Respiratory Path Flashcards
Conducting Zone
Mouth/Nose, pharynx, trachea, bronchi to bronchioles
-Has squamous epithelium and progresses to Pseudostratified cliliated columnar epithelium with goblet cells
Bronchi
-Have cartilage and goblet cells. Below have smooth muscle and club cells
Bronchioles to terminal bronchioles
- Smooth muscle with clara cells
- pseudostratified columnar epthelium
Respiratory zone
- Respiratory bronchioles, alveolar ducts, alveoli
- Cuboidal cells in respiratory bronchioles and squamous cells in alveoli
Alveolar Macrophages
-Defense cells of alveoli
Type I pneumocytes
- Thin simple squamous cells that participate in gas exchange
- Comprise 97% of surface area
Type 2 pneuomcytes
- Secrete surfactant to oppose surface tension
- Serve as reserve cells during damage of type 1 cells
- Contain lamellar bodies which are surfactant that will be secreted
- Cuboidal cells
Clara/Club Cells
- Located in the terminal bronchiole area and respiratory bronchiole.
- Secrete defense proteins (IgA components, lysozyme, etc)
- Chew up mucus that has been secreted and degrades surfactant
Collapsing pressure
- Directly proportional to 2*surface tension and inversely proportional to radius.
- Collapse is possible during exhalation.
Surfactant
- Secreted by type 2 pneumocytes and breaks surface tension
- Lecethin to sphingomyelin ratio of greater than 2:1 signals lung maturity
- Doesn’t mature until week 35 (26-35)
Aspiration
-Most likely to occur in the right lower lobe
Diaphragm Structures
- IVC at T8
- Esophagus at T10
- Aorta, azygous, thoracic duct at T12
- Innervation by C3-5, inflammation may lead to referred pain to shoulder
Congenital Diaphragmatic Hernia
-Most commonly on left pleurodiaphragm leads to unilateral lung hypoplasia
Accessory Muscles of inspiration
-External intercostals - Pull up and out
Expiration
-Internal intercostals pull down and in
FRC
- Expiratory reserve volume and residual volume
- The point at which the chest expansion and lung retraction are equalized and alveolar pressure is equal to atmospheric
Physiologic Dead Space
- Anatomic plus functional dead space
- Arterial co2-expired CO2 over arterial co2
Hemoglobin A
- Two alpha and 2 beta subunits
- Taught state has low affinity for oxygen and is observed in a right shift.
- Relaxed state has high affinity for oxygen and is seen in a left shift
- Shift to taught with increase CO2, H+, temp, Cl, 2,3 BPG (increased metabolic activity)
Hgb F
Has two alpha and 2 gamma
-Has decreased affinity for 2,3 BPG meaning it has a higher affinity for oxygen. 2,3 BPG causes increased release in tissues.
Methemoglobin
- Oxygen can only bind when Fe is reduced in the 2+ state.
- If oxidized to 3+ can’t bind oxygen, pulse ox shows decreased saturation
- Has higher affinity for Cyanide
- Can be caused by nitrites, drugs, pyruvate kinase and G6PD
- Cyanide poisoning treted with nitrates to form Fe3+ and take cyanide into hemoglobin and off cytochromes. Then give thisulfate to solubalize and methylene blue to reduce Fe
Carboxyhemoglobin
- Hemoglobin has higher affinity for CO and demonstrates as non-sigmoidal curve
- Causes shift to the left and down in oxygen binding capacity
- Pulse ox often shows normal, need to get a carboxyhemoglobin level
- Symptoms are red color, headache, vommiting, altered mental status
- Treat with hyperbaric oxygen
Pulmonary circulation
- High compliance low resistance circuit
- elevated CO2 causes contsritcion and O2 causes dilation
Perfusion limited
- Normal physiologic conditions all gases are perfusion limited except CO
- Equilibration along length
Diffusion Limited
- Equilibration doesn’t occur and gases are limited by their diffusing capacity
- Diffusion proportional to pressure difference and area and inversely proportional to thickness
- Emphysema causes a loss of area and fibrosis causes and increase in thickness both leading to diffusion limiting
Primary Pulmonary Hypertension
