Kidney Anatomy Notes PDF

INTRODUCTION...

INTRODUCTION OBJECTIVES Understand the normal gross anatomical structure and components Kidneys of the urinary system: Filter nearly 200 Kidneys - nephrons liters of fluid from our bloodstream Ureter Urinary bladder Urethra Toxins, metabolic wastes, and excess ions to leave the body in urine Position is maintained by: Supporting connective tissues : Overlying peritoneum 1. Fibrous capsule  collagen fibers Kidneys - anatomical location 2. Perinephric fat capsule  adipose tissue Contact with adjacent visceral organs 3. Renal fascia  dense, fibrous connective tissue Supporting connective tissues Retroperitoneal position  Left kidney  around T12 to L3 vertebrae Right kidney  is lower due to slight displacement by the liver. Upper portions of the kidneys  protected by the eleventh and twelfth ribs Superior surface capped by suprarenal (adrenal) gland https://images.app.goo.gl/FkhgmbuxjU1jaGvm9 Kidneys – the external view Kidneys – the internal view 3 cm Kidneys – internal anatomy Renal sinus Surrounded by a fibrous capsule Medial surface – Concave & has a vertical cleft  Frontal section through a kidney renal hilum Renal sinus reveals three distinct regions: 12 cm Lateral surface- Convex C 6 cm 1. Opens to an internal space Internal cavity within kidney Cortex (C) M known as renal sinus P 2. Point of entry of renal artery and Medulla (M) Lined by fibrous renal capsule: nerves stabilizes positions of ureter, renal Pelvis (P) 3. Point of exit for ureter and renal veins blood vessels, and nerves https://www.meiwoscience.com/urogenital-system/coronal-section-of-kidney- 3-quaters-plastinated-specimen.html  Minor calyce Renal columns Kidneys – internal anatomy Renal pelvis Bands of cortical tissue separate Cortex adjacent renal pyramids Funnel-shaped tube Frontal section through a kidney reveals Extend into medulla Renal three distinct regions: Medulla pelvis Branching extensions of the pelvis; Have distinct granular texture Forms 2-3 major calyces Cortex (Reddish brown and granular)  Kidney/renal lobe Major calyces subdivides to form several minor calyce Medulla  Consists of Pelvis  Renal pyramid Renal columns Minor calyce  cup-shaped areas that enclose the papillae  Overlying area of renal cortex Ureter Pelvis Major  Adjacent tissues of renal columns The calyces collect urine  empty it into calyces the renal pelvis  ureter  Produces urine Nephron – the functional unit Renal corpuscle Structural and functional units of the kidneys (>1 million) Urine drainage Each nephron consists of; 1. Renal corpuscle through the kidneys Spherical structure consisting of: Glomerulus Glomerular capsule  Cupshaped hollow structure (or Bowman’s capsule) 2. Renal tubule Long tubular passageway Begins at renal corpuscle Renal tubule Renal tubules & Collecting duct Renal corpuscle Blood  entry Blood  exit Renal tubule 3 cm long and has 3 major parts 1. Proximal convoluted tubule  located in cortex Exceptionally porous 2.Nephron loop/Loop of Henle  located partially capillaries  fenestrated into medulla epithelium external parietal 3. Distal convoluted tubule  located in cortex layer and internal visceral layer Collecting duct Receives filtrate from many nephrons. Podocytes are specialized epithelial Delivers urine into minor calyces via papillae Parietal layer  cells that cover the outer surfaces of of the pyramids. simple squamous Visceral layer  highly modified glomerular capillaries epithelium branching epithelial cells called podocyte  Classes of Nephron Blood vessels of Nephron 2 major groups  cortical and juxtamedullary Juxtamedullary nephrons are associated Nephron capillary bed with special capillaries called the vasa recta. Cortical Every nephron is closely associated with two nephron capillary beds: Vasa recta Juxtamedullary glomerulus Form bundles of long straight vessels nephron peritubular capillaries 85% of the nephrons in the kidneys Glomerulus Originate close to the cortex-medulla Specialized