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The Urinary System Dr. Ahmed Al-Dwairi Department of Physiology 1 Functions of the Urinary System Contributing to homeostasis Controlling electrolyte and water balance of the ECF, plus urinary output. If the ECF has an excess of water or electrolytes, the kidneys eliminate the excess. If there is a deficiency of these substances, the kidneys can reduce the loss of these from the body. Maintaining the proper osmolarity of body fluids Maintaining proper plasma volume Helping to maintain proper acid-base balance Excreting wastes of body metabolism Excreting many foreign compounds Producing erythropoietin and renin Converting vitamin D to an active form Gluconeogenesis 2 Excretion of Metabolic Waste Products • Urea (from protein metabolism) • Uric acid (from nucleic acid metabolism) • Creatinine (from muscle metabolism) Secretion, Metabolism, and Excretion of Hormones Hormones produced in the kidney • Renal erythropoetic factor • 1,25 dihydroxycholecalciferol (Vitamin D) • Renin Hormones metabolized and excreted by the kidney • Most peptide hormones (e.g. insulin, angiotensin II, etc.) Body fluid regulation 5 Guyton and Hall, Medical physiology 11th edition. • Appearance – – – – Clear = normal Cloudy = ? Infection If sediment = kidney disease Dark = ?blood, ?bilirubin, ?concentrated • Color – Urochrome pigment = yellow • comes from breakdown of hemoglobin – Concentration • More Concentrated = Deeper Yellow – Change of Color From: • Meds – Vitamin = yellow • Diseases – Blood = red-brown – Liver = Orange • Foods – Rhubarb = red-brown • Odor – Normal = ammonia-like smell • from breakdown of urea – Unpleasant = ? infection • Quantity – Average per 24 hours = 1500 cc • 60 cc per hour • GFR = 125 cc/min – Thus, 7500 cc/ hour • Urine Made Per Hour = 60 cc • GFR, Per Hour = 7500 cc – KEY: 1 % of filtered urine remains urine; 99 % becomes reabsorbed back into blood – Oliguria = 100 - 400 cc per day – Anuria = less than 100 cc per day – Polyuria = diabetes, nerves, diuretics • Specific Gravity – – – – Determines Concentration Compares Test Liquid to H2O Normal = 1010 - 1030 In many kidney diseases, one loses the ability to concentrate urine • Protein – OK to have a Trace in the urine – Benign Conditions: • exercise • exposure to cold • protein consumption – Generally Means Kidney Disease • Glucose • pH – Determines Acidity or Alkalinity – Normal = 6.0 – Range = 4.5 - 8.0 • Acidity example = diabetes • Alkaline example = UTI – Will only be in urine if exceed Renal Threshold. • Ketone – Ketones are products of Fat Metabolism – If cant breakdown Sugars for energy, the body will begin using Fat – Seen in: • Uncontrolled Diabetes • Starvation • Hi-Fat Diet Physiological Anatomy Kidneys– The functional units of the system Ureters Urinary Bladder Conducting & Storage components Urethra 9 Physiological anatomy: • 1. General organization : – 150 gm, size of a clenched fist. – Consists of capsule, outer cortex, and inner medulla. – Medulla (renal pyramids) papilla renal pelvis ureter bladder urethra • 2. Renal blood supply : – 22% C.O 1100 ml/min . – Renal artery interlobar arteries arcuate arteries interlobular arteries afferent arterioles glomerular capillaries efferent arterioles peritubular capillaries venous system . Physiologic Anatomy Each kidney is supplied by a renal artery and renal vein. The kidney acts on the blood plasma flowing through it. As urine is formed, it drains into the renal pelvis and is channeled into the ureter. The urine is stored in the urinary bladder. It is emptied periodically through the urethra. The urethra serves the urinary and reproductive tracts in the male. 12 13 Guyton and Hall, Medical physiology 11 th edition. The nephron; the functional unit of the kidney Nephron is the smallest unit that can perform all the functions of the kidney. Each kidney has about one million nephrons. Kidney layers: • Cortex: the outer layer, looks glomerular. • Medulla: the inner layer made up of striated triangles; the renal pyramids. The nephrons are arranged through the cortex and medulla of the kidney. Each nephron consists of: i. Vascular component ii. Tubular component. 