Pulmonary Flashcards
Metaplasia in smokers
Respiratory epithelium is replaced by stratified squamous epithelium
Loss of mucociliary elevator –> smoker’s cough
Where does pain from diaphragm irritation get referred?
To the shoulder (C5) or to the trapezius ridge (C3, C4)
C3, 4, 5 keeps the diaphragm alive (phrenic nerve)
Clara cells/Club cells
Non ciliated cells with secretory granules that are needed for detoxification of noxious gases, surfactant production, and act as bronchiolar stem cells
Type 1 vs Type 2 pneumocytes
Type 1: simple squamous cells of the alveoli (thin for optimal gas exchange)
Type 2: cuboidal cells that produce surfactant. Also act as precursors to type 1 pneumocytes
What increases surfactant production
Glucocorticoids
Thyroid hormone
Where is cross sectional area highest in the lung and what is the velocity of air here?
Cross sectional area increases from trachea to the respiratory zone. Inc area = dec velocity
Velocity = Flow/Cross sectional area
Under normal conditions, is gas transfer in the lungs perfusion limited or diffusion limited?
Perfusion limited: inc cardiac output causes increased perfusion and increased uptake of O2
What conditions cause O2 to become diffusion limited?
Thickened alveolar capillary membrane (ex. fibrosis)
Dec SA for diffusion (ex. emphysema)
High altitude
Increased pulmonary blood flow (blood moves rapidly through the lung and cannot be completely saturated)
What is the effect of dec PAO2 on pulmonary vessels?
Causes hypoxic vasoconstriction to shift blood away from poorly ventilated regions of the lungs to well-ventilated regions
\What diffuses faster, O2 or CO2?
Equilibrate in about the same amount of time .25 secs (O2 has a higher driving pressure but CO2 is more soluble)
What causes a right shift in the oxygen-hemoglobin association curve?
Occurs when affinity of Hb for O2 is decreased and this facilitates unloading of O2 to tissue
**Inc PCO2, H+, temperature, and 2,3-DPG
What causes a left shift in the oxygen-hemoglobin association curve?
Occurs when affinity of Hb for O2 is increased
**Dec PCO2, H+, temp, 2,3 DPG
Does fetal Hb have a left or a right shift?
Left shift because it has greater affinity for O2 (because it has a lower affinity for 2,3 DPG than adults)
Ensures that oxygen can be delivered from mom to fetus
patients present with cyanosis and chocolate colored blood
Methemoglobinemia: oxidized form of Hb (Ferric, Fe3+) cannot bind O2 as well and is treated with methylene blue
Effects of CO poisoning
o Reduced oxygen delivery: CO binds to hemoglobin and decreases the O2 content of the blood
o Binding of CO to hemoglobin increases the affinity of remaining sites for O2 – causing a left shift and decreased O2 delivery to the tissues (because it remains bound to hemoglobin)
CXR shows trachea moving away from side of penumothorax
Tension pneumothorax
due to penetrating chest wall injury → trachea pushes to opposite side due to compression from air accumulation in the pleura, treat with insertion of chest tube to release air
What accounts for the rubber like properties of elastin?
Interchain cross-links involving lysine
Why is the phospholipid content of amniotic fluid checked?
To determine fetal lung maturity and screen for likelihood of neonatal RDS
Lecithin to sphingomyelin ratio (>2 = mature)
Lecithin = phosphatidylcholine
A-a difference in diffusion limitation
Increased
A-a difference in hypoventilation
Normal
ex. opioid use, muscular dystrophy
A-a difference in V/Q mismatch
Increased
When some regions of the lung are hypoventilated
A-a difference in shunt
Increased
Some areas of the lung receive no ventilation
Lung compliance: when is it highest and when is it lowest?
Highest at FRC: lung isnt inflated
Lowest at TLC: lung is stretched as far as it can go
Laplace’s equation
PRessure in the alveolus due to surface tension is inversely related to radius (smaller alveoli have higher pressire- more susceptible to collapse)
Surfactant role
Decreases surface tension when the radius decreases
Increases surface tension when the radius increases
**Prevents the collapse of small alveoli
Compliance and regions of the lungs
Apex: low compliance because the alveoli are stretched
Base: high compliance
Elastase is found in which cells?
