Unit 4 Study Guide (Respiratory and Renal) PDF

PSIO441 – Unit 2 Study Guide Exam 4 will cover material from chapters 13 and 14. You should use PowerPoint slides and any notes you have taken as your primary study material. Reaching out to me, consulting the textbook and/or other online resources should be used when further or alternative explanat...

PSIO441 – Unit 2 Study Guide Exam 4 will cover material from chapters 13 and 14. You should use PowerPoint slides and any notes you have taken as your primary study material. Reaching out to me, consulting the textbook and/or other online resources should be used when further or alternative explanations are required. This study guide has been provided to act as a guide for your studying and to remind you of the main topics covered. Please do not rely solely on the topics listed here. Everything on the exam is on this study guide, but just because it is on the study guide does not mean it will be on the exam. This study guide is a comprehensive review of everything covered in this unit. Remember, the exam is 50 questions (1 pt each) and you will have 50 minutes to complete it. There are 23 questions from respiratory and 27 from renal. All questions will be multiple choice, true/false and after reading all the positive feedback on sequential order questions, there will be 2 sequential order questions: one for respiratory, one for renal. **REMEMBER REVIEW SESSION WILL BE ON SUNDAY NIGHT FROM 5-6PM IN OUR LECTURE HALL HOSTED BY PHYSIOLOGY GRADUATE STUDENTS Chapter 13 – Respiratory Pulmonary Physiology -What is respiration? What processes make it up? Respiration: sum of processes that accomplish ongoing passive movement of O2 from atmosphere to tissues to support cell metabolism and continuous passive movement of metabolically produced CO2 from tissues to the atmosphere. Cellular Respiration: intracellular metabolic processes carried out within the mitochondria which use O2 and produce CO2 while delivering energy from nutrient molecules External Respiration: entire sequence of events in the exchange of O2 and Co2 between external environment and the tissue cells. -What is the relationship between PO2 and Hb saturation? This is a proportional relationship: as PO2 increases, Hb saturation increases -What are the four steps to external respiration? 1.)Ventilation (mechanical process): movement of air into and out of the lungs 2.)Diffusion: of O2 and CO2 between air in alveoli and blood within the pulmonary capillaries 3.)Blood Transports: O2 and CO2 between lungs and tissues 4.)Diffusion: of O2 and CO2 between the tissues and blood across systemic (tissues) capillaries -Understand the difference between the tissue of the lungs vs. the airways of the lungs. Lungs are occupied in the thoracic cavity of the body. Lungs are divided into lobes which divide into segments Lobes consist of highly branched airways (tubes to bring air in), alveoli, pulmonary blood vessels, elastic connective tissue Outer Chest Wall: formed by 12 pairs of ribs and variety of skeletal muscle -Understand the anatomy of the lungs: conducting zone vs. respiratory zone, branching, bronchi vs bronchioles, alveoli Conducting Zone: ends after divisions (diameter shrinks with each branch division) No gas exchange (Dead Space: contain air, but no exchange between O2 and CO2, 150 mL of air) Trachea and Bronchi contain Cartilage (Cartilage Rings on Trachea: Give flexibility) Bronchioles: smooth muscle (no cartilage), regulate resistance (lets more or less air in) Respiratory Zone: Respiratory bronchioles to alveolar sacs (air filled sacs) Involved in gas exchange  High surface area for capillary exchange (more diffusion) -What is the mucociliary escalator? Why is it important? Where is it at? Within the conductive zone, the mucociliary escalator is a host defense mechanism that pushes mucous up and out of the system into the throat (keeps junk out) (In patients with asthma, CF, or COPD, the production and secretion of mucus is markedly upregulated) Iclicker: Are the cilia in your trachea beating up or down? - Up, a dust particle comes in and cilia pushes it back out. -What effect does surface area have on the alveoli? Within the respiratory zone, Alveoli’s main function: gas exchange Surface Area allows for the alveoli to have more options to pull from (air) Type 1 Alveolar Cells: walls of alveoli (single layer, flattened) Type 2 Alveolar Cells: Secrete pulmonary surfactant (chemical that helps keep your alveoli from collapsing) -Understand the anatomical set up of the alveoli and why its important to have capillaries nearby. Type 1 Alveolar Cells: walls of alveoli (single layer, flattened) Type 2 Alveolar Cells: Secrete pulmonary surfactant (chemical that helps keep your alveoli from collapsing) Importance of capillaries: pulmonary capillaries encircle each alveolus. Important for gas exchange of CO2 and O2 -Know the anatomical set up of the lungs, how do our different membranes interact to give us the pleural space and its corresponding relationship with thoracic wall and diaphragm. Inner to outer: 1.) The pleural sac encases the lungs 2.) Visceral Pleura: membrane that touches the lung (or organ) 3.) Parietal Pleura: outer membrane that touches the connected to the chest wall 4.) Chest (thoracic wall) 5.) Diaphragm -Know the three important pressures for ventilation: atmospheric pressure, intra-alveolar pressure and intrapleural pressure. Atmospheric Pressure: 760 mmHg at sea level Intra-Alveolar Pressure (lungs): pressure within the alveoli – 760 mmHg when equilibrated with atmospheric pressure Intrapleural Pressure (IPP) (lungs and chest interacting): pressure within the pleural sac – pressure exerted outside the lungs within