Fundamentals of Physiology
Fundamentals of Physiology BMS 360
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Date Created: 09/21/15
19 March Digestion of Food Digestion of complex structures polysaccharides proteins and triglycerides Absorption of small molecules monosaccharides amino acids and monoglyceridesfree fatty acidsglycerol Digestion of Carbohydrates Glucose polymers starch glycogen digest to disaccharides maltose sucrose lactose uses amylase Maltose maltase 9 2 glucose Sucrose sucrase 9 1 glucose 1 fructose Lactose lactase 9 1 glucose 1 galactose Digestion of Fat Triglyceride lipase colipase 9 monoglyceride free fatty acids Digestion of Proteins Endopeptidase digests internal peptide bonds Exopeptidase digests terminal peptide bonds to release amino acids Aminopeptidase H20 breaks off amino acid HZN end Carboxypeptidase H20 breaks off amino acid COOH end Absorption of Sugars Secondary active transport Facilitated diffusion Glucose enters the cell with Na on the SGLT symporter and exists on GLUTZ Fructose enters on GLUTS and exits on GLUTZ Absorption of Amino AcidsPeptides Di and tripeptidescotransport with H Amino acids costransport with Nal Small peptides are carried intact across the cell by transcytosis Objectives Understand digestion of polysaccharides and proteins Understand what is involved with digestion of lipids Regulation of digestion motility and phases Understand secretions involved in digestion Understand how digestion in small intestine affects stomach Figure 156 Chemical absorption and digestion Lumen Complex compounds Enzymes added to digest Epithelial wall Enzymes secreted Degradation smaller compounds Transporters to absorb simple compounds Carbohydrate digestion and absorption figure 158 Protein digestion and absorption figure 159 Lipid Digestion Bile Bile salts cholesterol derivative glycocholic acid Emulsify lipids to facilitate action of lipases Synthesized in liver Figure 1511 Emulsification speeds up digestion Lipid droplets are coated by bile salts and phospholipids Bile salts coat lipids to make emulsions Hydrophobic side associates with lipids Polar side chains associate with water Micelles are small disks with bile salts phospholipids fatty acids cholesterol and mono and diglycerides Figure 1512 Colipase binds lipase and coats droplet Lipases degrade triglycerides Bile salts also induct formation of micelles smaller lipid droplets Micelles and free fatty acids are in equilibrium Digestion and Absorption of Fats Bile salts from liver coat fat droplets Pancreatic lipase and colipase break down fats into monoglycerides and fatty acids stored in micelles Monoglycerides and fatty acids move out of micelles and enter cells by diffusion Cholesterol is transported into cells by a membrane transporter Absorbed fats combine with cholesterol and proteins in the intestinal cells to form chylomicrons Chylomicrons are released into the lymphatic system Figure 1531 Enterohepatic circulation Recycling pathway between liver and intestine Absorption water minerals vitamins Water absorbed by osmosis Most cases absorption minerals not regulated Vitamins B and C are water soluble Vitamin BIZ and intrinsic factor endocytosed in stomach Vitamins A D E K are fat soluble Regulation of GI Processes Processes Motility contraction and relaxation Secretion accessory glands Mechanisms Neural Via autonomic nerves long reflex loopsexternal stimuli Via nerve plexus in wall of gut local neural reflexlocal stimuli modulated by autonomic nerves Hormonal Via G hormones local reflexlocal stimuli modulated by autonomic nerves Behavioral and CNS reflex central Nerve plexuses in wall for local regulation Feedback regulation using hormones Figure 156 Regulation of Gastric Secretions 3 phases Cephalic phase sight smell taste touch of food Gastric phase presence of food in stomach digestion and peptides Intestinal phase entrance of chyme into duodenumdistention Figure 1514 Regulation of Gastric Secretions Cephalic phase Medulla oblongata 9 Action potential AP 9 vagus nerve 9 stomach 9 parietal chiefs and chief cells 9 l secretions Enteroendocrine cells 9 l gastrin 9 parietal cells and chief cells 9 l secretions Gastric phase Distention of stomach 9 mechanoreceptors 9 AP 9 enteric reflexes stomach 9 l secretions stomach Peptides in stomach I HCI Alcoholcaffeine l gastrin Intestinal phase Chyme 9 neural and hormonal mechanism pHlt 20 9 secretin 9 inhibits secretion gastrin stomach pH and duodenal wall extention 9 enterogastric reflex 9 inhibits gastric secretions FAlipids 9 gastric inhibitory peptide and cholecystokinin 9 inhibits gastric secretions 10 February Reticular activating system Percolates upwards Alters arousalalertness Influenced by circadian rhythms Brain 2 total body mass 20 25 total Oz supply Conscious Aware Awake state External sensory experiences Objects Events Internal states Moods happy sad Dreams Drives sex thirst hunger Memories thoughts Self awareness Selective attention Coma Unconscious External stimuli cannot arouse Cannot be awakened No response to stimuli No voluntary activities No sleepwake cycles EEG electroencephalogram Electrodes on skull surface Neurons activated alterations in extracellular ion concentration Measures electrical potentials being generated Alpha and beta rhythms Alpha relaxed Beta alert Sleep stages 4 stages Relaxed stagel 29394949392919REM Stages 14 are NREM REM Consolidating memory Dreaming Paradoxical sleep EEG is similar to aroused state but sleep is deep 45 full cyclesnight Apnea Disturbed sleep Respiratory drive problems Worsens w obstruction of noseairways Not enough Oz to brain Coma causes Head trauma Stroke Blood vessel burst Occlusion blood flow blocked Lack of Oz Metabolic state Diabetes excessive insulin too little sugar Narcolepsy Suddenly sound asleep Persistent vegetative state Initial brain damage with coma Brain damage extensive Can have sleepwake cycles Wa kefulness without awareness Eyes may open swallow vocalize No cognitive function No comprehension of environment Persists for more than few weeks Legal gray area Flat EEG criteria of death Selective awa reness Men can focus on one thing more than women can Figure 88 Lesion in right parietal lobe Cannot see left side loss of awareness in left visual field Shortterm memory primary memory Working memory Holding information available for use Generally under 30 seconds without rehearsal Memory span limited to 7 i 2 elements New displaces older memories Requires selective attention Does not require protein synthesis Anterograde amnesia patient with short but not longterm memory Shortterm memory can be blocked by Coma Anesthesia Anoxia Reduced brain temperature Reduced brain blood flow Blocked independently of longterm memory All block action potentials Longterm memory Rehearsal or associations can consolidate short to longterm memory Sleep may be required REM Requires protein synthesis May require LTP longterm potentiation dendritic spines Persist for days to decades Recall may be required to prevent forgetting Recall may modify memories Rats in enriched environment have more dendritic spines Hippocampal lesions Loss of memory consolidation Loss of longterm declarative memory Memory types Declarative memory can be described Episodic Events of specific time and place Autobiographical Semantic General knowledge facts Independent of where and when fact was learned Procedural memory Nondeclarative Motor skills Learned reflex Pavlovian Emotional memory Emotions strongly enhance memory Elicit physiological response Fears Amygdala 18 April Respiratory System Part Single celled vs multicellular organisms Fish gills Evolution to land vertebrates lungs Focus is normal respiratory physiology as basis for understanding its pathophysiology Respiration External respiration exchange of gases between the lungs and outside air Internal respiration the exchange of gases between blood and various tissues Cellular respiration utilization of oxygen at mitochondria Overview Respiration Organization of airways and lungs Ventilation and lung mechanics Gas exchange between alveoli and blood Gas exchange between blood and tissue Transport of oxygen and carbon dioxide in blood Control of respiration Ventilationperfusion abnormalities Functions of the Respiratory System Provides oxygen Eliminates carbon dioxide Regulates the blood s hydrogen ion concentration pH in coordination with the kidneys Forms speech sounds phonation Defends against microbes Influences arterial concentrations of chemical messengers by removing some from pulmonary capillary blood and producing and adding others to this blood Traps and dissolves blood clots arising from systemic usually leg veins Functions of the Conducting Zone of the Airways Provides a lowresistance pathway for air flow resistance is physiologically regulated by changes in contraction of airway smooth muscle and by physical forces acting upon the airways Defends against microbes toxic chemicals and other foreign matter cilia mucus and macrophages perform this function Warms and moistens the air Phonates vocal cords Figure 131 The major parts of the quotairwaysquot used in ventilation breathing The lungs have several lobes Figure 132 Conducting zone the relaxationcontraction of circular smooth muscle lining these quotairwaysquot determines how easily airflow can occur 39 vs lLLlUII Respiratory zone most gas exchange occurs in the 8000000 alveolar sacs Mucus elevator Goblet cells secrete mucus Columnar epithelial cells have cilia Cilia move mucus to pharynx Mucus layer traps inhaled particles Watery saline layer allows cells to push mucus toward pharynx Airways The respiratory zone has alveoli whereas the conducing zone does not Deliver oxygen from the air to the alveoli Vent carbon dioxide from the alveoli Respiratory defense system llMucous elevator extends from respiratory bronchioles upwards Lined with epithelial cells with beating cilia and mucus Clears dust debris bacteria upward into the pharynx Macrophages additionally clear bacteria and debris Attacks on Respiratory Defense System Tobacco smoke Chronic smoking poisons ciliary motion Mucus debris particles not cleared from airways Smoker s cough Stopping smoking mucociliary activity remains impaired Chronic bronchitis smokers or nonsmokers impairs ciliary activity Cystic fibrosis Most common lethal genetic defect in Caucasians Mutation in chloride channel gene prevents secretion of fluid that supports the mucous elevator Thick mucus blocks the airways and respiration Figure 133 Each of the clustered alveoli includes an abundance of pulmonary capillaries thereby assuring that the ventilated air is brought into close proximity to the quotpulmonaryquot blood allowing efficient and thorough gas exchange between the air and the blood Blood Supply to Lung Pulmonary circulation Pulmonary artery from the right heart supplies unoxygenated blood to pulmonary capillaries in close association with the alveoli Virtually all of cardiac output rest about 5 Lmin exercise 5 6 fold greater Pulmonary vein returns oxygenated blood to the left heart for delivery to the systemic circulation Systemic circulation Bronchial arteries of the systemic circulation also delivers oxygenated blood to the lungs Figure 134 Extensive alveoli produce lots of surface area for exchange between air and blood Alveolar and capillary walls are thin permitting rapid diffusion of gases Type alveolar cells for gas exchange Type II alveolar cells surfactant cells synthesize surfactant Alveolar macrophage ingests foreign material Alveoli Site of Gas Exchange Type alveolar cells very thin epithelial cells Forms 1 cell thick lining of the alveoli providing structure Important part of respiratory membrane Type II alveolar cells interspersed thicker cells Produce surfactant a detergentlike substance that reduces alveoli surface tension This helps prevent collapse of the alveoli Alveolarcapillary membrane aka respiratory membrane rapid diffusion of oxygen from air and carbon dioxide from blood About 02 pm thick total surface area is size of tennis court Alveolar pores alternate gas routes helps prevent alveolar collapse if an alveoli is obstructed Elastic fibers stretches like rubber band lung compliance Ventilation Ventilation exchange of air between the atmosphere and alveoli Inspiration inhalation is the inward movement of air through airways to alveoli Expiration exhalation is the outward movement of gases Respiratory cycle comprises inspiration and expiration About 5 seconds duration if respiratory rate is 12 breaths per minute Minute volume volume of air that enters and leaves the lungs each minute At rest about 5 Lmin heavy exercise about 20fold greater Figure 135 The space inside the lung is filled with air The intrapleural fluid is found between the lungs and the thoracic and diaphragm wall Movement of the thoracic wall and diaphragm drives the ventilation cycle Lungs chest wall diaphragm and pleurae Understood anatomical relationships ntercostal muscles and diaphragm regulate expansion of the thoracic space and pressure within the intrapleural fluid Pleura Visceral pleura pleural sac this thin sheet of cells is attached to and envelops all lung lobes completely Parietal pleura attached to and completely lines the thoracic cavity including chest wall and diaphragm Intrapleural fluid Very thin fluidfilled space pleural space between the visceral pleura and the parietal pleura Fluid lubricates between the lung and chest pleural surfaces so they can slide easily during breathing Example two glass plates with drop of water between Roles of Pleurae Inspiration muscles contract chest wall expands intrapleural pressure falls causing lungs to expand Expiration chest wall recoils passively intrapleural pressure increases causing lungs to recoil and contract Pleurisy or pleuritis inflammation of pleurae painful to breathe because of the friction between these layers Pleural effusion excess accumulate of intrapleural fluid This can limit lung expansion and ventilation Figure 136 Airflow in the lungs is called ventilation Gases exchange by diffusion Bloodflow through the pulmonary capillaries is driven by the contraction of the right ventricle 30 January Amino acid neurotransmitters Inhibitory GABA gammaaminobutyric acid Main inhibitory neurotransmitter GABA A R ionotropic Chloride channel Hyperpolarization GABA B R metabotropic Coupled to G protein Glycine Taurine GABA Benzendizepines increase frequency channel opening Requires GABA Antiseizure Sedatives Hyperpolarize further from threshold Ethanol binds to receptor 9 opens channel does not require GABA 9 ethanol is depressant inhibits neurons Barbiturates do the same Inhibiting NT glycine Glycine opens Cl channel in motor neuron hyperpolarizes Tetanus inhibits glycine release motor neuron fires uncontrolled contractions Strich nine rat poison blocks glycine receptor convulsions Neuromodulators Endogenous opioids Substance P involved in pain pathways particularly in spine Somatostatin regulates release of growth hormone Vasoactive intestinal peptide VIP Cholecystokinin Neurotensin Neuropeptide Y Other NeurotransmittersNeuromodulators Gases Nitric oxide Carbon monoxide Purines Adenosine ATP Somatic Sensations Sensations associated with sensory neurons Mechanoreceptors Touch light deep Pressure Vibration Nociceptors pain Stimulus that may harm tissue Heat chemicals trauma Thermal receptors Cold temp lt 35 C Hot temp gt 30 50 C Propioceptors In muscle tendons Limb position posture movement Chemoreceptors Chemicals Stimulus 9 sensory receptors signal transduction receptor potential 9 ifadequate above threshold action potential sensory information 9 sensation conscious 9 perception awareness of meaning of sensation Stimulus Duration Phasic Detects changes Action potential fires when stimulus starts and stops Not during Tonic Constant awareness Action potentials fire as long as stimulus is present 30 April Regulation of GFR Continuation The amount of metabolites ions and water that is excreted is dependent in part on the rate of GFR Blood pressure at the glomerulus determines GFR rate Constrictiondilation of afferent and efferent arterioles GFR increases 9 flow through tubule increases 9 flow past macula densa increases 9 paracrine diffuses from macula densa to afferent arteriole 9 afferent arteriole constricts 9 resistance in afferent arteriole increases 9 hydrostatic pressure in glomerulus decreases 9 GFR decreases Macula densa cells sense distal tubular flow and release paracrines Bladder at rest External sphincter skeletal muscle stays contracted Internal sphincter smooth muscle passively contracted Micturition Stretch receptors fire Parasympathetic neurons fire Motor neurons stop firing Smooth muscle contracts Internal sphincter passively pulled open External sphincter relaxes Urinary Incontinence Urinary incontinence is inability to voluntarily control urination micturition Females gt males Urethral external sphincter muscle pressure is normally gt bladder detrusor muscle pressure Stress incontinence Sneeze cough or exercise can cause detrusor pressure gt sphincter pressure Often due to reduced strength of supportive pelvic floor muscles Urge incontinence Idiopathic increased desire to urinate Incontinence in diabetes Diabetic autonomic neuropathy atonic bladder incomplete voiding Functional incontinence Functional