Alveolar macrophages and neutrophils
Excess activity of elastase is a major contributor to emphysema
Swanz Ganz catheter measures?
Closely reflects left atrial and left ventricular end diastolic pressures
Dorsiflexion of foot causing calf pain
Homan sign
Indicates DVT
What should you suspect in a child with nasal polyps?
Cystic fibrosis
Patient has a decreased FEV1/FVC ratio
Characteristic of obstructive lung disease
Very decreased FEV1, decreased FVC
Inc TLC (due to air trapping in the lung)
Decreased diffusing capacity for CO (DLCO)
Pathogenesis of Emphysema
Obstructive lung disease
Caused by an imbalance of proteases and antiproteases: alveolar macrophages produce proteases in response to inflammation. Antiproteases (like a1-antitrypsin) keeps these proteases in check to prevent damage
Unbalanced regulation leads to destruction of the alveoli
Centriacinar emphysema
Caused by smoking (upper lobe damage)
Inc proteases relative to antiproteases
Panacinar emphysema
Due to a1-antitrypsin deficiency that prevents regulation of proteases (lower lobe damage)
Associated with liver damage (A1AT accumulates in the ER of hepatocytes)
Sputum has spiral shaped mucus plugs and crystals
Asthma
Charcot-Leyden crystals = aggregates of eosinophil major basic protein
Curshmann spirals = shed epithelium
Kartagener syndrome
Inherited defect of dynein arm, which is necessary for ciliary movement
Clinical triad: situs inversus, chronic sinusitis, and bronchiectasis
Are also usually infertile due to immotil sperm or impaired cilia of the fallopian tube
Restrictive lung diseases include:
Idiopathic pulmonary fibrosis
Pneumoconiosis
Sarcoidosis
Hypersensitivity pneumonitis
What drugs can cause pulmonary fibrosis?
Bleomycin Busulfan Amiodarone Methotrexate Radiation
Anthracosis
Black dust accumulation in the lung
Caplan syndrome
Coal workers pneumoconiosis associated with rheumatoid arthritis
How does silica cause pneumoconiosis?
Silica is engulfed by macrophages and impairs phagolysosome formation
What pneumoconiosis inc the risk of TB?
Silicosis
Sarcoidosis appears identical to what pneumoconiosis?
Berylliosis
Cause non-caseating granulomas in multiple organs (lung, hilar lymph nodes, and systemic organs)
What pneumoconiosis (or multiple) inc risk of lung cancer?
Asbestosis and Berylliosis
“A + B = C”
Honeycombed or cobblestones pleura indicates
Idiopathic Pulmonary Fibrosis
Carboxyhemoglobin
Carbon monoxide bound to hemoglobin (increased in carbon monoxide poisoning)
Defective transmembrane protein in cystic fibrosis? What is it gated by?
- CFTR (ATP gated)
Increases Cl- secretion in the lungs and GI, and inc reabsorption of Cl- in sweat glands
- common defect is impaired post translational processing of CFTR which makes it degraded and can’t reach the cell surface
Varenicline
a partial agonist of nicotinic acetylcholine receptors. Used for smoking cessation by reducing withdrawal cravings and attenuating the rewarding effects of nicotine
Causes of decreased lung compliance
- Fibrosis
- Dec surfactant
- Fluid in pulmonary interstitium
Patient with femur fracture develops neuro abnormalities, hypoxia, and a petechial rash all over his body. What is the cause of this presentation?
Fat embolism- fat globules from the bone marrow travel and lodge into the pulmonary microvessels
Drug used for asthma challenge
Methacholine- muscarinic agonist (parasympathetic effects) that is used as a challenge test for diagnosis of asthma (stimulates bronchoconstriction)
Sweat in a person with cystic fibrosis
High Cl-
High Na+
What is normal in ARDS?
