Cardio
CARDIAC PHYSIOLOGY: PART 1
Cardiac Muscle and Coronary Circulation
Cardiovascular System
The Heart
Systemic and Pulmonary Circulation
Functions of the Heart
Generating blood pressure
Routing blood
Heart separates pulmonary and circulatory circulations
Ensuring one-way blood flow
Heart valves ensure one-way flow
Regulating blood supply
Changes in contraction rate and force match blood delivery to changing metabolic needs
Size, Shape and Position
Located in the mediastinum, between lungs
base = broad superior portion of heart
apex = inferior end, tilts to the left, tapers to point
3.5 in. wide at base
5 in. from base to apex
2.5 in. anterior to posterior
Weighs about 10 oz
Pericardium
Double-layer sac which surrounds heart
Provides room to expand
Resists excessive expansion
Fibrous Pericardium
Outer, tough, fibrous layer of CT
Anchors heart to surrounding structures:
diaphragm
Sternum
Great vessels that exit heart
Serous Pericardium
Thin serous membrane composed of two layers
Parietal Pericardium
Lines inner surface of fibrous pericardium
Visceral Pericardium
Also called epicardium
Covers heart surface
Pericardial Cavity
Cavity between parietal and visceral pericardia
Filled with serous fluid
Reduces friction
Pericarditis
inflammation of the pericardium
Usually results from local spread from adjacent mediastinal structures
Possible causes:
MI
Trauma
Surgery
Infections
Tumors
Primary pericarditis usually due to systemic viral infections
Hinders production of serous fluid
Roughens visceral/parietal surfaces
Pericardial layers may bind and stick together, forming painful adhesions
Adhesions interfere with heart movement
Pericarditis, cont’d
Creates a rustling sound called a pericardial friction rub
Can be heard with a stethoscope
Buildup of pericardial fluid may prevent pericardium from stretching
Can compress the heart, called cardiac tamponade
May result in heart failure
Cardiac Tamponade
Potentially fatal condition
Large volume of fluid or blood accumulates in pericardial cavity
Compresses heart from the outside
Prevents heart from expanding during diastole
Heart cannot effectively pump blood
Patient may die quickly unless fluid is removed
Possible causes:
Rupture of heart wall after MI
Rupture of blood vessels after malignant tumor
Radiation therapy
Trauma
Heart Wall
Epicardium
Also called visceral pericardium
Serous membrane covering heart
Myocardium
Thick muscular layer
Fibrous Skeleton
Network of collageous and elastic fibers
Provides structural support
Attachment for cardiac muscle
Acts as a nonconductor
Important in coordinating contractile activity
Endocardium
Smooth inner lining
Myocarditis
Inflammation of the myocardium
Causes
Infectious in origin
Immune mediated
Idiopathic
Most infections are Viral
Coxsackievirus
South America: Chaga’s disease
Acute rheumatic fever
Most often, cause is not identified
Pathologic Findings
Myocardium infiltrated with:
lymphocytes
Plasma cells
Replaced by fibrosis in chronic disease
Clinical Findings
Fever
Chest pain
Heart failure
Elevated CK-MB
Elevated Troponins
Cardiomyopathy
Primary noninflammatory disease of myocardium
Three major forms recognized:
Dilated Cardiomyopathy
Progressive hypertrophy and dilation of all four chambers
Leads to systolic failure
Heart cannot contract
Most common type
Cause often unknown
Possible causes:
Viral myocarditis
Drugs such as doxorubicin
Alcohol
Hemochromatosis
Hypertrophic Cardiomyopathy
Ventricular myocardial hypertrophy
Leads to diastolic failure
Ventricles cannot properly dilate
Often caused by a genetic disorder
Can affect:
myosin
Other proteins involved in cardiac myocyte contraction
Restrictive Cardiomyopathy
Rarest type
Characterized by ventricular noncompliance
Leads to diastolic failure
Heart becomes rigid
Chambers have difficulty filling with blood
Possible causes:
Systemic diseases
Protein buildups
Inherited genetic traits
Causes of Restrictive Cardiomyopathy
Cardiac Amyloidosis
Abnormal proteins build up in heart muscle
Causes stiffness
Most common cause
Sarcoidosis
