PATHOLOGY CRASH

COURSE

2nd prof MBBS University

exams
Dr. PRIYANKA SACHDEV , MD
 2nd prof MBBS University exams

•Long and short Question discussion

Dr. PRIYANKA SACHDEV

SYSTEMIC PATHOLOGY

Dr. PRIYANKA SACHDEV , MD

 CVS

Dr. PRIYANKA SACHDEV , MD

 ENDOCARDITIS
• Endocarditis is an inflammation of the inner layer of the heart,
i.e. endocardium

• Usually involve the heart valves (native or prosthetic).

• Other structures which may be involved are interventricular
septum, chordae tendinae, the mural endocardium, and
intracardiac devices

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
1. Rheumatic fever and rheumatic heart
disease (Endocarditis)

2. Non-rheumatic endocarditis

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Rheumatic fever &
rheumatic heart disease
Rheumatic fever

Dr. PRIYANKA SACHDEV

 OVERVIEW
• Introduction
• Etiology
• Pathogenesis
• Jones criteria
• Revised Jones criteria

• 1. Rheumatic heart disease (Heart)

• 2. Polyarthritis (Joints)
• 3. Sydenham’s chorea (Brain)
• 4. Erythema marginatum (Skin)
• 5. Subcutaneous nodules (Subcutaneous tissue)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Rheumatic fever

• Rheumatic fever (RF) is a systemic, post-streptococcal,

nonsuppurative inflammatory disease, principally
affecting the heart, joints, central nervous system, skin
and subcutaneous tissues.

Dr. PRIYANKA SACHDEV

 Rheumatic Fever
•Rheumatic fever (RF) is an acute, immunologically mediated,
multisystem inflammatory disease that occurs a few weeks
following an episode of group A streptococcal pharyngitis.

•Major involvement of systemic connective tissue, it often

violate connective tissue of heart, joint, skin, and
subcutaneous and CNS

•Key pathologic features is Rheumatic Granuloma.

Dr. PRIYANKA SACHDEV

 PATHOGENESIS
It is an autoimmune response associated with
streptococcal infection, but it is not caused by bacteria
directly effects

Dr. PRIYANKA SACHDEV

 A susceptible host

Group A Streptococcus infection (pharyngitis)

Antibodies are formed

These act as autoantibodies

These antibodies cause damage to human tissues due to cross-

reactivity between epitopes in bacteria and the host tissue
(N-acetyl glucosamine)
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• Molecular mimicry and cross-reactivity between
streptococcal M protein and the human endogenous
molecules forms the basis of autoimmune damage to
human target tissues in RHD

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JONES CRITERIA

Dr. PRIYANKA SACHDEV

 Major criteria:

•1. Carditis → Rheumatic heart

disease (Heart)
•2. Polyarthritis (Joints)
•3. Sydenham’s chorea (Brain)
•4. Erythema marginatum (Skin)
•5. Subcutaneous nodules
(Subcutaneous tissue)
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Dr. PRIYANKA SACHDEV
 Minor criteria
•1. Fever
•2. Arthralgia
•3. Previous history of RF
•4. Laboratory findings of elevated ESR,
raised C-reactive protein, and leucocytosis
•5. ECG finding of prolonged PR interval.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Revised Jones Criteria 2015
MAJOR Manifestations MINOR Manifestations GAS Infection

Carditis Fever GAS on Throat swab

(Culture)
Arthritis Arthralgia Anti-streptolysin O
titre (ASOT)
Sydenham’s Chorea ↑ PR interval on ECG Anti-
deoxyribonuclease B
(Anti-DNase B)
Erythema ESR ≥30mm/hr or CRP
marginatum ≥30mg/L
Subcutaneous
nodules
Dr. PRIYANKA SACHDEV
 Revised Jones Criteria

•2 MAJOR manifestations
OR
• 1 MAJOR and 2 MINOR manifestations

• Evidence of preceding Group A streptococcal infection (within

3 weeks before ARF symptoms)

Dr. PRIYANKA SACHDEV

Rheumatic heart disease

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Introduction

•The chronic stage of RF involves all the

layers of the heart (pancarditis) causing
major cardiac sequelae referred to as
rheumatic heart disease (RHD).

•The cardiac lesions of RF in the form of

pancarditis
Dr. PRIYANKA SACHDEV
• Rheumatic endocarditis
• Rheumatic myocarditis
• Rheumatic pericarditis

60% to 80% children associated with

pancarditis

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Dr. PRIYANKA SACHDEV
 PANCARDITIS

Endocarditis Myocarditis Pericarditis

Valvular Mural Aschoff bodies

Vegetations MacCallum’s patch Fibrinous pericarditis

(Verrucae) (Bread and butter)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Vegetations or Verrucae
•Small (1 to 3 mm in diameter)
•Multiple
•warty
•Soft and firm
•Sterile, bland

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Small vegetations (verruca) are visible along the line
of closure of the mitral valve leaflet (arrows).

Dr. PRIYANKA SACHDEV

 Valves
•Mitral alone = 37% cases.
•Mitral + aortic = 27% cases.
•Mitral + aortic + tricuspid = 22% cases.
•Mitral + tricuspid = 11% cases.
•Aortic alone = 2%.
•Mitral + aortic + tricuspid + pulmonary =
less than 1%
Dr. PRIYANKA SACHDEV
•Location → chiefly along the line of
closure of the leaflets and cusps.

•Deformity →Chronic healed mitral valve

in RHD is characteristically ‘fish mouth’
or ‘button hole’ stenosis.
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Mitral stenosis with diffuse fibrous thickening and distortion of
the valve leaflets, commissural fusion (arrows), and thickening
and shortening of the chordae tendineae.

Dr. PRIYANKA SACHDEV

Advanced: vegetations organization, recurrent organization cause
chronic heart valve disease ( valvular stenosis and / or valvular
insufficiency )

Dr. PRIYANKA SACHDEV

Mitral stenosis with diffuse fibrous thickening and distortion of
the valve leaflets, commissural fusion (arrows), and thickening
and shortening of the chordae tendineae.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 PANCARDITIS

Endocarditis Myocarditis Pericarditis

Valvular Mural Aschoff bodies

Vegetations MacCallum’s patch Fibrinous pericarditis

(Verrucae) (Bread and butter)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 PANCARDITIS

Endocarditis Myocarditis Pericarditis

Valvular Mural Aschoff bodies

Vegetations MacCallum’s patch Fibrinous pericarditis

(Verrucae) (Bread and butter)

Dr. PRIYANKA SACHDEV

 Microscopically
•The most characteristic feature is the
presence of distinctive Aschoff bodies.

•Aschoff bodies are pathogmatic of RHD

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Dr. PRIYANKA SACHDEV
 Aschoff bodies→

Granulomas with →

1. Central fibrinoid necrosis

2. Surrounded by palisade of Anitschkow cells and
multinucleate Aschoff cells.
3. There is infiltration by lymphocytes, plasma cells and
fibroblast

• Neutrophils (polymorphonuclear cells) are characteristically

absent
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• Aschoff cells→ Some of the larger macrophages
become multinucleated to form inflammatory giant
cells

• Anitschkow cells→ Modified macrophages having

abundant cytoplasm and central round-to-ovoid
nuclei in which the chromatin is disposed in a central,
slender, wavy ribbon (hence the designation
"caterpillar cells/ Owl 's eye cells).

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 RHEUMATIC PERICARDITIS

•The usual finding is fibrinous

pericarditis
•Two separated surfaces are shaggy due
likened to ‘bread and butter
appearance’

Dr. PRIYANKA SACHDEV

 PANCARDITIS

Endocarditis Myocarditis Pericarditis

Valvular Mural Aschoff bodies

Vegetations MacCallum’s patch Fibrinous pericarditis

(Verrucae) (Bread and butter)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Adhesive pericardit is in cardiac surface
of patients. From the epicardial surface
to the pericardial sac visible fibrinous
exudate, which is typical for a fibrinous
pericarditis.

Dr. PRIYANKA SACHDEV

FINALLY…

Dr. PRIYANKA SACHDEV

 PANCARDITIS

Endocarditis Myocarditis Pericarditis

Valvular Mural Aschoff bodies

Vegetations MacCallum’s patch Fibrinous pericarditis

(Verrucae) (Bread and butter)

Dr. PRIYANKA SACHDEV

 ENDOCARDITIS

•Endocarditis is an inflammation of the

inner layer of the heart, i.e.
endocardium

Dr. PRIYANKA SACHDEV

TYPES

Dr. PRIYANKA SACHDEV

1. Rheumatic fever and rheumatic heart
disease (Endocarditis)

2. Non-rheumatic endocarditis

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Non-rheumatic endocarditis

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Dr. PRIYANKA SACHDEV
 ATYPICAL VERRUCOUS
(LIBMAN-SACKS) ENDOCARDITIS

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 OVERVIEW
Introduction

Gross→

a) Vegetations or Verrucae
b) Valves
c) Location
d) Deformity

Microscopy
Dr. PRIYANKA SACHDEV
 Introduction

•It is one of the manifestations of

‘collagen diseases’

•Characteristic lesions of Libman-Sacks

endocarditis are seen in 50% cases of
systemic lupus erythematosus (SLE)
Dr. PRIYANKA SACHDEV
 Grossly
•Characteristic vegetations

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Dr. PRIYANKA SACHDEV
• The vegetations of atypical verrucous endocarditis
are

• Medium sized (1 to 4 mm in diameter)

• Multiple
• FLAT
• Granular
• Sterile, bland
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•Valve → occur most frequently on the
mitral and tricuspid valves

•Location → occur on both surfaces of

affected valves, in the valve pockets and
on the adjoining ventricular and atrial
endocardium.
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Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
1. Rheumatic fever and rheumatic heart
disease (Endocarditis)

2. Non-rheumatic endocarditis

Dr. PRIYANKA SACHDEV

NON-BACTERIAL THROMBOTIC
(CACHECTIC, MARANTIC)
ENDOCARDITIS (NBTE)

Dr. PRIYANKA SACHDEV

 Introduction
• Non-bacterial thrombotic,endocarditis is an
involvement of the heart valves by sterile
thrombotic vegetation

• Seen in patients having hypercoagulable state

from various etiologies e.g. advanced cancer (in
50% case of NBTE) especially mucinous
adenocarcinomas, chronic tuberculosis, renal
failure and chronic sepsis

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Grossly
•Vegetations/ verrucae of NBTE→

•Small (1 to 5 mm in diameter),
•Single or multiple,
•Brownish
•More friable than the vegetations of
RHD.
•Sterile, bland
Dr. PRIYANKA SACHDEV
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•Valves → chiefly mitral, and less often aortic
and tricuspid valve.