Pulmonary capillary edge pressure = normal
Abnormalities: diffuse alveolar damage causes inc capillary permeability Dec lung compliance Inc work of breathing V/Q mismatch
- will see hyalinization of alveolar membrane
Goodpasture syndrome
the production of autoantibodies directed against the basement membrane of glomeruli and lung alveoli, causing hemoptysis and hematuria
(type II hypersensitivity)
Relationship between radius and resistance in airways
Inverse fourth power relationship between resistance and radius
ex. If airway decreases by a factor of 4, then resistance will increased by 4^4 (256)
DL (lung diffusing capacity)
= permeability
Inc DL during exercise because there are more open capillaries and thus more SA for diffusion
Dec DL in emphysema (bc of dec SA due to alveolar destruction) and in fibrosis/pulmonary edema (bc of inc diffusion distance)
What is the major form of CO2 in the blood?
HCO3-
HCO3- leaves the RBCs in exchange for Cl- (chloride shift) and is transported to the lungs in the plasma for eventual expiration by the lungs
Where is the greatest airway resistance?
In medium sized bronchi
The smallest airways do not have the highest resistance because of their parallel arrangement
African American presents with dry cough,bilateral hilar adeniopathy, and elevate serum Ca2+ and ACE levels
Sarcoidosis
Noncaseating granulomas produce ACE and active vitamin D (which causes inc Ca levels). Broncholavage will show elevated CD4+ count
Most common primary lung cancer:
Adenocarcinoma
most common lung cancer overall is metastases
Which lung cancer is associated with hypercalcemia?
Squamous Cell carcinoma: produces PTHrP
Can cause osteolytic bone lesions
Which lung cancer is associated with Lambert Eaton syndrome
Small Cell Carcinoma: production of antibodies against the presynaptic Ca2+ channels
Which lung cancer is associated with SIADH
Small Cell Carcinoma: Produces SIADH
Which lung cancer is associated with Cushing syndrome
Small Cell Carcinoma: produces ACTH
Which lung cancer presents as a cavitary lesion?
Squamous Cell Carcinoma
Kulchitsky cells seen in histo of a patient with suspected lung cancer
Small cell carcinoma: small dark blue cells
Which lung cancers are centrally located?
Small cell
Squamous cell
“Sentrally located”
What is the natural tendency of the lungs? Of the chest?
o Lungs = collapse
o Chest = expand
This is what occurs in a pneumothorax! Air is introduced into the intraplueral space and the intrapleural pressure becomes equal to atmospheric pressure – lack of negative pressure causes lungs to collapse and chest to spring outward
What happens in the absence of surfactant?
Small alveoli collapse – atelectasis
Surfactant effects on compliance
Increases compliance (due to dec pressure)
C = V/P
Compliance in emphysema – is expiration or inspiration impaired?
Increased compliance – causes impaired expiration because there is less tendency for the lungs to collapse
Air becomes trapped in the lungs –causes inc functional residual capacity and leads to inc in chest AP diameter
Compliance in fibrosis – is expiration or inspiration impaired?
Decreased compliance – causes impaired inspiration because there is a greater tendency for the lungs to collapse (harder to inflate)
Lung diffusing capacity in emphysema
Decreases (due to dec surface area)
Lung diffusing capacity in exercise
Increases (more open capillaries = inc SA)
Lung diffusing capacity in pulmonary edema
Decreases (due to inc diffusion distances)
Lung diffusing capacity in fibrosis
Decreases (due to inc diffusion distances)
Adapting to high altitude
increased production of 2,3 DPG, which causes a right shift – oxygen is unloaded to the tissues
Central chemoreceptors are sensitive to what?
pH of the CSF
CO2 in the CSF combines with H2O to produce H2CO3, which then dissociates into H+ and HCO3-
The H+ is sensed by the central chemoreceptors
Response to dec pH in the CSF? Inc pH?
Dec pH means that there is an excess of CO2 –> stimulates hyperventilation
Inc pH means there is a lack of CO2 –> stimulates hypoventilation
Formation of hyaline membranes surrounding alveoli seen on histo
Acute Respiratory distress syndrome
Patient has an CXR performed that shows calcified lesions and pleural plaques. There is some evidence of pleural effusion. What was he likely exposed to?
