Course Outline

Instructor: Dr JMA Hannan

Class time: ST 11.20 am - 12.50 pm

Phone: 9885611 - 20 ext. 284

Human Physiology-1

General Policy

Examination Mark

1st Midterm - 30%Class tests/quizzes 10%Assignment/ Presentation 10%Class participation 5%Viva 5%Final exam - 40%

Total marks - 100

Grading PolicyNumerical Scores Letter Grade

93 and above A Excellent90 – 92 A-

87 – 89 B+

83 – 86 B Good80 – 82 B-

77 – 79 C+

73 – 76 C Average70 – 72 C-

67 – 69 D+

60 – 66 D PoorBelow 60 “F” (Fail)

If you are absent in 3 consecutive classes you will be given “F”

Textbook and reference books

• Text book of Medical Physiology. Guyton and Hall

• Review of the Medical Physiology. William F. Ganong

How to do well in this class?

1. Forget about your previous grade/result

2. Attend lectures and take notes

3. * Effort = Result.

4. Read the syllabus

5. Read exam questions carefully before answering

& answer all parts of a given question

6. Turn assignments in on time

7. Ask if you have questions

The Cardiovascular System The Heart

Cardiovascular SystemCardiovascular System

Anatomy of the HeartAnatomy of the Heart

• Heart chambers:– Left & right atria.

– Left & right ventricles.

• Heart valves:– Atrioventricular valves:

• Right: Tricuspid.

• Left: Bicuspid

– Semilunar valves• Right: Pulmonary valve.

• Left: Aortic valve.

Anatomy of the HeartAnatomy of the Heart

• EpicardiumEpicardium: : – Outer layerOuter layer

• MyocardiumMyocardium::– middle muscle walls.middle muscle walls.

• Endocardium:Endocardium: – Innermost surfaceInnermost surface

3 layers

• Endocardium: lines the lumen of the heart and is composed of simple squamous epithelium and a thin layer of loose connective tissue.

• Myocardium: consists of layers of cardiac muscle cells arranged in a spiral fashion about the heart’s chambers. The myocardium contracts to propel blood into arteries for distribution to the body.

• Epicardium: is the outermost layer of the heart and constitutes the visceral layer of the pericardium. It is composed of simple squamous epithelium on the external surface.

The Conduction System

Bundle of His

Purkinje fibre

Intrinsic Conducting System

• Sinoatrial nodeSinoatrial node– Electrical pace maker.Electrical pace maker.

• Atrioventricular nodeAtrioventricular node– Receives impulses Receives impulses

originating from SA node.originating from SA node.

• Bundle of HisBundle of His– Electrical link between atria Electrical link between atria

and ventricles.and ventricles.

• Purkinje fibresPurkinje fibres– Distribute impulses to Distribute impulses to

ventricles.ventricles.

• The impulse-generating and impulse conducting system of the heart comprises several specialized structures whose coordinated functions act to initiate and regulate the heartbeat.

1. The sinoatrial node, the “pacemaker” of the heart, is located within the wall of the right atrium. It generates impulses that initiate contraction of atrial muscle cells; the impulses are then conducted to the atrioventricular node. 70 - 80 impulse/min

2. The atrioventricular node is located in the wall of the right atrium, adjacent to the tricuspid valve. 40 - 60 impulse/min

3. The Bundle of His is the band of conducting

tissue radiating from the AV node into the

interventricular septum where it divides into

two branches and continues as Purkinje fibers.

30 - 60 impulses/min

4. Purkinje fibers are large, modified cardiac

muscle cells that make contact with other part

of the cardiac muscle. 15 - 40 impulses/min

Electrical impulses from your heart muscle (the myocardium) cause

your heart to beat (contract). This electrical signal begins in the

sinoatrial (SA) node, located at the top of the right atrium. The SA

node is sometimes called the heart's "natural pacemaker." When an

electrical impulse is released from this natural pacemaker, it causes

the atria to contract.

The signal then passes through the atrioventricular (AV) node. The

AV node checks the signal and sends it through the muscle fibers of

the ventricles, causing them to contract.

