Lecture 2 - The Renal System 1 PDF

Lecture 02: The Renal System 1 Human Systems Physiology 2 – NATS3054 Dr Kayte Jenkin (Unit coordinator) [email protected] PAGE 1 Lecture Overview  Overview of the renal system  Functions  Organs of the renal system  Neural and endocrine control  General Re...

Lecture 02: The Renal System 1 Human Systems Physiology 2 – NATS3054 Dr Kayte Jenkin (Unit coordinator) [email protected] PAGE 1 Lecture Overview  Overview of the renal system  Functions  Organs of the renal system  Neural and endocrine control  General Renal System Functions  Erythropoiesis  Micturition  Kidney‐Specific Functions  Kidney and nephron structure and function  Glomerular Filtration  Tubular Reabsorption  Tubular Secretion PAGE 2  Overview Amerman. Human Anatomy & Physiology – Chapter 24 PAGE 3 Functions of the Renal System  Regulate fluid and electrolyte balance by regulating osmolarity (blood solute concentration) by either conserving or eliminating water and electrolytes  Contributes to adjusting blood volume & pressure  Filter blood to remove metabolic wastes (incl. drugs and toxins) which are then eliminated when urine exits the body  Regulate acid‐base balance and blood pH by conserving or eliminating hydrogen ions (H+) and bicarbonate ions (HCO3)  Regulates erythropoiesis by releasing hormone erythropoietin  Vital to many other metabolic functions including: detoxifying substances in blood, activating vitamin D, and making new glucose (gluconeogenesis) PAGE 4 How does the renal system perform these roles?  The kidneys processes blood and create urine  Urine formation is important in many homeostatic processes  The kidneys are the target tissue for many hormones which regulate body processes.  Kidneys can also produce hormones and generate glucose!  Micturition allows the body to remove waste products Renal Structures: Kidneys  Kidneys are the organs responsible for creating urine  Structures known as nephrons process the blood by filtration, reabsorption and secretion final product exiting the kidneys is urine PAGE 6 Renal Structures: Ureters  Two tubes called ureters connect the kidney to the bladder  Ureter are made of two distinct layers:  Muscularis: smooth muscle cells which contract rhythmically to propel urine towards the bladder  Mucosa: made of mucous membrane made of transitional epithelium. These cells are capable of expanding and contracting PAGE 7 Figure 24.25b: Anatomy of the urinary tract. Renal Structures: The Bladder  Urinary bladder is a hollow organ capable of holding ~ 800 mL urine  Composed of three distinct layers with different functions Adventitia: Protects and anchors bladder in position Muscularis: Muscle fibres (detrusor muscle) run randomly in different directions, able to squeeze bladder and create a circular band (internal urethral sphincter) is at opening of urethra Mucosal: Transitional epithelium and mucous Ureter membrane that allows distention of bladder and Detrusor protects bladder from urine Ureteric orifices Adventitia Trigone Ureter Internal urethral sphincter Prostate Detrusor Ureteric orifices External urethral sphincter Internal urethral Male sphincter Trigone Urethra External urethral sphincter Urethra Female External urethral orifice Renal Structures: The Urethra  The urethra is a single tube which drains urine from urinary bladder to outside of body. It contains two features which regulate the movement of urine out of the body:  An internal urethral sphincter formed by smooth muscle of the bladder, opens only during urination  A second external urethral sphincter formed by skeletal muscle (located on the pelvic floor) allows for voluntary control of urination The internal and external sphincter are important structures to know for the micturition process! Renal Structures: The Urethra  There are structural and functional differences in the male and female urethra  Female: about four cm in length; opens at external urethral orifice between vagina and clitoris; serves primarily as an exit for urine  Male: about 20cm in length, consists of three regions (prostatic, membranous and spongy), allows both urine and semen to exit the body Figure 24.26: Comparison of urinary tract anatomy in the male and female. Neural Regulation of the Renal System  Most organs get dual innervation, but some organs, including the kidneys are only innervated by sympathetic nerve fibres (thoracic region)  Other structures like the bladder, are innervated by both sympathetic and parasympathetic nerve fibres (sacral region) PAGE 11 Endocrine Regulation of the Renal System  The kidneys produces many hormones and signalling molecules  The kidneys are a target tissue of many hormones, the