> increased quantity of deoxygenated hemoglobin in capillary blood
> late sign of low capillary O2 hemoglobin saturation
Differentiate peripheral vs central cyanosis on O2 sats.
> peripheral > normal O2 sats
> central > low arterial O2 sats
What are normal PO2 and saO2 levels?
> PO2 > 80 to 100 mmHg
> saO2 > greater than 94%
What are 2 categories of pathologies associated with peripheral cyanosis?
> decreased venous outflow (DVT, SVC syndrome)
> decreased arterial inflow (issue with cardiac output, arterial occlusion, cold exposure, Raynaud's)
What are the 2 categories of pathologies associated with central cyanosis?
> no actual hypoxemia (normal PaO2) > dyshemoglobinemias, CO toxicity, methemoglobinemia (Won't necessarily see cyanosis)
> true hypoxemia > can either be a normal A-aO or high A-aO gradient
Describe an A-aO gradient.
> A-aO2 = PAO2 - PaO2
> alveolar concentration of oxygen minus arterial concentration of oxygen
> normal value is an A-aO of less than 15 mmHg
What are the 2 categories of pathologies for central hypoxemic normal A-aO2 cyanosis?
> low atmospheric pO2
> hypoventilation (increased pCO2)
What are the two categories of pathologies for central hypoxemic normal A-aO2 hypoventilatory cyanosis?
> CNS issues
> PNS or muscle issues
What are the two categories of pathologies for central hypoxemic high A-aO2 cyanosis?
> V/Q mismatch (most of the pulmonary diseases here)
Is Methemoglobinemia acquired or congenital?
How has the iron changed in hemoglobin in Methemoglobinemia?
> one or more iron's are in the ferric (3+) state instead of ferrous
> ferric irons can't bind O2 and increase O2 affinity of the other ferrous irons in the tetramer
What is the color of blood in methemoglobinemia?
> chocolate brown
Describe the normal rate of auto-oxidation of oxyhemoglobin to MetHb?
Describe the chemical process by which oxyhemoglobin can be converted to MetHb?
> when O2 binds Fe, one electron is partially transferred from heme iron to bound O2, forms a ferric-superoxide anion complex
> when O2 leaves, it mostly leaves as dioxygen, but some leaves as a superoxide (O2-) radical
> the partially transferred electron is not returned to the iron, leaves it in the ferric state
How does methemoglobinemia effect the Hb oxygen dissociation curve?
> is a right shift, binds O2 at higher affinity at any pO2
What molecule does the reaction of Superoxide dismutase and Superoxide produce?
> hydrogen peroxide
Is hydrogen peroxide normally toxic? How can it be toxic?
> usually nontoxic unless its allowed to react with iron or copper to produce radical species (fenton reaction)
What is produced by hydrogen peroxide and catalase? Where does the reaction take place in cells?
> produces H2 and O2
> usually takes place in peroxisomes, but RBCs also contain a lot of this
What is produced by hydrogen peroxide and glutathione peroxidase reacting?
Is the NADPH dependent or NADH dependent pathway important physiologically for MetHb reduction?
> NADH dependent
Give the normal function, coenzyme, and required cofactors for Cytochrome b5 reductase (Cb5R).
> reduces MetHb to oxyHb
> requires FAD
> requires NADH
What is the normal source of energy for RBCs? How are they able to generate NADH?
> normally glycolysis only (normally produce NADH via TCA cycle)
> can only get it from anaerobic glycolysis of GAPDH
In the reduction of MetHb to OxyHb, describe the first step involving NADH and FAD in the Cytochrome b5 reductase?
> get transfer of electrons from NADH to the FAD to generate FADH2
After the generation of FADH2, describe the next step that takes place between FADH2 and cytochrome b5.
> get transfer of electrons from FADH2 to the ferric heme group of the cytochrome b5, a heme protein complexed with Cb5R, generates a ferrous heme group
After the transfer of electrons to Cb5R, describe what takes place between Cb5R and MetHb.
> get transfer of electrons from ferrous heme of Cb5 to the ferric heme of MetHb, generates Hb
Describe how NADPH methemoglobin reductase and methylene blue can diffuse a MetHb crisis.
