MEDICAL PHYSIOLOGY

2007 LECTURE SYLLABUS

MEDICAL PHYSIOLOGY
2007
COURSE ADMINISTRATION PERSONNEL
DEPARTMENT CHAIR MICHAEL L. JENNINGS, Ph.D. PROFESSOR Office: Biomedical Research II 206-2 686-5123 Fax # 686 - 8167

COURSE DIRECTOR JAMES N. PASLEY, Ph.D. PROFESSOR Assistant Dean Office: Shorey 6S/12 686-5128 Fax # 526 -7605

COURSE ADMINISTRATIVE ASSISTANTS STACY A. MAJOR DANNY McKAY

TABLE OF CONTENTS INTRODUCTION I. Course Objectives II. Course Materials III. Classes IV. Examinations Test Validation Procedure V. Lecture Schedule Key Physiology Equations Laboratory Values
MUS # 1 MUS # 2 MUS # 3 MUS # 4

Pasley

Page 3 3 4 4 7 8
98

99
Cornett Cornett Cornett Cornett Soulsby Soulsby Soulsby Soulsby Alan Alan Soulsby Soulsby Soulsby Coker Coker Ware Ware Ware Soulsby Soulsby Soulsby Jennings Jennings Jennings Jennings Jennings Jennings Jennings 14 15 16 17 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42

CV #1 CV #2 CV #3 CV #4 CV #5 CV #6 CV #7 CV #8 CV #9 EX #1 EX # 2 CV #12 CV#13 CV #14 CV #15 CV #16 CV #17 RS #1 RS #2 RS #3 RS #4 RS #5 RS #6 RS #7

Mechanics Of Skeletal Muscle Contraction Functional Properties Of Skeletal Muscle Neuromuscular Junction Smooth Muscle Introduction To Cardiovascular Physiology Electrophysiology Cardiac Cycle Ventricular Function and Energetics Basic Electrocardiography I Basic Electrocardiography II Cardiac Output The Peripheral Vascular System Arterial Blood Pressure Regulation Cardiovascular Responses To Exercise Skeletal Muscle Respon. and Fuel Use During Exercise. Hemodynamics Microcirculation Blood Coagulation, Hemostasis and Thrombosis Venous Return Cardiovascular Intrinsic and Extrinsic Control Cardiovascular Pathophysiology Airways; Ventilation; Properties Of Gases Pulmonary Gas Exchange; O2 Transport Tissue Gas Exchange; CO2 Transport Muscles Of Breathing; Pulmonary Pressures Lung & Thorax Compliance, Airway Resistance Regulation Of Breathing Pulmonary Blood Flow; Fluid Balance

RS #8 RS #9 R #1 R #2 R #3 R #4 R #5 R #6 R #7 R #8 A/B #1 A/B #2 A/B #3 GI #1 GI #2 GI #3 GI #4 GI #5 GI #6 GI #7 GI #8 Endo #1 Endo #2 Endo #3 Endo #4 Endo #5 Endo #6 Endo #7 Endo #8 Endo #9 Endo #10 Endo #11 Endo #12 Endo #13

Ventilation/Perfusion Relations (Air/Blood Matching) Pulmonary Pathophysiology Body Fluid Compartments Renal Anatomy and Function Tubular Fluid Processing Controlling and Measuring Renal Function Renal Concentrating and diluting Mechanisms Regulation of extracellular fluid osmolarity and Na+ concentration Electrolyte Balance Diuretics and Renal Related Diseases and Syndromes Introduction To Acid-Base Balance Regulation Of Acid-Base Balance Renal Regulation Of Hydrogen Ion Balance Introduction Of GI Physiology Mastication and Swallowing Swallowing Abnormalities and Gastric Motility Gastric Secretion and Small Intestinal Motility Pancreatic, Biliary and Intestinal Secretion Digestion and Absorption Of Macronutrients Water, Electrolyte, Vitamin and Mineral Absorption Lg. Bowel Motility, Gas In The Gut and Dietary Fiber Temperature Regulation Energy Balance and Obesity Neuroendocrine Hormones; Pituitary Endocrine Control Of Calcium Metabolism Endocrine Pancreas I Endocrine Pancreas II The Thyroid Gland Adrenal Gland I Adrenal Gland II Male Reproductive Physiology Female Reproductive Physiology I Female Reproductive Physiology II Neonatal Physiology

Jennings Jennings Kurten Kurten Kurten Safirstein Safirstein Safirstein Kurten Safirstein Wight Wight Wight Pasley Pasley Pasley Pasley Pasley Pasley Pasley Pasley Conaway Conaway Conaway Conaway Conaway Conaway Conaway Conaway Conaway Gaddy Gaddy Gaddy Jennings

43 44 46 48 50 52 53 55 56 58 60 61 62 64 65 67 69 71 73 75 76 79 80 81 82 83 84 85 86 87 89 92 94 96

MEDICAL PHYSIOLOGY (PHYSIOLOGY 500V) SPRING SEMISTER 2006 I. COURSE OBJECTIVES II. To provide students with an understanding of the normal function of cells, tissues, or organ systems of the human body To provide examples of how organ systems are integrated to maintain a normal physiological state. To provide students with knowledge on the topics of general cell physiology, cardiovascular, respiratory, renal, gastrointestinal and endocrine physiology. To provide both basic factual knowledge of fundamental concepts of physiology as well as clinical correlates of these concepts as applied to humans. To provide basic physiological principles that establish a solid foundation for future learning of pathophysiological and pharmacological concepts. COURSE MATERIALS Required Textbook: The following textbook is required for the course: - Medical Physiology, Guyton and Hall, 11th Ed., 2006 Other Recommended Concise Textbooks: Costanzo, Linda S., Physiology, W.B. Sanders, Philadelphia, 1998 Pasley, J.N., USMLE Road Map: Physiology, Lange/McGraw-Hill, 2006 Seidel, C., Basic Concepts in Physiology: A Students Survival Guide, McGraw-Hill, 2002 West J.B., Respiratory Physiology: The Essentials, 5th Edition, LWW, Philadelphia, 1995 William Ganong, Review of Physiology, Lange/McGraw-Hill, 2005

Learning Resource Center Reverences. The Learning Resource Center (located on the 5th floor of Ed. II bldg.) has a variety of audiovisual material covering various aspects of medical physiology. Recommended tapes and CAI presentations are listed below and in the syllabus under specific lectures. Interactive Physiology: Cardiovascular Interactive Physiology: Urinary Interactive Physiology: Respiratory Interactive Physiology: Musculoskeletal Interactive Physiology: Fluid and Electrolytes/Acid Base Essentials of Physiology Arterial Blood Gas SimBioSys Physiology Clinic Must stay in the LRC SimBioSys Physiology Lab Must stay in the LRC Mac & PC CD Mac & PC CD Mac & PC CD Mac & PC CD Mac & PC CD Mac & PC CD CD Mac & PC CD Mac & PC CD

Syllabus. A new vigilance on the part of publishers regarding the copyright of their materials requires us to redefine our policies on the distribution of course materials. Thus, the printed syllabus has been reduced to general information and lecture outlines to complement reading assignments and the lecture. Instructors may choose to cover all or only part of the material contained in the syllabus during a lecture period, particularly when the text adequately presents the same material. 3

Conversely, topics not mentioned in the syllabus but are in the textbook may be covered by course exams. Faculty use of copyrighted materials complies with the law as outlined in the Guidelines for Fair Use of Copyrighted Materials and is restricted to the use intended. You, the enrolled student, have certain rights under Fair Use. You may print or make a copy of the information FOR YOUR OWN USE but this information CANNOT BE DUPLICATED or copied to give to anyone else. III. Classes Lectures. Lectures will be approximately 50 minutes in length and generally will conform to the classical didactic pattern. Instructors have designed their lectures to present physiological principles in an organized and comprehensive fashion. Students are encouraged to ask questions during lecture periods. The course schedule in the syllabus indicates the dates, times, and location of all lectures. It is strongly recommended that students read the associated syllabus material and reading assignments prior to a scheduled lecture. Clinical Correlation Lectures. Clinical Correlation lectures are presented by clinicians (either UAMS faculty or private practice physicians) whose subspecialties are related to the organ system under discussion. These presentations are designed to demonstrate the relationship between medical physiology and clinical medicine. In addition, the Whitney Memorial Lecture is presented by a distinguished physiologist each year. PBL Case Conferences. For these conferences, the class will be divided into 10 small groups of 16 and will meet with assigned faculty members to discuss the designated case. Cases will be available on the web site approximately one week ahead. Attendance at these sessions is required. Group assignments will be posted on the web and the wailing wall. SIM -MAN PBL groups will be posted on the web and the wailing wall the location for the SIM MAN PBLs will be on the second floor of the OLD hospital room 2D/31. Attendance at these sessions is required. Review Sessions. Question based reviews will be presented at the end of each topic block prior to examination. Tutoring Sessions. Will be announced via certified mail and e-mail for students requiring further assistance. Students in academic jeopardy are required to attend all tutorial sessions until their cumulative percent score is consistent with a C letter grade. Students in academic jeopardy are also encouraged to meet with Dr. Judy Garrett, Office of Educational Development for individual counseling. IV. EXAMINATIONS Midterm Examinations. Four didactic computerized exams will be administered in the Computer Laboratories on the 8th Floor of the Education II Building. Student room assignments will be distributed either via the Medical Physiology web site and/or on the Wailing Wall on the G level of the Education II building prior to each examination. 4

Computerized Examination Instruction Summary:

1. Students should arrive 10 minutes prior to the start of the exam. Books, notes, paper,

coats, backpacks, etc. are to be left outside or in the back of the examination room. Late students will Not be given extra time. 2. Type your social security number in the box on the initial screen. Use the number keys at the top of the keyboard NOT the numeric keys on the right. 3. In the next box, type in your unique password. Your password will be given to you upon entrance into the exam room on a piece of scratch paper. Read the instructions and begin the examination. The scratch paper may be used for making notes during the exam but must be turned in before leaving the room. Follow all instructions, and be sure to use the scroll boxes to be sure you have read all of the question and examined all of the possible choices of answers. READ CAREFULLY! 4. Click on the ONE BEST response to each question. Click the Next Question

button when you are ready to leave the current question.

5. Students encountering problems with the computer, should notify the proctor in

the examination room. Queries regarding examination questions will not be addressed during an examination.
6. When you have completed answering the questions, you will be allowed to return to questions you have not answered as well as review all questions on the examination by clicking on the "Go To" button. 7. Warning screens will appear to indicate time remaining at 10, 5 and 1 minutes. When you type "QUIT" at the end of the examination, you cannot re-enter the examination. After quitting, you will be permitted to see your unofficial score, if you wish. 8. You may leave at any time after completing the examination.

The final examination in the course (the 5th examination) will be the National Board Subject Examination in Medical Physiology, and it will be administered in the 8th Floor laboratories (8A, 8C, 8B and 8D) in the Education II Building.

Midterm # 1 Midterm # 2 Midterm # 3 Midterm # 4 Quizzes Final Examination TOTAL

20% 15% 21% 14% 5% 25% 100%

TEST ITEM VALIDATION PROCEDURE (STUDENT INFORMATION) The faculty believes that detecting flawed questions on exams is the responsibility of the faculty and not the students. It is unfair to ask students to research a question for possible flaws. In a student appeal system, a student must take valuable time researching a question, when he or she may have an exam the next day in another course. Consequently, the following methods will be used to assure that all questions on exams are valid: 1) Questions will be faculty peer reviewed prior to each exam. 2) After exams, performance data on questions will be studied. 3) Any questions that fall within a pre-defined range of performance data that suggests a problem will be reviewed by both the question author and the Course Director. At this time, questions identified as weak, or flawed, will be deleted from the exam. After this process, which could take several days, a VALID KEY will then be posted. This validation process will assure with high probability that all items counted toward a students score on a test are without significant fault or flaw. ONLY IN CASES OF CLEAR AND OBVIOUS FLAWS OR ERRORS IN A TEST ITEM WILL ANY CHANGE IN TEST SCORES BE MADE. BECAUSE OF THE AUTOMATIC SCREENING OF TEST ITEM QUALITY, IT SHALL RARELY BE THE CASE THAT ANY ITEM WITH A CLEAR OR OBVIOUS FLAW REMAINS IN THE TEST AFTER THE SCREENING PROCESS. CONCEIVABLE ALTERNATE INTERPRETATIONS OF THE ITEMS STEM AND/OR ITS OPTIONS (i.e., ALTERNATIVE ANSWERS PROVIDED IN THE TEST) NEED NOT BE BROUGHT TO THE COURSE DIRECTORS ATTENTION (UNLESS SIMPLY FOR THE INTELLECTUAL EXERCISE) BECAUSE SUCH COMMENTS AND OBSERVATION SHALL NOT BE JUDGED OF SUFFICIENT MERIT TO JUSTIFY ANY CHANGES IN THE SCORING OF ANY TEST ITEM. This procedure obviates any need for a routine, formal student test item appeal process. Any student believing that a question counted toward the total test score was significantly flawed or faulty should bring that opinion to the attention of the Course Director in a prompt and timely manner. Comments regarding questions which you believe are flawed and were not deleted from the VALID KEY can be e-mailed or by filling out a form available in the LRC or Course Office in Shorey. Comments are due in the Course Office by 4:00 p.m. 48 hours following the posting of the VALID KEY.

As soon as a final computer rescoring is completed (about one or two more days), student percent scores will be posted. Final letter grades will be assigned based upon the following scale.

