pulmonary 1 Flashcards
How many periods does it take to develop the lung?
5
What are the periods of lung development?
1) Embryonic (weeks 4-7)
2) Pseudoglandular (weeks 5-16)
3) Canalicular (weeks 16-26)
4) Saccular (weeks 26-birth)
5) Alveolar (weeks birth-8 years)
Describe the embryonic stage of lung development.
Lung bud-> trachea-> mainstem bronchi-> secondary (lobar) bronchi-> tertiary (segmental) bronchi
Errors at this stage can lead to TE fistula.
Describe the Pseudoglandular stage of lung development.
Endodermal tubules-> terminal bronchioles. Surrounded by modest capillary network.
Respiration impossible, incompatible with life.
Describe the Canalicular stage of lung development.
Terminal bronchioles-> respiratory bronchioles-> alveolar ducts. Surrounded by prominent capillary network.
Describe the Saccular stage of lung development.
Alveolar ducts-> terminal sacs. Terminal sacs separated by primary septae. Pneumocytes develop.
Describe the Alveolar stage of lung development.
Terminal sacs-> adult alveoli (d/t secondary septation). In utero, “breathing” occurs via aspiration and expulsion of amniotic fluid-> increase in vascular resistance through gestation. At birth, fluid gets replaced w/ air-> decrease in pulmonary vascular resistance.
At birth: 20-70 million alveoli
By 8 years: 300-400 million alveoli.
What are the 2 congenital lung malformations?
1) Pulmonary hypoplasia= poorly developed bronchial tree w/ abnormal histology usually involving the right lung. Associated w/ congenital diaphragmatic hernia, bilateral renal agenesis (Potter Syndrome).
2) Bronchogenic cysts= Caused by abnormal budding of foregut & dilation of terminal or large bronchi. Discrete, round, sharply defined & air-filled densities on CXR. Drain poorly & cause chronic infections.
What are Type I pneumocytes?
Thin squamous cells present in the alveoli, functioning in optimal gas diffusion.
Where are Type I pneumocytes found?
97% of alveolar surfaces. (line the alveoli)
What is the role & epithelium of Type I pneumocytes?
Squamous. Thin for optimal gas diffusion.
How is collapsing pressure calculated?
P = (2 x surface tension) / radius.
What is the function of Type II pneumocytes?
Secrete pulmonary surfactant –> decrease alveolar surface tension; prevent alveolar collapse, decrease lung recoil & increase compliance.
What type of cells, histologically, are Type II pneumocytes?
Cuboidal.
Do Type II cells originate from Type I cells, or are Type II cells progenitors for Type I cells?
Type II cells are progenitors for Type I cells. Type II cells can also give rise to other Type II cells.
When do Type II cells proliferate?
In lung damage.
What is the Law of Laplace?
As the radius decreases upon expiration, alveoli have an increased tendency to collapse.
What does ‘atelectasis’ mean, and how is it caused?
DEFINITION collapse of alveoli.
CAUSES obstruction, compression, or contraction –> damage to Type II pneumocytes –> loss of surfactant.
Even reinflation may not return full function due to the loss of surfactant.
What is surfactant, chemically?
A complex mix of lecithins, most importantly dipalmitoylphosphatidylcholine.
What are Clara (Club) cells?
Nonciliated, columnar cells with secretory granules.
What do Clara cells secrete?
A “watery” component of surfactant.
What are the functions of Clara cells?
To secrete a component of surfactant, to degrade toxins, and to act as reserve cells.
When does surfactant synthesis begin?
Around week 26 of gestation.
When are mature levels of surfactant reached?
Around week 35 of gestation.
If a child is born premature, is it likely that they will produce sufficient levels of surfactant?
No.
At risk of developing atelectasis.
What measurement indicates if a fetus has mature lung function?
Lecithin : sphingomyelin above 2. This can be measured in the amniotic fluid.
What is the cause of neonatal respiratory distress syndrome?
