Physiology of Urinary System PDF

S 1 L1 Physiology of Urinary System Explain by Ahmed Basim Mohammed Prepared by Abbas Azhar Sahib The Objective: Functions of the kidneys in homeostasis Physiologic anatomy of the kidneys: 1-General orga...

S 1 L1 Physiology of Urinary System Explain by Ahmed Basim Mohammed Prepared by Abbas Azhar Sahib The Objective: Functions of the kidneys in homeostasis Physiologic anatomy of the kidneys: 1-General organization of the 2- The nephron is the functional kidneys and urinary tract unit of the kidney Regional differences in nephron 3- Blood Supply of Nephrons structure The Juxtaglomerular Apparatus The Objective: Urine Formation 1.Glomerular Filtration : Glomerular Capillary Membrane Glomerular Filtration Rate (Filtration Barrier) (GFR) Regulation of the GFR Net Filtration Pressure (NFP) * Glomerular capillary filtration coefficient (Kf) Functions of the kidneys in homeostasis 1- Regulation of water and electrolyte balances. 2- Excretion of metabolic waste products, like; urea, creatinine, uric acid, bilirubin and metabolites of various hormones. 3- Excretion of foreign chemical, like drugs, pesticides, and food additives. 4- Regulation of arterial blood pressure. Functions of the kidneys in homeostasis 5- Regulation of Erythrocyte production ; the kidneys synthesis and secrete erythropoietin (EPO). 6- Regulation of Vit D activity ; the kidneys produce 1, 25–dihydroxyvitamin D3 7- Gluconeogenesis: the kidneys synthesize glucose from amino acids. 8- Regulation of acid-base balance. Physiologic anatomy of the kidneys 1-General organization of the kidneys and urinary tract The two kidneys lie on the posterior wall of the abdomen, outside the peritoneal cavity. Each kidney of the adult human weighs about 150 grams and is about the size of a clenched fist. The kidney has outer cortex and the inner medulla. The renal pyramids base originates at the border between the cortex and medulla and terminates in the papilla, which projects into the renal pelvis. The outer border of the pelvis has major calyxes that divide into minor calyxes. The walls of the calyxes, pelvis, and ureter contain contractile elements that propel the urine toward the bladder. Physiologic anatomy of the kidneys 1-General organization of the kidneys and urinary tract Physiologic anatomy of the kidneys 2- The nephron is the functional unit of the kidney Each kidney in the human contains about 1 million nephrons, each nephron consists of a "filtering component" called the glomerulus (which is responsible for the initial step in urine formation, the separation of a protein-free filtrate from plasma), and a tubule extending out from the glomerulus. The glomerulus; consists of a compact tuft of interconnected capillary loops (the glomerular capillaries) and a balloon like hollow capsule (Bowman's capsule) into which the capillary tuft protrudes. One way of visualizing the relationship between the glomerular capillaries and Bowman's capsule is to imagine, a loosely clenched fist (the capillaries) punched into a balloon (Bowman's capsule). Physiologic anatomy of the kidneys 2- The nephron is the functional unit of the kidney The part of Bowman's capsule in contact with the glomerular capillaries becomes pushed inward but does not make contact with the opposite side of the capsule; a space (Bowman's space) still exists within the capsule, and it is into this space that fluid filters from the glomerular capillaries across the combined capillary-Bowman's capsule membranes. Physiologic anatomy of the kidneys 2- The nephron is the functional unit of the kidney Bowman's capsule connects at the side opposite the glomerular tuft with the first portion of the tubule (a single layer of epithelial cells resting on a basement membrane), into which this filtered fluid then flows into the proximal tubule (in the cortex), then into the loop of Henle (U-shaped), which dips into the renal medulla. Each loop consists of a descending and an ascending limb. The walls of the descending limb and the lower end of the ascending limb are very thin called the thin segment of the loop of Henle. After the ascending limb of the loop has returned partway back to the cortex, its wall becomes thicker called the thick