Pathology of Respiratory System Disorders

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Pathophysiology
Respiratory System
Dr. Venkatesh M. Shashidhar.
Associate Professor & Head of Pathology

PAS-Respiratory Pathophysiology
Introduction to Resp. Sys:
• 10,000L/day of air – filtered, moistened,
warmed, O2/Co2. exchanged.!
• Full capacity 6L. (500ml at rest)
• Sinusitis, pharyngitis, laryngitis…* URI
• Pneumonia: Inflammation of lung * LRI
• Chronic: COPD, Fibrosis – Smoking.
• Commonest internal Cancer.
• Respiratory tract inflammations -
commonest in medical practice.
• Enormous morbidity & mortality.
• Important medical learning. Doctors daily bread….!

Normal Lung

Respiration – Respiratory system:
5

Respiration – Respiratory system:
6

Alveolar Gas Exchange:
8
Co2
O2

Lung Function testing:
9
Expiration
0 ------- Volume ---------------6L
Inspiration

Lung Function Testing:
• Total Lung Capacity (TLC) 6L male/4.7L fem.
• Tidal Volume (TV) – 500 / 390ml
• Forced Vital Capacity (FVC) 4.8L / 3.7L
• Forced Expiratory Volume in 1 Sec - FEV1
• FEV1/FVC (FEV1%) - 75–80% normal.
1. In Obstructive diseases (COPD) FEV1 low
& FVC high. So FEV1/FVC is low (<80%).
2. In Restrictive diseases (fibrosis) the FEV1
and FVC are both low proportionally and the
FEV1/FVC value normal or high.
 Volume (%FYC)

MX1002-PAS-Wk7-RS
First step to make your
dreams come true
is to wake up!
— Paul Valery

Pneumonia: Infection of lung (LRT)
• Inflammation of alveoli
• Etiology: pathogens vs defence.
• Types: Bacterial, viral, fungal, other.
• Clinical: Lobar / Broncho pneumonia.
• Symptoms: Fever, cough, dyspnoea.
• Complications: Spread  septicemia,
abscess, scarring.

Pneumonia Types:
Etiologic Types:
• Infective
– Viral
– Bacterial
– Fungal
– Tuberculosis
• Non Infective
– Toxins
– chemical
– Aspiration
Morphologic types:
• Lobar
• Broncho
• Interstitial
Duration:
• Acute
• Chronic
Clinical:
• Primary / secondary.

1. Congestion 2.Red Hepatisation
Normal 4. Resolution 3. Grey Hepatization
Pathogenesis of Pneumonia

Pneumonia:

Lobar Pneumonia - Primary
in healthy people in community. Gram Positive Cocci, whole
lobe unilateral. heals without scar. Rare complications.

Bronchopneumonia - Secondary
in Sick patients, Gram Negative bacilli, bilateral,
basal. More complications, heals by scarring.

Broncho-pneumonia – Lobar-pneumonia
• Extremes of age.
• Secondary, in sick.
• Both genders.
• Klebsiella, E.coli
• Patchy, basal, bilateral.
• Around Small Bronchi
• Not limited by anatomic
boundaries.
• Usually bilateral.
• Middle age – 20-50
• Primary in a healthy adult.
• males common.
• 95% pneumococcus
• Entire lobe consolidation
• Diffuse
• Limited by anatomic
boundaries.
• Usually unilateral

Tuberculosis:
• Mycobacterium tuberculosis (typical)
• Primary & Secondary,
• Chronic, Hypersensitivity to bacteria,
• Caseating Granuloma + Fibrosis.
• debilitating, weight loss.
• Upperlobe, cavity + fibrosing.
• Systemic spread, miliary spread.
• Tuberculin Test – hypersensitivity.

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“Whether you think that you
can or that you can't,
you are right…!”
– Henry Ford

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Chronic Lung disorders:
Obstructive & Restrictive

Restrictive vs Obstructive
• Interstitial fibrosis
• Stiff hard lung
• Increased tissue
• Normal FEV1:FVC ratio
• Normal PEFR.
• Types:
– Fibrosis,
– Pneumoconiosis
• Obstruction to air flow.
• Soft lung
• Loss of tissue.
• Low FEV1:VC ratio
• Low PEFR.
• Types:
–COPD
–Asthma

Restrictive - Obstructive

• Irreversible, ﬁbrotic pulmonary
disease due to the inhalation
of large amounts of silica dust
over time.
• Road, civil & mining workers.
• Toxic  Inflam  fibrosis.
• dyspnea, fatigue, weight loss,
fever, and pleuritic pain.
• Multiple small, fibrotic Nodules
bilateral + emphysema.
• Restrictive pattern of PFT.
• TB association common.
Silicosis: Restrictive COPD
Fine nodular shadows

• Beaded protein covered
needle like microscopic .
Asbestos bodies
• Within alveoli & sputum.
• Dyspnoea, dry cough
• Diffuse fibrosis: Honey comb
lung  Pulmonary failure.
• Mesothelioma – pleural
cancer.
Asbestosis: Restrictive

MX1002-PAS-Wk7-RS
Pathology of
Chronic Obstructive
Pulmonary Diseases (COPD)
Dr. Venkatesh M. Shashidhar
Associate Professor of Pathology

Obstructive Airway Disease:
• Localized: Foreign body, aspiration, tumor..
• Diffuse – Distal airway diseases
– Transient reversible spasm - Asthma
– Chronic irreversible permanent – COPD.