•Location → Occur along the line of closure of

the leaflets

•Deformity → Organised and healed

vegetations appear as fibrous nodules
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
1. Rheumatic fever and rheumatic heart
disease (Endocarditis)

2. Non-rheumatic endocarditis

Dr. PRIYANKA SACHDEV

INFECTIVE (BACTERIAL)
ENDOCARDITIS

Dr. PRIYANKA SACHDEV

 OVERVIEW
Introduction
Types
Etiology
Predespositing factors
Pathogenesis
Gross→
a) Vegetations or Verrucae
b) Valves
c) Location
d) Deformity

Microscopy
Complications
Modified Duke criteria

Dr. PRIYANKA SACHDEV

INFECTIVE (BACTERIAL) ENDOCARDITIS
•Infective or bacterial endocarditis (IE or BE) is
serious infection of the valvular and mural
endocardium caused by different forms of
microorganisms

•Characterised by typical infected and friable

vegetations
Dr. PRIYANKA SACHDEV
 Types

1. Acute bacterial endocarditis (ABE)

2. Subacute bacterial endocarditis

(SABE) or endocarditis lenta (lenta =
slow)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
1. Acute bacterial endocarditis (ABE)

•Caused by highly virulent bacteria (staph

aureus)

•In a previously normal heart

•Runs a rapidly fatal course in a period of 2-6

weeks
Dr. PRIYANKA SACHDEV
2. Subacute bacterial endocarditis (SABE)
or endocarditis lenta (lenta = slow)

•Caused by less virulent bacteria (strep viridians)

•In a previously diseased heart

•Has a gradual downhill course in a period of 6

weeks to a few months and sometimes years.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 ETIOLOGY
• Infective agents About 90% cases of
BE are caused by streptococci and
staphylococci.

Dr. PRIYANKA SACHDEV

• In ABE→ the most common causative organisms are virulent
strains of staphylococci, chiefly Staphylococcus aureus

• In SABE →the commonest causative organisms are the

streptococci with low virulence, predominantly
Streptococcus viridans

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 REMEMBER
•VSD is the most common congenital
heart disease involved in infective
endocarditis.

•Infective endocarditis is rare in ASD

Dr. PRIYANKA SACHDEV

 Grossly
•The vegetations in SABE are more often
seen on previously diseased valves

•The vegetations of ABE are often found

on previously normal valves

Dr. PRIYANKA SACHDEV

 The vegetations are→

•Large
•Grey-tawny to greenish,
•Irregular,
•Single or multiple
•Typically friable
• The vegetations in ABE tend to be bulkier
and globular than those of SABE
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•Valve → The lesions are found most
frequently on the

Mitral > aortic > both mitral and aortic

valves > rarely on the valves of the right
heart.
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Dr. PRIYANKA SACHDEV
 REMEMBER
•Most commonly involved valve in
endocarditis is mitral valve.

•In intravenous drug users →Tricuspid valve

is most commonly involved valve

•In prosthetic valve endocarditis→ Aortic

valve is the most commonly affected valve
Dr. PRIYANKA SACHDEV
•Location → atrial surface of atrioventricular
valves and ventricular surface of the
semilunar valves
•(Upper surfaces of cusps)

•They begin from the contact areas of the

valve and extend along the surface of the
valves and on to the adjacent endocardium
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 Deformity →

•Ulceration or perforation of the

underlying valve leaflet
•Myocardial abscesses

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 REMEMBER

•Most destructive vegetations are of

infective endocarditis

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Dr. PRIYANKA SACHDEV
Modified Duke criteria

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Dr. PRIYANKA SACHDEV
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Dr. PRIYANKA SACHDEV
Blood vessels
Dr. PRIYANKA SACHDEV , MD
Dr. PRIYANKA SACHDEV
HYPERTENSIVE ARTERIOLOSCLEROSIS

•Hypertension is the term used to describe

an elevation in blood pressure

•Hypertension can cause end-organ

damage and is one of the major risk
factors for atherosclerosis
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•A small percentage of hypertensive persons
(5%) show a rapidly rising blood pressure
that, if untreated, leads to death within 1 to
2 years.
•This form of hypetension, called malignant
hypertension

•Characterized by severe hypertension (i.e.,

systolic pressure more than 200 mm Hg,
diastolic pressure more than 120 mm Hg),
Dr. PRIYANKA SACHDEV
Vascular Pathology in Hypertension

1. Hyaline arteriolosclerosis
2. Hyperplastic arteriolosclerosis
3. Necrotising arteriolitis

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Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
HYALINE ARTERIOLOSCLEROSIS
•In moderate hypertension , the visceral
arterioles are particularly involved.

Dr. PRIYANKA SACHDEV

 MORPHOLOGIC FEATURES
•The vascular walls are thickened and the
lumina narrowed or even obliterated.

•The thickened vessel wall shows

structureless, eosinophilic, hyaline material
in the intima and media
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 HYPERTENSIVE
ARTERIOLOSCLEROSIS
1. Hyaline arteriolosclerosis,
2. Hyperplastic arteriolosclerosis
3. Necrotising arteriolitis.

Dr. PRIYANKA SACHDEV

 HYPERPLASTIC ARTERIOLOSCLEROSIS

•Characteristic lesion of malignant

hypertension

Dr. PRIYANKA SACHDEV

 MORPHOLOGIC FEATURES
Onion-skin lesion
•consists of loosely-placed concentric layers
(laminated)of hyperplastic intimal smooth
muscle cells like the bulb of an onion.

•The basement membrane is also thickened

and reduplicated
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Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 HYPERTENSIVE
ARTERIOLOSCLEROSIS
1. Hyaline arteriolosclerosis
2. Hyperplastic arteriolosclerosis
3. Necrotising arteriolitis

Dr. PRIYANKA SACHDEV

 NECROTISING ARTERIOLITIS

•In cases of severe hypertension and

malignant hypertension, parts of small
arteries and arterioles show changes of
hyaline sclerosis and parts of these show
FIBRINOID necrosis, or necrosis may be
superimposed on hyaline sclerosis.
Dr. PRIYANKA SACHDEV
 MORPHOLOGIC FEATURES
•Besides the changes of hyaline sclerosis,
the changes of necrotising arteriolitis
include →

[Link] necrosis of vessel wall

[Link] inflammatory infiltrate of
neutrophils in the adventitia.
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Dr. PRIYANKA SACHDEV
 ATHEROSCLEROSIS

•Atherosclerosis is an thickening and

hardening of large and medium-sized
muscular arteries, primarily due to
involvement of tunica intima

Dr. PRIYANKA SACHDEV

•It is characterised by fibrofatty plaques or
atheromas /atheromatous / atherosclerotic
plaques protrude into vessel lumens.

•An atheromatous plaque consists of a raised

lesion with a soft core of lipid (mainly
cholesterol and cholesterol esters) covered
by a fibrous cap
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Most commonly affected arteries
•The most commonly affected arteries are →

•Abdominal aorta > Coronaries

(LAD>RCA>LCX) > Poplitial > Descending
thorasic > Internal carotid> cerebral
arteries(circle of willis)
Dr. PRIYANKA SACHDEV
MNEMONIC

Dr. PRIYANKA SACHDEV

 ETIOLOGY

1. Non modifiable risk factors

2. Modifiable risk factors
3. Emerging risk factors

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Dr. PRIYANKA SACHDEV
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Dr. PRIYANKA SACHDEV
 PATHOGENESIS
•The most acceptable hypothesis for the
pathogenesis of atherosclerosis is “the
response to injury hypothesis / Reaction-
to-Injury Hypothesis”

•According to this hypothesis,

atherosclerosis is a chronic inflammatory
response of the arterial wall initiated by
injury to endothelium
Dr. PRIYANKA SACHDEV
 Reaction-to-Injury Hypothesis
• Following steps →

• 1) Endothelial injury
• 2) Migration of leukocytes
• 3) Smooth muscle cell migration and proliferation
• 4) Maturation of plaque

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 1) Endothelial injury
•Injury to endothelium is the cornerstone in
the development of atherosclerosis.

•After injury, endothelium is activated and

there is increased expression of adhesion
molecule-VCAM-1 and there is increased
permeability to endothelium. TNF is the
major cytokine to induce this expression.
Dr. PRIYANKA SACHDEV
 Etiological culprits

Endothelium injury and /or dysfunction

Endothelium is activated

Release of TNF

There is increased expression of adhesion molecule- VCAM-1

Increased permeability to endothelium

With chronic hyperlipidemia, lipoproteins accumulate within the intima

Dr. PRIYANKA SACHDEV

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2) Migration of leukocytes

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 When VCAM-1 is expressed on endothelium

Leukocytes (monocytes and T lymphocytes) adhere to the

endothelium.

Leukocytes (monocytes and T lymphocytes) than cross the

endothelial barrier

Monocytes begin to accumulate in subendothelial intimal space

Become macrophages

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Activated macrophages form oxygen free radicals

Cause oxidation of LDL

Oxidized LDL (modified LDL)

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Oxidized LDL (modified LDL)

Ingested by macrophages (scavenger receptors)

Form foam cells (fatty streak)

Growth factors/cytokines
Toxic to smooth muscle and endothelium

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3) Smooth muscle cell migration and
proliferation

Dr. PRIYANKA SACHDEV

 Inflammatory cells (monocytes and T lymphocytes) in
subendothelial intimal space

Secrete cytokines, mainly PDGF, TGF-α and FGF

Migration of smooth muscle cells from media to subendothelial

intimal space

Proliferation of smooth muscle cells in intima

Smooth muscle cell also ingest lipid

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4) Maturation of plaque

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 Smooth muscle cells synthesize extracellular matrix
(especially collegen) in the intima

Convert a fatty streak into a mature fibrofatty atheroma

Progressive growth of atherosclerotic lesions.

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Dr. PRIYANKA SACHDEV
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REVISION

Dr. PRIYANKA SACHDEV

 Reaction-to-Injury Hypothesis
• Following steps →

• 1) Endothelial injury
• 2) Migration of leukocytes
• 3) Smooth muscle cell migration and proliferation
• 4) Maturation of plaque

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
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 Stages of development of
atheromatous plaque
•1. Type I (Initial/Fatty dot) lesion
•2. Type II lesion (fatty streaks)
•3. Type III (intermediate) lesion
•4. Type IV (atheroma) lesion
•5. Type V lesion (fibroatheroma or mature
atherosclerosis)
•6. Type VI (complicated) lesion
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Dr. PRIYANKA SACHDEV
 ISCHAEMIC HEART DISEASE/
Coronary artery disease (CAD)

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 Introduction

•Ischaemic heart disease (IHD) arise

from Imbalance between the
myocardial supply and demand for
oxygenated blood.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Blood supply of heart

1) Left anterior descending (LAD) artery

2) Left circumflex (LCX) artery
3) Right coronary artery

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Coronary artery

Left coronary artery Right coronary artery

LAD LCX
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Dr. PRIYANKA SACHDEV
 1) Left anterior descending (LAD)
artery
• It is a branch of left coronary artery
• supplies →
1. Apex
2. Anterior wall of left ventricle
3. Anterior two-third of ventricular septum.

• LAD artery is the most commonly involved artery in

atherosclerosis thus these sites are the most
common site of myocardial infarction
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 2) Left circumflex (LCX) artery

•It is a branch of left coronary artery

•supplies →
1. Lateral wall of left ventricle

•It is the least commonly involved site for

MI
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Dr. PRIYANKA SACHDEV
 3) Right coronary artery (RCA)

It supplies→
1. Posterior wall of left ventricle
2. Right ventricular free wall
3. Posterior one-third of ventricular septum

•It is the second most commonly involved

vessel in atherosclerosis and MI.
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Dr. PRIYANKA SACHDEV
Distribution→ (LAD) > (RCA) > (CXA)
• One-third of cases have single-vessel disease ie. LAD
involvement;
• Another one-third have two-vessel disease
• The remainder has three major vessel disease

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
EFFECTS OF IHD

Dr. PRIYANKA SACHDEV

ANGINA PECTORIS

Dr. PRIYANKA SACHDEV

 HEADINGS
•Definition
•Types

Dr. PRIYANKA SACHDEV

 ANGINA PECTORIS
•Angina pectoris is a symptom complex of
IHD characterized by paroxysmal and
recurrent attacks of substernal or
precordial chest discomfort caused by
transient myocardial ischemia

•The levels of cardiac markers remains

unchanged
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 TYPES

There are three patterns of angina→

•i) Stable or Classical angina
•ii) Unstable or crescendo angina
•iii) Prinzmetal’s variant angina

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Classical (stable) angina

• It is the most common form of angina

• It is caused by the reduction of coronary

perfusion to a critical level due to coronary
atherosclerosis without plaque rupture.