the thoracic cavity, usually less than atmospheric pressure at 756 mmHg -Be able to interpret spirometry tracing and its corresponding terms. Lung volumes are direct measurements from the tracing, capacities are calculated. Tidal Volume (TV): amount of air that enters or leaves the lung in a single respiratory cycle 500 mL Functional Residual Capacity (FRC): amount of gas in the lungs at the end of a passive expiration A marker for lung compliance Inspiratory Capacity (IC): maximal volume of gas that can be inspired from FRC  Deep inhalation Inspiratory Reserve Volume (IRV): additional amount of air that can be inhaled after a normal inspiration Amount of air that you can take in additionally after a title volume Expiratory Reserve Volume (ERV): additional volume that can be expired after a passive expiration Additional air you can force out of your lungs Residual Volume (RV): maximal volume that can be expired after a maximal inspiration Air left in lungs (will never be able to completely deflate your lungs) Vital Capacity (VC): volume that can be expired after a maximal inspiration Total Lung Capacity: amount of air in the lung after a maximal inspiration Respiratory System: Static Respiratory Mechanics -Understand all of the forces that are going into static mechanics. What are isolated recoil forces? How do they interact to give us FRC? Lung recoil represents the inward force (lungs always want to collapse) Created by the elastic recoil properties of lung tissue and the alveoli As the lungs expand, recoil increases; as the lungs get smaller, recoil decreases Chest wall recoil is the outward force Chest wall always wants to expand FRC: represents the point where the outward recoil of the chest wall is counterbalanced by the inward recoil of the lung. The forces moving in the opposite direction create the negative IPP Negative IPP: no air is moving -Why is the IPP negative (sub atmospheric)? What causes it to be that way? IPP: pressure in the thin film of fluid between the visceral and parietal pleura. The outward recoil of the chest and inward recoil of the lungs create a negative IPP If the pressure of the intrapleural space (756) is greater than the intra alveolar pressure (760), the lung WILL COLLAPSE. -Understand what a transmural pressure gradient is – specifically the transpulmonary pressure gradient. What does it mean when it's positive? More positive? Negative? *remember the bulk of those numbers were given to help you understand what’s going on, it's more important to understand the relationship (ex. What does it mean when Pa > Patm...air is leaving lungs) PTM = PInside - Poutside PTM = 760 -756 = +4 (At FRC, IPP is subatmospheric, so PTM is positive) The positive outward force counters the lung elastic recoil and prevents alveolar collapse PTM = Negative = lungs are collapsed PTM = Positive = lungs are inflated (when you inspire air, PTM increase) When Pa > Patm : air is leaving the lungs -Understand the relationship between compliance and elasticity. Compliance is important for inspiration where elasticity is important for expiration. Think about blowing up a balloon. Compliance (Breathing In): how much effort is required to stretch or distend the lungs The less compliant or stiff the lungs are, the more work required to produce a given degree of inflation High Compliance = High ability to expand Low Compliance = low ability to expand Elasticity (Breathing Out): Driving force going to make it come back to original shape High elasticity: easier to deflate Low Elasticity: harder to deflate -What are the two components of elastic recoil? Which contributes more? Why is it important to have elastic recoil? What happens if elastic recoil forces are too strong? What role does surfactant play in elastic recoil? Elastic Recoil Comes from: 1.) Tissue Itself: collagen and elastic fibers of the lung 2.) Surface Tension inward forces in fluid lining the alveoli where liquid air interface Greatest component of recoil Pulmonary Surfactant decreases surface tension by separating water molecules. Prevents alveoli collapsing and maintains lung volume 3.) Collapsing forces necessary to exhale, but must be countered at the end of expiration to prevent alveoli from collapsing completely during expiration -Be able to think through what happens when there is a deficiency in surfactant. Is it hard to breathe in or out? What are the two conditions we see with surfactant deficiency? If there is a decrease of activity of pulmonary surfactant: Increase surface tension Increase lung elasticity Increase risk of edema Increase lung resistance Decrease of lung compliance (stiff) Decrease of lung volume (collapse) (Patients struggle to breathe in) 1.) Infant Respiratory Distress Syndrome (IRDS): babies are born prematurely and have not produced sufficient surfactant 2.) Adult Respiratory Distress Syndrome (ARDS): caused by airway gastric aspirations, infect surfactant production -Describe Lungs at Rest At rest or FRC, muscles are relaxed Tendency of the isolated lung is to collapse Tendency of the isolated chest wall is to expand -Inspiration is an active process meaning it requires energy. What are the four forces to overcome for Inspiration? Dynamic Force (Use ATP) To actively inflate lungs, the muscles of the chest wall must exert energy to: 1.) Overcome elastic recoil of the pulmonary System 2.) Overcome friction caused by the moving tissue (lungs and chest) rubbing against tissues Tissue Resistance 3.) Overcome friction caused by the moving air rubbing against the conducting airways Flow Resistance 4.) Overcome the forces of inertia associated with the moving tissues and the flowing air -Know the steps for inspiration and expiration. Be able to