endocrine system has a huge role in renal function! Aldosterone Conserves Na+ and removes K+ Cortisol Increases filtration rate, remove phosphates ANP Helps remove water and Na+ Figure 24.3: Internal anatomy of the kidney, including the nephron. PAGE 12 Endocrine Function: Erythropoiesis PAGE 13 https://en.wikipedia.org/wiki/Doping_at_the_Tour_de_France Endocrine Role of Kidneys  Kidneys serve roles a number of endocrine functions: Erythropoietin (EPO): Stimulates the development of new red blood cells, or erythrocytes (erythropoiesis)  Renin: Maintains blood pressure and regulates glomerular filtration rate  Vitamin D: Is converted to its active form by the kidneys under the influence of parathyroid hormone. Vitamin D is important for the regulation of blood calcium levels. Activin A: Produced by kidneys when stressed, can induce muscle wasting in skeletal muscle PAGE 14 What is Erythropoiesis  Erythropoiesis is a process whereby red blood cells (RBC; erythrocytes) undergo a maturation process in the bone marrow  Erythropoiesis is essential for maintaining hematocrit levels (percentage of RBC’s in the blood) within normal range  RBC are primarily responsible for the transport of oxygen to tissues  Low blood oxygen levels could be due to not enough RBC’s to meet oxygen demands of the body, or due to hypoxic conditions (altitude, chronic pulmonary diseases) PAGE 15 Figure 19.4 Erythropoiesis: Formation of erythrocytes Importance of Kidneys in Erythropoiesis  Kidneys make a great organ to monitor what is happening in the blood – they receive 20% of cardiac output and filter 200L of blood every day!  Kidneys function within a very narrow range of blood Po2 (partial pressure of oxygen) – they rely on sufficient oxygenation  The kidneys mostly use oxygen to fuel the Na+/K+ pump, and drive the active transport of solutes and nutrients across the cell membrane  The kidneys are highly susceptible to hypoxic injury – the kidneys are one of the body’s most perfused organs and have high metabolic demands PAGE 16 Regulation of Erythropoiesis  Most erythropoietin is produced by the kidneys (over 90%) but EPO can also be made by the liver  Regulation of erythropoiesis is maintained via a negative feedback loop Stimulus: Blood levels of oxygen fall below normal Receptor: Kidney cells detect falling oxygen levels Control center: Kidney cells release erythropoietin into bloodstream Response: Rate of erythropoiesis in bone marrow increases, leading to an increase in the amount of RBC’s oxygen carrying capacity of blood increases PAGE 17 Regulation of Erythropoiesis PAGE 18 Figure 19.5 Regulation of Erythropoiesis Micturition PAGE 19 https://thenattybrofessor.wordpress.com Bladder Function  Every 24 hours, the kidneys create about 2 litres of urine  Urine formation by the kidneys is a continual process, the bladder is an important organ that stores urine until it can be emptied  The renal system contains a special type of epithelial tissue known as transitional epithelium, where dome-shaped cells can be stretched flat when required  The bladder is a hollow and distensible organ which can hold up to 800mL of urine  If the bladder does not empty properly, the risk of urinary tract infection and kidney infections increase PAGE 20 Micturition  Micturition: urination or voiding; discharge of urine from urinary bladder to outside of body  Urine produced by the kidneys, then flows down the ureters to the bladder. Urine is expelled from the body via one urethra Micturition is partially regulated by a reflex arc. Reflexes are programmed, automatic neural responses (occurs with little variability) PAGE 21 Figure 24.25a Anatomy of the urinary tract. Neural Regulation of Micturition  Micturition is controlled via neural regulation with both peripheral and central interactions required to coordinate events The Central Nervous System (CNS) The Peripheral Nervous System (PNS) Voluntary control of Sensory (afferent) division Motor (efferent) division micturition Somatic Visceral Somatic Motor Autonomic Nervous sensory sensory voluntary System (ANS) General: Stretch, involuntary movement General: Touch, pain, movement pressure, vibration, pain, temperature, (smooth muscle, cardiac chemical changes, (skeletal muscle) muscle and glands) temperature, proprioception irritation, nausea and Special: Hearing, hunger equilibrium, vision Special: Taste, smell Sympathetic Parasympathetic KEY division Division Fight or flight Rest and Digest → Towards CNS → Away from CNS Micturition reflex The Micturition Reflex  Micturition reflex – reflex arc mediated by parasympathetic nervous system:  When urine fills the bladder, this stretches the bladder walls  Stretch receptors send signal to sacral region of spinal cord via sensory afferent fibers  Parasympathetic efferent fibers stimulate detrusor muscle to contract and internal urethral sphincter to relax; allows for micturition Figure 24.27: Micturition. Voluntary Control of Micturition  If micturition is appropriate, the central nervous system facilitates the process by coordinating external sphincter relaxation and detrusor muscle contraction.  