•Chest discomfort occurs on exertion

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
• Patient complains chest discomfort, usually described as heaviness,
pressure, squeezing, chocking or smothering.
• It is not described as frank pain
• Chest discomfort occurs on exertion
• relieved by rest.
• When patient is asked to localize the sensation, he/she will typically
place their hand over the sternum with clenched fist → Levine’s sign
• Chest discomfort typically lasts 2-5 minutes.
• Pain can radiate to shoulder, arm, back, interscapular region, neck, jaw,
teeth, epigastrium.
• Stable angina is usually crescendo - decrescendo in nature.

Dr. PRIYANKA SACHDEV

 Unstable angina
•Unstable angina is due to disruption of
atherosclerotic plaque with thromosis.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Unstable angina is defined as chest discomfort that has at
least one of the three feature→

• It occurs at rest and lasting > 10 min.

• It is severe and of new onset (i.e. within prior 4-6
weeks).
• It occurs with a crescendo pattern
• The chest discomfort of US is described as pain (in
contrast to stable angina).

Dr. PRIYANKA SACHDEV

 Prinzmetal variant angina

•Due to focal spasm in right coronary

artery
•Pain occurs at rest.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
EFFECTS OF IHD

Dr. PRIYANKA SACHDEV

MYOCARDIAL INFARCTION

Dr. PRIYANKA SACHDEV

 HEADINGS
• Definition
• Etiopathogenesis
• Types of infacts
• Location of infacts
• Morphologic features (Gross and Microscopy)
• Clinical features
• Diagnosis
• Complications
• Salvage in early infacts
Dr. PRIYANKA SACHDEV
 MYOCARDIAL INFARCTION

•Infaction (ischemic necrosis) of

myocardium of heart due to decreased
blood supply

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 ETIOPATHOGENESIS
•i) Coronary atherosclerosis
•ii) Superadded changes in coronary
atherosclerosis
•iii) Non-atherosclerotic causes

Dr. PRIYANKA SACHDEV

TYPES OF INFARCTS

Dr. PRIYANKA SACHDEV

According to the degree of thickness of
the ventricular wall involved

•i) Full-thickness or transmural, when they

involve the entire thickness of the
ventricular wall.

•ii) Subendocardial when they occupy the

inner subendocardial half of the
myocardium
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 LOCATION OF INFARCTS

•Depends on which branch of coronary

artery is obstructed

Dr. PRIYANKA SACHDEV

 1. Stenosis of the left anterior
descending coronary artery
•It is the most common (40-50%).

•The region of infarction is the anterior

part of the left ventricle including the
apex and the anterior two-thirds of the
interventricular septum
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 2. Stenosis of the right coronary
artery
•It is the next most frequent (30-40%).

•It involves the posterior part of the left

ventricle and the posterior one-third of
the interventricular septum.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 3. Stenosis of the left circumflex
coronary artery

•It is seen least frequently (15-20%). Its

area of involvement is the lateral wall of
the left ventricle

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
MORPHOLOGIC FEATURES

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 GROSS
• Myocardial infarcts less than 12 hours old are usually
not apparent on gross examination.
• But, necrotic area can be visualized after 2-3 hours by
immersion of tissue slices in a solution of
triphenyltetrazolium chloride (TTC)

➢Non infarcted myocardium →TTC imparts brick red

color to it where the dehydrogenases enzymes are
preserved.
➢Infarcted area is appears as an unstained pale zone
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 MICROSCOPY

•The predominant mechanism of cell death

in heart is coagulative necrosis

•Coagulative necrosis starts between 4-12

hours after onset of ischemia.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
REVISION

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 HEADINGS
• Definition
• Etiopathogenesis
• Types of infacts
• Location of infacts
• Morphologic features (Gross and Microscopy)
• Clinical features
• Diagnosis
• Complications
• Salvage in early infacts
Dr. PRIYANKA SACHDEV
 Clinical features
• i) Pain: Usually sudden, severe, crushing and
prolonged, substernal or precordial in location,
unrelieved by rest or nitroglycerin, often radiating to
one or both the arms, neck and back.

• ii) Indigestion: Pain is often accompanied by epigastric

or substernal discomfort interpreted as ‘heartburn’
with nausea and vomiting.

• iii) Apprehension: The patient is often terrified, restless

and apprehensive due to great fear of death.
Dr. PRIYANKA SACHDEV
• iv) Shock: Systolic blood pressure is below 80 mmHg;
lethargy, cold clammy limbs, peripheral cyanosis, weak pulse,
tachycardia or bradycardia are often present.

• v) Oliguria: Urine flow is usually less than 20 ml per hour.

• vii) Acute pulmonary oedema: Some cases develop severe

pulmonary congestion due to left ventricular failure and
develop suffocation, dyspnoea, orthopnoea

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 DIAGNOSIS
1. ECG changes

2. Serum enzyme determinations/

Serum cardiac markers

Dr. PRIYANKA SACHDEV

ECG changes

Dr. PRIYANKA SACHDEV

 Serum cardiac markers

•Cardiac markers are intracellular

enzymes that leak out of dead
necrotic cells

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
R

Dr. PRIYANKA SACHDEV

i) Creatine phosphokinase (CPK)

3 forms—
•a) CK-MM derived from skeletal muscle;
•b) CK-BB derived from brain
•c) CK-MB derived from cardiac muscles

Dr. PRIYANKA SACHDEV

•CK-MB has further 2 forms—
1. CK-MB2 is the myocardial form
2. CK-MB1 is extracardiac form.

•A ratio of CK-MB2: CK-MB1 > 1.5 is highly

sensitive for the diagnosis of acute MI after 4-6
hours of onset of myocardial ischaemia.
•CK-MB disappears from blood by 48 hours
Dr. PRIYANKA SACHDEV
R

Dr. PRIYANKA SACHDEV

 ii) Lactate dehydrogenase (LDH)
•Total LDH estimation also lacks specificity
since this enzyme is present in various tissues
besides myocardium such as in skeletal
muscle, kidneys, liver, lungs and red blood
cells.

•LDH levels begin to rise after 24 hours, reach

peak in 3 to 6 days and return to normal in
14 days.
Dr. PRIYANKA SACHDEV
R

Dr. PRIYANKA SACHDEV

 iii) Cardiac-specific troponins (cTn)
There are two types of cTn→

•a) cardiac troponin T (cTnT)

•b) cardiac troponin I (cTnI)

•Most sensitive and specific marker for MI

Dr. PRIYANKA SACHDEV
R

Dr. PRIYANKA SACHDEV

 iv) Myoglobin
•Though myoglobin is the first cardiac marker
to become elevated after myocardial
infarction
•It lacks cardiac specificity

•It is excreted in the urine rapidly. Its levels,

thus, return to normal within 24 hours of
attack of acute MI.
Dr. PRIYANKA SACHDEV
R

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 COMPLICATIONS
•1. Arrhythmias are the most common
complication in acute MI.

•These occur due to ischaemic injury or

irritation to the conduction system,
resulting in abnormal rhythm

Dr. PRIYANKA SACHDEV

•2. Heart failure (Right or left)

•3. Cardiogenic shock

•4. Rupture → most often from the infarcted

ventricular wall into the pericardial cavity
causing haemopericardium
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
• 6. Cardiac aneurysm → It occurs in healed infarcts through
thin, fibrous, non-elastic scar tissue

• 7. Pericarditis Sterile pericarditis appearing on about the

second day is common over transmural infarcts

• 8. Postmyocardial infarction syndrome/ Dressler’s syndrome

→ It usually occurs 1 to 6 weeks after the attack of MI. It is
characterised by pneumonitis.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 HEADINGS
• Definition
• Etiopathogenesis
• Types of infacts
• Location of infacts
• Morphologic features (Gross and Microscopy)
• Clinical features
• Diagnosis
• Complications
• Salvage in early infacts
Dr. PRIYANKA SACHDEV
The Respiratory
System

Dr. PRIYANKA SACHDEV

 PNEUMONIAS

•Pneumonia is defined as acute inflammation

of the lung parenchyma distal to the terminal
bronchioles (consisting of the respiratory
bronchiole, alveolar ducts, alveolar sacs and
alveoli).

•There is consolidation of lung

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Routes
• The microorganisms gain entry into the lungs by
one of the following four routes:

• 1. Inhalation of the microbes present in the air.

• 2. Aspiration of organisms from the nasopharynx or
oropharynx.
• 3. Haematogenous spread from a distant focus of
infection.
• 4. Direct spread from an adjoining site of infection.

Dr. PRIYANKA SACHDEV

 PATHOGENESIS
The normal lung is free of bacteria because of
the presence of a number of lung defense
mechanisms at different levels such as →

1. Nasopharyngeal filtering action

2. Mucociliary action of the lower respiratory
airways
3. Cough reflex
4. The presence of phagocytosing alveolar
macrophages and immunoglobulins
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Failure of these defense
mechanisms
• 1. Altered consciousness The oropharyngeal contents
may be aspirated in states causing unconsciousness e.g. in
coma, cranial trauma, seizures, cerebrovascular acci
dents, drug overdose, alcoholism etc.

• 2. Depressed cough and glottic reflexes e.g. in old age,

pain from trauma or thoraco abdo minal surgery,
neuromuscular disease, weakness due to malnutrition,
kyphoscoliosis, severe obstructive pulmonary diseases,
endotracheal intubation and tracheostomy.

Dr. PRIYANKA SACHDEV

• 3. Impaired mucociliary transport eg. Cigarette smoking,
viral respiratory infections, immotile cilia syndrome,
inhalation of hot or corrosive gases and old age.

• 4. Impaired alveolar macrophage function e.g. by cigarette

smoke, hypoxia, starvation, anaemia, pulmonary oedema
and viral respiratory infections.

Dr. PRIYANKA SACHDEV

• 5. Endobronchial obstruction from tumour, foreign body,
cystic fibrosis and chronic bronchitis.

