Human Anatomy and Physiology II KAAP310-14S Lectures: Tue Thu 9:30-10:45 Kirkbride 004

1. Human Anatomy and Physiology II • KAAP310-14S • Lectures: Tue Thu 9:30-10:45 Kirkbride 004 • Labs (HSC 228) • 30: Mon 10:10-12:05 KellySebzda • 31: Thu 2:30-4:25 Kelly Sebzda • 32: Mon 2:30-4:25 Tyler Kmiec • 33: Mon 4:40-6:35 Bryce Muth • Run: Tue 2:15 From CSB entrance • Course Web Site www.udel.edu/sakai • William Rose rosewc@udel.edu Rust 148 • Kelly Sebzdaksebzda@udel.eduHSC 201 • Tyler Kmiectek@udel.eduHSC 201 • Bryce Muthbmuth@udel.eduHSC 201 Department of Kinesiology and Applied Physiology

2. Human Anatomy and Physiology II KAAP310-14S Grading – see syllabus. 75% Classroom 70%: Ten tests (worst is dropped so nine count) 5%: Clicker 25% Laboratory Department of Kinesiology and Applied Physiology

3. Human Anatomy and Physiology II KAAP310-14S UD Capture: Recording of what is projected on screen and classroom audio. http://udcapture.udel.edu/2013f/kaap310-010/ Clickers: Register your clicker on Sakai. Clicker questions: 1 point for answering, 1 more point if correct. Clicker grade: Full credit if you get 75% or more of the points available. Reduced proportionally if not. If a student is observed using more than one clicker, both clicker numbers will be noted and grades reduced for both students. • No adjustments for forgotten or broken clickers, low batteries, etc. Department of Kinesiology and Applied Physiology

4. Human Anatomy and Physiology II KAAP310-14S • Tips • This class is not the same as KAAP 309. • Do not rely on memorization. • Understanding physiology requires knowing more than the what or where. You need to understand the why and the how.

5. Human Anatomy and Physiology II KAAP310-14S • Tips • Everyone will work hard. • Read the book, come to class, ask questions. • Use the recorded lectures to review and not as a substitute for coming to class. • Use the online resources.

6. Exam Questions Knowledge Comprehension Application

7. Knowledge Question ________ are chemical messengers that are released in one tissue and transported in the bloodstream to alter the activities of specific cells in other tissues. Hormones Neuropeptides Neurotransmitters Humoral antibodies none of the above

8. Comprehension Question An activated G protein can trigger the opening of calcium ion channels in the membrane. the release of calcium ions from intracellular stores. a fall in cAMP levels. a rise in cAMP levels. all of the above

9. Application Question Destruction of the supraoptic nucleus of the hypothalamus would have which result? loss of emotional response loss of GH secretion loss of ADH secretion loss of loss of regulatory factor secretion loss of melatonin secretion

10. Endocrine System: Overview • Controls and integrates • Reproduction • Growth and development • Maintenance of electrolyte, water, and nutrient balance of blood • Regulation of cellular metabolism and energy balance • Mobilization of body defenses • Acts with the nervous system to coordinate and integrate the activity of body cells • Influences metabolic activities by means of hormones transported in the blood • Responses occur more slowly but tend to last longer than those of the nervous system • Endocrinology • Study of hormones and endocrine organs

11. Other tissues and organs that produce hormones: adipose cells, thymus, cells in walls of the small intestine, stomach, kidneys, heart Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus Adrenal glands Pancreas Ovary (female) Testis (male) Figure 16.1

12. Chemical Messengers • Hormones: long-distance chemical signals that travel in the blood or lymph • Autocrines: chemicals that exert effects on the same cells that secrete them • Paracrines: locally acting chemicals that affect cells other than those that secrete them • Autocrines and paracrines are local chemical messengers and will not be considered part of the endocrine system

13. Mechanisms of Hormone Action • Hormone action on target cells may be to • Alter plasma membrane permeability of membrane potential by opening or closing ion channels • Stimulate synthesis of proteins or regulatory molecules • Activate or deactivate enzyme systems • Induce secretory activity • Stimulate mitosis

14. Chemistry of Hormones • Two main classes 1. Amino acid-based hormones • Amino acid derivatives, peptides, and proteins 2. Steroids • Synthesized from cholesterol • Gonadal and adrenocortical hormones