Letter Grade A B C D F

Overall Score 85.50 100% 75.50 85.49% 65.50 75.49% 60.00 65.49% 0 59.99%

MEDICAL PHYSIOLOGY SPRING 2007 SCHEDULE All lectures will be held in Education Building 2 (G-131 A/B)

(The schedule is subject to change without prior notice)

Exam 1 / Week 1 Date Day Time 1/02 1/02 1/03 1/04 1/05 1/05 TU TU W TH F F 10 11 9 11 9 11 Time 9 11 10-12 9 9 11 10 11 MUS # 1 MUS # 2 MUS # 3 MUS # 4 Lecture CC 01 CV # 1 PBL 01 CV # 2 CV # 3 CV # 4 CV # 5 CV # 6 Lecture Title Introduction to Medical Physiology Role of Physiology in Clinical Medicine Mech. of Skeletal Muscle Contraction Funct. Properties of Skeletal Muscle Neuromuscular Junction Smooth Muscle Title Physiology Lecture Introduction to CV PBL : Muscle Electrophysiology The Cardiac cycle Ventricular Function and Energetics Basic Electrocardiography I Basic Electrocardiography II Instructor Pasley Marsh Cornett Cornett Cornett Cornett Instructor Soulsby Staff Soulsby Soulsby Soulsby Allan Allan

Exam 1 / Week 2 Date Day 1/08 1/08 1/09 1/10 1/11 1/11 1/12 1/12 M M TU W TH TH F F

Exam 1 / Week 3 Date Day 1/15 1/16 1/16 1/17 1/18 1/19 1/19 M TU TU W TH F F

Time

Lecture HOLIDAY

Title Martin Luther King Day Cardiac Output The Peripheral Vascular System Clinical Correlation: CV EKG LAB Arterial Blood Pressure Regulation Cardiovascular Responses to Exercise

Instructor

9 11 9 10-12 9 11

CV # 7 CV # 8 CC 02 9 C/D LAB CV # 9 EX # 1

Soulsby Soulsby Smith Staff Soulsby Coker

Exam 1 / Week 4 Date Day 1/22 1/22 1/23 1/25 1/26 1/26 M M TU TH F F

Time 11 1 10-12 11 9 10

Lecture EX # 2 CV # 12 PBL 02 CV # 13 CV # 14

Title Skeletal Muscle Resp. and Fuel Use During Exercise Hemodynamics PBL: CV / Exercise The Microcirculation Blood Coagulation, Hemostasis and Thrombosis Physiology Review

Instructor Coker Ware Soulsby Ware Ware Staff

Exam 1 / Week 5 Date Day Time 1/29 1/30 1/30 1/31 2/01 2/01 M TU TU W TH TH 8-10 :50 9 11 11 9 11

Lecture 8C LAB CV # 15 CV # 16 CV # 17 RS # 1 RS # 2 EXAM 1 Venous Return

Title

Instructor Soulsby Soulsby Soulsby Jennings Jennings

Cardiovascular Intrinsic and Extrinsic Control Cardiovascular Pathophysiology Airways; Ventilation; Properties of Gases Pulm. Gas Exchange; O2 Transport

Exam 2 / Week 6 Date Day Time 2/05 2/05 2/06 2/06 2/08 2/09 2/09 M M TU TU TH F F 1 3 9 11 10-12 10 11

Lecture RS # 3 RS # 4 RS # 5 RS # 6 9C/D Lab CC 03 RS # 7

Title Tissue Gas Exchange; CO2 Transport Airways; Muscles of Breathing; Pulm. Pressures Lung & Thorax Compliance, Airway Resistance Regulation Of Breathing Mechanics Of Breathing Lab Pediatric Pulmonary Mechanics Pulmonary Blood Flow; Fluid Balance

Instructor Jennings Jennings Jennings Jennings Staff Heulitt Jennings

Exam 2 / Week 7 Date Day Time 2/12 M 11 2/12 2/13 2/13 2/14 2/16 2/16 M TU TU W F F 1-5 8 1-5 9 10 11

Lecture RS # 8 PBL 03 RS # 9 PBL 04 CC 04

Title Ventilation/Perfusion Relations (Air/Blood Matching) SIM - MAN Pulmonary Pathophysiology SIM - MAN Adult Respiratory Diseases SIM - MAN Review Review

Instructor Jennings Staff Jennings Staff

Anderson

Staff Staff

Exam 2 / Week 8 Date Day Time 2/19 M 2/20 2/21 2/21 2/22 2/23 2/23 TU W W TH F F 8-10:50 9 11 10 10 1

Lecture HOLIDAY 8C LAB R#1 R#2 R#3 R#4 R#5 EXAM 2

Title PRESIDENTS DAY Renal Anatomy and Function Renal Blood Flow and Glomerular Filtration Tubular Transport in Nephron Segments Renal Concentrating and Diluting Mechanisms Fluid Shifts and Water Balance

Instructor

Kurten Kurten Kurten Safirstein Safirstein

Exam 2 / Week 9 Date Day Time 2/27 TU 10 2/27 2/28 2/28 3/01 3/02 TU W W TH TH 1-3 9 11 10 11

Lecture R#6 PBL 05 R#7 CC 05 R#8 A/B # 1

Title Sodium Balance PBL: Renal Case Conference Potassium Balance Clinical Correlation: Renal Ca2++, Mg2++, and PO4 Balance and the Urinary Tract Introduction To Acid Base

Instructor Safirstein Staff Kurten Andreoli Safirstein Wight

Exam 3 / Week 10 Date Day Time 3/06 3/06 3/06 3/07 3/07 3/07 TU TU TU W W W 10 11 1-3 9 10 11

Lecture A/B # 2 A/B # 3 PBL 06 CC 06

Title Regulation Of Acid-Base Balance Renal Regulation Of Hydrogen Ion Balance PBL A/B Computer Clinical Correlation: Physiology Lecture Physiology Lecture

Instructor Wight Wight Staff Wheeler TBA TBA

Exam 3 / Week 11 3/10 3/18 SPRING BREAK

Exam 3 / Week 12 Date Day Time 3/19 3/19 3/20 3/22 3/23 3/23 M M TU TH F F 9 11 10 10 9 11

Lecture GI # 1 GI # 2 GI # 3 GI # 4 GI # 5

Title Introduction to Gastrointestinal Physiology Mastication and Swallowing Swallowing Abnormalities and Gastric Motility Gastric Secretion and Small Intestinal Motility Pancreatic, Biliary and Intestinal Secretion Whitney Lecture

Instructor Pasley Pasley Pasley Pasley Pasley Schuster

10

Exam 3 / Week 13 Date Day Time 3/26 M 11 3/27 3/27 3/28 3/29 3/29 TU TH W TH TH 11 1-3 9 9 11

Lecture GI # 6 GI # 7 PBL 07 GI # 8 CC 07

Title Digestion and Absorption of Macronutrients Water, Electrolyte, Vitamin and Mineral Absorption PBL- GI Case Conference Lg. Bowel Motility, Gas in the Gut and Dietary Fiber Clinical Correlation Review

Instructor Pasley Pasley Staff Pasley Staff

Exam 3 / Week 14 Date Day Time 4/02 4/03 4/04 4/05 4/05 4/06 M TU W TH TH F 1-4 10 9 10 11 10

Lecture 8C Lab Endo # 1 Endo # 2 Endo # 3 CC 08 Endo # 4 EXAM 3

Title

Instructor

Temperature Regulation Energy Balance and Obesity Neuroendocrine Hormones: Pituitary Clinical Correlation: Pituitary Endocrine Control Of Calcium Metabolism

Conaway Conaway Conaway TBA Conaway

Exam 3 / Week 15 Date Day Time 4/09 4/10 4/10 4/11 4/12 4/12 M TU TU W TH TH 11 10 11 9 10 11

Lecture Endo # 5 Endo # 6 CC 09 Endo # 7 CC 10

Title Endocrine Pancreas I Endocrine Pancreas II Clinical Correlation: Diabetic Ketoacidosis The Thyroid Gland Clinical Correlation: Thyroid Physiology Lecture

Instructor Conaway Conaway Straub Conaway Straub TBA

Exam 4 / Week 16 Date Day Time 4/17 4/18 4/19 4/19 4/20 4/20 TU W TH TH F F 10 10 10 1-3 10 1

Lecture Endo # 8 Endo # 9 CC 11 PBL 08 Endo # 10 Endo # 11 Adrenal Gland I Adrenal Gland II

Title

Instructor Conaway Conaway TBA Staff Gaddy Gaddy

Clinical Correlation: Adrenal Problem Based Learning Male Reproductive Physiology Female Reproductive Physiology I

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Exam 4 / Week 17 Date Day Time 4/23 4/24 4/26 4/26 4/26 4/27 M TU TH TH TH F 10 10 9 11 1-3 10

Lecture Endo # 12 Endo # 13 CC 11 PBL 09

Title Female Reproductive Physiology II Neonatal Physiology Physiology Lecture Clinical Correlation: Reproduction Problem Based Learning Physiology Review

Instructor Gaddy Jennings TBA Kemp Staff

Exam 4 / Week 18 Date Day Time 4/30 5/4 M F 8-12 8-12

Lecture 8C LAB G-131

Title EXAM 4 NBME REVIEW

Exam 5 / Week 19 Date Day Time 5/7 M 8-12

Lecture 8C LAB

Title NBME EXAM

PBL Rooms In Education Building II B 106 B 108 G 108 G 110 G 112

MEDICAL PHYSIOLOGY SPRING 2007 WEB PAGE BOOKMARK THIS PAGE AND USE IT TO REACH LECTURE MATERIAL NEW INFORMATION WILL BE POSTED ON THIS PAGE ONLY

http://www.uams.edu/physiology/MedPhys/MedPhys.htm

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MUSCLE PHYSIOLOGY

L.E. CORNETT, Ph.D.

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Title of Lecture: (MUS-1) Mechanisms of Skeletal Muscle Contraction Instructor: Dr. Lawrence E. Cornett Biomedical Research Building II 159-2; lcornett@uams.edu; 686-5441 Required Reading: Medical Physiology, Guyton and Hall; 11th Ed., 2006, Chapter 6, pp 72-84

Suggested Reading: Diseases of the Skeletal Muscle, Ed., R.L. Wortmann, Lippincott, Williams and Wilkins, 2000 Objectives: Describe the relevant cellular structures and proteins involved in muscle contraction Describe the events that at the cellular level during the production of the force Lecture Outline: I. Introduction Muscle typesskeletal, smooth and cardiac Shared characteristics II. Skeletal muscle filaments and associated proteins Thick filamentmyosin Thin filamentactin and tropomyosin/troponin complex III. Contraction cycle Sliding filament hypothesis Ratchet theory of muscle contraction Biochemical events that occur during a contraction cycle

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Title of Lecture:

(MUS-2) Functional Properties of Skeletal Muscle

Instructor: Dr. Lawrence E. Cornett Biomedical Research Building II 159-2; lcornett@uams.edu; 686-5441 Required Reading: Medical Physiology, Guyton and Hall; 11th Ed., 2006, Chapter 6, pp 72-84 Suggested Reading: Exercise Physiology: Energy, Nutrition and Human Performance, Eds., W.D. McArdle, F.I. Katch and V.L. Katch, Lippincott, Williams and Wilkins, 2001 Objectives: Describe the molecular basis of the length-tension and force-velocity relationships Define a motor unit and its functional characteristics Identify energy sources used to produce ATP for muscle contraction Classify skeletal muscle fiber types and their functional characteristics Lecture Outline: IV. Mechanical properties of skeletal muscle Length-tension relationship Force-velocity relationship V. Motor units The functional unit of a muscle Motor unit recruitment VI. Summation and tetanus Cumulative effect of repeated stimulation of a muscle Tetanuselectrophysiological explanation Treppe or the staircase effect during repetitive stimulation of muscle contraction VII. Energy sources for skeletal muscle contraction Short-term regeneration of ATP Anerobicglycolysis AerobicKrebs Cycle/Oxidative Phosphorylation VIII. Skeletal muscle fiber types Fast twitchGlycolytic (White) 15

Title of Lecture: (MUS-3) The Neuromuscular Junction Instructor: Dr. Lawrence E. Cornett Biomedical Research Building II 159-2; lcornett@uams.edu; 686-5441 Required Reading: Medical Physiology, Guyton and Hall; 11th Ed., 2006, Chapter 7, pp 85-91 Suggested Reading: Diseases of the Skeletal Muscle, Ed., R.L. Wortmann, Lippincott, Williams and Wilkins, 2000 Objectives: Describe the microanatomy of the neuromuscular junction Explain the mechanism of the end-plate potential and its function in generating the muscle action potential Describe the effects and sites of action of drugs and toxins that affect neuromuscular transmission Explain the molecular basis of myasthenia gravis Lecture Outline: I. Anatomy and development Specialized cellular and subcellular structures Trophic factors that influence neuromuscular junction development Biosynthesis and metabolism of the neurotransmitter acetylcholine Synthesisthe key metabolic enzyme is choline-O-acetyltransferase Degradationacetylcholine esterase terminates the action of released acetylcholine Neuromuscular transmission Ionic basis of the resting membrane or end-plate potential Nicotinic acetylcholine receptors transduce the signal initiated by acetylcholine Excitation-contraction coupling Latent period Subcellular structures that carry the action potential to sarcoplasmic reticulum Calcium recycling Miniature end plate potentials Electrophysiological properties Physiological function Pathophysiology Changes in neuromuscular transmission following motor nerve section Toxins and other pharmacological agents that act on the neuromuscular junction Myasthenia gravis 16

II.

III.

IV.

V.

VI.

