Episode 82: Sample the Gold Standard USMLE Audio Reviews in this episode – decide for yourself if you like this Pharmacology of Asthma sample from a professional audiobook. If you do, we have an entire collection for every USMLE and medical school you take!
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I. A-a gradient – know how to calculate:
Alveolar O2 and arterial pO2 are never the same. The difference between the two is called alveolar arterial gradient.
Reasons for it: (1) Ventilation and perfusion are not evenly matched in the lungs. When standing up the ventilation is better than perfusion in the apex, whereas perfusion is better than ventilation at lower lobes. This explains why almost all pulmonary infarctions are in the lower lobes – perfusion is greater there. Also, this explains why reactivation TB is in the apex – TB is a strict aerobe and needs as more O2, and there is more ventilation in the upper lobes (higher O2 content). Normally, alveolar O2 is 100 and the arterial pO2 is 95. So, normally, the gradient is 5 mmHg. As you get older, the gradient expands, but not that much. Most people use their upper limit of normal – in other words, have a very very high specificity of 30 mmHg. If you have an A-a gradient of 30 mmHg or higher there is a problem. It is very high specificity (aka PPV – truly have something wrong). The concept is easy – you would expect the gradient btwn the alveolar O2 and the arterial O2 to be greater if you have primary lung dz. What will do this? Ventilation defects (produces hypoxemia, and therefore prolongs the gradient – dropping the PO2 and subtracting, and therefore a greater difference btwn the two), perfusion defect (ie pul embolus), and diffusion defect. But the depression of the medullary resp center by barbiturates does not cause a difference in A-a gradient. So, prolonged A-a gradient tells you the hypoxemia is due to a problem in the lungs (vent perfusion/diffusion defect). A normal A-a gradient tells you that something outside the lungs that is causing hypoxemia (resp acidosis – in resp acidosis, PO2 will go down). Causes of resp acidosis: pulmonary probs (COPD), depression of resp center (obstruct upper airway from epiglottitis, larygiotracheobronchitis, café coronary (paralyzed muscles of resp), Guillain Barre syndrome, amyotrophic lateral sclerosis, and paralysis of diaphragm. These all produce resp acidosis and hypoxemia, but the A-a gradient will be NORMAL). So, prolonged A-a gradient, something is wrong with the lungs. If A-a gradient is normal, there is something OUTSIDE of the lungs that is causing a resp problem. Few things must always be calculated: anion gap (with electrolytes) and A-a gradient for blood gases – all you need to do is calc alveolar O2. We can calculate the A-a gradient = 0.21 x 713 = 150 (0.21 is the atmospheric O2; and 760 minus the water vapor=713). So, 150 minus the pCO2 (given in the blood gas) divided by 0.8 (resp quotient). So, normal pCO2 = 40, and 40/.8=50 and 150-50 = 100; so, now that I have calc the alveolar O2, just subtract the measured arterial pO2 and you have the A-a gradient. This is very simple and gives a lot of info when working up hypoxemia.
II. Upper Respiratory Disease:
A. Nasal Polyps:
3 diff types of nasal polyps – MC is an allergic polyp. Never think of a polyp in the nose of kid that is allergic as an allergic polyp. Allergic polyps develop in adults after a long term allergies such as allergic rhinitis – Example: 5 y/o child with nasal polyp and resp defects, what is the first step in management? Sweat test – b/c if you have a polyp in the nose of the kid, you have cystic fibrosis; it’s not an allergic polyp.
B. Triad Asthma – take an aspirin or NSAID, have nasal polyps and of course have asthma. They don’t tell you the pt took aspirin and that the pt has a polyp. The aspirin or NSAID is the answer but this is how they will ask the question: 35 y/o woman with chronic headaches or fibromyalgia. Pt has some type of chronic pain syndrome and will not tell you that the pt is on medication, and she develops occasional bouts of asthma – what is the mech of the pt’s asthma? B/c she is taking an NSAID. What they won’t tell you that she has a polyp and that she is on an NSAID; however, if a pt is in pain or has chronic pain, it is safe to assume the pt is on pain medication (ie an NSAID, Motrin or aspirin). Mech of asthma from pain medication: what do aspirin/NSAIDs block? COX, therefore arachidonic acid cannot forms PGs but the Lipoxygenase pathway is left open. Some people are very sensitive to this and LT C4, D4, and E4 are formed, which are potent bronchoconstrictors, leading to asthma. It is NOT a type I HPY rxn. It is a chemical mediated non type I HPY rxn. So, chronic pain can lead to asthma b/c of aspirin sensitivity. Another assumption you have to make: any well built male on anabolic steroids (ie football player, wrestler) with intraperitoneal hemorrhage – produce benign liver cell adenomas which have the tendency of rupturing.
C. Laryngeal carcinoma (a squamous cell carcinoma)
Concept of synergism: MCC = Smoking; 2nd MCC = alcohol. Alcohol and smoking have a SYNERGISTIC effect which leads to laryngeal carcinoma.
Example: lesion in this slide is a laryngeal specimen – which of the following have the greatest risk factor? Answer – alcohol AND smoking (this is true for any squamous cancer from the esophagus to the mouth to the larynx). Smoking = MCC cancer in mouth, upper esophagus and larynx. Alcohol can do the same thing, so if you are smoker and alcohol consumer, you can double your risk. MC symptom assoc = hoarseness of the throat. Example: epiglottis; what can infect it? H. influenza – what is the symptom? Inspiratory strider.