Tiny clumps of inflammatory cells called granulomas form in heart
Radiation or Chemotherapy
Can scar heart muscle over time
Hemochromatosis
Excess iron accumulates
Damages heart tissue
Scleroderma
autoimmune disease
Causes tight, hardened tissue
Inherited Mutations
Faulty genes can alter sarcomeric proteins
Causes heart muscle rigidity
Cardiomyopathy Therapy
Only therapy listed in lecture: cardiac transplantation
Heart Chambers
FOUR chambers
Right and Left Atria
Two Superior, posterior chambers
Receive blood returning to heart
Right and Left Ventricles
Two inferior chambers
Pump blood into arteries
Atriventricular sulcus separates atria and ventricles
Anterior and posterior sulci separate the ventricles
Heart Chambers: Internal
Interatrial Septum
Wall separating the atria
Pectinate Muscles
Internal ridges of myocardium
Found in right atrium and both auricles
Interventricular Septum
Wall separating the ventricles
Trabeculae Carneae
Internal ridges in both ventricles
Heart Valves
Ensure one-way blood flow
Atrioventricular Valves
Right AV Valve
Has 3 cusps
Called tricuspid valve
Left AV Valve
Has 2 cusps
Called mitral or bicuspid valve
Chordae Tendineae
Cords connecting AV valves to papillary muscles
Semilunar Valves
Control flow into great arteries
Pulmonary Valve
Blood flows from right ventricle into ______________________________
Aortic Valve
Blood flows from left ventricle into ______________________________
Heart Valves Summary
Atrioventricular
______________________________ / mitral
Semilunar
Main purpose: prevent blood from flowing ______________________________
Valvular Function
Prevent back-flow
Chordae tendineae attach to A-V valves
Papillary muscles attach to chordae tendineae
Papillary muscles contract during systole.
Prevent valve back-flow
Velocity through aortic and pulmonary valves exceeds velocity through AV valves because of smaller opening
AV Valve Mechanics
Ventricles Relax
Pressure drops
Semilunar valves close
AV valves opens
Blood flows from atria to ventricles
Ventricles Contract
AV valves close
Papillary muscles contract
Pull on chordae tendineae to prevent prolapse
Pressure rises
Semilunar valves open
Blood flows into great vessels
Rheumatic Carditis / Rheumatic Fever
immune-mediated disease
Occurs in response to Group A streptococcal antigens
Commonly occurs around ages 5 to 15 years
Develops 1 to 5 weeks after Group A streptococcal pharyngitis
Example organism: →strep pyogenes (strep throat)
Antibodies develop against streptococcal M proteins
Cross-react with similar proteins in human tissue
Rheumatic Carditis Effects
Carditis
Inflammation of all layers of heart wall
Pericarditis
Precordial chest pain
friction rub
Myocarditis
Most common cause of death in acute disease
Endocarditis
Usually involves mitral valve first
Then aortic valve second
Mitral and/or aortic valve regurgitation may cause heart failure
Recurrent infection can lead to:
Mitral stenosis
Aortic stenosis
Mitral Valve Insufficiency / Regurgitation
Retrograde blood flow into ______________________________ during systole
Due to incompetent ______________________________ valve or dilated valve ring
Possible causes:
Mitral valve ______________________________
Infective ______________________________
Rupture or dysfunction of ______________________________ muscle
Volume overload in:
Left ______________________________
Left ______________________________
May lead to ______________________________ heart failure
Murmur occurs during ______________________________ systole
Mitral Valve Prolapse
Can lead to mitral ______________________________
Mitral leaflets billow into ______________________________ during systole
Characteristic ______________________________ click
Followed by high-pitched murmur
Possible symptoms:
Dyspnea
Chest pain
Heart failure
Rarely sudden death
Primary Mitral Valve Prolapse
Most ______________________________ form
Can occur randomly
Can be ______________________________
Linked to specific ______________________________
Secondary Mitral Valve Prolapse
Occurs due to an underlying condition damaging valve structure.
