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Physiology

& Pharmacology

BMSC/BIOL 243

Course Outline Pharmacology Lecture Notes

Lab Exercises

2013

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BMSC/BIOL 243

PHYSIOLOGY & PHARMACOLOGY

2013

Student Notes Book

Table of Contents Page No.

Title Page 1

Table of Contents 2

Course Description 3

Lecture Schedule – Part 1 – Lung, Heart, Gut 10

Lecture Schedule – Part 2 – Pharmacology 11

Lecture Schedule – Part 3 – Endocrinology 13

Respiratory, Cardiovascular, and Gut Physiology – Part 1 14

Study Guide – Part 1 15

Pharmacology – Part 2 21

Table of Contents - Pharmacology 22

1. Introduction 24

2. Drug Action 27

3. Agonists & Antagonists 39

4. Bioassays 51

5. Drug Administration 54

6. Absorption, Distribution, & Elimination 60

7. Pharmacokinetics 75

8. Case Study: Adrenoceptor Drugs and the Heart 81

Exercise Support Material 85

Lab Exercises 89

Lab Consent Form 91

Lab 1 – Haematology 93

Lab 2 – Human Respiration 101

Lab 3 – Human Circulation 115

Use of the ADI PowerLab System 128

Appendices 146

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VICTORIA UNIVERSITY OF WELLINGTON

SCHOOL OF BIOLOGICAL SCIENCES

BMSC/BIOL 243 (Physiology and Pharmacology) 2013

Course Coordinator: Prof John Miller, AM307, Tel 463 6082 Email john.h.miller@vuw.ac.nz

Prescription and The Paper The paper is divided into three parts, the lecturers-in-charge being Prof John Miller (Course Coordinator) (Physiology part I), Dr Brian Robinson (Pharmacology part II) and Assoc. Prof. Jim McIntosh (Physiology part III). Prof Miller is in charge of the laboratory part of the course.

Prof John Miller

Email john.h.miller@vuw.ac.nz

Work Phone 463 6082

Office Location AM307

Personal Link http://www.victoria.ac.nz/sbs/about/staff/john-h-miller

Course Coordinator

Dr Jim McIntosh

Email jim.mcIntosh@vuw.ac.nz

Work Phone 463 5577

Office Location AM323

Personal Link http://www.victoria.ac.nz/sbs/about/staff/jim-mcintosh

Dr Brian Robinson

Email: brian.robinson@vuw.ac.nz

Work Phone 463 6155Office Location: Graduate School of Nursing, Midwifery, and Health,

Central Services Block, Wellington Hospital

Personal Link http://www.victoria.ac.nz/nmh/about/staff/brian-robinson

The lecture course The major emphasis in this paper will be the correlation of molecular and cellular mechanisms with physiological functions in humans and other mammalian species. An integrative approach will be adopted in studying the roles of the central and peripheral nervous system and various organ systems in relation to the metabolic, hormonal and homeostatic mechanisms involved in circulation, respiration, and digestion. Renal excretion will be covered at 300-level in BMSC/BIOL 355. The modulation of physiological function will be explored in a series of pharmacology lectures. These will focus on the mechanisms of drug action from the intact organism to the molecular level. Learning objectives include understanding the terminology and concepts of physiology and being able to understand and carry out some of the methodology needed to study the physiology of human subjects.

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Course Delivery The course involves presentation of lectures on selected subjects in physiology, mostly via Powerpoint presentations. All Powerpoint slides will be available on Blackboard. The lab component of the course involves physiological experimentation and monitoring in human subjects. Lectures Take place on Mon, Wed, Thurs, Fri 9.00 am – 9.50 am in MC102. Labs

Take place on Tuesdays or Wednesdays from 13.10 – 17.00 in KK701. Key Dates Lectures by Dr Miller (Physiology 1): July 15 – Sept 18. Lectures by Dr Brian Robinson (Pharmacology 2): Aug 12 – Aug 23 Lectures by Dr McIntosh (Physiology 3): Sept 19 – Oct 18 Mid-trimester break (no lectures): Aug 26 – Sept 6 First terms test: Tuesday Sept 18 (Only Dr Miller‘s material) Second terms test: Friday Oct 11 (Only Dr McIntosh‘s material) Assignment: Monday Sept 9 (Only Dr Robinson‘s material). First Lab – Lab 2 - Human Respiration - Tues and Wed Streams, 24 and 25 Sept Second Lab – Lab 1 - Haematology - Tues and Wed Streams, 1 and 2 Oct Third Lab –- Lab 3 - Human Circulation Tues and Wed Streams, 8 and 9 Oct Full lab report due for Lab 3-Human Circulation Oct 15 (Stream 1) or Oct 16 (Stream 2) Practical test – Tues and Wed Streams, 15 and 16 Oct Trimester Dates:

Trimester 2 teaching begins on July 15th and ends on Oct 18th, 2013. The Final Examination period is between Oct 21st and Nov 15th, 2013.

