Bio 215 Endocrine and Renal

Bio 215 Endocrine and Renal - VERTEBRATE PHYSIOLOGY...

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Unformatted text preview: VERTEBRATE PHYSIOLOGY VERTEBRATE PHYSIOLOGY BIOL 215 Summer 2009 Amy I. Bentz, VMD, DACVIM University of Pennsylvania ENDOCRINOLOGY ENDOCRINOLOGY (Guyton, Boron) Coordinates body functions by chemical messengers Neural Endocrine Neuroendocrine Paracrine Autocrine NEURAL NEURAL Chemicals (neurotransmitters) are released at synaptic junctions and act locally to control cell function ENDOCRINE ENDOCRINE Glands or specialized cells release chemicals (hormones) into circulating blood that influence cell function at another location in the body Example: Growth hormone from ant. Pituitary Thyroxine from thyroid gland ENDOCRINE ENDOCRINE Pituitary gland (brain) Pineal gland Thyroid and parathyroid glands (neck) Thymus (thorax) Adrenal glands (next to kidney) Pancreas Reproductive glands www.drstandley.com/images/endocrine.bmp NEUROENDOCRINE NEUROENDOCRINE Neurons secrete substances (neurohormones) which enter circulating blood and influence cell function in another location in the body Example: Neuroendocrine cells located in the hypothalamus have axons which terminate in the post. Pituitary gland and secrete hormones (e.g. ADH, oxytocin) AUTOCRINE AUTOCRINE A cell secretes substances that affect the function of the same cell by binding cell surface receptors HORMONES HORMONES Most hormones are polypeptides and proteins Synthesized on rough ER of the different endocrine cells Usually synthesized as larger proteins, not biologically active (preprohormones) Cleaved to form smaller prohormones in ER Transferred to Golgi apparatus and packaged into secretory vesicles HORMONES HORMONES Vesicles are stored in cytoplasm Secreted when secretory vesicles fuse with the cell membrane and granular contents are extruded into interstitial fluid or directly into the bloodstream STEROID HORMONES STEROID HORMONES Usually synthesized from cholesterol and are not stored Lipid­soluble so can diffuse across cell membrane and enter interstitial fluid, then blood Examples: aldosterone, progesterone, cortisol NEGATIVE FEEDBACK NEGATIVE FEEDBACK Control of Blood Glucose by Insulin and Glucagon How the majority of hormones are controlled Stimulus causes release of hormone Then the product resulting from hormone release tends to suppress more hormone release (so the hormone or one of its products prevents oversecretion of the hormone, or overactivity at the target tissue instruct1.cit.cornell.edu/courses/biog105/p ages/demos/105/unit8/hormones.html POSITIVE FEEDBACK POSITIVE FEEDBACK Some hormones are controlled by positive feedback Example: Surge of Luteinizing hormone (LH) occurs as a result of the stimulatory effect of estrogen on the anterior pituitary before ovulation Secreted LH then acts on ovaries to stimulate additional secretion of estrogen, which leads to more LH secretion Eventually LH reaches the proper concentration, and negative feedback stops more hormone secretion http://www.tubal­reversal.net/images/LH­ FSH­surge.jpg PITUITARY HORMONES PITUITARY HORMONES Pituitary gland has 3 parts: Anterior lobe Posterior lobe Pars intermedia (larger in animals vs people) Located at the base of the brain just below hypothalamus Hormone release is controlled by hypothalamus Hypothalamus collects information from the body about internal well­being, then controls secretion of hormones from the pituitary through releasing and inhibtory hormones http://www.biologie.uni­ freiburg.de/data/bio1/varga/images/pituitary.jpg ANTERIOR PITUITARY ANTERIOR PITUITARY Secretes 6 peptide hormones which control metabolic functions throughout the body: Thyrotropin (Thyroid­stimulating hormone) Growth Corticotropin Follicle stimulating Luteinizing (LH) Prolactin ANTERIOR PITUITARY ANTERIOR PITUITARY Thyrotropin (Thyroid­stimulating hormone) Growth Promotes growth of entire body by affecting protein formation, cell multiplication and cell differentiation Corticotropin Controls rate