Asbestos
Patient can be asymptomatic for 20 years
Patient with a hx of smoking and dyspnea dies and on autopsy the bronchi show thickened bronchial walls, inflammatory infiltrate, hyperplasia of mucus secreting glands in the bronchi, and patchy squamous metaplasia
Chronic bronchitis
What causes hypoxemia with a normal A-a gradient?
Hypoventilation (usually due to obesity hypoventilation syndrome, neuromuscular disorders or opioid use)
Stimulation of what nerve can relieve OSA symptoms?
Hypoglossal nerve – moves the tongue slightly forward and opens up the back of the airway
What type of nighttime breathing do you see in patients with CHF?
Cheyne Stokes – apnea is followed by gradually increasing then decreasing tidal volumes until the next apneic period
Episodes of apnea cause hypercapnia, and then the body compensates by hyperventilating, which overshoots and causes hypocapnia → leads to another apneic episode to inc CO2 levels
*Also seen in neurologic disease (stroke, brain tumors, TBI) and is a poor prognostic sign
Normal A-a gradient
Between 5 and 15
What induces recruitment of eosinophils in an allergic reaction
IL 5 release by TH2 cells
CO Poisoning
PaO2:
SaO2:
O2 content:
PaO2: normal
SaO2: decreased
O2 content: decreased
What lung cancer stains for chromogranin A?
Small cell carcinoma or chbronchial carcinoid tumor
What lung cancer stains for neuron specific enolase?
Small cell carcinoma
Cyanide poisoning:
PaO2:
SaO2:
O2 content:
PaO2: normal
SaO2: normal
O2 content: normal
cyaNide = Normal
Anemia
PaO2:
SaO2:
O2 content:
PaO2: normal
SaO2: normal
O2 content: decreased
Polycythemia
PaO2:
SaO2:
O2 content:
PaO2: normal
SaO2: normal
O2 content: increased
High altitude
PaO2:
SaO2:
O2 content:
PaO2: decreased
SaO2: decreased
O2 content: decreased
“High altitude is decreased”
What causes green sputum?
Myeloperoxidase from neutrophils
What does egophany and inc fremitus indicate?
An area of lung consolidation – lobar pneumonia or pulmonary edema
Tracheal deviation towards side of lesion vs tracheal deviation away from side of lesion
Towards = atelectasis (bronchial obstruction)
Away = tension pneumothorax (turn away from a tense situation)
Patient was exposed to a toxic chemical at work and presents with reddish skin discoloration, tachypnea, headache, and tachycardia with N/V, confusion and weakness. What was he exposed to and what is the treatment?
Cyanide poisoning
Treat with amyl nitrite-
oxidizes ferrous iron (Fe2+) to ferric iron (Fe3+) generating methemoglobin – methemoglobin cannot carry O2 can it has a high affinity for cyanide – it binds and sequesters cyanide in the blood, freeing it from cytochrome oxidase and limiting its toxic effects
Can also use hydroxycobalamin (B12 precursor) which generates nontoxic metabolites that are easily excreted in the urine
Where is pulmonary vascular resistance lowest?
At Functional Residual capacity (FRC = RV + ERV)
What lung cancer is associated with paraneoplastic cerebellar degeneration?
Small Cell Carcinoma
due to an immune response against tumor cells that cross-reacts with Purkinje neuron antigens, leading to acute onset rapid degeneration of the cerebellum
• Anti-Yo, anti-P/Q, and anti-Hu antibodies are detectable in serum
Also seen in ovarian, breast, and uterine malignancies
Where should a thoracocentesis be performed? Why?
Just above the upper border of the rib to prevent injury to the intercostal vein, artery, and nerve (lie in the subcostal groove on the lower border of the rib)
Haldane effect
in the lungs, oxygenation of Hb promotes dissociation of H+ from Hb.
This shifts equilibrium toward CO2 formation and CO2 and H+ are released
