Transport across cell membrane (passive, active, vesicular)
Cardiac hyprtrophy and heart failure
2. Cardiac Structure and Specializations
0.4% to 0.5% of body weight
250 to 320 gm in female & 300 to 360 gm in male
wall thickness of right ventricle - 0.3 to 0.5 cm
Wall thickness of left ventricle - 1.3 to 1.5 cm
Hypertrophy= increased weight & thickness
Dilatation = an enlarged chamber size
Cardiomegaly = Increased cardiac weight or size resulting from
hypertrophy and/or dilation
3. OVERVIEW OF HEART DISEASE
Cardiovascular dysfunction can be attributed to
one (or more) of six principal mechanisms:
1. Failure of the pump
2. Obstruction to flow
3. Regurgitant flow
4. Shunted flow
5. Disorders of cardiac conduction
6. Rupture of the heart or a major vessel
4. Disruption of any element of the
heart can adversely affect
pumping efficiency
Myocardium
Valves
conduction system &
coronary vasculature
5. The blood in the heart chambers moves in a carefully prescribed
pathway:
venous blood from systemic circulation
right atrium → right ventricle
pulmonary arteries
Lungspulmonary veins
left atrium → left ventricle
aorta → systemic arterial supply
7. Learning outcomes
At the end of this lecture students should be able to
1. Discuss causes and mechanism of cardiac hypertrophy
2. Discuss the consequence of molecular and cellular changes in
hypertrophied heart
3. Define congestive heart failure
4. Explain the causes and pathology & clinical feature of left sided
heart failure
5. Explain the causes and pathology &clinical features of right
sided heart failure
8. CARDIAC HYPERTROPHY
defined as an increase in size & weight of the
myocardium
results from increased mechanical work due to pressure
or volume overload
mediated through the activation of β-adrenergic receptors
dependent upon increased protein synthesis, which
enables the assembly of additional sarcomeres
9. CARDIAC HYPERTROPHY
Hypertrophic myocytes contain
- increased numbers of mitochondria & enlarged nuclei due
to increases in DNA ploidy, which result from DNA
replication in the absence of cell division
Pattern of hypertrophy reflects the nature of the stimulus
i. Pressure-overload hypertrophy- concentric hypertrophy
ii. Volume-overload hypertrophy- eccentric hypertrophy
(ventricular dilatation)
10. Pressure-overload hypertrophy
in response to increased pressure load -hypertension or
aortic stenosis
causes a concentric increase in wall thickness
new sarcomeres are predominantly assembled in parallel
to the long axes of cells, expanding the cross-sectional
area of myocytes
11. Volume-overload hypertrophy
is characterized by ventricular dilation
results from increased volume load (valvular incompetence )
new sarcomeres assembled are largely positioned in series with
existing sacromeres
heart weight, rather than wall thickness, is the best
measure of hypertophy
wall thickness may be increased, normal, or less than
normal
12. Gross Morphology
Thickness of the left ventricular wall (excluding trabeculae
carneae and papillary muscles) above 15 mm is indicative of
significant hypertrophy
In concentric hypertrophy, the lumen of the chamber is
smaller than usual
In eccentric hypertrophy the lumen is dilated
13. Thickness of the left ventricular wall above 15 mm is indicative of
significant hypertrophy
In concentric hypertrophy, the lumen of the chamber is smaller than
usual
In eccentric hypertrophy the lumen is dilated
Gross Morphology
15. Important changes at the tissue and cell level occur with cardiac
hypertrophy.
increase in myocyte size is not accompanied by a
proportional increase in capillary numbers
supply of oxygen and nutrients to the hypertrophied heart, is
more tenuous than in the normal heart.
oxygen consumption by the hypertrophied heart is elevated
due to the increased workload that drives the process
Hypertrophy is also often accompanied by deposition of
fibrous tissue
Molecular changes include the expression of immediate-early
genes (e.g., c-fos, c-myc, c-jun, and EGR1)
16. cardiac hypertrophy
heightened metabolic demands due to increases in mass, heart rate,
& contractility
increase cardiac oxygen consumption
vulnerable to ischemia-related decompensation
cardiac failure and eventually lead to death
18. CARDIAC HYPERTROPHY
can be substantial in clinical heart disease
Heart weights of two to three times greater than normal
- systemic hypertension
- ischemic heart disease
- aortic stenosis
- mitral regurgitation
- dilated cardiomyopathy
Heart weights of threefold to fourfold greater than normal
- aortic regurgitation
-hypertrophic cardiomyopathy
19. is defined as the pathophysiologic state in which
impaired cardiac function is unable to maintain an
adequate circulation for the metabolic needs of the
tissues of the body
HEART FAILURE
Definition
20. HEART FAILURE
Heart failure generally is referred to as congestive heart
failure (CHF)
- is the common end point for many forms of cardiac
disease and
- typically is a progressive condition that carries an
extremely poor prognosis
21. HEART FAILURE
CHF occurs when the heart is
- unable to provide adequate perfusion to meet the
metabolic requirements of peripheral tissues
- inadequate cardiac output is usually accompanied by
increased congestion of the venous circulation
22. HEART FAILURE
It can be due to systolic dysfunction or diastolic dysfunction
Systolic dysfunction-inadequate myocardial contractile
function (cardiac muscle contracts weakly and the chambers cannot empty properly)
consequence of
- ischemic heart disease
- pressure or volume overload
(valvular disease ,hypertension & dilated cardiomyopathy )
