Introduction to Renal Structure and Function Renal Genital Urinary System 2019 INTRODUCTION TO RENAL STRUCTURE AND FUNCTION Orson W. Moe, M.D. Office: H05122; Phone: 82754 Email: [email protected] LEARNING OBJECTIVES: • Concept: The kidney is a homeostatic organ that maintains constancy of the composition and amount of internal environment. Deviations from normal are sensed and then rectified. Sensing is largely extrarenal but some mechanisms can be intrarenal. • The kidneys achieve homeostasis by executing three functions as an excretory, metabolic, and endocrine organ. • Anatomically identify the renal cortex, renal medulla, renal calyces, medullary pyramids, renal artery, renal vein, and ureter. Trace the renal circulation from the main renal artery to the glomerular blood vessels, peritubular capillaries, the vasa recta, and renal vein. • Appreciate the unique features of the renal circulation. • Learn the structural components of the glomerulus and the juxtaglomerular apparatus. Describe the three layers of glomerular filtration barrier separating the blood from urine. • Walk axially down the nephron and learn the different tubular segments traversed sequentially by the ultrafiltrate from Bowman’s space and finally reaching the renal pelvis. • Understand the difference between filtration, reabsorption, and secretion and how the three processes work in concert to achieve excretion. • Learn the generic design of a polarized transporting epithelium. Understand paracellular vs. transcellular transport, the model of an epithelial cell with polarized location of transporting proteins, and how the currency of energy is translated from metabolic substrates to ATP, and finally, to electrochemical gradients. • In addition to excretion, the kidney also has metabolic and endocrine functions. The kidney is a major site of gluconeogenesis. Certain endocrine hormones are secreted by the kidney into the circulation such as renin, vitamin D, and erythropoietin. I. Introduction Multicellular organisms evolved to house their cells in a constant organism world internal environment. The kidneys are regulatory organs poised at an interface between the organism and the external world that maintain a constant optimal internal environment in both composition and amount (Figure 1). Deviations of any parameter beyond the normal physiologic range are sensed, and corrective Maintain constancy measures are deployed to correct the parameter back to normal limits (Figure 2). Failure of correction sets the stage for disease. Composition Quantity Figure 1: Kidney: Interface between the organism and the world Introduction to Renal Structure and Function Renal Genital Urinary System 2019 There are mechanisms that monitor the physiologic parameter of interest and hence constitute the afferent arm of the loop (Figure 2). Effectors are the rectifying mechanisms that constitute the efferent arm of the homeostatic loop. Depending on the variable Physiologic sensed, the afferent sensing arms can be extra-renal or renal. Afferent parameter Efferent Sensor Effector One principal function of the kidney is excretion. The substances excreted can be exogenous toxins or drugs that are not normally present, or they can be endogenous substances that normally reside in the body but are present in excess. When the body is Figure 2: Renal homeostatic loop deficient of an endogenous substance, the kidney conserves it by decreasing its excretion. In addition to excretion, the kidney also achieves homeostasis by providing metabolic substrates such as glucose to the body. The kidney also acts an endocrine organ, secreting circulating hormones to act on other organs. The importance of renal function is easily appreciated in patients with either acute or chronic kidney disease where secondary failure of multiple organs ensues because of the disruption of the maintenance of the internal environment. Figure 3: Genitourinary system and gross anatomy of kidney II. Renal Anatomy The kidneys are seated against the posterior wall of the abdomen in the retroperitoneal space (Figure 3). The kidney is surrounded by a capsule. The bisected surface of the kidney has a lighter colored outer region called the cortex and the darker inner region called the medulla (Figure 3). The medulla is divided radially into outer and inner regions with the outer medulla subdivided into outer and inner stripes. The medulla has multiple conical contours called renal pyramids with their apices abutting on the renal pelvis to form the papillae. The contact points of the renal pelvis with the renal parenchyma are cup-like structures called calyces. Interpolated between the pyramids are centripetal extensions of cortical tissue into the medulla called columns of Bertin. In contrast to the human