Pulmonary Exam 1

What is the mechanism of action of B2 agonist bronchodilators (both short-acting and long-acting)

β2-adrenergic agonists effective for acute treatment of asthma target β2-adrenoceptors, working through GS to: 1. increase cAMP levels, 2. reduce myosin light chain phosphorylation (and hence contraction), and 3. open large-conductance calcium-activated potassium channels, hyperpolarizing airway smooth muscle, which further reduces contraction. All effects relax airway smooth muscle. β2-adrenergic agonists also inhibit degranulation of mast cells, which reduces inflammation.

PaO2 = 60 PAO2 = 68 so A-a = 8 What is the cause? a) Dead Space (V/Q mismatch) b) Alveolar Hypoventilation c) Diffusion Impairment d) Decreased Cardiac Output e) Left to Right shunt

b) Alveolar hypoventilation PaO2 and PAO2 are low, A-a is normal Hypoventilation is the only thing that would do this. All of the others would increase the A-a gradient.

SatO2 = 85% PaO2 = 50 mmHg PaCO2 = 75 mmHg What is the most likely cause? a) Pulmonary fibrosis b) Hypoventilation from Drug OD w/ no underlying lung abnormality c) Carbon monoxide poisoning d) Methemoglobin e) V/Q mismatch

b) Hypoventilation from Drug OD w/ no underlying lung abnormality. A-a is normal if you calculate it: PAO2 = 150 - 75/0.8 = 150 - 75 (5/4) = 94 mmHg A-a = 94 - 50 = 44 mmHg

2 types of emphysema: Centriacinar vs. Panacinar in terms of morphologic and radiologic features.

centriacinar and panacinar (acinus = lobe of lung) Centriacinar (centrilobular) -most common type (95%) -Upper lobes/apical -Heavy smokers, -Often a/w chronic bronchitis Panacinar (panlobular) -a/w α1 antitrysin (A1AT) deficiency -- A1AT deficient pts have pink globules inside liver cells (abnormal A1AT protein) that are PAS-positive diastase resistance -lower lung/base -may have cirrhosis -PiZZ homozygous state

Sarcoidosis: • Involves well-formed ___. • ___ lymphadenopathy is usually observed on CXR. • Presenting symptoms • Calcium levels? • Histology

chronic inflammatory disease in which small nodules (granulomas) develop in lungs, lymph nodes, and other organs. This is one of the two granuloma diseases of the lung, along with Hypersensitivity Pneumonitis. • Characterized by well-formed noncaseating granulomas in many tissues and organs. • 90% have hilar lymphadenopathy or lung involvement • Presents with insidious onset of dyspnea, cough, chest pain, hemoptysis, or constitutional symptoms. • Hypercalcemia • Histology: multiple well-formed epithelioid granulomas with multinucleated giant cells (blue arrows) and no necrosis.

If a child has chronic lung issues, it is most likely what disease?

Cystic Fibrosis Chronic lung diseases are rare in children. More common in adults, especially smokers. Cystic fibrosis is an inherited disease, and it appears during childhood. CF is the most common genetic disease in caucasians (1/2500 caucasians)

Diagnose: An 8-year-old girl is brought to the pediatrician because she is significantly shorter than her classmates. Her mother notes that she has had thick, oral secretions for the past several months, along with a chronic cough. Her exam is notable for clubbed fingernails.

Cystic Fibrosis If you see clubbing of fingernails, it's usually either cystic fibrosis (children) or lung cancer (adults). ___________________ Cystic Fibrosis is a multi-organ disease (other big system is GI problems), but pulmonary sxs are most important because most CF pts die of respiratory failure. But the CFTR protein (mutated in CF by definition) is found in bronchi, biliary tract, pancreas, intestines, and reproductive system

+++++++++++ Asthma Histology: - __ Spirals - ___ Crystals

- Curschmann spirals: mucous containing whorls of shedded epithelium - Charcot-Leyden crystals - crystalloids made of eosinophils - Also, ↑ eosinophils in lungs and peripheral blood

Chest XR appearaces of: - consolidations (airspace / air pathway problems) - interstitial problems - masses / nodules

That's actually what they look like on images, so think of these appearances.

Interstitium problems / Interstitial Lung Diseases on Chest CTs

For ILDs, you want to use a High Resolution CT (HRCT) Look for linear patterns / projections

Pathogenesis of a DVT: How does a DVT form? -- Virchow's Triad -- What 3 things must be true?

For a DVT to form, need Virchow's Triad to be true: Venous stasis, activation of coagulation, and damage to vascular endothelium. 1. Venous Stasis: When venous blood stays still (immobility), clots can form in the pooled venous blood (hard to do if venous blood is moving around). 2. Activation of Coagulation: Clot forms in the pooled venous blood. 3. Vascular Endothelial Damage: Clot starts to damage the vessel where it's located.

Motion of Intercostal Muscles during breathing: -What happens to a-p diameter during inspiration vs. expiration -If spinal injury prevents intercostal muscles from working, what two values are still normal?

During inspiration, those intercostal muscles grow closer, so the a-p diameter increases to make space. During expiration, intercostal muscles move further apart, so the the a-p diameter decreases to expel air. Spinal Injury that affects intercostal mm.: You can't expel all of air. Remember that any muscle other than the diaphragm is only used in labored breathing. FRC Normal Tidal Volume Normal Everything else is decreased, except for RV, which is increased (can't expel all air)

Describe the functions of the three shunts in the fetal circulation: ductus arteriosus, foramen ovale, and ductus venosus. For each, what direction does blood flow?

There are two Right to Left shunts in the fetal circulation: 1. The Ductus Arteriosus (DA) connects the pulmonary artery to the aorta. The right heart needs to pump a lot of blood to develop and strengthen. The DA allows the right heart to pump a high volume by shunting most of the RV output into the aorta. 2. The Foramen Ovale allows blood to go from the right atrium directly to the left atrium. This shunt is needed because, without it, the only blood entering the left ventricle would be the small amount coming from the fetal lungs. There is one Left to Right shunt: 3. The Ductus Venosus, which is the pathway for umbilical venous blood to bypass the hepatic circulation and reach the IVC.

+++++++++++ ON EXAM +++++++++++++ BUZZword: Hyaline membranes in alveoli

"If you see Hyaline Membranes on Histology, Know it means:" Diffuse Alveolar Damage Which indicates ARDS IMAGE - Likely ON EXAM - Heavily Emphasized.

Atmospheric Pressure is 438 mmHg. PCO2 is 20 mmHg. Respiratory exchange rate is still 0.8. At the end of inspiration, what will be the PO2 in this person's trachea?

(438 - 47) x (0.21) = 82 (Subtract 47 as part of the equation) Air is 21% oxygen

- - - - unless emphasized later, ignore; not clearly in objectives - - - - Major causes of Pulmonary Edema - ___ capillary hydrostatic pressure - ___ interstitial hydrostatic pressure - ___ plasma colloid osmotic P - ___ capillary permeability

- Capillary hydrostatic pressure increases (Left heart failure) - Interstitial hydrostatic P more negative than normal (inspiratory effort) - Plasma colloid osmotic P decreases - Capillary permeability increases (poison gas) - Loss of pulmonary surfactant (NRDS, ARDS) - Very high altitude (pulm. cap pressure increases from hypoxic vasoconstriction). - Lymphatic insufficiency

++++++++++ Clues to Pulmonary Hypertension due to Left Heart Disease (Group 2 Pulmonary Hypertension)

- LV is abnormal on echo or LA is dilated (elevated L filling pressures) - Patient presents with typical LV CHF and pulmonary edema

Elastin fibers are found where in the respiratory tree?

Alveolar septa

Alveolar Ducts: -Microscopic appearance -Do they have walls of their own? -Appearance of alveolar sac.

-Microscopic appearance: dotted line in image. They are white pathways. -No walls, like in image. These contain the pulmonary capillaries, which means that gas exchange occurs here.

What are the histological unique components of the trachea?

> THICK Basement Membrane visible > Elastic Lamina DOES NOT HAVE CILIA, but has plenty of seromucosal glands that produce mucus in the trachea.

Development of the Diaphragm -- Pleuroperitoneal folds What happens at: 5 weeks 6 weeks 7 weeks 8 weeks

A Congenital Diaphragmatic Hernia is caused by a failure of pleuroperitoneal membranes to form its normal contribution to the diaphragm.

A rich network of elastin / elastic fibers sourrounds what part of the resp. tract? What functions does elastin serve here? What happens when these fail? What disease?

A Rich Network of Elastin Fibers Surrounds the Alveoli and Contributes to Expiration and Protects Against Distention. Elastin surrounds alveoli. This allows a recoil function, making the alveoli elastic. There is no smooth muscle here to control size. Alveoli must snap back into proper size after expansion from air. So they help with expiration and prevent distention (permanent dilation / looseness). Emphysema occurs when these fail, and there is permanent distention of alveoli.

++++++++++++++++++++++++ - What is Cheyne-Stokes Breathing? - What happens to alveolar PCO2 during this? Compare PCO2 during apnea and hyperventilation) - Central Chemoreceptors detect level of CO2 in what location ONLY? L.O.: Describe the main features of Cheyne-Stokes breathing.

A weird type of breathing that involves periods of apnea, interrupted by periods of hyperventilation (i.e., periodic breathing). PCO2 in alveoli goes up and down. Follows its own trend. Rises during apnea and falls during hyperventilation. Central Chemoreceptors detect PCO2 ONLY in the brain and not in the alveoli. This is because they are located in the medulla of the brainstem. Brain PCO2 is delayed because arterial blood arrives in the brain several seconds after going through the lungs.

A 72 year old man has smoked 2 PPD for 40 years. He has daily productive cough and dyspnea on walking 2 blocks. What is his diagnosis? A. Chronic Bronchitis B. Moderate COPD C. Severe COPD D. Asthma

A. Chronic Bronchitis

++++++++++++ BUZZword: Pleural Plaques on Chest CT

Abestosis (one of the DPLDs/ILDs)

What is an Acute Lung Injury? How to diagnose it by radiograph. Severe ALI = ___.

Abrupt onset of significant hypoxemia and diffuse pulmonary infiltrates in the absence of cardiac failure. Radiography: Diffuse bilateral airspace disease w/o pleural effusion or cardiomegaly. Severe ALI = acute respiratory distress syndrome (ARDS)

What is the equation for air flow in terms of pressure and resistance? What are the main sources of resistance to air flow?

Air Outflow = PA/R Remember? Flow always equals pressure over a resistance. Sites of resistance: • Nose (Nasal airway resistance can be reduced in many people by using spring-loaded adhesive devices like Breath Right.) • Large to Medium Bronchi/Bronchioles (first several generations), where airflow is rapid and more likely to be turbulent • Small airways normally make minor contribution to airway resistance, because airflow is slow and laminar. Mechanical effects of small airway disease are hard to detect in early stages.

++++++++++++++++++++++++++ Emphysema symptoms in a young person indicates what cause?

Alpha-1 Anti-trypsin deficiency.

Alveolar Pressure (PA): -It is the pressure where? -It is the driving force for ___ What does each mean: PA = 0 PA < 0 PA > 0 -Equation

Alveolar Pressure - Pressure inside the lungs It is the driving force for airflow -- air flow direction (inhale or exhale) is determined by Pa, the pressure inside the lungs. PA = 0, No Airflow PA < 0, Inspiration PA > 0, Expiration Equation: Pa = Ppl - PL From the main equation: PL = Pa - Ppl

Pulmonary vascular resistance is higher or lower than systemic vascular resistance? Relationship between increased pressure and resulting pulmonary flow and resistance. 2 mechanisms to increase pulmonary blood flow

Always LOWER If Pulmonary Arterial P increases => Vascular R decreases => Flow INCREASES --- Q = P/R Pulmonary vascular resistance (PVR) is similar to SVR except it refers to the arteries that supply blood to the lungs. If the pressure in the pulmonary vasculature is high, the right ventricle must work harder to move the blood forward past the pulmonic valve.

When does an intrathoracic airway collapse occur? When does an extrathoracic airway collapse occur? LO: Explain the process of dynamic airway collapse and airway closure during forced expiration; distinguish between airway collapse in intrathoracic vs extrathoracic airways.

Analogous to how nostrils suck inward when sniffing really hard, really fast. That is a dynamic airway collapse.

History of Atopic Dermatitis is suggestive of what lung condition?

Asthma Both are allergic reactions, Type I Hypersensitivity

++++++++++++++++++++++++ How to calculate mL of O2 that can be bound based on grams of Hgb available. How many mL of O2 can be bound by each Hgb molecule?

At 100% Sat., 1 g of Hgb can bind 1.34 mL O2, so 15 g Hb can bind 15 x 1.34 = 20 ml O2. 1g Hgb binds 1.34 mL O2. So total volume (mL) of O2 that can be bound to Hgb is 1.34 x g Hgb.

+++++++++ At FRC, is the pulmonary vascular resistance high or low? What about RV and TLC? MEMORIZE!

At FRC: Pulmonary vascular resistance (PVR) is at a minimum. Thus, PVR is lowest at FRC. Increasing or decreasing the volume from FRC will increase PVR. "That's all you need to know"

++++++++++++++ Very important graph with Pressure (PL) vs. Volume: -What does the lung only plot look like? -What is the state of the lungs when PL = 0? Memorize the shapes of: -Lung only -Chest wall only -Lung + Chest Wall (Respiratory system)

At PL = 0, lung is collapsed to minimum volume (MV), and increasing PL causes increase in volume. Compliance (slope) gets smaller as lung inflates, just like graphs on previous slide. Graph: Describes change in lung volume for a given change in pressure (C = V/P) ↑ compliance in emphysema ↓ compliance in pulmonary fibrosis, pulmonary edema, ARDS, and chest wall disease Chest wall and Lung curves are equal and opposite. They always have the opposite volume and opposite pressure as you breathe!

Atelectasis: -Definition -Effect on blood shunting -3 Types

Atelectasis - lung collapse ^Airway spaces cannot expand Results in shunting of inadequately oxygenated blood from pulmonary arteries into veins. Ventilation-perfusion imbalance ==> Hypoxia Dyspnea and low oxygen saturation is expected. 3 Types: -Resorption -Compression -Contraction

Types of asthma: -Atopic Asthma -Non-atopic asthma -Drug-induced asthma -Occupational Asthma

Atopic Asthma -- Main Type!

A healthy subject has just finished a normal expiration and has not started inspiring the next breath. Airflow is 0 but the airway is open. Which of the following pressures is equal to atmospheric? A. Pleural Pressure B. Alveolar Pressure C. Transpulmonary Pressure D. Pulmonary arterial pressure at base of lung E. Pulmonary capillary wedge pressure

B. Alveolar Pressure There is no airflow and airway is open, so alveolar P must equal atmospheric (no driving force for airflow). Elastic recoil of lungs (inward) and chest wall (outward) makes pleural pressure negative (subatmospheric). Transpulmonary pressure must be positive to overcome elastic recoil of lung. Both the blood pressures are positive.

Consider two people, who have the same total Hb concentration (15 g/dl): Andy & Bill Andy has a faulty furnace that leaks CO into his house, and he breathes the CO-enriched air long enough for CO to occupy 25% of the O2 binding sites on his hemoglobin. The faulty furnace does not cause a significant drop in the PO2 in room air. Andy is conscious and still able to breathe well enough to keep his arterial PO2 at 90 mm Hg. Bill is on a mountain at an altitude sufficiently high that his arterial Hb saturation is 75%. He is otherwise healthy and has NOT been on the mountain long enough to have an elevated hematocrit or 2,3-BPG. From this information, whose carotid body chemoreceptors will be stimulated more to increase ventilation rate? Why? A. Andy B. Bill C. Both Andy's and Bill's carotid body chemoreceptors will be stimulated to the same extent. D. Neither Andy's nor Bill's carotid body chemoreceptors will be stimulated relative to those in a normal person breathing sea level air.

B. Bill ^ The carotid body chemoreceptors sense low arterial PO2, and Andy's PaO2 is normal. Bill's PaO2 is low enough to result in a saturation of only 75%, which puts PaO2 well below 60. (Remember the landmarks: 60 mm Hg ~ 90% saturation and 40 mm Hg ~ 75% sat.) If the dissociation curve is shifted to the left because of hyperventilation at high altitude, the PaO2 at 75% saturation will be even lower. So Bill's carotid body chemoreceptors will definitely be stimulated. Or, you could say that O2 won't affect Andy as much because Hgb prefers CO over O2. Meanwhile, Bill's problem is that there's not enough oxygen in the air around him, so he could benefit from increased oxygen and will increase RR. Remember, the peripheral chemoreceptors do not respond strongly to increased CO level. Breathing will be normal. MNEM: Peripheral chemoreceptors are naive and CO sneaks by.

A healthy 25 year old woman at rest is breathing atmospheric air at sea level. Her alveolar PO2 is 100. The PO2 in the blood at the pulmonary venous end of her pulmonary capillaries is: A. Equal to alveolar PO2 only during inspiration B. Over twice the PO2 of pulmonary arterial blood C. Several percent lower than alveolar PO2 D. Equal to alveolar PO2 only during expiration E. Slightly higher than alveolar PO2

B. Over twice the PO2 of pulmonary arterial blood Pulm arterial PO2 = 40, Pulm end cap PO2 = 100 The Pulmonary Artery carries deoxygenated blood away from the right ventricle to the lungs and returns oxygenated blood to the left atrium through the Pulmonary Veins. Not A or D b/c O2 reaches equilibrium during both inspiration and expiration. Not C or E b/c O2 reaches equilibrium, so end cap PO2 = Alv PO2

++++++++ EM pic of respiratory epithelium -- Be able to identify: - Basal cells - Goblet cells - Ciliated cells Which cell type produces mucous?

Basal cells are at the bottom. They become other types of cells. Goblet cells are the big goblets of white circles. -function: produce mucous Ciliated cells are tall and go up to the top where they have cilia.

Why is 50% HbCO usually lethal, but having 50% of the normal total amount of Hb (anemia) not lethal? Shape of O2 dissociation curve with CO poisoning

Because bound CO increases affinity for O2 and impairs O2 delivery to tissues.

Effect of exercise and fibrosis on diffusion rate of oxygen from lungs to pulmonary capillaries.

Both of them slow down diffusion rate. Exchange occurs over a greater length of the capillary before equilibrium is reached. Normally, all the oxygen enters the blood fast and over a short portion of the pulmonary capillaries, and equilibrium is reached way before the next cycle. But exercise and fibrosis make this take longer.

What level of the respiratory tree: -Smooth muscle deep to cartilage -Serous glands in the submucosa

Bronchi Smooth muscle and cartilage are both present in bronchi. Seromucosal glands are also present in bronchi, helping with mucus production.

Inflammation that damages hyaline cartilage: what part of the respiratory tree is affected?

Bronchi (bronchitis) NOTE - wrong image - those are pneumocytes in the alveoli. Note: Respiratory epithelium is ciliated columnar epithelium that lines most of the respiratory tract where it serves to moisten and protect the airways. Mainly in nasal passages. Respiratory membrane is different -- respiratory membranes are the wall of the alveoli across which gas exchange occurs.

What medications can be used to alleviate COPD?

Bronchodilators Some evidence that inhaled corticosteroids could work, but mainly the bronchodilators, like Methylxanthines and Anticholinergics. So NOT leukotriene inhibitors, eosinophil inhibitors, etc.