for filtration Location  cortex junction Fed and drained by arterioles—the afferent arteriole and efferent arteriole Short nephron loops Role  production of concentrated urine. Peritubular capillaries Cling closely to adjacent renal tubules and empty Have long nephron loops that deeply into nearby venules. invade the medulla Blood & Nerve supply Juxtaglomerular Complex (JGC)/apparatus Kidneys receive 20–25% of total cardiac output (1200ml blood each minute) Each nephron has a JGC Kidney receives blood through renal artery and exits through the renal JGC  regulate the rate of filtrate veins. formation and systemic blood pressure Renal plexus provides the nerve supply of the kidney and its ureter. 1. Macula densa (distal 3 populations of cells make up JGC: convoluted tubule): Salt sensor that generates paracrine chemical signals in JGC, to control vital kidney functions, including renal blood flow, glomerular  Takes place in the urinary tract: filtration, and renin release  Ureters 2. Granular/Juxtaglomerular  Urinary bladder cells -- smooth muscle cells  Urethra Transport, Storage & Elimination (afferent arteriole) Cells in the kidney that synthesize, store, and secrete the enzyme renin 3. Extraglomerular mesengial cells -- renal autoregulation of blood flow to the kidney and regulation of systemic blood pressure through the B. Hemabarathy Bharatham renin–angiotensin system NNPD 1032 Human Anatomy   Consists of 3 layers:  Pair of muscular tubes  retroperitoneal, attached to  Hollow, muscular organ  Mucosa posterior abdominal wall  Muscularis  Adventitia  Full bladder can contain 1 liter of urine  Continuation of the renal pelvis.  Located on the lower abdomen at the  Incoming urine distends the ureter pelvic region just posterior to the pubic  Penetrate posterior wall of the urinary bladder  stimulates muscularis contraction symphysis  at oblique angle  propelling of urine to bladder.  Bladder wall has three layers  similar to  Ureteral openings are slitlike rather than rounded ureter  helps prevent backflow of urine when urinary bladder contracts  The muscular layer is known as Detrusor Muscle Ureteral opening Urine does not reach the bladder through gravity alone. https://images.app.go o.gl/mmfVbPZWqP7q C3wj6 https://images.app.goo.gl/NmxumRBEmk2RKp4f8 Interior of the bladder:  Has 3 openings  2 ureters and the urethra  Area of opening  smooth, triangular region at Rugae the base of the bladder known as the TRIGONE Collapses into its basic pyramidal shape When empty Walls are thick and thrown into folds (rugae) Expands becomes pear shaped In males  The prostate lies inferior to the In females  The bladder is anterior to the Rises superiorly in the abdominal cavity, bladder neck, which empties into the urethra. vagina and uterus When full Walls stretches and thins – rugae disappear https://images.app.goo.gl/BCiAFuP2GLxtKDmX8  Male urethra  The Female Urethra  Approximately 20 cm (8 inches) long and has three regions.  Thin-walled muscular tube  Is very short (3–5 cm; 1-2 in.)  Prosthetic urethra  Drains urine from the bladder  Extends from bladder to vestibule  passes through center of prostate gland  Membranous urethra  External urethral orifice is near  Detrusor smooth muscle thickens to form the internal urethral sphincter  short segment that penetrates the urogenital anterior wall of vagina at the bladder-urethra junction diaphragm  Spongy urethra (penile urethra)  External urethral sphincter  Longest segment surrounds the urethra  skeletal muscle and is voluntarily  extends from urogenital diaphragm to external controlled urethral orifice  KIDNEY FUNCTION & GFR NB 1284 PM DR SATIRAH ZAINALABIDIN Homeostatic Functions of Urinary What u should know? System 1. Regulate blood volume and blood ❖Describe the functions of the urinary system. pressure: ◦ by adjusting volume of water lost in urine ❖Describe the glomerular filtration and factors affecting GFR: ◦ releasing erythropoietin and renin renal autoregulation 