Examples:
______________________________ syndrome
Ehlers-Danlos syndrome
Rheumatic heart disease
______________________________ heart disease
Prior heart attack damaging supporting muscles
Marfan Syndrome
Multi-systemic ______________________________ disorder
Affects ______________________________ tissue
Common features:
Tall and thin
Long arms and legs
Long fingers and toes
Flexible joints
Curved spine
Major cardiovascular complications:
Mitral valve ______________________________
Aortic ______________________________
Ehlers-Danlos Syndromes
Group of ______ genetic connective-tissue disorders
Symptoms may include:
Loose joints
Joint pain
Stretchy ______________________________ skin
Abnormal scar formation
Possible complications:
Aortic ______________________________
Joint dislocations
Scoliosis
Chronic pain
Early osteoarthritis
Mitral Stenosis
Caused by:
Scarring
calcification
Fusion of mitral valve
Interferes with valve opening
Most commonly caused by rheumatic heart disease
Associated with increased left atrial pressure
and Enlarged left atrium
Volume overload occurs in:
Left ventricle
lungs
Can lead to biventricular failure
Murmur:
Opening snap during diastole
Mid-diastolic rumbling murmur
Can eventually cause chronic afib
Raises risk of atrial thrombosis
Aortic Stenosis
Reduction in aortic valve orifice
Decreases cardiac output
Produces concentric left ventricular hypertrophy
Common causes:
Age-related sclerosis and calcification
Rheumatic heart disease
Congenital ______________________________ aortic valve
Possible presentation:
Angina
syncope
Heart failure
Often asymptomatic until late in course
Decreased cardiac output reduces filling of coronary arteries during diastole
Murmur: crescendo-decrescendo ejection murmur during systole
Can lead to sudden death due to:
Arrhythmia
Heart failure
Aortic Valve Insufficiency / Regurgitation
Left ventricle dilation and hypertrophy
Accommodates increased regurgitating diastole volume
Helps maintain adequate cardiac output
Possible causes:
Long-standing HTN
Congenital aortic valve disease
Rheumatic heart disease
Syphilis
Acute insufficiency may result from:
Perforations
Tears
Infective endocarditis
Murmur:
High-pitched “blowing” early diastolic murmur
Occurs immediately after S-2 heart sound
Valve replacement may use:
mechanical valves
Bioprosthetic valves
Infective Endocarditis
Infection of:
Heart valves
Endocardium
Types:
Acute
Subacute
Usually caused by:
Bacteria
Sometimes fungi
Common organisms:
Streptococci
Staphylococci
Staphylococcus aureus
Staphylococcus epidermidis
Viruses do NOT cause endocarditis
Sources of Bacteria
May originate from:
Mouth
Skin
Respiratory system
Urinary tract
Examples:
Dental procedures
IV drug abuse
Skin infections
Infective Endocarditis Complications
Can cause:
Myocardial abscesses
Tissue destruction
Conduction system abnormalities
Severe valvular ______________________________
Heart failure
Death
Embolization of vegetations
Distant organ:
Abscesses
Immune-mediated phenomena such as ______________________________
Infective Endocarditis Risk Factors
Valve abnormalities
Mitral valve ______________________________
Prosthetic valves
Rheumatic valvular disease
Congenital heart defects
Other risks:
Immunosuppression
IV drug abuse
Diagnosis:
Microorganisms demonstrated in ______________________________
Usually ______________________________
Treatment:
Prolonged ______________________________ therapy
Sometimes surgery
High-risk patients may receive prophylactic ______________________________ before procedures
Heart Skeleton
Plate of fibrous ______________________________ tissue between atria and ventricles
Fibrous rings around ______________________________ for support
Provides electrical ______________________________ between atria and ventricles
Site for muscle ______________________________
Coronary Circulation
Blood vessels nourish ______________________________ muscle
Left Coronary Artery
Anterior Interventricular Artery
Supplies:
______________________________ septum
Anterior walls of ventricles
Circumflex Artery
Passes around ______________________________ side of heart
Travels in coronary ______________________________
Supplies:
Left atrium
______________________________ wall of left ventricle
Right Coronary Artery
Marginal Artery
Supplies:
Lateral right ______________________________
Right ______________________________
Posterior Interventricular Artery
Supplies:
______________________________ walls of ventricles
Venous Drainage
______% drains directly into right ventricle
______% returns to right atrium
Great Cardiac Vein
Located in ______________________________ interventricular sulcus
Drains anterior surface
Middle Cardiac Vein
Located in ______________________________ interventricular sulcus
Drains posterior surface
Small Cardiac Vein
Located in ______________________________ sulcus
Drains right margin
Coronary Sinus
Located in posterior ______________________________ sulcus
Collects blood from cardiac veins
