Lectures 18-24 Final exam slidesNo pics.doc

Osmoregulation, Excretion and the Environment: Lecture 18 Environment: External world:Whole animal Extracellular fluid: Cell Cytosplasm:Intracellular enzymes Water Balance and Concentration Internal Enviro=Aqueous Sol’n -Vol and comp must be maintained within Narrow Limits Comp different from external Enviro -comp tends to change towards equilib with the enviro Organism must Control changes in Comp of Bodily Fluid -Overall Solute Concentration (osmotic concentration) -Concentration of Specific Solutes Major Types of Hydric Enviro Aquatic- High water availability -Marine (High Solute Concentration) -Fresh Water (Low Solute Concentration) Terrestrial -Low water availability Ionic and Osmotic Challenges Marine- Gain salts, Lose water Freshwater - Lose salts, Gain water Terrestial - Lose water Marine Invertebrates -Typically OsmoConformers --Body fluids are isosmotic to sea water Marine Vertebrates: Elasmobranchs -Strict Ionic Regulators - [(salt)~1/3 that of sea water] - Osmotic [ ] largely due to organic solutes - Urea -Salt lvls maintened at Low Levels -Kidney: Remove many ions - Rectal Gland - Excretes fluid with high [ NaCal ] -Body Fluids are slightly Hyperosmotic -Tends to draw water into body - Water used in Urine formation and Rectal Gland Secretion Freshwater Inverts -Osmoregulators -Maintain Hyperosmotic body fluids -Problems: -Water tends to flow into animal -Osmotic uptake - Ions tend to flow out - Diffusion and excretion FreshWater Teleosts -Hyperosmotic blood -Water enters gills -Excrete Dilute Urine - Lose lots of solutes (high vol) -Ions tend to be lost from the gills - Ions taken up in the food - Active uptake of ions into gills The Role of Epithelial Tissues -Form boundary between animal and environment -External : Skin, Gills -Internal : Lumen of digestive and excretory systems -Have Physiological fctns in Respiration, Digestion and ion and water Regulation Terrestrial Organisms Advantage -Easy access to O2 Disadvantage -Dehydration ---Water gain must equal Loss Ways of losing : Evaporation (Body surface, Resp Surface) Excretion/Secretion (Feces, Urine, Other) Gaining: Drinking/Eating (Imbibing water, water in food) Integumental Uptake (From water, air) Metabolic Water Approaches for Terrestrial Animals -Vapor-Limited System - Animals have permeable integuments - Rate of water loss determined by transfer of water to surrounding air -Membrane-Limited System -Surface provides resistance to evaporation -Rate of evaporation altered by changing membrane permeability The Integument is an Osmotic Barrier -Animals change in flux of water across body surface by mediating permeability of the integu- ment -Aquaporin proteins increase water permeability 100-fold -Typically animals need to reduce water flux -Cover external surfaces with layer of hydrophobic molecules -Mucus -Stratum Corneam with Keratin -Cuticle with Chitin Stratum Corneum Structure -All Tetrapods depend on Keratinized stratum corneum to minimize dessication -Is the Thickend external Layer or modified epithelium found in mammals -Keratinocytes Differentiate into Corneocytes= Waterproof Layer Amphibians -Highly permeable integument -Typically lives in moist -Some desert species Reptiles -Generally ImPermeable Intugement -1/10th to 1/100th that of amphib -come more imperm in species from drier habitats Insects and Arachnids -Evaporative water loss countermeasures -Highly impermeable intugement Animals use different Mechanisms to Control Ion and Water B(waxy cuticle prevents excessive loss) -Discontinous Ventilation Different combos of tissues: Kidney, gills, skin, d-Intermittent opening of spiracles reduces loss gestiive mucosa: to regulate water/ion balance Mammals and Birds -Kidneys produce urine with [ ] less than sea water Regulate 3 homeostatic processes: 1. Osmotic Regulation Control of tissue os- -Salt Glands -Near eye, drain into ducts near nostril motic pressure, determines driving force for the -Produce highly [ ] saline fluid (NaCl) (more movement of water across biological membranes than salt water) 2. Ionic Regulation Control of ionic composi- -Respond to increased salt load in plasma tion of bodily fluids 3. Nitrogen Excretion Pathway in which animals excrete end products of catabolism Osmotic Regulation -Osmoregulators - Maintain osmotic [ ] of body fluids in narrow limits independent of environmnent osmotic concentrations -- most vertebrates -Osmoconformers - allow body fluid osmotic concentration to vary with environmental concentration; No active control --- many inverts. Ionic Regulation -Ionoconformer - little control over ion profile within the extracellular space - exclusively found in marine animals (ie. inverts) -Ionoregulator - control ion profile of extracellular space (verts) Cells transport solutes in and out of the extracellular fluid to control cell volume -water follows solutes via osmosis - Animal regulates composition of the extracellular fluids - provides cells with external soln that allows them to maintain ppropriate cell volume 4 Features shared by epithelial tissues to affect ion movements Asymmetrical Distribution of membrane transporters solutes selectively transported across membrane Cells interconnected to form impermeable sheet of tissue little leakage between cells High Cell diversity within tissue Abundant mitochondria large energy supply Solutes move across epithelial tissues by paracellular and transcellular transport Epith. cells use two main routes of transport -Transcellular Transport Movement through the cell across membranes -Paracellular Transport Movement between cells Leaky vs tight epithelia Types of Transporters -Na+/K+ATPase -Ion Channels -Electroneutral cotransporters -Electroneutral exchangers Ion Transport by Fish Gills Freshwater gill -Acid secreting cells (PNA-) import Na from water; Base secreting (PNA+) import cl- and Ca2+ Saltwater Gill - Export Cl- and Na+ Nitrogen Excretion - Ammonia produced during amina acid breakdown is toxic; must be excreted - Ammonia Nitrogen excreted in 3 forms -Ammonia (ammonioteles) - fish n stuff Uric Acid -Uric Acid (uricoteles) -reptiles birds, terAdvantages restial mollucs Few toxic effects -Urea (ureoteles) -all mammals Excreted in small vol of water Dis Aquatic animals usually = ammonia Terrestial = urea or uric acid Expensive to produce Many animals change mode of nitrogen excre- tion in response to water availability Urea Adv. Ammonia only slightly toxic relatively inexpensive to produce Advantages released by Dis deamination of is a perturbing solute amino acids requires little en- ergy to produce Disadvantages highly Toxic Req large vol of water to store and excrete Vertebrate Renal Physiology: Lecture 19 Renal System Consists of: Kidney --> Produces Ureter --> Transports to Bladder Urinary Bladder --> Temp Store Urethra --> Conducts to exterior, males semen too Major Functions of Kidney 1. Ion Balance- Extracell fluid osmotically, loss of ions with important roles (Ca/F) 2. Osmotic Balance- Vol of urine produced, water balance 3. Blood Pressure - Control blood vol, Vol of ECF is under control 4. pH Balance - Retaining or excreting H+ or HCO3- 5. Excretion - Nitrogenous wastes and water - Soluble toxins 6. Hormone production - ie. Renin (controls bp, and erythropoietin which regulates red blood cell synthesis) FACTS <1% of body mass Blood flow > muscles in heavy excercise Process 4 liters of blood/kg/min (muscles 0.5) Many hormones and neurotransmitters ensure urine composition and release are matched to physio needs of animal Major Processes of Urinary System Filtration of blood at glomerulus Reabsorption specific molecs removed from filtrate Secretion specific molecs are added to filtrate Excretion urine from body Kidney Structure and Function Two layers outer cortex Inner Medulla Minor calyces collect urine and joins together to form major calyx leaves via the ureter and passes into bladder for storage, to then