INTERNAL MEDICINE

RESPIRATORY SYSTEM

® Acid – base balance is tested by blood sample from radial artery. The blood sample is collected in an
heparinized glass syringe.
® Normal PH of blood = 7.4 (7.357.45).
® Normal PCO2 is 40mmHg
® Normal HCO3 = 24m Eq/L
® PH = 7.3
PCO2 = 30mmHg
PO2 = 95 mm Hg
HCO3 = 14m Eq/L
® Ans: Metabolic Acidosis with Respiratory compensation.

® PH = 7.2
PO2 = 70 mm Hg
PCO2 = 80mmHg
HCO3 = 30 milli Eq/L (Normal = 24)
® Ans: Respiratory acidosis with metabolic compensation.

® PH = 7.6  Alkalosis
PCO2 = 20mmHgRespiratory Alkalosis
HCO3 = 18m Eq/L
® Ans: It is Respiratory alkalosis with metabolic compensation.

® In compensation, HCO3 goes in direction of CO2. If in opposite direction  mixed disorder.

® PH = 7.2
PCO2 = 55mHg
HCO3 = 20 m Eq/L
® Ans: Mixed Acid-base disorder (Both metabolic & Resp. acidosis.

RESPIRATORY ACIDOSIS

® It is characterized by  in PCO2
 in PH
® Serum HCO3 levels can  secondarily as a compensatory mechanism.
® Metabolic compensation is gradual & long lasting.
® Compensations are never complete.
® Causes of Respiratory acidosis:
1. Respiratory depression due to morphine overdose or general anesthesia.
2. Airway obstruction (CO2 cannot go out).
3. Cardiac arrest
4. Pulmonary edema
 5. COPD, chronic bronchitis.
6. Neuromuscular defects.
7. Diaphragm paralysis
8. Obesity
9. Sleep apnea
10. Hypoventilation.
11. ARDS
12. Pneumothorax

Rx:
Keep the airway patent
Monitored O2 therapy.

RESPIRATORY ALKALOSIS
® It is characterized by  in PCO2
 in PH
® Serum HCO3 levels are  as compensatory mechanism.
® Respiratory alkalosis – is the MC acid – base disorder encountered.
® Causes:
1. Anxiety
2. Fever
3. high altitude sickness
4. Pneumonia (Tachypnea)
5. Hypoxemia
6. Severe anemia
7. Hypotension
8. Ventilation – perfusion defects
9. Psychogenic / Voluntary – hyperventilation
® Rx :-
 Treat the primary cause
 Rebreathing in a paper bag
 Monitored O2 therapy.

METABOLIC ACIDOSIS
® It is characterized by  in HCO3
There could be gain in H+,   in PH.
® Metabolic acidosis is further classified based on anion gap.
® All the cations are always equal to the total anions present in the body.
® The anion gap is due to “UNMEASURED ANIONS” especially proteins like albumin.
® Anion gap is calculated as,
(Total No. of cations) - (Total No. of anions)
[Na+ + k+] - [HCO3 – + C1 –].
® Normal anion gap = 8- 12
® Causes of  anion – gap :
1. Methanol poisoning ‘MUD PILES’
2. Uremia
3. Diabetic ketoacidosis
4. Paraldehyde
5. Iron or Isoniazid
6. Lactic acidosis
7. Ethanol /Ethylene glycol poisoning
8. Salicylate poisoning
 Hypokalemia, Hypocalcemia, Hypomagnesemia & hyperphosphatemia also cause  anion gap.

®  anion – gap: is seen in,

 Hyperkalemia
 Hypercalcemia
 Hypermagnesemia
 Hypoalbuminemia (proteins are –ve charged)
 Lithium toxicity (Li+3)

® Normal Anion Gap: ‘HARD UP’.

 Hypoaldosteronism
 Acetazolamide
 renal tubular acidosis
 Diarrhoea
 Uretero sigmoidostomy
 Pancreatic fistulas.

® Normal anion gap is seen in hyperchloremic metabolic acidosis

® Anion – gap is done to know the etiology of metabolic acidosis.

METABOLIC ALKALOSIS
® It is due to  in serum HCO3 leading to  P , PCO2 levels  as a compensatory mechanism.
H

® Causes of metabolic alkalosis:

1. Vomiting
2. Gastric lavage
3. Na Hco3 infusion
4. Multiple blood transfusions.
5. Use of diuretics
6. Hyperaldosteronism
7. Cushing’s syndrome
8. Severe potassium depletion.

OBSTRUCTIVE LUNG DISEASE RESTRICTIVE LUNG DISEASE

 TLC (Total lung capacity)  - TLC 

 Residual Volume  - RV 
 Forced Vital capacity  - FVC 
 Forced expiratory volume - FEV 1 
FEV 1 
 FEV 1 - FEV 1
FVC is  FVC is 
- “Ratio rises in restrictive”
 Compliance is normal - Compliance is reduced ().
 DLCO (Diffusion lung capacity) is normal - DLCO is 
 Egs: Chronic bronchitis - Egs: interstitial lung disease
Emphysema (dilation of alveoli) Pulmonary Fibrosis
Asthma Pneumoconiosis
Bronchiectasis ARDS
 In emphysema, the DLCO is   Diaphragm paralysis
& lung compliance is  Myasthenia gravis
(due to septal wall damage Obesity
 Neuromuscular problems
Hyper inflated lungs) Kyphoscoliosis

All these are restrictive lung diseases with normal DLCO.

CHRONIC BRONCHITIS
® It is defined clinically as presence of productive cough for at least 3 months in 2 consecutive years.
® Causes:
Mc – Smoking
Cystic fibrosis

® Histological features:
 Chronic lymphocytic infiltration of airways
 Submucosal gland hypertrophy
 Hypersecretion of mucus in the bronchi.
 REID INDEX is  [Normal Reid Index =0.4]
 Reid Index – is the ration b/w mucus gland layer to the thickness of bronchial wall
 Bronchial epithelium shows squamous metaplasia.
 Mucus plugs are seen in terminal bronchioles.
 Patients of chronic bronchitis are called ‘BLUE BLOATERS’
& present with – productive cough
- Mild cyanosis &
- Recurrent infection
 Long standing cases develop ‘Cor pulmonale’.
 The patient develops Respiratory Acidosis
 Chest X-ray shows ‘Horizontally Oriented Heart’.