Withdrawal Dates:

See website below for withdrawal dates from the course. http://www.victoria.ac.nz/home/admisenrol/payments/withdrawlsrefunds.aspx

The laboratory course The practical part of the course will look at the composition of the blood (Lab 1), and lung function (Lab 2) and heart function (Lab 3) using a physiological monitoring system (ADI Powerlab). For labs 2 & 3, you must familiarize yourself with the ADI PowerLab system before you come to this lab (See ―Use of the ADI PowerLab System‖ in your Student Notes Book). The lab course will have two streams. Each stream will have 10 experimental set-ups or stations for the PowerLab Labs 2 and 3, and students will work in groups at each station. The number of students per group will depend on the total number of students enrolled in the course, but should not exceed 6 per group. The sign up for lab streams will be organized during the lectures. There will be a practical exam that includes some hands-on analysis and short-answer questions relevant to the laboratory exercises.

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No open-toed shoes or sandals are allowed in the laboratory, and you must have a labcoat to attend the lab. Labcoats, both paper (inexpensive) and cloth (expensive) are available from the VUW Bookstore on campus. The laboratory schedule is as follows: Week 9 of term Sept 24 or 25 - Lab 2 - Human Respiration Week 10 of term Oct 1 or 2 - Lab 1 - Haematology Week 11 of term Oct 8 or 9 - Lab 3 - Human Circulation Week 12 of term Oct 15 or 16 - Lab Test

Textbooks A Student Notes book is available from the VUW Bookstore for $34.95. It contains the Course Outline, the ―Pharmacology Text‖, and the Lab Handouts. This material will also be available on Blackboard. The textbook for the course (and also BMSC/BIOL 335 next year) is: Guyton AC and Hall JE, Textbook of Medical Physiology, 12th Ed (2011), W.B.

Saunders Company, Philadelphia. (approx. $187). Other similar books can also be used as the text, such as Principles of Anatomy and Physiology (by Totora and Grabowski (12th Edition), Physiology (by Berne, Levy, Koeppen, and Stanton) (5th Edition), Lecture Notes on Human Physiology (by Bray, Cragg, Macknight, and Mills) (4th Edition), Medical Physiology (by Boron and Boulpaep) (1st Edition), or Review of Medical Physiology (by Ganong) (21st edition).

The pharmacology section of the paper will cover 8 lectures and a student-centred learning exercise. As this forms only a minor component of the material for this paper, there is no expectation that students will buy a textbook. A number of pharmacology texts have been placed on closed reserve in the library. Extensive notes for the pharmacology material can also be found in this booklet. Other useful specialty reference books are available on 3-day loan from the VUW Library, including: Instant Pharmacology by Kourosh Saeb-Parsy, et al.. Pharmacology : drug actions and reactions by Ruth R. Levine in collaboration with Carol

T. Walsh and Rochelle D. Schwartz. Cardiovascular physiology by Robert M. Berne and Matthew N. Levy. Respiratory physiology− the essentials by John B. West.

Assessment and Examining 2013 The final grade for the paper will be derived from 60% In-Term Assessment (ITA) and 40% from one 2-hour Final Examination. The ITA marks will be obtained as follows:

(1) Two written theory tests, one for Part 1 and one for Part 3 that will contribute

15% each to the final ITA marks for a total of 30% of the course mark.

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(2) An assignment based on a component of the pharmacology material in Part 2.

This will be, in part, a student-centred learning exercise. It will contribute 10% to the course mark.

(3) A laboratory mark based on three lab reports worth 10% (two data sheets each

worth 2% (Labs 1 and 2), one full laboratory report worth 6% (Lab 3)), and a practical test worth 10% for a total laboratory component of 20% of the course mark.