14 i. The vascular component; the dominant portion of the nephron 15 ii. The tubular component; a hollow tube with different regions • Renal corpuscle – the glomerulus and its Bowman’s capsule Juxtaglomerular Apparatus Combined vascular/tubular microscopic structure in the kidney regulating the function of each nephron Between the vascular pole of the renal arterioles and the returning distal convoluted tubule of the same nephron Cellular components of the apparatus: Macula densa of the distal convoluted tubule, • Senses any increase in sodium chloride concentration in the distal tubule of the kidney and secretes a locally active (paracrine) vasopressor which acts on the adjacent afferent arteriole Smooth muscle cells of the afferent arteriole Juxtaglomerular cells (granular cells), Secrete renin 17 Types of Nephrons 1. Cortical nephron Glomeruli in outer cortex & short loops of Henle that extend only short distance into medulla Majority of nephrons Cortical interstitial fluid 300 mOsmolar 2. Juxtamedullary nephron Glomeruli in inner part of cortex & long loops of Henle which extend deeply into medulla Blood flow through vasa recta in medulla is slow This nephron maintains osmolality in addition to filtering blood and maintaining acid-base balance 18 Basic Processes of the Nephron Glomerular filtration is the first process. A protein-free plasma is filtered from the glomerulus into the Bowman’s capsule. Blood cells are not normally filtered. Normally about 20 % of the plasma is filtered. Glomerular filtrate is produced at the rate of 125 ml per minute (180 liters per day). • The 80% of the plasma not filtered passes into the efferent arteriole and through the peritubular capillaries. Tubular reabsorption, filtered substances move from the inside of the tubular part of the nephron into the blood of the peritubular capillaries. The reabsorption rates of most substances are very high. (of the 180 liters filtered, 178.5 liters are reabsorbed) Tubular secretion is a selective process by which substances from the peritubular capillaries enter the lumen of the nephron tubule. Urine excretion results from these three processes = GF – TR + TS 19 Renal Handling of Different Substances Figure 26-10 Glomerular Filtration 21 Renal Handling of Water and Solutes Filtration Reabsorption Excretion Water (liters/day) 180 179 Sodium (mmol/day) 25,560 25,410 Glucose (gm/day) 180 180 0 Creatinine (gm/day) 1.8 0 1.8 1 150 Glomerular Filtration GFR = 125 ml/min = 180 liters/day • Plasma volume is filtered 60 times per day • Glomerular filtrate composition is about the same as plasma, except for large proteins • Filtration fraction (GFR/Renal Plasma Flow) = 0.2 (i.e., 20% of plasma is filtered) Nephron Filtration Membrane 1. The wall of the glomerular capillaries, which is a single layer of flattened endothelial cells. It is perforated by many large pores that make it over 100 times more permeable to H2O and solutes than capillaries elsewhere in the body. 2. The basement membrane, which is an acellular (lacking cells) gelatinous layer. 3. The inner layer of Bowman’s capsule, which consists of podocytes, octopus-like cells that encircle the glomerular tuft. 24 The filtration membrane 25 Guyton and Hall, Medical physiology 11 th edition. Why huge GFR? • 1) Most waste product are removed rapidly • 2) Allow all body fluids to be filtered and processed by kidneys many times each day . 60 times/day high GFR provides precise & rapid control over body fluids (volume, composition) Effects of size and electrical charge of dextran on filterability by glomerular capillaries. Figure 26-12 Glomerular Filtration Forces No active transport mechanisms or local energy expenditure are involved in in moving fluid across the glomerular membrane into Bowman’s capsule. Passive physical forces, with the same principles of fluid dynamics are involved in filtration: 1. The glomerular capillary hydrostatic pressure is the result of the blood pressure pushing on the inside of the capillary wall (e.g., 60 mm Hg). • 2. The plasma-colloid osmotic pressure is due to the retention of plasma proteins in the blood of the glomerulus. • 3. It is the major force that induces glomerular filtration. Depends contraction of the heart, and afferent/efferent arteriolar resistance. The concentration of water is higher in the glomerulus. Water tends to return to the blood in the glomerulus by osmosis (32 mm Hg). The capsule hydrostatic pressure tending to move fluid from the Bowman’s capsule into the glomerulus (18 mm Hg). • Net filtration pressure PG – PB – VTG + VTB 60 – 18 – 32 + 0 = 10 mmHg • K= 12.5 ml/min/mmHg Glomerular Filtration Rate (GFR) Glomerular Filtration Rate (GFR): the total amount of filtrate formed per minute by the kidneys GFR regulation is mainly due to changes in the glomerular capillary blood pressure; a higher arterial blood pressure supplying the glomerulus can increase the GFR. 30 Factors that affect GFR 1. ↓ Glomerular capillary filtration coefficient ↓ GFR e.g.: chronic uncontrolled hypertension, DM 2. ↑ Bowman's capsule hydrostatic pressure ↓ GFR e.g.: stones Glomerular Capillary Filtration Coefficient (Kf) • Kf = hydraulic conductivity x surface area • Normally it is not highly variable • Disease that can reduce Kf and GFR - chronic hypertension - obesity/diabetes mellitus - glomerulonephritis 3. ↑ Glomerular capillary colloid osmotic pressure ↓ GFR: Averages 32 mmHg and this pressure is determined by: 1. Arterial plasma colloid osmotic pressure 2. Fraction of plasma filtered (filtration Fraction) increased by: ↑GFR or ↓renal plasma flow 4. ↑ Glomerular capillary hydrostatic pressure ↑ GFR : Important in physiological regulation of GFR this pressure is determined by: 1. Arterial pressure 2. Afferent arteriolar resistance 3. Efferent arteriolar resistance this has biphasic effect: Moderate ↑resistance slight ↑ GFR Severe constriction ↓ GFR Effect of change in afferent arteriolar resistance or efferent arteriolar resistance on glomerular filtration rate and renal blood flow. Regulation of GFR and renal blood flow Changes in the GFR primarily result from changes in glomerular capillary blood pressure. Changes in plasma colloid osmotic pressure and Bowman’s capsule hydrostatic pressure are not subject to regulation and do not vary much under normal conditions. Uncontrolled shifts in the GFR can lead to fluid and electrolyte imbalances. Three basic mechanisms to keep relatively constant GFR despite changing mean arterial pressure 1. Autoregulation 2. Tubuloglomerular feedback mechanism 3. ANS and Hormones. 37 38 Renal blood flow control • • • • Autoregulation of GFR and Renal blood flow : GFR remains constant if the Arterial pressure ranges from 75 to 160 mmHg. Normally filtration= 180 /day, reabs.= 178.5/day urine=1.5 /day Without autoregulation if pressure ↑ by 25% GFR = 225 L/day If reabsorption is constant urine= 46.5 L/day. 30 folds increase in urine formation depletes the body Renal blood flow: 1100 ml/min 22% c.o large fraction of O2 is consumed by the kidneys due to the high rate of active sodium reabsorption by the tubules Regulation of GFR 1. Autoregulation; myogenic, altering the caliber of the afferent arterioles due to stretch. • If the GFR rises by increased arterial pressure, the afferent arterioles constrict. This lowers the GFR. • If the GFR decreases, the afferent arterioles dilate. This increases the GFR. 41 Renal blood flow control (cont.) Sympathetic N.S : Strong activation↓GFR and flow Moderate activation little effect Sympathetic nervous system plays an important role on adjusting glomerular blood flow, while parasympathetic nervous system does not have any influence on the kidneys. Sympathetic innervation to afferent arterioles, vasoconstriction Stimulated when blood pressure drops to reduce GFR and conserve fluid volume. Stimulation of sympathetic nerves increases the release of renin by the kidneys Renal blood flow control(cont.) Hormones and autacoids: Norepinephrine , epinephrine, endothelin constrict renal blood vessels and decreases GFR Angiotensin II constricts efferent arterioles ↑GFR - ↑ Na, H2O reabsorption. Endothelial - Derived Nitric oxide decreases resistance and ↑ GFR Prostaglandins, bradykinin cause vasodilatation Regulation of GFR Tubuloglomerular feedback mechanism. sensing changes in flow in the nephron’s tubular component. • The cells of the macula densa monitor NaCl concentration in the fluid moving into the distal convoluted tubule. – If GFR increases, then NaCl movement also increases – Macula densa cells send a paracrine message causing the afferent arteriole to contract, decreasing GFR and NaCl movement 44 • Autoregulation and glomerulotubular balance try to maintain a constant GFR these processes are not 100% effective so ↑BP will always lead to ↑GFR (pr. Diuresis or pr. Natriuresis) . Baroreceptor reflex influence on the GFR in long-term regulation of arterial blood pressure 46