Med Bullets Q: Scientists are studying human lung development by trying to identify which proteins and signaling factors trigger lung bud division and bronchiole branching. Their main focus is particularly around the 20th week of gestation, during which terminal bronchioles branch into respiratory bronchioles and further into alveolar ducts. Which of the following phases of embryonic lung development is the stage in which the scientists are interested in studying? A. Embryonic B. Pseudoglandular C. Canalicular D. Saccular E. Alveolar

C. Canalicular Bullet Summary: During the canalicular phase of lung development (16-25 weeks), the terminal bronchioles branch into the respiratory bronchioles and alveolar ducts. Lung development occurs in five phases (Every Pulmonologist Can Spot Alveoli) = the embryonic phase (weeks 4-7), pseudoglandular phase (weeks 5-15), canalicular phase (weeks 15-25), saccular phase (weeks 25-birth), and alveolar phase (birth - 8 y/o). The canalicular phase is where the terminal bronchioles branch into the respiratory bronchioles and then the alveolar ducts. During this period the airways increase in diameter. Respiration becomes capable towards the end of this period around 25 weeks. _____________________ Incorrect Answers: A: During the embryonic phase (weeks 4-7) lung buds from the trachea branch up to the tertiary/segmental bronchi. B: During the pseudoglandular phase (weeks 5-16) endodermal tubules turn into the terminal bronchioles. Respiration is not possible at this phase. D: During the saccular phase (weeks 26-birth) the alveolar ducts form the terminal sacs and pneumocytes develop. E: During the alveolar phase (weeks 32-8 years) the terminal sacs form the adult alveoli.

++++++ KNOW THIS ++++++++ The fetal umbilical venous blood has a _____ PO2 and _______ O2 saturation than the maternal venous blood. A. Higher: Higher B. Higher; Lower C. Lower; Higher D. Lower; Lower

C. Fetus has: Lower PO2; Higher O2 saturation MNEM: Fetus doesn't have much oxygen, but the oxygen it does have is tightly bound to Hgb. PO2 - higher in mom O2 saturation - higher in baby

Is there more CO2 or Oxygen in the blood? Why, based on partial pressures and solubility coefficients?

CO2 has a HIGH solubility coefficient. It likes to dissolve in blood. O2 has low solubility. It doesn't like blood as much. So, like in image, CO2 is much higher in concentration in the blood while it has the same partial pressure as O2. Equilibrium is established based on partial pressures of gases, not concentrations.

Chronic bronchitis and emphysema are the 2 components of ___

COPD

Increased A-p diameter

COPD (chronic air trapping) -- specifically chronic bronchitis, NOT emphysema. Barrel chest. A-p is anterior-posterior

The central chemoreceptors (chemoreceptors in the medulla) are not stimulated by hypoxia. Instead, they are stimulated by a decrease in ___, which itself is caused by an increase in ___. Response of Central Chemoreceptors to high PaCO2 vs. low PaCO2.

Central Chemoreceptors Sense CO2 by Detecting pH The central chemoreceptors are not stimulated by hypoxia. Instead, they are stimulated by a decrease in pH, which in turn is caused by an increase in PaCO2. If PaCO2 is high because ventilation is not adequate, the increased CO2 will lower the pH of the central chemoreceptors, which signals the inspiratory neurons to increase ventilation and lower PaCO2 back to 40 mm Hg. Conversely, if PaCO2 goes below 40 mm Hg, the chemoreceptors detect the increased pH and will send inhibitory signals to the inspiratory neurons in the DRG and ventilation will decrease to bring PaCO2 back to 40 mm Hg.

Diagnose from these symptoms: Dusky cyanotic color Cough and copious sputum Edematous/overweight Dyspnea Clubbing of fingers Wheezing/rhonchi

Chronic Bronchitis - The Blue Bloater Narrowing of airways

Club Cells (aka Clara Cells): -MICROSCOPIC APPEARANCE (MNEM) -They are ONLY in what part of the respiratory tree? -3 functions: 1. Regenerate what? 2. Secrete what? 3. Degrade toxins using what famous protein?

Clara/Club cells are non-ciliated, non-mucous, secretory cells in respiratory epithelium. Microscopic: DO NOT have cilia! Very large with dark circles inside. -MNEM: Big Clara has no hair. Club Cells -- functions: (on another card) - regenerate bronchiolar epithelium - secrete surface acting agent that reduces surface tension. But don't secrete mucus. - degrade toxins via CytoP450.

Types of Atelectasis: Resorption L.O. - Describe the different forms of atelectasis.

Complete obstruction of an airway by secretions (mucus plug) Common Causes: -Post-op state -Bronchial asthma -Bronchiectasis -Chronic bronchitis -Aspiration of foreign bodies -Bronchial tumors

++++++ "IMPORTANT TO KNOW" ++++++ Equation for compliance. ^ Relationship between compliance and transpulmonary lung volume and between compliance and volume. Define compliance of lungs

Compliance = ΔV/ΔPL Where PL is transpulmonary pressure. Unit: L/cmH20 (volume / pressure) High Compliance = lung is easier to fill; and resultingly fills to higher volume. Compliance increases with increased volume (because compliance means accepting more volume) Compliance decreases with increased PL and thus increased Pa (PL = Pa - Ppl). See example problem in image.

Diagnose: • Involves the alveolar spaces more than the interstitial spaces • Pts present with cough and dyspnea • Balls of fibroblasts (Masson bodies) in alveolar spaces and bronchioles • Underlying lung architecture is otherwise normal • No interstitial fibrosis or honeycombing • Imaging: patchy consolidation and/or nodules

Cryptogenic Organizing Pneumonia (COP) If honeycombing, it's UIP/IPF. If not, it's NSIP or COP. COP has balls of collagen / fibrosis in the alveolar spaces. See Image.

Diagnose from these BUZZwords: •In infants & children: Infant born with Meconium ileus; Respiratory symptoms, failure to thrive. • In adults (only 7% of dxs): GI symptoms, Diabetes, Infertility (causes a problem w/ vas deferens)

Cystic Fibrosis

Bronchioectasis is a classic BUZZword for what condition?

Cystic Fibrosis Bronchiectasis: a chronic condition where the walls of the bronchi are thickened from inflammation and infection. Often, this symptom is in adults (20s) because it occurs from a long period of infections.

Nasal Polyps / Sinusitis -- BUZZword for what condition?

Cystic Fibrosis But not always; read carefully. CF should also have the pt being under-nourished.

Ivacaftor is a good treatment for patients with what condition?

Cystic Fibrosis CFTR modulator Increases activity of CFTR, the dysfunctional protein of CF.

++++++++ Know How to Work These +++++++ A boy chokes on a piece of candy that completely blocks ventillation of the Right lower lobe. 30 minutes later, what would be the PO2 and PCO2 states in the pulmonary end-capillary blood? PO2 // PCO2: a) 100 // 40 b) 150 // 0 c) 75 // 40 d) 40 // 46 e) <10 // 40

D) PO2 of 40, PCO2 of 46. This is a shunt and air can only get to the left lung. PO2 drops probably by about half since one lung is blocked. V/Q would be zero in the right lung because it's blocked off.

An O2 content vs PO2 curve for a person with higher than normal Hb concentration. The labeled point is at 15mL O2 Content and 25 mmHg PO2. What is the approximate hemoglobin saturation of this blood at the PO2 indicated by point A? A. 15% B. 30% C. 45% D. 60% E. 75%

D. 60% HOW TO DETERMINE: Point A (image) is the point of inflection. It is at 15 mL O2, which is 60% of the max O2 content which is 25 mL. So the Hgb saturation will be O2 content at point of inflection / Max O2 content.

Suppose someone starts out in a normal steady state with a breathing rate of 12/min (5 second cycle). At t = 0 she consciously hyperventilates for a few seconds by taking several deep breaths. She then stops hyperventilating and tries not to think about breathing and let the body take over. What do you think will happen? A. There will be a delay before the next breath because of the refractory period in the sodium channels in the diaphragm. B. She will immediately go back to breathing normally at a rate of 12/min and with the normal tidal volume. C. She will continue to breathe at an elevated rate for several seconds because of the oxygen debt generated by the period of hyperventilation. D. She will not breathe for well over 5 seconds because the alkalinization of her central chemoreceptors will inhibit the inspiratory neurons. E. She will not breathe for several seconds because of fatigue in her inspiratory muscles.

D. She will not breathe for well over 5 seconds because the alkalinization of her central chemoreceptors will inhibit the inspiratory neurons. ^Don't focus on 5 second part (resp. window). Hyperventilation gets rid of too much CO2. The body's response will be to slow the rate of CO2 expulsion, thus decreasing the RR. The increased pH at the central chemoreceptors of the medulla inhibits ventillation.

++++++++++++++++++++++++++++ Histology of alveoli in ARDS, compared to normal.

Diffuse alveolar damage in the acute phase. Some alveoli are collapsed, while others are distended; many are lined by bright pink hyaline membranes (Image). The healing stage is marked by resorption of hyaline membranes and thickening of alveolar septa by inflammatory cells, fibroblasts, and collagen. Numerous reactive type II pneumocytes also are seen at this stage (arrows), associated with regeneration and repair. Normal has nice, thin walls. In ARDS, fluid and immune cells fill the alveoli.

+++++++++++ Pulmonary Gas Exchange: Diffusion Rate of O2 & CO2 • EQUATION for rate of gas diffusion across a capillary. Directly proportional to the __, __, & __ of the vessel, but inversely proportional to the ___ of a vessel. • The rate of gas diffusion / exchange has WHAT proportionality to: - surface area - thickness of barrier, which is normally very thin. - partial pressure difference

Diffusion Rate Equation: MNEM: ADP/x V gas = A x D x (P1-P2)/Δx ➥ where A= area, Δx = alveolar wall thickness, D = diffusion coefficient of gas, P1 - P2 =difference in partial pressures, Δx is thickness of vessel (thicker vessel means slower exchange). • ↓ Area in emphysema. • ↑ Thickness in pulmonary fibrosis.

+++++++++++ Cystic Fibrosis: Chest Imaging looks like what?

Dilated bronchi from fluid accumulation (arrows in Image) Cloudy appearance of bronchii. Airways should get smaller and smaller as you move outwards, but in CF, you can see terminal enlargements. Thick airways seen even at periphery of lungs. This is showing bronchiectasis, which results from CF due to chronic infections. If bronchi are larger than blood vessels, it's bronchiectasis.

Do signals from the brain rapidly fire during inspiration or expiration?

During inspiration, action potentials to the diaphram become more and more frequent (inspiratory "ramp"), and then abruptly stop for the expiratory phase. Need more APs to contract diaphragm & don't need any to leave diaphragm relaxed.

Symptoms of Pulmonary Hypertension Signs that Right Heart Failure is present

Dyspnea, angina-like retrosternal chest pain, weakness, fatigue, peripheral edema, and effort syncope. Symptoms: - Dyspnea and/or fatigue on exertion - Syncope (when advanced) Signs of RV failure - Peripheral edema, hepatomegaly, ascites, effusions Test results (found unexpectedly or part of workup for something else) - Hypoxemia - Exercise desaturation - Decreased DLCO on PFT - Echocardiogram findings (best screening test)

As part of an experiment, a healthy 25 year old male breathes through a straw. Breathing through the straw increases his airway resistance by 50%, i.e., the new airway resistance is 1.5 times what it was. He maintains quiet breathing at the same respiratory rate and tidal volume as previously. How does breathing through the straw change his pulmonary mechanics? A. Transpulmonary pressure at end inspiration will be 50% higher than normal. B. Alveolar pressure at end expiration will be positive. C. Alveolar pressure at end inspiration will be negative. D. Pleural pressure at end expiration will be more negative than normal. E. Peak alveolar pressure during expiration will be 50% higher than normal.

E. Peak alveolar pressure during expiration will be 50% higher than normal. Ohm's law for airflow: Air Outflow = Pa/R Airway resistance matters only when there is airflow. If resistance is 1.5 times normal and airflow is the same, then alveolar pressure must be 1.5 times normal (i.e., 50% higher).

Complex Practice Q: Which of the following is equal to Vital Capacity? A. TLC - FRC B. VT + IRV C. FRC + IRV D. IRV + ERV E. TLC - RV F. IC + FRC You really need to know all of those equations!

E. TLC - RV Vital capacity is everything except the RV. >> Inspiratory Capacity = TV + IRV >> Functional Residual Capacity = ERV + RV >> Vital Capacity = IRV + TV + ERV >> Total Lung Capacity = IRV + TV + ERV + RV

++++++ "Something You Just Have To Memorize" +++++++ Graph of Lung Volume: Inspiration Reserve Volume Tidal Volume (TV, Vt) Expiration Reserve Volume Residual Volume Spirometry can measure all of these except ___ Volume Lung Volume vs. Lung Capacity

Easy way to remember this graph is that the different volumes do not overlap. Names of volumes make sense: -Tidal volume -- normal breathing in (increases) and breathing out (decreases) -- just like a tide. -Inspiration Reserve Volume -- everyone knows you can inspire air up until a certain point, and that maximum volume is the IRV. -Expiratory Reserve Volume -- you can also expire extra amounts of air, but never ALL the air. Which is why there is... -Residual Volume -- the volume of air in the lungs that cannot be expired. Spirometry can measure all of these except Residual Volume. You need He dilution or body box (PFT lab). Lung Capacity -- a sum two or more lung volumes. Separate card. Several different types of capacity w/ equations.

+++++++++++++++++++++++++++++++ Embryology -- B&B Starting with the Lung Bud at week 4 of gestation, name the 5 stages of lung development (and what structures form, generally) 1. Weeks 4-7 2. Weeks 5-15 3. Weeks 15-25 4. Weeks 25-birth 5. Birth to 8 years old At what week and in what stage is respiration possible due to development of all needed structures?

Embryonic, Pseudoglandular, Canalicular, Saccular, Alveolar. Every Pulmonologist Can Spot Alveoli. 1. Embryonic (wks 4 - 7): Lung bud → trachea → bronchial buds → mainstem bronchi → secondary (lobar) bronchi → tertiary (segmental) bronchi. 2. Pseudoglandular (wks 5 - 15): Endodermal tubules → terminal bronchioles, formation of a respectable capillary network. 3. Canalicular (wks 15 - 25): Terminal bronchioles - respiratory bronchioles - alveolar ducts -Surrounded by prominent pulmonary network- Respiration possible at 25 wks (compatible with life) 4. Saccular (wks 25 - birth): Alveolar ducts - terminal sacs. Pneumocytes develop 5. Alveolar (Birth - 8 y/o): Terminal sacs - adult alveoli - From ~50 millions at birth to ~350 millions (8 years)

Diagnose from these symptoms: Dyspnea Purse-lip breathing Slow prolonged expiration Use of accessory muscles to breath Thin anxious appearance Speaks in short jerky sentences Barrel chest (↑AP dimension on CXR) Hyper-resonance on chest palpation

Emphysema - The Pink Puffer Long Term Effects: Right Heart Failure & Lung Collapse (Atelectasis)

Common direct and indirect causes of ARDS. Classic pathology is ___ ___ ___.

Essentially, anything that blocks airways, preventing respiration = ARDS. Really bad pneumonia can do this Aspiration of gastric contents = choking on vomit

Trachea Histology: Part 2 - Microscopic Identify the elastic lamina. Microscopic images of the trachea contain what 3 unique features?

Factors that distinguish trachea histologically from other areas: 1. Thick Basement Membrane - VERY prominent -- usually cannot see BM under microscope. 2. Elastic Lamina - Separating the Mucosa and Submucosa 3. Seromucous Glands - Located in the Submucosa

++++++++++++++++++++++++ Maternal vs. Fetal Oxygen Dissociation Curves: -Know which is which; compare them. -Does maternal or fetal Hgb have a higher affinity for O2? -Is there a higher concentration of Hgb in maternal or fetal circulation? L.O.: Describe the process of diffusion of O2 in the placenta and the differences in O2 dissociation curves of maternal and fetal blood.

Fetal curve higher than Maternal curve. 1. Fetal hemoglobin (gamma chains instead of beta chains) has a higher affinity for O2 (fetal P50 ~ 19 mm Hg vs 26 mm Hg for adult). -The reason for the higher affinity is that fetal Hb has a lower affinity than adult Hb for 2,3-BPG. 2. There is a higher concentration of hemoglobin in fetal blood than in maternal blood. -So at 100% saturation, there is more O2 in 100 ml of fetal blood than there is in 100 ml of maternal blood. -From the dissociation curves, at a PO2 of 30 mm Hg, fetal umbilical venous blood has much more oxygen than maternal placental venous blood, because of the higher affinity and higher amount of hemoglobin.

++++++ KNOW THIS ++++++ Summary of the Effects of Ventilation on Alveolar (A) and Arterial (a) PCO2 and PO2 (CO2 and O2 levels in lungs): 1. For a given rate of CO2 production, Alveolar Ventilation (VA) and PACO2 are ___ proportional to each other. This has to be true, because you breathe off all the CO2 you produce. 2. If O2 consumption is constant and VA↑, then PACO2 __ and PAO2 __. 3. If O2 consumption is constant and VA↓, then PACO2 __ and PAO2 __.

First, understand that higher PO2 means more oxygen in lungs and decreased resp. Opposite for PCO2, which you want to expell. 1. VA & PACO2 are inversely proportional. 2. If VA↑, then PACO2↓ and PAO2↑. 3. If VA↓, then PACO2↑ and PAO2↓. Also, there is very little A-a gradient for CO2, so you can always assume that PACO2 = PaCO2.

+++++++++++++++ What is the effect of airway obstruction (COPD, asthma) on FEV1/FVC? This is the hallmark of obstruction.

Forced Expiratory Volume (FEV) is the total amount of air exhaled during the FEV test. FEV1 is the Y-axis value at 1 second. Less air is blown out; COPD is a problem with expiration. Decreased FEV1/FVC is the hallmark of obstruction.

What respiratory parameter is meaured to assess the status of Cystic Fibrosis patients?

Forced Expiratory Volume (FEV1) -- the one we did in the PFT lab.

Layers of the respiratory membrane in photomicrograph

GAS EXCHANGE OCCURS ACCROSS THE REPIRATORY MEMBRANE

++++++++ "Very beautiful picture as far as I'm concerned" ++++++++ ++++++++++++++++++++++++ ON EXAM +++++++++++++++++++++++++ Recognize: Electron micrograph of a pulmonary capillary cross section. What's going on across the wall? What 7 layers must oxygen cross to get into the capillary? Start with alveolar air. 3 main ones.

Gas exchange is occuring across the wall. O2 into the capillary, CO2 out (since it's pulmonary). Pathway: ASA i.e., PR -- in that order 1. Alveolar air 2. Surfactant Layer 3. Alveolar Epithelial Cell 4. Interstitial Fluid/Basement Membrane 5. Endothelial Cell 6. Plasma 7. Red Blood Cell Membrane (pathway not really emphasized or reviewed during lecture) He said this image shows how thin the layer is that oxygen crosses.

Identify the advantages of aerosol administration of medications for asthma and COPD.

Good: Aerosol administration accomplishes higher local delivery to the lungs and decreases systemic side effects. Aerosols represent a way to increase drug delivery to the bronchi selectively, which reduces the dose required, in turn reducing potentially serious side effects associated with higher dose systemic delivery. Bad: Most of the inhaled drug is actually swallowed.