disturbance prevents getting to bathroom in time Dementia mobility impairment inebriation Alzheimer s disease WaterNaCl Intake and Output Normally is Balanced Table 14 3 Table 14 4 Regulating inputoutput of NaCl and water to maintain a steadystate is important for maintaining blood volume and pressure Renal Tubules and Reabsorption Bowman s capsule Filtrate 180 Lday 300 mOsm Proximal tubules Reabsorbs most of metabolites and water Nai pumped out by NaiK ATPase Solutes from filtrate follow Na by cotransport Hi secreted into tubule by counter transport Water follows solute down its concentration gradient Remaining filtrate 54 Lday is isosmotic Loop of Henle Makes dilute filtrate Reabsorbs much of ions mostly Nai more than water Filtrate 18 Lday is hypoosmotic about 100 mOsm Distal tubules Hormones fine tune reabsorption output Filtrate 15 Lday osmolarity variable depending on need to secrete or excrete water and solutes in response to hormones such as aldosterone Figure 14 10 The luminal section of the plasma membrane of the tubule cells faces the filtrate whereas the basolateral section is in close proximity to the peritubular capillary The tubular epithelial cells have transporters to regulate the reabsorption of water and solutes Figure 14 14 A NaK ATPase transporter in the basolateral membrane of the collecting duct cell pumps Na toward the peritubular capillary Na in the tubules flows down its concentration gradient into the collecting duct cell K movements are in the opposite direction Figure 14 15 Water reabsorption is coupled to Na reabsorption Nai is pumped out to the interstitial fluid Tubular Nai flows downhill into the tubular epithelial cell The decreased tubular Na increases the H20 concentration and water flows downhill via aquaporins into tubular epithelial cells ADH Levels Determine Aquaporin Numbers and Water Reabsorption in Collecting Ducts Water polar flows via aquaporins down its gradient into cortical and medullary collecting duct cells Antidiuretic hormones ADH aka vasopressin or arginine vasopressin is released at the posterior pituitary Increased ADH binds to its receptor on the basolateral membrane of collecting duct cells Activates adenylatecyclase increases cAMP levels Protein kinase A is activated AQPZ in vesicles inserted into luminal membrane More AQPZ aquaporins increase water reabsorption Water flows out of duct cells via AQP3 and AQP4 towards peritubular capillaries Two Types of Diabetes Central diabetes insipidus Pituitary produces insufficient ADH Nephrogenic diabetes insipidus Kidneys insensitive to ADH Water is not reabsorbed in collecting ducts No increase in solute excretion so urine is dilute Water diuresis may reach 25 Lday Diuresis is increased urine flow due to any cause Diabetes mellitus Excess glucose in GFR filtrate exceeds kidney transport max Large concentration of glucose in tubules hyperosmolar retains water and cause osmotic diuresis Obligatory Water Loss Daily excretion of solutes 600 mOsmday Maximum solute concentration in urine 1400 mOsmL Obligatory water loss 600 mOsmday 1400 mOsmL 0444 Lday Dehydration will occur if water intake is lt0444 Lday When water is scarce survival is enhanced by water reabsorption This increases solute concentration in urine This means the ability of the kidneys to make concentrated hyperosmotic urine can be critical for survival 8 February Figure 740 Semicircular canals u 1 Three dimensions llyes no tilt to shoulder quotLabyrinthquot Figure 739 Ampulla swellings in semicircular canals Houses cupula 3 of them since there are 3 semicircular canals Saculla and utricle Figure 741 With ampulla cupula Supporting cells under hair cells w stereocilia Swelling is filled with fluid Stereocilia are bent by fluid movement during turning resistance to fluid Figure 742 Hair cells Resting or constant velocity base NT Stimulation depolarization 4 NT Inhibition hyperpolarization J NT Depends on which way stereocilia are bent Detects changes we don t feel the turn of the Earth Figure 743 Utricle and saccule Hair cells embedded in gelatinlike material Contain calcium carbonite crystals otolith Head position relative to gravity and acceleration or deceleration Otolith in gel gives gel greater mass to bend hairs Crystals can be dislodged in disease Vestibular System Information from hair cells 9 vestibular nerve 9 parietal lobe also receives information from proprioceptors sensory neurons from muscles tendons Feedback between parietal lobe eye eye movements Adjustments of posture Nystagmus Vestibularoccular reflex Fluid in head continues to turn while body is not Hair cells are bent still Eyes move as if still spinning Vestibular disease Person at rest no change Nystagmus occurs Meniere s disease Of vestibular system Poor balance etc Opticokinetic system Eyes tell position relative to environment Trucks on either side of you move forward feel like you re falling backward Vertigo on the edge ofa tall building Ear infection Crystals rolling around free of gel Hippocampus place cells Help navigation Recognition visual map of environment Figure 744 Taste Papillae contain taste bud cells Pore allows chemicals into taste bud cells 10000 different taste bud cells Receptor cells are activated 9 graded potential 9 action potential in nerve Sweet sour salty bitter umami MSG flavorfulness Chemicals can destroy receptors basal cells make new 23 January Gland secretes hormone 9 lumen 9 throughout the body exocrine Gland secretes hormone 9 interstitial fluid 9 cells endocrine Endocrine Neurotransmitters short distance Hormones long distance Paracrine nearby cells Autocrine self In cancer cells can mutate to create growth substances that are autocrine aids cancer s independence Messenger binds to receptor Specificity lock and key Subtypes Agonist ligand that binds to receptor generates cellular response Antagonist prevents agonist from binding inhibits action Homeostasis can be regulated at receptor level Downregulation too much stimulation number of receptors for cell decreased Upregulation not enough stimulation receptors increased Lipophilic messengers Ex steroids other hormones Enter cell bind inside Passive diffusion since it is lipophilic can pass through cell membrane Activates specific set of genes Signal amplification necessary messengers only present in low concentrations Hydrophilic messengers Cannot pass through plasma membrane Ionchannel Binding 9 ion channel gated Substance ion flows down concentration gradient into cell Eg Ca2 Ions amplify signal act as second messengers Enzyme Intrinsic section of receptor Protein inside cell is phosphorylated upon ligand binding activation JAK kinase Kinase activated but is not intrinsic to receptor Gprotein Trimeric 01 3 y Gprotein activated by receptor binding 01 subunit dissociated to act on other proteins Cyclic AMP Important second messenger Adenylyl cyclase creates from ATP Phosphodiesterase converts to AMP ends response Binds to kinases converts them to active form Calcium Usually kept in endoplasmic reticulum Also pumped out of cell on channels in endoplasmic reticulum can create rapid responses PIP2 acted on by phospholipase C 9 DAG IP3 Messenger binds to receptor G protein activates phospholipase C IP3 acts on endoplasmic reticulum 9 release Ca2 P3 and DAG act on protein kinase C to activate Activated by P3 and DAG Calmodulin activated by Ca2 Arachadonic acid Messenger receptor 9 activates phospholipase A Membrane phospholipid converted to 39 39 39 acid 9 39 and quot 1 IL I 1U convert to cyclic endoperoxides and leukotrienes respectively Prostaglandins and thromboxanes form from cyclic endoperoxides Hormones and behavior Male XY 9 castrate 9 female phenotypically Female XX 9 androgen 9 male phenotypically Brain structure is sexually dimorphic r 39toxin 39 C 39 c 39 9 gestation 9 alters adult behavior phenotype 10 April Neonatal Testis Testicular cords contain gonocytes and Sertoli cells Interstitium contains Leydig cells blood vessels Testicular cords in neonatal 9 seminiferous tubules in adult Tunica propria basement membrane Sertoli Cells Form tight junctions blood testis barrier Support germ cells physically nutrition Secrete fluids Secrete inhibin feedback to brain Phagocytose defective sperm Secrete androgen binding protein In fetal life secrete AMH anti Mullerian hormone Spermatogenesis Make lots of sperm spermatocytogenesis Make haploid sperm meiosis Metamorphosis spermiogenesis Spermiogenesis spermatid 9 spermatozoa Head Acrosome and nucleus Midpiece Centrioles and mitochondria Tail flagellum Microtubules Regulation of Spermatogenesis Testosterone Stimulates spermatogenesis Maintain Wolffian duct accessory glands External genitalia secondary sex characteristics Stimulate metabolism muscle growth Affect CNS functionbehavior Anabolic Steroids and Testicular Morphology Testosterone is an anabolic growth and storage promoting steroid Destroys testis through negative feedback Efferent ducts absorb fluid Sperm Transport Epididymis Head body and tail region Storage fluid reabsorption Acquire motility Transport is a result of muscular activity Vas deferens 3 layers of smooth muscle Storage and transport Accessory Glands Seminal vesicles prostate bulbourethral gland Seminal fluid nutrients buffers move sperm activate motility Figure 1710 Sperm exit through penis Objectives Explain the anatomy of the ovary Understand oogenesis and folliculogenesis Explain the twocell twogonadotropin model and the major functions of estradiol and progesterone Explain and distinguish the ovarian and uterine phases Germ cell loss and meiosis in the ovary Understand the ovarianuterine interaction during the menstrual cycle Know hormonal regulation of female reproductive cyclefunction Female Reproductive System Ovary Fallopian tubeoviduct Uterus Cervix Vagina Follicle Growth Primordial follicle 9 primary follicle Oocyte becomes bigger Oocyte is now its final size Zona pellucida mammalian version of eggshell Preantral follicle Theca cells female version of Leydig cells Early antral follicle Antrum cavity filled with fluid Antral follicle Large antrum Cumulus oophorus Primordial follicle oocyte and granulose cells Primary follicle fully grown oocyte zona pellucida and granulosa cells Preantral follicle oocyte zona pellucida granulosa cells and theca cells Antral follicle oocyte zona pellucida granulosa cells theca cells and antrum Mature follicle oocyte zona pellucida granulosa cells theca cells antrum and cumulus oophorus 23 April Diseases Increasing Airway Resistance Chronic obstructive pulmonary disease COPD Major cause of disability and death Emphysema Lung tissue loss around alveoli causing airway collapse Difficult to inflate lungs due to loss of elastic tissue Shortness of breath Smoking is a major cause Chronic bronchitis Loss of ciliated cells Excess mucous production in the bronchi causing obstruction chronic inflammation of small airways Airway resistance is very high Smoking is a major cause Emphysema with chronic bronchitis Smoking can cause both Similar to figure 13 18 Respiratory Volumes Tidal volume Volume ofair inhaled or exhaled in a single breath Relaxed breathing about 500 mL nspiratory reserve volume IRV The maximum volume in deep inspiration minus the relaxed tidal volume Functional residual capacity Volume of air remaining in the lungs after normal relaxed expiration Residual volume Amount ofair remaining in lungs after maximal exhalation Expiratory reserve volume ERV Volume that can be exhaled with maximal effort less the relaxed tidal volume Pulmonary Function Tests Vital capacity The maximal volume ofair that can be exhaled after maximal inhalation Equals tidal volume RV ERV about 47 L Forced expiratory volume 1 sec FEV1 Maximum inhalation followed by expiration as fast as possible in 1 sec Normal about 80 of the vital capacity Obstructive pulmonary disease emphysema bronchitis asthma Increased airway resistance cause low FEV1 values Narrowed airways may cause wheezing sound Vital capacity remains normal Restrictive lung disease Abnormal lung tissue fibrosis pleura chest wall respiratory muscles or respiratory nerves Impaired respiratory movement Restricted lung expansion reduces vital capacity Reduced FEVL Normal ratio FEV1vital capacity as both values are reduced about equally Alveolar Ventilation Minute ventilation rate Total ventilation in 1 minute respiratory rate x tidal volume Example Minute ventilation rate during quiet breathing 12 breathsmin x 500 mLbreath 6000 mLmin Not all of this air is available for respiration because some of it is dead space Physiological dead space Anatomical dead space is the volume of air which is NOT participating in diffusion which is the air in the conducting zone about 150 mL0 Alveolar dead space is due to some alveoli without blood supply Normally quite small but in disease can be larger Alveolar Ventilation Rate AVR AVR is the volume of air that is actually exposed to respiratory membrane over a certain period of time AVR in quiet breathing negligible alveolar dead space tidal volume dead space x respiratory rate 500 mLbreath 150 mLbreath x 12 breathsmin 4200 mLmin Table 13 4 Breathing and AVR Exchange of Gases Between Alveoli and Tissues Gases diffuse down their partial pressure gradients from areas of high pressure to low pressure Lungs Oxygen diffuses from alveoli into blood Note that the amount of oxygen utilized in the tissues is equal to the amount that is absorbed at the lungs Carbon dioxide diffuses from blood into alveoli The amount produced in the tissues is equal to the amount expired Figure 13 20 Pressures of Gases Gas pressure is the amount of force on a surface due to the number of collisions per unit time Depends on the concentration of gas molecules and temperature Sea level vs higher elevations Gas molecules are more concentrated there are more collisions hence atmospheric pressure is greater at sea level At higher temperatures molecules move faster there are more collisions per unit time and pressure is higher Breathing delivers air at a certain pressure but only some of the gases in air is oxygen available to the body Dalton s Law of Partial Pressures of Gases In a mixture of gases the pressure of each gas is independent of the pressure of other gases The pressure of the mixture of gases is equal to the sum of the partial pressure of each individual gas Atmospheric pressure p02 21 in dry air pNz 79 other gases Where other gases are lt1 water C02 others negligible for pressure Atmospheric pressure sea level 760 mm Hg Consequently p02 760 mm ng 021 160 mm Hg pNz is biologically inert so need not be discussed Henry s Law Governs Gas Diffusion Law states that at a constant temperature the gas in contact with a liquid will dissolve in proportion to the partial pressure of the gas A gas will diffuse into a liquid down its concentration gradient so long as its partial pressure is higher in the gas vs liquid phase A gas will diffuse out of a liquid down its concentration gradient so long as its partial pressure is higher in the liquid vs gas phase At equilibrium the partial pressure of the gas will be the same in the gas and in the liquid phase and net flux is zero This law governs diffusion between alveolibloodtissues Gas Laws The total pressure of a mixture of gases is the sum of the pressures of the individual gases Dalton s law Gases singly or in a mixture move from areas of higher pressure to areas of lower pressure If the volume of a container of gas changes the pressure of the gas will change in an inverse manner Boyle s law Fig 13 21 Sea level resting The partial pressures of oxygen in the alveoli determines its pressures in blood p02 is 160 mm Hg in the atmosphere vs only 105 mm in alveoli because some oxygen has diffused into blood p02 alveoli 105 mm nearly the same as in pulmonary vein 100 mm in accordance with Henry s Law slightly lower in the vein due to ventilationperfusion mismatching p02 in alveoli p02 lower in air and alveoli at higher elevations Faster ventilation rate increases alveolar p02 Faster oxygen consumption in tissues reduces alveolar pO2 pCOZ in alveoli pCOz of the atmospheric air is nearly zero at sea level so elevation has little effect Faster ventilation rate decreases alveolar pCOz Faster tissue carbon dioxide production increases alveolar pCO2 Figure 13 22 Changes in the rate of ventilation alter the concentration of gases in the alveolar air C02 Ventilation Relative to Its Production Adequacy of ventilation Hypoventilation Alveolar pCOz higher than normal Tissue production rate of C02 greater than its ventilation rate Example respiratory depression with opiates Hyperventilation Alveolar pCOz lower than normal Ventilation rate of C02 greater than its production rate Blood pCOz then falls Example panic attack Hyperventilation does NOT mean faster ventilation In exercise faster C02 production is proportionately matched to faster ventilation and pCOz remains normal 26 March Figure 167 Main responses of target cells to insulin Figure 168 Regulation of blood glucose levels Hypo low and hyper high glucemia glucose levels Figure 169 Control of insulin secretion Figure 1610 Blood plasma glucose and glucagon Negative regulators of blood glucose levels 9 oppose actions of insulin Glucagon liver Epinephrine Sympathetic nerves Cortisol Growth hormone Postabsorptive state J insulin 4 glucagon Figure 1611 Sympathetic