EMPHYSEMA
® It is an abnormal permanent dilatation of air spaces, distal to terminal bronchioles (Acinus).
® Associated with destruction of alveolar septal walls.
® Respiratory bronchioles, alveolar ducts & alveoli are involved.
® MC cause of Emphysema = Smoking.
 Other causes include – 1 antitrypsin deficiency.
  1 antitrypsin is normally synthesized in liver & has anti-elastase property preventing tissue
destruction by elastase.
 Elastase is released by macrophages & neutrophils in alveoli.
 The normal phenotype of  1 antitrypsin is called PIMM.
 The abnormal phenotype of  1 antitrypsin is PIZZ

TYPES:
1. CENTRi – ACINAR EMPHYSEMA:
 It is the involvement of central part of acinus (resp. bronchiole) with sparing of the alveoli.
 It si the MC emphysema in smokers.
 It usually affects the upper lobes.
 MC type seen clinically.

2. PAN – ACINAR EMPHYSEMA:

 It is the involvement of entire acinus.
  Seen with  1 – antitrypsin deficiency
 It usually involves lower lobes.

3. DISTAL – ACINAR EMPHYSEMA:

 In this, the distal part of acinus is involved.
 There is involvement of lung adjacent to pleura.
 “Sub-pleural Blebs” & “Spontaneous Pneumothorax” are associated with distal acinar emphysema.
 Seen in smokers.

4. IRREGULAR EMPHYSEMA:
 Irregular involvement of the acinus with fibrosis & scarring.
 It is the MC histological type of emphysema.

® Clinical features:
 Progressive dyspnea but
 No Cyanosis
 Patient uses accessory muscles of respiration
 Patients are called “PINK PUFFERS”
 Chest X-ray shows ‘Hyperlucent lung fields’.
 Antero-posterior diameter
Depressed diaphragm
Vertically Oriented Heart
 TLC  DLCO 
RV  Compliance is 
FEV 1 
FVC 
FEV 1 
FVC

® Rx:
 Cessation of smoking
 Maintenance of O2 saturation
 Bronchodilation
 Centri – acinar emphysema is commonly associated with chronic bronchitis.

BRONCHIECTASIS
® It is abnormal permanent dilatation of air spaces specially bronchi & bronchioles resulting from chronic
necrotizing infections which lead to destruction of bronchial cartilage.
® The MC cause of bronchiectasis = TB.
Other cause – Cystic Fibrosis.
® Obstruction & Infections are chief contributors to pathology.
® Bronchiectasis most commonly involves left lower lobe
® Clinical features:
 Chronic cough
 Fever
 Foul smelling sputum
 Recurrent pulmonary infections
 Amyloidosis (20)

® Complications:
 Massive hemoptysis
 Empyema
 Broncho –pleural fistula
  Multiple lung abscesses

® Investigation of choice in patients with bronchiectasis is HRCT (High Resolution Computed Tomography)
® Management:
 Chest physiotherapy
 Postural Drainage
 Antibiotics

® Causes of bronchiectasis
 TB – MC cause
 Cystic fibrosis – MC in western countries
 Staph aureus inf
 Aspergillus infections
 Tumour/Foreign body
 Kartagener’s syndrome/Immotile Cilia syndrome.

® Kartagener’s syndrome consists of

1. Bronchiectasis
2. situs inversus (Dextro cardia)
3. Sinusitis
There is also presence of 4. Infertility.

® Other causes – SLE

- RA
- Post – transplants.

ASTHMA
® Asthma is type I hypersensitivity reaction characterized by intermittent & reversible airway obstruction.
® There is hyperresponsiveness of airways.
® It is a chronic inflammatory disease of smaller & larger airways.
® Asthma is divided into extrinsic & intrinsic asthma.
® Extrinsic asthma has early onset.
 More common in children
 IgE levels are 
 Associated with environmental exposure
 Has a strong association with atopy.

® Intrinsic asthma
 Idiosyncratic asthma
 Has delayed onset ( Adult – onset asthma)
 It is not associated with atopy
 No history of environmental exposure
 IgE levels are normal
 Intrinsic asthma has strong association with use of aspirin,exercise induced or viral or cold
exposure ,nasal polyps & vasomotor rhinitis.
 It is more severe & persistent.

 The main cell in the pathogenesis TH2 cells (helper)

 IL – 4 stimulates IgE productions
 IL – 5 stimulates the Eosinophils.
 The early phase response of asthma is due to release of histamine & pre-formed mediators,along
with neuronal reflexes vagal causing broncho constriction.
  Late phase response of asthma is due to release of PGs & leukotrienes C4,D4 and E4.

® Histological features:
 There is hypertrophy of smooth muscle cells
 Airway epithelial shedding
 Mucus hypersecretion
 Thickening of basements membrane
 Airway edema
 Chronic inflammatory response.

® Microscopic features:
 CHARCOT – LEYDEN CRYSTALS which are Eosinophilic major basic protein.
 CURSH – MANN SPIRALS mucus plugs
 CREOLA BOIES – which are clumps of EPITHELIAL cells in the sputum.

® Genetic factors:
 ADAM -33 gene & IL – 13 polymorphism are associated with asthmatic patients.

® Rx of asthma
 DOC for acute asthma – Salbutamol (fastest acting 2 agonist)
[should not be given for prophylaxis CO 3 of receptor desensitization]
 DOC for prophylaxis – Inhalational steroids
 DOC for status asthmaticus – i.v. hydrocortisone.
® Hypocapnia
® Hypoxia
® Respiratory alkalosis  is seen in most asthmatics

® Hypercapnia &
® Respiratory acidosis  indicate ‘Severe’ asthma.