Pontine Micturition Centre (PMC) located in the pons (a structure of the brainstem) mediates the voluntary control of micturition  If the bladder is full, but voiding is inappropriate, the PMC will inhibit parasympathetic activity and increase somatic contraction of external sphincter  It takes time and training to coordinate these events and make micturition a voluntary process Figure: https://www.news‐medical.net/health/Micturition‐Reflex‐Neural‐Control‐of‐Urination.aspx Incontinence  Impaired ability to voluntarily control micturition is known as urinary incontinence  There are many forms of incontinence which have different underlying mechanisms  Stress incontinence occurs when urine leaks as a result of physical exertion, or during coughing or sneezing.  Can be due to hypermobility of the bladder or weakness of the external urethral sphincter  Common in women, particularly those who have birthed multiple children  Overflow incontinence occurs when the bladder becomes over‐ distended due to poor emptying  May be due to reduced contractility of the detrusor muscle or obstruction of the bladder outlet (or both)  Common in elderly men with prostatic enlargement  Kidney Structure and Renal Function PAGE 26 https://alevelbiologystudent.weebly.com/155‐mammalian‐kidneys.html Importance of Kidneys in Human Physiology  Kidneys are the site where renal system regulates many different homeostatic processes  The kidneys’ main role is to filter the blood and control how much fluid, electrolytes, acids/bases, nutrients, and waste products are lost in the form of urine Without the kidneys, waste products quickly build up in the blood. This has significant impact on fluid, electrolyte, and pH balance affect all body functions PAGE 27 Kidney Macrostructures  Renal cortex: superficial layer of kidney  Renal medulla: the deeper portion of the kidney containing structures known as pyramids and columns  Renal pelvis: cavity that houses the initial segments of the urine drainage system (calyxes) before it exits the kidneys via the ureters PAGE 28 Kidney Microstructures: The Nephron  There are 1.25 million nephron units within the kidney.  Nephron structures are the functional units which form urine.  Nephrons are microscopic structures formed by both endothelial and epithelial cell types  Different regions of the nephron are different histologically, as each region has a unique role to play in the formation of urine: filtration, reabsorption and secretion Figure 24.11: Three physiological processes carried out by the kidneys. Structure Of A Nephron  A nephron can be divided into two main structures 1. The renal corpuscle: Composed of the glomerular capillaries and the Glomerular Capsule (or Bowman’s Capsule). 2. The tubules: Composed of the proximal convoluted tubule (PCT), Loop of Henle (nephron loop) and distal convoluted tubule (DCT). Note: many nephrons drain into a single collecting duct! Types of Nephron in the Kidney  Cortical nephrons  Close to the kidney surface (cortex)  Have short nephron loops  80% of nephrons are this type  Juxtamedullary nephrons  Have very long nephron loops, which extend deep into the renal medulla  Maintain salt gradient within the kidneys  Required as part of the counter‐current mechanism, essential for water balance Figure 24.10: Cortical and juxtamedullary nephrons. Renal Blood Supply  The kidneys receive about 20% of cardiac output Focus on the vessels with a green circle for this subject PAGE 32 Figure 24.4 Blood flow through the kidney. Nephron– Blood supply  The kidneys contain an unusual capillary bed system; known as a portal system  Arterioles both supply and drain the glomerulus; before supplying blood to the peritubular and vasa recta capillaries Juxtamedullary nephrons also contain a specialised capillary bed surrounding the Loop of Henle called the vasa recta PAGE 33 Overview of renal physiology  Glomerular filtration – initial process of nephrons: to selectively filter blood (based on size). Large proteins are not filtered.  