Inadequate surfactant –> increased surface tension –> alveolar sac collapse after expiration –> formation of hyaline membranes.
What lecithin:sphingomyelin ratio in amniotic fluid is predictive of neonatal RDS?
Ratio <1.5.
With what is neonatal RDS associated?
Prematurity: adequate surfactant levels are not reached until week 35.
C-section: d/t lack of release of stress-induced steroids (fetal glucocorticoids) –> no increased synthesis of surfactant.
Maternal diabetes: increased fetal glucose-> increased fetal insulin-> decreased surfactant levels.
What are the clinical features of neonatal RDS?
Increasing respiratory effort after birth, tachypnea with use of accessory muscles, grunting, hypoxemia with cyanosis, CXR showing “ground-glass” appearance of lung.
What are the complications of neonatal RDS?
(1) Persistently low O2 tension –> hypoxemia –> increased risk of PDA, necrotizing enterocolitis.
(2) Therapeutic supplemental oxygen–> increased risk of free radical injury (O2 can be toxic!) –> “RIB”.
R= Retinopathy of prematurity
I= Intraventricular hemorrhage
B= Bronchopulmonary dysplasia.
What is the treatment for neonatal RDS?
Maternal steroids before birth; artificial surfactant for infant.
What is the order of structures in the Respiratory tree?
Trachea-> bronchi-> bronchioles-> terminal bronchioles-> respiratory bronchioles-> alveolar sacs.
What does smoking do to the epithelial lining of the trachea?
Pseudo stratified ciliated columnar-> squamous (via metaplasia & now sputum cannot be cleared).
Where is the highest & lowest resistance in the Respiratory Tree?
Highest= medium-size bronchi (turbulent airflow).
Lowest= terminal bronchioles (high CSA).
What is the conducting zone?
The larger airways that warm, humidify, and filter air without participating in gas exchange (i.e. anatomic dead space).
What are the large airways of the conducting zone?
Nose, pharynx, trachea, bronchi.
What are the small airways of the conducting zone?
Bronchioles and terminal bronchioles (large #’s in parallel-> least airway resistance).
To what level of the conducting zone will cartilage and goblet cells extend?
Bronchi.
To what level of the conducting zone will pseudostratified ciliated columnar cells extend?
Terminal bronchioles.
Clear mucus & debris from lungs (mucociliary escalator).
To what level of the conducting zone will smooth muscle cells extend?
Terminal bronchioles.
What is the respiratory zone?
The airways participating in gas exchange.
What are the airways of the respiratory zone?
Lung parenchyma; respiratory bronchioles, alveolar ducts, alveoli.
What is the histology of the respiratory bronchioles?
Cuboidal cells.
What is the histology of the alveoli?
Simple squamous cells.
You see simple squamous cells on a histology slide. From what level of the respiratory system is the slide?
Alveoli or alveolar ducts.
You see pseudostratified ciliated columnar cells on a histology slide. From what level of the respiratory system is the slide?
Terminal bronchioles or above.
You see cartilage on a histology slide. From what level of the respiratory system is the slide?
Bronchi or above.
You see goblet cells on a histology slide. From what level of the respiratory system is the slide?
Bronchi or above.
You see cuboidal cells on a histology slide. From what level of the respiratory system is the slide?
Respiratory bronchioles.
Are cilia present in the respiratory zone?
No.
Where in the respiratory system may macrophages be found?
Alveoli-> clear debris & participate in the immune response.
Which lung has three lobes?
Right lung.
Which lung has two lobes?
Left lung; in place of the middle lobe, the lung accommodates the space necessary for the heart.
Left Lung has Less Lobes.
Which lung has a lingula?
Left lung.
Lingula is a tongue shaped portion of the left lung.
Which lung is the more common site for inhaled foreign bodies and why?
Right lung; right main stem bronchus is wider and more vertical.
“Swallow a bite, goes down the right.”
The relation of the pulmonary artery to the bronchus at each lung hilum is described by?
