First Aid USMLE Step 1: Pulmonology

Pulmonary Hypoplasia

Poorly developed bronchial tree with abnormal histology usually involving right lung

Associated with congenital diaphragmatic hernia and bilateral renal agenesis (Potter sequence)

.

POTTER sequence associated with:

Pulmonary hypoplasia

Oligohydramnios (trigger)

• compression of developing fetus

Twisted face

Twisted skin

Extremity defects

Renal agenisis - Bilateral (in utero)

Bronchogenic cyst

Caused by abnormal buddy of foregut and dilation of terminal or large bronchi

Discrete round sharply defined and air-filled density on CXR

Drain poorly and cause chronic infections

Compliance and elastic recoil

Inverse related

compliance = distention or volume change with given pressure change

Elastic recoil = lungs intrinsic tendency to collapse

Increased compliance = decreased elastic recoil

Conditions that decrease compliance

Pulmonary fibrosis

Pneumonia

Pulmonary Edema

Note: the lower compliance the higher the elastic recoil of the lung and the smaller the FRC (chest wall tendency balanced at lower expansion or volume)

Conditions with increased compliance

Emphysema

Normal aging

Surfactant increases compliance

Note: the greater compliance the lower elastic recoil the higher the FRC (chest wall tendency to expand must be balanced)

Neonatal respiratory distress syndrome Pathophysiology

• how will it look on CXR

• Surfactant deficiency - increased surface tension - decreased compliance - increased elastic recoil of lung - increased work of breathing

• alveolar collapse (ground glass appearance of lung fields)

LACK surfactant = collapse and hyaline membrane formation

Neonatal Respiratory Distress Syndrome Screening Test

Lecithin-Sphingomyelin ratio (L/S) in amniotic fluid

• lectin is produced by surfactant

L/S > 2 indicates lung maturity

L/S > 1.5 is predictive of NRDS

Other tests include: foam stability index test and surfactant-albumin ratio

Risk factors for NRDS

Prematurity

• 28-35 w for surfactant to delop

Maternal diabetes

• increased insulin= decreased surfactant

C-section delivery

• decreased release of fetal glucocorticoids due to lack of stress= decrease surfactant production

Treatment of NRDS

Maternal steroids before birth

Artificial surfactant for infant

Therapeutic supplemental oxygen in Neonate

can result in

R I B

Retinopathy of prematurity

Intraventricular hemorrhage

Bronchopulmonary dysplasia

Epithelial Progression in airways

Pseudostratified columnar ciliated

Simple Columnar ciliated

Simple Cuboidal columnar ciliated

Simple Squamous

Foreign Body Obstruction

Right mainstem bronchus is wider and more in line position with trachea = most common path for foreign object

Aspiration while upright: enters inferior segment of inferior right lobe

Aspiration while supine: most dependent areas are superior segment of right lower lobe and posterior regions of upper lobes

Structures perforating diaphragm at T8

Inferior vena cava

Structures perforating diaphragm at T10 (esophageal hiatus)

Esophagus

Vagus nerve (2 trunks)

Structures perforating diaphragm at T12 (aortic hiatus)

Aorta

Thoracic duct

Azygous vein

Bifurcation of Trachea " BiFOURcation"

T4

Bifurcation of Abdominal Aorta "BiFOURcation"

L4

Bifurcation of Common Carotid "BiFOURcation"

C4

Tidal volume

Air that moves in and out with each normal inspiration and expiration

Normal TV = 0.5 L

Inspiratory reserve volume (IRV)

Air that can still be breathed in after normal inspiration

Inspiratory capacity

TV and IRV combined

Expiratory reserve volume (ERV)

Volume that can still be exhaled after normal exhalation

does NOT include residual volume

Residual volume (RV)

Volume left in lung after maximal exhalation

Normal RV = 1.2 L

Functional residual capacity

Volume of gas that remains in lung after normal expiration

FRC = ERV + RV

Vital capacity

Volume that can be maximally inhaled and exhaled

Total lung capacity - Residual volume

Total lung capacity

TLC = Inspiratory capacity + Functional residual volume

TLC = (IRV + TV) + (ERV + RV)

Volume present in lungs after maximal inspiration

Note: cannot be measured by spirometry

Normal TLC = 6 L

Capacity

Sum of 2 or more physiologic volumes

Physiologic Dead Space

Volume of air which is not involved in gas exchange

Includes anatomical dead space of conducting airways plus alveolar dead space (ventilated but not perfused regions)

Normal lungs: physiologic DS = anatomical DS

Conditions that improve with O2 administration vs those that don’t

• Conditions that improve with O₂ administration= increased PaO₂):
  - oxygen can still reach ventilated parts of the lung, but blood flow is obstructed.

