Cardiovascular Pathophysiology

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Cardiovascular Pathophysiology
Lectures 1-3 What can go wrong?
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What can go wrong?
Jot down your ideas
Hints Cardiac Output HR X Stroke Volume BP CO
X Total Peripheral Resistance
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Introduction

• A knowledge of normal cardiac structure and
  function is crucial to understanding diseases
  that affect the heart. (You should be familiar
  with the following diagrams and concepts!)
• What are the controlled variables?
• What are the basic equations?
• From your current knowledge, you will be invited
  to postulate what malfunctions may arise in the
  cardiovascular system.
• We will compare this with a brief systematic
  overview of selected aspects of cardiovascular
  pathophysiology (note the overlaps).
• Wherein lies the greatest risk? - i.e. what will
  most people die of?

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Heart - gross anatomy
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Heart - internal anatomy
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Cardiac output
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Reflex control of heart rate
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A-Z of cardiovascular pathophysiology

• Abnormal Heart Rhythms
• Aneurysms and Aortic Dissection
• Atherosclerosis
• Cardiomyopathy
• Coronary Artery Disease
• Heart Failure
• Heart Valve Disorders
• High Blood Pressure Low Blood Pressure
• Infective Endocarditis
• Pericardial Disease
• Peripheral Arterial Disease
• Venous Disorders
• What is Congestive Heart Failure?

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Abnormal Heart Rhythms

• Abnormal heart rhythms (arrhythmias) are
  sequences of heartbeats that are irregular, too
  fast, too slow, or conducted via an abnormal
  electrical pathway through the heart
• Disorders of impulse formation and conduction
  result in bradyarrhythmias and tachyarrhythmias
• Fast arrhythmias (tachyarrhythmias) may be
  triggered by exercise, emotional stress,
  excessive alcohol consumption, smoking, or use of
  drugs that contain stimulants, such as cold and
  hay fever remedies.
• Slow arrhythmias (bradyarrhythmias) may be
  triggered by pain, hunger, fatigue, digestive
  disorders (such as diarrhea and vomiting), or
  swallowing, which can stimulate the vagus nerve
  excessively. (With enough stimulation, which is
  rare, the vagus nerve can cause the heart to
  stop.) In most of these circumstances, the
  arrhythmia tends to resolve on its own.
• Careful analysis of ECG records distinguishes
  between the different disorders to allow
  appropriate therapy to be applied.

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Examples of ECGs seen with abnormal heart rhythms

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Abnormal Heart Rhythms

• Atrial Fibrillation and Atrial Flutter
• Atrial Premature Beats
• Bundle Branch Block
• Heart Block
• Pacemaker Dysfunction
• Paroxysmal Supraventricular Tachycardia
• Ventricular Fibrillation
• Ventricular Premature Beats
• Ventricular Tachycardia
• Wolff-Parkinson-White Syndrome - this is a
  disorder in which an extra electrical connection
  between the atria and the ventricles is present
  at birth

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The main mechanisms of Arrhythmogenesis
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Aneurysms and Aortic Dissection

• Disorders of the aorta include bulges (aneurysms)
  in weak areas of its walls and separation of the
  layers of its wall (dissection). These disorders
  can be immediately fatal, but they usually take
  years to develop. Aneurysms may also develop in
  other arteries.
• Aneurysms can develop anywhere along the aorta.
  Three fourths of aortic aneurysms develop in the
  abdominal aorta and the rest develop in the
  thoracic aorta.
• Aneurysms can also develop in the arteries at the
  back of the knee (popliteal arteries), the
  femoral arteries, the carotid arteries, the
  cerebral arteries), and the coronary arteries.
• The most common cause of aneurysms is
  atherosclerosis,
• An aortic dissection (dissecting aneurysm,
  dissecting hematoma) is an often fatal disorder
  in which the inner layer (lining) of the aortic
  wall tears.
• Most aortic dissections occur because the
  artery's wall deteriorates where such
  deterioration is usually associated with high
  blood pressure

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Aneurysms and Aortic Dissection
In an aortic dissection, the inner layer (lining)
of the aortic wall tears, and blood surges
through the tear, separating (dissecting) the
middle layer from the outer layer of the wall. As
a result, a new, false channel forms in the
wall.
Aneurysms can develop anywhere along the aorta.
Most develop in the abdominal aorta. The rest
develop in the thoracic aorta, most commonly in
the ascending aorta.
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Atherosclerosis

