Human Physiology Final Exam Study Guide
Human Physiology Final Exam Study Guide BIOL 3160
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This 38 page Study Guide was uploaded by MBattito on Thursday April 21, 2016. The Study Guide belongs to BIOL 3160 at Clemson University taught by Dr. Tamara McNutt-Scott in Fall 2015. Since its upload, it has received 83 views. For similar materials see Human Physiology in Biological Sciences at Clemson University.
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Date Created: 04/21/16
Chapter 16: Respiratory Physiology Respiration: • Ventilation o Breathing o Mechanical process to move air in and out of lungs • Gas exchange o Occurs between alveolar air and blood of pulmonary capillaries • Oxygen utilization o By tissues for energy-‐liberating reactions of cell respiration Steps of Respiration 1. Ventilation: exchange of air between atmosphere and alveoli by bulk flow 2. Exchange of O2 and CO2 between alveolar air and blood in lung capillaries by diffusion a. O2 concentration of air is higher in lungs than in blood – O2 from air of lungs à blood b. CO2 concentration in blood is higher than air of lungs – CO2 travels from blood à air of lungs c. Results in inspired air containing more O2 and less CO2 than expired air 3. Transport of O2 and CO2 through pulmonary and systemic circulation by bulk flow a. Pulmonary: blood leaving lungs – has higher O2 and lower CO2 concentrations because lungs function to bring the blood into gaseous equilibrium with air 4. Exchange of O2 and CO2 between blood in tissue and capillaries and cells in tissues by diffusion 5. Cellular utilization of O2 and production of CO2 • External respiration: ventilation and the exchange of gases between the air and blood • Gas exchange between air and blood occurs entirely by diffusion through lung tissue • Very rapid because of large lung surface area and small diffusion distance • Steps 1-‐2 • Internal respiration: gas exchange between the blood and other tissues and oxygen utilization by the tissues • Steps 4-‐5 Steps of Respiration Structure of the Respiratory System • Alveoli: tiny air sacs in the lungs o Site of gas exchange o Very numerous ~300 million § Provides large surface area for diffusion of gases o Very thin – forms short blood-‐air distance also aiding diffusion o 2 types of alveolar cells § Type I: comprise 95-‐97% total surface area of the lung • Gas exchange occurs primarily through type I • Very thin § Type II: • Secrete pulmonary surfactant and reabsorb Na+ and H2o • Prevent fluid build up within the alveoli o Although thin, not fragile – strong enough to withstand high stress during heavy exercise and high lung inflation § Strength provided by fused basement membranes of the blood capillaries and alveolar walls o Polyhedral shape that form clustered units § Air within one member of a cluster can enter other members through pores § Clusters usually occur at the ends of respiratory bronchioles (the very thin air tubes that end blindly in the alveolar sac) • Air passage of respiratory system is split into 2 functional zones o Respiratory Zone: § Region where gas exchange occurs § Includes respiratory bronchioles and terminal alveolar sacs o Conducting Zone: § Included anatomical structures through which air passes before reaching the respiratory zone • Mouth, nose, pharynx, larynx, trachea, primary bronchi, all successive branching up to and including terminal bronchioles § Functions to warm, humidify, filter and cleanse incoming air • Ensures air is always at temperature of 37 degrees Celsius and saturated with water vapor from wet mucus membranes that line respiratory airways – warming and humidifying function • Mucus secreted serves to trap small particles – filter function • Mucus is moved by cilia in conducting zone o Alveoli themselves are normally kept clean by resident macrophages o Cleansing action of cilia and macrophages in the lungs is diminished by cigarette smoke Thoracic Cavity • Diaphragm: dome-‐shaped sheet of striated muscle o Divides anterior body cavity into two parts § Abdominopelvic cavity – area below the diaphragm – contains liver, pancreas, GI tract, spleen and genitourinary tract § Thoracic cavity – area above the diaphragm – contains the heart, large blood vessels, trachea, esophagus, thymus, lungs • Within thoracic cavity, structures in the central region (mediastinum) are enveloped by pleural membranes o Pleural membrane: 2 layers of wet epithelial membrane § Parietal pleura: superficial layer – lines inside of thoracic wall § Visceral pleura: deep layer – covers the surface of the lungs o Visceral pleura of lungs normally is pushed against the parietal pleura lining the thoracic cavity – thus there is no air between the pleura under normal conditions § Intrapleural space: potential space between the pleura that can become a real space if they separate when a lung collapses Ventilation • Movement of air results from pressure differences between ends of airways induced by changes in lung volume • Physical properties of lung important component of functionality o Physical properties include: compliance, elasticity and surface tension • Airflow is directly proportional to pressure difference and inversely proportional to frictional resistance to flow Pressure Relationships in Thoracic Cavity • Respiratory pressures are always describes relative to atmospheric pressure (760 mmHg at sea level – pressure air exerts on body) o Negative respiratory pressure (subatmospheric) indicates value lower than 760 mmHg o Positive respiratory pressure indicates value higher than 760 mmHg • Intrapulmonary pressure: pressure within alveoli o Changes during phases of breathing – will equalize with atmospheric pressure o Air enters lungs during inspiration because atmospheric pressure is greater than intrapulmonary pressureàduring inspiration intrapulmonary pressure falls below atmospheric pressure § ~ -‐3mmHg during quiet inspiration o Expiration occurs when intrapulmonary pressure is greater than atmospheric pressure o ~ +3 mmHg during quiet expiration • Intrapleural pressure: pressure within pleural cavity outside lungs o Result of elastic tension of lungs with thoracic wall o Changes during breathing – always less than intrapulmonary pressure • Transpulmonary pressure: difference between intrapulmonary and Intrapleural pressures o Always positive during inspiration and expiration o Keeps air spaces in lungs from collapsing and lung volume changes parallel to thoracic volume during ventilation Boyle’s Law • Relationship between pressure and volume of gases is represented by Boyle’s law • States: “For an ideal gas, that if temperature is constant, then pressure of a gas varies inversely with its volume” o P V = P V 1 1 2 2 • Note that gases, unlike liquids, fill up the space of a container – so given a certain amount of air in a large volume will have less pressure than the same amount of air in a smaller volume, pressure will increase • Changes in intrapulmonary pressure occur as a result of changes in lung volume o An increase in lung volume during inspiration decreases intrapulmonary pressure to subatmospheric levels o A decrease in lung volume during expiration increases intrapulmonary pressure above atmospheric pressure Physical Properties of the Lungs • Compliance o Distensibility – stretchable § Consider it the inverse of stiffness o Defined as change in lung volume per change in Transpulmonary pressure § ΔV/ ΔP o Reduced by factors that produce resistance to distension § Low lung compliance makes it hard to breath – takes a lot of energy § Pulmonary fibrosis: infiltration of lung tissue with connective tissue proteins – decreases lung compliance • Elasticity o Refers to tendency of structure to return to its initial size after being distended o Normal lung is very elastic § High elastic protein content o The lungs are normally stuck to the chest wall – always in a state of elastic tension § Tension increases during inspiration when lungs are stretched § Tension decreases during expiration by elastic recoil • Surface tension o Force exerted by fluid in the alveoli that acts to resist distension o Lungs secrete and absorb fluid in 2 antagonistic processes § Cells move Na and Cl ions – Cl secretion and Na absorption • Both active processes • Water moves in with Na and out with Cl § Leaves very thin film of fluid on alveolar surface o At air-‐water interface, a tension exists due to attractive forces between water molecules that “shrink” alveoli and resist further stretching § Would make breathing very costly to organism – hard to change lung volume § Surfactant – made by type II alveolar cells • Detergent-‐like substances that reduces cohesive forces between water molecules on alveolar surface • Decreases surface tension and increases compliance • Makes lung expansion easier • Regular breathing decreases surfactant production à deep breaths stimulated to occur every once in a while to stimulate surfactant release by stretching type II pneumocytes o Law of Laplace § Describes relationship between pressure (P), surface tension (T) and radius (r) of the alveolus § P = 2T/r • P is directly proportional to T • P is inversely proportional to r Mechanics of Breathing • During ventilation, pressure in the alveoli changes due to thoracic cavity volume changes so that there is a pressure difference between the atmosphere and the alveoli in air flow o Breathing consists of 2 phases § Inspiration: alveolar pressure < atmospheric à air flows in • Results from muscle contraction § Expiration: alveolar pressure > atmospheric à air flows out • Results from muscle relaxation and elastic recoil o Mechanical process • RULE: volume changes lead to pressure changes which lead to the flow of gases o Volume is always changed first before pressure Mechanics of Pulmonary Ventilation • Diaphragm is the primary muscle of ventilation o Function is aided by intercostal muscles on the ribs o 2 layers of intercostal muscle between bony portion: external and internal o Only 1 layer between costal cartilages § Fibers oriented similar to internal intercostals à named interchondral part of the internal intercostals (also called parasternal intercostals) • Inspiration o Diaphragm contracts and moves downward à expands thoracic volume vertically o Parasternal and external intercostal muscles contract and raise ribs à expand thoracic volume laterally o Increases volume and lowers pressure o Nothing to connect lungs to ribs so when rig cage expands, lungs expand with it because they adhere to inner wall because the Intrapleural pressure is less than the intrapulmonary à suctions it to wall • Expiration o Diaphragm contracts – goes back up o Internal intercostal muscles relax o Decreased volume so increased pressure o Abdominal muscles aid expiration by forcing abdominal organs up against diaphragm and further decrease volume Gas Exchange in the Lungs • Gas exchange in the body occurs due to bulk flow of gases and diffusion of gases through tissues • Dalton’s Law of Partial Pressures o States that in a mixture of gases, the total pressure is the sum of the partial pressures exerted independently by each gas in the mixture • Note: air flow stops at terminal bronchioles; movement of gases from respiratory bronchioles to alveoli is by diffusion – will flow along concentration gradients Partial Pressure of Gases in Blood • Large surface area and short diffusion distance along with abundant capillariesà rapid gas exchange with gases reaching equilibrium quickly • Amount of gas dissolved in blood reaches a value in accordance to Henry’s Law: o If a mixture of gases is in contact with a liquid, each gas will dissolve into the liquid in proportion to its partial pressure à thus, the greater the concentration of a gas, the quicker and more of it will go into solution o Also must consider solubility of gas and temperature • Each individual alveoli has its own capillary network • Nitrogen is present in high concentrations but is not very soluble so it will not participate in gas exchange as much • Oxygen is present in higher concentrations and is semi-‐soluble so it will participate in gas exchange more than nitrogen • Even though CO2 is present in smaller concentrations than O2, CO2 is more soluble so they exchange at approximately the same rate Ventilation-‐Perfusion Coupling: • For efficient gas exchange, must have ventilation and perfusion coupled • Regulated by local autoregulatory mechanisms that monitor alveoli • Ventilation: air flow into alveoli • Perfusion: blood flow in capillary network • Keeping ventilation and perfusion synchronized leads to efficient gas exchange o They are kept synchronized by vasoconstriction and dilation of pulmonary and systemic arterioles § When alveolar oxygen partial pressure is low, pulmonary arterioles constrict to reduce blood flow to alveoli that are inadequately ventilated à reduces ventilation and perfusion § When alveolar oxygen partial pressure is low, systemic arterioles dilate to supply more blood and oxygen to the tissues • If ventilation and perfusion were not matched, blood from poorly ventilated alveoli would mix with blood from well-‐ventilated alveoli o Would result in a lower oxygen partial pressure in the blood leaving the lungs à dilution effect • Apex of the heart is over ventilated (or under perfused) – normal mismatch of ventilation/perfusion o Abnormally large mismatches can occur in cases on pneumonia, pulmonary emboli, edema and other pulmonary disorders Regulation of Breathing: • Motor neurons that stimulate the respiratory muscles are controlled by two major pathways – one that controls voluntary