think through which muscles contract (and why) and how those muscles cause volume changes to cause pressure changes. Remember we breathe air in and out of lungs because we change pressure gradients and the air simply follows its pressure gradient. Inspiration 1.) The diaphragm via phrenic nerve and external intercostal muscles contract  Phrenic nerve: C3, C4, and C5 of the cervical region of the spine 2.) Diaphragm moves down, ribs are elevated 3.) IPP falls from 756 → 752 because more stretch and recoil from the contracting muscles 4.) Lungs expand 5.) Intrapulmonary pressure then drops from 760 → 759 and air enters the lungs Boyle’s Law: Increased Volume, decreases pressure Resting Expiration Cause: relaxation of the muscles contracted during inspiration causes elastic recoil to kick in Relaxation of the diaphragm and muscles of chest wall and the elastic recoil of the alveoli: 1.) decrease the volume of the chest cavity 2.) intrapulmonary pressure increases leading to pressure increases above atmospheric from 759 → 761: air is driven out -When does the expiration stop: when in equilibrium with atmospheric pressure (FRC), marks the end of expiration -What does it mean when the diaphragm is contracted [flattened] relaxed [dome shaped]? Diaphragm is contracted [flattened]: inspiration Diaphragm is relaxed [dome-shaped]: expiration -How do we do a forced expiration? Who is more likely to do a forced expiration? Forced Expiration Includes muscles of anterior abdominal wall (Increases intra-abdominal pressure), Internal intercostals (depress rib cage) Active during high ventilation, compensation for COPD. Also essential for coughing, sneezing, straining Emphysema (Loss of elasticity): struggle to breathe air out! (uses forced expiration) -What does parasympathetic stimulation cause in the airways? Bronchoconstriction or bronchodilation? Anything else? BronchoConstriction: parasympathetic stimulation causes increased resistance leading to closing of the airways 2-Fold Protection System: 1.) Decreased Airflow 2.) Increase in mucus production -What does sympathetic stimulation cause in the airways? Bronchoconstriction or bronchodilation? Anything else? BronchoDilation: sympathetic stimulation increases radius and decreases resistance to airflow Hormonal Control of Epinephrine -Work of Breathing (Ventilation) Normally requires 3% of total energy expenditure for quiet breathing 3 factors must be overcome for ventilation: 1.) Elastic Recoil of Chest and Lung 2.) Frictional resistance to gas flow in exchange 3.)Tissue frictional resistance -Understand alveolar ventilation and that pressure gradients are what drive gases to move. This is the diagram that walks through the exchange of oxygen between blood and tissue. Alveolar Ventilation: the process of exchanging O2 and CO2 between the alveoli of the lungs and the outside environment. INVOLVES PRESSURE GRADIENTS -Gas Partial Pressure Gas Partial Pressure: gas exchange involves simple diffusion of O2 and CO2 down partial pressure gradients Partial Pressure: pressure exerted on gas x % of gas in mixture PO2atm = 760 mmHg x 0.21 (percent of O2) = 160 mmHg Once in the body, does O2 pressure increase or decrease? - Decrease -How is partial pressure affected when there is a change in atmospheric pressure? What if there are other gases around (think about when we breathe oxygen into our trachea (water vapor) and then into our alveoli (CO2)) PO2atm = 0.21 (760 mmHg) = 160 mmHg Inspired air warmed to 37°C and completely humidified Humidifying the air reduces the parietal pressure of other gasses. The -47 below is a correction factor for water vapor: PinspiredO2: 0.21 (760-47) = 150 mmHg -As the air gets into your alveoli, PO2 is going to drop even more to what number? Why? - PO2 will drop to 100 mmHg and this is because of CO2 -PO2: Alveolar Air PAO2= 100 mmHg -Alveolar PCO2 PCO2 = 40 mmHg ^Determined By: rate of CO2 production (VCO2), rate of CO2 removal from lungs (alveolar ventilation) PACO2: VCO2/VA Can be used evaluate alveolar ventilation -Know the two abnormal breathing patterns – what they do to CO2 levels and does it make you acidotic or alkalotic? Hyperventilation: When PACO2 is lower than normal If alveolar ventilation is doubled, PACO2 is cut in half Alkalotic: blood pH is higher is normal because the lungs aren’t removing CO2 Hypoventilation: When PACO2 is higher than normal If alveolar ventilation is cut in half, PACO2 is doubled Shallow Breathing Acidotic: blood pH is lower than normal because the lungs aren’t removing CO2 -Understand why arterial blood gases reflect lung function and venous blood gases reflect tissue function. -What is hemoglobin? How much oxygen does it carry? Hb Major Role: to store O2 and influences the total amount of O2 carried in the blood Only 1.5% of O2 in plasma, important regulator 1 Hb = 4 heme groups (each bind 1 O2) Blood leaving the lungs (arteries) PaO2: 100 mmHg, Hb Saturation: 98% -Be able to think about the relationship graphed on an oxygen-Hb dissociation curve. Right shift vs. left shift. What causes it to shift? How do I know it shifted? What does an increase/decrease in the P50 represent? What are the different points on the graph (arterial vs. venous blood)? What happens when I exercise? What happens to the affinity of oxygen on Hb when it shifts? PO2 is the main factor determining Hb. Saturation Site 4: PO2 = 100 mmHg, Lungs; 98% Hb Saturation Blood leaving the lungs; highest amount of oxygen present Site 3: PO2 = 40 mmHg, Tissue, O2 dissociates; 75% sat Difference between #4 and #3 represents amount of O2 the tissue extracted from the blood (only using 25% of oxygen of the tissue is extracted out of blood) Site 2: Normal PO2 = 26 mmHg P50 = PO2 