• Atherosclerosis is a condition in which patchy
  deposits of fatty material (atheromas or
  atherosclerotic plaques) develop in the walls of
  medium-sized and large arteries, leading to
  reduced or blocked blood flow (see figure under
  peripheral vascular disease section).
• In the United States and most other Western
  countries, atherosclerosis is the leading cause
  of illness and death..
• Atherosclerosis can affect the medium-sized and
  large arteries of the brain, heart, kidneys,
  other vital organs, and legs. It is the most
  important and most common type of circulatory
  disorder and is the underlying cause for several
  diseases in which result when the wall of an
  artery becomes thicker and less elastic.
• Despite significant medical advances, heart
  attacks due to coronary artery disease
  (atherosclerosis that affects the arteries
  supplying blood to the heart and strokes (due to
  atherosclerosis that affects the arteries to the
  brain are responsible for more deaths than all
  other causes combined.

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Cardiomyopathy

• Cardiomyopathy refers to progressive impairment
  of the structure and function of the muscular
  walls of the heart chambers.
• There are three main types of cardiomyopathy
  dilated, hypertrophic, and restrictive.
• In dilated cardiomyopathy, the ventricles enlarge
  and impair systolic function. Progressive left
  ventricular enlargement lead to heart failure
  ventricular arrhythmias and embolic
  complications.
• In hypertrophic cardiomyopathy, the walls of the
  ventricles thicken and become stiff and impair
  diastolic relaxation. The associated rise in LV
  pressure is transmitted back leading the elevated
  left atrial and consequently pulmonary capillary
  pressure.
• In restrictive cardiomyopathy, which is uncommon,
  the walls of the ventricles become stiff, but not
  necessarily thickened due to an infiltrated of
  fibrotic myocardium (sounds like?). Has a poor
  prognosis and leads ultimately to congestive
  heart failure.

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Coronary Artery Disease

• Coronary artery disease (CAD) is a condition in
  which the blood supply to the heart muscle is
  partially or completely blocked.
• CAD is almost always due to the build-up of
  cholesterol and other fatty materials (called
  atheromas or atherosclerotic plaques) in the wall
  of a coronary artery. Occasionally CAD results
  from a spasm of an artery, and rarely, the cause
  is a birth defect, or an infection leading to
  inflammation of the arteries (arteritis), or
  physical damage (from an injury or radiation
  therapy).
• CAD is the most common cause of myocardial
  ischemia. The major complications of coronary
  artery disease are chest pain due to myocardial
  ischemia (angina) and heart attack (myocardial
  infarction).
• CAD is the most common type of cardiovascular
  disease, occurring in about 5 to 9 of people
  aged 20 and older. The death rate increases with
  age and overall is higher for men than for women.
  After age 55, the death rate for men declines,
  and the rate for women continues to climb. After
  age 70 to 75, the death rate for women exceeds
  that for men who are the same age.

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Heart Failure

• Heart failure is a disorder in which the heart
  pumps blood inadequately, leading to reduced
  blood flow, back-up (congestion) of blood in the
  veins and lungs, and other changes that may
  further weaken the heart.
• Heart failure has two main forms the more
  common, systolic dysfunction and less common
  diastolic dysfunction.
• In systolic dysfunction, the heart contracts less
  forcefully and cannot pump out as much of the
  blood that is returned to it as it normally does.
  As a result, more blood remains in the lower
  chambers of the heart (ventricles). Blood then
  accumulates in the veins.
• In diastolic dysfunction, the heart is stiff and
  does not relax normally after contracting. Even
  though it may be able to pump a normal amount of
  blood out of the ventricles, the stiff heart does
  not allow as much blood to enter its chambers
  from the veins. As in systolic dysfunction, the
  blood returning to the heart then accumulates in
  the veins. Often, both forms of heart failure
  occur together.

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Heart Failure
Systolic Dysfunction Disorders that cause
systolic dysfunction may impair the entire heart
or one area of the heart. As a result, the heart
does not contract normally. Coronary artery
disease is a common cause of systolic
dysfunction. It can impair large areas of heart
muscle because it can reduce blood flow to
large areas of heart muscle.
Diastolic Dysfunction Inadequately treated high
blood pressure is the most common cause of
diastolic dysfunction. High blood pressure
stresses the heart because the heart must pump
blood more forcefully than normal to force blood
into the arteries against the higher pressure.
Eventually, the heart's walls thicken
(hypertrophy), then stiffen. The stiff heart does
not fill quickly or adequately, so that with each
contraction, the heart pumps less blood than it
normally does.
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Mechanisms and Examples that Cause Left Sided
Heart Failure
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Heart Valve Disorders