of secretion of thyroxine and triiodothyronine by thyroid gland, which control metabolic rate of most cells in the body Controls secretion of some of the adrenocortical hormones which affect fat, protein and glucose metabolism Follicle stimulating (FSH) } Controls ovarian and testicular Luteinizing (LH) } growth and hormonal activity Prolactin Promotes mammary gland development and milk production POSTERIOR PITUITARY POSTERIOR PITUITARY Posterior pituitary hormones are synthesized by cell bodies (large neurons) in hypothalamus, then transported down the axon to the posterior pituitary gland Antidiuretic hormone (ADH) or vasopressin Controls rate of water excretion into urine so aids in control of water concentration in body fluids Oxytocin Causes contraction of pregnant uterus Helps milk letdown from mammary glands http://www.biologie.uni­ freiburg.de/data/bio1/varga/images/p uitary.jpg HYPOTHALAMUS HYPOTHALAMUS Uses Releasing and Inhibitory hormones to control pituitary: Thyroid­releasing hormone Corticotropin­releasing hormone inhibits release of GH Gonadotropin­releasing hormone release of Growth hormone Somatostatin (growth hormone inhibitory hormone) release of adrenocorticotropin Growth hormone­releasing hormone release of thyroid­stimulating hormone release of LH and FSH Prolactin inhibitory hormone causes inhibition of prolactin secretion ADH anti diarrheic hormone ADH anti diarrheic hormone (VASOPRESSIN) Causes retention of water Without ADH, collecting tubules/ducts are mostly impermeable to water, so water is lost in urine dilute urine With ADH, collecting ducts/tubules develop aquaporins to allow water reabsorption concentrated urine http://www.uic.edu/classes/bios/bios100/lecture sf04am/adh02a.jpg ADH (VASOPRESSIN) ADH (VASOPRESSIN) Near the hypothalamus are neuron receptors (osmoreceptors) When extracellular fluid is too concentrated, fluid is pulled by osmosis out of the receptor, decreasing its size Nerve signals are passed to hypothalamus ADH secretionwater retention ADH (VASOPRESSIN) ADH (VASOPRESSIN) Higher concentrations of ADH arteriolar constriction throughout the body increased arterial BP (Vasopressin) Stimulation of ADH secretion: Decreased blood volume Right atrium has stretch receptors (excited by overfilling) send signals to decrease ADH release When unexcited, send signals to increase ADH release THE THYROID THE THYROID Produces, stores and secretes thyroxine (T4) and triiodothyronine (T3) Can store 2­3 months of hormone, so it takes awhile to see problems if synthesis is decreased T3 is more potent than T4 so it is present in the blood in lower quantity and persists for a shorter amount of time Iodine (in table salt) is required for formation of T4 Over 99% of T3 and T4 combine with plasma proteins in blood, so they are released slowly into tissue cells THE THYROID THE THYROID TRH from hypothalamus TSH from anterior pituitary controls anterior pituitary release of TSH increases thyroid hormonal secretion Increased thyroid hormone in body fluids decreases TSH secretion by anterior pituitary (negative feedback) Main effect of thyroid hormones is to activate nuclear transcription of large numbers of genes generalized increase in functional activity throughout the body (inc. metabolic rate) THE ADRENAL GLANDS THE ADRENAL GLANDS Above (superior) to kidneys, Made of: Adrenal medulla Central 20% of gland Functionally related to sympathetic nervous system http://www.web­ books.com/eLibrary/Medicine/Physio Secretes epi and norepi in response to sympathetic ogy/Endocrine/adrenal_gland.jpg stimulation Adrenal cortex (outer gland) Secretes corticosteroids (all synthesized from cholesterol) CORTICOSTEROIDS CORTICOSTEROIDS Secreted by adrenal cortex: Mineralocorticoids (e.g. Aldosterone) Affect elytes (e.g. Na+, K+) Glucocorticoids (Cortisol) Affect blood glucose concentration Affect protein and fat metabolism Androgenic hormones (small amounts) THE ADRENAL CORT EX THE ADRENAL CORT Three layers: Zona glomerulosa Just under capsule Secretes Aldosterone Zona fasciculata Zona