-Defect in BMPR2 leads to smooth muscle proliferation and constricion, poor prognosis
Secondary Pulmonary Hypertension
- Caused by anything that decreases oxygenation or increases CO2 levels leading to vasoconstriction
- Sleep Apnea, Altitude, Multiple Thromboemboli, Right to Left cardiac shunt, systemic sclerosis (scleroderma), Mitral stenosis, COPD
Cyanosis
- Occurs with elevated deoxyhemoglobin, not necessarily decreased oxygen levels
- Content is in bound to Hgb and unbound fractions
Alveolar Gas Equation
- PAo2= PIo2-PCO2/.8
- Alveolar oxygen is equiivlent to space not occupied by CO2
A-a Gradient
- Pressure gradient for oxygen to flow from alveoli to capillaries
- Will be increased in diffusion problems, V/Q mismatches, Shunting
Hypoxemia with normal A-a
- Means there is decreased alveolar oxygen
- Hypoventilation or altitude
Hypoxemia with increased A-a
- There is impaired blood flow/oxygen extraction
- Diffusion, V/Q mismatches, R to L shunt (decreased a of returning blood)
Hypoxia
-Decreased oxygen Delivery to tissues: Decreased CO, anemia, CO poisoning, hypoxemia
Ischemia
- Decreased blood flow to tissues
- Arterial block or venous congestion
V/Q mismatches
- Apex Ventilation 3 times perfusion Zone 1 (wasted ventilaton)
- Zone 2, middle: Ventilation almost equal to perfusion
- Zone 3, base: Ventilation less than perfusion: Physiologic dead space
- Ventialation and perfusion are both the greatest at the base of the lung, but perfusion is proportionally greater.
Exercise
-Capillaries open because of increased perfusion pressures leads to increased perfusion in apex
V/Q is 0
Airway obstruction, supplemental oxygen will not help
V/Q is infinite
- perfusion defect due to embolization etc.
- Leads to shunt and therefore oxygen will help
CO2 Transport
- Majority dissolved in bicarbonate. CA speeds up reaction. Turns to CO2 at lungs and is blown off
- 5% as CO2 bound to N terminus of Hgb, increases liklihiood of tught state and offloading in tissues
- 5% dissolved
- H+ offloaded in lungs increases affinity for O2 and H+ comes on in tissues, decreases affinity
High Altitude
- Acute hyperventiltion leads to alkalosis
- Respond: EPO, Elevated HCO3 excretion (Acetazolamide augments), Elevated 2,3 BPG (Stressed), Increased cellular mitochondria,
- Acute hypoxic vasoconstriction can lead to pulmonary edema
- Chronic hypoxic vasoconstriction can lead to RVH
Exercise
- Elevated CO2 production and O2 usage
- PaCO2 and PaO2 are normal but there will be a drop in the venous content of oxygen and increase in CO2
- VQ equalizes in lung by opening of unused capilaries.
DVT
-Thrombosis in deep veins of leg, caused by stasis, hypercoagulability, endothelial damage
Hypercoagulability
- Estogen Use, smoking
- Factor V Lieden
- Protein C or S deficency (S is cofactor for protein C inactiavtion of V and VII)
- Prothrombin 2010 ( mutation in 3’ UTR that leads to increased stability of mRNA and elevated prothrombine levels)
- Antiphospholipid (B2)
- PNH
- Cancer (adenocarcinoma)
- Nephrotic leads to ATIII loss (heparin increses activity. Activates serine proteases 2,7,9,10,11, also complement proteins.)
- Dysfibrinogenemia (increase clotting risk)
Sympotoms
-Positive Homan sign with pain on dorsiflexion
Pulmonary Embolism
- If small can reorganize and cause pulmonary hypertension due to scarring and fibrosis
- Saddle: RVH block leading to mechanical-electrical dissociation, JVD, parasternal heave and increased P2
- Pleuritic chest pain with hemoptysis
- Dx with spiral CT (CT angio)
Fat Embolism
- Post trauma, fracture of long bone leads to fat
- Chest pain, neurologic signs and petichiae on chest
Gas embolus
- Diving/decompression sickness
- Caissons disease
DVT Thrombus
See above
Amniotic
- Contains pro-clotting tissue factor and lipid
- Seen during pregnancy and also often with DIC
Obstructive Lung Disease
- Characterized by elevated FRC, and TLC due to air trapping.