required for 50% saturation Minimum desaturation under normal conditions -Decrease in HB Saturation in Venous Blood: More active Tissue GOOD -Decrease in Hb saturation in artery blood: lung dysfunction BAD Right Shift: a reflection of the decreased affinity (ability to hold on to something) of Hb in O2 Represents enhanced oxygen release from Hb to tissues under metabolic demand Are we releasing more or less oxygen with the blue curve? - a right shift means more O2 is released in the blood to be utilized by the tissues Are we releasing more or less oxygen with the green curve? - A left shift curve means that oxygen is staying in blood Normal Oxygen Release:Hb-75% saturated which means 25% was offloaded to tissue Enhanced Oxygen Release: Hb-55% saturated which means 45% was offloaded to tissue -What are the three ways that CO2 is transported in the blood? 1.) Dissolved in plasma: 5%, PaCO2 2.) Carbamino compounds: 5% 3.) Bicarbonate: 90% of CO2 is carried as plasma bicarbonate -What happens to Co2 when it gets into a RBC? What does that H+ ion cause? When CO2 gets into a RBC, it is converted to bicarbonate to be diffused into the blood. The H+ ion causes Hb to release oxygen. -What is the Bohr effect? Haldane effect? Bohr Effect: Binding of H+ to Hb to release oxygen Graphed as a right shift On average, body releases 25% total oxygen content for use by tissues (4 → 3) CO2 into tissue, O2 out of tissue Takes place in your tissues Haldane Effect: ability of deoxygenated blood to carry more CO2 than oxygenated blood Binding of O2 with Hb in the lungs promotes dissociation of CO2 from blood O2 into, CO2 out of Takes place in your lungs -What is the DRG? What does it control? DRG: Inspiratory Center of neural control regulation Controls Diaphragm -What are central chemoreceptors? What do they respond to? Where are they located? When are they stimulated (1st or 2nd)? Are they strong or weak? Do they adapt? Central Chemoreceptors : Located in the brain and respond to CO2, stimulated 2nd Actively increase ventilation Stimulated by changes is CSF pH via CO2 Main Drive (initial trigger) for ventilation is CO2 (H+) on the central chemoreceptors ^system ADAPTS within 12-24 hrs Produce significant increase in ventilation with hypercapnia (elevated CO2) There are no central PO2 receptors - What are peripheral chemoreceptors? What do they respond to? Where are they located? When are they stimulated (1st or 2nd)? Are they strong or weak? Do they adapt? Peripheral Chemoreceptors: O2, CO2, H+, Stimulated 1st in changes in arterial CO2 levels Carotid Bodies: near carotid sinus, afferents to CNS in glossopharyngeal nerve (IX) Aortic Bodies: near aortic arch, afferents to CNS in vagus nerve (X) Monitors CO2 and pH of arterial blood: Less sensitive than central, small contribution to normal drive.  Increases firing as PaO2 falls below 80 mmHg and becomes marked and progressive when PaO2 is less than 60 mmHg -What type of chemoreceptor is stimulated last (when O2 Levels have dropped below 60 mmHg)? -know the four types of hypoxia and just the general definition/cause of each. When O2 levels have dropped below 60 mmHg, stimulation of peripheral chemoreceptor -What’s different at altitude? What happens to our PaO2? How does our body respond? Altitude Stress → Abnormal Air Composition: symptoms occurs when atmospheric pressure falls to around 520mmHg If I drop you on the summit of Mount Everest, what is the 1st thing your body does? - hyperventilate because PaO2 dropped below 60 stimulated peripheral chemoreceptors -What happens during acclimatization? increase hematocrit = increase in RBCs = polycythemia Physiological Adjustments: 1.) Increase Ventilation (blow off CO2): peripheral chemoreceptors due to low arterial O2 2.) Increase Hematocrit: due to EPO, increase oxygen carrying capacity in blood EPO: kidney, PRO that tells you to make more RBCs -What is altered when someone has polycythemia/anemia? Lungs are fine, the number of RBCs is different so the total O2 content changes. No change in the P50, graph is not shifted Anemia: reduction in Hb concentration Polycythemia: higher than normal Hb concentration (more RBC) (Your lungs are fine. You have the right amount of O2 in your plasma and the right amount of O2 bound to Hb. You just have more or less RBCs = more or less Hb overall) -What happens with CO poisoning? Which way is the graph shifted? What happens to the P50? Affinity for oxygen? Carbon monoxide binds with Hb → carboxyhemoglobin (COHb) CO poisoning makes Hb affinity for CO be 200x more than for O2, so small amounts of CO tie up large amounts of Hb Co decreases functional concentration of Hb; form of acute-onset anemia (reduced arterial O2 content) What causes Hb to hold to oxygen and not to release it? - Carbon monoxide (very hard to release O2) Condition worsens because Hb-O2 dissociation curve shifts to the left, P50 is decreased, unloading of O2 is hindered Common Symptoms: Headache, nausea and vomiting, dizziness, lethargy and a feeling of weakness Numbers to know: Patm = 760 mm Hg, O2 Air composition = 21%, PO2 = 80-100 mm Hg, Hb saturation = 95-100% Total oxygen content = 20 mL oxygen/ 100mL of blood (20% volume) PAO2 = 100 mm Hg  PACO2 = 40 mm Hg PO2 = 40 mm Hg (in venous blood entering the pulmonary capillary) PCO2 = 46 mm Hg (in venous blood entering the pulmonary capillary) P50 = 26 [normal] Chapter 14 – Renal -What are the main functions of the kidney? Know the general structure/anatomical components. Kidney Functions (Receive 25% of CO, 1L of blood in your kidneys at any given time 1.) Changes in Blood Pressure Maintain H2O balance in body Maintain proper osmolarity Regulate quantity and concentration of most ECF ions Maintain