nervous system and blood glucose levels Figure 164 Glucose counter regulatory controls antiinsulin Cortisolgrowth hormone not coupled to absorptivepost absorptive state permissive facilitatory Cortisol permissive reduces sensitivity to insulin GH differential stimulates protein anabolism effects on carbohydrate and lipid metabolism are minor Diabetes quotto pass through Diabetes mellitus high blood sugars glucose levels hyperglycemia Type 1 9 loss of insulin producing beta cells immune disease Delivery of insulin to prevent diabetic ketoacidosis Type 2 9 reduced insulin sensitivity early stage or insulin resistance leads to increased insulin levels Improve insulin sensitivity or reduce glucose production by liver Exercise diet decrease carbohydrate intake Diabetes insipidus excretion of large amounts of dilute urine due to vasopressin ADH deficiency Figure 1620 Ketoacidosis Severe insulin deficiency diabetes mellitus Figure 1614 Hunger regulation Feeding center in hypothalamus Arcuate nucleus secretes neuropeptide Y NPY Stimulates eating creates hunger sensation Leptin Secreted by adipose tissue Has negative effect on NPY Ghrelin Stimulated by fundus top region of stomach Has positive effect on NPY Fasting or low carb diet stimulates ghrelin secretion inhibits leptin release Stomach bypass surgery decreases ghrelin release Figure 1613 Leptin control of body energy stores Key role in controlling energy intake and energy expenditure including appetite and metabolism Energy Balance in the Body Energy input Hungerappetite Satiety Social and psychological factors All influence diet Energy output Heat 50 Unregulated Thermoregulation TNZ thermal neutral zone heat created by reactions in body Work 50 Transport across membranes Mechanical work Movement Chemical work Synthesis for growth and maintenance Energy storage Highenergy phosphate bonds ATP phosphocreatine Chemical bonds glycogen fat 20 January Nai concentration higher outside the cell Ca2 Cl39 HCO Glucose K concentration higher inside the cell Mg2 Pi Amino acids ATP Protein Four Primary Transporters NalK ATPase 3 Nal out 2 W in HiK ATPase 1 Hi out 1 W in Ca2 ATPase Ca2 out Hi ATPase Hi out They use 13 cellular ATP Uphill transport Secondary Active Transport Cotransport Primary transporter eg NaiK ATPase Second transporter is coupled to primary eg pump Nai in downhill while moving another molecule uphill Energy of Na leaking back into the cell used to move other molecule In countertransport a molecule is pulled out of the cell while another is moved downhill into the cell or vice versa Two molecules involved in countertransport move in opposite directions Pure water 555 M Solute 1 M glucose 1 Osm 9 545 M H20 1 M NaCl 2 Osm 9 535 M H20 1 M MgCIZ 3 Osm 9 525 M H20 Osmolar shows moles of solute 1 M NaCl 9 1 M Nai 1 M CI 2 M High osmolarity lower water concentration V1C1 VZCZ sotonic same concentration of nonpenetrating solutes on either side of membrane Greater solute concentration outside hypertonic cell shrinks Lower solute concentration outside hypotonic cell swells Endocytosispinocytosis Cell wall invaginates engulfs material Exocytosis Vesicle with solutes fuses with plasma membrane disgorges solutes Eg nerve terminal neurotransmitters released into synaptic cleft Luminalapicalmucosal membrane Cavity side Basolateralsersosal membrane Blood side 16 April Progesterone gt estrogen throughout most of pregnancy Progesterone has relaxing effect on uterine wall No contractions Estrogen gt progesterone switch occurs right before parturition Stimulates contraction Prostaglandin release Puberty E2 increases duct growth and branching P4 promotes alveoli growth Pregnancy E2 P4 prolactin promote breast enlargement No milk production E2 and P4 block prolactin s effect on milk production After pregnancy E2 and P4 drop 9 prolactin stimulates milk production Lactation Milk Secretion The hormonal control of milk secretion and release Suckling crying 9 hypothalamus 9 pituitary Increase oxytocin contraction myoepithelial cells 9 milk ejection Increase prolactin milk production Dopamine opposes prolactin levels drop Maternal age I 9 l spontaneous abortions J fertility Sperm count declines with age Assisted Reproductive Techniques ART Artificial insemination Hormone assisted ovulation In vitro fertilization IVF Louise Brown 1978 Intracytoplasmic sperm injection ICSI In Vitro Fertilization IVF Egg production stimulated by hormone therapy FSH LH Eggs retrieved from ovary Sperm sample provided Eggs and sperm combined to allow fertilization Fertilized eggs introduced into uterus once it reaches blastocyst stage Ovaries may become highly sensitized due to hormone therapy 10 15 K Intracytoplasmic sperm injection ICSI Sperm injected directly into oocyte Sperm not motile or some other problem Stem Cells and Cloning Totipotent cells Can be anything Zygote 4 cell stage Pluripotent cells Can be any cells in body not placenta Derived from inner cell mass Blastocyst Bone marrow skin GI tract testis hair follicles Have stem cells in adults Stem cells can renew themselves or divide Therapeutic Cloning Develop patient compatible pluripotent stem cells Treatment of diabetes Alzheimer s Parkinson s disease spinal cord injuries cardiovascular disease etc Problems getting oocytes blastocyst must be killed Things to Consider AlIVRICSI donor anonymous donor paid Embryo transfer embryo selection Prenatal diagnostic testing sex genetic disease Cloning reproductive therapeutic Cloning someone very talented Preimplantation genetic diagnosis for a phenotype such as stature or eye color 25 April Respiration and pH The C02 produced in tissues is converted in RBC to carbonic acid which dissociates to release HC03 and Hi Where does this acid go Deoxyhemoglobin reversibly binds Hi and transports it This reduces free Hi so venous blood pH 736 is only slightly more acidic than arterial blood pH 740 At the lungs this reaction is reversed to produce C02 and water With adequate ventilation none of the Hi from cellular respiration normally enters arterial blood Respiratory acidosis arterial pH lt 735 Due to hypoventilation and increased arterial pCO2 and H Respiratory alkalosis arterial pH gt 745 Due to hyperventilation and reduced arterial pCOz and Respiratory Control Localization of peripheral and center control systems that regulate ventilation The focus will be on chemoreceptors Peripheral chemoreceptors Carotid body Aortic arch Central chemoreceptors in medulla oblongata Hg13 33 Chemosensory neurons are located in the aorta aortic bodies and in the left and right carotid artery carotid bodies These sensory afferent neurons alter CNS regulation of the rate of ventilation Hgl3 36 Chemoreceptors are sensitive to small changes in the carbon dioxide content of the arterial blood to change ventilation rate Figure 13 34 A severe reduction in the arterial concentration of oxygen in the blood can stimulate hyperventilation Carotid and Aortic Arch Chemoreceptors The glomus cells are the chemoreceptors located near the baroreceptors They increase rate and depth of ventilation in response to arterial Increase in pCOz This is the primary stimulus and helps match ventilation to C02 production Decrease in pH acidosis Decrease in p02 requires large drop to lt60 70 mm Hg COPD elevations gt 3000 m or 10000 feet Carotid and aortic arch chemoreceptors when pOzlt 60 70 mm Hg Low pO2 K channels close Cell depolarizes Voltage gated Ca2 channel opens Ca2 entry Exocytosis of dopaminecontaining vesicles Signal to medullary centers to increase ventilation Figure 13 35 Chemosensory neurons that respond to decreased oxygen levels in the arterial blood stimulate the ventilation control center in the medulla to increase the rate of ventilation pCO2 increases H in CSF stimulating increased ventilation Central Chemoreceptors and Ventilation Figure 1 Volunta Increased pCO2 increases the ventilation rate The effect of C02 is indirect and works by increasing hydrogen ion concentration in the CSF Hydrogen ion in peripheral blood does not readily cross the BBB so is normally less important Chronic high pCO2 such as in COPD pCOz chemoreceptors adapt after few days p02 sensed by peripheral chemoreceptors becomes the main driver of ventilation Danger in administering Oz may stop breathing because the pCOZ chemoreceptors have adapted 3 40 Increased arterial pCO2 and quot quot p02 are U in 39 39 U the rate of ventilation Extremely high C02 levels inhibit medullary respiratory neurons and breathing can stop ry Ventilation Voluntary holding of breath Little children and tantrums pCOz and H increases due to ongoing tissue metabolism and the intense stimuli causes breathing to resume r Voluntary hype will hyperventilate to reduce pCOz as low as possible so that they can hold their breath longer Danger the respiratory drive is not being stimulated by pCOz at the time when p02 levels become very low and there can be loss of consciousness and drowning Anxiety and hyperventilation Low pCO2 causes vasoconstriction of cerebral vessels and dizziness Breathe into a paper bag to prevent fainting Figure 13 43 An integrated perspective recognizes the variety and diversity of factors that alter the rate of ventilation Medullary Respiratory Center Dorsal respiratory center DRG Signals spinal motor neurons to cause contraction of muscles of r the quot r39 g and39 Imuscles Ventral respiratory group VRG Upper VRG Respiratory rhythm generator contains pacemaker cells to regulate basal ventilation rate Lower VRG Neurons regulating normal inspiration Neurons regulating normal expiration The two above show reciprocal inhibition Neurons regulating forced expiration exercise Drug inhibition of medulla opiates barbiturates alcohol 18 January Stimulus 9 Receptor 9 Afferent pathway 9 Integrating center 9 Efferent pathway 9 Effector 9 Response If response is opposite to stimulus negative feedback System can be anticipatory neurons sense lowered temperature start response before core body temp actually lowers Childbirth example of positive feedback Body water 23 intracellular fluid 80 extracellular is in interstitial fluid 20 extracellular is in plasma Molecular weight 18 daltons Velocity 1500 mph Glucose Molecular weight 360 daltons Velocity 510 mph Diffusion random movement Molecules change direction as they hit others Downhill High 9 low High temp 9 molecules move faster 9 faster diffusion Larger mass 9 slower diffusion Greater viscosity 9 slower diffusion Larger surface area 9 faster diffusion Higher concentration 9 faster diffusion Net flux difference between flux in and flux out fluxin fluxom Cells are roughly 10 pm It takes glucose 35 sec to diffuse in If they were 10 cm it would take 11 years Rate of diffusion is proportional to the square of the distance Circulatory system is necessary in a multicellular system for gasses to diffuse into the cell at a reasonable rate Fatty acids Cis is unsaturated Trans is saturated Membrane contains both Aquaporins pore allowing water to travel in and out of cells on channels can be opened or closed gated Gating is voltage ligand or stretch Passive diffusion is not saturated not dependent on concentration At equilibrium inside outside net flux 0 Mediated transport Facilitated diffusion polar or ionic compounds Energy not required Downhill transport Saturates limited by number of transporters At equilibrium Ci C0 Primary active transport Uphill Uses ATP cellular energy Saturates limited by number of transporters Cigt C0 only possible with energy use 13 April Objectives Explainunderstand what puberty is Explain the process leading up to fertilization Explain the processes underlying fertilization Understand early embryo development and maternal recognition Understand the signaling between fetus and mom Explain parturition and lactation Puberty Hypothalamicpituitarygonad axis pretty inactive pre puberty Sex steroids low prepuberty unchanged at onset of puberty then adult level Feedback operative and sensitive 9 decreasing in sensitivity 9 operative at adult level Gonadotropins low 9 increasing 9 adult level kisspeptin protein Derived from kissl gene Gene is turned on by estrogens Girls require 17 body fat to start puberty Minimum amount of body fat must be maintained for regular cycles Leptin related Egg viable after ovulation for 24 48 hours Average sperm production 300 millionday Viable for 72 hours Average 180 millionejaculation 3 mL Fertilization occurs in fallopian tube Female reproductive tract is acidic Cervix is barrier due to mucus Have to choose correct fallopian tube Uterotubal junction 1001000 sperm reach this point Reach egg 20200 sperm Fertilization Capacitation Final maturation of sperm Occurs in the female reproductive tract Increase in membrane fluidity Increase in motility Hyperactivation Bind to zonapellucida Acrosome reaction Membrane of acrosome and sperm membrane fuse Enzymes from acrosome released Eats through cells to reach oocyte 5 10 minutes Fusion Sperm contents dumped into oocyte Oocyte nucleus completes meiotic division Egg and sperm pronucei fuse to form zygote nucleus One sperm fuses to one egg Block to polyspermy Change in membrane potential of oocyte Cortical reaction oocyte releases enzymes from cortical granules causing zona pellucida to harden and fewer receptors Oocyte completes meiosis Extrusion 2nd polar body male and female pronucei fuse Activation of enzymes in oocyte 9 embryogenesis Zygote Development Ovulation Fertilization and Implantation Day 1 fertilization Days 2 4 cell division takes place Days 4 5 blastocyst reaches uterus Days 5 9 blastocyst implants Ectopic pregnancy In fallopian tube In abdomen 1 in 100 96 in fallopian tube so 4 in abdomen Lithopedians llstone babies Become calcified 50 of all fertilizations abort Compact morula So many cells packed together Appears one mass Blastocyst is next Split at twocell stage identical twins Blastocyst nner cell mass ICM Rest of interior liquid blastocoel Implantation Trophoblast cells proliferate and penetrate the endometrium 9 implantation Maternal Recognition of Pregnancy If pregnancy occurs the trophoblast produces human chorionic gonadotropin hCG The corpus luteum does not regress and continues to produce progesterone in response to hCG Thus the developing embryo signals the mother and preserves the corpus luteum Maternal Hormone Levels in Pregnancy Progesterone estrogen produced by corpus luteum in early pregnancy Later increases produced largely by the placenta after the first trimester the precursors to estrogens are maternal and fetal androgens Placenta product of fetal and maternal tissues Chorion from trophoblast Amnion membrane from inner cell mass Filled with fluid Contains sloughed cells from embryofetus Placenta Semipermeable membrane retrieve Oz and nutrients excrete CO and waste Endocrine function estrogen and progesterone No mixing of blood but exchange of material Fetal and maternal component Umbilical vein to fetus Umbilical artery from fetus Regulation of Uterine Contractions by Oxytocin and Prostaglandins in Labor in Humans Oxytocins and prostaglandins promote uterine contractions in labor estrogens are important in promoting increased prostaglandin production There are a number of positive feedback loops that reinforce contractile activity Uterine contractions become progressively stronger more coordinated and directional as labor progresses 27 April Introduction The concentration and only the concentration determines whether a substance is a toxin Paracelsus Steadystate level ofany chemical in the body is based on input production ingestion administration and output metabolism elimination The liver and kidneys play major roles in inputoutput and regulate homeostasis of soluble molecules Table 14 1 The kidneys are located retroperitoneally at the level of the lower ribs Structure of the Kidney Massive parallel processing of blood Renal arteries take blood to the cortex Afferent arterioles and glomeruli are all found in the cortex Juxtamedullary boundary between cortex and medulla There are about 1 million nephrons in each kidney The Nephron basic unit of the kidney A nephron is comprised of Renal corpuscle glomerulus Bowman s capsule Proximal convoluted tubule Loop of Henle Distal convoluted tubule The glomerulus is the capillary network within the renal corpuscle Structures associated with but not part of the nephron Afferent and efferent arteriole Peritubular capillaries Collecting ducts multiple nephrons feed into a duct Each nephron has two arterioles and two sets of capillaries associated with it The diameter of the afferent arteriole is larger than the efferent arterioles increasing blood pressure within the glomerulus capillaries to promote filtration 20 of the plasma from the afferent arteriole is filtered into Bowman s capsule Figure 14 5 The macula densa cells in the distal tubule plus the juxtaglomerular cells secretes renin within the afferent arterioles forms the juxtaglomerular apparatus Similar to fig 14 3 overview Blood Flow and Glomerular Filtration Resting cardiac output approximately 5 Lmin 20 of cardiac output goes to two kidneys 1 Lmin GFR is normally about 180 Lday 70 kg person GFR will be affected by factors that alter arterial flow and pressure Glomerular Filtration Glomerular capillary endothelial cells have pores Basement membrane forming outside wall of capillary is leaky connective