Cardiovascular System:

The Heart

Heart Size, Shape, Mass• About the size of a

closed fist:– 3.5” wide (at widest

pt) X 5” long. 2.5” thick

• Cone-shaped: Base & Apex

• 8 oz in adult females, 10 oz in adult males

Heart Location

• In the mediastinum (tissue between sternum & vertebral column)

• 2/3 of its mass is left of midline

• A cone lying on its side:– Base is toward your right shoulder,

apex points to your left hip

• Anterior surface - deep to sternum

• Inferior surface – on diaphragm

• Right border – against right lung.

• Left border (pulmonary border) – against left lung

PERICARDIUMFibrous, Serous (Visceral & Parietal)

Fibrous & Serous pericardium

• Pericardium – the sac that surrounds, protects, anchors heart to diaphragm. It is composed of 2 layers - the fibrous & serous (visceral & parietal layers) pericardium

The FIBROUS Pericardium

• FIBROUS PERICARDIUM– Outermost layer– Tough, inelastic, dense irregular CT– Prevents overstretching of heart– Anchors heart to diaphragm. Prevents rising of heart

The SEROUS PERICARDIUMSEROUS pericardium: thinner, delicate, inner layers that form a fluid-filled sac. It has 2 continuous layers:

1. Parietal layer: is adhered to fibrous pericardium

2. Visceral layer aka “Epicardium”: is adhered to heart

– The pericardial cavity is filled with Pericardial fluid. The pericardial cavity is the space between parietal & visceral layers.

– The pericardial fluid PREVENTS FRICTION

Systemic & Pulmonary Circulations

• Two closed circulatory systems:1. Body 2. Lungs

• The output of one becomes the input of the other with each beat of the heart

Blood Flow Within the

4 Heart Chambers

FYI: is it just a pump?

Cardiac Output (CO)

Heart pumps 5 L bloodPER MINUTE

• Total volume of blood in the body is approximately 5L. CO is typically about 5L/min

• CO= Amount of blood pumped by left or right ventricle PER MINUTE

• CO depends on Heart Rate & Stroke Volume

1. HEART RATE ie number of beats per minute. Normal is 75BPM

2. STROKE VOLUME ie. the amount of blood ejected from one Ventricle PER BEAT. Normal is 70ml/beat in a 70 kg healthy man

ELECTRICAL ACTIVITY OF THE HEART

Autorhythmic vs Contractile myocytes

• The Heart has 2 kinds of cells:– Autorhythmic myocytes (purple circle / yellow cell) spontaneously

depolarize and generate action potentials

– Contractile myocytes (pink cells) contract together to pump blood as the action potential spreads across them

The Sinoatrial (SA) Node or Pacemaker

• The SinoAtrial (SA) node is an area of modified cardiac myocytes within the R atrium.– Cells here spontaneously depolarize (become more positive) 100 x/min

a) Pacemaker potential: the spontaneous depolarization from -60 to -35mV that precedes the action potential

b) Action potential: the depolarization that occurs after threshold of -35 mV

Action Potential at the SA Node

1. SA node cells do not “rest”2. Na+ channels spontaneously open at -60mV. Thus Na+ leaks into SA

node cells which initiates the pacemaker potential (If –funny current)3. Then Ca2+ enters the cell. 2nd part of pacemaker potential & depolarizes

cell to reach action potential4. Finally, K+ exits cell which repolarizes the cell membrane to -60mV

Features of Cardiac Contractile Cells

• Exhibit branching• Intercalated disks: at end of

each myocyte, its sarcolemma thickens– Stair-step appearance– 2 disks are held together

by Desmosomes • Gap junctions connect

cytoplasm of adjoining cells• Striated/Sarcomeres: same

structure as skeletal muscle cells: bands & zones of actin &myosin, z-discs, m-lines

• Sarcoplasmic reticulum: smaller w less Ca2+ reserve

• T-tubules: 1 per sarcomere. located at the z-disk

• Mitochondria: Larger, more numerous (25% of cytosol)

• One central nucleus: cardiac myocytes are shorter in length

Positive ions pass from SA to Contractile Cells through Gap Junctions

• Gap junction: a channel formed between two cells by 2 adjoined connexons. Connects cytoplasm of 2 cells, allowing ions & small molecules to pass through to adjoining cells quickly.

• Positive ions (Ca2+ & Na+) from autorhythmic cells enter the adjacent contractile cells through gap junctions

Contractile Cell Depolarization –

Fast Na Channels

1. Gap Junction: Positive ions (Na+ & Ca2+ enter through gap junctions which triggers:

2. Rapid Depolarization: Fast voltage-gated Na+ channels on the sarcolemma open. The cell instantly becomes positive on the inside.