A Final Exam worth 40% of the course mark. The final exam will be of 2 hours duration. It will be in three parts. The questions in any one part will be derived from the lecture material taught by a single lecturer. You will be required to answer at least one question from each part, and 4 questions overall.

Mandatory Paper Requirements To pass this paper you must satisfy the Mandatory Paper Requirements outlined below. These include reaching a satisfactory standard in ITA theory tests and in the pharmacology assignment and turning in all the required lab assessments. An overall mark of 50% is required to pass the course. The pharmacology assignment and full lab report must be submitted by their deadlines. Work handed in after its deadline, without supported extenuating circumstances (for instance, a doctor‘s note confirming illness), may not be marked. For the lab component of the course, you must attend all three labs. Should you miss any labs, you will need to present a medical certificate to obtain an aegrotat for that lab, and you will still be responsible for the missed material in the lab test.

Awareness of Student Problems The staff in charge of this paper acknowledge that students may variously be presented with either personal, health and/or academic problems. In such instances the academic in charge of the lectures at that time should be made aware of these concerns in order that the individual‘s academic performance can be aided and more accurately assessed under such circumstances.

Workload Guidelines For BMSC/BIOL 243 there will be 4 hours of lectures per week. Students may expect to spend 6-8 out of class hours per week reading and studying of this material as an average workload. Three 4-hour labs for the course, an open-book lab test, and the lab write-ups will require additional time in and out of class. The remainder of any time available outside of class hours is to be utilised for reading, additional revision work, etc.

Other issues Students experiencing difficulties with timing, venue or availability of required resources for this paper are encouraged to contact the coordinator Prof Miller to explore possible solutions.

Feedback

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Feedback to students includes: discussion and written comments of marked work such as internally assessed examinations, and individual discussions on performance at the request of a student. Feedback from students will be a request for students to evaluate the BMSC/BIOL335 course or a lecturer‘s contribution to the course. A class representative will be elected in one of the first classes, and that person‘s name and contact details will be made available to VUWSA, the Course Coordinator and the class. The class representative provides a communication channel to liaise with the Course Coordinator on behalf of students.

Communication of additional information Additional information, test results, changes in room assignments, changes in assessments, and important information on other changes to the course will be conveyed through Blackboard as an Announcement. Every student enrolled in BMSC/BIOL 243 must ensure that they have access to Blackboard.

GENERAL UNIVERSITY POLICIES AND

STATUTES

Students should familiarise themselves with the University‘s policies and statutes, particularly the Assessment Statute, the Personal Courses of Study Statute, the Statute on Student Conduct and any statutes relating to the particular qualifications being studied; see the Victoria University Calendar or the University‘s policy website,

http://www.victoria.ac.nz/home/about/policy

Where to find more detailed information

Find key dates, explanations of grades and other useful information at www.victoria.ac.nz/home/study. Find out about academic progress and restricted enrolment at www.victoria.ac.nz/home/study/academic-progress. The University‘s statutes and policies are available at www.victoria.ac.nz/home/about/policy, except qualification statutes, which are available via the Calendar webpage at www.victoria.ac.nz/home/study/calendar (See Section C). Further information about the University‘s academic processes can be found on the website of the Assistant Vice-Chancellor (Academic) at www.victoria.ac.nz/home/about_victoria/avcacademic/default.aspx

Student and staff conduct

The Statute on Student Conduct together with the Policy on Staff Conduct ensure that members of the University community are able to work, learn, study and participate in the academic and social aspects of the University‘s life in an atmosphere of safety and respect. The Statute on Student Conduct contains information on what conduct is prohibited and what steps are to be taken if there is a complaint. For information about complaint procedures under the Statute on Student Conduct, contact the Facilitator and Disputes Advisor or refer to the statute on the Victoria policy website at:

http://www.victoria.ac.nz/home/about/policy

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The Policy on Staff Conduct can be found at:

http://www.victoria.ac.nz/home/about/policy

Academic grievances

If you have any academic problems with your course you should talk to the tutor or lecturer concerned; class representatives may be able to help you in this. If you are not satisfied with the result of that meeting, see the Head of School or the relevant Associate Dean; The VUWSA Student Advocate is available to assist in this process. If, after trying the above channels, you are still unsatisfied, formal grievance procedures can be invoked. These are set out in the Academic Grievance Policy which is published on the Victoria website at:

