Kidney Functions and Mechanisms of Urine Formation Notes Urinary System Organs The urinary system includes the kidneys, ureters, urinary bladder, and urethra. Kidney Functions Removal of toxins, metabolic wastes, and excess ions from the blood. Regulation of blood volume, chemical composition, and pH. Gluconeogenesis during prolonged fasting. Endocrine functions:Renin: regulation of blood pressure and kidney function. Erythropoietin: regulation of RBC production. Activation of vitamin D. Kidney Anatomy Supportive tissue layers include the fibrous capsule, perirenal fat capsule, and renal fascia. Internal Anatomy Renal cortex, renal medulla, major and minor calyces, renal pelvis, ureter, renal column, renal pyramid, and renal hilum are key structures. Blood and Nerve Supply Renal arteries deliver approximately 1/4 (1200 ml) of cardiac output to the kidneys each minute. Arterial flow into and venous flow out of the kidneys follow similar paths. Nerve supply is via sympathetic fibers from the renal plexus. Blood Flow Through Renal Blood Vessels The sequence of blood flow is: Aorta, Renal artery, Segmental artery, Interlobar artery, Arcuate artery, Cortical radiate artery, Afferent arteriole, Glomerulus (capillaries), Efferent arteriole, Peritubular capillaries and vasa recta, Cortical radiate vein, Arcuate vein, Interlobar vein, Renal vein, Inferior vena cava. Nephrons Structural and functional units that form urine. Approximately 1 million per kidney. Renal Corpuscle Consists of the glomerulus and its glomerular capsule. The fenestrated glomerular endothelium allows filtrate to pass from plasma into the glomerular capsule. Renal Tubule Glomerular capsule:Parietal layer: simple squamous epithelium. Visceral layer: branching epithelial podocytes.Extensions terminate in foot processes that cling to the basement membrane. Filtration slits allow filtrate to pass into the capsular space. Proximal Convoluted Tubule (PCT) Cuboidal cells with dense microvilli and large mitochondria. Functions in reabsorption and secretion. Confined to the cortex. Loop of Henle Descending and ascending limbs. Thin segment (usually in descending limb):Simple squamous epithelium. Freely permeable to water. Thick segment of ascending limb:Cuboidal to columnar cells. Distal Convoluted Tubule (DCT) Cuboidal cells with very few microvilli. Function more in secretion than reabsorption. Confined to the cortex. Collecting Ducts Receive filtrate from many nephrons. Fuse together to deliver urine through papillae into minor calyces. Contain:Principal cells: Cuboidal cells without microvilli that help maintain the body's water and salt balance. Intercalated cells: Cuboidal cells with microvilli that function in maintaining the acid-base balance of the body. Types of Nephrons Cortical nephrons:Have short loops of Henle and glomerulus further from the corticomedullary junction. Efferent arterioles supply peritubular capillaries. Juxtamedullary nephrons:Have long loops of Henle and glomerulus closer to the corticomedullary junction. Efferent arterioles supply vasa recta. Nephron Capillary Beds Glomerulus:Afferent arteriole to glomerulus to efferent arteriole. Specialized for filtration. Blood pressure is high because efferent arterioles are smaller in diameter than afferent arterioles. Arterioles are high-resistance vessels. Peritubular capillaries:Low-pressure, porous capillaries adapted for absorption. Arise from efferent arterioles. Cling to adjacent renal tubules in the cortex. Empty into venules. Vasa recta:Long vessels parallel to long loops of Henle. Arise from efferent arterioles of juxtamedullary nephrons. Function in the formation of concentrated urine. Juxtaglomerular Apparatus (JGA) One per nephron; important in the regulation of filtrate formation and blood pressure. Involves modified portions of:The distal portion of the ascending limb of the loop of Henle. Afferent (sometimes efferent) arteriole. Granular cells (juxtaglomerular, or JG cells):Enlarged, smooth muscle cells of arteriole. Secretory granules contain renin. Act as mechanoreceptors that sense blood pressure. Macula densa:Tall, closely packed cells of the ascending limb. Act as chemoreceptors that sense NaCl content of filtrate. Extraglomerular mesangial cells:Interconnected with gap junctions. May pass signals between macula densa and granular cells. Filtration Membrane Allows passage of water and solutes smaller than most plasma proteins. Fenestrations prevent filtration of blood cells. The negatively charged basement membrane repels large anions such as plasma proteins. Slit diaphragms also help to repel macromolecules. The filtration membrane consists of:Capillary endothelium. Basement membrane. Foot processes of podocyte of glomerular capsule. The kidneys filter the body’s entire plasma volume 