Next Tues Dr. Jacobson, next Thurs Dr. Padgett! Hip! Hip! Hooray!!
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1 BI 358 Lecture 10 Next Tues Dr. Jacobson, next Thurs Dr. Padgett! Hip! Hip! Hooray!! I. Announcements Guest lectures all next week! Quiz after lecture in Discussion on Tuesday. Q? II. CVD-Atherosclerosis Connections: Lecture 9 slides # 34 III.Endocrinology Overview G&H ch 74+75, LS, Norris, Fox... A. Endocrine vignette: Cushing s Syndrome LS B. What s an endocrine? Hormone criteria & classifications? C. Mechanisms of hormonal action fig 74-6, 74-2, 74-7,... D. Endocrinology focuses on the relationship between the Hypothalamus - Controller Pituitary - Subcontroller E. Endocrine organ & hormonal overview fig 74-1, tab 74-1 F. Hypothalamus-Post & Ant Pituitary fig 75-9, 75-4, 75-2 G. Anterior pituitary hormone functions tab 75-1, Fox + LS H. Negative feedback loops G&H p LS I. Growth Hormone (GH/STH) fig 75-5, 75-6, tab 75-3 Body builder's dream or fountain of youth? Neither! IV.Peripheral Endocrine Organs G&H ch 76, 77, 78 A. Pancreas: insulin vs. glucagon, diabetes, G&H ch 78 + Fox B. Thyroid: T3 & T4 G&H fig 76-2 thru fig DC C. Adrenal cortices G&H fig 77-1 & DC
2 L Sherwood 2004 p 336
3 What is the Ultimate Cause of Death?. 1. Q, CO or Cardiac Output 2. Pulmonary damming w/edema 3. Cardiac fibrillation 4. Thromboembolism 5. Cardiac rupture G&H 2011 p 250
4 Systolic Stretch Due to Necrotic Tissue Normal Muscle Nonfunctional Muscle Systolic Stretch G&H 2011 fig 21-7
5 G&H fig 21-8
6 Treatment Triad NB: Last blasted resort!! Drugs/Surgery Exercise Dietary Modification
7
8
9 Sizer & Whitney
10 F Sizer & E Whitney 2003 p 147 +
11
12 Selected Atherosclerotic Genetic Determinants Ultra-short List!?? Genes for HDL, LDL+ receptors, Apolipoproteins Apo B-100, Apo-E, Apo-M, lipoprotein a/lp a, homocysteine metabolism enzymes N5,N10- methylene-tetrahydrofolate reductase, cystathione beta-synthase, Type I antithrombin, mitochondrial haplogroup A, Protein tyrosine phosphate PTPN22 C/T single nucleotide polymorphism , HMG COA reductase, SNPs in TNF-alpha, IL- 1beta & TGF-beta1, IL-6, IL-10, CD14, TLR-4 receptors, Human Leukocyte Antigens HLA- DRB1*01, HLA-B*07 + haplotype LTA+253a- LTA+633g-C4A3-C4B1, HDL-associated paraoxonase (PON1), lysosomal acid lipase (LAL), MEF2A protein affecting artery walls
13 Bruce Kottke s Bathtub Analogy 5 forms of cholesterol: Bruce Kottke Chylomicrons, VLDL, LDL, IDL, HDL β Atherogenic Anti-Atherogenic Biological Artifact!? β -VLDL + LDL Total Cholesterol Level = Faucet Bathtub HDL = Drain
14 Historical Hypotheses for Atherosclerosis Development Ross & Glomset Steinberg & Witztum Endothelial Injury High Plasma LDL Platelet Adherence PDGF Release Cell Proliferation Other Growth Factors LDL Infiltration into Intima Oxidized LDL + Macrophages Foam Cells Advanced Lesion Fatty Streak
15 How Inflammation Attacks the Heart LDL Oxidized Monocytes Migrate Monocytes Macrophages Fatty Streak Fibrous Plaque Cap Breakdown Cap Rupture Clot Formation NAHL Jan/Feb 2009, p 5
