Overview of Cardiac Pathophysiology

Slide 1 · Overview of Cardiac Pathophysiology

Six mechanisms that connect cardiovascular lesions to dysfunction

Mechanism → hemodynamic stress → functional consequence

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · What a cardiac lesion can disrupt

Effective contraction and relaxation of myocardium

One-way movement of blood through valves and vessels

Electrical sequencing of atrial and ventricular contractions

Integrity of the vascular circuit and adequate coronary perfusion

Slide 3 · Six routes to cardiovascular failure

Pump failure

Impaired ejection or filling

Obstruction

Resistance to forward flow

Regurgitation

Backward movement of blood

Shunt

Inappropriate communication

Conduction disorder

Ineffective electrical coordination

Rupture

Loss of circulatory continuity

Slide 4 · An abnormality can have several effects

Primary lesion

Altered pressure, volume, rhythm, or flow

Compensatory adaptation

Clinical dysfunction

A structural lesion may disturb both loading conditions and effective cardiac output.

Compensation can initially preserve perfusion yet become maladaptive.

Slide 5 · The heart is two pumps in series

RA

RV

Pulmonary circuit

LA

LV

Systemic circuit

Systemic veins

Venous return

Schematic: The cardiovascular system is a closed circuit

Slide 6 · Systole and diastole answer different demands

Systole

Ventricular myocytes contract

Effective chamber emptying

Failure reduces forward ejection

Diastole

Myocardium relaxes

Ventricles accept filling blood

Failure raises filling pressure

Slide 7 · Myocardial fiber orientation supports pumping

Left ventricle

Spiral and circumferential fibers

Coordinated apex-to-base contraction

Supports high-pressure systemic output

Right ventricle

Longitudinal shortening

Inward free-wall movement

Bellows-like ejection

Slide 8 · The myocardium has high oxygen dependence

Oxidative phosphorylation

Continuous oxygenated coronary flow

ATP-dependent contraction and relaxation

Ischemic vulnerability

Mitochondria occupy approximately 20%–30% of myocyte volume.

Limited ability to regenerate myocytes magnifies the consequences of injury.

Slide 9 · Coronary arteries supply contractile tissue

Coronary ostia at aortic root

Epicardial arteries

Intramural arteries and arterioles

Myocardial capillaries

Coronary arteries function physiologically as end arteries.

Collateral anastomoses exist but do not eliminate ischemic susceptibility.

Slide 10 · Left ventricular perfusion favors diastole

Ventricular systole

Intramural microvessels compressed

Coronary delivery constrained

Myocardial force generated

Ventricular diastole

Aortic valve closed

Reduced myocardial compression

Coronary flow permitted

Slide 11 · Tachycardia shortens perfusion opportunity

Higher heart rate

Shorter relative diastole

Less coronary perfusion time

Potential ischemic stress

Increased heart rate can coincide with increased myocardial oxygen demand.

Shorter diastole is particularly important when coronary reserve is limited.

Slide 12 · Four valves preserve unidirectional flow

Right atrium

Tricuspid valve

Right ventricle

Pulmonary valve

Left atrium

Mitral valve

Left ventricle

Aortic valve

Atrioventricular: Tricuspid and mitral

Semilunar: Pulmonary and aortic

Stenosis obstructs forward flow; Incompetence permits reverse flow.

Slide 13 · Mitral and tricuspid competence requires support

Valve leaflets

Chordae tendineae

Papillary muscles

Ventricular geometry

Failure of any element may prevent leaflet coaptation.

Ventricular dilation can create insufficiency despite anatomically intact leaflets.

Slide 14 · Semilunar valve competence needs intact geometry

Valve cusps

Cuspal attachments

Aortic root geometry

Competent diastolic closure

Dilation of the aortic root can produce aortic regurgitation.

A valve need not have a primary cusp lesion to become incompetent.

Slide 15 · Three connective-tissue layers support valve function

Fibrosa

Dense collagen

Spongiosa

Loose connective tissue

Ventricularis / atrialis

Elastin-rich recoil

Schematic valve leaflet architecture; Not a histologic specimen

Slide 16 · Normal electrical activation is ordered

SA node

Atrial myocardium

AV node delay

His–Purkinje system

Sinoatrial node initiates the predominant rhythm.