2. Regulate plasma ion concentrations: neural factors ◦ Na+, K+, Cl-, HPO42- (by controlling hormonal factors quantities lost in urine) ◦ calcium ion levels (through synthesis of calcitriol) Homeostatic Functions of Urinary System Kidney Functions Organic Waste Products 3. Help stabilize blood pH:  To concentrate filtrate by glomerular  Organic wastes that are dissolved in ◦ by controlling loss of H+ and HCO3- filtration: bloodstream: 4. Conserve valuable nutrients: ◦ failure leads to fatal dehydration ◦ Urea, creatinine, uric acid ◦ by preventing excretion while excreting  Absorbs and retains valuable materials for  Are eliminated only while dissolved in organic waste products (urea, uric acid) use by other tissues: urine 5. Assist liver to detoxify poisons ◦ sugars and amino acids  Removal is accompanied by water loss ◦ waste and foreign substances excretion  Usually produce concentrated urine: 6. Regulation of osmolarity ◦ 1200–1400 mOsm/L (4 times plasma 7. Regulation of blood glucose concentration)  Blood and Nerve supply of Basic Processes of Urine Formation Renal Physiology - Urine Formation the Kidneys 1. Filtration 1. Glomerular filtration 2. Tubular reabsorption Blood supply ◦ At the renal corpuscle 3. Tubular secretion Although kidneys constitute less than 0.5% of total ◦ Glomeruli produce about 150-180 L of body mass, they receive 20–25% of resting cardiac filtrate per day (70 times plasma volume) output II. Water and solute reabsorption: ◦ primarily along proximal convoluted tubules III. Active secretion: Nerve Supply ◦ primarily at proximal and distal convoluted tubules Renal Nerves primarily carry sympathetic outflow They regulate blood flow through the kidneys Urinary system - The nephron Excretion of a solute = glomerular filtration + secretion - reabsorption Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. https://www.youtube.com/watch?v=hiNEShg6JTI&t=24s Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Forms of Membrane Transport Basic processes of Urine Formation 1. Filtration ◦ At the renal corpuscle ◦ Glomeruli produce about 180 L of filtrate per day (70 times plasma volume) II. Water and solute reabsorption: ◦ primarily along proximal convoluted tubules III. Active secretion: ◦ primarily at proximal and distal convoluted tubules Figure 19-2 1. Glomerular Filtration Filtration Filtration  Passive  Hydrostatic pressure forces water through  Blood pressure:  Driven by gradient membrane pores: ◦ forces water and small solutes across  Nonselective (as long as the ◦ small solute molecules pass through pores membrane into capsular space molecule fits through the ◦ larger solutes and suspended materials are retained membrane)  Larger solutes, such as plasma proteins,  Occurs across capillary walls: are excluded  Heavily regulated ◦ as water and dissolved materials are pushed into  Solutes enter capsular space in renal  Glomerular filtrate interstitial fluids corpuscle: ◦ The fluid that enters the capsular space  In some sites, such as the liver, pores are large: ◦ Daily volume is 150 L in females, 180 L in males ◦ metabolic wastes and excess ions ◦ plasma proteins can enter interstitial fluids ◦ More than 99% of glomerular filtrate reabsorped into ◦ glucose, free fatty acids, amino acids, and  At the renal corpuscle: vitamins bloodstream ◦ specialized membrane restricts all circulating ◦ Only 1~2 L excreted as urine proteins Juxtaglomerular Apparatus Glomerular Filtration Glomerular Filtration  An endocrine structure that secretes:  Involves passage across a filtration membrane ◦ hormone erythropoietin  3 Components of glomerular membrane: 1. Capillary endothelium ◦ enzyme renin ◦ Are fenestrated capillaries  Plays an important role in regulation of BP and ◦ Prevent passage of blood cells extracellular fluid volume ◦ Allow diffusion of solutes, including plasma proteins 2. Lamina densa Protein Efferent arteriole is smaller ◦ Is more selective than arteriole 3. Filtration slits to produce high resistance ◦ Are the finest filters to the outflow of blood from the glomerulus ◦ Prevent passage of most small plasma proteins Figure 26–10 Net Filtration Pressure Net Filtration Pressure Net Filtration Pressure 2. Capsular hydrostatic pressure (CHP) 3. Blood Colloid Osmotic Pressure (BCOP) ◦ Pressure resulting from the presence of ◦ Opposes glomerular hydrostatic pressure suspended proteins (albumin, globulin, fibrinogen) ◦ Pressure by fluid already in the capsular ◦ Opposes filtration space & renal tubule Tends to draw water: – out of filtrate into plasma ◦ Pushes water and solutes:  Formula NFP is: Principal of microcirculation (Starling law)  out of filtrate into plasma  NFP = GBHP – CHP – BCOP 1. Glomerular blood hydrostatic pressure (GBHP)  NFP is the pressure needed to filter blood plasma from the glomerulus into the ◦ Tends to push water and solute molecules: capsular space  out of plasma into the filtrate Glomerular Filtration Rate Net Filtration Pressure Edema (GFR)  Some kidney diseases can cause edema  Is the amount of plasma ultrafiltrate that  Damaged kidneys are permeable to proteins kidneys produce each minute  Proteins are lost into the urine → blood  Averages 125 ml/min for male and 105 oncotic pressure decrease ml/min for female  interstitial fluid increased  GFR stays nearly constant, independent of  Filtrate’s oncotic pressure draw water out of systemic BP blood → NFP elevated What if the GFR is too low or too high?  GFR 3 Levels of GFR Control 3 Levels of GFR Control  Glomeruli generate about 180 liters of 1. Autoregulation (local level) 1. Autoregulation (local level) filtrate per day: 2. Hormonal regulation (initiated by 2. Hormonal regulation (initiated by ◦ 99% is reabsorbed in renal tubules kidneys) kidneys)  Glomerular filtration rate depends on 3. Autonomic regulation (by sympathetic 3. Autonomic regulation (by sympathetic filtration pressure division of ANS) division of ANS)  Any factor that alters filtration pressure alters GFR eg. drop in renal BP Renal Autoregulation Neural Regulation Hormonal Regulation 1. Myogenic Mechanism  Kidneys are richly supplied by sympathetic  Angiotensin II constricts afferents and fibers that release NE. efferents, diminishing GFR. Smooth muscle cells in afferent arterioles contract in response to elevated blood pressure  Strong stimulation (exercise or  Atrial Natriuretic Peptide relaxes mesangial hemorrhage)–afferent arterioles cells, increasing capillary surface area and 2. Tubuloglomerular Feedback constriction predominates. GFR. High GFR diminishes reabsorption ◦ Urine output is reduced, and more blood is  ANP is secreted in response to stretch Macula Densa inhibits release of nitric oxide available for other organs. of the cardiac atria due to hypervolemia. Afferent arterioles constrict Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Clinical Indication Creatinine Clearance Test  Clinical importance?  GFR is clinically important because it is a ◦ Renal disease eg. failure (acute or chronic)  Commonly used marker to estimate measurement of renal function →monitor [creatinine] in urine in a 24-hour ◦ Inability to remove excess water from body  GFR is estimated by clearance of a filtered period ◦ No/minimal urine production (oliguria/anuria) substance which is neither reabsorbed,  Creatinine is normally eliminated in the urine ◦ Edema, ascites metabolized or secreted eg. inulin, – not reabsorbed by significant amount creatinine  Creatinine is by-product of muscle metabolism  Renal clearance: and has fairly constant plasma level  If filtering by kidneys deficient, plasma Urine production is evidence of ◦ ability of kidneys to clear substance from plasma creatinine levels rises (BUT only when >60% a functioning kidneys ◦ ie. Plasma clearance = plasma volume from loss of kidney function) which substance is removed by kidney (mL/min)  RENAL What u should know? REABSORPTION  Describe the reabsorption and secretion & SECRETION processes at: ◦ proximal convoluted