reticularis Deep layer of cortex Secretes dehyroepiandrosterone (DHEA) http://www.scielo.br/img/revistas/rbt Secretes Cortisol in response to ACTH i/v18n1/a14fig01.gif (adrenocorticotropic hormone from pituitary) HORMONES HORMONES Adrenocortical hormones are bound to plasma proteins (90­95% of cortisol in the plasma is bound to proteins) Slows elimination of cortisol from plasma So cortisol ½ life is 60­90 min ALDOSTERONE ALDOSTERONE Increases renal tubular reabs of Na+ and secretion of K+ into urine Addisons Disease (adrenal cortex affected): Deficiency causes renal wasting of NaCl and hyperkalemia death in a few days without treatment Glucocorticoid deficiency lack of normal blood glucose conc between meals CORTISOL CORTISOL Most types of stress cause inc. ACTH by ant. Pit cortisol release from adrenal cortex (fight or flight) Stimulates gluconeogenesis (forms carbs from proteins and other substances) by liver Decreased glucose utilization by the cells Increased blood glucose concentration Stimulates insulin to be released by pancreas Reduces protein stores (decreased protein synthesis and increased catabolism of protein already in the cells) Mobilizes fatty acids from adipose tissue Blocks inflammation (e.g. steroids) CUSHINGS SYNDROME Hypersecretion of cortisol Muscle wasting on dorsum Poor wound healing Skin disease THE PANCREAS THE PANCREAS Made of : Acini secrete digestive juices into duodenum Made of : Islets of Langerhans Secretes into blood Insulin (β cells) Glucagon www.montana.edu/wwwai/imsd/alc ohol/Vanessa/vwpancreas_files/ima ge002.jpg INSULIN INSULIN When there is an abundance of E­food in diet, it is stored (e.g. carbs, protein) Insulin is used to store the excess E Excess carbs stored as glycogen (in liver and muscle) or converted into fat, stored in adipose tissue Excess fatstored in adipose tissue INSULIN INSULIN After high­carb meal, Glucose is absorbed into blood Insulin is released Causes rapid uptake, storage and use of glucose by tissues in body, esp. mm, adipose tissue and liver http://www.humanillnesses.com/original/images/hdc_0001_000 1_0_img0082.jpg GLUCAGON GLUCAGON Secreted by α cells of the islets of Langerhans when blood glucose concentration falls (hypoglycemia) Increases blood glucose concentration Breakdown of liver glycogen (glycogenolysis) Increased gluconeogenesis in the liver DIABETES MELLITUS DIABETES MELLITUS Type I: juvenile, needs insulin Type II: older adult, overweight, insulin­ resistance (treatment – weight loss, insulin) Eat food (e.g. carbs) GI tract Glucose for energy Absorbed into bloodstream hyperglycemia (high glucose level e.g. 180 mg/dL)­renal capacity­ glucosauria (glucose spills into urine) High glucose level (e.g. 180 mg/dL) High glucose level (e.g. 180 mg/dL) Pancreas releases insulin from β cells in pancreas to bring glucose blood levels back to normal (e.g. 80­120 mg/dL) 1. Homeostasis – drives glucose into cell to be used for E If no endogenous insulin, supplement with Vetsulin Aim is to correct to homeostasis Type I – insulin dependent Type I – insulin dependent Dogs midage and older Insulin deficiency – little/no insulin production Type II – non­insulin dependent Cats, neutered males>females Older/obese animals Abnormal insulin production/insulin resistance Can develop remission with diet/exercise/weight loss If blood glucose levels are If blood glucose levels are abnormal.. Hyperglycemia (high glucose levels ~250­300mg/dL) Osmotic diuresis­ diabetics will have watery urine (glucose has water follow it) Polyuria/Polydipsia (↑urination/drinking) Ketoacidosis Hypoglycemia (low glucose levels) Coma due to brain requires constant levels of glucose (can’t survive for long without it) Ketoacidosis Ketoacidosis Hyperglycemia (high levels), excessive hormones (cortisol, epi, norepi etc) and insulin deficiency break down of lipidsfatty acid release (liver oxidizes them and instead of forming triglycerides, without insulin, they are converted to ketones (acetoacetic acid, acetone and β­hydroxybutyric acid) liver prod. glucose but