http://www.victoria.ac.nz/home/about/policy

There is also a leaflet explaining the grievance process available from the AVC(Academic) website at:

http://www.victoria.ac.nz/home/about/avcacademic/Publications.aspx#grievances

Students with Impairments

Refer to the Meeting the Needs of Students with Impairments Policy, available on the University’s policy website. http://www.victoria.ac.nz/home/about/policy The University has a policy of reasonable accommodation of the needs of students with impairments. The policy aims to give students with disabilities the same opportunity as other students to demonstrate their abilities. If you have a disability, impairment or chronic medical condition (temporary, permanent or recurring) that may impact on your ability to participate, learn and/or achieve in lectures and tutorials or in meeting the course requirements, please contact the course coordinator as early in the course as possible. Alternatively, you may wish to approach a Student Adviser from Disability Support Services (DSS) to discuss your individual needs and the available options and support on a confidential basis. DSS are located on Level 1, Robert Stout Building: telephone: 463-6070 email: disability@vuw.ac.nz The name of your School‘s Disability Liaison Person is in the relevant prospectus or can be obtained from the School Office or DSS.

Student Support

Staff at Victoria want students to have positive learning experiences at the University. There are a number of support services available to help you directly if your academic progress is causing concern or if there are elements in your life that are affecting your ability to study. These include:

Your course coordinator or programme director;

Staff in your Faculty Student Administration Office Student Dedicated learning support through Student Learning Support Service; Kaiwawao Māori ;Maanaki Pihiphipinga; Disability Support Services and Victoria International;

Wider holistic support through the Health Service; Counselling Service; Financial Support and Advice; Accommodation Service and Career Development and Employment. Find out more at

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www.victoria.ac.nz/st_services/ or email student-services@vuw.ac.nz;

VUWSA employs a Student Advocate who deals with academic problems and provides support, advice and advocacy services, as well as training and supporting class representatives and faculty delegates. The Education Office is located on the ground floor, Student Union Building. Email education@vuwsa.org.nz or tel. 463-6716 or 463-6984.

Academic integrity and plagiarism Academic integrity means that university staff and students, in their teaching and learning are expected to treat others honestly, fairly and with respect at all times. It is not acceptable to mistreat academic, intellectual or creative work that has been done by other people by representing it as your own original work.

Academic integrity is important because it is the core value on which the University‘s learning, teaching and research activities are based. Victoria University‘s reputation for academic integrity adds value to your qualification.

The University defines plagiarism as presenting someone else‘s work as if it were your own, whether you mean to or not. ‗Someone else‘s work‘ means anything that is not your own idea. Even if it is presented in your own style, you must acknowledge your sources fully and appropriately. This includes:

Material from books, journals or any other printed source

The work of other students or staff

Information from the internet

Software programs and other electronic material

Designs and ideas

The organisation or structuring of any such material

Find out more about plagiarism, how to avoid it and penalties, on the University‘s website: www.victoria.ac.nz/home/studying/plagiarism.html

Use of Turnitin

Student work provided for assessment in this course may be checked for academic integrity by the electronic search engine http:/www.turnitin.com. Turnitin is an online plagiarism prevention tool that compares submitted work with a very large database of existing material. At the discretion of the Head of School, handwritten work may be copy-typed by the School and subject to checking by Turnitin. Turnitin will retain a copy of submitted material on behalf of the University for detection of future plagiarism, but access to the full text of submissions is not made availa ble to any other party.

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BMSC/BIOL 243 – PHYSIOLOGY & PHARMACOLOGY - 2013