tubules ◦ loop of Henle ◦ distal convoluted tubules ◦ collecting ducts PM DR SATIRAH ZAINALABIDIN REABSORPTION Reabsorption routes Reabsorption  Paracellular reabsorption ◦ 50% of reabsorped material, passive process that occurs in between adjacent tubules  Useful materials are recaptured before filtrate leaves kidneys  Transcellular reabsorption  Most of the filtered water (99%) and solutes ◦ Movement through a tubule cell into the bloodstream are returned, especially in PCT  By active and passive processes ◦ eg. glucose, amino acids, urea, Na+, K+, Ca2+, Cl-, HCO3-, HPO4-  Small proteins and peptides reabsorbed by pinocytosis Reabsorption Routes Reabsorptive & Secretory SECRETION The Transport Mechanism  Ejects unwanted substances from blood into  Solutes move in one direction urine.  Either passive or active  Is the transfer of materials from the blood  Involve combination of: and tubule cells into tubular fluid ◦ Diffusion  Eg. H+, K+, NH4-, creatinine, drugs ◦ Osmosis  Purpose: ◦ Channel-mediated diffusion ◦ Secretion of H+ controls blood pH ◦ Carrier-mediated transport: 1. Primary active transport – uses ATP eg. Na+/K+ ◦ Elimination of toxic wastes pumps Transport Mechanism https://www.youtube.com/watch?v=Jc1tnPN_lzY Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.  2. Secondary active transport: Renal transport systems  Facilitated diffusion (ion’s electrochemical gradient)  Symporters (substrate bound to carrier protein – 2 substances in 1 direction) Lots of transporter proteins  Antiporters (2 transported ions move in opposite directions for different molecules/ions eg. PCT, DCT, collecting system) so they can be reabsorbed. They all have maximum transport (TM) capacities where transport saturates i.e. 10mmol/l for glucose. Over this value, you excrete the excess in urine, so can be useful sign of disease either in kidneys or other systems.  Normally, plasma proteins and nutrients: Amino acids also have a high ◦ are removed from tubular fluid TM value because you try and ◦ by cotransport or facilitated diffusion preserve as much of these useful nutrients as possible. Renal Threshold Proximal Convoluted Tubule (PCT) Water Reabsorption  Obligatory reabsorption (90%)  Is the plasma concentration at which: ◦ a specific compound or ion ◦ “Water follows salt” ◦ begins to appear in urine ◦ Na+ Cl- ◦ At PCT and LOH  Varies with the substance involved  Transport maximum (Tm) – limit to the amount of solute that can be reabsorbed (all transporters saturated)  PCT is the  If Tm for glucose is exceeded main site for ◦ glucosuria/glycosuria reabsorption  Facultative reabsorption (10%)  If Tm for amino acids is exceeded (especially after ◦ By ADH protein-rich meal) ◦ At collecting duct ◦ aminoaciduria ◦ Via aquaporins PCT: Reabsorption Functions of the PCT PCT: Transport Mechanisms Antiporter  Reabsorption of organic nutrients Symporter ◦ > 99% glucose, amino acids, organic nutrients reabsorped via facilitated transport/cotransport.  Active reabsorption of ions ◦ Na+, K+, HCO3-, SO4-  Reabsorption of water ◦ Filtrate in PCT has the same osmotic conc. as surrounding peritubular fluid.  Passive reabsorption of ions  PCT is where the largest amount of solute ◦ Cl-, Ca2+, Mg,2+, urea via passive diffusion (especially Na+) and water reabsorbed.  Secretion  Each reabsorbed solute increase osmolarity  ◦ Eg. ammonia, toxins, organic acid & base (bile Na+- Glucose Symporters creates osmotic gradient salts, oxalates, urate, catecholamines) Na+- H+ Antiporters Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.  Transport Activities at the PCT Significance of PCT Reabsorption Loop of Henle (LOH) 65% Na , Cl and H 0 reabsorbed across the PCT + - 2 into the vascular system.  