Title of Lecture:

(MUS-4) Smooth Muscle

Instructor: Dr. Lawrence E. Cornett Biomedical Research Building II 159-2; lcornett@uams.edu; 686-5441 Required Reading: Medical Physiology, Guyton and Hall; 11th Ed., 2006, Chapter 8, pp 92-100 Suggested Reading: Cellular Aspects of Smooth Muscle Function, Eds., C.Y. Kao, M.E. Carsten, Cambridge University Press, 1997 Objectives: Describe the microanatomy of the smooth muscle Distinguish the functional differences between visceral and multi-unit smooth muscle Describe the differences in excitation-contraction coupling between smooth and skeletal muscle Lecture Outline: I. Structure of smooth muscle Cellular characteristics favor response to circulating hormones Individual smooth muscle cells can be functionally linked by gap junctions II. Physiology of smooth muscle Visceral smooth muscle Multi-unit smooth muscle III. Innervation of smooth muscle Diffuse junctions Contact junctions

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CARDIOVASCULAR / EXERCISE PHYSIOLOGY

M. E. SOULSBY, Ph.D. M.C. ALLAN, M.D. R. COKER, Ph.D.

J. WARE, Ph.D.

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Title of Lecture: (CV-1) Introductory Overview Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006, Chapter 9; pp. 103-104 and Chapter 14; pp. 161-167. Suggested Reading: Medical Physiology, Guyton and Hall., 10th Ed., pp. 144-151. Objectives: Appreciate the series arrangement of right and left hearts Appreciate the parallel arrangement of the systemic circulation Appreciate the blood pressures and oxygen content around the heart Become familiar with the hemodynamic equivalent of OHMs Law Learn the relation between blood flow and blood velocity Lecture Outline: I. Heart in the Systems Center A. Pressures B. Volumes C. Oxygen Saturations II. Hemodynamic equivalent of OHMs Law A. Pressure B. Flow C. Resistance III. Pressures Around the Circuits IV. Velocities Around the Circuits

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Title of Lecture: (CV-2) Electrophysiology Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006, Chapter 5; pp. 66-68, and Chapter 9; pp. 103-106; Chapter 10; pp. 116-122. Suggested Reading: Medical Physiology, Guyton and Hall; 10th Ed., pp. 64-64, 107-112.

Objectives: Recognize the varied myocardial action potential forms Know the phases of these action potentials Associate transmembrane ion movements with phases Appreciate the importance of the relationship between myocardial electrical (refractory) and mechanical periods Differentiate firing frequency from conduction velocity Lecture Outline: I. II. III. Myocardial Fibers Gap Junctions and the Functional Syncytium Myocardial Fiber Types A. Fast Response with Phases B. Slow Response with Phases IV. Firing Frequency versus Conduction Velocity

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Title of Lecture: (CV-3) The Cardiac Cycle Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006, Chapter 6; pp. 77-78, Chapter 9; pp. 106 - 111. Suggested Reading: Medical Physiology, Guyton and Hall; 10th Ed., pp. 100 106.

Objective: Appreciate the events of a cardiac cycle from the perspective of the electrocardiogram, the phonocardiogram, pressures, volumes, and events. Become familiar with the cardiac pressure - volume loop. Lecture Outline: I. II. III. Physiologic Parameter Relationships Preload and Afterload The Cardiac Cycle PressureVolume Loop

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Title of Lecture: (CV-4) Ventricular Function And Energetics Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006, Chapters 9; pp. 110 -114. Suggested Reading: Medical Physiology, Guyton and Hall, 10th Ed., pp. 99-106.

Objectives: Appreciate how changes in preload and afterload can influence stroke volume. Learn what is described as the cardiac function relationship Learn the energy requirements of the cardiac function

Lecture Outline: I. II. Use of Starlings Mechanism to develop the Ventricular Function Relationship Myocardial Energetics A. Dynamic Work Energetics B. Static Work Energetics C. The Law of Laplace

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Title of Lecture: (CV-5 & 6) Basic Electrocardiography Instructor: Dr. M. Christian Allan, M.D. Chief Fellow in Cardiology Department of Medicine, UAMS Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006, Chapters 11, 12, 13; pp. 123 -157. Suggested Reading: Medical Physiology, Guyton and Hall, 10th Ed., pp. 114-142.

Objectives: Learn the concept of a vector Appreciate the principles of measurement of the vector from the surface of the organism Appreciate the relationship between vector and lead Appreciate the types and locations of leads. Lecture Outline: I. II. III. Principles of Voltage Recording in a Volume Conductor Recording Standards and Conventions Vector Analysis of ECGs

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Title of Lecture: (CV-7) Cardiac Output Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006, Chapter 20; pp. 232-236; Chapter 20; pp. 243-245. Suggested Reading: Medical Physiology, Guyton and Hall; 10th Ed., pp. 210-221.

Objectives: Recognize what alters the cardiac function relationship Appreciate the equality between cardiac output and venous return Understand the Fick principle for measurement of cardiac output.

Lecture Outline: I. Factors Affecting Stroke Volume A. Preload B. Afterload II. Factors affecting Cardial Output A. Heart Rate B. Myocardial Contractility C. Total Peripheral Resistance III. Measurement of Cardiac Output A. Ficks Principal B. Thermodilution

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Title of Lecture: (CV-8) The Peripheral Vascular System Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006, Chapters 15; pp. 171 -180. Suggested Reading: Medical Physiology, Guyton and Hall 10th Ed., pp. 152-160. Objectives: Appreciate what is meant by compliance Learn the various arterial pressures Learn the changes in flow velocity from central to peripheral arteries and back through veins

Lecture Outline: I. Arterial Wall Compliance A. Hydraulic filter B. Changes with Aging C. Arteries Versus Veins II. Arterial Pressures A. Systolic B. Diastolic C. Pulse D. Mean III. IV. Arterial Pressure Regulation Regional Velocity of Blood Flow

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Title of Lecture: (CV-9) Arterial Blood Pressure Regulation Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 17, pp. 195-203 ; Chapter 18, pp. 204 214; Chapter 19, pp. 216-231. Suggested Reading: Medical Physiology, Guyton and Hall, 10th Ed.; pp. 184-193,195-208. Objectives: Appreciate the factors regulating arterial blood pressure Recognize the temporal relationship of these factors Recognize the relative gains of these factors Lecture Outline: I. Arterial mean pressure regulation A. Chemoreceptors B. Volume Receptors C. Dual Innervation & Negative Feedback D. Endocrine Regulation 1. Renin Angiotensin Aldosterone 2. Atrial Natriuretic Factor II. Integration of Mechanisms A. B. In time Relative gains

26

Title of Lecture: (EX-1) Cardiovascular Responses to Exercise. Instructor: Robert Coker, Ph.D. Center on Aging, CokerRobert@uams.edu 526-5707 Required Reading: Guyton and Hall, Textbook of Medical Physiology, 11th Ed., 2006. Chapter 21, pp. 246-249. Supplemental Reading: Physiology of Sport and Exercise, 2nd Ed., 1999. Eds.: Wilmore and Costill, Human Kinetics. Textbook of Work Physiology, 4th Ed., 2003. Eds.: Astrand, Rodahl, Dahl, and Stromme, Human Kinetics. Human Cardiovascular Control, 1993. Ed.: Rowell, Oxford University Press. Objectives: Describe the Fick principle and the concept of oxygen uptake during rest and exercise Describe the methodologies used to measure oxygen uptake during exercise. Describe the components of oxygen uptake and how they change with exercise training. Describe the influence of posture and gravity on the cardiovascular responses to exercise. Lecture Outline: I. Fick principle of oxygen uptake Submaximal Maximal II. Measurement of the energy cost of exercise Direct Indirect III. Changes in the components of oxygen uptake with exercise Maximal oxygen consumption Oxygen requirement Blood volume Heart rate Stroke volume Cardiac output Arteriovenous difference Comparison: Untrained, Trained, and Mitral Stenosis IV. Postural and gravitational influences on the cardiovascular system Rest Exercise 27

Title of Lecture: (EX-2) Skeletal Muscle Responses and Fuel Use During Exercise. Instructor: Robert Coker, Ph.D. Center on Aging, CokerRobert@uams.edu 526-5707 Required Reading: Guyton and Hall, Textbook of Medical Physiology, 11th Ed., 2006. Chapter 84, pp 1055-1066. Supplemental Reading: Physiology of Sport and Exercise, 2nd Ed., 1999. Eds.: Wilmore and Costill, Human Kinetics. Textbook of Work Physiology, 4th Ed., 2003. Eds.: Astrand, Rodahl, Dahl, and Stromme, Human Kinetics. Objectives: Describe the concept of classification of muscle by fiber type and their associated characteristics. Describe the general adaptations of muscle to increased and decreased activity. Describe the fuel stores in the body available for energy expenditure during exercise. Describe the response to feeding during and between exercise bouts. Lecture Outline: I. Skeletal muscle fiber types Type I Type IIa Type IIx II. Skeletal muscle responses to activity Aerobic training Strength training Disuse or immobilization III. Fuel stores in the body Carbohydrate Fat Protein IV. Fuel use during exercise Effects of feeding during exercise Effects of feeding before and after exercise

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Title of Lecture: (CV-12) Hemodynamics Instructor: Dr. Jerry Ware Biomedical Research Building II, 263-2; jware@uams.edu; 526-6096 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 14, pp. 161 170.

Objectives: Learn factors regulating blood velocity Appreciate the hemodynamic equivalent of OHMs Law Learn the Poiseuille Equation Calculate resistance to flow in parallel and series circuits Learn the significance of murmurs, turbulence and bruits Lecture Outline: I. Factors Affecting Velocity of Blood Flow A. Poiseuille-Hagan Relationship II. Factors Affecting Resistance to Flow A. Series circuits B. Parallel circuits III. Turbulence C. Reynolds Factors D. Murmurs E. Bruits

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Title of Lecture: (CV-13) The Microcirculation Instructor: Dr. Jerry Ware Biomedical Research Building II, 263-2; jware@uams.edu; 526-6096 Required Reading: Medical Physiology, Guyton & Hall, 11th Ed. Chapter 16 pages 181 194 The Microcirculation and the lymphatic system: capillary fluid exchange, interstitial fluid and lymph flow Objectives: 1. Understand the capillary structure critical to function 2. Understand the forces that regulate capillary filtration and reabsorption 3. Understand the role of the lymphatic system in controlling interstitial fluid protein concentration, interstitial fluid volume and the interstitial fluid pressure Lecture Outline: I. Structure of the microcirculation and capillary system II. Exchange of water, nutrients, and other substances between the blood and interstitial fluid III. Fluid filtration across capillaries and the forces involved IV. Lymphatic System

30

Title of Lecture: (CV-14) Blood coagulation, Hemostasis and Thrombosis Instructor: Dr. Jerry Ware Biomedical Research Building II, 263-2; jware@uams.edu; 526-6096 Required Reading: Medical Physiology, Guyton & Hall, 11th Ed. Chapter 36 pages 457 - 468 Hemostasis and Blood Coagulation Objectives: 1. 2. 3. To distinguish between hemostasis and thrombosis To understand the differing contributions of coagulation and plateletmediated hemostasis to the arrest of blood flow To define the temporal sequence of events that constitutes the platelet functional triad (adhesion, activation and aggregation) and the consequences of thrombocytopenia or aspirin ingestion To distinguish between the intrinsic and extrinsic pathways of blood coagulation To understand the importance of vitamin K for blood coagulation and the effects of Coumadin (warfarin) To have a brief understanding of the importance of the following proteins for hemostasis; collagen, von Willebrand factor, integrins, fibrinogen, fibrin, factor V, factor V (Leyden), factor VIII, factor IX, and thrombin To understand the importance of fibrinolysis in blood coagulation, specifically tissue plasminogen activator (TPA), protein C, protein S, antithrombin III and heparin

4. 5. 6.

7.

Lecture Outline: I. II. III. IV. V. The temporal sequence of events leading to hemostasis The role of the platelet in hemostasis and thrombosis The protease-mediated events of blood clotting The fibrinolytic system and its relevance to coagulation The molecular basis of bleeding disorders

31

Title of Lecture: (CV-15) Venous Return Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 20, pp. 238 243. Suggested Reading: Medical Physiology, Guyton and Hall, 10th Ed., pp. 215-220. Objectives: Appreciate the development of the vascular function (venous return) relationship Learn those factors influencing the basic relationship Appreciate factors regulating venous return Lecture Outline I. II. Development of the Vascular Function Relationship Factors Affecting the Relationship A. Vasoconstriction B. Venoconstriction C. Skeletal Muscle Pump D. Respiration

32

Title of Lecture: (CV-16) Cardiovascular Intrinsic and Extrinsic Control Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 17, 18, 19 ; pp. 195 -231. Suggested Reading: Medical Physiology, Guyton and Hall, 10th Ed., pp. 175-182, 253-263. Objectives: Become familiar with local factors regulating vascular control Appreciate characteristics of flow through special tissues Lecture Outline: I. Intrinsic Factors A. Local tissue Metabolism B. Properties of Vascular Muscle C. Humeral Control D. Ionic Control II. Special Circulations A. Kidney B. Brain C. Coronary D. Splanchnic E. Skin F. Lung

33

Title of Lecture: (CV-17) Cardiovascular Pathophysiology Instructor: Dr. Michael E. Soulsby Biomedical 241B-2; MSoulsby@uams.edu; 686-5127 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 20; pp. 234-238; Chapter 22, 23, 24 ; pp. 258 -288. Suggested Reading: Medical Physiology, Guyton and Hall 10th Ed., 203-206, 229-262.

Objectives: Apply what you have learned to pathological states: Heart failure Low pressure shock High pressure hypertension Know the types of: Shock Hypertension Heart failure Lecture Outline: I. Shock A. B. C. D. E. Reversible Irreversible Types (Causes) Hypertension Types

II. Goldblatt Models A. Heart Failure B. Cardiac Function Changes C. Vascular Function Changes D. Combined Functional Changes

34

RESPIRATORY

PHYSIOLOGY

M.L. JENNINGS, Ph.D.

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Title of Lecture: (Resp.-1) Airways; Ventilation; Properties of Gases Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu 296 - 1438 Reading Assignment: Guyton and Hall 11th Edition pp. 475-482; 491-494 Additional Reading: West pp. 1-18; 89-116 Vander pp. 463-467; 475-477 Rhoades and Tanner, pp. 309-311;313-314; 316-318; 319-322 Objectives Understand the functions of conducting airways. Know the definitions of lung volumes and capacities. Understand the meaning of anatomic dead space and its effect on alveolar ventilation. Understand the meaning of partial pressure and gas solubility. Understand the principles governing diffusion of a gas between air and liquid. Lecture Outline Functions of conducting airways: Conduct air in and out of alveoli Warm, humidify inspired air Remove inspired particulates by filtration, impaction, mucociliary escalator Geometry of conducting airways Pulmonary Volumes: Inspiratory Reserve, Tidal, Expiratory Reserve, Residual Pulmonary Capacities (Sums of Volumes): Total Lung Capacity Vital Capacity Functional Residual Capacity Effect of Anatomic Dead Space on Alveolar Ventilation Each inspired breath, new air to alveoli = Tidal Vol. Anat. Dead Space Properties of Gases Gas Law PV = nRT applies to each gas in mixture, e.g., PO2 = nO2RT/V Partial pressure difference drives diffusion between gas and liquid Gas Solubility: Dissolved gas conc. = Partial pressure x solubility coeff.