unable to be used by cells due to lack of insulin SO body can’t use glucose and ketones for E without insulin and they spill into urine (osmotic diuresis) and Acid builds up in bodyacidosis Ketoacidosis Ketoacidosis Can be ok for up to 6 months dehydration, weakness, depression, Inc. RR, vomiting Smell of acetone on breath (human – alcoholic) Abdominal pain Obtunded Glycemic index Glycemic index Foods high in carbs (starch and sugar) Quickly broken down in intestinehigh levels of glucose in bloodinsulin hypoglycemiahungereat sugar again Refined foods (white rice, white bread, white sugar, potatoes etc) have high glycemic index Oats, barley, bran, whole wheat, raw sugar THE KIDNEYS THE KIDNEYS (Boron, Guyton) Functions: Process waste and excrete it Regulate water and electrolyte balance Regulate body fluid osmolality, elyte concentration Regulate acid­base balance Regulate arterial pressure Secrete, metabolize, excrete hormones Gluconeogenesis THE KIDNEYS THE KIDNEYS Process waste and excrete it: Urea (from aa metabolism) Creatinine (from mm creatine) Uric acid (from nucleic acids) End products of hemoglobin breakdown (e.g. bilirubin) Metabolites of different hormones Toxins and other foreign substances THE KIDNEYS THE KIDNEYS Regulate water and electrolyte balance To maintain homeostasis, balance excretion of water and elytes with intake THE KIDNEYS THE KIDNEYS Regulate arterial pressure Kidneys have dominant role in long­term regulation of arterial pressure by excreting sodium and water Also short­term regulation by secretion of vasoactive substances (renin) leads to angiotensin II http://www.actelion.com/uninet/www/www_main_p.nsf/Content/Cardiovascular %20&%20Renal%20Disease/$File/renin2.jpg THE KIDNEYS THE KIDNEYS Dec. arterial pressure (Guyton) renin release (enzyme stored in juxtaglomerular cells in walls of afferent arterioles) acts on renin substrate (angiotensinogen) to release angiotension I. Enzyme work on it and turns into Angiotensin II (in lung) 1. Powerful vasoconstrictor 2. Renal retention of salt and water (directly and by inc. aldosterone release increase retention of salt, water reabsorption by kidney Inc. arterial pressure http://upload.wikimedia.org/wikipedia/commons/thumb/a/a2/Renin­ angiotensin­aldosterone_system.png/800px­Renin­angiotensin­ aldosterone_system.png THE KIDNEYS THE KIDNEYS Acid­base balance: Excreting acid (H+) and regulating buffer stores Also excretes other types of acid from protein metabolism (e.g. sulfuric acid, phosphoric acid) THE KIDNEYS THE KIDNEYS Regulate erythrocyte production by secretion of erythropoietin (stimulates rbc production) Synthesis glucose from aa and other precursors during prolonged fasting (gluconeogenesis) http://www.tarleton.edu/~anatomy/erythro.jpg THE KIDNEYS THE KIDNEYS Produce active form of Vitamin D (1,25­Dihydroxy Vitamin D3) = calcitriol by hydroxylating this vitamin Needed for calcium deposition in bone and calcium reabs from GI tract http://www.mayoclinicproceedings.com/images/8103/8103r1­ fig1.jpg ANATOMY OF THE KIDNEYS ANATOMY OF THE KIDNEYS (Guyton) Called Retroperitoneal Renal artery and vein Lymphatics, nerve supply Ureter (carries urine to bladder) Cortex (outer part) Medulla (inner part) Outside of peritoneal cavity Size of clenched fist Divided into papilla, project into renal pelvis (upper part of ureter) galileo.phys.virginia.edu/classes/304/kidney.gif THE KIDNEYS THE KIDNEYS Blood flow to kidneys is ~22% of Cardiac Output 1100 ml/min Renal artery branches to afferent arterioles glomerular capillaries (where fluid and solutes (except plasma proteins) are filtered to begin urine formation Distal ends of the capillaries form efferent arteriolesperitubular capillaries (surround renal tubules) http://www.ivy­rose.co.uk/Topics/Urinary/Kidney THE KIDNEYS THE KIDNEYS Renal circulation is unique: 2 capillary beds separated by efferent arterioles to regulate pressure in each set of capillaries Adjusting afferent and efferent arterioles can change rate of glomerular filtration/tubular reabs Glomerular capillaries (~60mmHg) High hydrostatic pressurerapid fluid filtration Peritubular capillaries (~13 mmHg) Lower hydrostatic pressurerapid fluid reabsorption http://www.ivy­ rose.co.uk/Topics/Urinary/Kidney_Nephron_cIvyRose.jpg THE NEPHRON THE NEPHRON Functional unit of kidney Each kidney contains ~1 million nephrons (each capable of forming urine) Cannot regenerate new nephrons (unlike liver)­ which is why can end up with renal failure &dialysis Lose about 75% nephrons before see clinical changes (e.g. bloodwork abnormalities) http://www.ivy­rose.co.uk/Topics/Urinary/Kidney_Nephron_cIvyRose.jpg THE NEPHRON Each nephron contains: Glomerulus (glomerular capillaries) which filters large amounts of fluid Encased in Bowman’s capsule Tubule, which converts filtered fluid into urine, out renal pelvis www.engin.umich.edu/~CRE/web_mod/viper/pics/nephron.gif THE NEPHRON THE NEPHRON Fluid filtered from glomerulus flows into: Bowman’s capsule Proximal tubule (in cortex of kidney) Loop of Henle (renal medulla) Descending limb Ascending limb Thin segment of Loop of Henle­ Loop Diarrhetics (this is where acting) Descending limb Lower end of Ascending limb Thick segment of the ascending limb www.engin.umich.edu/~CRE/web_mod/viper/pics/nephron.gif THE NEPHRON THE NEPHRON Macula densa (after thick ascending limb) Controls nephron function Distal tubule (renal cortex) Connecting tubule Cortical collecting tubule Cortical collecting duct Medullary collecting duct Renal pelvis http://kcampbell.bio.umb.edu/December01/Juxtaglo.gif THE NEPHRON THE NEPHRON Two types depending on location: Cortical nephrons (glomeruli located in outer cortex) Short loops of Henle that penetrate a short distance into medulla Tubular system is surrounded by peritubular capillaries Juxtamedullary nephrons 20­30% of nephrons Glomeruli lie deep in renal cortex near medulla Long loops of Henle reach into medulla Efferent arterioles extend from glomeruli, then divide into special peritubular capillaries (vasa recta) Vasa recta return towards cortex and empty into cortical veins Essential for forming concentrated urine http://anatomy.iupui.edu/courses/histo_D502/D50 2f04/lecture.f04/urinaryf04/Ross193.jpg URINE FORMATION URINE FORMATION Rate at which different substances are excreted in the urine: Glomerular filtration Reabsorption of substances from renal tubules into blood Secretion of substances from blood into renal tubules Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion rate http://faculty.etsu.edu/currie/images/renal3.jpg URINE FORMATION URINE FORMATION Begins with fluid (contains no protein) filtration from glomerular capillaries into Bowman’s capsule Most substances in plasma are freely filtered (except plasma protein) so their conc in glomerular filtrate is ~same as in the plasma Filtered fluid leaves Bowman’s capsule, passes through tubules It is modified by reabsorption of water and specific solutes back into blood or by secretion of other substances from peritubular capillaries into tubules www.engin.umich.edu/~CRE/web_mod/viper/pics/nep hron.gif URINE FORMATION URINE FORMATION Example: creatinine­ important to measuring functioning (kidneys should be excreting it) Freely filtered by glomerular capillaries by neither reabsorbed nor secreted Excretion rate is equal to rate at which it is filtered (so excretion of essentially all that is filtered) Cr, BUNitrogen renal tests URINE FORMATION URINE FORMATION Example: Electrolytes Substance is freely filtered but also partially resorbed from tubules back into blood So, rate of urinary excretion is less than rate of filtration at glomerular capillaries Excretion rate = filtration rate – resorption rate URINE FORMATION URINE FORMATION Example: AA, glucose Substance is freely filtered at glomerular capillaries but is not excreted into urine because all the filtered substance is reabsorbed from the tubules back into the blood Except diabetes – glucosuria (>180 mg/dL) Tubular damage – glucosuria Osmotic diuresis URINE FORMATION URINE FORMATION Tubular Filtration, Reabsorption, Secretion of