tissue Podocyte foot processes surround each capillary leaving slits 110 115 13 through which filtration occurs Slit molecular weight cutoff approximately 60 kDa Immunoglobulin 160 kDa Serum albumin 65 kDa Insulin 58 kDa Filters small polar ionic molecules Retains cells retains large proteins needed for oncotic pressure Binding large proteins reduces GFR for small molecules Blood total protein 60 80000 mgL globulins albumin Normal total protein in urine lt80 mgL Fig 14 2 Fluid filtered from the blood in the glomerular capillaries is altered by reabsorption and secretion along the length of the 1000000 nephronskidney Localization of Nephrons Cortical nephrons 85 Renal corpuscles located in outer cortex Henle s loop penetrates shallowly into medulla Functions in secretion and reabsorption of solutes Juxtamedullary nephrons 15 Renal corpuscles in cortex close to corticalmedullary boundary Henle s loop penetrates deep into the medulla Vasa recta capillaries follow loop deep into the medulla Main nephrons for making osmotic gradients and dilute urine in long tubules Rea bsorption and Secretion Lipophilic molecules Generally bound to serum proteins Subject to reabsorption and secretion by passive diffusion across epithelial cells More difficult to excrete free fatty acids Vit A DDT Ionic and polar molecules Reabsorption and secretion are regulated by mediated or active transporters in tubule epithelial cell membranes The transport maximum is due to saturation of available transporters Co and counter transporters generally coupled to NaiKi ATPase Table 14 2 Reabsorption conserves valuable metabolites ions and water and is regulated Glomerular Pressure Causes Filtration Net glomerular filtration pressure about 16 mm Glomerular capillary fluid pressure about 60 mm Hg Less fluid pressure in Bowman s space 15 mm Hg Less protein osmotic gradient avg about 29 mm Hg Protein more concentrated due to water loss in glomerulus and this opposes filtration of water Protein essentially zero in Bowman s space Osmotic gradient pressure between these two Net pressure 60 15 29 about 16 mm Hg GFR is not very sensitive to the normal range of blood pressures Concentration and Dilation of Renal Arterioles Regulate GFR Neuronal and hormonal factors locally alter GFR Unique glomerular capillaries lie between two sets ofarterioles Afferent arterioles Constriction decreases pressure Dilation increases pressure Efferent arterioles Constriction increases pressure dams up Dilation decreases pressure Mesangial cells surround the glomerular capillaries Constriction reduces GFR Figure 14 9 As vasodilation and vasoconstriction of the afferent and efferent arterioles alter the glomerular capillary blood pressure PGC GFR is altered 31 January Strength of a signal can be relayed by the frequency of signals and the number of units signaling they are all or none Lateral inhibition Inhibitory neurons block action potentials of adjacent neurons Sharpens acuity Better understanding of location Stimulus properties Sensory type modality Nociceptor mechanoreceptor etc Perception is dependent on receptors Signal transduction Stimulus intensity Firing frequency Number of neurons activated Stimulus location Size of receptive field Overlapping receptive fields Higher convergence lower precision Lateral inhibition higher precision Doctrine of specific nerve energy Receptors can respond to more than one type of energy Can give rise to only one type of sensation Neurotransmitters can be reduced Opiates lessen release of Substance P Morphine has the same effect Signals cross to the other side of the spinal cord before travelling to the brain Signal from right arm goes into right side of spinal cord then crosses to left side and goes to left side of the brain Applies to sensory signals Crossover in brainstem for sensory signals other than temperature and touch Somatosensory cortex in parietal lobe maps the body Surprisingly large area of somatosensory cortex for handsface Chronic pain Allodynia lower threshold for pain Hyperalgesia greater pain to stimulus Both can be seen in diabetes Referred pain Visceral and somatic ascending axons Convergence on some interneurons Crossing of signals Example heart attack incorrect localization of pain site to left arm Pain control using inhibitory paths Stimulation produced anesthesia Acupuncture endogenous opiates Phantom pain Amputated leg Pain in nonexistent leg Heroin and morphine dissociate sensation from perception Exa m Multiple choice 30 questions 2 May Regulation of Hydrogen on Concentration High concentrations of acid can be extremely damaging to proteins and cellular processes and must be closely regulated Acid can alter the structure of and denature enzymes and other proteins Normal range of pH 738 742 Acidosis low pH CNS depression confusion coma respiratory inhibition Alkalosis high pH Overactive neurons paresthesia muscle twitches muscle tetanus with paralysis of respiratory muscles Regulation Respiratory and renal systems work together Hydrogen on Sources Cell metabolism 20000 mmol COzday CA HC0339 H Normal ventilation the C02 is exhaled Hypoventilation Net C02 is retained causing acidosis Hyperventilation CO2 net loss causing alkalosis Nonvolatile acids produced 40 80 mmolday Lactic acid fatty acids Phosphoric acid Sulfuric acid amino acids Much of nonvolatile acids is metabolized to HC0339 Gastrointestinal production H in stomach HC03 in intestines loss equivalent to increased H Renal adjusts secretion or excretion of H Table 14 6 Hydrogen on Regulation The role of ventilation in regulating H via C02 ventilation was discussed earlier This is the predominant compensatory mechanism for regulating H The role of the kidneys in regulating Hi excreted is discussed next This is an important of the y 39 39 The kidneys filter about 400 g bicarbonate per day and this is reabsorbed in the proximal tubules to maintain buffering capacity in the blood Proximal Tubule Secretes H and Reabsorbs Bicarbonate Acidosis overview Tubular epithelial cell secretes H via NaH ATPase into proximal tubule lumen Urine carries H in buffered form reservoir as HZPO4 law of mass action and Hi concentration NH4 Tubular epithelial cells allow reabsorption of HCOg into peritubular capillaries and adds to buffering capacity Alkalosis overview Reverse of above eg rea bsorb H secrete HCOg Na H antiport secretes H 9 H in filtrate combines with filtered HCOg to form C02 9 C02 diffuses into cell and combines with water to form Hi and HCOg 9 H is secreted again and excreted 9 HCO is reabsorbed 9 glutamine is metabolized to ammonium ion and HCOg 9 NH4 is secreted and excreted 9 HCOg is reabsorbed The Distal Nephron Controls Acid Excretion fine tuning ntercalated cells in the distal nephron contain high amounts of carbonic anhydrase Type A intercalated cells During acidosis Secrete Hi reabsorb bicarbonate Type B intercalated cells During akaosis Reabsorb Hi secrete bicarbonate Vs the type A cells the transporters on the basolateral and luminal membranes on the type B cells are simply reversed Table 14 8 Bicarbonate and arterial pCOZ are increased in respiratory whereas decreased in metabolic acidosis Bicarbonate and arterial pCOz are decreased in respiratory whereas increased in metabolic akaosis Toxicity of Compounds II II39 I Steadystate 39 of ingested material or drugs can build up to toxic levels if their renal elimination were impaired Renal function diminishes in elderly Nephropathy can develop in diabetes Renal tumors Endstage renal disease Pharmacokinetics Figure 14 36 In a kidneyfailure patient undergoing dialysis the blood is briefly removed from the body to be circulated through a dialyzer where dialysis fluid and blood move in counter current directions to remove nitrogenous and other wastes and adjust osmolarity before the blood is returned to the body About Exam and Friday Final exam See schedule for date and time May 10 Thurs 730 am Approximately 40 Q 100 points Friday study prepare for exam no class 1 May The Countercurrent Multiplier System Concentrates Solutes in Urine Terms isosmotic 300 mOsm hypoosmotic hyperosmotic Example of countercurrent exchange system A hot water pipe flowing to left Closely adjacent and parallel is a cold water pipe flowing to the right The hot water will warm the cold water by countercurrent heat exchange Renal countercurrent multiplier system The descending proximal and ascending distal tubules in the loop of Henle is a countercurrent osmotic exchange system The solute becomes hyperosmotic multiplied in the interstitial fluid of the kidney medulla This system is cleverly controlled simply by the distribution of ion pumps and aquaporins along the tubules and ducts Figure 14 18 Consider the long loop of the juxtamedullary nephrons ADH and aquaporins H20 flows downhill to hyperosmolar gradient in medullary interstitial fluid to vasa recta Note Net water flux out of descending tubule until mOsm gradient becomes equal in nearby interstitial fluid to that in descending tubule Water flows downhill into interstitial fluid from the descending proximal tubule quotmultiplyingquot solutes from 300 to 1400 mOsm at the hairpin Pumping Na and Cl39 out of the ascending tubule low aquapoins reduces mOsm to 100 mOsm at the distal convoluted tubule Figure 14 19 The vasa recta follows the descending and ascending limbs of the tubules in the loop of Henle in the renal medulla Interstitial fluid and solutes enter passively Twice as much flow exits as enters the vasa recta The geometry of the vasa recta parallels the renal countercurrent multiplier system assuring that the blood in these vessels does not llwash outquot the osmotic gradient Renal Sodium Regulation Despite a wide range of Na intake its amount in the body is normally tightly regulated in a narrow range The amount of Na excreted equals Amount filtered by GFR Less amount reabsorbed from tubules Nai is pumped out of cells low in intracellular fluid comprising 67 water volume Nai comprises 90 of solutes in extracellular fluid Nai levels regulate extracellular volume and blood pressure Baroreceptors responsive to blood pressure and renin regulate Na reabsorption and extracellular volume Figure 14 21 A reduction in plasma volume reduces GFR and amount of Na and water excreted Baroreceptor activation of sympathetic nerves constricts renal afferent arterioles smooth muscles reducing GFR Figure 14 22 Renin and angiotensin system regulating Nai reabsorption plasma volume and blood pressure Increased synthesis of NalKi ATPase in distal tubule and cortical collecting ducts Figure 14 23 Baroreceptors control renin release as well as GFR Tubule cells release paracrines Renal juxtaglomerular cells surround renal afferent arteriole respond to stretch so act as ba roreceptors Mineralocorticoids Aldosterone Binds to mineralocorticoid receptor to increase NaK ATPase mRNA and protein levels Cortisol While a glucocorticoid it crossoccupies the mineralocorticoid receptor and significantly contributes to Na reabsorption Addison s disease Characterized by low cortisol levels low Na and hypotension Cushing s disease Characterized by high glucocorticoid levels high Naland hypertension Treatment of Hypertension Hypertension May result from quot renin U39 system diet a number of potential causes Angiotensin converting enzyme ACE inhibitors Lisinopril blocks production of angiotensinll and aldosterone AngiotensinII receptor blockers Losartan blocks production ofaldosterone Aldosterone receptor blockers Eplerenone blocks production of NaK ATPase mRNA and protein Atrial Natriuretic Peptide ANP and GFR Atrial natriuretic peptide ANP is a 28 amino acid peptide Aka atrial natriuretic factor ANF Stimuli for ANP release Elevated Na levels hypernatremia Stretching of myocytes in the cardiac atrium Hypervolemia exercise AngiotensinII Sympathetic Badrenergic agonists ANP receptor Dilates afferent arteriole constricts efferent arteriole relaxes mesangial cells increases blood pressure at glomeruli and GFR decrease renin decrease Nai reabsorption and increase its excretion Similar to Figure 14 24 Renal Water Regulation Need The amount of water and NaCl consumed can vary To maintain osmolarity 300 mOsm water reabsorption is regulated independently of Na Amount of water excreted amount filtered by GFR amount reabsorbed Distribution 67 intracellular So extracellular fluid volume would only increase 33 and is relatively insensitive to a water load Osmoreceptors stimulate firing of hypothalamic neurons with axons that release ADH vasopressin in the pituitary to regulate the amount of water absorbed ADH is the most important factor determining water excretion Figure 14 25 Osmoreceptor pathway allows water reabsorption to be independent of Na reabsorption ADH regulates numbers ofaquaporin molecules inserted into the duct membrane ADH levels determine whether urine will be concentrated or dilute hyper or hypoosmotic with Nai Ethanol reduces ADH release and is a diuretic Figure 14 26 Baroreceptors additionally regulate ADH A large change in blood pressure is required for activation Figure 14 27 Severe sweating reflex to reduce water and Na loss Recruits baroreceptor osmoreceptor renin and ADH pathways Sweat is hypoosmotic Regulating of Water and NaCl Intake Ingestion must replace the daily loss of water and NaI Survival without water is 10 days lt50 F or 5 days at 100 F Loss of 2L will decrease body performance hyperosmolarity Thirst is stimulated by Increased osmolarity Decreased extracellular fluid volume Activation of osmoreceptors and ba roreceptors Dryness of mouth and throat Salt appetite Average USA consumption 10 15 gday Recommendation ingest lt38 g NaClday to reduce risk of hypertension Regulation of Potassium Levels Intracellular KI is the most abundant ion Extracellular K is critical for nerve muscle and cardiac function Hypokalemia Abnormally low K concentration Hyperkalemia Abnormally high K concentration K excreted ingested loss in sweat loss in feces amount secreted in tubules Recall the mechanism for tubular epithelial cell NalK ATPase Most of K in GFR filtrate is reabsorbed from the proximal tubules Figure 14 29 Potassium regulation Most W reabsorbed Figure 14 14 Almost all K is reabsorbed in the proximal tubule But in the collecting duct K can be secreted into the tubule The NalKi ATPase controls how much W is excreted Ki secretion is linked to Nai reabsorption A high K diet increases the exchange of K for Nai at the NalK ATPase It also increases aldosterone production Figure 14 31 Summary Kl effect on the aldosterone pathway in collecting duct High dietary Ki Increases NaiKi exchange at the NaiKi ATPase Stimulates greater aldosterone secretion to increase NaiK ATPase production Diseases Abnormal Potassium Levels Primary aldosteronism Conn s syndrome Adenoma ofadrenal gland increasing aldosterone production Hypernatremia and hypokalemia Hypervolemia and hypertension Low renin and angiotensinll levels Treatment Unilateral adrenalectomy Cushing s disease Excess glucocorticoid cortisol production 3 February Wavelengths of light not absorbed by an object are reflected to our eyes Figure 722 White portion of eye sclera Tough connective tissue Rectus muscles attached to sclera Cornea Transparent light gets through Break in sclera Anterior chamber of eye Contains aqueous humor Between cornea and lens Lens Made of elastic protein material Strings zonular fibers connect lens to ciliary muscle Muscle pulls lens flattens Muscle relaxes lens becomes rounded Posterior chamber Contains vitreous humor Choroid in back of eye Picks up stray light 9 sharper vision Retina In front of choroid Contains photoreceptors sensitive to light In some diseases blood vessels in eye proliferate blocking flow of light 9 bl39ndness Light 9 surface of cornea 9 bent refracted 9 again on hitting surface of lens Lens elasticity changes angle light is refracted Light focused on back of eye in fovea centralis Optic disk No photoreceptors Entrance of optic nerve Blind spot Figure 726 Astigmatism deformation in cornea or lens Light is not focused where it should be Near sighted Eyeball too long Myopia Image focused in front of the retina Corrective lens concave changes angle of light Far sighted Eyeball too short Hyperopia Image focused behind the retina Corrective lens convex changes angle of light Glaucoma Excessive pressure from fluid Degeneration of retina cells Cataract Lens becomes cloudy Light does not pass through Presbyopia In older people reading glasses Lens becomes less elastic Cannot correct for close objects Retinal Image Refraction Cones Lens Astigmatism Accommodation Far objects lens flattened Near objects lens more spherical Presbyopia Construction of pupils Bright iris sphincter constricts Dark radical dilator muscle opens Convergence Four rectus muscles Near objects medial rotation of eyes Inverted image on retina Brain compensates Tracking Compensation for head movement Saccade Scan across visual field Jerky eye movements Figure 727 Rods Retina Rods and cones photoreceptors Cells that receive the light Contain photopigment Horizontal cells make connections Bipolar cells Make connections with cones or rods Pass information to ganglion cell axons go into optic nerve 9 brain 100 million None at center of vision fovea Density increases towards periphery Dim light Rhodopsin forms only in dim light Shades of darklight