Trachea Histology: Part 1 - Gross Contains C-shaped ___ Cartilage Rings connected to each other by ___ ___ Tissue The Trachealis is what type of muscle that connects what?

Hyaline cartilage Fibroelastic Connective Tissue Trachealis: Smooth muscle that connects the ends of the cartilage rings.

Effect of Hyperventilation and Hypoventilation on oxygen vs. CO2 pressures in the alveoli. What about acidity / pH?

Hyper: ↑O2, ↓CO2 Hypo: ↓O2, ↑CO2 More CO2 = More acidic = Respiratory Acidosis Less CO2 = Less acidic = Respiratory Alkalosis

Diagnose: • 54y/o male presents to ED with 4 days of progressive dyspnea • Previously was an avid jogger, now barely made it from parking lot • Recently started remodeling old house • Associated with subjective fever, non-productive cough • No wheezing, orthopnea, chest pain, or LEE Physical Exam: • Afebrile, 89% on Room Air at rest • Mild conversational dyspnea Lung Bx: • Poorly formed granuloma CT Chest: • small nodules, ground glass attenuation, and air-trapping (very subtle)

Hypersensitivity Pneumonitis Multiple possible etiologies, such as Farmer's Lung, Bird Fancier's Lung, etc.

++++++++++++++++++++++++++++++++++++++++++ All questions about the pressure vs. volume curves of lungs, chest wall, or both will ask you about one of these: -Where is FRC on the combination curve? -At which point on that curve is the chest wall at its relaxed volume, i.e., neither pulling inward or pulling outward? -At which point on that curve are both the thorax and the lungs pulling inward? Dr. Jennings said that himself.

IMAGE: -Point C: FRC (point of inflection) -Point D: Chest wall is at relaxed volume -Point E: Both thorax and lungs are pulling inward

What would happen if bronchi were too large or too small?

If too small, not enough air gets to bottom of resp. tree. If too big, air won't want to flow down the tree. There's more space for the air to occupy.

++++++++++++++++++ Overview of Body's Adaptation to High Altitude -Function of increased 2,3-DPG -WHAT HAPPENS TO HEMATOCRIT? Time comparison: If stem says high altitude for short time 24-48 hrs, or longer times (weeks onwards). What happens right away and what happens over time?

Immediate response: Increase RR, which leads to low CO2 / alkalosis. Hgb has higher affinity for O2, better absorption of O2 from alveoli. Days: Increase oxygen unloading to tissues by increasing 2,3-DPG, which decreases Hgb affinity for O2 (Right-shift). Weeks: Epo, increased Hct - Over the first 24-48 hours at high altitude, there is slow transport of H+ and/or HCO3- across the blood brain barrier to partially relieve the alkalinization caused by low PCO2. This removes some of the braking effect of low CO2, and ventilation increases to further alleviate the hypoxemia. The alkalosis resulting from increased ventilation helps O2 loading in the lung at high altitude. - At longer times (several days), the kidneys partially correct the respiratory alkalosis associated with increased ventilation, further lowering the braking effect of the central chemoreceptors. - Over even longer times (weeks), there is an increase in hematocrit because of increased EPO produced by the kidneys. The increase in hematocrit is the most important long-term adaptation to high altitude, because it increases the O2 carrying capacity of blood. Increased hematocrit means lots of available Hgb / RBCs. -There is also a change in red cell metabolism and an increase in the concentration of 2,3-DPG (2,3-bisphosphoglycerate), which shifts the hemoglobin dissociation curve to the right and facilitates O2 delivery to the tissues.

Kartagener's syndrome

Immotile cilia 2° to defective dynein arms infection, situs inversus (everything on wrong side), sterility Immotile cilia due to a dynein arm defect. Results in male and female infertility (sperm immotile), bronchiectasis, and recurrent sinusitis (bacteria and particles not pushed out); associated w/ situs inversus.

What is the overall problem in pulmonary hypertension that causes symptoms?

Inability to maintain Cardiac Output, and thus failure to supply tissues with enough O2. Initially, dyspnea only on exertion, but eventually at rest too.

Effect of Bronchial Stretch Receptor activation on breathing.

Increased pressure in bronchioles activates these stretch receptors, which inhibit the Dorsal Respiratory Group to inhibit inspiration.

Lung crackles indicate what 3 main possible conditions? Wheezing indicates what 2?

Indic: Pneumo, atelectasis, pulm edema; pulm fibrosis, acute bronchitis, bronchiectasis Wheezing: asthma, COPD (bronchitis, emphysema)

Activation of Irritant Receptors in the airway has what effect on breathing?

Induces a cough These are activated when you breathe in something that's not air, and it tries to expell whatever you inhaled. These receptors respond to both mechanical and chemical stimuli. ________________________ -Rapid inspiration of more than a normal tidal volume of air. -Glottis/epiglottis closes to block airflow. -Expiratory muscles (abdominals and internal intercostals) contract forcefully against the closed airway to create a high pressure. -Glottis/epiglottis opens to allow very rapid expulsion of air, mucus, inhaled particulates, and sometimes cells.

What is a forced expiration test? (Lab) How do you determine the Forced Vital Capacity & FEV from the volume plot? Define each.

Inhale, then exhale as hard as you can. Total air expired is "Forced Vital Capacity" FVC. Volume expired in 1 sec = FEV1 (normally ~80% of FVC) FVC = highest volume - lowest volume FEV = highest volume - volume at 1 second

Pathology of Idiopathic Pulmonary Fibrosis (IPF) / Usual Interstitial Pneumonia (UIP) Interstitial fibrosis in UIP/IPF is believed to result from repeated injury and defective repair of what part of the lungs? Possibly excessive activation of ___, a pro-fibrotic factor, by inflammatory cells.

Interstitial fibrosis in UIP/IPF is believed to result from repeated injury and defective repair of alveolar epithelium. Possibly excessive activation of pro-fibrotic factor TGF-β from inflammatory cells. Ultimately, Repeat injury w/o repair of alveoli

Interstitial Lung Diseases / Diffuse Parenchymal Lung Diseases (DLPDs): What is the interstitium? What happens in all of these conditions?

Interstitium is labeled F in Image. If nice and clean, oxygen can easily travel across interstitium to reach blood vessel. But if it's clogged up, O2 has a hard time getting across. Alveolar endothelial cells are damaged in all of the DLPDs from irritants. NOTE: DLPD is different from COPD, asthma, etc. but all of them have some overlapping symptoms, such as dyspnea. All DLPDs have overlapping symptoms: 1. Exertional dyspnea (doesn't always mean COPD!) 2. Diffuse infiltrates on CXR 3. PFT shows Restrictive Disease 4. Impaired oxygenation These also overlap woth COPD, so you need more information. Common DPLDs: Idiopathic Pulmonary Fibrosis, Sarcoidosis, Hypersensitivity Pneumonitis, Asbestosis.

What is the relationship between lung volume and resistance to air flow? What molecules induce relaxation vs. contraction of bronchial smooth muscle?

Inversely proportional -Relaxation: ß2 Adrenergic, Nitric oxide (NO) -Contraction: Acetylcholine, histamine, prostaglandin F2a

What class of asthma medication is only clinically used to potentiate the effects of corticosteroids?

LABAs (Long-Term Beta Agonists) These don't target the cause of asthma. They just produce some bronchodilation for 12-24 hours. But alone, these do not properly treat asthma. But they make the effects of corticosteroids even stronger and they are only used in combination with corticosteroids, not alone. Salmeterol, Formoterol

The ratio of what to what in amniotic fluid is used to determine fetal lung maturity. Mature fetal lungs should have more ___ than ___. Healthy lungs -- ratio is at least ___.

Lecithin : Sphingomyelin ^ AKA L/S ratio Healthy, mature fetal lungs should have more LECITHIN, which is the primary component of surfactant. Remember that the big danger is Neonatal Respiratory Distress Syndrome which is caused by a lack of surfactant. And surfactant is made later in development. So all this makes sense. Specific values: • If L/S ratio >2, healthy • If L/S ratio < 1.5, higher NRDS risk

Histology of Usual Interstitial Pneumonia / Interstitial Pulmonary Fibrosis (UIP/IPF): - What does subpleural fibrosis look like? - What does the honeycomb lung look like?

Left Image: Subpleural fibrosis (thick pink) -- Fibrosis (F) with interspersed normal lung (N). "Notice subpleural fibrosis." Right Image: Honeycomb cysts (white pockets) within the fibrotic areas. Not solid anymore. Meanwhile, still areas of normal lung.

Types of Atelectasis: Contraction L.O. - Describe the different forms of atelectasis.

Local or generalized fibrotic change in the lung or pleura: -Scarring due to injury -lung disease -surgery Prevents full expansion

Name, identify, and give the location of the lung layer from which a mesothelioma can arise. Briefly, compare and contrast this layer to endothelium.

Malignant mesothelioma is a type of cancer that occurs in the thin layer of tissue that covers the majority of your internal organs (mesothelium). Function of Mesothelium: It makes serous fluid and is the outermost layer of visceral pleura, which is attached to the lung. Fluid prevents friction as pleura slide.

+++++++ ON EXAM +++++++ The septum transversum arises from

Mesoderm

Define minute ventilation and alveolar ventilation in terms of respiratory rate, tidal volume, and dead space volume. Equations for Minute Ventilation and Alveolar Ventilation

Minute Ventillation: V̇e = Tidal volume x Respiratory Rate Alveolar Ventilation: V̇a = (Vt - Vd) x Respiratory Rate - not all of inspired air reaches alvoli due to dead space, which is why you have to take that volume into account here. Vt = tidal volume Vd = volume of dead space (conductive path with no gas exchange)

PO2 = 26 PCO2 = 49 SatO2 = 45% O2 content = 9 mLO2/dL blood. This is ___ blood from a person doing what?

Mixed venous blood from a healthy adult who is exercising.

++++++++++++++ Overall equation for Oxygen Content in blood. (will come back to this in later cards from PI #2)

O2 Content = (1.34) (% Sat./100) (Hgb Conc.) + (0.003)(PO2)

+++++++ Important primarily for boards ++++++++ What gene is associated with Congenital Central Alveolar Hypoventilation Syndrome (basically sleep apnea in INFANTS). Might not be on this exam (unclear) but always shows up on boards, including pulmonary boards. "Easy test question because it has one correct answer."

Mutation of the PHOX2B gene is present MNEM: Sleepy Phox

Forced Expiration Flow-Volume Curve -- how to interpret; what is the relationship between flow and volume of air expired.

NOTE- this is the basic part of the flow-volume loops. As you move towards the right, increased expiration volume and decreased volume in actual lungs. The rapid increase at the beginning -- ignore -- that's just where you inspire as much as possible very quickly. Also know that X-axis is NOT a good indicatior of time! The first second is really long on these plots.

Diagnose: • Excessive daytime sleepiness • Cataplexy: brief, emotionally-triggered episodes of muscle weakness • CSF hypocrein‐1 Level <110ng/L • Had a sleep study done that ruled out apneas and other sleep DOs.

Narcolepsy with Cataplexy Cataplexy: emotionally-triggered muscle weakness (e.g., see an old friend, and drop the glass you were holding) If no cataplexy, its Narcolepsy w/o Cataplexy.

++++ EXAM QUESTION FROM THIS SLIDE ++++ Side-by-Side Comparison of Nasal Mucosa vs. Olfactory Mucosa Histology -- UNIQUE FEATURES FOR EACH -- Identify each and which type each goes with / which picture each is in (can be both): Bold = what to focus on/ recognize - Ciliated cells - Basal cells - Seromucous gl. - DNES, brush and serous cells - Goblet cells - Olf. cells - Sustentacular cells - Bowman's glands (serous) - Olfactory nerve bundles

Nasal: • Shorter epithelial cells - short and fat • Motile cilia - Mnem: Nose filters air before it goes to lungs, so motile cilia are needed catch particles and move them out. • UNIQUE: ➥ Cilia / Hairs -- on top -- you can see more prominent hairs on top compared to olfactory, and they go in different directions. ➥ Look at BOTTOM -- DNES (Brush Serous Border) -- texture at bottom that's not in the olfactory pic. ➥ Seromucosal glands ➥ Goblet cells in the top layer -- white ovals -- NOT PRESENT IN OLFACTORY epithelium Olfactory: • Taller epithelial cells - tall and skinny • Non-motile cilia • UNIQUE: ➥ Cilia / Hairs -- on top -- are shorter and more uniform. They are used to help you cough up any particles in lungs. ➥ Bottom: Nothing special. Remember, only these pictures are testable. Dr. Phelan: -Focus on Goblet, Basal, and Ciliated cells up in that top layer. -NO GOBLETS in olfactory

A woman is on mechanical ventilation with supplemental O2. pH = 7.48 PCO2 = 28 mmHg PO2 = 150 mmHg Hgb = 12 What should be done to fix her problem?

Need to decrease ventilation rate and decrease the inspired O2 Her problem is that she is ventilating too much and her PCO2 is too low. So she needs to ventilate less. You can lower her O2 because it's at a very high 150 mmHg.

++++++++++++++ What is the normal mmHg of O2 in: -Inspired Air (PiO2) -Alveolar (PAO2) -Pulmonary End-Capillary Blood (PO2) -Arterial Blood (PaO2) -Central (mixed) venous PO2

O2 high at first; keeps going down as it's delivered. -PiO2 = 150mmHg -PAO2 = 100 mmHg -PO2 = 100 mmHg -PaO2 = 80-100 mmHg -MVP = 40 mmHg ^ (MVP depends on the tissues)

+++++++ Important to Know ++++++++ The FEV value is most decreased is obstructive or restrictive diseases?

Obstructive "Most important one to note from that chart"

Which asthma medication is a humanized monoclonal antibody that targets IgE produced by T2H cells? How is it administered? 3 Indications

Omalizumab Omalizumab is a genetically humanized monoclonal antibody that targets the region of the IgE that binds to its FCε-R1 receptors on mast cells and thus inhibits the binding of IgE to mast cells without activating the IgE already bound to those cells. • administered subcutaneously every 2-4 weeks • decreases the amount of corticosteroid needed. • Omalizumab is most effective with patients with a high corticosteroid requirement, poor pulmonary function, and frequent exacerbations. VERY EXPENSIVE

What happens to the levels of each of these as a result of progressive exercise (increasing rate of oxygen consumption)? -Ventilation (RR) -Alveolar PO2 -Arterial PO2 -Arterial PCO2 -Mixed Venous PO2 -Arterial pH

Overall, the oxygen and CO2 pressures remain fairly constant despite heavy exercise. • Ventilation (VE): rises in parallel (orange dashed curve) with O2 consumption. • Alveolar PO2: PAO2 (blue) is constant. because the increased ventilation matches the increased O2 consumption. • Arterial PO2: PaO2 (red) is constant. • Arterial PCO2: PaCO2 (purple) is also constant, again because the increase in ventilation matches the increase in CO2 production. • Mixed venous PO2: PvO2 (green) is not constant, because, even at relatively low work levels, working muscle extracts a higher fraction of O2 from blood than at rest. It slightly decreases. • At very extreme exercise, arterial pH drops because the exercise has become anaerobic (i.e., lactic acid production). First Aid: Graphless summary of what happens: • ↑ CO2 Production • ↑ O2 consumption • ↑ ventilation rate to meet O2 demand • ↑ pulmonary blood flow due to ↑ cardiac output • ↓ pH during strenuous exercise (lactic acidosis) • ↑ in venous CO2 content and ↓ in venous O2 content • No change in PaO2 and PaCO2 • V/Q ratio from apex to base more uniform

Treatment of PAH -- primarily involves what medications (1 solo, plus 2 in a combo)? Treatment of Groups 2-5 PH?

PAH: Epoprostenol to improve outcome. Improve exercise tolerance. Ambrisentan + Tadalafil is standard recommendation. MNEM: Use A+T for PAH. PH: Treat the underlying condition (Left heart failure, lung disease, pulmonary artery obstruction, etc.)

PO2 = 25 O2 sat = 75% O2 content = 15 a) Polycythemia b) Anemia c) Left-shifted Hgb d) Low C.O. e) Fever

PO2 is low, O2 sat and content are normal. c) Left-shifted Hgb -Fick's principle: amount of O2 removed from blood depends on availability and how much is being used. -PO2 is low, but saturation is normal. So this would be a left shift. Know axes! Anemia would affect O2 content Low C.O. -- changes O2 content Fever causes a R-shift

Which Pulmonary Pressure is the pressure in the thin layer of fluid between visceral and parietal pleura? Is it usually positive, negative, or equal to zero? Equation

Pleural Pressure (Ppl) ^ AKA Intrapleural pressure It is usually negative. Pleural pressure refers to the pressure within the pleural cavity, between the visceral and parietal pleura. Normally, the pressure within the pleural cavity is slightly less than the atmospheric pressure, in what is known as negative pressure. The elastic recoil of the lungs is balanced by the outward pull of the thorax during inspiration. Equation: Ppl = Pa - PL From the main equation: PL = Pa - Ppl

What long-term condition can result from having a DVT? What does this look like clinically?

Post-thrombotic syndrome -- skin problems: scaling, sores. Varicose veins. Occurs in 30% of DVT patients. e.g., The same patient presents 2 years later (never came back for follow-up after treatment for her DVT/PE) complaining of swelling, pain, increased warmth and scaling of her left leg for the past few months.

Vertical Lung -- Common STEP Q's -- Basics Ppl is usually -5cmH2O but how does it differ when the lung is upright / vertical (sitting up or standing)? What about Transpulmonary pressure? Higher at top or bottom? > Pa > Ppl > PL

Ppl (pleural pressure) is less negative (larger) at the lower parts of the lungs. Think of it like a slinky. PL is larger at the top of the lungs.

The simple columnar to simple cuboidal transition occurs where?

Primary Brochioles Bronchi --> Bronchioles: -columnar to cuboidal -no more cartilage -no more submucosal glands

++++++++++ ON EXAM ++++++++++++++ Inhaled Corticosteroids: -2 Prototypes -MoA

Prototypes: fluticasone, budesonide MoA: Inhibit IL-4 and IL-5 to reduce the amount of IgE produced. This results in less inflammation of the airway system. Apoptosis of TH2 cells and Eosinophils. Use: Prophylaxis of asthma -- treats the cause of it. -But still doesn't cure asthma.

What is the initial histological change in a patient with cancer in the false vocal cords (of trachea)?

Pseudostratified ciliated columnar => Stratified squamous epithelium Ciliated columnar is respiratory; more in the true vocal cords.

Pulmonary Hypertension - Classifications: Groups 1-5 -- what is each group? Difference between Pulmonary Arterial Hypertension and Pulmonary Hypertension. Major causes of Pulmonary Hypertension

Pulmonary Hypertension = increased pulmonary artery pressure. Pulmonary arterial hypertension (PAH) -used to denote idiopathic pulmonary hypertension and related disorders in Group 1 Pulmonary hypertension (PH) - Refers to increased pressures in the pulmonary circulation in general and is the term used for all of the other "secondary" categories. PAH is when the hypertension is idiopathic or due to something not listed in Groups 2-5. Pulmonary Hypertension - due to: 2. Left heart disease 3. Chronic lung disease (COPD, ILD/DPLD, or Sleep apnea) &/or Hypoxemia 4. Pulmonary artery obstructions 5. Multifactoral mechanisms (e.g., renal failure, sarcoidosis)

Diagnose: • Histology: multiple well-formed epithelioid granulomas with multinucleated giant cells (blue arrows) and no necrosis. • Hilar lymphadenopathy or lung involvement • Presents with insidious onset of dyspnea, cough, chest pain, hemoptysis, or constitutional symptoms. • May also affect skin, eye, spleen, liver, bone marrow, oral mucosa, and salivary glands.