- There will be a decresed FEV1 and slightly decreased FVC. The FEV1/FVC ratio will be decreased
- V/Q mismatches are common
Chronic Bronchitis
- Inflammation and irritation cause hyperplasia of the mucous glands and serrous glands to account for more than 50% of the wall diameter
- Pts will have productive cough, dyspnea, wheeze
- Decreased PaO2 and increased PaCO2
- small airway disease
Centriacinar emphysema
-Irritation and inflammation due to smoking leads to increased protease activity from alveolar macrophages. This leads to destruction of the center of the accinus. Respiratory bronchiole etc.
Panacinar Emphysema
- Alpha 1 antitrypsin deficency due to misfolded protein from liver.
- Accumulation in liver leads to PAS positive staining of eosinophilic bodies in the ER of hepatocytes
- Leads to panacinar emphysema as there is little opposition to elastase
- PiM is normal allele and PiZ is abnormal PiZM has increased susceptability to emphysema with smoking, PiZZ has panacinar emphysema
- May cause chirrosis in liver
Emphysema
- Cough without spututum. Wheezes will be present
- There will be hyperlucency of lung fields
- Pink puffers. Pursed lips allow for positive end expiratory pressure leading and keeps airways from collapsing
Asthma
- Type 1 hypersensitivity characterized by TH2 release of IL-4 (switch to IgE) IL-5 (Eosinophils) IL-10 (Suprress TH1 and increase TH2)
- IgE crosslinked on mast cells causes release of histamine causing vasodilation in arterioles and leakage in post capillary venules
- Late phase characterized by eosinophilic infiltrate and MBP release inflammation
- Leukotrienes C-E cause bronchocontriction
- (Leukotriene B4 is chemotactic to neutrophils and not involved in this process)
- Charcot-Leyden crystals (MBP from neutrophils)
- Crushman’s spirals are epithelial cells that are shed.
- Wheezing, dyspnea, pulsus paradoxus, mucous plug.
Bronchiectasis
- Necrotizing infection of the lower airways leading to dilation and obstructive lung disease
- Recurrent infections, hemoptysis, foul smelling sputum
- Irreversible
- S Aureus, Pseudomons, BPA
- Karterenger, CF
Bronchiolitis Obliterans
- Formation of poorly healing scar fibrosis and epihelial debris in small airways of lungs.
- Presents with obstructive pattern with increased FRC and decreased FEV1/FVC.
- Most commonly seen in lung transplants and in GVHD in stem cell transplants
Restrictive Lung Disease
- Decreased FRC and increased FEV1/FVC
- Mechanical: Normal A-a (expiration is passive)
- INterstitial: Elevated A-a (Diffusion Barrier)
Mechanical Restriction
- Motor dysfunction: Myasthenia Gravis, Polio, ALS
- Structural: Scoliosis, Obesity
ARDS
- Many causes
- All classified by endothelial and epithelial damage leading to cytokine release and recruitment of neutrophils and T cells
- Inflammation and exudation leading to hyaline membrane formation, leads to diffusion barrier and increased A-a gradient
- Destruction of type 1 and type 2 pneumocytes leads to decrease in durfactant and widespread atelectasis, may be treated with PEEP
- Loss of type 2 can lead to scarring rather than repair with further problems
- Atlectasis causes shunt leading to increased A-a gradient
- CXR will show diffuse white-out appearance
Neonatal Respiratory Distress
- Decreased Lecethin:Sphingomyelin ratio leads to increase surface tension and diffuse alveolar collapse
- Hypoxemia and cyanosis
- Increased risk in premature (lungs don’t develop until 36 weeks), C-Section (No cortisol release, cortisol stimulates maturation), Diabetic Mothers (insulin is inhibitory to lung maturation)
- Can treat by giving mother steroids intrapartum/prepartum and also giving surfactant to baby
- Tx: PEEP oxygen until lungs mature.