breathing and one for involuntary breathing • Unconscious rhythmic control is influenced by sensory feedback from receptors sensitive to partial pressures of O2, CO2 and pH • Inspiration/expiration produced by contraction/relaxation of skeletal muscles in response to somatic neuron activity o Controlled by respiratory centers in the medulla and input from cerebral cortex § Rhythmicity center – controls autonomic breathing • Observe inspiratory neurons – DRG and part of VRG – and Expiratory neurons – part of VRG • DRG = for inspiration • VRG – sets basal rate of breathing o Modified by centers in the pons § Apneustic and pneumotaxic centers • Apneustic control stimulates inspiration neurons • Pneuomotaxic center (now referred to as pontine respiratory center) antagonizes apneustic center – inhibits inspiration Chemoreceptors • Automatic control of breathing influenced by chemoreceptors o Found in central and peripheral locations § Central chemoreceptors found in medulla § Peripheral chemoreceptors contained within small nodules associated with the aorta and carotid arteries à include aortic and carotid bodies • Control breathing indirectly through sensory nerve fibers to the medulla o Relay information on changes in pH and brain interstitial fluid and cerebral spinal fluid as well as blood partial pressures of O2, CO2 and pH • Chemoreceptors information to the brain modifies rate and depth of breathing Effects of Blood CO2 and pH on Ventilation • Hypoventilation (inadequate ventilation) à causes P CO2 to rise (hyprecapnia) à pH quickly falls o Fall in pH because CO2 can combine with water to form carbonic acid – carbonic acid is a weak acid and thus can release H+ ions into the solution • Hyperventilation (excessive ventilation) à causes P CO2 to drop (hypocapnia) à pH rises o Rise in pH because of the excessive elimination of carbonic acid • Oxygen content of the blood decreases much more slowly because of the large reservoir of oxygen attached to hemoglobin • So, blood CO2 and pH are more immediately affected by changes in ventilation than oxygen • Changes in CO2 are the most potent stimulus for the reflex control of ventilation o Ventilation is adjusted to maintain constant P CO2 h proper oxygenation occurring as a natural side effect of this reflex control • Immediate increase in ventilation due to activation of peripheral chemoRs – sustained rise in CO2 activated central ChemoRs that take longer to respond Effects of Blood O2 Ventilation • Chemoreceptor sensitivity to P CO2 augmented by a loO2 P and is decreased by a highO2 P o Blood P O2affects breathing only indirectly • Breathing increases linearly with increasing CO2 • O2 must decrease by half before breathing is stimulated • Hypoxic drive: significant stimulation of ventilation caused when blood CO2 is held constant by experimental techniques and blood O2 lls from 100mmHg to 70 mmHg o Due to direct effect oO2 P on carotid bodies – become depolarized and allows entry of Ca2+ à stimulates release of neurotransmitter à increases ventilation • Change in CO2 responds more quickly Effects of Pulmonary Receptors on Ventilation • Lungs contain various types of receptors that can influence brainstem respiratory centers • Unmyelinated C fibers: sensory neurons in the lungs that can be stimulated by capsaicin (chemical in hot peppers that produces burning sensation) o Produce an initial apnea, followed by rapid shallow breathing when peppers are eaten or pepper spray is inhaled • Rapidly adapting receptors: cause a person to cough in response to components of smoke and smog and inhaled particulates o Stimulated most directly by increase in the amount of fluid in the pulmonary interstitial tissue à the unmyelinated C fibers can cause such an increase and thus explains the coughing after eating a hot pepper • Hering-‐Breuer Reflex: stimulated by pulmonary stretch receptors o Activation of receptors during inspiration inhibits respiratory control centers making further inspiration difficult o Prevents over-‐inflation o Not as active in adults during normal tidal breathing but become more active during higher tidal volumes such as during exercise Hemoglobin and Oxygen Transport • Bond strength between hemoglobin and oxygen, and thus the extend of oxygen unloading in systemic circulation, is changed under different conditions • Total oxygen concentration depends on the PO2 and hemoglobin concentration o Anemia: abnormal or below normal hemoglobin levels § Oxygen content of blood with be abnormally low o Polycythemia: have above normal