Example: 3 month old child died with inspiratory strider – dx? Croup – parainfluenza; this is a TRACHEAL inflammation. Whereas epiglottitis is elsewhere. Both produce upper airway obstruction.
III. Respiratory Distress Syndromes:
A. Hyaline membrane dz (Neonatal Resp distress syndrome) If something has a lot of pink in it, what is it? Hyaline. Key to understanding this dz is massive atelectasis.
1. What is atelectasis? Collapse of airways. Why did these airway collapse? No. surfactant (aka lecithin/phosphotidyl choline/phosphotidyl glycerol – they are all surfactant). So, deficient of surfactant causes atelectasis b/c:
Collapsing pressure in the airways = surface tension/radius of airway. So, on expiration, normally the airway will be smaller b/c there is a pos intrathoracic pressure. If you decrease the radius, you will increase the collapsing pressure in the airways. Therefore, on expiration (in all of us), we have to decrease surface tension (which is what surfactant does) – by doing this, it keeps the airways open on expiration, preventing atelectasis.
2. Three causes of RDS:
a. Prematurity: surfactant begins syn early, but it peaks at 32-35 week, so if you are born prematurely, you will not have enough surfactant, and baby will develop increased risk of developing RDS. Sometimes mother has no choice and must deliver baby, or else it will die, and there is something you can do to the mom so the baby has more surfactant: give mother glucocorticoids b/c they stimulate surfactant synthesis. Example: what can you do to increase surfactant (but glucocorticoids wasn’t one of the answer choices) – thyroxine (thyroid hormone) (as does prolactin); does that mean you give thyroxine b4 delivering the baby? No, will give mom and baby hyperthyroidism.
b. Diabetes: gestational diabetes = woman who wasn’t pregnant, becomes pregnant, and then obtains glucose intolerance after delivery – so if a diabetic gets pregnant, this is not called gestational diabetes, but a diabetic that got pregnant. Its imp that a woman in pregnancy has good glucose control b/c if she is hyperglycemic, baby will be, too. B/c baby is hyperglycemic, it will stimulate insulin synthesis, and insulin has a negative effect on surfactant syn and will decrease its synthesis. c. C section – b/c the baby is not delivered vaginally, there is no stress. B/c the baby has not been stressed, the ACTH and cortisol are not released, and surfactant is not made. Whereas a child that is delivered vaginally has a lot of stress and therefore a lot of ACTH and cortisol is being released, which stimulates surfactant release. So, C section predisposes to RDS. So, these are the three main causes (prematurity, diabetes, and C section).
3. Complications and associated conditions:
a. Example: why are the babies of poor glycemic control big (macrosomial)? The baby’s insulin is increased to keep the glucose down. Insulin will increase storage of triglyceride in adipose (it increases fat storage). Where is most of the adipose located? Centrally. So, one of the reasons why they have macrosomia is b/c insulin stimulates synthesis of TG and deposition of fat. Also, insulin increases uptake of aa’s in muscle (like growth hormone). So, it will increase muscle mass. So, the reason for macrosomia is increased adipose and muscle mass, both due to insulin. This also explains why they get hypoglycemia when they are born. The mother’s hyperglycemia is coming into the baby, causing the baby to release insulin; the moment insulin is made and the cord is cut, and no more increase in glucose, glucose goes down, and leads to hypoglycemia.
b. Superoxide free radical damage seen in retinopathy of prematurity and blindness and bronchopulmonary dysplasia.
c. Why do babies with RDS commonly have PDA? B/c they have hypoxemia. When a normal baby takes a breath, it starts the process of functional closure of the ductus. However, with hypoxemia after they are born, it remains open, and they have a machinery murmur.
d. Hyaline membranes are due to degeneration of type II pneumocytes and leakage of fibrinogen, and it congeals to form the membrane. So, they will give a classic history for RDS, and then will ask for the pathogenesis of hypoxemia in the baby. This is a massive ventilation defect b/c everything is collapsing. This is a SHUNT problem, which leads to a massive interpulmonary shunt. Rx=PEEP therapy – positive end exp pressure b/c these airways are collapsed and you need to get O2 into them and surfactant. So, give O2 and at the end of expiration, pump in pressure, which keeps airways open on expiration, so you can keep O2 in them.
Example: pic with type II pneumocyte (with lamellar bodies – look like onion, and hyperplastic arteriolosclerosis b/c they are concentrically shaped). These lamellar bodies contain surfactant. This would ID it as a type II pneumocyte. They commonly give EMs of the lung with an alveolar macrophage. Macrophage has ‘junk’ in the cytoplasm. The type II pneumocyte is the repair cell of the lung and synthesizes surfactant.
B. Adult Respiratory Distress Syndrome (ARDS)
In terms of ARDS, essentially it is the same as RDS in pathophys, but is NEUTROPHIL related injury. In RDS you’re not making surfactant b/c you are too premature or have too much insulin and just have collapsed alveoli. BUT in ARDS its b/c you have too much inflammation; there is no inflammation in RDS.
MCC ARDS = septic shock (MCC septic shock = E coli from sepsis from an indwelling catheter; MCC DIC = septic shock). Example: In the ICU – if a pt come in with dyspnea and its within 24 hrs of having septic shock, pt has ARDS. If pt is in septic shock and within 48 hrs of admission and is bleeding from every orifice, he has DIC. So, first day = septic shock, second day = ARDS, third day = DIC. Pathogenesis: Neutrophils get into the lung in septic shock and start destroying all the cells of the lung (type I and II pneumocytes). So surfactant production decreases and result is massive atelectasis (collapse). However, this is neutrophil related (the neutrophils are destroying the type II pneumocyte. The reason why they get hyaline membranes in the ARDS is b/c the neutrophils have to get in the lungs by going through the pulmonary capillaries, so they put holes in them as they get out of the bloodstream and into the lungs (this is why it is called leaky capillary syndrome). All the protein and fibrinogen get in and produce hyaline membranes. Therefore, you can actually see hyaline membranes in ARDS. So, there is massive collapse and the pathophys is intrapulmonary shunting. This is the same in RDS, but ARDS is neutrophil related, which is a bad prognosis.