36

Title of Lecture: (Resp.- 2) Pulmonary Gas Exchange; O2 Transport Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu 296 - 1438 Reading Assignment: Guyton and Hall 11th Edition pp. 492-499; 502-503

Additional Reading: West pp. 21-30 Vander et al. pp. 501-509 Rhoades and Tanner, pp. 309-311; 322-323; 350-355 Objectives Know the relationships among O2 content, partial pressure, total Hb, and saturation. Know the events that take place during diffusion of O2 from air to pulmonary capillary blood. Understand the effect of alveolar ventilation on alveolar gas composition. Know the relationship (alveolar gas equation) among inspired PO2, PACO2, and PAO2. Lecture Outline Diffusion of O2 from air to blood Diffusion of O2 into alv. capillary (equilib. when PO2 in air and blood equal) Diffusion of O2 into RBC and binding to hemoglobin (4 steps) Saturation vs PO2 is sigmoid (positive cooperative) relationship. P50 is PO2 at 50% Saturation; P50 increased by: High temp, low pH, high CO2, high 2,3-bisphosphoglycerate (2,3-DPG) Pulse oximeter measures Saturation (%), not the amount (content) of O2 Oxygen content (ml O2/100 ml blood) depends on Saturation (which depends on PO2 and dissociation curve) Total concentration of Hb (g Hb/100 ml blood) Rate of Diffusion from air to blood: Proportional to surface area of barrier Inversely proportional to thickness of barrier Both PO2 and PCO2 reach equil. with air by the time blood is ~ 1/3 through capillary Steady state: PACO2 = 40; PAO2 = 100 mm Hg (only minor fluctuations breath to breath) (PACO2)x(Alveolar Vent.)/760 = Rate of CO2 Production (ml/min) If Ventilation decreases, PACO2 increases and PAO2 decreases

37

Title of Lecture: (Resp.- 3) Tissue Gas Exchange; CO2 Transport Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu 296 - 1438 Reading Assignment: Guyton and Hall 11th Edition pp. 503-513

Additional Reading: West pp. 71-88 Vander pp. 483-490 Rhoades and Tanner pp. 354-355; 357-358 Objectives Understand the relationship (Fick Principle) among blood flow, arterial O2 content, venous O2 content, and O2 consumption. Understand the effect of the HbO2 dissociation curve on tissue O2 delivery. Know the various forms of CO2 in blood. Know the relationship between CO2 content and PCO2 in arterial and venous blood. Understand the relationship between the Bohr effect and Haldane effect. Lecture Outline Mitochondrial PO2 of only ~ 3-5 mm Hg needed for maximal respiration Blood PO2 must be much higher than 3-5 mm Hg because of diffusion gradient High arterial PO2 does not, by itself, ensure adequate tissue oxygen supply Factors important for tissue oxygenation: O2 consumption and blood flow. Fick : VO2 = O2 Conta-v x Blood flow Arterial PO2 HbO2 Dissociation curve (ability of Hb to release O2 at high PO2) Different tissues have very different local (capillary and venous) PO2 Mixed venous PO2 is about 40 mm Hg; weighted average of all venous return Two safety factors in Dissociation curve: Flat at high PO2 ensures nearly complete loading in lungs Steep portion at PO2 < 40 to ensure more O2 delivery for small drop in PO2 Many conditions cause abnormal O2 content vs. PO2 Anemia Genetic Hb variant with shifted P50 CO poisoning (more in Lecture 9) Blood doping (high Hct.) Cyanide poisoning does not interfere with Hb but instead blocks O2 use

38

Title of Lecture: (Resp.-4) Muscles of Breathing; Pulmonary Pressures Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu 296 - 1438 Reading Assignment: Guyton and Hall 11th Edition pp. 471-475 Additional Reading: West pp. 1-18; 89-116; Vander pp. 467-473 Rhoades and Tanner, pp. 312-316; 326-330 Objectives Identify the muscles of inspiration and expiration. Know the reasons for the collapse tendency of the lung and the significance of pulmonary surfactant. Know the definitions and relationships among pleural, alveolar, and transpulmonary pressures. Understand the effects of muscle paralysis on the maximum inspiratory and expiratory pressures. Lecture Outline Muscles of breathing Inspiration: Diaphragm, External Intercostals, other accessory muscles Expiration: Internal Intercostals, abdominals Collapse tendency of lung: Elastic fibers Surface tension Surface tension normally minimized by presence of pulmonary surfactant Surfactant secreted by type II alveolar epithelial cells, late in gestation Inadequate surfactant causes infant respiratory distress syndrome Mechanical pressures in lung are all expressed relative to atmospheric Pleural pressure Ppl (normally negative, i.e., subatmospheric) Alveolar pressure PA (negative during inspiration, positive during exp.) Transpulmonary Ptp = PA Ppl (pressure that determines lung inflation) Examples: pressures generated by positive and negative pressure ventilators Function of resp. muscles can be tested by measuring max. insp., exp. pressures

39

Title of Lecture: (Resp.- 5) Lung Compliance, Thorax Compliance; Airway Resistance Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu 296 - 1438 Reading Assignment: Guyton and Hall 11th Edition pp. 473; 478-481 Additional Reading: West pp. 1-18; 89-116; Vander pp. 472-475; Rhoades and Tanner pp. 323-326;330-331
Objectives Know the definitions of lung and thorax compliance. Understand the definition of the compliance of the lungs and thorax combined. Know the changes in pleural pressure and alveolar pressure that take place during normal breathing. Know the factors that influence airway resistance. Be able to distinguish between compliance work and resistance work of breathing.

Lecture Outline Lung compliance, CL = Volume/ Ppl; signs are defined to make CL positive At high lung volume, CL is low (lung is stiffer and harder to expand further) Gravity affects degree of inflation of vertical lung: At apex, Ptp is higher, and local compliance is lower, than at base Thorax wall also has compliance (similar to lung compliance at FRC) Compliance of lung/thorax combined: 1/CCombined= 1/CL + 1/CThorax Pneumothorax (air in lung): Lung collapses and thorax springs outward Airway Resistance: Ohms Law, Force = Flow X Resistance Driving force for airflow is Alveolar Pressure, so Airway R = Flow/PA As is true of compliance, airway resistance is always a positive number Laminar vs turbulent Flow Flow is laminar (layered) when velocity is low, as in smaller airways Flow is turbulent at higher flow rates, as in upper airway Main sites of resistance are nose and large to medium bronchi (turbulent flow) If lung volume increase, airway resistance decreases because caliber increases Many factors influence airway resistance via effects on bronchial smooth muscle: Beta adrenergic agonists, nitric oxide cause relaxation, R decreased Cholinergic agonists, histamine, PGF2: contraction, R increased Resistance Work of Breathing: Minimized by slow breathing Compliance Work of Breathing: Minimized by shallow breathing

40

Title of Lecture: (Resp.- 6) Regulation of Breathing Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu 296 - 1438 Reading Assignment: Guyton and Hall 11th Edition pp. 514-523 Additional Reading: West pp. 117-132;136-140 Vander pp. 490-498; 500 Rhoades and Tanner pp. 363-374
Objectives Identify the major centers in brain that are responsible for regulation of breathing. Know the locations and functions of central and peripheral chemoreceptors. Know the integrated ventilatory responses to changes in arterial PO2 and PCO2. Know the main features of Cheyne-Stokes breathing. Know the mechanisms of effects of high altitude on ventilation.

Lecture Outline Respiratory Centers (Brain Stem) Pontine Respiratory Group (Pneumotactic Center, Apneustic Center) Medullary Respiratory Centers (Central Pattern Generator) Ventral Respiratory Group (VRG) Dorsal Respiratory Group (DRG) Central Inspiratory Activity Integrator Input from inspiratory off-switch neurons and chemoreceptors Normal output is inspiratory ramp, followed by termination of insp. Pulmonary receptors: Stretch, Irritant, C-fiber (Juxtacapillary) Central Chemoreceptors Not stimulated by hypoxia Respond to local (interstitial fluid and CSF) H+, which depends on PaCO2 If PaCO2 increases, central chemoreceptors stimulated and VA increases Peripheral chemoreceptors (carotid and aortic bodies) Stimulated by low pH and/or low PaO2, esp. PaO2 below ~80 mm Hg Solely responsible for stimulation of breathing during hypoxemia Response is to PaO2, not O2 content; insensitive to anemia or CO Integrated responses Response to low O2 and high CO2 (low pH) are interdependent If PaO2 is low, response to high CO2 is exaggerated Examples of regulation of breathing under special circumstances Sleep, High altitude, Periodic breathing, Oxygen therapy, Exercise 41

Title of Lecture: (Resp.-7) Pulmonary Blood Flow; Fluid Balance Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu 296 - 1438 Reading Assignment: Guyton and Hall 11th Edition pp. 483-490 Additional Reading: West pp. 31-50 Vander pp. 399-400; 465-466; 500 Rhoades and Tanner, pp. 337-345 Objectives Know the major similarities and differences in blood pressures and vascular resistances between pulmonary and system circulations. Understand the effect of gravity on regional blood flow in the vertical lung. Learn the factors influencing pulmonary vascular resistance. Understand the factors regulating fluid balance in the lung. Learn the major metabolic functions of the pulmonary circulation. Lecture Outline Blood pressures in the pulmonary circuit: much lower P than systemic Pulmonary wedge pressure: Estimates left atrial pressure Pulmonary vascular resistance much lower than systemic If cardiac output increases, pulm. vasc. R decreases, for two reasons Recruitment of new open vessels Distension of previously open vessels Low pressure implies that gravity has major effect on blood distr. in lung Very low flow at apex of upright lung Hypoxic Vasoconstriction: Observed only in the pulmonary circuit Effect of lung volume on pulmonary vascular resistance R Increasing or decreasing lung volume increases total pulm. vasc. R Low volume: R high in larger (extra-alv.) vessels, loss of radial traction High lung volume: R high in small (alveolar) vessels Fluid exchanges in pulmonary capillaries Same principles (Starling forces) apply as in systemic circulation Imbalance between capillary fluid filtration and lymph removal: Edema Edema caused by High capillary Pressure, high capillary permeability, loss of surfactant, severe hypoxia, lymphatic blockage Functions of pulmonary circulation other than gas exchange Filtration to prevent emboli from reaching brain, other organs Metabolic functions: Hormone removal; conversion of angiotensin by ACE 42

Title of Lecture: (Resp.-8) Ventilation/Perfusion Relations (Air/Blood Matching) Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu 296 - 1438 Reading Assignment: Guyton and Hall 11th Edition pp. 499-501 Additional Reading: West pp. 51-69 Vander p. 483 Rhoades and Tanner pp. 346-348; 359-361 Objectives Understand that the ratio of ventilation to perfusion determines local gas composition. Understand the effect of air-blood mismatch on the alveolar to arterial (A-a) PO2 difference. Know the distinction between absolute and physiologic (right to left) shunt. Understand the reason why air-blood mismatch has a larger effect on arterial O2 than on CO2. Know the definition of physiologic dead space. Lecture Outline Normally there is only a small alveolar to arterial (A-a) PO2 gradient In many pulmonary diseases, there is a large A-a PO2 gradient Cause of A-a PO2 gradient is usually regional mismatch between ventilation (VA) and blood flow (perfusion, Q) Local PO2 in lung depends on the ratio of ventilation to perfusion VA/Q high (> 0.8), PO2 > 100; PCO2 < 40 VA/Q low (< 0.8), PO2 < 100; PCO2 >40 Blood from poorly ventilated parts of the lung cause PaO2 to be low (A-a gradient) Extreme example of VA/Q mismatch: absolute right to left shunt: Systemic venous blood mixes with arterial; Venous admixture lowers PaO2 Bronchial circulation normally causes ~ 2% absolute shunt Less extreme: regions with very low (but not zero) VA/Q: physiologic shunt Still causes low PaO2 and A-a PO2 gradient Breathing pure O2 has large effect on PaO2 in physiologic shunt Overventilating rest of lung does not correct low PaO2 caused by local low VA/Q VA/Q mismatch has only minor effect on PaCO2 Normal vertical lung has small VA/Q mismatch because of effect of gravity on Q Physiological dead space (wasted ventil.): Caused by regions with high VA/Q Sometimes (e.g., pulmonary embolism), there will be large physiologic shunt and physiologic dead space present at the same time. 43

Title of Lecture: (Resp.-9) Pulmonary Pathophysiology Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu 296 - 1438 Reading Assignment: Guyton and Hall 11th Edition pp. 524-533 Additional Reading: Rhoades and Tanner pp. 318-319; 331-334; 355-356; 358-361 West pp. 133-149 Vander pp. 498-499 Objectives Understand the conditions that can cause arterial hypoxemia, tissue hypoxia, and elevated tissue CO2. Know the factors that determine PAO2, the A a PO2 difference and the a-v PO2 difference. Understand the nature of carbon monoxide poisoning and the effects of maternal CO on oxygen delivery in the fetal circulation. Understand the use of the forced expiration test and the information derived from this test. Know the potential dangers of O2 therapy. Lecture Outline Resp. muscles, lung and pulmonary circulation normally maintain PaO2, PaCO2 Hypoventilation causes low PAO2 and low PaO2 but does not increase A-a gradient Hypoventilation always causes elevated PACO2 and PaCO2 (hypercapnia) Other causes of hypoxemia, none of which cause major hypercapnia: Diffusion impairment (pure diffusion impairment is unusual) V/Q mismatch (always causes increased A-a PO2 gradient): Absolute shunt Physiologic shunt (underventilated parts of lung, VA/Q very low) Pulmonary embolism (part of lung with VA/Q extremely high) Tissue hypoxia can be present even if PaO2 is normal; low tissue PO2 caused by: Inadequate blood flow relative to metabolic demand (Fick Principle) Left-shifted hemoglobin (need more PO2 drop to release O2 Anemia (if not compensated by increased blood flow) Carbon monoxide poisoning (less total O2 and also left-shift) Forced Expiration Test FEV1 is volume of air expired in 1 sec at max effort Normally FEV1 is about 80% of FVC (forced vital capacity) Forced expiration text characterized by flow-volume loop During forced expiration, dynamic airway collapse limits airflow Hazards of oxygen therapy Removal of ventilatory drive in patients with COPD Absorption atelectasis (collapse) is more rapid when breathing high O2 44