Shapes and movement Vitamin A deficiency night blindness Cones 7 million Concentrated at fovea centralis Photopsin Blue red and green sensitive cones Color vision Visual acuity Requires bright light Figure 730 We can only see 01 of the entire electromagnetic spectrum Light changes conformation of opsins Figure 728 In cones 9 in disks No light Molecule converts GTP 9 cGMP Gates NaCa2 channel Channel opens 9 depolarization llDark current Light Opsin converted Activates transduction 9 activates phosphodiesterase cGMP destroyed Channels close Hyperpolarization 27 January Gap junction protein channels connect cells Ca2 can flow through Cells act together if one is activated Electric synapse Gap junction with Na flowing through Depolarizing 9 action potential Synaptic Effectiveness Residual Ca2 from previous action potential Amount of NT released per action potential Presynaptic synapse One axon modifies amount of NT released from second axon Presynaptic inhibition reduced NT release Presynaptic facilitation increased NT release Neurotransmitters Bind to NT receptors Acts in milliseconds Neuromodulators Indirect effect On NT release On NT receptors On response to NT Slow more lasting events eg learning Corelease with NT eg ATP or Agrin with Ach Neurotransmitters Biogenic Amines Catecholamines Dopamine Norepinephrine Epinephrine adrenaline Serotonin 5 hydroxytryptamine 5HT Histamine Nomenclature quotergicquot Aderengic sympathetic nervous system Epinephrinenorepinephrine as neurotransmitters Vasoconstrictor increases heart rate Taken back up into presynaptic neuron after released Cocaine blocks reuptake also amphetamines These are sympathamimetic amines More neurotransmitter at synapse l HR Vasoconstrict J BP Myocardial infarct or blood vessels in brain can burst stroke Cholinergic Receptors Nicotinic multiple 01 and B receptors Skeletal muscle NMJ Ganglionic Sympathetic Parasympathetic Muscarinic R M1 M2 M3 amp M4 Smooth muscle Cardiac muscle Gland cells Some CNS neurons Some autonomic ganglia Amino Acid Neurotransmitters Excitatory Aspartate Glutamate in CNS very important onotropic R gated ion channels 15 member family AMPA NMDA Kainate Metabotropic R coupled to G proteins mGlu R 1 8 AMPA and NMDA R NmethyIDaspartate Learning LTP longterm potentiation Enhanced synaptic transmission Excitotoxicity Receptors gated with magnesium ion 2 April Pineal Gland The pineal gland is a peasized structure buried deep in the brain of humans Nearly 2000 years ago this llseat of the soul was thought to act as a valve that regulated the flow of vital spirits and knowledge into the brain By 1950 however scientists had decided that it was a vestigial structure with no known function Melatonin An amine hormone derived from the amino acid tryptophan Melatonin is the lldarkness hormonequot secreted at night as we sleep It is the chemical messenger that transmits information about lightdark cycles to the brain center that governs the body s biological clock Objectives Understand the hypothalamicpituitary regulation of the adrenal and thyroid gland Know the adrenal hormonal secretions and their function Understand the general adrenal anatomy Know how thyroid hormones are synthesized and their function Understand primary versus secondary pathologies related to adrenal and thyroid glands Adrenal cortex secretes steroids androgens cortisol aldosterone Adrenal medulla secrets catecholamines epinephrine norepinephrine Adrenal medulla epinephrine Epinephrine adrenaline CNS sympathetic nervous system ACTH Table 114 The ReninAngiotensin System RAS Controls aldosterone secretion by adrenal cortex J blood pressure 9 kidney produces renin which converts angiotensinogen from liver to angiotensin I 9 ACE converts to angiotensin II acts on arterioles cardiovascular control center in medulla oblongata hypothalamus adrenal cortex to raise blood pressure Stress 9 l cortisol 9 J immune system I gluconeogenesis 4 protein catabolism in muscle 4 lipolysis in adipocytes Net increase in blood glucose level Adrenal Cortex Cortisol Nonstress conditions Permissive action blood vessels blood pressure Permissive action on liver regulating blood glucose levels during postabsorptive state Antiinflammatory Stress conditions Table 113 Endocrine Pathologies Exogenous medication Replaces and exceeds normal Cause atrophy of gland Hypercortisolism Cushing s syndrome Hypocortisolism Less common than Cushing s syndrome Addison s disease Hyposecretion of all adrenal steroid hormones Autoimmune destruction of adrenal cortex Loss salts and water hypotension Thyroid Structure Follicular cells secrete thyroid hormone Colloid is a glycoprotein C cells secrete calcitonin Follicle is colloid surrounded by follicular cells Thyroid hormones are made from iodine and tyrosine T4 T3 Figure 1122 Thyroid hormone action Acts through nuclear receptors Increases Oz consumption thermogenesis Increases catabolism in adults anabolism in children Increases activity metabolic enzymes Development nervous system Endocrine Pathologies Hypothyroidism Hyperthyroidism and hypothyroidism Both can result in goiter Hypothyroidism Slow metabolic rate and oxygen consumption Decreases protein synthesis Slowed reflexes slow speech and thought processes and feelings of fatigue Cretinism in infants Bradycardia 24 January Neuron structure Dendrites on receiving end Information received from many other cells Long axon with terminals Axon collaterals branch off main axon Initial segmentaxon hillock most sensitive to starting action potential Varicosities can also release neurotransmitters Anterograde transport cell body to periphery Retrograde periphery to cell body Transport via microtubules and kinesinsdyneins Neurofilaments form spirals inside axons determine width of axon Glial cells Schwann cells Wraps around axon Forms myelin Increases conduction velocity Also produce growth substances In between Schwann cells are nodes of Ranvier In central nervous system oligodendrocyte Forms myelin sheath around axons Astrocyte Form bloodbrain barrier Pick up excess neurotransmitters Produce growth substances Signal to change blood flow Microglia Originate in bone marrow Scavenging Clean up breakdown products Involved in immunologic response Glial cells 90 ofvolume in brain Due to extensive myelination Ependymal cells Line brain cavities Produce substances eg cerebrospinal fluid Neuron classification Afferent periphery 9 CNS Efferent CNS 9 periphery nterneurons connect neurons in the CNS integrate information 99 of all neurons Electrogenic pump NaK maintains potential across membrane negative on inside Negativity also attributable to negatively charged proteins inside cell Depolarization Depolarizing signal makes cell more positive Past zero overshoot Hyperpolarized signal makes cell more negative Further from threshold harder to fire Graded potentials die away over distance Stronger stimulus stronger reaction Useful over relatively short distances 4 April Graves disease Hyperthyroidism Hypothalamus 9 l TRH 9 no stimulus Anterior pituitary 9 l TSH Thyroid gland enlarges 9 I T3 T4 Strong negative feedback to hypothalamus and anterior pituitary Results in goiter Autoimmune disease Hyperthyroidism Increases oxygen consumption and metabolic heat production Increase protein catabolism and may cause muscle weakness Hyperexcitable reflexes and psychological disturbances Influence Badrenergic receptors in the heart Exophthalmus caused by hypertrophy of tissues in the eye socket is a sign of hyperthyroidism Objectives Understand the hypothalamicpituitary regulation of growth hormone control Understand how bone formation and resorption occurs Understand the connection between bone formation and calcium balance Know how plasma calcium levels are regulated by hormones Understand the role of vitamin D in calcium plasma regulation Normal Growth Growth hormone and other hormones An adequate diet Absence of stress Genetics Tissue and Bone Growth Tissue growth requires hormones GH and lGFs required for protein and cell division Thyroid hormone plays permissive role Insulin supports tissue growth Bone growth requires adequate dietary calcium Figure 1126 Long bone during growth Epiphyseal growth plate active proliferating cartilage Osteoblast turn cartilage into bone Chondrocytes synthesize new cartilage in center growth plate Growth continues until closure of growth plate at puberty epiphyseal closure Shaft diaphysis Figure 1129 Cross section through piece of bone Osteoblast bone forming Osteocytes osteoblasts surrounded by calcified matrix Osteoclasts break down bone bone resorption Secrete hydrogen ions and hydrolytic enzymes Crystal hyd roxya pa tite Contains Ca2 Pi Bone growth Linear growth of long bones takes place at the epiphyseal plates Chondrocytes most die at puberty Endocrine Pathology Growth Hormone Severe GH deficiency leads to dwarfism Oversecretion of GH in children leads to giantism Oversecretin of GH in adults leads to acromegaly malformation of bone Calcium balance 99 body calcium calcified matrix of bone Movement calcium in and out of bone determines blood plasma calcium levels Approximately 13 of bone consists of collagen matrix called osteoid Crystals of calcium and phosphate hydoryxapatite are deposited on osteoid Bone remodeling involves osteoblasts and osteoclasts Calcium Important signal molecule Part of intercellular cement that holds cells together at tight junction Cofactor in the coagulation cascade Affects the excitability of neurons Table 117 Calcium Balance Parathyroid hormone PTH Mobilizes calcium from bone Enhances renal reabsorption Indirectly increases intestinal absorption Calcitriol 9 form of vitamin D3 active form Calcitonin 9 limited role Opposes PTH by inhibiting osteoclasts Figure 1130 Parathyroid gland Chief cells synthesize store excrete PTH Have calcium sensing receptors G protein coupled Activates phospholipase C 9 IP3 DAG DAG 9 protein kinase C IP3 9 l intracellular Ca2 Leads to PTH synthesis and storage release in vesicles Forms of Vitamin D Vitamin D2 and D3 Active form is 125 dihydroxy metabolites 125 dihydroxy Vitamin D3 calcitrol Large pool in body only 2 turn over each day Rickets disease in children Unmineralized bone Vitamin D deficiency Figure 1132 Generation of the active form of vitamin D Figure 1131 PTH and restoration of Ca2 blood levels 9 April Sexual Differentiation Secondary Sex Determination Alfred Jost Summary Exp 1 remove gonads XX and XY 9 Mullerian ducts Exp 2 remove gonads testosterone XX and XY 9 Wolffian Mullerian ducts Exp 3 remove gonads of XX testis fragment XX 9 Wolffian ducts Phenotypic sex Require testosterone AMH to form Wolffian ducts and degenerate Mullerian duct AMH anti Mullerian hormone Development of External Genitalia Starts the same Urethral fold urethral groove within fold Fold fuses 9 groove disappears in male Remains separate in female Genital tubercle forms penis or clitoris Development of Male External Genitalia Testosterone Setreductase 9 dihydrotestosterone DHT More potent Disorders of Sex Development Chromosomal nondisjunction One gamete receives both sex chromosomes One gamete receives no sex chromosomes If the error is in meiosis I all gametes have problems If the error occurs in meiosis half of gametes are normal Klinefelter s syndrome 47 XXY The extra X chromosome can come from either ovum or sperm Turner s syndrome 45 X0 Y0 is lethal Klinefelter s Turner Variable 1 in 500 Generally infertile Hypogonadism Relatively rare 50 embryos with this genotype die Small stature Webbed neck Infertile XX infant extra testosterone can masculinize external genitalia Complete androgen insensitivity syndrome Cannot respond to testosterone Appears female Chromosomal sex XY Gonadal sex undescended testes Phenotypic sex female No Wolffian or Mullerian duct Testosterone 9 estradiol E2 Enzyme aromatase Testosterone 9 dehydrotestosterone DHT Enzyme Setreductase Objectives Explain the anatomy of the testis Distinguish the different components of the male reproductive tract and explain their function Explain the functions of Sertoli cells and testosterone Understand spermatogenesis and know the different germ cell types in the testes Explain sperm transport through and exit from the reproductive tract Know hormonal regulation of male reproductive function Sex Steroid Hormones Androgens Testosterone ovaries and testes Dihydrotestosterone Estrogens Estradiol ovaries and testes Progesterone Precursor Steroid hormones Lipophilic Intracellular receptors Transcription Testis Anatomy Seminiferous tubules sperm production Interstitial space testosterone production Epididymis vas deferens Testis Function Requires optimal temperature 2 3 C lower Pampiniform plexus countercurrent Testicular descent Pampiniform plexus Blood going towards the testis cooled by neighboring veins Testicular descent Abdominal translocation Insulinlike 3 ns l 3 Moves away from kidneys Transinguinal migration Moves through canal nguinoscrotal migration Testosterone Descends to bottom of scrotum Testicular Pathology Cryptorchidism undescended testes Most common birth defect on male genitalia in human infants Failure of testes to descend into the scrotum Reduced fertility increased risk of testicular cancer Hormonal abnormalities genetic environment 11 April Meiosis in the Ovary Oocytes are arrested in meiosis at birth Follicle growth and maturation Oocyte completes meiosis and ovulates Ovulated oocyte arrests in meiosis Menopause follicles no longer grow LH 9 theca cells 9 testosterone FSH 9 granulosa cells Testosterone 9 granulosa cells 9 estradiol Granulosa cells 9 inhibin 9 l FSH Estradiol levels low Comes from growing follicles Negative feedback High levels of estradiol Come from dominant follicle Positive feedback to brain l LH Two ovarian phases follicular and luteal phase Follicular phase 1 bleeding starts 7 follicle becomes dominant 14 ovulation Luteal phase Corpus luteum CL derived from left over cells Secretes progesterone estradiol low levels of inhibin Functions for 11 days then dies Continues function if pregnant Ovarian cycles Follicular phase FSH stimulates follicle growth estrogen levels are low little negative feedback Growing follicles secrete estrogen Dominant follicle secretes large amounts of estrogen High levels of estrogen causes LH surge Completion meiosis Ovarian cycles Luteal phase Ovulation occurs formation of corpus luteum Corpus luteum secretes large amounts of estrogen and progesterone Negative feedback to brain FSH LH levels drop Corpus luteum degenerates estrogen and progesterone levels drop FSH and LH start to increase again 9 new cycle Ovarianuterine interaction The rise and fall of estrogens and progesterone influence the endometrium in a cyclic manner giving rise to menstrual cycle Progesterone estrogen grows epithelium Corpus luteum dies epithelial cells slough off Major functions of estrogen estradiol Follicle growth Development secondary sex characteristics Growth and proliferation epithelial lining of the reproductive tract Feedback to the brain Inhibits milk production Major function of progesterone Preparation of the endometrium for embryo implantation Stimulates breast growth Negative feedback to the brain Inhibits milk production Inhibits myometrial contractions Pregnancy Prevention Contraceptives Barriers Surgical Pills Oral contraception Combination of estrogen and progesterone Inhibits LH and FSH release Ca uses Prevents ovulation Thickens cervical mucus 25 January Excitable membrane has voltagegated ion channels Stimulus 9 graded potential Stimulus reaching threshold 9 action potential Sodium voltagegated channel Resting conditions closed Depolarization opens if greater than threshold Nai flows in down concentration gradient Shortly afterward inactivated Cannot open if inactivated Closing pushes out inactivation gate Potassium voltagegated channel Opens more slowly than Nai channels Opens after depolarization K flows out down concentration gradient Action potentials are not degenerative when channels are activated more channels in the vicinity become activated Signal spreads travels down the axon Only goes in one direction because the area the signal has just passed is in its refractory period Myelin Saltatory conduction signal jumps over myelin from node to node Fast movement conduction velocity Less ion leakage due to the insulation Potassium channels located in myelin part of why they open slowly Also because W travels through gap junctions towards bloodstream Astrocytes pick up W travelling this way Most synapses are chemical Action potential propagated down axon Ca2 enters axon terminal due to depolarization Flows down concentration gradient Vesicles release neurotransmitter into synaptic cleft Vesicles fuse with membrane by aid of SNARE proteins and synaptotagmin bound with Ca2 Neurotransmitter binds to postsynaptic cell Opens channels Graded potential Neurotransmitter can be degraded by enzymes or taken back into presynaptic cell Chemical synapses can be axon to dendrite axon to axon dendrite to dendrite or dendrite to cell body Converge multiple presynaptic neurons one postsynaptic neuron Divergence single presynaptic neuron multiple postsynaptic neurons 14 February Muscles are excitable cells Can generate action potentials Figure 91A Muscle fiber has multiple nuclei Myoblasts fuse 9 one fiber Striations on skeletal muscle Figure 