• 6. Immunocompromised states Disorders of lymphocytes

including conge nital and acquired immunodeficiencie

Dr. PRIYANKA SACHDEV

 CLASSIFICATION
•Based on the anatomic region of the lung
parenchyma

•Based on etiology and pathogenesis

•Based on the clinical settings in which

infection occurred
Dr. PRIYANKA SACHDEV
On the basis of the anatomic region
of the lung parenchyma

•1. Lobar pneumonia

•2. Bronchopneumonia (or
Lobular pneumonia)
•3. Interstitial pneumonia

Dr. PRIYANKA SACHDEV

Based on etiology and pathogenesis

•A. Bacterial pneumonia

•B. Viral pneumonia
•C. Pneumonias from other
etiologies

Dr. PRIYANKA SACHDEV

Based on the clinical settings in
which infection occurred

•1. Community-acquire pneumonia

•2. Health care-associated
pneumonia/Nosocomial (including
hospital acquired pneumonia)
•3. Ventilator-associated
pneumonia
Dr. PRIYANKA SACHDEV
 CLASSIFICATION
[Link] Pneumonia →
•Lobar
•Lobular (Bronchopnemonia)

[Link] pneumonia → Intertitial / atypical

pneumonia

[Link] pnemonia
Dr. PRIYANKA SACHDEV
 Bacterial Pnemonia

[Link] pneumonia
[Link] pneumonia
(Bronchopnemonia)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Lobar Pneumonia

•Lobar pneumonia is an acute bacterial

infection of a part of a lobe, the entire
lobe, or even two lobes of one or both
the lungs

•The condition is frequent in adults

Dr. PRIYANKA SACHDEV
 ETIOLOGY
• 1. Pneumococcal pneumonia More than 90% of all lobar
pneumonias are caused by Streptococcus pneumonia(type 3
S. pneumoniae )
• 2. Staphylococcal pneumonia Staphylococcus aureus
• 3. Streptococcal pneumonia B-haemolytic streptococci cause
pneumonia such as in children after measles, in severely
debilitated elderly patients and in diabetics.
• 4. Pneumonia by gram-negative aerobic bacteria
Haemophilus infl uenzae, Klebsiella pneumonia
(Friedlander’s bacillus), Pseudomonas, Proteus and
Escherichia coli, H. influenzae causes pneumonia in children
below 3 years of age after a preceding viral infection
Dr. PRIYANKA SACHDEV
 4 pathologic phases of
pnemonia
• Laennec’s divides lobar pneumonia into 4
sequen tial pathologic phases:

[Link] of congestion (initial phase),

[Link] hepatisation (early consolidation),
[Link] hepatisation (late consolidation)
[Link]

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 1 STAGE OF CONGESTION:
INITIAL PHASE

•The initial phase represents the

early acute inflamatory response
to bacterial infection that lasts for
1 to 2 days.

Dr. PRIYANKA SACHDEV

 Grossly

•The affected lobe is enlarged, heavy,

dark red and congested.

•Cut surface exudes blood-stained

frothy fluid.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Histologically
• i) Dilatation and congestion of the capillaries in the
alveolar walls.

• ii) Pale eosinophilic oedema fluid in the air spaces.

• iii) A few red cells and neutrophils in the intra-

alveolar fluid.

• iv) Numerous bacteria demonstrated in the alveolar

fluid by Gram’s staining
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 2. RED HEPATISATION: EARLY
CONSOLI DATION

• This phase lasts for 2 to 4 days.

•The term hepatisation in pneumonia

refers to liver-like consistency of the
affected lobe on cut section.

Dr. PRIYANKA SACHDEV

 Grossly
•The affected lobe is red, firm and
consolidated.

•The cut surface of the involved lobe is

airless, red-pink, dry, granular and has liver-
like consistency.

•The stage of red hepatisation is accompanied

by serofibrinous pleurisy.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Histologically
•i) The oedema fluid of the preceding stage is
replaced by strands of fibrin.

•ii) There is marked cellular exudate of

neutrophils and extravasation of red cells.

•iii) Many neutrophils show ingested bacteria

•iv) The alveolar septa are less prominent than

in the first stage due to cellular exudation
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 3. GREY HEPATISATION: LATE
CONSOLIDATION

•This phase lasts for 4 to 8 days

Dr. PRIYANKA SACHDEV

 Grossly
•The affected lobe is firm and heavy.

•The cut surface is dry, granular and grey in

appearance with liver-like consistency
•
•The change in colour from red to grey begins at
the hilum and spreads towards the periphery.

•Fibrinous pleurisy is prominent. Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Histologically
• i) The fibrin strands are dense and more numerous.

• ii) The cellular exudate of neutrophils is reduced due to

disintegration of many inflammatory cells as evidenced by
their pyknotic nuclei. The red cells are also fewer. The
macrophages begin to appear in the exudate.

• iii) The cellular exudate is often separated from the septal

walls by a thin clear space.

• iv) The organisms are less numerous and appear as

degenerated forms.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 4. RESOLUTION
•This stage begins by 8th to 9th day if no
chemotherapy is administered and is
completed in 1 to 3 weeks.

•However, antibiotic therapy induces

resolution on about 3rd day
Dr. PRIYANKA SACHDEV
 Grossly
• The previously solid fibrinous constituent is
liquefied by enzymatic action, eventually restoring
the normal aeration in the affected lobe.

• The process of softening begins centrally and

spreads to the periphery.
• The cut surface is grey-red or dirty brown and frothy,
yellow, creamy fluid can be expressed on pressing.

• The pleural reaction may also show resolution

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Histologically
• i) Macrophages are the predominant cells in the alveolar
spaces, while neutrophils diminish in number. Many of the
macrophages contain engulfed neutrophils and debris.

• ii) Granular and fragmented strands of fibrin in the alveolar

spaces are seen due to progressive enzymatic digestion.
• iii) Alveolar capillaries are engorged.

• iv) There is progressive removal of fluid content as well as

cellular exudate from the air spaces, partly by
expectoration but mainly by lymphatics, resulting in
restoration of normal lung parenchyma with aeration
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 CLASSIFICATION
[Link] Pneumonia →
• Lobar
• Lobular (Bronchopnemonia)

[Link] pneumonia → Intertitial / atypical

pneumonia

[Link] pnemonia
Dr. PRIYANKA SACHDEV
 Lobular Pneumonia /
Bronchopneumonia
• Bronchopneumonia or lobular pneumonia is infection
of the terminal bronchioles that extends into the
surrounding alveoli resulting in patchy consolidation
of the lung.

• The condition is frequent at the extremes of life (i.e. in

infancy and old age), in chronic debilitating diseases
and as a secondary infection following viral
respiratory infections
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 ETIOLOGY
•Staphylococci,
•Streptococci,
•Pneumococci,
•Klebsiella pneumoniae,
•Haemophilus influenzae,
•Gramnegative bacilli like Pseudomonas and
coliform bacteria
Dr. PRIYANKA SACHDEV
 Grossly
•Patchy areas of consolidation affecting one
or more lobes,
•Frequently found bilaterally
•More often involving the lower zones of the
lungs due to gravitation of the secretions.
•On cut surface, these patchy consolidated
lesions are dry, granular, firm, red or grey
in colour, 3 to 4 cm in diameter, slightly
elevated over the surface
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Histologically
•i) Acute bronchiolitis.

•ii) Suppurative exudate, consisting chiefly of

neutrophils, in the peribronchiolar alveoli.

•iii) Thickening of the alveolar septa by

congested capillaries and leucocytic infiltration.

•iv) Less involved alveoli contain oedema fluid.

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 VIRAL/ mycoplasma PNEUMONIA
INTERSTITIAL PNEMONIA
PRIMARY ATYPICAL PNEUMONIA

• Viral pneumonia is characterised by patchy inflammatory

changes, largely confined to interstitial tissue of the lungs,
without any alveolar exudate.

• Also called interstitial pneumonitis due to interstitial

location of the inflammation

• Also called primary atypical pneumonia, atypicality being

the absence of alveolar exudate which is commonly present
in other pneumonias.
Dr. PRIYANKA SACHDEV
 ETIOLOGY
[Link] syncytial virus (RSV) (most
common)

[Link] are Mycoplasma pneumonia,

influenza and para influenza viruses,
adenoviruses, rhinoviruses, coxsackieviruses
and cytomegaloviruses (CMV).
[Link], psittacosis (Chlamydia) and Q
fever (Coxiella)
Dr. PRIYANKA SACHDEV
 Grossly

•Patchy to massive and widespread

consolidation of one or both the lungs.

•The lungs are heavy, congested and

subcrepitant.

•The pleural reaction is usually infrequent and

mild
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Histologically
[Link] of viral pneumonias is the
interstitial nature of the inflammatory
reaction comprised by lymphocytes,
macrophages and some plasma cells.

[Link] is thickening of alveolar walls due

to congestion, oedema and interstitial
inflammation Dr. PRIYANKA SACHDEV
3. Reactive changes →The lining epithelial
cells of alveoli proliferate in the presence of
virus and may form multinucleate giant
.Occasionally, viral inclusions are found,

[Link] of alveolar exudate

Dr. PRIYANKA SACHDEV
•3. Necrotising bronchiolitis → foci of
necrosis of the bronchiolar epithelium

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 CLASSIFICATION
[Link] Pneumonia →
• Lobar
• Lobular (Bronchopnemonia)

[Link] pneumonia → Intertitial / atypical

pneumonia

[Link] pnemonia
Dr. PRIYANKA SACHDEV
FUNGAL / mycotic PNEUMONIAS

•These infections are rare in healthy

individuals

•Common in immunosuppressed
individuals
Dr. PRIYANKA SACHDEV
 Pneumocystis Pneumonia
• Pneumocystis is an opportunistic fungal infection of the
lungs.

1. P. carinii infects rats

2. P. jirovecii causes pneumonia by inhalation of the
organisms in immunosuppressed people.

• Almost 100% cases of HIV/ AIDS develop opportunistic

infection during the course of disease, most commonly
Pneumocystis pneumonia.
Dr. PRIYANKA SACHDEV
 Grossly
•The affected parts of the lung are
consolidated, dry and grey.

Dr. PRIYANKA SACHDEV

 Microscopically
1. Interstitial pneumonitis

2. Thickening of the alveolar

walls

3. No significant inflammatory
exudate is seen in the air
spaces. Dr. PRIYANKA SACHDEV
4. Alveolar lumina contain pink frothy fluid
having the organisms

[Link] Grocott’s methenamine-silver (GMS)

stain, the characteristic oval or crescentic cysts,
about 5 μm in diameter and surrounded by
numerous tiny black dotlike organism P. jirovecii
are demonstrable in the frothy fluid

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE (COPD)

•Chronic obstructive pulmonary disease

(COPD) are clinical terms for a group of
pathological conditions in which there is
chronic, partial or complete, obstruction
to the airflow at any level from trachea to
the smallest airways resulting in
functional disability of the lungs
Dr. PRIYANKA SACHDEV
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE (COPD)

•I. Chronic bronchitis

•II. Emphysema
•III. Bronchial asthma
•IV. Bronchiectasis
•V. Small airways disease
(bronchiolitis)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 CHRONIC BRONCHITIS
•Chronic bronchitis is a common condition
defined clinically as persistent cough with
expectoration on most days for at least
three months of the year for two or more
consecutive years.

•More common in middle-aged males

Dr. PRIYANKA SACHDEV
 Pathogenesis
•The cough is caused by over secretion
of mucus due to increase in number
and size of submucosal gland of
trachea and bronchi

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 ETIOLGY
• 1. Smoking →Heavy cigarette smokers have 4 to 10
times higher proneness to develop chronic bronchitis.

• i) It impairs ciliary movement.

• ii) It inhibits the function of alveolar macrophages.
• iii) It leads to hypertrophy and hyperplasia of mucus-
secreting glands.
• iv) It causes considerable obstruction of small airways.
• v) It stimulates the vagus and causes
bronchoconstriction.

Dr. PRIYANKA SACHDEV

•2. Atmospheric pollution
•3. Occupation Workers engaged in certain
occupations such as in cotton mills (byssinosis),
plastic factories etc. are exposed to various
organic or inorganic dusts
•4. Infection Bacterial, viral and mycoplasmal
infections

Dr. PRIYANKA SACHDEV

 Grossly

•The bronchial wall is thickened,

hyperaemic and oedematous

•Lumina of the bronchi and

bronchioles may contain mucus
plugs and purulent exudate
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Microscopically
•1. Increased Reid index (normal 04 )

•Reid index is the ratio between thickness

of the submucosal mucus glands (i.e.
hypertrophy and hyperplasia) in the
cartilage-containing large airways to that
of the total bronchial wall
Dr. PRIYANKA SACHDEV
2. Goblet cells are increased

3. The bronchial epithelium may show

squamous metaplasia and dysplasia.