PART 1 – CARDIOVASCULAR, RESPIRATORY, AND GASTROINTESTINAL

PHYSIOLOGY

LECTURE SCHEDULE

Mon, Wed, Thurs, Fri 9.00 - 9.50 am Prof John H Miller

MC102 AM307; Ext. 6082

john.h.miller@vuw.ac.nz

Page Numbers Guyton & Hall 12th

Ed

July 15 Autonomic Nervous System 729-41

17 Cardiac Anatomy 101-2

18 Cardiac Electrophysiology 102-4, 115-20, 121-7, 143-53

19 Mechanical Events of Cardiac Cycle 104-7

22 Control of the Heart 110-3, 118-20, 229-31

24 Vascular Flow: Arteries and Arterioles 157-9, 168-71, 191-7

25 Capillaries 177-86

26 Veins, & Lymphatics 171-6, 186-9

29 Cardiovascular Regulation 199-209, 229-30, 243-5, 273-9

31 Blood Clotting & Anaemias 420-1, 451-7

August 1 Pulmonary Mechanics 465-72

2 Airway Resistance & Compliance 467-8, 471-2, 515-23

5 Gas Exchange 485-494

7 Blood Gas Transport 495-504

8 Central Regulation of Breathing 505-8

9 Peripheral Control of Breathing 508-11

12 - 23 PHARMACOLOGY LECTURES – Part II

(Dr Brian Robinson)

Aug 26 – Sept 6 AUGUST BREAK

Sept 9 GI Tract Anatomy, Electrical Activity, & Motility 753-9, 763-72

9 Pharmacology Assignment Due

11 GI Secretions - Mouth, Esophagus 773-7

12 GI Secretions – Stomach, Pancreas 777-83

13 GI Secretions –Intestine, Liver 783-7, 799-805

16 REVIEW of Part I

18 Theory Test I – (Part I only)

Sept 19- Oct 18 Part III lectures (Dr McIntosh)

Oct 11 Theory Test II – (Part III only)

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BIOL/BMSC 243—PHYSIOLOGY & PHARMACOLOGY, 2013

LECTURE SCHEDULE—Pharmacology PART 2

1. Introduction

1.1. What is pharmacology

1.2. Scope of this section of the course

1.3. Link to other courses

1.4. Definitions

1.5. History

2. Drug action

2.1. Drug targets

2.1.1. Receptors

2.1.2. Enzymes

2.1.3. Nucleic acids

2.2. Mechanisms and Specificity of Drug Binding

2.2.1. Covalent bonds

2.2.2. Van der Waals forces

2.2.3. Electrostatic forces

2.2.4. Hydrogen bonds

2.2.5. The Hydrophobic interaction

2.2.6. Conformation effects

2.2.7. Configuration effects

2.2.8. Dynamics

2.3. Selectivity, toxicity and therapeutic index

2.4. Summary

3. Agonists & antagonists

3.1. Activity

3.2. Concn vs response curves

3.2.1. Quantised data

3.2.2. Continuous data

3.3. Some Physical Chemistry

3.3.1. Agonist binding

3.3.2. Competitive Antagonists

3.4. Summary

4. Bioassays

4.1. Clinical trials

5. Drug administration

5.1. Enteral administration

5.2. Parenteral administration

6. Absorption, distribution & elimination

6.1. Bioavailability and crossing membranes

6.1.1. pH effects

6.2. Drug distribution

6.2.1. Fat

6.2.2. Plasma proteins

6.2.3. Body fluid compartments

6.3. Elimination

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6.3.1. Metabolism

6.3.2. Excretion

7. Pharmacokinetics

7.1. Single compartment model

7.2. Effect of dosing regimes

8. Case Study: Adrenoceptor agonists and antagonists and control of cardiac

function

8.1. Adrenoceptors

8.2. Presence and function of adrenoceptors and the heart and vascular system.

8.3. Adrenoceptor agonists

8.4. Adrenoceptor antagonists

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SCHOOL OF BIOLOGICAL SCIENCE

BIOL/BMSC 243—PHYSIOLOGY & PHARMACOLOGY, 2013

LECTURE SCHEDULE—PHYSIOLOGY PART 3

Mondays, Wednesdays, Thursdays, Fridays 9:00 - 9:50 in MC102

Topic

1. Regulation: homeostasis

2. Food intake Hunger, satiety and body weight

3. Metabolism, energy conservation, and BMR

Energy storage, utilization

4. Basic metabolic rate

5. Body calcium Parathormone, vitamin D, and calcitonin

6. Thermoregulation Central, peripheral control

7. Blood glucose Absorptive state and insulin

8. Post absorptive state; other hormones

9. Pituitary hormones

10. Neuroendocrinology Growth and GH

11. Milk production and Prl

12. Stress, ACTH and the adrenals

13. The thyroid, TSH and thyroid hormones

TERMS THEORY EXAMINATION II FRIDAY OCT 11

14. Reproduction Determination of sex

15. Organogenesis

16. Cycles, seasons, pheromones

17. Conception and contraception

Dr Jim McIntosh, AM323, ext. 5577

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Part I

Cardiovascular, Respiratory, & Gastrointestinal Physiology

STUDY GUIDE

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BMSC/BIOL 243 – PHYSIOLOGY – 2013