  • Example conditions:

    • Pulmonary embolism (PE)

    • Chronic obstructive pulmonary disease (COPD) with significant airflow obstruction

    Why they improve with O₂: increases the available oxygen in the blood, as some areas of the lung are still able to ventilate despite poor blood flow (in PE, for example).

• Conditions that do not improve with O₂ administration = no increase in PaO₂

  • perfusion problems, where blood flow is compromised 

  • Example conditions:

    • Intrapulmonary shunt (e.g., pneumonia, ARDS)

    • Foreign body aspiration (airway obstruction)

    • Atelectasis

    Shunting or Obstructions prevent 02 from reaching the areas in which perfusion occurs

Hemoglobin

Deoxygenated form (T or Taut): low affinity for oxygen: promotes release or unloading of oxygen in tissues

Oxygenated form (R or Relaxed): high affinite for oxygen

Positive cooperativity and negative allostery

Factors that Decrease Oxygen Affinity of Hb

Chloride

H+ (hypoxia or anemia - lactic acidosis)

Carbon dioxide (increased metabolic activity)

2,3 BPG (elevated in setting of hypoxia: chronic high altitude, chronic lung disease, heart failure)

Increased temperature

High altitude

Low affinity = improved unloading = shift to right

Methemoglobinemia

Methemoglobinemia = Fe3

• Oxidized form (Fe 3+) Hb has decreased oxygen

•   increased affinity for cyanide

Presets with chocolate colored blood: dusky discoloration of skin (similar to cyanosis).

Treated with methylene blue and vitamin C

Causes of Methemoglobinemia

Nitrites (dietary intake or polluted/high altitude H2O)

Benzocaine

Dapsone

TMP-SMX

Induced Methemoglobinemia

Patients with cyanide poisoning can be treated wit nitrites followed by thiosulfate

Carboxyhemoglobin

Hb bound by CO: decreased oxygen binding capacity with left shift in oxygen-hemoglobin dissociation curve (increased affinity) = impaired unloading in tissues

Hb has 200 fold affinity for CO compared to O2

Treatment: 100% O2 and hyperbaric O2

Fetal Hemoglobin HbF (alpha-gamma)

Higher oxygen affinity due to decreased affinity for 2,3-BPG (negative allosteric regulator of oxygen affinity)

High Altitude Physiology: Initial first 2 days

Less oxygen in air so the first effect is hypoxia and decreased dissolved oxygen in the blood.

The immediate response will be stimulation of peripheral chemoreceptors which in turn in send signals to respiratory drives to breath more.

Hyperventilation develops which in turn leads to Respiratory Alkalosis (Altitude sickness)

Respiratory alkalosis will shift the hemoglobin dissociation curve to the left so that Hb can pick up O2 easier.

The kidney will respond to alkalosis by generating hydrogen ions and this will correct the pH back to normal.

Hemoglobin deoxygenation curve

• right =

right = release of O2

High Altitude Physiology: After 2-3 Days

After 2-3 days the 2,3 BPG level in RBC will increase and this will shift the Hb curve (this time) to the right making O2 delivery easier to tissues.

Increase of EPO secretion (takes about 1 week) leading to polycythemia and increased hematocrit level.

Finally there is an increase in mitochondria

Note that no matter how long you stay in high altitudes the PAO2, PACO2, and Hemoglobin saturation will remain decreased as we breath less FIO2 and we continue to hyperventilate

CO poisoning: Findings

Hb concentration

SaO2

PaO2

oxygen content

Normal Hb concentration

Decreased SaO2

Normal PaO2

Decreased oxygen content

Anemia: Findings

Hb concentration

SaO2

PaO2

oxygen content

Decreased Hb concentration

Normal SaO2

Normal PaO2

Decreased oxygen content

Polycythemia Findings

Hb concentration

SaO2

PaO2

oxygen content

Increased Hb

Normal SaO2

Normal PaO2

Increased oxygen content

Perfusion-limited Gas exchange

Oxygen (normal healthy individual)