The SA node sends electrical impulses at a certain rate, but your

heart rate may still change depending on physical demands, stress,

or hormonal factors.

The Conduction SystemMechanism of heart contraction

Cardiac Electro-Physiology• Phase 0: Rapid depolarisation of the cell membrane and it is associated

with the inflow of the Na+ ions.

• Phase 1: A short initial phase of rapid repolarisation due to activation of

a Cl- current (inflow). K+ channel rapidly open and close causing a

transient outward current.

• Phase 2: Action potential plateau. A period of more gradual repolarisation

in which there is a movement of Ca2+ ion into the cell.

• Phase 3: Final repolarisation. A second period of rapid repolarisaion

during which K+ move out of the cell.

• Phase 4: A fully repolarised state during which K+ channel opens. K+ move

into and Na+ out of the cell again to enable the next cycle to begin.

3

4

0

12

4

The Cardiac Cycle

• Systole:Systole: – Period of ventricular contraction.Period of ventricular contraction.– Blood ejected from heart.Blood ejected from heart.

• DiastoleDiastole::

– Period of ventricular relaxation.Period of ventricular relaxation.– Blood filling.Blood filling.

Blood Vessels and Blood Pressure

Blood Vessels

ArteriesArterioles

Capillaries

Venules

Veins

Blood Vessels

• Arteries and veins consist of 3 layers.Arteries and veins consist of 3 layers.– Tunica internaTunica interna (tunica intima): endothelium (tunica intima): endothelium– Tunica media:Tunica media: smooth muscle layer smooth muscle layer– Tunica externaTunica externa (tunica adventitia): connective tissue (tunica adventitia): connective tissue

• Capillaries consist of simply endotheliumCapillaries consist of simply endothelium– Single flattened layer of epithelial cells resting on Single flattened layer of epithelial cells resting on

basement membrane.basement membrane.

Veins vs ArteriesVeins vs Arteries

• Veins– Relatively thinner walls (less smooth muscle).

– Less elastin fibres.

– Some have valves to prevent backflow of blood.

• Arteries– Thick muscular walls (more smooth muscle).

– Have layers of elastin fibres.

– No valves.

Capillaries

• Site of exchange between blood and tissues.Site of exchange between blood and tissues.

• Thin-walled (0.2-0.4 µm).Thin-walled (0.2-0.4 µm).

• 5-9 µm in diameter. 5-9 µm in diameter.

• Arranged into capillary beds.Arranged into capillary beds.

Capillary FunctionCapillary Function

• Diffusion through gaps or fenestrations.Diffusion through gaps or fenestrations.– Small molecular weight molecules (eg. Glucose).Small molecular weight molecules (eg. Glucose).

• Vesicular transport.Vesicular transport.– Endocytosis of material from blood.Endocytosis of material from blood.

Blood Pressure

Blood pressure is the measurement of force applied to the artery walls

The pressure is determined by the force & amount of blood pumped (CO)

& the size and flexibility of the arteries (PR).

Systole heart muscle contraction. Creates high pressure in chamber.

Systolic blood pressure is the pressure generated when the heart beats.

Diastole heart muscle relaxes. Drops pressure in chamber.

Diastolic blood pressure is the pressure in the vessels when the heart is at rest.

Systolic & Diastolic BP

Cardiac Output

Amount of blood pumped into the aorta each minute by the heart.

C.O. (vol/min) = heart rate (beat/min) x stroke volume (vol/beat)

= 75 beat/min x 70 ml/beat

= 5250 ml/min

= 5.25 L/min

Venous return

Quantity of blood flowing from the veins into right atrium each min.

VR = CO

Peripheral resistance

It is the impediment (resistance) to blood flow through the vessel.

BP = Cardiac output x Peripheral resistance

• Short-term BP regulation (Neural mechanisms)

• Long-term BP regulation (Endocrine mechanisms)

(The renin-angiotensin-aldosterone system)

Blood pressure regulation

BP is directly proportional to the production of CO and PR ( CO or PR = BP).

To maintain normal BP - CO and PR are controlled by 2 overlapping control mechanisms.