Sarcoidosis

Diagnose: • 23y/o African American female presents with dyspnea beginning 2 months ago • Progressive, unable to climb stairs • Exacerbated by exertion, relieved with rest • Associated with wheezing, non-productive cough, malaise, and subjective fever • No associated chest pain, orthopnea, or PND Physical Exam: -Rash / skin patches on upper back. -97% on Room Air at rest, 93% when walking -No conversational Dyspnea -Mild expiratory wheezes, some inspiratory crackles Imaging: Infiltration; moreso in upper lobe. Lung Bx: Well formed, non-necrotizing granuloma with surrounding fibrosis. PFTs: Restrictive F/V Shape • FEV1/FVC ratio: 65% • FVC: 68% of predicted • FEV1: 44% of predicted • DLCO: 52% of predicted • Total lung capacity: 64% of predicted • Residual volume: 72% of predicted

Sarcoidosis The growth of tiny collections of inflammatory cells in different parts of the body. Young, African-American Female - Clue for Sarcoidosis Lymphadenopathy, Skin patches / rash common. This is one of the DPLDs / ILDs; characteristic decreased DLCO, respiratory crackles.

Silicosis histology

Silicotic nodules are circumscribed nodules of fibrosis (arrow) (scar tissue), often with prominent dense pink collagen formation. Pigmented macrophages may or may not be present.

+++++++++++++ When there is tissue hypoxia, WHAT HAPPENS TO THE SIZE OF PULMONARY VESSELS?

Size of vessels decreases in tissue hypoxia. It is the ONLY tissue that vasoconstricts in response to hypoxia! Common board question. So there is less blood flow because there isn't enough available oxygen anyways. Might as well send it out to rest of body. Blood diverted away from hypoxic regions to the better ventilated parts of the lung to minimize mismatch of ventilation and perfusion. Usually, the lungs are a low-resistance, high-compliance system, so hypoxia is a deviation from that.

Proper VTE workup: - If imaging is indicated for a suspected PE (meets Well's criteria, meaning high suspicion), what is the best imaging modality to visualize a PE? - What about D-dimers?

Spiral CT scan. Lets you see exactly where the clot is. D-dimers are also often measured for suspected PEs. D-Dimers are breakdown products of clots. However, while highly sensitive for PE, not specific (could be other things). So not a first-line diagnostic, but if you see elevated D-dimers, think PE. Other imaging: Duplex lets you see clots in the leg (ultrasound + doppler).

- - - - unless emphasized later, ignore; not clearly in objectives - - - - Level of gas exchange based on severity / level of pulmonary edema: Stage 1 - Interstitial Stage 2 - Crescentic filling Stage 3 - Alveolar Flooding

Stage 1: Interstitial Very little effect on gas exchange Stage II: Crescentic filling Some effect on gas exchange Stage III: Alveolar Flooding Gas exchange blocked

Static Compliance vs Dynamic Compliance -- definitions What events, conditions, or substances would decrease static compliance? What would decrease dynamic compliance?

Static compliance is determined by the elastic properties of the lungs and thorax and is measured under conditions of no airflow. -decreased by NSAIDS, obesity, fibrosis, etc. Dynamic compliance is determined by static compliance and the contribution of airway resistance. Dynamic compliance is lower than static compliance. How much lower depends on airway resistance. -decreased by anything that increases airway resistance: • Asthma • COPD • Bronchitis • Bronchiectasis

++++ Could be a pathway question; repeated several times++++ Pathway of oxygen from lungs to tissues and back; include gas exchange part of this loop/cycle.

Steps in moving O2 from atmosphere to tissue and CO2 from tissue to atmosphere: 1. Ventilation: Moving new air into alveoli and expiring alveolar air. 2. Gas Exchange: O2 diffusing from air to pulmonary capillary blood and CO2 moving in the opposite direction. 3. Transport of O2 and CO2 in the blood. 4. Tissue Gas Exchange: Diffusion of O2 from blood to tissue and CO2 from tissue to blood in systemic capillaries. 5. Cellular O2 use and CO2 production. 1-3 had a red box around them in the other slide about the pathway.

Chemical spill results in damage to olfactory region only. What type of cells are in this region, but not in surrounding regions?

Sustentacular Cells (support) Bowman's glands -- NO seromucosal glands because you don't want mucus in olfactory path.

2 main diagnostic tests that are diagnostic of cystic fibrosis if positive

Sweat Chloride Test IRT (Immunoreactive Trypsinogen) test Even though CF involves retention of Cl, a large amount of Cl in sweat indicates CF.

What immune cell is responsible for asthma?

TH2 cells (Type 2 Helper T cells) Usually, there is a balance between Type 1 and Type 2, but in asthma, Type 2 is over-active. See Image: TH2 => Eosinophils + Mast Cells (e.g., leukotrienes) + IgE => Asthma / Bronchoconstriction Corticosteroids, Leukotriene Inhibitors, Mast cell degranulation inhibitors, and IgE inhibitors: Control asthma at the level of eosinophils, mast cells, and IgE. Beta agonists merely relieve symptoms, but don't fix those underlying causes.

Describe primary changes in respiratory tree tissues leading to or resulting in asthma. What decreases in diameter?

Terminal BRONCHIOLES decrease in size (intermittent bronchoconstriction). And have excess mucus. Eosinophils are a key unique feature of asthma because asthma is an allergic response. - Reduced opening and excess mucous - Smooth muscle layers undergo prolonged contraction during expiration

If a person has inflamed cartilaginous structures in the respiratory tree, what is the smallest/lowest level of the respiratory tree affected?

Tertiary Bronchi Bronchi have hyaline cartilage, Bronchioles don't.

Larynx: • The larynx is made of / strengthened by what 2 types of Cartilage? • The larynx is lined by ___ ___ ___ epithelium, EXCEPT for what 2 parts of the larynx, which contain what type of epithelium?

The Larynx is lined by pseudostratrified ciliated columnar epithelium ..... EXCEPT for 2 parts that are lined by stratified squamous non-keratinized epithelium: 1. Epiglottis (superior surface) 2. Vocal cords/folds (Both are hard surfaces -- makes sense w/ keratinization)

Nasal Cavity (part of Extrapulmonary Conducting Portion): PART 1 • 3 distinct regions • The Respiratory part of the Nasal Cavity is Lined by ___ ___ ___ Epithelium and has a ___ ___ Tightly Bound to the underlying Bone or Cartilage. • What is the mucoperiosteum?

The Nasal Cavity Consists of Three Distinct Regions: 1. The Vestibule (inside of nose) 2. The Respiratory Portion 3. The Olfactory Portion • The respiratory portion of the nasal cavity is lined by Pseudostratified Ciliated Columnar Epithelial Cells. • It has a Lamina Propria tightly attached to the bone/cartilage in the nose. -- LP contains the mucoperiosteum which is richly vascularized. Characteristics of this pseudostratified epithelium (in next card): -CONTAINS Specialized Olfactory Cells -DOES NOT CONTAIN Goblet Cells

++++++++++++++++++ Compare fetal vs. maternal Chest Wall and Lung Curves on % Total Lung Capacity vs. Pressure graphs. (P/V relationships for chest wall and lungs -- how is it different in a fetus?)

The curves for the adult (right) are similar to what we talked about in the pulmonary mechanics lecture. The dotted curve labeled "W" is for the chest wall (including diaphragm) during passive inflation involving no muscles. The adult chest wall at Functional Residual Capacity (FRC) is pulling outward, and a negative pressure is needed to keep it at FRC. The same is true of the neonatal chest wall (left), except that the neonatal chest wall has a much higher compliance and is not pulling outward as vigorously, and the balance between the inward pull of the lungs and the outward pull of the thorax is shifted to lower lung volumes. Therefore, FRC relative to total lung capacity is lower in the neonate (upward red arrows).

Man with pulmonary fibrosis at rest: PaO2 = 60 mmHg PCO2 = 40 mmHg pH = 7.40 He then begins exercising. Why does his PO2 drop?

The fibrosis causes a diffusion impairment that is even worse during exercise because the pulmonary capillary transmit time decreases (faster) Pulmonary fibrosis scars and thickens the tissue around and between the air sacs (alveoli) in your lungs. This makes it more difficult for oxygen to pass into your bloodstream.

Control of breathing by the Brainstem 1. What part of the medulla is active during inspiration? 2. What part is activate during expiration and heavy exercise, but inactive during normal quiet breathing? 3. Signals are transmitted by which 2 CNs?

The rhythm of breathing comes from the medullary and pons respiratory center in the reticular formation of the brain stem. It is normally involuntary, but can be voluntary for singing, swimming, etc. Voluntary vs. Involuntary are controlled by different parts of the brainstem. The medullary respiratory center is divided into Dorsal and Ventral Respiratory Groups: > Dorsal Respiratory Group (DRG) is activate during inspiration. > Ventral Respiratory Group (VRG) contains the main expiratory neurons, which are inactive during quiet breathing but active during exercise. > Signals are carried by the vagus and glossopharyngeal nerves -- 9 & 10 are the ones that control systemic stuff.

Diagnose: • 65 y/o F presents to clinic with dyspnea -Began 6 months ago -Progressive and is now unable to walk to mailbox -Exacerbated by exertion, relieved by rest -Associated with non-productive cough -No associated fever, chest pain, orthopnea, LEE, or wheezing. • No Hx of smoking • Physical Exam: - Saturation: 91% on Room Air at rest, 85% when walking - Conversational Dyspnea - Dry, "Velcro" crackles in bilateral lung bases, no wheezing • CXR and Chest CT: Diffuse infiltrates; Usual Interstitial Pneumonia (UIP) pattern; honeycombing. • PFTs: Restrictive pattern on F/V loop. - FEV1/FVC ratio: 94% - FVC: 65% of predicted - FEV1: 62% of predicted - DLCO: 44% of predicted - Total lung capacity: 54% of predicted - Residual volume: 46% of predicted

These findings point towards a DPLD / ILD. DLCO is low, which is highly indicative of this. Also, honeycombing (Image). Older patient, velcro crackles -- clues for IPF. History revealed nothing suspicious, like handling birds, so good guess is Idiopathic Pulmonary Fibrosis.

++++++ RECOGNIZE ON EXAM Q! ++++++ Dust Cells: -What are they? -Where are they? -Function? -Point out on a microscopic image.

They are simply macrophages in the alveoli that gobble up fine-particle debris (dust). They look like dust on a microcope -- dark black.

Hypersensitivity Pneumonitis: -3 main causes -Type ___ & ___ Hypersensitivity Reactions -You should see what on imaging? Histology?

This is one of the two granuloma diseases of the lung, along with Sarcoidosis. Caused by intense, often prolonged exposure to inhaled organic antigens 3 Main Causes: • Farmer's lung (exposure to thermophilic actinomycetes in moldy hay) • Bird fancier's/Pigeon breeder's lung (exposure to avian proteins in feathers, serum and excreta) • Humidifier/Air condition lung (exposure to water contaminated by thermophilic bacteria) Types III & IV Hypersensitivity Reactions CXR: diffuse and nodular infiltrates Histology: poorly-formed interstitial granulomas with chronic inflammation (lymphocytes + Multinucleated giant cell granulomas). Sxs: recurring episodes of fever, dyspnea, cough, leukocytosis

What treatment would you use in a VTE (DVT/PE) patient with hypotension / shock (hemodynamically unstable)

Thrombolytic Therapy (thrombolytic agents) Use for patients who are hemodynamically unstable. Hypotension or shock!

Effect of Anatomical Dead Space: The first portion of air inhaled in each breath is actually what?

Tidal volume is inhaled in 2 stages: First portion inhaled is residual volume from previous inhalation. Second portion is new air. Dead space air (air that did not undergo gas exchange) is about 1/3 of the total tidal volume. - Each Inspiration: New air reaching alveoli = VT - VD. - Same idea applies to expiration: first 150 ml expired is dead space air that has not exchanged gas with blood. Alveolar air expired is VT - VD. - So Alveolar Ventilation VA= (VT - VD) x RR - Normally, Dead Space is about 30% of Tidal Volume: VD/VT = 0.3 - If there is severe mismatch of ventilation and blood flow in parts of lung, there can be Alveolar Dead Space, to be discussed later this week.

Respiratory Distress Syndrome -- Cell Type involved?

Type 2 Pneumocytes Functions: 1. Stem Cells 2. Produce surfactant Thus, surfactant is not produced in alveoli and Neonatal RDS results.

+++++++ Differentiate between Type I Pneumocytes and Type II Pneumocytes -Microscopic appearance -Function of Type II -These are both ONLY located in what part of the respiratory tree?

Type I is most common -- 95% of lung cells -- it's just the epithelial cell composing the alveoli. Type II Pneumocytes Are Stem Cells that Regenerate Type I and Type II Pneumocytes (proliferate after injury) -- and produce Surfactant. Without Type II, you cannot breathe ==> Respiratory Distress Syndrome. Located in the simple squamous epithelium of Alveoli. (analogous to those club cells that were located in the simple cuboidal epithelium / respiratory epithelium of bronchioles). Microscope: Type 1 has a crescent shape in it. Type 2 has a lighter purple circular shape in it.

Explain the reasons for the O2 saturation levels in different parts of the fetal circulation, including the umbilical vein, IVC, left ventricle right ventricle, aorta, SVC. +++++++++++++++++++++++++++ Rank those in order of oxygen saturation of Hgb -- i.e., higher vs. lower oxygen at blood -- it's not as uniform as adult circulation. ^ "You don't need to memorize all the saturations, but you should know, qualitatively, the relative saturation of blood in various parts of the circuit." Where is it the highest? Where is it the lowest?

Umbilical vein blood has the highest amount of oxygen. Makes sense -- this is the only source of oxygen inside the womb. Then oxygen gets dropped off at various locations. The umbilical vein is long though, so Maternal PO2 is higher. Allows O2 to travel towards fetus. Fetal Hgb concentration is higher than maternal, and fetal P50 is lower than maternal to help with O2 unloading. MNEM, in order: UILAR DS (DA, SVC) > Umbilical vein (NOT artery), IVC, & LV have high O2 saturation. > Aorta and RV have a moderate level of O2 saturation (~50%) > SVC and other vv. returning from lower body have the lowest O2 saturation. Blood has dropped off a lot of its oxygen at this point. > Umbilical artery has even lower O2 sat. That's because it's going into placenta, wheras vein is leaving placenta with O2-rich blood. IMAGE: The focus of this ILA is on O2 delivery to fetal tissue. The figure shows the schematic of fetal circulation. ______________________________ Extra info for reasons for trend in levels: - Umbilical Vein: The exchange of O2 between maternal and fetal blood in the placenta gives in umbilical venous blood the highest saturation (80%) in the fetal circulation. - IVC: Umbilical venous blood returns to the IVC via the ductus venosus and mixes with venous blood (26%) coming from the lower body, resulting in a final saturation of ~67%. The volume of blood coming back from the placenta is higher than that from the rest of the lower body. - LV: The oxygenated IVC blood comes back into the RA but does not mix thoroughly with the low-O2 blood from the SVC. Instead, more of the oxygenated IVC blood goes into the LA via the Foramen Ovale, resulting in LV blood with 62% saturation. The arterial blood perfusing the upper body therefore has 62% saturation. - RV & Ductus Arteriosus: Some of the oxygenated IVC blood goes from the RA to RV, but much of the blood going to the RV comes from the SVC, which is less oxygenated. As a result, the saturation in the RV is only 52%. Some of this blood goes to the lung, but most goes to the aorta via the Ductus Arteriosus. - Descending Aorta: Blood from the LV mixes with other fetal venous blood to give a lower fetal arterial saturation (~60%). So the arterial blood going to the fetal brain has a higher saturation (62%) than the arterial blood supplying the fetal kidneys, GI tract, and lower limbs (58%). In adults, systemic arterial blood has the same O2 saturation everywhere.

PaO2 = 55mmHg SatO2 = 88% PaCO2 = 40 mmHg What is the likely issue?

V/Q abnormality, causing an elevated A-a gradient. Normal CO2, normal ventilation, so PAO2 should be 100. Observed is 55, therefore there's an elevated A-a gradient.

(Vertical Lung Question) A man is standing at rest. ↑ or ↓ : -V/Q -PO2 -PCO2

V/Q: ↑ PO2: ↑ PCO2: ↓ There is less perfusion at the apex. Q is very low, so V/Q is high. V/Q is highest at apex, lowest at the base.

++++++++ IMPORTANT TO KNOW THIS ++++++++++ Primary neurotransmitter that induces sleep. Other: What two substances induce the waking cycle, and are deficient in narcolepsy?

VLPO (thalamus) causes release of GABA, which induces sleep. KNOW THAT!!! The GABA channel is a chloride channel that inhibits neuron firing. Everything that makes you sleep (e.g., benzos, propofol & other anesthetics, barbituates, etc.) works on this channel. Hypocretin & Orexin are released later in sleep to induce the waking cycle. These are often deficient in narcolepsy. Learn this diagram because it'll help you understand the sleep breathing conditions.

+++++++++++++++++++ Diagnose: > Normal Chest X-ray > Abnormal Pulse Ox / SatO2 (low, <94%) -- blood is not getting enough oxygen anymore.

Venous Thromboembolism (DVT w/wo PE) Normal Chest X-ray (but not normal CT). Most CXRs in patients with a PE are normal. Abnormal Pulse Ox (low) -- blood is not getting enough oxygen anymore. Symptoms of pulmonary embolism include: > difficulty breathing > chest pain on inspiration > palpitations Clinical signs: > low blood oxygen saturation & cyanosis > rapid breathing (tachypnea) > rapid heart rate (tachycardia). Severe cases of PE can lead to collapse and abnormally low blood pressure

Response of Peripheral Chemoreceptors in aorta and carotids to Carbon Monoxide?

WEAK or NO response to CO. For this lecture, the point is that the peripheral chemoreceptors are not stimulated strongly during CO poisoning. This is because O2 is normal. MNEM: Peripheral chemoreceptors are naive and CO sneaks by. _______ Explanation: The peripheral chemoreceptors are sensitive to PaO2 and not arterial O2 content. This is because blood flow to the carotid and aortic bodies is high, and O2 extraction is therefore low (Fick principle). A consequence of this is that the carotid bodies do not respond strongly to CO poisoning as long as PaO2 is normal (which it can be if someone is ventilating normally and the inspired air has normal PO2).

+++++ IMPORTANT CONCEPT (but simple to understand) +++++ Oxygen diffuses from lungs (air) into blood until an equilibrium is reached. This equilibrium is when the ___ of oxygen in the air and blood are equal.

When the partial pressures are equal. NOT concentration. Only a small fraction of lung O2 diffuses into blood to meet equilibrium. Also, as expected, if one pressure drops, equilibrium will be re-established by having oxygen flow towards the side of the capillary where O2 pressure dropped.

- - - - unless emphasized later, ignore - - - - Simplified way to determine net osmotic pressure.