The main 100% glucose, amino acid reabsorbed. function of LOH 80~90% HCO3- reabsorbed. is reabsorption of Reabsorption occurs constantly regardless of water and salt hydration state. ▫ Not subject to hormonal regulation. Energy expenditure is 6% of calories consumed at rest. Aquaporin – 1: Membrane protein permeable to water The Loop of Henle: Reabsorption The Thin Descending Limb The Thick Ascending Limb  PCT reabsorped 65% of the filtrate (~80  Impermeable to water  Is permeable to water, but impermeable ◦ Osmosis cannot happen mL/min) to solutes  Contains active transport mechanisms:  Fluid enters LOH at ~45mL/min  As tubular fluid flows along thin ◦ Na+ - K+- 2Cl– symporters  No glucose and amino acid present in LOH descending limb: ◦ To pump 2/3 Na+ and Cl— from tubular fluid into  LOH reabsorbs about 1/2 of water, and 2/3 ◦ osmosis moves water into interstitial fluid, interstitial fluid of medulla of sodium and chloride ions remaining in leaving solutes behind  Create ↑ osmotic concentration in peritubular tubular fluid by the process of ◦ osmotic concentration of tubular fluid around thin descending limb (the opposite limb) increases  more concentrated  Cause water to move out by osmosis along countercurrent exchange  Water movement helps concentrate descending limb (+ve feedback) tubular fluid  When Na+ & Cl— removed, solute concentration in tubular fluid declines  more diluted Reabsorption in the ascending Loop Countercurrent Multiplication Main function: Reabsorp Na+ and Cl-  Is exchange that occurs between 2 parallel segments of loop of Henle:  1. The ascending loop: ◦ Actively cotransports Na+ and Cl- ions out of the tubule lumen into the interstitium. It is impermeable to H2O.  2. The descending loop: ◦ is freely permeable to H2O but relatively impermeable to NaCl  The H2O that moves out of tubule into the interstitium is removed by vasa recta Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Vasa recta Benefits of Countercurrent Multiplication  Vasa recta maintains the layers of osmotic gradients by acting as countercurrent 1. Efficiently reabsorbs solutes and water: exchanger ◦ before tubular fluid reaches DCT and  Provide O2 & nutrient to the loop of Henle and collecting system duct cells 2. Establishes concentration gradient:  Form loops like nephron loops in the medulla ◦ that permits passive reabsorption of water  Incoming and outgoing blood will have from tubular fluid in collecting system similar osmolarity. ◦ Is regulated by antidiuretic hormone  This maintains medulla (ADH) concentration gradient. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Distal Convoluted Tubule (DCT) Reabsorption & Secretion at DCT Reabsorption at DCT  Only 15–20% of initial filtrate volume  Actively transport Na+ and Cl— out of reaches DCT tubular fluid by Na+ - Cl– symporters  The main  80% H2O already reabsorped at this point  Also reabsorb tubular Na+ in exchange function for DCT is  Concentrations of electrolytes and organic for K+ secretion (Na+-K+ pumps) secretion of H+ wastes in arriving tubular fluid no longer  The ion pumps are also controlled by and wastes resemble blood plasma aldosterone  Selective reabsorption or secretion,  The DCT is also the primary site for Ca2+ primarily along DCT, makes final adjustments in solute composition and reabsorption  regulated by parathyroid volume of tubular fluid hormone (PTH) & calcitriol Secretion at DCT Secretion at DCT Tubular Secretion and Solute Reabsorption at DCT  Rate of K+ and H+ secretion rises or falls  By H+ removal and bicarbonate according to concentrations in interstitial fluid production at kidneys  important in  K+ is secreted in exchange with Na+ blood pH control  H+ is secreted by dissociation of carbonic acid ◦ by enzyme carbonic anhydrase  Aldosterone also stimulates H+ secretion ◦ associated with reabsorption of Na+  Bicarbonate is produced by tubular amino  H+ secretion accelerates when blood pH falls as in: acid deamination ◦ Lactic acidosis:  develops after exhaustive muscle activity ◦ Ketoacidosis:  develops in starvation or diabetes mellitus  Reabsorption and Secretion along Reabsorption in the Collecting System Collecting Tubule (CD) the Collecting System  90~95% of filtrate already reabsorped 