® GRADES OF ASTHMA:

Symptoms Mild Moderate Severe Impending Resp. failure

Breathlessness Active Talking At rest At rest

Speech Speak sentences Phrases Words Mute
Body posture Able to recline Prefer sitting Unable to recline Unable to recline
Breath sounds Mild to end Loud wheezing Both inspiration & No wheezing (no air
expiratory wheeze through out expiration expiratory wheezing movement)

Heart rate <100 100120 >120 Relative Bradycardia

Pulses paradoxus <10 or normal 1025 >25 Often Absent
Peak Expiratory
flow >80%(N) 5080 <50% <50%
Accessory muscles Not used Commonly used Usually used Paradoxic Thoraco
abdominal movement

Pa Co2 <42 <42 >42 >42

RESTRICTIVE LUNG DISEASES

® INTERSTITIAL LUNG DISEASE (ILD): characteristised by chronic inflammation & fibrosis of lung interstitium.
® ILD shows restrictive pattern with exertional dyspnea & non-productive cough.
® Earliest feature – Alveolitis
® Chest X-ray show “GROUND GLASS APPEARANCE”.
® Advanced ILD shows “HONEY COMB APPEARANCE”.

CAUSES OF ILD:
 Idiopathic pulmonary fibrosis
 Pneumoconiosis
 Collagen – vascular disease like scleroderma, SLE
 Radiation – Pneumonitis
 Gaseous fumes
 Drugs like Bleomycin & Busulfan
 Granulomatous diseases like sarcoidosis
 Hypersensitivity pneumonitis
 Pulmonary alveolar proteinosis.

® PNEUMOCONIOSIS:
 Pneumoconiosis is occupational lung disease due to inhalation of mineral dust organic or inorganic
particles.
 A particle size of 15 is the most dangerous particle size responsible for pneumoconiosis

® COAL WORKER’S PNEUMOCONIOSIS/ANTHRACOSIS:

(Focal dust emphysema)
 It is also called Anthracosis.
 It is due to coal dust, occurs in coal miners.
 Upper lobes are most frequently involved.
 Alveolar macrophages engulf the anthracotic pigment & are called dust cells.
 Coal dust is least fibrogenic.
 Coal worker’s pneumoconiosis does not  the risk of TB or lung cancer.
 Coal worker’s pneumoconiosis is associated with centri acinar emphysema
 Coal worker’s pneumoconiosis is a restrictive lung disease with a component of obstructive pattern.

® SILICOSIS:
 Silicosis is the MC occupational lung disease.
 Silica has highest fibrogenic potential
 It is seen in workers of 1. Hard rock mining
2. Pottery
3. Sand blasters &
4. Glass workers.
 Quartz (Silicon dioxide) is the most frequent form involved in silicosis.
 Silicosis usually involves upper lobes.
 It produces nodular fibrosis disease with “EGG SHELL CALCIFICATION” on X-ray.
 There is  risk of TB with silicosis.
  Polarizing microscopy shows ‘birefringent silica particles’.

Egg shell calcification Silicosis

 Sarcoidosis

® ASBESTOSIS:
 Asbestosis has the highest carcinogenic potential.
 Produces diffused interstitial fibrosis
 Seen in patients of 1) Mining
2) Breaking
3) Insulation industries.
 Asbestosis usually affects lower lobes.
 MC manifestation of asbestosis is pleural thickening & pleural plaques.
 The MC cancer seen with asbestosis is bronchogenic carcinoma
 The most specific cancer seen with asbestosis is pleural mesothelioma.
 Asbestosis shows presence of Ferruginous bodies & Asbestos bodies.

® Byssinosis – is inhalation of cotton dust seen in textile industry.

® Stannosis – Occurs due to deposition in Tin oxide.
® Berylliosis – is diffused interstitial fibrosis & Granulomas occurring in workers of nuclear & Aerospace
industries.
® Baggosis – is inhalation of sugarcane dust
® All occupational lung diseases present with
 Progressive dyspnea
 Non-productive cough
 Cor-pulmonale &
 Restrictive pattern of lung disease.

® Investigation of choice for pneumoconiosis is HRCT (Bronchiectasis also)

® Investigation of choice for all interstitial lung diseases = HRCT.
® Caplan syndrome – any pneumoconiosis with Rheumatoid arthritis.
® Investigation of choice for
1. Pneumonia – chest X-ray
2. Asthma – reversibility with salbutamol
3. Bronchiectasis – HRCT (Helical CT always)
4. Pneumoconiosis – HRCT
5. Pulmonary Embolism – Spiral CT.
6. ILD – HRCT
7. Bronchiogenic CA – Bronchoscopy with Biopsy.

® Confirmatory Gold standard diagnosis of pulmonary embolism is, pulmonary angiography.

® IOC for bronchogenic CA – Bronchoscopy with Biopsy.

SARCOIDOSIS: It is a chronic granulomatous disease with production of non-caseating granulomas

® More common in female between 2040 yrs of age.
® Clinical features: Shortness of Breath, Dyspnea
® DD of Sarcoidosis from TB:
1. –ve Mantoux test
2. Non – caseating granulomas
3. Bilateral lymphadenopathy
4. Egg shell calcification

® X-ray shows Bilateral Hilar lymphadenopathy

® It is associated with HLA – Markers HLA1 & HLA – B8
 ® The CD4 :CD8 ratio is  to 15:1 & is very diagnostic.
® Patients shows anergy to skin Antigens
® Sarcoidosis shows false –ve Mantoux test.
® It is a systemic disease involving multiple organs most commonly the lungs.
® Bilateral Hilar Lymphadenopathy is the Hall mark
® Pleural involvement in the form of pleural Effusion is seen in 5% of patients.
® Lung cavitation are rare.
® Parenchymal involvement may or may not be present with clear lung fields.
® Egg shell calcification of Hilar lymph nodes is seen.
® Involvement of skin in the form of Violaceous Rash is Lupus vulgaris – cutaneous TB
called as “Lupus pernio” on the cheeks & lips. - Apple jelly nodules
® There is presence of painful subcutaneous nodules Lupus erythematosus – SLE
on legs called ‘Erythema nodosa’. Lupus pernio – Sarcoidosis.
® Involvement of the eye is in the form of Uveitis. -
® Enlarged salivary & lacrimal glands.
® Uveitis can cause glaucoma.
® Lacrimal gland involvement produces Dry eye.
® Parotid gland involvement produces dry mouth.
® There is presence of arthritis, DI & Renal hypercalcemia.
® LOF-GREN SYNDROME: is Hilar Lymphadenopathy
Arthritis
Erythema Nodosa seen in Sarcoidosis.
® HEER – FORDT WALDEN STROM SYNDROME: Fever
Parotid Enlargement
Uveitis
Facial palsy seen in sarcoidosis
® LAB FINDINGS:
 The confirmatory test for sarcoidosis is Biopsy.
 Broncho-Alveolar lavage (not in blood) shows  CD4:CD8 count
 Patients have increased Angiotensin Converting Enzyme Levels  (ACE).
 Gallium 67 scan shows diffuse uptake
 There is anergy to skin antigens.
 Patients have hypercalemia Ca+2 [Egg shell Calcification]
 Kveim – Siltzbach test is a skin test for Sarcoidosis Using Sarcoid spleen extract – Kveim – Siltzbach.