Whereas hydrostatic pressure forces fluid out of the capillary, osmotic pressure draws fluid back in.

PFT F/V Loop shape for DPLDs/ILDs What about: -FEV1 -FVC -FEV1/FVC -TLC -DLCO

Witch Hat shape on PFT. Restrictive. DLCO low -- VERY IMPORTANT ^ Oxygen is not crossing alveolar wall properly.

Chest XRay for DPLDs/ILDs What 3 ILDs tend to affect the upper lobes? What 2 ILDs tend to affect the lower lobes?

You can see infiltration into the lungs. Sarcoidosis, Coal Worker's Pneumonitis, and Abestosis tend to affect upper lobes. IPF and Silicosis tend to affect lower lobes.

Chest CT for DPLDs/ILDs

You can see infiltration. Much more diagnostic than a CXR. Honeycombing - pretty much diagnostic for one of the DPLDs / ILDs

Woman has shortness of breath and: > PO2 is normal > SatO2 is normal > but O2 content is low What does she have? a) Chronic blood loss b) Cyanide intoxication c) At high altitude d) Morbid obesity e) Tetralogy of Fallot

a) Chronic blood loss (similar to anemia) -- these affect O2 content b) CN intoxication would be normal everything -- PO2, SatO2, and O2 content c - e) These would have abnormal PO2 &/or SatO2 e) this is a shunt, which means low everything

Pleural effusion appearance on CT

abnormal accumulation of fluid in the pleural space

Which lung volume and which 2 capacities cannot be measured by spirometry?

anything with RV Capacities: total lung capacity functional residual capacity RV is literally the volume of air you cannot expel, so spirometry could not possibly measure that.

Diffusion Capacity in the lungs really means what?

diffusion capacity of the lung for carbon monoxide

++++++++++++++ Emphysema: Histology What do the alveoli look like in emphysema?

dilated alveoli The alveoli are large and spread out. Larger spaces.

What is Hypercapnia?

too much CO2 in the blood. E.g., chronic obstructive pulmonary disease (COPD) and anything else that slows exhalation of CO2.

Clinical features of Restrictive Lung Diseases Honeycomb lung? Sign of what? Appearance? Late complications of RLDs

• Restrictive: Can't inhale as much air. ==> Dyspnea, Tachypnea. • Also have dry cough and cyanosis. • NO WHEEZING! Wheezing = Obstructive. • Honeycomb change = bad prognosis; end stage of Pulmonary Fibrosis (usually pneumonia) • Late complications: Secondary pulmonary HTN, right heart failure and cor pulmonale.

++++++++++++++++++ DLCO: - What does it really mean? - Expected level in emphysema / chronic bronchitis / COPD - Expected level in asthma

Diffusion capacity -- ability to get O2 from lungs to blood -- depends on surface area of lungs -- carbon monoxide is easiest way to measure, which is why it's used. Decreased in Emphysema - classic sign - because of decreased alveolar surface area for gas exchange. Normal or increased in asthma - increased volume of O2 in air without destruction of alveoli. DECREASED IN ILD's!!!!!!!!

+++++++++++++++ Oxygen Saturation Curve: -What is the relationship between % O2 saturation of Hgb and PO2? (Saturation vs. Partial Pressure of oxygen) -What does the point of inflection represent? What is the normal pressure at which this occurs?

Oxygen saturation vs. content / pressure: PO2 is how much oxygen there is total and % Saturation is how much of the O2 is bound to Hgb. > Overall, they are directly proportional, which makes sense. More oxygen, more Hgb available. Eventually this tapers off as there is less free Hgb. > Sigmoidal curve. > Point of inflection = 50% saturation. Usually occurs around 26 mmHg.

+++++++++ Laplace's Law: P = ___ Relationship between air pressure in lungs, the tension in airways, and the radius of airways. Pressure is directly proportional to ___ and inversely proportional to ___. What does this mean for lungs? Test your knowledge: Would a higher pressure be required to maintain expansion in a larger or smaller sac (analogy -- ballon submerged in water)? i.e., to keep it from collapsing

P = 2T/r Pressure and Tension are directly proportional. Pressure and radius are inversely proportional. Pressure needed to keep balloon inflated is highest for small baloons. What does this mean for lungs? Alveoli have an increased tendency to collapse on expiration as the radius decreases.

We breathe off all the CO2 we produce, so CO2 levels from expiration are a good measure of CO2 production in system. At steady state breathing / CO2 excretion What is the equation / relationship for PA CO2 (alveolar CO2 pressure)? Example: If VCO2 = 0.2 L/min and VA = 4 L/min, then PACO2 = ???

PACO2 = 760 x (VCO2 / VA) If VCO2 = 0.2 L/min and VA = 4 L/min, then PACO2 = ??? (0.2/4)*760 = 38 mm Hg.

+++++++++++++++++++++++++++++ We will use this equation A LOT. Alveolar Gas Equation: Equation for PAO2 (oxygen pressure in the alveoli) -relationship between PAO2, PIO2, PaCO2 Shortcut equation at sea level with normal air. What does it say about supplemental O2? What does this fix, and what does it not fix in hypoventilation? Example: Calculate PaO2 for a person with a PACO2 of 80 and a PIO2 of 150.

PAO2 = PIO2 - [PaCO2/0.8] Where 0.8 = R = respiratory quotient = VCO2/VO2 (CO2 produced/O2 consumed.) PIO2 is the oxygen pressure of humidified inspired air. Usually 150, but if, for example, only 30% oxygen coming in, Equals 713 x FIO2 (e.g., 713 x 0.30). Roughly equal to 150-PaCO2/0.8 at room air at sea level. Example: PAO2 = 150 - (80/0.8) = 50 --- much lower than normal Big Disease Correlation: Severe Hypoventilation According to the alveolar gas equation, supplemental O2 fixes lack of O2 problem, but does not fix the issue of too much CO2.

PCO2 = 25 mmHg PO2 = 80 mmHg What is the state of the A-a gradient?

PCO2 is low (less than ~40) PO2 is normal, but a little low (80-100 normal) According to the Alveolar gas equation , PAO2 is higher, which means A-a gradient is higher.

Chemoreceptor control of respiration: CO2 -- Negative Feedback - Normal CO2 level (PaCO2) = ~ ___ mmHg. - What is the ventilatory response to PCO2 increase and decrease? - Why is it important to keep a tight leash on PCO2? - Why is it easier to regulate respiration by changing CO2 than O2?

Pretty intuitive - Normal: 35-45 mmHg (around 40 mmHg) (even during exercise) - If PCO2 drifts upward, chemoreceptors signal the respiratory center to increase ventilation and lower PaCO2 back to the set-point of 40 mmHg (negative feedback). - Opposite if decreased PCO2. This keeps a tight leash on the PaCO2. The PaCO2 needs to be regulated closely because an increase in PaCO2 causes a drop in blood pH (respiratory acidosis) and a decrease causes respiratory alkalosis. Why does it make sense to regulate CO2 rather than O2? Answer: The normal PaO2 of 90 mm Hg is in the flat part of the HbO2 dissociation curve and small variations in ventilation will not strongly affect arterial saturation. IMAGE: Helpful, from internet, shows how chemoreceptors interact with brainstem centers to control breathing. ___________________________ Along with the brainstem, mechanical receptors, etc., chemoreceptors are one of the several integrated mechanisms that controls RR.

Describe the changes in lung volume, airflow, pleural pressure, and alveolar pressure that take place during normal breathing -- Graphs

Pretty intuitive, but First Aid added these diagrams. These images are normal. Inspiration is left half, Expiration is right half (follow the lung volume plot -- top graph) During inspiration and then expiration, you can see that Pa starts at zero, drops down for inspiration, goes back to zero, then increases for expiration, then returns to zero. Things to Remember: Alveolar pressure negative during inspiration, positive during expiration, and zero at the end of each. Pleural pressure gets more negative while lungs are at rest and are normal -5 when inspiring or expiring (compliance). Ppl is MOST NEGATVE at FRC / Tidal volume; MOST POSITIVE while breathing in and breathing out.

+++++++++++ Flow/Volume Loop appearance for COPD

Problem is with expiration in COPD. Can't expire all of air. As a result, the flow/volume loop will have that little dip in it.

Microscopic and histological (particularly smooth muscle) features of Bronchi Do they contain glands?

Secondary and Tertiary Bronchi are Characterized by Irregular Plates of Cartilage and Two Smooth Muscle Layers that Spiral in Opposite Directions Between the Lamina Propria and the Submucosa Yes, they contain seromucosal glands that make mucus, unlike bronchioles. If you see a dark wavy ring, you're either in bronchi or bronchioles.

Chronic interstitial diseases & Chest wall disorders cause what kind of lung disease? e.g., Big Ones: • Idiopathic pulmonary fibrosis (IPF/UIP) • Nonspecific interstitial pneumonia (NSIP) • Cryptogenic organizing pneumonia (COP) • Connective tissue disease associated (CTD) • Hypersensitivity Pneumoconiosis (Occupational) • Granulomatous: - Sarcoidosis - Hypersensitivity pneumonitis

See Image All restrictive lung diseases (RLDs) are essentially decreased ability to fill lungs. All of these would: • ↓ FEV1 • ↓↓ FVC (can't fill) • FEV1/FVC normal or ↑ (usually >80%)

Emphysema vs. Chronic Bronchitis

See Image emphysema: decreased recoil in alveoli - dilated, can't expell air. Extra: > PaO2 - decr > PaCO2 - normal/decr > pH - normal/incr > cyanosis - absent chronic bronchitis: narrowed airways Extra: > PaO2 - decr > PaCO2 - incr > pH - decr > cyanosis - present

- How does maternal blood flow through a placenta? - How is O2 transferred from maternal to fetal blood? - Compare the normal PO2 values for maternal vs. fetal blood in arteries vs. veins. - Who has a higher venous blood PO2? Fetal umbilical cord or Maternal placenta?

- Flow of maternal blood through the placenta is less orderly than through other microcirculatory beds. Instead of red blood cells moving single file through capillaries, there is a pool of maternal blood in the intervillus space that is constantly being replaced by new maternal arterial blood. - O2 is transferred from maternal to fetal blood by diffusion of dissolved O2 down its partial pressure gradient, just as in the adult lung.... > In the placenta: Maternal Arterial Blood: PO2 = 90 mm Hg; Sat = 97% Maternal Venous Blood: PO2 = 35 mm Hg; Sat = 70% Fetal Umbilical Arterial Blood: PO2 = 22 mm Hg; Sat = 58% (Less saturated than maternal venous blood) Fetal Umbilical Venous Blood: PO2 = 30 mm Hg; Sat = 80% (Highest saturation of any blood in the fetal circulation) ^Note that fetal umbilical venous blood has a lower PO2 (30 mm Hg) than the maternal venous blood (35 mm Hg) -- but fetal umbilical venous blood is more saturated w/ O2 than maternal venous blood.

++++++ UNDERSTAND THIS ++++++ Venous Thromboembolism (VTE): -Define -Difference between a DVT and PE

- VTE = Either a DVT or a PE. VTE is an umbrella term for DVTs and PEs, which are not the same thing. - DVT is when a clot forms in a deep vein (usually leg). They usually result from staying still too long (e.g., recovering from surgery, sitting on a flight). 50% of them are asymptomatic. - PE is when that clot breaks off and goes to lungs, which can block lung vessels and cause damage. PE is not its own disease. It is a complication of DVTs. If you prevent or treat DVTs, you can prevent a PE. - DVT arises due to the Virchow triad: venous stasis, coagulation activation, and injury to vascular endothelium.

Which pressure would you look at to determine: - if a person is inhaling or exhaling - if the lung is inflated

- alveolar pressure - transpulmonary pressure See IMAGE

+++++++++++ As the bronchial tree decreases in size (1' -> 2' -> 3' bronchi, then terminal then respiratory bronchioles), what are the trends in the amount of cartilage vs. the amount of muslce (smooth & elastic)?

- decrease in cartilage - increase in smooth muscle and elastic tissue (with respect to wall thickness)

Helpful: Pattern of tissue type changes throughout the respiratory system. - Where along the resp. pathway do goblet cells stop being present? - Cartilage and glands are absent where?

- goblet cells, cartilage, and glands ALL end at the bronchi => bonchiole transition (so they end where the conduction pathway ends; thus they are not present in the respiratory pathway). - epithelium lines entire system - As cartilage disappears, smooth muscle appears. - etc. -- see IMAGE and notice where the colored wedges end. Phelan said not to memorize all of these details

Coal Worker's Pneumoconiosis (CWP): -What is anthracosis? -CWP tends to affect upper or lower lobes? -Usual occupational history -What causes CWP? -Massive pulmonary ___, leading to what complications? -Do CWP pts have increased risk for cancer / TB?

-Anthracosis: Macrophages with carbon (black) (Image) -Tends to affect upper lobes (unlike silicosis) -Inhalation of coal -- massive pulmonary FIBROSIS. Lungs that have undergone progressive massive fibrosis appear as "black lungs." Leads to pulmonary dysfunction, pulmonary HTN, and cor pulmonale. -No increased risk for cancer. Usually benign. Unlike silicosis.

Nasal Cavity (part of Extrapulmonary Conducting Portion): PART 2 The Pseudostratified Olfactory Epithelium (that lines the OLFACTORY part of the nasal cavity) is characterized by the Presence of ___ Cells and the Absence of ___ Cells. SMELLING part of nasal cavity.

-CONTAINS Specialized Olfactory Cells -DOES NOT CONTAIN Goblet Cells

+++++++ ON EXAM +++++++++ Neonatal Respiratory Distress Syndrome: -Caused by a lack of what? -Failure of what cell type? -High risk if mother has what condition? -Treatment Covered in 3+ lectures

-Caused by a lack of surfactant in alveoli, due to failure of Type II Pneumocytes. Causes collapsed alveoli. -The production of surfactant by type II pneumocytes normally begins late in gestation, so if born prematurely, this function might be absent. -High risk in Maternal Diabetes --- high level of insulin can inhibit surfactant production Baby will be cyanotic since there's not as much gas exchange. From Dr. Jennings lecture: Insufficient surfactant, increased surface tension, harder to inflate lungs, alveolar collapse, "ground glass" appearance in CXR. Risk Factors: Prematurity, maternal diabetes (increased fetal insulin), Caesarian section (less stress, lower glucocorticoid level, less surfactant) Treatment: Artificial surfactant. Supplemental O2 can be used, but with risks: o Retinopathy of prematurity o Intraventricular hemorrhage o Bronchopulmonary dysplasia

Silicosis: -Cause / Def; usual occupational history -Imaging: Where in lungs will you see nodules? -Classic and Unique CXR appearance -Associated with increased risk of ___ and ___.

-Caused by inhaling silica dust (quartz) in the lungs and usually occurs after working in occupations including ceramics, glass work, and sandblasting. It's the most prevalent chronic occupational disease in the world. >> Inhaled rock dust leads to activation and release of inflammatory mediators by pulmonary macrophages with subsequent fibrosis. >> Silicosis presents after decades of exposure and slowly progress to massive fibrosis (as in CWP). - As disease progresses, lung nodules combine to form hard collagen scars. - A/w increased susceptibility to tuberculosis and developing lung cancer. Imaging: - nodules in the upper lobes of the lungs, fibrotic lesions in pleura and hilar lymph nodes. - Eggshell calcifications - when hilar nodes undergo calcification - Essentially glass in lungs

Bronchioles: -Tissue type -Here, ___ and ___ are absent. -Key histological feature is ___ cells that serve as stem cells. -Histological appearance

-Ciliated, Simple Cuboidal -Cartilage and seromucosal glands no longer present. Smooth muscle is. -Club cells that serve as stem cells that regerate bronchiolar epithelium. They appear in the first bronchioles and end at the respiratory bronchioles.

+++++++++++ How is the work of breathing affected by: - Resistance - Compliance

-Increase resistance, increase work. Caused by obstructive diseases of lung that make exhalation difficult. E.g., COPD -- labored breathing (more work). -Decreased compliance also increases work. This is caused by restrictive diseases of lung that make inhalation difficult.

What changes in each of these parameters would result in increased work in breathing? -Airway Resistance -Lung Compliance -Thorax Compliance

-Increased Airway Resistance -Reduced Lung Compliance (harder to expand lungs) -Reduced Thorax Compliance (harder to move thorax and abdomen to accomodate inspiration). This is why obsese people have trouble breathing on their back. All of these increase the amount of work required for breathing.

Type of lung disease: -FEV1/FVC is increased or normal -FEV1/FVC is decreased

-Increased or normal: Restrictive (e.g., fibrosis) -Decreased: Obstructive (e.g., COPD)

+++++++++++++ Cromolyn: -Drug type -MoA -Compare to corticosteroids in effectiveness

-Mast Cell Degranulation Inhibitor -MoA: Inhibit Chloride transport in airway nerves and inhibit mast cells, eosinophils, etc. to reduce inflammation. So these are asthma prophylactic medications. -Less effective than corticosteroids, but may be indicated in children.

++++++ Bronchioles: -Microscopic appearance -Contain ___ muscle -Uniquely contain ___ cells which have what 3 main functions? -Glands present? -Type of epithelium -Goblet cells?

-Microscopic: see image -Smooth muscle -- a LOT of it -- to regulate bronchiole diameter. -Unique: Club cells (aka Clara cells) -Epithelium: simple cuboidal (more flexible) -NO goblet cells Note: Red dotted line (Image) is showing that the cartilage support ends when bronchi => bonchioles. Club Cells -- functions: (on another card) - secrete surface acting agent that reduces surface tension - degrade toxins via CytoP450 (SER) - regenerate bronchiolar epithelium

Pretty Easy -- Flow-Volume Loops -- characteristic shapes for: -Obstructive diseases -Restrictive diseases

-Obstructive: Concave dip in it -Restrictive: smaller and off to the right.

Alveoli -- Microscopy -What happens in alveoli? -What are alveolar ducts? -Microscopic appearance in bronchiole sections

-gas exchange -alveolar ducts are the subdivisions of the respiratory bronchioles, which run between alveoli and terminate in the alveolar sacs; resemble clusters of grapes. -microscope: Blue asterisks in Image. Little outpouchings in the terminal and respiratory bronchioles (TB & RB in image). All of the closed circles are alveoli. Alveoli are surrounded by a rich network of elastin (different card) alveoli ==> alveolar ducts ==> alveolar sacs

Control of breathing by the Pons: 1) The Pneumotaxic Center is active during what type of breathing, but inactive for what type? i.e., what does it do to breathing? Effect of activation on breathing rate. 2) A transection (damage) in the brainstem between the Apneustic Center in the lower pons causes what type of breathing? What does apneustic breathing mean? Effect of Apneustic Center on breathing rate.

1) The Pneumotaxic Center in the upper pons is inactive during quiet breathing but is active during exercise and signals the DRG to terminate inspiration, which shortens the breathing cycle to increase the breathing rate. 2) Transection of the brainstem between the Apneustic Center in the lower pons and the Pneumotaxic Center causes breathing with deep, prolonged inspiratory gasps (Apneustic Breathing), especially when both vagus nerves are transected. The apneustic (stimulating) and pnuemotaxic (limiting) centers of the pons work together to control rate of breathing.

