders.

Question 12

What diseases can cause pH extremes - alkaline?

Answer 12

Urinary tract obstruction, some respiratory disorders - hyperventila

Question 13

What acidic substances in diet can cause risk of stones?

Answer 13

Uric acid, cystine

Question 14

What alkaline substances in diet can cause risk of stones?

Answer 14

Ca2+, MgPO4, CaCO3

Question 15

Why is creatinine clearance (CC) a good GFR indicator?

Answer 15

In muscles, phosphocreatine acts as a major energy reserve.
1-2% of the muscle pool spontaneously degrades to creatinine by the activity of creatine kinase, daily at a constant rate in good health and glomerular filtration with minimal tubular reabsorption/secretion.

Question 16

When is CC a less useful indicator of GFR?

Answer 16

GFR might increase if there is an excessive meat diet.

GFR might decrease during wasting disease, malnutrition (or strict vegetarianism), or poor renal blood flow or function.

Question 17

Pre-renal disorders

Answer 17

• Kidney function is normal

Overspill due to:
• increased solution filtration due to increased production in the body
• abnormal metabolite (no suitable transporter)

Decreased solute filtration
• decreased production in the body
• decreased delivery (e.g. cardiac failure, haemorrhage, burns)

Question 18

Renal disorders

Answer 18

• Kidney is abnormal

Glomerular malfunction:
• infection, autoimmune disease, inflammation
• allows leakage of proteins

Tubular malfunction:
• infection, autoimmune disease, inflammation, necrosis, drugs, toxins
• causes defective reabsorption e.g., of glucose
• causes defective secretion e.g., of H+

Question 19

What two kinds of disorder can cause abnormal solute excretion?

Answer 19

Pre-renal and renal

Question 20

What factors increase the output of urea?

Answer 20

• excess protein intake (more deaminated amino acids) - surplus excreted
• factors that trigger greater protein catabolism:
  • protein energy malnutrition (negative nitrogen balance degrades body protein to use the ketogenic amino acids for energy)
  • uncontrolled type 1 diabetes
  • infections, burns, wasting diseases, trauma inclined surgery or a broken limb/GI bleeding.

Question 21

Factors decreasing excretion of urea?

Answer 21

• low protein diet, severe liver disease/genetic defects (liver struggles to perform the urea cycle)
• glomerular nephritis, acute tubular necrosis
• poor renal blood supply or renal obstruction - stones, tumour

Outcomes: hyperammonaemia, NH4+ crosses the blood brain barrier (BBB). Causes lethargy, irritability and finally coma.

Question 22

Normal amount of glucose excreted in the urine

Answer 22

Excrete <0.2% of the glucose normally

Question 23

Normal amount of glucose excreted in the urine

Answer 23

Excrete <0.2% of the glucose normally filtered by the glomerulus (0.03-0.3 g/day)

Question 24

How to test for glucose in the urine?

Answer 24

Reagent strip (glucose oxidase)
Bleaching effect occurs of the dye to give a visible colour change

Question 25

What happens if glucose is elevated in the urine?

Answer 25

Metabolic hyperglycaemia (high in the urine because it is high in the blood)
E.g., due to diabetes mellitus type 1. Might be due to anxiety or stress. Might be in response to phaeochromocytoma (tumour of adrenal medulla) due to excess of adrenaline.

2% of pop have a reduced renal threshold. So output of glucose is always above the usual range. In pregnancy or renal glycosuria (genetic).

Tubular malfunction: generalised tubular dysfunction that is secondary to other damage e.g. heavy metal poisoning, drugs, Fanconi syndrome = defective tubular re absorption of most amino acids, glucose, urate, phosphate etc.

Question 26

Other sugars abnormally excreted in the urine

Answer 26

Galactose - galactose (spill over of galactose -1-phosphate. Positive test for reducing substances.
Lactose - lactation; primary lactase deficiency, coeliac disease
Fructose - fructose intolerance, essential fructosuria
Pentoses- essential pentosuria

Question 27

Ketones in the urine

Answer 27

Elevated ketones in uncontrolled diabetes type 1 and in starvation

Question 28

Amino acidurias

Answer 28

Elevated amino acid content in the urine due to:

• generalised tubular damage
• specific transporter defects (cystinuria, Hartnup’s disease)
• raised plasma amino acids (PKU, cystinosis)

Question 29

Conjugated bilirubin in the urine

Answer 29

Presence is reflective of liver damage or obstructed bile ducts

Question 30

Proteinuria

Answer 30

Elevated output of protein in a persons urine. Proteinuria >200mg/24hrs of proteins

Pre-renal problem: overflow due to presence in plasma of a high concentration of a low molecular weight protein, which is filtered in a quantity exceeding tubular reabsorptive capacity, e.g. Bence Jones protein.

Renal problem: glomerular due to increased glomerular permeability; tubular due to impaired or saturate reabsorption of protein filtered by normal glomeruli; secreted due to secretion by kidneys or epithelium of urinary tract.

Question 31

How does protein size in proteinuria determine whether it is a pre-renal or renal problem?

Answer 31

Low molecular weight - kidney is typically normal, e.g., myoglobin
Medium to high molecular weight - a damaged kidney, e.g., albumin

Question 32

Phenylketonuria

Answer 32

• results in excretion of phenylpyruvate
• Phe - by protein synthesis it is converted by Phe hydroxyl add to tyrosine.
• genetic deficiency of Phe hydroxyl are results in classical PKU.
• Phe acetate overspills into urine
• early diagnosis is vital to minimise neurological damage