> methylene blue enters cells
> is reduced by NADPH methemoglobin reductase
> methylene blue reduces any oxidized heme groups, including MetHb
How does NADPH methemoglobin reductase get its electrons?
> pentose phosphate pathway
> glucose 6 phosphate being broken down by G6PD and generation of NADPH
Give the inheritance of cytochrome b5 reductase deficiency (NADH methemoglobin reductase deficiency).
In type I cytochrome b5 reductase deficiency, where do you get dysfunction of Cb5R? What are the MetHb concentrations seen? What are some symptoms?
> functional deficiency in RBCs only
> MetHb concentrations > 10-35%
> have cyanosis but usually asymptomatic
> mutation affects stability of the enzyme, gets rapidly degraded
In type II Cb5R deficiency, where is the functional deficiency seen? What are symptoms?
> functional deficiency in all cells
> cyanosis, mental retardation, failure to thrive, death in infancy
> mutation disprupts catalytic function or biosynth of the enzyme
Give the inheritance, protein in which there is a mutation, and the most common mutations for Hemoglobin M (HbM) disease.
> mutation in either alpha or beta globin
> mutation in proximal or distal histadine in the heme pocket is mutated to tyrosine
> formation of iron-phenolate complex that resists reduction to the divalent state
Does HbM respond to methylene blue treatment? Why?
> structural defect in the hemoglobin itself leads to resisting reduction
Describe acquired methemoglobin. What usually causes it? What MetHb levels are life threatening?
> usually from drugs (DAPSONE, BENZOCAINE, OTHER TOPICAL ANESTHETICS)
> life threatening when MetHb > 50%
What would happen if you have methylene blue to someone with G6PD defiency?
> ascorbate is better in these people
Define sulfhemoglobin. What color is it?
> incorporation of sulfur atom into porphyrin ring of hemoglobin by oxidant stress
> cannot transport O2
Is sulfhemoglobin normally produced like MetHb? Does the body recycle it?
> doesn't normally occur
> no normal mechs for fixing
What color cyanosis do you get in sulfhemoglobin?
What kind of shift is produced in the O2 binding curve in sulfHb?
> left shift, doesn't want to bind O2
Describe the symptoms of sulfHb?
> normally asymptomatic unless another hemoglobinopathy is present
> can get tachycardia, tachypnea, dyspnea, altered level of consciousness
What are the 3 general causes of mediastinal masses?
> tumors, cardiovascular lesions, others
What kind of masses would you expec to see in anterior masses?
> thyroid, parathyroid tumors
> lymphomas, thymomas, teratomas, esophageal tumors
> aortic aneurysms, pericardial cyst
> diaphragmatic hernias
What kind of masses would you expect to see in middle mediastinal masses?
> bronchogenic and lymphoma tumors
> aortic aneurysms, pericardial cysts
> bronchogenic cysts
> infectious, metastatic, sarcoid adenopathy
What kind of masses would you expect to see in the posterior mediastinal masses?
> neurogenic, carcinoid, esophageal tumors
> aortic aneurysms, pericardial cysts
> enteric cysts, hiatal hernia, diaphragmatic herna
> infectious, metastatic, sarcoid adenopathy
Which of these Mycobacteria can cause TB? (Tuberculosis, bovis, africanum, microti, canetti, avium complex)
> all but avium complex
Define drug resistant TB.
> caused by m. tuberculosis that is resistant to at least one of these drugs:
> isoniazid, rifampin, pyrazinamide, ethambutol
Differentiate between primary and secondary resistance.
> primary > bacteria that initially infects is resistant
> secondary > resistance develops during treatment (patient didn't get appropriate treatment or did not follow treatment regimen as prescribed)
Differentiate between monoresistant, polyresistant, multidrug resistant (MDR), and Extensively drug resistant (XDR) TB.
> mono > resistant to any TB treatment drug
> poly > resistant to any 2 TB drugs BUT NOT both isoniazid and rifampin
> MDR > resistant to at least isoniazid and rifampin (the 2 first line drugs)
> XDR > resistant to isoniazid, rifampin, plus resistant to any fluoroquinolone AND at least one of the 3 injectable second line drugs (amikacin, kanamycin, capreomycin)
Define Latent TB infection. Are they infectious or not? How do you detect a latent infection?