HISTOLOGY:
 Shows non-caseating granulomas with presence of
Schaumann Bodies – Ca+2 aggregates
Asteroid Bodies
Residual Bodies
 Schaumann bodies are laminated aggregations of calcium.
 Rx: Most people have spontaneous remission within 2 yrs.
 Corticosteroids are given if necessary.

 Concept of DLCO:
 DLCO is done to know the diffusion lung capacity.
 DLCO depends on, 1) Alveolar pressure gradient of gases.
2) Surface area of alveolo – capillary membrane.
3) Thickness of alveolo – capillary membrane &
4) Diffusion coefficient of gas.

 DLCO is  in – 1) Emphysema (as septal wall damage occurs).

2) ILD like (deposits & fibrosis)
- Asbestosis, Sarcoidosis, SLE
 - Pneumonia.
3) Pulmonary Emboli or pulmonary HTN.
4) Anemia (No carrier molecules).

 DLCO is  in - 1) Alveolar hemorrhages (Good Pasteur’s syndromedestruction of pulmonary

membrane)
2) CHF
3) Polycythemia (RBC )
4) Left Right shunt

® DLCO is normal in neuromuscular disorders like,

- Myasthenia gravis
- Diaphragm paralysis &
- Most Obstructive diseases.

® Diffusion capacity CO> CO2>O2.

® Hypersensitivity pneumonitis: It is extrinsic allergic pneumonitis due to inhaled antigens [Extrinsic – dust,
paddy etc.].
® Can present as ‘Farmer’s lung’.
® It is a type III hypersensitivity reaction (Immune-complex disease due to thermophilic actinomycetes).

® Drugs causing pulmonary fibrosis: Bleomycin

Busulfan
Amiodarone
Methysergide
Cyclophosphamide.

® ARDS: [Acute Respiratory Distress Syndrome]/SHOCK LUNG: or Hyaline membrane disease

® Dx of ARDS is done based on the following criteria:
1. Acute onset
2. Bilateral pulmonary infiltrates on C x-ray.
3. Pulmonary – Artery Wedge Pressure (PAWP) <18 mmHg.

PaO2 < 200mHg O2 refractive respiratory failures

Fio2

® In ARDS, there is damage to alveolar cells & capillaries with O 2 refractory respiratory insufficiency.
® The compliance of the lung is reduced.
® The MC cause of ARDS is Septicemia (indirect lung injury)
® Other causes include, - aspiration of gastric contents into the lung producing chemical pneumonitis
(MENDELSON’S SYNDROME).
® Mendelson’s Syndrome occurs in unconscious, comatose, anaesthetized or convulsing patient.
® There is diffuse alveolar damage with neutrophilic infiltration & damage to type I & type II pneumocyte.
® There is  - Vascular permeability.
- Alveolar exudates.
-  in diffusion capacity.
-  surfactant
-  compliance of lung producing stiff lung.
- Fibrin & Exudates
- Coagulate cells & produce the Hyaline membrane.
® The patient presents with – Tachypnea
- Dyspnea (within 24 72 hrs of the causative event.
® There is Hypoxemia
 Hypocapnia (Breaths heavily)
Respiratory Alkalosis &
Type I Respiratory Failure
® The Tidal Volume is reduced.
® Chest x-ray shows Bilateral Diffuse Infiltrates with a “White-Out Lung”.
® Has  mortality – 50%
® Causes of ARDS:

® DIRECT LUNG INJURY INDIRECT LUNG INJURY

- Pneumonia - Sepsis (MC)
- Aspiration of gastric contents - Head Injury
- Inhalation of toxic gases - Acute Pancreatitis
- Near drowning - Cardio – pulmonary bypass
- Pulmonary contusion - Heroine /as Methadone or Barbiturate
- Fat Embolism
- Post-lung Transplant - Massive Transfusions

® PCWP : Pulmonary arterial Wedge Pressure

 Is an indirect measure of left atrial pressure.
 The normal PCWP is 12 mmHg.
 PCWP >18 mmHg is due to cardiogenic causes.
 PCWP about 1218 mmHg is due to respiratory causes EX: ARDS.
® Rx of ARDS
 Ventilatory support with high frequency jet ventilation.
 CPAP is the ventilatory mode used

® NEONATAL RESPIRATORY DISTRESS SYNDROME: also called as ‘Hyaline membrane disease is due to
deficiency of surfactant seen commonly in 1) Premature babies & 2) In infants of diabetic mothers & also in
3) Hypothyroid patient.
® The chemical name of surfactant is dipalmityl phosphatidyl choline or lecithin.
® Prevention is done by – delaying the onset of labor & - by administration of glucocorticoids to mother.
® Rx – is done by giving surfactant by aerosols & O 2 therapy.
® Steroids & Thyroxine  surfactant production
® Insulin  surfactant production.

® RESPIRATORY FAILURE:

Type I Respiratory Failure Type II Respiratory Failure

- Due to failure of oxygenation - Also called ‘Hypercapnic Respiratory Failure’ (PaCO 2 )
(produced in arteries) - It is due to defect in ventilation (Hypoventilation)
- PaO2 is  - PaO2 is 
- PaCO2 is  or normal - PaCO2 is 
- Alveolo – arterial gradient of O2,Pa- aO2 is  - PA- aO2 is Normal
- Hypoxemia with  PaCO2 - Hypoxemia with  Pa CO2
Causes: Causes:
- Parenchymal diseases - Any cause causing hypotension
- Vascular shunts (Rt Lt shunt) - Obstructive lung diseases like
- ARDS - COPD
- Emphysema - Foreign body
- Pneumonia - Respiratory drive as in Brain injury
- ILDs (Interstitial Lung Disease) - Weakness of Resp. muscles as in – Myasthenia gravis
- Kyphoscoliosis &
- ILD
® Type III Resp. failure = Peri-operative lung atelectasis.
Is usually managed consecutively with upright posture, pain Rx & O 2 therapy.
® Type IV Resp. failure is due to hypoperfusion of respiratory muscle as in shock.