92 Fiber contains myofibrils contracting unit Fiber connected to tendon on each end Basic unit Between 2 2 lines discs H zone in center Titin filaments bind to 2 line and myosin Thick filament myosin Thin filament actin w troponin tropomyosin Figure 96 Actin anchored at one end on 2 line Myosin has arms that grab actin Actin strands pulled toward center Figure 99 Relaxed state Low levels of Ca Myosin heads energized but cannot bind Tropomyosin blocking held by troponin Activated state High levels of CaH Binds to troponin tropomyosin moves out of the way Myosin binds Figure 98 Energized myosin head ADP bound Myosin binds 9 ADP release 9 arm moves ATP binds to myosin head 9 release from actin Death no ATP production Crossbridges stuck Rigor mortis Figure 911 Pores on fiber membrane allow access into transverse tubules Sarcoplasmic reticulum has swellings lateral sacs Figure 912 Depolarizing signal travels into transverse tubules CaH ion channel between T tubule and lateral sac Ca moves down concentration gradient into cytosol Figure 914 Graded potential in muscle membrane Large enough 9 actin potential in muscle Figure 913 Motor unit Single motor neuron connected to a number of different muscle fibers Motor neuron fires 9 fibers contract together More muscle fibers a neuron connects to more force it can generate Figure 916 Length does not change Isometric same length If attached to a constant load sotonic same force Mechanics of muscle contraction Isometric muscle contraction load tension Muscle length remains constant Crossbridges can t move Muscle doesn t shorten Force is exerted on thin filaments Isotonic muscle contraction tension gt load Load remains constant Crossbridges move Muscle shortens Lengthening muscle contraction Muscle length is increased relax tension heavy load Reduced overlap between thin and thick filaments f excess load muscle tears Figure 921 Less overlap between fibers less tension Figure 920 Action potential muscle twitch Restimulation before twitch ends Greater force summation Unfused tetanus Large tension Fused tetanus Maximum tension Figure 922 Muscle cell contains enough ATP for a few seconds of contraction Glycogen linked polymeric glucose Provides energy to produce more ATP Enough for 10 minutes After than runs out glycogen from liver Glucose released into blood Next 30 minutes More than 30 minutes adipose tissue Anaerobic Lacking Oz pH lowers Produce lactic acid Leads to muscle fatigue 23 March Atherosclerosis Restricted blood flow due to buildup of plaque macrophages cholesterol in arteriole wall Statins Prevent synthesis of cholesterol in liver Figure 1613 Cholesterol balance liver Figure 166 Fat and glucose metabolism Metabolism Refers to all chemical reactions in which complex molecules are broken down to produce energy and by which energy is used to build up complex molecules Involves catabolic breakdown complex molecules and anabolic reactions Amino acids free fatty acids and glucose all exist in body quotpoolsquot All needed for energy production synthesis storage Catabolism break down yield energy Anabolism synthesis use energy Gluconeogenesis Lactate glycerol amino acids 9 glucose Only occurs in liver Glycogenolysis Glycogen 9 glucose Occurs in liver Glycogen 9 ATP Occurs in muscle Glycogenesis Glucose 9 glycogen Occurs in liver and muscle Absorptive and posta bsorptive states Functional states of the body to provide energy for cellular activities Absorptive state nutrients enter blood stream from GI tract Postabsorptive state GI tract is empty cellular stores provide most energy Figure 161 Major metabolic pathways absorptive state Amino acids Some converted to keto acids in liver for energy Most used in cells for proteins Glucose Glycogen in liver Combed with fatty acids to store as triglycerides liver adipose Energy Triglycerides VLDL Adipose tissue as fatty acids 9 triglcyerides Figure 163 Major metabolic pathways postabsorptive state Lipolysis Glucose sparing Brain requires glucose Amino acids converted to ketoacids 9 glucose Fatty acids from adipose tissue Generate energy Used to generate ketones longer fasting Lactate and pyruvate from muscle glycogenolysis Converted to glucose in liver Events that provide sources of blood glucose during postabsorptive state Reactions that provide source of blood glucose Glycogenolysis glycogen hydrolysis liver Gluconeogensis from products as a result of protein and fat breakdown can not supply whole body energy needs Glucose sparing Most tissues reduce glucose catabolism increase fat catabolism switch from glucose to fat as energy source Gluconeogenesis Glycerol from lipidssome amino acids 9 glucose Betaoxidation of fatty acids Lipolysis Hydrolysis of fatty acids Acetyl CoA Citric acid cycle Keto acids produced Overnight fasting glucose production by liver during fasting conditions gluconeogenesis and glycogenolysis Prolonged fasting ketone production by liver during fasting conditions ketosis Ketogenesis Prolonged fasting low carb diet untreated diabetes Incomplete FA oxidation production of ketone bodies in liver CNS can consume hydroxybutyrate or acetoacetate to produce acetylCoA Figure 164 2 hormones from pancreas control switch between feasting and fasting Exocrine Chymotrypsinogen Trypsinogen Lipase Amylase Endocrine Alpha cells glucagon Beta cells insulin Homeostatic Control Fed state insulin dominates l glucose oxidation l glycogen synthesis l fat synthesis l protein synthesis Fasted state glucagon dominates l glycogenolysis l gluconeogenesis l ketogenesis Insulin Major regulator of metabolism Figure 165 Figure 166 Insulin action on muscle and adipose cells Tyrosine kinase pathway Vesicles containing glucose transporters inserted into plasma membrane 9 March Objectives Know the function of the GI tract Understand what is involved with digestion Know the general structure of the GI tract Be able to correlate structure of the GI tract with function Understand the relationship between the GI tract and blood vascular system Nutritional Content of a WellBalanced Diet Carbohydrates 330 g daily Main source of energy fiber confers to many health benefits Protein 100 g daily Major structural building blocks Fat 75 g daily Energy storage synthesis and repair of cell parts Water 2000 g daily Solvent lubricant medium for transport and temperature regulation Vitamins lt300 mg daily Enable chemical reactions in the body Minerals 5 10 g daily Aid enzyme function electrical balance generate nerve impulses bone structure Functions Digestive System Move food through GI tract Mechanicalphysical breakdown food Chemical breakdown food Absorption food particles and water Eliminate waste Digestion involves Secretion Absorption Motility Cell Specializations Absorption and Secretion Secretory granules Cilia and microvilli Overview GI tract 9 m30 ft long hollow tube Accessory glands secrete substances into GI Digestion and absorption Small intestine Duodenum Jejunum leum Increase in Peyer s patches lymphoid tissue the farther along the small intestine Figure 153 Figure 154 GI is designed to optimize absorption Figure 155 Mucosa composed of epithelial cells Lamina propria part of mucosa loose connective tissue Gastric glands in stomach or crypts in intestines Submucosa Muscularis mucosa circular and longitudinal Serosa Circular muscle controls radius Longitudinal muscle controls length Surface area increasing Plica folds Villi folds on plica Cells on villi have microvilli Villi contain venule arteriole lacteal lymphatic capillary Figure 156 Chemical absorption and digestion Lumen Complex compounds Enzymes added to digest Epithelial cell Enzymes secreted Degradation of smaller compounds Transporters to absorb simple compounds 28 March Lipophobic hydrophilic quotlikequot H20 Lipophilic hydrophobic quotlikequot lipids Peptide Hormone Receptor Complex Peptide hormones H cannot enter their target cells and must combine with membrane receptors R that initiate signal transduction processes Signal peptide hormone 9 receptor 9 intracellular signaling molecules 9 target protein 9 response Intracellular signaling molecules are amplifier enzymes or second messengers GProtein Coupled Receptors Coupled to GTP binding protein LH FSH TSH receptors 9 cAMP GnRH receptors 9 IP3Ca2 All cross membrane 7 times Binding 9 conformation change 9 01 subunit 9 GTP is activated 9 enzyme activated eg adenylylcyclase which turns ATP 9 cAM P cAMP is 2quotd messenger Activates protein kinase A Proteins phosphorylated Adenylylcyclase is quotamplifier enzyme activated then processes many molecules not just one cAMP second messenger figure 59 P3 and DAG second messenger fig 510 Phospholipase C activated 9 PIP2 acted on 9 IP3 travels to ER 4 Ca2 and DAG activates PKC protein kinase CD 9 phosphorylates proteins 9 call response Ca2 second messenger figure 511 Receptor tyrosine kinase signaling Ligand EG F binding and receptor aggregation 9 autophosphorylation of tyrosines 9 binding of cytosolic proteins with SH2 domains 9 activated PLCy stimulates nsP3DAG pathway 9 activated GRBZSos stimulated Ras pathway Steroid Hormones Action Most hydrophobic steroids are bound to plasma protein carriers Only unbound hormones can diffuse into the target cell Steroid hormone receptors are typically in the cytoplasm or nucleus Some steroid hormones also bind to membrane receptors that use second messenger systems to create rapid cellular responses The receptorhormone complex binds to DNA and activates or represses one or more genes Activated genes create new mRNA that moves into the cytoplasm Translation produces new proteins for cell processes Steroid hormone receptor domains DNA binding Transactivation Hormoneligand binding Figure 1108 Possible fates and actions of hormones Law of mass action H X R 9 HR Hx R Affinity kd HR kd low 9 most is HR high affinity kd high 9 most is H R low affinity 24 April Figure 13 23 Oxygen diffusion along the length of the pulmonary capillaries quickly achieves diffusional equilibrium unless disease processes in the lung reduce the rate of diffusion About 1 sec for RBC to flow through pulmonary capillary About sec for alveolar O2 to bind to hemoglobin within 13 length of capillary Reserve pulmonary capillary capacity At rest capillaries are closed at the apex top of lungs due to low blood pressure standing These capillaries provide reserve capacity Due to gravity the transit time for blood is fastest at the lower lungs and slower at the upper lungs During exercise the blood pressure in apex of lungs increases the capillaries open so more capillaries are participating in gas exchange Fick s Law of Gas Diffusion This law determines gas exchange across the respiratory membrane A greater partial pressure of the gas or a greater surface area results in a greater volume of gas that diffuses The thicker the membrane the less gas diffusion Effect of Disease on Alveolar Gas Exchange Pulmonary edema Increased pulmonary vein pressure causes fluid accumulation in interstitial space lung cells and alveoli Alveoli are compressed and respiratory membrane thicker reducing gas exchange Emphysema The loss of lung tissues and decrease in total number of working alveoli would decrease the total area available for diffusion reducing gas exchange Diffuse interstitial fibrosis Alveolar cell walls thicken fibrotic the diffusing distance is increased and gas exchange is reduced Lung cancer Surface area available for gas diffusion can be substantially decreased Matching Ventilation and Perfusion Ventilationperfusion inequality This occurs when there is mismatch between alveolar airflow ventilation and pulmonary capillary blood flow perfusion Hypoxemia Decreased p02 in the pulmonary veins due to mismatching of ventilationperfusion Hypoxemia can normally occur when standing because gravity causes greater perfusion in the lower vs upper lung This explains why p02 is 105 mm Hg in alveoli whereas only 100 mm in the pulmonary vein Disease Mismatch can be caused by diseases affecting lung compliance airway resistance or vascular resistance Clots may block blood supply Figure 13 24 Oxygen Transport in Blood Oxygen is carried in the blood in two forms Oxygen dissolved according to Henry s Law 15 In plasma and RBC cytosol The solubility of oxygen in water in about 3 mLL This limits oxygen transport Hemoglobin is necessary to overcome this limitation Oxygen reversibly bound to hemoglobin 985 In erythrocytes is about 197 mLL Greatly increases 02 carrying capacity of blood Figure 13 25 Hemoglobin is the gastransport molecule inside erythrocytes Each Hb comprised of4 globin polypeptides Hemoglobin and Oxygen Transport Hemoglobin is 100 saturated when the oxygen carrying capacity of hemoglobin in blood is maximized 50 saturated means only half of the total oxygen carrying capacity is bound to oxygen The total amount of oxygen carried by hemoglobin in blood depends partly on Percent saturation of hemoglobin RBC per unit blood HbRBC Anemia Decreased RBC or amount of Hb in blood Transfusion Whole blood vs plasma Figure 13 27 Adding Hb to compartment B substantially increases its total amount of oxygen The p02 at equilibrium is based predominately on free 02 not Hbbound Oz reservoir Figure 13 26 As the concentration of oxygen increases the percentage of hemoglobin saturated with bound oxygen increases until 100 saturation Curve is Sshaped positive cooperativity Note that venous blood is typically 75 saturated with oxygen Hemoglobin and Oxygen Unloading in Tissues Plateau 80 100 mm Change in p02 in this range has little effect on Hb saturation Systemic arterial blood p02 100 mm Hb 100 sat Systemic venous blood p02 40 mm Hb 75 sat Tissue unloading 100 75 is 25 There is reserve Hb 75 sat in tissues Exercise Tissue p02 becomes lt40 mm and reserve provides additional tissue unloading of oxygen Hyperemia is increased blood flow providing even more oxygen Fetal hemoglobin binds 02 more easily than adult Hemoglobin and Carbon Monoxide About C0 Cause for accidental death and suicides It is colorless and odorless Hb has 210 times greater affinity for CO vs oxygen Binding of CO to one heme group increases Hb affinity for oxygen on remaining heme groups Thus it is more difficult to unload oxygen at tissues The p02 in tissue can be normal but there can be severe hypoxia CO poisoning targets brainheart Cherry red lips cadaver No change in ventilation to CO unlike C02 Prevention Gas furnaces incomplete combustion can result in CO backup Cars need to be checked for exhaust lea ks Treatment Administer 100 oxygen to compete vs CO Figure 13 29 Chemical and thermal factors that alter hemoglobin s affinity to bind oxygen alter the ease of quotloadingquot and quotunloadingquot this gas in the lungs and near the active cells Figure 13 38 Regardless of the source increases in the acidity of the blood cause hyperventilation Figure 13 39 An increase in the acidity of blood causes hyperventilation independently of carbon dioxide levels Factors that Reduce Hb Affinity for Oxygen Figure 13 8 Increased temperature Exercise less effect than below factors Increased 23diphosphoglycerate DPG From RBC Example chronic lung disease anemia congestive heart high altitude adaptive to low oxygen levels by greater unloading O2 to tissues Increased HI concentration lower pH Alkalosis increases affinity Increased pCOz CO2 creates more bicarbonate and H which reduces affinity Disorders of Oxygen Transport Resulting in Hypoxia Hypoxic hypoxia Low arterial pO2 due to poor ventilation Typical causes high altitude alveolar hypoventilation decreased lung diffusion capacity abnormal ventilationperfusion ratio Anemic hypoxia Decreased total amount of O2 bound to hemoglobin Typical causes blood loss anemia low Hb ofaltered HbOZ binding carbon monoxide poisoning Ischemic hypoxia Reduced blood flow Typical causes heart failure wholebody hypoxia shock peripheral hypoxia thrombosis hypoxia in a single organ Histotoxic hypoxia Failure of cells to use Oz because cells have been poisoned Typical causes Cyanide and other metabolic poisons Carbon Dioxide Transport C02 is transported in blood in three forms The exact percentages can vary depending on conditions Dissolved 7 10 Bound to Hb as carbaminohemoglobin 23 30 Deoxyhemoglobin Hb wo oxygen has a higher affinity for CO2 than 02 As the bicarbonate ion HC0339 60 70 Carbonic anhydrase located in the RBC converts CO2 plus water to carbonic acid which dissociates to HC0339 plus Hi Note that venous blood is more acidic than arterial blood Chloride shift HC03 is transported out of RBC in exchange for CI The high pCOZ in tissues drives carbonic acid production by law of mass action 20 April Air Flow Air flow F AP R where R is airway resistance F Palv Palm R AP aka P is the difference between the pressure ofair in the atmosphere and the pressure of air in the alveoli Airflow is always down the air pressure gradient Between breaths Paw Palm F is 0 and there is no airflow Inspiration Palvlt Palm F is negative and airflow goes into lungs Expiration When Palvgt Palm F is positive and airflow goes out of lungs Figure 138 Boyle s law states that the pressure of a fixed number of gas molecules is inversely proportional to the volume of the container Boyle s Law and Air Flow V x P K constant at a constant temperature and constant number of gas molecules Shows pressure and volume are inversely related Pressure is number of