Empties into ______________________________
Ohm’s Law
Flow:
Q = ______________________________ / ______________________________
Decreased driving pressure = decreased ______________________________
Increased resistance = decreased ______________________________
Driving Pressure Through Coronary Arteries
Determined by:
Right atrial pressure
Equals:
______________________________ pressure minus ______________________________ pressure
Increase in aortic pressure → ______________________________ coronary blood flow
Increase in right atrial pressure → ______________________________ coronary blood flow
Coronary Vascular Resistance
Determined by:
Coronary artery ______________________________
Degree of compression from ______________________________ contraction
Coronary Artery Diameter
Continuously adjusted to meet ______________________________ needs of myocardium
Controlled by:
Nervous control
Control of Coronary Blood Flow
Local Muscle Metabolism
______________________________ controller of coronary blood flow
Increased vigor of cardiac contraction → increased ______________________________
Increased metabolism → increased coronary ______________________________
Decreased heart rate → decreased ______________________________
Blood flow regulated nearly in proportion to myocardial ______________________________ needs
Autoregulation of Flow
Capillary structure allows metabolic end products to diffuse near:
Precapillary sphincters
Metabolites that stimulate vasodilation:
K+
H+
Bradykinin
Nitric oxide
Prostaglandins
CO2
Tissue maintains ______________________________ despite changes in arterial pressure
Nervous Control of Coronary Blood Flow
Autonomic stimulation can affect flow:
Direct Effects
Parasympathetic
Vagal stimulation releases ______________________________
Directly ______________________________ coronary arteries
Vagal innervation is relatively limited
Sympathetic
Releases:
Beta-2 receptors:
Cause ______________________________
Alpha-1 receptors:
Cause ______________________________
Nervous Control: Indirect Effects
Far more ______________________________ than direct effects
Sympathetic
NE and EPI increase:
Heart rate
Overall heart metabolism
Increased metabolism increases ______________________________ consumption
Causes release of local blood flow regulatory substances
Coronary arteries ______________________________
Flow ______________________________
Parasympathetic
ACh slows:
Metabolism
Decreases O2 consumption
Indirectly ______________________________ coronary arteries
Summary of Coronary Blood Flow Control
______________________________ factors are major controllers
Especially myocardial ______________________________ consumption
Metabolic control can override direct ______________________________ effects within seconds
Coronary Flow and the Cardiac Cycle
Ventricular Contraction
Coronary blood flow ______________________________
Arteries are ______________________________
Ventricular Relaxation
Coronary blood flow ______________________________
Coronary arteries fill as blood surges back toward ______________________________ valve
Endothelial Cells in Cardiovascular Regulation
Functions:
Provide smooth ______________________________ surface
Secrete vasoactive ______________________________
Express receptors that recruit ______________________________ during injury and inflammation
Regulate growth and behavior of vascular ______________________________ cells
Metabolic Needs of the Myocardium
Heart requires continuous:
Nutrients
Disruption of coronary blood flow = ______________________________
Ischemia reduces ______________________________ ability
Severe ischemia can cause myocardial ______________________________
Myocardial ischemia can result from:
Reduced coronary blood flow
Increased ______________________________ needs of heart
Causes of Myocardial Ischemia
Reduced ______________________________ pressure
Low aortic pressure
High right atrial pressure
Reduced vessel ______________________________
Atherosclerosis
Arteriosclerosis
Thrombosis
Vasoconstricting chemicals
Reduced perfusion ______________________________
High heart rate
Some arrhythmias
Increased metabolic ______________________________
Fever
Sepsis
Anemia
Structure of Cardiac Muscle
Short, thick, ______________________________ cells
About – µm long
– µm wide
Usually one central ______________________________
Reduced ______________________________ reticulum
Large ______________________________
Must admit more Ca2+ from ______________________________ during excitation
Intercalated Discs
Join ______________________________ end to end
Interdigitating Folds
Increase ______________________________ area
Mechanical Junctions
Tightly join myocytes
Examples:
______________________________ adherens
Desmosomes
Electrical Junctions
______________________________ junctions
Form channels allowing ______________________________ to flow directly between cells
Cardiac Muscle
Elongated, ______________________________ cells
Contain – centrally located nuclei
