How 'bout a little Lung Pathology

Good evening all! I'm trying to give some quick-hit reading and "to know" for those preparing for USMLE Step 1. This will continue for a couple more weeks. Most of those who will be taking this exam will be completing their preparation during the next 3 weeks and then entering the wards, where I could then become their intern when they rotate through their internal medicine clerkship at the University of Kansas. That is when the fun begins. Right now, it is time to focus on preparing to take THE test that either opens or closes future doors of opportunity. Sadly, this exam does weigh that heavily.

All of you preparing for this exam and have scheduled to take it in the middle to late June should be doing lots and lots of questions from a question bank, such as USMLE world or Kaplan. I would also recommend as you go back through your question bank to have your FirstAid book handy and write in the margins those explanations that really make it stick for you.

You should have or should be thinking about taking a full, mock exam. This will build your stamina for THE day and make you work that recall muscle I blogged about earlier this month.

Build your confidence, daily! Know you are in the right place, at the right time to do well.

Make sure you are exercising and eating right.

Make a plan, do your plan, believe in your plan and execute!

Alright... enough soap box stuff. As important as it is, here is some lung path to work your brain over.

Make sure to inhale! ;)



Interstitial Lung Diseases

Acute Lung Injury- rapid onset, short duration
- Diffuse Alveolar Damage (DAD)- specific cause, rapid progression-infiltrates
- Acute Interstitial Pneumonia (hamman-rich disease)- like DAD, only no specific cause, fulminant course- need biopsy
o The above two present with pretty severe respiratory symptoms

- Bronchiolitis Obliterans (BOOP)- only one with a good prognosis, air space disease- fibroid polyps filling airspaces

o Presents with fever, cough, dyspnea, bilateral infiltrates

Chronic Interstitial Pneumonia
- Usual Interstitial Pneumonia- varying histology- fibrosis, inflammation
o Infiltrates periphery, base
o Worse prognosis, older people 55

- Desquamative Interstitial Pneumonia- uniform, macrophages in airspace
o Better prognosis---younger 45

Honeycomb lung- dilation/mucous filling air spaces/cyst formation/obliteration of small airspaces to create big ones---end stage
- Acute lung injury- DAD
- Chronic- BOTH UIP, DIP
- Asbestos
- Interstitial glanulomatous diseases
- Eosinophillic granuloma


Hypersensitivity Pneumonitis= Extrinsic Allergic Alveolitis

Non-Necrotizing Granuloma: Hypersensitivity Pneumonitis
Necrotizing Granuloma: Wegener's granulomatosis

Cyclophosphamide
- UIP
- Wegener's Granulamatosis

Diffuse Pulmonary Hemorrhage Syndromes
- Goodpasture's Syndrome---young males, kidney too
o Hemorrhage in intraalveolar spaces

- Vasculitis assoc- both have good prognosis with treatment
o Wegener's granulomatosis-- 50 y/o males, kidney too--mostly other organs
Necrotizing granuloma in lung and vasculature (necrotizing vasculitis)
C-ANCA

o Chrug-Strauss- ASTHMA, P-ANCA, RARE kidney: skin, nerves, heart, looks like eosinophilic pneumonia

Pulmonary Eosinophilia
- eosinophills in BLOOD or SPUTUM…NOT IN LUNG TISSUE ITSELF
- DISEASES:
o Churg-strauss (see above)
o Eosinophilic pneumonias
Simple- LOEFFLER'S SYNDROME- transient infiltrates
Tropical- filiarial
Chronic- only one that needs biopsy, assoc w/ASTHMA
• Responds well to steroids, lots of diff causes

o Allergic bronchopulmonary aspergilliosis- NO BIOPSY
Hypersens to aspergillius (acute branching hyphae)
Ab to aspergillius, central bronchiectasis (dilation)

Immune, not infectious- treat w/ steroids

Pulmonary Eosinophilic Granuloma (histiocytosis X)
- is NOT A PULMONARY EOSINOPHILIA!!!!!!!!
- the eosinophils are located in the lung tissue, NOT the peripheral blood/sputum
- histocyte proliferation, with a pneumothorax (air in pleural cavity)
- langerhans cells w/ bierbeck granule(ovoid nucleus with central line, stain with S-100) CD 1+
- treatment: stop smoking, corticosteroids

Diseases associated with ASTHMATICS- all have pulmonary eosinophilia (makes sense)

- Churg-Strauss
- Chronic eosinophilic pneumonia
- Allergic bronchopulmonary aspergilliosis

