Cardiovascular System Pathology 2014v2 edited by @drjennings argwings
-
Upload
jayneincs -
Category
Health & Medicine
-
view
579 -
download
14
description
Transcript of Cardiovascular System Pathology 2014v2 edited by @drjennings argwings
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 1
MODULE: CLINICAL PATHOLOGY
UNIT 1 - The Cardiovascular System
By OKINDA, B, Carey Francis
September 2014
OUTLINE
Topic Sub Topics Hours
1. Introduction to
CVS Pathology
Review of Anatomy and Physiology
Pathophysiology of Cardiovascular Disease
Investigations in Cardiovascular Disorders
2
2. The Heart Congenital Disorders 1
Cardiac Failure 2
Ischaemic Heart Disease 1
Valvular Heart Disease 1
Acute Rheumatic Fever and Rheumatic Heart Disease 1
Myocardial and Pericardial Disorders 1
3. Arteries Aneurysms 1
Hypertension and Hypertensive Heart Disease 1
Atheroma/atherosclerosis and Arteriosclerosis 1
4. Veins DVT and PE 1
Varicosities and Haemorrhoids 1
Tumours of Blood Vessels 1
TOTAL 15
Lesson 1: Introduction to Pathology of the Cardiovascular System
Learning Outcomes
At the end of the lesson the learner shall be able to: -
1. Describe the anatomy and physiology of the cardiovascular system
2. Describe mechanisms of cardiovascular disease
3. Discuss investigations in cardiovascular disease
1.0. INTRODUCTION
Cardiovascular pathology is the study of causes and effects of disease on the
cardiovascular system. It comprises the heart and blood vessels (arteries, veins and the
capillaries).
2.0. THE HEART
The function of the heart is to pump sufficient oxygenated blood containing nutrients,
metabolites and hormones to meet the moment to moment metabolic needs and preserve a constant internal milieu. The heart has three muscles layers - endocardium
(inner muscles of the heart, myocardium (provides contractile force to push blood)
and pericardium (outer covering). The heart has 4 valves namely the aortic,
pulmonary, tricuspid and the mitral valves. Heart muscle has two essential
characteristics of contractility and rythymicity. The conducting system contains
specialized cells for initiation and transmission of signals in a co-coordinated manner. It
comprises the Sino-atrial node (SAN), the atrio-ventricular node (AVN), the Purkinje
tissues (fibres) and the bundle of His. Physiological function of the heart is maintained
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 2
by healthy muscles, efficient valves, the conducting system and co-ordination of chambers
and normal peripheral resistance
Diagram 1.1: Normal Heart
Functioning of the Heart
The heart has three major types of cardiac muscle namely the atrial, ventricular and
the specialized excitatory and conductive muscles. The heart muscle is organized in
two syncytium with the many cells connected in series with intercalated discs with specialized structures such as fascia adherens (mechanical links), mascula adherens
/desmosome (lattice structure and site for cytoplasmic filaments) and gap junction
(makes the adjacent cells loose and is permeable to ions). This arrangement facilitates
the all or nothing principle.
The Cardiac Cycle
The cardiac cycle comprises of
Phase I – Atrial Contraction - period of rapid refilling of ventricles in the first 1/3 of
diastole, blood moves slowly into the ventricles in the middle of 1/3 of diastole and
atrial contraction pushes more blood into the ventricles (20 – 30% of ventricular
refilling) in the last 1/3 of diastole.
Phase II – isovolumic ventricular (isometric) contraction - emptying ventricles during
the beginning of ventricular contraction when no emptying takes place hence the
name isovolumic or isometric (i.e. is there is no increase in tension of muscle but no
shortening of muscle fibres)
Phase III – ventricular systole – period of ejection with ventricular systole when there
is fast and slow ejection of blood. Left ventricular pressure rises slightly above 80
mmHg and right ventricular pressure rises slightly above 8 mmHg forcing open the
mitral and tricuspid valves respectively; this is fast ejection that accounts for 70% of
ventricular emptying. There is the period of slow ejection that lasts the last 2/3 of
systole.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 3
Phase IV – period of isovolumic ventricular (isometric) relaxation- ventricular
relaxation begins allowing ventricular pressure to fall. Increased pressure in the
distended arteries pushes blood back towards the ventricles closing the aortic and
pulmonary valves. The ventricular muscles contract but the ventricular volume stays
– isometric relaxation.
Phase V – ventricular diastole relaxation (period of ventricular diastole relaxation
overlaps with atrial contraction.
3.0. CARDIAC OUTPUT
The normal cardiac output for young healthy male adult is 4 – 8 litres/minute (average
5.6 litres/min) with females at 10% less. Five basic mechanisms controlling cardiac output include heart rate, ventricular filling pressure, ventricular distensibility,
systemic vascular resistance and ventricular contractility. Cardiac output (CO) =
Heart rate (HR) x Stroke volume (SV) of the left ventricle
The Stroke volume
Stroke volume is the diastolic volume of the ventricle minus the volume of blood in the
ventricle at the end of systole. Stroke volume output is the amount of blood emptied by
the ventricles during systole (usually 70 mls). The Cardiac Index (CI) is the cardiac
output per square metre of body surface area. The normal is 3.0 litres/minute and
changes with age.
Ejection Fraction
End-diastolic volume is the volume of blood in the ventricles at the end of diastole
when the filling of ventricles increases volume of each ventricle to 120 – 130 mls while the End-systole volume is the blood remaining in the ventricles at the end of systole
(usually 50 – 70 mls).
Ejection Fraction = 70 x 100 = 58.3% (60%)
120
4.0. THE LAWS
1. Poiseulle’s Law Blood flow = Pressure x diameter of blood vessel
Length of vessel x viscosity of blood
2. Starling’s Law – increase in dilatation leads to increased filling, contraction and stroke
volume
3. Frank-Starling – within physiological limits, the heart pumps all the blood that comes to
it without allowing excessive damming of blood in the veins. The greater the heart is
filled during diastole, the greater will be the amount of blood pumped into the aorta.
4. Laplaces Law – the circumferential force tending to stretch the muscle fibres in the
vessel wall is proportional to the diameter of the muscle x the pressure inside the vessel
(F = D x P). The wall tension require to counteract a given pressure in a spherical
cavity is proportional to the radius of the cavity.
5.0. PRINCIPAL MECHANISMS OF CARDIOVASCULAR DISEASE
Many diseases can involve the heart and blood vessels but generally cardiovascular
dysfunction results from five main mechanisms: -
1. Failure of the pump
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 4
2. An obstruction to flow
3. Regurgitation flow
4. Disorders of cardiac conduction
5. Disruption of the continuity of the circulatory system
6.0. INVESTIGATIONS IN CARDIOVASCULAR DISEASE
1) IMAGING
a) Chest X-Ray
Is taken in postero-anterior (PA) direction at maximum inspiration.
The heart is close to the X-ray film to minimize magnification of the chest with
respect to the thorax.
Lateral view chest X-ray may give more information when PA is abnormal.
Look at the heart size, calcification and lung fields
Interpretation
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 5
Heart Size
i) The cardio-thoracic Ratio (CTR)
The maximum transverse diameter of the heart is compared with the maximum
Transverse diameter of the chest measured from the inside of the ribs.
Is usually less than 0.5 (50%) except in:-
1) Neonates
2) Infants
3) Athletes
4) Patients with skeletal deformities (Scoliosis, funnel chest)
A transverse cardiac diameter of more than 15.5 cm is abnormal.
Pericardial effusion or cardiac dilation increases the ratio.
ii) Patterns of specific chamber enlargement seen on the chest X-ray
a. Left Atrial dilatation
Prominence of the left atrial appendage on the left heart boarder.
A double atrial shadow to the right of the sternum.
b. Left ventricular enlargement
Increased CTR
Smooth elongation and increased convexity of the heart border.
c. Right Atrial enlargement
Right boarder of the heart projects into right lower lung field.
d. Right ventricular enlargement
Increased CTR
Upward displacement of the apex of the heart.
e. Ascending aortic dilatation/enlargement
Prominence of the aortic shadow
f. Dissecting of the ascending aorta
Widening of the mediastinum
Calcification
Occurs due to tissue degeneration
Seen on the lateral or a penetrated PA view but best studied by CT scanning
Calcification can be seen in:- Pericardial
Valvular
Lung Fields
Increased in vascularity an in size of hilar vessels seen when there are left to right
shunts.
When there is pulmonary ligaemia there is a paucity of vascular markings and a
reduction in diameter of arteries.
Prominence of pulmonary arteries hili and pruned (reduced in size) at the
peripheral Lung fields as seen in pulmonary arterial hypertension.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 6
Kerley Lines
Septal lines seen when the interlobular septa in the pulmonary interstitium become
prominent
May be because of lymphatic engorgement or oedema of the connective tissues of
the interlobular septa.
Usually occur when pulmonary capillary wedge pressures reach 20 - 25 mmHg.
Kerley A lines
o Are 2-6 cm long oblique lines that are < 1 mm thick and course towards the hilar
o Represent thickening of the interlobular septa that contain lymphatic connections
between the perivenous and bronchoarterial lymphatics deep within the lung
parenchyma
o On chest radiographs they are seen to cross normal vascular markings and
extend radially from the hilum to the upper lobes
Kerley B lines
o These are 1-2 cm thin lines in the peripheries of the lung
o Are perpendicular to, and extend out to the pleural surface
o Represent thickened sub pleural interlobular septa and are usually seen at the
lung bases.
Kerley C lines
o Short lines which do not reach the pleura (i.e not B or D lines) and do not course
radially away from the hila (i.e not A lines).
Kerley D lines
o Are exactly the same as Kerley B lines, except that they are seen on lateral chest
radiographs in the retrosternal air gap
Causes
1) Pulmonary Oedema
2) Neoplasm
a. Lymphangitic spread Of Cancer (E.G Lymphangitis Carcinomatosis) : Kerley
Lines With A Fine Peripheral Reticular Pattern e.g. breast, stomach, pancreatic
and lung cancers
b. Lymphoma - pulmonary lymphoma
3) Pneumonia
a. Viral Pneumonia
b. Mycoplasma Pneumonia
c. Pneumocystis Pneumonia
4) Interstitial Pulmonary Fibrosis
5) Pneumoconiosis
6) Sarcoidosis
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 7
Pleural Effusion
Abnormal pulmonary vasculature
Fluid level
Opacity
Loss of costo-phrenic and cardio-phrenic angles
b) MRI (Magnetic Resonance Imaging)
Non-invasive imaging technique
A powerful magnetic field is used
Cardiac MRI that uses radio waves, magnets, and a computer to create pictures of
the heart. This gives a 3D image of the moving as well as still pictures of the heart.
c) Nuclear Imaging
Primarily used is Ischaemic Heart Disease
Myocardial structure & function can be assessed by radio-nucleide imaging
techniques
Thallium (with behaves as potassium) is taken up by healthy myocardium
Ischaemia or infarction produces unclear image with a “cold” spot.
d) CT Scanning
Useful showing the size and shape of the cardiac chambers as well as the thoracic
abdominal aorta and Mediastinum.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 8
2) ELECTROCARDIOGRAM (EGG)
Is a recording of the electrical activity of the heart
Is the only way of diagnosing rhythm and conduction problems
Is the vector sum of the depolarization and repolarization potential of the myocardial
cells (Summation of action potentials of all myocardial cells)
The shape of the wave form of the EGG depends on the speed and direction of the
depolarization process through the heart
Depolarization initiating each heart beat begins at Sino-Atrial node and spreads as
an advancing wave through the atria which are depolarized simultaneously to the A-
V Node
Depolarization spreads from the atria to ventricles via the Bundle of HIS that begins
at A-V Node passing into the interventricular septum where it divides into right and
left branches
Left branch divides into 2 smaller branches (fascicles) which supply anterior and
posterior parts of left ventricle respectively
Bundle branches subdivide into the Purkinje fibres that form a network of cells to
carry the depolarization wave to the myocardial cells
Return of ventricular muscle cells to their resting electrical state is called
repolarization
EGG Waveform
Terminology
P wave - 1st deflection corresponds to depolarization and the atria
QRS Complex - 3 deflections - 1st downwards (Q wave), 2nd upwards (R wave) and
3rd downwards (S wave) corresponds to depolarization of the ventricle.
T Wave - repolarization of ventricular muscles.
Upward deflection is a depolarization wave is moving towards recording electrodes
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 9
Downward deflection repolarization wave is moving away from the recording
electrodes.
Time intervals
All EGG recorders run a standard paper speed of 25 mm/s.
EGG paper is standardized so that 5 large squares pass under the recorder stylus
each second.
One large square is equivalent to 0.2 sec.
Each large square is subdivided into five small squares each equivalent to 0.04s.
Heart rate can be calculated from the number of squares between QRS complexes.
Time taken by each part of the depolarization sequence in each cardiac cycle is
Calculated by the number of small squares it occupies.
PR interval
Is the time taken for depolarisation to spread from SAN to Atria to AVN through the
Bundle of HIS bundle to the ventricle
Shown by number of small squares between beginning of P wave and the beginning
of the ORS complex.
Normal upper limit 0.20 seconds.
Width of QRS complex indicates the time taken by the depolarisation wave to spread
throughout the ventricles.
QT intervals
Time taken for the whole depolarization sequence in ventricles.
Obtained from the number of squares between beginning of QRS complex and of T
wave.
Abnormalities of Conduction
(a) AV Node/Bundle of HIS
Prolonged PR interval
1) 1st degree heart block - P Wave is followed by QRS complex.
2) 2nd degree heart block - some P waves are followed by QRS complexes but
others are not. There are 3 varieties of 2nd degree heart block
3) 3rd degree (complex) – no P waves are conducted, ventricular escape rhythm
controls the heart with a slow rate, QRS complexes are wide and abnormal.
(b) His bundle branches
Right bundle - branch block, broadening of QRS complex
Left bundle branch block - wide QRS complex, inverted T wave
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 10
3) ECHOCARDIOGRAPHY
- Use echoes of ultrasound waves to map the heart and study its function.
4) PHONOCARDIOGRAPHY
Application of a sensitive microphone to the chest which allows heart sounds and
murmurs to be recorded.
5) CARDIAC CATHETERIZATION
Is introduction of a thin radio-opaque tube (catheter) into the circulation
The pressure in the right heart chambers, left ventricle, Aorta and pulmonary artery
can be measured.
During the procedure blood samples can be taken to measure the concentration of
Ischaemic metabolites e.g. lactate oxygen content.
Radio opaque contrast material is injected.
Quality intra-cardiac shunts
6) URINALYSIS
Amount
Haematuria
Culture
Microscopy
Proteins
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 11
7) TOTAL BLOOD COUNT
Red blood cells
White blood cells
Platelets
8) Urea And Electrolytes
9) C-Reactive Proteins
10) Blood sugars
11) Liver Function Tests
12) Blood Cultures
13) Blood Lipid Profiles
Total cholesterol - below 200 milligrams per deciliter (mg/dL), or 5.2 millimoles
per liter (mmol/L).
Low-density lipoprotein (LDL) cholesterol - less than 130 mg/dL (3.4 mmol/L),
and under 100 mg/dL (2.6 mmol/L) is even better.
High-density lipoprotein (HDL) cholesterol - 60 mg/dL (1.6 mmol/L) or higher,
though it's common that HDL cholesterol is higher in women than men.
Triglycerides - be less than 150 mg/dL (1.7 mmol/L)
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 12
Lesson 2: Congenital Heart Diseases
Learning Outcomes
At the end of the lesson the learner shall be able to: -
1. Describe the pathology of congenital heart disorders
1.0. INTRODUCTION
Congenital heart disease is the abnormality of the heart or blood vessels present from
birth. It is the most important cause of heart disease in the early years of life and the
incidence is higher in premature infants. Cardiac malformations occur during the stage
of cardiac development (3rd - 8th week of gestation). Cardiac abnormalities could be
incompatible with intrauterine life, manifest shortly after birth when foetal circulation
changes to the postnatal circulation, cause cardiac malfunction only in adult life or be
entirely innocent.
Congenital anomalies are morphologic defects that are present at birth. These anomalies may occur are malformations, disruptions, sequences and syndromes.
Malformations are primary errors of morphogenesis where there is an intrinsic
abnormal development process. They are as a result of multiple causes. Disruptions result from secondary destruction of an organ or body region that was
previously in normal development. Results from extrinsic disturbance in
morphogenesis. Deformations result from extrinsic disturbance of morphogenesis through local or
generalized compression of the growing foetus by abnormal biomechanical forces
e.g. uterine constraints such as maternal factors (which ones?) and foetal factors
(such as?). Sequence – a pattern of cascade anomalies (examples?)
Syndrome - collection of congenital anomalies
2.0. DEVELOPMENT OF THE HEART
The remarkable development of the heart occurs in 6 – 7 days but becomes obvious
at day 18 or 19 in the cardiogenic area of the mesoderm layer where a paired mass of specialized cells called the heart cords form
After a short time a hollow centre develops in each cord to form a heart tubes
The heart tubes begin to migrate towards each other during day 21 and soon fuse to form a single median endocardial heart tube
The process of fusion is accompanied by dilatations and constrictions of the tube so
that when fusion is completed during the 4th week five distinct regions can be seen
These regions are the truncus arteriosus, bulbous cordis, ventricle, atrium and
sinus venosus.
3.0. AETIOLOGY
1. Idiopathic/unknown (90%)
2. Genetic – arise from karyotypic aberrations, gene mutations and multifactorial
inheritance. Examples - chromosomal abnormalities e.g. Trisomy 21 (Down’s
syndrome)
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 13
3. Environmental factors such as infections in the mother during pregnancy e.g.
rubella, drugs and alcohol and cigarette smoking, radiation, maternal diabetes
4. Multifactorial causes
4.0. PATHOGENESIS
The timing of prenatal teratogenic determines the occurrence and type of anomaly
produced. The embryogenic period which takes first 9 weeks (early - 1st 3 weeks) and
foetal period (10 weeks to birth) determine the outcomes as organogenesis occurs
mainly during embryogenic whereas during the foetal period there is growth and
development of organs with reduced susceptibility to teratogenic agents but
susceptible to growth retardation.
5.0. CLINICAL EFFECTS/FEATURES
Children with significant congenital anomalies have disturbance in the haemodynamics
of blood flow, failure to thrive, cyanosis, increased risk to recurrent or chronic
infections and high risk of infective endocarditis.
6.0. CLASSIFICATION
1. Malposition of the heart
2. Shunts (Cyanotic Congenital Heart Disease) - Left-to-right shunts and Right-to-left
shunts
3. Obstructions (Obstructive Congenital Heart Disease)
7.0. MALPOSITIONS
1. Ectopia Cordis
This is a birth defect in which the abnormally located outside the thoracic cavity and
has defective heart muscles and coverings
Diagram 2.1: Ectopia Cordis
Most commonly the heart protrudes outside the chest through a split sternum and
less often the heart may be situated in the abdominal cavity or neck
Condition is fatal in first days of life. It is associated with other malformations such as
Tetralogy of Fallot, pulmonary atresia, atrial and ventricular septal defects, and
double outlet right ventricle. Other non-cardiac malformations may be present such
as cleft palates
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 14
Most cases result in stillbirth or death shortly after birth. Depending on the position
of the heart from birth ectopia cordis can be classified into four categories namely -
cervical, thoracic, thoracoabdominal and abdominal.
2. Malposition (Dextrocardia)
Dextrocardia is the presence of the heart ion the right hemithorax with the apex of the
heart points to the right side of the chest. It is usually associated with major anomalies of
the heart e.g. transposition of the atria or great arteries.
Diagram 2.2: Dextrocardia
8.0 SHUNTS (CYANOTIC CONGENITAL HEART DISEASES)
8.1 Introduction
A shunt is an abnormal communication between heart chambers, between blood
vessels or between the heart chambers and blood vessels. The pressure differences in
heart chambers determines the direction of shunting of the blood - left-to-right shunting
(more common) or right-to-left shunting.
8.2 Classification
1. Left-to-right shunts (late cyanosis or acyanotic heart diseases)
a. Atrial Septal Defect (ASD)
b. Ventricular Septal Defect (VSD)
c. Patent Ductus Arteriosus (PDA)
d. Atrioventricular Septal Defect (AVSD)
2. Right-to-left shunts (early cyanosis or cyanotic heart diseases ) – 5TS
a. Tetralogy of Fallot (TOF)
b. Transposition of great arteries
c. Truncus arteriosus and stenosis
d. Tricuspid atresia and stenosis
e. Total anomaly of pulmonary venous drainage/connection
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 15
8.3 LEFT-TO-RIGHT SHUNTS (Acyanotic Heart Disease)
These cause cyanosis several months or years after birth.
1. Atrial Septal Defect (ASD)
ASD is an abnormal opening in the atrial septum that allows free communication
between the left and right atria
Accounts for 10% of congenital heart diseases
Usually asymptomatic until in adulthood when pulmonary hypertension (in 10%
cases) is induced causing late cyanotic heart disease and right-sided heart failure
Effects are produced due to left-to-right shunt at the atrial level with increased
pulmonary flow
Result in hypertrophy of the right atrium and ventricle, enlargement and
haemodynamic changes in tricuspid and pulmonary valves, reduction in size of left
atrium and left ventricle and reduction in size of the mitral and aortic orifices.
Diagram 2.3: ASD
Features
1. Right ventricular hypertrophy
2. Cardiac failure
3. Cyanosis (late)
4. Haemodynamic changes + Murmur
5. Failure to thrive
2. Ventricular Septal Defect (VSD)
Most common congenital anomaly of the heart in which there is incomplete closure
of the ventricular septum allowing free communication between the left and right
ventricles
Usually recognized early in life
30% cases occur in isolation but it is frequently associated with other structural
anomalies especially the Tetralogy of Fallot
Explain the pathophysiology of these features.
How will use elicit them on physical examination
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 16
50% of the smaller defects of less than 0.5 cm in diameter close spontaneously
Clinical features range from asymptomatic murmurs to late cyanosis and fulminant
chronic heart failure depending on the size of the defect
Effects are produced due to left-to-right shunt at the ventricular level, increased
pulmonary flow and increased volume in the left side of the heart
Result in hypertrophy and dilatation of the right atrium and ventricle, endocardial
hypertrophy of the right ventricle and enlargement and haemodynamic changes in
all the heart valves
Diagram 2.4: VSD
Features
1. Hypertrophy and dilatation of the right atrium
2. Hypertrophy and dilatation of the right ventricle
3. Murmur
4. Cardiac failure
5. Failure to thrive
Diagram 2.5: Effects of VSD
Explain the pathophysiology of these features.
How will use elicit them on physical examination
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 17
3. Patent/Persistent Ductus Arteriosus (PDA)
The ductus arteriosus (DA) is a normal vascular connection between the aorta and the
bifuractaion of the pulmonary artery which allows communication between the aorta
and the pulmonary artery in the foetus (foetal life). Normally at term the ductus closes
within the first 1-2 days of life as a result of muscular contraction due to the effect of
relatively high oxygen tension and reduced local prostaglandin E (PGE2) synthesis.
Persistence of ductus arteriosus beyond 3 months of life is usually permanent and
abnormal. PDA which accounts for 10% of congenital heart diseases usually occurs as
an isolated anomaly in 85-90% cases. It may be associated with VSD, coarctication of the
aorta and pulmonary or aortic stenosis. There is an accompanying left ventricular
hypertrophy and pulmonary artery dilatation.
The cause for patency of the DA is idiopathic but it is associated with continued
synthesis of PGE2 after birth. This has been established by evidence of association of
respiratory distress syndrome (RDS) with PDA and pharmacologic closure of PDA with
administration of indomethacin to suppress PGE2 synthesis
Diagram 2.6: PDA
Pathophysiology
PDA allows the shunting of blood from the high pressure aorta to the low pressure
pulmonary artery, increasing the volume of blood passing through the lungs and
returning to the left atrium.
This is similar to an increased preload and leads to left atrial dilation, increased LA
pressure, increased PV pressure and ultimately pulmonary congestion (left-sided
congestive heart failure).
Bulging of the aorta and pulmonary artery proximal to the PDA occurs as a result of
increased blood volume and turbulent flow.
There is always a pressure difference between the aorta and pulmonary artery
(greatest during systole), and consequently continuous flow through the PDA
producing the characteristic continuous murmur.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 18
The increased flow through the pulmonary artery can result in pulmonary
hypertension. When the pressure in the pulmonary artery equals or even exceeds
that of the aorta, either the diastolic portion of the murmur or the complete murmur
may disappear due to flow reversal (reverse shunting PDA)
Blood then bypasses the lungs and the patient presents with cyanosis and a
compensatory polycythaemia.
Effects
1. Loud murmur (machinery murmur)
2. Pulmonary hypertension
3. Right ventricular hypertrophy
4. Right atrial hypertrophy
5. Dilated ascending aorta
Diagram 2.7: Effects of PDA
1.0. RIGHT-TO-LEFT SHUNTS (Cyanotic Congenital Heart Disease)
In right-to-left shunts there is shunting of blood from the right side of the heart to the left
side allowing entry of poorly oxygenated blood into the systemic circulation. This results in early cyanosis hence the description of congenital cyanotic heart disease.
These shunts (communication channel) can allow movement of emboli from venous
sources to pass directly into the systemic circulation resulting in what we would call paradoxical emboli.
1. Tetralogy of Fallot (TOF)
TOF accounts for 10% of children born with heart abnormalities. It is composed of four
(tetralogy) cardinal anomalies namely: - 1) VSD (the shunt), 2) displacement of the
aorta to the right side (dextraposition of the aorta) so as it overrides the VSD, 3)
pulmonary stenosis (obstruction) with ventricular outflow obstruction and 4) right
ventricular hypertrophy. Severity of symptoms in TOF is determined by the extent of
right ventricular outflow obstruction and the size of the VSD. A large VSD and a mild
pulmonary stenosis lead to a left-to-right shunt without cyanosis and a severe
pulmonary stenosis results in a cyanotic right-to-left shunt. When there is complete
obstruction survival can only occur through a patent ductus arteriosus (PDA) or dilated
bronchial arteries.