CO2

N2O

Gas equilibrates along the length of the capillary: diffusion can be increased only with increased blood flow

Diffusion limited Gas exchange

O2 (Emphysema and fibrosis)

CO

Gas does not equilibrate by the time blood reaches the end of the capillary

A-a Gradient

Difference in between partial pressures of oxygen in Alveoli versus arterioles

A-a = PAO2 - PaO2

Causes of increased A-a gradient

Shunting

VQ mismatch

Fibrosis (impaired diffusion)

Causes of Hypoxia (decreased oxygen delivery to tissues)

Decreased Cardiac output

Hypoxemia

Anemia

CO poisoning

Causes of Hypoxemia (decreased PaO2)

Normal A-a gradient:

• High altitude or hypoventilation

Increased A-a gradient:

• VQ mismatch, diffusion limitation or right to left shunt

Causes of Ischemia (loss of blood flow)

Impeded arterial flow

Impaired venous drainage

Perfusion and Ventilation of lung zones

Both ventilation and perfusion are highest at the base of the lung (zone 3)

Perfusion (Q) increases more rapidly as you move from apex to base

V/Q decreases as you move from apex to base

V/Q at apex = 3

V/Q at base = 0.6

Bohr effect

High H+ concentration in peripheral tissues - binds Hb decreasing its affinity for O2 - facilitates oxygen unloading

Causes of Rhinosinusitis

Acute: viral URI

Most common superimposed bacterial infections:

S. Pneumoniae

H. influenzae

Moraxella Catarrhalis

Epistaxis

Most common: mild epistaxis from anterior inferior part of nasal septum: Kiesselbach plexus

Life-threatening hemorrhages can occur in posterior segment: sphenopalatine artery (branch of maxillary artery)

Head and Neck cancers

Mostly squamous cell carcinoma

Risk factors: tobacco, alc and HPV 16 (oropharyngeal) and EBV (nasopharyngeal)

Field cancerization: carcinogen exposure damages wide mucosal area: multiple tumors

Nasopharyngeal carcinoma may present with

unilateral nasal obstruction, discharge, epistaxis.( nose bleeds)

Eustachian tube obstruction may lead to otitis media +/– effusion, hearing loss.

Laryngeal papillomatosis

also called recurrent respiratory papillomatosis.

Common benign laryngeal tumor (eg, vocal cords), especially in children. Associated with HPV-6 and HPV-11.

DVT

Swelling of extremity

Redness and warmth

Pain

Homan sign: dorsiflexion of foot produces calf pain

Labs: elevated D-dimers (highly sensitive but non-specific)

Most common in proximal deep veins of the leg: femoral vein

Treatment of DVT

Use unfractionated heparin or low-molecular

weight heparins (eg, enoxaparin) for

prophylaxis and acute management.

.

Use direct anticoagulants (eg, rivaroxaban,

apixaban) for treatment and long-term

prevention.

Virchows Triad

Stasis (post-op immobility)

Hypercoagulability (defects in coagulation cascade, malignancy, OCP, smoking)

Endothelial damage (exposed collagen triggers clotting cascade)

PE

• V/Q

VQ mismatch: ventilated sections without perfusion: increased physiologic dead space

• normal V/ decreased Q

PE Presentation

Sudden onset dyspnea

Pleuritic chest pain

Tachypnea and tachycardia ( EKG)

Lines of Zahn

Distinguish a pre-mortem from a post-mortem thrombus

Interdigitating areas of pink (platelets and fibrin) and red blood cells found in thrombi formed before death

Types of Emboli that can cause PE

FAT BAT

Fat

Air

Thrombus

Bacteria

Amniotic fluid

Tumor

Fat Embolus

• triad

Associated with long bone fractures and liposuction

Classic triad:

Hypoxemia

Neurologic abnormalities

Petechial rash

Amniotic fluid embolus

Anaphylactoid reaction: amniotic fluid causes

• occlusion and vasospasm of the maternal pulmonary circulation leading to RIGHT ventricular failure decreased CO and severe ventilation perfusion mismatch. Resulting hypoxia and hypotensive shock ultimately causes cardiopulmonary arrest

Tissue factor (thromboplastin) is released from amniotic fluid and triggers DIC

Fetal squamous cells and mucin are found in amniotic fluid emboli occluding maternal pulmonary arteries

Air emboli

Caisson Disease or Decompression sickness: Nitrogen bubbles precipitate in ascending divers

• “A 42-year-old professional diver presents to the emergency department 2 hours after surfacing from a deep-sea dive. He reports severe joint pain, nausea, and weakness. On examination, he is tachypneic and has cyanosis. Which of the following best explains the pathophysiology of this condition?”