LUNG CANCERS
® Squamous Cell Carcinoma: MC lung cancer in smokers & in India.
 Most commonly affects males, usually central n location.
 SCC arises generally from segmental bronchi.
  frequency of P53 mutation (Tumour suppressor gene)
 Histology shows presence of – Keratinization
- Keratin pearls
- Intercellular bridges.
 Hypercalcemia is a common paraneoplastic syndrome seen in SCC due to parathormone related
peptide (PTHRP).

® Adenocarcinoma:- MC type of lung cancer in the world.

 It is MC type of cancers in non-smokers & in females.
 Usually peripheral in location.
 Associated with K-RAS mutation
 Cells are +ve for mucin & thyroid transcription factor (TTF).
 Broncho – alveolar CA is a type of adeno CA with invasion & growth along the alveolar septum.
 Broncho – alveolar CA has aerogenous spread (can affect the opposite lung) & the patient dies of
suffocation.

® Small cell cancer/Oat –cell CA – commonly seen in smokers & is central in location
® It is the most aggressive lung cancer with worst prognosis.
® Best response is by Radiotherapy & chemotherapy
® Surgery is not possible (as patient dies in <1year).
® The cells have “SALT & PEPPER APPEARANCE” with scanty cytoplasm & Granular Chromatin.
® Small cell cancer shows basophilic staining of the vascular walls called as AZOPARRDI EFFECTS
® Electron microscopy shows presence of neurosecretory granules
® Small cell cancers are derived from neuro-endocrine cells.
® Most paraneoplastic syndromes are seen with small cell cancer
® These cancers are +ve for Synaptophysin and chromogranin
® Most aggressive & is commonly associated with, - Superior Venacaval Compression Syndrome.

® Large Cell CA – is peripheral in location & is associated with Gynecomastia.

® The paraneoplastic syndrome of lung cancers include:-

1. Cushing’s syndrome (due to ectopic ACTH production)

2. SIADH (due to production of ADH)
3. Hypercalcemia (due to PTHRP).
4. EATEN – LAMBERT Syndrome – due to Auto Abs against Ca +2 channel similar presentation as myasthenia
i.e., Abs against NM receptors.
5. Gynecomastia due to gonadotropins.
6. Acanthosis Nigricans – Blackish pigmentation of axilla
7. Hypertrophic pulmonary Osteoarthropathy with – (clubbing)it is a feature of (Non) small cell cancer.

Bone growth of distal phalanges).

® The MC symptom of lung cancer is cough followed by weight loss & Dyspnea.
® Hemoptysis & anorexia can occur.
® Lung cancers most commonly metastasize to Adrenals.
® Involvement of recurrent laryngeal nerve can produce hoarseness of voice.
® Clubbing does not occur in small cell cancers.
® PANCOAST TUMOUR:- is apical lung tumour which can cause compression of sympathetic chain producing
Horner’s Syndrome (ptosis, miosis & anhidrosis and loss of cilio spinal reflex)

® AIR EMBOLISM : MC cause – Iatrogenic

 It is due to faulty insertion of central venous line in the jugular vein.
 It can also occur due to neck injuries.
 Minimum of 100 ml of air is required to produce air embolism.
 Air embolism blocks blood supply leading to respiratory distress..
 There is sudden fall in systolic BP.
 Rx – Immediate change of posture .
 Make the patient lie in left lateral decubitus position & then in Trendelenburg position where the foot
end of patient is raised.

PULMONARY EMBOLISM

 It presents with sudden onset of severe dyspnea.

 Mc symptoms Dyspnea; MC sign Tachypnea.
 Risk factors : 1) Factor V mutation / Leiden mutation . 2) Obesity 3) age. 4) Antithrombin III deficiency . 5)
> 4 days in bed (i.e., fractured/Comatose patient)6) Prgn & puerperium 7) Estrogen therapy (all OCPs  risk
of thrombosis). 8) Homocystinemia(occurs in B12 or folate deficiency)
9) Major trauma or surgery (activates tPA). 10) Pelvic or Abd cancers . 11) Cardiac failure .
12) Polycythemia(Hyper viscous blood). 13) Nephrotic Syndrome . 14) Paroxysmal Nocturnal Hemoglobinuria
PNH . 15) Leg paralysis 16) Severe infections.
17) Protein C & S deficiency (Anticoagulants). 18) Dysfibrinogenemia. 19) Lupus anticoagulant
/Antiphospholipid Ab 20) Plasminogen deficiency. 21) Varicose veins. 22) Behcet Syndrome: Recurrent oral
ulcers & Uveitis.

® COMPLICATIONS: 1) RHF Cor pulmonale 2) Dyspnea is MC symptom & chest pain is 2 nd MC symptom.

® ECG CHANGES: MC ECG abnormality is Sinus Tachycardia.

 The characteristic ECG findings include,
 Deep S waves in lead I
 Deep Q waves in lead III &
 Inverted T waves in lead III
® Arterial Blood Gas Analysis in pulmonary embolism shows,
 Hypoxemia
 Hypocapnia ( PaCO2)
  Alveolar – arterial pr. Gradient (P A – aO2)

® The investigation of choice is Multidetectors Spiral CT

® Most sensitive/Screening test of choice is  D – Dimer (Fibrin degradation product)
® Lung Ventilation Perfusion Scan is 2nd line Dx test for PE.
® The Gold standard/Confirmatory test /Most specific test for definitive Dx of PE is Pulmonary Angiography.
® MC cause of PE is large vein thrombosis (Pelvic or Femoral Veins).
® 2nd MC cause of PE is Deep vein thrombosis (popliteal vein thrombosis)
® Rx:
1. Pulmonary Thrombo Embolectomy
2. tpA like Alteplase are given in massive
pulmonary thromboembolism
 3. Heparin & Anticoagulant therapy is given in small
pulmonary thromboembolism.