Spontaneous pneumothorax and tension pneumothorax
A. Spontaneous pneumothorax
MCC spontaneous = ruptured subpleural bleb – have pleura and right underneath is a bleb (air pocket). The bleb (air pocket) ruptures causing a hole in the pleura, so that part of the lung collapses. B/c what’s keeping it expanded is neg intrathoracic pressure, which keeps the lungs expanded. So, if you put a hole in the pleura, then the atmospheric pressure is not negative, but is the same as the air you are breathing. So, there is nothing to hold it open and therefore it collapses. When parts of the lung collapse, there are things that will take up the slack. One of those is the diaphragm. If you collapse part of the lung, the diaphragm will go up on that side to take up the open space on that has been left. Not only that, if there is a collapse on one side, the trachea will go to the side that there is space. So, will have tracheal deviation to the side of the collapse, and the diaphragm is up, leading to spontaneous pneumothorax. Usually seen in tall male – they have blebs that rupture and lead to spontaneous pneumothorax. Can also get in scuba divers b/c they come up too quickly, which leads to rupture of the blebs.
B. Tension pneumothorax
Diff from spontaneous pneumothorax. MC due to knife injuries into the lung. There’s tear of pleura (flap), sp when you breathe in the flap goes up and on expiration it closes. So, the air stays in the pleural cavity. So, every time you breathe, the flap goes up, air stays in, and on expiration it closes. So, for every breath you take, it keeps increasing and the pressure in the lung. The lung hasn’t collapsed yet. The increase in pressure starts pushing the lung and the mediastinum to the opposite side. When it pushes it, it compresses the lung and it leads to compression atelectasis (it is not deflated b/c of a hole – there isn’t a hole – it’s a tear that when the air went in it went up and it shut on expiration, and that pos pleural pressure is pushing everything over to the opposite side). This compression will push on the SVC, right vent, and left atrium on the opposite side. This will compromise blood return and breathing, leading to a medical emergency. So, it’s like filling tire up with air, but cannot get out. Air is filling pleural cavity and cannot get out. It keeps building up and starts pushing everything to the opp side. With a pos intrathoracic pressure, the diaphragm will go down (goes up in spontaneous pneumothorax).
V. Pulmonary Infection
1. 2 kinds – Typical and Atypical
Typical – wake feeling normal, then suddenly develop a fever, productive cough
Atypical – slow, insidious onset (feel bad over few days)
2. Community vs. Nosocomial (hospital acquired)
If you get pneumonia in the community and it’s typical, it is Strep pneumoniae. If you get pneumonia in the community and it is atypical, it’s mycoplasma pneumoniae. Organisms in the hospital (nosocomial) = E coli, Pseudomonas, Staph aureus (will not get strep pneumoniae in the hospital).
3. Productive cough in Typical pneumonia
Reason for productive cough in typical pneumonia: have exudate (pus) and signs of consolidation in the lung – Slide: yellow areas with microabcesses which are consolidation in the lung. Ie lobar pneumonia = see consolidation in lung, within alveoli, causing consolidation. Therefore, with typical, see consolidation and pus in the lung. Physical dx’tic tools of lung consolidation: decreased percussion, increased TVF (when the person talks, feel vibrations in chest – if have consolidation in ie the upper left lobe, will have increased TVF b/c it is a consolidation, compared to the other side – so, increased TVF indicates consolidation), having an “E to A” (egophony) sign (pt says E and you hear A), whispered pectoriloquy (pt whispers “1, 2, 3” and I will hear it very loud with the stethoscope). Therefore, decreased percussion, increased TVF, egophony, and pectoriloquy = consolidation. What if there is a pleural effusion overlying the lung? Only thing you would have is decreased percussion (this separates pleural effusion from pneumonia).
4. Atypical pneumonias
They do not have a high temp and do not have productive cough b/c they are interstitial pneumonias. They have inflammation of the interstitium – there is no exudate in the alveoli – which is why you are not coughing up a lot, and therefore do not have signs of consolidation. So, will not have increase TVF, “E to A”, with an atypical. Atypical pneumonia has an insidious onset, relatively nonproductive cough, no signs of consolidation.
MCC typical pneumonia = strep pneumoniae (know the pic) – gram “+” diplococcus (aka diplococcus) – Rx = PCN G
MCC atypical pneumonia = mycoplasma pneumoniae; 2nd MCC = Chlamydia pneumoniae; which are all interstitial pneumonias.
Bronchopneumonia: MC due to strep pneumonia, and community acquired. Lobar pneumonia. Slide: lobar consolidation on chest x-ray – strep. Pneumonia.
a) Viral pneumonias
1) Rhinovirus = MCC common cold; they are acid labile – meaning that it won’t lead to gastroenteritis in the stomach b/c is destroyed by the acid in the stomach. Never will have a vaccine b/c 100 serotype.
2) RSV – MCC bronchiolitis – whenever you inflame small airways, its leads to wheezing. This is a small airway dz and bronchiolitis is MC due to RSV and pneumonia. So, pneumonia and bronchiolitis is MC due to RSV in children.