leave through urethra The Nephron is the Functional Unit of the Kidney tubular structures : Produce Urine Kidney fctn depends on interplay between renal epithelium and the cardiovascular sys- tem. Main unit of Nephron Vasculature is the Glomerulus (cluster of capillaries that performs the first step of filtering blood) Nephron Structure Exist mostly within the cortex or within the medulla. Cortical nephrons: Make up ~85% of nephrons - Short loop of Henle Juxtamedullary Nephrons: Make up 15% of nephrons - Long Loop of Henle Cortical Nephrons Perform most of the reabsorptive and secretory fctns of kidney (Blood Enters through afferent Arterioles, to Glomerulus, goes to Efferent arteriole, and then to peritubular capills then venules) The Peritubular capills surround the whole loop Juxtamedullary Nephrons and the Vasa Recta are important in producing concentrated Urine (Peritubular capills connected to the Vasa Recta- long straight capillaries that are paral- lel to the nephron) 3 Basic processes of urine Formation Glomerular Filtration: Blood pressure forces solutes across the wall of the glomerular capills and into the capsular space Reabsorption is the removal of water and solutes from filtrate and their movement across the tubular epithelium and into the peritubular fluid. Secretion transport of solutes from the peritubular fluid across the tubular epithelium and into the tubular fluid Filtration occurs at the glomerulus -Wall of glomerular capillary retains blood cells and large macromolecules but lets liquid components and small solutes into the lumen of the Bowman’s Capsule -Fenestrated glomerular capillaries are very leaky Podocytes with foot processes form filtration structure -Mesangial Cells Control Blood pressure and Filtration in Glomerulus -Filtrate flows from Bowman’s Capsule into proximal tube of nephron. ( Bowmans capsule is like a bulb that the afferent arteriole flows into and the efferent ar- teriole flows out. the capillaries are surrounded by the podocytes on the sides, with mesangial cells inbetween the capillaries (at cross-sections). The foot processes of the podocytes are around the walls of capills. and allows the blood vessel lumen out. ) Glomerular Filtration Rate GFR - the amount of filtrate the kidneys produce each minute (~ 125 ml/min) One day : Glomeruli generate ~180 L of filtrate As filtrate passes through the renal tubules about 99% of it is Reabsorbed OVERALL NEURON So.. Blood enters Glomerulus (Bowmans Capsule) via the Afferent Arteriole Is then Filtrated through the capillaries into the lumen, done via Podocytes, and Mesan- gial cells control the rate (and Blood pressure The filtrated blood exits via the Efferent Arteriole, while the Filtrate goes to the Proximal Tubule. Here there is Reabsorption of water, ions, organic nutrients. (Proximal convoluted tubule)/Renal Tubule The Descending limb of the Loop begins, enter Thin Descending limb, Water move out Loops, Ascending Limb allows solutes to move out Ends, is now back in the Renal Tubule (part 2), Moves to Distal Convoluted Tubule, Secretion (into) of ions, acids, drugs and toxins, Reabsorption (out) of water/solutes. Now enters Collecting Duct, More reabsorpt. of water. Reabsorption or Secretion of solutes (depending on need) Delivery of urine to minor calyx Transport across the proximal Convoluted Tubule 60-70% of vol of filtrate Reabsorbed; 99-100% of the organic substrates; 60-70% of Na / Cl Na+/K+ Exchanger - Needs ATP Co-Transporter - for glucose (org solutes) - via secondary active transport Countertransporter - Like ^ but two ions move in opp directions Diffusion - Solutes Osmosis - Water Reabsorbed molec taken up by blood Transport Mechanisms across the loop of Henle Reabsorbs 25% water , 20-25% Na / Cl Thing Descending limp of loop - water reabsorbtion Thick Ascending Limp of loop - Active Transport of Na and Diffusion of Cl Loops of Henle: Countercurrent Multiplier Descending limb is Permeable to water water is reabs Vol