++++++ Identify respiratory tree transition zones where: 1) Simple columnar meets simple cuboidal epithelium 2) Simple cuboidal meets simple squamous epithelium 3) Cartilage ends 4) Goblet cells end but ciliated cells continue 5) Club cells appear; club cells end

1) bronchi to bronchioles 2) terminal bronchioles to respiratory bronchioles 3) bronchi to bronchioles 4) large bronchioles to terminal bronchioles 5) bronchioles; respiratory bronchioles

What are the 3 classic descriptions of a person with a DPLD/ILD?

1. Diffuse infiltrates on CXR 2. Decreased lung volumes / TLC 3. Impaired oxygenation (low O2) Be able to recognize these!

++++++++++++ Cystic Fibrosis: Pathogenesis How does the mutated CFTR lead to excess fluid in the lungs? How does it lead to bronchioectasis?

1. CFTR mutation traps chloride inside the cells. 2. Na+ flows into the cell to balance Cl-. 3. Water follows Na+ into the cells. 4. Less water outside of the cells results in a very thick fluid due to lack of water. Hard to expell. 5. This causes increased infections and inflammation in the lungs as pathogens get trapped inside the lungs. 6. Eventually, bronchi are permanently damaged, leading to Bronchiectasis, a chronic condition where the walls of the bronchi are thickened from inflammation and infection. Summary of pathogenesis: Chronic lung infections and inflammation lead to progressive tissue damage in the airways. ^ Common in stems: Multiple sputum cultures positive for Pseudomonas. -- Recurrent infections

Explain the multiple effects of maternal carbon monoxide (HbCO) on delivery of O2 to fetal tissue. Effect of high maternal CO on: 1. Maternal arterial O2 content 2. Dissociation curve -- direction of shift 3. Umbilical venous pressure 4. Fetal O2 content How does the CO get into fetal circulation? Big example - smoking.

1. CO in maternal blood lowers the maternal arterial O2 content. -adding CO takes away O2 2. CO shifts the dissociation curve for the remaining Hb to the left (higher affinity, more difficult for Hgb to deliver its O2). Therefore, the maternal blood does not release O2 as easily as it should. 3. The higher affinity and lower O2 content of maternal arterial blood causes the PO2 in the placenta to be lower, which lowers umbilical venous PO2. 4. Although CO binds tightly to Hb, the binding is reversible, and, over time, CO diffuses from maternal blood to fetal blood and competes with O2 for binding to fetal Hb. This lowers the O2 content of umbilical venous blood. 5. CO in the umbilical venous blood results in CO presence in the fetal arterial blood, which lowers the arterial O2 content and shifts the dissociation curve to the left, making it harder for O2 to be delivered to the fetal tissue. So fetus gets less O2 due to inc. CO. In summary, even though the percent CO in maternal hemoglobin may be only a few percent, CO has effects on every stage of O2 delivery to the fetus, and the cumulative effects are significant. This is one of many reasons why pregnant women should not smoke.

++++++++++++++++ Effect of Altitude on breathing: Scenario 1: Person is at high altitude. The air at 15,000 feet above sea level is still 21% O2, but the total atmospheric pressure is only about 429 mm Hg. 1. At an altitude of 15,000 feet, the atmospheric pressure is 429 mm Hg. What is the PO2 of humidified inspired air at this altitude? A. 150 mm Hg B. 130 mm Hg C. 100 mm Hg D. 80 mm Hg E. 60 mm Hg 2. At an altitude of 15,000 feet, inspired PO2 is 80 mmHg. If alveolar ventilation is the same as at sea level, PACO2 would be 40 mmHg, and PAO2 would therefore be: A. 70 mmHg B. 60 mmHg C. 50 mmHg D. 40 mmHg E. 30 mmHg ______________ Scenario 2: PaO2 is normally a few mm Hg below PAO2, so the low PAO2 results in low PaO2 and causes the peripheral chemoreceptors to stimulate ventilation. From the response to low PO2 from previous scenario, that PaO2 of 30 mm Hg should cause ventilation to increase by a factor of roughly 1.6. The next two questions are about how the increase in ventilation affects PaCO2 and PaO2. 3. If PACO2 starts at 40 mm Hg and alveolar ventilation increases by a factor of 1.6, what will be the new PACO2, assuming that the increased work of breathing is not sufficient to change total CO2 production rate? A. 40 mm Hg B. 35 mm Hg C. 30 mm Hg D. 25 mm Hg E. 20 mm Hg 4. If the new PACO2 is 25 and inspired PO2 is 80, what is the new PAO2? Assume that the respiratory exchange ratio is still 0.8. A. 65 mm Hg B. 55 mm Hg C. 49 mm Hg D. 40 mm Hg E. 30 mm Hg These questions were in the ILA on separate slides, so KNOW THIS.

1. D. 80 mmHg ^ Total pressure is 429, but 47 of this is water vapor. O2 represents 21% of what is not water, or 0.21 x (429-47) = 80.2 mmHg. 2. E. 30 mmHg ^ Alveolar Gas Equation: PAO2 = PIO2 - (PaCO2/0.8) (PACO2 and PaCO2 are interchangeable) If PaCO2 = 40 and PIO2 is 80, then: PAO2 = 80 - (40/0.8) = 80-50 = 30 mmHg. 3. D. 25 mmHg -My reasoning: ~1.5 x 40 would be around 25 (somewhere between 20 and 30) -Explanation: Even at high altitude, alveolar ventilation is inversely proportional to alveolar PCO2. If the rate of CO2 production has not increased, and the old PCO2 is 40, then the new PCO2 must be 40/1.6 = 25 mm Hg. 4. C. 49 mmHg Alveolar gas equation says the new PAO2 = 80 - (25/0.8) = 80 - 31 = 49 mm Hg.

Diagnose each: 1. Calf pain, tenderness, swelling, and redness. 2. Sxs: Dyspnea/SOB (episodes), pleuritic pain (define), cough. Signs: Tachypnea, rales, and tachycardia. Abnormal Pulse Ox with normal CXR.

1. Deep Venous Thrombosis (DVT) 2. Pulmonary Embolism (when DVT breaks off and travels to lungs) NOTE: For DVT, those 3 sxs are not reliable for diagnosis; could be other conditions. Wells Criteria / score is more specific. Pleuritic Pain - sudden and intense sharp, stabbing, or burning pain in the chest with deep breathing.

Progressive Exercise Practice Qs: 1. During exercise at 50% of maximum O2 consumption, which of the following is changed the most compared with rest? A. Alveolar PO2 B. Alveolar PCO2 C. Arterial PO2 D. Arterial O2 content E. Venous O2 content 2. At the very highest exercise rates, which of the following relationships is no longer true? A. Alveolar Gas Equation B. Henderson-Hasselbalch Equation C. Effect of PaCO2 on ventilation D. Fick Principle for arterial and venous CO2 E. Fick Principle for arterial and venous O2

1. E. Venous O2 content ^ Only thing that isn't constant. ^ Conceptual: increased O2 extraction from working muscle causes PvO2 to be lower during exercise than at rest. 2. C. Effect of PaCO2 on ventilation ^ Normally, low PCO2 would inhibit ventilation, because the central chemoreceptors would be alkalinized. But during extreme exercise, there is so much lactic acid from anaerobic glycolysis (which can cross the BBB) that the central chemoreceptors are in an acidic environment no matter what PaCO2 is.

Overall, what are the 4 types of Obstructive Lung Disease, and the key features of each? Note: useful to classify all the diseases. These 4 all involve obstruction of the airway.

1. Emphysema - Alveolar wall destruction - Overventilation 2. Chronic Bronchitis - Productive cough - Airway inflammation 3. Asthma - Reversible obstruction - others aren't - Essentially, bronchial hyperresponsiveness triggered by allergens, infection, etc. 4. Bronchioectasis is also obstructive. Obstruction = Air trapping in lungs. Not all air is exhaled. Emphysema and Chronic Bronchitis are often considered together because they are so similar and the two together = COPD. Asthma has some overlap with those, but is mostly its own thing. All of those are obstruction of bronchioles except for emphysema, which is alveolar destruction.

++++++++++++++++++++++++++++ Know these BUZZwords for DPLDs: 1. Older patient, velcro crackles 2. Mediastinal Lymphadenopathy, non-necrotizing Granuloma 3. Young, African-American Female; non-necrotizing Granuloma 4. Birds/Hot tubs/Farmers; poorly-formed Granuloma 5. Shipbuilder/Insulation/Pipe-fitter 6. Eggshell calcification

1. Idiopathic pulmonary fibrosis 2. Sarcoidosis, Fungal infection 3. Sarcoidosis 4. Hypersensitivity Pneumonitis 5. Asbestosis 6. Silicosis

Embryology -- B&B 1. Lungs develop from the ___. 2. The first stage is a ___. 3. This occurs at Week ___ of development.

1. Lungs develop from the GI tract. 2. Lung Bud = 1st version of lung. 3. Lung bud appears at Week 4 of development. From the lung bud, it develops into the lungs in 5 classic stages (different card) -- Embryonic, Pseudoglandular, Canalicular, Saccular, Alveolar. Every Pulmonologist Can Spot Alveoli.

Diagnosing Pulmonary Hypertension: 1. Right heart catheterization - PHTN if pulmonary artery pressure is greater than ___. ^ Also, if high, it reflects problems in which part of the heart? 2. Echocardiogram Which method is the gold standard for diagnosing PHTN?

1. Right heart catheterization: measure PA pressures -- PHTN if >20 mmHg. Best tool for diagnosis. Probe goes through right heart and then into the pulmonary artery in the lungs. If high, strong indication for left heart problems (hypertension, failure) because that's what the PA pumps against. 2. Echocardiogram - if systolic for PA is > 50 mmHg, likely PHTN, and PHTN is unlikely if it's < 35 mmHg. Useful for ruling out PHTN, but not as accurate for diagnosing.

+++++++++ KNOW THESE ++++++++++ Tissue type in: 1. Nasal Vestibule 2. Nasal Cavity: Respiratory portion 3. Nasal Cavity: Olfactory portion 4. Trachea & Primary Bronchi 5. Primary bronchioles 6. Tertiary Bronchioles

1. Stratified Squamous Keratinized 2. Respiratory epithelium (Pseudostratified ciliated columnar) 3. Olfactory epithelium 4. Respiratory epithelium; simple columnar 5. Simple cuboidal replaces simple columnar 6. Simple cuboidal

Respiratory Control Centers in the brainstem: Name the structure that: 1. controls voluntary forced exhalation and acts to increase the force of inspiration. 2. controls mostly inspiratory movements and their timing. What part of the brain sends signals to the DRG to terminate inspiration, which shortens the breathing cycle to increase the breathing rate?

1. Ventral Respiratory Group (VRG) in medulla 2. Dorsal Respiratory Group (DRG) in medulla Pneumotaxic Center (pons) inhibits DRG and makes breathing more rapid.

++++++++++ What type of epithelial cells are present in each section of the nasal cavity: Vestibule Respiratory section -- and cell types Olfactory section

1. Vestibule: keratinized, stratified, & squamous epithelium 2. Respiratory: respiratory epithelium -all those special cells -- basal, goblet, ciliated, DNES (Diffuse NeuroEndocrine Cells) -if these cells are present, that epithelium is serving a respiratory function. -(DNES are just interesting bc they are related to GI tract embryologically) 3. Olfactory: olfactory epithelium -smell IMAGE: Just shows the respiratory part of the chart. Don't worry about all columns. Just epithelium type and, for respiratory, cell types present.

• 68y/o male presents with progressive dyspnea beginning 2 years ago • Now unable to climb stairs • Exacerbated by exertion, relieved with rest • No associated CP, cough, wheezing, orthopnea • Diagnosed with COPD, no improvement with inhalers • Served in Navy , age 18-22 Physical Exam: • Afebrile, 92% on Room Air at rest • No conversational dyspnea • No crackles, no wheezing CT Chest: • Interlobular septal thickening - Reticular infiltrates - Worst in lower lobes ("Interesting") • Traction bronchiectasis • Pleural plaques (usually the key to diagnosis on tests) PFTs: Restrictive F/V Loop shape • FEV1/FVC ratio: 89% • FVC: 65% of predicted • FEV1: 75% of predicted • DLCO: 52% of predicted • Total lung capacity: 67% of predicted • Residual volume: 72% of predicted

Abestosis Clue: Worked on ships

ARDS without any identifiable etiology (idiopathic) is called what?

Acute Interstitial Pneumonia (AIP) High mortality rate.

Define the anatomic "dead space" of the respiratory system.

Anatomical dead space = the conducting pathway - Because here, there is no gas exchange.

+++++++++++++++++++++ Proper treatment for VTE/DVT/PE - Traditional and NEW What if pt has hypotension?

Anticoagulate! Break that clot up. Ultimately, if someone says "Hey I have a DVT, what should I do," you should give them one of the -ans, which are DOACs (direct oral anti-coagulants). But he gave some other information... Traditional: Initial Treatment: Heparin or Fondaparinux Long-term Management: Warfarin; monitor PTT / INR. New ones to replace warfarin because they're better: DOACs (direct oral anti-coagulants) Dabigatran Rivaroxaban Apixaban Edoxaban etc. Inhibit factor Xa or other factors. These -ans are better because you don't have to monitor blood tests, like PTT/INR. Heaprin likely still needed. If patient is hemodynamically unstable (e.g., hypotension), use thrombolytic therapy.

++++++ Q like this highly possible ++++++ Among the following sites in the fetal circulation, which has the highest O2 saturation? A. Superior vena cava B. Inferior vena cava C. Left Ventricle D. Ductus arteriosus E. Ascending aorta

B. Inferior vena cava This blood is a mixture of umbilical venous blood (80% Sat.) with blood from lower body. Because of the high circulation to the placenta, the saturation of IVC blood (67%) is closer to that of umbilical venous blood than it is to lower body venous blood.

Obstructive Sleep Apnea • General Sxs • Common clues: What Mouth abnormalities? What Bite abnormality? • Basic definition

Basic Definition: Sleep apnea occurs when the airway is blocked during sleep. This causes periodic lapses in breathing during sleep because of the enclosed airway. General Symptoms: • Loud snoring • Witnessed breathing pauses • Excessive daytime sleepiness • Cognitive dysfunction • Decreased energy • Insomnia Unique: • Retrognathia (chin is inwards) • Bite: Overbite • Mouth: Large Tongue, or Narrowed Mouth Opening -- makes inhalation more difficult. Risk Factors: Male Obesity Facial structural abnormality

Why does the airway collapse towards the top during rapid forced expiration?

Because the pressure surrounding the airway increases during this type of breathing, namely the pleural pressure. At the top of the airway, the pressure is lower than at the bottom, so if surrounding pressure is higher, it will collapse that part of the airway. This is intrathoracic collapse.

Differences between obstructive and central apnea

Bottom Line: - Central: No breathing signal comes from brain; no breathing effort made. - Obstructive: Like choking; Effort is made to breathe, but air can't get in. Central sleep apnea is thought to be associated with a number of different neurologic problems, as well as heart or kidney failure. During the night, people with central sleep apnea stop breathing when signals in the brain that tells the body to breathe don't work properly. No effort is even made to inhale. In contrast, with Obstructive sleep apnea, an effort is made to breathe in, but because of collapse in the upper airways, air can't get into the lungs. Central Sleep Apnea: Caused by brain problem -- Brain signals telling you to breathe don't work properly during the night. No effort is made to breathe. One of the hallmarks of central sleep apnea is Cheyne-Stokes breathing, where after a long pause, due to gradually increasing levels of carbon dioxide (CO2), shallow breathing is triggered which gradually becomes deeper and deeper, and then once CO2 reaches a safer level, the breathing becomes more shallow again. Obstructive Sleep Apnea: Efforts are made to breathe, but due to obstruction, air can't get through to the lungs. They tend to wake up from this, which is why there is insomnia. Treatment: Fairly easy to treat Obstructive Sleep Apnea with CPAP. Central sleep apnea is difficult to treat.

+++++ TEST Q -- MEMORIZE THESE FACTS & PICS ++++++ 1. Differentiate between the microscopic appearances of Bronchi vs. Bronchioles. 2. Characteristics of Bronchi vs. Bronchioles: • Hyaline Cartilage -- present or not present? • Amount & features of smooth muscle • Seromucosal glands -- present or not present? • Type of Epithelium • Any special cells.

Bronchi: - Hyaline cartilage (rings/plates) - Smooth muscle (circular) -- Irregular Plates of Cartilage and Two Smooth Muscle Layers that Spiral in Opposite Directions Between the Lamina Propria and the Submucosa - Seromucous glands in submucosa - Epithelium type: Respiratory Bronchioles: - NO cartilage - Extensive smooth muscle to regulate bronchiole diameter. - NO submucosal glands - bronchioles do not produce mucous - Epithelium type: simple columnar / cuboidal (more flexible) w/ some Club cells (aka Clara cells) Microscopic: - If you see a dark wavy ring, you're either in bronchi or bronchioles. That ring is more wavy in bronchioles and bronchioles obviously have a smaller opening. - Note the big white circles in the periphery of bronchi (I believe these are developing alveoli) - If you see cartilage (hyaline -- glassy), it MUST be bronchus. Bronchioles are soft, they would not contain cartilage.

+++++++++++++++++++++++ What condition is defined as: - Permanent dilation of bronchi and bronchioles caused by destruction of the smooth muscle and supporting elastic tissue. - Destruction results from or is a/w chronic necrotizing infections that arise from chronic obstruction. - Symptoms: > Paroxysms of cough when pt rises in the morning and change in position. > Chronic cough with production of copious purulent (foul-smelling greenish/bloody) sputum.

Bronchiectasis Bronchi are very dilated Associated with Cystic Fibrosis & Kartagener Syndrome

+++++++++ 100 % Embryology Test Q +++++++++ A 4-day old male is brought to the clinic because he is having difficulty breathing and poor feeding. He coughs, chokes, and spits up milk very soon after beginning to suckle. Which of the following is the likely etiology of the baby's condition? A. Pulmonary agenesis B. Congenital lobar emphysema C. Failure of the tracheoesophageal ridges to fuse D. Congenital bronchogenic cysts that permeated the lungs E. Congenitial diaphragmatic hernia causing pulmonary hypoplasia What is this condition called? "If you can answer these questions, you will do well on exam questions"

C. Failure of the tracheoesophageal ridges to fuse Tracheoesophageal Fistula Problem in development of esophagus in which it closes off early; discontinuous with esophagus. So the baby will drink milk and spit it back up because it's not going down to the stomach. Lungs and trachea have a connection as well. Thus, any food in the stomach will go into the lungs. Symptoms: Gastrointestinal: Infants cough and choke when swallowing because of accumulation of excessive saliva in mouth and upper respiratory tract. Milk is regurgitated immediately after feeding. Respiratory: Gastric contents may also reflux into the trachea and lungs, causing choking and often leading to pneumonitis. There will be a question about abnormal connection between the esophagus and the trachea.

