Patofisiologi Jantung

Fika Ekayanti

ANATOMI JANTUNG
1.Pericardium: lapisan-lapisan,sinus pericardii pendarahan/persarafan,pungsi pericardium 2.Jantung: anatomi permukaan,interior,katup-katup,sistem konduksi,proyeksi,vaskularisasi,persarafan otonom,aliran limfe

Bentuk jantung vertikal dan horisontal

Arah aliran darah: Perhatikan sirkulasi kecil (pulmonal) dan sirkulasi besar (sistemik)

SIRKULASI

Coronary Artery Disease

NORMAL BLOOD VESSEL

Atherosclerotic and Endothelial dysfunctions

ATHEROSCLEROSIS

Macrophage Functions in Atherogenesis

Attachment

Macrophage Functions in Atherogenesis

Penetration

Macrophage Functions in Atherogenesis

Activation

Macrophage Functions in Atherogenesis

Division

Molecular Mediators of Atherogenesis

VCAM-1

MCP-1

M-CSF

Anatomy of the Atherosclerotic Plaque

Fibrous cap

Lumen Lipid Core

Intima
Media Elastic lamin Internal External

Shoulder

Matrix Metabolism and Integrity of the Plaques Fibrous Cap

IFN-

CD-40L +

Collagen-degrading Proteinases

Fibrou s cap

+ + + +
+

IL-1 TNF- MCP-1 M-CSF

Lipid core
Libby P. Circulation 1995;91:2844-2850.

Tissue Factor Procoagulant

Smoking, hyperlipidemia, hypertension, hyperglycemia Endothelial dysfunction Activation of NF-kB

+ +

CD40L
+

Adhesion molecules
+

TNF-a
+

Interleukins

VCAM-1

P-selectin

ICAM-1

IL-1

IL-6

IL-8

Matrix metalloproteinases Inflammation Plaque destabilization Acute phase proteins

Serum amyloid-A

CRP

Fibrinogen

Pathophysiology of Atherosclerosis
Endothelial Dysfunction
Foam Cells
oxidized LDL homocysteine smoking aging hyperglycemia hypertension

Fatty Intermediate Fibrous Complicated Streak Lesion Atheroma Plaque Lesion/Rupture

35-45 yrs 45-55 yrs 55-65 yrs >65 yrs Endothelial Lipid accumulationInflammation adhesion molecules MMP's injury continued macrophage/lipid (ICAM, VCAM)
nitric oxide endothelin-1 vasodilation monocyte adhesion macrophage LDL uptake accumulation leukocyte accumulation cytokines (IL-6,TNFa, IFNg)

CRP (hepatic)

Pathophysiologyof Atherosclerosis
Endothelial dysfunction :

Monocyte Lipid Cluster -

Endothelial barrier Monocyte

Subintima Endothelial permeability Monocyte migration Endothelial adhesion Monocyte adhesion 0.5 m

10.078x

Vesselwall

Monocyte transmigration

Ross R, NEngl J Med 340 (1999) & Lusis AJ, Nature 407 (2000)

Pathophysiology of Atherosclerosis
Plaquewith stable fibrous cap formation :

Macrophage accumulation

Formation of necrotic core

Fibrous cap formation

Vesselwall

Coronary plaque with lipid core

mod. nach Ross R, Engl J Med 340 (1999) & Falk et al., N Circulation (1995) 92

Pathophysiology of Stable and Unstable Plaques

Plaque Rupture with Thrombosis

Thrombus Fibrous cap

1 mm
Illustration courtesy of Frederick J. Schoen, M.D., Ph.D.

Lipid core

Angina Pectoris
Stable : There is no

substantial deterioration in symptoms over several weeks. Stability or quiescence of an atherosclerotic plaque; depending on increased oxygen demand Unstable : symptom pattern worsen abruptly without an obvious caused of increased oxygen consumption, decreased supply . Unstable plaque: ACS
Adapted from Weissberg. Atherosclerosis. 1999;147:S3S10

 Variant/Printzmetal Angina : focal coronary artery spasm

without overt atherosclerotic lesions (may involve endothelial dysfunction-vasodilator response low & increased symphatetic activity) Syndrome X : typical symptoms of angina without evidence of significant coronary stenoses (due to inadequate vasodilator reserve of coronary resistance vessels, microvascular dysfunction, vasospasm or hypersensitive pain perception

Risk Factors Analysis

Major risk factors 1. 2. 3. 4. 5. 6. high blood pressure high cholesterol tobacco low fruit and vegetable intake physical inactivity Obesity > tobacco, high blood pressure, high cholesterol or a combination of three.

