1
Q
Dyslipidemia is aka?
A
Hyperlipidaemia
2
Q
causes of Primary Dylipideaemia
A
1) Primary (Genetic): Single or multiple gene
mutations that result in:
* Either overproduction or defective clearance
of Triglycerides and LDL Cholesterol
* Or underproduction or excessive clearance of
HDL
3
Q
causes of Secondary Dyslipidaemia
A
- A sedentary lifestyle in conjunction with
excessive dietary intake of saturated fat,
Cholesterol, and trans fats - Diabetes Mellitus (DM) type 2
- Alcohol overuse
- Chronic kidney disease
- Hypothyroidism
- Drugs, such as thiazides, beta-blockers,
oestrogen and progestins and glucocorticoids
4
Q
what are 3 types of Primary Dyslipidaemia
A
1) FAMILIAL HYPERCHOLESTEROLAEMIA
2) FAMILIAL COMBINED HYPERLIPIDAEMIA
3) FAMILIAL TYPE III HYPERLIPIDAEMIA
5
Q
which Fredrickson phenotype has elevated Chylomicrons (Lipoprotein) and elevated Triglycerides
A
Phenotype I (primary chylomicronaemia)
6
Q
which Fredrickson phenotype has elevated LDL (Lipoprotein) and elevated Cholesterol
A
IIA (Familial Hypercholesterolaemia)
7
Q
which Fredrickson phenotype has elevated LDL &VLDL (Lipoprotein) and elevated Cholesterol & Triglycerides
A
IIB (Familial Combined Hyperlipoproteinaemia)
8
Q
which Fredrickson phenotype has elevated Chylomicron remnants &VLDL (Lipoprotein) and elevated Cholesterol & Triglycerides
A
III (Familial Dysbetalipoproteinaemia)
9
Q
which Fredrickson phenotype has elevated VLDL (Lipoprotein) and elevated Triglycerides
A
IV (Familial Hypertriglyceridaemia)
10
Q
which Fredrickson phenotype has elevated Chylomicron &VLDL (Lipoprotein) and elevated Cholesterol & Triglycerides
A
V (Familial Mixed Hypertriglyceridaemia)
11
Q
Macrovascular complications for Dyslipidaemia
A
- Unstable Angina (Chest Pain)
- Myocardial Infarction (Heart Attack)
- Ischaemic Cerebrovascular Disease (Stroke)
- Coronary Artery Disease
12
Q
Microvascular complications of Dyslipidaemia
A
- Retinopathy
- Nephropathy
- Neuropathy
13
Q
Cause of ischaemic heart disease
A
Atheroma formation within coronary
arteries, aggravated by thrombosis or vasospasm
14
Q
Risk factors of ischaemic heart disease
A
- Central obesity
- Atherogenic lipid patterns
- Hypertension
- Insulin resistance (overt DM)
- Elevated C-reactive protein
15
Q
what is Ischaemic heart disease clinically identified as ?
A
Clinically silent or manifested as angina pectoris, myocardial infarction or chronic IHD
16
Q
complications of Ischaemic heart disease
A
1) Atherosclerosis
2) Angina pectoris (stable, unstable)
3) MI (STEMI, NSTEMI)
6) Chronic ischaemic heart disease
17
Q
causes of atheroscelrosis
A
A.
➢ Gradual occlusion of coronary vessel(s) →
➢ Gradual reduction in blood flow →
➢ Mismatch btw. demand and supply of
O2/nutrients to the myocardium →
➢ Ischaemia = Reversible process that is associated with tissue dysfunction, due to interference with blood flow to a tissue
B.