3) Influenza – drift and shift – have hemagglutinins, which help attach the virus to the mucosa. Have neuraminidase bore a hole through the mucosa. Antigenic drift = minor change/mut’n in either hemagglutinins or neuraminidase; do not need a new vaccine; antigenic shift= major change/mut’n in either hemagglutinins or neuraminidase need a vaccine. The vaccine is against A Ag.
b) Bacterial pneumonias
1) Chlamydia psittacosis – from birds (ie parrots, turkeys).
2) Chlamydia trachomatis – a little kid was born and a week later he was wheezing (big time), pneumonia, increased AP diameter, tympanic percussion sounds, no fever, eyes are crusty (both sides), weird cough – staccato cough (short coughs). He got it from his mom’s infected cervix. (MCC conjunctivitis in 2nd week = Chlamydia trachomatis). (MC overall of conjunctivitis is inflammation of erythromycin drops).
c) Hospital-acquired gram-negative pneumonias
1) Pseudomonas – water loving bacteria, therefore see in pt in ICU when on a RESPIRATOR. pt water unit with green productive cough with.
2) Klebsiella – famous in the alcoholic; however, alcoholic can also get strep pneumonia. So, how will you know strep vs. Klebsiella? Alcoholic with high spiking fevers, productive cough of MUCOID appearing sputum – the capsule of Klebsiella is very thick. Lives in the upper lobes and can cavitate, therefore can confuse with TB.
3) Legionella – atypical cough, nonproductive cough, very sick can kill you, from water coolers (water loving bacteria), seen in mists in groceries or at restaurants.
Example: classic atypical pneumonia, then pt had hyponatremia – this is Legionella. Legionella just doesn’t affect the lungs, also affects the other organs such as liver dz, interstial nephritis and knocks off the juxtaglomerlur cells, and kills the renin levels, low aldosterone and therefore lose salt in the urine, leads to hyponatremia (low renin levels with low aldosterone). Rx = erythromycin
B. Fungal Infections
The two systemic fungus are Candida and Histo
1. Candida – seen in indwelling catheters (usually those in the subclavian). And get Candida sepsis
2. Histoplasmosis = Midwest (Ohio/Tennessee valley) carried by dung of starlings and bats – often seen in cave explorers, or spelunkers. They develop non-productive cough. Histo is the only systemic fungus that has yeasts phagocytosed by alveolar macrophages.
3. Cryptococcus = Pigeons– looks like mickey mouse – yeast forms are narrow based buds. Example: NY exec with pigeons roosting in air conditioner and developed non productive cough. Example: painter developed resp infection worked on Brooklyn bridge with pigeons, how do you treat? Amphotericin B.
4. Blastomycosis = SE USA = skin and lung infections; broad based bud
5. Coccidioidomycosis: SW USA (new Mexico, Arizona, southern Cal. = coccidiomycose – has spherule endospores (know the pic). Example: in LA earthquake, a # of people had nonproductive cough–the arthrospore (the infectious form) is in dust. With the earthquake, dust comes up, breathe it in. Example: man that is an Indian artifact explorer in the sonaran desert, which is in Arizona, and is a CAVE explorer that developed nonproductive cough – this is COCCIOMYCOSIS (not Histo b/c not the Midwest).
6. Aspergillus – 3 different manifestations/dz’s:
1) loves to inhabit abandoned TB fungus cavities – fungus ball (aspergilloma, a very common cause of massive hemoptysis). Example: left upper lobe cavitary lesion and asp love to live in there = fungus ball
2) vessel invader; therefore will invade the vessels in lung, leading to thrombosis and infarction
3) allergies the mold, leading to extrinsic asthma and type I HPY. So, three manifestations: fungus ball, invasive vascular dz producing hemorrhagic infarctions of the lung, and asthma. Example: pic of corona – component of Aspergillus (looks like a crown) – septate is very characteristic (mucormycosis is nonseptate and has wide angles, while Aspergillus has narrow angles in its budding and corona’s).
7. PCP (Pneumocystitis carinii pneumonia. Fungus (used to be a protozoa) – b/c more things in the cell wall that look like a fungus. It’s associated with HIV, MC AIDs defining lesion (as soon as the helper T cell ct is 200, it usually shows up). Used to be MCC death in AIDs pt, but now has gone down, b/c as soon as your CD4 ct is 200, dr. will put pt on prophylactic therapy with TMP-SMX. When taking TMP-SMX and protecting against PCP, would other organism is the pt protected from? Toxoplasmosis. (so, you get 2 for 1). MCC space occupying lesion within the brain in a pt with AIDs= Toxoplasmosis.
Seen with silver stain: cysts of PCP can be seen – look like ping pong balls, seen in alveoli, leading to alveolar infiltrate, leading to dyspnea, tachypnea, foamy bubbly infiltrate, on chest x-ray, looks all white out b/c of the involvement of the lung – however, not only seen in lungs, can be seen in any part of the body– also seen in lymph nodes of HIV “+”. Other organisms that are only seen with silver stain: bartenella henselae (bacillary angiomatosis), Legionella (not visualized with gram stain, therefore use butuly??? silver stain)
Organism in upper lobe of lungs – (play odds) – TB – see cavitary lesion, which is reactivation TB (not primary). Primary TB is the lower part of the upper lobe or the upper part of the lower lobe and close to the pleura (kind of in the middle of the lobe). Primary TB has a Ghon focus and a Ghon complex. Most people recover; when pt is immunocompromised, it leads to reactivation and goes into the apex and produces a cavitary lesion. There is no Ghon focus or complex in reactivation TB, only primary TB.