segment of the ascending limb. Physiologic anatomy of the kidneys 2- The nephron is the functional unit of the kidney At the end of the thick ascending limb is a short segment, which is a plaque in its wall, known as the macula densa. Beyond the macula densa, fluid enters the distal tubule in the renal cortex. Physiologic anatomy of the kidneys 2- The nephron is the functional unit of the kidney This is followed by the cortical collecting tubule then cortical collecting duct. The initial parts of 8 to 10 cortical collecting ducts join to form a single larger collecting duct that runs downward into the medulla and becomes the medullary collecting duct. The collecting ducts combine to form progressively larger ducts that empty into a calyx of the renal pelvis, the calyx is continuous with the ureter, which empties into the urinary bladder, where urine is temporarily stored. In each kidney, there are about 250 of the very large collecting ducts, each of which collects urine from about 4000 nephrons. Physiologic anatomy of the kidneys 3- Blood Supply of Nephrons The renal artery enters the kidney through the hilum and then branches progressively to form the interlobar arteries, arcuate arteries, interlobular arteries (also called radial arteries) and afferent arterioles, which lead to the glomerular capillaries (Thus, the afferent arteriole is the "arm" to which the "fist" is attached). Normally, only about 20% of the plasma (without erythrocytes) entering the glomerular capillaries is filtered into Bowman's capsule. Physiologic anatomy of the kidneys 3- Blood Supply of Nephrons The distal ends of the capillaries of each glomerulus coalesce to form the beginning of the venous system. The glomerular capillaries instead recombine to form another set of arterioles called the efferent arterioles, which leads to a second capillary network, the peritubular capillaries that surrounds the renal tubules, an arrangement that permits the movement of solutes and water between the tubular lumen and capillaries. Physiologic anatomy of the kidneys 3- Blood Supply of Nephrons The renal circulation is unique in that it has two capillary beds, the glomerular and peritubular capillaries, which are arranged in series and separated by the efferent arterioles. The peritubular capillaries empty into the vessels of the venous system, which run parallel to the arteriolar vessels and progressively forms the interlobular vein, arcuate vein, interlobar vein, and renal vein, which leaves the kidney beside the renal artery and ureter. Physiologic anatomy of the kidneys 3- Blood Supply of Nephrons Physiologic anatomy of the kidneys Regional differences in nephron structure: In humans, approximately 80% of the nephrons originate in glomeruli located in the outer cortex (superficial and intermediate areas of the cortex), and have relatively short loops of Henle, which may extend only into the outer medulla ; they are known as outer cortical nephrons. The remaining 20% of originate in glomeruli located in innermost cortex or juxtamedullary cortex (cortex just adjacent to the medulla), and have long loops, which extend deep into the medulla, these so called inner cortical nephrons (juxtamedullary nephrons). Physiologic anatomy of the kidneys Regional differences in nephron structure: The vascular structures supplying the juxtamedullary nephrons also differ in that their efferent arterioles drain not only into the usual peritubular- capillary network of the cortex and outer medulla but also into thin hairpin-loop vessels (vasa recta capillaries), which run parallel to the loops of Henle and collecting ducts in the inner medulla ; this arrangement has considerable significance for renal function, as will be described later. The vasa recta return toward the cortex and empty into the cortical veins. Physiologic anatomy of the kidneys Interstitial cells; which are located between adjacent tubules and capillaries, are thought to synthesizeand release prostaglandins in response to appropriate stimuli. We take it later The Juxtaglomerular Apparatus The juxtaglomerular apparatus (JGA). The JGA includes the macula densa and juxtaglomerular cells. The macula densa is a short segment of the distal convoluted tubule that is located