RALS: Right Anterior; Left Superior.
If a patient aspirates a peanut while upright, where in the lungs will it be found?
Inferior (AKA basilar) portion of the right inferior lobe.
If a patient aspirates a peanut while supine, where in the lungs will it be found?
Superior portion of the right inferior lobe OR posterior portion of the right upper lobe.
What structures perforate the diaphragm at T8, T10, and T12, respectively?
T8= IVC
T10= esophagus, vagus nerve (CN 10)
T12= aortic (red), thoracic duct (white), azygous vein (blue).
“I 8 10 Eggs At 12.”
What is the innervation of the diaphragm?
C3, C4, C5 (phrenic nerve).
–C3, 4, and 5 keep the diaphragm alive–
Where might pain from the diaphragm be referred?
Shoulder (C5), trapezius ridge (C3, C4).
Name the bifurcations for the common carotid, trachea & abdominal aorta.
C4= common carotid
T4= trachea
L4= abdominal aorta.
“biFOURcates.”
In quiet breathing, what muscle is responsible for inspiration?
Diaphragm.
In quiet breathing, what muscle is responsible for expiration?
None (passive process).
In exercise, what muscles are responsible for inspiration?
External intercostals, scalenes, sternocleidomastoid.
–inSpiration: external, Scalene, Scm–
In exercise, what muscles are responsible for expiration?
Rectus abdominus, internal obliques, external obliques, transversus abdominis, internal intercostals.
What is the IRV?
Inspiratory Reserve Volume: the air that can still be breathed in after normal inspiration.
What is the TV?
Tidal Volume: air that moves into lung with each quiet inspiration.
What is the normal TV?
500.
What is ERV?
Expiratory Reserve Volume: air that can still be breathed out after normal expiration.
What is RV?
Residual Volume: the air in lung after maximal expiration.
Which lung volume measurement cannot be read by spirometry?
RV (residual volume).
How is IC calculated?
Inspiratory Capacity = IRV + TV.
How is FRC calculated?
Functional Residual Capacity = RV + ERV.
Volume of gas in lungs after normal expiration; cannot be measured on spirometry.
How is VC calculated?
Vital Capacity = IRV + TV + ERV.
Maximum volume of gas that can be expired after a maximal inspiration.
How is TLC calculated?
Total Lung Capacity = IRV + TV + ERV + RV.
Volume of gas present in the lungs after a maximal inspiration; cannot be measured on spirometry.
What is physiologic dead space?
Anatomic dead space of conducting airways plus alveolar dead space (capable of gas exchange but no exchange occurs) in alveoli; volume of inspired air that does NOT take place in gas exchange.
How is physiologic dead space calculated?
Vd = Vt x [(PaCO2 - PeCO2) / PaCO2].
“Taco, PAco, PEco, PAco.”
What is the largest contributor of alveolar dead space?
Apex of the lung d/t not enough blood flow.
When is the physiologic dead space = anatomic dead space?
Normal lungs.
When is the physiological dead space greater than the anatomic dead space?
Lung diseases w/ V/Q defects.
What is pathologic dead space?
When part of the respiratory zone becomes unable to perform in gas exchange. Ventilation but no perfusion.
Equation for Minute Ventilation
Total volume of gas entering lungs per minute.
*Ve= VtRR.
Equation for Alveolar Ventilation
Volume of gas per unit of time that reaches alveoli.
*Va= (Vt-Vd)RR.
What are the normal values for RR, Vd & Vt?
RR= 12-20 breaths/min
Vd= 150 mL/breath
Vt= 500 mL/breath.
There is a tendency for the lungs to _____ _____ and chest wall to ____ ______.
Collapse inward; spring outward.
At FRC, what is the system pressure?
Atmospheric; the inward pull of the lung is balanced by the outward pull of the chest wall.
What determines the combined volume of the chest wall and lungs?
Their elastic properties.
At FRC, what is the airway pressure?
0.
At FRC, what is the alveolar pressure?
0.