Other things that cavitate in upper lobes:
- Which systemic fungus is the “TB” of the lungs? Histoplasmosis
- Which cancer can cavitate in the lung? Squamous Cell carcinoma of the lung
- Which bacteria (that has a big mucous wall around it) can also produce cavitations in the upper lobe? Klebsiella pneumoniae.
- What is acid fast stain staining? Mycolic acids. So, just b/c something is cavitating the upper lobe, it is not necessarily TB.
C. Foreign Bodies
If you are standing or sitting up, foreign bodies will go to posterobasal segment of the right lower lobe. This is the most posterior segment of the right lower lobe.
If you are lying down (MC way to aspirate things), foreign body will go to superior segment of the right lower lobe.
If you are lying on the right side, can go to 2 places – 1) middle lobe 2) posterior segment of right upper lobe (this is the ONLY one that is in the upper lobe.
If you are lying down on your left, and aspirate, it will go to the lingula.
Sitting/standing = posterobasal segment of right lower lobe
Back: superior segment of right lower lobe
Right: middle or sup segment of right lower lobe
MCC abscess = aspiration of oropharyngeal material
Seen commonly in street people that do not have good dentition, may be drunk and fall and oropharyngeal material will be aspirated. Aspirate consists of aerobes and anaerobes, leading to putrid/stanch smell. The aspirate is a mixture of all these organisms: Mixed aerobes and anaerobes, fusobacterium, bacteroides. Can get absecces in the lung from pneumonia: staph aureus, Klebsiella (however, MCC is aspiration), see fluid cavities in lung on x-ray.
VI. Pulmonary Vascular Disease:
A. Pulmonary Embolus
2 types of emboli – tiny ones that produce wedge shaped hemorrhagic emboli or can chip off large ones. Where do most Pul emboli embolize from? MC SITE for thrombosis is the deep veins of the lower leg. This is NOT the most common site for embolization; it is the femoral vein (this is the MC site for embolization). Makes sense b/c venous clots propagate toward the heart (deep veins to the femoral vein, and the femoral vein is a larger vessel, therefore it is more likely to chip off). So, the femoral vein is the MC site for embolization to the lung. The deep veins are the MC site where deep venous thrombosis begins. (when it get to the femoral vein, it is dangerous for embolization). So, small ones produces hemorrhagic infarct that is only if you have an underlying lung dz. If I have a small embolus, prob won’t infarct b/c don’t have abnormal lungs. However, if you have preexisting lung dz you will infarct. 85% of the time embolus will not produce infarct. However, in the 15%, most of the pts with infarcts have preexisting lung dz (ie they are smokers). The other type of embolus is a saddle embolus (it is huge) and blocks off the orifices of the pulmonary vessels and pulmonary arteries. If you knock off at least 3 out of the 5 orifices, you are dead in a millisecond, so there is no infarction b/c you don’t have time to infarct. It produces acute right heart strain and immediate death. Screening test of choice: Ventilation perfusion scan – will have ventilation, no perfusion; confirmatory test is pulmonary angiogram.
VII. Restrictive Pulmonary Disease
Restrictive – something is restricting it from filling. Example: restricted filling of the heart = restrictive cardiomyopathy. Or restriction in filling up of the lungs with air. Have 2 terms: compliance (filling term, inspiration term) and elasticity (recoil, expiration term); For restrictive lung dz, picture a hot rubber bottle for restrictive lung dz. The hot rubber bottle is difficult to ‘blow up’, therefore compliance is decreased and it is hard to fill the lung up with air. So, what’s preventing it from blowing up? Fibrosis (interstial fibrosis, MC’ly). If you get the hot water rubber bottle filled with air and let the air out, what happens to the elasticity? Increases. So, compliance is decreased and cannot fill it up, but once you do fill the lung up, it comes out quickly (elasticity increases).
Example: pt with sarcoid – diff to fill lungs, but get it out fast (due to fibrosis). So, all TLC, RV, TV (all lung capacities have all equally decreased). FEV1/FVC on spirometer – take a deep breath (ie pt with sarcoid) – FEV1 (amount you get out in one sec – normally it is 4 liters) is decreased, FVC (total that got out after deep inspiration) is decreased (b/c increased elasticity) – this is the same as FEV1, so the ratio is often 1. Normally, the FVC is 5 liters, and the FEV1 is normally 4 liters – so, the normal FEV1/FVC ratio is 4/5 =80%. B/c the elasticity is increased, the FVC is the same as FEV1, and therefore the ratio is increased to 1 instead of 0.8.
Examples of restrictive lung dz’s:
1. Pneumoconiosis – airborne/dustborne dz’s – famous in big cities (LA, NY). Cole worker pneumoconiosis – esp. in west Virginia/Penn, have an anthrocotic pigment that causes a fibrous rxn in the lung, leading to restrictive lung dz. Have an increased incidence of TB, but not cancer.
2. Silicosis – Sandblasters get graffiti off things, or work in foundries and deal with rocks (ie quartz), and break them down, and breathe in dust, leading to silicoses). Have nodules in the lung that are hard has rock (literally) b/c there is quartz in them and it looks like metastatic dz in the lung (silica dioxide – which is sand in the lung) – again, increased of TB, not cancer. If pt happens to have rheumatoid arthritis, and also has one of these pneumoconiosis (ie Cole workers), have a potential for a syndrome, which is called caplan syndrome. Caplan syndrome consists of rheumatoid nodules in the lung (same as extensor surfaces in the arm). Rheumatoid arthritis commonly involves the lung with fibrosis. And rheumatoid nodules can form in the lung. The combo of rheumatoid arthritis (rheumatoid nodules) in the lung, plus pneumoconiosis (silicosis/asbestosis/Cole workers) = caplan syndrome.