Asthma Clinical Pathology:
Chronic hypersensitivity inflammatory
disease of bronchi  excess mucous
and spasmodic occlusion.
Causes
• Allergic: allergens, infection
• non-allergic:neurogenic,
psychogenic
Signs and symptoms
• dyspnea, wheezing, catching for air.
• cough – viscous thick sputum
• Tachycardia & chest pain

Bronchial
Inflammation
TRIGGERS
Allergens, Exercise,
Cold Air, SO2 Particulates
Airway
Hyperresponsiveness
Genetic*
INDUCERS
Allergens,Chemical sensitisers,
Air pollutants, Virus infections
Airflow Limitation

Chronic Obstr. Pulm Disease: COPD
• Chronic, irreversible airway obstruction with
destruction of bronchi & alveoli.
• Clinical: Chronic bronchitis, Emphysema or
COPD (combined).
• Smoking / pollution – commonest cause
• 15% smokers develop COPD.
• Finally leads to lung failure or Cancer.

Smoking – Pathogenesis
• Increase in
– Alveolar marcrophages
– CD8 Lymphocytes
– Neutrophils
– Proteases.
• Tissue irritation / destruction
• Airway damage- Bronchitis
• Alveoli damage- Emphysema.
Emphysema Bronchitis

Smoking effects: FEV 1 & Age

Pathogenesis – Smoke - Lung Dis.
CancerInflam COPD
Irritation  Inflammation  Mucous  Infections  destr. COPD  Cancer

Normal - COPD

Combined  COPD (common)

Lung Normal & in Smokers:

Smokers lung – COPD Bronchitis

Emphysema

Emphysema:
Pink Puffer:
• Lean/weight loss
• Forward stooping
• Barrel chest
• Flat diaphragm
• Hyperlucent Lung

Complications of COPD:
1. Cor Pulmonale – Heart failure.
2. Acute Exacerbations.
3. Recurrent pneumonia.
4. End-stage lung disease.
5. Polycythemia – hypoxia.
6. Bronchiectasis.
7. Lung Cancer.

Bronchiectasis:
• Permanent dilatation of
bronchi with pus.
• Cough, copious purulent
sputum (pus).
• Lower lobes common
• Complications -
Pneumonia, septicemia,
meningitis.
• Management – surgical
resection.

MX1002-PAS-Wk7-RS
“Get me well so I can get on
television and tell people to
stop smoking…!”
-- Nat King Cole

“Troubles are often the tools by which
nature fashions us for better things”
- Henry Ward Beecher

Life’s battles don’t go always to the stronger or
faster man, sooner or later, The man who wins is
the man who thinks he can….!

MX1002-PAS-Wk7-RS
Pathology of
Lung tumors
(Lung Cancer)
Dr. Venkatesh M. Shashidhar
A/Prof. & Head of Pathology
School of Medicine
45

Lung Cancer Intro:
• Most common & fatal cancer (internal
malignancy)
• Kills more people than colorectal,
breast, and prostate cancers combined.
• Significant increase in incidence..
(developing countries*)
• Now Increasing in females > breast
cancer.
• 90% of lung cancers are related to
smoking..! (passive smoking in 5%)
• Mutagen sensitive genotype : P-450
enzyme
• Poor prognosis ~ 5% 5y survival *
46

Lung Cancer Incidence:
47

Lung Cancer & Smoking:
• Proportional to duration, amount & quality of smoking &
deep inhaling.
• 90% are smokers and 10% are non smokers
• 20 fold risk if >40cigarettes per day
• >100 fold combined with Asbestos, coal, radon, etc.
• Atypical cells in sputum in 96.7% of smokers - 0.9% in non
smokers.
• Smoke has several irritants & carcinogens.
– Initiators – Benzo[o]pyrenes
– Promoters – Phenol derivatives
– Radioactive substances – Polonium, C14, K40
48

Lung tumors Classification:
• Benign tumours – rare (Adenoma, Hamartoma)
• Malignant (common):
– Bronchogenic Carcinoma: (95%)
– Bronchial Carcinoid Tumor (5%)
– Other Tumors (<1%)
– Metastasis (common)
• Tumors of Pleura
– Mesothelioma – asbestosis *
49

Types of Bronchogenic Ca.:
• Bronchogenic Carcinoma (95%)
– Small cell ca. SCC – 15-20% (oat cell carcinoma)
– Non Small cell NSCC– 80%
• Squamous cell carcinoma – 20-30%
• Adeno carcinoma – 30-40%
• Large cell anaplastic carcinoma
• Clinical / prognostic classification:
SCC - small cell Ca
Early spread
Surgery not possible.
Responds to chemo
50
Non-SCC
Late spread – localized
Staging & Surgery
Does not respond to chemo.