> occurs when tubercle bacilli are in the body, but immune system is keeping them under control
> people are not infectious w/ LTBI
> detected by mantoux tuberculin skin test
What changes from LTBI to TB disease?
> when immune system cannot keep tubercle bacilli under control
> people are with TB disease are often infectious
Describe the general steps in TB pathogenesis.
> enter lungs via inhaled droplets
> bacilli multiply in alveoli
> small number of bacilli enter blood stream and spread throughout body
> within 2-8 weeks macrophages surround tubercle bacilli, form granuloma
Give the TST (tuberculin skin test), chest x-ray, sputum smears and cultures, symptoms, infectivity for active TB infection.
> TST > positive
> CXR > abnormal
> sputum smears and cultures > positive
> symptoms > cough, fever, weight loss
> infectious before treatment
When after initial infection is risk of developing TB infection highest?
> first 2 years
What are some conditions that increase the probability of LTBI developing into active TB?
> HIV, drugs, immunosuppresive therapy, DM, kidney disease, silicosis, cancers, malnutrition
Describe the location in the body and frequency/special populations for Pulmonary, extrapulmonary, and miliary TB.
> pulmonary > in lungs, most frequent type of TB
> extrapulmonary > larynx, lymph nodes, pleura, brain, kidneys, bones and joints, seen in immunosuppressed patients and young children
> miliary > carried to all parts of body through blood stream, rare form
Give the oxygen use, apperance (both gram and association with other bacilli), cell wall composition, and special staining for TB.
> slender rods in straight or branching chains
> waxy cell wall composed of mycolic acid
> acid fast
> weakly gram positive
What about the immune system does a positive TST indicate?
> T cell mediated immunity to mycobacterial antigens
> can get false negatives in overwhelming active TB disease
Describe the immune responses to TB, the pathologic manifestations, and how the immune system mediates these manifestations.
> Immune system basically develops delayed hypersensitivity (Type IV?) to TB antigens
> get caseating granulomas and cavitation (result of hypersensitivity)
What is the primary cell infected by TB?
> enter via glycolipid-mannose receptor interactions
Once inside the macrophage, what happens?
> get multiplication and blocking of phagosome formation
> eventually get signals from TH1 cells that activate macrophages to become bactericidal (IFNg)
What are the main cytokines active in mediating TB disease?
> IFNg > activates macrophages to form granulomas and kill TB
> TNFa > released by macrophages, which promotes more monocyte recruitment
> can also get some NKT cell involvement
Describe the clinical appearance of primary tuberculosis.
> looks like acute bacterial pneumonia
> lower and middle lobe consolidation, hilar adenopathy, pleural effusions on CXR
What is secondary TB?
> arises from a previously sensitized host
> appears years after initial infection, stems from reactivation of latent infection
Describe the clinical features of secondary TB.
> insidious onset
> malaise, anorexia, weight loss, fever (low grade and remitting), night sweats
> increasing amounts of sputum, first mucoid, later purulent
> pleuritic pain
> consolidation or cavitation on CXR
> expectoration of blood from respiratory tract below level of larynx
If you see hemoptysis in children, what 3 things is it usually?
> congenital heart disease infection
> tracheostomy complications
What are the 3 branch points for hemoptysis?
> pulmonary causes (bronchitis, malignant lung cancers)
> vascular disorders (pulmonary thromboemboli, septic emboli from endocarditis, collagen vascular disorders (SLE, Wegener's, Goodpasture's)
> other medical disorders (coagulopathies, platelet disorders, cocaine, others)
Describe the deletion in DiGeorge Syndrome.
> encodes TBX1 transcription factor
Describe the immune deficiency in DiGeorge.
> selective T cell deficiency and thymic aplasia
> susceptible to viral infections (lack CTLs), mycobacterial infections (lack cytokines from TH1 cells), fungal infections (Pneumocystis)
What cytokine is crucial for early T cell development?
Describe the function of the stromal cells in the thymus.
> creates microenvironments that participate in differentiation and education of T cell progenitors from bone marrow
Do T cell progenitors express CD3, zeta chain, or CDR when entering the thymus?
> are double negative thymocytes or T cells
After rearranging TCRbeta chain and TCRa chain, what will they express?
> will express TCR, zeta chains, CD4, CD8
> double positive T cells or thymocytes
> also express CCR7
Describe positive and negative selection in the thymus.