The closure of the foramen ovale is caused by which of the following? A. Drop in prostaglandin E2 levels. B. Increased venous return to the right atrium. C. Increased left atrial pressure and decreased right atrial pressure D. Platelet recruitment and subsequent thrombotic sealing of the flap of tissue covering the foramen ovale. E. Increased aortic pressure

C. Increased left atrial pressure and decreased right atrial pressure Changes in Circulation at Birth 1. Closure of the Foramen Ovale A. Loss of blood flow to the placenta causes a ~2x increase in vascular resistance of the fetal circulation, increased aortic pressure, decreased venous return to the right atrium, and decreased right atrial pressure. B. When the lungs become inflated, pulmonary vascular resistance decreases, pulmonary blood flow increases, and left atrial pressure increases. C. The increase in LA pressure and decrease in RA pressure causes blood to start flowing backward through the foramen ovale, but the flow is stopped by the small flap of tissue on the LA side, which closes the foramen ovale (becoming the fossa ovalis). 2. Closure of the Ductus Venosus A. Loss of placental blood flow lowers pressure in the ductus venosus. Within 1-3 hours smooth muscle contracts and partially occludes flow. B. Lower flow through ductus venosus increases portal venous pressure and increases portal blood flow. C. Over next several days, the ductus venosus closes completely. Mechanism of closure is believed to involve a signaling pathway that includes the aryl hydrocarbon receptor AhR. Ignore -- if not certain, not testable. 3. Closure of the Ductus Arteriosus A. Increased aortic pressure causes distension and myogenic vasoconstriction of the ductus arteriosus. This is the same kind of myogenic response that happens during autoregulation of blood flow in the adult; stretching the smooth muscle causes a contraction that lowers the diameter of the vessel. B. Shortly after the first breath, the PO2 in the DA rises from the low level that had existed in fetal life (~ 20 mm Hg) to about 90 mm Hg. The rise in PO2 causes contraction of vascular smooth muscle in the DA and further lowers blood flow. This effect of O2 is similar to that in the microcirculation. C. In the fetus, Prostaglandins E2 and E1 (mainly PGE2) keep the ductus arteriosus open. After birth, a drop in Prostaglandin E levels (PGE1 & PGE2) (from loss of placenta) and in the number of PG receptors causes the closure of the ductus arteriosus over the first several days of post-natal life. D. Growth of fibrous tissue over the next 3-4 months causes anatomic closure of the ductus arteriosus.

+++++++++ 100 % Embryology Test Q +++++++++ A newborn baby is born cyanotic and is having great difficulty breathing. The baby is tachypneic (breathing rapidly) and does not improve with time. An autopsy indicates lungs that are wet and heavy with areas of collapsed lung interspersed with areas of dilated alveoli. Which of the following is the likely etiology of the baby's condition? A. Maternal steroid abuse prior to delivery B. Iatrogenic (caused by medical procedure) injury to the phrenic nerve during delivery C. Insufficient levels of surfactant production D. Diaphragmatic hernia leading to pulmonary hypoplasia E. Congenital bronchogenic cysts that permeated the lungs "If you can answer these questions, you will do well on exam questions"

C. Insufficient levels of surfactant production There will be a question about Surfactant. This baby has Neonatal Respiratory Distress Syndrome. What is surfactant? It's a surface-active protein formed by type II alveolar cells. By adsorbing to the air-water interface of alveoli, it reduces surface tension. Without surfactant, the lungs collapse = Respiratory Distress Syndrome.

+++++++++ 100 % Embryology Test Q +++++++++ An infant is born in respiratory distress. A CT scan of the thorax indicates a loop of gut in the left pleural cavity that has compressed the left lung. Improper development of which of the following is most likely the cause of this condition? A. Septum transversum B. Left pleuropericardial fold C. Left pleuroperitoneal fold D. Tracheoesophageal fold E. Cephalocaudal folding "If you can answer these questions, you will do well on exam questions"

C. Left pleuroperitoneal fold A Congenital Diaphragmatic Hernia is caused by a failure of pleuroperitoneal membranes to form its normal contribution to the diaphragm. These result in pulmonary hypoplasia.

+++++++++++++++ Cystic Fibrosis: Genetics • Caused by a mutation in what protein? • This protein has what function? • The most common mutation (ON EXAM) is called the ___.

CFTR - Cystic Fibrosis Transmembrane Regulator. This protein regulates chloride channels, causing the retention of chloride. This causes Na+ to then move into the cell to balance out chloride. Water follows Na, so this reduces water outside of cells, producing a very thick fluid outside of lung cells. See Image. A normal CFTR moves Cl out of cells. A mutated CFTR cannot move Cl out of cells. Most common mutation: ΔF508 (deletion of F508) -Likely will be the correct answer option. A mutatuin results in the classic, high-salt content in the sweat of patients with cystic fibrosis. ^ "Woe to that child that, when kissed on the forehead, tastes salty. He is bewitched and soon must die." - 16th century

Patients with COPD have difficulty with what part of breathing? How does this affect breathing during exercise?

COPD is an expiratory problem -- not all air is exhaled. Thus, when exercising, there's no room for new air to go. Simplified: > Normal lungs in exercise -- increase tidal volume and RR, and still have room for a large IRV (HUGE inhalation is possible). > COPD lungs in exercise -- High residual volume eventually makes it impossible for a large IRV (HUGE inhalation is not possible). That's why they run out of breath so easily. Inspiratory residual volume (IRV) increases with exertion in COPD.

Lung cancer is best seen with what imaging modality?

CT is best

Pneumothorax appearance CT

Can't see vessels on pt's left lung due to air.

Diagnose: Which type of sleep apnea? • Daytime sleepiness • Awakening short of breath • Snoring • Witnessed apneas • Atrial fibrillation/flutter, congestive heart failure, or a neurological disorder commonly present. • Five or more episodes per hour of sleep.

Central Sleep Apnea with Cheyne-Strokes Breathing Central Sleep Apnea is almost identical to Obstructive Sleep Apnea when it's with Cheyne-Stokes Breathing. The primary difference between Central and Obstructive is that an effort is made to breathe in obstructive, but not in central because the issue is that the brain (hence, central) is not sending signals to breathe during the night.

Emphysema: -Defined as reversible/irreversible enlargement of which airspaces? -Does it involve fibrosis? -How is emphysema defined, compared to chronic bronchitis.

Characterized by irreversible enlargement of airspaces distal to the terminal bronchioles (i.e., alveoli) and destruction of their walls without significant fibrosis. Symptoms: The Pink Puffer Dyspnea Purse-lip breathing Slow prolonged expiration Use of accessory muscles to breathe Thin anxious appearance Speaks in short jerky sentences Barrel chest (↑AP dimension on CXR) Hyper-resonance on chest palpation Emphysema is defined on the basis of morphologic and radiologic features, whereas Chronic Bronchitis is defined on the basis of clinical features. Also, emphysema involves acinus where as chronic bronchitis initially involves large airways.

++++++++++++++ Very important graph with Pressure (PL) vs. Volume: -What does the chest wall only plot look like? What will the pressure be at FRC vs. RV (Relaxed Volume of thorax) -State of chest wall when: P = 0 P > 0

Chest wall curve: > Represents the pressure of the chest wall alone, as if there were no lungs inside and no movement. > If P = 0 for chest wall, thorax is relaxed and chest wall volume is higher than FRC. > If P > 0 for chest wall, it will expand to a larger volume. > To get chest wall volume to FRC, need negative P. > To get chest wall volume to RV, need large negative P to counter outward recoil of chest. Chest wall and Lung curves are equal and opposite at FRC. They have the opposite volume and opposite pressure as you breathe!

++++++++ ON EXAM ++++++++++ Pressure volume curve for lungs: -What does it look like when there is low compliance (Fibrosis)? -What does it look like when there is high compliance (Emphysema)?

Compliance - slope of line since Compliance = ΔV/ΔPL "If you see a pressure/volume curve, know the question is probably about compliance, and compliance is the slope of the curve. If slope is high, compliance is high, and lungs can accept more air. And vice versa. That's the bottom line" The slope decreases with increasing pressure and volume -- why? -- because after you inhale a bunch of air and have high pressure in lungs, the lungs are less compliant -- less willing to accept more air. Already has plenty. Low compliance, like in fibrosis, means lungs accept less air and the slope is low right from the get-go. High compliance, like in empysema, means lungs have more available space, so the slope is really high -- volume is high even at lower pressure.

If VO2 is constant, decreasing VA would have what effect Alveolar PO2? A woman is breathing atmospheric air at sea level. At the end of a normal inspiration, the PO2 in the air in her bronchi is closest to _____ mm Hg: A. 160 B. 150 C. 130 D. 100 E. 70

Decreased alveolar oxygen pressure. Oxygen volume and PO2 in Alveoli are directly proportional. It's the opposite of what happens with CO2. Hyperventiliation: ↑ O2 pressure in alveoli (PaO2) Hypoventilation: ↓ O2 pressure in alveoli (PaO2) ^ Trends for oxygen and CO2 are opposite. Practice problem: B. 150 mmHg -see graph in IMAGE -in a healthy person, like this example, O2 increases towards atmospheric O2 at sea level pressure during inspiration, which is about 150 mmHg.

++++++++++++++ Very important graph with Volume vs. Pressure (PL): -What does the Lung + Chest Wall as a combined system (Respiratory System) plot look like? -AT WHAT POINT ON THIS CURVE IS FRC? -Intersection with the lung curve indicates? -Compliance (ΔV/ΔP) of the lung-chest system is always ___ than that of either lung alone or chest alone.

FRC is at the point of inflection of the lung + chest wall curve. Here, the chest is pulling outward and the lungs are pulling inward. The compliance is always lower -- Remember, compliance is the SLOPE. The slope of this curve is always lower than the slope of the other two curves at any point. Intersection is when the chest wall is completely relaxed. Think about it. Here, the lungs and the lungs + thorax pressures are the same, so chest wall pressure must be zero here.

+++++++++++++++++ Causes of Hypoxia: What are the states of O2 content, PaO2, and % O2 saturation in: Hypoxemia Heart Failure Anemia Carbon Monoxide

Hypoxia - Insufficient O2 delivery to tissues Hypoxemia - Reduced O2 in blood Hypoxemia --> Hypoxia. But hypoxia can occur w/o hypoxemia. Causes of Hypoxia w/o Hypoxemia: 1. Heart Failure - No problem getting O2 into blood, but can't get blood to tissues due to reduced CO. 2. Anemia - Too few Hgb molecules, so not enough O2 is carried to tissue. PaO2 and Hgb-O2 Saturation are still normal. 3. Carbon Monoxide - Classic cause of Hypoxia w/o Hypoxemia. PaO2 is normal, but Hgb-O2 saturation is low. Functional anemia here. CO takes up O2 sites on Hgb.

+++++++++++++ O2 Content vs PO2 plots -- Two Different Hgb Concentrations How is the 50% saturation pressure affected by the amount of hemoglobin? What about the Oxygen Content?

IMAGE: Shows curve for a person with 15g Hgb vs. a person with 7.5 g Hgb. The 50% saturation point occurs at the same PO2 no matter what. But the Oxygen Content will be lower for a person with less Hgb.

++++++++++++++++++ Diagnose: • Gradual deterioration of lung function ±acute exacerbations, despite treatment (which includes steroids, cyclophosphamide, azathioprine) • Insidious onset • Firm rubbery white areas on cut surface of lung • Microscopy: patchy interstitial fibrosis with adjacent normal lung. • Fibrosis is more pronounced in subpleural regions and along interlobular septa. • Fibrosis ranges from early fibroblastic proliferation to late more collagenous areas. • Imaging: cystic spaces and honeycomb lung

Idiopathic Pulmonary Fibrosis (IPF) / Usual Interstitial Pneumonia (UIP) ^ Histologic pattern of fibrosis is referred to as Usual Interstitial Pneumonia (UIP) -- referred to as UIP/IPF to avoid confusion. (Just like DAD is the histological term for ARDS, really same thing). To make a diagnosis of IPF, UIP finding is required in histology / pathology. This is the prototypic restrictive lung disease. Causes difficulty inhaling enough oxygen, so expect: • ↓ FEV1 • ↓↓ FVC (can't fill) • FEV1/FVC normal or ↑ (usually >80%) Honeycomb Lung: End-stage UIP/IPF; very bad prognosis.

++++++++++++++++++ Effect of COPD on FEV1/FVC ratio

If FEV/FVC (expired volume / inhaled volume) is less than 0.7, the patient has COPD.

+++++++++++++++++++ What is the basic difference between obstructive and restrictive lung diseases? What happens to the Total Lung Capacity (TLC) of restrictive diseases (think about it)? Obstructive vs. Restrictive in: > FEV1 > FVC > FEV1/FVC

In Obstructive lung disease, air gets trapped in the lungs (pts have trouble breathing out). In contrast, in restrictive lung disease, the lungs are stiff and hard to expand, it's hard to fill the lungs. Restrictive: Decreased total lung capacity (↓ TLC). Hard to fill the lungs. Due to reduced expansion of lung parenchyma. Background: Forced vital capacity (FVC) is the total amount of air exhaled during the FEV test. FEV1 is how much is expired in the first second. Should be around 80% of the total volume in the first second of forced exhalation. Restrictive: • ↓ FEV1 • ↓↓ FVC (can't fill) • FEV1/FVC normal or ↑ (usually >80%) Obstructive: • ↓ FEV1 • FVC normal or ↑ • ↓ FEV1/FVC - HALLMARK Two classic types of Restrictive Diseases (later cards): 1. Chronic interstitial diseases 2. Chest wall disorders

Hypersensitivity Pneumonitis: -You should see what on histology?

Inhaled antigenic organic dusts: Farmer's lung (moldy hay). Humidifier lung (thermophilic bacteria). Bird-fancier's lung (avian proteins). Acute and chronic forms. Chronic disease findings: Interlobular and intralobular interstitial thickening. This is one of the two granuloma diseases of the lung, along with Sarcoidosis. • Histology: poorly-formed interstitial granulomas with chronic inflammation > Excessive lymphocyte infiltration (not present in sarcoidosis) > Multinucleated giant cell granulomas

Describe the treatments to contemplate for increasing severity of asthma. -Intermittent asthma -Persistent asthma -- mild, moderate, severe

Intermittent asthma: SABA (Albuterol inhaler) Persistent asthma: 1. Low dose of Inhaled Corticosteroid (ICS) 2. Medium dose of ICS + LABA 3. High dose ICS + LABA + oral corticosteroid + possibly Omalizumab. If pt is having to use Albuterol inhaler too often, step up the treatment and give them an ICS. Then you can keep increasing the dose of that ICS, but adding other medications to improve effects of ICS, such as LABA and then an oral corticosteroid, and possibly Omalizumab if their problem is allergy related (blocks IgE). Critical Point: In all except intermittent (mild) asthma, use an inhaled corticosteroid! Remember, the best ICSs are Fluticasone and Budesonide

If Volume of CO2 is constant, what is the relationship of alveolar volume and CO2 pressures? If PaCO2 is >45 (hypercapnia), what is the breathing rate? Hyp__ventilation. If PaCO2 is <35 (hypocapnia), what is the breathing rate? Hyp__ventilation.

Inversely proportional b/c PACO2 = 760 x (VCO2 / VA) If PaCO2 is >45 (hypercapnia), think hypoventilation. Not breathing off enough CO2. If PaCO2 is <35 (hypocapnia), think hyperventilation. Breathing off too much CO2.

++++++ "Something You Just Have To Memorize" +++++++ Lung Capacity Equations and Definitions: 1) Inspiratory Capacity (IC) 2) Functional Residual Capacity (FRC) 3) Vital Capacity (VC) 4) Total Lung Capacity (TLC) EXTREMELY IMPORTANT THAT YOU WRITE ALL OF THESE OUT ON SCRATCH PAPER! FRC would be high in what type of lung conditions?

Lung Capacity = a sum two or more lung volumes. IMAGE -- See that top of both diagrams is maximum volume after inspiration, and bottom of both diagrams is minimum volume after expiration. Gradient -- inspiration to expiration is top to bottom. >> Inspiratory Capacity (IC) = TV + IRV -- (T+I) >> Functional Residual Capacity (FRC) = ERV + RV -- (E+R) >> Vital Capacity (VC) = IRV + TV + ERV -- (I+T+E or T+I+E) >> Total Lung Capacity (TLC) = IRV + TV + ERV + RV -- (everything) >> Inspiratory Capacity (IC) - how much air you can inspire. >> Functional Residual Capacity (FRC) - normal amount of air in lungs after expiration, which is why it's the ERV + RV, which are both volumes after expiration. If it's high, not getting all of air out. This definition is a "good thing to remember." >> Vital Capacity (VC) - how much you can expire after a maximum inspiration. >> Total Lung Capacity (TLC) - combination of all the volumes. FRC (see def. above) would be high if you still have a lot of air in lungs after expiring, so it's often high in people with obstructive breathing conditions.

Joints and skeletal muscles have ___ receptors, which contribute to the increase in ventilation during exercise.

Mechanoreceptors (and chemoreceptors)

First breath of life -- How does it occur? Need a large negative ___ pressure Trend of pleural pressures in fetus required for 1st breath, then 2nd, then 3rd.

Need large negative pleural pressure. The fetal lung contains fluid rather than air, and the fluid is replaced with air during the first few breaths. How do the lungs go from being filled with fluid to being filled with air? The compliance of the thorax of the fetus/neonate is high, and, during passage through the birth canal, some of the fluid is squeezed from the lungs. Therefore, just before the first breath, lung volume is lower than it had been in the fetus. The first breath is stimulated by the asphyxia of birth, the drop in temperature, and tactile stimulation. When the first breath is drawn, air replaces the fluid that had been in the fetal lungs. IMAGE description: The figure shows the change in lung volume (not the total volume) for the first three breaths: 1) The first inspiration requires a very negative pleural pressure. The first expiration also is quite abnormal, because the pleural pressure is positive, similar to what happens in a cough. -- unique feature !!! 2) The second inspiration still requires a very negative pleural pressure, but not as extreme as the first, and during expiration of the second breath, the pleural pressure is only slightly positive. 3) The third breath requires even less negative pleural pressure during inspiration.

Just in case, how can you easily tell central from obstructive sleep apnea on the sleep diagrams? Central apnea has what feature?

Only in central sleep apnea will you see the flat lining circled in Image. Look for those long pauses of nothing. If they are there, it's central sleep apnea. If not, obstructive sleep apnea.

Transpulmonary Pressure (PL): -EQUATION -- MNEM: TAP (or LAP) -It is the difference in the pressures of what two parts of the lung? -Is it usually positive, negative, or equal to zero? -Determines the degree of ___ of the lungs -- so a higher PL would mean the lung is more ___. Why?

PL = Pa - Ppl WRITE THIS EQUATION ON SCRATCH PAPER ^ MNEM: TAP Transpulmonary pressure = Alveolar pressure - Pleural pressure. ~~ or ~~ LAP: PL = Pa - Ppl -- easier if looking at table of values. PL is always positive (greater than atmospheric pressure) Definition: the pressure gradient between the inside of the lung and the pleural cavity -- transpulmonary -- pressure across the lungs. PL determines degree of inflation of the lung Higher PL means lung is more inflated. Why? -- High PL, from equation, means Pa is really high compared to Ppl. If the pressure inside the lungs (Pa) is particularly high, the lungs are more inflated. If transpulmonary P (PL) increases, lung volume increases. How much? Depends on Lung Compliance CL: CL = ΔV/ΔPL Compliance is a measure of how easy it is to expand the lung. ^ (Later card)

Pulmonary Vascular Resistance (PVR) equation/relationship with Pulmonary Arterial Pressure (PAP). Significance? How can right heart failure result from PVR increase?