At FRC, what is the intrapleural pressure?
Negative (This prevents pneumothorax). PVR is at a minimum.
What is compliance?
The change in lung volume for a given change in pressure.
[C= V/P].
**Higher compliance= lung easier to fill.
**Lower compliance= lung hard to fill.
In what processes does compliance decrease?
Pulmonary fibrosis, pneumonia, pulmonary edema.
**FRC decreases b/c the lungs are now exerting more inward collapsing pressure.
What are the causes of pulmonary edema?
HEMODYNAMIC: increased vascular pressure, decreased oncotic pressure.
MICROVASCULAR DAMAGE: infection, ARDS, DIC, UNCLEAR: neurogenic, high altitude.
In what processes does compliance increase?
Emphysema, normal aging.
**FRC increases because the lungs don’t do a good job of resisting the outward pull of the chest wall.
Does surfactant increase or decrease compliance?
Increase.
What happens to intra-thoracic volume when the lung collapses?
Increases d/t unopposed chest expansion.
Discuss PVR for extra alveolar vessels & alveolar vessels at RV & TLC.EDIT?UNCLEAR
RV= extra alveolar vessels have highest PVR.
TLC= alveolar vessels have highest PVR.
What are the subunits of hemoglobin?
4 polypeptide subunits: 2 alpha, 2 beta.
Which form of hemoglobin has a low affinity for oxygen?
T (taut; deoxygenated)-> promotes release/unloading of O2.
–Taut in Tissues–
Which form of hemoglobin has a high affinity for oxygen?
R (relaxed; oxygenated).
–Relaxed in Respiratory–
Hemoglobin exhibits ____ cooperativity and negative _____.
Positive cooperativity; negative allosterity.
What are the subunits of fetal hemoglobin (HbF)?
2 alpha, 2 gamma.
HbF has a lower affinity for _____ than adult hemoglobin, allowing it a _____ affinity for O2.EDIT?/unclear
Lower.
What promotes the release/unloading of O2?
T (taut; deoxygenated)
Taut in Tissues
Which form of hemoglobin has a high affinity for oxygen?
R (relaxed; oxygenated)
Relaxed in Respiratory
What type of cooperativity does hemoglobin exhibit?
Positive cooperativity
What type of allosterity does hemoglobin exhibit?
Negative allosterity
What are the subunits of fetal hemoglobin (HbF)?
2 alpha, 2 gamma
What is the affinity of HbF for 2,3-BPG compared to adult hemoglobin?
HbF has a lower affinity for 2,3-BPG, allowing it a higher affinity for O2
This drives diffusion of O2 across the placenta from mother to fetus.
Which binds oxygen better: adult or fetal hemoglobin?
Fetal hemoglobin
What factors favor the taut form over the relaxed form of hemoglobin?
Cl-, H+, CO2, 2,3-BPG & increased temperature
What does the taut form of hemoglobin favor?
Unloading of oxygen into tissues
How does the dissociation curve shift with the taut form?
Shifts to the right
Why do HbS molecules sickle in sickle cell anemia?
HbS allows hydrophobic interaction among hemoglobin molecules, leading to polymerization of HbS and sickling in hypoxia
What effect do modifications to hemoglobin have on O2 saturation and content?
Decreased O2 saturation and content, leading to tissue hypoxia
What is methemoglobin?
An oxidized form of hemoglobin (Fe2+ –> Fe3+) that does not bind O2 as readily
What is a ferric ion?
Fe3+
How is iron in hemoglobin normally found?
Fe2+ (ferrous; reduced state)
Fe2+ binds O2
What does methemoglobin have an increased affinity for?
Cyanide
How does Methemoglobinemia present?
Cyanosis & chocolate-colored blood
What effect do nitrates have on iron?
They oxidize Fe2+ to Fe3+
Note: There will be normal readings of PaO2, but decreased levels of Hb O2 saturation.
What is the use of nitrates followed by thiosulfate?