Substances Tubular Secretion: K+, H+ Reabsorption mostly occurs in: Proximal tubule AA, glucose (completely reabs) Elytes (Na+, Cl­, HCO3­) (highly reabs) Urea, cr, uric acid, some meds (poorly reabs) http://ex­anatomy.org/image/5.gif URINE FORMATION URINE FORMATION Tubular Filtration, Reabsorption, Secretion – work together to excrete substances Regulated according to body’s needs Example: Excess Na+ (french fries) Na+ filtration rate increases, smaller amt is reabsorbed So increased urinary excretion of Na+ Clinically, tubular damage also causes inc. Na+ excretion Why? Why? Why filter large amounts of water and solutes then reabsorb most of these substances? High GlomerularFiltrationRate allows kidneys to rapidly remove waste products (most waste products are poorly reabs from tubules) Allows body fluids to be filtered and processed by the kidneys many times a day Can filter plasma 60x/day GLOMERULAR FILTRATION GLOMERULAR FILTRATION Urine formation begins with large amt of fluid through glomerular cap, into Bowman’s capsule Glomerular cap are relatively impermeable to proteins and free of cellular elements (rbc, wbc) Glomerular filtrate fluid conc is similar to conc in plasma http://faculty.etsu.edu/currie/images/kidney3.jpg GLOMERULAR FILTRATION GLOMERULAR FILTRATION GFR = glomerular filtration rate Determined by: Hydrostatic pressure Colloid pressure Capillary filtration coefficient Product of permeability and filtering surface area of cap GLOMERULAR FILTRATION GLOMERULAR FILTRATION Glomerular capillaries have much higher rate of filtration than other capillaries due to High glomerular hydrostatic pressure Large capillary filtration coefficient Average adult person, GFR = 125 ml/min (180 L/day) GLOMERULAR CAPILLARY GLOMERULAR CAPILLARY MEMBRANE (Guyton) Similar to other cap membranes except has 3 (instead of usual 2) layers for filtration barrier: Endothelium Perforated by fenestrae Endothelial cells (– charge) prevent plasma protein passage (albumin) Basement membrane Large spaces to filter water and small solutes Proteoglycans (– charge) prevent plasma protein passage Epithelial cell layer (podocytes: ­ charge) surrounding outer surface of cap basement membrane Slit pores through which glomerular filtrate moves www.bio.davidson.edu/courses/immunology/Students/spring 2000/carter/restricted/download.jpg POSTERIOR PITUITARY POSTERIOR PITUITARY Posterior pituitary hormones are synthesized by cell bodies (large neurons) in hypothalamus, then transported down the axon to the posterior pituitary gland Antidiuretic hormone (ADH) or vasopressin Controls rate of water excretion into urine so aids in control of water concentration in body fluids Oxytocin Causes contraction of pregnant uterus Helps milk letdown from mammary glands http://www.biologie.uni­ freiburg.de/data/bio1/varga/images/p uitary.jpg ADH (VASOPRESSIN) ADH (VASOPRESSIN) Near the hypothalamus are neuron receptors (osmoreceptors) When extracellular fluid is too concentrated, fluid is pulled by osmosis out of the receptor, decreasing its size Nerve signals are passed to hypothalamus ADH secretionwater retention ADH (VASOPRESSIN) ADH (VASOPRESSIN) Causes retention of water Without ADH, collecting tubules/ducts are mostly impermeable to water, so water is lost in urine dilute urine With ADH, collecting ducts/tubules develop aquaporins to allow water reabsorption concentrated urine http://www.uic.edu/classes/bios/bios100/lecture sf04am/adh02a.jpg ADH (VASOPRESSIN) ADH (VASOPRESSIN) Higher concentrations of ADH arteriolar constriction throughout the body increased arterial BP (Vasopressin) Stimulation of ADH secretion: Decreased blood volume Right atrium has stretch receptors (excited by overfilling) send signals to decrease ADH release When unexcited, send signals to increase ADH release ...
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This note was uploaded on 11/24/2011 for the course BIO 215 taught by Professor Bentz during the Summer '09 term at Central Pennsylvania.

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