> double postive T cells must bind self MHC with self peptides weakly
> if don't bind or bind too strongly, will apoptose
After negative selection, what do T cells lose?
> lose CD4 or CD8 and become mature naive CD4 or CD8 T cells
Describe the inheritance, symptoms, T cell numbers, Ig levels for DiGeorge Syndrome.
> sporadic, non familial inheritance
> loss of T cell immunity, congeital defects in hear and great vessels, Tetany (from hypoparathryroidism), and abnormal appearance of the face (mouth and ears)
> low T cell and Ig counts
> need to avoid live viral vaccines
Describe immunologic associations of Myasthenia gravis.
> associated with thymic hyperplasia or thymoma
> low PaO2 in blood
> low O2 saturation is called desaturation
1. A person is ascending to high altitude (5,000M) over a 3 day period. What alterations to their physiological system would most likely occur between the start of the trip and the 3rd day?
• A. Decreased pH in their blood
• B. Decreased pH in their CSF
• C. Decreased pCO2
• D. Decreased urinary excretion of HCO3
• E. Decreased respiration rate
￼2. The pulmonary edema in person who has rapidly ascended to high altitude is most likely due to what physiological alteration?
• A. Decreased cardiac output
• B. Decreased pH
• C. Increased pulmonary vascular resistance
• D. Decreased % of oxygen in the atmosphere
> can treat someone with carbonic anhydrase inhibitors (diamox?), causes them to have excess bicarb, remove it from blood, will help compensate for respiratory alkalosis that will develop, will also have sodium follow and remove water as well, acts as mild diuretic
3. The most likely treatment for pulmonary edema and cerebral edema is which of the following?
• A. An exogenous steroid
• B. A diuretic to lower blood pressure
• C. A diuretic to decrease blood volume
• D. A beta-2 blocker
• E. An alpha agonist
A (or C as pre-treatment)
4. The graph below is give to illustrate the difference in the amount of oxygen measured in mountain and sea level dwellers. The left shift in the curve reported for the mountain dwellers in mostly likely due to which of the following?
A. Increased 2,3 BPG
B. More efficient cellular
C. Increased lung volume D. Increased red blood
E. All of the above
. When the cabin of a commercial airliner loses pressure, oxygen mask drop will from the overhead compartment. As compared to the situation that existed when the cabin was pressurized, breathing from these masks is designed to do which of the following?
• A. Increase the pO2 in your blood by increasing atmosphere pressure to control values.
• B. Increase the pO2 in your blood by increasing the percent of blood saturation above control values.
• C. Increase to percentage of O2 you breathe to help keep the amount of oxygen in your blood from decreasing
• D. Decrease the amount of N2 dissolved in you plasma
If an individual breaths 100% oxygen at 30,000 ft altitude, the saturation of oxygen in her blood will most likely do which of the following as compared to her sea level values ?
• A. Stay near 100%
• B. Decrease by the ratio of atmospheric pressure at 30,000ft
divided by the atmospheric pressure at sea level.
• C. Decrease to approx. 70%
• D. Decrease to less than 50%
As you acclimatize to high altitude over an extended period of time, which of the following will most likely happen to the capillaries in your systematic circulation?
• A. Increase the velocity of blood flow in the capillaries to increase the exchange of oxygen
• B. Increase the diameter of capillaries to increase blood flow without increasing velocity
• C. Increase the length of the capillaries to allow more time for oxygen exchange to occur
• D. Increase the number of capillaries to increase the delivery of oxygen
Chronic mountain sickness is characterized by which of the following?
A. Extreme increase in HCT
• B. Increased cardiac output
• C. Decreased blood volume
• D. Decreased pulmonary artery pressure • E. Increased ejection fraction
Acetazolamide (Diamox) prevents the proximal tubule in the kidney from reabsorbing HCO3. This drug is given to help individuals acclimatize to high altitude. Which of the following is mostly likely the reason this drugs helps increase the rate at which people acclimatize when it is taken before the trip to altitude is started?
• A. Makes you excrete more HCO3 which helps you breathe faster
• B. Makes your glaucoma better
• C. Makes you retain more Na+ in your body • D. Makes you lose K+ in your urine
10. The pilot of the plane show in the figure below will most likely experience which of the following? (flying down)
• A. Red out
• B. Blue out
• C. Grey out
11. How can the effect of + G forces most effectively reduced?
• A. Compressing you leg muscles
• B. Holding your breath.