Atrioventricular node delays transfer to the ventricles.

His–Purkinje network rapidly distributes ventricular activation.

Slide 17 · The fastest normal pacemaker governs rhythm

Sinoatrial node

Normally 60–100 beats/min

Outpaces subsidiary pacing sites

Initiates usual sinus rhythm

Escape pacemakers

May take over when SA node fails

Typically slower spontaneous rate

Can preserve limited cardiac activity

Slide 18 · Atrioventricular delay protects filling sequence

Atrial activation

AV nodal delay

Atrial contraction precedes ventricle

More coordinated ventricular filling

AV nodal conduction is physiologically delayed.

Loss of proper sequencing can impair effective pumping.

Slide 19 · Electrical function responds to physiology

Neural input

Vagal stimulation

Adrenergic drive

Circulating adrenaline

Oxygenation

Hypoxia

Electrolytes

Potassium disturbances; Hyperkalemia may block transmission

Slide 20 · Pump failure has two fundamental modes

Systolic dysfunction

Weak ventricular contraction

Incomplete chamber emptying

Reduced ejection

Diastolic dysfunction

Impaired ventricular relaxation

Restricted filling

Elevated filling pressures

Slide 21 · Contractile impairment reduces forward output

Myocyte dysfunction or loss

Weaker ventricular contraction

Less blood ejected per beat

Reduced tissue perfusion

Ischemic injury and chronic overload are examples.

Compensatory systems may initially mask inadequate myocardial performance.

Slide 22 · Diastolic stiffness raises upstream pressure

Fibrosis, hypertrophy, or infiltration

Reduced ventricular compliance

Higher filling pressure

Backward pulmonary congestion

Diastolic failure can occur without marked impairment of ejection fraction.

Amyloid deposition and constrictive pericarditis are identified contributors or mimics.

Slide 23 · Ejection fraction measures relative ejection

LVEF (%) = 100 × (end-diastolic volume − end-systolic volume) / end-diastolic volume

Normal LVEF as approximately 50%–70%.

A reduced LVEF supports systolic impairment but does not characterize every form of cardiac dysfunction.

Slide 24 · Reduced and preserved EF identify different patterns

HFrEF

LVEF ≤40%

Systolic dysfunction predominates

Reduced ejection fraction

HFpEF

LVEF ≥50%

Diastolic dysfunction is prominent

Adequate EF does not exclude failure

Slide 25 · Forward and backward failure coexist

Forward failure

Inadequate tissue perfusion

Reduced downstream oxygen delivery

Organ hypoperfusion

Backward failure

Raised venous pressure

Pulmonary congestion or systemic edema

Fluid accumulation

Slide 26 · Acute stresses may overwhelm reserve

Abrupt perturbation

Myocardial infarction

Sudden valvular failure

Acute fluid overload

Chronic workload

Systemic hypertension

Longstanding valve disease

Progressive ischemic myocardial damage

Slide 27 · Frank–Starling compensation has a limit

More ventricular filling

Greater myocyte stretch

Stronger systolic contraction

Temporary support of output

Increased filling volume can support stroke output early.

Persistent overload may eventually exceed this compensatory capacity.

Slide 28 · Neurohumoral adaptation maintains perfusion

Adrenergic activation

Increases rate and contractility

RAAS activation

Retains salt/water and increases tone

Natriuretic peptides

Promote natriuresis and vasodilation

Myocardial remodeling

Adapts structure to workload

Slide 29 · Sympathetic signaling supports output acutely

Adrenergic nerve activity

Norepinephrine release

↑ rate and contractility

Short-term circulatory support

Adrenergic stimulation also raises vascular resistance.

Persistent neurohumoral activation contributes to the burden of heart failure.

Slide 30 · Renin–angiotensin–aldosterone activation raises load

Perceived underperfusion

RAAS activation

Salt and water retention

Higher vascular and filling loads

Volume expansion can temporarily support perfusion.