Clinical features & complications.
• Local:
– Obstruction
– Effusion
– Pneumonia* lipid, other.
– Bronchiectasis
– Atelectasis
– Haemoptysis
– COPD (risk)
• Systemic:
– Cachexia
– Paraneoplastic sy
– Clubbing
– Pulm. Osteoarthropathy.
– Bone pain
– CNS dysfunction
51

Pathogenesis – Smoke - Lung Dis.
CancerInflam COPD
Multiple mutations in oncogenes  Cancer
K-RasC-myc
p53

53
Lung Ca – AP & Lateral view
Histological Type ? NSCC

Squamous Cell Carcinoma:(CT)
54
NSCC

Squamous carcinoma:
55
Origin in main bronchus
NSCC

Lung
Adenocarcinoma:
Peripheral
Non smokers
Females
56
NSCC

SCC Small Cell Ca.
Infiltrative pattern around
major bronchi.
57
SCC

Lung Metastasis
(Numerous metastases from a renal cell ca.)
58

TNM: Staging of Lung Ca.
59
T – Tumor (T1-4)
N – Node (N1-3)
M – Metastasis (M0-1)
Lung Cancer Staging:
I - T1 N0 M0
II - T1 N1 M0
III - Tn N2 M0
IV - Any M1
Based on Anatomical structure involved.

Complications:
60

Cushing’s syndrome in SCC
61
Paraneoplastic syndrome:
• Tumour producing ACTH hormone.
• Excess adrenal glucocorticoids.
• Central obesity, diabetes etc..

Mesothelioma:
• Tumor of Pleural covering.
• Asbestosis – risk factor.
• Poor prognosis
• 50% mortality in first year.
62

Bernie Banton
Asbestosis victim died Aug 2007.
Had Asbestosis, asbestos-related pleural
disease (ARPD),
stomach cancer & Peritoneal mesothelioma.
He became the face of the fight to get
compensation for affected workers and won
his final victory less than a week before his
death..!.
Mr Banton was awarded Order of Australia.
“until they put me in the box, I'll be out there fighting…!".
-- Bernie Banton, in his speech to ABC.
Commitment always wins….!

Clinical Case 1:
A 28y Indonesian student presents with weight loss over a four-
month period and the recent onset of fever and chills at night.
Had several courses of antibiotics from his GP without
improvement. Admission chest x-ray revealed an irregular opacity
of the right apical lobe of lung with pleural effusion. Clinical
examination revealed cervical and axillary lymphadenopathy.
What is the likely problem? Chronic, infection, TB.
country of origin? Epidemiology.
What further tests? Bacterial culture, biopsy, PCR.
What is the prognosis? resistant, imm, risk factors.
64
Tuberculosis

Clinical Case 2:
• An 18y student from Tully, presented with wheezing and
difficulty in breathing. These attacks occurred
intermittently since childhood worse during winter. An x-
ray of the chest was normal, but lung function tests
during attack demonstrated a markedly decreased
FEV1, which improved significantly after he inhaled
bronchodilator. The patient was prescribed
bronchodilator & steroid inhalers which some relief, but
the patient continued to experience episodes of
breathlessness in the coming years.
• What is the likely problem? Chronic, recurrent, seasonal
• Why many attacks ? hypersensitivity/allergy.
• What is the prognosis? Nature, preventive only.
65
Asthma

Clinical Case 3:
• A 41y man was brought to emergency with high fever, shaking chills,
coughing up rusty sputum. On history, he'd been fine the day before
but that morning he had begun to shake uncontrollably and felt
alternately cold then hot and sweaty. His chest hurt on breathing. On
examination, thin white male who was anxious and mildly cyanotic,
tachypnea, fine rales and decreased breath sounds by auscultation
over the right lower chest. Temp100.2°F, but his pulse was normal.
WBC high, with 70% polys, 18% bands, and 12% lymphocytes.
Blood gases hypoxia & respiratory alkalosis. sputum gram-positive
diplococci.
• What is the problem? Acute infection of lungs – pneum.
• What & Why is he cyanotic? Co2 excess. Gas exch.
• Fine rales over RLL? Fluid – lobar pneumonia.
• Why his WBC count is high? – Acute inflammation.
• Gram Positive Diplococci ? – common, Strep. pneumoniae.
66
Pneumonia

“A good scare is worth more to
a man than good advice."
- Edgar Watson Howe - Country Town Sayings (1911)
That’s why we have
Exams!

Learning Objectives:
• Respiratory anatomy, upper & lower resp. tracts.
• Review the process of ventilation & respiration.
• Pulmonary function tests (FVC, FEV1, FEV1/VC)
• Overview of chest radiograph & imaging.
• Respiratory infections - pneumonia and TB.
• Overview of obstructive and Restrictive
pulmonary disorders, Asthma, COPD, Fibrosis.
• Describe respiratory failure and its causes *
• Lung cancer, etiology, types and features.
68

Pathology of Respiratory System Disorders

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