• C. Swallowing repeatedly
• D. Flexing your arms
12. While in space, fluids shift toward the head of the astronaut. Within minutes after return to earth the individual will most likely experience which of the following?
• A. A rapid weight gain
• B. Increased arterial blood pressure
• C. Decreased central venous pressure (CVP)
• D. Syncope
13. The bends can be induced by what activity?
• A. Snorkeling
• B. Not exhaling as you surface from a dive • C. Surfacing too rapidly
• D. Breathing a He-O2 mixture
14. What can be done to help reduce the risk of the bends?
• A. Surface rapidly before gas bubbles can form in your blood
• B. Breath diving gases with lower O2 and higher N2 percentage
• C. Use mixtures with less N2 and surface slow
• D. Go into a hyperbaric chamber after you surface
15. If you go to extreme depths, you will usually use a diving mixture with lower O2 percentage in the gas. This is because of which of the following?
• A. The hemoglobin will carry more O2 at depth
• B. The amount of dissolved O2 in the blood is adequate to
maintain muscle function
• C. The O2 will reach toxic levels if 21% O2 is used
• D. The reduced level of exercise seen in divers requires less O2
16. Which of the following is the best analogy of the bubbles that form in the diver's blood as she returns to the surface too quickly after being at a depth of 100 ft for 30 min?
• A. Bubbles that form in a bath water
• B. Bubbles that form when Mentos dropped into a Coke
• C. Bubbles that form in a soft drink when it is opened
• D. Bubbles that form when dry ice is placed in hot water
7. Helium gas is often used in ultra depth dives to help reduce the risk of the diver getting the bends. The advantage is due to which of the following?
• A. The low cost of the He-O2 diving gas
• B. Ease with which He moves through the tissue
• C. The binding of He to the hemoglobin
• D. The inability of He to complex with other compounds since it is a noble gas
18. Oxygen toxicity seen in divers breathing O2 at high pressure is thought to be associated with which of the following?
• A. Increased amount of O2 bound to hemoglobin
• B. Increased pH caused by the increased 02
• C. Decreased amount of dissolved O2 in the blood
• D. Oxygen free radicals in the tissue
19. Individuals trapped in a house fire often experience lung damage. What is the most frequent cause of this damage?
• A. Heat
• B. CO
• C. CN
• D. Smoke
20. Fluid often accumulates in the lung tissue after smoke damage to the lungs. The damage is thought to be caused by which of the following?
A. Rapid decrease in the protein content of the blood
• B. Increased capillary permeability (Kf) allows proteins to enter lung tissue
• C. Increase in the blood volume increases pressure in the capillaries
• D. Decrease in HCT
> get neutrophilic invasion, damages lung tissues, get pulmonary edema
21. What should a physician watch for in a person who has been exposed to smoke from a burning building?
• A. Decrease HCT
• B. increased blood volume
• C. Elevated Cardiac Output
• D. Pulmonary edema
• E. Elevated WBC
A person is ascending to high altitude (5,000M) over a 3 day period. What alterations to their physiological system could be expected?
The pulmonary edema in person who has rapidly ascended to high altitude is most likely due to what physiological alteration?
The bends can be induced by what activity? What can be done to help reduce the risk of
What is a positive and negative G- force?
How can the effects of + and - G forces be reduced?
How ae the lungs damaged by smoke inhalation?
What should a physician watch for in a person who has been exposed to smoke from a burning building?
Explain how smoke injury can alter lung physiology?
Describe the differences between chronic and acute mountain sickness.
> acute > hydrostatic pulmonary edema due to pulmonary hypertension and increased pulmonary capillary pressure, normal left vent function
> chronic > hematocrit goes way up, pulmonary arterial pressure goes way up, right side of heart hypertrophies, peripheral arterial pressure falls, get CHF
What is grey out due to?
> positive G forces
> red shift is color vision
> flying up really fast
What is redout due to?
> negative G
> blood is centrifuged up
> flying down really fast
Describe the effects of space on blood volume, red cell mass, muscle strength, work capacity, maximum cardiac output, and bone mineralization and mass.