• Heart valves regulate the flow of blood through
  the atria and the ventricles
• Each ventricle has a one-way inlet valve and a
  one-way outlet valve and each valve consists of
  flaps (cusps or leaflets
• In the right ventricle, the inlet valve is the
  tricuspid valve, which opens from the right
  atrium, and the outlet valve is the pulmonary
  (pulmonic) valve, which opens into the pulmonary
  arteries.
• In the left ventricle, the inlet valve is the
  mitral valve, which opens from the left atrium,
  and the outlet valve is the aortic valve, which
  opens into the aorta.
• The heart valves can malfunction either by
  leaking (causing regurgitation) or by not opening
  adequately and thus partially blocking the flow
  of blood through the valve (causing stenosis).
  Either problem can greatly interfere with the
  heart's ability to pump blood. Sometimes a valve
  has both problems.

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Systole
Diastole
In mitral stenosis, the mitral valve opening is
narrowed, and blood flow from the left atrium
into the left ventricle during diastole is
reduced.
In mitral regurgitation, the mitral valve leaks
when the left ventricle contracts (during
systole), and some blood flows backward into the
left atrium.
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High Low Blood Pressure

• High blood pressure (hypertension) is abnormally
  high pressure in the arteries. High blood
  pressure is defined as a systolic pressure at
  rest that averages 140 mm Hg or more, a diastolic
  pressure at rest that averages 90 mm Hg or more,
  or both
• Low blood pressure (hypotension) is blood
  pressure low enough to cause symptoms such as
  dizziness and fainting.
• Normally, the body maintains the pressure of
  blood in the arteries within a narrow range. If
  blood pressure is too high, it can damage a blood
  vessel and even rupture it, causing bleeding or
  other complications.
• If blood pressure is too low, not enough blood
  reaches all parts of the body as a result, cells
  do not receive enough oxygen and nutrients, and
  waste products are not adequately removed. Even
  so, having low blood pressure is generally better
  than having high blood pressure.
• Healthy people who have blood pressure that is
  low but still in the normal range (when measured
  at rest) tend to live longer than those who have
  higher normal blood pressure

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Factors that influence MAP
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Pressure, resistance flow

• Pressure gradient in the blood vessels. Mean
  systemic blood pressure ranges from 93 mm Hg in
  the arteries to about 10 mm Hg in the venae cava.
• The velocity of the flow depends on the total
  cross sectional area.
• Flow is slowest in the capillaries and most rapid
  in the aorta major arteries

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Why systemic blood pressure?
Systolic arterial pressure.
Pulse pressure Systolic arterial pressure -
Diastolic arterial pressure.
Diastolic arterial pressure.
Mean arterial pressure can be estimated as
diastolic pressure plus one-third pulse pressure.
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Pericardial Disease

• Pericardial disease affects the pericardium,
  which is the flexible two-layered sac that
  envelops the heart.
• The pericardium helps keep the heart in position,
  prevent the heart from overfilling with blood,
  and protect the heart from being damaged by chest
  infections. The pericardium is not essential to
  life if the pericardium is removed, there is
  little effect on cardiac function.
• Acute pericarditis is inflammation of the
  pericardium that begins suddenly, is often
  painful, and causes fluid and blood components
  such as fibrin, red blood cells, and white blood
  cells to pour into the pericardial space.
• Chronic pericarditis is inflammation that begins
  gradually, is long-lasting, and results in fluid
  accumulation in the pericardial space or
  thickening of the pericardium.
• Symptoms of pericarditis include shortness of
  breath, coughing, and fatigue. Coughing occurs
  because the high pressure in the veins causes
  pulmonary oedema

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Cardiac tamponade is the most serious
complication of pericarditis and most commonly
caused by accumulation of fluid or blood between
the two layers of the pericardium. This may
result from cancer, injury, surgery, viral and
bacterial infections and kidney failure. The
accumulating fluid or blood puts pressure on the
heart, interfering with its ability to pump
blood. As a result, when a person breathes in,
blood pressure may fall rapidly to abnormally low
levels and the pulse may correspondingly weaken.
When a person breathes out, blood pressure
increases and the pulse becomes stronger. This
exaggeration in the variation in blood pressure
and pulse that occurs with breathing is called a
paradoxical pulse.
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Peripheral Arterial Disease

• Peripheral arterial disease results in reduced
  blood flow in the arteries of the trunk, arms,
  and legs. Disorders affecting arteries that
  supply the brain are considered separately as
  cerebrovascular disease.
• Peripheral arterial disease may be described as
  occlusive or functional.
• Occlusive peripheral arterial disease is due to
  structural changes that narrow or block arteries
  and often results from atherosclerosis.
• Functional peripheral arterial disease is usually
  due to a sudden temporary narrowing (spasm) or,
  rarely, to a widening (vasodilation) of arteries.
  Raynaud's disease and Raynaud's phenomenon are
  conditions in which small arteries (arterioles),
  usually in the fingers or toes, constrict more
  tightly in response to exposure to cold.
• Functional peripheral arterial disease usually
  occurs when the normal mechanisms that dilate and
  constrict these arteries are exaggerated. The
  affected arteries constrict more tightly and more
  often.