FAT EMBOLISM
® MC cause Fracture of long bones esp. Shaft of femur.
® Can also occur due to osteolytic metastasis.
® It leads to Ventilation – perfusion mismatch with severe resp. distress, hypoxia, &  coma.
® Fat globules can cause petechial skin rash
® Fat globules can be seen in sputum or urine on staining with Sudan – Black (or) Oil – Red ‘O’ (fat).
® Investigation of choice is XENON SCAN.
® Rx: Thrombolytic Therapy
® Spraying of Ethyl alcohol using Swan – Ganz Catheter.

PULMONARY HTN
® Pul artery HTN is  in pul. Artery pr. > 25mmHG
® Classified into 2 types.

Precapillary Pulmonary HTN Postcapillary Pulmonary HTN

1. Abnormality is in pul. Artery 1. Beyond pul. Artery.
2. Left atrial pr. Is normal 2. Lt. atrial pr. Is 
3. The pul artery – left atrial pressure <12 mm
gradient is > 12 mm. Causes: a. LVF
b. Mitral valve prolapse
Causes: a. 10 pulmonary HTN c. Left atrial myxoma
b. disorders of ventilation d. Congenital Vein stenosis.
c. pulmonary Embolism
d. Sickle cell anemia
e. Collagen – vascular disorders (sclerosis)
f. Schistosomiasis.

 Familial cases of pul HTN ar associated with mutations in BMPR – 2 gene.

(Bone morphogenic protein receptor -2).
 Pul. HTN is also caused by Hypoventilation
 The arterial wall thickens  DLCO .
 Idiopathic 10 pul HTN is MC in young male between 2040 yrs of age.
 Mc symptom is dyspnea.
 The pulmonary function tests are normal with  DLCO.
 PFT – Normal; DLCO .

® Rx: Bosentan – (Endothelial Antagonist).

Sildenafil – (PDE -5 inhibitor).

® Cor – pulmonale – Right side heart failure.

 Mc cause of acute Cor – pulmonale is pulmonary thromboembolism.
 Mc cause of chronic Cor- pulmonale is COPD.
® Features of CHF are:
1. Enlarged cardiac shadows on X-ray.
2. Ground – Glass Appearance due to pulmonary Edema.
3. Kerley – B lines. Cough, dyspnea, Hemoptysis
4. Prominence of upper lobe vessels. 
5. Bilateral Pleural Effusions. Left sided HF
 Kerley B lines are septal lines due to dilated lymphatics & septa. Edema, Organomegaly
MC in patients of pul. Edema due to congestive cardiac failure 
Rt sided HF

PNEUMOTHORAX

® Traumatic pneumothorax occurs due to penetrating injuries

® Iatrogenic pneumothorax occurs during thoracocentesis during insertion of central vein or during
mechanical ventilation.

® Spontaneous pneumothorax usually occurs in tall thin males.

® Males between 1030 yrs with no preexisting lung disease.
® There is a strong +ve family history with presence of subpleural blebs in young males between 1030yrs.
® Pneumothorax is associated with  breath sounds, & Hyper resonant percussion note.
® The common clinical symptoms are dyspnea & pleuritic chest pain.
® Tension pneumothorax is an acute medical emergency presenting, with 1) Severe Breathlessness. 2) Absent
breath sounds 3) Neck vein distensions 4) Collapse of lung &
5) Mediastinal Shift.
® Rx: should not be delayed. a) Immediate insertion of a large bore needle thru the 2nd ICS should be life
saving. b) Chest tube draining is also done in a water-sealed drainage.
® Left sided pneumothorax produces Right Axis deviation.

PLEURAL EFFUSIONS
EXUDATIVE TRANSUDATE
® Total serum protein in exudates is >3g/dl  < 3 g/dL
® Pleural /build LDH > 0.6 (lactate Dehydrogenase)  < 0.6
® _____ cells are seen in exudates  No cells n transudate
® Pleural fluid protein
Serum protein >0.5  <0.5
® Causes:  Causes:
 Neoplastic disease - CHF
 Infections - liver cirrhosis
 GI perforations - Nephrotic syndrome
 Pancreatitis - SVC obstruction
 RA
 Post coronary bypass
 Abd surgeries
 Collagen – Vascular disorders like SLE.

® Predominantly left sided pleural effusion is by,

a) Acute pancreatitis b) esophageal rupture & c) Dressler’s syndrome
® Predominantly Right sided pleural effusion is by,
a) Amoebic abscess b) Liver cirrhosis c) CHF . D) Meigs syndrome (Ovarian fibroma with ascites & pleural
effusion)

® Pleural Effusion with  Blood glucose is seen in;

a. Malignant Effusion
 b. RA
c. Tuberculous Effusion
d. Bacterial infections &
e. Hemothorax

® Pleural Effusion with  Amylase levels (produced by pancreas)

a. Esophageal rupture.
b. Pancreatic pleural effusion (pancreatitis or pancreatic cyst)
c. Malignancies like adenoca of pancreas.
d. Ruptured Ectopic prgn.

® MC cause of pleural eff. In India is TB.

® Tuberculous pleural eff. Is Exudative pleural Effusion with  levels of Adenosine –D – Amylase & Interferon.
® Presence of cholesterol crystals in pleu. Eff. Is seen in Hypothyroidism TB & Rheumatoid Arthritis.
® Drainage of pleural Effusion is done by performing thoracocentesis with the needle usually in 7th ICS in mid
axillary line. The needle is inserted in lower part of ICS, taking support of upper border of rib.
® Physical Findings: Diminished movements of chest; Diminished Vocal Fremitus, tactile fremitus; Movement
of trachea to opposite side; & Homogenous opacity on X-ray.

® Horizontal fluid levels & Succussion splash are features of Hydropneumothorax.

PNEUMONIAS

® MC cause = Strep pneumonia (Rusty brown sputum)

® MC cause of nosocomial pneumonia is Staph aureus (single) or G-ve bacteria (group)
® Pneumonia  Typical & Atypical; Typical  lobar & broncho pneumonia.
 Lobar pneumonia is usually consolidation of entire lobe of lung
 Broncho pneumonia is patchy consolidation of lung is usually bilateral & basal in location.