1. Sodium on reabsorption  The amount of water & solute loss is ◦ The aldosterone-sensitive ion pumps exchange Na+ for K+ into the tubular fluid regulated by:  CD is ◦ Bicarbonate reabsorption ◦ Aldosterone important for ◦ Also in exchange with Cl- in interstitial fluid ◦ ADH (aquaporin-2) urine 2. Urea reabsorption formation  Secretion of H+ or bicarbonate ions ◦ Urea concentration is relatively ↑ in CD (dilute/ ◦ Controls body fluid pH ◦ Urea diffuses into interstitial fluid within the concentrated) medulla The processes along the nephron Kidney Diseases Kidney Diseases (continued) Acute renal failure: ▫ Ability of kidneys to excrete wastes and regulate Renal insufficiency: homeostasis of blood volume, pH, and electrolytes ▫ Nephrons are destroyed. impaired. ▫ Clinical manifestations: ฀ Rise in blood [creatinine]. ฀ Salt and H20 retention. ฀ Decrease in renal plasma clearance of creatinine. ฀ Uremia. ฀ Elevated plasma [H+] and [K+]. Glomerulonephritis: ▫ Inflammation of the glomeruli. Dialysis: ▫ Autoimmune disease by which antibodies have been raised against the glomerulus basement membrane. ▫ Separates molecules on the basis of the ability to ฀ Leakage of protein into the urine. diffuse through selectively permeable membrane. Clinical application: Diuretics Videos to watch RAAS &  Drugs to promote diuresis for Urine formation (filtration, reabsorption, URINE FORMATION  heart disease treatment secretion):  Loop Diuretics : Furosemide ◦ https://www.youtube.com/watch?v=8UVlXX- ◦ inhibit Na+-K+-Cl- co-transporter in the thick ascending limb of 9x7Q (by Biomed Session) Loop of Henle ◦ https://www.youtube.com/watch?v=9_h0ZXx ◦ Cause decreased renal vascular 1lFw (by Alila Medica) resistance and increased renal BF  Thiazide diuretics ◦ inhibit Na+- Cl- co-transporter at distal tubule PM DR SATIRAH ZAINALABIDIN What you should know? The 3 Levels of GFR Control 1. Autoregulation of GFR  After completion of this topic, students 1. Autoregulation (local level)  Intrinsic feedback should be able to: 2. Hormonal regulation (initiated by  Maintains renal blood flow and GFR constant kidneys) despite systemic fluctuation in blood pressure ◦ Describe pathway of the renin-angiotensin-  Able to adjust systemic BP 80~160mmHg 3. Autonomic regulation (by sympathetic aldosterone system (RAAS). ◦ What happens if less or more that this range? division of ANS) ◦ Describe the functions of juxtaglomerular  By changing diameters of afferent/ efferent apparatus and macula densa. arterioles and glomerular capillaries ◦ Explain the regulation of urine volume in 1. Myogenic tone exercise and hypovolemic conditions. 2. Tubuloglomerular feedback A. Myogenic tone  Myogenic alter the caliber of afferent arterioles due to stretch  If GFR rises by increased arterial pressure, the afferent arterioles constrict  GFR lowers  If GFR decreases, the afferent arterioles dilate  GFR increases Autoregulation reflex https://www.youtube.com/watch?v=kM4FaSOA-G0&t=1s The JGA in autoregulation through myogenic tone B. Tubuloglomerular Feedback Juxtaglomerular apparatus and tubuloglomerular feedback  A slower mechanism compared to myogenic response  The macula densa provide feedback to the glomerulus  The JGA includes: ◦ the macula densa cells that line the thick ascending or DCT limb at its junction with the distal tubule ◦ granule cells in the afferent arteriole wall that release the enzyme renin into the circulation ◦ mesangial cells that lie between these structures The macula densa cells sense the distal tubular load of Na+ by swelling and which may relay signals between them in response to high Na+ loads Signals from the macula densa cells are believed to be relayed by mesangial cells to smooth muscle granular cells in the wall of the afferent arteriole. x6 RBF high Tubuloglomerular Feedback ↑ of NaCl delivery to MD Tubuloglomerular feedback Paracrine/Signal: RBF low https://www.youtube.com/watc ↓ NO/ bradykinin h?v=CF0Ahawshzg&t=41s ↑ Tromboxane/ ANG II/ adenosine