15. 1. Water-soluble hormones (all amino acid–based hormones except thyroid hormone) • Two mechanisms, depending on their chemical nature • Water-soluble hormones (all amino acid–based hormones except thyroid hormone) • Cannot enter the target cells • Act on plasma membrane receptors • Coupled by G proteins to intracellular second messengers that mediate the target cell’s response Extracellular fluid Hormone (1st messenger)binds receptor. G protein (GS) Receptor • Cannot enter the target cells. Act on plasma membrane receptors. Coupled by G proteins to intracellular second messengers that mediate the target cell’s response Cytoplasm

16. 2. Lipid-soluble hormones (steroid/thyroid hormones) Steroidhormone Plasmamembrane Extracellular fluid The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor that directly activates genes. Cytoplasm Receptorprotein Receptor-hormonecomplex Nucleus

17. Plasma Membrane Receptors and Second-Messenger Systems - cAMP Extracellular fluid 1 Hormone (1st messenger)binds receptor. Adenylate cyclase G protein (GS) 5 cAMP acti-vates proteinkinases. Receptor Activeproteinkinase GDP Inactiveprotein kinase 2 3 4 Receptoractivates Gprotein (GS). G proteinactivatesadenylatecyclase. Adenylatecyclaseconverts ATPto cAMP (2ndmessenger). Hormones thatact via cAMPmechanisms: Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.) GlucagonPTHTSHCalcitonin EpinephrineACTHFSHLH Cytoplasm Figure 16.2

18. Plasma Membrane Receptors and Second-Messenger Systems • cAMP signaling mechanism • Activated kinases phosphorylate various proteins, activating some and inactivating others • cAMP is rapidly degraded by the enzyme phosphodiesterase • Intracellular enzymatic cascades have a huge amplification effect

19. Plasma Membrane Receptors and Second-Messenger Systems • PIP2-calcium signaling mechanism PIP2 – phosphatidyl inositol bisphosphate • DAG activates protein kinases; IP3 triggers release of Ca2+ • Ca2+ alters enzymes or channels or binds to the regulatory protein calmodulin http://www.ruf.rice.edu/~rur/issue1_files/barron.html

20. Other Signaling Mechanisms • Cyclic guanosine monophosphate (cGMP) is second messenger for some hormones • Some work without second messengers • E.g., insulin receptor is tyrosine kinase enzyme that autophosphorylates upon insulin binding  docking for relay proteins that trigger cell responses

21. Intracellular Receptors and Direct Gene Activation Steroidhormone Plasmamembrane Extracellular fluid 1 The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor. Cytoplasm Receptorprotein Receptor-hormonecomplex 2 The receptor-hormone complex entersthe nucleus. Hormoneresponseelements Nucleus 3 The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence). DNA 4 Binding initiatestranscription of thegene to mRNA. mRNA 5 The mRNA directsprotein synthesis. New protein Figure 16.3, step 5

22. Intracellular Receptors and Direct Gene Activation Steroidhormone Plasmamembrane Extracellular fluid 1 The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor. • Steroid hormones and thyroid hormone • Diffuse into their target cells and bind with intracellular receptors • Receptor-hormone complex enters the nucleus • Receptor-hormone complex binds to a specific region of DNA • This prompts DNA transcription to produce mRNA • The mRNA directs protein synthesis Cytoplasm Receptorprotein Receptor-hormonecomplex 2 The receptor-hormone complex entersthe nucleus. Hormoneresponseelements Nucleus 3 The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence). DNA 4 Binding initiatestranscription of thegene to mRNA. mRNA 5 The mRNA directsprotein synthesis. New protein • Promote metabolic activities, or promote synthesis of structural proteins or proteins for export from cell Figure 16.3

23. Target Cell Specificity • Target cells must have specific receptors to which the hormone binds • ACTH receptors are only found on certain cells of the adrenal cortex • Thyroxin receptors are found on nearly all cells of the body

24. Target Cell Activation • Hormones influence the number of their receptors • Up-regulation—target cells form more receptors in response to the hormone • Down-regulation—target cells lose receptors in response to the hormone • Target cell activation depends on three factors • Blood levels of the hormone • Relative number of receptors on or in the target cell • Affinity of binding between receptor and hormone

25. Hormones in the Blood • Hormones are removed from the blood by • Degrading enzymes • Kidneys • Liver Half-life—the time required for a hormone’s blood level to decrease by half • Hormones circulate in the blood either free or bound • Steroids and thyroid hormone are attached to plasma proteins • All others circulate without carriers • The concentration of a circulating hormone reflects: • Rate of release • Speed of inactivation and removal from the body

26. Interaction of Hormones at Target Cells • Multiple hormones may interact in several ways • Permissiveness: one hormone cannot exert its effects without another hormone being present • Synergism: more than one hormone produces the same effects on a target cell • Antagonism: one or more hormones opposes the action of another hormone • Permissiveness: one hormone cannot exert its effects without another hormone being present • Synergism: more than one hormone produces the same effects on a target cell • Antagonism: one or more hormones opposes the action of another hormone

