Pathology-II

PD-505
1

D R . S H U M A I L A A M A N , R.PH., PH.D.
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACOLOGY
 Pathological Basis of :
2

1. Cardiovascular System and

Blood Diseases
2. Central Nervous System
Diseases
3. Respiratory Tract Diseases
4. Infectious Disease
5. Neoplasia
 Reference Books
3

 Kumar Cortan Robin, Basic Pathology W. B.

Saunders, Company Philadelphia.
 Pathological Basic of Diseases, Robbins and
Cotran
 Rubin’s Pathology, by Emanuel Rubin,
Wolters Kluwer Publisher.
 Walters and Israel, General Pathology,
Churchill Livingstone, London.
 Diseases of
Cardiovascular System
4

LEC # 1
Diseases of Cardiovascular System
5

 A. Blood vessels (Vascular Diseases)

1. Hypertensive Vascular Disease
2. Arteriosclerosis and Atherosclerosis
3. Vasculitis
4. Aneurysms
 B. Heart
1. Heart failure (CHF)
2. Ischemic heart disease
3. Angina
4. Myocardial infarction
5. Arrhythmias
 C. Blood
1. Anemia
2. Bleeding disorders
 Overview of Cardiac
Structure and Function
6
 Anatomy
7

 The Heart resides in the:

 anterior Mediastinum,
 behind the Sternum,
 slightly left of midline,
 surrounded by the Lungs,
 in a sac called the Pericardium

 The heart is normally about the size of a clenched

fist, and weighs 250-300 grams in females and 300-
350 grams in males
 Parts of the Adult Heart
8

1. Coronary Arteries

2. Heart Valves

3. Conducting System

4. Myocardium
1- Coronary Arteries
10
 Mechanism
15

 Normal Regulation of Blood Pressure

 In both normal and hypertensive individuals

 BP = CO × PVR
 CO -- cardiac output
 PVR-- peripheral vascular resistance

 Anatomic sites:
 Arterioles
 Postcapillary venules (capacitance vessels)
 Heart
 Kidney
 Mechanism
16
 Autonomic nerves:
 Baroreflexes:
1. Postural: central sympathetic neurons arising from the vasomotor area of the medulla
2. Carotid: stretch of the vessel walls the internal pressure (arterial blood pressure).

 Renin-angiotensin-aldosterone system

 Vasopressin from posterior pituitary

 Local release of vasoactive substances from vascular endothelium:

endothelin-1 constricts, nitric oxide dilates

 In hypertensive patients baroreceptors and the renal blood volume-

pressure control systems appear to be “set” at a higher level of blood
pressure.
 Hypertensive
vascular/heart disease
19
 Objectives
20

 Provides the basis for understanding:

1. The mechanism of disease

2. The classification of diseases
3. The diagnosis of diseases
4. The basis of treatment
5. Monitoring the progress of disease
6. Determining prognosis
7. Understanding complications
Intoduction to HTN
21
 Hypertensive vascular/heart disease
22
Epidemiology
 Most common
cardiovascular disease
 Marked geographical and
racial variability
 Prevalence varies with
age, race, education and
other variables
 Incidence thought to be
as high as 25 – 30% in
western countries
Aetiology
 95% are of unknown causes
 5% of cases are due to
 chronic kidney disease
 pheochromocytoma
 adrenal cortical adenoma
 coarctation of aorta
 pregnancy
 contraceptive pills
 Obesity
 Alcohol
 Stress
 Cont..
23

 Single-gene disorders:
 cause hypertension (and hypotension) by affecting renal
sodium resorption.

1. Gene defects in enzymes involved in aldosterone

metabolism
 aldosterone synthase, 11β-hydroxylase, 17α-hydroxylase: leading to
increased aldosterone secretion, increased salt and water resorption,
and plasma volume expansion
2. Mutations in proteins that affect sodium resorption
 Liddle syndrome: caused by mutations in ENaC, leading to increased
distal tubular resorption of sodium induced by aldosterone
Classification
24
Classification of hypertension on the
basis of blood pressure
25

Ref: Joint National Committee on prevention, detection, evaluation,

and treatment of high blood pressure. JAMA 2003;289:2560.
 Classification of hypertension on the
basis of Etiology
26

Primary/Essential
Secondary Hypertension
Hypertension

 Cause unknown in 90 to 95% of  5 to 10% cases

cases  Kidney Abnormalities
 No underlying medical illness  Narrowing of renal arteries
 Multifactorial (atheromatous plaque) –
 Multiple genetic polymorphisms & renovascular HTN
interacting environmental factors,
psychological factors  Rare tumors
 Dietary , increased salt, decreased  Adrenal gland abnormalities
sodium and potassium (Conn’s syndrome, Cushing
 Controlled = compatible & syndrome,
asymptomatic unless MI, pheochromocytoma)
cerebrovascular accident etc  Pregnancy
supervenes
 Drugs
27
 Malignant HTN / Malignant HTN Syndrome
28

