The outer region of the cortex houses the glomerulus of each superficial nephron, with approximately 10 superficial nephrons for each juxtamedullary nephron. The loops of Henle associated with these superficial nephrons are short, and the efferent arterioles branch into peritubular capillaries surrounding the nephron segments and adjacent nephrons. This network of capillaries transports oxygen and essential nutrients to the cortex nephron segments, facilitates the secretion of substances into the tubular fluid, and allows reabsorbed water and solutes to return to the circulatory system. Polycystin 1 (PKD1 gene) and polycystin 2 (PKD2 gene) are expressed in the primary cilia membrane and enable the entry of Ca++ into cells. These genes play a significant role in flow-dependent K+ secretion by the principal cells of the collecting duct. Increased flow in the collecting duct triggers K+ secretion by activating the PKD1/PKD2 Ca++-conducting channel complex, leading to an increase in intracellular [Ca++]. This increase in [Ca++] activates K+ channels in the apical plasma membrane, enhancing the secretion of K+ into the tubule fluid. Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited kidney disease, affecting approximately 1 in 1000 individuals worldwide. The majority of ADPKD cases (85%-90%) are caused by mutations in the PKD1 gene, while around 15% of cases are caused by mutations in the PKD2 gene. ADPKD is characterized by kidney enlargement due to the presence of numerous renal cysts, which can reach sizes of up to 20 cm in diameter. Cysts may also develop in other organs such as the liver. About 50% of ADPKD patients progress to renal failure by the age of 60. The mechanism through which PKD1 and PKD2 mutations cause ADPKD is not fully understood, but it is believed that defects in Ca++ uptake disrupt Ca++-dependent signaling pathways involved in kidney cell proliferation, differentiation, and apoptosis. Additionally, some species possess superficial nephrons with very short loops of Henle that never extend into the medulla. The glomerulus of each juxtamedullary nephron is located in the cortex region adjacent to the medulla.
Fig. 33.2 ), with approximately 10 superficial nephrons for each juxtamedullary nephron. The 585 • Fig. 33.3 Diagram of a nephron including cellular ultrastructure. Inner medulla collecting duct Ascending thin limbThick ascending limb Descending thin limb Proximal tubule Macula densa Cortical collecting duct Distal tubule Principal cell Intercalated cell OutermedullaInner medulla Cortex • Fig. 33.4 Scanning electron micrograph illustrating primary cilia (C, ≈2 to 30 µm long and 0.5 µm in diameter) in the apical plasma membrane of principal cells in the cortical collecting duct. Note that intercalated cells (IC1 and IC2) do not have cilia but have numerous microvilli. CD, collecting duct principal cells with short microvilli (arrowhead); straight ridges (open arrow) represent the cell borders between principal cells; IC1 and IC2, intercalated cells with numerous long microvilli in the apical membrane. (From Kriz W, Kaissling B. Structural organization of the mammalian kidney. In: Seldin DW, Giebisch G [eds]. The Kidney: Physiology and Pathophysiology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2000.) glomerulus of each superficial nephron is located in the outer region of the cortex. The corresponding loops of Henle are short, and associated efferent arterioles branch into peritubular capillaries that surround its associated nephron segments as well as adjacent nephrons. This capillary network conveys oxygen and important nutrients to the nephron segments in the cortex, delivers substances to individual nephron segments for secretion (i.e., movement of a substance from blood into tubular fluid), and serves as a pathway for return of reabsorbed water and solutes to the circulatory system. A few species, including humans,
Polycystin 1 (encoded by the PKD1 gene) and polycystin 2 (encoded by the PKD2 gene) are expressed in the membrane of primary cilia and mediate entry of Ca++ into cells. PKD1 and PKD2 are thought to play an important role in flow-dependent K+ secretion by principal cells of the collecting duct. As described in more detail in
Chapter 36, increased flow of tubule fluid in the collecting duct is a strong stimulus for secretion of K+ . Increased flow bends the primary cilium in principal cells, which activates the PKD1/PKD2 Ca++-conducting channel complex and allows Ca++ to enter the cell and increase intracellular [Ca++]. The increase in [Ca++] activates K+ channels in the apical plasma membrane, which enhances secretion of K+ from the cell into the tubule fluid.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, occurring in about 1 in 1000 people. Approximately 12.5 million people worldwide have ADPKD, which is caused primarily by mutations in PKD1 (85%–90% of cases) or PKD2 (≈15% of cases). The major phenotype of ADPKD is enlargement of the kidneys due to the presence of hundreds or thousands of space-occupying renal cysts that can be as large as 20 cm in diameter. Cysts are also seen in the liver and other organs in this condition. About 50% of patients with ADPKD progress to renal failure by the age of 60. Although it is not clear how mutations in PKD1 and PKD2 cause ADPKD, renal cyst formation may result from defects in Ca++ uptake that alter Ca++-dependent signaling pathways, including those controlling kidney cell proliferation, differentiation, and apoptosis.
also possess very short superficial nephrons whose loops of Henle never enter the medulla.
The glomerulus of each juxtamedullary nephron is located in the region of the cortex adjacent to the medulla (see