Professional Documents
Culture Documents
-Anaerobic(extremely common)
-Staph Aureus, , Klebsiella,
Streptococcus pyogenes
The Pneumonia Syndromes
bacteria multiply in
alveoli, dilated
alveolar capillaries,
early fluid exudation
infection controlled
Gray hepatization
dry, gray, firm
exudation and
hyperemia stop
red cells
depleted
Resolution
Removal of exudate
complete resolution can occur
because structure of alveoli not
damaged in lobar pneumonia
Bronchopneumonia has structural
damage
Complications of pneumonia
Pleural effusion
Lung abscess: anaerobic bacteria,
Staphylococcus aureus, Klebsiella
pneumoniae, Streptococcus
pyogenes
Empyema
Meningitis, bacteremia, endocarditis,
arthritis
Lung Abscess
Copious, foul sputum, hemoptysis,
fever, malaise
Complications bronchopleural
fistula, empyema, septicemia,
amyloidosis
Treat with antibiotics
Psuedomonas aeroginosa
Cystic fibrosis
Nosocomial, neutropenic patients,
burns
Vasculitis and vascular spread
Psuedomonas septicemia is a very
fulminant disease
Staph. aureus pneumonia:
After viral respiratory illness -
secondary
Nosocomial (MRSA Penicillin
resistance)
Abscess formation, empyema
I/V drug abusers- endocarditis
Klebsiella Pneumonia
Most frequent gram negative
pneumonia
Debilitated and malnourished
Chronic alcoholics
Thick gelatinous sputum ( viscid
capsular material)
Extensive destruction
Moraxella catarrhalis
Elderly individuals
Second most common cause of
pneumonia in COPD
Otitis media in children
Pneumococcal pneumonia
Settings- usually nil, viral infection,
CHF, COPD, immune
deficiency, splenectomy (auto)
Sputum - gram positive diplococci- look
for intracellular in pmn
Blood culture - more specific
Vaccines
H. Influenzae pneumonia
After viral respiratory illness - secondary
Common cause of community acquired
pneumonia in adults
With routine use of the vaccine, the
incidence of disease caused by the b
serotype has decreased significantly
Can cause endocarditis
Most common cause of acute
exacerbation of COPD
Legionella pneumonia
Sporadic, epidemic
Artificial water pools- tubing, cooling
towers
In chronically ill patients, post
transplant
High fatality
Culture- best for diagnosis, others-
sputum, urine
Vascular and Hemodynamic
Pathology
Topics Covered In This
Lecture
1.Pulmonary Edema
2.Acute respiratory distress
syndrome (ARDS)
3.SARS (Severe acute
respiratory syndrome)
4.Pulmonary Embolism
5.Pulmonary Hypertension
Case History
72 yr old extremely pleasant
Caucasian male with a past medical
history of CABG and multiple stents,
unstable angina and myelodysplastic
syndrome, presented with left arm
pain
He was admitted, but died within 24
hours
A post mortem was performed.
Post mortem findings
Right lung weighed 1,100 g and the
left lung weighed 750 g
Severe coronary atherosclerosis was
noted
There was evidence of acute
myocardial infarction and massive
pulmonary edema
Causes of Pulmonary
Edema
Hemodynamic disturbances
Increased hydrostatic pressure
Left sided congestive heart failure
Heavy wet lungs (basal regions of lower lobes)
Alveolar capillaries engorged
Intra-alveolar granular pink precipitate
Heart failure cells; brown discoloration
Impairs pulmonary function and predisposes
to infection
Pulmonary Edema- Causes
Hemodynamic
Increased hydrostatic pressure
Left ventricular failure (common)
Excess IV fluids
Decreased oncotic pressure
Severe hypoproteinemia, Liver disease,
Nephrotic syndrome
Other
Lymphatic obstruction (carcinoma, rare)
Pulmonary edema--Causes
Microvascular Injury
Damage to vascular endothelium
Leekage of fluid and proteins into
interstitium and lumen
Diffuse edema is a contributor to
acute respiratory distress syndrome
Microvascular injury
Infections: Pneumonia, septicemia
Inhaled gases: Oxygen, smoke
Liquid aspiration: Gastric contents
Drugs and chemicals:Chemotherapy
agents, heroin, cocaine, paraquat
poisoning
Shock, trauma
Radiation
Transfusion related
Adult(Acute) Respiratory
Distress Syndrome (ARDS)
Syn. Shock Lung Syndrome, Diffuse
alveolar damage (DAD), Acute lung
injury (ALI)
(cf. RDS in neonates due to
deficiency of surfactant)
Clinical syndrome caused by diffuse
alveolar damage
Mechanism of ARDS
Imbalance between pro-inflammatory
and anti inflammatory cytokines
Toll like receptors activate NF-kB, a
transcription factor controlling
expression of pro-inflammatory
genes
IL-10 is anti-inflammatory cytokine
Modification of the transcription
cascade may be a logical future
target for ALI
ARDS
ARDS
Endothelium
necrosis
Type I alveolar
cells necrosis
Fibrin
Edema
Waxy Hyaline
membranes
Shock lung
Endothelial damage, damage to type 1
pneumocytes
Exudate, impaired gas exchange
Hyaline membrane (necrotic debris from
epithelial cells plus edema fluid coagulate)
Type II pneumonocyte necrosis- loss
of surfactant- microatelectasis
What Causes ARDS?