kidney, the rodent kidney (which is used extensively as an experimental model) has only one pyramid and papilla. Introduction to Renal Structure and Function Renal Genital Urinary System 2019 Each kidney usually receives blood from a single renal artery (although there can be two or more renal arteries per kidney). Just before or after the renal artery enters the kidney, it divides into a series of smaller branches. These branches give rise to smaller interlobar arteries that pass between the pyramids of the kidney radially up the Columns of Bertin (Figure 4). Figure 4: Renal vasculature hierarchy (left). Latex casts of renal vessels (right) Interlobar arteries divide to form smaller vessels, arcuate arteries, which run along the junction of the medulla and cortex parallel to the surface of the kidney (Figures 4). Arcuate arteries give rise to still smaller arteries, cortical ascending arteries, which carry blood from the deep part of the cortex to the superficial cortex. As glomeruli are located exclusively in the cortex, it is the cortical ascending arteries that bring arterial blood in proximity to glomeruli. Afferent arterioles then distribute blood from cortical ascending arteries to individual glomeruli. In each glomerulus, the incoming afferent arteriole forms a highly branched network of specialized glomerular capillaries. There are four unique features of the renal circulation (Table 1). Feature Implication Little or no anastomoses Very prone to regional disruption of blood flow High blood flow per gram tissue Lowest oxygen extraction (lowest A-VO2 difference) Functional arteriovenous shunts Solutes and gases (e.g., O2) can diffuse directly from artery to vein without passing through the capillaries Multiple capillaries in tandem The two capillaries serve difference functions in sequence Table 1: Four salient feature of the renal circulation Introduction to Renal Structure and Function Renal Genital Urinary System 2019 Figure 5: The glomerular and peritubular capillaries are in tandem (left). The intrarenal vasculature is shown with arteries and veins shown under red and blue shaded areas, respectively (right). The glomerular capillaries provide the site for glomerular ultrafiltration, the first step in making urine (Figure 5). The plasma that is not filtered at the end of each glomerular capillary network enters the efferent arteriole that conveys blood out of the glomerulus. Note that even though this “arteriole” is situated after a capillary system (glomerular capillary), it is not called a venule. It is an arteriole because it is in front of a second capillary system- the peritubular capillaries. surrounding the tubular elements in both the cortex and medulla. The peritubular capillaries provide oxygen and nutrients for the bulk of the kidney. They work with the tubules by collecting the fluid and solutes reabsorbed by tubules to return to the circulation. They also deliver solutes that are secreted by tubules from the blood into urine. Blood in the peritubular capillaries is returned to the circulation by a venous system that follows the architectural structure of the arterial supply: interlobular vein, arcuate vein, interlobar vein, and renal vein (Figure 5). IV. Renal Excretion Excretion of a substance can be mediated by one or a combination of three processes: 1) Filtration, 2) Secretion, and 3) Reabsorption. Figure 6 compares two systems – pure filtration vs. filtration-reabsorption – and shows what they imply in Figure 6: Functional implications of filtration, secretion, and reabsorption. terms of demands on regulation. Consider the excretion of 1L/day by purely filtration. A 5% error (reduction in filtration) will mean that only 0.95 L/day will be excreted - a 50 ml error. Now compare this to a filtration-reabsorption model where 170 L/day is filtered and 169 L/day is reabsorbed resulting in the same 1 L/day excretion. A 5% error (reduction in reabsorption) will mean 160L/day of reabsorption resulting in excretion of 10L/day and an absolute error of 9L. A clear consequence of a filtration-reabsorption design is that regulation has to be exquisitely tight and even small errors are not tolerated. Introduction to Renal Structure and Function Renal Genital Urinary System 2019 V. Microscopic Anatomy A. The Nephron The kidney is composed of a large number of functional units called nephrons (Figure 7). Each human kidney has approximately 1 million nephrons. The nephron is composed of multiple different types of cells. Approximately 30% of nephrons have their glomeruli situated deep in the cortex near the medulla; these are called juxtamedullary nephrons. The nephrons whose glomeruli are located in the mid or superficial cortex are called superficial or cortical nephrons. The different cell