4. There is little chronic inflammatory cell

infiltrate.
Dr. PRIYANKA SACHDEV
•In most severe cases, there maybe
oblitration of lumen due lo fibrosis -
Bronchiolitis obliterans.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 CLINICAL FEATURES
• 1. Persistent cough with copious expectoration of
long duration; initially beginning in a heavy smoker
with ‘morning catarrh’ or ‘throat clearing’ which
worsens in winter.
• 2. Recurrent respiratory infections are common.
• 3. Dyspnoea
• 4. Patients are called ‘blue bloaters’ due to cyanosis
• 5. Features of right heart failure (cor pulmonale) are
common.
• 6. Chest X-ray shows enlarged heart with prominent
vessels.
Dr. PRIYANKA SACHDEV
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE (COPD)

•I. Chronic bronchitis

•II. Emphysema
•III. Bronchial asthma
•IV. Bronchiectasis
•V. Small airways disease
(bronchiolitis)
Dr. PRIYANKA SACHDEV
 EMPHYSEMA
•The WHO has defined pulmonary
emphysema as combination of permanent
dilatation of air spaces distal to the
terminal bronchioles and the destruction
of the walls of dilated air spaces.

•Thus, emphysema is defined

morphologically, while chronic bronchitis is
defined clinically.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 REMEMBER
•Destruction of walls is necessary to
define emphysema.

•Enlargement of airspaces without

destruction of their walls is termed
overinflation
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 ETIOPATHOGENESIS
1. Protease-antiprotease hypothesis→The alveolar
wall destruction results from an imbalance between
proteases (mainly elastase) and antiproteases in the
lung.

➢Proteases (elastase) cause destruction of alveolar

wall

➢Antiproteases (antielastase) prevent this damage.(

α1-antitrypsin is the major antiprotease secreted
by neutrophils during inflammation)
Dr. PRIYANKA SACHDEV
• The mechanism of alveolar wall destruction in
emphysema is based on the imbalance between
proteases (chiefly elastase) and anti-proteases
(chiefly antielastase):

• i) By decreased anti-elastase activity i.e. deficiency

of a-1 antitrypsin.
• ii) By increased activity of elastase
Dr. PRIYANKA SACHDEV
Smoking promotes emphysema by
both →

➢BY decreasing the amount of

antielastase
➢By increasing the protease in
the lungs.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
CLASSIFICATION

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Centriacinar (centrilobular)
emphysema
• Centriacinar emphysema is the most common
type of emphysema seen clinically

•It is chracterized by involvement of respiratory

bronchioles, i.e. central (proximal) part of the
Ainus

•So, both emphysematous and normal airspaces

exist within the same acinus and lobule.
Dr. PRIYANKA SACHDEV
•The lesions are more common and more
severe in the upper lobe, particularly in
the apical segments.

•This is the type of emphysema that

occurs predominantly in heavy smokers
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Panacinar (Panlobular) emphysema

• The acini are uniformly

enlarged from the level of the
respiratory bronchiole to the
alveoli.

Dr. PRIYANKA SACHDEV

•This type of emphysema tends to occur
more commonlv in the lower zones and in
the anterior margins of the lung, and it is
usually most severe at the base.

•This type of emphysema is associated with

α1-antitrypsin deficiency
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Distal acinar (Paraseptal)
emphysema
•This type of emphysema involves distal
part of the acinus , while proximal part is
normal

Dr. PRIYANKA SACHDEV

•It is localized adjacent to the pleura, along
perilobular septa.
•Usually more severe in the upper half of
lungs.

•This type of emphysema is a common

cause of spontaneous pneumothorax in
young adults.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 4. Irregular emphysema
(Para-cicatricial
emphysema)
• The acinus is involved irregularly
• Almost invariably associated with
scarring.

•It is the most common type of

emphysema histologically Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 REMEMBER
•Most common type of emphysema is
irregular emphysema but it is not
clinically significant as most patients are
asymptomatic and it is only an autopsy
finding.

•Most common type of emphysema seen

clinically is centracinar emphysema.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Grossly
•The lungs are voluminous, pale with
little blood.
• The edges of the lungs are rounded.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
• Advanced cases show subpleural bullae and blebs bulging
outwards from the surface of the lungs with rib markings
between them.

➢ Bullae are air-filled cyst-like or bubble-like structures,

larger than 1 cm in diameter. They are formed by the
rupture of adjacent air spaces
➢ Blebs are the result of rupture of alveoli directly into the
subpleural interstitial tissue

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Microscopically
[Link] portions of acini are distended—
respiratory bronchioles, alveolar ducts and
alveoli
[Link] dilated
[Link] walls stretched and thin
[Link] alveolar walls and spurs of
broken septa are seen between the
adjacent alveoli
[Link] changes are usually absent
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 CLINICAL FEATURES

•There is considerable overlap

between the clinical features of
chronic bronchitis and emphysema,

Dr. PRIYANKA SACHDEV

• 1. There is long history of slowly increasing severe
exertional dyspnoea

• 2. Patient is quite distressed with obvious use of

accessory muscles of respiration.

• 3. Chest is barrel-shaped and hyperresonant

• 4. Cough occurs late after dyspnoea starts and is

associated with scanty mucoid sputum

Dr. PRIYANKA SACHDEV

• 5. Recurrent respiratory infections are not frequent.

• 6. Patients are called ‘pink puffers’ as they remain well

oxygenated

• 7. Weight loss is common

• 8. Features of right heart failure (cor pulmonale)

• 9. Chest X-ray shows small heart with hyperinflated lungs.

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE (COPD)

•I. Chronic bronchitis

•II. Emphysema
•III. Bronchial asthma
•IV. Bronchiectasis
•V. Small airways disease
(bronchiolitis)
Dr. PRIYANKA SACHDEV
 BRONCHIAL ASTHMA

Asthma is a disease of airways that is

characterised by increased responsiveness of
the tracheobronchial tree to a variety of stimuli

Widespread spasmodic narrowing of the air

passages

Relieved spontaneously or by therapy

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•It is a chronic inflammatory disorder of
airway

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
•Asthma is an episodic disease manifested
clinically by
[Link] of dyspnoea,
[Link]
[Link]

•A severe and unremitting form of the disease

termed status asthmaticus may prove fatal.
Dr. PRIYANKA SACHDEV
•At all ages In adults
•Both sexes are affected equally
•In children there is 2:1 male-female
ratio.

Dr. PRIYANKA SACHDEV

 PATHOGENESIS

Asthma is an example of type I

hypersensitivity

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
During first contact of the host with the antigen, (sensatising / priming
dose ) sensitization takes place

Antigen is captured by the antigen presenting cells

It is presented to the T cell which then differentiates into TH2 cell.

The TH2 cell releases mediators like IL-3, IL-4 and IL-5.

IL-4 causes activation of B cell

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Activated B cells

differentiate to form IgE-secreting plasma cells

IgE antibodies so formed

Bind to the Fc receptors present on mast cells and basophils

Mast cells are the main effector cells of type I reaction.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Thus, these cells are now fully sensitised for the next event.

During the second contact with the same antigen (shocking dose )

IgE antibodies on the surface of mast cells-basophils are activated

They cause cell damage—membrane lysis, influx of sodium and water

Degranulation of mast cells-basophils.

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
• The released granules contain important chemicals and enzymes with
proinflammatory properties

• Histamine
• Serotonin
• vasoactive intestinal peptide (VIP)
• chemotactic factors of anaphylaxis for neutrophils and eosinophils
• Leukotrienes B4 and D4
• Prostaglandins (thromboxane A2, prostaglandin D2 and E2)
• Platelet activating factor.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Chemical Mediators
•2 types—

[Link] mediators which are the preformed

contents of mast cell and basophil granules

[Link] mediators which are newly

formed upon stimulation of mast cells,
basophils and other leucocytes
Dr. PRIYANKA SACHDEV
CAUSES→

• Bronchoconstriction
• Increased secreation from glands

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 2 PHASES

•Acute immediate response

•Late phase reaction

Dr. PRIYANKA SACHDEV

 Acute immediate response
• Acute immediate response is initiated by IgE-sensitized mast
cells (tissue counterparts of circulating basophils) on the mucosal
surface.
• Mast cells on degranulation release mediators like histamine,
leukotrienes, prostaglandins, platelet activating factor and
chemotactic factors for eosinophils and neutrophils.

• The net effects of these mediators are bronchoconstriction,

oedema, mucus hypersecretion and accumulation of
eosinophils and neutrophils

Dr. PRIYANKA SACHDEV

 Late phase reaction:

•It is caused by excessive mobilisation of

blood leucocytes that include basophils ,
eosinophils and neutrophils.
• These result in further release of
mediators
•Accentuate the above-mentioned effects.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
TYPES

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Grossly
•The lungs are overdistended due to over-
inflation.

•The cut surface shows characteristic

occlusion of the bronchi and bronchioles
by viscid mucus plugs.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Microscopically
•SPUTUM

•BRONCHIAL WALL

Dr. PRIYANKA SACHDEV

 SPUTUM

• 1. The mucus plugs contain normal or degenerated respiratory

epithelium forming twisted strips called Curschmann’s spirals.

• 2. The sputum usually contains numerous eosinophils and

diamond-shaped crystals derived from eosinophils called Charcot-
Leyden crystals.

• 3) Creola bodies: Ciliated columnar cells sloughed from bronchial

mucosa.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 BRONCHIAL WALL

The bronchial wall shows → Airway remodelling

[Link] basement membrane of the bronchial

epithelium
[Link] cell hyperplasia
[Link] oedema
[Link] infiltrate consisting of lymphocytes
and plasma cells with prominence of eosinophils
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 CLINICAL FEATURES
• Episodes of acute exacerbations interspersed with symptom free
periods.
• Characteristic clinical features are paroxysms of
1. Dyspnoea
2. Cough
3. Wheezing
• Most attacks typically last for a few minutes to hours.

• When attacks occur continuously, it may result in more serious

condition called status asthmaticus.
Dr. PRIYANKA SACHDEV
 Diagnosis
•Eosinophilia

•Sputum demonstration of Curschmann’s

spirals and Charcot-Leyden crystals.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE (COPD)

•I. Chronic bronchitis

•II. Emphysema
•III. Bronchial asthma
•IV. Bronchiectasis
•V. Small airways disease
(bronchiolitis)
Dr. PRIYANKA SACHDEV
 BRONCHIECTASIS
•Bronchiectasis is defined as abnormal and
irreversible dilatation of the bronchi and
bronchioles (greater than 2 mm in diameter)
developing secondary to inflammatory
weakening of the bronchial walls.

•The most characteristic clinical manifestation of

bronchiectasis is persistent cough with
expectoration of copious amounts of foul-
smelling, purulent sputum.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 ETIOPATHOGENESIS
[Link] obstruction
[Link]

Dr. PRIYANKA SACHDEV

Endobronchial obstruction by foreign body, neoplastic growth or enlarged lymph
nodes

Resorption of air distal to the obstruction

Atelectasis

Retention of secretions

Promoting bacterial growth

Infection and inflammation

Abnormal and irreversible dilatation of the bronchi and bronchioles

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
•It is a visious cycle

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Grossly
•The lungs may be involved diffusely or
segmentally.