RENAL / ACID BASE PHYSIOLOGY

R. KURTEN, Ph.D. R. SAFIRSTEIN, M.D. P. WIGHT, Ph.D.

45

Title of Lecture: (Renal 1) Body Fluid Compartments Instructor: Richard C. Kurten, Ph.D. Biomed B212C; KurtenRichardC@uams.edu 686-8269 Required Reading: Medical Physiology 11th ed., Guyton and Hall; Chapter 25 Objectives Identify the body water compartments and understand the nature of fluid shifts between them Use the indicator dilution method to measure the size of different body water compartments Calculate fluids shifts after infusion of different solutions Understand clinical conditions that are associated with fluid shifts Understand the nature and sources of edema Lecture Outline Fluid intake and output are balanced at steady state Sources of water Water losses Body fluid compartments Intracellular fluid Extracellulular fluid: interstitial fluid, plasma Measuring body fluid compartment volumes by indicator dilution Fluid shifts between compartments Osmosis and osmotic pressure Concept of osmotic equilibrium Osmolarity of body fluids Isotonic, hypotonic, hypertonic fluids Isosmotic, hyperosmotic, hypo-osmotic fluids Calculating fluid shifts after infusion of: Isotonic saline Hypertonic saline Hypotonic saline

46

Hyponatremia and hypernatremia Hypo-osmotic dehydration (contraction): Diarrhea, Vomitting, Overuse of diuretics, Addisons disease Hypo-osmotic overhydration (expansion): Excessive secretion of argninine vasopressin Hyperosmotic dehydration: diabetes insipidus, excessive sweating Hyperosmotic overhydration: Cushings disease, primary aldosteronism Edema Intracellular edema Extracellular Edema Factors that increase capillary filtration Lymphatic blockage Some conditions that cause edema Heart failure Decreased renal excretion of salt and water Decreased plasma proteins Safety factors that prevent edema Low compliance of the interstitium in the negative pressure range Increased lymph flow Washdown of interstitial fluid protein Edema in potential spaces is called effusion: ascites

47

Title of Lecture: (Renal 2) Renal Anatomy and Function Instructor: Richard C. Kurten, Ph.D. Biomed B212C; KurtenRichardC@uams.edu 686-8269 Required Reading: Medical Physiology 11th ed., Chapter 26 Objectives Know the functions of the kidneys Review gross and microscopic anatomy of the kidneys Understand the micturition process Know the basic renal processes Understand how renal blood flow and glomerular filtration are autoregulated Lecture Outline Functional Renal Anatomy The nephron is the basic unit of renal structure and function Not all nephrons are alike The kidneys have a rich blood supply and innervation Micturition Physiologic anatomy and connections of the bladder Ureters transport of urine from the kidney into the bladder The cystemetrogam plots pressure in the bladder as it fills and shows pressure waves caused by micturition reflexes Abnormalities of micturition Atonic bladder Automatic bladder Uninhibited neurogenic bladder The formation of urine Urine is formed by the combined effect of filtration, reabsorption and secretion Large amounts of solutes are filtered and then reabsorbed for rapid homeostasis

48

The formation of urine: Step 1. Glomerular Filtration Glomerular filtration rate (GFR), filtration fraction and the filtered load The glomerular filtration barrier has three layers Size, shape and electrical charge affect the filterability of macromolecules GFR is determined by Starling forces The pressure profile along a glomerular capillary is unusual Several factors can affect GFR The glomerular ultrafiltration coefficient Glomerular capillary hydrostatic pressure Hydrostatic pressure in Bowmans capsule Glomerular capillary colloid osmotic pressure Renal Blood Flow The kidneys have a high blood flow Blood flow is higher in the renal cortex than in the renal medulla The kidneys autoregulate GFR and blood flow Renal sympathetic nerves and various hormones change renal blood flow Importance of autoregulating GFR in preventing extreme changes in renal excretions Tubuloglomerular feedback and the juxtaglomerular apparatus Macula densa feedback mechanism Myogenic autoregulation of renal blood flow and GFR Effects of a high protein diet and elevated blood glucose on renal blood flow and GFR

49

Title of Lecture: (Renal 3) Tubular Fluid Processing Instructor: Richard C. Kurten, Ph.D. Biomed B212C; KurtenRichardC@uams.edu 686-8269 Required Reading: Medical Physiology 11th ed., Chapter 27, pages 327-339 Objectives Understand the mechanisms for transport across the tubule epithelium Describe the major transport process occurring at each part of the tubule Understand the Starling forces responsible for peritubular capillary reabsorption and how they relate to those responsible for glomerular filtration Understand the mechanisms for pressure diuresis and natriuresis Lecture Outline The formation of urine: Step 2. Tubular processing of the glomerular filtrate Key Concept: Excretion = Filtration Secretion + Reabsorption Tubular reabsorption is selective and quantitatively large Mechanisms for tubular reabsorption Transcellular and paracellular routes Primary active transport Secondary active transport Glucose Amino acids Hydrogen ions The transport maximum describes the rate at which a substance can be transported Graphical description of renal glucose handling (Figure 27-4) Water reabsorption is passively coupled to sodium reabsorption Reabsorption of other solutes by passive diffusion Tubular secretion Transport along the tubule Transport in the Proximal Tubule The proximal convoluted tubule reabsorbs about 65% of the filtered load of sodium and water Proximal tubular fluid is essentially iso-osmotic to plasma Contransporters reabsorb glucose and amino acids The proximal tubule secretes organic acids and bases

50

Tubular transport in the loop of Henle Descending and ascending limbs differ in water permeability The luminal cell membrane of the thick ascending limb contains a 1-Na+, 2-Cl-, 1-K+ co-transporter that is the target for the powerful loop diuretics Tubular transport in the distal nephron The luminal cell membrane of the distal convoluted tubule contains a Na+, Cl- cotransporter Late distal tubule and cortical collecting tubule Composed of intercalated cells and principal cells Principal cells reabsorb sodium and secrete potassium in response to aldosterone and other factors Water reabsorption is regulated by vasopressin to regulate the degree of urinary concentration or dilution Medullary Collecting Ducts Water reabsorption is regulated by vasopressin to regulate the degree of urinary concentration or dilution Capable of secreting hydrogen ions against a large concentration gradient Glomerulotubular balance: Where do the transported fluids and solutes go? Starling forces in the peritubular capillaries and the renal interstitial fluid Regulation of peritubular capillary Starling forces Pressure natriuresis and pressure diuresis mechanisms

51

Title of Lecture: (Renal 4) Controlling and Measuring Renal Function Instructor: Richard C. Kurten, Ph.D. Biomed B212C; KurtenRichardC@uams.edu 686-8269
Required Reading: Medical Physiology 11th ed., Chapter 27, pages 339-347

Objectives Understand the hormones that regulate renal function and their mechanisms of action Understand the clearance concept and how it is used to calculate GFR and renal blood flow Use the clearance concept to determine if a compound undergoes net secretion or reabsorption by the kidney Lecture Outline Hormonal control of tubular reabsorption Angiotensin II is a potent vasoconstrictor that also increases Na+ and water reabsorption Aldosterone increases Na+ reabsorption and increases K+ secretion Vasopressin increase water reabsorption Atrial natriuretic peptide decreases sodium and water reabsorption Parathyroid hormone increases calcium reabsorption and reduces phosphate reabsorption Sympathetic nervous system activation increases sodium reabsorption Using clearance methods to quantify kidney function The clearance rate equation Inulin clearance as an estimate of GFR Creatinine clearance and plasma creatinine concentration as estimates of GFR Applying the Fick principle to PAH handling Using PAH clearance to estimate renal plasma flow Use the hematocrit to convert plasma flow to blood flow Calculating the filtration fraction Calculating tubular reabsorption or secretion rates from clearances Fractional excretion can be used clinically to understand what the kidney is doing.

52

Title of Lecture: (Renal 5) Renal Concentrating and Diluting Mechanisms Instructor: Richard C. Kurten, Ph.D. Biomed B212C; KurtenRichardC@uams.edu 686-8269 Required Reading: Medical Physiology 11th ed., Chapter 28, pages 348-357 Objectives Understand how the kidney produces a dilute urine Know the relation between cortico-medullary osmotic gradient in the interstitium and concentrating ability Understand the concept of active countercurrent multiplication Know how NaCl reabsorption in the thick ascending limb of the loop of Henle relates to formation of concentrated and dilute urine Know how and where arginine vasopressin (AVP) acts on the nephron Know what is meant by passive countercurrent exchange in the vasa recta Know the role of urea in the formation of concentrated urine Understand the concepts of osmolar and free-water clearance Lecture Outline Renal mechanism for excreting a dilute urine Rapid diuresis follows the ingestion of a large volume of water Tubular fluid remains iso-osmotic in the proximal tubule (~300 mOsm/L Tubular fluid becomes dilute in the ascending loop of Henle (~100 mOsm/L) In the absence of vasopressin, tubular fluid is further diluted in the distal and collecting tubules (~50 mOsm/L) Renal mechanism for concentrating urine Obligatory urine volume Requirements for excreting a concentrated urine: vasopressin and hyperosmotic medullary interstitium The countercurrent multiplier mechanism produces the hyperosmotic medullary interstitium countercurrent flow in the loop of Henle differential permeability of the loop of Henle and collecting tubules/ducts to water, NaCl and urea critical role of the 1 Na+- 2 Cl--1 K+co-transporter

53

Relative contribution of the distal tubule and the collecting ducts Urea contributes significantly (40-50%) to the interstitial hyperosmolality Countercurrent arrangement of the vas recta preserves hypertonicity Mechanism of action for vasopressin Using clearance to quantify urine concentration and dilution Osmolar clearance Free water clearance

54

Title of Lecture: (Renal 6) Regulation of extracellular fluid osmolarity and Na+ concentration Instructor: Richard C. Kurten, Ph.D. Biomed B212C; KurtenRichardC@uams.edu 686-8269 Required Reading: Medical Physiology 11th ed., Chapter 28, pages 357-364 Objectives Know how changes in plasma osmolality influence the release of vasopressin Know how changes in blood volume or blood pressure influences vasopressin release Know some stimuli that arouse thirst Know what is meant by diabetes insipidus and how to distinguish between central and nephrogenic forms Lecture Outline Extracellular fluid sodium concentration and osmolarity are tightly linked Relationship between sodium concentration and extracellular fluid osmolarity At steady-state, water input and output are equal Arginine vasopressin is critical in the control of renal water output and plasma osmolality Factors affecting AVP release Osmoreceptor-ADH feedback mechanism Cardiovascular reflexes Other stimuli Interaction between stimuli affecting AVP release Habit and thirst govern water intake CNS centers for thirst Stimuli for thirst Osmolar threshold for thirst Integration of the osmoreceptor-ADH and thirst mechanisms in controlling ECF osmolarity Disorders of urinary concentrating ability Central diabetes insipidus: inappropriate vasopressin secretion Nephrogenic diabetes insipidus: Defects in the countercurrent mechanism Inability of the kidney to respond to vasopressin Administration of vasopressin can be used to distinguish between central and nephrogenic diabetes insipidus

55

Title of Lecture: (Renal 7) Electrolyte Balance Instructor: Robert Safirstein, M.D. VA6A116; SafirsteinRobertL@uams.edu 257-5866 Required Reading: Medical Physiology 11th ed., Chapter 29 Objectives Understand how the kidneys handle potassium and factors that influence potassium excretion Understand how the kidney regulates plasma [Mg++] Understand how PTH regulation of TMP04 regulates plasma phosphate levels Know the tubular mechanisms for reabsorption of Na+ and the relative amounts reabsorbed by each nephron segment Know the concept of glomerulotubular balance as it pertains to Na+ Know the factors that influence Na+ excretion Know the mechanisms that detect and respond changes in volumes of ECF and blood. Know what stimuli causes release of renin and how renin is related to sodium balance Know what stimulates secretion of atrial natriuretic peptide (ANP) and possible actions of ANP Know how GFR, Starling forces and endocrine mechanisms are integrated to adjust renal Na+ excretion Lecture Outline Regulation of potassium excretion and extracellular K+ concentration Special problems related to the predominantly (98%) intracellular distribution of K+ Factors regulation the internal distribution of K+ Insulin Aldosterone -adrenergic stimulation acid-base abnormalities cell lysis, strenuous exercise increased extracellular fluid osmolarity Potassium secretion by principal cells Cellular mechanisms Na+-K+-ATPase Luminal K+ channel (ROMK) Factors regulating K+ secretion Stimulated by increased extracellular fluid K+ Stimulated by aldosterone Stimulated by increases in tubular flow 56

Reduced by acidosis Potassium reabsorption by intercalated cells Changes in Na+ excretion do not change K+ excretion Regulation of renal calcium excretion and extracellular Ca++ concentration Regulation of renal phosphate excretion Overflow mechanism PTH suppresses Tm for phosphate to enhance excretion Regulation of renal magnesium excretion and extracellular Mg++ concentration Integration of mechanism for salt and water balance Two major sensors Mean arterial pressure Retain sodium when pressure is low. Excrete sodium when pressure is high. Major effector is Angiotensin II Plasma osmolality Retain/drink water when osmolality is high. Excrete water when osmolality is low. Major effector is vasopressin Sodium excretion is controlled by altering GFR or tubular sodium reabsorption rates via a hierarchy of interrelated mechanisms pressure diuresis and natriuresis glomerulotubular balance tubuloglomerular feedback sympathetic nervous system control baroreceptor and lowpressure stretch receptor reflexes angiotensin II amplifies the pressure natriuresis mechanism: elevated angiotensin II makes blood pressure very sensitive to changes in sodium intake angiotensin II blockade shifts pressure natriuresis to lower blood pressure levels aldosterone stimulates Na+ reabsorption in cortical collecting ducts aldosterone escape adrenal insufficiency in Addisons disease leads to increased excretion of salt and water and a tendency toward volume depletion atrial natriuretic peptide released by stretch of the atria acts to increase GFR slightly and to suppress collecting duct Na+ reabsorption Integrated response to increased Na+ intake Activation of low pressure receptor reflexes (first few hours) small increases in arterial pressure result in pressure natriuresis suppression of angiotensin II formation stimulation of natriuretic systems 57