molecules striking a surface per unit time When chest wall expands V of the lungs increase consequently P must decrease P in this case is Paw Air flows into the alveoli inspiration because Pavlt Palm When the chest wall contracts V of the lungs decrease and P must increase Air moves out of the alveoli because Palvgt Palm Fig 1310 Resting Table 133 Determinants of lung volume Convention Palm 0 Between breaths Pip is negative due to passive elastic recoil of lungs and chest wall Pneumothorax Hole in chest wall and its pleura due to stabbing or chest wall surgery Pip becomes 0 Plp 0 0 0 No transpulmonary pressure to keep the lungs open and it collapses atelectasis The chest wall also expands because its elastic recoil is not opposed This lung is nonfunctional Fortunately there are two independent lungs with separate plurae Q How would you re inflate the lung Pneumothorax when excess pressure applied during artificial respiration of premature baby Lungs still fragile Perforation of lung causing Pip 0 Hg13 13 Hg13 12 Inspiration is the result of the expansion of the thoracic cage in response to skeletal muscle contraction The expansion reduces alveolar pressure Paw below atmospheric pressure Palm so air moves into the lungs Figure 13 15 Expiration is the result of reducing the volume of the thoracic cage in a resting person this occurs in response to skeletal muscle relaxation The volume reduction increases alveolar pressure Paw above atmospheric pressure Palm so air moves out of the lungs Muscles Inspiration Diaphragm Most important breathing muscle Phrenic nerve Aps cause diaphragm to contract towards the abdomen This causes the thorax to expand Intercostal muscles Simultaneously the intercostal nerves fire causing contraction of intercostal muscles The rib cage moves upward and outward expanding the thorax during inspiration Pip becomes more negative Pp increases and the lungs expand for inspiration Muscles relax during normal expiration There is passive elastic recoil of the chest wall to its original position Muscles Breathing Exercise There is a need for greater ventilation This is achieved by activating a different set of intercostal and diaphragm muscles to actively increase the magnitude of thoracic volume changes Chest wall condition If the muscles are paralyzed or the ribs are calcified it would be more difficult to develop P The lungs will not inflate as easily if the rib cage is not able to move effectively NMJ blockers Tubocurarelike drugs blocks ACh R Toxins Bungarotoxin or botulinum toxin can paralyze the breathing muscles Figure 13 16 Lung compliance is a measure of the lung s strechability When compliance is abnormally high the lungs might fail to hold themselves open and are prone to collapse When compliance is abnormally low the work of breathing is increased Lung Compliance Compliance is lung elasticity The greater the compliance the more the lung expands at a given transmural premonary pressure Factors affecting lung compliance Composition of lungs If less elastic compliance declines Requires more effort to create negative Pip to expand the lungs Patients breathe more shallowly and rapidly Pulmonary fibrosis idiopathic Scar tissue reduces compliance Chronic asbestos silicon fibrotic lung disease Emphysema loss of elastic tissue Surfactant mixture of phospholipid lipids and proteins produced in response to stretch They reduce the surface tension of water lining the alveolar sacs reducing the force required for lung expansion Without surfactant alveoli would collapse Surfactant After thoracic or abdominal surgery Patients should breathe deeply often despite pain to increase production of surfactant Respiratory distress syndrome of newborn a leading cause of death in premature infants Prebirth amniotic fluid filling lungs supplies air There is no airwater interface have no surface tension Surfactant is produced near end of gestation so premature infants lacks surfactant production The high surface tension causes low compliance a much greater breathing force is needed Babies become exhausted trying to breathe they can die Treatment ventilator and addition of surfactant via trachea Airway Resistance Air flow F AP R Airflow is inversely related to R airway resistance A Paw Palm of only 1 mm Hg can produce air flow of 500 mLbreath because R is normally very small Medium sized bronchi and bronchioles are the major determinants of airway resistance Resistance is inversely proportional to the 4 h power of the bronchi radius Thus a small decrease in the radius will cause a very large increase in airway resistance Regulation of Bronchi Radius Transpulmonary pressure distends and opens the airways critical factor Pressure increases during inspiration increasing bronchi radius thereby reducing resistance Pip decreases during respiration radius is reduced increasing resistance see figure 13 13 Lateral traction Elastic connective tissue fibers are attached to bronchi at one end and to lung tissue on the other end Inspiration lung expands pulling on the elastic fibers to increase the radius of bronchi This works together with transpulmonary pressure Forced expiration Forced compression of the chest wall increases Pip compresses lung tissue reduces the radius of bronchi and increases resistance The greater the forced expiration the greater the resistance Regulation of Bronchi Radius Epinephrine relaxes the smooth muscles of the airways betaadrenergic receptors The sympathetic nervous system generally dilates the airways Epinephrine iv to treat severe bronchoconstriction Parasympathetic nervous system ACh binds muscarinic receptors to cause bronchial constriction and asphyxiation Nerve gas inhibits acetylcholinesterase increases ACh and causes severe bronchial constriction and asphyxiation 39 39 39 quot 39 increasesr 39 39 ofthis 39 quotinthe lung causing bronchoconstriction Histamine Strong bronchoconstrictor allergic reaction Carbon dioxide Expired CO2 causes bronchodilation Diseases Increasing Airway Resistance Asthma Chronic inflammation with release ofI 39 causingI 39 lLLiUII Among many causes allergens such as pollen infections environmental factors cigarette smoke pollutants Treatments Betaadrenergic agonists mimic epinephrine vasodilates Antagonists of muscarinic cholinergic receptors block constriction Leukotriene inhibitors block bronchoconstriction Glucocorticoids block inflammation 17 February Figure 104 Extrafusal muscle Skeletal ntrafusal muscle Embedded in extrafusal muscle Aka spindle fibers Stretch receptors around them Figure 105 Passive stretch Hold weight passively Muscle stretches Nerve terminals contain stretch receptors Stretch increases firing frequency Tells how much muscles are being stretched Contract Lift weight Muscle contracts ntrafusal muscle slackens action potential goes down slackens Lower muscle neurons within spine Contraction based on alpha motor neurons Gamma motor neurons to spindle fibers Fire 9 increase tension on spindle fiber No longer slack Figure 106 Knee jerk reflex Tendon hit stretched Muscle pulled forward passive stretch Stretch receptors activated Signal enters spinal cord Alpha motor neurons to extensor muscle activated Contraction nterneuron activated 9 inhibits alpha motor neuron to flexor Shows Stretch receptors are activated Alpha motor neurons to extensor and flexor functional Inhibitory interneuron functional Neuromuscular junctions functional Muscles functional Figure 107 Golgi tendon organ embedded in tendon Passive stretch low rate of firing from Golgi tendon organ Contraction pulls on tendon faster action potentials greater firing frequency Figure 108 Figure 109 Step on tack Nociceptors activated Sends signal through dorsal ganglia into spinal cord Relax muscle on top of thigh contract muscle on back of thigh Entirely within spinal cord Opposite happens to other leg Stiffen that leg 9 compensates for other leg being lifted Walking is automatic Separate cerebellum from spinal cord Put on moving treadmill Can move legs on surface Figure 1010 Sensorimotor proprioceptors vestibular 9 cerebellum Planning timing coordinating Lesion in cerebellum uncoordinated movement Figure 1012 Pyramidal tract Most cross over Right side of brain controls left side of body Regulates peripheral muscles Extrapyramidal tract Mostly uncrossed Help regulate skeletal muscles Two pathways closely integrated to regulate muscles Neuroleptic drugs for schizophrenics can cause Tardodyskinesia Uncontrollable grimacing can be irreversible Spastic toticalis Uncontrollable spasms Inject botuline toxin Paralyze to stop spasms Alzheimer s has close link to diabetes 17 January Genome Project Started mid 80 s Entire genome sequence of an organism Genome size Bacteria yeast 5000 genes Fly 14000 genes Worm 20000 genes Human 2025000 genes Chimps 985 identical Rice 50000 genes Can be used to trace evolution through amount of similarity between organisms Other human species overlapped in existence with modern humans H sapiens sapiens now to 200000 years ago Central Africa H floresiensis 12 100000 years ago H neanderthalensis 30 350000 years ago Denisova Siberia DNA 40000 years ago H rhodesiensis 120300000 years ago H sapiens ideltu 150250000 years ago Africa 200K YA Middle East 70K YA Europe 50K YA Asia 50 70K YA North America 12K YA Adaptations Africa Tropical sun 300 fold higher risk for skin cancer Dark skin kinky hair longer limbs Asians Siberian migration Epicanthal fold short limbs nose N European Weak sun Dark skin until 67000 YA Vit D Ricketts light skin 23 genes control skin color What do we mean by quotracequot From Unicellular to Multicellular Dictylstelium Single undifferentiated cell Environmental signals Cell migration Cell segregation Differentiation Each cell in the body has the same number of genes Certain genes are turned on or off each cell expresses only a subset of its genes Epithelial connective tissue nerve and muscle cells 4 types of cell Adhere to form tissues Aggregates come together to create organs Groups of organs form organ systems 6 February Figure 729 Optic nerves cross in optic chiasm Information travels to visual cortex Information from the right half of both eyes goes to the right lateral geniculus and to the right visual cortex So information from right half of left eyes crosses over in optic chiasm Convergence leads to depth perception Oncenter bipolar neuron Best stimulus small spot of light on center Depolarization light on center Hyperpolarization annular light Annular light is on edges of receptor field Offcenter bipolar neuron Best stimulus annular light Depolarization annular light Hyperpolarization light on center Shape Perception Offcenter bipolar cells detect edges Depolarize 9 fire Oncenter bipolar cells detect corners Hyperpolarization does not fully cancel depolarization Perception of Contrast The brain perceives relative contrast not absolute level of light Deprivation of information to neurons during development means they fail to make their connections Brain is a lluse it or lose itquot organ 20 March Macromolecule breakdown Polysaccharides 9 simple sugars Proteins 9 amino acids Fats 9 free fatty acids FFA Salivary glands in mouth Amylase breaks down polysaccharides Stomach Pepsinogen pepsin HCI break down proteins Liver Bile breaks down fats Pancreas Amylase breaks down polysaccharides Proteases break down proteins ex trypsin carboxypeptidase Lipases break down fats S mucosa Sugar enzymes break down polysaccharides Aminopeptidase breaks down proteins Resultant simple compounds can be taken up by cells Simple sugarsamino acids 9 hepatic portal vein 9 liver 9 hepatic vein 9 vena cava 9 heart Fatty acids 9 lacteals 9 lymph 9 heart Anabolism Fat stored in fatadipose tissue as triglycerides Amino acids and simple sugars stored in fatadipose tissue or goes to muscleliver 9 simple sugars stored as glycogen amino acids stored as protein Catabolism Glycogen 9 glucose Proteins 9 amino acids Triglycerides 9 glycerolfatty acids Used for glycolysis citric acid cycle energy Figure 1516 Upper part of the GI tract Mouth Chewing Glands Salivary amylase Regulation primarily neural reflexes Figure 1517 Stomach Digestion Body secretes mucus pepsinogen and HCI Antrum secretes mucus pepsinogen and gastrin No absorption On average 100 empty takes 4 hours Figure 1518 Secretions through specialized cells Parietal 9 HCI intrinsic factor Chief 9 pepsinogen Enteroendocrine 9 gastrin Enterochromaffinlike 9 histamine Endocrine D cells 9 somatostatin Figure 1519 Parietal cells Secrete 2 L HClday HCOgCl39 and HiKi ATPase pumps H2C03 HCOg and Hi HCOg39 transported out CI in Figure 1522 Chief cells Synthesize and secrete pepsinogen zymogen Release parallels that of HCI Stimulated by enteric nervous system Pepsin accelerates protein digestion Enteroendocrine cells Secrete gastrin Stimulates stomach muscle for mixingemptying Stimulates HCI secretion Stimulates smooth muscle of small intestine Enterochromaffinlike cells Secrete histamine Stimulates HCI secretion Endocrine cells Secrete somatostatin Inhibits HCI secretion Secretion of Gastrin and Histamine Increased by presence of food in stomach Inhibited by secretin and gastric inhibitory peptide from small intestine Secretin and gastric inhibitory peptide are released when chime enters small intestine Figure 1520 Regulation of Hi secretion 4 by gastrin histamine ACh J bysomatosta tin Figure 1521 Figure 1525 Intestinal phase Secretin Cholecystokinin CCK GIP Empty 50 small intestine 3 hours Figure 1526 Cholecystokinin secretin Act on pancreas stomach Inhibit stomach action Bicarbonate from pancreas neutralizes acids Secretin acts on duct cells bicarb CCK acts on exocrine cells enzymes opens sphincter of Oddi 9 bile release Figure 1527 Pancreas secretes inactive enzymes trypsinogen Trypsinogen 9 trypsin Figure 1528 Hormonal regulation of pancreatic bicarbonate secretin Figure 1534 colon Watersalt absorption storage 30 40 hours Regulation of GI activities Smooth muscle contractions for movement Peristalsis wave of contractions and relaxation movement Segmentation contraction and relaxation of short segments mix Figure 1523 Peristalsis Peristaltic waves over the stomach Progressive waves of contraction and relaxation Generated by pacemaker cells in longitudinal smooth muscle layer Figure 1533 Segmentation Rhythmic stationary contraction and relaxation of intestinal segments Initiated by electrical pacemaker cells in circular smooth muscle layer Segmentation and movement After absorption segmentation stops and replaced by pattern of peristaltic activity Migrating myoelectric complex Sphincters Upper esophageal Lower esophageal Pyloric Oddi leocecal Internal anal External anal Peristalsis Propulsion Esophagus stomach less in small and large intestine Rhythmic segmentation Mixing Small and large intestine Tonic contraction Functional compartmentalization Sphincters and proximal stomach 7 February Figure 733 Tuning fork bends compresses the air in front of it Sound waves Amplitude loudness Period T time between one peak and the next Frequency pitch lT Hertz HZ cyclessecond Human range 2020000 Hz 30 dB empty room 100 dB enough to damage ears Speed of sound is a constant 340 msec 1100 ftsec in air Figure 734 Pinna Outside of ear Capture sound waves Direct inward Auditory canal 9 eardrum tympanic membrane 9 maeus connected to eardrum incus stapes connected to cochlea Eustachian tubes open to relieve pressure between inner ear and rest of body Sound waves move tympanic membrane back and forth Therefore bones move Air pressure waves converted to mechanical movements of bone Converted to fluid pressure Figure 735 Stapes connected to oval window 9 scalavestibuli 9 turns corner at helicotrema 9 scala tympani 9 round window bulges Cochlear duct separated from scala vestibule and scala tympani by basilar membrane Figure 737 On basilar membrane is organ of Corti Connects to cochlear nerve Hair cells embedded Have projections stereocilia Stick into tectorial membrane Fluid causes basilar membrane to move hair cells to rub against tectorial membrane Bent one direction hyperpolarization Other direction depolarization Alters release of neurotransmitter firing of nerve End of basilar membrane near stapes Stiffer Detect treble high frequency Other end Less stiff more flexible Detect bass low frequency Lose hair cells on treble end Aging Difficulty with high frequency Too much movement of cells 9 breakage 9 deafness Placing sounds in space Sound hits one ear sooner thanlouder than in the other Tinnitus Ringing in the ears Ear inflammation irritates nerve endings Gives sensation of sound in its absence Auditory hallucination Perception of sound with no external stimulation 75 of schizophrenics have these 27 March Figure 1517 Peripheral and central thermoreceptors Figure 1612 Objectives Understand the difference between endocrine and exocrine cellssignaling Know the different classes of hormones and how their physical properties affect their signaling Understand how hormones signal through their receptors Understand how endocrine activity is regulated and the overall layout of the endocrine system Signaling systems in the body Neuronal signaling Endocrine signaling Neuroendocrine signaling Endocrine system Group of secretory cells that release a chemical hormone in the bloodstream which acts on a target cell and modulates its activity