Study Guide for Part I

Respiratory, Cardiovascular, and Gastrointestinal Physiology

CARDIOVASCULAR SYSTEM

I. AUTONOMIC NERVOUS SYSTEM

A. General Function

B. Anatomy

1. Sympathetic Division

2. Parasympathetic Division

II. DESIGN OF CARDIOVASCULAR SYSTEM

A. Pulmonary and systemic circuits

B. Parallel circuits to tissues except for two series (portal) circuits

III. CARDIAC PUMP

A. Cardiac Anatomy – chambers, chorda tendinae, nodal areas, and valves

B. Electrical Activity

1. Heart Rate Automaticity - pacemakers

2. Conduction Pathways

Nodal regions with automaticity and decremental conduction

Atrial internodal pathways

Bundle of His

Ventricular Purkinje fibres

3. Cardiac Action Potentials

Fast responses – myocardial cells, conductile tissue

spike, plateau, rapid repolarisation, threshold, refractory period

Slow responses – nodal tissue

spontaneous depolarisation of RMP

4. ECG (P, QRS, T waves; PR and QT Intervals)

5. Arrhythmias

Sinus arrhythmia, bradycardia and tachycardia

Ectopic beats

AV block

Fibrillation

C. Cardiac Cycle Events

1. ECG

2. Heart Sounds

3. Pressures in Atria, Ventricles, and Aorta

4. Blood Flow Into and Out of Ventricle

5. Opening and Closing of AV and Aortic Valves

D. Control of the Heart - CO = HR x SV, SV = EDV-ESV

1. HR Control

a. ANS - SNS and PSNS on SA node cells

b. Hormonal

c. Other - temperature, ions, pH, gases, reflexes, etc

2. SV Control

a. EDV Control – Control of ventricular filling

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VR rate and venous pressure

Filling time

Intraventricular and intrathoracic pressure

Atrial contraction

Pericardial restraint

b. ESV Control – Control of inotropy

Heterometric autoregulation: Frank-Starling Law of the Heart

preload effects

Homeometric autoregulation

afterload effects

ANS control of inotropy (contractility)

HR effect on intracellular calcium

Hormones

Plasma Ca2+

Other - ions, pH, gases, etc

Heart failure and positive and negative inotropic drugs

IV. VASCULATURE

A. Flow Principles Flow=(Pi - Po)/R R=8L/r4

B. Summary of Vascular Parameters - capacity, velocity, x-sec area, pressure

C. Arteries MBP=CO.TPR MBP=DP + PP/3

D. Arterioles

1. Local Control

Myogenic

Metabolic (active & reactive hyperaemia)

2. Neural Control

SNS - 1 adrenergic vasoconstriction (Major control)

Temperature regulation

Sympathetic 2 adrenergic vasodilation in muscle

Sympathetic cholinergic vasodilation in muscle (before exercise)

PSNS - cholinergic vasodilation in GI & urogenital tract

Peptidergic - neuropeptide Y constrict; VIP & Substance P dilate

Nitroxidergic - vasodilation

3. Hormonal

Vasoconstriction - adrenalin, Ang II, AVP, Endothelin (ET)

