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

14. Microscopic Morphology
increase in size of individual
muscle fibres

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

32. LEFT-SIDED HEART FAILURE
Causes
(1) ischemic heart disease
(2) Systemic hypertension
(3) aortic and mitral valvular diseases
(4) myocardial diseases cardiomyopathies, myocarditis

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

36. .
Pulmonary edema
heart failure cells

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

44. FATIGUE
“Dependent” edema
Hepatomegaly (congestion)
ASCITES, PLEURAL EFFUSION
Cyanosis
Increased peripheral venous
pressure (CVP) (nl = 2-6 mm Hg)
Increased JVP
RIGHT -SIDED HEART FAILURE

45. Measuring Jugular Venous Pressure

47. Backward heart failure
- increased congestion of the venous circulation
Forward heart failure
- inadequate cardiac output

48. Reference
1. Robbins & Cotran Pathologic Basis of Disease, 9th Edition
2. Textbook of Pathology; Mohan Harsh Jaypee Brothers, Medical Publishers
Pvt. Limited, 1 Feb 2010