Functions of endocrine system Maintain optimal biochemical environment in the body metabolism homeostasis water and nutrient balance Integrate and regulate growth and development Control maintain initiate sexual reproduction Hormones llTo excite or arouse Amines modified amino acids Modified fatty acids Peptide hormones Steroid hormones Amine hormones structure Tyrosinederived amine hormones Modified free fatty acids structure Prostaglandins derived from arachidonic acid created by action of phospholipase Arachidonic acid 9 cyclooxygenase pathways 9 PG E2 vasodilation GI tract muscle PGcml uterine lLLlUII 39 39 clotting Peptide hormones structure Example releasing hormones pituitary hormones GI tract hormones pancreatic hormones Peptide Hormone Synthesis Packaging and Release Messenger RNA on the ribosomes binds amino acids into a peptide chain called a preprohormone The chain is directed into the ER lumen by a signal sequence of amino acids Enzymes in the ER chop off the signal sequence creating an inactive prohormone The prohormone passes from the ER through the Golgi apparatus Secretory vesicles containing enzymes and prohormone bud off the Golgi The enzymes chop the prohormone into one or more active peptides plus additional peptide fragments The secretory vesicle releases its contents by exocytosis into the extracellular space The hormone moves into the circulation for transport to its target Steroid hormones structure Steroid hormones are derived from cholesterol Cholesterol 9 pregnenolone 9 adrenal cortisol aldosterone ovary estrogen progesterone testis testosterone Statins inhibit cholesterol synthesis so would inhibit steroid hormone synthesis Pituitary 9 peptide hormone 9 receptors on cell surface 9 cAMP 9 protein kinase 9 phosphorylate proteins 9 cholesterol esterases 9 LDL 9 cholesterol 9 pregnenolone in mitochondria 13 February Figure 817 Most language comprehension comes from left half Wernicke s area Temporal lobe Comprehension Broca s area Expression of language Articulation PET scan positron emission tomography Monitors use of glucose Activity marker Figure 815 Hearing Wernicke Speaking Broca See words occipital lobe visual cortex Generate words frontal lobe Declarative memory language Localized to left hemisphere of brain Language is learned Conceptualization of speech and writing Integration of speech and writing Recent verbal memories Left hemisphere lesion Aphasia Impaired language capacity Figure 816 Male left hemisphere activated Female left and right hemispheres activated Same language task occurring Split brain Sever corpus callosum blindfold Ball in right hand can describe ball Ball in left hand can t describe object Memory disruption Retrograde amnesia can t recall prior memories Anterograde amnesia unable to form new memories Brain trauma concussion Retrograde amnesia few days Memories may return Memory retrieval blocked not storage Electroconvulsive therapy ECT Disrupts memories lt2 years old No effect on older memories Memory storage changes with time Alzheimer s disease 50 risk at age 85 Unable to access memory storage Recognition of speech ability to articulate impaired Shrinking of brain loss of neurons initially in hippocampus Amygdala loss more emotional may act out Less and less functional eventually bedridden Anxiety disorders Anxiety is important in increasing chances of survival Situational resolves after a specific event Generalized chronic Panic attacks Epinephrine release Sweat trembling 4 HR 4 BP Fight or flight response Sympathetic activation Fear of death Obsessivecompulsive disorder OCD Childhood origins Obsession internal anxiety Compulsion external behavior May worsen if untreated agoraphobia Unable to go outside interact Treatment Cognitive behavioral therapy SSRI drugs Combo treatment better Mood disorders Depression Situational Chronic Pervasive sadness Helplessness Often belief in diseased body parts High suicide risk Treatment Psychotherapy Drugs SSRI SNRI others Combo therapy best ECT if unresponsive Hippocampus Atrophy Reduced neurogenesis Bipolar disease manicdepressive Mania Extreme elation Racing thoughts Grandiose schemes Physical exhaustion Maniadepression cycles Treatment Neuroleptic drugs plus lithium Withdraw neuroleptic Chronic lithium treatment Figure 89 Reward system in brain Dopamine Locus cereleus in brainstem 9 nucleus accumbens Cocainemethamphetamine increased amount of dopamine Can be stimulated electrically Opiates agonists Opium Laudanum Morphine Heroin more lipophilic crosses bloodbrain barriers more quickly than morphine changed to morphine in brain Methadone Codeine oxycontin many others Effects Sedation nodding out Euphoria Emetia causes purging Separates sensation from perception Analgesic Respiratory depression main cause of death Endogenous Opiates Endogenous opiates peptides Endorphins Dynorphin Enkephalin Endomorphins Nociceptin antianalgesic modulates nociception Opiate antagonists Naloxone Naltrexene Receptors for endogenous opiates Delta analgesia dependence antidepressant Kappa sedation spinal anesthesia Mu euphoria physical dependence respiratory depression supraspinal analgesia Nociceptin R anxiety depression Components of opiate addition Euphoria Psychological dependence Physical dependence Dysphoria opposite of euphoria feel terrible Nausea Goosebumps Restlessness and agitation Not as severe as in alcoholism Drug tolerance Increased dose Increased cost Burglary robbery prostitution Tolerance to euphoria Drug withdrawal Syndrome of physical dependence Sickwell cycle Collapsed veins Methadone agonist stays in the body longer Cold turkey often voluntary Overdose respiratory depression Schizophrenia Auditory hallucinations Paranoia suspicions Delusions of grandeur Can become dangerous due to paranoia Enlarged ventricles structural change in brain Frontal lobe atrophy Abnormal connections perception of reality 6 April Kidney 9 Calcitrol Vitamin D3 9 Increase Ca2 absorption GI increase Ca2 absorption kidney facilitates effect PTH on bone all increase Ca2 blood plasma Calcium and Phosphate Balance Calcium and phosphate homeostasis are linked Phosphate is key ingredient of hydroxyapatite Phosphate has other roles Energy transfer and storage Activation and deactivation of enzymes transports and ion channels Part of DNA and RNA backbone PTH Bone 9 l P04 Intestine 9 4 P04 no need calcitriol Kidney 9 4 P04 secretion Objectives Explain chromosomal sex determination Distinguish between primary and secondary sex determination Apply the results from Alfred Jost s experiments to explain secondary sex determination Explain what drives male and female reproductive tract differentiation Explain what drives male and female external genitalia differentiation Environmental sex determination 9 temperature Geneticchromosomal sex determination Sex Determination Chromosomes Autosomes 22 pairs Sex chromosomes XandY XXY Klinefelter XO Turner Syndrome Fetal gonad development Genital ridgebipotential gonad Sox 9 gene 9 testis Activated by SRY Somatic support cells 9 granulosa cells in ovary 9 sertoli cells in testis Steroidogenic cells 9 theca cells in ovary 9 Leydig cells in testis Germ cells 9 oogonia in ovary 9 spermatogoniagonocytes in testis Mesonephros Gonad stuck on top Contains male and female ducts Gives rise to internal tract Secrets retinoic acid 9 enters gonad 9 presence of CYP 2631 enzyme Ovary 9 no 9 meiotic entry of germ cells Testis 9 yes 9 no meiotic entry of germ cells Testicular cords Contain Sertoli cells Germ cells Phenotypic sex secondary sex characteristics Development and differentiation of the genital duct system Male Wolffian duct Becomes epididymis vas deferens seminal vesicle Female Mullerian duct Becomes oviduct uterus upper portion of vagina 15 February Figure 928 different types of muscle fibers Slowoxidative fibers smallest Fine control Fastoxidative fibers Intermediate sized Fastglycolytic fibers largest Pick something up Use small muscle fibers at first then recruit intermediate fibers more force then recruit large muscle fibers maximal force Figure 925 Slowoxidative Lots in legs Longdistance running Usable for a long time without fatiguing Maintainable force Eventual buildup of lactic acid depletion of glycogen Takes time to refill glycogen reserves Fastoxidative 10 minutes Also present in legs Fastglycolytic Use for weight lifting Depleted of glycogen after a few minutes Buildup of K in Ttubules Takes time to clear tubules Ionic gradient lost action potential in Ttubule fails Low intensity longduration exercise Swim run ampc over many weeks Increase of mitochondira Increase of capillaries Increase endurance Small decrease in fiber diameter and muscle strength Increase in number of fastoxidative fibers red muscles Decrease in number of fastglycolytic fibers white muscle Reverts when exercise is stopped Short duration high intensity exercise Weight liftingampc over many weeks Fast glycolytic fibers increase in diameter and muscle strength increases Increased synthesis of myosin and actin filaments Increased synthesis of glycolytic enzymes Muscles fatigue rapidly Increase in number of fast glycolytic fibers Decrease in number of fast oxidative fibers Reverts when exercise is stopped Figure 927 Biceps Elbow tendon connects to bone Figure 929 Holding a weight Isometric tension on biceps At equilibrium Force must be generated to counterbalance downward pull of weight Figure 930 Velocity advantage mechanical disadvantage Move weight using pivot point Muscle contracts short distance moves lever of lower arm greater distance Aging Lose muscle mass Exercise helps maintain regain Weightbearing exercise particularly important in women Strengthens bones Help with osteoporosis Alcoholic myopathy Painful cramps Loss of muscle tissue Associated with neuropathy nerve damage Diabetic neuropathy Involves muscle weakness Lack of use of nerves Muscle atrophy due to loss of nerve supply Disuse atrophy Myasthenia gravis Profound weakness Muscular dystrophy Dystrophin gene on X chromosome Recessive disorder More common in males Varying severity Degeneration of skeletal muscle fibers Figure 91 smooth muscle Not multinucleated No striations Figure 933 Actin and myosin spread anchored to membrane Not ordered arrays like in skeletal muscle Figure 934 Signal 9 increase in CaH within cell CaH ion channels Calmodulin activated Myosin lightchain kinase activated by CaHcalmodulin Pi added to crossbridges No troponin in smooth muscle Crossbridges bind as soon as they are phosphorylated Contractions continue until CaH pumped out Figure 938 Singleunit smooth muscle Neuron runs through with varicosities which release NT Coupled to other cells through gap junctions Ca flows through Singleunit smooth muscle Uterus smalldiameter blood vessels etc Gap junctions couple cells together Depolarization spreads from cell to cell All the connected cells can respond together as a group Autonomic nerves can regulate the frequency of pacemaker cells these are coupled to the other cells Responsive to stretch Responsive to hormones and other factors Figure 937 Multiunit All fire together each by a varicosity Dependent on sympatheticparasympathetic nerves No gap junctions Multiunit smooth muscle Lungs large arteries etc Few gap junctions Each muscle cell acts independently Most have individual contact with autonomic varicosities Generally an action potential does not fire Depolarization below threshold is sufficient for contraction Not responsive to stretch Responsive to hormones 30 March Sensitivity Specificity 1 hormone 1 receptor Affinity Stickiness Control of Endocrine Activity Physiologic effects of hormones depend largely on their concentration in blood and extracellular fluid Concentration of hormone as seen by target cells is determined by three factors Rate of production Rate of delivery Rate of degradation and elimination Hormone Interactions Synergism multiple stimuli and more than additive response Permissive need second hormone to get a full response Antagonism opposing responses Peptide vs Steroid signaling Synthesis storedon demand Solubility HzOlipid Receptor membraneintracellular Transport bloodplasma proteins Half life shortlong Duration effect min or hrshrs or days Figure 1114 General layout of the endocrine system Hypothalamus 9 releasing hormone 9 pituitary gland 9 tropic hormone 9 endocrine organ 9 hormone Negative Feedback Controls Longloop feedback Shortloop feedback Objectives Understand the relationship between the hypothalamus and the pituitary Know the difference between posterior and anterior innervationregulation of the pituitary by the hypothalamus Know the relation and function of the releasing hormones trophic hormones and hormones mentioned in class Understand primary versus secondary pathologies The hypothalamus and pituitary Endocrine feedback autonomic function higher centers environmental cues 9 hypothalamus 9 pituitary 9 endocrine glands The Pituitary Gland Anatomy Anterior pituitary is a true endocrine gland of epithelial origin Posterior pituitary is an extension of the neural tissue Infundibulum is the stalk that connects the pituitary to the brain Development of the pituitary gland Anterior pituitary gland adenohypophysis Posterior pituitary gland neurohypophysis Pituitary stalk infundibulum Contains hypothalamic hypophyseal portal system The HypothalamicHypophyseal Portal System Neurons synthesizing tropic hormones release them into capillaries of the portal system Portal vessels carry the tropic hormones directly to the anterior pituitary Endocrine cells release their hormones into the second set of capillaries for distribution to the rest of the body The Pituitary Gland Two Fused The posterior pituitary gland Vasopressin l osmolarity J blood volume 9 l vasopressin 9 collecting ducts 4 H20 reabsorption 9 4 blood volume 9 4 cardiac output 9 l arterial blood pressure Oxytocin Hypothalamicanterior pituitary system fig 1118 Endocrine disorders Hyposecretionhypersecretion primary or secondary n 39 1r I quotHIM r 21 March Endocrine secreted into blood Exocrine secreted into duct Salivary glands ANS stimulus autonomic nervous system Exocrine saliva mucus amylase Stomach Stimulus food Regulated by ANS and ENS enteric Endocrine gastrin 9 I HCI motility histamine 9 I HCI Exocrine pepsinogen 9 pepsin from chief cells transformed by pepsin HCI mucus S mucosa Stimulus chyme Endocrine secretin CCK both inhibit gastrin histamine CCK acts on pancreas Enterokinases activate zymogens Pancreas Stimulus CCK 9 zymogens trypsin chymotrypsin amylase lipase carboxypeptidase Stimulus secretin 9 bicarbonate Liver Bile Objectives Understand functions of liver related to metabolism Understand blood supply to liver hepatic portal vein hepatic artery entero hepatic circulation Understand absorption of fatty acids Understand what lipoproteins are and their transport Understand cholesterol balance Understand the relationship between fat and glucose metabolism Liver metabolic organ Detoxification Synthesize bile salts enterohepatic circulation lipid metabolism Glycogen store Hepatic Portal System Most fluid is absorbed in the small intestine Figure 1530 Amino acids sugars fatty acids Portal triads Branch of bile duct Hepatic portal vein Hepatic artery Entero hepatic circulation Recycling pathway of bile between liver and intestine Figure 1512 Absorption of fat in small intestine 9 chylomicrons Lipoproteins Lipids bound to proteins Way fats can be transported through vascular system Categorized by size and density Chylomicrons Large Lipoproteins Triglycerides phospholipids cholesterol apolipoprotein B 48 Carry triacylglycerolfat from intestine to liver skeletal muscle adipose tissue LDL has higher cholesterol content than HDL Both contain more than chylomicrons Lipid transport and absorption Fatty acids and monoglycerides 9 small intestine epithelial cells 9 triglycerides 9 chylomicrons 9 lacteals 9 thoracic duct 9 vena cava Lipid transport system Heart 9 arterial system 9 liver and capillaries skeletal muscle adipose tissue Capillary walls 9 lipases 9 free fatty acids 9 absorption in skeletal muscle cells and adipocytes for oxidation and storage respiration Lipoprotein transport endogenous pathway Chylomicron remnants transformed into very low density lipoproteins VLDL by liver VLDL Transported back to muscle and adipose Broken down into IDL IDL converted into LDL LDL 9 liver and remainder to adipose and muscle LDL major source of cholesterol LDL and HDL Transport of fatty acids and cholesterol through circulatory system LDL bad low density lipoproteins Deliver fats to cells 9 building blocks HDL good high density lipoproteins Carry fats to liver 9 excess material HDL good high density lipoprotein HDL picks up excess cholesterol from tissuecells and returns it to liver A way to transfer cholesterol back to VLDL IDL LDL VLDL IDL LDL transferred back to liver HDL 9 reduces amount of free cholesterol 50 cholesterol Recepto rmediated endocytosis LDL brought into cells Cholesterol not a metabolic fuel source ChylomicronsVLDL Release FA to tissue Remnants in circulation as lipoprotein Added to circulation liver Accepts cholesterol from lipoproteins in bloodcell Adds cholesterol to chylomicronsVLDL 9 LDL Primary source of cholesterol in blood Deliver cholesterol to cells LDL removed by livercells
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