Immunologic lung diseases
- Goodpastures
- Allergic bronchopulm aspergilliosis

Sarcoidiosis- multisystem granulomatosis disease
- multiple non caseating, non necrotizing granulomas, usu along lymph pathways (different from TB- which would caseate)
- black, female, 20-40 y/o
- bilateral infiltrates, hilar lymphadenopathy
- increased serum angiotensin converting enzyme
- increased 24 hour calcium secretion

Necrotizing Granulomas along blood pathways- Wegener's granulomatosis
Non-necrotizing granulomas along lymph pathways- sarcoidiosis

Pneumonconiosis
- non-neoplastic rxn in lung to inhaled mineral/organic dust
- Asbestos Diseases
o Asbestosis- pulmonary parenchymal interstitital fibrosis
o Pleural plaque
o Pleural effusion
o Bronchogenic carcinoma
o Malignant mesothelioma
o Laryngeal/extrapulmonary neoplasms

Lung Biopsies
- OLB- gold standard
- VALB- not good for central biopsy
- TBB- good for sarcoid, cancer, infections

o Bad for UIP, DIP

COPD/PFT

Chronic Obstructive Diseases
- Chronic Bronchitis
- Emphysema
o Above two are usually considered COPD
- Asthma
- Bronchiectasis


Chronic Bronchitis
- middle ages, smokers, males
- hallmarks:
o hypertrophy/hyperplasia of submucosal glands (ried Index)
RIED index- meas ratio of submucosal gland thickness to thickness of bronchial wall..>0.4 is bad
o goblet cell metaplasia in bronchi

Remember----terminal bronchiole---respiratory bronchiole---alveolus

Emphysema: enlargement of airspaces, distal to terminal bronchiole
- pathogenesis: protease/antiprotease balance
- defined in morphologic terms
- males, smoking, 50-80 y/o
Types
- centrilobular: most common, resp bronchioles, UPPER lobes
- panlobular: involves BOTH resp bronch and alveoli (whole acinus), LOWER lobes
o alpha-1-antitrypsin defiency (PiZZ genotype)
- localized - (paraseptal), enlargement distal acinus, upper lung, usu asymptomatic

o young adults- spontaneous pneumothorax
- Irregular (paracicatricial emphysema)- fibrosis
- Bullous- occurs w/ other emphysemas

Asthma:
- smooth musc contraction, mucous secretion, increased vascular permeability-edema---leads to bronchial obstruction
- thickened bronchial basement membrane of bronchioles, hypertrophy of bronchial smooth muscle, mucous plugs

Bronchiectasis
- irreversible dilation of bronchi- due to elastic/muscular elements in wall

- Immotile cilia syndrome
o Inherited non-obstructive cause
o Includes Kartagener syndrome: dextrocardia, bronchiectasis, sinusitis, rhinitis, nasal polyps, otitis media

Non Productive cough: Asthma
Productive Cough: bronchiectasis (mucopurulent sputum)

Middle Aged men
- UIP
- DIP
- Hypersensitivity pneumonia
Pulmonary fxn tests
- when have pulmonary function tests: the percent predicted is the "percentage that the "ideal" predicted value that the patient has achieved
- Forced Expiratory Flow :slope of line through volume/time graphs
o FEF 25-75%- small airway disease
o FEF 200-1200- large airway disease

Infectious Lung Diseases

Productive Cough: Bacterial Pneumonia

Bacterial Pneumonia
- Community Acquired Pneumonia: mild- bad if co-morbidities
- Nosocomial
- Opportunistic
- Abscess is complication of bacterial pneumonia
Viral Pneumonia: usu kids, immunocomp
- chronic interstitial pneumonia- lymphocytes
- diffuse alveolar damage- hyaline membranes
- Cytomegalovirus
o Immunocomp,
o Fever, non productive cough, diffuse infiltrates
o Intranuclear inclusion bodies, intracytoplasmic inclusions
Pneumocystis Pneumonia
- immuno comp
- fever, dry cough,
- inter-alveolar FOAMY exudates

Pulmonary Fungal Infections
- Histoplasmosis
o Soil, bird/bat droppings
o Granulomatous inflammation, small black budding yeast
- Coccidiodomycosis
o Southwest
o Necrotizing granulomatous inflammation

- Cryptococcosis - india ink stain
o Soil, PIGEON poop
o Mucin positive
- North american blastomycosis
o mid west river valleys
o pus forming (suppurative)/granulomatous
o BROAD based budding

- Aspergillosis
o Allergic bronchopulmonary aspergillosis- immunologic
o Aspergilloma- colonizes pulmonary cavity- fungus ball
o Invasive aspergillosis- opportunistic infection
Vascular invasion, thrombus + infarct
Can see hyphae and fruiting bodies

