Renal Pathology week 1

• The lower urinary tract extends from calyces to urethra and transmits urine from the kidney to exterior

  
• The bladder acts as a reservoir and is lined by urothelium (transitional cell epithelium) which resists osmotic stresses of contact with urine

  
• Disorders of the lower urinary tract

  • Infection
  • Obstruction

  
• Infection


  Often secondary to stasis
• Obstruction


  • Intrinsic e.g. Stone formation
  • Extrinsic e.g. Tumour, pregnancy
• Infections are usually due to Gram-negative bacteria E.coli or Gram-positive Staphylococcus saprophyticus which are commensals in the large bowel
• Women are particularly prone to urinary tract infections
• Diabetes mellitus also predisposes to infection
• Infections largely remain localised to urethra and bladder but may ascend to the ureter and enter the renal pelvis

  
• Acute bacterial urethritis and cystitis may lead to inflammation of the ureter, renal pelvis and calyces, enabling organisms to enter the renal parenchyma and cause kidney inflammation

  
• Symptoms of urinary tract infection

  • Pain when urinating/burning sensation
  • Urinating small amounts frequently
  • Cloudy/foul smelling urine
  • Blood in urine
  • Confusion and/or agitation (particularly in the elderly)

  
• Diagnosis of urinary tract infection

  • Urine sample (ideally clean, mid-stream, first of the day)
  • Dip stick (nitrite, WBCs, haematuria)
  • Microscopic analysis (bacteria and WBCs)
  • Culture, not routine but useful to test antibiotic resistance

  
• Infection treatment


  • Some infections can clear without treatment
  • Cranberry juice/ sodium citrate sachets often used to relieve symptoms (scientific evidence not strong)
  • Antibiotic treatment usually fast and effective
  • Antimicrobial resistance varies in different areas of the country
  • Trimethoprim/Sulfamethoxazole for three days is good mini-dose therapy, but resistance rates are high in many areas
  • Nitrofurantoin is a good choice for uncomplicated UTIs, but it is bacteriostatic, not bacteriocidal, and must be used for 5 to 7 days

  
• Obstruction of the ureter can lead to dilation of the ureter and renal pelvicalyceal system, and reabsorption of fluid by the kidneys

  
• Obstruction of the urethra can lead to bladder dilation, hypertrophy of the bladder wall, and predisposition to outpouching

  
• Urinary calculi


  Solid aggregates of dietary minerals, most commonly calcium oxalate or phosphate (75%)
• Predisposing factors for urinary calculi include increased solute concentration in the urine, reduced solubility of solute in urine, low fluid intake, urine stasis, persistent urinary tract infections, and primary metabolic disturbances

  
• Pelvicalyceal calculi


  • Often multiple and small (gravel like)
  • Predispose to infection, squamous cell metaplasia, and carcinoma in metaplastic areas
• Staghorn calculi


  Most commonly made up of struvite (magnesium ammonium phosphate) and calcium carbonate apatite, strongly associated with UTIs caused by organisms that produce the enzyme urease
• Ureter calculi mostly develop in the renal pelvis and pass down the urinary tract, associated with loin pain

  
• Treatment of urinary calculi

  Small stones can pass naturally, larger stones require surgical removal (shockwave lithotripsy, ureteroscopy, percutaneous nephrolithotomy)

  
• Bladder stones are often large, spherical and laminated, associated with stasis and chronic infection, and can cause squamous metaplasia in the urinary bladder

  
• Transitional cell carcinoma


  • Majority occur in the bladder
  • Have a papillary growth pattern
  • Vary from low grade to cytologically abnormal
• Low-grade transitional cell carcinoma

  Urothelial lining is thickened with minimal cytologic and architectural atypia
• High-grade transitional cell carcinoma


  Architectural disorganisation, significant cytological atypia, loss of nuclear polarity, large variation in nuclear size, shape and chromatin content, frequent and abnormal mitosis, no papillary pattern, severe cell abnormalities
• Carcinoma in situ of transitional-cell epithelium

  Large disorganized cells with irregular nuclei
• Squamous cell carcinoma


  Most common in bladder and renal pelvis, derived from metaplastic epithelium, commonly associated with chronic irritation from a calculus, associated with schistosomiases
• Congenital abnormalities of the lower urinary tract

  • Ureterocele - Distal ureter balloons at its opening into the bladder, often associated with duplicated collection systems
  • Exstrophy - Part of the urinary bladder is present outside the body, due to failure of the abdominal wall to close during fetal development

  
• Diseases of the kidney, glomerular, tubular, and blood vessels may progress to end-stage kidney disease/renal failure
• Partial renal failure


  Only affects some parts of renal function
• Types of partial renal failure

  • Nephritic syndrome
  • Nephrotic syndrome
• Nephritic syndrome


  Results from disturbances in glomerular structure, reduced blood flow, leakage of red blood cells, retention of waste products, activation of renin-angiotensin system
• Nephrotic syndrome


  Glomerulus loses ability to selectively retain protein, leading to proteinuria, hypoalbuminaemia, and oedema
• Acute renal failure (ARF)


  Total renal failure, majority of nephrons cease functioning, reduced/no urine output, disturbed fluid and electrolyte balance, can be pre-renal, renal (intrinsic), or post-renal, and is reversible
• Chronic renal failure (CRF)

  Total renal failure, progressive destruction of individual nephrons, uraemia, failure of tubular function, polyuria, secondary to vascular, glomerular, tubular and interstitial disease, and is irreversible
• Syndromes


  • Nephritic syndrome - Partial, glomerular perfusion failure
  • Nephrotic syndrome - Partial, glomerular permeability increase
  • Acute renal failure - Total, acute glomerular perfusion failure & tubular epithelial failure (reversible)
  • Chronic renal failure - Total, chronic irreversible nephron failure, both glomerular and tubular failure
• Renal cell carcinoma is the majority of malignant renal tumours, originating from renal tubular epithelium
• Nephroblastoma (Wilms' tumour) predominantly affects young children
• Congenital diseases of the kidney

  • Agenesis - failure of kidneys to develop
  • Horseshoe kidney - kidneys are fused together
  • Renal ectopia - kidney develop in the wrong place
• Polycystic kidneys


  Autosomal dominant, progressively enlarge over time, function deteriorates as cysts compress and replace functioning tissue, leading to chronic renal failure and hypertension