proper plasma volume 2.) Factor of eliminating Waste Help maintain proper acid-base balance Eliminating waste of bodily metabolism, especially urea Excreting Foreign Compounds 3.) Endocrinology Function: Hormones Producing Erythropoietin (kidneys tell to make RBC) Producing Renin Converting vitamin D into its active form General Renal Structure 1.) Kidneys supplied by single renal artery and vein 2.) Body roughly divided into cortex (outer region) and medulla (inner region) 3.) Human kidneys are partially segmented with the medulla consisting of pyramids (partially segmented) 4.) The urine is collected by minor and major calyces; drains into pelvis and to ureter 5.) Abundant sympathetic innervation of vasculature and tubules Increase in Sympathetic Activity = Increase in BP Particle X is a waste product produced via cellular metabolism in the body. Particle X is measured in the renal artery. Would you expect the amount of particle X to increase, decrease, or stay the same in the renal vein? - Decrease (Theoretically if you compare the renal artery to the renal vein, you’ll be able to figure out what the kidney did.) -What is the nephron? What are the vascular components? Tubular components? What are the two types of nephrons? Which is more numerous? What are there different functions? Nephron: Functional unit of kidney Consisting of glomerulus and tubule system surrounded by capillaries 2 Types of Nephrons: Superficial (cortical) nephrons, juxtamedullary nephrons Cortical Nephrons (70-80%): short loops of Henle surrounded by peritubular capillaries, found only in the cortex. Juxtamedullary Nephrons (20-30%): long loops of Henle surrounded by vasa recta (contributes to vertical osmotic gradient), found in cortex and medulla Vascular Components: Afferent arteriole, Glomerulus capillary , Efferent Arteriole (involved in filtration of blood) Peritubular capillaries (function in reabsorption and secretion), vasa recta (with peritubular capillaries function in reabsorption and secretion) Tubular Components Bowman’s Capsule  Proximal convoluted tubule Loop of Henle Distal Tubules Collecting Ducts -Know the pathway of blood through the kidney focusing on only the pieces I said you needed to know. Don’t worry about all those extra arteries. Heart → Aorta → Renal Artery → Afferent Arteriole (“dirty blood”) → Glomerulus (capillaries) → Efferent arterioles → Peritubular Capillaries (“Clean Blood”) → Renal Vein → Inferior Vena Cava → Heart -Renal Blood/ Fluid Flow Renal Blood Flow: 20-25% of CO or approximately 1200 mL/min or 1 L Glomerular Filtration Rate (GFR): approx. 100-120 mL/min How much Bowman’s Capsule collects in a minute (Primary way of measuring kidney function) Urine Flow Rate: approx 1 mL/min Urine Production: 1-1.5 L/day (Human physiology tends to favor water conservation by producing concentrated urine: dark urine) -Big picture: our kidney’s job is to filter the blood, we want to keep the good stuff and get rid of the bad via urine. Blood enters the kidney which then (1) filters into the tubular components. That filtrate then traverses the tubular components where it undergoes (2) reabsorption and (3) secretion until eventually We have produced urine. Urine is excreted via the ureters, bladder, urethra. Urine Formation Blood is filtered creating a fluid known as renal filtrate Filtration occurs in specialized capillary beds known as the glomerulus (GFR) Filtrate passes through various regions of the tubule Filtrate is modified by reabsorption and secretion and what is left behind is excreted as urine -Know the difference between tubular reabsorption and tubular secretion Tubular Reabsorption: selective transfer of specific substances in the filtrate back into the blood of capillaries On average, of 180 L of plasma filtered in a day, 178.5 L are reabsorbed Tubular Secretion: selective transfer of substances from the peritubular capillary blood into the tubular lumen Provides an additional route for substances to enter the renal tubules from the blood -Know the micturition reflex. Where is there smooth muscle? Skeletal muscle? Where can we control? Where can we not control? Micturition Reflex: Process of elimination Urine, stored in the bladder and emptied by micturition Peristalsis: pushing urine from kidney (ureters) into the bladder Bladder can stretch from 200-400 mL of urine before stretch receptors are activated for reflex Reflex causes involuntary emptying of the bladder Bladder contraction and opening of both the internal and external urethral sphincters Voluntarily prevented by tightening of the external sphincter and pelvic diaphragm -What does sympathetic activity do during the micturition reflex? What does parasympathetic activity do during the micturition reflex? 1.) Sympathetic activity relaxes the bladder allowing it to fill (Relaxes Bladder) 2.) Urine accumulation in bladder stimulates stretch receptors  3.) Stretch receptors trigger parasympathetic reflex that causes smooth muscle in bladder wall to contract and internal sphincter opens (Contracts bladder) 4.) Stretch receptors send input to the cortex signaling bladder is full 5.) Urine is only expelled if we relax the external urethral sphincter via somatic motor system GLOMERULUS -Go back and review the general rules of bulk flow across capillary beds. hydrostatic pressure (55 mmHg) > colloid osmotic pressure = ultrafiltration [ in glomerulus] Hydrostatic Pressure: Filtration, pushes things out of blood Colloid Osmotic Pressure: pulls back into blood hydrostatic pressure < colloid osmotic pressure = reabsorption [in peritubular capillaries] -What are the three things that allow the glomerulus a greater rate of exchange? 