23. diastolic dysfunction - inability of the heart to adequately
relax and fill (the muscle cannot relax sufficiently to permit ventricular
filling)
such as in
- left ventricular hypertrophy
- myocardial fibrosis
- amyloid deposition
- constrictive pericarditis
HEART FAILURE
It can be due to systolic dysfunction or diastolic dysfunction
24. HEART FAILURE
It may be Acute or Chronic
Chronic CHF
end stage of many forms of chronic heart disease
develops insidiously due to the cumulative effects of chronic
work overload such as in -
- valve disease
- Hypertension
- ischemic heart disease - following myocardial infarction
with extensive heart damage
25. HEART FAILURE
It may be Acute or Chronic
Acute Hear Failure
develops rapidly or suddenly
occur in acute hemodynamic stresses
- fluid overload
- acute valvular dysfunction
- a large myocardial infarction
26. COMPENSATORY MECHANISMS
When cardiac function is impaired or the work load
increases, several physiologic mechanisms maintain arterial
pressure and perfusion of vital organs
Frank-Starling mechanism
Myocardial adaptations, including hypertrophy with or without
cardiac chamber dilation
Activation of neurohumoral systems- release of
norepinephrine ,activation of the renin-angiotensin-
aldosterone system, & release of atrial natriuretic peptide
27. CAUSES OF HEAR FAILURE
1. INTRINSIC PUMP FAILURE
2. INCREASED WORKLOAD ON THE HEART
3. IMPAIRED FILLING OF CARDIAC CHAMBER
28. CAUSES OF HEAR FAILURE
INTRINSIC PUMP FAILURE
i) Ischemic heart disease
ii) Myocarditis
iii) Cardiomyopathies
iv) Metabolic disorders (beriberi)
v) Disorders of the rhythm (atrial fibrillation and flutter)
29. CAUSES OF HEAR FAILURE
INCREASED WORKLOAD ON THE HEART
Increased pressure load (pressure overload)
- Systemic and pulmonary arterial hypertension
- Valvular disease : mitral stenosis, aortic stenosis, pulmonary stenosis
- Chronic lung diseases
Increased volume load (volume overload)
30. CAUSES OF HEAR FAILURE
INCREASED WORKLOAD ON THE HEART
Increased volume load (volume overload)
- Valvular insufficiency
- Severe anaemia
- Thyrotoxicosis
- Arteriovenous shunts
- Hypoxia due to lung diseases
31. CAUSES OF HEAR FAILURE
IMPAIRED FILLING OF CARDIAC CHAMBER
Cardiac failure may result from extra-cardiac causes or defect in
filling of the heart:
a) Cardiac tamponade - haemopericardium, hydropericardium
b) Constrictive pericarditis
33. LEFT-SIDED HEART FAILURE
Pathologic changes and clinical effects result from
congestion of the pulmonary circulation
stasis of blood in the left-sided chambers
hypoperfusion of tissues leading to organ dysfunction
34. LEFT-SIDED HEART FAILURE
Morphology
Depend on the disease process;
- gross structural abnormalities
- hypertrophy and dilatation of left ventricle
- microscopic changes are non-specific, consisting mainly
of myocyte hypertrophy and variable degrees of interstitial
fibrosis
35. Pulmonary congestion and edema produce heavy, wet lungs
perivascular and interstitial edema, particularly in the interlobular
septa
progressive edematous widening of alveolar septa
accumulation of edema fluid in the alveolar spaces
Extravasation of RBCs from the leaky capillaries into alveolar
spaces, phagocytosed by macrophages, subsequent breakdown
of hemoglobin leads to the appearance of hemosiderin-laden
alveolar macrophages called heart failure cells—that reflect
previous episodes of pulmonary edema
LEFT-SIDED HEART FAILURE
Morphology
37. Features of pulmonary congestion and edema
Cough
dyspnea with exertion
dyspnea at rest
orthopnea
paroxysmal nocturnal dyspnea
Basal lung crackles
Presence of the third heart sound
LEFT-SIDED HEART FAILURE
Clinical Features
Progressive
38. Salt & Fluid retention due to activation of RAAS system
impaired excretion of nitrogenous products may cause
azotemia
LEFT-SIDED HEART FAILURE
Clinical Features
39. cerebral hypoxia can give rise to hypoxic encephalopathy
with irritability, loss of attention span, and restlessness
In end-stage CHF, this can even progress to stupor and
coma.
LEFT-SIDED HEART FAILURE
Clinical Features
40. RIGHT -SIDED HEART FAILURE
As a consequence of left ventricular failure.
Cor pulmonale in which right heart failure occurs due to
intrinsic lung diseases
Pulmonary or tricuspid valvular disease
Pulmonary hypertension secondary to pulmonary
thromboembolism.
Myocardial disease affecting right heart.
Congenital heart disease with left-to-right shunt
41. RIGHT -SIDED HEART FAILURE
pathologic changes are as under:
Systemic venous congestion in different tissues and
organs e.g. subcutaneous oedema on dependent parts, passive
congestion of the liver, spleen, and kidneys ascites, hydrothorax,
congestion of leg veins and neck veins
Reduced cardiac output resulting in circulatory stagnation
causing anoxia, cyanosis and coldness of extremities
42. RIGHT -SIDED HEART FAILURE
Congested Hepatomegaly- Nutmeg liver
- red-brown centrilobular discoloration & pale peripheral regions
Cardiac sclerosis & cirrhosis
- Centrilobular necrosis and fibrosis in longstanding severe case
Congested splenomegaly
GI congestion
Subcutaneous edema - dependent portions of the body,
especially ankle (pedal) and pretibial edema, is a hallmark of right-
sided heart filure, in chronically bedridden patients - presacral
edema
43. RIGHT -SIDED HEART FAILURE
Congestion of the kidneys is more marked with right-sided
than left-sided heart failure, leading to greater fluid retention
and peripheral edema, and more pronounced azotemia
Venous congestion and hypoxia of the central nervous
system can produce deficits of mental function