 Accelerated HTN
 Uncommon clinical syndrome (5%)
 Severe HTN

 (SP> 200 mm Hg, DP> 120 mm Hg)

 Small vessel damage

 Renal failure

 Retinal hemorrhages (papilledema)

 Hypertensive encephalopathy

 Normotensive or pre-existing benign HTN

Mechanisms of Essential Hypertension
29

 Reduced renal sodium excretion: Decreased sodium excretion causes an

obligatory increase in fluid volume and increased cardiac output, thereby elevating
blood pressure (Fig. 9–3). At the new higher blood pressure, the kidneys excrete
additional sodium. Thus, a new steady state of sodium excretion is achieved, but at
the expense of an elevated blood pressure.

 Increased vascular resistance may stem from vasoconstriction or

structural changes in vessel walls: chronic vasoconstriction may result in
thickening of the walls of vessels and reduced lumen. Large vessel collagen increase,
calcium deposition

 Genetic factors: Hypertension has been linked to specific angiotensinogen

polymorphisms and angiotensin II receptor variants; polymorphisms of the renin-
angiotensin system also may contribute to the known racial differences in blood
pressure regulation. Susceptibility genes for essential hypertension in the larger
population are currently unknown but probably include those that govern renal
sodium handling, pressors, and smooth muscle cell growth.

 Environmental factors: such as stress, obesity, smoking, physical inactivity, and

high levels of salt consumption, modify the impact of genetic determinants
 Diagnosis
30

 CLINICAL PICTURE
 Repeated, reproducible measurements of elevated blood
pressure
 Usually NO SYMPTOMS!
 The Silent Killer
 May have:
 Headache
 Blurry vision
 Chest Pain
 Frequent urination at night
 Most patients are asymptomatic and diagnosed when blood
pressure is measured
 Other present with symptoms related to end organ damage
caused by the hypertension e.g., intracerebral haemorrhage, left
ventricular failure, chronic kidney disease
Investigations
31
Hypertensive heart
disease
32
 Pathology
33

 Hypertensive heart disease:

 Cardiac complications of hypertension, which result from
pressure overload (vascular) or ventricular hypertrophy
(heart)
 Causes compensatory left ventricular hypertrophy
because of increased cardiac workload
 Left ventricular wall and intraventricular septum
thickened, thickness can exceed 2.0 cm (normal, 1.2 to
1.4 cm)
 The heart weight can exceed 500 g (normal: 320 to 360
g)
 Myocardial cells increase in diameter, enlarged,
hyperchromatic, rectangular nuclei
 34

 1- Systemic (Left-Sided) Hypertensive

Heart Disease

 2- Pulmonary Hypertensive Heart

Disease—Cor Pulmonale
 1- Systemic (Left-Sided) Hypertensive
Heart Disease
35

 Diagnosis
1. left ventricular hypertrophy
2. a history or pathologic evidence of hypertension
(even mild hypertension (above 140/90 mm Hg), if
sufficiently prolonged, induces)
Left ventricular hypertrophy
36
 Symptoms
37

 Left ventricular hypertrophy progresses, with

symptoms:

 Shortness of breath
 Fatigue
 Chest pain, often after exercising
 Sensation of rapid, fluttering or pounding heartbeats
(palpitations)
 Dizziness or fainting
 Causes
38

 Increase in the size of heart muscle cells

 abnormal tissue around the heart muscle cells.

 Factors that can cause your heart to work harder include:

 High blood pressure (hypertension)
 Aortic valve stenosis. narrowing of the aortic valve requires the left
ventricle to work harder to pump blood into the aorta.
 Athletic training. Intense, prolonged endurance and strength training
can cause the heart to adapt to handle the extra workload, can lead to
stiffening of the heart muscle and disease.
 Abnormalities in heart muscle cell structure that result in increased heart
wall thickness include:
 Hypertrophic cardiomyopathy. This genetic disease occurs when the
heart muscle becomes abnormally thick, even with completely normal
blood pressure
 Amyloidosis. A condition that causes abnormal protein deposits around
the organs, including the heart
 Clinical features
39

 As a result of these changes, complications of left ventricular

hypertrophy include:
 Reduced blood supply to the heart
 Inability of the heart to pump enough blood to your body
(heart failure)
 Abnormal heart rhythm (arrhythmia)
 Irregular, often rapid heartbeat that increases the risk of
stroke
 Insufficient supply of oxygen to the heart (ischemic heart
disease)
 Stroke
 Sudden, unexpected loss of heart function, breathing and
consciousness (sudden cardiac arrest)
 40