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The fingertips of the hand on the right have
turned blue due to Raynaud's disease (i.e.
unknown cause).
How Atherosclerosis Develops
This patient's toes have a whitish discoloration
due to Raynaud's phenomenon caused by
scleroderma.
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Venous Disorders

• The main problems that affect the veins include
  inflammation, clotting, and defects that lead to
  distension and varicose veins. The veins in the
  legs are particularly affected because when a
  person is standing, blood must flow upward from
  the leg veins, against gravity, to reach the
  heart.
• Venous disorders results from poor blood flow can
  be classified as follows
• An arteriovenous fistula is an abnormal channel
  between an artery and a vein.
• Deep vein thrombosis is the formation of blood
  clots (thrombi) in the deep veins. Thrombi can
  occur either in the deep leg veins, causing deep
  vein thrombosis, or in the superficial leg veins,
  causing superficial thrombophlebitis
• Superficial thrombophlebitis (superficial
  phlebitis) is inflammation and clotting in a
  superficial vein.
• Varicose veins are abnormally enlarged
  superficial veins in the legs.

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Valves in Varicose Veins
One-Way Valves in the Veins
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What is Congestive Heart Failure?

• Congestive heart failure leads to a reduction in
  Cardiac output
• Reflex sympathetic compensation can increase
  Cardiac Output
• Consequently elevated afterload reduces Cardiac
  Output
• A cascade of events can lead to left ventricular
  hypertrophy (see diastolic dysfunction)
• Angiotesin II also increases Cardiac Output
  sodium retention
• However the angiotensin induced increase in
  Cardiac Output raises preload and Left
  Ventricular Diastolic Pressure which in turn
  leads to pulmonary oedema and premature death

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Factors that lead to Congestive Heart Failure
1. See bullet points 1- 5 for explanation
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Frank Starling curve Congestive Heart Failure

• Normal Cardiac Output is determined by the
  pressure in the left ventricle at end diastolic
  volume In SHF the set point for cardiac output is
  reduced and CO is reduced (1)
• Compensation by sympathetic action (NA AD) are
  activated and increase End Diastolic Pressure and
  increase Cardiac Output. This can lead to
  backward heart failure (2).
• Positive iontrophic agents increase cardiac
  output (3)
• This improves Cardiac Output and reduces drive to
  increase end diastolic pressure and allow new set
  point (4) just short of backward failure.

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Drugs used in the treatment Congestive Heart
Failure
Note the normal decline in SVF and its
exacerbation by disease
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Drug mechanisms and Congestive Heart Failure

• Normal CO is determined by the pressure in the
  left ventricle at end diastolic volume.
• The course of CHF, without further intervention
  leads to forward failure (1) resulting from
  increased cardiac afterload caused by peripheral
  vasoconstriction and pulmonary congestion
• Venodilation, diuretic therapy and ACE inhibitors
  reduce backward failure, the symptoms of oedema
  and congestion by reducing end diastolic
  pressure.
• This improves cardiac output by reducing cardiac
  afterload and provides a new set point outside
  the forward and outward failure domains (2)

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Summary

• Mean arterial pressure, the primary regulated
  variable in the cardiovascular system, equals the
  product of cardiac output and total peripheral
  resistance.
• Why because Blood flow between two points in the
  cardiovascular system is directly proportional to
  the pressure difference between the points and
  inversely proportional to the resistance. The
  resistance of the arterioles and the
  pre-capillary sphincters supplying the
  capillaries determines the flow. This is
  regulated.
• Homeostatic regulation of the cardiovascular
  system (via a range of reflex loops) maintains an
  adequate blood flow to the brain, heart and
  tissues.
• Failure of this control leads to heart failure in
  its various guises that can be understood by
  consideration of basic physiological mechanisms.
• Failure of sub-components of the circulatory
  system lead to a wide range of common diseases
  that reveal the subtleties of CVS control
  mechanisms.