3. Plateau Phase: at +20mV Ca2+ & K+ channels open. Influx and efflux of positive ions is balanced so AP graph plateaus.

Calcium-Triggered Calcium Release – plateau and contraction• Na+ & Ca2+ influx from an

adjacent cell changes voltage (key) – NOT NEUROTRANSMITTERS

• Voltage-gated Ca channels in T-tubules open & Ca enters cell from ECF

• Calcium-triggered calcium release: Ca entering cell binds to ryanodine receptors, which are Ca channels on the sarcoplasmic reticulum

• Sarcoplasmic Ca stores are released into cell…

• Ca binds to troponin,

tropomyosin moves off myosin binding sites, myosin binds to actin & the sarcomeres shorten

Plateau, Contraction, Repolarization

• Ca2+ channels and K+ channels are open at the same time.

• Ca2+ enters the cell, while K+ leaves, creating a plateau in the AP graph

• Ca2+ channels close, while K+ channels remain open – so the cell becomes more negative inside, or, repolarizes

cardiac excitation-contraction coupling

Action potential vs contraction

• Action potential is generated first in the SA node, • Then the action potential spreads to the contractile myocytes.• After the contractile myocytes depolarize, the sarcomeres

shorten and a contraction is generated.

Tetanus• Unlike skeletal muscle,

cardiac muscle cannot enter tetanus (sustained contraction).

• The cardiac cell has a refractory period that is almost as long as the entire muscle twitch

HEART RATE REGULATIONSympathetic & Parasympathetic

Parasympathetic Vagus Nerve (ACh) Slows HR

• Parasympathetic Vagus nerve innervates SA & AV nodes and atrial myocardium. It releases ACETYLCHOLINE which binds to muscarinic receptors on cardiac mm. Binding of Ach & muscarinic receptors causes K+ to leave the cells so:

• SLOWS rate of depolarization of SA & AV nodes, thus HEART RATE DECREASES• (Contractile Fibers: little effect on contractility because does not innervate ventricles)• Vagus N. slows SA node to normal HR. Normal HR = 70-100 BPM.

Sympathetic Nerves (NE) Increase HR & Contractility

• Sympathetic “Cardiac Accelerator Nerves” innervate SA & AV nodes, and most of the myocardium. They release NOREPINEPHRINE NT which binds to β1 receptors. Binding of NE to β1 enhances Ca2+ entry to cell, thus, at:– SA & AV nodes, it speeds rate of depolarization so HEART RATE INCREASES– Contractile Fibers,more crossbridges form and CONTRACTILITY INCREASES– 100-150 (simple tachycard), 150-200 (paroxysmal), 250-350 (flutter), 350+ (fibrillation)

Input for Heart Rate Regulation

• Input to the Cardiovascular Center in medulla oblongata comes from:– Brain - cortex, limbic system (eg anxiety), hypothalamus – Sensory Receptors - proprioceptors (limb position), chemoreceptors,

baroreceptors (artery & vein stretch, blood pressure changes)

Chemical & Other Regulation of HR

INCREASES HEART RATE & CONTRACTILITY– Hormones:

• Epinephrine• Norepinephrine• Thyroid hormones

– Cations:• Ca2+

– Other:• Increased body

temperature (fever, exercise)

TACHYCARDIA: increased resting heart rate (>100bpm for adult)

DECREASES HEART RATE & CONTRACTILITY– Cations:

• K+ blocks generation of AP (Hyperkalemia)

• Na+ blocks Ca inflow during AP

– Other:• Decreased body

temperature (hypothermia)

BRADYCARDIA: decreased resting heart rate (<50bpm for adult)

Damage to pacemaker, or Ectopic pacemakers

produce Arrhythmias

THE CARDIAC CYCLE & EKG

Sequence Of Cardiac Conduction & Contraction• The Sinoatrial (SA) node

generates action potentials (AP)

• AP propagates through walls of both atria via gap junctions.

• ATRIA CONTRACT

• Atrioventricular (AV) node in inter-atrial septum slows AP conduction

• AP can only pass from atria to ventricles through AV bundle (Bundle of His)

• AP propagates down inter-ventricular septum to apex via Right and left bundle branches

• Purkinje fibers conduct AP from apex up walls of ventricles.

• VENTRICLES CONTRACT.

