polycystic kidney disease or PKD is a genetic disease in which the kidneys become filled with hundreds of cysts or fluid-filled sacks causing them to be larger than normal and to quit functioning over time these cysts develop in the outer layer the cortex as well as the inner layer the Medela of both kidneys these cysts which are aligned with renal tubular epithelium fill up with fluid and get larger and larger over time making the kidneys much larger than normal the blood vessels that feed neighboring healthy nephrons can get compressed by growing cysts which literally starves them of oxygen poorly profused kidneys respond by activating the renin Angiotensin aldosterone system which facilitates fluid retention and leads to hypertension also expanding cysts can compress the collecting system causing urinary stasis and in some cases this can lead to kidney stones additionally destruction of the normal renal architecture can cause symptoms like flank pain and hematuria or blood in the urine over time as enough nephrons are affected it leads to renal insufficiency and eventually renal failure now the first type of PKD is autosomal dominant PKD or ad PKD which used to be called adult PKD since symptoms usually manifest in adulthood the first Gene responsible for adpkd is pkd1 which when mutated causes a more severe and earlier onset variety and pkd2 which when mutated causes less severe disease and is also later in onset pkd1 and pkd2 code for the polycan 1 and polycin 2 proteins respectively which are components of the primary psyllium now the primary psyllium is an appendage that's sticks out from most cells in the body and receives developmentally important signals more specifically in the nefron as the urinary filate flows by and causes it to bend polycin 1 and polycin 2 respond by allowing calcium influx which activates Pathways in the cell that inhibit cell proliferation if either component's absent that signal to inhibit cell growth isn't received and so cells proliferate abnormally and start to express proteins that cause water to be trans transported into the Lumin of the cyst which makes them get larger and larger compressing the surrounding tissue more and more and this is how cyst develop and grow as expected for a dominant disease a person who develops adpkd would have inherited a single heterozygous mutation in pkd1 or pkd2 this leaves one functional copy of the gene in every cell and this turns out to actually produce enough polyc one or polycan 2 to prevent cyst formation so how does this occur then well it turns out that a random mutation in the remaining good copy of the gene is almost guaranteed to happen in some of the tubular cells as the kidney develops this second hit causes polyst one or two to be absent and is what impaires normal signaling through the psyllium and leads to cyst formation so on the level of the person as a whole adpkd shows a pattern of dominant inheritance but on the cellular level it's technically a recessive tra polyc are important in the kidney but are developmentally important in other places in the body too patients can have cysts that are typically benign pop up in the liver seminal vesicles and pancreas the vascular CH can also be affected for example individuals might develop aortic root dilation which can lead to heart failure and have Berry aneurysms of the cerebral arteries usually in The Circle of Willis these aneurysms can have a wall allowing them to rupture and develop into a subarachnoid hemorrhage autosomal recessive PKD or ar PKD used to be called infantile PKD since symptoms usually manifest in infancy arpkd happens when someone inherits a mutation on both copies of the pkd1 gene which codes for the fibros sytin protein fibros colocalizes with polyc 2 where although largely clear it might be involved in the regulation pathway and calcium signaling described with adpkd and therefore it's thought that a similar mechanism might cause cyst formation in arpkd in any case with arpkd this cyst formation can lead to renal failure even before birth which means the fetus has trouble producing urine and since amniotic fluid comes from the fetal urine fetuses with arpkd can develop oligo hydramnios or low amniotic fluid in fact if enough amniotic fluid is missing then it can cause Potter sequence without the amniotic fluid the uterine walls actually compress the fetus which causes physical developmental abnormalities like club feet and a flattened nose also as a part of Potter sequence is pulmonary hypoplasia or underdeveloped lungs since the amniotic fluid is important in helping the lungs expand and develop normally under veloped lungs can cause respiratory insufficiency after birth which ends up being fatal in a lot of cases of arpkd for diagnosis arpkd is one of the many conditions that can be picked up via prenatal ultrasound which could show bilaterally large kidneys with cysts and oligohydramnios arpkd also causes congenital hepatic fibrosis which over time can cause portal hypertension or compromise blood flow through the portal Venus system portal hypertension can cause esophagal veraces upper GI bleeds hemorrhoids and splenomegaly from blood being shunted through the collateral veins since colang oyes or the epithelial cells that line the bod ducts also have primary cyia that Express fibrocystin arpkd can also cause defects in the bod ducts which leads to dilation dilated intrahepatic ducts can cause colestasis or poor bile secretion and dilation of the common bile duct can lead to ascending colangitis the treatment of PKD is usually directed at specific symptoms and organ dysfunction for example for hypertension medications like Angiotensin converting enzyme Inhibitors or Angiotensin receptor blockers can be used to counteract activation of the renin Angiotensin aldosterone system also urso is sometimes taken to help treat chasis since it slows down the rate at which cholesterol is absorbed by the intestines in cases of kidney failure dialysis or kidney transplants are sometimes needed for individuals with portal hypertension a portal caveal shunt which bypasses the liver by connecting the portal vein to the inferior vnea or again a liver transplant might be needed all right as a quick recap polycystic kidney disease is a genetic disorder in which the kidneys become filled with hundreds of cists causing them to be larger than normal and to fail over time PKD comes in two varieties autosomal dominant which presents in adulthood and autosomal recessive which presents in infancy or even before birth helping current and future clinicians Focus learn retain and Thrive learn more