1.) Higher Permeability Fenestrations: pores in capillary wall, allow materials to be filtered 2.) Higher Capillary Hydrostatic Pressure 2 Arterioles: Afferent and efferent Dilate and constrict to very tightly regulate pressure in the glomerulus 3.) BP is constant across glomerulus Renal Autoregulation: regulating the afferent and efferent arteriole diameter to maintain pressure -Be able to think through what happens when I...what does this do to GFR? (1) constrict the afferent arteriole, leave efferent alone – decrease GFR (increase resistance, decrease blood flow) (2) constrict the afferent arteriole and constrict the efferent – GFR generally decreases (3) constrict the afferent arteriole and dilate the efferent – GFR decreases (4) dilate the afferent arteriole leave efferent alone — GFR increases (2) dilate the afferent arteriole and constrict the efferent – GFR increases (3) dilate the afferent arteriole and dilate the efferent – GF may slightly increase or stay the same -what is NFP? What are the three pressures that go into it? What happens to GFR when NFP goes up? Down? Net Filtration Pressure: net difference in these various forces favoring filtration 1.) Glomerular capillary blood pressure (hydrostatic) = 55mmHg 2.) Plasma-colloid osmotic pressure = 30 mmHg (due to plasma proteins, opposes filtration) 3.) Bowman’s capsule hydrostatic pressure = 15 mmHg (fluid accumulates in capsule, opposes filtration) NFP = 55-30-15 = 10 mmHg (Greater force on inside than outside, glomerulus wins) What happens if Bowman’s Capsule hydrostatic pressure goes up? - GFR decreases How does the Bowman’s Capsule Hydrostatic pressure go up? - kidney stone blocking ureter, enlarged prostate squeezing on urethra -How are we able to keep the BP across the glomerulus constant? What is renal autoregulation? We keep the BP of the glomerulus constant because of dilation of arterioles which increases blood flow Renal Autoregulation: regulating the afferent and efferent arteriole diameter to maintain pressure -What is the filtering membrane? What are the three components that make it up? Filtering Membrane: membrane of the glomerulus consisting of 3 structures (Makes up Glomerular Exchange Pathway)  1.) Capillary endothelial wall with Fenestrations (pores): promote filtration, prevents proteins from moving into the filtrate (except albumin) 2.) Glomerular Basement Membrane: negatively charged proteins (difficult for (-) PROs to cross) 3.)Epithelial Cell Layer of Podocytes: Filtration slits, openings for particles to move into the filtrate Pathology – Nephrotic Syndrome Nephrotic Syndrome: marked disruption of the filtering membrane, results in loss of negative charges from filtration barrier (basement membrane) Proteins now pass, a non-inflammatory injury Called Minimal Change Disease in Children -Most common clinical signs: Marked Proteinuria: > 3.5 gm/day Edema (loss of colloid pressure) Hypoalbuminemia (albumin lost in urine) -What effect does sympathetic stimulation have on GFR? Autoregulation prevents spontaneous GFR changes Kidney regulates itself via intrinsic controls (constrict or dilate afferent arteriole) Sympathetic control of GFR is involved in long-term regulation of arterial blood pressure ex.) dehydration, sympathetic overrides autoregulation and decreases GFR to conserve salts and water -What is tubuloglomerular feedback (TGF) and how does it further autoregulate GFR? What cells are important in this feedback system and where are they located? Increased Pressure, arteriole constricts to decrease flow and maintain GFR Decreased Pressure, arteriole dilated to increase flow and increase GFR When this is not enough to maintain GFR, the kidney uses tubuloglomerular feedback (TGF) to further autoregulate GFR. As GFR changes, so does the amount of sodium that is delivered to cells in the distal tubule; these cells monitor sodium levels as a reflection of GFR and then trigger TGF Juxtaglomerular Apparatus: macula densa cells are located in the distal tubule and detect salt levels to monitor GFR. They send signals to the afferent arteriole to adjust GFR back to normal. -Understand why the filtrate in Bowman’s capsule reflects the composition of the blood. Why don’t we see proteins in the filtrate under normal physiological conditions? Reflect composition of plasma Contains same solutes and concentrations of plasma except for proteins (includes water, nutrients, electrolytes and wastes) 300 mOsm (isotonic: same osmolarity of blood) Most of the solutes and water are reabsorbed in the proximal tubule YOU HAVE TO KNOW THE PERCENTAGES AND WHERE THEY ARE AT THROUGHOUT THE NEPHRON PCT Overview - 67% of filtered Na+ reabsorbed back into the blood - 67% of filter water reabsorbed: tight coupling of Na and water isosmotic reabsorption (important for maintaining ECF volume  - 67% of other electrolytes reabsorbed (Cl-, K+, Ca, Mg) - 100% of nutrients (glucose, AAs) reabsorbed - 80% of filtered HCO3 is reabsorbed here - 50% of the urea (waste product) reabsorbed -understand secondary active transport and that Na is required for glucose to gain entry to proximal tubule Cells. Secondary active Transport: Na+ is co-transported with glucose, AAs, phosphate, lactate or citrate down their concentration gradients Enter through apical side of proximal tubule (Facilitated diffusion: no ATP) Solutes exit the cell via specific transporters on basolateral side of proximal tubule to be reabsorbed back into the blood Na uses Na-K pump requiring ATP to get Na+ back out into the blood to continue going back in -Know the process for water reabsorption (2 methods) -Know the process for glucose reabsorption. SGLT1/2 transporter on apical membrane and GLUT transporter and Na/K pump on basolateral membrane. Revisit transport