Induced methemoglobinemia for treatment of cyanide poisoning
How do you treat methemoglobinemia?
Methylene blue & Vitamin C
METHemoglobin needs METHylene blue.
What is carboxyhemoglobin?
Form of hemoglobin bound to CO in place of O2
What is the affinity of CO for hemoglobin compared to O2?
200X that of O2
How does the oxygen-hemoglobin curve shift in carboxyhemoglobinemia?
Causes a decrease in O2-binding capacity with a left shift
This decreases O2 unloading in tissues.
How are PaO2, percent saturation, and O2 content changed in carboxyhemoglobinemia?
PaO2: normal, percent saturation: decreased, O2 content: decreased
What shape does the oxygen-hemoglobin dissociation curve have?
Sigmoidal due to positive cooperativity
A tetrameric hemoglobin molecule can bind 4 oxygen molecules and has a higher affinity for each subsequent oxygen molecule bound.
What shape does the oxygen-myoglobin dissociation curve have? Add picture
Hyperbolic due to monomeric nature that does not show positive cooperativity
What does a right shift of the oxygen-hemoglobin dissociation curve denote?
Decreased affinity of hemoglobin for O2, indicating unloading of O2 to tissue
What causes a right shift of the oxygen-hemoglobin dissociation curve?
Acid (H+), CO2 (hypoxemia), CHF, chronic lung disease, exercise, BPG (2,3-BPG), temperature
What happens when there is a left shift physiologically?
Decreased O2 unloading leads to renal hypoxia, increased EPO synthesis, and compensatory erythrocytosis
Which direction is the HbF curve shifted and why?
Left: fetal hemoglobin has a greater affinity for O2
Describe the Hb concentration, O2 saturation of Hb, Dissolved O2 (PaO2) & total O2 content for CO poisoning.(why total 02 content- EDIT/UNCLEAR)
Normal Hb concentration, decreased Hb saturation, normal PaO2, decreased total O2 content
Describe the Hb concentration, O2 saturation of Hb, Dissolved O2 (PaO2) & total O2 content for anemia.
Decreased Hb concentration, normal Hb saturation, normal PaO2, decreased total O2 content
Describe the Hb concentration, O2 saturation of Hb, Dissolved O2 (PaO2) & total O2 content for polycythemia.
Increased Hb concentration, decreased Hb saturation, normal PaO2, increased total O2 content
What happens when there is a decrease in Hb to O2 content, O2 saturation & PaO2?
Decrease in O2 content of the blood, but no change in O2 saturation & PaO2
Does a decrease in PAO2 cause vasoconstriction or vasodilation?
Hypoxic vasoconstriction; blood moves away from poorly ventilated regions of the lung to well-ventilated regions
How can diffusion across perfusion limited lung membranes increase?
If blood flow increases
What is the equation for diffusion?
Vgas = A x Dk x (P1-P2)/T
How does the diffusion equation change in emphysema?
Area decreases
How does the diffusion equation change in pulmonary fibrosis?
Thickness increases
In normal, healthy lungs, is the circulation perfusion or diffusion limited?
Perfusion limited
In perfusion limited circulation, when does gas equilibrate?
Early along the length of the capillary
In diffusion limited circulation, when does gas equilibrate?
At no point; gas does not equilibrate by the time the blood reaches the end of the capillary
Is O2 in normal health perfusion or diffusion limited?
Perfusion limited
Is O2 in emphysema or fibrosis perfusion or diffusion limited?
Diffusion limited
Is CO2 perfusion or diffusion limited?
Perfusion limited
Is N2O perfusion or diffusion limited?
Perfusion limited
Is carbon monoxide perfusion or diffusion limited?
Diffusion limited
What is DLCO?
The extent to which O2 passes from air sacs of lungs into the blood
What is the flow of events in COPD?
Lungs encounter a decrease in PAO2, leading to chronic pulmonary vasoconstriction, chronic pulmonary HTN, cor pulmonale, and subsequent right ventricular failure
