Autosomal-dominant (adult) polycystic kidney disease (ADPKD) o characterized by multiple expanding cysts of both kidneys that ultimately destroy

the renal parenchyma o cause renal failure. (MCQ) o autosomal dominant with high penetrance. o Despite the autosomal dominant inheritance, the manifestation of the disease requires mutation of both alleles of either PKD gene o universally bilateral o cysts initially involve only portions of the nephrons, so renal function is retained until about the fourth or fifth decade of life. o genetically heterogeneous o caused by mutations in genes located on chromosome 16p13.3 (PKD1) (Most common) (MCQ) chromosome 4q21 (PKD2), o Mutations of PKD1 (MCQ) account for about 85% of cases associated with a more severe disease, end-stage renal disease or death o Genetics and Pathogenesis. PKD1 gene encodes a large (460-kD) integral membrane protein named polycystin-1, (MCQ) localized to tubular epithelial cells, particularly those of the distal nephron. (MCQ) PKD2 gene product polycystin-2 is an integral membrane protein. localized to all segments of the renal tubules and is also expressed in many extrarenal tissues. (MCQ) functions as a Ca2+-permeable cation channel a basic defect in ADPKD is a disruption in the regulation of intracellular Ca2+ levels. (MCQ) Morphology. o microscopic examination reveals functioning nephrons dispersed between the cysts. o cysts arise from the tubules throughout the nephron Extrarenal congenital anomalies. o About 40% have one to several cysts in the liver (polycystic liver disease) that are usually asymptomatic. (MCQ) cysts are derived from biliary epithelium. Cysts occur much less frequently in the spleen, pancreas, and lungs. o Intracranial berry aneurysms arise in the circle of Willis(MCQ) o subarachnoid hemorrhages (MCQ) o Mitral valve prolapse (MCQ) chronic renal failure is remarkable in that patients may survive for many years with azotemia slowly progressing to uremia(MCQ) about 40% of adult patients die of coronary or hypertensive heart disease, (MCQ)

Autosomal-recessive (childhood) polycystic kidney disease (ARPKD) Perinatal, neonatal type are the most common(MCQ) serious manifestations are usually present at birth young infant might succumb rapidly to renal failure. most common mutations are due to PKHD1 gene o maps to chromosome region 6p21p23. (MCQ) o encodes a large novel protein, fibrocystin(MCQ) Morphology. o Dilated elongated channels are present at right angles to the cortical surface, completely replacing the medulla and cortex o saccular dilation of all collecting tubules. (MCQ) o cysts have a uniform lining of cuboidal cells, reflecting their origin from the collecting ductS o In almost all cases the liver has cysts associated with portal fibrosis and proliferation of portal bile ducts. o Patients who survive infancy (infantile and juvenile forms) may develop a peculiar type of hepatic fibrosis ,termed congenital hepatic fibrosis. (MCQ)