Vasodilation - kinin, bradykinin, ANP, nitric oxide (NO), prostaglandins

E. Capillaries

1. Structure

Capillary Endothelium

Microcirculatory Bed – arteriole, metarteriole, capillary sphincter,

capillary, venule

2. Vasomotion and Flow Characteristics

3. Capillary Exchange

Diffusion – passive diffusion through pores and cytopempsis

Bulk Flow - Starling Forces (Pc Pt c t ) and Kf

F. Veins

1. Control of Pveins or VR

blood volume, skeletal muscle-respiratory pumps, venoconstriction

2. Postural Effects on Venous Pooling

G. Lymphatic Vessels

1. Lymph System

a. Anatomy

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b. Function

2. Mechanism of Lymph Flow

3. Model of Lymphatic Function

V. CARDIOVASCULAR REGULATION

A. Blood Pressure Control - MBP=COxTPR

1. Regulated Parameter - MBP

2. Sensor - baroreceptor in carotid sinus

3. Effectors - ANS control of CO & TPR

4. Regulatory Centre - Cardiovascular Centre (CVC) in Medulla

B. Integration by CVC

1. Baroreceptor Input - carotid sinus reflex

2. Chemoreceptor Input

3. Hypothalamic Input - Emotion, Temperature Regulation

4. Cerebral Cortex Input

5. Spinal Cord Reflexes (local bypass of CVC)

C. Responses to Haemorrhage

1. Neural Reflex Compensations

2. Hormonal Compensations

3. Capillary Fluid Shifts

4. Replacement of RBCs and Albumin

D. Responses to Exercise

VI. BLOOD CLOTTING & ANAEMIAS

A. Vascular Spasm

B. Platelet Aggregation and Transformation

C. Blood Clotting

1. Stage I - Activation of Stuart-Prower Factor (X)

2. Stage II - Formation of thrombin (II)

3. Stage III - Formation of fibrin threads (I)

D. Fibrinolytic Systems

1. Plasmin activation

2. Protein C activation - thrombomodulin activation of Protein C

3. Tissue plasminogen activator (TPA)

E. Prevention of blood clotting – in the body and in test-tubes

F. Diseases of blood clotting - haemophilia (VIII)

G. Anaemias

RESPIRATORY SYSTEM

I. FUNCTION OF LUNGS - Gas Exchange & Accessory Functions

II. PULMONARY ANATOMY

A. Thoracic Cage

B. Airways

1. Conducting Zone

2. Respiratory Zone

C. Alveolus

III. AIRFLOW MECHANICS

A. Muscle Mechanics - diaphragm, intercostals, abdominals

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B. Pressure-Flow Relationships - Ppl PL Pel Prc

C. Work of Breathing

1. Airway Resistance - Effect of asthma

2. Compliance

Lung & rib cage elasticity - Effect of fibrosis and emphysema

Surface tension in alveoli - Role of surfactant

IV. GAS EXCHANGE

A. Definitions

1. Pulmonary Volumes (VT, IRV, ERV, VC, RV)

2. Dead Space (Vds)

3. Minute Ventilation (VE)

4. Alveolar Ventilation (VA)

5. Gas Partial Pressures (Pa O2 & CO2 Pv O2 & CO2 PA O2 & CO2 & H2O)

B. Gas Exchange

1. Model of Lung Unit

2. Diffusion Equilibrium in Lungs

a. Perfusion Limited O2 Uptake

b. Diffusion Limited O2 Uptake

3. Ventilation-Perfusion Relationships (VA/Q ratio)

a. Uneven blood flow in upright lung

b. Uneven airflow in upright lung

c. Local control of VA/Q ratio

VA control bronchoconstriction and dilation

Q control vasoconstriction and dilation

C. Blood-Gas Transport

1. O2 Transport

a. Dissolved O2

b. Hb-O2 dissociation curve; myoglobin

2. CO2 Transport

a. Dissolved CO2

b. Carbaminohaemoglobin

c. HCO3-

V. CONTROL OF BREATHING

A. Central Control

1. Central Pattern Generator in Medulla

a. Dorsal respiratory group (DRG) - inspiratory neurons

b. Ventral respiratory group (VRG) - expiratory & inspiratory neurons

c. Pre-Bötzinger complex

d.NTS (nucleus tractus solitarius) & NA (nucleus ambiguous)

2. Pontine respiratory group

a. nucleus parabrachialis (NPBL)

3. Hypothalamus

a. Emotive effects on breathing

b. Central command centre (exercise)

4. Cerebral Cortex - voluntary control (talking, singing, breathholding, etc.)

B. Peripheral Control

1. Chemoreceptors - O2 , CO2 , and pH - carotid and aortic bodies

- CO2 & pH - ventral floor of medulla

2. Pulmonary Stretch Receptors in airways

3. Baroreceptors

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4. Proprioceptors in muscles and joints

5. Complex Reflexes - sneeze, cough, yawn

C. Gas Tensions During Exercise

D. Diseases of Breathing

COPD, Sleep apnea, Ondine’s curse (CCHS), Cot death (SIDS)

GASTROINTESTINAL TRACT

I. GI TRACT MOTILITY

A. Anatomy

1. Alimentary Tract

2. Intestinal Wall – Meissner’s and Auerbach’s plexi

B. Electrical Activity (slow waves & spikes)

C. Neuroendocrine Control

1. Nervous Innervation - PSNS, SNS, Enteric Nerves

2. Hormonal Control

CCK (from I cells of duodenum & jejunum)

Secretin (S cells of duodenum)

Gastrin (G cells of stomach)

Gastric Inhibitory Peptide (duodenum & jejunum)

Motilin (duodenum & jejunum)

Others: noradrenalin, adrenalin, serotonin, etc.