maximums and what it means for glucose reabsorption. Should we see glucose in the urine under normal physiological conditions? Major Mechanism for glucose entry: Sodium glucose linked transporter (SGLT) Mechanism for Glucose exit: GLUT2 transporter Does not rely on sodium Why does someone with diabetes have glucose in their urine? - The ECF is fully saturated with glucose. When plasma glucose is normal, no glucose excreted in the urine because all the glucose is reabsorbed (N) filtration = reabsorption Renal Threshold (T): is plasma [glucose] when glucose first starts to appear in urine. At this point, not all glucose can be reabsorbed. Glucose filtration > reabsorption -Understand the process for Urea reabsorption and why we reabsorb a waste product. As water is reabsorbed, the urea concentration within the tubular fluid increases A concentration gradient is created for urea to passively be absorbed (unintentional) 50% of the filter urea is reabsorbed this way BUN (Blood urea nitrogen): level of urea in the blood, increases BUN means impaired function -PCT is known for reabsorption of molecules, what is the main thing being secreted by the PCT? Main thing being secreted by the Proximal Tubule: foreign organic molecules (from capillary back into the proximal tubule) Acts as a supplement to glomerular filtration to help eliminate these compounds -Think about active vs passive transport. Where is ATP being used? Within the proximal convoluted tubule: Passive transport (Reabsorption): HCO3-, Urea, H2O Active Transport (Reabsorption): NaCl, glucose and amino acids Active Transport (Secretion): Waste Products LOOP OF HENLE -know the osmolarity of the filtrate as it moves through the tubule components. (isotonic, hypertonic, hypotonic) -what is reabsorbed in the descending limb? Why? Descending Limb: water is reabsorbed or drawn out by the vertical osmotic gradient (15% reabsorbed into vasa recta) -what is reabsorbed in the ascending limb? Why? What’s the difference between thin and thick limb? Ascending Limb: NaCl is reabsorbed Thin ascending Limb: Passive process, NaCl moves out due to high concentration of its ownself. The Concentration of the filtrate is greater than the osmotic gradient as you go up Thick Ascending Limb: Active transport -know the process of Na reabsorption in the thick ascending limb. NKCC2 transporter on apical membrane, Na/K pump Cl channel and K channel on the basolateral membrane. -Where does most of the K go (which membrane channel does it pass through)? Why? What affect does a net positive voltage in the urine have? What ions move as a result? Most of the K+ goes to the apical membrane because it is more permeable. Net positive voltage of urine promotes reabsorption of calcium and magnesium between cells -where do all those ions go that are moved by the NKCC2 transporter? Vertical osmotic gradient this is Why do we say the loop of Henle creates the VOG. -How does Lasix work? What do they target? Loop Diuretics: Lasix/Furosemide: inhibit NKCC2 transporters (blocks ions) More electrolytes left in filtrate, so water remains in filtrate Weakens the vertical osmotic gradient, less water reabsorbed in collecting ducts (really dilute, high volume urine) Causes electrolyte loss DCT -Know the differences in the early and late distal tubules. For Na+ reabsorption: 1.) Early DT: 5% of Na+ reabsorption, utilizes Na/Cl co-trasnporter on apical surface, involved in controlled calcium reabsorption via parathyroid hormone (PTH) 2.) Late DT: Principal Cells, 2-3% Na+ reabsorption, variable control via aldosterone, utilizes epithelial Na channels (ENaC) on apical surface -What two ions are secreted by the DCT? Secretion of H+ and K+ -Early DCT: Know the process of Na reabsorption through the Na/Cl cotransporter NaCl crosses apical membrane through NaCL cotransporter Na+ is pumped across basal membrane via Na/K-ATPase Cl- diffuses down its electrochemical gradient through channels -Early DCT: know the process of Ca reabsorption via hormone regulated calcium channels and what hormones control them. Calcium enters DT through hormone-regulated calcium channel under control of parathyroid hormone (PTH) Calcium exits basolateral side via active transport (Ca-ATPase or 3 Na-Caantiporter) -Late DCT: what are principal cells? What do they do? What hormone do they respond to? Principal Cells: site of controlled Na+ reabsorption 3% and K+ secretion Controlled by aldosterone (concentration determines how much Na+) Aldosterone comes from adrenal glands Aldosterone release is stimulated by angiotensin 2 (RAAS system) -know the relationship between macula densa cells and JG cells. What are they detected, what are each communicating with, who produces Renin? Juxtaglomerular Apparatus 1.) Macula Densa (distal convoluted tubule) Intrarenal chemoreceptors (monitor filtrate for Na levels) Sensitive to NaCL moving past them and into the tubular lumen Stimulates JG cells in response to: decreased Na concentration, decreased urine velocity 2.) Juxtaglomerular (Granular) Cells Functions as intrarenal baroreceptors Innervated by sympathetic nervous system Stimulated by the macula densa Secrete renin in response to: low BP, low blood volume -Once produced, where does Renin go? What does it do? Increased Renin secretion: Increased Na+ reabsorption by the distal and collecting tubules (water follows Na+ being reabsorbed, increasing ECF and restoring plasma volume) -What is the RAAs system? How is it activated? What are it’s components? What does it ultimately do? ** you have to know the RAAS system. -Late DCT: What are the three things aldosterone does to principal cells to enhance Na reabsorption? 