Lecture – 1: Introduction to renal system RENAL SYSTEM PHYSIOLOGY Dr Shahab Shaikh PhD, MD College of Medicine Al Maarefa Colleges of Science & Technology College of Medicine Al Maarefa Colleges of Science & Technology

INTRODUCTION Kidneys, Ureters, Bladder and Urethra make up the Renal or Urinary system. The kidneys play a major role in maintaining homeostasis through the regulation of water homeostasis, electrolyte composition, regulation of extracellular volume (thus blood pressure), and acid– base homeostasis. 2

3 Kidneys are paired retroperitoneal organs lying on the posterior abdominal wall, extending from approximately T12 to L3. Each kidney consists of an outer renal cortex and an inner renal medulla. Kidney The renal medulla is divided into, the renal pyramids. The apex of each renal pyramid (renal papilla) is surrounded by a minor calyx. Several minor calices unite to form a major calyx, and two or three major calices unite to form the renal pelvis, which is the superior end of the ureters.

4 Excretion – metabolic end product, e.g. urea, uric acid, creatinine, bilirubin etc. – foreign substances, e.g. drugs, toxins, pesticides, food additives etc. Homeostatic function – regulate water and electrolyte balances. – regulate the osmolality of ECF. – regulate plasma ions concentration. – regulate acid-base balance. – regulate the volume of ECF. – regulate arterial blood pressure. FUNCTIONS OF KIDNEYS

5 Biosynthesis/Metabolism – Renin – Erythropoietin – Calcitriol (1,25 dihydroxy vitamin D) Converts Inactive form of Vitamin D to Active form – Other substances: Prostaglandin, Adenosine, Endothelin, Nitric Oxide, Bradykinin, Epidermal growth factor, Insulin like growth factor Glucose (gluconeogenesis) FUNCTIONS OF KIDNEYS

6 Commonly occurring clinical conditions include – Acute Kidney Injury, – Chronic Kidney Disease, – Diabetic Kidney Disease, – Nephritic And Nephrotic Syndromes, – Polycystic Kidney Disease, – Urinary Tract Obstruction, Urinary Tract Infection, – Renal Cancer Two diseases that cause the largest prevalence of kidney dysfunction (Nephropathy) are Diabetes and Hypertension. Clinical Significance

Ureters Smooth muscle-walled duct Exits each kidney at the medial border in close proximity to renal artery and vein Carry urine to the urinary bladder

Urinary Bladder Temporarily stores urine Hollow, distensible, smooth muscle-walled sac Periodically empties to the outside of the body through the urethra

Urethra Conveys urine to the outside of the body Urethra is straight and short in females In males – Much longer and follows curving course from bladder to outside – Dual function Provides route for eliminating urine from bladder Passageway for semen from reproductive organs

10 Functional unit of the kidney is the Nephron. Each human kidney has approximately 1.2 million nephrons. Based on location in kidney the nephrons are of two types: – Juxtamedullary Nephrons – Cortical Nephrons Each nephron has two components – Vascular component – Tubular component Nephron

11 The kidney cannot regenerate new nephrons. Therefore, with renal injury, disease, or normal aging, there is a gradual decrease in nephron number. Nephron After age 40, the number of functioning nephrons usually decreases about 10 percent every 10 years; thus, at age 80, many people have 40 percent fewer functioning nephrons than they did at age 40.

12 Nephron

13 Nephron

14 Types of Nephrons CORTICAL NEPHRONSJUXTA MEDULLARY NEPHRONS About 80 percent About 20 percent Glomeruli located in the outer cortex Glomeruli lie deep in the cortex Short loops of Henle that penetrate only a short distance in the medulla Long loops of Henle that extend deeply into the medulla Extensive network of peritubular capillaries Specialized peritubular capillaries called Vasa Recta.

15 Glomerulus Renal corpuscle Glomerulus Glomerular (Bowman’s) capsule Afferent arteriole Capsular space Parietal layer Visceral layer (Podocytes) Efferent arteriole

16 Glomerulus

17 The Filtration membrane is made up of three layers: 1.Capillary Endothelium 2.Basement Membrane 3.Podocytes (Epithelium) The filtration membrane allows the substances to pass through it according to their sizes and the electrical charge that they contain. THE FILTRATION MEMBRANE

18 The endothelium of the glomerular capillaries is fenestrated, with pores that are 70–90 nm in diameter. Fenestrae are relatively large but endothelial cells have negative charges that restrict the passage of plasma proteins 1. Capillary Endothelium Fenestrations Capillary endothelium Fenestrations Capillary endothelium

19 The Glomerular basement membrane is acellular and consists of meshwork of collagen and proteoglycan (extracellular matrix). It effectively prevents filtration of plasma proteins due to strong negative charges on proteoglycans. Stellate(star like) cells called mesangial cells are located between the basal lamina and the endothelium. The mesangial cells are contractile and play a role in the regulation of glomerular filtration. Mesangial cells secrete the extracellular matrix, take up immune complexes, and are involved in the progression of glomerular disease. 2. Basement Membrane Capillary endothelium Basement membrane

20 These cells have long foot-like processes that are separated by gaps called slit pores. These cells also possess negative charges. Thus essentially all layers of glomerular capillary membrane provide a barrier to the filtration of plasma proteins. 3. Podocytes Capillary endothelium Basement membrane Podocytes Filtration slits Pedicels

21 The filtration membrane is much more porous than other capillaries and so filters fluid at a high rate. Despite the high filtration rate, the filtration membrane is selectively permeable on the basis of molecular size and charge of macromolecules. – Substances <4nm are freely filtered. – 4-8nm negatively charged substances are poorly filtered, compared to neutral and positively charged ones. – Substances >8nm are not filtered. Permeability of Filtration Membrane Molecular diameter (nm) Anionic (proteins) Neutral Cationic Relative Filterability

22 It is the cup-like sac at the beginning of the tubular component of a nephron in which glomerulus is enclosed. It consists of following layers: Bowmans Capsule Visceral layer—Lies just above the glomerular basement membrane and is made of podocytes. Bowman's space (or "urinary space", or "capsular space")— Between the visceral and parietal layers, into which the filtrate enters after passing through the filtration slits. Parietal layer—A single layer of simple squamous epithelium. Does not function in filtration.

23 The juxtaglomerular apparatus is part of the kidney nephron, next to the glomerulus. It is found between where blood enters a renal corpuscle and the distal convoluted tubule of the same nephron. The juxtaglomerular apparatus consists of three cell types: – The Macula Densa Cell of the part of TAL/DCT in contact with afferent & efferent arterioles of Glomerulus of the same nephron. Detect & respond to changes in the sodium chloride levels in the distal tubule of the kidney. – Juxtaglomerular Cells specialized smooth muscle cells of the afferent arteriole going to the glomerulus secrete renin – Extra Glomerular Mesangial Cells Juxtaglomerular Apparatus

24 Urine results from these three processes. 1.Glomerular filtration - GF 2.Tubular reabsorption - TR 3.Tubular secretion - TS Urine Formation

References Human physiology by Lauralee Sherwood, 8 th edition Text Book Of Physiology by Guyton & Hall, 11 th edition Review of Medical Physiology by Ganong. 24 th edition

26 THANK YOU