hemoglobin levels – what athletes want § Can occur as an adaptation to life at a high altitude o Normal levels allow blood to carry ~ 20mL o2 O per 100mL of blood • Most of the oxygen in the blood is contained within the red blood cells chemically bonded to hemoglobin o Each hemoglobin molecule can attach to 4 oxygen molecules à 280 million hemoglobin molecules per RBCà each RBC can carry over a billion molecules of oxygen • Normal heme contains iron in its reduced form – in this form it can bind with oxygen to form oxyhemoglobin o When oxyhemoglobin releases oxygen, it is still in its reduced form and forms deoxyhemoglobin o Oxygen binding is cooperative § To unload: first is the hardest to remove and the last is the easiest § To add: first is the hardest to add and the last is the easiest o Methemoglobin: oxidized hemoglobin – iron in its oxidized state § Lacks the electrons it needs to form a bond with oxygen à cannot participate in oxygen transport § Blood contains a small amount o Carboxyhemoglobin: carbon monoxide binds with reduced hemoglobin instead of oxygen § Binds with a higher affinity so it will not release • Percent Oxyhemoglobin Saturation: percentage of oxyhemoglobin to total hemoglobin o Measured to assess how well the lungs have oxygenated the blood o Normal amount ~ 97% Oxygen-‐Hb Dissociation Curve • Graphical representation that relates saturation of hemoglobin to P – O2ot a linear relationship • Blood in systemic arties at a O2 P of 100 mmHg has a percent oxyhemoglobin saturation of 97% o Blood is delivered to tissue and oxygen is diffused into cells à blood leaving systemic veins have reduced oxygen concentration o Blood P O2 40 mmHg and percent oxyhemoglobin saturation of ~ 75% at rest Oxygen Transport • Effected by pH, Temperature and 2,3-‐DPG • Loading and unloading reactions influenced by changes in the affinity of hemoglobin for oxygen – ensure active skeletal muscles will receive more oxygen o Occurs as a result of lower pH and increased temperature in exercising muscles • Effects of Temperature: o Increased temperature à increases metabolic rate § Increasing the temperature weakens the bond between oxygen and hemoglobin thus decreasing the affinity o Increased temp – easier to release oxygen o Decreased temp – harder to release oxygen • Effects of pH: o Bohr effect: when you increase acidity and decrease pH, its easier to unload oxygen § In low acidity or high pH it is harder to unload § Thus, increase pH increases affinity for hemoglobin to oxygen and decrease pH decreases affinity o During exercise, CO2 levels increase, thus decreasing the pH and allowing more oxygen to be released • Effects of 2,3-‐DPG o DPG: byproduct of glycolysis o When metabolism increases – DPG increases à curve moves to the right because oxygen is easier to unload o The enzyme that produces 2,3-‐DPG is inhibited by oxyhemoglobin § When oxyhemoglobin concentration is lowered, production of 2,3-‐DPG is increased § 2,3-‐DPG binds to deoxyhemoglobin and makes it more stable à favors the conversion of oxyhemoglobin to deoxyhemoglobin aka releases oxygen Carbon Dioxide Transport • Transport can occur in 3 ways o Dissolved in plasma o Bound to Hb (carbaminoHb) o As HCO3-‐ (bicarbonate) – accounts for most of CO2 in blood • Internal respiration: converts CO2 to make various elements o Makes hydrogen ions and bicarbonate à affects acidity o The H+ ions are trapped in the red blood cells causing a net positive charge à attracts Cl-‐ ions which move into the red blood cells as bicarbonate moves out à this anion exchange is termed chloride shift • Due to Bohr effect and increase of CO2, Hemoglobin-‐oxygen bonds are weakened – enhances O2 unloading Hb-‐NO partnership in Gas Exchange • NO (vasodilator) secreted by lungs or vascular endothelial cells causes vasodilation that plays an important role in blood pressure regulation o However, hemoglobin is a vasoconstrictor because it scavenges NO • Scenario o As O2 binds to Hb, it changes shape such that it enables NO to bind to it à protects NO o As O2 is unloaded at tissues, so is NO, which causes a local vessel dilation and aids in O2 delivery o When CO2 binds, NO is picked up as well and carried back to the lung o Bottom line à it appears that Hb carries along its own vasodilator Acid-‐Base Balance of Blood • Changes in blood pH, produced by alterations in either respiratory or metabolic component of acid-‐base balance can be partially compensated for by change in other component • Blood pH kept within narrow range o Function of lungs (regulate blood