Ongoing fluid retention can aggravate edema and congestion.

Slide 31 · Natriuretic peptides oppose salt retention

ANP

Granules in atrial myocytes

Released with stretch

Promotes diuresis and vasodilation

BNP

Found in ventricular myocytes

Related to myocardial stretch

Promotes natriuresis and vasodilation

Slide 32 · Remodeling begins as an adaptive response

Hemodynamic stress

Myocyte growth and protein synthesis

Changed ventricular geometry

Potentially impaired function

Ventricular remodeling includes molecular, cellular, and structural changes.

Increased workload may be due to pressure loading, volume loading, or regional injury.

Slide 33 · Pressure overload favors concentric hypertrophy

Sustained pressure load

Sarcomeres mainly in parallel

Greater myocyte width

Thicker ventricular wall

Hypertension and aortic stenosis exemplify pressure loading.

Compensatory myocardial growth can create increased oxygen demand.

Slide 34 · Volume overload favors chamber dilation

Chronic volume load

Sarcomeres mainly in series

Greater myocyte length

Ventricular enlargement

Regurgitant valves are a typical volume-load stimulus.

Wall thickness alone can underestimate hypertrophy in a dilated heart.

Slide 35 · Cardiomegaly includes distinct structural changes

Hypertrophy

Increase in myocardial mass

Often accompanies sustained workload

Myocytes become enlarged

Dilation

Increase in chamber dimensions

Reflects altered loading or failure

May coexist with hypertrophy

Slide 36 · Hypertrophic myocytes change microscopically

Myocytes enlarge and synthesize additional contractile proteins.

Cardiomyocyte nuclei may be enlarged or multiple.

DNA replication without cell division contributes to nuclear ploidy.

Associated interstitial fibrosis reflects fibroblast matrix synthesis.

Slide 37 · Hypertrophy creates supply–demand mismatch

More myocardial mass

Greater oxygen requirement

No proportional capillary expansion

Higher vulnerability to ischemia

Pressure-overloaded hearts are especially vulnerable to inadequate perfusion.

Reduced coronary reserve can contribute to decompensation.

Slide 38 · Fibrosis compounds filling impairment

Mechanical stress

Fibroblast extracellular matrix synthesis

Interstitial fibrosis

Stiffer myocardium

Fibrosis increases resistance to diastolic filling.

Functional impairment may be greater than gross morphology suggests.

Slide 39 · Adaptation may become decompensation

Persistent workload

Hypertrophy and remodeling

Ischemia / fibrosis / dysfunction

Heart failure or arrhythmia

Initial compensatory growth is not indefinitely protective.

Gross size alone does not explain the full burden of functional impairment.

Slide 40 · Obstructive lesions impose pressure work

Narrowed outflow or high afterload

Higher ventricular pressure

Increased myocardial work

Pressure-overload remodeling

Valve opening restriction and elevated systemic pressure are distinct causes.

Maintaining flow across resistance increases chamber workload.

Slide 41 · Aortic valve stenosis obstructs ejection

Stenosis: Opening restriction

Restricted opening

Higher upstream pressure

Calcific aortic valve stenosis restricts valve opening.

The left ventricle works against increased outflow resistance.

Sustained pressure stress may promote ventricular hypertrophy.

Slide 42 · Systemic hypertension raises ventricular afterload

Elevated systemic arterial pressure

Greater LV pressure requirement

Sustained wall stress

Concentric hypertrophic response

This mechanism does not require an anatomic valve obstruction.

Hypertension also appears among common causes of heart failure.

Slide 43 · Aortic coarctation increases upstream pressure

Anatomic aortic narrowing

Resistance to systemic outflow

Higher ventricular pressure work

Pressure-load consequences

Coarctation as an obstruction-to-flow example.

The key mechanism is increased work needed to maintain output.

Slide 44 · Pressure loading remodels without guaranteeing output

Persistent high pressure

Greater muscle mass

Higher oxygen demand / fibrosis

Possible ventricular dysfunction

Hypertrophy can restore wall performance transiently.