BP

BP

Sympatheticactivity

Activation of 1 adrenoceptors

on heart

Activation of 1 adrenoceptors On smooth muscle

Na+ & H2Oretention

Glomerular filtration rate

Renin Renal flow

Blood volume

Aldosterone

Long-term mechanism

Short-term mechanism

Cardiac output

Peripheral resistance

Angiotensin II

Ref: Lippincott’s Pharmacologyp181

Contraction of vascular smooth muscle cells & Cardiac cells& role of intracellular Ca2+.

Action in vascular tissue: 3 mechanisms may be possible for the contraction of vascular smooth muscle cells.

First, Voltage sensitive Ca2+ channels open in response to depolarization of the membrane and extracellular Ca2+ enters the cells. Second, hydrolysis of phosphatidylinositol to formation of inositol triphospahete (IP3) which acts as a second messenger to release intracellular Ca2+ from sarcoplasmic reticulum. Third, this intracellular Ca2+ may trigger further infloux of Ca2+ through VDC channel.

This increase in cytosolic Ca2+ results in enhanced binding of Ca2+ to the protein calmodulin. The Ca2+ calmodulin complex activates myosin light-chain kinase which phosphorylates the light chain of myosin. Such phosphorylation promotes interaction between actin and myosin and contrtraction of smooth muscle. Ca2+ channel blockers inhibits the voltage dependant Ca2+ channel.

Action in cardiac cells: Within the cardiac myocytes, Ca2+ binds to troponin and uncovering myosin binding sites on actin, therefore, formation of cross-linkages between actin and myosin, producing shortening and contraction of cardiac muscle.

Ca2+ Channel

Ca2+

Ca2+ calmodulin complex

Active MLCKMyosin LC kinase (MLCK)

Myosin light chain (MLC) Myosin LC-PO4

ContractionContraction

Calmodulin

ActinActin

Na+

Na+

K+

K+

ATPase

Na+

Na+Ca2+

Ca2+

Ca2+

Ca2+

SR

Ca2+

The renin-angiotensin-aldosterone system

BP

CO

Blood Vol.

Blood vessel

BP

Hypertension

SBP DBP

Category of BP (mm Hg) (mm Hg)

Normal < 130 < 85

High-normal 130-139 85-89

Grade 1 hypertension (mild) 140-159 90-99

Grade 2 hypertension (moderate) 160-179 100-109

Grade 3 hypertension (severe) > 180 > 110

WHO Guidelines Subcommittee J Hypertens 1999; 17:151

Hypertension is defined conventionally as blood pressure >140/90 mmHg.

Types of hypertension

Essential hypertension

95%

No underlying cause

Secondary hypertension

5%

Underlying cause

Consequence of specific disease.

Abnormality leading to Na+ retention or peripheral

vasoconstriction

Ref: Davidson’s Medicine, p388

A. Essential Hypertension Genetic factor (American black, Japanese; 40-60%)

Dietary factors (high salt intake, alcohol intake, obesity, lack of exercise)

Stress

Age > 60 years

Factors responsible for developing hypertension

B. Secondary Hypertension Pregnancy (pre-eclampsia) Renal disease

Glomerulonephritis)

Renal vascular disease

Polycystic kidney disease

Endocrine diseaseHyperaldosteronism

Hyperthyroidism

DrugsOral contraceptic containing estrogens

Anabolic steroids

Corticosteroids

NSAIDS (Non-steroidal anti-inflammatory drugs)

Untreated hypertension

DEFINITION

• Congestive heart failure is a condition in which the heart is unable to to pump sufficient blood to meet the needs of the body.

• It can be caused by an impaired ability of the heart muscle to contract or an increased workload imposed on the heart.

CONGESTIVE HEART FAILURE

•A clinical syndrome caused by an accumulation of fluid peripherally (right ventricular failure) or in the lungs (left ventricular failure), or both, from inadequate functioning of the heart. Congestive heart failure is a complication of an underlying disease process.

•Systolic heart failure (the more common form) is due to impaired systolic pumping action of the heart. Diastolic heart failure occurs when the systolic function is normal but the filling of the heart is impaired.

Types of heart failure

Systolic dysfunction or systolic heart failure:

The ventricles are dilated and unable to develop

sufficient wall tension to eject adequate quantity

of blood.