of primary urine Decreases becomes more Concentrated Ascending Limb is Impermeable to water Ions Reabs (active transport) Primary urine becomes dilute (since there is less ions) Reabsorbed ions accumulate in interstitial fluid an osmotic gradient created in the medulla (because the beginning of the ascend loop puts lots of ions out, the de- scend loops loses more water to balance. this ensure it keeps losing water as it de- scends) Countercurrent mechanism performs two functions 1. Efficiently reabsorbs water and solutes (descend and ascend) 2. Establishes a Concentration Gradient that permits the Passive Reabsorbtion of water from the tubular fluid in the collecting system Transport Mechanisms across the distal convoluted tubule (after thick ascending limb Reabsorbs a variable amount of water (~5%) under Antidiuretic Hormone (ADH) Stimulation and a variable amount of Na Ions under Aldosterone stimulation Primary site of Ca Reabsorbtion (regulated by Parathyroid Hormone and Calcitriol) Aldosterone released from suprarenal cortex works on DCT and collecting duct to stimulate Na Reabs (so less Na in Urine) Effects of ADH on the DCT and CD Antidiuretic hormone controls the permeability of the DCT and DC to water --Presence of ADH = More permeable, loses more water =Small volume of concentrated urine (rather than a large volume of dilute) Vertebrate Renal Physiology Part 2 : Lecture 20 Kidney Blood Supply Afferent Arterioles deliver blood to capills supplying individual nephrons Functional Anatomy of Nephron Made of : Renal Corpuscle (Glomerus, bulb) Renal Tubule Convoluted segments=in cortex Loops of Henle = Extends partially into medula Renal Tubule (recieves filtrate) 1) Reabsorption of organic nutrients 2) Reabsorpton of 90% of water 3) Secreting waste INTO tubule that did not enter renal corpuscle Regulation of Urinary Function Hormones affect Kidney function -Steroids ie aldosterone = slow response -Peptide ie Vasopressin = rapid response Dietary Factors that affect urine output -Diuretics Stimulate excretion of water Antidiuretics Reduce excretion of water Nephrons Contribute to acid-base balance -Acid/Base balance is regulared by conditions in the Tubule Lumen, Interstitial Fluid and by Hormones -Transport in each segment of tubule contribute to the changes in pH of urine as a way to control body pH Main way is via transport of H+ and HCO3- -Na/H+ Exchanger -H+ ATPase -HCO3-/Cl- Exchanger Fluid and Solute Movement across Capillaries Determined by pressure across Glomerular wall 3 Main Forces - Glomerular capillary hydrostatic pressure - Bowman’s Capsule hydrostatic pressure -Oncotic Pressure - Osmotic pressure due to protein concentration in blood Balance between Hydrostatic pressure (fluid) and Oncotic Pressure (due to materials in soln on either side of capill walls) Filtration Pressures -Hydrostatic Glomerular Capillary Hydrostatic Pressure (GHP) Blood pressure in the glom capills Favours Filtration Pushes water and solute molecules Out of plasma Bowman’s Capsule Hydrostatic Pressure (BCHP) From resistance to flow into the capsule and along the nephron Opposes Filtration (resistance of filtrate to flow along the nephron) Pushes water and solutes out of filtrate and into plasma net hydrostatic pressure (NHP) Difference between the GHP and BCHP NHP=(GHP-BCHP) = (60mmHg - 15 mmHg) =45 mmHg Filtration Pressures : Colloid Osmotic Blood oncotic pressure (BOP) Osmotic pressure resulting from the presence of suspended proteins Opposes Filtration (Tends to draw water out of filtrate and into plasma) Filtration Pressure (FP) at Glomerulus Balance between -Hydrostatic P (fluid) -Blood oncotic P (materials in soln on either side of capil walls) (FP) At the Glomerulus is the difference between the Net hydo P and the blood Colloid osmotic pressure FP= (NHP-BOP) = (45 mmHg - 30mmHg) = 15mmHg (favours filtration) Control of GFR Glom Filt is the first vital step essential to all other kidney fctn Three interacting levels of