Structural compensation can eventually reduce diastolic compliance.

Slide 45 · Regurgitant valves add volume workload

Regurgitation: Closing failure

Incomplete closure

Reverse flow

Incomplete valve closure permits backward flow.

The involved chambers handle recirculated blood volume.

Sustained overload can overwhelm contractile reserve.

Slide 46 · Mitral regurgitation can follow chamber dilation

Left ventricular dilation

Papillary muscle displacement

Poor leaflet coaptation

Mitral regurgitation

A torn chord or papillary muscle dysfunction can also cause incompetence.

Regurgitation may result from a damaged supporting apparatus.

Slide 47 · Aortic regurgitation may arise from root dilation

Aortic root dilation

Changed cuspal relationships

Incomplete semilunar closure

Reverse diastolic flow

Leaflet motion and attachment geometry together determine competence.

Structural failure outside the valve cusp can cause insufficiency.

Slide 48 · Volume overload can amplify dysfunction

Regurgitant blood volume

Higher chamber filling volume

Chamber dilation and remodeling

Reduced pumping reserve

Added volume workload is different from pressure-obstruction workload.

Dilation and regurgitation can reinforce one another.

Slide 49 · Pressure load and volume load produce different patterns

Pressure overload

Resistance to ejection

Sarcomeres predominantly in parallel

Greater wall thickness

Volume overload

Excess circulating chamber volume

Sarcomeres predominantly in series

Greater chamber dilation

Slide 50 · A shunt reroutes blood across an abnormal connection

Congenital or acquired defect

Abnormal interchamber or vessel flow

Altered chamber loading

Pressure / volume overload

A shunt is not synonymous with simple valve regurgitation.

The hemodynamic burden depends on the communication and resulting flow.

Slide 51 · Interchamber shunts bypass intended pathways

Chamber A

Abnormal communication

Chamber B

Blood crosses an inappropriate cardiac connection.

Receiving and upstream chambers may experience abnormal loading.

The overview identifies both pressure and volume overload as possible outcomes.

Slide 52 · Vessel-to-vessel shunts alter the closed circuit

Vessel A

Abnormal communication

Vessel B

Pathologic communication may occur between major vessels.

Flow is diverted away from its intended pathway.

Downstream loading consequences depend on shunt physiology.

Slide 53 · Shunts can impose coupled hemodynamic stresses

Volume component

Extra flow through involved chambers

Increased filling burden

Potential chamber dilation

Pressure component

Abnormal load or resistance

Higher pressure work

Potential hypertrophic response

Slide 54 · Conduction disorders disrupt coordinated contraction

Impulse initiation or propagation abnormality

Arrhythmia or conduction block

Ineffective chamber timing

Reduced pumping effectiveness

Disorganized impulses can compromise effective ejection.

A conduction defect may be hemodynamically important without valve damage.

Slide 55 · Conduction block can slow ventricular activity

Blocked conduction pathway

Failed transmission of impulses

Slow or absent ventricular activation

Inadequate cardiac output

Subsidiary pacemakers may provide slower escape activity.

Severe interruption can prevent effective pumping.

Slide 56 · Uncoordinated activation impairs flow

Coordinated sequence

Atrial contraction precedes ventricular systole

Ventricular activation is organized

Effective pressure generation

Disorganized impulses

Abnormal contraction sequence

Reduced mechanical efficiency

Risk of impaired output

Slide 57 · Electrophysiology and structure interact

Hypertrophy / ischemia / fibrosis

Electrical substrate changes

Arrhythmia risk

Further circulatory dysfunction

Myocardial remodeling may culminate in arrhythmias.

Pump failure and conduction problems can therefore coexist.

Slide 58 · Rupture causes immediate circuit failure

Wall or major vessel rupture

Loss of circulatory continuity

Rapid blood loss

Hypotensive shock

Unlike slow myocardial remodeling, major rupture may be immediately lethal.

Thoracic aortic injury and dissection as examples.

Slide 59 · Aortic dissection is a rupture-related threat

Aortic wall disease or injury

Dissection involving major vessel

Potential wall disruption

Hemorrhage and shock

The overview refers to aortic dissection in its discussion of rupture.