❖ Complete occlusion of coronary vessel(s) →
❖ Sudden reduction in blood flow →
❖ Infarction = Irreversible process that is related to tissue death (necrosis) , because of disturbances in the blood flow to a tissue
18
Q
cause of Stable Angina
A
Stable, but gradually enlarging plaque
→ Severe narrowing of atherosclerotic coronary vessels
19
Q
clinical manifestaions of Stable Angina
A
Predictable cardiac-type
pain, which shows following characteristics:
1) Precipitation by exertion
2) Duration of 1-2 min
3) Relief of pain by rest or intake of Glyceryl
trinitrate
20
Q
causes of Unstable (“Crescendo”)Angina
A
- Disruption of atherosclerotic plaque with
superimposed thrombosis - Embolisation
- Vasospasm
21
Q
clinical features of Unstable Angina
A
(at least one of the following
three, present):
1. Occurs at rest (or with minimal exertion),
usually lasting 3–5 minutes
2. Is severe and of new onset (i.e. within the
prior 4–6 weeks)
3. Occurs with a crescendo pattern (i.e.
distinctly more severe, prolonged, or
frequent than before)
22
Q
cause of MI
A
Coagulative necrosis of myocardium, due to
coronary artery occlusion
23
Q
cellular components of MI
A
Neutrophils, macrophages
and fibroblasts
24
Q
what are the 2 patterns of MI necrosis
A
- Transmural infarction: Whole thickness of
myocardium - Subendocardial infarction: Inner 1/3 of left
ventricular wall
25
cause of STEMI
Occurs when a coronary artery is totally
occluded → Trans-mural myocardial infarction
26
ECG findings of STEMI
* ST-segment elevation with pathological Q-waveformation
* Sometimes, T-wave inversion
27
Blood test findings of STEMI
Cardiac markers:
1) ↑ of Troponin T, Troponin I, and CK-MB (Creatine Kinase Myocardial Band)
--> Troponin T and Troponin I start to rise at 4-6 hours and remain high for up to 2 weeks
--> CK-MB starts to rise at 4-6 hours and falls to
normal within 48-72 hours
Full blood count:
* ↑ of White Blood Cell (WBC) count
* ESR and CRP may elevate
28
Cause of NSTEMI
Occurs when a coronary artery is partially
occluded → Sub-endocardial MI
29
Clinical feature of NSTEMI
Ischaemic pain
30
ECG findings of NSTEMI
ST depression and/or T wave inversion
31
Laboratory findings of NSTEMI
Delay in rise of troponin levels
32
State the difference between NSTEMI and Unstable Angina
* Difference in severity of myocardial ischaemia;
NSTEMI > Unstable Angina
* NSTEMI: Elevation of cardiac enzymes; Unstable
Angina: No or only very minimal elevation
33
what are 4 sequence of events of MI?
1. Myocyte necrosis
2. Induction of an inflammatory response
(Infiltration of neutrophils)
3. Organisation (Replacement of dead cells by
granulation tissue; First step of the repairprocess)
4.Scar formation (Progressive scar tissue
deposition; Second step of the repair-process)
34
Microscopic features:
* Contraction band necrosis
* Loss of cross striations
* Irregular darker pink wavy contraction bands
* Not clearly visible nuclei
* Many neutrophil infiltrates
with karyorrhexis
* Many macrophages
* Numerous capillaries
* Fibroblast proliferation
Are the features of which heart disease?
MI
35
complications of MI
1) Arrhythmia → Death, within first hours
2) Myocardial failure → Congestive heart failure
or shock
3) Myocardial rupture → Cardiac tamponade
(4-7 days)
4) Ruptured papillary muscle
5) Mural thrombosis → Left sided embolism
6) Ventricular aneurysm
36
pathogenetic mechanism of Chronic ischaemic heart disease
* **Gradual enlargement of stable plaque**→
* Gradual stenosis of the lumen →
* Low grade chronic myocardial ischaemia →
* Progressive fine diffuse myocardial fibrosis →
* **Reduction in contractile function** but also enough time for compensatory changes → **LV hypertrophy** →
→ Maintenance of cardiac output [No
symptomatology] BUT
* … → Finally, myocardium decompensates →Onset of progressive Chronic Heart Failure →**↓ Cardiac output**
37
casue of Cardiomyopathy
unexplained ventricular dysfunction:
* Heart failure unresponsive to digitalis (drug
causing increase in cardiac contractility)
* Ventricular enlargement