Infections*
Sepsis*
Head injuries*
Gastric aspiration*
Pancreatitis
Burns
Trauma
Fractures with fat embolism
Clinical features
Serious disorder
Respiratory difficulty- acute
Gasping for breath
Severe hypoxemia, cyanosis, unresponsive to
oxygen
Bilateral infiltrates on chest X-ray
Absence of clinical features of LVF
High mortality: 40% in 190,000 ARDS cases/yr
Patchy distribution
Healing may result in diffuse interstitial fibrosis
Phases of ARDS
Exudation- 0-7 days
Proliferation - 1-3 weeks
macrophages phagocytose dead
cells and hyaline membrane, type
II pneumonocytes proliferate
mature in to type I cells
Fibrosis- TGF-, PDGF
SARS
(Severe acute respiratory syndrome)
First appeared in China in Nov 2002; last case 2004
Cause -- Corona virus; 8000 cases; 774 deaths
2-10 day incubation period;begins with dry cough,
malaise, myalgia, fever, chills
1/3rd fight infection, but 2/3rd progress to severe
respiratory disease, shortness of breath, tachypnea,
and pleurisy
10% of patients die from illness
First transmitted through wild masked palm civets
Patho-physiology unknown; how virus moved from
animals to humans unknown
Pulmonary embolism
Pulmonary Infarction
Causes more than 50,000 US deaths/year
Large pulmonary embolus is a cause
sudden instantaneous death
Blood clots that occlude large pulmonary
vessels are embolic
Usual source of pulmonary emboli are the
deep veins of the leg
Pulmonary embolism
95% from deep leg veins
Sick, bedridden patients with
pulmonary, cardiovascular
disease
BIG -> bifurcation of PA, sudden
death from acute right heart
failure - no time to develop any
changes in lungs
Pulmonary embolism
MEDIUM -> hemorrhage, infarction
only if circulatory status already
compromized
SMALL -> usually no infarct because
of dual supply, resolve ( lysis),
if recurrent- pulmonary hypertension
Infarction
Clinically resembles myocardial
infarction - chest pain, dyspnea,
shock
Gross: Wedge shaped, hemorrhagic
infarct, may be multiple
Micro: coagulation necrosis
Pulmonary Hypertension
Case Vignette
47 yr old male, non-smoker presents
with worsening and progressive
dyspnea
On exam., bi-basilar crackles,
rhonchi and wheezes were noted
Past history is significant for
Osteogenesis Imperfecta, Spinal mid
thoracic kyphoplasty, hip and knee
surgery
Case Vignette
Patient also has renal failure,
cardiomegaly, pleural effusion,
coronary atherosclerosis and
pulmonary edema
CT scan shows bilateral interstitial
infiltrates
Bronchosopic biopsies to rule out
interstitial disease/ infection
What does the patient have?
