Human ANATOMY AND PhySiology II

1. Part A Human ANATOMY AND PhySiology II

2. Chief Complaint: 8 year old girl with excessive thirst, frequent urination, and weight loss History: History: Cindy Mallon, an 8-year-old girl in previously good health, has noticed that, in the past month, she is increasingly thirsty. She gets up several times a night to urinate, and finds herself gulping down glassfulls of water. At the dinner table, she seems to be eating twice as much as she used to, yet she has lost 5 pounds in the past month. In the past three days, she has become nauseated, vomiting on three occasions, prompting a visit to her pediatrician. CASE STUDY

3. At the doctor's office, blood and urine samples are taken. The following lab results are noted: blood glucose level = 545 mg/dl (normal 50-170 mg/dl) blood pH level = 7.23 (normally 7.35-7.45) urine = tested positive for glucose and ketone bodies (normally urine is free of glucose and ketone bodies) CASE STUDY

4. The diabetes epidemic

5. Acts with nervous system to coordinate and integrate activity of body cells • Influences metabolic activities via hormones transported in blood • Response slower but longer lasting than nervous system • Endocrinology • Study of hormones and endocrine organs Endocrine System: Overview Slide 1

6. 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 Endocrine System: Overview Slide 2

7. Exocrine glands • Nonhormonal substances (sweat, saliva) • Have ducts to carry secretion to membrane surface • Endocrine glands • Produce hormones • Lack ducts Endocrine System: Overview Slide 3

8. Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands • Hypothalamus is Neuroendocrine organ • Some have exocrine and endocrine functions • Pancreas, gonads, placenta • Other tissues and organs that produce hormones • Adipose cells, thymus, and cells in walls of small intestine, stomach, kidneys, and heart Endocrine System: Overview Slide 4

9. Figure 16.1 Location of selected endocrine organs of the body. Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus Adrenal glands Pancreas Gonads • Ovary (female) • Testis (male) Slide 5

10. Hormones: long-distance chemical signals; travel in blood or lymph Autocrines: chemicals that exert effects on 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; not considered part of endocrine system Chemical Messengers Slide 6

11. Two main classes • Amino acid-based hormones • Amino acid derivatives, peptides, and proteins • Steroids • Synthesized from cholesterol • Gonadal and adrenocortical hormones Chemistry of Hormones Slide 7

12. Though hormones circulate systemically only cells with receptors for that hormone affected • Target cells • Tissues with receptors for specific hormone • Hormones alter target cell activity Mechanisms of Hormone Action Slide 8

13. Hormone action on target cells may be to • Alter plasma membrane permeability and/or membrane potential by opening or closing ion channels • Stimulate synthesis of enzymes or other proteins • Activate or deactivate enzymes • Induce secretory activity • Stimulate mitosis Mechanisms of Hormone Action Slide 9

14. Hormones act at receptors in one of two ways, depending on their chemical nature and receptor location • Water-soluble hormones (all amino acid–based hormones except thyroid hormone) • Act on plasma membrane receptors • Act via G protein second messengers • Cannot enter cell Mechanisms of Hormone Action Slide 10

15. 2. Lipid-soluble hormones (steroid and thyroid hormones) • Act on intracellular receptors that directly activate genes • Can enter cell Mechanisms of Hormone Action Slide 11

16. cAMP signaling mechanism: • Hormone (first messenger) binds to receptor • Receptor activates G protein • G protein activates adenylate cyclase • Adenylate cyclase converts ATP to cAMP (second messenger) • cAMP activates protein kinases that phosphorylate proteins Plasma Membrane Receptors and Second-messenger Systems Slide 12

17. cAMP signaling mechanism • Activated kinases phosphorylate various proteins, activating some and inactivating others • cAMP is rapidly degraded by enzyme phosphodiesterase • Intracellular enzymatic cascades have huge amplification effect Plasma Membrane Receptors and Second-messenger Systems Slide 13

18. Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone (1st messenger) Receptor G protein Enzyme 2nd messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Adenylate cyclase G protein (Gs) cAMP activates protein kinases. 5 cAMP GTP Receptor GTP ATP Active protein kinase Inactive protein kinase GDP GTP Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Cytoplasm 2 3 4 Receptor activates G protein (Gs). G protein activates adenylate cyclase. Adenylate cyclase converts ATP to cAMP (2nd messenger). Slide 14

19. Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone (1st messenger) Receptor G protein Enzyme 2nd messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Receptor Cytoplasm Slide 15

20. Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone (1st messenger) Receptor G protein Enzyme 2nd messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid G protein (Gs) Receptor GTP GDP GTP Cytoplasm 2 Receptor activates G protein (Gs). Slide 16

21. Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone (1st messenger) Receptor G protein Enzyme 2nd messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Adenylate cyclase G protein (Gs) GTP Receptor GTP GDP GTP Cytoplasm 2 3 Receptor activates G protein (Gs). G protein activates adenylate cyclase. Slide 17

22. Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone (1st messenger) Receptor G protein Enzyme 2nd messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Adenylate cyclase G protein (Gs) cAMP GTP Receptor GTP ATP GDP GTP Cytoplasm 2 3 4 Receptor activates G protein (Gs). G protein activates adenylate cyclase. Adenylate cyclase converts ATP to cAMP (2nd messenger). Slide 18

23. Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone (1st messenger) Receptor G protein Enzyme 2nd messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Adenylate cyclase G protein (Gs) cAMP activates protein kinases. 5 cAMP GTP Receptor GTP ATP Active protein kinase Inactive protein kinase GDP GTP Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Cytoplasm 2 3 4 Receptor activates G protein (Gs). G protein activates adenylate cyclase. Adenylate cyclase converts ATP to cAMP (2nd messenger). Slide 19

24. PIP2-calcium signaling mechanism • Involves G protein and membrane-bound effector – phospholipase C • Phospholipase C splits PIP2 into two second messengers – diacylglycerol (DAG) and inositol trisphosphate (IP3) • DAG activates protein kinase; IP3 causes Ca2+ release • Calcium ions act as second messenger Plasma Membrane Receptors and Second-messenger Systems

25. Ca2+ alters enzyme activity and channels, or binds to regulatory protein calmodulin • Calcium-bound calmodulin activates enzymes that amplify cellular response Plasma Membrane Receptors and Second-messenger Systems

26. 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 Other Signaling Mechanisms

27. Steroid hormones and thyroid hormone • Diffuse into target cells and bind with intracellular receptors • Receptor-hormone complex enters nucleus; binds to specific region of DNA • Prompts DNA transcription to produce mRNA • mRNA directs protein synthesis • Promote metabolic activities, or promote synthesis of structural proteins or proteins for export from cell Intracellular Receptors and Direct Gene Activation

28. Steroid hormone Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Extracellular fluid Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Cytoplasm Receptor protein Receptor- hormone complex The receptor- hormone complex enters the nucleus. 2 Receptor Binding region Nucleus 3 The receptor- hormone complex binds a specific DNA region. DNA 4 Binding initiates transcription of the gene to mRNA. mRNA The mRNA directs protein synthesis. 5 New protein

29. Steroid hormone Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Extracellular fluid Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Cytoplasm Receptor protein Receptor- hormone complex Nucleus

30. Steroid hormone Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Extracellular fluid Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Cytoplasm Receptor protein Receptor- hormone complex The receptor- hormone complex enters the nucleus. 2 Nucleus

31. Steroid hormone Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Extracellular fluid Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Cytoplasm Receptor protein Receptor- hormone complex The receptor- hormone complex enters the nucleus. 2 Receptor Binding region Nucleus 3 The receptor- hormone complex binds a specific DNA region. DNA