* Ventricular arrhythmias
38
classifications of Cardiomyopathies
1) Congestive or Dilated Cardiomyopathy
2) Restrictive Cardiomyopathy
3) Hypertrophic Cardiomyopathy
4) Arrhythmogenic Right Ventricular Cardiomyopathy
39
mechanism (of heart failure) of congestive/Dilated cardiomyopathies
Impairment of contractility (systolic dysfunction)
40
Epidemiology of congestive/dilated cardiomyopathies
Most common form;M > F
41
Etiology of congestive/dilated cardiomyopathies
* Unknown (most often)
* Alcohol
* Thiamine (Vitamin B1) deficiency (beri-beri)
* Myocarditis
* Mutations of cytoskeletal proteins [dystrophin, desmin] or sarcomeric proteins [cardiac myosin heavy chain or actin]
* Mutations in mitochondrial genes
42
pathogensis of congestive/dilated cardiomyopathies
* **Damage of the muscle tissue** → Weakening of the myocardium → Insufficient pumping action of the heart
* **Increase in fluid retention (↑ blood volume)** → Expansion (dilatation) of heart ventricles
* Stretching of the heart muscle → Enlargement of the heart (**Cardiomegaly**)
* Long term effect: Development of both right and left-sided intractable heart failure
43
Macroscopic findings:
* **Globular-shaped heart**
* Increased heart weight
* **Biventricular/Four-chamber dilatation**
* Normal or diminished LV thickness
* Mural thrombi
* Prominent **LV endocardial trabeculations**
* Annular dilatation of atrio-ventricular valves
* Endocardial fibrous thickening of septal portion of left ventricle
are the features of which heart condition?
CONGESTIVE OR DILATED CARDIOMYOPATHY
44
Microscopic findings:
* **Myocyte hypertrophy** (nuclear size/shape)
* Interstitial/perivascular fibrosis
* Interstitial lymphocytes and macrophages
* **Reduced number of myocytes** (myofibrillar loss)
are the features of which heart malformation?
CONGESTIVE OR DILATED CARDIOMYOPATHY
45
complications of congestive or dilated cardiomyopathy
1) Heart failure
2) Heart valve disease
3) Irregular heart rate (arrhythmias)
4) Formation of blood clots in the heart that leads to:
* Pulmonary embolism
* Stroke or myocardial infarction
46
Restrictive cardiomyopathy is aka?
Infiltrative Cardiomyopathy
47
mechanism (of heart failure) of Restrictive cardiomyopathy
Impairment of compliance (diastolic dysfunction)
48
cause of restrictive cardiomyopathy
* Idiopathic
* **Cardiac amyloidosis (“stiff heart syndrome”)**
* **Haemochromatosis** (build-up of iron in the body)
* Sarcoidosis
* Radiation fibrosis
* Metastatic tumours
49
pathogensis of restrictive cardiomyopathy
* Infiltrative processes within heart muscle →
* → Stiffening of myocardium →
* → Restriction of the heart to stretch properly →
* → Affects the filling capacity of the
heart ventricles →
* → Reduction in blood flow →
* → Blood backs up in the circulation →
* → Heart Failure
50
Mechanism (of heart failure) of hypertrophic cardiomyopathy
: Impairment of
compliance (diastolic dysfunction)
51
Cause of hypertrophic cardiomyopathy
**100% Genetic**; Autosomal dominant
characteristic
52
pathogensis of Hypertrophic cardiomyopathy
Myocardial hypertrophy → Poorly compliant left ventricular myocardium → Abnormal diastolic filling → and intermittent ventricular outflow obstruction → Danger of syncope and sudden death (unexpectedly, in athletes)
53
Macroscopic findings:
* Markedly **thick-walled left ventricle** (asymmetric [septal hypertrophy]/symmetric)
* **Whorled appearance of septal musculature**
* Normal or **reduced left ventricular cavity**
* Endocardial thickening or mural plaque
formation in the left ventricular outflow tract
* **Thickening of the anterior mitral leaflet**
* Increase in the right ventricular wall thickness
are the features of which cardiac malformation?
Hypertrophic cardiomyopathy
54
Microscopic findings:
*Marked **myocyte hypertrophy**
* **Myocyte disarray** pattern (irregularly arranged, interwoven myocyte fibers)
* Interstitial and perivascular fibrosis
* Endocardial fibrosis
* Fibrous mural changes in intra-myocardial
arteries
Are the features of which heart disease ?