CO2 levels) and kidneys (regulate bicarbonate ion) o pH of 7.35-‐7.45 • Major buffer in plasma – bicarbonate ion • Acidosis: blood pH fall below 7.35 o Respiratory acidosis caused by hypoventilation § Causes increased blood CO2 and thus carbonic acid o Metabolic acidosis results from excessive production of nonvolatile acids or loss of bicarbonate • Alkalosis o Respiratory alkalosis is caused by hyperventilation § Hyperventilation o Metabolic alkalosis results from too much bicarbonate or inadequate nonvolatile acids § May be caused by excessive vomiting through loss of acid in gastric juice • Respiratory component of acid-‐base balance is represented by the plasma carbon dioxide concentration • Metabolic component of acid-‐base balance is represented by the free bicarbonate concentration • Proper pH can be achieved when a good balance of CO2 and bicarbonate is reached Chapter 17: Physiology of the Kidneys Primary function of kidneys is in the regulation of the extracellular fluid (plasma and interstitial fluid) environment of the body • Accomplished through formation of urine o During this process, kidneys regulate § Volume of blood plasma à contribute significantly to the regulation of blood pressure § Concentration of waste products in blood § Concentration of electrolytes (Na, K, HCO3, etc.) § pH of plasma • Kidneys considered most potent acid-‐base regulator Gross Anatomy of the Urinary System • Kidneys: lie on either side of the vertebral column below the diaphragm and liver o About the size of a fist o Coronal Section of kidney has 2 regions § Outer renal cortex – reddish brown and granular because of numerous capillaries § Deeper renal medulla – striped due to the presence of microscopic tubules and blood vessels • Composed of 8-‐15 conical renal pyramids separated by renal columns o Cavity of the kidney is divided into several portions § Minor calyx – small depression that each pyramid projects into § Major calyx – formed by union of several minor calyces à major calyces join to form renal pelvis • Renal pelvis: cavity where urine produced in the kidneys is drained to o Urine then channeled from the kidneys to the urinary bladder through the ureters o Ureters: long ducts that undergo peristalsis (wave-‐like contractions) § Pacemaker of these peristaltic waves is located in the renal calyces and pelvis, which contain smooth muscle – renal calyces and pelvis also undergo peristalsis to aid emptying of urine from kidney • Urinary bladder: storage sac for urine o Shape is determined by amount of urine it contains § Empty = pyramidal § As it fills = ovoid and bulges into abdomen o Drained inferiorly by urethra o Has a muscular wall – detrusor muscle Microscopic Anatomy of the Kidney • Nephron – functional unit of the kidney o Responsible of urine formation o Comprised of renal corpuscle and renal tubules § Renal corpuscle – glomerulus and Bowman’s capsule • Glomerular filtration § Renal tubules – proximal convoluted tubule, distant convoluted tubulues and Loop of Henle • Tubular secretion • Tubular absorption o 2 types: § Cortical – original in the outer 2/3 of the cortex • More numerous § Juxtamedullary – originate in the inner 1/3 of the cortex (next to the medulla) • Have longer nephron loops • Play an important role in kidney’s ability to produce a concentrated urine • Glomerular (Bowman’s) capsule: surrounds the glomerulus o Contains an inner visceral layer and outer parietal layer o Space between the two layers is continuous with the lumen of the tubule o Filtrate that enters glomerular capsule passes into lumen of the proximal convoluted tubule § Proximal convoluted tubule contains millions of microvilli to increase surface area for reabsorption § See absorption o Fluid passes from the proximal convoluted tubule to the nephron loop (Loop of Henle) § This fluid is carries into the medulla in the descending limb of the loop and returns to the cortex in the ascending limb o Distal convoluted tubule: coiled tubule in the cortex § See secretion § Shorter than proximal tubule § Relatively few microvilli § Terminates as it empties into a collecting duct o Collecting duct: receives fluid from the distal convoluted tubule of several nephrons § Fluid is drained by the collecting duct from the cortex to the medulla as the collecting duct passes through a renal pyramid § Fluid is now called urine à passes into minor calyx à funneled through renal pelvis out of the kidney into the ureter • Vasculature o Renal artery: where arterial blood enters kidney o Renal artery divides into interlobular