Other causes: iatrogenic secondary to invasive procedures (central line placement)

PFT picture in Obstructive lung diseases

DECREASED FEV1/FVC ratio = HALLMARK

• Severely decreased FEV1

increased TLC

.

retention of CO2!!!

• vasoconstriction

VQ mismatch: increased physiologic dead space

Chronic Bronchitis Diagnosis (Clinical)

Classified as Chronic Obstructive Pulmonary Disease (COPD)

Productive cough for > 3 months (does not have to be consecutive) for more than 2 consecutive years

Most common in smokers

SYMP in Chronic Bronchitis

Wheezing

Crackles

Cyanosis: early-onset hypoxemia due to shunting: perfusion of mucus plugged region of the lung with no ventilation

Late-onset dyspnea (live at low SaO2)

CO2 retention and hypercapnea

Secondary (reactive) polycythemia (increased EPO)

Histological Findings in Chronic Bronchitis

Hypertrophy and Hyperplasia of mucus-secreting glands in bronchi:

Increased Reid Index > 0.5

Pathophysiology of Emphysema

Enlargement of air spaces due to destruction of alveolar walls:

Increased activity of neutrophil elastase leading to destruction of elastic fibers

Increased compliance = decreased elastic recoil

Increased FRC

Decreased diffusion capacity for CO resulting from destruction of alveolar walls and capillaries (decreased Surface area)

Emphysema findings

PINK PUFFER - Pursed lip breathing (increased resistance - increased intraluminal airway pressures prevents premature collapse on exhalation)

Barrel shaped chest (increased AP diameter)

Cachexia: increased energy expenditure due to respiratory efforts

Flattened diaphragm (increased TLC)

Increased lung field lucency

Panacinar Emphysema

Alpha-1-Anti-trypsin deficiency

Lower lobes

Centriacinar Emphysema

Smoking

Upper lobes

Asthma def

Bronchial hyper responsiveness causing reversible broncho constriction

Asthma Histological findings

Smooth muscle hypertrophy

Curschmann spirals (shed epithelium forming whorled mucus plugs)

Charcot-Leyden crystals (eosinophilic hexagonal double-pointed needle-like crystals formed from breakdown of eosinophils)

Types of Asthma

Allergic (extrinsic) asthma

Non-allergic (intrinsic) asthma: normal IgE (triggered by pulmonary infections, aspirin ingestion, cold air, inhaled irritants, stress and or exercise)

Intrinsic Asthma

Non-allergen mediated

Causes:

Viral URI (RSV, rhinovirus, and parainfluenza virus)

Behavioral: exertion and stress

Chemical

Drug sensitivity (NSAIDs and aspirin)

Diagnosis of Asthma

• symptoms

• Inspiratory/ expiratory

• test

Clinical picture: cough wheezing tachypnea dyspnea hypoxemia

decreased inspiratory/expiratory ratio

• expiration is prolonged due to increased airway resistance.

Methacholine challenge

Spirometry: obstructive pattern

during serious attack of asthma we can see

pulsus paradoxus

A drop in systolic blood pressure (SBP) >10 mmHg during inspiration.

Bronchiectasis

• symptoms

Chronic necrotizing infection of bronchi leading to permanently dilated airways

Recurrent infections

Hemoptysis

Digital clubbing

Fowl smelling breath and purulent sputum

Conditions associated with bronchiectasis

Impaired ciliary motility:

• Smoking

• Kartagener Syndrome

Cystic fibrosis

Allerigc Bronchopulmonary Aspergillosis

• type 1 HS

• eosinophillia

Restrictive Lung Diseases

FEV1 / FVC

lung volumes

Decreased lung volumes: decreased TLC

FEV1/FVC = normal or increased

Restrictive Lung Diseases related to poor breathing mechanics

Extra-pulmonary causes: Peripheral hypoventilation with normal A-a gradient

Poor muscular effort: polio Myasthenia Gravis Guillain-Barre Syndrome

Poor structural apparatus: scoliosis or morbid obesity

Interstitial lung diseases

Pulmonary causes of restrictive lung disease with decreased diffusion capacity and increased A-a gradient