Tubular reabsorption – a process where filtered substances are returned to the blood as the filtrate it flows through tubules  Tubular secretion – process where substances are added into filtrate from capillaries to be excreted in the urine  Helps maintain electrolyte and acid‐base balance  Removes substances from blood that were not filtered initially (medication, metabolic waste products, toxins etc.) PAGE 34 OVERVIEW Urine is formed by the kidneys via these three processes: Figure 24.11: Three physiological processes carried out by the kidneys. PAGE 35  Glomerular Filtration PAGE 36 Colorized scanning electron micrograph shows glomeruli, the filtering units of the kidneys. The Renal Corpuscle  The very first step in creating urine is glomerular filtration  This process occurs in the renal corpuscle, which is made from: 1. Glomerulus – group of looping fenestrated capillaries; extremely “leaky,” or permeable 2. Glomerular capsule (Bowman’s capsule) – double‐layered outer sheath of epithelial tissue which contains the filtrate  The capillaries of the glomerulus are fenestrated and have specialized epithelial cells wrapped around them called podocytes PAGE 37 Kidneys- Blood Filtration  Filtration of the blood is selectively based on size  Cells and large proteins are not filtered and remain in circulating blood  Smaller substances exit blood to enter capsular space and becomes the filtrate. Small substances which are filtered include: water electrolytes (sodium and potassium ions) acids and bases (hydrogen and bicarbonate ions) organic molecules (glucose) metabolic waste (urea, creatinine, uric acid, lactic acid) PAGE 38 Glomerular filtration rate  The amount of filtrate formed by both kidneys in one minute is known as glomerular filtration rate (GFR)  A healthy GFR rate is typically 90 – 125 mL/min  GFR must be precisely controlled to regulate fluid balance and electrolyte balance (including metabolic waste products).   GFR: urine output increases can lead to dehydration and electrolyte depletion   GFR: urine output decreases, wastes don’t get removed and metabolic acidosis can occur PAGE 39 Factors Determining GFR  To achieve filtration, net movement of water is established from the glomerular capillaries glomerular capsule  Net filtration pressure at glomerulus is determined by three driving forces: + 1. Glomerular hydrostatic pressure (GHP) – determined mostly by systemic blood pressure and has the biggest influence on GFR 2. Glomerular colloid osmotic pressure (GCOP) – as only small molecules can be filtered, the larger molecules which remain ‐ in the capillaries (including proteins) generate an osmotic pressure gradient. This pressure opposes filtration. 3. Capsular hydrostatic pressure (CHP) – As the glomerular capsule fills with filtrate, the fluid within the capsule generates hydrostatic pressure which opposes filtration. PAGE 40 Glomerular Hydrostatic Pressure and GFR  One of the easiest ways to directly affect GFR is to adjust the diameter of the afferent or efferent arteriole, as this alters the glomerular hydrostatic pressure.  Dilation of afferent OR constriction of efferent =  GFR  Constriction of afferent OR dilation of efferent =  GFR Think of “filling a sink” – you can change flow from the tap (afferent), or change how well the sink PAGE 41 drains (efferent); the more that is in the “sink” (glomerulus), the more will be filtered. Calculating Net Filtration Pressure  Net filtration pressure (NFP) is combination of these three forces NFP = GHP – (GCOP + CHP)  Typically the NFP = 10mmHg. This equates to about 125mL of filtrate being produced by the kidneys each minute (GFR). PAGE 42 Figure 24.13: Net filtration pressure in the glomerular capillaries. Glomerular filtration rate PAGE 43 Tubular Reabsorption and Secretion PAGE 44 Image: lab.anhb.uwa.edu.au/mb140/CorePages/Urinary/urinary.htm Tubular Structure  Newly formed filtrate enters renal tubules where it can be further modified in three structurally and functionally distinct regions: proximal tubule, Loop of Henle (nephron loop), and distal tubule PAGE 45 Figure 24.7 Structural characteristics of the renal tubule. Tubular Reabsorption & Secretion  In tubular reabsorption, substances must pass from filtrate tubule cells interstitial fluid peritubular capillaries blood  In tubular secretion, substances move in opposite direction  Movement can occur through tubular cells (transcellular transport) or if a substance is small enough, can pass between tubular cells (paracellular transport) The kidney tubules contain a variety of transporters, channels and pumps to allow movement of substances across the cell membrane in both directions (reabsorption and secretion) PAGE 46 Figure: Vander’s Human Physiology, Widmaier, Raff and Strang, 2019, McGraw Hill Education. Transcellular Transport  The majority of substance reabsorbed and secreted by the tubules occurs via the transcellular pathway.  