control stabilize GFR 1. Autoregulation -Local Level 2. Hormonal Regulation - initiated by the kidneys 3. Autonomic Regulation- Primarily sympathetic division of the autonomic nervous system Autoregulation Maintains an adequate GFR despite changes in local blood pressure and blood flow Maintenance of the GFR is accomplished by changing the diameters of Afferent Arteri- oles, Efferent Arterioles and Glomerular Capillaries Reduction in blood flow. and decline in glom bp 1. Dilation of afferent arteriole 2. Dilation of glomerular capills (relaxation of supporting cells) 3. Constriction of efferent arteriole Increase in renal blood pressure stretches afferent arterioles and smooth muscles con- tract decreasing glomerular blood flow. Hormonal Regulators of GFR Hormones -Vasopressin (Antidiuretic, ADH) and Aldosterone -Renin-Angiotensin-Aldosterone (RAA) Pathway -Atrial Natriuretic Peptide Regulation of GFR - Hormonal Regulation :Vasopressin (aka ADH) -Peptide Hormone -Produced in Hypothalamus, released by Posterior Pituitary Gland - Increases water reabsorption from CD by increasing number of Aquaportins - Release stimulated by increasing plasma osmolarity detected by osmoregulators in the hypothalamus - Release is inhibited by increasing BP detected by stretch receptors in atria and barore- ceptors in carotid and aortic bodies Vasopressin hormone bind to G-protein linked receptor activates Adenylate Cyclase Increasing cAMP and activating Protein Kinase A Phosphorylation of cytoskeletal and vesicle proteins occurs Triggers Translocation of vesicle to cell membrane with insertion of Aquaporins Aldosterone enters via diffusion binds to transcription factor (nucleus) Activated it stimulates transcription of genes For transporters New Transporter proteins are made in ER and exported in vesicles Vesicles containing proteins are sent to plasma membrane Hormones called Mineralcorticoids control ion excretion Produced by Adrenal Cortex in tetrapods -Steroid hormone -Target cells in distal Tubule and CD - Stimulates Na+ reabs from urine - Enhances K+ secretion - Also stimulated by increases in circulating K+ Regulation of GFR - Hormonal Regulation Renin-Angiotensin-Aldosterone Pathway Renin secreted when BP or GFR lower than normal (Angiotensin activated, raises BP and Bvol.) Secretion of Renin controlled 3 ways Baroreceptors in juxtaglomerular cells release renin in response to Low BP Sympathetic neurons in cardiovascular control center of Medulla oblongata trig- ger renin secretion in response to Low BP Macula Densa cells in Distal Tubule respond to decreases in flow by releasing a Paracrine signal that induces Juxtaglomerular cells to release renin 1. Juxtaglomerular cells secrete enzyme Renin 2. Renin converts Angiotensinogen to Angiotensin I (Angiotensinogen an inactive protein in plasma) 3. Angiotensin converting enzyme (ACE) on epithelia of blood vessels converts an- giotensin I to Angiotensin II 4. Angiotensin II causes synthesis and release of Aldosterone from adrenal cortex Autonomic Regulation Most of the autonomic innervation of the kidnets consists of Sympathetic Post- ganglionic Fibers Sympathetic activation leads to Vasoconstriction of Afferent Arterioles and there- fore decreases GFD and slows the production of filtrate This Overrides the local regulatory mechanisms, example during an acute fall in BP - Heart Attack Hormonal Regulation of BP and Bvol Atrial Natriuretic Peptide -Produced in cardiac muscle cells in the right atrium (Heart) -Released in response to excessive stretching during diastole -Inhibits secretion of Vasopressin -increases urine output -lowers BP and Bvol -Acts as an Antagonist with RAA pathway -Increases excretion of Na+ in Urine -Increases GFR by relaxing contractile cells that control size of filtration slits of glomerulus (up water loss, Na+loss, Reduce thirst = Reduce Bvol) ( peripheral vasodilation, Block ADH, aldosterone, nor/epinephrine release = reduce BP) Decrease BP and Vol Short Term -