3. Asbestos – asbestos fibers look like dumbbells (therefore ez to recognize). These are called ferruginous bodies. Asbestos fibers coated with iron, therefore can call them either asbestos bodies or ferruginous bodies. MC pulmonary lesion assoc with asbestos is not cancer – it is a fibrous plaque with a pleura, which is b9 (not a precursor for mesothelioma). MC cancer assoc with asbestos = primary lung cancer, 2nd MCC = mesothelioma, which is a malignancy of the serosal lining of the lungs. If you are a smoker and have asbestos exposure, you have an increased chance of getting primary lung cancer. This is a good example of synergism (other causes of lung cancer (SCC) include smoking, alcohol). Asbestos + smoker = will get cancer. There is no increased incidence of mesothelioma with smoking (not synergistic).
Example: Roofer for 25 years, nonsmoker (do tell you, but you had to know that 25 years ago, all the roofing material had asbestos in it; in other parts of NY, many buildings were torn down, and there was asbestos in the roofing of those buildings, which was inhaled by many people, and 10-30 years later they developed primary lung cancer or another complication of asbestosis). What would he most likely get? Primary lung cancer (primary pleural plaque was not there). If he was a smoker? Primary lung cancer.
Mesothelioma takes 25-30 years to develop. Lung cancers take about 10 years to develop. Lung cancers are more common, and you die earlier. What is the main cause of asbestos exposure? Roofers or people working in a naval shipyard (b/c all the pipes in the ship are insulated with asbestos), also in brake lining of cars and headgear.
4. Sarcoidosis =2nd MCC restrictive lung dz.
Example: classic x-ray – lymph nodes (hilar lymph nodes are big), haziness seen, too, which is interstial fibrosis. Sarcoid is a granulomatous dz that has NO relationship to infection (cause = unknown). Causes a noncaseating granuloma (not caseating b/c no relationship to TB and systemic fungal infections). The lungs are ALWAYS involved (lungs are the primary target organ), and more common in blacks.
Example: black person, 35 y/o, with dyspnea, see hilar nodes on x-ray, uviitis (blurry vision – this is inflammation of the uveal tract – this dz always affects something in the face, and the face the 2nd MC site a lesion will occur with this dz, can also involve salivary glands or lacrimal glands – something in the head/neck/face area (behind the lungs). This dz is a dx of exclusion, therefore must rule out anything that causes granuloma (TB, Histo), along with the correct physical presentation = Sarcoidosis. Rx = steroids. ACE enzymes are very high in these pts b/c granulomas in kidney; hypercalcemia – macrophages (epitheloid cells) make 1-alpha-hydroxylase. If they are making 1-alphahydroxylase, what is the mech of hypercalcemia? Hypervitaminosis D. you are second hydroxylation more vit D and therefore have excess vit D, and vit D promotes reabsorption of calcium and phosphorus, leading to hypercalcemia. This is the MC noninfectious cause of granulomatous hepatitis (TB is the MCC of infectious hepatitis, 2nd MC = pneumoconiosis).
5. Hypersensitivity pneumonitis (farmer’s lung, silofillers dz, bysinosis) These are restrictive lung dz’s. Don’t confuse farmer’s lung and silofillers dz – they are BOTH seen in farmers. So, remember one, the other is the other! Silofillers dz – put things in silos, which is a closed space, and fermentation of gas occurs, the gas is nitrogen dioxide – Example: farmer went into a room in his barn and suddenly developed wheezing and dyspnea, why? B/c he took in nitrogen dioxide, which is a fermenting problem. (silo can explode b/c gas from fermentation).
Farmer’s lung – thermophilic actinomyces (a mold).
Example: on tractor, dust being blown up in the air and thermophilic actinomyces (which is a mold) is inhaled; leading to hypersensitivity and HPY pneumonitis and they end up with a restrictive lung dz.
Bysinosis – worker in textile industry, and they get dyspnea. These are the HPY and restrictive lung dz’s.
Goodpasture syndrome – Begins in the lungs with a restrictive lung dz (with coughing up blood – hemoptysis), and ends up very shortly with renal dz (therefore, it starts in the lung and ends in the
kidneys). This is a restrictive lung dz.
VIII. Obstructive lung Dz
A. Deals with compliance/elasticity concept
In obstructive lung dz, no prob getting air in, but have a problem in getting the air out. Why don’t you have a problem getting it in? B/c the elastic tissue support is destroyed, so it is very ez to fill up the lungs. However, b/c the elastic tissue support is destroyed, it is very difficult hard to get it out b/c it collapses on expiration, so you can get air in, but cannot get air out. In a pt with obstructive air dz, they breathe in with no problem, but have trouble getting it out. So, something is left over in the lung – cannot get all the air out, therefore the residual volume is increased (whenever something is left over, it is called the ‘residual’). So, if you cannot get air out, then the residual volume increases, which means that the TLC will increase, which means that the diaphragm will go down b/c as the lungs are over inflated, and the AP diameter will go out. So, with obstructive lung dz, you have increased AP diameter and diaphragms go down (depressed). There is only a certain amount of expansion your chest can go. Eventually, the chest starts to compress other volumes (as you trap air and residual volumes go up). So, tidal volume starts decreasing, vital capacity goes down b/c the residual vol is increasing and you are compressing other volumes. So, TLC and RV increases, everything else decreases. On spirometer, FEV1 is very low (usually 1 – normally it is 4). In other words, you have a better FEV1 with restrictive lung dz b/c you can get air in. The FVC (total amt they can get out) is 3 liters (vs. 5 liters). When you do a ratio of FEV1/FVC, the ratio has decreased, hence distinguishing restrictive from obstructive dz’s. Classic COPD x-ray: hard to see the heart, with depressed diaphragms (at level of umbilicus), increased AP diameter – dx? Classic obstructive dz x-ray – prob getting air out, therefore the diaphragm is down and AP diameter is increased.