Why is PDA classified as a left-to-right shunt disorder?
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 19
Effects
1. Hypertrophy of the right atrium and right ventricle
2. Cyanosis
3. Failure thrive
4. Cardiac failure
5. Murmurs
Diagram 2.8: Tetrology of Fallot (TOF)
1 - Pulmonary stenosis (a form of right ventricular outflow tract obstruction)
2 - Right ventricular hypertrophy
3 - Overriding aorta
4 - Ventricular septal defect
2. Transposition of Great Arteries (TGA)
The aorta arises from the right ventricle while the pulmonary artery emanates from the
left ventricle. TGA is common in children of diabetic mothers. The 2 common types are regular transposition (commonest) where the aorta is displaced anteriorly and the to
the right of the pulmonary trunk type) and corrected transposition. In majority of the
cases children die within the first few weeks/months if untreated and the prognosis
depends on severity of tissues hypoxia and the ability of the right ventricle to maintain
aortic blood flow.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 20
Diagram 2.9: Transposition of Great Vessels
3. Truncus Arteriosus
This is a rare abnormality with a poor prognosis associated with numerous connected defects of the heart. The embryological structure known as the truncus arteriosus
never properly divides into the pulmonary artery and aorta resulting in a single large
common vessel receiving blood from both the left and right ventricle. There is an
associated VSD. The patient presents with early cyanosis due to the right-to-left shunt
but the flow later reverses and the patient develops right ventricular hypertrophy with
pulmonary vascular hypertension.
Diagram 2.10: Truncus Arteriosus
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 21
Clinical Features
Cyanosis at birth, cardiomegaly and biventricular hypertrophy, heart failure occurs
within weeks, loud second heart sound with a systolic ejection murmur, widen pulse
pressure and bounding arterial pulses
4. Tricuspid Atresia and Stenosis
Is an abnormality often associated with pulmonary stenosis and atresia with an inter-
atrial defect through which right-to-left shunting of blood occurs. There is absence of
tricuspid orifice in tricuspid atresia and a small tricuspid ring with malformed valve
cusps in tricuspid stenosis. Children with tricuspid atresia are cyanotic since birth and
live for a few weeks or months.
Features
Progressive cyanosis
Poor feeding
Tachypnea over the first 2 weeks of life
Holosystolic murmur due to the VSD
Left axis deviation on electrocardiography and left ventricular hypertrophy (since it
must pump blood to both the pulmonary and systemic systems)
Normal heart size
5. Total Anomaly of the Pulmonary Venous Drainage (TAPVD)
TAPVD is a rare cyanotic congenital heart defect (CHD) in which all four pulmonary
veins are malpositioned and make anomalous connections to the systemic venous
circulation. There are no pulmonary veins directly joining the left atrium hence
drainage is into the left innominate vein or to the coronary sinus.
Features
Volume and pressure hypertrophy of the right atrium and right ventricle, cyanosis,
murmur (systolic ejection) right ventricular heave, RHV, cardiomegaly, cardiac
failure, splitting of S2, S3 gallop, Failure to thrive
2.0. OBSTRUCTIVE CONGENITAL ANOMALIES
They result in obstruction to blood flow from the heart and are classified as obstruction
in the aorta e.g. coarctication of the aorta, obstruction to outflow from the left ventricle –
aortic stenosis and atresia and obstruction to outflow from the right ventricle –
pulmonary stenosis and atresia
1. Coarctication of the Aorta
The aorta is compressed or contracted and 50% cases occur as isolated defects with the
remaining occurring with multiple other anomalies of the heart. There is localized
narrowing of the aorta in any part with the constriction being more often distal to the
ductus arteriosus (post-ductal or adult type) or occasionally proximal to the ductus arteriosus (pre-ductal or infantile type) on the transverse aorta. Causes of Death:
Chronic cardiac failure, aortic dissection, intracranial haemorrhage and infective
endocarditis
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 22
Diagram 2.11: Coarctication of the Aorta
2. Aortic Stenosis and Atresia
The most common abnormality of the aorta is bicuspid aortic valve, which has less
functional significance but predisposes to calcification. Complete aortic atresia is rare
and incompatible with neonatal survival. Aortic stenosis may be congenital or acquired.
Congenital aortic stenosis is of three types –
(1) Valvular stenosis where there valves cusps are irregularly thickened and
malformed
(2) Subvalvular where there is a thick fibrous ring under the aortic valves causing
subaoratic obstruction and
(3) Supravalvular stenosis that has a fibrous constriction above the sinuses of valsalva.
Effects
1. Left ventricular hypertrophy (pressure overload)
2. Post-stenotic dilatation of the aortic root
3. Infective endocarditis
4. Sudden death (rare)
3. Pulmonary Stenosis and Atresia
This is the commonest form of obstructive congenital heart disease where there is fusion
of the cusps of the pulmonary valve forming a diaphragm like obstruction to blood flow
and it may also occur as a component of TOF or may occur in conjunction with
transposition abnormalities. In pulmonary stenosis there is no communication between
right ventricle and the lungs so blood bypasses the right ventricle through an inter-atrial septal defect and enters the lungs via the PDA. WHAT ARE THE FEATURES?
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 23
Lesson 3: Cardiac Failure (Heart Failure)
Learning Outcomes
At the end of the lesson the learner should be able to: -
1. Define cardiac failure
2. Describe the causes of cardiac failure
3. Describe the pathology of cardiac failure with respect to each cause
1.0. DEFINITION
Cardiac failure is a situation when the ventricular myocardium fails to maintain a
circulation adequate for body requirements despite adequate venous return
The heart is unable to deliver a supply of oxygenated blood that is adequate for
meeting metabolic needs of peripheral tissues both at rest and during exercise
Physiologically heart failure is a state in which an increase in filling pressure and
therefore fibre length causes a fall rather than a rise in cardiac output.
Heart failure (HF) is a syndrome of ventricular dysfunction
Heart failure is a clinical syndrome in which patients have the
Symptoms typical of heart failure (breathlessness at rest or on exercise, fatigue,
tiredness, ankle swelling)
Signs typical of heart failure (tachycardia, tachypnoea, pulmonary rales, pleural effusion, raised jugular venous pressure, peripheral oedema, hepatomegaly)
Objective evidence of a structural or functional abnormality of the heart at rest (cardiomegaly, third heart sound, cardiac murmurs, abnormality on the
echocardiogram, raised natriuretic peptide concentration)
2.0. RISK FACTORS
Age, Hypertension, Physical inactivity, Diabetes, Obesity, Smoking, Gender , Nutrition ,
Family history of heart failure, Enlargement of the left ventricle, Some types of valvular
heart disease, including, infection, Coronary artery disease, High cholesterol and
triglycerides, Excessive alcohol consumption, Prior heart attack, Certain exposures,
such as to radiation and some, Types of chemotherapy, Infection of the heart muscle
(usually viral)
3.0. CAUSES OF CARDIAC FAILURE
The causes of cardiac failure include: -
1) Intrinsic pump failure
2) Increased work load on the heart - Pressure overload and Volume overload
3) Impaired filling of the cardiac chambers
4) Multifactorial ( a combination of the above factors)
3.1. Pump Failure
Intrinsic pump failure is the most common and important cause of heart failure. The
heart has 2 main pumps: - the left pump which pumps blood to the peripheral organs
and the right one that pumps blood to the lungs. Pump failure frequently results from
weakness of ventricular contractions.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 24
Causes of Intrinsic Pump Failure
1. Myocardial weakness
2. Cardiac rhythm disorders
3. Reduced or poor myocardial response
4. Multifactorial (multiple causes)
Myocardial Weakness
A situation where muscle weakness leads to unsatisfactory pumping action of the heart
muscles due to reduced contractibility of myocardium leading to secondary reduction
of Blood supply.
Causes
The causes of myocardial weakness can classified based on aetiology or function.
a) Aetiological Classification
1. Myocardial Ischaemia and infarction
2. Infections
3. Nutritional Deficiency states- Beri Beri (Thiamine)
4. Systemic connective Tissue Disorders - rheumatoid arthritis, systemic lupus
erthromatosus (S.L.E) and polyarteritis Nodosa.
5. Cardiomyopathies - reduces the contractibility of the myocardium
6. Metabolic/Endocrine - diabetes mellitus, altered Thyroid function
[Hyperthyroidism/Hypothyroidism], adrenal cortical insufficiency and acromegaly.
7. Storage disorders - Glycogen storage disease
8. Infiltrations – Amyloidosis, Sarcoidosis, Heamochromatosis
9. Sensitivity and Toxic reactions - drugs e.g. cytotoxic drugs, alcohol, cobalt and
barbiturates
10. Physical agents - Irradiation
b) Functional Classification
This is based on whether the chambers are dilated or not. Dilatation can be generalized
or focal. Myocardial weakness may be due to hypertrophic and/or restrictive
cardiomyopathy
Pathology of Myocardial Weakness
1. Expulsion of blood by the ventricles during systole is reduced due to the weak
pumping action of the ventricles leaving a residual blood volume. 2. During diastole the chambers dilate to contain both residual and incoming blood
causing dilatation of the ventricles putting the ventricles at a greater disadvantage
as more force will be required to pump out the increased volume of blood (Frank-Starling Law). But due to the weakness of the myocardium, this is will not achieved
and therefore blood pools in the ventricles.
3. If the destruction is not halted, dilatation of the ventricles and failure are
progressive.
4. Ventricular dilation (left ventricle and right ventricle) leads to the stretching of the
respective valves (mitral and tricuspid) resulting in valve incompetence of the Mitral
and Tricuspid valves respectively.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 25
5. This worsens the situation due to reduced cardiac output and damming of blood in
veins which increase systemic venous pressure (systemic venous pressure) slowing
the general circulation.
CARDIAC RHYTHM DISORDERS
Effective pumping action of the heart is achieved by alternate relaxation and
contraction allowing blood to enter the chambers (during relaxation – diastole) and force in out during contraction (systole). This is achieved by the co-ordination,
conduction and rhythmicity of the cardiac muscle together with the efficiency of the
conducting system of the heart, which comprises of the sino atrial Node (SAN), atrial
Ventricular Node (AVN), the Purkinje tissue and the Bundle of His.
Circus Movement
The cardiac impulse conduction around the heart without stopping hence there is
continuous impulse conduction due to an enlarged heart (long pathway), slow
conduction e.g. failure of the purkinje tissue, decreased refractory period which results
from epinephrine, sympathetic stimulation and irritation of the heart by disease and
transmission of impulses in figures of 8’s for example in ventricular fibrillation
Rhythm Disorders
Arrhythmias can be can disorders of impulse conduction at sites such as the SAN, AVN,
atria, Ventricles and Purkinje tissues or disorders of impulse formation in the form of
abnormal site of origin or abnormal rate of impulse discharge.
Tachycardia
This is a rhythm rate greater than 100 beats per minute. Causes of tachycardia include:
exercise, anxiety and any disorder that increases the sympathetic nervous system
stimulation
Pathology
Tachycardia impairs diastolic refilling of ventricles and shortens the coronary artery
diastolic filling reducing blood supply to the heart. This results in decreased stroke
volume and cardiac output thus decreasing blood supply to the myocardium resulting in ischaemia [Myocardial], which reduces the performance of the heart. Examples of
Tachycardia are: - atrial fibrillation, atrial flutter, paroxysmal Tachycardia and
atrial tachycardia
Atrial fibrillation
Atrial fibrillation is an impulse transmission of 350 – 600 beats per minute. The impulse
is irregular in time and force. It is worse on exercise.
Pathology
Fewer impulses reach the ventricles to effect contraction and therefore the stroke
volume and cardiac output reduce hence compromising blood supply and there is
irregular ventricular response to transmission of impulses from the atria. The resulting
incompetent emptying of the ventricles causes pooling of blood in the heart chambers
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 26
leading to dilatation and hypertrophy of the ventricles and cardiac failure if the situation
is not reversed
Causes
Rheumatic Heart Disease (RHD), coronary Heart disease, hypertensive heart disease.
Thyrotoxicosis, cardiomyopathies (Dilated and hypertrophic cardiomyopathy),
constrictive pericarditis, pulmonary embolism and alcohol abuse
Atrial Flutter
Atrial flutter is an impulse frequency of 125– 300 beats per minute. It is usually regular
but can become irregular if there is fluctuating heart block.
Pathology
Fewer impulses reach the ventricles to effect contraction and therefore the stroke
volume and cardiac output are reduced hence compromising blood supply. There is
irregular ventricular response and the resulting incompetent emptying of the ventricles
causes pooling of blood in the heart chambers leading to Dilatation and
Causes
Digoxin toxicity, cardiomyopathy, chronic ischaemic heart disease and rheumatic heart
Disease (RHD) Paroxysmal Tachycardia
Is an impulse transmission of 150 – 250 beats per minute and it is intermittent
Bradycardia
Bradycardia is an impulse rate of below 60 beats per minute
Pathology
In partial heart block at SAN some impulses reach ventricles to effect contraction but
stroke volume cardiac output and heart rate are reduced but in total heart block at SAN
no impulses pass to effect ventricular contraction hence the ventricles contract at 25
beats/min. (Normal for ventricular Tissue). This is inadequate to sustain required blood
supply.
Causes
Physiological (athletes and during sleep) and pathological - cardiac - acute Myocardial
infarction, drugs (Beta blockers, Digoxin) and heart block; non cardiac -
hypothyroidism, obstructive jaundice and increased intracranial pressure
Heart Block
Interferes with the conduction process and impulses are blocked from getting through
the ventricular myocardium resulting in ventricles contracting at a much slower rate
than normal. This can occur at the SAN, AV – Block; 1st degree there is delayed impulse
transmission from to ventricles; 2nd degree there is intermittent failure of impulse
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 27
transmission (Mobitz I block, Mobitz II block and 2:1 or 3:1 (advanced) block and 3rd
degree where there is complete A–V block
Causes
Myocardial infarction, digoxin toxicity, idiopathic fibrosis, congenital heart disease,
aortic valve disease, infiltration - tumours, syphilis, endocarditis, inflammation -
rheumatoid arthritis, ankylosing spondylitis, Reiter’s syndrome and sarcoidosis,
rheumatic fever and diphtheria
3.2. Increased Workload on the Heart
Pressure Overload
This is a situation where there is increased resistance to the expulsion of blood from
the ventricles or inflow of blood into ventricles.
Causes
1. Left Ventricle - aortic stenosis and systemic hypertension
2. Right ventricles - pulmonary hypertension, mitral stenosis and lung Disease
Pathology
This can be considered in two groups of ventricular outflow obstruction and ventricular
inflow obstruction.
Ventricular Outflow Obstruction
This can be as a result of hypertension (pulmonary and systemic hypertension), aortic
stenosis and pulmonary Stenosis
Pathology
1. Obstruction to out flow of blood from the ventricles causes increased afterload (ventricular) with the response of ventricular hypertrophy but the ventricular
capacity remains (Starling’s Law)
2. Increased in ventricular muscle bulk causes muscles stiff and this will require higher atrial pressure for refilling and so there occurs Atrial hypertrophy
3. With the increased load due to increased afterload the ventricles dilate needing
high wall tension to maintain the systolic pressure (Laplace’s Law)
4. Coronary vessels are unable to supply the increased muscle bulk with adequate
blood so the muscle fibres become ischaemic and die off. The ischaemic muscle tissue is replaced by fibrous tissue, which has poor contractibility.
Ventricular Inflow Obstruction
Causes
This can result from mitral stenosis, tricuspid stenosis, cardiac tumours, external
Pressure or Constriction e.g. constrictive pericarditis and endomyocardial fibrosis
Pathology
1. Obstruction of in flow of blood from the atria causes increased afterload (atrial) with the response of atrial hypertrophy but the atrial capacity remains (Starling’s Law)
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 28
2. Increase in atrial muscle bulk makes them stiff and this will require higher systemic venous pressure for refilling and emptying and so there occurs atrial hypertrophy
3. With increased load (due to increased afterload) the atrial dilatation requires high
wall tension to maintain the systolic pressure (Laplace’s Law) hence there occurs
pooling of blood in the systemic and pulmonary vessels. This reduced ventricular
filing
4. Reduced ventricular filling cardiac output is reduced
5. Coronary vessels are unable to supply the increased muscle bulk with adequate
blood so the muscle fibres become ischaemic and die off. The ischaemic muscle
tissue is replaced by fibrous tissue, which has poor contractibility 6. The increased atrial action causes hypertrophy and dilatation, which result in Atrial
fibrillation
Volume Overload
This occurs when the ventricles are required to expel more than the normal amount of
blood
Causes
1. Incompetent valves that allow blood to flow back into the chambers increasing the
blood volume e.g. aortic regurgitation and pulmonary regurgitation.
2. States with high general circulation (High Output States) such as severe anaemia,
thyrotoxicosis, Beriberi and patent Ductus Arterious (PDA).
3. Hypoxia resulting from lung disease (increase circulation) e.g. cor pulmonalae
which leads to an increase in circulation.
4. Arterio-venous shunts between the left and right sides of the circulation causing
cyanosis and hence hypoxia which causes increased circulation
Explanation/Pathology
The pathology is based on the effects of ventricular hypertrophy and dilatation, Frank-
Starling’s Law and Laplace’s Law
3.3. Impaired Filling of the Cardiac Chambers
The cardiac output is decreased and cardiac failure ensues due to extra cardiac causes or defects in the filling of the heart chambers as seen in cardiac tamponade and
constrictive pericarditis
3.4. Multiple Factors
This involves a combination of the above-mentioned factors.
4.0. COMPENSATORY MECHANISMS
The functioning of the heart is guided by intimate integrating four principle determinants that regulate the stroke volume and cardiac output. There are two
intrinsic factors - preload (ventricular end-diastolic volume) and afterload
(intraventricular systolic tension during ejection) and two extrinsic autonomic
modulations - contractility (variable force of ventricular contraction independent of
loading) and heart rate (frequency of contraction).
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 29
The Basic Adaptive Mechanisms
The cardiovascular system maintains arterial pressure and perfusion of vital organs
when there is huge haemodynamic burden or disturbance in myocardial
contractility through a number of adaptive mechanisms geared to sustaining
adequate cardiac performance.
These adaptive mechanisms include
o Frank-Starling mechanism
o Myocardial structural changes (dilatation and hypertrophy)
o Activation of neuro-hormonal systems (adrenaline, RAA and ANP).
Frank-Starling Principle
Describes the relationship between preload and cardiac performance
Sates that, normally, systolic contractile performance (represented by stroke volume
or CO) is proportional to preload within the normal physiologic range
Normally (top curve), as preload increases, cardiac performance also increases.
However at a certain point, performance plateaus, then declines. In heart failure (HF)
due to systolic dysfunction (bottom curve), the overall curve shifts downward, reflecting
reduced cardiac performance at a given preload, and, as preload increases, there is
less of an increase in cardiac performance. With treatment (middle curve), performance
is improved, although not normalized.
Compensatory Enlargement of the Heart
Compensatory enlargement of the heart prevents heart failure or postpones heart failure. This is achieved through three processes namely: - hypertrophy (results from
increased demand for pumping) dilatation (accommodation of excessive blood) and
remodelling (change in structure of myocytes)
Classification
The compensatory changes in heart failure can be classified as: -
Local
1. Chamber enlargement
2. Myocardial hypertrophy
3. Increased heart rate
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 30
Systemic Changes
1. Activation of the sympathetic nervous system and RAAS
2. Release of ANP and ADH
5.0. PATHOPHYSIOLOGY OF CARDIAC FAILURE
Systolic dysfunction
HF with reduced EF (ejection fraction)
The ventricle contracts poorly and empties inadequately, leading initially to
increased diastolic volume and pressure and decreased ejection fraction
Diastolic dysfunction
In diastolic dysfunction (also called HF with preserved EF)
Ventricular filling is impaired, resulting in reduced ventricular end-diastolic volume,
increased end-diastolic pressure, or both
Contractility and hence EF remain normal; EF may even increase as the poorly filled
LV empties more completely to maintain CO
Markedly reduced LV filling can cause low CO and systemic symptoms.
Cardiac response
If ventricular function is impaired, a higher preload is required to maintain CO
Ventricles are remodelled over time
LV becomes less ovoid and more spherical, dilates, and hypertrophies while the RV
dilates and may hypertrophy
Initially compensatory, these changes eventually increase diastolic stiffness and wall
tension (ie, diastolic dysfunction develops), compromising cardiac performance,
especially during physical stress. Increased wall stress raises O2 demand and
accelerates apoptosis (programmed cell death) of myocardial cells
Dilation of the ventricles can also cause mitral or tricuspid valve regurgitation with
further increases in end-diastolic volumes.
Haemodynamic responses:
With reduced CO, O2 delivery to the tissues is maintained by increasing O2
extraction and sometimes shifting the oxyhemoglobin dissociation curve to the right
to favour O2 release.
Reduced CO with lower systemic BP activates arterial baroreflexes, increasing
sympathetic tone and decreasing parasympathetic tone. As a result, heart rate and
myocardial contractility increase, arterioles in selected vascular beds constrict,
venoconstriction occurs, and Na and water are retained
These changes compensate for reduced ventricular performance and help maintain
hemodynamic homeostasis in the early stages of HF
However, these compensatory changes increase cardiac work, preload, and
afterload; reduce coronary and renal perfusion; cause fluid accumulation resulting in
congestion; increase K excretion; and may cause myocyte necrosis and arrhythmias.
Renal responses:
Decreased perfusion of the kidneys (and possibly decreased arterial systolic stretch
secondary to declining ventricular function) activates the renin-angiotensin-
aldosterone system
The renin-angiotensin-aldosterone-vasopressin (antidiuretic hormone [ADH])
system causes a cascade of potentially deleterious long-term effects
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 31
Angiotensin II worsens HF by causing vasoconstriction, including efferent renal
vasoconstriction, and by increasing aldosterone production, which enhances Na
reabsorption in the distal nephron and causes myocardial and vascular collagen
deposition and fibrosis
Angiotensin II increases norepinephrine release, stimulates release of vasopressin,
and triggers apoptosis
Angiotensin II may be involved in vascular and myocardial hypertrophy, thus
contributing to the remodelling of the heart and peripheral vasculature, potentially
worsening HF. Aldosterone can be synthesized in the heart and vasculature
independently of angiotensin II (perhaps mediated by corticotropin, nitric oxide,
free radicals, and other stimuli) and may have deleterious effects in these organs.
Neurohumoral responses
Help increase heart function and maintain BP and organ perfusion, but chronic
activation of these responses is detrimental to the normal balance between
myocardial-stimulating and vasoconstricting hormones and between myocardial-
relaxing and vasodilating hormones.
6.0. MANIFESTATIONS OF CARDIAC FAILURE
Manifestations of cardiac failure depend on the rate of development of the casual
factors and the side of the heart affected. Development of causal factors can results in
acute or chronic cardiac failure. The side of the heart involved that is left side (Left
ventricular failure - LVF), right side (Right Ventricular Failure - RVF) and total heart
failure (congestive cardiac failure) when both sides of the heart are [Congestive cardiac
failure - CCF (LVF + RVF)]
Grading Of Cardiac Failure - New York Heart association (NYHA) Classification Grade I No limitation of physical activity. Ordinary physical activity does not cause undue
fatigue, palpitation, or dyspnoea. Grade II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity
results in fatigue, palpitation, or dyspnoea. Grade III Marked limitation of physical activity. Comfortable at rest, but less than ordinary
activity results in fatigue, palpitation, or dyspnoea.
Grade IV Unable to carry on any physical activity without discomfort. Symptoms at rest. If any physical activity is undertaken, discomfort is increased.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 32
6.1. ACUTE CARDIAC FAILURE
Causal factors develop rapidly or suddenly as in myocardial infarction (massive),
gross pulmonary embolism, cardiac arrhythmias, acute bacterial toxaemia, rheumatic
fever and rapture of Ventricles and valve cusps. In severe cases of acute cardiac failure
(due to myocardial infarction) there is marked reduction in cardiac output with selective peripheral vasoconstriction following sympathetic activity causes CARDIOGENIC
SHOCK with central venous pressure increased (different for Hypovolaemic shock and
hence the different principles of management). There is decreased cardiac output that
leads to cerebral hypoxia
6.2. CHRONIC HEART FAILURE
The causal factors develop gradually (slowly) as in myocardial ischaemia due to
artheroma, severe systemic hypertension, chronic valvular disease/lesions and chronic
lung disease causing hypoxia leading to Pulmonary Hypertension. In this regard
cardiac output is diminished and tissue hypoxia results.
Dominant clinical
feature
Symptoms Signs
Peripheral
oedema/congestion
Breathlessness;
Tiredness, fatigue;
Anorexia
Peripheral oedema; Raised jugular
venous pressure; Pulmonary oedema;
Hepatomegaly, ascites; Fluid overload
(congestion); Cachexia
Pulmonary oedema Severe
breathlessness at rest
Crackles or rales over lungs, effusion;
Tachycardia, tachypnoea
Cardiogenic shock
(low output
syndromes)
Confusion; Weakness
Cold periphery
Poor peripheral perfusion; SBP ,90
mmHg; Anuria or oliguria
High blood pressure
(hypertensive heart
failure)
Breathlessness Usually raised BP, LV hypertrophy, and
preserved EF
Right heart failure Breathlessness
Fatigue
Evidence of RV dysfunction, Raised
JVP, peripheral oedema,
hepatomegaly, gut congestion
6.3. LEFT SIDED HEART FAILURE (LEFT VENTRICULAR FAILURE, LVF)
Introduction
The left ventricle is more commonly affected than the right ventricle. Left ventricular
failure leads to right ventricular failure then total heart failure (CCF).
Causes of LVF
1. Ischaemic Heart Disease (IHD) particularly Myocardial Infarction
2. Chronic Hypertension/Hypertension
3. Aortic valvular disease due to rheumatic endocarditis, aortic stenosis (calcific),
syphilitic heart disease and congenital heart disease
4. Mitral incompetence/mitral valve disease
5. High output conditions – severe anaemia, AR, fever, thyrotoxicosis, A-V
malformations, Beri Beri
6. Cardiomyopathy
7. Adhesive mediastino-pericarditis
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 33
Pathology
1. During systole the left ventricle fails to expel all the blood it receives hence contains
an increasing volume of blood at the end of systole
2. During the next diastole there is accumulation of the residual blood (left during
systole) and the incoming blood during diastole. Increased diastolic volume causes
dilatation of the ventricle further increasing inadequacy of contraction.
