Control systems and congenital disorders

• Bartter’s syndrome (type 1) is characterised by impaired SLC12A2 protein (chloride/potassium/sodium co-transporter) in the thick ascending limb, resulting in the in loss of sodium, potassium and water and hypercalcuria.
• Giteiman’s syndrome is characterised by impaired SLC12A3 protein (sodium/chloride co-transporter) in the distal tubule, resulting in loss of sodium, potassium and modest loss of water.
• Liddle’s syndrome is characterised by hyper activity of the epithelial sodium channel (ASC, ENaC) protein in the collecting duct, which has the opposite affect of any diuretic as it increases plasma volume and blood pressure (volume expansion and hypertension), and can be treated with amiloride.
• Pseudohypoaldosteroneism is characterised by an inactive ENaC protein in the collecting duct, has a similar effect as amiloride diuretic (loss of sodium, potassium retention, and high aldosterone)
• Inactivating mutations of aquaporins result in inactivated aquaporins in the collecting duct, presenting as nephrogenic DI (polyuria, polydipsia).
• Addison’s disease is characterised by the destruction of the adrenal glands which leads to low aldosterone, presenting as the same renal result of treatment with spironolactone, with hypovolaemia, sodium loss and potassium retention.
• Psychogenic polydipsia results in whole body hypo-osmolarity.
• The collecting duct develops from the nephric duct
• The nephron (except for collecting duct) develops from the mesenchyme
• The mesenchyme forms the mesonephros, which is a temporary embryonic kidney
• The mesonephros is co-opted by the testis to form a drainage system for the testis (epididymis)
• The nephric duct forms the vas deferens
• Nephrons are formed from stem cell populations that specialize into epithelium and cap the branching bud tips
• bladder forms from where the nephric duct and the ureteric bud diverge (as they connect to the cloaca), and the flow of the cells separates and pushes the nephric duct so that it connects below the bladder, where the prostate will form in the males
• In females, the nephric duct is "destroyed"
• A branch from the nephric duct forms the seminal vesicle and the rest of the duct is then called the ductus deferens
• Components of semen:

  • Sperm is produced from the testis
  • Citric acid, enzymes, and acidic proteins are produced from the prostate
  • Fructose and basic proteins are produced from the seminal vesicle
• In males, indifferent gonads develop into the testis cord, which connects to some mesonephric tubules (epididymis)
• In males, the mullerian duct regresses
• In males, the distal nephric duct sprouts seminal vesicles, and the part distal to it is the ejaculatory duct
• In males, the urethra sprouts the prostate and bulbourethral glands
• In females, indifferent gonads develop into an ovary
• In females, upper mullerian ducts become fallopian tubes
• In females, mullerian ducts converge and fuse to become the uterovaginal canal
• In females, nephric ducts and mesonephros degenerate
• In females, the uterovaginal canal forms the uterus and the upper part of the vagina (lower part from the urogenital sinus)
• Development of external genitalia:

  • Glans develops into the urethral orifice in males and the glans clitoris in females
  • Urogenital fold develops into the scrotum in males and labium majus in females
  • Urogenital groove develops into the Raphe (closure) in males and the labium minus in females
• Genital mutilation:

  • In males, it involves the removal of the foreskin
  • In females, it involves labial fold removal
• Renal agenesis is the most dramatic form of congenital abnormality
• Bilateral renal agenesis: no kidneys form, rare and fatal after birth. Lack of amniotic fluid causes Potter’s facies (flat nose/chin, ears against head)
• Unilateral renal agenesis: one kidney missing, common (1/500) and often no clinical implications
• Congenital polycystic kidney disease:

  • Forms cysts which compress the healthy kidney until it stops functioning
• Supernumerary ureter:

  • Two ureter branches emerging from one kidney, typically of no consequence if both end up united in bladder
  • Sometimes the second ureter attaches below the bladder, leading to constant urine leakage and increased risk of renal infection
• Pelvic kidney:

  • Normal developed kidney remains in the pelvis
• Horseshoe kidney:

  • Kidneys fuse and are jammed down by blood vessels
• Congenital abnormalities of cloacal development:

  • Failure of correct positioning of Rathke and Tourneaux folds results in various conditions such as rectovaginal fistula, retroprostatic fistula, and retroclocal canal
  • In males, incomplete migration of the urethral groove results in hypospadias
• Rathke and Tourneaux folds are folds of tissue which grow from the embryo into the cloacal space to divide it