Contain:
Intercalated disks = specialized ______________________________ contacts
Desmosomes hold cells ______________________________
Gap junctions allow ______________________________ potentials
Electrically, cardiac muscle acts as a ______________________________ unit
Sarcomere
Extends from one ______________________________ disk to the next
Thin filament contains:
Troponin
Nebulin
Troponin
Troponins ______ and ______ are used as markers of ______________________________ cell death
Subunits:
Troponin ______
Troponin ______
Troponin ______
Ca2+ binds to ______________________________
Thick Filament
Made primarily of ______________________________
Myosin head groups oriented in ______________________________ directions
Phosphorylation of regulatory light chain increases:
Myosin activity
Rate of ______________________________ cycling
Contraction of Myocardium
Myocytes have stable resting potential around ______ mV
Action potential approximately ______ mV
Depolarization
Stimulus opens voltage-regulated ______________________________ channels
______ rushes into cell
Membrane rapidly ______________________________
Action potential peaks around ______ mV
Na+ channels close ______________________________
Plateau Phase
Lasts about – sec in ventricular muscle
Much longer than in ______________________________ muscle
Slow ______________________________ channels open
Ca2+ enters cell
Ca2+ binds to receptors on ______________________________
More Ca2+ released into cytosol
T-tubules are an important source of ______________________________
T-tubule Ca2+ depends strongly on ______________________________ Ca2+ concentration
Repolarization
Ca2+ channels ______________________________
K+ channels ______________________________
K+ moves ______________________________
Membrane returns to ______________________________ potential
Action Potential of Myocyte
Voltage-gated ______________________________ channels open
Na+ rushes ______________________________ → rapid depolarization
Na+ gates close, some ______________________________ channels open
K+ exits → partial ______________________________
Slow ______________________________ channels open
Ca2+ enters → ______________________________ phase
Ca2+ channels close
K+ channels open
K+ exits → rapid ______________________________
Calcium-Induced Calcium Release
Ca2+ enters through voltage-gated ______________________________ channels
Interacts with ______________________________ receptors
Located on sarcoplasmic reticulum
Causes additional Ca2+ release into ______________________________
Calcium initiates ______________________________
Ca2+ is rapidly captured by ______________________________ pumps
Located on ______________________________ membrane
Cross-Bridge Cycle
Step A
Myosin hydrolyzes ATP to:
Pi
Step B
Ca2+ binds to ______________________________
______________________________ moves away
Exposes actin-binding sites
Myosin binds ______________________________
Step C
ADP and Pi are released
______________________________ stroke occurs
Step D
New ATP binds myosin
Myosin affinity for actin ______________________________
Myosin releases actin
Each cross-bridge cycle uses ______ ATP molecule
Duration of Contraction
Determined by duration of ______________________________ potential
Approximate durations:
Atrial muscle: ______ sec
Ventricular muscle: ______ sec
When HR increases:
Contraction duration ______________________________
Relaxation duration ______________________________
______________________________ decreases more than systole
Normal HR:
Around ______ bpm
Contraction ≈ ______% of cardiac cycle
At 3× normal HR:
Contraction ≈ ______% of cycle
Diastolic period can become significantly ______________________________
May cause incomplete ventricular ______________________________
Metabolism of Cardiac Muscle
Primarily ______________________________ respiration
Rich in:
Glycogen
Large ______________________________
Organic fuels:
Fatty acids
Ketones
Cardiac Fuel Use
Fasting
Fatty acids ≈ ______%
Glucose ≈ ______%
Postprandial
Fatty acids ≈ ______%
Glucose ≈ ______%
Cardiac muscle is highly ______________________________ resistant
Myocardial Energy Balance
______________________________ is a marker of myocardial cell death
Creatine kinase reaction:
Creatine + ATP ⇄ ____________________ + ____________________
Coronary Artery Disease
Significance
About ______ of all deaths due to CAD
______% of deaths are cardiovascular
About ______% due to cancer
Clinical syndromes:
Acute coronary syndrome
Chronic ischemic heart disease
______________________________ cardiac death
Coronary Artery Disease Etiology
Coronary ______________________________
Progressive formation of elevated ______________________________ plaques
Occur in the ______________________________ of coronary arteries
Causes narrowing of vessel ______________________________
Decreases blood flow
May lead to ______________________________
CAD Risk Factors: Not Reversible
Male sex
Genetic ______________________________