3. Ventricular dilation causes stretching of valve rings (mitral 10cm) resulting in incompetence (Mitral Regurgitation - MR)
4. Mitral regurgitation allows some blood expelled during systole passes through the
valve to the left atria increasing pressure here (left atria) causing venous congestion in the pulmonary system causing oedema of the lungs (pulmonary oedema)
5. Pulmonary congestion leads to shortness of breath, orthopnoea, PND and
haemoptysis.
6. This retrograde loss of blood through the leaking valve further compromises the
ventricular output and cardiac output.
7. Decreased output causes renal ischaemia (acute tubular necrosis, oliguria), CNS
ischaemia -anoxic neuronal changes (dizziness, confusion), bowel ischaemia –
mucosal or transmural necrosis (GI bleeing, sepsis) and skeletal ischaemia
(weakness, fatigue, reduced exercise tolerance)
8. With the situation persisting there is ventricular dilatation and hypertrophy.
Clinical Features (Manifestation)
The clinical manifestations result from insufficient blood flow through the various body
organs and tissues plus the pulmonary congestion due to stasis of blood in the
pulmonary circulation. The clinical manifestations include or involve the heart (size,
abnormal heart sounds, pulse), the lungs (dyspnoea, orthopnoea, paroxysmal nocturnal
dysnpoea (PND), cough, and cyanosis), pedal oedema, kidneys, brain and the liver
1) The Heart
a) Size – cardiomegaly
b) Abnormal heart sounds
c) The Pulse rate – there can be tachycardia or bradycardia
d) Pulse rhythm and pulse character
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 34
Cardiomegaly
Increase in the heart side due to dilatation and hypertrophy of the heart chambers.
Assessment of cardiomegaly is based on subjective visual impression, physical
examination (palpation of the apex beat), determination of the cardio-thoracic ratio
and volume measurement (length x width x depth x 0.63)
Abnormal Heart Sounds
There may be a third or fourth heart sound. The third Heart sound (S3 Gallop) occurs
due to rapid ventricular filling. This can be due to young age (normal), constrictive
pericarditis, rheumatic mitral stenosis, severe non-rheumatic mitral regurgitation and valvular heart disease – mitral/Aortic regurgitation. The fourth heart sound (S4
Gallop) occurs in situations of increased atrial activity due to left ventricular disease,
left ventricular hypertrophy, dilated heart cavity, pulmonary stenosis, pulmonary
hypertension and acute myocardial infarction
2) The Pulse
Pulsus paradoxicus (Kussmal’s sign) or Pulsus alternans
3) The Lungs
The effects seen in the lungs are dyspnoea, cyanosis, cough and crepitations.
Congestion and oedema occur in the pulmonary venous circulation and the alveolar
capillaries as the fluid collects in alveoli (pulmonary) and in severe cases rhexis of red
blood cells into the capillaries occurs causing haemorrhage into alveolar spaces. Dyspnoea occurs due to inadequate oxygenation of blood flowing though functionally
impaired lungs, anoxaemia of respiratory centre and the carotid sinus and decreased
vital capacity of lungs due to vascular distension
PND (Paroxysmal Nocturnal Dyspnoea)
Pulmonary congestion and oedema are worsened by severe functional imbalance of
ventricles
Paroxysmal (nocturnal) dyspnea is a sudden-onset of severe shortness of breath and
coughing, awakening the patient.
Factors that produce paroxysmal dyspnoea include:
1. Depression of respiratory centre during sleep (decreases arterial oxygen)
2. Decreased ventricular function due to decreased sympathetic tone (decrease
myocardial contractility and hence cardiac output) and
3. Redistribution of fluid to the chest.
Pathophysiology of PND
1. Excessive sympathetic activity causes venoconstriction so blood moves from the
systemic veins to the pulmonary circulation.
2. During sleep, irritability of CNS decreases hence accumulation of oedema with
provoking defence system e.g. cough
3. Decreased muscular activity allows pooling of blood in veins and change in position
or movement expels blood causing sudden increase volume in the lungs.
Explain the pathophysiology of orthopnoea. How will you determine orthopnoea
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 35
4. Reabsorption of interstitial fluid in recumbence causing increase blood volume.
5. In active state, hydrostatic pressure at the capillary level is high leading to fluid
effusion into the interstitial spaces. At night (inactive) the reverse happens leading to
net fluid flow in the vascular system, heart and pulmonary circulation leading to
congestion causing paroxysmal dyspnoea
6. The patient lying down improves the venous return from the limbs worsening the
situation.
Cough occurs as a result of irritation of mucosa (oedema fluid). The cough may be
productive of blood-streaked, frothy sputum due to pulmonary congestion and oedema
Pulmonary oedema occurs due to venous congestion in the lungs and causes wheezy
respirations “Cardiac asthma” Rhonchi, basal crepitations and Chyne-strokes respiration in chronic pulmonary oedema. Cyanosis may be present or not.
4) Kidneys
Reduced cardiac output causes low glomerular filtration rate (GFR) reducing the renal
blood flow, which results in renal anoxia and vasoconstriction reflexes. There is sodium
retention leading to oedema formation.
5) Brain
Reduced cardiac output compromises blood flow to the brain resulting in cerebral
anoxia, irritability, and loss of attention span, restlessness, stupor and coma.
6) Liver
Increased systemic venous pressure causes hepatic congestion (Tender hepatomegaly)
with minor abnormalities such increased SGOT, SGPT, serum Bilirubin and
abnormalities in BSP excretion
6.4. RIGHT VENTRICULAR FAILURE (RVF)
Introduction
RVF usually combined with LVF and pure RVF occurs in few instances. RVF is usually
caused by left ventricular failure (LVF). When caused by pulmonary diseases it is described as the heart of pulmonary disease (cor pulmonale).
Causes
1. Myocardial Infarction (not severe than the left ventricle)
2. Chronic Destructive Pulmonary Disease - chronic Bronchitis, emphysema,
pulmonary fibrosis, pulmonary abscess and pulmonary tuberculosis (PTB).
3. Massive pulmonary embolism
4. Pulmonary hypertension following LVF secondary to IHD
5. Viral myocarditis
6. Constrictive pericarditis
7. Valvular lesions (Tricuspid stenosis and congenital pulmonary stenosis)
8. Left sided failure
9. Congenital heart disease
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 36
Pathology
1. Left ventricular failure causes increase left atrial pressure and the pressure in the
pulmonary arterial pressure which increases the workload on the right ventricle
leading to right ventricular hypertrophy and eventually failure.
2. The failing right ventricle is unable to expel all the blood received hence becomes
dilated.
3. The dilatation results in the stretching of the Tricuspid valve ring leading to
Tricuspid regurgitation (incompetence) and blood accumulates in the right atrium,
systemic and portal venous systems leading to systemic venous congestion and
causing “Cardiac” type of oedema.
4. There is increased diastolic volume which causes visceral congestion and effusions,
peripheral congestion and oedema (stasis, pitting oedema and distended neck
veins).
Manifestations (Features)
Primary physiologic disturbance involves damming of blood in the spleenic, systems
and portal system and inadequate flow from lungs to left ventricle. Venous congestion
and Stagnation occurs throughout the body causing renal anoxia, which results in
Sodium and water retention hence increasing the blood volume.
The Heart - As LVF
Liver
Congested and enlarged (hepatomegally). In severe cases there is central
haemorrhagic necrosis of liver and healing occurs by formation of a Fibrous tissue a
situation that causes “Cardiac Cirrhosis”
Raised JVP and Oedema
There is congestion of the peripheral venous system resulting in raised jugular venous
pressure and pitting pedal oedema.
Kidneys
Congestion and Renal anoxia causes disturbed renal function
Pedal oedema
Brain - As in LVF
Portal system
Spleen – may become congested and enlarged
Therefore is a systemic venous congestion syndrome
Radiographic signs of RV failure:
Increased VPW1 due to dilatation of the superior vena cava
Dilatation of azygos vein
Dilatation of the right atrium
In many cases there will be both signs of RV and LV failure
1 vascular pedicle width
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 37
Sonographic signs of RV failure:
Dilatation of the inferior vena cava (IVC) and hepatic veins
Hepatomegaly
Ascites
6.5. CONGESTIVE (TOTAL) HEART FAILURE (CCF)
It involves failure of both Right and Left Ventricles which may fail spontaneously for
example in severe myocardial infarction, severe toxic myocarditis e.g. Diphtheria, Beri
beri and congestive cardiomyopathy
Causes
1. Increased workload for both ventricles e.g. RHD with lesions involving mitral and
Aortic valves
2. Increased Cardiac Output e.g. in severe anaemia and thyrotoxicosis (In high output
failure - the fall in cardiac output is relative from a previously high cardiac output).
But may still be low output failure with an abnormally low output
3. Ventricular stiffness that follows poor response to SAN and hypertrophic
cardiomyopathy NB: Thromboembolic phenomenon is common in CCF due to blood stagnation. This
increases the risk of pulmonary embolism
Low Output Failure – Causes
1. Myocardial disease
2. Ischaemic heart disease (IHD)
3. Myocarditis
4. Cardiomyopathy
5. Arrthymias
6. Hypertension
7. Valve stenosis
8. Cor pulmonalae
Cardinal Signs of CCF
The cardinal signs of CCF include: -
1. Pedal oedema
2. Raised JVP
3. Tender Hepatomegally
4. Cardiomegally
5. Gallop rhythm
6. Basal crepitations
Explain the pathophysiology of
these signs
Describe how you can elicit these
features on physical examination
What are the differentials of these
signs?
Explain the evolution of congestive
cardiac failure and its effects based
on the concepts of forward and
backward failure
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 38
7.0. STAGES OF CARDIAC FAILURE
8.0. CAUSES OF CARDIAC ENLARGEMENT
Enlargement of the heart occurs due to increased workload (volume and pressure).
1. Left Ventricular Hypertrophy (LVH)
Common causes of marked left ventricular hypertrophy include: -
1. Systemic Hypertension
2. Aortic stenosis and regurgitation or mitral regurgitation
3. Mitral insufficiency
4. Coartication of the Aorta
5. Collusive coronary artery disease
6. Congenital abnormalities e.g. septal defects - PDA
7. High Cardiac output states- thyrotoxicosis, severe anaemia and A – V fistula
Mild left ventricular hypertrophy is caused by hypertrophic cardiomyopathies and left
ventricular failure of any cause
2. Right Ventricular Hypertrophy (RVH)
1. Left ventricular hypertrophy (LVH)
2. Chronic Lung disease – e.g. chronic emphysema, bronchioectasis, pneumoconiosis,
pulmonary vascular disease
3. Pulmonary stenosis and insufficiency
4. MitraI regurgitation (MR), Mitral Stenosis (MS)
5. Congenital heart disease (C.H.D) with shunts
6. Pulmonary stenosis (PS)
7. LVH/LVF
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 39
3. Compensatory Dilatation
Follows valve incompetence or shuts and is usually accompanied by hypertrophy of the
respective ventricles.
Causes
1. Valvular insufficiency – mitral and/or aortic regurgitation in Left ventricular
dilatation and tricuspid and/or pulmonary regurgitation in right ventricular
dilatation.
2. Left-to-right shunts e.g. VSD
3. Conditions with high output states – give examples
4. Myocardial diseases e.g. cardiomyopathy (which type?)
5. Systemic hypertension
9.0. DIAGNOSIS
Framingham Criteria
Simultaneous presence of at least 2 major criteria
Simultaneous presence of at least 1 major + 2 minor criteria
Major criteria
o PND; Neck vein congestion; Rales; Radiographic cardiomegaly; Acute pulmonary
oedema; S3 gallop; Increased CVP > 16 cm at right atrium; Hepatojugular reflux;
> 4.5 kg weight loss in 5 days of diuresis
Minor criteria
o Bilateral ankle oedema; Nocturnal cough; Dyspnoea on ordinary exertion;
Hepatomegaly; Pleural effusion; Reduced vital capacity; Tachycardia > 120 bpm
Framingham Criteria for Congestive Heart Failure
Activity Major Minor
History Paroxysmal nocturnal dyspnea X
Orthopnea X
Dyspnea on exertion X
Nocturnal cough X
Weight loss in response to treatment X
Physical
examination
Neck vein distention X
Rales X
S3 gallop X
Hepatojugular reflux X
Hepatomegaly X
Bilateral ankle oedema X
Tachycardia X
Chest radiograph X
Cardiomegaly X
Pulmonary oedema X
Pleural effusion X
Pulmonary
function
testing
Vital capacity decreased one third from
maximum
X
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 40
10.0. LUNG-HEART INTERACTIONS
The normal pulmonary circulation is high capacitance, low resistance and the right
ventricle is thin. LVF causes pulmonary congestion which decreases PO2 resulting in
impaired left ventricular function. Chronic LVF causes chronic pulmonary congestion
and vascular changes (pulmonary hypertension) which results in right ventricular
hypertrophy (also occur in VSD).
Right ventricular hypertrophy or pulmonary disease lead to high pulmonary vascular
resistance (PVR) resulting in high pulmonary artery and high right ventricular
pressures, which affect left ventricular function. Congenital heart disease e.g. VSD
causes a left-right shunt which leads to increased right ventricular pressure.
11.0. COMPLICATIONS
1) Renal failure
2) CVA (stroke)
3) Valvular heart disease
4) Hepatic failure
5) Cardiac arrhythmias
6) Anaemia
7) Venous stasis
8) DVT
9) Pulmonary embolism
10) Cardiac arrest
Explain the pathophysiology of these complications
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 41
Lesson 4: Ischaemic Heart Disease (IHD)
Learning Outcomes
At the end of the lesson the learner should be able to: -
1. Define ischaemic heart disease
2. Describe blood supply to the heart
3. Evaluate risk factors in and causes of IHD
4. Describe the pathophysiology and pathology of IHD
5. Discuss the clinical features and complications of IHD
1.0. INTRODUCTION
Ischaemic heart disease is a situation when there is diminished myocardial blood
supply due to arterial blood flow obstruction or vasoconstriction. It is an acute or
chronic state of cardiac disability arising from an imbalance between the supply of
oxygen and myocardial demand for these nutrients. Obstruction or narrowing of the
coronary arterial system is the most common cause of myocardial anoxia hence the
term coronary artery disease is used synonymously with IHD.
2.0. BLOOD SUPPLY TO THE MYOCARDIUM
Diagram 4.1: Blood supply to the Myocardium (Anterior)
Coronary Circulation
There are two coronary (the left and right coronary artery) arteries responsible for
blood supply to the myocardium
The dominant artery is the one that gives off the AV nodal artery and supplies the posterior descending artery. In 95% of males and 85% of females, the right
coronary artery is dominant while in the remaining 5% and 15% respectively, the
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 42
circumflex artery is dominant. Some individuals have collateral channels that
connect the major coronary arteries.
The coronary arteries are good examples of end arteries but there exists a
collateral cardiac and extra-cardiac collateral circulation with a rich
anastomososes even though the blood vessels involved are usually very small and
can only open if occlusion of the coronary arteries is gradual
There is a rich anastomosis of very small vessels between the right and left coronary
arteries in the myocardium. The extra-cardiac anastomosis occurs through the
pericardium from four pulmonary branches, two caval branches that anastomose
with the branches of internal thoracic, bronchial and phrenic arteries.
Venous Drainage
Coronary veins run parallel to major coronary arteries draining blood into the coronary
sinus, which empties blood directly into the right atrium.
3.0. RISK FACTORS
1. Fixed factors e.g. age, male sex and positive family history
2. Potentially changeable with treatment
a. Strong Association - hyperlipidaemia, cigarette smoking, hypertension and
diabetes mellitus
b. Weak Association – personality, obesity and physical inactivity, gout,
contraceptive pill and heavy alcohol consumption
4.0. AETIOPATHOGENESIS
.
IHD is mainly caused by disease affecting coronary arteries which is majorly due to
atherosclerosis (90% cases). The aetiology of IHD falls under three broad headings of
coronary atherosclerosis, superadded changes in coronary atherosclerosis and non-
atherosclerotic causes.
Diagram 4.2: Effects of Coronary Artery Disease
5.0. CAUSES OF IHD
1. Reduced coronary blood flow due to obstruction
a. Atheroma/artherosclerosis (depends on the distribution, location and fixation of
the atherosclerotic plaques)
b. Arteritis e.g. inflammation
c. Thrombosis – e.g. hypercoagubility states
d. Vascular spasms
e. Embolus
Coronary Artery Disease
Angina Pectoris
Asymptomatic state
Myocardial
Infarction
Chronic Ischaemic Heart disease
Sudden Death
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 43
f. Coronary ostial stenosis (e.g. syphilis)
g. Coronary arteritis (e.g. polyarteritis)
h. Aneurysm – coronary artery
i. Trauma - contusion
j. Compression - tumours
2. Decrease in the flow of oxygenated blood
a. Anaemia
b. Carbohyhaemaoglobinaemia
c. Hypotension – coronary perfusion pressure
3. Increased demand for oxygen
a. Increased cardiac output - thyrotoxicosis
b. Myocardial hypertrophy - aortic Stenosis, hypertension
6.0. PRESENTATION
The presentation depends on the characteristics of the lesion in the coronary arteries in
terms of onset, duration, degree, location and extent. This influences the effects of
myocardial ischaemia which may present as: -
1. Asymptomatic state
2. Angina pectoris
3. Myocardial infarctions (acute and chronic)
4. Cardiac arrhythmias
5. Cardiac Failure
6. Sudden death
ANGINA PECTORIS
1.0 INTRODUCTION
Angina pectoris is a clinical syndrome associated with transient sudden, severe
paroxysmal substernal pain due to diminished blood flow through the coronary artery
(inadequate perfusion). Angina means strangling. The pain is prompted by exertion,
cold and emotional stress and lasts a short time. The pain radiates to the shoulder
(jar, check, left arm) and is usually relieved by rest and drugs (vasodilatation -TNT)
Angina occurs because myocardial cells become ischaemic but the damage is
reversible. Reduced blood supply can be as a result of stable or unstable plaques in
the vessels. Stable plaques narrow coronary arteries so that blood flow is insufficient
for even a moderate increase in cardiac work (e.g. climbing stairs) and the patient
complains of chest pain (angina) which is relieved on rest.
Unstable plaques only produce clinical problems when an acute event occurs
causing the fibrous cap of the plaque splits and blood from the lumen can reach the
soft necrotic centre. Rupture of the plaque causes distortion and enlargement of the
plaque as well as releasing the plaque contents which activate the thrombotic
cascade. Platelets and fibrin aggregate blocking the lumen and the platelet
constituents (TXA2, histamine and serotonin) promote vasospasm which worsens the
situation.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 44
2.0 CAUSES
1. Coronary artery disease resulting in impaired perfusion – atheroma, syphilis, valve
disorders (AS, AR, severe MS) and vasospasm
2. Myocardial infarction - promotes Angina by decreasing blood supply to the
surviving myocardium around the infarction. It also relieves angina by eliminating
the dead tissue
3.0 PREDISPOSING FACTORS
The predisposing factors include those that result in increased myocardial oxygen
demand such as: -
1. Increased ventricular preload e.g. exercise, anaemia and thyrotoxicosis
2. Increased ventricular afterload e.g. hypertension, valvular lesions – AS and
obstructive cardiomyopathy.
3. Increased ventricular wall tension due to dilation and hypertrophy
4. Decreased heart function e.g. myocarditis and tachycardia
Factors Prompting Attacks
The factors prompting attacks include physical activity, exposure to cold, exercises,
injury, shock and coronary artery spasm
Risks
The main risk factors are myocardial infarction, cardiac failure and sudden death
(ventricular filtration)
Pathology
a. Coronary artery shows arteriosclerosis, patchy fibrous intimal thickening,
calcification, accumulation of lipid debris and fibrosis
b. Myocardium exhibits ischaemic changes and fibrosis
c. ECG shows abnormal conduct
Classification
1. Class 0: Asymptomatic
2. Class 1: Angina with strenuous Exercise
3. Class 2: Angina with moderate exertion
4. Class 3: Angina with mild exertion
1. Walking 1-2 level blocks at normal pace
2. Climbing 1 flight of stairs at normal pace
5. Class 4: Angina at any level of physical exertion
4.0 PRESENTATION and CLINICAL PATTERNS OF ANGINA
There are 3 overlapping clinical patterns of angina pectoris namely stable (typical)
angina, Prinzmetal’s variant angina and unstable (crescendo) angina.
Stable (Typical) Angina
Most common pattern (also described as classical or exertional) characterized by
attacks of pain following emotional or physical exertion due to chronic stenosing
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 45
coronary atherosclerosis and relieved by rest. This is because the coronary artery
cannot perfuse the myocardium adequately when the workload on the heart increases.
The ECG shows depression of the ST segment due to poor perfusion of the
subendocardial region of the left ventricle. There is no elevation of enzymes in blood
because there is no irreversible myocardial injury.
Prinzmetal’s variant Angina
Variant (Prinzmetal’s) angina is characterized by pain which occurs at rest with no
relationship with physical activity. This is mainly due to sudden vasospasm of the
coronary trunk induced by coronary atherosclerosis or release of humoral
vasoconstrictors by mast cells in the coronary adventitia. The ECG shows ST segment
elevation due transmural ischaemia. The patients respond well to vasodilators.
Unstable (Decrescendo) Angina
This is also called pre-infarction angina or acute coronary insufficiency due to multiple
factors. It is the most serious variety characterized by more frequent onset of pain,
prolonged duration pain, often occurring at rest. Indicates impending myocardial
infarction and has multiple aetiology.
5.0 INVESTIGATIONS
1) ECG
2) Coronary angiography
3) Chest X-Ray
4) VDRL
5) Haemogram + ESR
6) Echocardiography
MYOCARDIAL INFARCTION
1.0 INTRODUCTION
MI is a lethal disease of modern times which occurs as a result of reduced blood supply
(ischaemia) and affects mainly the ventricular myocardium. The cardiac muscle cells
die because of lack of nutrients primarily oxygen resulting from poor blood flow to the
myocardium because of narrowing or total occlusion of one or more coronary arteries. The magnitude of infarction depends on amount of collateral flow, metabolic
requirements of the cells and duration of ischaemia. Atheroma of the coronary
vessels accounts for the majority of cases but rarer causes include vascular spasm,
emboli, arteritis and anaemia.
2.0 INCIDENCE
Higher in industrialized countries due to association with atherosclerosis
Affects more males than females
3.0 CAUSES
– See the causes of ischaemic heart disease
Why are these investigations above necessary?
What parameters will you look for when the results are out?
What are the important findings on examination of cardiovascular
system of a 50 year old man who presents with angina pectoris
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 46
4.0 PATTERNS AND TYPES OF INFARCTS
Classified according to the anatomic regions of the left ventricle involved (anterior,
posterior or inferior, lateral, septal and circumferential; combinations –
anterolateral, posterolateral and anteroseptal) or degree of thickness of the
ventricular wall involved (full thickness or transmural, subendocardial) or laminar or
age (newly-formed or acute/recent/fresh; advanced – old/healed/organized)
Three main patterns namely regional infarct, transmural infarct and
subendocardial infarct
Regional myocardial infarcts (RMI)
Accounts for 90% cases. It results from occlusion of a single vessel
Occupies the segment of myocardium that is normally supplied by a particular
coronary artery
May involve a variable thickness of the myocardial wall
Important arteries supplying which whose occlusion result in regional infracts of the
heart are: -
1) Left anterior artery which supplies the anterior wall, lateral wall of the left
ventricle, part of inter-ventricular septum and the apex
2) Left circumflex artery that supplies the posterior wall of the left ventricle.
3) Right coronary artery supplying the right ventricle
4) The left circumflex and right coronary supplying the posterior part of intra-
ventricular septum.
Transmural Infarct
Results from occlusion of a single coronary vessel and involves full thickness of the
myocardial wall
Majority result from thrombosis complicating atheroma.
Diagram 4.3: Blood Vessel Blockage Sites
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 47
Subendocardial Infarcts
Affect the inner wall of left ventricle and account for 10% cases of myocardial
infarcts
Result from generalized widespread atherosclerosis in all coronary vessels but with
no specific occlusion
Subendocardial region is most vulnerable part of the myocardium because 1) any
collateral supply that is developed tends to supply the subendocardial part of the
myocardium and 2) the subendocardium is under the greatest tension from the
compressive forces of the myocardium.
May be confined to the inner half of the myocardium and may be regional or
circumferential.
5.0 CLINICAL PRESENTATION
May present as acute or chromic myocardial infarction
Acute myocardial infarction is the most important consequence of coronary artery
disease and many patients die within the first few hours of the onset and the
remaining ones suffer impaired cardiac function.
Diagnosis
Diagnosis of AMI is based on three types of features – clinical features, ECG changes
and serum enzymes determinants.
Clinical Features
Chest pain(what characteristics?), indigestion, apprehension, oliguria, low grade
fever, shock and acute pulmonary oedema
ECG Changes
ST segment elevation
T wave inversion
Wide deep Q waves
Serum cardiac Markers
Certain proteins and enzymes are released into blood from the necrotic heart
muscle after myocardial infarction
6.0 PATHOLOGY
Structural changes
Microscopy
Microscopy
Structural Changes
The infarcts have variation in size > 2 cm affecting the inner part of myocardium.
Majority of the infarcts are transmural (whole thickness of myocardium). The right coronary artery blockage leads to formation of a posterior, inferior infarct affecting the
apex down to the inferior wall of the left ventricle, the adjacent inter-ventricular septum
and the adjacent inferior wall of the right ventricle. 15% of the cases involve the left
circumflex artery affecting the lateral margins of the left ventricle.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 48
Macroscopy
1. Congestion (Blotchy congestion)
2. Pale myocardium
3. Haemorrhagic margins
4. Softened patch (dead tissue)
5. Colour change from grey brown to yellow green
6. Red zone of vascular granulation (later)
Diagram 4.4: Myocardial Infarction
Microscopy
1. Coagulative necrosis changes
2. Polymorphonuclearr leucoytes (neutrophils, monocytes)
3. Digestion of tissues by macrophages
4. Show necrotic changes at the margins
7.0 DIFFERENTIAL DIAGNOSIS
1. Aortic dissection
2. Pulmonary embolism
3. Spontaneous pneumothorax
4. Pericarditis
5. Oesophageal rupture
6. Peptic Ulcer disease
7. Pancreatitis
What are the differentiating features of these conditions?