Typical Pneumonia (productive cough Atypical Pneumonia (non-productive cough)

- Usually caused by extracellular organism - By intracellular organisms.
- Alveolar exudates are present so productive - Alveolar exudates are absent but interstitial
cough inflammation is seen
- Infiltrated cells are  neutrophils - Infiltrated cells are lymphocytes
- Symptoms:  grade fever, productive cough, - Cough is less & there is no mucopurulent sputum
mucopurulent sputum. -Causes: 1) MCC of atypical pneumonia –Myco
- Most bacterial pneumonias plasma 2) All viral pneumonias (Bird flu, swineflu)
3) Chlamydial (obligate, intracellular) 4) PCP
5) Legionella pneumonia.
® CF: high grade fever, Tachypnea, Cough with sputum(typical), Headache +Myalgia (viral)
® Klebsiella pneumonia: Red currant jelly sputum & lung abscess “(Bulging Fissure Sign).”
® Complications: Lung abscess (pus in lungs), Emphyema (pus in pleural space), metastatic abscess,
endocarditis, meningitis, suppurative arthritis.
® Legionella pneumonia:
 Is a G –ve bacilli causes Legionnaires disease presenting as atypical pneumonia
 Usually occurs in elderly smokers, immune compromised individuals with a history of contact of
portable water source (cooler’s AC).
 Spreads by aerosols from water (person to person transmission doesn’t occur).
 CF:  fever, hyponatremia, neurological symptoms (dementia, confusion, headache)
 Legionella = pneumonia with Diarrhoea .
 Dx – gram staining shows numerous neutrophils but no organisms
 Legionella stained by – silver stain: Culture – charcoal Yeast Extract.
 DOC of Legionella – Azithromycin , Fluoroquinolone or Erythromycin
® PCP: (Pneumocystis Carini Pneumonia) – Opportunistic Fungal infection.
 MCC of pneumonia in AIDS patients (CD4 <200) is PCP. In this, there is damage to Type I pneumocyte &
compensatory hypertrophy of Type II pneumocyte; produces predominantly interstitial inflammation
with lymphocytic & plasma cell infiltrates in interstitium. There is presence of foamy vacuolated
eosinophilic exudates.
 CF – Dyspnea, Fever, non-productive cough, Tachypnea & Cyanosis.
 The classical X-ray findings bilateral diffuse infiltrates beginning in the peri-hilar region. PCP also
produces pneumatocele (PCP & staph aureus) & Cavitary lesions. The principle host cell acting against
pneumocystic is alveolar macrophages. PCP is Dx by sputum examination.
 Mainstay of diagnosis – Bronchoscopy with bronchoalveolar Lavage.
 PCP is stained with Methenamine silver & Toluidine Blue or Wright Giemsa.
 Most sensitive test is DNA amplification with PCR.
 Patients at risk of PCP are 1) AIDS patients 2) Immunocompromised patients 3) Organ transplantation
patients 4) children with immunodeficiency.
 Rx: DOC for PCP prophylaxis = Cotrim oxazole (TMP SM2).
 DOC for PCP Rx = Cotrim oxazole (TMP SM2).
 Alternatives are =Clindamycin + primaquine
Clindamycin + pentamidine
Trimethoprim + Dapsone.
 PCP prophylaxis is indicated when 1. CD 4 count <200
2. Oropharyngeal candidiasis.
3. Prior PCP pneumonia.

® RSV produces atypical pneumonia in children.

DOC  Ribavirin.
® Bird Flu is caused by H5N1
Swine Flu is caused by H1N1 } DOC = Oseltamivir (Neuraminidase inhibitor).
® DOC for strep pneumonia = i.v penicillin G or Erythromycin (if allergic to penicillin)
® DOC for Chlamydia pneumonia = Doxycycline (tetracycline)
® DOC for Mycoplasma = Erythromycin 1st line
(MCC for atypical pneumonia) = Azithromycin 2nd line (for legionella 1st line)
= Doxycycline

® Mycoplasma pneumonia lacks cell wall & cannot be seen on gram staining. It produces cold agglutinins.
® DOC for staph aureus = Methicillin

® Concept of Alveolo – arterial gradient: It is the difference between alveolar pr. Of O2 & PaO2. It is usually
due to mismatch between ventilation & perfusion.
- (A-a)gradient is  due to ventilatory defects like ARDS.
- (A-a)gradient is  due to perfusion defects like pulmonary Embolism
- (A-a)gradient is  due to diffusion defects like interstitial fibrosis.
_____________________________________________

® TUBERCULOSIS:
 TB is caused by acid fast bacillus (Mycobacterium tuberculosis)  G +ve rod shaped bacteria.
 Acid fast staining is done by Ziehl-Nelson staining.
 Acid fastness of mycobacteria is due to presence of mycolic acid.
 The culture medium for mycobacteria is Lowenstein Jensen medium (LJ medium) & Bactec medium.
 Bactec medium is a liquid medium (Broth) more preferred culture media.
 TB is Type IV hypersensitivity reaction.
 Silicosis increases the risk of TB.
 The reservoir of infection is a person with active TB.
 TB. Spreads by respiratory droplets.
® PATHOGENESIS OF TB:
 TB is usually asymptomatic, develops in a unexposed unsensitized individual.
 In 10 TB, the inhaled bacilli are lodged in the lower part of upper lobe or upper part of lower lobe (in &
around the oblique fissure).
 The immunity specially macrophages limit the lesions.
 The bacteria are not killed but are walled off in caseous granulomas called as “GHON’S FOCUS”.
 Ghon’s focus with peri-hilar lymph nodes & enlarged lymphatics is called ‘GHON’S COMPLEX’(RANKE’S
COMPLEX when calcified)
 If the immunity overcomes the infection, the granulomas heals with fibrosis & calcification.
 The Ghon’s focus is usually sub-pleural.
 Sometimes, the 10 TB can become symptomatic in immunocompromised children & elderly.
 Pleural involvement is common, usually unilateral with unilateral – hilar lymphadenopathy.
Secondary TB.
 It develops in a previously sensitized host, usually arises from the reactivation of 1 0 lesions when the
host immunity is reduced.
 20 TB usually affects the apical lobes of the lung.
 Histologically, the active lesions shows characteristic granulomas both caseating & non-caseating.
 A tuberculoma (caseous necrosis) consists of central caseous necrosis with presence of Langhans type of
giant cells, large no. of epitheloid cells, [modified macrophages] surrounded by a rim of fibroblasts &
lymphocytes.
 20 TB is usually symptomatic presenting with low grade fever, night sweats, wt. loss, productive cough,
dyspnea, hemoptysis, cavitary lesions & pleural effusion.
 Cavitary lesions are common in 20 TB.
 The blood in hemoptysis comes by erosion of bronchial artery.