Pulmonary hypertension
Pulmonary edema
Heart failure Cells (cor pulmonale)
No interstitial disease
No atypical pneumonia
Pulmonary hypertension
When pulmonary pressure reaches 1/4th
of systemic levels
Primary- BMPR2 locus mutations
Rare, young women,recurrent
dyspnea ,syncope
Reynauds phenomenon (vasopasm
of peripheral vessels)
? Neurohormonal hyperactivity
? Vasotropic virus- HSV 8
Pulmonary hypertension
Secondary
COPD - Chronic bronchitis,
emphysema, diffuse fibrosis
Congenital shunts- VSD
Recurrent pulmonary
thromboembolism in small sized
vessels
Pulmonary hypertension
Mild
Elastic
Normal duplication
pulmonary Medial
artery hypertrophy,
Intimal fibrosis
Severe -
Plexiform
lesions
Pulmonary hypertension
Plexiform lesions
Morphology of pulmonary
hypertension
Changes in medium sized arteries
Medical thickening
Intimal hyperplasia / fibrosis
Reduplication of elastica,
Morphology of pulmonary
hypertension
Plexiform changes in severe
varieties only (primary)
Necrosis of wall (fibrinoid)
Thrombosis
Rupture, bleed
Dilation lesions, angiomatoid
lesions
Hemosiderin
Primary pulmonary hypertension-
clinical
Symptoms appear late
Fatigue, dyspnoea
Syncope on exercise
Chest pain
Respiratory insufficiency, cyanosis
Cor pulmonale
Restrictive lung disease
Case history
69 yr female with 3 month history of
dyspnea (shortness of breath)
Lung CT shows bilateral interstitial
infiltrates
A bronchoscopic biopsy is performed
Diagnosis
Restrictive lung disease
Usual Interstial Pneumonitis with end
stage lung disease
Honey comb lung
Restrictive lung disease
Extrinsic causes
Intrinsic causes
Extrinsic
Chest wall injury,deformity
( kyphoscoliosis)
Severe obesity
Neuromuscular (Guillain Barre
Syndrome)
Intrinsic
Acute - with known cause
ARDS following shock, pancreatitis
Acute - without known cause AIP
Chronic- without known cause
Idiopathic Interstitial Pneumonias
UIP, DIP/RBILD, NSIP, LIP, COP
Chronic with known cause
Pneumoconiosis
Immunologic
Sarcoidosis
Hypersensitivity pneumonitis
International Consensus Classification
Idiopathic Interstitial Pneumonitis
Formulated in 2002
7 categories
No BOOP
Instead COP
International Consensus
Classification
Histologic Patterns
2002Clinical-radiologic diagnoses
<70%
FEV1 : FVC
>70%
Restrictive lung disease
Idiopathic-IPF, UIP, NSIP etc
Occupational- inorganic-
pneumoconiosis, organic-
hypersensitivity pneumonitis
Drug- chemotherapy, radiation,
oxygen therapy
Immunological- autoimmune
diseases, sarcoidosis
Idiopathic pulmonary fibrosis
Clinical-Radiologic diagnosis
Usual interstitial Pneumonitis histologic
pattern; chronic disease
Acute form is Hamman Rich Syndrome
(AIP, acute interstitial Pneumonitis/DAD)
(Honey comb Lung; end stage disease)
Cause not known
Diffuse fibrosis in alveolar septa
M>F
40-70 years age
Idiopathic pulmonary
fibrosis/UIP
40 yr old
male smoker,
presents
with dyspnea
CT shows
bilateral
interstitial
infiltrates
Case history
48 yr old female with bilateral lung
infiltrates simulating pneumonia
Diagnosis
RBILD
Respiratory bronchiolitis interstitial lung
disease
Case history
52 years female with bilateral interstitial
infiltrates
Patient is HIV positive, and Hepatitis C
positive
Patient has a past history of
Pneumocystis Pneumonia
Diagnosis
Lymphocytic Interstitial Pneumonitis
Can occur in patients with HIV
LIP can range from follicular bronchitis
to indolent lymphoma
Bronchiolitis
Idiopathic
Organizing fibrosis in bronchioles
Cigarette smoke settling on
respiratory bronchioles and setting
up inflammation and fibrosis
Seen with 30 pack year history
Sarcoidosis -
In the lung - restrictive disease
Multisystem involvement,
noncaseating epitheloid
granulomas
Differentiate from Tb, berylliosis,
fungal infections
Cell mediated hypersensitivity to
some unidentified antigen
Case history
43 yr old female with bilateral nodular
infiltrates
Hilar adenopathy noted
Sarcoidosis
Lymph nodes, lungs, skin, eye,
spleen, liver etc
Asteroid bodies, Schaumann bodies
- suggestive but not diagnostic
Sarcoidosis
May be associated with
hypercalcemia (activation of vit. D
by epitheloid cells)
Raised serum angiotensin
converting enzyme (ACE) - 60%
Sarcoidosis
Mikulicz Syndrome - Parotid,
sublingual, submaxillary, Uveal
Bilateral uniform enlargement
Sarcoid, lymphoma-leukemia,
Sjogrens syndrome
Hypersensitivity pneumonitis
Allergic alveolitis (not bronchioles)
Granulomas in alveolar walls, less
fibrosis
Acute (type III) or Chronic (type IV)
Irritation, complement, immune
complex damage
Farmers lung (hay), Bagassosis (sugar
cane), Pigeon breeders lung etc.