1.) Synthesis and insertion of new epithelial Na channels (ENaC) to move sodium into the cell 2.) Synthesis and insertion of new Na/K ATPase, to move sodium into interstitial space to be reabsorbed into the blood 3.) Changes in metabolic pathways inside the cell to promote ATP Production -Late DCT: now the late DCT is impermeable to water under normal conditions. -Late DCT: What are the three things aldosterone does to principal cells to enhance potassium secretion? Understand this process. 1.) Synthesis and insertion of new Na/K ATPase to move K+ into the cell 2.) Increase in activity of ROMK channels in apical surface which allows potassium to enter filtrate to be excreted 3.) Changes in metabolic pathways to promote ATP production -Potassium homeostasis. Why do we so tightly regulate K levels in the blood? Where is most of our K in our body? What happens when we have hyperkalemia? What hormones help to “hide” K and stimulate the release of aldosterone by bypassing the RAAS system? Why do we so tightly regulate K levels in the blood? - to maintain normal membrane excitability in muscles and nerves. Where is most of our K in our body? - ICF (98%) (Body has more K+ than Na+) What happens when we have hyperkalemia? - Elevated ECF [K] ^ stimulates release of insulin, epinephrine to stimulate release of aldosterone to increase Na reabsorption -What causes K to enter the ECF (Blood)? Lack of insulin, blockage of Na/K pump Damaged Tissues such as burns and crush injuries -What is our body's immediate response to elevate K levels in the blood? Long term response? Immediate response: insulin and epinephrine stimulating Na/K pump Long term: K+ secreted over several hours via aldosterone stimulation -Late DCT:What are alpha-intercalated cells and what do they secrete? Alpha-intercalated cells: help maintain acid-base balance H+ created from CO2 via activity of carbonic anhydrase H+ secretion in urine, buffered by phosphate and ammonia  Formation of new bicarbonate which enters the blood During Acidosis, these cells secrete H+ into the urine and create bicarbonate which helps stabilize pH Acidosis: low blood pH, increase in H+ (increased CO2 levels in blood = hypoventilation) COLLECTING DUCTS -What depends on the action of the thick ascending limb of the loop of Henle to move salts into the interstitial space AND the collecting ducts to move variable amounts of urea into the interstitial space? What depends on these two things is variable water reabsorption (Vertical Osmotic Gradient) in the collecting ducts via ADH Loop of Henle creates Vertical osmotic Gradient Vasa Recta maintains vertical osmotic gradient -When there is a weak VOG...what is creating it? Vs a strong VOG? Weak Gradient: (On its own) Thick ascending limb can create a gradient range of 300-600 mOsm Absence of ADH Most NaCl that contributes Large volumes of dilute urine Strong Gradient: (Under water conservation) Collecting Ducts become permeable to urea Gradient ranges from 300-1299 mOsm Urea enters deepest portions of the medulla Small amount of concentrated urine -Understand which portions of the nephron are water permeable, impermeable, and have variable water Permeability. Controlled water reabsorption via ADH at collecting ducts -What effect does ADH have on the collecting duct? ADH = water reabsorption = water conservation = small concentrated urine no ADH = water loss = large volumes of dilute urine -Which aquaporin protein is dependent on ADH? Where is it located? Aquaporin 1 (front half of nephron): most important water channel NOT SENSITIVE TO ADH Aquaporin 2 (2nd half of nephron) most important ADH-sensitive water channel  SENSITIVE TO ADH -What type of urine is produced in the absence of ADH? Why? What type of urine is produced in the presence of ADH? Why? -Know that ADH = vasopressin (two names for the same hormone) -Know the process by which ADH inserts AQ2 into the apical membrane of the collecting ducts. 1.) V2 receptor activated by ADH 2.) More AQ2 channels in apical membrane 3.) Water leaves cell by AQ3/4 (not dependent on ADH) channels on basolateral membrane to go back into the blood ADH is secreted by the posterior pituitary and is released when very sensitive osmoreceptors in the brain detect the slightest change (1%) in ECF osmolarity. Osmolarity > 300 = dehydrated = more ADH = conserve water Osmolarity < 300 = hydrated = less ADH = get rid of water Terms to know: cortex, medulla, renal artery, renal vein, pyramids, calyx, renal pelvis, ureter, nephron, afferent arteriole, glomerulus, efferent arteriole, peritubular capillaries, vasa recta, Bowman’s capsule, PCT, Loop of Henle (descending and ascending limb), DCT, collecting ducts, superficial or cortical nephrons, juxtamedullary nephrons, vertical osmotic gradient, detrusor muscle, internal sphincter, external sphincter, net filtration pressure, fenestration, glomerular basement membrane, podocytes, filtration slits, nephrotic syndrome, macula densa cells, isosmotic reabsorption, secondary active transport, osmosis, aquaporins, transport maximum, renal threshold, BUN test, organic ion secretion, Loop diuretics [ Lasix/furosemide], PTH, aldosterone, juxtaglomerular apparatus, hyperkalemia, insulin, epinephrine, aldosterone, Numbers to know: Kidney receives 20-25% of cardiac output = 1 – 1.2 L/ min (or 1,000/1,200 mL/min) GFR = 100-120 mL/min Urine flow rate = 1 mL/min Urine production = 1.0-1.5 L/day with a range of 0.5-15 L/day PCT: 67% Na reabsorbed 100% glucose 67% water reabsorbed 80% HCO3- 67% electrolytes 50% Urea Loop of Henle: Descending limb: 15% of water reabsorbed  Ascending limb: 25% Na reabsorbed DCT: Early: 5% Na reabsorbed Late: variable 2-3% Na reabsorbed regulated by aldosterone Collecting Ducts 8-17% of water reabsorbed regulated by ADH