•More vertical air passages of left lower

lobe are more often involved than the
right.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
• i) Cylindrical: the most common type characterised by tube-
like bronchial dilatation.
• ii) Fusiform: having spindle-shaped bronchial dilatation.
• iii) Saccular: having rounded sac-like bronchial distension.
• iv) Varicose: having irregular bronchial enlargements.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
•Cut surface of the affected lobes shows
characteristic honey-combed
appearance→ The bronchi are
extensively dilated, their walls are
thickened and the lumina are filled with
mucus or mucopus.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Microscopically

[Link] and bronchioles are dilated

[Link] bronchial epithelium may be normal,
ulcerated or sloughed
[Link] bronchial wall shows infiltration by acute
and chronic inflammatory cells
[Link] the bronchial wall there is destruction of
normal muscle and elastic tissue with
replacement by fibrosis
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 CLINICAL FEATURES
1. Chronic cough with foulsmelling sputum
production
2. Haemoptysis
3. Recurrent pneumonia

• Bronchiectasis is not a premalignant condition

Dr. PRIYANKA SACHDEV

 Kartagener's syndrome
Triad→

Bronchiectasis
Sinusitis
Situs invertus (including dextrocardia)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Goodpasture’s syndrome

•Goodpasture’s syndrome is the

characteristic example of anti BM disease

Dr. PRIYANKA SACHDEV

• Antigen appears to be a component of noncollagenous domain of
the a-3 chain of type IV collagen in BM (Fixed Ag.)

Ab are formed against it

Form immune complexes in GBM (In situ deposition against fixed

AG)

ARF

Cross react with alveolar BM

Pulmonary haemmorhages

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Goodpasture syndrome, immune reaction is type II
hypersensitivity

Dr. PRIYANKA SACHDEV

 Lung
1. The lungs are heavy, with areas of red brown consolidation.

2. There is focal necrosis of alveolar walls associated with

intraalveolar hemorrhages

3. Alveoli contain hemosiderin-laden macrophages

4. Linear deposits of immunoglobulins along the basement

membranes of the septal walls.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Kidney

• There is diffuse proliferative rapidly progressive

glomerulonephritis.

• There is Linear deposits of immunoglobulins and complement

along glomerular basement membrane

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 TUMOURS OF LUNGS
•Lung cancer is the most common cause
of cancer related death.

•Occurs most often between ages 40 and

70 years.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Histological Types
•There are 5 main histologic types of lung
cancer:

Dr. PRIYANKA SACHDEV

 TYPES
•i) Squamous cell or epidermoid carcinoma
•ii) Small cell carcinoma
•iii) Adenocarcinoma (including bronchioalveolar
carcinoma)
•iv) Large cell carcinoma
•v) Combined squamous cell carcinoma and
adenocarcinoma (adenosquamous carcinoma).

Dr. PRIYANKA SACHDEV

 Clinical types
•However, for therapeutic purposes,
bronchogenic carcinoma can be
classified into 3 groups:

Dr. PRIYANKA SACHDEV

•1. Small cell carcinomas, SCC (20-25%)

•2. Non-small cell carcinomas, NSCC (70-75%)

(includes squamous cell carcinoma,
adenocarcinoma, and large cell carcinoma)

•3. Combined/mixed patterns (5-10%).

Dr. PRIYANKA SACHDEV
BRONCHOGENIC CARCINOMA

Dr. PRIYANKA SACHDEV

 ETIOLOGY
• 1. SMOKING

• 2. OTHER FACTORS →

• i) Radiation exposure
• ii) Atmospheric pollution
• iii) Occupational causes
• iv) Dietary factors
• v) Chronic scarring

Dr. PRIYANKA SACHDEV

 1. SMOKING

•Th most important factor for high incidence

of all forms of bronchogenic carcinoma is
tobacco smoking.

•About 80% of the lung cancer occurs in

active smokers
Dr. PRIYANKA SACHDEV
Total dose There is a direct correlation between death rate
from lung cancer and the total amount of cigarettes smoked

• a) An average active smoker has 13 times higher risk while a

passive smoker has 1.5 times risk of lung cancer than a
nonsmoker.

• b) The risk of smokers of more than 2 packs (40 cigarettes)

per day for 20 years is 60-70 times greater than a non-
smoker.

Dr. PRIYANKA SACHDEV

•c) Cessation of smoking by a regular smoker
results in gradual decline in the chances of
developing lung cancer. After 10 years of
abstinence from smoking, the risk declines
but never returns to the non-smoker level.

•d) Pipe and cigar smokers have higher

chances of developing lung cancer.
Dr. PRIYANKA SACHDEV
• Sequential epithelial changes in the respiratory
tract in the form of

1. Hyperplasia
2. Squamous metaplasia,
3. Dysplasia
4. Carcinoma in situ
5. Carcinoma
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Tar from cigarette smoke contains
→

1. Carcinogens (e.g. polycyclic aromatic

hydrocarbons, nitrosamines)

2. Tumour promoters (e.g. phenol

derivatives) →
Dr. PRIYANKA SACHDEV
 ETIOLOGY
• 1. SMOKING

• 2. OTHER FACTORS →

• i) Radiation exposure
• ii) Atmospheric pollution
• iii) Occupational causes
• iv) Dietary factors
• v) Chronic scarring

Dr. PRIYANKA SACHDEV

 2. OTHER FACTORS
•i) Radiation exposure Long-term exposure to
radon or patients receiving thoracic radiation
have increased risk of lung cancer.

•ii) Atmospheric pollution Th ere is increased

risk of developing bronchogenic carcinoma in
non-smokers living in industrialised and smoky
cities than in the less polluted rural areas.

Dr. PRIYANKA SACHDEV

• iii) Occupational causes There are a number of occupational
causes of lung cancer like asbestos, bis-ethers, nickel,
beryllium, arsenic, metallic iron and iron-oxide.

• iv) Dietary factors → vitamin A deficiency

• v) Chronic scarring Peripheral adenocarcinomas occur more

frequently in areas of chronic scarring caused by chronic
inflammatory changes, old tuberculosis, asbestosis, chronic
interstitial fibrosis, old infarcts and in scleroderma

Dr. PRIYANKA SACHDEV

 ETIOLOGY
• 1. SMOKING

• 2. OTHER FACTORS →

• i) Radiation exposure
• ii) Atmospheric pollution
• iii) Occupational causes
• iv) Dietary factors
• v) Chronic scarring

Dr. PRIYANKA SACHDEV

 MOLECULAR PATHOGENESIS
•i) EGFR mutations
•ii) VEGF over expression

Dr. PRIYANKA SACHDEV

Grossly

Dr. PRIYANKA SACHDEV

 1. Hilar type →
• Most commonly, the lung cancer arises in the main bronchus or
one of its segmental branches in the hilar parts of the lung,

• More often on the right side.

• The tumour begins as a small roughened area on the bronchial
mucosa at the bifurcation.
• As the tumour enlarges, it producing nodular or ulcerated
surface.
• The nodules coalesce, the carcinoma grows into a friable
spherical mass, 1 to 5 cm in diameter, narrowing and occluding
the lumen.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 2. Peripheral type →
•Originate from a small peripheral
bronchiole
• The tumour may be a single nodule or
multiple nodules in the periphery of the
lung producing pneumonia like
consolidation of a large part of the lung.
• The cut surface of the tumour is greyish and
mucoid

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 TYPES
•i) Squamous cell or epidermoid carcinoma
•ii) Small cell carcinoma
•iii) Adenocarcinoma (including
bronchioalveolar carcinoma)
•iv) Large cell carcinoma
•v) Combined squamous cell carcinoma
and adenocarcinoma (adenosquamous
carcinoma).
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Remember
•Adenocarcinoma is the overall most common type
of lung carcinoma
•Squamous cell (epidermoid) carcinoma is the
most common type of lung carcinoma in lndia

•Adenocarcinoma is the most common type of

lung carcinoma in non-smokers and females.
•Squamous cell carcinoma is the most common
type of lung carcinoma in smokers and males
Dr. PRIYANKA SACHDEV
 TYPES
•i) Squamous cell or epidermoid carcinoma
•ii) Small cell carcinoma
•iii) Adenocarcinoma (including
bronchioalveolar carcinoma)
•iv) Large cell carcinoma
•v) Combined squamous cell carcinoma
and adenocarcinoma (adenosquamous
carcinoma).
Dr. PRIYANKA SACHDEV
 Squamous cell carcinoma
•Most common type of lung cancer in India

•Most commonly found in men and is

closely related with smoking history

•They arise centrally (hilar) from the

segmental or subsegmental bronchi
Dr. PRIYANKA SACHDEV
 Histologically
•Characterized by the presence of
keratinization and intracellular bridges

•Keratinization may take the form of squamous

pearls (eddy pearl) or individual cells with
markedly eosinophilic dense cytoplasm.

•Marker of squamous cell carcinoma is

cytokeratin
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 TYPES
•i) Squamous cell or epidermoid carcinoma
•ii) Small cell carcinoma
•iii) Adenocarcinoma (including
bronchioalveolar carcinoma)
•iv) Large cell carcinoma
•v) Combined squamous cell carcinoma and
adenocarcinoma (adenosquamous
carcinoma).
Dr. PRIYANKA SACHDEV
 Small cell carcinoma (Oat-cell
carcinoma)

• Small cell carcinoma have a strong

relationship to cigarrete smoking (also
squamous cell carcinoma).

•They occur both in major bronchi

(central) and in the periphery of lung.
Dr. PRIYANKA SACHDEV
 Histologically
Tumour cells →
• Scant cytoplasm
• Ill defined cell borders
• Small -» Smaller than small resting lymphocytes
• High mitotic count
• Finely granular nuclear chromatin (salt and pepper
pattern)
• Absent or incospicuous nucleoli
• Necrosis is common and extensive.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•Marker → Neuroendocrine markers ->
chromogranin , Synaptophysin,

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Remember
• Small cell carcinoma of lung is the most aggressive and most
malignant lung tumor, with worst prognosis

• It characterized by widespread metastasis early in the course, with

common spread to mediastinal (hilar) lymph nodes , liver, bones,
adrenal gland and brain.

• Most common site of metastasis is brain

• Small cell carcinoma is most common type of lung cancer associated
with ectopic horomone production and paraneoplastic syndrome
• It is the most common type of lung cancer responsive to
chemotherapy and radiotherapy

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 TYPES
•i) Squamous cell or epidermoid carcinoma
•ii) Small cell carcinoma
•iii) Adenocarcinoma (including
bronchioalveolar carcinoma)
•iv) Large cell carcinoma
•v) Combined squamous cell carcinoma and
adenocarcinoma (adenosquamous
carcinoma).
Dr. PRIYANKA SACHDEV
 3. Adenocarcinoma
• Adenocarcinoma is the most common lung cancer, overall

• Also the most common type of lung cancer in women and

nonsmokers

• Peripheral carcinoma

• Adenocarcinomas grow more slowly than squamous cell

carcinomas but tends to metastatize widely and earlier

Dr. PRIYANKA SACHDEV

 TYPES
• i) Acinar → predominance of glandular structure
• ii) Papillary→ pronounced macropapillary
configuration
• iii) Bronchioalveolar / Lepidic → cuboidal to tall
columnar and mucus-secreting epithelial cells
growing along the existing alveoli
• Bronchioloalveolar carcinoma consists mucin secreting bronchiolar cells, clara cells,
or rarely type II pneumocytes.
• iv) Solid with mucin production

Dr. PRIYANKA SACHDEV

•Marker → CK 7

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 TYPES
•i) Squamous cell or epidermoid carcinoma
•ii) Small cell carcinoma
•iii) Adenocarcinoma (including
bronchioalveolar carcinoma)
•iv) Large cell carcinoma
•v) Combined squamous cell carcinoma and
adenocarcinoma (adenosquamous
carcinoma).
Dr. PRIYANKA SACHDEV
 4. Large cell carcinoma

•It is characterized by cells with large nuclei,

prominent nucleoli and a moderate
amount of cytoplasm.