Effects of prolonged microgravity
- (1) decrease in blood volume,
- (2) decrease in red blood cell mass,
- (3) decrease in muscle strength and work capacity,
- (4) decrease in maximum cardiac output, and
- (5) loss of calcium and phosphate from the bones, as well
as loss of bone mass.
Describe nitrogen narcosis.
> similar to alcoholic intoxication
> alters ionic conductance believed through membranes, reduces neuronal excitability
Describe decompression sickness.
> as you swim up quick, formerly supercompressed gasses get decompressed and bubbles
> blocks vessels
Why do you use helium in diving gasses?
> lighter, less resistance, easier to breathe
> less narcotic effect of nitrogen
> less helium dissolves in body tissues
What are the 2 first line drugs for active and latent TB?
How does isoniazid work? Describe some adverse effects.
> inhibits cell membrane/mycolic acid assembly
> leads to peripheral neuropathy (treated with B6), seizures w/ benzo's, liver toxicity
How does rifampin work? Describe some adverse effects.
> binds beta subunit of DNA dependent RNA polymerase, blocks transcription
> leads to oral contraceptive failure (b/c of CYP induction), diarrhea (kills normal flora), stains body fluid orange, liver toxicity
What is an alternative treatment for latent TB?
How does Rifapentine work? Describe some adverse effects.
> same mech as rifampin
> same AE's as rifampin
What 2 drugs are first line for active initial TB?
How does ethambutol work? Give some adverse effects.
> inhibits mycobacterial cell wall synth by inhibiting arabinosyl transferase
> optic neuritis (vision loss), hepatotoxicity
How does pyrazinamide work? Give some adverse effects.
> lowers intrabacterial pH, may impair cell wall synth via inhibiting fatty acid synthase I activity
> hepatotoxicity, gout (competes with urate secretion at OAT-1 in kidney)
What is used as an antidote for isoniazid toxicity?
> pyridoxine (b6)
What 2 drugs are used for MDR TB?
How does moxifloxacin work? What are some side effects?
> inhibits topo II (DNA gyrase), blocks DNA replication, repair
> leads to prolonged QT, arrhythmias, tendon rupture, liver toxicity?
How does streptomycin work? What are some side effects?
> (aminoglycoside) > binds 30s subunit of ribosome, inhibits protein synth
> limited host cell penetration, mostly effective against extracellular bacilli
> nephrotoxic, ototoxic, vestibulotoxic
What are 3 diffuse pulmonary hemorrhage pathologies?
> Goodpasture's, Idiopathic pulmonary hemosiderosis, wegener's
Define Goodpasture syndrome.
> autoimmune disease in which kidneys and lungs are injured by circulating antibodies
What are the antibodies in Goodpasture against?
> alpha 3 chain of collagen
What happens with the antibodies when they infiltrate the lung and kidney in Goodpasture's?
> initiate inflammation and destruction of basement membrane in renal glomeruli and pulmonary alveoli
> leads to rapidly progressive glumerulonephritis and necrotizing hemorrhagic interstitial pneumonitis
What is the gender and age of those with Goodpasture?
> teens or 20s
> also seen in SMOKERS
Give the morphology of Goodpasture's.
> red brown consolidation
> necrosis of alveoli w/ hemorrhages
> hemosiderin laden macrophages
> fibrous thickening in later stages
Give the clinical and radiographic features of Goodpasture's.
> hemoptysis and lung symptoms first
> focal pulmonary consolidations on CXR
> then glomerulonephritis and renal failure
> uremia and death
Define idiopathic pulmonary hemosiderosis.
> intermittent diffuse alveolar hemorrhage
Give the ages for idiopathic pulmonary hemosiderosis.
> young children
Give the onset, presentation, and CXR features for pulmonary hemosiderosis
> insidious onset
> productive cough, hemoptysis, anemia, weight loss
> diffuse pulmonary infiltration
Give the lung involvement and common presenting symptom of Wegener's Granulomatosis.
> presents with hemoptysis
> will see capillaritis and scattered poorly formed granulomas (unlike sarcoidosis)
What are the three types of precursor lesions in lung cancer.
> squamous dysplasia and carcinoma in situ
> atypical adenomatous hyperplasia
> diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
Where in the lung do cancers most often arise?
hilum of the lung and bronchi
Where are the most common sites for lung cancer metastasize?