ARDS

NRDS (hyaline membrane disease)

Pneumoconioses (anthracoses silicosis asbestosis)

Sarcoidosis (bilateral LAD non-caseating granulomas increased ACE and vitamin D = increased calcium)

Idiopathic pulmonary fibrosis: increased collagen deposition and fibrosis leading to honeycomb appearance and digital clubbing

Goodpasture Disease

• Linear IF + antibodies BM

• hematuria

Granulomatosis with Polyangiitis (Wegeners)

• Negative IF/Pauci-immune (no IgC3 deposition)

• PR3-ANCA/c-ANCA,

Pulmonary Langerhans cell Histiocytosis (eosinophilic granulomas CD1a CD14 positive Bierbeck granules)

Hypersensitivity Pneumonitis

Drug toxicity: bleomycin Busulfan amiodarone MTX

Hypersensitivity Pneumonitis

Mixed type III and IV HSR to environmental antigen

NONcaseating granulomas

Dyspnea cough chest tightness headache

fever when acute ( self resolving)

,

Classic script: farmer or pet store owner with exposure to envioemental factors ( hay, birds ect )

elevated serum levels of…..

• sarcoidsois

Hyper CA ( bc noncaseating granuloma)

ACE

elevated CD4/CD8 ratio in bronchoalveolar lavage fluid

who will we see sarcoidosis in

Black

young female

key word for sarcoidosis

bilateral lymohadenopathy

hilar nodularity

Sarcoiddosis Mneumonic

SARCOIDS

Associated with granulomas (noncaseating epithelioid, containing microscopic Schaumann and Asteroid bodies),

Rheumatoid arthritis–like arthropathy,  Calcium ( HYPER)

Ocular uveitis,

Interstitial fibrosis,

vitamin D activation (due to  1a-hydroxylase in macrophages),

Skin changes (eg, lupus pernio, erythema nodosum)

Arsenic poisoning

inhibits lipoic acid.

clinical findings: imagine a vampire (pigmentary skin changes, skin cancer), vomiting and having diarrhea, running away from a cutie (QT prolongation) with garlic breath.

c

squamous cell carcinoma

angiosarcoma

Cyanide vs CO posoning

Burn patient will have what kind of presentation ?

• infection ?

LOW bp + high HR

• bc increased permiability and decreased intraVascular volume

Psuedomonas ( with FEVER )

smoke inhalation will cause what kind of presentation

• cause

seen in CO, Cyanide, Arsenic

.

soot in oropharynx

singed nasal hairs

Bronchoscopy = congestion, soot and edema

• CAUSE = edema, pneumonia , ARDS ( endothelial damage and increased permiability )

mesothelioma markers

Calretinin and cytokeratin 5/6 ⊕ in almost all

mesotheliomas

Mesothelioma is malignancy of

• associated with what dissorder

• how does it appear in Histology

• may result in

Malignacy of pleura

• asbestos predisposes

• Histology may show psammoma bodies.

  EM may show polygonal tumor cells with microvilli, desmosomes, tonofilamen

• may cause pleural thickening and hemorraghic pleural effusion

“whitish cancer “

_____is from the roof ____, but affects the _____

______from the ____, but affect the ____

Asbestos is from the roof (was common in insulation), but affects the base (lower lobes).

Silica, coal, and berries are from the base (earth), but affect the roof (upper lobes).

Complications seen in Pneumoconioses

Cor pulmonale (right-sided HF secondary to pulmonary HTN)

Cancer

Caplan syndrome: rheumatoid arthritis and pneumoconioses with intrapulmonary nodules

Asbestosis

• who

• how does it present in lungs

Shipbuilding

roofing

plumbing

.

Ivory white calcified supra-diaphragmatic and pleural plaques

.

Asbestos bodies (ferruginous): golden-brown fusiform rods resembling dumbbells found in alveolar septum sputum sample

Asbestos bodies are visualized with Prussian blue stain and obtained via BAL