arteries that pass between pyramids through the renal columns o Arcuate arteries branch from interlobular arteries at the boundary of the cortex and medulla o Afferent arterioles: microscopic arterioles formed from branching of Arcuate arteries § Deliver blood into glomeruli (capillary network that produce a blood filtrate that enters the urinary tubules) o Efferent arteriole: where remaining blood in the glomerulus leaves through § Delivers blood into another capillary network – peritubular capillaries surrounding the renal tubules § This blood is drained into veins that parallel the course of the arteries in the kidney à interlobular, arcuate, and interlobar veins § Interlobar veins leave kidney as a single renal vein à empties into inferior vena cava o Arrangement of blood vessels is unique § Only one in which capillary bed is drained by an arteriole instead of a venule and delivered to a second capillary bed downstream Glomerular Filtration • Urine formation begins with the filtration of plasma from glomerular capillaries into Bowman’s capsule à glomerular filtration – results in formation of filtrate • Process utilizes a pressure gradient • Endothelial cells of the glomerular capillaries have large pores (fenestrae) o Causes glomerular capillaries to be 100-‐400x more permeable to plasma water and dissolved solutes than skeletal muscle capillaries o Pores are still small enough to prevent entry of RBC, WBC and platelets • Before fluid in blood plasma can enter the interior of the glomerular capsule, it must pass through 3 layers of selective filters o Fluid entering is referred to as filtrate – will become modified as it passed through the different segments of the nephron tubules to become urine o Capillary fenestrae – first potential filtration barrier § Large enough to allow proteins to pass but are surrounded by charges that may present some barriers to plasma proteins o Glomerular basement membrane – second potential barrier § Layer of collagen and proteoglycans lying immediately outside the endothelium § Most resists fluid flow into the capsule lumen § Offer some barrier to plasma proteins o Slit Diaphragm – third potential barrier § Visceral layer of glomerular capsule is made up of podocytes § Unique epithelial cells with a bulbous cell body, primary processes and thousands of foot processes § Processes are attached to the basement membrane § Narrow slits between adjacent foot processes provide passageways for molecules entering the interior of the glomerular capsule as glomerular filtrate § Slit diaphragm – links interdigitating foot processes and presents the last potential filtration barrier Forces Involved in Filtration • Filtration occurs due to opposing forces o Important elements § Blood pressure § Protein concentration in plasma compared to filtrate (not many proteins in filtrate) • Glomerular filtration rate (GFR) o Volume filtered from the glomeruli into Bowman’s capsule per unit time § Average ~115-‐125mL/min § Consider average blood volume is 5.5L à total blood volume is filtered every 40 minutes • Osmotic pressure established by presence of protein in plasma and not really in filtrate o Greater colloid osmotic pressure of plasma promotes the osmotic return of filtered water o Net filtration pressure of about 10 mmHg – since glomerular capillaries are extremely permeable and have a large surface area, this modest filtration pressure produces an extraordinary large volume of filtrate Regulation of GFR • Vasoconstriction or vasodilation of afferent arterioles affects rate of blood flow into glomerulus • Observe variety of intrinsic and extrinsic mechanisms to ensure GFR is high enough to eliminate wastes and regulate blood pressure – but not too high as to cause excessive water loss o Sympathetic nerve endings § Vasoconstriction occurs in afferent arterioles § Helps to preserve blood volume and divert blood to the muscles and heart o Renal auto regulation § Observe relatively constant GFR with fluctuation BP • Afferent arterioles dilate when BP falls below average and constrict when BP is above average • Changes in efferent arterioles are of secondary importance § Myogenic regulation • Smooth muscle of afferent arterioles sensitive to stretch – result in vasoconstriction when stretched § Result of effects of locally produced chemicals on the afferent arterioles • Tubuloglomerular feedback o Macula densa: specialized cells that act as the sensor – part of a larger functional unit (Juxtaglomerular apparatus) •
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