Its detailed vascular pathology belongs to the preceding chapter.

Slide 60 · Mechanism dictates tempo of deterioration

Typically progressive

Chronic pressure overload

Progressive regurgitation

Compensated remodeling → failure

Potentially sudden

Abrupt myocardial injury

Conduction interruption

Rupture with hemorrhagic shock

Slide 61 · Aging changes myocardial filling and valves

Chambers

Smaller LV cavity; Larger LA

Myocardium

Myocyte attrition; More connective tissue

Valves

Calcification and fibrous thickening

Coronary arteries

Tortuosity, atherosclerosis, reduced compliance

Slide 62 · Aging provides a substrate—not one mechanism

Aging-related structural change

Greater susceptibility to dysfunction

Pressure, valve, or coronary disease

Clinical cardiac disorder

Amyloid deposits in older hearts can increase stiffness and impair filling.

Several six-mechanism pathways may operate together in one patient.

Slide 63 · Inherited susceptibility and environment interact

Genetic variants and inherited disease

Environmental and acquired exposures

Cardiac structural / functional changes

Variable individual phenotype

Genetic and environmental contributions across heart disorders.

Molecular diagnostics can help investigate selected cardiac diseases.

Slide 64 · The six mechanisms can be distinguished clinically

Mechanism

Primary disturbance

Typical burden

Pump failure

Contraction or relaxation

Low flow / high filling pressure

Obstruction

Resistance to forward flow

Pressure work

Regurgitation

Reverse valve flow

Volume work

Shunt

Inappropriate flow route

Pressure ± volume work

Conduction disorder

Abnormal electrical timing

Ineffective pumping

Rupture

Loss of circuit integrity

Hemorrhage / shock

Slide 65 · Case: Aortic stenosis and wall thickening

Teaching scenario

A patient has restricted aortic cusp opening and a thickened left ventricular wall. Which primary mechanism accounts for the remodeling?

Which explanation is most consistent with the mechanism?

Obstruction → pressure overload

Regurgitation → volume overload

Rupture → loss of continuity

Slide 66 · Case: Ventricular enlargement with mitral leak

Teaching scenario

A dilated left ventricle displaces papillary muscles and produces incomplete mitral valve closure. Identify the causal sequence.

Which explanation is most consistent with the mechanism?

Dilation → altered apparatus → regurgitation

Regurgitation → primary conduction block

Rupture → chronic coronary insufficiency

Slide 67 · Case: Congestion despite preserved EF

Teaching scenario

A patient has ventricular stiffness, elevated filling pressure, pulmonary congestion, and a preserved ejection fraction. Which pump defect predominates?

Which explanation is most consistent with the mechanism?

Diastolic filling dysfunction

Ventricular rupture

Isolated forward-flow obstruction

Slide 68 · Case: Loss of normal ventricular sequencing

Teaching scenario

A conduction pathway is interrupted; Ventricular activation slows despite no stated valve lesion. Why can circulatory output fall?

Which explanation is most consistent with the mechanism?

Abnormal timing reduces effective pumping

Valves must be stenotic

A shunt must be present

Slide 69 · Case: Abrupt hypotension after aortic injury

Teaching scenario

After major thoracic aortic injury, a patient develops rapid blood loss and profound hypotension. Which failure pathway is operating?

Which explanation is most consistent with the mechanism?

Rupture and loss of circuit integrity

Slow pressure hypertrophy

Chronic diastolic stiffening

Slide 70 · Link lesion to load, adaptation, and failure

Identify primary mechanism

Define pressure, volume, timing, or integrity defect

Predict ventricular response

Anticipate perfusion / congestion effects

One patient may show more than one of the six mechanisms.

Mechanical and electrical disturbances often converge on impaired tissue delivery.

Slide 71 · Reference and source boundary

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026).

Core sections: “Cardiac Structure and Specializations” and “Overview of Cardiac Pathophysiology.”

Adjacent explanatory context: “Heart Failure” and “Pathophysiology and Progression to Heart Failure.”