Tuburculosis
- Gohn complex: peripheral granuloma, involvement w/ mediastinal lymph node

Stuff that forms Granulomas
Necrotizing
- TB
- Coccidiomycosis

Non-Necrotizing
Lung Cancer
Men, 60-70 y/o
Central Tumors
- small cell carcinoma
- squamous cell carcinoma
- branchial carcinoids
Peripheral Tumor
- adenocarcinoma
- hamartoma

Malignant
Epithelial Tumors
- squamous cell carcinoma
o smoking males, central lung- keratin pearls
o hemotypsis, symp due to obstruction
o superior vena cava syndrome- compression, dilation of upper body veins
o pancoast syndrome- shoulder pain- ulnar distribution: b/c tumor at apex compresses parts of brachial plexis
o Horner syndrome- b/c pancoast tumor that involves cervical symp plexus- ptosis, miosis, anhydrosis, endopthalmosis
o Massive hemorrhage, dilated bronchi mucopurulent secretions,
o 5 years, 15%

- adenocarcinoma
o peripheral, assoc with scars
o 5 year 15-20%
o Types
Acinar adenocarcinoma
• Gland arrangement, mucous secretions
Broncho-alveolar carcinoma
• Male female 1:1, 5 year 42%, multicentric/diffuse forms worse
• Neoplastic cells line "normal" alveolar architecture
• Types
o Solitary mass
o Multiple nodules- resembles metastatic cancer
o Multicentric diffuse infiltrate- resembles interstitial disease
Solid carcinoma w/ mucous cell formation
• Undifferentiated, anaplastic
Papillary adenocarcinoma
• Papillary structures with central fibrovascular core

Neuroendocrine Carcinomas (small and large cell carcinomas): acts like neuroendocrine system

Small cell carcinoma
o Males, smoking
o Worst prognosis 5 yr 4%, already metastatic by time of diagnosis
o Best response to cancer- important to ID as small cell for TX
o Central
o Types
Oat Cell
Intermediate
• Similar clinically
Combined- oat cell + any other type of tumor (squamous or adenoma)
• Perform surgery to remove

- Large cell carcinoma
o Poorly differentiated- no observable org via light microscopy
Electron microcsopy shows some organization
o cells with lots of cytoplasm (+ lymphocytes…not oat cells)
o Treat with SURGERY NOT CHEMO

Bronchial Carcinoids
- M=F, 45 y/o
- Central, peripheral, atypical
- Central
o GOOD PROGNOSIS- 5-10 y 50-95%!
o Maj metast to lymph, minor to liver
o YELLOWISH color
o Mass invading lumen of larger bronchi (more central)
o Invade bronchial wall into lung tissue
o Uniform cells, strippled chromatin, positive stain for chromogranin
o Can UNUSUALLY cause carcinoid syndrome (via seretonin secretion- skin flush, broncho const, cyanosis, R heart prob, hypotension,edema)

Metastatic Tumors
- lung 2nd most freq after lymph node
- Types
o Multiple- usu late stage cancers
o Lymphangitic- usu from adenocarcinoma
o Solitary- must distinguish from primary tumor
- usu from stomach, breast, colon, uterus, pancreas
Malignant Mesothelioma
- males, 40-70 y/o
- increasing in freq
- asbestos exposure (20-40 year lag)
- PLEURAL EFFUSION
- Pleural tumor encasing the lung- can extend to diaphragm
- Biphasic: epithelial/spindle
Benign
Hamartoma
- Peripheral, well defined
- hamartoma means like tumor, but due to faulty development
o microscopically can reproduce any component of bronchial tissue- cartilage, muscle, fat, cleft like spaces
Putting it all together….

Small cell carcinoma: major one for chemo
All other tumors- surgery is treatment of choice!!

Overall cancer survival rate: 5 years, 8-10 %
In order of better to worse
- squamous, adeno, small, large
Squamous cell, adeno= better prog
Small/Large cell= bad prog
Metastasis: most likely to least likely: lymph nodes, liver, adrenal, bone, brain

Paraneoplastic syndromes
Squamous cell carcinoma: hypercalcemia- PTH
Small cell carcinoma: cushing's (ACTH), inapprop ADH, carcinoid, gyneocmastia, acromegaly
Squamous cell and adenocarcinoma ( prob most frequent and increasing!)are most frequent lung tumors
- small cell and large cell also considered frequent

Drugs with Lung Toxicity:
Bleomycin
Busulfan
Amiodarone
Cyclophosphamide
Methotrexate and methysergide
Nitrosourea and nitrofurantoin