•It is located peripherally

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 5. Adenosquamous carcinoma
•These are a small proportion of
peripheral scar carcinomas having clear
evidence of both keratinisation and
glandular differentiation

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 TYPES
•i) Squamous cell or epidermoid carcinoma
•ii) Small cell carcinoma
•iii) Adenocarcinoma (including
bronchioalveolar carcinoma)
•iv) Large cell carcinoma
•v) Combined squamous cell carcinoma and
adenocarcinoma (adenosquamous
carcinoma).
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
SPREAD

Dr. PRIYANKA SACHDEV

 1. Direct spread →
•Extension of the cancer located at the
apex of the lung into the thoracic cage
may involve brachial plexus and the
sympathetic chain causing pain and
sensory disturbances, so called
Pancoast’s syndrome
Dr. PRIYANKA SACHDEV
 2. Lymphatic spread
•Initially, hilar lymph nodes are affected.
Later, lymphatic metastases occur to the
other groups like mediastinal, cervical,
supraclavicular and para-aortic lymph
nodes.

Dr. PRIYANKA SACHDEV

 3. Haematogenous spread →
•liver, adrenals, bones, pancreas, brain,
opposite lung, kidneys and thyroid

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Paraneoplastic syndromes
in lung carcinoma

•Lung carcinoma can be associated with

a number of paraneoplastic syndromes

Dr. PRIYANKA SACHDEV

 Hormones or hormone-like factors
elaborated include :
1. ADH →Causing SIADH
2. ACTH → Causing cushing syndrome
3. PTH (parathormone related peptide →
Causing hypercalcemia
4. Calcitonin →Causing hypocalcemia
5. Gonadotropins →causing gynaecomastia
Dr. PRIYANKA SACHDEV
6. Lambert eaton syndrome

7. Acanthosis nigricons

8. Hypertrophic pulmonary
oseoarthropathy (clubbing & periosteal
reaction).
Dr. PRIYANKA SACHDEV
 REMEMBER
1. Tumors that produce ACTH and ADH are
predominantly small cell carcinomas,

2. Tumours that produce hypercalcemia (due to

PTH) are mostly squamous cell tumors

3. Gynaecomastia (due to gonadotropin) is

associated with large cell carcinoma.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Investigations for Lung Cancer

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 TREATMENT
1. Surgery
2. Chemotherapy
3. Radiotherapy

Dr. PRIYANKA SACHDEV

• Small cell carcinomas are highly chemosensitive with an
overall 90% regression rate with chemotherapy

Dr. PRIYANKA SACHDEV

 Horner syndrome
• Horner syndrome is caused due to compression of
sympathetic nerve plexus by an apical tumor
called as Pancoast tumor

• It is usually an adenocarcinoma.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 LIVER
Dr. PRIYANKA SACHDEV
 IMPORTANT TOPICS
• Jaundice

• CVC Liver / Nutmeg liver

• Hepatitis

• Cirrhosis

• Tumours of liver
Dr. PRIYANKA SACHDEV
 ANATOMY
•The liver is the largest organ in the
body

•Weighing 1400-1600 gm in the males

and 1200-1400 gm in the females.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
•There are 2 main anatomical lobes —right
and left

•The right being about six times the size of the

left lobe

•The right lobe has quadrate lobe on its

inferior surface and a caudate lobe on the
posterior surface.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 The right and left lobes are
separated by
➢Anteriorly by a fold of peritoneum called the
falciform ligament

➢Posteriorly by the fissure for the

ligamentum venosum

➢Inferiorly by the fissure for the ligamentum

teres
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•Liver is covered by a firm smooth layer
of connective tissue called Glisson’s
capsule

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Dual blood supply
•The liver has a double blood supply—

➢The portal vein brings the venous blood from

the intestines and spleen (providing 70% of
hepatic blood flow)

➢The hepatic artery coming from the coeliac

axis supplies arterial blood to the liver
(providing 70% of hepatic blood flow)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Portal triad
•Glisson’s capsule extend into the liver
around branches of hepatic artery, portal
vein and bile ducts as branching
trabeculae called as portal tracts (portal
canals).

•The combination of a bile ductule, branch

of hepatic artery, and branch of portal vein
is referred to as portal triad.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Portal triad contains
1. Bile ductule
2. Branch of hepatic artery
3. Branch of portal vein

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
HISTOLOGY

Dr. PRIYANKA SACHDEV

 Lobular model →

•The hepatic parenchyma is composed of

numerous hexagonal or pyramidal
structures→ Classical lobules each with a
diameter of 0.5 to 2 mm.

•They are the functional unit of liver

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Each classical lobule has
1. A central hepatic vein (branch of hepatic vein)

2. 4 to 5 portal tracts or triads at the periphery →

containing branches of bile duct, portal vein and
hepatic artery.

3. Cords of hepatocytes (which are one cell thick)

and blood containing sinusoids radiate from the
central vein to the peripheral portal triads.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•Hepatocytes around portal triad form a
limiting plate.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Sinusoids
•Between the hepatic cords lie venous
sinusoids.

•Sinusoids between cords of hepatocytes are

lined by discontinuous endothelial cells
and scattered flat Kupffer cells belonging to
the reticuloendothelial system.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Space of Disse
• Hepatocytes of hepatic cords are separated from venous
sinusoids by perisinusoidal space of Disse

• The space of Disse is the space between hepatocytes and

sinusoidal lining endothelial cells.

• A few scattered fat storing Ito cells / stellate cells lie within
the space of Disse.
• Ito cells store fat and vitamin A
• They get transformed into collagen producing myofibroblasts
during hepatic inflammation.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Bile canaliculi
• There are bile canaliculi interposed between the
adjacent hepatocytes.

• The bile canaliculi are simply grooves between the

contact surfaces of the liver cells and are covered by
microvilli.

• These canaliculi join at the periphery of the lobule to

drain eventually into terminal bile ducts

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Finally diagram of normal liver

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 FUNCTIONS of Liver
•1. Manufacture and excretion of bile.
•2. Manufacture of several major plasma
proteins such as albumin, fibrinogen and
prothrombin.
•3. Metabolism of proteins, carbohydrates and
lipids.
•4. Storage of vitamins (A, D and B12) and iron.
•5. Detoxification of toxic substances such as
alcohol and drugs. Dr. PRIYANKA SACHDEV
 Zones of liver
•Accordingly, the hepatic parenchyma of liver
lobule is divided into 3 zones→

1. Zone 1
2. Zone 2
3. Zone 3

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Zone 1 (Periportal or peripheral)
area
•Zone 1 is closest to the arterial and portal
blood supply
•Hepatocytes of this zone are exposed to
blood having high nutrients, and oxygen

•Least susceptible to ischemic necrosis

• Most susceptible to toxic injury.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Zone 3 (Centrilobular area)
•Zone 3 surrounds the central vein
•It is most remote from the blood supply
•Most susceptible to ischemic necrosis

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Zone 2 (Midzonal)
•Zone 2 is the intermediate midzonal area.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Zonal necrosis

•Identical regions of all liver lobules are

involved.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 It is divided into 3 types →

i) Centrizonal (centrilobular) necrosis

ii) Peripheral zonal (periportal) necrosis
iii) Midzonal necrosis

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
i) Centrizonal (centrilobular) necrosis

•Necrosis is seen around central hepatic vein.

•It is seen in→

1. Cardiac failure /shock (chronic passive
congestion (CPC)due to right heart failure
2. Chloroform toxicity
3. Carbon tetra chloride (CCl4 toxicity)
4. Halothane
5. Viral hepatitis Dr. PRIYANKA SACHDEV
 ii) Peripheral zonal (periportal)
necrosis

• Necrosis is seen around portal tracts

•It is seen in→

1. Eclampsia
2. Phosphorus poisoning
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 iii) Midzonal necrosis

•It is rare and is seen in yellow fever

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Polls 1

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
D

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
C

Dr. PRIYANKA SACHDEV

Chronic venous congestion (CVC)

Dr. PRIYANKA SACHDEV

•In left-sided heart failure → pulmonary
congestion (or CVC lungs) results

•In right-sided heart failure → systemic

venous congestion (i.e. CVC of systemic organs →Liver,
spleen ) results

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 CVC/ CPC Liver
Grossly→

• The liver is enlarged and tender

•Capsule is tense.
•Cut surface shows characteristic nutmeg
appearance due to red and yellow mottled
appearance, corresponding to congested
centre of lobules and fatty peripheral zone
respectively
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Microscopically→

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
•The central veins is distended and filled with blood.

•The centrilobular hepatocytes undergo

degenerative changes and Centrilobular
haemorrhagic necrosis occurs.

•The peripheral zone of the lobule is less severely

affected by chronic hypoxia and shows fatty change
in peripheral zone hepatocytes

•So nutmeg appearance

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Polls 2

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
A

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
A

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
C

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
A

Dr. PRIYANKA SACHDEV

HEPATITIS

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 VIRAL HEPATITIS/ Infectious
Hepatitis
• Hepatitis A virus (HAV), causing a faecally-spread
selflimiting disease.
• Hepatitis B virus (HBV), causing a parenterally
transmitted disease that may become chronic.
• Hepatitis C virus (HCV), previously termed non-A,
non-B (NANB) hepatitis virus involved chiefly in
transfusion-related hepatitis.
• Hepatitis delta virus (HDV) which is sometimes
associated as superinfection with hepatitis B
infection.
• Hepatitis E virus (HEV), causing water-borne
Dr. PRIYANKA SACHDEV
infection
•HBV is a DNA virus
•All other human hepatitis viruses are
RNA viruses.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Hepatitis A virus (Infectious
Hepatitis)
•Causative agent : HAV is an unenveloped,
,icosahedral single stranded RNA virus
belonging to Picornavirus family.

Dr. PRIYANKA SACHDEV

 Mode of Infection

1. Feco-oral route is the predominant

route of spread.

Dr. PRIYANKA SACHDEV

•Incubation period → 2-6 weeks.

•It is present in the liver, bile, blood and

stools

Dr. PRIYANKA SACHDEV

 Clinical features
•HAV causes only acute hepatitis.
•It is a benign and self-limiting disease
•It is the most common cause of acute
hepatitis in children.

•It does not cause chronic hepatitis or

carrier state in hepatitis
Dr. PRIYANKA SACHDEV
Clinical spectrum

Dr. PRIYANKA SACHDEV

 Serum markers for hepatitis
A infection
•HAV is present in stools 2-3 weeks before and 1
week after onset of jaundice.

•1. IgM anti-HAV antibody appears in the serum at

the onset of symptoms of acute hepatitis A.

•2. IgG anti-HAV antibody is detected in the serum

after acute illness and remains detectable indefi
nitely. It gives lifelong protective immunity against
reinfection with HAV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Hepatitis B virus (Serum Hepatitis)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
REMEMBER

Dr. PRIYANKA SACHDEV

 Remember

•Presence of HBe Ag denotes high

infectivity

•Its absence and presence of Anti HBe Ab

denotes low infectivity.