Hypertrophic Cardiomyopathy
55
cause of Arrhythmogenic right ventricular cardiomyopathy
Defective cell adhesion proteins in desmosomes of adjacent cardiac myocytes
56
pathogenetic mechanism of Arrhythmogenic right ventricular cardiomyopathy
* **Gradual replacement of right ventricular muscle by adipose and fibrous tissue**
* The right ventricle inflow tract, apex, and outflow tract are involved → Dilatation of right ventricle and attenuation of the free wall
* The left ventricle can also be affected, but usually in conjunction with right ventricle disease
57
Naxos syndrome?
--> Associated with mutations in genes desmoplakin and plakoglobin
--> **includes Arrhythmogenic Right Ventricular Cardiomyopathy**
--> Palmo-plantar keratoderma
58
Clinical features of Arrythmogenic right ventricular cardiomyopathy
1) Palpitations and fainting after physical activity
2) Dizziness and lightheadedness
3) Ventricular arrhythmias → Sudden cardiac death
59
Macroscopic findings:
* **Replacement of myocardial tissue by adipous and fibrous tissue**
* Dilatation of the right ventricle and attenuation of the free wall ventricle
are the features of what heart condition
ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY
60
Microscopic findings:
* Markedly decreased numbers of myocytes
* Extensive fatty infiltration and fibrosis
* In some cases, collections of mononuclear inflammatory cells are found within the adipose tissue
Are the features of what heart condition
ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY
61
Clinical features of Myocarditis
Manifests as biventricular heart failure in young persons, without valvular, rheumatic or congenital heart disease
62
* **scalloped of myocytes**
* inflammatory cells infiltrates
* Fragmentation of myocytes with remnants of cytoplasm or **“bare nuclei”**
are the Histopathological features of what heart condition?
Myocarditis
63
causes of Lymphocytic myocarditis
**Coxsackie B** (Enterovirus), Echovirus,
Adenovirus
64
pathogensis of Lymphocytic myocarditis
* Post-viral autoimmunity mechanisms
* Direct viral cytopathic injury
* Induction of viral-specific immune response
through mediators (ILs, TNF, IFN, NO)
* Viral mediated endothelial injury → Intima
proliferation → Ischaemic sequelae
65
Macroscopic findings:
* Range from normal cardiac configurations to
four-chamber dilatation and cardiac enlargement
* Flattening of the papillary muscles and
trabeculae
* Pale and flaccid appearance of the myocardium
* Myocardium’s cut surface: Usually pale with foci of haemorrhage or haemorrhagic necrosis
* Many cases have fibrinous pericarditis and
exudative effusions
Are the features of which heart condition?
Lymphocytic myocarditis
66
Microscopic findings:
* Architectural patterns include focal, multifocal
and diffuse interstitial infiltrates
* Interstitial widening caused by tissue oedema
and inflammation
* Majority of lymphocytes: CD3(+), both helper
and suppressor subtypes
* Presence of macrophages and natural killer cells
* Infrequent or absent B lymphocytes
Are the features of which heart condition?
Lymphocytic myocarditis
67
causative agents of infectious myocarditis
Bacteria, fungi, protozoa, rickettsiae
68
Epidemiology of infectious myocarditis
Affects mainly individuals with:
1) AIDS
2) Advanced stages of malignancy
3) Transplantation-associated immunosuppression
69
Causative drugs of Hypersenisitvity myocarditis
Antibiotics, diuretics, and antihypertensive drugs, prolonged infusion (7% of patients undergoing cardiac transplantation)
70
clincial signs of Hypersensitivity Myocarditis
1)Rash
2)Fever
3)Peripheral eosinophilia
4)Arrhythmias, sudden death, and congestive
heart failure (occasionally)
71
* Temporally uniform lesions; distributed in the subendocardial, perivascular, and interstitial tissues between bundles of myocytes
* Eosinophils (predominant inflammatory cell), but also variable numbers of histiocytes and
scattered lymphocytes (T cell phenotype) present
* Oft, infiltration of vessel walls by eosinophils
* Collections of histiocytes centered on degenerated collagen bundles form ill-defined granulomas in up to 25% of cases
* Myocyte necrosis usually absent or very focal,
except in severe cases
* Hypersensitivity vs. Drug induced Giant-cell
Myocarditis: Absence of diffuse myocardial
necrosis and giant cells
* Hypersensitivity vs. Acute Necrotising Eosinophilic Myocarditis: Absence of extensive necrosis, dense interstitial inflammatory cell infiltrates and systemic allergic symptoms
Are the histopathlogical features of what cardiac malformation?