60 times each day. Filtrate:Blood plasma minus proteins. Urine:<1% of total filtrate. Contains metabolic wastes and unneeded substances. Glomerular filtration. Tubular reabsorption:Returns all glucose and amino acids, 99% of water, salt, and other components to the blood. Tubular secretion:Reverse of reabsorption: selective addition to urine. Glomerular Filtration Passive mechanical process driven by hydrostatic pressure. The glomerulus is a very efficient filter because:Its filtration membrane is very permeable and it has a large surface area. Glomerular blood pressure is higher (55 m m H g 55 \, mm \, Hg 55 mm H g Molecules >5 nm are not filtered (e.g., plasma proteins) and function to maintain colloid osmotic pressure of the blood. Net Filtration Pressure (NFP) The pressure responsible for filtrate formation (10 m m H g 10 \, mm \, Hg 10 mm H g Factors Determining Net Filtration Pressure Glomerular (blood) hydrostatic pressure: H P g = 55 m m H g HP_g = 55 \, mm \, Hg H P g = 55 mm H g Blood colloid osmotic pressure: O P g = 30 m m H g OP_g = 30 \, mm \, Hg O P g = 30 mm H g Capsular hydrostatic pressure: H P c = 15 m m H g HP_c = 15 \, mm \, Hg H P c = 15 mm H g N F P = H P < e m > g − ( O P < / e m > g + H P c ) NFP = HP<em>g - (OP</em>g + HP_c) N F P = H P < e m > g − ( O P < / e m > g + H P c ) Glomerular Filtration Rate (GFR) Volume of filtrate formed per minute by the kidneys (120 – 125 m l / m i n 120–125 \, ml/min 120–125 m l / min Governed by (and directly proportional to):Total surface area available for filtration. Filtration membrane permeability. NFP. Regulation of Glomerular Filtration GFR is tightly controlled by two types of mechanisms:Intrinsic controls (renal autoregulation): Act locally within the kidney. Extrinsic controls: Nervous and endocrine mechanisms that maintain blood pressure but affect kidney function. Intrinsic Controls Maintains a nearly constant GFR when MAP is in the range of 80 – 180 m m H g 80–180 \, mm \, Hg 80–180 mm H g Two types of renal autoregulation:Myogenic mechanism. Tubuloglomerular feedback mechanism, which senses changes in the juxtaglomerular apparatus. Intrinsic Controls: Myogenic Mechanism Increase in BP leads to constriction of afferent arterioles:Helps maintain normal GFR. Protects glomeruli from damaging high BP. Decrease in BP leads to dilation of afferent arterioles:Helps maintain normal GFR. Intrinsic Controls: Tubuloglomerular Feedback Mechanism Flow-dependent mechanism directed by the macula densa cells. If GFR increases, filtrate flow rate increases in the tubule. Filtrate NaCl concentration will be high because of insufficient time for reabsorption. Macula densa cells of the JGA respond to increased NaCl by releasing a vasoconstricting chemical that acts on the afferent arteriole, which decreases GFR. The opposite occurs if GFR decreases. Extrinsic Controls: Sympathetic Nervous System Under normal conditions at rest:Renal blood vessels are dilated. Renal autoregulation mechanisms prevail. Under extreme stress:Norepinephrine is released by the sympathetic nervous system. Epinephrine is released by the adrenal medulla. Both cause constriction of afferent arterioles, inhibiting filtration and triggering the release of renin. Extrinsic Controls: Renin-Angiotensin Mechanism Triggered when the granular cells of the JGA release renin:A n g i o t e n s i n o g e n → r e n i n A n g i o t e n s i n I → a n g i o t e n s i n c o n v e r t i n g e n z y m e ( A C E ) A n g i o t e n s i n I I Angiotensinogen \xrightarrow{renin} Angiotensin \, I \xrightarrow{angiotensin \, converting \, enzyme \, (ACE)} Angiotensin \, II A n g i o t e n s in o g e n r e nin A n g i o t e n s in I an g i o t e n s in co n v er t in g e n z y m e ( A C E ) A n g i o t e n s in I I Effects of Angiotensin II Constricts arteriolar smooth muscle, causing MAP to rise. Stimulates the reabsorption of N a + Na^+ N a + Acts directly on the renal tubules. Triggers adrenal cortex to release aldosterone. Stimulates the hypothalamus to release ADH and activates the thirst center. Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid reabsorption. Causes glomerular mesangial cells to contract, decreasing the surface area available for filtration. Triggers for Renin Release by Granular Cells Reduced stretch of granular cells (MAP below 80 m m H g 80 \, mm \, Hg 80 mm H g Stimulation of the granular cells by activated macula densa cells. Direct stimulation of granular cells via β 1 β_1 β 1 Other Factors Affecting GFR Prostaglandin E 2 E_2 E 2 Vasodilator that counteracts vasoconstriction by norepinephrine and angiotensin II. Prevents renal damage when peripheral resistance is increased. Intrarenal angiotensin II:Reinforces the effects of hormonal angiotensin II. Adenosine:A vasoconstrictor of renal vasculature.