What investigations will be crucial in
differentiating these diagnoses
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 49
8.0 COMPLICATIONS
Explain how these complications occur? Pathophysiology
How will they present?
How will you investigate for these complications?
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 50
Lesson 5: Valvular Heart Disease (VHD)
Learning Outcomes
At the end of the lesson the learner should be able to: -
1. Outline the anatomy of the heart valves
2. Describe the causes and mechanisms of valvular damage
3. Explain the pathology and clinical presentation of valvular heart disease
4. Investigations in valvular heart disease
5. Evaluate complications of valvular heart disease
1.0 INTRODUCTION
Valvular heart diseases comprise of the disorders of the heart valves. Normal function of
the heart depends on the mechanical efficiency of the valves whose malfunction
contributes immensely to the disability of heart function.
2.0 VALVE DEFORMITY
A valve deformity can be a stenosis or regurgitation. : Stenosis - a reduction in the
valve aperture and increases pressure load in the preceding chambers. Any time there
is an obstruction to blood flow across the heart three adjustments may occur: - pressure
proximal to the obstruction increases in an attempt to maintain same quality of flow;
amount of flow reduces and hence require less pressure difference across the obstruction and duration of flow past the obstruction may be prolonged Regurgitation
– incompetence of valves that result in failure of the valve to close completely and
increases volume load on both sides of the valve
Diagram 5.1: Valve Deformities
3.0 CAUSES OF DEFORMITY/DISORDERS
1. Congenital – usually associated with other congenital disorders
2. Acquired - E.g. Rheumatic fever (the commonest cause)
a. Post-inflammatory scarring
b. Degenerative changes with aging
c. Dilatation of the valve ring e.g. in ventricular dilatation
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 51
d. Degeneration of collagen support tissue of the valve
e. Acute destruction by acute necrotizing inflammation
The Mitral Valve
1.0 INTRODUCTION
Normal function of the mitral valve depends on the mechanical efficiency of the cusp,
chordae, papillary muscle, pliability and size of fibrous ring or annules and adequacy of
left ventricular contraction. Normal size of circumference is 5 – 12 cm. The valve
consists of 2 leaflets (cusps) - a larger anterior leaflet and a small posterior leaflet,
annules, the chordae tendineae and papillary muscles
Diagram 5.2: Mitral Valve
2.0 PHYSIOLOGY
Has a cross-sectional area of 5 cm2 and allows ventricular filling at peak rate of 500 –
1000 mls/s
Mitral Stenosis (MS)
Rheumatic Heart disease resulting from acute rheumatic fever is a major cause of mitral
stenosis affecting more female than males. In 2/3 cases the aortic valve is also affected
1.0 AETIOLOGY
a. Congenital b. Acquired - rheumatic fever /rheumatic heart disease/ (commonest), calcification,
infective endocarditis, rheumatoid arthritis and Systemic Lupus Erythromatosus
(S.L.E.)
2.0 PATHOPHYSIOLOGY
Disturbance in left ventricular filling due to reduced mitral valve area (1 - 2.5 cm2),
which causes a reduction in peak left ventricular filling rate and loss of normal
period of diastasis.
During exercise as heart rate increases a pressure gradient develops with an
increase in mean left atrial pressure in an effort to improve ventricular filling. This will result in left atrial hypertrophy and dilatation.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 52
There is chronic left atrial hypertension that causes elevation of pulmonary capillary, venous and arterial pressures favouring transudation of fluid resulting in oedema
(pulmonary oedema) formation.
Pulmonary hypertension leads to right ventricular hypertrophy, dilatation and
failure.
There will also be congestion in systemic veins (raised JVP, hepatomegally and
pedal oedema).
There is reduced cardiac output due to poor left ventricular filling and right
ventricular failure eventually ending up in cardiac failure.
3.0 PATHOLOGY
There is distortion of normal mitral valve anatomy with fusion of commisures.
1. The cusps:
a) Are thickened, distorted and vascularized throughout (normally they are
vascularized at the base only)
b) Consists of dense fibrous tissue with infiltrations of lymphocytes and plasma cells
c) They are fused along the free margins forming a “Button Hole” or “Fish mouth”
opening
d) There is thrombus formation and calcification
e) Great thickening and rigidity causes stenosis and regurgitation
2. Chordae - shows thickening, fusion and contraction
3. The valve ring is calcified
4.0 CLINICAL FEATURES
Symptoms
The symptoms include - reduction in exercise tolerance, breathlessness, fatigue,
heaviness of limb, palpitations, cough (productive of blood-tinged, frothy sputum and at
times frank haemoptysis), Haemoptysis (due to chest infection, pulmonary infarction,
acute pulmonary oedema and rupture of small blood vessels in lungs. Massive or
recurrent haemoptysis may be the presenting or only symptom of mitral stenosis.),
angina (due to pulmonary hypertension, right ventricular failure and previous coronary
embolism), nocturnal dyspnoea (late complain), recurrent chest infection associated
with cough, purulent sputum and fluid retention (pulmonary oedema), fluid retention
such as pedal oedema, ascites, pleural effusion and pulmonary oedema and features of
embolic phenomenon where any organ could be affected.
Physical Examination (Signs)
General Examination
On general examination there is weight loss, peripheral cyanosis, “Malar flash”, the
pulse is irregular (Atrial fibrillation), rapid with a normal character (but amplitude may
be reduced) or slow rising (small volume, slow rising) and raised JVP if there is right
ventricular failure
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 53
The Pericardium
There is a “tapping apex” due to a palpable first heart sound with a left parasternal
heave due to right ventricular hypertrophy. Loud Hs (first heart sound) with a rumbling
mid-diastolic murmur/thrill.
Effects (Other features)
1. Left atrial myocardial hypertrophy is limited causing increase in pressure in LA and
accumulation of blood in LA and pulmonary veins leading to pulmonary venous
congestion. There is also dilatation of the left atrium
2. Increased pulmonary venous pressure (PVP) causes pulmonary arterial
hypertension leading to right ventricular hypertrophy (RVH) exhibiting features
such as dyspnoea, persistent cough, pulmonary oedema, paroxysmal nocturnal
dyspnoea (PND) and haemoptysis due to engorged blood vessels
3. Right ventricular hypertrophy results in tricuspid regurgitation
4. Congestive cardiac failure
5. Thrombosis
6. Systemic Embolism (worst being cerebral infarction)
7. Atrial fibrillation
8. Pulmonary hypertension results in pulmonary valve regurgitation that produces an
early diastolic murmur (Graham-Steell murmur)
5.0 EFFECTS
1. Left atrial dilatation and hypertrophy
2. Left ventricular hypertrophy and dilatation
3. Diastolic murmur
6.0 INVESTIGATIONS
1. Chest X-ray
a. Heart size is normal or increased (commonly left atrial enlargement)
b. Calcification may be visible
c. The Lung fields show dilated veins with an increase in size of main pulmonary
artery (pulmonary hypertension)
d. Evidence of pulmonary oedema - lymphatic lines, generalized hazy shadowing
and obvious interstitial oedema
e. Pulmonary haemosiderosis in long standing cases
2. E.C.G. shows atrial fibrillation and left atrial hypertrophy (bifid “p” wave)
3. Echocardiogram
4. Cardiac catheterisation.
5. Full haemogram and ESR
7.0 COMPLICATIONS
1. Atrial fibrillation
2. Systemic embolism
3. Pulmonary hypertension
4. Pulmonary infarction
5. Chest infection
6. Infective endocarditis
7. Tricuspid regurgitation
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 54
Mitral Regurgitation (MR)
1.0 AETIOLOGY
Rheumatic heart disease (accounts for 50%) and prolapsing mitral valve are the most
common causes of mitral regurgitation. Any disorder that causes dilatation of the left
ventricle causes mild mitral regurgitation.
Table 5.1: Causes of MR
Structure Anatomical Pathogenesis
Affected Fault
1. Valve cusps Congenital cleft Atrial Septal Defects (ASD)
Redundant cusps - Marfan’s syndrome,
- Floppy valve syndrome, loss of collagen
Perforation - Infective endocarditis
Distortion/Scarring - Rheumatic fever
Iatrogenic - Floppy Valve
2. Chordae Redundant chordae - Marfan’s syndrome, Floppy valve
Ruptured chordae - Floppy valve, Marfan’s syndrome
- Infective endocarditis/Rheumatic
Chordal shortening - Rheumatic, endomyocardial, fibrosis
3. Papillary muscle Dysfunction - IHD and cardiomyopathy
Prolapsing mitral valve ring - Various
Rupture - Acute myocardial infarction
4. Valve ring Dilatation - severe LV disease
Calcification - Various
2.0 PATHOPHYSIOLOGY
In pure mitral stenosis, there is a large increase in LV output since the pressure in
the left atrium is lower than that in the aorta and resistance to left ventricular ejection
is reduced so the stroke volume increases up to three fold. Ejection of blood begins
almost immediately after start of ventricular contraction and by the time the aorta
valve opens ¼ of the stroke volume has already entered the left atria.
Incompetence of the mitral valve allows regurgitation of blood into the left atrium during systole producing LA dilatation.
During diastole the additional blood volume freely moves into the left ventricle stretching the left ventricle. This increased volume load leads to LV dilatation and
hypertrophy and eventually left ventricular failure.
Pressure rise in the left atrium during ventricular systole leads to pulmonary
congestion and oedema.
There is increased volume in the atria and ventricle leading to dilatation and
hypertrophy of left ventricle.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 55
3.0 CLINICAL FEATURES
Symptoms - As in mitral stenosis
Signs
On palpation of the praecordium, there is a laterally displaced apex beat (diffuse and
thrusting). Soft 1st heart sound due to incomplete closure of the heart valves with
systolic thrill. A prominent 3rd heart sound resulting from sudden rush of blood into the
dilated left ventricle in early systole. Apical pansystolic murmur (regurgitation occurs
throughout systole) radiating to axilla
Effects
1. Regurgitation of blood into left atrium during ventricular systole
2. Left ventricular Dilatation and Hypertrophy
3. Right ventricular hypertrophy and dilatation
4. Congestion of the lungs and pulmonary hypertension
5. Atrial fibrillation
6. Left ventricular failure leading/right ventricular failure/CCF.
Compensated MR
The volume in left atria increases during ventricular systole but emptied during diastole
with the pressure in the left ventricle remaining about normal (Starling’s Law). In
combined MR/MS there is pulmonary congestion, oedema, hypertension (pulmonary)
and right ventricular hypertrophy.
4.0 INVESTIGATIONS
1. Chest X-ray – shows left atrial and left ventricular enlargement, increased cardio-
thoracic ratio (CTR), valve calcification
2. ECG (bifid p wave)
3. Echocardiogram – dilated left atrium and left ventricle
4. Cardiac catheterisation – prominent left atrial systolic pressure
5. Full Haemogram + ESR.
THE AORTIC VALVE
ANATOMY
The aortic valve consists of 3 semi lunar segments/cusps. The orifice of the aorta
surrounds the cusps. There are 2 posterior cusps (the left and right cusp) and one
anterior cusp. The cusps are larger, thicker and stronger attachments and opposite the
cusps of the aorta there are 3 slight dilatations (Aortic sinuses). Aortic valve disease is a
common cause of sudden cardiac deaths.
Aortic Stenosis (AS)
1.0 INTRODUCTION
Aortic stenosis is an important cause of cardiac disability that represents a fixed
obstruction to the left ventricular ejection at the level of the valve cusps. Aortic stenosis
becomes symptomatic when the valve orifice is reduced to 1 cm2 (normal is 3 cm2).
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 56
Diagram 5.3: Aortic Stenosis
2.0 CAUSES
1. Valvular
a. Calcified bicuspid valve
b. Rheumatic(post inflammatory scarring)
c. Senile degeneration (wears & tear) which results from arteriosclerotic
degeneration and calcification
d. Congenital – Valve with a single commissure and Bicuspid valve
e. Infective endocarditis (rare)
f. Hyperlipidaemia (rare)
2. Fixed sub-aortic stenosis (sub-valvular) for example congenital fibrous ridge or
diaphragm.
3. Supravalvular stenosis e.g. congenital fibrous diaphragm above the aortic valve
4. Hypertrophic cardiomyopathy e.g. septal muscle hypertrophy obstructs left
ventricular outflow.
3.0 PATHOPHYSIOLOGY
Pressure resulting from the aortic stenosis leads to development of a pressure
gradient between the left ventricular cavity and aorta.
This resistance is fixed hence differs from the increased peripheral resistance of
systemic hypertension which fails during exercise (pressure overload)
The resultant obstructed left ventricular emptying leads to increased left
ventricular pressure and compensatory left ventricular hypertrophy.
Left ventricular hypertrophy (LVH) causes an increase in the diastolic stiffness of the
cavity and therefore end-diastolic pressure increase causing pulmonary vascular
congestion.
The increased ventricular wall thickness (hypertrophy) results in relative ischaemia
of left ventricular myocardium leading to – angina, arrthymias and left ventricular
failure.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 57
4.0 PATHOLOGY
1. Post-Rheumatic aortic stenosis the cusps are thickened, rigid and partly adherent.
2. Calcification: - the cusps are thickened by fibrosis, have irregular nodules and are
not fussed or vascularized.
5.0 CLINICAL FEATURES
Symptoms
There is breathlessness (paroxysmal nocturnal dyspnoea – PND), chest pain due to
Ischaemic heart disease (IHD) and angina and syncope
Signs
The pulse - Is slow rhythm, low volume, slow rising/plateau; on palpation of the
praecordium the apex beat is not usually displaced because hypertrophy (as opposed
to dilatation) does not produce noticeable cardiomegaly, there is sustained and obvious
(heaving) apex beat; systolic thrill on palpation. On auscultation the first heart sound is
normal or reduced and a 4th heart sound is present with a systolic murmur that is a low-
pitched ejection murmur that radiates to the carotids (Diamond shaped – crescendo-
decrescendo pattern).
Effects
1. Left ventricular hypertrophy and dilatation as a result of pressure overload and
ischaemia.
2. Angina and myocardial infarction
3. Ventricular fibrillation
4. Pulmonary congestion and oedema
5. Right ventricular failure
6. Congestive cardiac failure.
6.0 INVESTIGATIONS
1. Chest X-ray shows: -
a. Left ventricular hypertrophy (LVH) and dilatation
b. Dilated aortic root and ascending aorta
c. Calcification of the aorta (may be present)
d. CTR increases if heart failure is present
2. ECG shows: -
a. Left ventricular hypertrophy (LVH)
b. Bifid “p” wave
c. Conduction disturbances such as complete heart block and prolonged PR
interval.
3. Echocardiogram reveals disruption of normal anatomy of the heart and thickened,
calcified and immobile aortic valve
4. Cardiac catheterisation.
Differential Diagnosis
1. Hypertrophic cardiomyopathy
2. Congenital stenosis
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 58
3. Heart block
4. Fixed sub-valvular stenosis
Causes of Death
1. Pulmonary oedema
2. Ventricular fibrillation
3. Left ventricular failure (LVF)
Aortic Regurgitation (AR)
Aortic regurgitation increases the workload (volume) on the left ventricle.
The commonest causes are Rheumatic fever and Infective endocarditis.
1.0 CAUSES
1. The Cusps
a. Distortion of cusps as in rheumatic fever and rheumatoid arthritis
b. Perforation of cusps as in infective endocarditis and trauma
2. Valve Ring Dilatation - dissecting aneurysm, Marfan’s syndrome, syphilis,
Ankylosing spondylitis and Reiter’s syndrome
3. Loss of support associated with Ventricular septal defect (VSD)
4. Stretching/Distortion of roof of aorta in rheumatic heart disease (RHD), which causes
Fibrous thickening and distortion and calcification.
2.0 PATHOPHYSIOLOGY
There is reflux of blood from the aorta into the left ventricle during diastole
The total volume of blood pumped into the aorta must increase hence there is
increased volume of blood in left ventricle causes increased ventricular mass and
size of chamber.
There is associated with increased left ventricular stroke volume.
The aortic run off of blood during diastole reduces the diastolic blood pressure
compromising coronary perfusion.
The large ventricular size makes it mechanically less efficient (ischaemic)
The walls become stiffer and end diastolic pressure increase leading to pulmonary
congestion (pulmonary oedema).
The large stroke volume and peripheral dilatation up-stroke with a larger blood
volume leads to a high systolic and low diastolic pressure leading to a bounding
pulse or collapsing pulse.
3.0 PATHOLOGY
In Chronic Rheumatic the Cusps are thickened with fused commisures and have rolled
edges with calcification. Thrombosis may be present or absent. In Infective
endocarditis the cusps are destroyed and perforation may be present. Spread to the
AVN, sinus of vasalva and inter-ventricular septum
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 59
Diagram 5.4: Aortic Regurgitation
4.0 CLINICAL FEATURES
Symptoms - there is dyspnoea, breathlessness and chest pain (angina pectoris)
Signs
The Physical signs due to hyper-dynamic circulation and reflux of blood into left
ventricle are pulse is bounding/collapsing/water hammer; Quincke’s sign (capillary
pulsation in nail beds), De Musset’s sign (head nodding with each heart beat),
Durozier’s sign (systolic bruit over femoral arteries), pistol shot femorals (a sharp bang
heard on auscultation over the femoral ) and Corrigan’s sign (visible arterial pulsation
in the neck).The apex beat displaced laterally and downwards and there is a diastolic
thrill. On auscultation - a high pitched diastolic murmur (Austin Flit murmur)
Differential Diagnosis
1. PDA
2. Coronary A – V fistula
3. Ruptured sinus of valsalva aneurysm.
5.0 INVESTIGATIONS
1. Chest X-ray
2. ECG
3. Echocardiogram
4. Cardiac catheterisation.
5. Full haemogram
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 60
TRICUSPID VALVE
ANATOMY
The tricuspid valve has three triangular cusps namely the anterior, inferior and median
with small intermediate segments seen in the angles between the cusps. The anterior
cusps are the largest. Central parts of the cusps are thick and d strong while the
margins are thin and translucent. The bases of the cusps are attached to the fibrous ring.
TRICUSPID STENOSIS (TS)
Causes
1. Rheumatic heart disease
2. Usually coexists with mitral valve disease or aortic valve disease
Pathophysiology
1. Causes obstruction to right ventricular filling with a diastolic pressure gradient
across the valve
2. Causes increased right atrial pressure causing fluid retention (ascites and
peripheral oedema)
3. There is systemic venous congestion producing hepatomegally
4. Results in reduced cardiac output.
Clinical Features
Symptoms: There is abdominal pain due to hepatomegally, abdominal swelling due to
ascites and leg swelling (oedema)
Signs
There is raised jugular venous pressure (JVP), oedema/ascites, presystolic pulsation
over the liver, murmur (rumbling, mid-systolic murmur best heard at the lower left
sternal boarder and is loud on inspiration) and hepatomegally
Investigations
1. Chest X-ray
2. ECG
3. Echocardiogram
4. Cardiac Catheterisation.
TRICUSPID REGURGITATION
This is frequently functional and occurs in association with dilatation of the right
ventricular cavity. It is common in patients with cor pulmonalae, myocardial infarction
and pulmonary hypertensive disease.
Causes
1. Organic causes such as rheumatic fever, infective endocarditis, ischaemia of
myocardium, Ebstain’s anomaly (congenitally malpositioned valve), prolapsing
cusp, endomyocardial fibrosis
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 61
2. Congenital
3. Functional causes such as right ventricular dilatation, congenital heart disease with
left to right shunt and chronic Cor pulmonalae
Pathophysiology
There is severe and chronic elevation of the venous pressure (right atrial and systemic
congestion)
Clinical Features
1. Symptoms of right ventricular failure
2. Signs - raised JVP, oedema/ascites, hepatomegally, pulsation of the liver and
pansystolic murmur.
THE PULMONARY VALVE
PULMONARY STENOSIS (PS)
There is obstruction to blood flow between the right ventricle and the main pulmonary
artery.
Causes
1. Infundibular Stenosis – this is the narrowing of the valve below the pulmonary valve.
a. Accompany valve Stenosis
b. Congenital abnormalities e.g. ventricular septal defect (VSD)
2. Valvular Stenosis - abnormal valve, congenital
3. Supravalvular Stenosis – narrowing above the pulmonary valve.
Pathophysiology
1. During ventricular systole the valve domes upwards but its excursion is limited
2. A jet of blood passes through the narrowed valve and is very turbulent with
disturbed pattern of flow.
3. The disturbed floe causes dilatation of the pulmonary artery above the valve (post-
stenotic dilatation).
Pathology
The valve is thickened and the valve commissures are fused along part of their length
leaving a central or slightly eccentric orifice.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 62
Lesson 6: Acute Rheumatic Fever (ARF) & Rheumatic Heart Disease
(RHD)
Learning Outcomes
At the end of the lesson the student should be competent to: -
1. Define acute rheumatic fever (ARF)
2. Discuss causes of ARF
3. Describe the pathogenesis and pathophysiology of ARF
4. Explain the basis of signs and symptoms of ARF and RHD
5. Describe features of ARF
6. Investigate and diagnose ARF
7. Discuss complications and prevention measures of ARF
Acute Rheumatic Fever (ARF)
1.0. INTRODUCTION
Rheumatic fever is an immunologically mediated inflammatory disorder of
connective tissue that occurs as a sequael of infection by beta haemolytic
Streptococci Group A type 12 affecting especially the heart, joints and
subcutaneous tissues
ARF is predominantly an illness of childhood (children & young adults) resulting
from an abnormal immune reaction with the major symptoms being arthritis and
carditis. It is delayed non-suppurative sequels of upper respiratory tract infection
with group A streptococci. ARF is an acute febrile illness with lesions occurring in
the heart, skin, joints, tendons and fascia, subcutaneous tissues, respiratory system
and the central nervous system. This occurs in individuals who are genetically
susceptible.
2.0 AETIOLOGY
Associated with -haemolytic Streptococci group A type 12 infection. Streptococcus may
share antigens with human tissues particularly the heart muscle and cardiac valves.
Usually occurs usually 2 – 4 weeks after a throat infection by streptococcus pyogenes.
3.0 PATHOGENESIS
Pathogenesis of rheumatic fever is based on: -
3.1 Immunological Factors
Based on toxic products of streptococci, immunological cross-sensitivity between
streptococcal substances and heart muscle (heart reactive antibodies) and presence
of sensitized T-lymphocytes may mediate cardiac injury
The streptococci produce toxic products (streptolysins S and O) capable of causing
tissue injury (infective component) and the host where there is inflammation
mediated by antigen-antibody complexes and the autoimmune phenomenon that is
capable of causing damage (autoimmune component).
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 63
The Streptococcus (The infection) – The Infective Component
The organism attaches firmly to pharyngeal cells with the assistance of lipotechoic
acid producing a brisk antigenic response.
Enters the body through mucosa of the upper respiratory tract, through wounds,
breaches of body surface.
Have numerous surface antigens that provoke formation of antibodies, which react
with the antigens to form antigen-antibody complexes.
Cause local inflammatory reaction (lesion) and spreads along the lymphatic and
tissue planes to reach bloodstream.
Protected from phagocytosis by the M-protein (main virulent factor)
Produce toxins and enzymes – Toxins - streptolysins (streptolysin O, SLO and
streptolysin S, SLS) cause haemolysis and damage of many cells such as the white
blood cells, liver and heart muscles. Enzymes produced digest macromolecules,
activate fibrinolysis, hyaluronidase breaks down the connective tissue and
streptodornase liquefies purulent discharges.
Diagram 6.1: The Mechanism
Host Reaction – Autoimmune component
1. Autoimmune reaction resulting from invasion by the streptococci organisms to which
the host responds by producing corresponding antibodies resulting in high anti
streptococcal titres.
2. Antigen-antibody complexes formed trigger tissue destruction resulting in an
inflammatory response with the appearance of the circulating immune complexes.
3. Individuals with autoimmune tendencies tend to be more adversely affected and this
is supported by the presence of antibodies and the capacity for experimental
induction.
3.2 Epidemiological Factors
Suggestive of familial occurrence and in crowding conditions, seasonal prevalence of
rheumatic fever and streptococcal pharyngitis, rheumatic fever follows streptococcal
infection by 2 – 3 weeks, age 6 – 15 years (peak 8 years), Anti-streptolysin O titres rises
during rheumatic fever attack, prophylactic antibiotic therapy in military camp reduces
upper respiratory tract infections and rheumatic fever, socio-economic considerations,
geographical distribution and individual susceptibility
Throat infection due to -
haemolytic streptococcus
(Group A)
IMMUNE
RESPONSE
Cell mediated and
Antibodies to
streptococcal antigens
Cross-reaction with Cardiac and
connective tissues of susceptible
individuals
Streptococcal antigens
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 64
4.0 PATHOLOGY
ARF is characterized with exudative and proliferative inflammatory lesions in the
connective tissues especially the heart, joints and subcutaneous tissues. The
manifestations of the disease are as a result of cardiac damage and inflammation at local
sites. The Classical features of ARF are the Aschoff Nodules (Dr. Ludwig Aschoff,
German Pathologist, 1905)
Aschoff Nodules
Aschoff nodule is the pathognomonic feature of ARF. It is degenerated collagen
surrounded by activated histiocytes and lymphoid cells. The nodes are widespread in
connective tissue of the joints, tendons, blood vessels and the heart (Heart – myocardial
tissue and valves). Development of the Aschoff nodule takes place in 3 stages namely
early stage, intermediate and late stages.