HYPERSENSITIVITY MYOCARDITIS
72
mechanism of Toxic Myocarditis
Direct myocyte cytotoxicity
73
causative agents of Toxic Myocarditis
Cyclophoshamide, *Doxorubicin, Catecholamines, Cocaine, Fluorouracil, Lithium
compounds
74
Histopathology:
* Lymphocytes
* **Neutrophils**
* **Pyknotic debris**, associated with myocyte damage
Are the features of what heart condition?
Toxic Myocarditis
75
Causes of Hydropericardium
Congestive heart failure, Hypoproteinaemia (Nephrotic syndrome), Chronic liver disease
76
Causes of Haemopericardium
Traumatic perforation of heart or aorta,
myocardial rupture after acute myocardial
infarction
77
Haemopericardium vs Hydropericardium:
Hydropericardium: Accumulation of serous transudate in pericardium
Haemopericardium: Accumulation of blood in pericardium
78
Causes of Acute Pericarditis
1) Infectious
➢ Bacterial [Gram (+), Gram (-) bacteria, Mycobacteria, Spirochetes]
➢ Fungal, Viral, Parasitic
2) idiopathic
3) Post-myocardial infarction
4) Iatrogenic (postsurgical, radiation therapy, drug reaction)
5) Metastatic neoplasm
6) Systemic disease (autoimmune, renal failure, endocrine)
7) Traumatic
79
causes of Serous Pericarditis:
SLE, Rheumatic Fever and Viral infections
80
Macro-/Microscopic picture:
**Clear, straw-colored, protein-rich exudate** with a few inflammatory cells
are the features of what cardiac defect?
ACUTE PERICARDITIS
81
causes of Fibrinous or Sero-Fibrinous Pericarditis:
: Uraemia, Myocardial infarction, Acute
Rheumatic Fever
82
* Macro-/Microscopic picture:
Fibrin-rich exudate
are the features of what cardiac defect?
Fibrinous or Sero-Fibrinous Pericarditis
83
causes of Purulent or Suppurative Pericarditis:
Bacterial infection
84
Macro-/Microscopic picture:
Cloudy or frankly purulent inflammatory exudate
are the features of what cardiac disease?
Purulent or Suppurative Pericarditis
85
causes of Haemorrhagic Pericarditis
Tumour invasion of the pericardium, Tbc
or other bacterial infections
86
Macro-/Microscopic picture:
Bloody inflammatory exudate
are the features of what cardiac malformation?
Haemorrhagic Pericarditis
87
Causes of Chronic/Constrictive Pericarditis
1) Idiopathic
2) Following episode of acute pericarditis
3) Infectious (Mycobacteria [e.g. Tbc], fungal)
4) Post-surgical (including transplantation)
5) Systemic disease (autoimmune, renal failure)
6) Radiation therapy
7) Neoplasms (usually metastatic tumours)
88
pathogenesis of chronic (constrictive) pericarditis
* Organisation of an acute pericarditis and healing with dense fibrosis and calcifications →
Results in a thickened, scarred pericardium →
Loss of elasticity → Inability of pericardium to stretch → Interference with cardiac action and venous return (mimics right-sided heart failure)
89
Macro-/Microscopic picture:
proliferation of fibrous tissue and focal calcification
Are the features of what heart condition
Chronic (Constructive) Pericarditis
90
what heart malformation has the follwing characteristics :
**“scintillating (sparkling) gold paint appearance”**, due to the cholesterol crystals in the fluid
Idiopathic cholestrol pericarditis
91
Idiopathic Cholesterol pericarditis has been associated with?
1) Hypothyroidism,
2) Rheumatoid Arthritis, and
3) Tuberculosis
4) recurrent pericardial effusions