27. Control of Hormone Release • Blood levels of hormones • Are controlled by negative feedback systems • Vary only within a narrow desirable range • Hormones are synthesized and released in response to • Humoral stimuli • Neural stimuli • Hormonal stimuli

28. Humoral Stimuli • Changing blood levels of ions and nutrients directly stimulates secretion of hormones • Examples:

29. Humoral Stimuli (a) Humoral Stimulus Capillary blood contains low concentration of Ca2+, which stimulates… 1 • Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) • PTH causes Ca2+ concentrations to rise and the stimulus is removed Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid glands Parathyroidglands PTH …secretion of parathyroid hormone (PTH) by parathyroid glands* 2 Figure 16.4a

30. Neural Stimuli (b) Neural Stimulus Preganglionic sympathetic fibers stimulate adrenal medulla cells… 1 • Nerve fibers stimulate hormone release • Sympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary …to secrete catechola- mines (epinephrine and norepinephrine) 2 Figure 16.4b

31. Hormonal Stimuli (c) Hormonal Stimulus The hypothalamus secretes hormones that… 1 • Hormones stimulate other endocrine organs to release their hormones • Hypothalamic hormones stimulate the release of most anterior pituitary hormones • Anterior pituitary hormones stimulate targets to secrete still more hormones • Hypothalamic-pituitary-target endocrine organ feedback loop: hormones from the final target organs inhibit the release of the anterior pituitary hormones Hypothalamus …stimulate the anterior pituitary gland to secrete hormones that… 2 Pituitary gland Thyroid gland Adrenal cortex Gonad (Testis) …stimulate other endocrine glands to secrete hormones 3 Figure 16.4c

32. Nervous System Modulation • The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms • Example: under severe stress, the hypothalamus and the sympathetic nervous system are activated • As a result, body glucose levels rise

33. Interaction with a membrane-bound receptor will transduce the hormonal message via __________. • depolarization • direct gene activation • a second messenger • endocytosis

34. Receptors for steroid hormones are commonly located _________. • inside the target cell • on the plasma membrane of the target cell • in the blood plasma • in the extracellular fluid

35. The Pituitary Gland and Hypothalamus • The pituitary gland (hypophysis) has two major lobes • Posterior pituitary (lobe): • Pituicytes (glial-like supporting cells) and nerve fibers • Anterior pituitary (lobe) (adenohypophysis) • Glandular tissue

36. Case Study History of Present Illness: Lucia Sanchez is a 24 year-old woman who presented to her physician with a chief complaint of urinary frequency (polyuria) and excessive thirst (polydipsia). Her polyuria began abruptly two weeks prior to her doctor's appointment. Prior to that time, Lucia voided approximately five times per day. She estimated that she was now voiding twenty times per day. Two days prior to her visit to the doctor's office she was advised to collect her urine in order to check its volume in a 24 hour period; her total urine volume measured 12 liters. Lucia also noticed an intense craving for ice water that began at about the same time as her polyuria. If she did not have access to water, she would become extremely thirsty and dizzy. She denied any change in her appetite. She also denied the use of any medications.

37. Pituitary-Hypothalamic Relationships • Posterior lobe • A downgrowth of hypothalamic neural tissue • Neural connection to the hypothalamus (hypothalamic-hypophyseal tract) • Nuclei of the hypothalamus synthesize the neurohormones oxytocin and antidiuretic hormone (ADH) • Neurohormones are transported to the posterior pituitary

38. Paraventricular nucleus Hypothalamus 1 Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH). Posterior lobe of pituitary Optic chiasma Supraoptic nucleus Infundibulum (connecting stalk) 2 Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary. Inferior hypophyseal artery Hypothalamic- hypophyseal tract Axon terminals 3 Oxytocin and ADH are stored in axon terminals in the posterior pituitary. Posterior lobe of pituitary 4 When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood. Oxytocin ADH

39. Pituitary-Hypothalamic Relationships • Anterior Lobe: • Originates as an out-pocketing of the oral mucosa • Hypophyseal portal system • Primary capillary plexus • Hypophyseal portal veins • Secondary capillary plexus • Carries releasing and inhibiting hormones to the anterior pituitary to regulate hormone secretion