Cardiovascular risk factors and mortality analysis

Confidence Interval Risk Factor Sex Female Male Age (year) 2549 5054 5559 6064 Blood Pressure Normal High normal Grade 1 Hypertension Grade 2 Hypertension Grade 3 Hypertension Smoking Never Ex-smoker Smoker 1.00* 4.87 4.99 1.8312.97 2.569.73 0.002 0 1.00* 1.34 1.61 2.29 5.96 0.543.28 0.833.14 1.184.48 2.6913.21 0.527 0.16 0.015 0 1.00* 5.63 5.96 10.13 2.5112.62 2.7512.92 4.7921.43 0 0 0 1.00* 1.68 0.893.18 0.107 Hazard Ratio -95% P

Confidence Interval Risk Factor Diabetes Mellitus No 1.00* Hazard Ratio -95% P

Yes
Body Mass Index (kg/m )
2

2.74

1.375.47

0.004

13.7925.99
26.0029.99 30.0035.58 Physical Exercise/Activity No Low Medium High

1.00*
0.85 2.18

0.481.51 0.945.10

0.578 0.071

1.00* 0.45 0.32 UC

0.270.76 0.150.70 -

0.003 0.004 -

*Used as reference, World Health Organization criteria, UC = uncountable. p calculated using Cox regression analysis.

Risk Factors of Coronary Heart Disease

Modifiable
Dyslipidemia (LDL ,HDL) Tobacco smoking Hypertension Diabetes Mellitus, Metabolic Syndrome Lack of Physical Activity

Non Modifiable
Advanced age Male gender (post menopausal women) Family history (1st degree relatives <55 male or <65 female)

Novel
Homocysteine Lipoprotein (a) CRP & other inflammatory markers

CARDIOMYOPATHY
A group of heart disease in which the major structural abnormality is limited to the myocardium

Dilated CM

Hyperthrophic CM

Restrictive CM

Ventricular enlargement Impaired systolic function

Thickened myocardium Abnormal diastolic function

Stiffened myocardium Impaired diastolic function

41

DILATED CARDIOMYOPATHY
Dilated all 4 chamber (typical DCM) Decrease contractile function (systolic) Low CO MR or TR or both Arrythmia

42

 Idiopathic Inflammatory
Infection Noninfection : Viral, bacterial, parasit : Sarcoidosis, peripartum CM

Toxic
Alcohol Chemotherapeutic agent

Metabolic
Hypothyroidism Chronic Hypocalcemia or HypoPO4

Neuromuscular
Muscular or myotonic dystrophy
43

PATHOPHYSIOLOGY
Pulmonary congestion
Dyspneu, orthopneu, rales

MYOCYTE INJURY Contractility

Systemic congestion
Edema, ascites, JVD

SV

Fatigue
Weakness

Ventricular filling pressure

LV Dilatation
Mitral Regurgitasi

Forward CO

44 Lilly L.S, 2007, Pathophysiology of Heart Disease

CLINICAL PRESENTATIONS
Heart failure symptoms

Anginal chest pain

Emboli (systemic or pulmonary)

45

Hyperthrophic CARDIOMYOPATHY
LV hyperthrophy Cardiac cause (-) Systemic cause (-) Small LV cavity Contractile function is vigorous Impaired ventricular relaxation High diastolic pressure
46

47

Etiology
HCM is the most common genetic cardiovascular disease. Mutations of the cardiac sarcomere myofilaments Affected genes :
-myosin heavy chain, myosin-binding protein C cardiac troponin T and I -tropomyosin actin myosin light chains.

inherited in an autosomal dominant

48

49

Pathophysiology
Myocyte hyperthrophy
Ventricular arrhythmia Dynamic LVO obstruction

LVH

Systolic pressure Mitral regurgitation

LVDEP

MVO2 Failure to CO with exertion

Sudden death

Syncope

Dyspneu

Angina
50

RESTRICTIVE CARDIOMYOPATHY
Restrictive filling Normal or reduced LV and RV volumes Abnormal diastolic function Normal or nearly normal systolic (LV and RV) function
51

Etiology
Myocardial Non infiltratif Idiopathic Scleroderma Infiltratif Amyloidosis Sarcoidosis Storage disease Hemochromatosis Glycogen storage diseases Endomyocardial Obliterative Endomyocardial fibrosis Hypereosinophilic syndrome Nonobliterative Carcinoid Malignant infiltration Iatrogenic (radiation therapy)

52 Lilly L.S, 2007, Pathophysiology of Heart Disease

MYOCARDITIS
An acute or chronic inflammatory process affecting the myocardium Produced by : Toxins and drugs (cocaine, interleukin-2, sulfonamides, anticonvulsants and antiinflammatories) Infectious agents (viral, bacterial, fungal, parasit) Immune (giant cell myocarditis)
53

Clinical Presentation
Asymptomatic --- chest pain that mimics ACS pericarditis associated
Fever, myalgia & malaise consistent with viral infection 710 days after onset. Hallmark of heart failure

54

55

 A syndrome :
typical chest pain a pathognomonic pericardial friction rub specific ECG changes

Hursts, The Heart 12th Ed.

ETIOLOGY
IDIOPATHIC INFECTION Viral (Coxsackievirus type B, Echovirus) Tuberculosis Pyogenic bacteria NON INFECTIOUS post myocardial infarction Neoplastic Radiation induce Connective tissue diseases Drugs
Lilly L.S, 2007, Pathophysiology of Heart Disease 57

 PERICARDIAL FRICTION RUB : Superficial Creaky Scratchy The sound of walking on dry snow / the squeak of a leather saddle Between the lower left sternal edge and the cardiac apex
58

Slides compiled from lectures of Prof Dede Kusmana in Cardiac Module