directly adjacent to the afferent and efferent arterioles at the vascular pole of the glomerulus. Physiologic anatomy of the kidneys The Juxtaglomerular Apparatus Physiologic anatomy of the kidneys The Juxtaglomerular Apparatus *‫ﻟﻠﺘﻮﺿﻴﺢ‬ Physiologic anatomy of the kidneys The Juxtaglomerular Apparatus The juxtaglomerular cells are within the interstitium between the macula densa and the vascular pole The macula densa cells sense sodium chloride concentration in the lumen and stimulates the juxtaglomerular cells to synthesize and release renin into the bloodstream. This happens in states of hypovolemia or low sodium chloride concentration in the blood (and in the urinary filtrate). Physiologic anatomy of the kidneys The Juxtaglomerular Apparatus This activates the renin-angiotensin-aldosterone system (RAAS) and triggers several key important steps to help improve blood pressure. The release of renin in the bloodstream causes hydrolysis of angiontensinogen to form angiotensin I. Angiotensin I is converted by angiotensin- converting enzyme (ACE) to angiotensin II. Angiotensin II triggers the adrenal glands to produce and release aldosterone, whichacts on tubules to upregulate sodium and water reabsorption back into the blood. Urine Formation Urine formation is a blood cleansing function. Approximately 20% of cardiac output enters the kidneys to get rid of unwanted substances. Kidneys excrete the unwanted substances in urine. Normally, 99% of this filtrate is returned to circulation by reabsorption, so that only about 1 to 1.5 L of urine is formed every day. The mechanism of urine formation includes three processes: I. Glomerular filtration II. Tubular reabsorption III. Tubular secretion. Among these three processes filtration is the function of the glomerulus. Reabsorption and secretion are the functions of tubular portion of the nephron.  Urine Formation Urinary excretion rate = Glomerular filtration rate – Tubular reabsorption rate + Tubular secretion rate Urine Formation 1.Glomerular Filtration : The filtered fluid is the first process of urine formation, when the blood passes through the glomerular capillaries, the plasma is filtered into the Bowman’s capsule via the filtration membrane. The filtered fluid is essentially protein-free and devoid of cellular elements. Urine Formation 1.Glomerular Filtration : Glomerular Capillary Membrane (Filtration Barrier) This glomerular filtration barrier consists of three layers: 1. Capillary Endothelium 2. Basement membrane 3. Epithelial Cells layer 1.Glomerular Filtration : Glomerular Capillary Membrane (Filtration Barrier) 1. Capillary Endothelium : It is a single layer of endothelial cells attached to the basement membrane, containing many pores perforate called fenestra or filtration pores with a diameter of 0.1 μ. 2. Basement Membrane : The basement membrane is a relatively homogenous a cellular meshwork of glycoproteins and mucopolysaccharides. The basement membrane separates the endothelium of glomerular capillary and the epithelium of visceral layer of Bowman’s capsule. 1.Glomerular Filtration : Glomerular Capillary Membrane (Filtration Barrier) 3. Epithelial Cells layer: This is composed of a single layer of capsular epithelial cells resting on a basement membrane. The epithelial cells in this region of the glomerulus are called Podocytes; they have an unusual octopus like structure in that they possess a large number of extensions, or foot processes, which are embedded in the basement membrane, foot processes from adjacent podocytes manifesting a great degree of interdigitation (intertwine). Filtration Slits exist between adjacent foot processes and constitute the path through which the filtrate fluid, a thin diaphragm between the slits acts as a final filtration barrier before the fluid enters Bowman's space. 1.Glomerular Filtration : Ultrafiltration : The glomerular filtration is called ultrafiltration because even the minute particles are filtered. But, the plasma proteins are not filtered due to their large molecular size. The protein molecules are larger than the slit pores present in the endothelium of capillaries. Thus, the glomerular filtrate contains all the substances of plasma except the plasma proteins. Despite the high filtration rate of the glomerular capillary membrane, it has a high degree of selectivity. 