Response to Reduction in GFR 2. Hormonal Regulation of GFR A. Renin–angiotensin-aldosterone system (RAAS)  3 triggers cause the JGA to release renin 1. Decline in blood pressure at glomerulus:  due to ↓ in blood volume/↓systemic BP/ renal arteries blockage 2. Stimulation of juxtaglomerular cells by sympathetic innervation 3. Decline in osmotic concentration of tubular fluid at macula densa Effects of ANG II at the kidney Effects of ANG II in Effects of ANG II in the CNS Peripheral Capillary Beds  Constricts efferent arterioles of nephron:  Stimulates thirst  Causes brief, powerful ◦ elevate the resistance and decrease GFR  Triggers release of antidiuretic hormone vasoconstriction:  Stimulates reabsorption of Na+ and water (ADH): ◦ of arterioles and at PCT ◦ stimulates reabsorption of water in DCT and precapillary sphincters  Stimulates secretion of aldosterone by collecting system  Elevating arterial adrenal cortex  ↑ Na+ reabsorption in  Increases: pressures throughout DCT & collecting system ◦ sympathetic motor tone body ◦ mobilizing the venous reserve ◦ Increasing CO ◦ stimulating peripheral vasoconstriction Sodium regulation through RAAS https://www.youtube.com/watch?v=HZVKVjojpfE B. Natriuretic Peptides Natriuretic Peptides 3. Neural Regulation of GFR  Are released by the heart:  Trigger dilation of afferent arterioles and  Kidneys are richly supplied by sympathetic fibers. ◦ in response to stretching walls constriction of efferent arterioles  ?  Mostly consists of sympathetic postganglionic  Relaxes mesangial cells & increasing capillary fibers that release NE (binds to alpha-1 receptors ◦ due to increased blood volume or blood which is abundant in afferent) surface area pressure  Sympathetic when stimulated: ◦ ↑ glomerular pressures and ↑ GFR  Atrial natriuretic peptide (ANP) is  ↓ tubular reabsorption of Na+ ions at PCT & ◦ constricts afferent arterioles released by atria ◦ decreases GFR CD  natriuresis ◦ slows filtrate production  Brain natriuretic peptide (BNP) is  Inhibit aldosterone & ADH  Strong stimulation (exercise or hemorrhage)– released by ventricles ◦ ↑ urine production (diuresis) afferent arterioles are constricted. ◦ ↓ blood volume and pressure ◦ Urine output is reduced, and more blood is available for other organs. Autonomic Regulation of GFR Hormonal regulation of tubular reabsorption and secretion  Changes in blood flow to kidneys due to sympathetic stimulation: 1. ANG II ◦ may be opposed by autoregulation at local level  ◦ ANGII decrease GFR via vasoconstriction override by sympathetic to stabilize the GFR ◦ ANG II enhance reabsorption of Na+, Cl- and water in PCT by stimulating Na+/H+ ◦ Warm weather dilate superficial vessels Shunts antiporter blood away from kidney  GFR ↓ ◦ Increase blood volume ◦ Strenuous exercise  blood perfusion more to skeletal muscle & skin & less to kidney  2. Natriuretic Peptide corrected by autoregulation ◦ Inhibit Na+ & water reabsorption in PCT & CD  natriuresis and diuresis ◦ Hemorrhage  vasoconstriction of afferent ◦ Suppress ADH, aldosterone predominate  GFR ↓ 3. Aldosterone 4. ADH Regulation of Water ◦ Released by posterior pituitary due to Reabsorption by ADH  Produced by adrenal cortex  Increased osmolarity of extracellular fluid  Decreased blood volume  Stimulated by ANGII to enhance Na+, Cl- reabsorption and excrete more K+ ◦ Regulates facultative reabsorption Facultative Reabsorption  Stimulates synthesis and incorporation of Na+ ◦ ADH stimulates insertion of aquaporin-2 (water pumps and channels: channels) into the membranes especially in CD Negative Feedback ◦ In cell membranes along DCT and collecting duct ◦ Increase water reabsorption and body volume ◦ Increase Na+, Cl- reabsorption  Reduces Na+ lost in urine  Aldosterone increase reabsorption of water and blood volume in the body  ANP & BNP oppose secretion of aldosterone  Hypokalemia: ◦ Produced by prolonged aldosterone stimulation ADH, Aldosterone, ANP ◦ Dangerously reduces plasma concentration