> hilar lymph nodes
What are symptoms associated with lung cancer?
> weight loss
> chest pain
Give the morphological development for Squamous cell carcinomas.
> preceded by squamous metaplasia or dysplasia
> may transform into carcinoma in situ
Describe the morphology of Squamous cell carcinoma.
> well defined tumor mass
> obstructs lumen of bronchi, produces distal atelectasis and infection
> keratinization or intercellular bridges
Describe the morphology of Adenocarcinoma.
> malignant epithelial tumor with glandular differentation and or mucin production by tumor cells
Describe the morphology of bronchioalveolar carcinoma.
> occurs in pulmonary parenchyma in terminal bronchioalveolar regions
> mucinous gray translucence and solid gray white areas
> grow along preexisting structures w/o destruction
Give the morphology for small cell carcinoma.
> relatively small epithelial cells with scant cytoplasm, ill defined cell borders, finely granular nuclear chromatin border
> round, oval, or spindle shaped cells
> get lots of mitoses and necrosis
Give the morphology for large cell carcinoma.
> undifferentiated malignant cell tumor
> large nuclei, prominent nucleoli, moderate amount of cytoplasm
What are some abnormalities seen in non-small cell lung cancer?
> EGFR (tyrosine kinase inhibitor)
> ALK (tyrosine kinase inhibitor)
What are some molecular abnormalities most commonly seen in small cell lung cancer?
> MYC (MYCN or MYCL)
What are the 2 most common genes mutated in adenocarcinoma?
> EGFR or ALK
What are the precursor lesions to squamous cell carcinoma of the lung?
> squamous dysplasia
> carcinoma in situ
What is the precursor lesion to adenocarcinoma of the lung?
> atypical adenomatous hyperplasia
What is the precursor lesion to carcinoid tumor or small cell carcinoma of the lung?
> diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
Give the order of most common lung tumors in men and women (adeno, large cell, small cell, squamous cell).
> adenocarcinoma, squamous cell, large cell, small cell
> adeno, squamous, small cell, large cell
What 2 lung cancers have the strongest relationship with smoking?
> squamous cell carcinoma
> small cell
Describe the differences in how early they metastasize, ability to treat with surgery, degree of aggressivity, and responsiveness to chemo for Small cell and non small cell lung cancers.
> metastasize early
> surgery isn't used
> high response to chemo
> metastasize more slowly
> surgery is used
> low response to chemo
What routes are used for lung carcinomas to metastasize? What organ is most commonly metastasized to?
> lymphatics or hematogenous
> adrenals involved most commonly
What gender is squamous cell lung cancer more common in?
What can be seen on CXR when squamous cell carcinoma undergoes central necrosis?
> get cavitation on CXR
What can be some sequelae of squamous cell carcinoma in the lung?
> bronchial obstruction leading to atelectasis or infection
Describe the morphology of squamous metaplasia, squamous dysplasia, and carcinoma in situ as related to squamous cell carcinoma.
Where do squamous cell carcinomas appear in the lungs? What do they look like grossly?
> originate in the central portion of the lung from major or segmental bronchi
> gray/white to yellow tan
> necrosis and cavitation are seen
What is seen microscopically in squamous cell carcinoma of the lung?
> keratinization and or intercellular bridges
> keratin pearls > nests of eosinophilic aggregates surrounded by layers of squamous cells
What kind of differentiation is seen in Adenocarcinoma?
> glandular differentiation w/ mucin production
Where in the lung do Adenocarcinomas occur? How fast do they grow and how early do they the metastasize relative to squamous cell carcinoma?
> occur peripherally in the lung
> grow slower than Squamous cell, but metastasize earlier
How does bronchioalveolar carcinomas differentiate in origin in the lung from other adenocarcinomas?
> in terminal bronchioalveolar regions
Describe the gross appearance of bronchioalveolar carcinomas.
> single or multiple nodules
> mucinous gray or gray white
> can coalesce to form a pneumonia-like consolidation
Describe the microscopic appearance of bronchioalveolar carcinomas.
> tumor grows in a bronchioalveolar growth pattern along alveolar septa without destruction of alveolar architecture
Describe the differences between the mucinous and nonmucinous subtype bronchioalveolar carcinomas?