 The mechanisms by which hypertension leads to

heart failure are incompletely understood
 Hypertrophic myocytes fail to contract efficiently,
possibly due to structural abnormalities in newly
assembled sarcomeres
 Vascular supply is inadequate to meet the demands
of the increased muscle mass
 2- Pulmonary Hypertensive Heart
Disease—Cor Pulmonale
41

 Cor pulmonale consists of right ventricular

hypertrophy and dilation
 Accompanied by right heart failure
 Caused by pulmonary hypertension attributable to
primary disorders of the lung parenchyma or
pulmonary vasculature
 Can be acute in onset, or can have a slow and
insidious onset
 42

 Acute cor pulmonale is an abrupt occurrence of pulmonary

hypertension
 Commonly due to sudden, massive pulmonary embolization.
 This condition causes acute right sided heart failure and is a
medical emergency.
 At autopsy, the only cardiac findings are severe right ventricular,
and sometimes right atrial, dilation.

 Chronic cor pulmonale is a common heart disease,

 Prevalence of lung disease, chronic bronchitis and emphysema.
 Pathology
43

 Chronic cor pulmonale is characterized by right

ventricular hypertrophy
 May exceed 1.0 cm in thickness (normal, 0.3–0.5
cm).
 Right ventricular and right atrial dilatation are
present.
 Interventricular septum is concave to the left (i.e., it
is part of the left ventricle).
 When right ventricular hypertrophy is severe, the
interventricular septum remodels by straightening or
even becoming concave to the right.
 Hypertensive heart disease
44
 Systemic (left-sided) hypertensive  Chronic cor pulmonale
heart disease  right ventricle dilated and
 thickening of the left ventricular hypertrophied with a thickened
wall free wall
 left atrial dilation
 45

This left ventricle is

very thickened
(slightly over 2 cm
in thickness), but
the rest of the heart
is not greatly
enlarged.
This is typical for
hypertensive
heart disease.
The hypertension
creates a greater
pressure load on
the heart to induce Pathology
the hypertrophy.
 46

Left:
normal myocardium

Right:
1-hypertrophic
myocardium, thicker
fibers
2-Enlarged hyper
chromatic, rectangular
nuceli
Microscopically, the
transverse diameter of
myocytes is increased
and there is prominent
nuclear enlargement
and hyperchromasia Hypertensive heart disease with
(“boxcar nuclei”), as
well as intercellular myocardial atrophy
fibrosis
 47

Main pathologic findings:

• Increase in heart mass

caused principally by
left ventricular
hypertrophy.
• Histologically, the
individual myocytes
are enlarged and show
nucleomegaly (“box
car” nuclei).
Hearts that are enlarged
secondary to
hypertension have an
increased incidence of
arrhythmia and death.
 Clinical Feature
48

 Hypertrophy aids ability of heart to increase

workload, but to a limit, beyond which no
compensate
 Increased cardiac workload (systolic dysfunction)
 Diastolic dysfunction, leads to CHF
 Interstitial fibrosis, leads to LV stiffness
 Increased severity of atherosclerosis
 Prognosis
49

 Untreated or undertreated disease increase the risk

of left ventricular failure, intracerebral hemorrhage,
chronic kidney disease, aortic aneurysm
 CHF is the most common cause of death in untreated
HT patients
 Fatal intracerebral hemorrhage
 Coronary atherosclerosis
 Myocardial infarction
 Renal failure by nephrosclerosis
Treatment
50
 Treatment
51

 Effective pharmacologic lowering of blood pressure

has been shown to prevent damage to blood vessels
and to substantially reduce morbidity and mortality
rates.
 Diet control, low sodium intake
 Physical exercise
 Stress control
 Medication for High Blood Pressure
52
 Diuretics
 Sympatholegics:
1. Centrally acting: Methyldopa, clonidine
2. Adrenergic neuron blockers: guanethidine
3. Ganglion blockers: abandonment

 Adrenoceptor antagonist
1. Beta-blockers: propranolol, atenolol, pindolol, esmolol
2. Alpha blockers: prazosin, terazosin, phentolamine

 Vasodilators: hydralazine, minoxidil

 Calcium channel blockers: verapamil, diltiazem, dihydropyridines

 Inhibitors of angiotensin
1. ACE inhibitors: captopril
2. Angiotensin receptor blocker: losartan, valsartan
 References
53

 https://www.mayoclinic.org/diseases-
conditions/left-ventricular-hypertrophy/symptoms-
causes/syc-20374314
 https://www.medscape.com/answers/241381-
7644/what-are-the-main-pathologic-findings-of-
hypertension-high-blood-pressure
 Robbins Basic Pathology
 Pathologic Basis of Diseases