ΔF508-CFTR gene mutation, which occurs in >90% of patients in the U.S., creates a protein that does not fold normally and is not appropriately transported to the cell membrane, resulting in its degradation.Other mutations result in proteins that are too short (truncated) because production is ended prematurely. Other mutations produce proteins that do not use energy (in the form of ATP) normally, do not allow chloride, iodide, and thiocyanate to cross the membrane appropriately, and degrade at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced.The protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lungs, pancreas, and all other remaining exocrine glands in the body. The protein spans this membrane and acts as a channel connecting the inner part of the cell (cytoplasm) to the surrounding fluid. This channel is primarily responsible for controlling the movement of halide anions from inside to outside of the cell; however, in the sweat ducts, it facilitates the movement of chloride from the sweat duct into the cytoplasm. When the CFTR protein does not resorb ions in sweat ducts, chloride and thiocyanate released from sweat glands are trapped inside the ducts and pumped to the skin. Additionally hypothiocyanite, OSCN, cannot be produced by the immune defense system. Because chloride is negatively charged, this modifies the electrical potential inside and outside the cell that normally causes cations to cross into the cell. Sodium is the most common cation in the extracellular space.
Vesicouterine fistula refers to an abnormal communication between the bladder and uterus. The first case of vesicouterine fistula was reported in 1908. It was however first described in 1957 by Abdel Fattah Youssef, an obstetrician and gynaecologist in Kasr el-Aini hospital, Cairo, Egypt. It is characterized by a vesicouterine fistula above the level of the internal os, absence of menstrual bleeding, cyclical presence of blood in urine and absence of urinary incontinence with a patent cervical canal following a lower segment caesarean section. Six of such cases had been reported by other clinicians before the term Menouria was coined by Youssef. Pathology
Vesicouterine fistula is the least common type of urogenital fistula accounting for 1-4% of urogenital fistulas. It occurs following lower segment caesarean section and the incidence is increasing due to the increasing incidence of caesarean deliveries. The occurrence of menoruria in the absence of vaginal bleeding or passage of urine from the vagina is attributed to a sphincteric mechanism of the uterine isthmus.Jozwik and Jozwik classified vesicouterine fistula into three types based on the route of menstrual flow;I - Menstrual flow from the bladder only without urinary incontinence
II - Menstrual flow from both the bladder and vagina with urinary incontinence
III - Normal menstrual flow from the vagina only (no menouria) with urinary incontinence
Youssef syndrome corresponds to a type I vesicouterine fistula. Causes
Vesicouterine fistulas occur most commonly after lower segment caesarean sections (about 83-93% of cases).