- Long term O2 risks retinopathy of prematurity (blindness by free radicals) and Bronchopulmonary dysplasia (necrotizing bronchitis and fibrosis (mechanical and free radical))
- Low oxygen tension can keep PDA open
Anthracosis
- Coal miners lung
- Diffuse black infiltrate in macrophages causes fibrosis
- Patients may also have RA associated
Silicosis
- Sand blasters and miners
- Generally in upper lobes with fibrosis
- Impairs phagolysosome fusion leading to increased risk of TB infection
Berryliosis
- Aerospace
- Noncasseating granulomas (sarcoidosis look a like) increase risk for carcinoma
Asbestos
- Macrophages consume asbestos and becomes Fe bound ferruginous bodies
- Increased risk for Lung cancer and mesothelioma
- Generally subpleural
Sarcoidosis
- Generally effects young adult/middle aged african american females
- Noncasseating granulomas most commonly effect the lungs, but can effect anywhere
- Asteroid bodies and shumman bodies (Ca inside giant cells)
- Granulomas make ACE and also alpha 1 hydroxylase leading to elevated vitamin D and elevated Ca
- May present anywhere in the body: Erythema multiforme, uveitis, sjoggrens syndrome like
Systemic Sclerosis
-Can also show interstitial fibrosis with restrictive lung pattern
Idiopathic Pulmonary Fibrosis
- Repeated cycles of injury and fibrosis lead to eventual progression to honeycomb lung and often need transplant
- Related to tgf-B and collagen production
Goodpastures
-Collagen 4 type 2 hypersentivity
Wegners
-c-anca
Langerhans Cell Histiocytosis
-Bierbeck granules and many other systemic symptoms
Hypersensitivity Pneumonitis
- Type 3 and type 4 hyperssensitivities related to environmental exposure
- Poorly formed granulomas, can have systemic symptoms
- Occupational exposure, farmers are classic example
- Inflammation and fibrosis progress to restrictive presentation
Drugs
Bleomycin and Buslfan for chemo
- Methotrexate
- Amiodarone
Central Sleep Apnea
-Loss of respiratory drive in the medulla
Obstructive sleep apnea
- Blockage of breathing during night
- Hypoventilation leads to decreased O2 and mildly elevated CO2
- Can cause switch to oxygen mediated respiratory drive
- Present with fatigue and may present with depression like symptoms. Rule out hypothyroid
- Can cause pulmnary hypertension, arrythmias, death
- Also commonly see polycythemia
Spontaneous Pneumothorax
- Rupture of emphysematous bled, generally in hypervetilated upper lobes
- Commonly presents in tall, marfanoid young men
- Hyperresonant with absent breath sounds. Trache deviated towards
Tension Pneumothorax
- Trauma induced sucking chest wound causing increase pressure and tracheal deviatoin opposite of injury.
- Emergenty thoracocentesis is necessary.
Lung Cancer Presentation
- Presents late as a coin lesion on CXR
- Differentiate from histo/TB with biopsy
- Often presents with cachexia or with paraneoplastic syndrome
- Poor prognosis
- Smoking and radon are main risk factors
- May caues wheezing, obstruction, and hemptysis
Lung Cancer metastasizes from
- Most commonly the breast
- Also bladder, prostate, colon
Metastasizes to
- The most common is adrenals causing addisons like syndrome. By far most common met to adrenals
- Bone, brain, liver
Superior Vena Cava syndrome
- Tumor obstruction of the superior vena cava leads to backup into face and upper extremeties
- Facial edema, headache, arm pain
- Emergency because can raise intracranial pressure and increase risk of anyeurism
Pancoast Tumor
Tumor in the upper lobe of the lung that can compress local structures
- Horners syndrome
- Laryngeal nerve compression leading to hoarsness
- Brachiocephalic, phrenic, subclavian compresion
Horners Syndrome
- Compression of the sympathetic chain and superior ganglia leading to: Anhidrosis, miosis, ptosis
- Compression of second order neuron
- Primary from hypothalamus (post) to IML
- Secondary (presynaptic) exit chord and run to ganglion
- Third from ganglion along carotid to long cilliary nerves
Effusions
Possible pericardial or pleural effusions