D. Type of Movements - Propulsion & Mixing

E. Control of Movements

1. Gastric Emptying - mainly CCK (also secretin, gastrin, ANS)

2. Ileocecal Valve Contraction - distension

3. Colon Movements - Haustrations & Mass Movements

4. Defecation - internal (ANS) and external (conscious) anal sphincters

II. GI TRACT SECRETIONS

A. Saliva

1. Acinar Primary Secretion - ptyalin, mucous, isotonic fluid

2. Ductal Modification - NaCl reabsorption & KHCO3 secretion

3. Final Composition of Saliva

4. Function of Saliva – lubrication, digestion, oral hygiene

5. Control of Saliva

Brainstem - superior and inferior salivatory nuclei

Stimuli - taste & tactile stimuli; appetite centre in hypothalamus;

noxious or nauseous signals from GI tract; SNS; others

6. Diseases - blocked salivary duct, vomiting (chemoreceptor trigger zone CTZ

and vomiting centre in medulla), nausea

B. Esophageal Secretion - mucous

C. Gastric Secretion

1. Oxyntic Glands

Mucous from Neck Cells

Pepsinogen from Chief (Peptic) Cells

HCl and Intrinsic Factor from Parietal (Oxyntic) Cells

2. Pyloric Glands

Mucous

Pepsinogen

Gastrin - stimulates parietal cells to secrete HCl

3. Surface Mucous Cells

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4. Control of HCl Secretion

ACh from nervous control - vagus nerve & local wall reflexes

Gastrin (G cells of stomach)

Histamine

5. Control of Pepsinogen Secretion

ACh from vagus nerve

Acid in stomach

6. Phases of Secretion - cephalic (20%), gastric (70%), intestinal (10%)

7. Diseases - gastritis, peptic ulcer

D. Pancreatic Secretion

1. Enzymes - trypsin, amylase, lipases - primary acinar secretion

2. HCO3- & H2O - ductal secretion

3. Control of Pancreatic Secretion

ACh from PSNS (stimulates acinar enzymes)

CCK from I cells of duo & jejun (stimulates acinar enzymes)

Secretin from S cells of duodenum & jejunum (stimulates HCO3-)

4. Phases of Secretion - cephalic (20%), gastric (5%), intestinal (75%)

5. Diseases - pancreatitis E. Intestinal Secretion

1. Mucous - Brunner's Glands (early duodenum)

controlled by ACh from vagus & tactile stimuli

2. Mucous, Water, & Salts - Crypts of Lieberkühn

3. Control of Intestinal Secretion

Local stimulation by chyme (major)

Secretin & CCK (minor)

4. Diseases - malabsorption syndrome (eg celiac disease), Crohn's Disease

(autoimmune), GI tract obstruction

F. Colonic Secretion

1. Mucous from Crypts of Lieberkühn (tactile stimuli)

2. H2O & Salts (irritation) cause diarrhea (fluids normally absorbed in colon)

3. Diseases - constipation, megacolon (Hirschsprung's Disease),

diarrhea (enteritis from bacterial infection, cholera toxin, psychogenic nervous

diarrhea, flatus

G. Liver Bile Secretion

1. Hepatocyte Secretion

bile acids, cholesterol, lecithin, bilirubin, H2O, and salts

2. Ductal Modification - H2O & salts secreted into duct

3. Storage and Concentration in Gall Bladder

4. Composition of Bile

5. Control of Bile Secretion

gall bladder contraction; peristalsis of duct,; sphincter of Oddi relaxation

CCK due to fatty acids in duodenum

ACh from PSNS

Secretin - increased ductal secretion of HCO3- & H2O

6. Role of Bile Salts and Lecithin (micelles & chylomicron formation)

7. Enterohepatic Circulation of Bile Salts

8. Diseases of the liver- jaundice, hepatitis, cholesterol and gallstones

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LABORATORY EXERCISES

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