💡 Learning Outcomes:

1. Describe the tubular handling of calcium, phosphate, urea, magnesium, uric acid and amino acids
2. Describe the sensory and motor innervation of the kidneys, ureter, urinary bladder and discuss mechanisms of referred pain
3. Discuss the predisposing factors, aetiopathogenesis and clinical course of nephrolithiasis
4. Describe the different types of renal calculi.
5. Justify the choice of investigations in a case of nephrolithiasis.
6. Outline the principles of treatment of nephrolithiasis
7. Describe the mechanism of action of antibiotics used in urinary tract infections 

1. Tubular Handling of Substances

A. Calcium

• Reabsorption Sites:
  • Proximal convoluted tubule (PCT) (approximately 65%)
  • Loop of Henle (approximately 25%)
  • Distal convoluted tubule (DCT) (approximately 8-10%)
  • Collecting duct (approximately 3-5%)

B. Phosphate

• Reabsorption Sites:
  • Proximal convoluted tubule (PCT) (approximately 80%)

• Regulation: Influenced by parathyroid hormone (PTH), which decreases phosphate reabsorption.

C. Urea

• Reabsorption Sites:
  • Proximal convoluted tubule (PCT) (approximately 50%)
  • Loop of Henle (some)
  • Collecting duct (variable)

• Mechanism: Passive reabsorption influenced by osmotic gradients.

D. Magnesium

• Reabsorption Sites:
  • Loop of Henle (approximately 70%)
  • Distal convoluted tubule (DCT) (approximately 15%)

• Regulation: Influenced by dietary intake and renal function.

E. Uric Acid

• Reabsorption Sites:
  • Proximal convoluted tubule (PCT) (approximately 90%)

• Secretion: Some uric acid is secreted back into the tubular fluid.

F. Amino Acids

• Reabsorption Sites:
  • Proximal convoluted tubule (PCT) (approximately 99%)

• Mechanism: Active transport mechanisms are involved in amino acid reabsorption.

2. Sensory and Motor Innervation

A. Kidneys

• Innervation:
  • Primarily sympathetic fibers from the renal plexus.
  • Sensory fibers convey pain from the kidneys.

B. Ureters

• Innervation:
  • Sympathetic innervation via the renal and hypogastric plexuses.
  • Sensory fibers transmit pain, especially during obstruction (e.g., renal colic).

C. Urinary Bladder

• Innervation:
  • Parasympathetic fibers from the pelvic splanchnic nerves stimulate bladder contraction.
  • Sympathetic fibers inhibit bladder contraction.

D. Mechanisms of Referred Pain

• Pain from the kidneys may be referred to the lower abdomen, groin, labia, or testicles due to shared spinal nerve pathways (T11-L2).

3. Nephrolithiasis (Kidney Stones)

A. Definition

• Urolithiasis: The formation of urinary calculi in the kidney, which may deposit along the urinary tract from the renal pelvis to the urethra.

B. Epidemiology

• More common in males than females.

• Peak age: 20-30 years.

C. Types of Renal Calculi

1. Calcium Oxalate Stones (75%)
2. Struvite Stones (Magnesium Ammonium Phosphate) (10%)
3. Uric Acid Stones (10%)
4. Calcium Phosphate Stones (< 5%)
5. Cystine Stones (< 5%)
6. Xanthine Stones (< 5%)

D. Predisposing Factors

• Dehydration
• Hypercalciuria
• Hyperoxaluria
• Dietary factors (e.g., excessive vitamin C)
• Inherited disorders (e.g., cystinuria)

E. Clinical Features

• Asymptomatic in some cases.
• Severe unilateral colicky flank pain (renal colic) radiating to the lower abdomen and groin.
• Hematuria (painless).
• Nausea and vomiting.
• Dysuria, frequency, and urgency (may mimic urinary tract infection).

F. Diagnostic Methods

• Urine Analysis: Hematuria, urine pH.
• • pH > 7 suggests struvite stones; pH < 5 suggests uric acid stones.

• Urine Microscopy: To identify crystals.

• Abdominopelvic CT: Gold standard for diagnosis.

• Ultrasound: For patients requiring minimized radiation exposure.

• KUB X-Ray: Mainly for larger stones.

G. Treatment Principles

• Conservative Management: Hydration, pain management.

• Medications: Thiazide diuretics for calcium stones, potassium citrate for uric acid stones.

• Surgical Options:
  • Ureteroscopy
  • Shockwave lithotripsy
  • Percutaneous nephrolithotomy

4. Mechanism of Action of Antibiotics in Urinary Tract Infections (UTIs)

• Antibiotics Used:
  • Trimethoprim-Sulfamethoxazole: Inhibits bacterial folic acid synthesis.
  • Nitrofurantoin: Disrupts bacterial cell wall synthesis and metabolism.
  • Ciprofloxacin: Inhibits bacterial DNA gyrase and topoisomerase IV.
  • Amoxicillin: Inhibits bacterial cell wall synthesis.

5. Urine Sediment Analysis: Urinary Crystals

A. Calcium Oxalate Crystals

• Appearance: Colorless, “picket fence” (monohydrate) or “envelope” shape (dihydrate).

• Associated Conditions: Ethylene glycol toxicity.

• Urine pH: Found in acidic, neutral or alkaline pH.

B. Calcium Phosphate Crystals

• Appearance: Colorless, blunt-ended needles or prisms, rosettes.

• Urine pH: Found in neutral to alkaline pH.

C. Triple Phosphate Crystals (Struvite)

• Appearance: Rectangular or coffin-lid shape.

• Association: Bacterial urinary tract infections with urea-splitting bacteria.

• Composition: Magnesium, ammonium and phosphate

• Urine pH: Found in alkaline pH.

D. Uric Acid Crystals

• Appearance: Rhomboids, parallelograms, amber color.

• Clinical Significance: Seen in acidic or normal urine; indicators of acute uric acid nephropathy or urate nephrolithiasis.

E. Cysteine Crystals

• Appearance: Flat, colorless plates with a hexagonal shape.

• Clinical Significance: Seen in acidic urine that are associated with an inherited disorder, indicates proximal tubular defect in amino acid reabsorption.