40. Hypothalamus Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. Anterior lobe of pituitary Superior hypophyseal artery 1 When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus. 2 Hypothalamic hormones travel through portal veins to the anterior pituitary where they stimulate or inhibit release of hormones made in the anterior pituitary. Hypophyseal portal system • Primary capillary plexus A portal system is two capillary plexuses (beds) connected by veins. 3 In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation. • Hypophyseal portal veins • Secondary capillary plexus GH, TSH, ACTH, FSH, LH, PRL Anterior lobe of pituitary

41. Anterior Pituitary Hormones • Growth hormone (GH) • Thyroid-stimulating hormone (TSH) or thyrotropin • Adrenocorticotropic hormone (ACTH) • Follicle-stimulating hormone (FSH) • Luteinizing hormone (LH) • Prolactin (PRL) • All are proteins • All except GH activate cyclic AMP second-messenger systems at their targets • TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands)

42. Growth Hormone (GH or Somatotropin) Hypothalamus secretes growth hormone—releasing hormone (GHRH), and somatostatin (GHIH) Inhibits GHRH release Stimulates GHIH release Feedback Anterior pituitary Inhibits GH synthesis and release • Stimulates most cells, but targets bone and skeletal muscle • Promotes protein synthesis and encourages use of fats for fuel • Most effects are mediated indirectly by insulin-like growth factors (IGFs) Growth hormone Direct actions (metabolic, anti-insulin) Indirect actions (growth- promoting) Liver and other tissues Produce Insulin-like growth factors (IGFs) Effects Effects Carbohydrate metabolism Extraskeletal Skeletal Fat Increases, stimulates Reduces, inhibits Increased protein synthesis, and cell growth and proliferation Increased cartilage formation and skeletal growth Increased fat breakdown and release Increased blood glucose and other anti-insulin effects Initial stimulus Physiological response Result Figure 16.6

43. Growth Hormone (GH or Somatotropin) Hypothalamus secretes growth hormone—releasing hormone (GHRH), and somatostatin (GHIH) Inhibits GHRH release Stimulates GHIH release Feedback Anterior pituitary Inhibits GH synthesis and release • GH release is regulated by • Growth hormone–releasing hormone (GHRH) • Growth hormone–inhibiting hormone (GHIH) (somatostatin) Growth hormone Direct actions (metabolic, anti-insulin) Indirect actions (growth- promoting) Liver and other tissues Produce Insulin-like growth factors (IGFs) Effects Effects Carbohydrate metabolism Extraskeletal Skeletal Fat Increases, stimulates Reduces, inhibits Increased protein synthesis, and cell growth and proliferation Increased cartilage formation and skeletal growth Increased fat breakdown and release Increased blood glucose and other anti-insulin effects Initial stimulus Physiological response Result Figure 16.6

44. Homeostatic Imbalances of Growth Hormone • Hypersecretion • In children results in gigantism • In adults results in acromegaly • Hyposecretion • In children results in pituitary dwarfism

45. Thyroid-Stimulating Hormone (Thyrotropin) Hypothalamus TRH Regulation: • Stimulated by thyrotropin-releasing hormone (TRH) • Inhibited by rising blood levels of thyroid hormones that act on the pituitary and hypothalamus Anterior pituitary TSH Thyroid gland Thyroid hormones Stimulates Target cells Inhibits Figure 16.7

46. Thyroid-Stimulating Hormone (Thyrotropin) Hypothalamus TRH • Produced by thyrotrophs of the anterior pituitary • Stimulates the normal development and secretory activity of the thyroid Anterior pituitary TSH Thyroid gland Thyroid hormones Stimulates Target cells Inhibits Figure 16.7

47. Adrenocorticotropic Hormone (Corticotropin) • Secreted by corticotrophs of the anterior pituitary • Stimulates the adrenal cortex to release corticosteroids • Regulation of ACTH release • Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm • Internal and external factors such as fever, hypoglycemia, and stressors can alter the release of CRH

48. Gonadotropins • Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) • Secreted by gonadotrophs of the anterior pituitary • FSH stimulates gamete (egg or sperm) production • LH promotes production of gonadal hormones • Absent from the blood in prepubertal boys and girls • Regulation of gonadotropin release • Triggered by the gonadotropin-releasing hormone (GnRH) during and after puberty • Suppressed by gonadal hormones (feedback)

49. Prolactin (PRL) • Secreted by lactotrophs of the anterior pituitary • Stimulates milk production • Regulation of PRL release • Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine) • Blood levels rise toward the end of pregnancy • Suckling stimulates PRH release and promotes continued milk production

50. The Posterior Pituitary • Contains axons of hypothalamic neurons • Stores antidiuretic hormone (ADH) and oxytocin • ADH and oxytocin are released in response to nerve impulses • Both use PIP-calcium second-messenger mechanism at their targets