Adenocarcinoma
- Most common subtype worldwide
- Arises in women and in nonsmoker
- Peripheral location
- k-ras or EGFR (non-smoker, may be treated with her2-neu) mutation
- Relatively good prognosis
- Not associated with any paraneoplastic
- Clubbing possible
Bronchoalveolar carcinoma
- Tumor of cuboidal cells that runs along the inerstitum of alveoli and bronchus
- May appear like an interstitial pneumonia on CXR
- Relatively good prognosis
Squamous Cell Carcinoma
- Most common in male smokers
- Centrally located lesion arising from squamous cells of bronchus (Metaplasia due to irritation)
- Poor prognosis but resection is attemptable
- Keratin perals and intercellular (desmosome) bridges
- Associated with PTHrP and often causes hypercalcemia
- May also cause local mass effect problems leading to respiratory compromise, atelectasis and infection in involved bronchus
Small Cell Carcinoma
- Centerally located and most common in male smokers
- Neuroendocrine origin with chromogranin and synaptophysin stain
- Aggressive with early metastasis, no surgery possible
- SIADH
- ACTH leading to cushings
- Lambert Eaton
- Myc oncogene often involved
Large Cell Carcinoma
- Poorly differentiated anaplastic pleiomorphic giant cells
- Located in periphery (Diff from adenocarcinoma)
- Poor prognosis
- Surgical resection may be attempted.
Bronchial Carcinoid Tumor
- Tumor of well differentiated neuroendocrine cells (synatophysin and chromogranin)
- Located in bronchus and has good prognosis, rarely metastaszes and can be resected
- May rarely cause carcinoid syndrome
- Mass effect with respiratory obstruction is common
Mesothelioma
- Rare tumor of pleural fluid producing mesothelial cells
- Associated with asbestos (although lung cancer more common)
- Malignant with poor prognosis, grows around encasing lungs leading to respiratory compromise
- Often is calcified and may have psammoma bodies
- Hemorrhagic effusions.
Lobar Pneumonia
- CXR shows lobar involvment
- Massive exudate into alveolar lumen
- Most common is strep Pneumo then klebsiella (Aspiration of GI, not gastric contents)
- Congestion: Bacterial infiltration, edema, hyperemia
- Red hepatization: Transudate RBC, neutrophils show up and fibrin deposits
- Grey Hepatization: Degredation of fibrin and RBC
- Recovery: Type 2 pneumocytes proliferate and debris removed, coughing
Bronchopneumonia
- CXR shows patchy infiltrate often involving multiple areas
- Bacterial and neutrophil exudate into bronchioles and nearby alveoli
- S Aureus
- S Pneumo
- H Flu (following influenza)
- Klebsiella
Interstitial (atypical) Pneumonia
- Inflamation of interstitium with relative sparing of exudate into alveolar spaces
- Generally leads to a more indolent course and CXR will show large areas of opacification without focal opacities
- Viral (RSV in Kids, Flu in elderly, adenovirus in recruits)
- Mycoplasma is most common, no gram stain and IgM cold agglutinins
- Chlamydia is second most common and can infect infants born to infected mothers
- Legionella: Intracellular silver stain, water resivoir, fever and GI often accompany, SIADH
- CMV high risk in post transplant and AIDS
- Coxiella: Q fever, ricketsia that forms a spore, inhaled by vets/farmers. High spiking fevers
- Candida
Lung Abcess
- Collection of pus and necrotic debris in lung parenchyma
- Generally occurs secondary to blockage of bronchus/bronchile
- Cancer SCC may be a cause, but more likely to be infectous
- S Aureus is most common
- Can be oropharyngeal anaerobes (peptococcus, fusobacterium, bacteroides)
- Klebsiella also possible
- Pseudomonas, candida also possible
Empyema
- Collection of pus in the pleural space
- Usually secondary to pneumonia
- Must drain or else could harden and permanently damage lung parenchyma
Transudate
- Low protein count
- CHF, nephrotic syndrome, cirrhosis
Exudate
- High protein count
- Malignany, infection, trauma
- Can be a nidus for infection and should be drained
Chylothorax
- Disruption of the thoracic duct
- Secondary to trauma or lymphoma.