ECG & Cardiac Cycle

• P- atrial depolarization• QRS complex: Q- septal depolarization, R- early ventricular depolarization, S- late

ventricular depolarization• T- ventricular repolarization

Cardiac Depolarization

• SA node: 60-100 bpm• Atrial cells: 55-60 bpm• AV node: 45-50 bpm• HIS bundle: 40-45 bpm• Bundle branch: 40-45 bpm• Purkinje cells: 35-40 bpm• Myocardial cells: 30-35 bpm

Large P waves: enlargement of atriaLarge R waves: enlarged ventricles

FYI: EKG leads• Electrodes are placed on:

– arms & legs (limb leads: I, II, III, AVR, AVL and AVF)

– 6 positions on chest (chest leads: V1, V2, V3, V4, V5, V6).

• limb leads provide views of cardiac activity in frontal plane

• chest leads provide views in horizontal plane

• 12 different tracings are produced

• Can tell:1. Abnormal conducting pathway2. Enlarged heart3. Damaged regions of heart4. Cause of chest pain

Normal Lead II Tracing• movement of charges (ions)

generate an electrical current

• electrical currents from cardiac action potentials can be detected on the surface of the body

• Electrocardiogram: recording of electrical signals.

• Electrocardiograph: instrument used

Cardiac Cycle = one heartbeat

• Systole= Contraction

• Diastole = Relaxation

• Cardiac cycle = one heartbeat:– systole & diastole

of atria+

– systole & diastole of ventricles

Cardiac Cycle

1) START: Passive ventricular filling. 80% of the ventricle fills at rest, or DIASTOLE. Approximately 105mL.2) Atria contract & pump 25mL (20%) more into ventricles so the End Diastolic Volume is about 130mL.3) QRS - ventricular DEPOLARIZATION.4) Isovolumetric Ventricular contraction - AV valves shut (ventricles are exerting force but not shortening)5) Ventricular ejection or SYSTOLE. SL valves open as ventricular pressure exceeds aortic/pulmonary pressure6) 70mL ejected into aorta & pulm trunk. Volume remaining in each ventricle(~60mL) is End Systolic Volume

S1

S2

HEART VALVES Closing Valves Produce Heart Sounds – S1 & S2

4 Heart Valves: 4 Fibrous rings (valve annuli)

• 4 Dense connective tissue rings surround the valves & are fused together. Creates an electrical barrier.

Electrical insulation. Prevents valve overstretching

Fibrous Skeleton Of The Heart

• *Rings prevent valve overstretching• *Act as electrical insulation between atria & ventricles• Insertion points for cardiac muscle fibers• The 4 rings merge with the interventricular septum

Heart Valves: 2 AV & 2 Semilunar valves

• When the 2 atria contract: AV or atrioventricular valves (tricuspid + mitral) valves open

• When 2 ventricles contract: Semilunar (aortic+ pulmonic)valves open

Atrioventricular or “AV” Valves, S1

• AV valves: TRICUSPID & BICUSPID VALVES • When AV valves are Open, during ventricular filling:

– Atria are pumping blood into ventricles– Valve cusps project into ventricle– Chordae tendinae are slack & papillary muscles relaxed

• When AV valves are Closed, during ventricular contraction, S1:– AV cusps meet & close– chordae tendinae are taught & papillary muscles contracted

• **AV valves prevent backflow of blood to atria when ventricles are contracting

Chordae tendinae & papillary muscles of AV valves

• Structures on Mitral & tricuspid valves only• When atria contract, chordae tendinae are slack, hanging threads of

connective tissue• When ventricles contract, blood pushes up against bottom of valve leaflets

causing them to close & balloon up, like a parachute.• Papillary muscles contract, pulling on chordae tendinae to keep valve closed

Semilunar (SL) Valves, S2

• Semilunar Valves = AORTIC & PULMONARY VALVES

• SL valves open when

pressure in the ventricles exceeds pressure of blood sitting in the arteries

• SL valves close when ventricles relax.