Title of Lecture: (Renal 8) Diuretics and Renal Related Diseases and Syndromes

Instructor: Robert Safirstein, M.D. VA6A116; SafirsteinRobertL@uams.edu 257-5866

Required Reading: Medical Physiology 11th ed., Chapter 31

Objectives Understand the mechanisms of action of diuretics Be able to distinguish causes and consequences of acute and chronic renal failure Understand the role of the renin in clinical hypertension Recognize the condition, molecular basis and clinical features arising from inherited defects in kidney tubule epithelial cells Lecture Outline Diuretics increase urinary output and are used to reduce extracellular fluid volume osmotic diuretics: alter driving forces for bulk flow of water loop diuretics: block the 1 Na+- 2 Cl--1 K+co-transporter thiazide diuretics: block a Na+-Cl-co-transporter in the distal tubule carbonic anhydrase inhibitors: proximal tubule aldosterone antagonists (K+-sparring): principal cell collecting tubule Na+ channel blockers (K+-sparring) Acute renal failure Prerenal acute renal failure Intrarenal acute renal failure Postrenal acute renal failure Physiological effects of acute renal failure Chronic renal failure Viscous circle leading to end-stage renal disease The most common causes of end-stage renal disease are Diabetes mellitus and hypertension Injury to the vasculature Injury to the glomeruli Injury to the interstitium Nephrotic Syndrome

58

Effects of renal failure on the body fluids Hypertension and renal disease Renal lesions that reduce the ability of the kidneys to excrete sodium and water promote hypertension Goldblatt hypertension Hypertension caused by patchy renal damage and renin secretion Hypertension caused by excessive Na+ reabsorption: Liddles syndrome Inherited Defects in Tubular Epithelium Condition renal glucosuria cystinuria Bartters syndrome Gitlemans syndrome Liddles syndrome Molecular Defect Na+-dependent glucose cotransporter amino acid cotransporter Na-K-2Cl cotransporter, K channel or Cl channel in TAL thiazide sensitive Na-Cl cotransporter in DCT increased open time and number of ENAC decreased activity of ENAC intercalated cell Cl/HCO3- exchanger, H+ ATPase vasopressin-2 (V2) receptor or aquaporin-2 Clinical Features glucosuria, polydipsia kidney stone disease salt wasting, hypokalemic metabolic alkalosis salt wasting, hypokalemic metabolic alkalosis, hypocalciuria hypertension, hypokalemic metabolic alkalosis salt wasting, hyperkalemic metabolic acidosis metabolic acidosis, osteomalacia polyuria, polydipsia

pseudohypoaldosteronism type I distal renal tubular acidosis type I nephrogenic diabetes insipidus

59

Title of Lecture: (AB-1) Introduction To Acid-Base Balance Instructor: Dr. P. Wight Biomedical Research Center B212B; pwight@uams.eu 686-5366 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. (Acid-Base lectures I-III) Chapter 30, pp. 383 - 400 Suggested: Understanding Acid-Base, Benjamin Abelow, 1st Ed. (1998) Objectives: Identify the normal range of pH values in the bodys fluids compartments, and the upper and lower limits of pH compatible with life Understand the difference between volatile and nonvolatile acids, the average daily amount of acid produced via ingestion and cellular metabolism, and the mechanisms by which the body rids itself of this daily acid load Understand the role of buffers in regulating (maintaining) pH and their relative importance (amounts) in the different fluid compartments Understand the concepts of buffer strength, buffer capacity, and the isohydric principle Lecture Outline: I. II. III. IV. V. VI. Overview of Acid-Base Balance Definition of Acid and Base Henderson-Hasselbalch equation Buffering Power Isohydric Principle Body Buffers

60

Title of Lecture: (AB-2) Regulation Of Acid-Base Balance Instructor: Dr. P. Wight Biomedical Research Center B212B; pwight@uams.eu 686-5366 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. pp. (Acid-Base lectures I-III) Chapter 30, pp. 383 - 400 Objectives: Know the 3 lines of defense to minimize changes in plasma pH Know the 4 primary disturbances in acid-base balance Know what is meant by the term compensation Know the role of the respiratory system in regulating [H+] Understand the tubular mechanisms for reabsorption of filtered HCO3- and the factors that influence it Lecture Outline: I. II. III. IV. V. VI. VII. Introduction to Body Buffering Chemical Buffering (Bicarbonate Buffer System) Regulation of Arterial PCO2 Primary Respiratory Acid-Base Disturbances & Compensation Metabolic Production of Acids and Bases Bicarbonate Reabsorption & Factors That Influence Bicarbonate Reabsorption

61

Title of Lecture: (AB-3) Renal Regulation Of Hydrogen Ion Balance Instructor: Dr. P. Wight Biomedical Research Center B212B; pwight@uams.eu 686-5366

Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. (Acid-Base lectures I-III) Chapter 30, pp. 383 - 400 Objectives: Understand the concept of titratable acid Understand the role of ammonium secretion in the excretion of H+ Know how to analyze acid-base disturbances Understand how tubular H+ secretion is related to reabsorption of filtered bicarbonate and the formation of new bicarbonate which is returned to the body Lecture Outline: I. II. III. Endogenous Acid Production (EAP) and Renal H+ Excretion Titratable Acid (T.A.) Acid Excretion/Bicarbonate Regeneration T.A. Excretion Ammonium Excretion IV. V. VI. Metabolic Disturbances Anion Gap Analysis of Acid-Base Disorders

62

GASTROINTESTINAL PHYSIOLOGY

J.N. PASLEY, Ph.D.

63

Title of lecture: (GI-1) Introduction of Gastrointestinal Physiology Instructor: Dr. James N. Pasley Shorey 6/S12; PasleyJamesN@uams.edu; 686-5128 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 62; pp.777-781 ; Chapter 71; pp. 867-872, Suggested Reading: Gastrointestinal Physiology, L.R. Johnson, 6th Ed. Mosby, 2001 Objectives: Describe the overall role of the gastrointestinal tract with respect to whole body caloric needs. Describe the major constituents and role of splanchnic circulation. Include major regulatory mechanisms. Describe the importance of mind/body factors in GI tract health and disease. Give examples. Describe CNS and peripheral (gut and metabolic) factors that influence food intake. Lecture outline: I. Function of the GI tract

General tasks Splanchnic Circulation

II. The GI tract in health and disease III. Control of food intake

Appetite and hunger Hypothalamic control factors Feeding center Satiety center Peripheral control factors

64

Title of Lecture: (GI-2) Mastication and Swallowing Instructor: Dr. James N. Pasley Shorey 6/S12; PasleyJamesN@uams.edu; 686-5128 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 62; pp. 771-777; Chapter 63; pp. 781-784; Chapter 64; pp. 791-795 Suggested Reading: Gastrointestinal Physiology, L.R. Johnson, 6th Ed. Mosby, 2001 Objectives: Contrast sympathetic and parasympathetic modulation of the entire nervous system and the effect on organs of the GI tract Contrast the plasma and saliva concentrations of Na+, Cl- and HCO3- at low and high secretion rates State substrates and digestion products of salivary amylase Identify the function of salivary mucus State the components of saliva that are important in oral hygiene Discuss stimuli and control salivary secretion Describe the pressure changes that occur in the esophagus as the bolus moves from the pharynx to the stomach Contrast primary and secondary peristalsis in the esophagus Contrast the patterns of external and internal innervation of the upper, middle, and lower esophagus Lecture outline: I. Salivary secretion

Anatomical considerations Secretory composition Organic constituents Functions of salivary secretion Regulation of secretion

65

II.

Musculature of the Digestive Tract

Structure and function Motility Patterns Role of Calcium

III. IV. V.

Enteric Nervous System Integration and control of motor activity Swallowing

Oropharyngeal Phase Esophageal Phase Lower Esophageal Sphincter (LES

66

Title of Lecture: (GI-3) Swallowing Abnormalities and Gastric Motility Instructor: Dr. James N. Pasley Shorey 6/S12; PasleyJamesN@uams.edu; 686-5128 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 63; pp. 784-786; Chapter 66; pp. 819 Suggested reading: Gastrointestinal Physiology, L.R. Johnson, 6th Ed. Mosby, 2001 Objectives: Contrast LES pressure; innervation and motility defects between reflux (GERD) and achalasia Describe the storage, digestive and motility roles of the stomach Define receptive relaxation of the stomach and state mechanisms and consequence of loss Describe the origin and form of electrical activity and progression of peristaltic waves across the stomach Describe the role of peristaltic waves in mixing and propulsion of contents and how the frequency is changed by volume Predict the effect of meal content (osmolarity, fat, acid, etc.) particle size, and volume on the rate of gastric emptying Know one cause of delayed gastric emptying and increased gastric emptying Lecture outline: I. Esophageal Motor Dysfunction

GERD Achalasia

II. Gastric Motility

Anatomic Considerations Reservoir Function (Receptive Relaxation)

Pacemaker Activity

67

Basic Electrical Rhythm (BER)

Contractile activities

Leading Contraction Trailing Contraction

Stomach emptying (Fed Pattern)

Regulation of Emptying

Kind of Meal Duodenal Factors

Fasted pattern

Migrating Motor Complex (MMC)

Pathophysiology

Delayed Gastric Emptying Rapid Gastric Emptying

68

Title of Lecture: (GI-4) Gastric Secretion and Small Intestinal Motility Instructor: Dr. James N. Pasley Shorey 6/S12; PasleyJamesN@uams.edu; 686-5128 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 63; pp. 786-788 ; Chapter 64; pp. 795-799 ; Chapter 66 ; pp. 819-822 Suggested reading: Gastrointestinal Physiology, L.R. Johnson, 6th Ed., Mosby, 2001. Objectives: Contrast the Na+, K+, and Cl- concentrations of gastric secretion with that of plasma at low and high secretion rates Know how an alkaline tide is produced following a meal Know the role of the stomach in preventing pernicious anemia Describe the modulation of gastric acid secretion by vagal stimulation, gastrin, histamine, and somatostatin Identify the stimuli that increase and decrease gastrin release Contrast intestinal motility patterns during the absorptive phase (segmentation) with that of the interdigestive phase (MMC) Know the motility changes and CNS areas associated with vomiting Lecture outline: I. Gastric secretion

Composition of Gastric Secretion Two Functional Mucosal Regions Cell Types The Two Component Theory of Secretion Functions of Gastric Secretions Mechanisms of Control 3 Phases of Secretion 69

Secretagogues Inhibitors of Secretion Gastric mucosal barrier

Hypersecretion of acid Hyposecretion of acid

Pathophysiology

Peptic Ulcer Disease

II. Motility of the small intestine

Overview Contractile behavior Fed Pattern Segmentation Peristalsis Power Propulsion Migrating motor complex (MMC) Fasting Patterns Motor dysfunction

Physiologic Ileus Vomiting

70

Title of Lecture: (GI-5) Pancreatic, Biliary and Intestinal Secretion Instructor: Dr. James N. Pasley Shorey 6/S12; PasleyJamesN@uams.edu; 686-5128 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 64; pp. 799-806; Chapter 66; pp. 821-824 Suggested Reading: Gastrointestinal Physiology, L.R. Johnson, 6th Ed., Mosby, 2001 Objectives: Understand pancreatic secretion Learn secretions of the exocrine pancreas Know factors regulating pancreatic secretion Understand biliary tract secretion Learn the enterohepatic circulation of bile acids Know factors regulating biliary tract secretion Understand intestinal secretion Understand integration of duodenal cluster unit responses Lecture Outline I. II. III. V. VI. A. B. C. Introduction and Overview Exocrine Pancreatic Fluid Secretion Enzyme Secretion - acinar cell secretion Control of Pancreatic Secretion Biliary Tract Secretion Components Primary & Secondary Bile Acids Regulation of secretion 71

D. E. F. G. VI.

Enterohepatic Circulation Gallbladder Function Regulation of Secretion Gallstones

Intestinal Secretion

Types of Secretion Control Pathophysiology

72

Title of Lecture: (GI-6) Digestion and Absorption of Macronutrients Instructor: Dr. James N. Pasley Shorey 6/S12; PasleyJamesN@uams.edu; 686-5128 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 65; pp. 808-814 Suggested Reading: Gastrointestinal Physiology, L.R. Johnson, 6th Ed., Mosby, 2001 Objectives: Know the role of specific secretions in the processes of digestion and absorption Know the sites at which digestion of macronutrients occurs Understand general conditions which may result in macronutrient maldigestion and/or malabsorption Lecture outline: I. II. III. The Absorptive Area of the Small Intestine Mechanisms of Absorption Digestion and absorption of carbohydrate

Digestion in Different Parts of GI Tract Carbohydrate Transport Mechanisms Pathophysiology of Carbohydrate Absorption

IV.

Digestion and Absorption of Protein

Source of Protein in the Diet Digestion 73

Transport Pathophysiology of Protein Absorption

V.