Diagram 6.2: Aschoff Nodules
Early (Exudative or degenerative) stage
This is non-specific mucoid degeneration of cells (neutrophils, lymphocytes, plasma
cells) in 4th week of illness resulting in oedema of the connective tissue. There is
increased acid mucopolysaccharide that destroys collagen fibres. Fibrinoid
degeneration occurs too.
Intermediate (proliferative or granulomatous) stage
This entails formation of well-defined nodules – Aschoff nodules during the 4th – 13
week period.
Late (healing or fibrosis) stage
Healing of tissues destroyed occurs in about 12 – 16 weeks after the illness. There is
healing stage with progressive fibrosis hyalinization and accumulation of cells
(lymphocytes, monocytes, initially leucocytes) with the resultant fibrinous Aschoff
nodule. The nodules heal by fibrosis
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 65
5.0 PATHOLOGICAL LESIONS/CHANGES
The manifestations of ARF are grouped into three categories
1. General manifestations
2. Cardiac manifestations in the heart walls (pancarditis – endocarditis, myocarditis
and pericarditis), heart valves (rheumatic valvulitis) and blood vessels (rheumatic
arteritis)
3. Extra-cardiac manifestations – depict inflammation at local sites
a. Joints – arthralgia and arthritis
b. Serous membranes
c. Skin – subcutaneous nodules, erythema marginatum
d. CNS - chorea
6.0 GENERAL MANIFESTATIONS
General manifestations are indications of inflammation at local sites. These include
fever with sweating, malaise, raised ESR, and raised C - reactive protein and neutrophil
leucocytosis
7.0 CARDIAC LESIONS (MANIFESTATIONS)
The inflammation is widespread throughout the heart resulting in pancarditis and
involvement of the heart valves. Involves the heart walls - pancarditis (pericarditis,
myocarditis and endocarditis), heart valves and blood vessels
3.3 Heart Walls - Pancarditis
The Pericardium
Pericarditis occurs during the early phase of the illness. The features of pericarditis
include pericardial effusion and fibrinous pericarditis.
Myocardium
Inflammation of the myocardium (myocarditis) is usually mild and occurs during the
acute phase of the illness.
Endorcarditis
The endocardium shows gross changes because its surfaces are usually subjected to the
greatest pressures and traumas. There is diffuse (widespread) inflammation with
development of inflammatory oedema and light cellular infiltration. Development of Aschoff nodules occurs at the posterior wall of the left ventricle above the insertion of
the posterior mitral cusps. It affects the heart valves leading to valvular heart disease.
The inflammation leads to ulceration of the valve surface, which encourages
accumulation of platelets, exudates and fibrin thrombosis forming small masses called
vegetations. Endocardial thrombotic vegetations, which are the most prominent
features, develop on valves.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 66
3.4 The Heart Valves (Rheumatic valvulitis)
The injury to the valve surfaces results in healing by fibrosis and compensatory
mechanisms of the heart, there occurs destruction of the heart valves. The valves mainly
after are the mitral and aortic valves. Valve abnormalities include thickening of the
valve leaflets, impaired valve closure due to ring dilatation and deformity, shortening
and fusion of chordae, fusion of leaflet & chordal and fibrosis and calcification destroys
the structure of the valves
Microscopy
Increased weight of heart, cardiac hypertrophy, flabby myocardium and small pale
focal lesions. There is also thickening of the valves and loss of translucency. Small,
multiple wary vegetations are found along the line of closure of the leaflets and cusps.
Microscopy
Aschoff Nodules, highly vascularized valve cusps, oedema with infiltration with
polymorphs, macrophages, lymphocytes and plasma cells. There is proliferation of
fibroblasts and fibrinoid necrosis of valve cusps.
3.5 Blood vessels - Rheumatic Arteritis
Inflammation of arteries in ARF involves the coronary arteries, renal, mesenteric and
cerebral arteries
8.0 EXTRA-CARDIAC MANIFESTATIONS
Local inflammation is usually encountered in joints and adjacent musculofascial tissues,
serous membranes, the skin and the central nervous system.
3.6 The Joints
There is involvement of joints and adjacent musculofascial tissues causing arthritis with
effusion, muscle pains and weakness.
Polyarthritis
There are inflammatory changes in the synovium with cellular infiltration resembling
Aschoff nodules. It is migrating polyarthritis that commonly affects larger joints of the
wrist, elbow, knee and angle with the joints of the hips and small joints of the hands
being occasionally affected. Polyarthritis usually involves two or more joint at a time.
The synovial fluid contains numerous polymorph nuclear leucocytes. It usually lasts
about 4 weeks and resolves without any residual damage
Arthralgia
Arthralgia causes minor discomfort to severe pain
Serous Membranes
There is involvement of the serous membranes in the pericardium and sometimes the
pleura with resultant pleural effusion. The lungs are congested; firm and rubbery
(rheumatic pneumonitis) with the alveolar ducts being lined with fibrin
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 67
3.7 The Skin
Subcutaneous Nodules
These are firm and painless subcutaneous lesions (nodules) varying in size (0.5 – 2 cm)
palpable over bony prominences that are subject to pressure with a predilection of
arms and legs or tendons on the extensor surfaces of the elbows, knees, the occiput and
the scapulae. The nodules consist of eosinophilic hyaline swelling of collagen. It
contains cells like the lymphocytes, plasma cells, macrophages and fibroblasts.
The nodules occur in 3rd week and last 1-2 weeks and are usually associated with
carditis. They may occur in crops (Differential diagnosis - S.L.E. Rheumatoid arthritis)
Diagram 6.3: Subcutaneous Nodules
Erythema marginatum
Erythema marginatum is a non-pruritic erythymatous rash that begins as a non-itchy
faint red macule and the erythema spreads on forward while the centre returns to
normal. They are associated with carditis and subcutaneous nodules.
The lesions may be raised or flat with and irregular margin outline mainly on the trunk
and proximal parts of the extremities. The Lesions are migratory with the skin rash
fading in 24 hours with no residual scarring
Diagram 6.4: Erythema Marginatum
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 68
3.8 Central Nervous System
The Brain
Sydenhan’s chorea [St. Vitu's dance] named after Dr. Thomas Sydenham (1686) results
from encephalitis (inflammation of the brain tissue). The lesion consist of small haemorrhages, oedema and perivascular infiltration by lymphocytes. The lesions are
located in the cerebral hemispheres, brainstem and basal ganglia. Chorea is
characterized by distorted and involuntary jerky movements of the trunk and the
extremities accompanied by some degree of emotional instability.
9.0 CLINICAL FEATURES
Clinical features depend on organs involved
9.1. General Features
The general features are which are of sudden onset include fever, joint pains, general
malaise and loss of appetite.
9.2. Cardiac Features
These include cardiomegaly, congestive cardiac failure (CCF), pericardial effusion,
ECG changes (raised ST segment in pericarditis and inverted or flat T-wave in
myocarditis), AV block, cardiac arrthymias and changing murmurs (Diastolic mitral -
Carey Coomb’s murmur)
9.3. Extra-Cardiac Features
a) Respiratory System – epistaxis, tachypnoea
b) Musculo-skeletal system - fleeting polyarthritis (knees, elbows, ankles, wrists),
swollen, red and tender joints
c) The Skin - erythema marginatum (trunk and limbs) and subcutaneous nodules
(tendons and joints bony prominences)
d) The Central Nervous System - chorea
10.0 DIAGNOSIS
Based on the Ducket Jones Criteria (Revised) that comprises of the major and minor
criteria
Made when 2 major criteria and 0 minor or 1 major and 2 minor criteria are
evident.
Major Criteria – SPACE
1. Subcutaneous nodules
2. Pancarditis (friction rub, murmur, cardiomegaly, CCF, and ECG changes)
3. Arthritis (migratory polyarthritis, swollen, tender, red)
4. Chorea
5. Erythema marginatum
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 69
Minor Criteria – LEAF
1. Leucocytosis
2. ESR – raised - acute phase proteins (ESR, positive C-reactive proteins, leucocytosis)
3. Arthralgia (joint pain without arthritis)
4. Fever
5. Prolonged P-R interval on ECG
6. Previous rheumatic fever or rheumatic heart disease
Evidence of antecedent Strep infection:
ASO / Strep antibodies / Strep group A throat culture / Recent scarlet fever / anti-
deoxyribonuclease B / anti-hyaluronidase
11.0 INVESTIGATIONS
1. Chest X-Ray
2. ECG
3. Throat swab – culture
4. Blood culture
5. Total blood count (TBC)
6. C-R proteins
7. ASOT titres
8. Urinalysis
9. Renal function tests
10. Liver biochemistry
12.0 COMPLICATIONS
1. Heart Failure
2. Atrial fibrillation
3. Infective endocarditis
Rheumatic Heart Disease (RHD)
1.0. INTRODUCTION
Occurs as an aftermath (post inflammatory scarring) of destructive effects of
rheumatic fever on the endocardium and the heart valves
Destruction results in healing by fibrosis of the damaged surfaces resulting in valve disorders and incompetence (stenosis and regurgitation). This includes the aortic,
mitral, tricuspid and pulmonary valves. RHD can be acute or chromic RHD.
2.0. ACUTE RHD
This presents as acute rheumatic fever (ARF) which occurs mainly in children. It
presents with cardiac and extra-cardiac features. It recurs in 50 – 70% of young children
and causes chronic rheumatic valvulitis. The cardiac features which are elaborate
include pancarditis (occurs in 40% of acute RHD presenting as: -
1. Endocarditis (verrucous) – valve destruction and murmurs of stenosis
2. Myocarditis – cardiac enlargement, cardiac failure, dilatation of ventricles and mitral
ring resulting in mitral regurgitation (insufficiency), aschoff nodules
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 70
3. Pericarditis – friction rub
The other features of ARHD include rheumatic polyarthritis, subcutaneous nodules,
erythema marginatum and Sydenham’ chorea.
3.0. CHRONIC RHD
Chronic RHD occurs mainly in adults as a sequale of earlier ARF (ARHD) with
destruction of heart valves. It presents mainly as valvular heart disease predominantly
affecting left sided valves (almost always the mitral valve). It affects the valves in the
following order of decreasing frequency – mitral, aortic, tricuspid and pulmonary. The
mitral valve is affected alone in 48% of cases and together with the aortic valve in 42%
cases. The right sided valves are rarely affected but tricuspid regurgitation
(insufficiency) is usually due to congestive cardiac failure.
4.0. MITRAL VALVE
There is thickening of valve leaflets especially at the lines of fusion, fusion of the
commissures and thickening, shortening and fusion of the chordae tendinae resulting in mitral stenosis (MS), mitral regurgitation (MR) or both.
Effects of the destroyed heart valves result in changes in the heart and lungs depending
on the severity of valve disease. MS causes left atrial hypertrophy and dilatation which
results in atrial fibrillation, mural thrombosis and systemic embolization with eventually
cause chronic passive congestion of the lungs with resultant pulmonary hypertension
and right ventricular hypertrophy.
Mitral regurgitation causes left ventricular hypertrophy and dilatation leading to left
atrial dilatation. Chronic left ventricular failure causes right ventricular failure and
tricuspid regurgitation.
Diagram 6.5: Mitral Valve Destruction
5.0. AORTIC VALVE
There is thickening of the valve cusp especially along the lines of fusion and fusion of commissures resulting in aortic stenosis (AS) and aortic regurgitation (AR) or often
both. The damage to valves produces changes in the heart with AS causing left
ventricular hypertrophy and AR left ventricular hypertrophy and dilatation.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 71
Infective Endocarditis
1.0. INTRODUCTION
Endocarditis is an inflammatory condition of the mural endocardium characterized by
large crumbling vegetations toxaemia and bacteraemia. Infective endocarditis is
caused by infection of the heart valves or other areas of the endocardium. There is the
growth of microorganisms on an endothelium usually a valve that occurs in a pre-
existing cardiac lesion. The offending organism is usually present in masses of thrombus (vegetation). Multiple embolic episodes occur.
2.0. TYPES OF ENDOCARDITIS
1. Infective (microbial)
Mainly bacterial or fungal
Rarely viral and rickettsial
Destroys valve tissue in contrast with non-infective
Forms thrombosis with microorganisms deep within it (vegetations)
Associated with thrombus formation
2. Non-infective (non-microbial) endocarditis
Verrucous (acute rheumatic fever)
Atypical verrucous (Libman-Sacks in S.L.E)
Non-bacterial thrombotic endocarditis (NBTE)
3.0. AETIOLOGY
The infective organisms with low virulence pathogenecity are derived from normal
commensal organisms of the skin, mouth, urinary tract and gut. The organisms enter the
blood in inconsequential events of bacteraemia and become entangled in platelet
aggregations on the surface of the abnormal endocardium and grow to cause persistent
infection. It may occur due to infection of normal valves as seen in drug addicts, after
open heart surgery and septicaemia.
Valvular abnormalities produce turbulent flow, which damages the endocardium
causing deposition of platelets and fibrin forming vegetations. The vegetations fall
downstream from an area of relatively higher pressure.
1. Alpha –haemolytic streptococci low virulence organisms e.g. S. viridans (mouth and
pharynx commensals), S. sanguis and S. feacalis
2. Staphylococcus aureas
3. Streptococcus boris (GIT)
4. Staphylococcus epidermidis(skin) –indwelling venous catheters, artificial pacemaker
wires
5. Streptococcus pneumoniae
6. Haemophilus ssp.
7. Diptheroids - skin/GIT
8. Colliform bacilli - “
9. Bacteroides
10. Coxiella burnetti
11. Neiserria
12. Gram negative bacilli- pseudomonas aeruginosa
13. Fungal – drug addicts/Immunosuppresed e.g. Candida, Aspergilla’s, Histoplasma
14. Rickettsia
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 72
4.0. PREDISPOSING FACTORS
1. Conditions causing bacteraemia, septicaemia and pyaemia e.g. dental
carries/extraction, boils/Carbuncles, U.T.I, pneumonia,
tonsillectomy/Adenoidectomy, surgery (G.I.T, G.U.T, billiary and open Heart) and
drug addicts
2. Cardiac lesions - valve abnormalities, abrasions, mechanical & biological prosthetic
valves, endocardial sutures & patches and degenerative heart disease
3. Immunosuppression - decreased specific immunity, complement deficiency and
inadequate function of lymphocytes
4. Haemodynamic factors
5. Portals of entry of the organisms – blood.
5.0. PATHOGENESIS
The pathogenesis of infective endocarditis is a result of three interactive processes
namely: -
1. Host factors that predispose the endothelium to infection
2. Circumstances enhancing bacteraemia
3. Tissue tropism and virulence of circulating microorganisms
Host factors
The local host factors include damaged endothelium, prosthesis, and infection and
valve abnormalities while systemic host factors are usually loss of systemic host
defences. An episode of bacteraemia coincides with small thrombi on the valve. The
vegetation composed of platelets, fibrin, macrophages and organisms is the initial
lesion. Blood borne organisms adhere to the vegetations and provoke further
deposition of platelets, fibrin and macrophages. There is a 24h lag period before rapid
bacterial growth occurs. The vegetation lesion grows and may become obstructive,
erosive and proliferative. The infection may spread directly or via septic embolization.
Pericarditis may follow direct spread. Systemic embolic phenomenon may occur.
Immunology
Persistent bacteraemia challenges antibody production by B-lymphocytes and plasma
cells. The increased antibody levels and hypergamonaglobinaemia leads to formation
of rheumatoid factors and antiglobulins (False positive for syphilis VDRL, ANF). Tissue
damage is caused by excess circulating antigen-antibody complexes.
6.0. CLASSIFICATION
1. Acute bacterial/Infective endocarditis (ABE and SABE)
2. Sub-acute bacterial/Infective endocarditis
Pathogenesis of ABE and SABE
The jet and venture effects damage the endothelial surface which is exposed to platelet
activity and results in fibrin thrombosis. The microbes in the thrombus multiply and
bacteraemia occurs. High titres of agglutinating antibodies lead to clumping of bacteria
(sticking to the thrombus).
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 73
Acute Infective Endocarditis
Acute infective endocarditis is usually caused by virulent pyogenic bacteria e.g.
Staphylococcus aureus and Streptococcus feacalis present in a local suppurating lesion
and causes focal destruction. The bacteria proliferate and mix with the leucocytes
forming large and crumbling vegetations that are deposited on the diseased. It results
in rapid destruction of cusps and chordae and spread of suppuration to adjacent heart
muscle culminating in acute heart failure. ABE runs a fulminant course for weeks only.
Occurs in a previously normal. The symptoms of ABE are of sudden onset and include
high fever, prostrated patient with heart murmurs. Death occurs due to heart failure,
valve perforation and sepsis.
Subacute Infective Endocarditis (SABE)
Subacute infective endocarditis is caused by low-grade bacteria e.g. Staphylococcus
viridans, coliform bacteria, Staphylococcus albus and results in formation of large
vegetations gradually increasing damage to the valve cusps with minimal spread to
adjacent structures causing gradual cardiac failure.
The symptoms of SABE are variable, insidious and often misdiagnosed. They include
low grade fever, malaise, fatigue, anaemia and murmurs. It runs a lengthy course
(months) and diagnosis includes a series of positive blood cultures.
Special Considerations
Endocarditis in drug addicts is often due to Staph aureaus or fungal (from skin,
contaminated drugs or cutting materials). Right sided endocarditis is more common in
addicts but left sided endocarditis forms the bulk of cases. Fungal endocarditis is
associated with bulkier vegetations that obstruct the valves, embolize and obstruct
large vessels. It occurs as a complication of open heart surgery or narcotic addiction. It
may present with signs of emboli such as hemiplegia.
7.0. PATHOLOGY
Macroscopy (Gross Appearances)
The Heart
Heart reveals features of chronic rheumatism or features of congenital valvular heart
disease e.g. floppy mitral valve, bicuspid aortic valve and calcific aortic Stenosis
Vegetations
The vegetations which are the pathognomonic lesion comprise of large masses of
thrombus that are adherent to valve cusps or endocardium. They may be single, sessile,
polypoidal or cauliflower and may spread outside the cusp. The size is influenced by
the haemodynamics of blood circulation and organism responsible.
Invasion by microorganisms
The organisms invade the underlying cusps causing necrosis leading to aneurysm
formation, rupture of cusps and rupture of chordae
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 74
Destructive effects of lesions
The destructive effects of infective endocarditis depend on the size of the emboli (mall
and big emboli). These cause infarcts in internal organs due to embolism in the liver,
spleen, petechial haemorrhage, retinal haemorrhage, splinter haemorrhage, Janeway
lesions and subconjuctiral Haemorrhage
Renal Glomerulonephritis
Is to due to glomerular lesion causing haematuria, uraemia and renal failure
Microscopy
1. The Vegetations - composed of platelets, fibrin, and colonies of microorganism,
scanty polymorphs and calcification. Below the vegetation there is heavy
inflammation and vascularization.
2. The Cusps are hyperaemic, vascularized, thickened, fibrosed and oedematous with
necrotic tissues.
3. Cellular infiltration with polymorphs, macrophages and giant cells
4. The Kidneys are described as “flea-bitter” because of the pinpoint red spots on
subcapsular (small haemorrhages at site of tuff capillaries) due to immune – complex
deposition. They allow blood into glomeruli and renal tubules causing haematuria.
8.0. CLINICAL FEATURES
The clinical features relate to cardiac failure, systemic emboli and immunological
manifestations.
Cardiac Failure: Cardiac failure results from volume overload on left ventricle and
myocardial damage due to embolic and immune mechanisms.
Systemic emboli: Involves the spleen, mesenteric arteries, kidney (58% cases) and
cerebral lesions. They account for 20% cases and increase the mortality and morbidity
leading to neurological problems – hemiplegia, blindness, and dementia.
Immunological Complications
The release of bacterial antigens into circulation leads to immune complex formation.
The high levels of circulating immune – complexes are associated with the arthritis,
subungual splinter haemorrhages, purpura and glomerulonephritis. The Osler’s nodes
(small red tender nodes) are embolic in origin.
9.0. CRITERIA FOR DIAGNOSIS (DUKE’S CRITERIA)
Major criteria
1) Two positive blood cultures for organisms typical of endocarditis
2) Three positive blood cultures for organisms consistent with endocarditis
3) Serologic evidence of Coxiella burnetii (or one positive blood culture)
4) Echocardiographic evidence of endocardial involvement
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 75
Minor criteria
1) Predisposing heart disorder
2) IV drug abuse
3) Fever ≥38° C
4) Vascular phenomena - arterial embolism, septic pulmonary embolism, mycotic
aneurysm, intracranial haemorrhage, conjunctival petechiae and Janeway lesions
5) Immunologic phenomena - Glomerulonephritis, Osler nodes, Roth spots,
Rheumatoid factor
6) Microbiologic evidence of infection consistent with but not meeting major criteria
7) Serologic evidence of infection with organisms consistent with endocarditis
Definite Diagnosis
2 major or 1 major + 3 minor or 5 minors
Possible Diagnosis
1 major + 1 minor or 3 minor
10.0. INVESTIGATIONS
1. Full heamogram and ESR - reduced haemoglobin (Hb), increased wbc’s, reduced
platelets and increased C – reactive proteins
2. Blood cultures At least six samples
3. Liver biochemistry (LFTS) - reduced Serum alkaline Phosphotase
4. Immunoglobins and complement - raised Serum Ig, reduced total complement and
C3 complement due to immune-complex formation, circulating immune complexes
and rheumatoid factor
5. Serological tests
6. Urea/Electrolytes
7. Urinalysis
8. ECG – evidence of myocardial infarction
9. Echocardiography
10. Chest X-Ray - evidence of Heart failure and emboli in right-sided endocarditis.
11.0. COMPLICATIONS
1. Intracardiac
a) Severe valve deformities and obstruction of valves or outlet tract
b) Rupture of chordae tendinae
c) Perforation of cusps/leaflet
d) Abscess
e) Fistula
f) Obstruction
g) Embolism into coronary artery (ischaemic heart disease)
h) Cardiac failure
2. Extra-cardiac
a) Systemic emboli to major organs - Kidney (renal failure), Liver (hepatic failure),
Retina (retinopathy) and Brain (cerebro-vascular accident – CVA)
b) Mycotic aneurysm formation
c) Pyemia and septicaemia
d) Glomerulonephritis (secondary to immune complexes)
e) Anaemia
f) Other toxic or allergic inflammation of vessel walls leading to petechiae and/or
splinter haemorrhages in the skin, mucosa, conjunctiva and retina.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 76
Lesson 7: Disorders of the Myocardium and Pericardium
Learning Outcomes
At the end of the session the learner should be able to: -
1. Outline causes of pericarditis and cardiomyopathy
2. Outline the pathology, features and effects of pericarditis
3. Describe the pathology and pathophysiology of the disorders of the myocardium
4. Outline the pathology, features and effects of cardiomyopathy
5. Describe the pathology of pericarditis and myocarditis
THE MYOCARDIUM
1.0 ANATOMY
Is the muscle tissue of the heart composed of syncytium of branching and
anastomosing, transversely striated muscles fibres
Consists of two layers – the superficial and deep layers. The superficial layer is the
same in the ventricles and atria but the arrangement of the muscles in the deep layer
is more complex in the ventricles where the left ventricle has large deep layer. The
myocardium is very rich in mitochondria that provide the ATP required for cardiac
function
Has plentiful sarcoplamic endothelium an equivalent of endoplasmic reticulum of
other cells that is that houses ribosomes responsible for synthesis of proteins.
2.0 DISORDERS OF THE MYOCARDIUM
1. Cardiomyopathy
a. Dilated (Congestive) cardiomyopathy
b. Hypertrophy cardiomyopathy
c. Restrictive cardiomyopathy
2. Myocarditis
3. Myocardial Ischaemia
4. Miscellaneous - fatty infiltration, fatty change and atrophy
CARDIOMYOPATHIES
1.0 INTRODUCTION
Cardiomyopathy is a general term indicating disease of the cardiac muscle. It can be
divided into primary cardiomyopathy (cause is unknown) and secondary
cardiomyopathy (cause is known). Usually the term cardiomyopathy may be
synonymous with primary cardiomyopathy. The WHO definition of cardiomyopathy
excludes heart muscles diseases of known aetiologies.
2.0 CLASSIFICATION
Cardiomyopathy can be into two main groups based on the aetiology into primary
cardiomyopathy (no known cause) and secondary cardiomyopathy which is myocardial
disease with known underlying cause.
1.0 PRIMARY CARDIOMYOPATHY
Primary cardiomyopathy is a group of myocardial diseases of unknown aetiology.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 77
Diagram 7.1: Types of Cardiomyopathy
Primary cardiomyopathy can be classified based on predominant clinical
presentations and pathophysiology into three groups namely: -
1. Dilated (Congestive)m cardiomyopathy – there is ventricular dilatation
2. Hypertrophic cardiomyopathy – myocardial hypertrophy
3. Restrictive(obliterative) cardiomyopathy – impaired ventricular filling
Diagram 7.2: Varieties of Cardiomyopathy
Dilated Cardiomyopathy (DCM)
Dilated cardiomyopathy is characterized by gradual progressive cardiac failure associated with dilatation and hypertrophy of the four heart chambers. Because of
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 78
dilatation of the chambers and the ensuing heart failure DCM is also called congestive
cardiomyopathy. Patients with DCM present with unexplained heart failure usually
between the ages of 30 – 60 years.