32. Steroid hormone Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Extracellular fluid Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Cytoplasm Receptor protein Receptor- hormone complex The receptor- hormone complex enters the nucleus. 2 Receptor Binding region Nucleus 3 The receptor- hormone complex binds a specific DNA region. DNA 4 Binding initiates transcription of the gene to mRNA. mRNA

33. Steroid hormone Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Extracellular fluid Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Cytoplasm Receptor protein Receptor- hormone complex The receptor- hormone complex enters the nucleus. 2 Receptor Binding region Nucleus 3 The receptor- hormone complex binds a specific DNA region. DNA 4 Binding initiates transcription of the gene to mRNA. mRNA The mRNA directs protein synthesis. 5 New protein

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

35. Target cell activation depends on three factors • Blood levels of hormone • Relative number of receptors on or in target cell • Affinity of binding between receptor and hormone Target Cell Activation

36. Hormones influence number of their receptors • Up-regulation—target cells form more receptors in response to low hormone levels • Down-regulation—target cells lose receptors in response to high hormone levels Target Cell Activation

37. Blood levels of hormones • Controlled by negative feedback systems • Vary only within narrow, desirable range • Endocrine gland stimulated to synthesize and release hormones in response to • Humoral stimuli • Neural stimuli • Hormonal stimuli Control of Hormone Release

38. Changing blood levels of ions and nutrients directly stimulate secretion of hormones • Example: Ca2+ in blood • Declining blood Ca2+ concentration stimulates parathyroid glands to secrete PTH (parathyroid hormone) • PTH causes Ca2+ concentrations to rise and stimulus is removed Humoral Stimuli

39. Figure 16.4a Three types of endocrine gland stimuli. Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid glands Parathyroid glands PTH Stimulus: Low concentration of Ca2+ in capillary blood. Response: Parathyroid glands secrete parathyroid hormone (PTH), which increases blood Ca2+.

40. Figure 16.4a Three types of endocrine gland stimuli. Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid glands Parathyroid glands

41. Figure 16.4a Three types of endocrine gland stimuli. Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid glands Parathyroid glands PTH Stimulus: Low concentration of Ca2+ in capillary blood. Response: Parathyroid glands secrete parathyroid hormone (PTH), which increases blood Ca2+.

42. Hormones stimulate other endocrine organs to release their hormones • Hypothalamic hormones stimulate 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 final target organs inhibit release of anterior pituitary hormones Hormonal Stimuli

43. Figure 16.4c Three types of endocrine gland stimuli. Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Gonad (Testis) Adrenal cortex Stimulus: Hormones from hypothalamus. Response: Anterior pituitary gland secretes hormones that stimulate other endocrine glands to secrete hormones.

44. Figure 16.4c Three types of endocrine gland stimuli. Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Gonad (Testis) Adrenal cortex

45. Figure 16.4c Three types of endocrine gland stimuli. Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Gonad (Testis) Adrenal cortex

46. Figure 16.4c Three types of endocrine gland stimuli. Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid gland Gonad (Testis) Adrenal cortex Stimulus: Hormones from hypothalamus. Response: Anterior pituitary gland secretes hormones that stimulate other endocrine glands to secrete hormones.

47. Nerve fibers stimulate hormone release • Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines Neural Stimuli

48. Figure 16.4b Three types of endocrine gland stimuli. Neural Stimulus Hormone release caused by neural input. CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary Stimulus: Action potentials in preganglionic sympathetic fibers to adrenal medulla. Response: Adrenal medulla cells secrete epinephrine and norepinephrine.

49. Figure 16.4b Three types of endocrine gland stimuli. Neural Stimulus Hormone release caused by neural input. CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary

50. Figure 16.4b Three types of endocrine gland stimuli. Neural Stimulus Hormone release caused by neural input. CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary Stimulus: Action potentials in preganglionic sympathetic fibers to adrenal medulla. Response: Adrenal medulla cells secrete epinephrine and norepinephrine.