Digestion and Absorption of Fats

Lipid Digestion Role of Bile Salts Enterocyte resynthesis Chylomicron Secretion Pathophysiology of Lipid Absorption

74

Title of Lecture: (GI-7): Water, Electrolyte, Vitamin and Mineral Absorption Instructor: Dr. James N. Pasley Shorey 6/S12; PasleyJamesN@uams.edu; 686-5128 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 65; pp. 814-817 ; Chapter 71; pp. 875-879 Suggested Reading: Gastrointestinal Physiology, L.R. Johnson, 6th Ed., Mosby, 2001 Objectives: Know the sites at which absorption of water, electrolytes and minerals occur Understand the mechanisms mediating absorption of water, electrolytes, minerals and water-soluble vitamins Understand the basic mechanisms governing the absorption of calcium and iron in the GI tract Lecture outline: I. Absorption of Water and Electrolytes

Absorption of water from small intestine Sodium transport Chloride and bicarbonate Potassium transport Pathophysiological alterations of salt and water absorption Mechanism of H20 absorption

II. Fat Soluble Vitamins (A, D, E, K) III. Water soluble vitamins (C, B1, B2, B6, B12, Niacin, Biotin, Folic Acid) IV. Calcium Absorption V. Iron Absorption

75

Title of Lecture: (GI-8) Large Bowel Motility, Gas in the Gut and Dietary Fiber Instructor: Dr. James N. Pasley Shorey 6/S12; PasleyJamesN@uams.edu; 686-5128 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 63; pp 788-791; Chapter 66; pp. 822-823, 825 Suggested Reading: Gastrointestinal Physiology, 6th Ed., L.R. Johnson, Mosby, 2001

Objectives: Compare colonic motility with small intestine motility including slow wave differences Contrast haustral shuttling with mass movements Describe the sequence of events occurring during the defecation reflex including those voluntary and involuntary control Understand the basic pathophysiology of constipation, diarrhea Discuss dietary fiber and its effects on the gastrointestinal tract Compare and contrast Hirschsprungs Disease with Achalasia Know sources of gas in the gut Lecture Outline: I. Motility of colon
Anatomical considerations Functional differences between right transverse and left colon Physiology of the rectosigmoid Region

II. Motility of colon III. Transit Time

76

 Anal continence

IV.

Pathophysiologic Disorders
Constipation Diarrhea Aganglionosis

V. VI.

Role of dietary fiber in gastrointestinal health Gas in the gut

77

ENDOCRINOLOGY

H.H.Conway, Ph.D. D. Gaddy, Ph.D.

78

Title of Lecture: (Endo-1) Temperature Regulation Instructor: Dr. Howard H. Conaway Biomed 241C-2; conawayhowardh@uams.edu ; 686-5125 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed. 2006, Chapter 73 pp. 889-901. References: Review of Medical Physiology, Ganong, 22nd Ed., 2005. pp. 251-255, Objectives: Review normal body temperature Describe heat production, heat loss and temperature regulating mechanisms Know physiological mechanisms activated by increased and decreased body temperatures Understand the theory of fever production Outline body temperatures under different conditions Lecture Outline: I. II III. IV V. VI VII. VIII. IX. X. XI. Normal body temperature Feedback mechanisms How the body produces heat Heat loss Temperature regulation mechanisms Set point Mechanisms activated by increased body temperature Mechanisms activated by decreased body temperature Fever Body temperatures under different conditions Cold-induced vasodilation

79

Title of Lecture: (Endo-2) Energy Balance and Obesity Instructor: Dr. Howard H. Conaway Biomed 241C-2; conawayhowardh@uams.edu ; 686-5125 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed. 2006, Chapter 71 pp. 871-874, Chapter 72 pp. 884-888, References: Science, Obesity Declared a Disease, Vol. 227, pp. 1019-1020, 1985. Science, Why Do People Get Fat? Vol. 227, pp. 1327-1328, 1985. Science, Obese Children: A Growing Problem, Vol. 232, pp. 20-22, 1986. Science, Regulation of Body Weight, Vol. 280, pp. 1363-1387, 1998. Objectives: Review caloric consumption, energy equivalents of foodstuffs and the respiratory quotient Describe basal metabolic rate (BMR) Define normal weight and obesity Know risks and health problems associated with obesity Indicate theories of the causes of obesity Introduce the hyperinsulinemia of obesity Review treatments for obesity Lecture Outline: I. II. III. IV. V. VI. VII. III. IX. X. I. Energy expenditure Energy equivalents of foodstuffs Basal Metabolic Rate (BMR) Normal weight Obesity Risk factors and health problems associated with obesity Theories of the cause(s) of obesity Hyperinsulinemia Social consequences of obesity Treatments for obesity Energy expenditure: 80

Title of Lecture: (Endo-3) Neuroendocrine Hormones, Pituitary Instructor: Dr. Howard H. Conaway Biomed 241C-2; conawayhowardh@uams.edu ; 686-5125 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed. 2006, Chapter 75 pp. 918-930. References: Review of Medical Physiology, Ganong, 22nd Ed. 2005, pp. 242-252, Objectives: Review pituitary anatomy and blood supply Know posterior pituitary hormones and functions Understand hypothalamic releasing and inhibiting hormones Outline anterior pituitary hormones Describe secretion, function and feedback control of growth hormone Introduce secretion, function and feedback control of prolactin Lecture Outline: I. II. III. IV. V. VI. VII. VIII. IX. The pituitary Pituitary anatomy The posterior pituitary and hormones The pituitary blood supply and its functional significance Hypothalamic releasing and inhibitory hormones Pre proopiomelanocortin Anterior pituitary cells and hormones Growth hormone The pituitary

81

Title of Lecture: (Endo-4) Endocrine Control of Calcium Metabolism Instructor: Dr. Howard H. Conaway Biomed 241C-2; conawayhowardh@uams.edu ; 686-5125 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed. 2006, Chapter 79 pp. 978-995. References: Review of Medical Physiology, Ganong, 22nd Ed., 2005 pp. 382-395. Principles of Physiology, Berne and Levy, 3rd Ed. 2000, pp. 519-532 Objectives: Understand calcium balance Review intestinal absorption of calcium Describe plasma calcium fractions Give the different types of bone List the cells of bone and their functions Know parathyroid hormone (PTH) actions Outline calcitriol (1,25(OH)2-vitamin D3) metabolism and functions Define regulatory controls of plasma Ca++ Explain the relationship of calcitonin to calcium metabolism Introduce abnormalities involving PTH and plasma Ca++ Lecture outline: I. II. III. Calcium metabolism Hormonal regulation of calcium metabolism Abnormalities involving PTH and serum Ca++

82

Title of Lecture: (Endo-5) Endocrine Pancreas I Instructor: Dr. Howard H. Conaway Biomed 241C-2; conawayhowardh@uams.edu ; 686-5125 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed. 2006. Chapter 78 pp. 961-977 References: Principles of Physiology, Berne an Levy, 3rd Ed., pp. 508-518, 2000. Review of Medical Physiology, Ganong, 22nd Ed. 2005, pp. 333-355. Objectives: Know endocrine hormones of the pancreas Introduce diabetes mellitus Describe the insulin molecule Outline insulin production and release Know factors influencing insulin release Discuss possible mechanisms of insulin action Lecture outline: I. II. III. IV. V. VI. Endocrine hormones of the pancreas Diabetes mellitus The human insulin molecule Insulin production and release Factors influencing insulin release Insulin action

83

Title of Lecture: (Endo-6) Endocrine Pancreas II Instructor: Dr. Howard H. Conaway Biomed 241C-2; conawayhowardh@uams.edu ; 686-5125 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed. 2006, Chapter 78 pp. 961-977. References: Review of Medical Physiology, Ganong, 22nd Ed., pp. 333-355, 2005. Principles of Physiology, Berne and Levy, 3rd Ed., pp. 508-518, 2000. Objectives: Know actions of insulin Understand glucagon secretion and function Outline insulin, glucagon and somatostatin interactions Introduce type 1 and type 2 diabetes Lecture outline: I. II. III. IV. V. Insulin action Specific actions of insulin Glucagon Relationships between insulin, somatostatin and glucagon secretion Diabetes mellitus

84

Title of Lecture: (Endo-7) The Thyroid Gland Instructor: Dr. Howard H. Conaway Biomed 241C-2; conawayhowardh@uams.edu ; 686-5125 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed. 2006, Chapter 76 pp. 931-943. References: Review of Medical Physiology, Ganong, 22nd Ed., pp. 317-332, 2005. Principles of Physiology, Berne and Levy, 3rd Ed., pp. 548-558, 2000. Objectives: Compare inactive and active thyroid follicles Give structures of thyroxine, T3 and rT3 Understand thyroid hormone biosynthesis Outline feedback of the thyroid hormones and iodide involvement in thyroid function Introduce pharmacological agents altering thyroid function Show the relationships between production and plasma levels of the thyroid hormones Define the importance of the thyroid hormone binding proteins in plasma Know actions of the thyroid hormones Lecture outline: I. II. III. IV. V. VI. VII. VIII. IX. General information Formation of the thyroid hormones Iodide uptake and thyroid hormone synthesis Feedback and thyroid function Iodide involvement in thyroid hormone homeostasis Pharmacological intervention Quantitative aspects of the thyroid hormones Thyroid hormone binding proteins Actions of the thyroid hormones

85

Title of Lecture: (Endo-8) Adrenal Gland I Instructor: Dr. Howard H. Conaway Biomed 241C-2; conawayhowardh@uams.edu ; 686-5125 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed. 2006, Chapter 77 pp. 944-960. References: Principles of Physiology, Berne & Levy, 3rd Ed., pp. 559-571, 2000. Review of Medical Physiology, Ganong, 22nd Ed., pp. 356-381, 2005. Objectives: Review anatomy of the adrenal gland Give the hormones secreted by the adrenal gland Introduce steroid hormone structure Know biosynthesis of mineralocorticoids, glucocorticoids and adrenal androgens Show consequences of adrenal enzyme deficiencies Understand feedback control of steroid hormones produced by the adrenal gland Know biosynthesis and release of adrenal medulla catecholamines Lecture outline: I. II. III. IV. V. The adrenal glands Steroid hormone structure Adrenal steroid hormone biosynthesis Control of adrenal cortical secretions Catecholamine hormone synthesis and release

86

Title of Lecture: (Endo-9) Adrenal Gland II Instructor: Dr. Howard H. Conaway Biomed 241C-2; conawayhowardh@uams.edu ; 686-5125 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed. 2006, Chapter 77 pp. 944-960. References: Review of Medical Physiology, Ganong, 22nd Ed., pp. 356-381, 2005. Principles of Physiology, Berne and Levy, 3rd Ed., pp. 559-578, 2000. Objectives: Outline adrenocortical hormone transport and excretion Define permissive, direct and pharmacological actions of the glucocorticoids Show chemical modifications of the glucocorticoid molecule Understand feedback recovery of the glucocorticoid axis Describe glucocorticoid and mineralocorticoid receptors Review the relationship of the adrenal medulla to the autonomic nervous system Give mechanisms of action of the catecholamines Introduce pheochromocytoma Compare physiological responses of epinephrine and norepinephrine Know metabolic actions of epinephrine Emphasize interactions of the major metabolic hormones Reference actions mediated by adrenergic receptors Lecture outline: I. II. III. IV. V. VI. VII. VIII. Adrenocortical hormone transport and excretion Glucocorticoid actions Pharmacology of glucocorticoids Steroid-receptor interactions The adrenal medulla Chromaffin tumors - pheochromocytoma Metabolic actions of epinephrine Actions mediated by adrenergic receptors 87

Title of Lecture: (Endo-10) Male Reproductive Physiology Instructor: Dr. Dana Gaddy Biomed 2-Rm 210-2; GaddyDana@uams.edu 686-5918

Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 80, pp. 996-1009 Suggesting reading: Vander, Sherman and Lucianos Human Physiology, 9th Edition, by Widmaier, Raff and Strang, 2004 Chapter 17, pp. 671-694 Objectives: Describe the differentiation of the male reproductive tract including the role of in utero androgen production and Mllerian Inhibitory Factor List testosterone induced changes that occur at puberty Diagram cellular actions of testosterone Describe the hormonal control of the testis Describe the hormonal control of spermatogenesis Know the role of male accessory glands in reproduction Contrast hypergonadotropic and hypogonadotrophic hypogonadism in the male Lecture Outline: I. Testis

Development

Cryptorchidism

Sertoli cell

Leydig cell 88

II. Testis

III. Male sexual response

IV. Testosterone secretion and effects

Secretion Metabolism Cellular action Androgenic effects Anabolic effects Testosterone absence

Before Puberty

After Puberty

V. Hypothalamic/pituitary regulation

Pulsatile GNRH Secretion

Feedback Regulation

89

VI. Fertility Control

VII. Pathophysiology

Hypogonadotropic Hypogonadism

Kallmanns Syndrome

Panhypopituitarism

Hypergonadotropic hypogonadism

Klinefelters syndrome

Testicular feminization (AIS)

5 - reductase deficiency

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Title of Lecture: (Endo-11) Female Reproductive Physiology Instructor: Dr. Dana Gaddy Biomed 2-Rm 210-2; GaddyDana@uams.edu 686-5918

Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 81, pp. 1011-1026 Suggested reading: Vander, Sherman and Lucianos Human Physiology, 9th Edition, by Widmaier, Raff and Strang, 2004 Chapter 17, pp. 658-671 Objectives: Pulses of hypothalamic GnRH regulate the secretion of LH and FSH, which enhance follicular development, steroid genesis, ovulation, and formation of the corpus luteum. LH and FSH, in coordination with ovarian theca and granulosa cells, regulate the secretion of follicular estradiol. Ovulation occurs as the result of a positive feedback of follicular estradiol on the hypothalamic-pituitary axis that induces LH and FSH surges. Follicular development occurs in distinct steps: primordial, primary, secondary, tertiary, and Graafian (preovulatory) follicle stages. Follicular rupture (ovulation) requires the coordination of appropriately timed LH and FSH surges that induce inflammatory reactions in the graafian follicle, leading to dissolution at midcycle of the follicular wall by several ovarian enzymes. Follicular atresia results from the withdrawal of gonadotropin support. The formation of a functional corpus luteum requires the presence of an LH surge, adequate numbers of LH receptors, sufficient granulosa cells, and significant progesterone secretion. The uterine cycle is regulated by estradiol and progesterone, such that estradiol induces proliferation of the uterine endometrium, whereas progesterone induces differentiation of the uterine endometrium and the secretion of distinct products. During puberty, the hypothalamus begins to secrete increasing quantities of GnRH, which increases LH and FSH secretion, enhances ovarian function, and leads to the first ovulation. Menopause ensues from the loss of numerous oocytes in the ovary and the subsequent failure of follicular development and estradiol secretion. LH and FSH levels rise from the lack of negative feedback by estradiol.