® MILIARY TB:
 It is a widespread Lympho hematogenous spread of TB.
 It involves multiple organs like liver, bone marrow, spleen etc.
 Almost every organ in the body can be affected.
 Military TB can occur from 10 TB in immunocompromised or in 20 TB.

® EXTRA PULMONARY TB:

 The MC site for extra pulmonary TB is Cervical lymphadenitis called as SCROFULA.
 Involvement of vertebral column produces POTT’S spine (tuberculous spine).
 The main cell responsible in the pathogenesis of TB TH1 cell.
 TH1 cell produces IFN, which activates the macrophages to form epitheloid cells, which limit the
infection of TB.
 The mycobacteria can survive & multiply within the macrophages.

® Dx of TB:
 Chest X-ray shows involvement of upper lobes with cavities & infiltrates.
 The Dx of TB is done by sputum culture & DNA probes.
 Sputum culture is the gold standard of diagnosis . & provides confirmatory evidence of TB.
 Routine cultures are done on LJ medium (Lowenstein Jensen) & takes about 46 weeks for the results.
 The faster methods of culture include bactec medium & rapid slide technique.
 Tuberculin test or Mantoux test is done with Subcutaneous injection of 0.1 ml of tuberculin.
Purified protein given on the flexor surface of forearm.
 Mantoux is usually read after 72 hrs.
 Check for induration that develops after 72 hrs.
 If the induration is >10mm, it is +ve Mantoux
 If the induration is 510mm, it is said to equivocal
 If the induration is <5mm, it is considered –ve.
 A +ve Mantoux means that the patient is infected or exposed to TB, but does not mean that the patient
has active TB.
  Mantoux test or Tuberculin test helps in excluding TB, rather than diagnosing it.
 A +ve Mantoux can occur in active infection, latent infection, in patients cured of TB.
 False +ve Mantoux can occur with BCG vaccination (bacillus Calmette Guerin) & infection with other
atypical mycobacteria.
 False –ve Mantoux is when the patients have TB, but do not react to purified derivative.
 (False –ve Mantoux is seen with miliary TB, severe malnutrition, Sarcoidosis, convulsions of measles,
Hodgkin’s lymphomas & other lymphoid malignancies).

® Newer methods of Dx
- Radioimmunoassay
- Fluorescent Ab test
- ELISA against tuberculous Ags.
- PCR test with amplifications of mycobacterial nucleic acid.
- But these tests are highly expensive.

® Rx of TB:
- Minimum 6 months of Rx is required.
- 2 months of initiation phase with HRZE &
- 4 months of continuation phase with HR.
- Hypersensitivity reactions to TB include,
- erythema nodosa
- Phlyctenular conjunctivitis

® Cavitary lesions in the lung:

1. TB
2. Staph aureus infection
3. Fungal infection (like histoplasmosis)
4. Lung CA mainly squamous cell CA.
® Rasmussen Aneurysm is dilatation of medium sized pulmonary artery within a tuberculous cavity.
® Cutaneous TB = lupus vulgaris
- Apple Jelly nodules.

ASPERGILLOSIS
® Mc cause of aspergillosis is Aspergillus fumigatus usually causes pulmonary aspergillosis.
® Aspergillosis usually occurs in severely immunocompromised.
® Pulmonary aspergillosis occurs in 4 forms
1. ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS (ABPA)
2. ASPERGILLOMA (fungus ball)
3. CHRONIC NECROTIZING ASPERGILLOSIS
4. INVASIVE ASPERGILLOSIS.
® ABPA:
 It is a hypersensitivity reaction to aspergillus fumigatus in patients with long standing asthma or cystic
fibrosis.
 Thick mucus plugs are produced.
 There is  in levels of eosinophils in the blood & lungs.
 It is a type I hypersensitivity reaction with  in IgG & IgE.
 The bronchial wall is damaged leading to bronchiectasis due to immune complex deposition.(Type III
hypersensitivity).
 There are fluting alveolar infiltrates which are usually bilateral involving the upper lobes.
 Main diagnostic criteria for ABPA are:
 i) Presence of bronchial asthma
ii) Pulmonary infiltrates
iii) Eosinophilia
iv) Elevated serum IgE
v) Central bronchiectasis.

® Aspergillosis is not a contagious disease (not transmitted from person to person).

® Aspergilloma:
 Aspergilloma are fungus balls
 It is the MC type of pulmonary aspergillosis.
 The fungus balls are formed in pre-existing cavities of TB, sarcoidosis or bronchiectasis.
 It is a non-invasive condition.

® Central cyanosis – (CVS & resp. cyanosis) Cardiac, tongue, extremities

® Peripheral cyanosis – (Exposure to cold) Extremities.
® Minimum of 5g of reduced Hb is to be present for cyanosis.
® Hypoxia – 4 types  in O2 level
1. Hypoxic hypoxia -  altitude sickness (PO2 , Pa O2)
2. Anemic hypoxia – in severe anemias (PO2 – N, PaO2 (blood) )
3. Stagnant hypoxia – CHF (PO2 atm – N, PO2 blood )
4. Histotoxic hypoxia - cyanide poisoning.

In stagnant hypoxia, - Venous O2 cone is 

(or)
(as blood stays more) Arterio –Venous O2 gradient .

 His toxic hypoxia : CN blocks mitochondria

O2 comes, no usage
Venous O2 cone is 
Arterio – (or) Venous O2 gradient .
® Transport of gases

____________________________________
 
O2 CO2
 Hb (95%)  HCO3 in plasma (>90%)
dissolved O2 (5%)  Hb CO2  (<5%)
Responsible for PaO2 other carbonate compounds

 O2 dissociation curve: sigmoid curve.

 Condition causing Bohr effect/Shift to Rt (Hb is getting deoxygenated)

 H+   PH
CO2

Temp
 2,3 BPG
( PH)
Lt shift:  H+   PH
 CO2
T
 2,3 BPG.

 HbF also causes Left shift.

Has  affinity to O2 than adult Hb.