CAD Risk Factors: Reversible
______________________________ smoking
Increased ______________________________
Obesity
Left ventricular ______________________________
Smoking:
Decreases ______________________________
Increases risk of death from heart attack
High blood pressure:
Causes vascular ______________________________
Partially Reversible CAD Risk Factors
Increased ______________________________
Increased triglycerides
Hyperglycemia
______________________________ mellitus
Low ______________________________ levels
Other CAD Risk Factors
Physical ______________________________
Personality type
______________________________ protein
Pathogenesis of Atherosclerosis
Lipid accumulates in ______________________________ wall
______________________________ infiltrate wall
Lipids become ______________________________
Inflammation develops
Local ______________________________ factors released
Plaque forms on ______________________________ wall
Mini thrombi may become incorporated into plaque
Plaque ______________________________ can occur
Vessel wall ______________________________ occurs
Atherosclerosis Sequence
Chronic endothelial injury
Endothelial dysfunction
Increased permeability
Activated monocytes infiltrate wall
Smooth muscle ______________________________
Macrophages engulf lipid
Become ______________________________ cells
Lipid core forms
______________________________ cap develops
Demand > Supply: Angina
Decreased Supply
Decreased perfusion ______________________________
Fixed ______________________________
Decreased oxygen ______________________________
Increased Demand
Increased ______________________________
Increased contractility
Increased ______________________________
Increased heart rate
Increasing Supply / Decreasing Demand
Increase Supply
______________________________ with stent
CABG
Decrease Demand
Medications:
______________________________ blockers
Ca2+ channel blockers
Pathogenesis of Acute Coronary Syndrome
Plaque disruption or ______________________________
Tissue ______________________________ exposed
Platelet aggregation activated
______________________________ cascade activated
Thrombus formation
Acute ______________________________
Ischemic Syndromes
Stable Angina
Fixed stenosis > ______%
Pain:
Relieved by rest
Usually – min
Serum enzymes: ______________________________
Unstable Angina
Thrombus with ______________________________
Pain:
Unpredictable
Not relieved by ______________________________
Serum enzymes: ______________________________
Myocardial Infarction
Thrombus with ______________________________
Pain:
Unpredictable
Not relieved by rest
Often > – min
Serum enzymes: ______________________________
Treatment of Acute Coronary Syndrome
If ECG shows ischemia:
Continuous ______________________________ monitoring
Labs
Give ASA
Relieve pain with:
Sublingual ______________________________
Morphine
Evaluate for ______________________________ therapy
Decrease myocardial O2 demand
Manage:
Dysrhythmias
Myocardial Infarction
Sudden ______________________________ of heart tissue
Caused by interruption of ______________________________
Due to vessel narrowing or ______________________________
Anastomoses
Provide ______________________________ blood pathways
Help defend against interruption of flow
Examples:
Circumflex + ______________________________ coronary artery → posterior interventricular artery
Anterior + posterior interventricular arteries connect at ______________________________
Sequela of Myocardial Infarction
Decreased myocardial ______________________________
ST changes
Q waves
Elevated ______________________________
Partially ischemic cells:
Switch toward ______________________________ metabolism
ATP becomes reduced
Totally ischemic cells:
No ______________________________
Ion leak across cell membrane
Cell ______________________________
Cell death
Cardiac Catheterization
Comprehensive, ______________________________ procedure
Catheter threaded into ______________________________
Can diagnose:
Coronary artery disease
Narrowed heart ______________________________
Congenital heart defects
Can treat:
______________________________ with stent placement
Valve repair
Valve replacement
Catheter Insertion
Catheter inserted into an ______________________________
Common sites:
Groin
Guided toward the ______________________________
Coronary Angiogram
Imaging component of catheterization
______________________________ dye injected through catheter
Used to visualize arterial ______________________________
Uses ______________________________ imaging
Rapid series of pictures/videos is taken
Cardiac Catheterization Intervention
If angiogram reveals a ______________________________
Procedure may immediately proceed to:
Stent placement
CABG and Angioplasty
Angioplasty
Used to reopen ______________________________ coronary artery
Often followed by placement of a ______________________________
CABG
Creates an alternate route for blood around a ______________________________ coronary vessel