16 NAHL CSPI Jan-Feb 2014
17 MRI Hyperintensities, Hypertension & Dementia NAHL CSPI, Jan-Feb 2014
18 SOURCE: Lifeline Screening, 2007
19 Middle Cerebral Artery Branches L Cerebral vasculature! Oh my! R SOURCE: McMinn & Hutchins, 1977.
20 SOURCE: Liebman, = Artery of Stroke
21 The Window to the CV System?
22 SOURCE: McMinn & Hutchins, Renal Vasculature
23 SOURCE: Willerson & Cohn, 2000.
24 SOURCE: Pollock & Wilmore, 1990.
25 SOURCE: Kahn & Clark, National Geographic, Feb 2007.
26 SOURCE: Kahn & Clark, National Geographic, Feb 2007.
27 SOURCE: Kahn & Clark, National Geographic, Feb 2007.
28 CABG = Coronary Artery Bypass Graft Double? Triple? Quadruple? Quintuple? SI Fox 2013 fig 14.19
29 SOURCE: Torstar 1984 p 128.
30 National Geographic, 2007
31
32 CardioWest artificial heart = $106,000! 3000 await transplants, but only 2100 donors are available
33 02/hearts/hearts-text.html Photograph by Robert Clark
34 Discussion Comments Q?
35 Cushing s Syndrome = Hypersecretion of Cortisol: Hypothalamic (CRH), Pituitary (ACTH), or Adrenal (Cortisol) T = 0, near normal T = 4 months later
36 Endocrine/Hormone? 1 2 Made by gland? Secreted into blood? 3 Acts on target?
37 Hormone/Endocrine Classifications Exogenous Endogenous
38 Steroid Hormone Structure: Cholesterol Backbone G&H 2011 fig 74-3; cf: fig 77-2
39 Lipophilic (Steroid+Thyroid) Hormone Mechanisms Steroid Thyroid G&H 2011 fig 74-6
40 Peptide Hormone Synthesis & Secretion G&H 2011 fig 74-2
41 camp 2 nd Messenger Mechanism G&H 2011 fig 74-7
42 G-Protein Coupled Receptor (blue) sits within lipid bilayer (green) to respond to hormone (yellow) Robert Lefkowitz, MD Duke University Cardiologist 2012 Nobel Prize in Chemistry Image by Wayne Decatur
43 Table 74-2 Hormones That Use the Adenylyl Cyclase Cyclic AMP Second Messenger System Adrenocorticotropic hormone (ACTH) Angiotensin II (ANG II, epithelial cells) Calcitonin Catecholamines (β receptors) Corticotropin-releasing hormone (CRH) Follicle-stimulating hormone (FSH) Glucagon Human chorionic gonadotropin (hcg) Luteinizing hormone (LH) Parathyroid hormone (PTH) Secretin Somatostatin (SS, GH RIH) Thyroid-stimulating hormone (TSH) Vasopressin (ADH, VP, V 2 receptor, epithelial cells) G&H 2011
44 Phospholipase C 2 nd Messenger Mechanism G&H 2011 fig 74-8
45 Table 74-3 Hormones That Use the Phospholipase C Second Messenger System Angiotensin II (ANG II, vascular smooth muscle) Catecholamines (α receptors) Gonatotropin-releasing hormone (GnRH) Growth-hormone-releasing hormone (GHRH) Oxytoxin (OXY, hypothalamus production, posterior pituitary storage) Thyrotropin releasing hormone TRH) Vasopressin (ADH, VP, V 1 receptor, vascular smooth muscle G&H 2011
46 Leptin: Enzyme-Linked Hormone Receptor Homodimer receptor Janus-kinase 2 enzyme Signal transducer & activator of transcription proteins (STAT) transcription of target genes Protein synthesis G&H 2011 fig 74-5
47 ANP = Atrial Natriuretic Polypeptide 1 2 Vasodilation BP G&H 2011
48 Krieger & Hughes 1980
49 Hypothalamus Posterior Pituitary Nervous Connection OXY ADH/VP Contraction of sexual smooth m H 2 O retention by kidneys G&H 2011 fig 75-9
50 Hypothalamus Anterior Pituitary Vascular Connection Releasing (RH)/ Release-Inhibiting (RIH) Hormones 1 of 6 Trophic/ Nourishing Hormones G&H 2011 fig 75-4
51 Capillary-Venule-Capillary Circulation NB: Ensures RH/RIH superconcentrated upon anterior pituitary! Krieger & Hughes 1980
52 Infindibulum/stalk Long hypophysealportal veins Pituitary removed! Krieger & Hughes 1980
53 G&H 2011
54 Anterior Pituitary Metabolic Functions G&H 2011 fig 75-2
55 Fox 2008
56 LS 1991
57 GH, a Protein Hormone (191 AA) G&H 2006
58 LS2 2006
59 Progression & Development of Acromegaly LS 2012 fig 17-11
60 Growth Hormone Somatotrophic Hormone Body Builder s Dream?
61 GH/STH Effects: Insulin Resistance/Type II Diabetes? Amino acid uptake & protein synthesis Lipolysis & fatty acid mobilization Glucose uptake (skeletal muscle & adipocytes) Glucose production (liver glycogenolysis) Insulin secretion
62 Increase GH naturally with exercise & sleep!! cf: G&H 2011 fig 75-6
63 Proinsulin with C-Connecting Peptide DO Norris 1980
64 Times of Plenty!! NB: Diabetics have problems either here or here. Fox 1987 Store!
65 Diabetic & Normal Response to Glucose Load G&H 2000 cf: G&H 2011 fig 78-12
66 Glucose: Sugar in Blood Normal: Pre-Diabetes: Diabetes: 126 mg/dl
67 DC 2003
68 DC 2003
69 DC 2003
70 G&H 2011 fig 76-3
71 G&H 2011 fig 76-4
72 TRH TSH Thyrotropin Inadequate Iodine Promotes Goiter! Iodine present? T 3 + T 4 Iodine G&H 2011
73 DC 2003
74 cf: G&H 2011 fig 76-8 DC 2003
75 Near absence of thyroidhormone function + myedema G&H 2006
76 DC 2003 Scoop of ice cream on North pole!
77 Adrenal Cortex Zones Epi + NE during fight/flight G&H 2011 fig 77-1
78 Stress Hypothalamus Diurnal Rhythm CRH = ACTH-RH Metabolic Fuels Building Blocks Relieve Stress Anterior Pituitary Corticotropin = ACTH Glucose, Amino Acids, Fatty Acids SOURCE: Modified after D Chiras 2003 Adrenal Cortices Cortisol
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