• This creates the heart sound – S2

• Prevent backflow of blood from arteries into ventricles

Heart Sounds: S1, S2• Auscultation – listening to

sounds within the body

• First sound, S1, “lubb” is louder, longer– AV valves close due to– VENTRICULAR SYSTOLE /

contraction

• Second sound, S2, “dupp” is shorter, not as loud– Semilunar valves close

due to– VENTRICULAR DIASTOLE /

relaxation

STROKE VOLUMEPreload, Contractility, Afterload

Stroke Volume (think “Beat volume”) Stroke volume depends on:

1. PRELOAD - volume of blood in the ventricle before it contracts (ie end diastolic volume) • Frank-Starling law: increased venous

return = increased stroke volume (because more ventricular stretch= greater contraction)

2. CONTRACTILITY (Inotropy) – muscular strength of the contraction• Positive inotropic agents Ca2+ thus

# of cross bridges & force of contraction: Ca, Epi, NE

• Negative inotropic agents- # of cross bridges, force of contraction: Ca channel blockers, ß-blockers

3. AFTERLOAD – the pressure behind the semilunar valves that must be exceeded for blood to be ejected from ventricles (ie mean arterial pressure)

CORONARY (CARDIAC) CIRCULATION

Blood flow and oxygen supply to the heart muscle

Coronary (Cardiac) Circulation

• The myocardium (heart muscle) has its own blood supply, the coronary, or cardiac, circulation

Right Coronary Artery supplies Right & Back

of heartRight coronary artery

supplies:

– R atrium via Atrial branches

– R ventricle, Lateral side via Right marginal branch

– Posterior walls of 2 ventricles via Posterior interventricular branch

Coronary Veins

• Coronary Sinus – a large vessel on posterior surface of the heart

– Drains all deoxygentated myocardium blood into R atrium

– Collects blood from• Great (front), Middle

(back), Small (R) & Anterior (R) cardiac veins

Cardiac Circulation

• 2 Coronary arteries (R & L coronary aa) branch off from the ascending aorta

• When ventricles contract, coronary arteries are squeezed shut

• When ventricles relax, blood from the aorta rushes into the coronary arteries, oxygenating the myocardium

ATP synthesis

• ATP production in cardiac myocytes is mostly made by AEROBIC cellular respiration in cardiac mitochondria

• Aerobic ATP synthesis requires oxygen for oxidative phosphorylation of ADP to ATP

• O2 is supplied by myoglobin in cardiac cells or hemoglobin from cardiac circulation

• Some ATP is produced from creatine phosphate– If creatine kinase (CK-MB) is

found in blood (leaked from damaged cells) it’s a sign of myocardial infarction

Fuels for ATP production in Cardiac Myocytes

– Fuels at rest:• 60% fatty acids• 35% glucose

– Fuels during exercise:• Above fuels +• Amino acids, ketone bodies & lactic acid from skeletal muscle

Coronary artery disease

• Myocardial Ischemia: narrowed artery reduces blood/ oxygen supply (hypoxia), weakening myocardium & producing squeezing pain (angina pectoris)

• Myocardial Infarction: blocked artery, complete obstruction of blood flow to myocardium resulting in distal tissue death

Angiogram, angioplasty, stent

Reperfusion Damage

• “Reperfusion” = reestablishing blood flow to myocardium after blockage of a coronary artery

• Reperfusion damages heart tissue further due to formation of oxygen free radicals from reintroduced oxygen, and Ca2+, and activation of the immune system

• Antioxidants like glutathione peroxidase, Catalase can mitigate the effects.

HEART VALVE DISORDERSStenosis & Insufficiency

Heart Valve Disorders: Stenosis

• Age-related Aortic stenosis is most common type

• Mitral Valve Stenosis is most commonly due to Rheumatic fever. 2-3 wks after strep infxn - antibodies inflame the CT of joints, heart valves (usually mitral) and other organs.

Heart Valve disorders: Insufficiency

• Valve Insufficiency / incompetence – failure to close fully leads to backflow of blood (regurgitation). May be due to HTN, post-infection…

Hear Valve Disorders: Stenosis

• Stenosis (narrowing) – valve leaflets thicken, stiffen, or fuse together so it cannot fully open.

• May be due to calcification, post-inflammation, scar formation, tumors, congenital

• Age-related Aortic Stenosis from calcification is most common type

Heart Valve Disorders: Insufficiency w Regurgitation

Most common valves affected:

• Mitral insufficiency – backflow of blood from L ventricle to L atrium

– Mitral valve prolapse (MVP) – one or both valve cusps protrude into L atrium during ventricular contraction

• Aortic insufficiency – backflow of blood from aorta into L ventricle

Congestive Heart Failure• In CHF, the heart is a failing pump:• Stroke Volume decreases, blood

remains in ventricle (end systolic volume increases)

• End diastolic volume increases gradually (ventricle enlarges)– If Left ventricle fails first,blood

backs up into lungs, get Pulmonary edema

– If Right ventricle fails first, blood backs up in body, get Peripheral edema

• CHF may be due to: coronary artery disease, congenital defects, long-term high blood pressure (increases afterload), myocardial infarctions, valve disorders.