Example: 3 month old can have this same finding due to RSV
Example: Newborn with Chlamydia trachomatis pneumonia b/c he is trapping air.
B. There are 4 type of obstructive lung dz’s: chronic bronchitis, bronchiectasis, emphysema, asthma. The ones associated with smoking are bronchitis and emphysema.
1. Chronic Bronchitis
Purely a clinical dx = Pt has productive cough for 3 months out of the year for 2 consecutive years. Where is the dz? Terminal bronchioles (you have main stem bronchus, segmental bronchi, terminal bronchioles, resp bronchioles, alveolar ducts, alveoli). As soon as you hit the terminal bronchioles, these are small airway; it is all turbulent air up to terminal bronchioles. After that, it is parallel branching of the airways. The turbulent air hits the terminal bronchioles and then hits a massive cross sectional airway where you can go diff path’s b/c parallel branching of the small airways. So, the airflow changes from turbulent to laminar airflow. By the time you hit the resp unit, it is not moving the air. Most small airway dz’s are inflammation of the terminal bronchioles, leads to wheeze. Terminal bronchioles are the site of chronic bronchitis. This is the same area as asthma and bronchiolitis. More prox to the terminal bronchioles, in bronchitis, you will get a mucus gland hyperplasia, and a lot of crap is coming up (that’s the productive part). The actual area of obstruction is the terminal bronchiole. Have goblet cell metaplasia and mucous plugs. Think about having one terminal bronchiole and one mucous plug – this is affecting a major cross sectional area of lung b/c all the parallel branches that derive from here will not have CO2 in them, and they are trying to get air past the mucous plug, but cannot. So, there is a HUGE ventperfusion mismatch. This is why they are called blue boaters – they are cyanotic. They have mucous plugs in the terminal bronchioles and cannot rid CO2.
Not in the terminal bronchioles. It is in the resp unit (resp unit is where gas exchange occurs – cannot exchange gas in the terminal bronchioles – aka nonresp bronchiole); it is the primary place for expiratory wheeze and small airway dz, however. Gas exchange occurs in the resp bronchiole, resp alveolar duct and alveoli. Only need to know 2 emphysemas: centrolobular and panacinar. Emphysema affects gas exchange and where it affects the airway is more distal, compared to chronic bronchitis (proximal). So, when you have emphysema with all the inflammation associated with it, not only destroy the resp unit, but also the vasculature associated with it. Therefore, there is an even loss of ventilation and perfusion. So, will NOT have retention of CO2 in these pts. When you have a problem with a mucous plug in the terminal bronchiole, which is way more prox and a great cross sectional area of the lung is affected, there is gonna be a problem there; however when you are out this far (in emphysema) and also destroying the vessels, you will not have an increase in CO2. This is why they are called pink puffers, and this is why many of them have resp alkalosis.
a) Centrolobular – most associated with smoking and involved with the upper lobes. So, it is an upper lobe emphysema, and the primary portion of the resp unit that is destroyed is the resp bronchiole (this is the very first thing that smoke hits). Neutrophils will damage it b/c all people that smoke have more neutrophils in their lungs, and smoke is chemotactic for neutrophils. ALL smokers have increased neutrophils in their lungs. What does alpha-1 antitrypsin do? It’s an antielastase (its only purpose is to destroy elastases produced by neutrophils – that is its function. If you are a smoker, that is denatured. So, you also have an acquired alpha-1 antitrypsin def). Don’t have adequate alpha-1 antitrypsin, and have too many neutrophils in the lungs. This is a terrible combo. This why neutrophils have no problem in destroying the elastic tissue support of the respiratory bronchioles. So, you breath air in, which is no problem; but you try to get it out, and there is no elastic tissue support and leads to lung expansion – this is why blebs are found – there are big cystic spaces in the lung – it has trapped air in there b/c there is no elastic tissue, so when it tries to get by, it just expands. This is centrolobular emphysema of the UPPER lobes.
b) Panacinar Emphysema (remember ‘pan’ means everything – ie in pancytopenia, ALL the cells decreased). So, panacinar means that the ENTIRE resp unit is decreased b/c it is associated with NO alpha 1 antitrypsin. This is a genetic dz – auto rec – the LIVER does not make it. So, at a young age, you develop destruction of entire resp unit of the LOWER lobes, so this is a LOWER lobe emphysema. So, you can see that the resp bronchioles are knocked out, the alveolar ducts are knocked out, alveoli knocked out. So, you breathe in, and this entire resp unit catches it – this is in the lower lobes. Smokers, which have an acquired alpha-1 antitrypsin def, can get an element of panacinar emphysema in the lower lobes, too. So, smokers can get 2 emphysema’s: centrolobular emphysema in the upper lobes (which knocks off the resp bronchiole) and in the lower lobes, get a panacinar type of pattern. Therefore, can get upper AND lower lobe emphysema, and 2 diff types of emphysema.