Hypersensitivity lesions
Size of particles
Hay fever (type I)
Bronchitis / asthma
Bronchiolitis obliterans
Pneumonitis (type III,IV)
Diffuse pulmonary hemorrhage
Younger patients
Cause not known - no antibodies, no
renal involvement
Recurrent hemorrhage, fibrosis
Pneumoconiosis
(Revise environmental pathology)
Anthracosis, silicosis, asbestosis,
berylliosis, Popcorn Lung ->
Restrictive lung disease
Other causes of interstitial fibrosis
<70%
COPD
Chronic Obstructive
Pulmonary Disease-COPD
Emphysema and Chronic bronchitis
are the two main conditions
causing COPD
Definition of Emphysema is based on
morphological changes that occur
and the definition of Chronic
bronchitis is based on clinical
features
Emphysema
Permanent enlargement and destruction
of airspaces beyond terminal bronchioles
( not just overinflation )
There is no real obstruction for a long time
after the disease starts and hence no
symptoms develop.
When symptoms develop it means
obstruction has occurred.
Emphysema
Permanent dilation of terminal air
spaces with destruction of their
wall.
Elasticity lost, cannot recoil to expel
air
(Inspiration is active, expiration is
passive).
Emphysema
Elderly males and females with
dyspnea (after significant damage).
No organic obstruction - only failure
of recoil.
May develop chronic bronchitis in
addition.
Emphysema-Types
1 Centriacinar ( Centrilobular)
2 Panacinar ( Panlobular)
Normal
Panacinar
Centriacinar
Septal
Megha Joshi S. Bhusnurmath- 142
Centrilobular emphysema
Damage is at respiratory bronchioles
(central and proximal part of
acinus)
Distal alveoli spared,
Common in upper lobes (apex)
Occurs in Smokers, Smog filled city
dwellers
Panacinar emphysema
Uniform enlargement from respiratory
bronchioles, alveolar ducts and
alveoli,
Common in lower lobes.
Seen in A1 AT deficiency
Septal emphysema
Rare variety (distal
acinar)
Next to scars
May form bullae
Chances of
pneumothorax
Pathogenesis of emphysema
Genetics and COPD
The ADAM33, a disintegrin and metallo-
proteinase gene, has been shown to be
associated with asthma and bronchial
hyper-responsiveness.
This relationship, however, has not
been investigated in tobacco smokers
who are susceptible to COPD.
Only 25 % of smokers get COPD
March 12, 2009 BMC Journal
Researchers from the Wake Forest
School of Medicine, NC, genotyped 880
long-term heavy smokers for 25 single
nucleotide polymorphisms (SNPs) in
ADAM33.
287of the study subjects had COPD and
311 did not.
All of them were older than age 50 years
and all had a cigarette smoking history
of at least 20 pack-years.
March 12, 2009 BMC Journal
Identified five SNPs in ADAM33 that occurred
more frequently in the COPD group than in
the group of smokers without COPD.
All five SNPs (Q-1, S1, S2, V-1 and V4) were
associated with COPD, and the S1
polymorphism had the strongest degree of
association with COPD
The investigators say functional studies are
needed to "evaluate the biologic significance
of these polymorphisms in the pathogenesis
of COPD."
Pathogenesis of emphysema
Bronchoscopy
Bronchoscopic cytology, biopsy
Bronchoalveolar lavage
Investigations for lung cancer