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Lecture Outline: I. II. III. IV. V. VI. VII. VIII. IX. X. Female reproductive system Hypogonadal axis regulation of reproduction Follicular development 2-cell Hypothesis of steroidogenesis Role of Estrogens Role of Progesterone Hormonal integration of ovarian cycle with uterine changes In vitro fertilization Luteal insufficiency Ovulation and fertilization

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Title of Lecture: (Endo-12) Female Reproductive Physiology II Instructor: Dr. Dana Gaddy Biomed 2-Rm 210-2; GaddyDana@uams.edu 686-5918

Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 82, pp. 1027-1041 Suggested reading: Vander, Sherman and Lucianos Human Physiology, 9th Edition, by Widmaier, Raff and Strang, 2004 Chapter 17, pp. 671-694 Objectives: Fertilization of the ovum occurs in the oviduct. Progesterone and estrogen released from the ovary prepare the oviduct and uterus for receiving the developing embryo. The blastocyst enters the uterus, leaves the surrounding zona pellucida, and implants into the uterine wall on day 7 of gestation. Human chorionic gonadotropin (hCG), produced by trophoblast cells of the developing embryo, activates the corpus luteum to continue producing progesterone and estradiol beyond its normal life span to maintain pregnancy. Shortly after the embryo implants into the uterine wall, a placenta develops from embryonic and maternal cells and becomes the major steroidsecreting organ during pregnancy. Major hormones produced by the fetoplacental unit are progesterone, estradiol, estriol, hCG, and human placental lactogen. Elevated estriol levels indicate fetal well-being, whereas low levels might indicate fetal stress. Human placental lactogen has a role in preparing the breasts for milk production. The pregnant woman becomes insulin-resistant during the latter half of pregnancy in order to conserve maternal glucose consumption and make glucose available for the developing fetus. The termination of pregnancy is initiated by strong uterine contractions induced by oxytocin. Estrogens, relaxin, and prostaglandins are involved in softening and dilating the uterine cervix so that the fetus may exit. Lactogenesis is milk production, which requires prolactin (PRL), insulin, and glucocorticoids. Galactopoiesis is the maintenance of an established lactation and requires PRL and numerous other hormones. Milk ejection is the process by which stored milk is released; milk letdown is regulated by oxytocin, which contracts the myoepithelial cells surrounding the alveoli and ejects milk into the ducts. Lactation is associated with the suppression of menstrual cycles and 93

anovulation due to the inhibitory actions of PRL on GnRH release and the hypothalamic-pituitary-ovarian axis. The hypothalamic-pituitary axis becomes activated during the late prepubertal period, resulting in increased frequency and amplitude of GnRH pulses, increased LH and FSH secretion, and increased steroid output by the gonads. Most disorders of sexual development are caused by chromosomal or hormonal alterations, which may result in in-fertility, sexual dysfunction, or various degrees of intersexuality (hermaphroditism). Lecture outline: I. Pregnancy Fertilization and implantation Associated maternal endocrine changes Maternal metabolism changes Fetal metabolic regulation II. Parturitionhormonal control III. Chromosomal abnormalities IV. Lactation regulation V. Pubertymenarche Factors involved in timing of puberty VI. Adrenarche VII. Menopause Symptoms Hormonal changes Physiological changes Hormone Replacement Therapy

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Title of Lecture: (Endo-13) Neonatal Physiology Instructor: Dr. M.L. Jennings Biomedical 209-2; JenningsMichaelL@uams.edu) 296-1438 Required Reading: Medical Physiology, Guyton and Hall, 11th Ed., 2006. Chapter 83, pp. 1042-1052 Objectives: Understand the general time course of growth of the fetus. Understand the respiratory system changes that occur at birth Understand the changes in the circulatory/cardiovascular system in the fetus during gestation and at parturition Know the functional problems of organ systems that are specific to the neonate Understand the major functional consequences of premature birth

Lecture Outline: I. Fetal Metabolism and Development of Organ Systems II. Adjustment of neonate to extrauterine life Breathing at birthcauses, delays and abnormalities Hypoxia Lung Expansion, surfactant deficiencyRespiratory Distress Syndrome III. Circulatory adjustments at birth Important anatomical structures involved in fetal circulation Changes in fetal circulation at birth Altered pulmonary and systemic vascular resistance at birth Closure of the foramen ovale, ductus arteriosus, and ductus venosus

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IV. Functional Problems of the neonate Respiratory system Circulation Fluid balance, acid-base balance, renal function GI and Liver Metabolic rate and body temperature Nutritional needs early post-natal: Calcium, Vitamin D, Iron, Vitamin C

V. Problems associated with prematurity

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Key Physiology Equations

Equation Name
Mean arterial pressure

Equation
Pa = CO X TPR

Resistance Compliance Cardiac output Cardiac output (measurement)

8 1 r 4

C = V/P CO = SV X HR
CO = O2 [O ]
2 pulmonary vein 2

consumption
pulmonary artery

[O ]

Ejection fraction Starling equation Physiologic dead space

EF = SV/EDV J2 = Kf [(Pc Pi) (c - I)] VD = VT X

Paco 2 PECO 2 Paco 2

Alveolar ventilation Renal clearance

VA = (VT VD) X breaths/min

C=

U V
x

Px U
inulin

GFR GFR =

Pinulin

Free water clearance Henderson-Hasselbalch equation Serum anion gap

C H 2 O = V C osm
pH = pK + log

A HA

Anion gap = Na+ - (Cl- + HCO3-)

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LABORATORY VALUES * Included in the Biochemical Profile (SMA-12) REFERENCE RANGE BLOOD, PLASMA, SERUM * Alanine aminotransferase (ALT, GPT at 30C) Amylase, serum * Aspartate aminotransferase (AST, GOT at 30C) Bilirubin, serum (adult) Total//Direct * Calcium, serum (Ca ) * Cholesterol, serum Cortisol, serum
2+

SI REFENCE INTERVALS

8-20 U/L 25 -125U/L 8-20 U/L 0.1-1.Omg/dL//0.0-0.3mg/dL 8.4-10.2mg/dL Rec:<200mg/dL 0800 h: 5-23 g/dL // 1600 h: 3-15 g/dL 2000 h:50% of 0800 h Male: 25-90U/L Female: 10-70U/L 0.6-1.2 mg/dL 136-145mEq/L 95-105mEq/L 3.5-5.0mEq/L 22-28 mEq/L 1.5-2.0mEq/L

8-20 U/L 25 -125U/L 8-20 U/L 2-17mol/L// 0-5 mol/L 2.1-2.8 mmol/L <5.2 mmol/L 138-635 nmol/L // 82-413 nmol Fraction of 0800 h: 0.50 25-90 U/L 10-70 U/L 53-106 mol/L 136-145 mmol/L 95-105 mmol/L 3.5-5.0 mmol/L 22-28 mmol/L 1.5-2.0 mmol/L

Creatine kinase, serum Creatinine, serum Electrolytes, serum Sodium (Na+) Chloride (Cl) * Potassium (K+) Bicarbonate(HCO3) Magnesium(Mg2+) Estriol, total, serum (in pregnancy) 24-28 wks// 32-36 wks 28-32 wks//36-40wks Ferritin, serum Follicle-stimulating hormone, serum/plasma

30-170ng/mL // 60-280ng/mL 40-220ng/mL // 80-350 ng/mL Male: 15-200ng/mL Female: 12-150ng/mL Male:4-25mlU/mL Female: premenopause 4-30 mlU/mL midcycle peak 10-90 mlU/mL postmenopause 40-250 mlU/mL 7.35-7.45 33-45 mmHg 75-105 mmHg Fasting: 70-110 mg/dL 2-h postprandial: < 120 mg/dL Fasting: <5ng/mL provocative stimuli: > 7 ng/mL

104-590// 208-970 nmol/L 140-760// 280-1210 nmol/L 15-200 g/L 12-150 g/L 4-25 U/L 4-30 U/L 10-90 U/L 40-250 U/L [H+] 36-44 nmol/L 4.4-5.9 kPa 10.0-14.0 kPa 3.8-6.1 mmol/L <6.6 mmol/L < 5 g/L > 7 g/L

Gases, arterial blood (room air) pH PCO2 PO2 * Glucose, serum

Growth hormone - arginine stimulation Immunoglobulins, serum IgA IgE IgG IgM Iron Lactate dehydrogenase, serum Luteinizing hormone, serum/plasma

76-390mg/dL 0-380 IU/mL 650-1500mg/dL 40-345mg/dL 50-170g/dL 45-90U/L Male:6-23mlU/mL

0.76-3.90 g/L 0-380 klU/L 6.5-15 g/L 0.4-3.45 g/L 9-30 mol/L 45-90 U/L 6-23 U/L

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Osmolality, serum Parathyroid hormone, serum, N-terminal * Phosphatase (alkaline), serum (pNPP at 30C) * Phosphorus (inorganic), serum Prolactin, serum(hPRL) * Proteins, serum Total(recumbent) Albumin Globulin Thyroid-stimulating hormone, serum or plasma Thyroidal iodine (120I) uptake Thyroxine (T4),serum Triglycerides, serum Triiodothyronine (T3), serum (RIA) Triiodothyronine (T3) resin uptake * Urea nitrogen, serum (BUN) * Uric acid, serum Cerebrospinal Fluid Cell count Chloride Gamma globulin Glucose Pressure Proteins, total Hematologic Bleeding time (template) Erythrocyte count Erythrocyte sedimentation rate (Westergren) Hemoglobin A1C Hemoglobin, blood Hemoglobin, plasma Leukocyte count and differential Leukocyte count Segmented neutrophils Bands Eosinophils Basophils Lymphocytes Monocytes Mean corpuscular hemoglobin Mean corpuscular hemoglobin concentration Mean corpuscular volume Partial thromboplastin time (activated)

Female: follicular phase 5-30 mlU/mL midcycle75-150mlU/mL postmenopause 30-200 mlU/mL 275-295mOsmol/kg 230-630 pg/mL 20-70 U/L 3.0-4.5 mg/dL < 20 ng/mL 6.0-7.8 g/dL 3.5-5.5 g/dL 2.3-3.5 g/dL 0.5-5.0U/mL 8-30% of administered dose/24 h 5-12 g/dL 35-160 mg/dL 115-190 ng/dL 25-35% 7-18mg/dL 3.0-8.2 mg/dL 0-5 cells/mm3 118-132 mEq/L 3-12% total proteins 40-70 mg/dL 70-180 mm H2O <40 mg/dL 2-7 minutes Male: 4.3-5.9 million/mm3 Female: 3.5-5.5 million/mm3 Male: 0-15 mm/h Female: 0-20 mm/h 6% Male: 13.5-17.5 g/dL Female: 12.0-16.0 g/dL 1-4 mg/dL 4500-11,00/mm3 54-62% 3-5% 1-3% 0-0.75% 25-33% 3-7% 25.4-34.6 pg/cell 31-36% Hb/cell 80-100 mm3

5-30 U/L 75-150 U/L 30-200 U/L 275-295mOsmol/kg 230-630 ng/L 20-70 U/L 1.0-1.5 mmol/L <20 g/L 60-78 g/L 35-55 g/L 23-35 g/L 0.5-5.0 mU/L 0.80-0.30/24 h 64-155 nmol/L 0.4-1.81 mmol/L 1.8-2.9 nmol/L 0.25-0.35 1.2-3.0 mmol urea/L 0.18-0.48 mmol/L 0-5 x 106/L 118-132 mmol/L 0.03-0.12 2.2-3.9 mmol/L 70-180 mm H2O <0.40 g/dL 2-7 minutes 4.3-5.9 x 1012/L 3.5-5.5 x 1012/L 0-15 mm/h 0-20 mm/h 0.06% 2.09-2.71 mmol/L 1.86-2.48 mmol/L 0.16-0.62 mmol/L 4.5-11.0 x 109/L 0.54-0.62 0.03-0.05 0.01-0.03 0-0.0075 0.25-0.33 0.03-0.07 0.39-0.54 fmol/cell 4.81-5.58 mmol Hb/L 80-100fl

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Platelet count Prothrombin time Reticulocyte count Thrombin time Volume Plasma Red cell SWEAT Chloride URINE Calcium Chloride Creatinine clearance Estriol, total (in pregnancy) 30 wks 35 wks 40 wks 17-Hydroxycorticosteroids 17-Ketosteroids, total Osmolality Oxalate Potassium Proteins, total Sodium Uric acid

25-40 seconds 150,000-400,000/mm3 11-15 seconds 0.5-1.5% of red cells < 2 seconds deviation from control Male: 25-43 mL/kg Female: 28-45 mL/kg Male: 20-36 mL/kg Female: 19-31 mL/kg 0.35 mmol/L 100-300 mg/24h Varies with intake Male: 97-137 mL/min Female 88-128 mL/ 6-18 mg/24h 9-28 mg/24h 13-42 mg/24h Male: 3.0-10.0 mg/24 Female: 2.0-8.0 mg/24h Male: 8-20 mg/24h Female: 6-15 mg/24h 50-1400 mOsmol/kg 8-40 g/mL Varies with diet < 150 mg/24h Varies with diet Varies with diet

25-40 seconds 150-400 x 109/L 11-15 seconds 0.005-0.015 < 2 seconds deviation from control 0.025-0.043 L/kg 0.028-0.045 L/kg 0.020-0.036 L/kg 0.019-0.031 L/kg 0-35 mmol/L 2.5-7.5 mmol/24h Varies with intake

21-62 mol/24h 31-97 mol/24h 45-146 mol/24h 8.2-27.6 mol/24h 5.5-22.0 mol/24h 28-70 mol/24h 21-52 mol/24h 90-445 mol/L Varies with diet < 0.15 g/24h Varies with diet Varies with diet

100