PHA112 Renal Student Handout 2023-24 PDF

WEEK 16 MPharm Programme Renal Dr Praveen Bhugra PHA112 Slide 1 of 41 PHA112 Renal WEEK Learning Objectives 16 From this lecture you should be able to:  Understand and explain briefly the organs and function of the urinary system  Understand and explain in detail the anatomy of kidney in...

WEEK 16 MPharm Programme Renal Dr Praveen Bhugra PHA112 Slide 1 of 41 PHA112 Renal WEEK Learning Objectives 16 From this lecture you should be able to:  Understand and explain briefly the organs and function of the urinary system  Understand and explain in detail the anatomy of kidney including location, internal and external structure, the blood and nerve supply and also the function of the kidney.  Understand and describe in detail the structure of the nephron and the organisation of its blood supply including its function  Understand and explain in detail the renal physiology including mechanism of urine formation, glomerular filtration, tubular reabsorption, tubular secretion and hormonal regulation and homeostasis Slide 2 of 41 PHA112 Renal WEEK 16 Slide 3 of 41 Urinary System PHA112 Renal WEEK 16 Slide 4 of 41 Urinary System PHA112 Renal WEEK 16 Urinary System •Are paired, bean-shaped organs •Located along the back body wall below the diaphragm and adjacent to the vertebral column • Right kidney lower than the left because liver occupies larger area above the kidney on the right side Slide 5 of 41 PHA112 Renal WEEK 16 Structure of Kidney 8-18 2-3 Slide 6 of 41 PHA112 Renal WEEK 16 Slide 7 of 41 Structure of Kidney MPharm PHA112 Renal WEEK 16 Blood and Nerve Supply • Renal arteries deliver ~ 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 Slide 8 of 41 PHA112 Renal WEEK 16 Slide 9 of 41 Blood Supply of Kidney PHA112 Renal WEEK 16 Slide 10 of 41 Renal Blood Supply PHA112 Renal WEEK 16 Functions of the Kidney • 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 Slide 11 of 41 MPharm PHA112 Renal WEEK 16 Functions of the Kidney 1,25 dihydroxycholecalciferol or 1,25-dihydrooxyvitamin D3 or calcitriol Slide 12 of 41 PHA112 Renal WEEK 16 Nephron • Structural and functional units that form urine • ~1 million per kidney • Each nephron consists • Renal corpuscle: an initial filtering component • Renal tubule: Extends from the renal corpuscle Slide 13 of 41 PHA112 Renal WEEK Nephron 16 Slide 14 of 41 PHA112 Renal WEEK Nephron 16 Slide 15 of 41 PHA112 Renal WEEK Nephron 16 • Cortical nephrons make up about 80–85% of the 1 million microscopic nephrons • Their renal corpuscles are located in the outer portion of the cortex, with short loops of Henle that penetrate only a small way into the medulla. • The ascending limbs of their loops of Henle consist of only a thick segment, lacking any thin portions. • Nephrons with short loops receive their blood supply from peritubular capillaries that arise from efferent arterioles. Slide 16 of 41 PHA112 Renal WEEK Nephron 16 • The other 15–20% of the nephrons are juxtamedullary nephrons . • Their renal corpuscles lie deep in the cortex, close to the medulla, and they have long loops of Henle that extend into the deepest region of the medulla. • The ascending limbs of their loops of Henle consist of both thin and thick segments. • Nephrons with long loops receive their blood supply from the vasa recta that arise from peritubular capillaries before becoming peritubular venules Slide 17 of 41 MPharm PHA112 Renal WEEK Nephrons 16 Slide 18 of 41 PHA112 Renal WEEK Nephrons 16 • The distal convoluted tubules of several nephrons empty into a single collecting duct. • Collecting ducts unite and converge into several hundred large papillary ducts which drain into the minor calyces, major calyces, renal pelvis, and ureters. Slide 19 of 41 PHA112 Renal WEEK 16 Functions of Nephron Slide 20 of 41 PHA112 Renal WEEK 16 Slide 21 of 41 Renal Corpuscle Glomerular (Bowman’s) capsule and glomerulus PHA112 Renal WEEK 16 Slide 22 of 41 Renal Corpuscle Glomerular (Bowman’s) capsule and glomerulus PHA112 Renal WEEK 16 Slide 23 of 41 Glomerular Filtration PHA112 Renal WEEK Glomerular Filtration 16 Total Amount in Plasma Amount in 180 L of filtrate (/day) Amount returned to blood/d (Reabsorbed) Amount in Urine (/day) Water (passive) 3L 180 L 178-179 L 1-2 L Protein (active) 200 g 2g 1.9 g 0.1 g 3g 162 