Causes
The cause is unknown but associated factors exist
1. Familial (autosomal dominant)
2. Viral infection – Coxsackie’s virus , HIV
3. Alcohol toxicity (chronic alcoholism)
4. Peri-partum
Pathogenesis
1. Genetic defect along the family pedigree
2. Post viral myocarditis
3. Effects of alcohol or alcohol metabolites
4. Dilated heart discovered within several months before or after delivery due to
effects of hypertension, volume overload and nutritional effects
Pathology
Macroscopy: Cardiomegaly, increased weight of the heart, dilatation of the heart
chambers, thickening of ventricular walls and thrombosis (mural)
Microscopy: Hypertrophy of heart muscle cells, degenerative changes and cellular
infiltration with mononuclear inflammatory cells
Diagram 6.3: Dilated (Congestive) Cardiomyopathy
Clinical Features
1. Right ventricular failure
2. Left ventricular failure
3. Congestive cardiac failure
4. Cardiac arrhythmias
5. Embolism (how will this present and what is the mechanism)
Investigations
1. Chest X-ray – cardiac enlargement
2. ECG – diffuse non-specific ST segment and T wave abnormalities
3. Echocardiogram – dilatation of the left ventricle and/or right ventricle with poor
global contraction
4. Full haemogram
Differential Diagnosis
1. Cardiovascular disease (ischaemic, rheumatic, congenital, systemic hypertension)
2. Generalized disease e.g. sarcoidosis
3. Connective tissue disorders e.g. systemic lupus erythromatosus, systemic sclerosis
4. Neuromuscular disease e.g. muscular dystrophy
5. Alcohol excess
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 79
6. Glycogen storage disease
7. Cytotoxic drug therapy - cyclophosphamide
Hypertrophic Cardiomyopathy (HCM)
Hypertrophic cardiomyopathy is an inherited disorder of the heart muscle characterized by a variable hypertrophy of the right ventricle without a cardiac or
systemic cause. It exhibits massively thickened (hypertrophied) inter-ventricular
septum that results in distorted ventricular contraction with abnormal valve movement
during systole. Mitral stenosis may be present. Apposition of the anterior mitral leaflet
to the thickened septum causes obstruction to left ventricular emptying. HCM is also called idiopathic hypertrophic subaortic stenosis and hypertrophic obstructive
cardiomyopathy.
Diagram 7.4: Hypertrophic Cardiomyopathy
Causes
1. Familial (autosomal dominant)
2. Collagen disease/storage disease
3. Increased circulating catecholamines
4. Infants of diabetic mothers
Pathogenesis
1. Autosomal dominant resulting from mutations in the genes controlling sarcomeric
proteins on chromosome 14.
2. Collagen disease and myocardial ischaemia cause fibrosis of the intracardial
arteries and compensatory hypertrophy
3. Increased circulating catecholamines may cause hypertrophy of the myocardial
fibres
Pathology
Microscopy: Cardiomegaly, hypertrophy, asymmetrical septal hypertrophy – more
thickening of the septum than left ventricular wall, left ventricle cavity is compressed
into a banana-like configuration and thickening of the basal septum at the level of the
mitral valve results in obstruction
Microscopy: Myocardial cell disorganization, hypertrophy of muscle cell with large
prominent nuclei. And replacement fibrosis
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 80
Clinical Features
1. Cardiac arrhythmias
2. Cardiac failure
3. Sudden death
4. Syncope
5. Dyspnoea
6. Chest pain
7. Disturbed systolic ventricular function (double apical pulsation, jerky carotid pulse,
ejection systolic murmur, pansystolic murmur and fourth heart sound)
Complications
1. Atrial Fibrillation
2. Mural Thrombosis
3. Embolization
4. Infective endocarditis
5. Congestive cardiac failure
6. Chronic Heart failure
7. Sudden death
Investigations
1. Chest X-ray
2. ECG – is diagnostic as it shows ventricular hypertrophy
3. Pedigree analysis
4. Genetic analysis
Differentials
1. Hypertensive heart disease
2. Aortic stenosis
Restrictive Cardiomyopathy
This is a form of cardiomyopathy characterized by restriction in ventricular filling
due to reduction in the volume of the ventricle. The myocardium does not relax
properly in diastole as it is restricted resulting in reduced ventricular filling and hence
reduced cardiac output. The restriction stems from fibrosis of the ventricular muscle.
Causes/associated conditions
1. Idiopathic/Familial
2. Amyloidosis
3. Sarcoidosis
4. Loeffler’s endocarditis
5. Endomyocardial fibrosis
6. Endocardial fibroelastosis
Pathogenesis
1. Endomyocardial fibrosis (EMF) is characterized by fibrosis of the endocardium and
tissues underlying the myocardium of inflow tracts of both or either ventricles. The
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 81
fibrosis involves the papillary muscles and chordae tendinae resulting in mitral
and/or tricuspid incompetence. The fibrous tissue restricts ventricular muscle
contraction.
2. Endocardial fibroelastosis is rare and involves formation of a diffuse layer dense,
white avascular tissue composed of elastic fibres. The fibres are formed in the
endocardium where they interfere with the endocardial surface, papillary muscles
and chordae tendinae as well as causing thickening of the mitral or aortic valve
cusps. The resulting mechanic effects cause cardiac failure.
Clinical Features
1. Dyspnoea
2. Fatigue
3. Embolic features
4. Features of constrictive pericarditis such as a high JVP with diastolic collapse –
Friedreich’s sign and elevation of venous pressure with inspiration – Kussmaul’s sign
5. Heart – cardiomegaly with a third or fourth heart sound
Investigations
1. Chest X-ray – confirms enlarged heart
2. ECG – low voltage and ST segment and T wave abnormalities
3. Echocardiogram – asymmetrical myocardial thickening, impaired ventricular filling
4. Endomyocardial biopsy
Complications
1. Cardiac Failure
2. Valvular heart disease
3. Thrombosis (mural)
4. Embolism
4.0 SECONDARY CARDIOMYOPATHY
Introduction
Secondary cardiomyopathy is a group of myocardial diseases with known aetiologies or
clinical associations but they are poorly defined. This group excludes well defined
entities such as ischaemic, hypertensive, and valvular, pericardial, congenital and
inflammatory conditions of the heart.
The Disorders
The main disorders include: -
1) Nutritional disorders such as thiamine deficiency, Beri beri heart disease and those
associated chronic alcoholism
2) Toxic chemicals - Cobalt , Arsenic, Lithiu, Hydrocarbons
3) Drugs – Cyclophosphamide, Catecholamines
4) Metabolic diseases – Diabetes mellitus, Amyloidosis, Glycogen storage disease,
Hyperthyroidism and Hypothyroidism
5) Neuromuscular diseases e.g. muscular dystrophy
6) Connective tissue diseases - Rheumatoid arthritis, S.L.E
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 82
MYOCARDITIS
Definition - Myocarditis is an inflammatory lesion of the myocardium
Aetiology
1. Infections
a. Viruses - Coxsackie Group A, B, Echovirus type 8, Infleunza, Adenoviruses, Polio,
HIV
b. Bacterial toxins/bacteria – Staphylococcus, Syphilis, Streptococcus, Diphtheriae
c. Protozoal - Trypanosomiasis (T. cruzi – Chaga’s disease)
d. Parasites - Trichinosis spiralis and Toxoplasmosis
e. Fungal -Candida albicans, Aspergillus
2. Poisons and chemicals - Drugs - cytotoxics – daunorubicin; Alcohol
3. Physical agents - severe hypothermia, irradiation
4. Hypersensitivity reactions/connective tissues disorders - Rheumatic fever,
Rheumatoid arthritis and S.L.E
5. Endocrine/metabolic disorders - Diabetes mellitus, hypothyroidism,
hyperthyroidism
6. Idiopathic
Features
1. Acute unexplained heart failure
2. Cardiac Arrthymias
3. Chest pain
4. Gallop rhythm
5. Cardiac enlargement
Viral Myocarditis
Presents as acute myocarditis and is usually accompanied by mild acute pericarditis
Incidence
Infants, Outbreaks in nurseries
Young adults
Microscopy - Shows widespread interstitial oedema
Microscopy
There is infiltration of the myocardium by:
1. Macrophages
2. Lymphocytes
3. Minimal plasma cells
4. Minimal eosinophils
This condition is usually mild and complete recovery is the rule however it may be fatal.
It is a common feature of intra-uterine rubella and may occur as a complication of
poliomyelitis and influenza infection.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 83
Toxic Myocarditis
Toxic myocarditis is a major feature of diphtheria and may be seen in pneumococcal
pneumonia, typhoid fever, septicaemia, severe acute bacterial infections
Microscopy: There is gross oedema with fibres that are swollen and glassy
Microscopy
1. Numerous small foci of coagulative necrosis
2. Loss of striations and nuclei
3. Cellular infiltration with macrophages, lymphocytes and occasionally polymorphs
****Myocarditis due to diphtheria, the conducting system is severely affected with
resultant heart block.
Suppurative Myocarditis
Aetiology
1. Pyogenic bacteria - Staphylococcus aureus (localized infection) and Streptococcus
pyogenes (spreading infection)
2. Occurs in septicaemia and pyaemia
****In cases of strep pyogenes there is spreading infection with extensive necrosis and
haemorrhage.
Hypersensitivity
Results from hypersensitivity reactions to antigens shared by causal strep and heart
muscle e.g. in rheumatic fever. It may complicate rheumatoid arthritis, S.L.E, syphilitic
gumma and sarcoidosis
THE PERICARDIUM
1.0. ANATOMY
Comprises of the fibrous pericardium and the serous pericardium membranes
enclosing the heart. It holds about 50 mls of fluid that is usually formed by the serous
pericardium and is similar to lymph
Fibrous pericardium is the outer pericardial layer that limits sudden distension of the
heart
Serous pericardium is a thin delicate membrane found within the fibrous
pericardium and covers the heart. Has an outer or parietal layer that lines the fibrous
pericardium and the inner or visceral layer that covers the outer surface of the heart
and adjoining parts of the great vessels.
The pericardium has two recesses – (1) the transverse sinus, which is behind the
commencement of aorta and pulmonary trunk in front of the two atria, and (2) the
oblique sinus found behind the left atrium extending to oesophagus and descending
thoracic aorta.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 84
2.0. THE PERICARDIAL FLUID
The fluid forms a thin film on the surface of the pericardium and acts as a lubricant
facilitating movements of the heart within the pericardial cavity. The pericardium and
pericardial fluid lubricate the surface of the heart, limit distension of the heart
contributing to haemodynamic interdependence of the ventricles and acts as a barrier
to infections.
3.0. PERICARDITIS
Inflammation of the pericardium
Aetiology
1. Idiopathic
2. Infections
i. Bacterial
a) Complication of septicaemia, pyaemia, empyema; ulcerating ca bronchus and
ulcerating ca oesophagus
b) Pyogenic cocci - Streptococcus pyogenes, Streptococcu pneumoniae,
Staphylococcu aureus
c) Tuberculosis
ii. Viral – Echovirus, Coxasackie virus
iii. Protozoal/Parasitic – amoebiasis, toxoplasmosis, ecchninococcal
iv. Fungal - Histoplasmosis (H. capsulatum), Actinomycosis
3. Myocardial infarction
4. In association with connective tissue disorders such as S.L.E, Rheumatoid arthritis,
Acute rheumatic fever and Polyarteritis nodosa
5. Metabolic – uraemia and hypothyroidism
6. Neoplastic – primary and secondary
7. Physical agents – radiation, blunt trauma
8. Haemorrhage due to trauma, aortic dissection and anticoagulant therapy
9. Drug induced
4.0. ACUTE PERICARDITIS
Introduction
Acute pericarditis is an acute inflammatory process of the pericardium involving the
serosal lining of the pericardium. It is characterized by active hyperemia, inflammatory
oedema, leucocyte emigration and exudate accumulates in the pericardial sac with
fibrin deposition on the surface giving the “bread and butter” appearance. The
inflammation is usually fibrinous accompanied by an effusion, (serous, haemorrhagic or purulent). The exudation fluid accumulates in the pericardial sac (pericardial effusion)
increasing the pericardial pressure interfering with atrial filling and circulation in general (cardiac tamponade). Fibrin deposited is removed by process of organization
with subsequent fibrous thickening of the pericardial layers with formation of adhesions (constrictive pericarditis) leading to cardiac failure.
Aetiology
1. Infective (Infections)
a. Bacterial as a complication of septicaemia, pyaemia, bacterial pneumonia,
empyema, ulcerating ca oesophagus/ca bronchus and tuberculosis OR pyogenic
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 85
cocci – Streptococcu pyogenes, Streptococcu pneumoniae and Staphylococcu
aureus
b. Viral - Group B coxsackie, Echovirus
c. Parasites
2. Non-Infective
a. Acute and previous rheumatism
b. Immunological
c. Myocardial infarction
d. Metabolic
e. Ureamia following nephrotic syndrome where pericarditis is usually a terminal
event as a result of metabolic derangement
f. Complication of malignancy, trauma
3. Idiopathic
In pyogenic infections, acute pericarditis occurs from adjacent lesion e.g. empyema
thoracis, there is suppuration into the pericardium or the whole of the mediastinum is
involved or from an adjacent ulcerating lesion e.g. oesophageal lesions. In majority of
cases the infection is usually due to haematogenous spread (septicaemia) and may be
lymphatic extension. It is mainly due to streptococcus.
Diagram 7.5: Pericarditis
Pathology
1. The diagnostic feature at autopsy is usually the “bread and butter” appearance
2. The exudate first appears around the great vessels at the base of the heart as
opaque, dull and roughened layer. If this exudate becomes abundant it forms a
rough fibrinous covering (in fibrinous pericarditis) over the heart which gives the
heart irregular projections 3. The effusion can be serous (in acute rheumatism, myocardial infarction) ,
haemorrhagic (in tuberculosis, uraemia, infective microbes, secondary metastatic
tumour) and purulent (suppuration) in septic pericarditis, pyogenic pericarditis
Pericarditis can be: -
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 86
1. Serous (as in non-bacterial inflammation, rheumatic fever, S.L.E, tumours,
myocardial infarction and viral infection) 2. Serofibrinous/Fibrous – is the most frequent )as in rheumatic fever (commonest
cause), myocardial infarction and ureamia 3. Suppurative/Suppurative – septic/pyogenic (mode of infection - Direct extension,
Blood stream, Lymphatics; organisms - Strep., Staph., Meningococcus,
Mycobacterium, Gonococcus) 4. Haemorrhagic (as in tuberculosis, tumours, infective microbes)
5.0. CHRONIC PERICARDITIS
Chronic pericarditis results from inadequately treated bacterial pericarditis especially
TB. It is rarely idiopathic.
TB Pericarditis follows chronic pulmonary tuberculosis and the phe presumed route of
infection is by lymphatic or extension from the infected pleura. The exudate formed is
turbid or blood stained. There are tubercles visible on pericardial surface. Calcification
may lead to constrictive pericarditis
Constrictive Pericarditis is evident by the obliteration of the pericardial sac by the
thick layer of dense fibrous tissue. It is seen in pyogenic pericarditis, tuberculosis and
rheumatoid arthritis Hydropericardium is accumulation of clear transudate or clear fluid seen in conditions
of generalized oedema. The pericardial surfaces are smooth and shinny in appearance.
Haemopericardium is haemorrhage into the pericardial sac which may result from
rupture of the heart secondary to infarction, rupture of aortic aneurysm and stab
wounds on the heart and great vessels. Its rapid development leads to cardiac
tamponade
6.0. PRESENTATION OF PERICARDITIS
Pericardits presents as CCF, low stroke volume and a small heart
Pericardial Effusion
Pericardial effusion occurs when an inflammatory exudate collects in the closed
pericardium. It may give rise to mechanical embarrassment of the circulation by
reducing ventricular filling leading to cardiac tamponade.
Pathophysiology & Clinical features
1. Raised JVP
2. Raised JVP with sharp diastolic collapse (Friedreich’s sign)
3. A paradoxical pulse (BP falls during inspiration)
4. Kussmal’s sign (increased neck vein distension during inspiration)
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 87
Lesson 8: Hypertension and Hypertensive Heart Disease
Learning Outcomes
At the end of the lesson the learner should be able to: -
1. Describe blood pressure control mechanisms
2. Describe the role of risk factors in causation of hypertension.
3. Classify and describe causes of hypertension
4. Describe the pathological processes in hypertension
5. Describe the complications and investigations in hypertension
BLOOD PRESSURE
1.0. INTRODUCTION
BP is the force exerted by the blood against any unit area of the vessel wall. It is
usually measured in millimetres of mercury
Normal BP is a systolic pressure of 100 – 140 mmHg and diastolic at 60 –90 mmHg
Systolic pressure is produced by transmission of left ventricular systolic pressure
while vascular tone and an intact aortic valve maintain the diastolic pressure
Hypertension increases the risk of cardiovascular disease mainly left ventricular
failure and ischaemic heart disease that could result in cardiac failure or/and sudden
death and cerebrovascular accident (CVA, stroke) due to cerebral haemorrhage or
infarction. Mathematically speaking, Blood Pressure (BP) = Cardiac Output (CO) x
Peripheral Resistance (PR). Therefore an increase in CO, or PR or both increases BP
(PR is the total peripheral resistance [sum total])
2.0. BLOOD PRESSURE CONTROL MECHANISMS
1. Nervous mechanism – comprises of the baroreceptor mechanisms, central nervous
system (vasomotor centre, sympathetic autonomic nervous system and the vagus
nerve) and chemoreceptors
2. Capillary fluid drift activation
3. Kidneys - Rennin-Angiotensin-Aldosterone (R.A.A) mechanism.
4. Hormonal mechanisms
The Nervous Mechanism
This comprises the baroreceptors and chemoreceptors through the vagus and
glossopharyngeal nerves. Aortic baroreceptor conveys information through the vagus
nerve while the carotid body sends through the Hering’s nerve to the glossopharyngeal
nerve. This is also called pressure buffer system (Buffer nerves). The baroreceptor
stimulation causes vasodilatation and decreases the heart rate and strength of
contraction.
Chemo-receptors
Chemoreceptors control the blood pressure through effects of oxygen lack on arterial
pressure. They are capable of detecting oxygen level in blood and carbon dioxide
concentration in blood via the Hering’s and vagus nerves, which in turn influence the
response through the autonomic nervous system.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 88
Baroreceptors (Pressure)
Diagram 8.1: BP Control by Baroreceptors (Pressure receptors)
Capillary Fluid Shift Mechanism
The capillary shift mechanism works by altering the amount of fluid present in the
capillaries in that when the capillary pressure falls too low, there is absorption of fluid
from the tissues into the circulation through the process of osmosis hence elevating the
blood volume and in turn the blood pressure and when the capillary pressure rises too
high, fluid is lost out of the circulation reducing blood volume and pressure.
Diagram 8.2: Capillary Fluid Shift Mechanism
Hormonal Mechanism
This involves three hormone mechanisms namely norepinephrine/epinephrine,
vasopressin and tenin-Angiotensin (see RAA system). Epinephrine, which is usually
after 3 minutes destroyed after constricts blood vessels and excites the heart while
vasopressin, causes sympathetic stimulation of the vascular system.
SYSTEMIC HYPERTENSION
1.0. INTRODUCTION
Hypertension is a high arterial blood pressure. WHO working definition of
hypertension of normotension is systolic blood pressure (SBP) of 140 mmHg and
below and a diastolic blood pressure (DBP) of 90 mmHg and below. Therefore,
hypertension is SBP of 160mmHg and above and/or DBP of 95 mmHg and above.
Borderline hypertension is SBP of more than 140 mmHg and less than 160 mmHg and/or
DBP of more than 90 mmHg and less than 95 mmHg
Increased extra-cellular fluid volume leads to Changes in pressure after the capillary
Increased blood volume
Increased mean circulating filling pressure
Increased venous return
Increased
cardiac output
Increased blood
pressure
Decreased BP
Increased BP Decreased BP
Increased BP
Baroreceptors CNS ANS
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 89
2.0 CLASSIFICATION
Hypertension can be classified according to the clinical course and the cause. The
classification according to the clinical course entails the benign and malignant
hypertension whereas the one for the cause can be primary (essential/idiopathic) or
secondary hypertension.
1. Primary (Essential) hypertension (90%)
a. Benign hypertension (90%)
b. Malignant hypertension (10%)
2. Secondary hypertension
a. Benign hypertension (80%)
b. Malignant hypertension (20%)
Primary hypertension is elevated blood pressure with no known cause and accounts
for 90% of the cases but secondary hypertension, which accounts for 10% of the cases,
have known causes.
Benign hypertension
Benign hypertension is a stable elevation of blood pressure over years (long clinical
course) associated with few symptoms and causes disabilities when it is poorly
controlled
Malignant/accelerated hypertension
Malignant hypertension is fatal and has rapid elevation of blood pressure. It may
complicate either primary or secondary hypertension. It usually causes eye damage
with retinal Haemorrhage, exudates and papilloedema, renal damage and hypertensive
encephalopathy. (This is a hallmark of fibrinoid necrosis of arterioles)
3.0 RISK AND ASSOCIATED FACTORS
1. Family history and genetic background – hypertension has a polygenic
susceptibility.
2. Foetal factors – children born with low birth weight due to intrauterine malnutrition
have been found to have changes in their blood vessels as result of the adaptive
mechanisms they adopt in utero.
3. Environmental factors
a. Salt intake – the cell membrane transport defect therefore increased intracellular
sodium and high intake changes the cell physiology
b. Diet and obesity
c. Alcohol consumption (causes skin vasodilatation and vasoconstriction in muscle
bed)
d. Coffee – 200 mg caffeine increase BP by 10/8mmHg for 1 – 2 hours.
e. Abnormal blood lipids
f. Stress/noise – acute pain or stress can raise blood pressure
4. Age
5. Gender – women withstand raised BP before menopause
6. Glucose intolerance (Insulin resistance).
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 90
4.0 AETIOLOGY
4.1. Primary Hypertension
Essential hypertension has a multifactorial aetiology and that no single aetiology can be
identified that there is no obvious hence the term essential hypertension (a diagnosis of
exclusion).
4.2. Secondary Hypertension
1. Renal
a. Unilateral - renal artery stenosis due to atheroma and trauma, pyelonephritis,
obstructive nephropathy, tumours, tuberculosis and irridiation
b. Bilateral – glomerulonephritis, interstitial nephritis, pyelonephritis, polycystic
kidney, analgesic induced, collagen vascular disease (Systemic Lupus
Erythromatosus (S.L.E), Polyarteritis nodosa (P.N)), gouty, diabetes mellitus,
chronic renal failure of any cause, tumours and nephropathies
2. Adrenal disorders - primary aldosteronism (Conn’s syndrome), Cushing’s
syndrome, phaechromocytoma, congenital adrenal hyperplasia and acromegaly
3. Drug associated - oral contraceptives, corticosteroids and sympathomimetics
4. Others such as acute lead poisoning, pre-ecclampsia, pregnancy and coartication of
the aorta
5.0 PATHOPHYSIOLOGY
Blood pressure (BP) = Cardiac output (CO) x Peripheral resistance (PR) and Cardiac
output (CO) = Stroke volume (SV) x Heart rate (HR). There are two basic mechanisms
that are involved in the pathophysiology of hypertension.
1. Volume loading
2. Vasoconstrictor hypertension
Volume Loading
This occurs when excess extra-cellular fluid volume accumulates in the body if all
other functions of the circulation are normal
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 91
Vasoconstrictor Hypertension
Vasoconstrictor hypertension is caused by a continuous infusion of a vasoconstrictor
agent or excess secretion of a vasoconstrictor by one of the endocrine organs.
Vasoconstrictors include: - angiotensin II, norepinephrine and epinephrine
6.0 PATHOLOGY
Hypertension mainly affects the heart, systemic arterial tree, brain and the kidneys.
BLOOD VESSELS
Changes in the blood vessels are widespread from the aorta to vessels of 1 mm
diameter (hypertensive arteriosclerosis). The changes in the large vessels are the same
in all types of hypertension but vary in small vessels particularly the arterioles in
benign and malignant hypertension. Blood vessels develop degenerative changes in
response to persistent elevation in blood pressure resulting in reduced vascular lumen,
ischaemia, increased fragility and haemorrhage. The aorta is mainly involved
(atheroma, aneurysms, dissection).
In hypertension, severely elevated blood pressure damages the tunica intima of small
vessels resulting in fibrin accumulation in the vessels, local oedema and intravascular
clotting. Increased intra-arterial pressure damages the endothelium and angiotensin II
induces endothelial wall contraction allowing plasma to leak through interendothelial
spaces. The plasma constituents deposited in the vessel wall cause medial necrosis.
Large and Middle sized arteries
As a result of expose to increased intra-luminal pressure: -
1) Hypertrophy/thickening: Hypertrophy and thickening of the media due to an
increase in size and number of smooth muscle cells and increased elastic tissue
2) Arteriosclerosis: Long standing hypertension leads to hypertrophic changes that
culminate in fibrous replacement of smooth muscle. The elastic tissue breaks way
and partial reabsorption may occur.
3) Thickening and rigidity of arterial walls – this reduces the capacity of the vessels
to expand and contract
4) The medial smooth muscle is replaced by collagen causing dilatation and
lengthening of the aorta and its branches accompanied by loss of arterial
compliance (vessels become elongated and tortuous). This increases systolic blood
pressure. Dilatation is accompanied by intimal thickening
Effects of vessel pathology
1) Ischaemia
2) Aneurysm formation
3) Rupture of aneurysm
4) Predisposes to development and rupture of “berry aneurysm” causing sub-
arachnoid haemorrhage.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 92
Differential Diagnosis
1) Senile arteriosclerosis
The difference is: - patient is normotensive, features are less pronounced and the media
is fibrosed but not thickened
Small Arteries and Arterioles
These are vessels of less than 1 mm diameter
a) Benign Hypertension
Show features of arteriosclerosis
1. Medial thickening
2. Pronounced intimal thickening
3. Lumen narrowing
4. Hyaline thickening (hyaline arteriosclerosis – also seen in diabetes mellitus)
The common sites where benign hypertension affects small arteries and arterioles are
the abdominal viscera, retina, adrenal glands and the kidneys (affects the afferent
arteries severely). It rarely affects the heart, skin and skeletal muscles.
The effects of destroyed vessels are: -
1) Accentuation of atheroma
2) Ischaemic heart disease
3) Cerebral infarction
4) Ischaemia of lower limbs
5) Mesesenteric ischaemia
b) Malignant Hypertension
Malignant hypertension shows fibrinoid necrosis of small arterial walls and arterioles
resulting in: -
1. Necrosis of vessel wall causing cell damage
2. Gross thickening due to permeation of the necrotic tissue by plasma contents
3. Reduction of lumen diameter as the lesion affects the whole thickness and
circumference of the vessel
4. Intravascular thrombosis and formation of small infarcts
5. Passage of blood through damaged arterial bed causes red cell fragmentation
(macro-angiopathic haemolytic anaemia) caused by intravascular deposition of
fibrin.