1.Glomerular Filtration : This selectivity of the glomerular capillary membrane depends on: 1- Size of the molecules (filterability is inverselyrelated to the size of the molecules). Thismeans the red and white blood cells, platelets, albumin, and other proteins are too large to pass through the filter (remain in capillary πG =32). 1.Glomerular Filtration : This selectivity of the glomerular capillary membrane depends on: 2- Electrical charge of the molecules (negatively charged molecules are restricted during filtration unlike positively charged molecules of equal size, this due to the negative charges present in all 3 layers of the glomerular capillary membrane which restrict filtration of plasma proteins). The diameter of the albumin (protein) is about 6 nanometers, whereas the pores of the glomerular membrane are about 8 nanometers but albumin is restricted from filtration. Glomerular Filtration Rate (GFR) The volume of filtrate formed by both kidneys per minute. It is a valid indicator of kidney function. The heart pumps about 5 L blood per minute under resting conditions. Approximately 20 % or 1 L enters the kidneys to be filtered. In this Litter, The Normal GFR is 125 mL (0.125 L) per minute, or about 180 L per day. Factors that regulate GFR at the capillary beds are: 1. Filtration membrane permeability. 2. Net filtration pressure (NFP). 3. Total surface area available for filtration (Kf). Glomerular Filtration Rate (GFR) Regulation of the GFR GFR = Kf Χ Net filtration pressure According to Starlings hypothesis, the Net filtration pressure (NFP) for any capillary is the algebraic sum of the opposing hydraulic and colloid osmotic (oncotic) pressures acting across the capillary. This Law also applies to the glomerular capillaries : Regulation of the GFR NFP = (PG + πB) – (PB + πG) Forces inducing filtration. Forces opposing filtration. Where PG = Glomerular Capillary Hydrostatic Pressure πB = Bowman’s Capsule Colloid Osmotic Pressure PB = Bowman’s Capsule Hydrostatic Pressure πG = Glomerular Capillary Colloid Osmotic Pressure Regulation of the GFR Because there is virtually No protein in Bowman’s Capsule, πB may be taken as zero so that the equation becomes : Net Filtration Pressure (NFP) NFP = PG – PB – πG (1)Forces Favoring Filtration (mmHg) NFP = 60 –18 – 32 = Glomerular Hydrostatic Pressure (PG) 60 +10 mm Hg. Bowman’s Capsule Colloid Osmotic Pressure (πB) 0 (2)Forces Opposing Filtration (mmHg) Bowman’s Capsule Hydrostatic Pressure (PB) 18 Glomerular Capillary Colloid Osmotic Pressure (πG) 32 Regulation of the GFR * ↑ PB (Kidney stones), ↓ GFR and vice versa but it is not a primary factor regulating GFR. * ↑ πG (↑ plasma proteins concentration, no filtration), ↓ GFR, and vice versa * ↑ PG (is the primary factor for regulation of GFR), ↑ GFR and vice versa. PG is affected by renalartery pressure or renal blood flow (positive relationship), and resistance R (negative relationship). Regulation of the GFR * Vasodilation in afferent arterioles ↑diameter ↓ RA leads to ↑ RBF , ↑ PG , and ↑ GFR. Conversely in vasoconstriction ↓diameter ↑ RA leads to ↓ RBF , ↓ PG , and ↓ GFR. * Vasodilation of efferent arterioles ↑diameter ↓ RE leads to ↑ RBF , ↑ πG , and ↓ GFR. -Moderate vasoconstriction ↓diameter ↑ RE leads to ↓RBE (slight),↑PG ,and ↑GFR (slight). - But in Sever vasoconstriction leads to ↓GFR Regulation of the GFR Regulation of the GFR * Glomerular capillary filtration coefficient (Kf): Kf is the product of the permeability and filtering surface area of the capillaries, and it is 400 times higher than other capillary systems of the body. Kf is decreased by increasing the thickness and decreasing the number of functional glomerular capillaries by disease (Hypertension). Although ↑ Kf ↑GFR and ↓Kf ↓GFR but it is not a primary factor regulating GFR. Kf = GFR/Net filtration pressure = 125 ml/min/ 10 mmHg * Normal Kf = 12.5 ml/min/mmHg of filtration pressure. Renal Handing of Some Substances A. Waste products such as creatine. B. Many electrolytes. C. Nutritional substances, such as glucose and amino acids. D. Organic acids and bases, some foreign compounds and some drugs.  S 1 L1 THANK YOU