Have bronchiectasis – see bronchi going out to the pleura (abnormal). When you see bronchi going out further than the hilum, this is bronchiectasis.
Mech: infection, destruction of the elastic tissue support, dilatation of the airways. Segmental bronchi; fill with pus. Example: pt has a productive cough of “cupfuls” (not just a tablespoon) of pus, b/c they are trapped.
1) MCC bronchiectasis in USA = cystic fibrosis. If parent with child has cystic fibrosis, will see huge pus coming out of bronchi, a couple times per day.
2) MCC bronchiectasis in 3rd world countries = TB.
3) Kartagener’s syndrome (aka immotile cilia syndrome). 9+2 configuration arrangement with cilia and microtubules. The problem with immotile cilia syndrome is an absent dynein arm. The 9 microtubules on the outside have arms that keep them together – these dynein arms are missing. So, when these arms are missing, the cilia cannot move. So, the places with cilia not moving are affected: these places are sinuses (why sinusitis is a problem), bronchiectasis (b/c there is cilia – psuedostratified columnar epithelium is affected), males and females are infertile (b/c the tail on the sperm cannot move – the tail is a modified cilia – they head is moving, but the tail is weak. Women are infertile; too, b/c the fallopian tube needs cilia to carry the egg down. Organs are located on the opposite side (dextrocardia, withOUT transposition of great vessels).
Can be extrinsic (type 1 HPY) and intrinsic: Involves chemicals – people in the workplace can get triad asthma, which involves people taking NSAIDs Many people, ie athletes will get exertional asthma and wheeze – cromolyn Na is the DOC for these patients. Cold temps can cause asthma. Type I HPY has nothing to do with these causes of asthma. The wheezing is due to inflammation of the terminal bronchioles – it is not due to smoking, but b/c factors like LT C4, D4, E4, PG’s causing inflammation and narrowing of the airways.
IX. Lung Cancer
A. Peripherally located vs. centrally located
1. Centrally located (mainstem bronchus):
Have the highest association with smoking. Include squamous cell carcinoma and small cell carcinoma. These are generally centrally located, hence mainstem bronchus types of locations. Squamous cell are more common than small cell carcinomas.
2. Peripherally located:
Adenocarcinomas (the more common primary lung cancer, more common than squamous) are more peripheral than central. Shifted to the periphery b/c of the filters of the cigarettes. The filters prevented the large carcinogens from passing in, but the small carcinogens still passed through, and they are not trapped in the main stem, but trapped in the periphery.
There are at least 3 or 4 types of adenocarcinoma. One obviously does have a smoking relationship, while the others do not. The ones that do not have a smoking relationship include bronchiolar alveolar carcinoma, and large cell adenocarcinoma of the lung (scar cancers).
B. Cytology: know what squamous cancer looks like with a pap smear. A lot of people think that the Papanicolaou stain is only done for cervical carcinoma. This is not the case. This is a famous stain (pap smear) used for all cytological specimens on for all organs. The stain stain’s keratin bright red. Slide: (pic) pt that is a smoker with a centrally located mass. Showing sputum sample with a Papanicolaou (pap smear) stain – has red keratin, which is squamous cell carcinoma. If this were a cervical pap smear from a woman that is 40 years of age, this is squamous cell carcinoma. The keratin is staining bright red! (bright red cytoplasm = keratin = squamous cell carcinoma). Papanicolaou stains keratin bright red. Example: small cells that look like lymphocytes – this is small cell carcinoma. This is more difficult to dx, b/c sometimes diff to tell the difference from lymphocytes. Slide shows malignant cells. Small cell carcinoma is the most malignant cancer of the lung. Rx? Radiation and chemo (not surgery). These are auput tumors with neurosecretory granules and S-100 Ag positive. They can make ADH and ACTH. A slightly less malignant tumor with auput origin is the bronchiocarcinoid. It is a low grade malignancy of the same types of cells that produce small cell carcinoma. So, they can invade, met, and produce carcinoid syndrome if they make increased amount of serotonin. They don’t have to mets to produce carcinoid syndrome – it just goes straight into the bloodstream. It is very uncommon.
MC cancer of lung = mets – ie see many metastatic nodules all over lung; if you play odds, what is the primary cancer? breast (which the MC met to the lung, or in other words, it is the MC cancer of the lung).
Summary of lung cancer in the lung:
- MC cancer = mets
- MC primary cancer = primary adenocarcinoma of the lung, followed by squamous and small cell carcinoma.
- Worst cancer (worst prognosis): small cell carcinoma.
Horner’s syndrome – pancoast tumor/superior sulcus tumor – tumors that are in the upper lobe posteriorly (in post mediastinum); most of the time is caused by squamous carcinoma in that area. What’s happening here? Tumor is locally invading into the local part of the lower trunk of the brachial plexus, so can get lower trunk brachial plexus like findings, and can also affect the superior cervical ganglion. This is in the posterior mediastinum, therefore will end up with Horner’s syndrome; as a result, will end up knocking OFF sympathetic activity – ptosis (lid is lower), anhydrous (lack of sweating), miosis (in sympathetic, which is fight or flight, normally have mydriasis, which dilates the pupil – with fight or flight, want as much light as possible, therefore dilating pupil, but this is cut off, leading to miosis). Do not confuse with SVC syndrome; this is just blocking off SVC.
Myasthenia has to do with thymoma, which is located in the anterior mediastinum. Exudate vs. transudate (< 3 grams, without many cells in it). MCC pleural effusion due to transudate = HF.
Exudate = protein > 3 grams, and has cells in it (ie pneumonia’s, pulmonary infarction)