PVR = PAP - PCWP / CO Don't need to memorize or calculate, but significance is that increased PVR (vascular resistance in pulmonary vessels) can lead to Pulmonary Hypertension as increased PVR is associated with increasde PAP. Connection: Right Heart Failure -Right heart pumps blood into lungs. If PVR is high, right heart hypertrophies until it eventually gives out. Having to push too hard to get blood into lungs. Pulmonary Vascular Disorder → Increased Pulmonary Vascular Resistance → Pulmonary Hypertension → Increased Right Ventricular Work → Cor Pulmonale and Death

What is Diffuse Alveolar Damage (DAD)? Indicates what condition?

Pathology term for ARDS. Essntially SAME THING! •Damage to type I pneumocytes produce flooding of alveloli with edema •Hyaline membranes form and line distal airways and alveoli •Type II pneumocytes proliferate to reline denuded alveolar surfaces •Fibroblastic tissue is generated in and around airspaces Indicates ARDS.

Peripheral Chemoreceptors: -Located where, monitor level of what chemical? -Main Function: They freak out when that chemical is below what value?

Peripheral Chemoreceptors are in the carotids & aorta and primarily monitor blood O2 level to help regulate ventilation rate. If O2 is high, they slow breathing. Usually, CO2 level controls RR, but there are these receptors in the large arteries that monitor O2. Main Function: PCs fire when O2 drops below 60mmHg. These aortic and carotid chemoreceptors are not activated as long as arterial PO2 is above about 60 mm Hg. IMAGE shows the response of ventilation to low PaO2. Ventillation decreases when O2 increases.

Types of Atelectasis: Compression L.O. - Describe the different forms of atelectasis.

Pleural cavity is filled by one of the following, which compresses the lungs, resulting in inability of alveoli to expand: -Fluid - exudate (tumor effusions, TB), transudate (CHF) -Tumor -Blood - hemothorax -Air - pneumothorax Contralateral mediastinal shift -- Mediastinum is shifted to side opposite to compression.

At FRC (end of expiration / beginning of inspiration), what is the normal value of: - Pleural Pressure (Ppl) - Alveolar pressure (PA) - Transpulmonary pressure (PL)?

Ppl should be around -5. Pa should be around 0. PL should be +5 [0-(-5)]. Automatically assume PA = 0 if it says that there is an open airway; no flow; etc. PA is the driving force for air flow, so if there is no air flow, PA = 0. In this case, the value PL will be equal and opposite to the value of Ppl (see IMAGE). They balance eachother. During quiet breathing, the pleural pressure is negative

Diagnosis AND Treatment: A 32 year old woman is referred to clinic for evaluation of shortness of breath. She is a non-smoker and has no prior illnesses and takes no medications. She describes gradually worsening dyspnea and fatigue on exertion; she can still perform errands and light housework, but finds herself having to stop and rest. On physical exam lungs are clear, Heart has increased P2, and she has no edema CXR: enlarged central pulmonary arteries, clear lungs. ECG : R axis deviation Full PFTs normal spirometry, normal lung volumes but diffusing capacity (DLCO) was 50% predicted. An echocardiogram shows RV hypertrophy and estimated PA systolic pressure of 60 mmHg. On a 6-minute walk test, her distance is only 450 feet and her SpO2 is 95 % at rest but drops to 85% during the walk.

Pulmonary Arterial Hypertension (not pulmonary hypertension) Idiopathic Normal pulmonary artery pressure is 8-20 mmHg. Pulmonary HTN if >25 mmHg. Echocardiogram showed RV hypertrophy, but NOT a Left Heart Problem. So it's idiopathic. CXR shows enlarged pulmonary aa. suggesting pulmonary HTN. Look for the CONVEX shape at the top of the Left heart -- Left Pulmonary Artery is large. Normal heart has concave shape there where it goes in. But if it is going outwards, pulm. HTN very possible. This patient is concerning for PAH and needs more definitive evaluation. She underwent R heart cath with L heart cath for LVEDP and results were c/w moderately severe pulmonary hypertension without significant vasoreactivity and with no evidence of Left heart disease. Other lab tests r/o any evidence of collagen-vascular dz , HIV, liver dz She is diagnosed with idiopathic PAH with NYHA Class II symptoms and will be started on treatment, possibly ambrisentan + tadalafil. She will be followed closely in clinic for symptoms and with repeat 6-min walk test and BNP for improvement and likely will improve initially, then progress and require more advanced therapies and may ultimately decision +/- referral for transplantation.

Diagnose: A 62 year old woman presents to your office complaining of episodes of SOB. These episodes occur sporadically and last only a few minutes. They have occurred 4 times in the past 2 days. She had sharp chest pain with deep breathing on the last 2 occasions that resolved within 5 minutes. Her breathing is normal in between these episodes. She has no cough, fever, chills or other new complaints. History: • Sedentary lifestyle • Has struggled with trying to lose weight most of her life and has a BMI of 33. • Smoked 2ppd x 30 years • Taking estrogen. Physical: • VS: HR = 108; BP = 148/96; T = 100.1; RR = 24. • Left leg is 6 cm larger than right with localized tenderness, erythema, warmth and pitting edema.

Pulmonary Embolism (VTE) Sxs to watch for: ✔ Shortness of breath / Dyspnea episodes ✔ Pleuritic pain (sharp chest pain w/ breathing) ✔ DVT signs: one leg is swollen, tender, red. ✔ Tachycardia & Tachypnea. Sedentary lifestyle is a big risk factor. Lack of movement allows DVTs to form more easily. Once sxs move to chest (SOB, pleuritic pain), DVT most likely broke off to form a PE.

Understand the differences between the pressures in the LV and systemic circulation vs the RV and pulmonary circulation.

Pulmonary circulation: Low pressure, Low resistance circuit. Systemic circulation: High pressure, High resistance circuit. The PAP should be about 15. This is the pressure the RV is pumping against. If too high => Right Heart failure. Systemic pressure is around 100. If PVR rises, lungs can increase the number of vessels the blood goes through and/or increase size of vessels to compensate. But in some lung diseases, those properties are lost. Pulmonary Vascular Disorder → Increased Pulmonary Vascular Resistance → Pulmonary Hypertension → Increased Right Ventricular Work → Cor Pulmonale and Death

- - - - - Review just in case - - - - - Risk factors for VTE (DVT / PE) -- what makes them more likely? Risk factors for hypercoaguable states.

Risk Factors for VTE: See Image. These will show up in the patient's history. ^ One example he gave had estrogen replacement therapy (BIG risk factor), smoking hx, obesity, sedentary lifestyle in the hx. Risk factors for Hypercoaguable states: -Genetic: Factor V Leiden mutation; Prothrombin G20210A mutation; etc. -Acquired: Antiphospholipid syndrome (Lupus)

What are the 3 main classes of bronchodilators for asthma? Which is the drug of choice for short term treatment? Drug of choice for asthma prophylaxis? For each class, describe its mechanism of action and route of administration. For each class, give the prototype(s)

Short-acting B2 agonists: -Immediate relief of an asthma attack (drug of choice) -Prototype: Albuterol -MoA: Activates B2 receptors short-term, resulting in bronchodilation. -RoA: Inhalation (aerosol) 2-4 hrs -Albuterol just treats the symptoms, and temporarily. It is unlikely that albuterol alone is the best treatment for any patient with asthma, but definitely should be given with other drugs, like corticosteroids. Long-acting B2 agonists: -Long-term relief of asthma -Prototypes: (SIF) Salmeterol, Formoterol, Indacaterol (MNEM: Indicate Forms of Salmon) -MoA: Activates B2 receptors long-term -RoA: Inhalation (aerosol) 12-24 hrs -No anti-inflammatory action, so really just used to potentiate the effects of corticosteroids. Corticosteroids: -Prophylaxis of asthma -Inhaled: Fluticasone, Budesonide, Beclomethasone (drugs of choice) -Oral: Prednisone -MoA for both forms: Inhibits Phospholipase A; Reduces COX. -Most important asthma drug because it targets the cause of asthma, whereas the others just treat the sxs. Other notable ones: - Ipratropium is an Anti-muscarinic -- blocks the Ach receptors. Ach is responsible for bronchoconstriction in asthma (PNS).

Does Carbon Monoxide diffuse faster or slower than Oxygen? Explain the distinction between perfusion-limited and diffusion-limited gas exchange (L.O.). O2 and CO2 are ___-limited in diffusion rate. O2 and CO are ___-limited in diffusion rate.

Slower -- mainly because it attaches to hemoglobin so easily, so that's a major sink for CO partial pressure in the blood. From First Aid: -Perfusion limited - O2 (normal health), CO2, N2O. Gas equilibrates early along the length of the capillary. Exchange can be ↑ only if blood flow ↑. -Diffusion limited - O2 (emphysema, fibrosis, exercise), CO. Gas does not equilibrate by the time blood reaches the end of the capillary. -Diffusion of CO is the extent to which CO, a surrogate for O2, passes from air sacs of lungs into blood.

Emphysema: Pathogenesis from tobacco -- Smoking inhibits what protein, and what is the effect?

Smoking inhibits A1AT which inhibits elastase, leading to deficiency of elastin: ↑ lung capacity ↓ elastic recoil ^ Inhale more air, but cannot expel all of it. Smoking causes tissue damage to alveoli, and neutrophils infiltrate (Image).

++++++++++++ Emphesyma: -Microscopic appearance -What fails here? What PROTEIN is released that does this? -Describe the process of how smoking causes emphysema.

Summary: smoking destroys a1-antitrypsin, allowing elastase to destroy all of the elastin. Basic def of emphysema: a condition in which the alveoli of the lungs are damaged and enlarged, causing breathlessness. Caused by failure of elastic fibers / elastin network surrounding alveoli and providing them with recoil ability. When this fails, permanent distention occurs. Macrophages and neutrophils release elastase which destroys the elastic fibers in the lungs (normal process). Normally, the a1-antitrypsin protein protects against the elastase. But long term smoking inhibits a1-antitrypsin and overwhelms the system leading to a loss in the elasticity of the lungs. This results in large fluid-filled spaces that decrease gas exchange capability.

++++++++++++ A 55 year old man is referred to clinic for severe swelling of his legs and feet. He is a loud snorer and takes frequent naps during the day. On exam he is morbidly obese with a BMI of 42. Breath sounds are reduced due to obesity but no abnormal sounds are heard. Heart distant but no m heard. He has 3 + pitting edema of feet and legs. CXR is clear. Full PFTs show mild restrictive defect that is c/w obesity. Echocardiogram shows normal LV but dilated RV with estimated PA systolic of 55. An ABG on RA shows pH = 7.36, PCO2 = 60, and PaO2 = 58. He is referred for polysomnogram (sleep study) which shows severe obstructive sleep apnea and frequent prolonged oxygen desaturation, with nadir of SpO2 75%, which were almost fully abolished on BiPAP pressures of 15/10 with 2 liter/min O2 bled in. What is the patient's diagnosis? What type of PHTN? Does he need further testing? What is his treatment?

This patient was diagnosed with severe obstructive sleep apnea and obesity hypoventilation syndrome with both resting hypoxemia and severe nocturnal desaturation. He has Group 3 pulmonary hypertension that appears explainable by his degree of chronic hypoxemia, and he does not need a right heart cath based on information so far, and does not need advanced therapies that are used for PAH. His treatment is: Treat Sleep Apnea ◦ Supplemental O2 during day, BiPAP/O2 during sleep, modest diuretics, weight loss program. ◦ Follow-up for clinical response (For groups 2-5, treat the underlying condition)

++++++++++++++ Asthma: -Pathogenesis: __ cells are activated -4 Key features / abnormalities - 2 airway, 2 vessel -Asthma is a Type __ Hypersensitivity Reaction mediated by Ig_.

Type I IgE-mediated hypersensitivity rxn 4 Abnormalities: 1. Bronchoconstriction 2. Vasodilation 3. Increased vascular permeability 4. Airway remodeling - bronchial smooth muscle hypertrophy/hyperplasia Pathogenesis: The classic atopic form is associated with excessive type 2 helper T (TH2) cell activation. Cytokines produced by TH2 cells account for most of the features of asthma —IL-4 and IL-13 stimulate IgE production, IL-5 activates eosinophils, and IL-13 also stimulates mucus production. IgE coats submucosal mast cells, which on exposure to allergen release their granule contents and secrete cytokines and other mediators. Pathway: See Image 1. Allergen enters bronchial epith -> Type 2 helper T cell (Th2). 2. TH2 is responsible for most of the features: TH2 -> IL4->IgE B cell -> IgE -> Mast cell degranulation -> IL3, IL5 -> Eosinophil recruitment/activation -> Bronchoconstriction + increased Mucus production TH2 -> IL3, IL5, GM-CSF -> Eosinophil recruitment and activation

++++++++++++ In the alveoli, what cell type is responsible for producing surfactant in its lamellar bodies? What is the function of surfactant? Primarily composed of what?

Type II Pneumocytes Lamellar bodies in Type II cells produce and secrete Pulmonary Surfactant - Dr. Jennings Type II Pneumocytes Are Also Stem Cells that Regenerate Type I and Type II Pneumocytes. They proliferate after an injury to lungs. Without these, you can't breathe -- neonatal respiratory distress syndrome. Surfactant decreases surface tension preventing atelectasis (collapse of the alveolus). -- Major concept. Lung would naturally collapse if it wasn't for surfactant. Surfactant is primarily composed of: dipalmitoyl LECITHIN. ^ Mixture of protein (SP-A, SP-B) and lipid, mainly dipalmitoyl lecithin. Low lecithin would mean less surfactant

~~~ Conceptual - Basics about Pressure before diving in ~~~ What unit is pressure measured in for pulm? Pressure is measured relative to what pressure? P = 0 means what? Negative pressure? Positive pressure? What are the 3 pulmonary pressures we measure?

Unit: cmH2O Air pressure in lungs is measured relative to atmospheric pressure. "e.g., if alveolar pressure is 0, that means it's the same as the atmospheric pressure." "e.g., if I say that alveolar pressure is subatmospheric, that means there is negative pressure in the lungs." if pressure is negative, the pressure in lungs is less than atmospheric pressure, so air will want to go into lungs. if pressure is positive, the pressure in the lungs is greater than atmospheric pressure, and air will want to leave lungs. as in CPAP, coninuous positive airway pressure. 3 Pulmonary pressures: Pleural PPl, Alveolar PA, and Transpulmonary PL, aka PTP (next 3 cards)

++++Tricky Concept++++ How does the area of the respiratory tree change as you go from the bronchioles to later generations (alveolar stuff)? Thus, what happens to velocity and airway resistance as you move further down the tree?

When we say area, we mean total area. Because of branching, higher generations means larger area. Velocity of airflow and airway resistance therefore decrease in the higher generations. So the lower down you are, the lower the resistance, the slower the velocity of air, and the greater the area. Analogy from Dr. Jennings: Imagine the respiratory system as a river getting wider as it goes down. As a river widens / increases in area, water flows more slowly (because there's more space for it to occupy), and there is less resistance. For the purpose of thinking of these types of concepts, just imagine the airway passages as getting bidder as you go down, and don't get bogged down in that it's the total area unless you need to. Just imagine that picure on the right side of the IMAGE.

What are the differences between the conduction and the respiratory portions of the respiratory pathway? Include functions of each. What anatomical structures are in each? (Basically, where does it turn from the conduction to the respiratory pathway?) ^ This is also the pathway of air from the nose through the lungs.

• Conducting portion: Prepares air - situated outside and within the lungs - conveys air to the lungs - filters, moistens, & warms inspired air • Respiratory portion: Uses air for GAS EXCHANGE - located strictly within the lungs - functions in exchange of oxygen for carbon dioxide ANATOMY: Color-Coded Nasal cavity → Pharynx → Larynx → Trachea → Bronchi (1', 2', 3') → Bronchioles (primary, terminal, respiratory) → Alveolar ducts → Alveolar sacs → Alveoli Nasal cavity to trachea is extrapulmonary. Bronchi onwards is pulmonary. The respiratory portion starts at the respiratory bronchioles; the bottom-most bronchioles. But mostly in alveoli. (HINT: essentially all respiratory portions are alveoli-related)

++++++ Smoking and other chronic irritants: How is the respiratory epithelium affected? -what happens to goblet cells? -what happens to ciliated cells? -what happens to seromucosal glands in the lamina propria? Histology -- progression of lung damage: From Normal => Squamous Metaplasia => Mild Dysplasia => Carcinoma ^ In terms of how the cells are stacked -- memorize appearance

• Increase in the number of goblet cells • Decrease in the number of ciliated cells (ciliotoxic) -- 1 & 2 combo: Results in increased production of mucus (inc. goblet cells) but reduced rate of elimination (lack of ciliated cells) • Seromucous glands in lamina propria increase in size, forming more copious secretions (productive/wet cough of heavy smokers) In IMAGE -- see how cells are normally, then how they change with smoking. More stacked, less stacked, thin, thick, color of stain, etc.

Leukotriene Pathway Inhibitors: -3 prototypes -MoA for each -Administration

• Leukotrienes play a central role in late phase bronchoconstriction in asthma. • Zileuton inhibits 5-lipoxygenase, the enzyme that converts arachidonic acid to leukotriene A4, thus reducing the production of leukotrienes. • Leukotriene A4 is converted into cysteinyl leukotrienes C4, D4 and E4, which bind to the cysteinyl leukotriene receptor CysLT1. Montelukast and Zafirlukast are CysLT1 antagonists. • Leukotriene pathway inhibitors produce a rapid, small improvement in lung function in moderate or severe asthma, but chronic administration improves control of asthma, reducing the frequency of use of adrenergic agonists. • While many patients do respond to leukotriene pathway inhibitors, many do not. • Zileuton and zafirlukast are administered at least twice daily, but montelukast only requires daily treatment, causing it to be the most prescribed of the leukotriene pathway inhibitors. • The leukotriene pathway inhibitors are administered orally, unlike most other asthma medications, a benefit in the case of children (who may have a hard time with inhalers).

Nonspecific Interstitial Pneumonia (NSIP): -Comparison to UIP/IPF (HOW TO DIFFERENTIATE) -Sxs -Histology

• Unknown etiology (Idiopathic) • Dyspnea and cough for several months • Better prognosis than UIP • Pts are relatively younger (45 - 55 yrs) than those with UIP • No fibroblastic foci or honeycombing • Imaging: ground-glass attenuation, reticular opacity or irregular lines • Image: Two histologic patterns: cellular NSIP and fibrotic NSIP. > Thickened alveolar walls in both. > Compared to UIP/IPF, the fibrosis is mild to moderate. > Cellular NSIP has lots of inflammatory cells in the interstitium (blue dots) > Fibrotic NSIP has increased collagen/fibrosis (pink). So, to determine if it's UIP/IPF (more likely since it's the prototype) or NSIP: > NSIP won't be as bad. No honeycombing. > For age, NSIP patients are younger (45-55 y/o) than UIP patients (older).

Typical symptoms of DLPDs

•Symptoms - Cough - Dyspnea (esp. exertional) - Hypoxemia - BIG CLUE ^ Walk down the hall, and then their O2 saturation decreases. • Chest pain uncommon - unless sarcoidosis or concomitant pleurisy • Wheezing unusual • Hemoptysis unusual Clues: Velcro breath sound Arthritis in hands Clubbing of digits Dyspnea from talking. CXR is cleaer in 10% of patients! So don't rule out based on CXR. Signs: • Bibasilar inspiratory "Velcro" crackles