Case 1

1. Case 1 Andy and Rick

2. Trigger 1 • Vincent, 32 y.o. ♂ • Employment medical • Tests + urine sample • Dipstick = microscopic haematuria

3. Q.1. Briefly explain the sensitivity and specificity of dipstick testing in relation to the detecting of blood (specifically mention the amount of blood which can be detected, and any substances present which may cause false negatives or false positives.) • Dipsticks have a sensitivity ofclose to 100% and a specificity of85-98% in detecting 1-5 RBCs per high-power field (hpf) • Microscopic hematuria may be discovered incidentally when heme (either red blood cells or hemoglobin) is detected on a dipstick. • Dipsticks for hemoglobin detect 1 to 2 RBCs per high powered field and are therefore at least as sensitive as urine sediment examination, but result in more false positive tests. • False positive results may occur with alkaline urine with a pH greater than 9, contamination with oxidizing agents used to clean the perineum, and semen present in the urine after ejaculation. • By comparison, false negative tests are unusual; as a result, a negative dipstick reliably excludes abnormal hematuria. • Although red cells may be lysed in dilute urine, the hemoglobin that is released will be detected by the dipstick.

4. Q.2. What history questions will you ask in relation to this finding? Explain how the answers to the questions will help you refine your list of differential diagnoses for his haematuria. • Should attempt to distinguish glomerular causes of hematuria from extraglomerular ones, as this helps in prioritizing the investigations. • A history of passage of clots in urine suggests an extraglomerular cause of hematuria. • A history of fever, abdominal pain, dysuria, frequency, and recent enuresis in older children may point to a urinary tract infection as the cause of hematuria. • A history of recent trauma to the abdomen may be indicative of hydronephrosis. • A history of early-morning periorbital puffiness, weight gain, oliguria, the presence of dark-colored urine, and the presence of edema or hypertension suggests a glomerular cause. • Hematuria due to glomerular causes is painless. • A history of a recent throat or skin infection may suggest postinfectious glomerulonephritis. • A history of joint pains, skin rashes, and prolonged fever in adolescents suggests a collagen vascular disorder. • The presence of anemia cannot be accounted for by hematuria alone, and, in a patient with hematuria and pallor, other conditions such as systemic lupus erythematosus and bleeding diathesis should be considered. • Skin rashes and arthritis can occur in Henoch-Schönlein purpura and systemic lupus erythematosus. • Information regarding exercise, menstruation, recent bladder catheterization, intake of certain drugs or toxic substances, or passage of a calculus may also assist in the differential diagnoses. • Because certain diseases that present with hematuria are inherited or familial, asking for a family history that is suggestive of Alport syndrome, collagen vascular diseases, urolithiasis, or polycystic kidney disease is important.

5. Differential diagnoses for haematuria • Acute Poststreptococcal Glomerulonephritis • Anti-GBM Antibody Disease • Benign Prostatic Hyperplasia • Endocarditis, Bacterial • Hemolytic-Uremic Syndrome • Henoch-Schoenlein Purpura • Hypercalciuria • IgA Nephropathy • Systemic Lupus Erythematosus • Urinary Tract Infection • Urolithiasis • Most common in bold

6. Q.3. • There is more professional satisfaction and less cost to the system if a patient is referred to the most appropriate specialist first. In the case of a patient with haematuria, this may be to a urologist or a nephrologist. If the microscopic haematuria is persistent according to dipstick testing, what else would you order that would assist you to determine whether the bleeding was from the renal parenchyma – especially the glomerulus, (in which case you would refer to a nephrologist)  or from another source in the urinary tract (in which case a urologist may well be more appropriate.) • To sum up a long winded question…. • What test can determine a renal source from a urinary tract source of blood in the urine?

8. Trigger 2 • “Some months ago” had one episode of severe back pain • Hospital said “you have kidney stone” • After heaps of blood tests, prescribed allopurinol and told to keep fluids up • He admits he doesn’t take tablets reg. or drink enough3 • Now scared he’s in for another ‘attack’

9. Q.5. What is the MOA of Allopurinol? • MOA – competitively inhibits xanthineoxidase, therefore ↓ uric acid levels by inhibiting the metabolism of xanthine to uric acid. Also does some inhibition of purine synthesis. • Xanthineis a product of purine degradation (guanine) • Guanine – (guanine deaminase)  Hypoxanthine/Xanthine – (xanthineoxidase)  uric acid • Allopurinol– (xanthineoxidase) alloxanthine • Alloxathinehas a half life of 18-30hrs and is a non-competitive inhibitor of xanthineoxidase. Greatest effect • In this way, it reduces the insoluble [uric acid and urates] and increases the soluble [xanthines] ↓ in urate crystals

10. Q.4. What do you now think is the likely explanation for his haematuria? Try to work out the pathophysiologic steps, from the assumed biochemical problem to the eventual haematuria. Draw it as a concept map or algorithm. • See Rick’s word doc

11. Q.6. What other co-morbidities would you consider when planning his management? • Gout? Allopurinol can exacerbate acute attacks. May also need to increase dose as he may have an inability to effectively excrete ammonia, diminished renal clearance of urate or excessive urate production • Does he have a cause of high cell turnover? Leukaemia? • Allopurinol↑ the effect and toxicity of azathioprine and mercaptopurine by inhibiting their metabolism (both drugs are used as immunosuppressants with potent anti-inflam properties, acting against rapidly dividing cells). Used in IBD and as anti-rheumatics • Chronic diarrhoea – replacement of bicarb is required (sodium bicarb). Increases risk of calcium stones!!! • Help me!!!

12. The End