g 162 g 0g 1g 40 g 24 g 30 g (about 1/2) (about 1/2) Glucose (active) Urea (passive) 0.03 g Creatinine Slide 24 of 41 PHA112 1.6 g Renal 0g (all filtered) 1.6 g (none reabsorbed) WEEK 16 Glomerular Filtration Net filtration pressure = 55-30-15=10mmHg Slide 25 of 41 PHA112 Renal WEEK 16 Glomerular Filtration Regulation Slide 26 of 41 PHA112 Renal WEEK 16 Glomerular Filtration Regulation • Two hormones contribute to regulation of GFR • Angiotensin II is a potent vasoconstrictor of both afferent and efferent arterioles (reduces GFR). • A sudden large increase in BP stretches the cardiac atria and releases atrial natriuretic peptide (ANP). • ANP causes the • glomerulus to relax, • increasing the surface • area for filtration Slide 27 of 41 PHA112 Renal WEEK 16 Glomerular Filtration Regulation Slide 28 of 41 PHA112 Renal WEEK Reabsorption Routes 16 Tubule cell Fluid in tubule lumen Na+ Peritubular capillary Na+ Na+ Paracellular reabsorption ATP ADP Na+ Na+ Na+ Na+ Key: Transcellular reabsorption Diffusion Basolateral membrane Apical membrane Slide 29 of 41 Sodium–potassium pump (Na+/K+ ATPase) Tight junction Interstitial fluid PHA112 Active transport Renal Reabsorption in PCT WEEK 16 Fluid in tubule lumen Proximal convoluted tubule cell ATP 2 Na+ Glucose Na+ Peritubular capillary Na+ Na+ ADP Key: Glucose Tight junction Glucose Interstitial fluid PHA112 Na+–glucose symporter Glucose facilitated diffusion transporter Diffusion Sodium–potassium pump Brush border (microvilli) Slide 30 of 41 Other Na+ symporters in the PCT follow similar way • HPO42- (phosphate), SO42- (sulfate) ions • all amino acids and lactic acid Renal WEEK 16 Reabsorption in PCT Na+ reabsorption and H+ secretion via secondary active transport through apical membrane CO2=Carbon dioxide H2CO3=carbonic acid CA=carbonic anhydrase Slide 31 of 41 PHA112 Renal WEEK 16 Reabsorption in PCT HCO3 reabsorption CO2=Carbon dioxide H2CO3=carbonic acid CA=carbonic anhydrase Slide 32 of 41 PHA112 Renal WEEK 16 Reabsorption in PCT Passive reabsorption in second half of the PCT Slide 33 of 41 PHA112 Renal WEEK 16 Reabsorption in Thick ascending limb of Loop of Henle Reabsorbs 15% of filtered water;20-30% filtered Na+ and K+; 35% of filtered Cl-;10-20% of filtered HCO3- and variable amount of filtered Ca2+ and Mg2+ Slide 34 of 41 PHA112 Renal WEEK 16 Reabsorption in Distal convoluted tubule and in collecting duct Reabsorption of Na+ and secretion of K+; Slide 35 of 41 PHA112 Renal Hormones and Homeostasis WEEK 16 •Five hormones affect the extent of Na+, Cl–, Ca2+, and water reabsorption as well as K+ secretion by the renal tubules. These hormones, all of which are key to maintaining homeostasis of not only renal blood flow and B.P., but systemic blood flow and B.P., are: • angiotensin II • antidiuretic hormone (ADH) • aldosterone • atrial natriuretic peptide (ANP) • parathyroid hormone (PTH) Slide 36 of 41 PHA112 Renal WEEK 16 Slide 37 of 41 Hormones and Homeostasis PHA112 Renal Hormones and Homeostasis WEEK 16 • Antidiuretic hormone (ADH) is released by the posterior pituitary in response to low blood flow in this part of the brain. • ADH affects facultative water reabsorption by increasing the water permeability of principal cells in the last part of the distal convoluted tubule and throughout the collecting duct. • In the absence of ADH, the apical membranes of principal cells are almost impermeable to water Slide 38 of 41 PHA112 Renal Hormones and Homeostasis WEEK 16 • Parathyroid hormone (PTH) is released by the parathyroid gland. • Stimulates cells in early distal convoluted to reabsorb Ca2+ into the blood • Inhibits HPO42- (phosphate) reabsorption in proximal convoluted tubule thereby promoting phosphate excretion Slide 39 of 41 PHA112 Renal WEEK 16 Summary of filtration, reabsorption and secretion in nephron and collecting duct Slide 40 of 41 PHA112 Renal WEEK 16 Further Reading refer to the following textbooks • Ross and Wilson Anatomy and Physiology in Health and illness 13th Edition • Gerard J. Tortora and Byran H. Derrickson Principles of Anatomy and Physiology 13th Edition • Frederic H. Martini Fundamentals of Anatomy & Physiology 7th Edition • Lauralee Sherwood Human Physiology From Cells to Systems 7th Edition • Robert G. Carroll Elsevier’s Integrated Physiology Slide 41 of 41 PHA112 Renal