The vascular changes are widespread and mainly notable in internal organs such as the
brain, kidneys (severely affected), the gut and pancreas.
THE HEART
The changes seen in the heart as a result of hypertension are responsible for
hypertensive heart disease which include left ventricular failure and right ventricular
failure (cor pulmonale) due to left and right ventricular hypertrophy and dilatation,
myocardial ischaemia and infarction and cardiac arrthymias
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 93
THE KIDNEY
There is renal failure due to involvement of small blood vessels supplying the kidneys.
Atherosclerosis results in ischaemia of the nephron, glomeruli and the renal tubular
system causing benign hypertensive nephrosclerosis. It is common in middle aged and
elderly persons.
THE BRAIN
Destruction of vessels in the brain results in intracerebral haemorrhage and formation
of microinfarcts.
7.0 PATHOPHYSIOLOGIC ABNORMALITIES IN HYPERTENSION
Consider the: Cardiac output, Vessel resistance, Cell membrane abnormalities,
Central nervous system, Sympathetic nervous system, Circulating pressor agents,
Vasodilator agents
Cardiac Output
Cardiac output is increased in patients with labile and borderline hypertension while in
established hypertension, the cardiac output is normal and increased peripheral
resistance sustains the blood pressure.
Vessel resistance
This is increased due to hypertrophy of the vessels
Cell membrane abnormalities
Abnormalities in membrane transport systems affected are channels for calcium,
sodium and potassium; exchangers for sodium & hydrogen and sodium & calcium and
pumps for calcium and sodium/potassium. All these functions are related to the
membrane lipids
Central Nervous System
The vasoactive agents have a central action. Angiotensin II acts centrally to produce
thirst and water resistance.
Sympathetic Nervous System
There is sympathetic over-reactivity and stimulation causes release of rennin.
Circulating pressor agents
There are catecholamines circulating in the body and the rennin-angiotensin system is
activated too.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 94
Clinical Features
Benign/chronic/essential hypertension
Blood pressure rises gradually over the years. Common symptoms include headache,
palpitations, dizziness on stooping, reduced exercise tolerance and audible pulsations
in the head. Features of affected organ dysfunction are evident.
Malignant (accelerated) hypertension
Develops in 10% of benign cases causing cardiac failure or cerebral haemorrhage.
Without treatment the injury is severe and fatal
Eye changes
The lesions in small arteries in the retina result in oedema, haemorrhage, infarcts and
exudate formation causing blindness. Papilloedema may be associated with cerebral
oedema.
The Brain
Hypertensive encephalopathy is characterized by epileptiform fits and transient
paralysis.
7.0 INVESTIGATIONS
1. Urinalysis (Sugar, proteins, blood, microscopy, culture)
2. Blood
a. Full haemogramme and ESR
b. Urea & electrolytes
c. Fasting blood sugars
d. Fasting blood lipids
e. Blood uric acid levels
f. Creatinine clearance
g. Serum catecholamines (VMA –vinillyl mendelic acid)
h. Hormonal assay- cortisol and aldosterone
3. Imaging
a. Chest X-ray
b. ECG
c. Renal ultrasound
d. Imaging – MRI, IVP/IVU
e. Renal angiography
4. Renal biopsy
5. Fundoscopy
Keith-Wagner Classification Grade 1 - Increased tortuosity of retinal arteries and increased reflectiveness (silver wiring) Grade 2 - Grade 1 plus the appearance of arteriovenous nipping produced when thickened retinal
arteries pass over the retinal veins. Grade 3 - Grade 2 plus flame-shaped haemorrhages and soft “cotton wool” exudates
Grade 4 Grade 4 - Grade 3 plus papilloedema (bulging and blurring of edges of the optic disc)
What are the parameters of measurements?
What is the significance of these investigations?
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 95
Complications
1. Cardiovascular System - congestive cardiac failure (CCF), myocardial
infarction/IHD, peripheral vascular disease and arteriosclerosis
2. Central nervous system - cerebrovascular accident (CVA) and hypertensive
encephalopathy
3. Eyes - Retinopathy
4. Genitourinary tract (G.U.T) – nephropathy and renal failure
5. Gastrointestinal tract (G.I.T) - liver infarcts and pancreatic infarcts
6. Respiratory System - Pulmonary oedema
7. In pregnancy
a. Small for gestational age (SGA)
b. Intrauterine foetal death (IUFD)
c. Prematurity
d. P.E.T
e. Loss of foetus
Hypertensive Heart Disease
Hypertensive heart disease or hypertensive cardiomyopathy is the disease of the heart
resulting from systemic hypertension of prolonged duration. It is the second most common after ischaemic heart disease. It manifests as left ventricular failure or right
ventricular failure (cor pulmonale) or congestive cardiac failure. Hypertension is
associated with coronary atherosclerosis, congestive heart failure, cerebrovascular
accidents (CVA), renal failure following arteriolar nephrosclerosis and dissecting
aneurysms of the aorta.
1.0. LEFT VENTRICULAR FAILURE (LVF)
Pressure overload in the systemic hypertension is associated with hypertrophy of the
left ventricle. The stress of pressure on the left ventricular wall causes increased
production of myofilaments, myofibrils and other organelles and nuclear agents. Adult
myocardial fibres do not divide hence the fibres hypertrophy. The sarcomeres may
divide to increase the cell width. This put the muscle under pressure for increased
demand for oxygen supply and eventually myocardial ischaemia and infarction sets in
compromising the heart function.
2.0. COR PULMONALE
Cor pulmonale (Cor = heart: pulmonale = lung) or pulmonary heart disease is the
disease of the right side of the heart resulting from disorders of the lung. It is the right
sided part of hypertensive heart disease. Cor pulmonale may be acute or chronic
depending on rapidity of development.
Acute Cor Pulmonale
Acute cor pulmonale occurs following massive pulmonary embolism resulting in
sudden dilatation of the pulmonary trunk, lungs and right ventricle.
What is the pathophysiology of these complications
How will you establish the presence of these complications
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 96
Chronic Cor Pulmonale
Chronic cor pulmonale is more common and often preceded by pulmonary
hypertension caused by various chronic lung diseases such as chronic emphysema,
chronic bronchitis, pulmonary tuberculosis (PTB), cystic fibrosis and Pickwickian
syndrome (hyperventilation in marked obesity)
3.0. ISCHAEMIC HEART DISEASE (IHD)
HYPOTENSION
1.0. INTRODUCTION
Hypotension is a physiologic state in which the arterial blood pressure is abnormally
low. For an adult, hypotension exists when the systolic pressure is less than 90
mmHg and the diastolic pressure is less than 60 mmHg. Because arterial pressure is
determined by cardiac output, venous pressure and systemic vascular resistance. A
reduction in any of these variables can lead to hypotension. Hypotension may result
from:
1. Reduced cardiac output
2. Hypovolemia
3. Blood volume redistribution
4. Reduced systemic vascular resistance
5. Vascular obstruction (e.g., pulmonary embolism)
2.0. ISCHAEMIC HEART DISEASE (IHD)
Explain the pathophysiology of IHD in hypertension
What investigations will be relevant?
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 97
Lesson 9: Aneurysms
Learning Outcomes
At the end of the learner should be able to: -
1. Define and classify aneurysm
2. Discuss causes of aneurysms
3. Explain the pathogenesis of aneurysms
4. Discuss pathology and features of aneurysms
5. Outline the complications of aneurysms
1.0 INTRODUCTION AND ANATOMY
The anatomy is based on the size of the blood vessels and the histological features. The arteries are divided into three main categories namely large (elastic) arteries e.g. the
aorta; medium sized (muscular) arteries e.g. the distributing arteries and small
arteries and arterioles- these are less than 2 mm in diameter and are found in tissues
and organs. Capillaries are about the size of the red blood cells (7 – 8 um) and have a
layer of endothelium but no media. Blood from capillaries return to the heart via post-
capillary venules and then veins.
Histologically, all arteries have three coats called- tunica intima (smooth muscle layer),
tunica media (muscular layer rich in elastic tissue) and tunica adventitia (poorly
defined layer found in the connective tissue in which elastic and nerve fibres, small and
thin walled nutrient vessels, the vaso vasora are dispersed). The layers progressively
decrease with diminution in size of the vessel.
Diagram 9.1: Cross Section of Blood Vessels
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 98
2.0 DISORDERS OF ARTERIES
Diseases of the arteries can be divided into three major categories of artheosclerosis, arteritis (vasculitis) and aneurysms. The three main pathological processes are
atheroma (elastic arteries), calcification (muscular arteries) and arteriosclerosis (small
arteries)
A. Congenital Disorders e.g. congenital or “Berry” aneurysm, hypoplasia of aorta, A-V
fistula or aneurysm
B. Degenerative Changes
a) Atherosclerosis
b) Arteriosclerosis
c) Marfan’s syndrome
C. Inflammation (Arteritis) - non-specific, Polyarteritis nodosa (P.N), Thrombo-angitis
obliterans - T.A.O (Buerger’s disease), Syphilitic, Rheumatic, Rheumatoid,
Takayashu's disease
D. Neutrophil Vascular Disorders e.g. Raynaud’s disease
E. Systemic Hypertension (already considered)
Aneurysms
1.0 INTRODUCTION
An aneurysm is a permanent, abnormal, irreversible localized dilatation of
arteries/blood vessel. It is a dilatation that is localized in a blood vessel.
2.0 RISK FACTORS
Advancing age
Alcohol consumption (especially binge drinking)
Atherosclerosis
Cigarette smoking
Use of illicit drugs, such as cocaine or amphetamine
Hypertension (high blood pressure)
Trauma (injury) to the head
Infection
3.0 AETIOLOGY
Congenital, Atheroma, Syphilis, Trauma., Hypertension, Infection (Staphylococcus
aureas, pyogenic abscess), Connective tissue disorders e.g. Marfan’s syndrome
4.0 PATHOGENESIS
1. An arterial lesion weakens the media locally This could congenital (deficiency of
media and elastic lamina) and acquired (atheroma/arteriosclerosis, syphilis,
inflammation(arteritis), infection and degenerative changes)
2. Force expanding the aneurysm is the blood pressure.
3. The stretching of the blood vessel results in further weakening
4. Once started the aneurysm expands and commonly it ruptures
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 99
5.0 CLASSIFICATION
Aneurysms can be classified according to various features: -
1. Shape
a) Fusiform aneurysm – results from symmetrical stretching involving the whole
circumference.
b) Saccular aneurysm - involves part of the circumference which dilates
Diagram 9.2: Types of Aneurysms
c) Cylindrical
d) Varicose/sepenteine – tortuous dilatation of arteries
e) Racemose – interconnecting small arteries and veins
2. Pathologic mechanisms
a) Congenital
b) Berry aneurysm
c) Atherosclerosis (arteriosclerotic)
d) Syphilitic
e) Mycotic – weakening resulting from infection by microbes.
f) Dissecting aneurysm
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 100
3. Size
a) Small aneurysms have a diameter of less than 15 mm
b) Larger aneurysms include those classified as large (15 to 25 mm.)
c) Giant (25 to 50 mm.)
d) Super giant (over 50 mm.)
4. Composition of the wall
a) True aneurysm – composed of all the layers of the vessel wall
b) False aneurysm (pseudoaneurysm) – have a fibrous wall
6.0 SITES OF ANEURYSMS
Diagram 9.3: Sites of Aortic Aneurysms
7.0 INDIVIDUAL ANEURYSMS
1. Congenital
Congenital aneurysm is usually symptomless and mainly affects the brain and it is found
at autopsy.
2. Cerebral Aneurysm
A cerebral aneurysm affects the major cerebral arteries. Is commonly called “berry
aneurysm” which is usually symptomless and the diagnosis is made at autopsy but it
may rupture and bleed into the subarachnoid space.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 101
A cerebral aneurysm (intracranial aneurysm or brain aneurysm) is a bulging,
weakened area in the wall of an artery in the brain, resulting in an abnormal widening,
ballooning, or bleb. Because there is a weakened spot in the aneurysm wall, there is a
risk for rupture (bursting) of the aneurysm. More frequently occurs in an artery located
in the front part of the brain that supplies oxygen-rich blood to the brain tissue. The
most common type of cerebral aneurysm is called a saccular, or berry, aneurysm,
occurring in 90 percent of cerebral aneurysms. This type of aneurysm looks like a
"berry" with a narrow stem. More than one aneurysm may be present. Two other types
of cerebral aneurysms are fusiform and dissecting aneurysms. A fusiform aneurysm
bulges out on all sides (circumferentially), forming a dilated artery. Fusiform aneurysms
are often associated with atherosclerosis.
Diagram 9.4: Cerebral Aneurysm
Sites
The most common sites include the:
Anterior Communicating artery (30 - 35%)
Bifurcation of the Internal Carotid and Posterior Communicating artery (30 - 35%)
Bifurcation of Middle cerebral (20%)
Basilar artery bifurcation (5%)
Remaining posterior circulation arteries (5%)
Features
The symptoms of an unruptured cerebral aneurysm include, but are not limited to, the
following:
Headaches (rare, if unruptured)
Eye pain
Vision deficits (problems with seeing)
Eye movement deficits
The first evidence of a cerebral aneurysm is most frequently a subarachnoid
haemorrhage (SAH), due to rupture of the aneurysm. Symptoms that may occur at the
time of SAH include, but are not limited to, the following:
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 102
Initial sign (rapid onset of severe headache)
Stiff neck
Nausea and vomiting
Changes in mental status, such as drowsiness
Pain in specific areas, such as the eyes
Dilated pupils
Loss of consciousness
Hypertension (high blood pressure)
Motor deficits (loss of balance or coordination)
Photophobia (sensitivity to light)
Back or leg pain
Cranial nerve deficits (problems with certain functions of the eyes, nose, tongue,
and/or ears that are controlled by one or more of the 12 cranial nerves)
Coma and death
3. Mycotic (Infective) Aneurysm
An infected embolus leads to localized infection and destruction of the tunica media
weakening it. For example, direct extension of organisms from vegetations in bacterial
endocarditis (Staphylococcus aureas), Infection from abscess, TB – may cause fatal
haematemesis
4. Syphilitic (Luetic) Aneurysm
Syphilitic aneurysm complicates syphilitic aortitis commonly affecting the aortic arch
and the ascending aorta as a result of losing the elastica and muscle of the arteries. It
usually develops earlier (in young people). It forms a saccular aneurysm and
occasionally fusiform aneurysm and can grow forwards eroding the sternum or
backwards eroding the vertebrae (not the inter-vertebral disc) causing pain in the
back.
Pathogenesis
There is inflammatory infiltrates around the vasa vasorum of the adventitia followed by
endarteritis obliterans which results in ischaemic injury to the media causing
destruction of the smooth muscle and elastic tissue of the media and scarring. It is most
frequent in the ascending aorta and aortic arch.
Effects
1. Pressure/compression effects
a. Syndrome of superior mediastinal compression
b. Displaced great veins with thrombosis causing congestion of head and neck
vessels and enlargement of collateral veins
c. Oesophagus causing dysphagia
d. Bronchus causing chronic cough and suppurating pneumonia
e. Trachea causing dyspnoea
f. Left laryngeal nerve (transverse aorta) – left vocal cord paralysis, aphonia and
horse voice.
2. Ruptures leading to massive haemorrhage into the trachea, oesophagus,
pericardium, pleural cavity and peritoneum
3. Embolism/thrombosis
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 103
4. Cardiac dysfunction – when the aortic root and valve are involved, syphilitic
aneurysm produces aortic incompetence and cardiac failure. narrowing of the
coronary ostia aggravates cardiac disease
Microscopy
The aneurysm sac consists of the adventitia only, the media and tunica usually
disappear and the adjourning parts of the walls show microscopic changes of syphilitic
aortitis
5. Atheromatous (Atherosclerotic) Aneurysm
This is common in advanced age affecting more males than females mainly affecting the
abdominal aorta and common iliac artery. It causes fusiform aneurysm, which may
rupture when still small. It results from an artheromatous plague weakens the media or
extends into the media.
Pathogenesis
There is severe atherosclerotic lesions which cause thinning and destruction of the
medial elastic tissue resulting in atrophy and weakening of the arterial wall. There is
also degeneration of the media.
Effects
1. Rupture into the peritoneum causing peritoneal and intraperitoneal haemorrhage
leading to an acute abdomen.
2. Thrombo-embolic
3. Pressure/compression effects – ureter
4. Arterial occlusion - inferior mesenteric artery
Table 9.1: Types of Aneurysms Type Site Cause Incidence
Atherosclerotic Abdominal aorta Thinning and fibrous replacement of
media
Common
Syphilitic Ascending aorta
and arch
Inflammatory destruction of media
and fibrous replacement
Now rare
Berry Cerebral
arteries
Congenital defect(s) in elastic
lamina/media
Common
Infective
(mycotic)
Any Destruction of wall by bacteria in
infected thrombus
Rare
6. Dissecting Aneurysm
A dissecting aneurysm is not a true aneurysm because the vessel is not dilated. Usually
a tear occurs in the media and blood enters and tracks between the inner and outer
parts of the media dissecting the wall into inner and outer layers. The blood tends to
encircle the aorta and may pass along the entire length of the bifurcation tracking
distally and proximally. In majority of the cases, the primary lesion causes necrosis of
tunica media with the tunica intima becoming hypertrophic and sclerosed.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 104
Aetiology
The aetiology includes trauma, hypertension, necrosis, connective tissue disorder,
congenital, atheroma and physical exertion e.g. pregnancy.
Pathology
There is a weakened media which result in dissection of the aorta. In a hypertensive
state there is degeneration of the media while in the non-hypertensive state there is
some local or systemic connective tissue disorder.
Effects
1. Rupture - externally (haemorrhage) or internally (double barrel aorta),
2. Ischaemia due to obstruction – leads to renal infarction, cerebral infarction and
infarction of the spinal cord
3. Thrombosis
4. Cardiac disease
5. Haemorrhage into the Mediastinum, pleura, peritoneum and retro-peritoneal
6. Pressure effects leading to ischaemia which causes myocardial infarction and renal
necrosis
Diagram 9.4: Dissecting aneurysm
7. Artero-venous Aneurysm
This is an abnormally acquired communication between a vein and an artery due to
simultaneous laceration that allows blood to pass from the artery to the vein producing a
local dilatation of the vein, which pulsates as forcefully as the artery. A thrill can be felt
or a bruit can be heard over the aneurysm. It is also called cirsoid/racemorse
aneurysm, false/traumatic.
6.1 COMPLICATIONS OF ANEURYSMS
1. Local pressure effects
2. Rupture – haemorrhage
a. Cerebral berry aneurysm – subarachnoid haemorrhage
b. Dissecting aneurysm of thoracic aorta – blood into pericardium – cardiac failure
(cardiac tamponade)
c. Abdominal aortic aneurysm – massive retroperitoneal haemorrhage
3. Thrombosis and embolism
4. Ischaemia
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 105
Lesson 10: Atheroma (Atherosclerosis/Arteriosclerosis)
Learning Outcomes
At the end of the lesson the learner should be able to: -
1. Define atheroma and atherosclerosis
2. Outline the causes of atheroma
3. Describe the risk and predisposing factors of atheroma
4. Describe the pathogenesis and pathology of atheroma
5. Outline the effects and complications of atheroma
1.0 INTRODUCTION
Atherosclerosis is a disease of the intima associated with deposition of sterols,
triglycerides and lipoproteins resulting in narrowing of the vessel lumen, thrombosis or obstruction in large and medium sized arteries. Arteriosclerosis affects the media
causing proliferation or hyaline changes that result in an increase in wall thickness and
decreased vessel elasticity (arteriosclerosis = hardening of vessels).
Atheroma is an intimal plague (patch) created by the focal deposition of lipids in the
subendothelial connective tissue of the inner intima due to accumulation of lipids,
proliferation of smooth muscle cells and formation of fibrosis tissue. They have a soft
lipid rich part (athere = porridge) and a hard (sclerotic) fibrous component. The
principal changes occur largely within the intima of the medium and large arteries.
Diagram 10.1: Atheroma Plaques
2.0 LIPID METABOLISM
There are two important pathways of lipid metabolism namely exogenous and
endogenous. Endogenous (dietary) lipids are digested to release triglycerides (TG)
and cholesterol esters which combine with phospholipids and specific apoproteins to become water soluble chylomicrons.
The TG component of chylomicrons can move from the circulation into cells under the
influence of lipoproteins lipase enzyme which is found on the endothelial surface of
cells. Within the cell it is then converted to glycerol and non-esterified fatty acids (a
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 106
major source of energy). Chylomicron without TG is called chylomicron remnant
particle (CMR) which is rich in cholesterol and attaches to liver receptors to enter the
hepatocytes.
Endogenous lipids are various lipids produced by the liver from building blocks of
glycerol and fatty acids from the fat stores or synthesized from glucose and cholesterol
derived from lipoproteins (e.g. CMR) or locally synthesized. Glycerol and fatty acids
combine to produce TG. The liver releases VLDL rich in TG and 25% cholesterol. Loss
of TG produces IDL and further loss of TG results in release of cholesterol rich LDL. LDL
is removed from circulation and broken down to amino acids and cholesterol.
3.0 AETIOLOGY
Poorly understood or unknown but risk factors exist based on epidemiological studies,
intervention trials and biochemical investigations. Risk factor detection and uses
ischaemic heart disease (IHD) as an indicator.
4.0 THE RISK FACTORS
Grouped into major risk factors and minor risk factors with the major risk factors being
further divided into major constitutional risk factors which are non-modifiable and
include increasing age, sex, genetic factors, familial and racial predisposition; and the
major acquired factors which can be controlled and include hyperlipidemia,
hypertension, diabetes mellitus and smoking.
Major Risk Factors
Major Constitutional Risk Factors
1. Age: Atheroma affects different vessels at different ages and death resulting from
IHD increases with advancing age.
2. Gender/Sex: The death rate from IHD affects more males than females up to the age
of 55 years after which the incidence is the same among the different sexes.
3. Genetic Factors: Genetic influences on the cardiovascular system include genes
associated with predisposition to hypertension, diabetes, LDL receptor changes,
altered activation of nicotine (reduces likelihood of smoking), and altered ion
channels proteins which influence arrhythmias.
4. Familial and Racial Factors: Familial factors may be related to other risk factors such
as diabetes, hypertension and hyperlipoproteinaemia.
Major Acquired Risk Factors (Hard risk factors)
1. Hypertension: Hypertension is a major risk factor in development of atherosclerotic
IHD and cerebrovascular disease.
2. Hyperlipidaemia: Cholesterol is essential building material for cell membranes and
hormones. Is transported by lipo-proteins in blood (HDL from peripheral to the liver
and LDL from the periphery to the liver and other systems). Oxidation of LDL
encourages atherosclerosis.
3. Cigarette Smoking: The extent and severity of atherosclerosis is much greater in
smokers than non-smokers. Smoking is associated with increased incidence of
atherosclerotic IHD and sudden cardiac death. Smoking increases catecholamines
level as with one cigarette the blood pressure is elevated by 10 mmHg for 20
minutes. Smoking 1 packet/day increases the likelihood of myocardial infarction by
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 107
300%. It encourages thrombosis by increasing the aggregation of thrombocytes and
diminishes coronary flow. Smoking encourages oxidation of LDL. Women who
smoke have increased risks. Use of safer cigarettes which contain low tar and
nicotine content only manage to reduce the risk of bronchial carcinoma and not
coronary heart disease
4. Diabetes mellitus: The risk of developing IHD and cerebrovascular disease is
doubled in diabetes mellitus due to increased aggregation of platelets, increased
LDL and decreased HDL.
Minor Risk Factors (Soft risk factors)
These are less important factors which have a lesser role in aetiology of atherosclerosis.
1. Environmental factors: there is high prevalence in developed countries and low in
poorly developed countries.
2. Diet: Obesity and fatty acids and cholesterol. Overweight of 20% or more increases
the risk
3. Hormonal: Use of exogenous hormones (e.g. oral contraceptives) or endogenous
oestrogen deficiency (post-menopausal women) increases the risk of developing
myocardial infarction or stroke.
4. Physical inactivity: Inactivity enhances fat deposition.
5. Stressful life style: Type A personality characterized by aggressiveness, competitive
drive, ambitiousness and as sense of urgency increases the risk as compared to type
B personality of relaxed and happy-go-lucky type.
5.0 SITES
The common sites in order of decreasing frequency are abdominal aorta, aorta – arch,
transverse; proximal coronary arteries, descending thoracic aorta, femoral and
popliteal arteries, internal carotid artery, vertebral, basilar and middle cerebral
arteries (Circle of Willis)
6.0 PATHOGENESIS
Theories
Development of atheromatous plaques can be explained by the “reaction to injury”
theory which incorporates the ideas of Virchow, Duguid and Rokitansky. Virchow’s
“Insudation” or “Infiltration” hypothesis suggested that leakage of plasma proteins and
lipids from the blood to the subendothelial tissue stimulated intimal cell proliferation a
form of low-grade inflammation. Karl von Rokitansky’s “Encrustation” theory suggested
that thrombi forming on damaged endothelium could be organized to form a plaque.
The Modern “Reaction to injury” theory by Ross and John Glomset (1976) explains that
some change or damage to the vascular endothelium causes increased permeability of
the vessel wall to proteins and lipids leading to aggregation of platelets and monocytes.
Aggregated platelets and monocytes release substances to promote smooth muscle
proliferation and the influx of more leucocytes.
The leucocytes release various enzymes and growth factors which promote smooth
muscle cell proliferation. Monocytes migrate from the blood into the subendoethelial
layers where they become macrophages and ingest lipids.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 108
Process of Atheroma formation
1. Endothelial cell damage
2. Focal degenerative changes in the subendothelial tissue of intimal ground
substances and fat deposition
3. Fatty deposits
4. Fatty macrophages (foam cells)
5. Release of fats stimulates connective tissue proliferation
6. Capillaries from – Haemorrhage
7. Low grade inflammatory reaction
8. Cell proliferation
7.0 CELLS INVOLVED IN ATHEROGENESIS
1. Endothelium
2. Smooth muscle
3. Monocytes/macrophage
4. Platelets
5. Lymphocytes
Diagram 10.2: Cells Involved in Atherogenesis
Endothelial Cells: Have the functional capacity to modify and transport lipoproteins,
participate in adherence of leucocytes, form vasoactive substances, participate in
procoagulant and anticoagulant activity and form growth factors.