Dr. PRIYANKA SACHDEV

 Immunology concept

•Immunization for HBV is based on the fact

that anti HBs Ab is protective in nature.

•So, vaccination with non- infectious HBs Ag

still retaining its immunogenic potential is
done.
Dr. PRIYANKA SACHDEV
 Mode of Infection

1. Parenteral →Blood products, needle

sticks etc. (30%)
2. Sexual transmission
3. Vertical transmission is responsible for
development of carrier state

Dr. PRIYANKA SACHDEV

•Incubation Period → 30-180 days.

•HBV is present in all physiologic and

pathologic body fluids, except in stools
(unlike HAV).

Dr. PRIYANKA SACHDEV

 Clinical features
It can cause →
1. Acute hepatitis
2. Non-progressive Chronic hepatitis,
3. Progressive chronic hepatitis leading to cirrhosis
4. Fulminant hepatitis
5. Carrier state
6. Hepatocellular carcinoma.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
POLLS 3

Dr. PRIYANKA SACHDEV

First antibody to appear in hepatitis
•a) IgM anti-HBe
•b) IgG-anti-HBe
•c) IgM anti-HBc
•d) IgM anti-HBs

Dr. PRIYANKA SACHDEV

C

Dr. PRIYANKA SACHDEV

Recent Hepatitis infection is best
diagnosed by-
•a) HbsAg
•b) Ig G Anti HBe abs
•c) Anti HBsAg abs
•d) IgM anti HBc abs

Dr. PRIYANKA SACHDEV

D

Dr. PRIYANKA SACHDEV

Infection/ multiplication of HBV is
best/commonly diagnosed by -
•a) HBeAg
•b) HbsAg
•c) HBVDNA
•d} AntiHBsAg

Dr. PRIYANKA SACHDEV

A

Dr. PRIYANKA SACHDEV

Anti HBs Ab indicates -
•a) Resistance to Hepatitis B
•b) Acute infection
•c\ Good Prognosis
•d) Hepatocellular Carcinoma
Dr. PRIYANKA SACHDEV
A

Dr. PRIYANKA SACHDEV

 Epidemiologic study of Hepatitis B is -
•a) HBeAg
•b) HBcAg
•c) HBs Ag
•d) Anti HBc

Dr. PRIYANKA SACHDEV

C

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
3. Hepatitis C virus (Transfusion
Associated Hepatitis)

•Causative agent : HCV is a single stranded

RNA virus belonging to Flaviviridae family.

•Parentrally transmitted non-A non-B virus

Dr. PRIYANKA SACHDEV

 Mode of Infection
1. Parenteral→ through exposure to infectious blood. This can
occur through:
➢ (a) receipt of contaminated blood transfusions, blood products
and organ transplants
➢(b) injections given with contaminated syringes and needle-stick
injuries in health-care settings
➢(c) injection drug use

2. Perinatal
3. Sexual

Dr. PRIYANKA SACHDEV

•Incubation Period → 2-26 weeks.

Dr. PRIYANKA SACHDEV

 Clinical features
• 15% Acute illness is usually asymptomatic/mild.

• About 75-85% of newly infected persons develop

chronic disease

• 60- 70% of chronically infected people develop

chronic liver disease;
• 5-20% develop cirrhosis
• 1-5% die from cirrhosis or liver cancer.
Dr. PRIYANKA SACHDEV
 Serum markers for hepatitis B
infection
1. HCV RNA

2. Anti-HCV → Initially, there is IgM anti-

HCV followed by the presence of IgG
anti-HCV antibodies.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Anti-HCV antibodies
3 generations of anti-HCV assays are available:
• i) First generation antibodies are against C100-3 region
proteins and appear 1 to 3 months after infection.

• ii) Second generation antibodies are against C200 and

C33c proteins and appear about one month earlier than
the first generation.

• iii) Third generation antibodies are against C22-3 and

NS-5 region proteins and are detected even earlier.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 REMEMBER
•IgG anti-HCV does not provide
effective immunity because the virus
demonstrates genomic instability and
antigenic variability.

Dr. PRIYANKA SACHDEV

 4. Hepatitis D virus
•Causative agent → It is a single stranded
RNA virus, delta virus (HDV)
•HDV is a defective virus for which HBV is the
helper.

•Replication is defective and can cause

infection only when encapsulated by HBs
Ag
Dr. PRIYANKA SACHDEV
 Mode of infection
1. It is transmitted by parenteral route

Incubation period → 30 – 50 days

Dr. PRIYANKA SACHDEV

 Clinical features
•So, it can cause infection in 2 conditions:

Dr. PRIYANKA SACHDEV

 Acute co-infection
•In which there is simultaneous exposure
to both HBV and HDV.
•However, HBV must establish first.
•This is associated with 90% chances of
recovery and only rare chances of
development of chronic hepatitis.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Super infection
•In which chronic carriers of HBV get
infected with HDV.
•This is associated with majority
developing chronic hepatitis.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Serum markers
•The serology shows the presence of IgM
Anti HDV which is the most reliable
marker of recent infection

Dr. PRIYANKA SACHDEV

 Hepatitis E virus
•Causative agent →HEV belongs to
calciviridae.
• It is also known as enterically transmitted
non-A non-B (NANB)

•Hepatitis E was first documented in New

Delhi in 1955 when 29000 cases of icteric
hepatitis occured
Dr. PRIYANKA SACHDEV
 Mode of infection
1. It is transmitted by fecal-oral route.

Dr. PRIYANKA SACHDEV

•Incubation period → 15-60 days.

Dr. PRIYANKA SACHDEV

 Clinical features
• It is the most common cause of acute viral hepatitis
in adults
• It is the overall most common cause of acute viral
hepatitis in India

• A unique feature is Fulminant hepatitis of high

case fatality rate of 20-40 % in pregnant women,
especially in the last trimester of pregnancy
• No chronic hepatitis
Dr. PRIYANKA SACHDEV
 REMEMBER
•Enterically transmitted non-A non-B
(NANB) virus is hepatitis-E virus

•Parenterally transmitted non-A non-B

virus is hepatitis-C virus

Dr. PRIYANKA SACHDEV

 Hepatitis G virus
•It is a single stranded RNA virus
•Transmitted by the parenteral route i.e. by the
contaminated blood or blood products and
possibly by the sexual route.
•The site of HGV replication is mononuclear
cells, so, it does not cause any rise in serum
amino transferases
•Non pathogenic.
•It co-infects patients with HIV and the dual
infection is protective against HIV disease.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 CLINICOPATHOLOGIC
SPECTRUM

•i) Carrier state

•ii) Asymptomatic infection
•iii) Acute hepatitis
•iv) Chronic hepatitis
•v) Fulminant hepatitis
(Submassive to massive necrosis)
Dr. PRIYANKA SACHDEV
 CLINICOPATHOLOGIC SPECTRUM
1. Acute hepatitis
2. Chronic hepatitis
3. Fulminant hepatitis (Submassive to
massive necrosis)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Acute Hepatitis
•In general, type A, B, C, D and E run
similar clinical course and show
identical pathologic findings

Dr. PRIYANKA SACHDEV

 Histologically
•1. Hepatocellular injury → most
marked in zone 3 (centrilobular zone):

Dr. PRIYANKA SACHDEV

• i) Mildly injured hepatocytes appear swollen with granular cytoplasm →
Ballooning degeneration

• ii) Some hepatocytes show acidophilic degeneration in which the cytoplasm

becomes intensely eosinophilic, the nucleus becomes small and pyknotic ,
leaving behind necrotic, acidophilic mass called Councilman body or
acidophil body

• iii) Dropout necrosis →Small clusters of hepatocytes undergo lysis

• iv) Bridging necrosis characterised by bands of necrosis linking

❑portal tracts to central hepatic veins,(porto-central)
❑one central hepatic vein to another (centro-central)
❑a portal tract to another tract (porto-portal)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•2. Inflammatory infiltrate →There is
infiltration by mononuclear inflammatory
cells, usually in the portal tracts, but may
permeate into the lobules.

•3. Kupffer cell hyperplasia →There is

reactive hyperplasia of Kupffer cells
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 CLINICOPATHOLOGIC SPECTRUM
1. Acute hepatitis
2. Chronic hepatitis
3. Fulminant hepatitis (Submassive to
massive necrosis)

Dr. PRIYANKA SACHDEV

 Chronic Hepatitis
•HCV infection accounts for 40-60% cases of
chronicity in adults.

•HBV causes chronic hepatitis in 90% of infected

infants and in about 5% adult cases of hepatitis B.

•HDV superinfection on HBV carrier state may be

responsible for chronic hepatitis in 10-40% cases.

•HAV and HEV do not produce chronic hepatitis.

Dr. PRIYANKA SACHDEV
 Histologically
•1. Limiting plate lesion

i. Piecemeal necrosis → Piecemeal necrosis

is defined as periportal destruction of
hepatocytes at the limiting plate (piecemeal
= piece by piece).

ii. Interface hepatitis

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 2. Portal tract lesions
•i) Inflammatory cell infiltration by
lymphocytes, plasma cells and
macrophages (triaditis).

•ii) Proliferated bile ductules in the

expanded portal tracts.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 3. Intralobular lesions
•Scattered acidophilic bodies in the lobule.
• Kupffer cell hyperplasia.
•More severe form of injury shows bridging
necrosis (i.e. bands of necrosed hepatocytes
that may bridge portal tract-to-central vein,
central vein-to-central vein, and portal tract-
to-portal tract).
•Regenerative changes in hepatocytes in cases
of persistent hepatocellular necrosis.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 4. Bridging fibrosis
• i) At first, there is periportal fibrosis at the sites of interface
hepatitis giving the portal tract stellate-shaped appearance.

• ii) Progressive cases show bridging fibrosis connecting portal

tract-to-portal tract or portal tract-to-central vein traversing

• iii) End-stage of chronic hepatitis is characterised by dense

collagenous septa destroying lobular architecture and
forming nodules resulting in cirrhosis

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 REMEMBER
•Chronic hepatitis due to HBV shows
ground-glass hepatocytes

•HBs Ag in cytoplasm of hepatocytes produce

finely granular appearance.

Dr. PRIYANKA SACHDEV

 CLINICOPATHOLOGIC SPECTRUM
1. Acute hepatitis
2. Chronic hepatitis
3. Fulminant hepatitis (Submassive to
massive necrosis)

Dr. PRIYANKA SACHDEV

Fulminant Hepatitis (Submassive to
Massive Necrosis)
•Fulminant hepatitis is the most severe
form of acute hepatitis in which there is
rapidly progressive hepato cellular failure

Dr. PRIYANKA SACHDEV

 Histologically
•i) In submassive necrosis

•ii) In massive necrosis

Dr. PRIYANKA SACHDEV

 i) In submassive necrosis
•Large groups of hepatocytes in zone 3
(centrilobular area) and zone 2 (mid zone) are
wiped out leading to a collapsed reticulin
framework.

•Regeneration in submassive necrosis is more

orderly and may result in restoration of normal
architecture.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 ii) In massive necrosis

•The entire liver lobules are necrotic.

•As a result of loss of hepatic parenchyma,
•Inflammatory infiltrate is scanty.
•Regeneration, if it takes place, is disorderly
forming irregular masses of hepatocytes.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
REVISION

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Dr. PRIYANKA SACHDEV