Ion pumps, aquaporins, and protein channels allow movement of substances into and out of tubular cells.  Typically, moving substances this way requires energy, but some movement occurs by diffusion (passive transport)  All secretion occurs via the transcellular pathway PAGE 47 Figure 24.15 Barriers to tubular reabsorption and secretion. Paracellular Transport  Some substances (water, some ions) are small enough to move between cells.  Movement of substances occurs due to diffusion from high concentration low concentration  Paracellular transport is exclusively passive (does not require ATP) and only occurs in tubular reabsorption. PAGE 48 Figure 24.15 Barriers to tubular reabsorption and secretion. Reabsorption and Secretion in the PCT  The proximal convoluted tubule (PCT) is the first tubular structure filtrate passes through  Reabsorption of ~65% of glomerular filtrate into peritubular capillaries which is ~108 L of water/day  Reabsorbs >99% of glucose, amino acids, and organic nutrients  Reabsorbs sodium, potassium, bicarbonate magnesium, phosphate and sulfate ions  Water follows via osmosis  Secretion of some H+ and ammonia (NH4+) ions, and some PAGE 49 drugs (penicillin and morphine) Reabsorption in the nephron loop  Only reabsorption occurs in the Loop Of Henle (no secretion)  Primary function of nephron loop  The countercurrent mechanism: Generates salinity gradient, allows conducting ducts to concentrate urine and conserve water  Water gets reabsorbed in the descending loop.  Filtrate becomes more concentrated going down the loop  Sodium and chloride ions get reabsorbed from the ascending loop  Filtrate becomes less concentrated going up the loop PAGE 50 Reabsorption & Secretion in the DCT  By the time filtrate reaches first segment of distal tubule (DCT), about 85% of water and 90% of sodium ions have been reabsorbed  Reabsorption of Na+, Cl‐, Ca2+ and water  Secretion of some K+, H+ ions, some drugs and metabolic waste  The DCT contain hormone receptors that regulate water, electrolyte, and acid‐base balance PAGE 51 Reabsorption & Secretion in the Collecting Duct  Collecting ducts drain filtrate from multiple nephrons.  These structures run from the cortex to the medulla  The collecting duct can further modify filtrate before it exits kidney  Similar reabsorption and secretion profile as the DCT  The collecting duct is also the target of various hormones which regulate water and electrolyte balance PAGE 52 Figure 24.9: Structural characteristics of the collecting system. Key Role of Sodium in Tubular Transport  Sodium: is key for reabsorption of all other solutes as it creates an osmotic and electrical gradient that drives reabsorption of water and other solutes. Figure 24.16: Glucose reabsorption in the proximal tubule. Key Role of Sodium in Tubular Transport  Sodium: is key for reabsorption of bicarbonate ions and secretion of hydrogen ions (acids)  Hydrogen ion secretion is essential for removing waste products (that cannot be removed via breathing or in the faeces)  Bicarbonate ions are really important component of the chemical buffering system of the blood Figure 24.17: Bicarbonate ion reabsorption in the proximal tubule. Key Role of Sodium in Tubular Transport  Sodium: is key for reabsorption of water in the kidneys. The countercurrent mechanism ensures that the medulla of the kidney is more concentrated than the kidney cortex  When ADH is present, aquaporins are expressed on the apical and basolateral membrane of kidney tubules  Water moves via osmosis, from an area of low concentration (filtrate) to high concentration (blood) Figure 24.18: Obligatory water reabsorption in the proximal tubule. The big picture…Tubular Reabsorption & Secretion PAGE 56 Figure 24.19: The Big Picture of Tubular Reabsorption and Secretion. Putting It All Together – Renal Physiology  The main function of the kidneys is to create urine  This process is accomplished by filtration, reabsorption and secretion  What is left in the filtrate as it collects into the drainage system of the kidneys (calyxes) will be excreted as urine  This fluid cannot be altered further once it leaves the final structures of the nephron Silverthorn, Figure 19.3: Solute movement through the nephron PAGE 57 Next Week  Lecture 03: The Renal System 2  Learning Workshop 1: Fluid Balance / Renal System 1 Contribute towards participation grade Workshops will cover content from Lecture 01 and 02 Workshops are a great way to form study groups and meet people! Great practice preparation for Quiz 1  Download (or update) Minecraft Education before attending the workshop! 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