Diastolic dysfunction or diastolic heart failure:

The ventricular wall is thickened and unable to

relax properly during diastole, ventricular filling is

impaired and output is low.

Signs & symptoms of congestive heart failureSigns & symptoms of congestive heart failure

heart rate.

• Rapid muscular fatigue.

• Short breath due to pulmonary edema

• Myocardial hypertrophy ( size of heart) Renal output

• Congestion (excessive amount of fluid) in the chest

Main causes

Coronary artery disease (atherosclerosis)

Long standing hypertension

Valvular heart disease

Congenital heart disease

Dilated cardiomyopathy (disease associated with enlargement of left ventricle)

Factors aggravating heart failure

Myocardial ischemia or infarction

Dietary sodium excess

Excess fluid intake

Arrhythmias

Conditions associated with increased metabolic demand (eg pregnancy, thyrotoxicosis, excessive physical activity)

Administration of drug with negative inotropic properties or fluid retaining properties (e. NSAIDs, corticosteroids)

Alcohol

Pre-loadPre-load After-loadAfter-loadHeart disease

Renin releaseRenin release

Angiotensin IIAngiotensin II

AldosteroneAldosterone

EdemaEdema

NaNa++ & H & H22O O retensionretension

+

+

Tissue perfusion

C.O.

-

-

Renal blood flowRenal blood flow Venous pressureVenous pressure

+

Pathology of Heart FailurePathology of Heart Failure

•‘Angina pectoris’ is a Latin phrase that means "strangling in

the chest." Unlike a heart attack, the heart muscle is not

damaged forever, and the pain usually goes away with rest.

DEFINITION

Heart disease characterized by chest pain that occurs as a result

of inadequate oxygen and blood supply to the myocardium.

Angina is characterized by a sudden, severe pressing substernal

pain radiating to the left arm.

ANGINA PECTORISANGINA PECTORIS

TYPES

1. Stable Angina

2. Unstable Angina

3. Myocardial Infarction

1. Stable Angina

Predictable pattern of exertional pressure sensation in the

anterior chest relieved by rest or nitroglycerin.

History: Chest pain described as tightness, pressure or aching that

is typically located in the substernal area, radiating down one or

both arms for 5 minutes or less, precipitated by exercise or

emotional stress and relieved by rest or nitroglycerin.

2. Unstable Angina

This is characyerized by pain that occurs at rest.

History: More severe anginal pain that lasts more than

30 minutes or that occurs during rest and is not

relieved by rest or sublingual nitroglycerin.

3. Myocardial Infarction

This type of angina refer to "Emergencies of the

Cardiovascular System.

It is the interruption of blood supply to the heart due to

block of coronary artery by thrombus, resulting in

ischemic injury and necrosis of a portion of the

myocardium.

Angina pectoris is the result of myocardial ischemia, which

occurs when the cardiac workload and myocardial oxygen

demands exceed the ability of the coronary arteries to supply

oxygenated blood.

It is the main clinical expression of coronary artery disease

(subintimal deposition of atheromas in the large and

medium-sized arteries serving the heart) (atherosclerosis of

coronary arteries).

CAUSES OF CAUSES OF

ANGINAANGINA

• Hypertension

• Hyperlipidemia

• Diabetes mellitus

• Cigarette smoking

• Family history of premature coronary artery disease

(e.g., father died of coronary artery disease before

reaching 60 years of age).

• Use of oral contraceptives.

• Sedentary lifestyle.

• Obesity

Risk FactorsRisk Factors

DEFINITION

Abnormal heart rhythm that is abnormalities in impulse formation and conduction in the myocardium.

It is the disorder in rate and rhythm of cardiac contraction due to myocardial damage is called cardiac arrhythmia. Types

Bradycardia

Heart rate < 60 bpm; impulse originates in SA node

Tachycardia

Heart rate >100-160 bpm; impulse does not originate in SA node

ARRHYTHMIAS

- irregular heartbeat

- Palpitations

- Chest discomfort

- Shortness of breath

- Dizziness

- Weakness

- Nausea

Signs & symptoms