Kidney stone pathophysiology

https://https://www.youtube.com/watch?v=uloDkeBOxGQ%7C350}}

Kidney stone Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Kidney stone from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X Ray
Ultrasonography
CT
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Kidney stone pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Kidney stone pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
National Guidelines Clearinghouse
NICE Guidance
FDA on Kidney stone pathophysiology
CDC on Kidney stone pathophysiology
Kidney stone pathophysiology in the news
Blogs onKidney stone pathophysiology
Directions to Hospitals Treating Kidney stone
Risk calculators and risk factors for Kidney stone pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Pathophysiology

Pathogenesis

• It is understood that nephrolithiasis is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
• [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
• Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
• [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
• The progression to [disease name] usually involves the [molecular pathway].
• The pathophysiology of [disease/malignancy] depends on the histological subtype.

		Cause	Pathophysiology	Stone composition	Clinical clues
All stones	Low urine volume (raises production of solutes)	Reduced intake or increased loss of water	Renal water conservation	All stones	Urine volume <1 L per day Osmolarity >600 mOsm/kg
Calcium stones	Hypercalciuria (raises saturation of calcium salts)	Absorptive hypercalciuria	Increased absorption in gut	Calcium oxalate or phosphate	Urine calcium concentrations >6 mmol/L (240 mg) per day
		Hyperparathyroidism	Increased absorption in gut and bone release		High concentrations of parathyroid hormone
		Immobilisation	Bone resorption		High concentrations of vitamin D
		Excess of sodium in diet	Sodium-induced physiological renal calcium leak. Possible component of gut hyperabsorption		Urine sodium concentrations >200 mmol/L per day
		Excessof protein or acid in diet	Protein-induced bone loss and renal leak.		Urine ammonium iron concentrations high
					Urine sulphate concentrations high
					Urine pH low
					Urine citrate concentrations <1·7 mmol/L per day
		Range of monogenic disorders	Bone loss, gut hyperabsorption, and renal leak in various combinations
	Hypocitraturia (raises levels of ionised calcium and reduces inhibitor activity against calcium salts)	Renal tubular acidosis (distal type)	Renal defence of acid–base balance	Calcium phosphate	Urine citrate concentrations <1·7 mmol/L per day
					Urine pH high
		High acid load (absence of detectable acidemia)	Physiological hypocitraturia	Calcium oxalate or phosphate	Urine citrate concentrations <1·7 mmol/L per day
					Urine pH low
	Hyperoxaluria (raises saturation of calcium oxalate)	Excess of oxalate in diet	Increased delivery of luminal oxalate	Calcium oxalate	Urine oxalate concentrations >70·7 mmol/L per day
		Bowel pathology	Reduced formation of luminal calcium and calcium-oxalate complex
		Increased production of endogenous oxalate	Primary hyperoxaluria (type 1 and type 2)
	Hyperuricosuria (sodium urate precipitation causes crystallisation of calcium salts)	High purine intake	Raised production and urinary excretion of sodium and urate	Calcium oxalate	Urine uric acid concentrations >600 mg per day
					Hyperuricaemia
		Myeloproliferative diseases
		Enzymatic defects			Urine uric acid concentrations >600 mg per day
		Uricosuric drugs			Hypouricaemia
		Genetic primary renal leak	Increased excretion of uric acid
	Uric acid stones
	Low urine pH or hyperuricosuria	High acid load	Titrates urate to poorly soluble uric acid	Uric acid	Urine pH <5·5
		Metabolic syndrome
	Cystine stones
	Cystinuria	Congenital mutations of dibasic aminoacid transporter subunits rBAT and b0+AT	Renal leak of basic aminoacids	Cystine	Urine concentrations of cystine high (>150 μmol/mmol creatinine)
	Infection stones
	Urinary tract infection	Urea-splitting organisms	Production of ammonium and bicarbonate from urea	Magnesium ammonium phosphate	Urine pH high
					Pyuria

Genetics

• Nephrolithiasis can be passed on to following generations due to rare causes of hypercalciuria:
  • Hereditary distal renal tubular acidosis
  • Dent disease
  • Bartter syndrome types III and IV
  • Autosomal dominant hypocalcemic hypercalciuria
  • Familial hypomagnesemia

Associated Conditions

• Hyperparathyroidism
• Gout
• Hypocitaturia
• Sarcoidosis
• Chronic urinary tract infections
• Obesity

Gross Pathology

• On gross pathology, the characteristic findings of nephrolithiasis are:
  • Location = 80% unilateral, usually in calyces, pelvis or bladder
  • Size=variable, 2-3 mm usually
  • All stones contain an organic matrix of mucoprotein
  • Shape:
    • Struvite stone= staghorn calculus

• 

  Nephrolithiasis, Source: Wikimedia commons

• 

  Staghorn shape of struvite stones, Source: Wikimedia commons

• 

  Renal calculi, different shapes and sizes, Source: Wikimedia commons

• 

  Kidney stone with a maximum dimension of 5mm, Source: Wikimedia commons

Microscopic Pathology

• On microscopic histopathological analysis, the characteristic findings of nephrolithiasis are:
  • Shapes of different stones/crystals are different:
    • Cysteine= hexagonal
    • Struvite= coffin lid shape
    • Calcium oxalate= pyramid shape
    • Calcium oxalate= dumbbell shape
    • Uric acid= rectangular/rhomboidal
  • Oxalate crystals are highlighted by polarized light
  • Foreign body giant cells and macrophages are seen with the stones

• 

  Type of stones. Light microscopy of urine crystals. (A) Hexagonal cystine crystal (200X); (B) coffin-lid shaped struvite crystals (200X); (C) pyramid-shaped calcium oxalate dehydrate crystals (200X); (D) dumbbell-shaped calcium oxalate monohydrate crystal (400X); (E) rectangular uric acid crystals (400X); and (F) rhomboidal uric acid crystals (400X).

• 

  Deposits of oxalate with variable size and form; they occupy mainly distal tubules. The asterisks indicate proximal tubules, which usually do not contain these crystals, H&E seen with polarized light, X200

• 

  Medullary interstitial urate crystal deposits in chronic nephropathy by urates as seen after Masson's trichome stain X400

• 

  Calcium oxalate dihydrate crystals under Scanning Electron Micrograph (SEM) taken at 30 KV. Source: Wikimedia commons

• 

  Density-dependent color scanning electron micrograph of kidney stone, Source: Wikimedia commons