Smooth Muscle: Is the principal source of connective tissue in the fibrous plaques and
forms growth factors.
Monocytes/Macrophages: When activated can secrete growth factors for connective
tissue cells e.g. fibroblasts and smooth muscles. The scavenge cells can be injurious to
neighbouring cells e.g. endothelium and smooth muscle and cause mitogenic
stimulation of smooth muscle cells.
Platelets: platelets are a rich source of growth factors and participate in coagulation
and thrombosis (thrombi organize by growth and proliferation of smooth cells
responsible for deposition of new connective tissue)
Lymphocytes: Suggests involvement of immune or auto-immune responses
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 109
8.0 PATHOLOGY
Lesions of atherosclerosis
The principal lesions are fatty streaks, fibrous plaque and complicated lesion
Fatty Streaks
Fatty streaks are found throughout the arterial tree at all stages and they depend on
dietary habits and life styles of an individual. They consist of monocytes-derived
macrophages that have entered the intima. The macrophages take up large amounts of
lipid in the form of lipid droplets containing cholesterol. The streaks can regress and
disappear, progress to become fibrous plaque or remain unchanged.
Fibrous Plaque & Complicated Lesion
The fibrous plaques and complicated lesions result in clinical sequels. The complicated
lesion is a fibrous plaque that has become altered by calcification, or developed cracks
or fissures or undergone ulceration leading to haemorrhage and thrombosis. The
thrombosis leads to clinical sequels such as myocardial infarction, cerebral infarction
and gangrene.
Macroscopy
Slightly raised yellow spots in the luminal surface, spots enlarge, coalesce forming
irregular yellow streaks (PLAQUE) Microscopy: Lipid droplets, smooth muscle cells and macrophages, dense connective
tissue matrix, intimal thickening (ischaemia causes necrosis – aseptic necrosis). Plaque
– are disc-like yellowish smooth glistering surface that enlarges and intimal thickening
occurs. They can be yellow or white depending on the amount of connective tissue
present.
Lipids & Lipoproteins in Atherosclerosis
Hyper-cholesterolaemia is a major risk factor associated with atherosclerosis. Many
lesions of atheroma contain relatively little lipid but effects of lipid on endothelium,
monocytes and smooth muscle and accumulation of lipids in lesions is critical in
atherogenesis. Concentrations of cholesterol and triglycerides are controlled by
several metabolic processes and influenced by a variety of factors.
The sources of lipids are exogenous dietary fat and endogenous fats of hepatic origin.
Cholesterol forms mammalian membrane and is a precursor formation of bile acids and
adrenal/gonadol hormones. Triglycerides are derived from dietary carbohydrates
9.0 CLINICO-PATHOLOGICAL CONSEQUENCES
1. Reduction of blood flow through arteries - Ischaemic heart disease (IHD), peripheral
vascular disease e.g. gangrene, cerebrovascular disease
2. Predisposition to thrombosis - complete occlusion of arteries, thrombosis,
haemorrhage and embolism
3. Bleeding into a plaque – coronary arteries leading to myocardial infarction
4. Weakening of vessel walls leading to aneurysm formation and rupture. This is
common in the abdominal aorta
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 110
10.0 COMPLICATIONS
1. Ischaemia
2. Haemorrhage
3. Rupture
4. Ulceration
5. Occlusive thrombosis, which leads to ischaemia, necrosis, infarction and embolism.
6. Embolism
7. Aneurysm
8. Gangrene
9. Hypertension
Vasculitis
Definition
Vasculitis is inflammation and damage to the vessel wall. It affects capillaries, venules,
arterioles, arteries and occasionally large veins. Severe cases of vasculitis produce
irreversible wall damage while mild cases will result in transient damage with marked
cellular infiltration resulting in leakage of red blood cells.
There are three main groups of vasculitis syndromes namely hypersensitivity
vasculitis, multiorgan autoimmune diseases and systemic vasculitides.
Hypersensitivity vasculitis is the most common and affects mainly the capillaries and
venules and usually manifests as a skin rash. It is often a manifestation of allergy.
Vasculitis can be a major factor in autoimmune diseases such as rheumatoid disease
and S.L.E. Systemic vasculitis is characterized by different patterns of vessel wall
destruction as for example in polyarteritis with various clinical implications.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 111
Lesson 11: Disorders of Veins
Learning Objectives
At the end of the lesson the learner should be able to:-
1. Outline anatomy of the veins
2. Outline disorders of veins
3. Explain the pathology of thrombophlebitis and phlebothrombosis
4. Discuss the pathology of varicose veins
5. Discuss the pathology of haemorrhoids
1.0 ANATOMY – STRUCTURE & FUNCTION
Veins have the basic structure similar to that of arteries as they comprise of the
intima, media and adventitia, which are less clearly defined as in arteries
Have a large calibre with low venous pressure insufficient to return blood to the
heart
Structure varies depending on the mechanical conditions e.g. intra-luminal
pressure. It changes when mechanical conditions are altered. The structure also will
vary as one ascends the venous tree. Veins collapse when not filled with blood.
Walls of the veins are thinner; the three tunicae (intima, media and adventitia) are
less clearly demarcated. The elastic tissue is scanty and not clearly organized into
internal and external lamina. The media has small amounts of smooth muscle cells
with abundant collagen
All veins except vena cavae and common iliac veins have valves which are made of
delicate folds of intima. The valves are located every 1 – 6 cm to the point of a
tributary. The valves are well developed in the lower limbs. Veins prevent
retrograde venous blood flow.
Diagram 11.1: Anatomy of Veins
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 112
2.0 DISEASES OF THE VEINS
1. Thrombosis
2. Phlebitis
3. Thrombophlebitis and phlebothrombosis
4. Varicosities
i) Varicose Veins
ii) Varicoceole
iii) Oesophageal varices
iv) Haemorrhoids
3.0 THROMBOPHLEBITIS AND PHLEBOTHROMBOSIS
Thrombophlebitis refers to the primary inflammation of the vessel wall followed by
thrombosis upon the inflammation
Phlebothrombosis refers to a condition in which a thrombus forms in the vessel wall
due to secondary infection leading to acute inflammation of the vein.
Aetiopathogenesis
Thrombosis that precedes thrombophlebitis is initiated by the Virchow’s triad
Predisposing factors include cardiac failure, malignancy, and use of oestrogen-
containing compounds, post-operative state and immobility
Most common in the deep veins of the legs with the other sides being periprostatic
venous plexus in the males, pelvic veins in the females and near the foci of infection
in the abdominal cavity (acute appendicitis, peritonitis, acute salpingitis and pelvic
abscess).
Effects
Local - oedema, heat, swelling, tenderness, redness and pain.
Systemic - embolic phenomenon with pulmonary thrombo-emboslim being the most
common and most important. Others are bacteraemia and septic embolization to
brain meninges.
4.0 VARICOSITIES
Introduction
Varicosities are abnormal dilated and tortuous veins
Usually due to chronic continuous increase in pressure of blood in the veins.
Physiologically, a varicose vein is a superficial vein that permits blood flow in the
reverse direction due to incompetent valves in the veins
Varicose veins are usually dilated, lengthened and tortuous
Veins involved include
i) Lower extremities (involved most frequently) – called varicose veins. ii) Lower oesophagus (oesophageal varices)
iii) Anal region (haemorrhoids)
iv) Spermatic cord (varicocoele)
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 113
4.1. VARICOSE VEINS
Varicose veins are swollen and enlarged veins, usually blue or dark purple in colour.
They may also be lumpy, bulging or twisted in appearance. They mostly occur in the
legs.
Predisposing Factors
Pregnancy, pelvic tumours, age, sex, race, weight, height, diet, side (left > right),
bowel habit, occupation, heredity, clothes, erect stance
Aetiopathogenesis
Involves various factors such as
i) Familial weakness of vein walls
ii) Increased intraluminal pressure due to prolonged upright posture (e.g.
police, nurses, surgeons), compression of iliac veins (e.g. pregnancy,
intravascular thrombosis, growing tumour)
iii) Hormonal effects on smooth muscles
iv) Obesity and chronic constipation.
Increased Pressure
Effects of pregnancy – the presenting part presses on the iliac veins impending
blood flow leading to pooling with subsequent dilatation of veins in the lower limb
because of the ever-increasing pressure.
In obstruction, the obstruction of the main vein leads to increase I pressure in the
collateral veins leading to dilatation and destruction of valves hence the varicosity
and incompetence of valves in the veins.
Diagram 11.2: Aetiopathogenesis of Varicose Veins
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 114
Pathology
1. Weakness of veins and vein wall damage
2. Valve incompetence and valve failure
3. Obstruction
4. Increased pressure
Diagram 11.3: Pathology of varicose veins
Classification
Two classes namely primary varicose veins and secondary varicose veins
Primary varicose veins - results from the changes in the vein wall, progressive
venous dilatation and valvular failure. Congenital predisposition and occupation
influence development of the varices
Secondary varicose veins - occur due to thrombosis with resulting valvular damage,
increased venous pressure in the superficial veins leading to varicosities and
arteriovenous malformations
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 115
Sites
1. Legs
2. Arms
3. Scrotum
4. Lower end of the oesophagus
The dilatation of vessels and stasis of blood is usually a high risk factor in thrombus
formation leading to increased chances of embolism.
Types of varicose veins
There are several types of varicose veins, such as:
i) Trunk varicose veins are near to the surface of the skin and are thick and
knobbly. They are usually visible, often quite long and can look unpleasant.
ii) Reticular varicose veins are red and are sometimes grouped close together in a
network.
iii) Telangiectasia varicose veins, also known as thread veins or spider veins, are
small clusters of blue or red veins that sometimes appear on your face or legs.
They are harmless and, unlike trunk varicose veins, do not bulge underneath
the surface of the skin.
Features
Diagram 11.4: Features of Varicosities
Gravitational Varicosity
Usually occurs in the long saphenous vein. It is commoner in females than males
Predisposition
1. Hereditary
2. Continuous standing without much movement leads to increase in pressure hence
dilatation and tortousity of the veins. Veins have valves and depend on muscular
activity for movement of blood upwards and due to inactivity, stasis, pooling and
dilatation of the veins is usually the rule.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 116
3. Pregnancy – the gravid uterus usually causes pressure on the pelvic veins leading to
increased pressure in the venous system at the point of the legs. Usually such
varicosities are particularly worse in individuals with hereditary predisposition.
4. Obesity – usually inactive and therefore the venous return is usually defective
because it depends on muscular activity and hence stasis, pooling of blood and
dilatation of veins occur leading to varicosity. They usually tend to have more fat
than musculature and hence muscular contractibility is even further defective
Complications
1. Valve atrophy
2. Replacement of elastic tissue by fibrous tissue
3. Necrosis (varicose ulcer)
4. Haemorrhage
5. Thrombosis
6. Embolism
4.2. VARICOCELE
A varicocele is a gravitational varicosity that involves dilatation of veins draining the
testis
The veins draining the testis and the epidydimis form a bulky plexus called the pampiniform plexus
The distention and pooling of blood depresses the optimal temperature for
spermatogenesis hence the patient presents with seminalysis that reveals
oligospermia and azospermi
Diagram 10.5: Varicocele
4.3. HAEMORRHOIDS (ANAL PILES)
Haemorrhoids = Greek – haima = blood; rhoos = flowing; Piles = Latin (pila – a ball).
Haemorrhoids are veins occurring in relation to the anus. This is the dilatation and
turtuosity of the haemorrhoid plexus situated around the ano-rectal junction.
Haemorrhoids or piles are the varicosities of the haemorrhoidal veins
Common in elderly persons and women mainly due to increased venous pressure.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 117
Aetiology
1. Hereditary - congenital weakness of vein walls and abnormally large arterial supply
2. Morphological - gravity aid
3. Anatomical – collecting radicles of superior haemorrhoidal vein lie unsupported in
the very loose submucous connective tissue of the ano-rectum.
4. Portal hypertension
5. Chronic constipation
6. Venous stasis
7. Tumours
8. Exacerbating factors – straining, constipation, diarrhoea, dysentery
Classification
Haemorrhoids may be external or internal in relation to the anal orifice
External haemorrhoids involve the inferior haemorrhoidal plexus and are covered
by the skin
Internal haemorrhoids involve the superior haemorrhoidal plexus and are covered
by mucous membrane. When the two are associated, they are referred to interoexternal (mixed) haemorrhoids.
Diagram 11.6: Types of haemorrhoids
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 118
Internal Haemorrhoids
This is a dilatation of the internal venous plexus within an enlargement displaced anal
cushion. The existing communication between the internal and external plexus leads to
dilatation of the internal plexus with a possibility of involvement of the external plexus.
Pathology
The haemorrhoids are arranged in 3 groups at 3, 7 and 11 o’clock positions following
the arterial supply of the anus (2 divisions on the right branch and a single left
branch). Smaller secondary haemorrhoids exit between the three primary ones.
Diagram 11.7: Haemorrhoids
Each principal haemorrhoid has three parts: -
i) The pedicle (situated at the anorectal ring, covered with a pale mucosa,
pulsating artery is felt, usually seen on autopsy)
ii) Internal haemorrhoid (commences just below the anorectal region, bright red
or purple in colour, covered by mucous membrane, variable size)
iii) An external associated haemorrhoid (lies between dentate line anal region,
covered by the skin, blue veins seen unless when fibrosis is present)
Clinical Features
May be symptomatic of some other conditions (symptomatic haemorrhoids) such as
Ca rectum (compresses and causes thrombosis of superior rectal vein), pregnancy
(compression of superior rectal vein and the relaxing effects of progesterone on
smooth muscle of veins and the increased circulating pelvic volume), straining at
micturition and from chronic constipation
1. Bleeding - slight and bright red and occurs during defecation
2. Prolapse – 2nd and 3rd degree haemorrhoids
3. Heaviness in the rectum (3rd degree)
4. Discharge - mucoid (mucous from the engorged mucous membranes) and leakage
of ingested liquid paraffin
4. Pruritis – due to the discharge
5. Pain
6. Anaemia
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 119
Diagnosis
1. History
2. Physical examination - Per rectal examination – inspection and digital examination
3. Protoscopy
4. Sigmoidoscopy
Grading of Haemorrhoids
First degree haemorrhoids: these bleed but do not prolapse
Second degree haemorrhoids: these prolapse but reduce spontaneously
Third degree haemorrhoids: these prolapse but can be reduced manually
Fourth degree haemorrhoids: these are permanently prolapsed and cannot be
reduced
Diagram 11.8: Grading of Haemorrhoids
Complications
1. Profuse Haemorrhage
2. Strangulation
3. Thrombosis
4. Ulceration – accompanies thrombosis and strangulation
5. Gangrene
6. Fibrosis/scarring
7. Suppuration/inflammation
8. Pyephlebitis (portal pyemia).
External Haemorrhoids
External comprise of distinct clinical entities.
1. A thrombosed external haemorrhoid (perianal haematoma) is a small clot in the
perianal subcutaneous connective tissue formed due to backpressure on anal veins
due to straining, coughing and lifting heavy weights.
2. Dilatation of the veins of anal verge
3. Sentinel pile.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 120
4.4. OESOPHAGEAL VARICES
Oesophageal varices are swollen veins in the lining of the lower oesophagus near
the stomach Causes
1) Portal hypertension, which is most commonly caused by liver cirrhosis.
2) Portal vein thrombosis (blood clots inside the portal vein)
3) Portal vein obstruction
4) Idiopathic portal hypertension Risk factors
Size of the varices—the larger they are, the more easily they can rupture
Red colour signs—during an endoscopic examination, the varices may reveal red
markings or spots
High portal vein pressure
Severe cirrhosis
Continued alcohol use—consuming alcohol despite pre-existing liver problems
Bacterial infection
Oesophageal varices are unlikely to display symptoms unless they have ruptured
When ruptured
o Hematemesis (blood in vomit)
o Abdominal pain
o Light-headedness
o Melena (black stools)
o Bloody stools (only in severe cases)
o shock (only in severe cases, due to blood loss)
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 121
4.5. VENOUS THROMBOSIS
A venous thrombus is the formation of a semi-solid coagulum within flowing blood in the
venous system. Venous thrombosis of the deep veins of the leg is complicated by the
immediate risk of pulmonary embolus and sudden death. Patients are at risk of
developing a post-thrombotic limb and venous ulceration.
Aetiology
Revolves around three factors (Virchow’s triad) namely changes in the vessel wall
(endothelial damage), changes in flow of blood (stasis) and changes in blood
composition (e.g. coagulability of blood - thrombophilia). There are many predisposing
causes of venous thrombosis. Development of deep vein thrombosis is multifactorial but
immobility remains one of the most important factors.
Pathology
A thrombus often develops in the soleal veins of the calf, initially as a platelet
aggregate. Subsequently, fibrin and red cells form a mesh until the lumen of the vein
wall occludes. 4.5.1. DEEP VENOUS THROMBOSIS (DVT)
Definition
Deep Vein Thrombosis (DVT) is a clot that most commonly occurs in one leg, but can also occur
in the arm, abdomen or around the brain. Symptoms may involve the foot, ankle, calf, whole leg
or arm. These include pain, swelling, discoloration (bluish, purplish or reddish skin colour) and
warmth. These symptoms can develop slowly or suddenly.
Risk Factors
1) Immobility
Hospitalization, Being paralyzed, Prolonged sitting, Limb immobilized by plaster
cast (< 1 month)
2) Surgery and Trauma
i) Major surgery (especially of the pelvis, abdomen, hip, knee)
ii) Bone fracture or cast
iii) Catheter in a big vein (central venous catheter)
iv) Major trauma (< 1 month)
v) Acute spinal cord injury (< 1 month)
vi) Recent surgery (< 1 month)
vii) Limb trauma and/or orthopaedic procedures
3) Increased oestrogens
i) Birth control pills, patches, rings
ii) Pregnancy, including up to 6 weeks after giving birth
iii) Oestrogen and progestin hormone therapy
4) Medical conditions:
i) Cancer and chemotherapy
ii) Heart failure (< 1 month)
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 122
iii) Inflammatory disorders (lupus, rheumatoid arthritis, inflammatory bowel
disease)
iv) The kidney - nephrotic syndrome
v) Coagulation abnormalities
vi) Stroke (< 1 month)
vii) Serious lung disease including pneumonia (< 1 month)
viii) Abnormal pulmonary function (COPD)
ix) Indwelling central venous catheter
x) Acute infection /severe sepsis (< 1 month)
xi) Hypertension
xii) Hyperlipidemia
xiii) Autoimmune disease, including systemic lupus erythematosus
xiv) Myeloproliferative disorders
5) Other risk factors:
i) Previous blood clot
ii) Family history of clots
iii) Clotting disorder (inherited or acquired)
iv) Obesity (BMI > 25 kg/m2)
v) Older age (over 40 - incidence increase with age)
vi) Cigarette smoking
vii) Varicose veins
viii) Previous DVT or family history of thrombosis
ix) Pregnancy or postpartum period
PATHOGENESIS
Virchow’s triad
INVESTIGATIONS
1) Blood tests:
a. D-dimer is a substance found in blood which is often increased in people with blood
clots. A blood test can be used to rule out presence of a DVT. If the D-dimer test is
negative and you are determined to have a low-risk for DVT (based upon the history and
physical examination), further testing with an imaging study to rule out a blood clot may
not be needed. However, if the suspicion that you have a blood clot is intermediate or
high, an imaging study needs to be done.
2) Imaging studies which diagnose DVT:
a. Doppler ultrasound (Duplex) is a painless and non-invasive test used to diagnose DVT.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 123
b. Contrast venogram is often reserved for situations in which a Doppler ultrasound is not
feasible.
c. Magnetic resonance imaging (MRI) uses a strong magnet to create an image of inside the
body
d. Computer tomography (CT) venography or MRI venography are the preferred
tests to look at blood clots in the pelvis or the abdomen.
Hamilton Score
Characteristics Score
Plaster immobilization of lower limb 2
Active malignancy (within 6 months or current) 2
Strong clinical suspicion of DVT by emergency department physicians
and
no other diagnostic possibilities
2
Bed rest (>3 days) or recent surgery (within 4 weeks) 1
Male sex 1
Calf circumference >3 cm on affected side (measured 10 cm below tibial
tuberosity)
1
Erythema 1
A score of 2 represents unlikely possibility for deep venous thrombosis (DVT)
A score of 3 represents likely probability for DVT.
Modified Wells Score
Clinical Characteristics Score
Active cancer (patient receiving treatment for cancer within previous 6 months
or currently receiving palliative treatment)
1
Paralysis, paresis, or recent plaster immobilization of lower extremities 1
Recently bedridden for 3 days or more, or major surgery within previous 12
weeks requiring general or regional anaesthesia
1
Localized tenderness along distribution of deep venous system 1
Entire leg swollen 1
Calf swelling at least 3 cm larger than that on asymptomatic side (measured 10
cm below tibial tuberosity)
1
Pitting oedema confined to symptomatic leg 1
Collateral superficial veins (non-varicose) 1
Previously documented DVT 1
Alternative diagnosis at least as likely as DVT -2
A score of 2 indicates that probability of deep venous thrombosis (DVT) is likely
A score of <2 indicates that probability of DVT is unlikely.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 124
Wells Criteria /scoring for DVT Present Score
Lower limb trauma or surgery or immobilisation in a plaster cast +1
Bedridden for more than three days or surgery within the last four week +1
Tenderness along line of femoral or popliteal veins (NOT just calf tenderness) +1
Entire limb swollen +1
Calf more than 3cm bigger circumference, 10cm below tibial tuberosity +1
Pitting oedema +1
Dilated collateral superficial veins (non-varicose) +1
Past Hx of confirmed DVT +1
Malignancy (including treatment up to six months previously) +1
Intravenous drug use +3
Alternative diagnosis as more likely than DVT -2
Pre-test Clinical probability of a DVT with score:
DVT "Likely" if Well's > 1
DVT "Unlikely" if Wells< 2
COMPLICATIONS
4.6. PULMONARY EMBOLISM
Acute respiratory consequences of pulmonary embolism include the following:
o Increased alveolar dead space
o Hypoxemia
o Hyperventilation
Additional consequences that may occur include regional loss of surfactant and
pulmonary infarction (see the image below)
Arterial hypoxemia is a frequent, but not universal, finding in patients with acute
embolism
Mechanisms of hypoxemia include ventilation-perfusion mismatch, intrapulmonary
shunts, reduced cardiac output, and intracardiac shunt via a patent foramen ovale.
Pulmonary infarction is an uncommon consequence because of the bronchial arterial
collateral circulation.
Haemodynamic consequences
Pulmonary embolism reduces the cross-sectional area of the pulmonary vascular
bed, resulting in an increment in pulmonary vascular resistance, which, in turn,
increases the right ventricular afterload
If the afterload is increased severely, right ventricular failure may ensue
In addition, the humoral and reflex mechanisms contribute to the pulmonary arterial
constriction. Following the initiation of anticoagulant therapy, the resolution of
emboli usually occurs rapidly during the first 2 weeks of therapy; however, it can
persist on chest imaging studies for months to years.
What are the complications of DVT?
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 125
Chronic pulmonary hypertension may occur with failure of the initial embolus to
undergo lyses or in the setting of recurrent thromboemboli.
Wells criteria / scoring for PE
Present Score
Clinical Signs and Symptoms of DVT? +3
PE is No. 1 Dx or Equally likley Dx +3
Heart Rate > 100 +1.5
Immobilization at least 3 days, or Surgery in the Previous 4 weeks +1.5
5 Previous, objectively diagnosed PE or DVT? +1.5
Haemoptysis? +1
Malignancy with treatment within 6 months, or palliative? +1
Pre-test clinical probability of a PE:
Wells Score > 4 - PE likely. Consider diagnostic imaging.
Wells Score 4 or less - PE unlikely. Consider D-dimer to rule out PE.
Disorders of Lymphatics and Blood Vessel Tumours
The lymphatic system is made up of lymphatic capillaries, lymphatic vessels and the
lymph nodes. The lymphatic capillaries resemble blood capillaries and the larger
lymphatics are identical to veins but are lined up by a single layer of endothelium with
thinner muscle walls. Lymphatic capillaries and lymphatics form plexuses around
tissues and organs. Lymphatic capillary walls are permeable to tissue fluid, proteins
and particular matter.
Lymphangitis
Lymphangitis is inflammation of the lymphatic that can be acute or chronic.
ACUTE LYMPHANGITIS
Acute lymphangitis results from many bacterial infections most commonly beta
haemolytic streptococci and staphylococci and is often associated with lymphadenitis.
CHRONIC LYMPHANGITIS
Chronic lymphangitis is due to persistent and recurrent acute lymphangitis or from
chronic infections like tuberculosis, syphilis and actinomycosis and usually results in
permanent obstruction due to fibrosis.
Lymphoedema
Lymphoedema is swelling of soft tissues due to localized increase in the quantity of
lymph. It can be primary (idiopathic) or secondary (obstructive).
Primary (Idiopathic) lymphoedema
Primary lymphoedema occurs without any underlying secondary cause e.g. congenital
lymphoedema.
UNIT 1: CARDIOVASCULAR PATHOLOGY
Carey F. Okinda Page 126
Secondary lymphoedema
Is the more common form of lymphoedema resulting from obstruction of the lymphatic
channels due to: -
a) Lymphatic invasion by malignant tumour
b) Surgical removal of lymphatics
c) Post-irradiation fibrosis
d) Parasitic infestations e.g. filariasis
e) Lymphangitis causing scarring and obstruction
Obstructive lymphoedema occurs when the obstruction is wide spread since collaterals
develop.
Tumours of Blood Vessels
1. Name the tumours that affect blood vessels 2. How will these tumours present? 3. How will you investigate for them? 4. What is Kaposi’s sarcoma (KS)? 5. How many forms of KS are there? 6. What are the complications of KS?