> mucinous > tall columnar cells with cytopalsmic and intraalveolar mucin, tendency to form satellite tumors
> nonmucinous > columnar or cuboidal cells
Describe the precursor lesion/development of adenocarcinoma of the lung.
> develops in a process involving atypical adenomatous hyperplasia
Give the definition for small cell carcinoma.
> malignant epithelial tumor that has neuroendocrine features
What paraneoplastic syndromes can be seen in small cell carcinoma?
> Lambert Eaton myasthenic syndrome
> ADH production
> ACTH production
Describe the gross appearance of Small cell carcinoma.
> perihilar mass
> white tan soft with necrosis
Describe the microscopic appearance of small cell carcinoma.
> sheets of small round oval spindle chaped cells with scant cytoplasm
> finely granular nuclear chromatin (salt and pepper)
> high Nuclear to cytoplasmic ratio
> high mitotic count
> nuclear molding, necrosis
Define large cell carcinoma, its location in the lung, and microscopic appearance.
> undifferentiated malignant epithelial tumor
> occur in periphery of lung
> large cells with large nuclei, prominent nucleoli, moderate cytoplasm
Describe the general and pulmonary symptoms of lung cancer.
> anorexia, weight loss, fatigue
> cough, hemoptysis, dyspnea, wheezing, postobstructive pneumonia
> chest pain if it involves pleura or chest wall
Describe ADH paraneoplastic syndrome.
Describe ACTH paraneoplastic syndrome.
Describe PTH related peptide syndrome. What cancer is it commonly associated with?
> causes hypercalcemia
> seen with squamous cell carcinoma
Describe Lambert Eaton Myasthenic syndrome.
> muscular weakness (especially of proximal muscles in the limbs)
> easy fatigueability
Describe carcinoid tumors of the lung.
> characterized by neuroendocrine differentiation
> low grade malignant epithelial tumors that can be classified as typical or atypical
Describe the gross appearance of carcinoid tumors.
> originate centrally or peripherally in the lung
> central carcinoids commonly project into the bronchial lumen and are generally covered by mucosa
Describe the microscopic appearance of carcinoid tumors.
> aggregates of cells that have round uniform nuclei and eosinophilic cytoplasm
Describe the symptoms of carcinoid tumors.
> cough, hemoptysis, obstruction of drainage
> infections, bronchiectasis, atelectasis
> carcinoid syndrome > release of vasoactive substances and include intermittent attacks of flushing and diarrhea (rare)
Give the definition of lung hamartoma.
> mixture of mature mesenchymal tissue elements that are normally found within the lung
Describe the gross appearance of lung hamartoma.
> peripheral location
> well circumscribed lesions
Describe the microscopic appearance of lung hamartoma.
> cartilage, fibromyxoid connective tissue, fat, bone, smooth muscle
> interspersed with clefts lined by respiratory epithelium
Describe the clinical symptoms of lung hamartoma.
> cough, hemoptysis, obstructive pnuemonia
> popcorn pattern of calcifications on CXR
Describe the microscopic appearance and common age and clinical presentation of inflammatory myofibroblastic tumor.
> proliferation of fibroblasts, myofibroblasts, lymphocytes, plasma cells
> more common in children
> cough, fever, chest pain, hemoptysis
Describe solitary fibrous tumor.
> soft tissue tumor that tends to occur in the pleura but can involve other sites as well
Describe the gross and microscopic appearance of solitary fibrous tumor.
> well circumscribed and consist of dense fibrous tissue
> whorls of reticulin and collagen fibers as well as interspersed spindle cells that resemble fibroblasts
Describe the presenting symptoms of mesothelioma.
> chest pain, dyspnea, recurrent pleural effusions
> death within a few years
Describe the gross morphology of mesothelioma.
> encase and compress the lung and directly invade thoracic structures
> see pleural effusions as well
Describe the microscopic appearance of mesothelioma.
> epitheliod, sarcomatoid, or mixed types
Define an empyema and the most common source.
> purulent pleural exudate resulting from seeding by bacteria or fungi
> most often from contiguous spread of intrapulmonary infection
> yellow green creamy pus
What can an empyema form if it doesn't resolve?
> dense tough fibrous pleural adhesions
> restrict pulmonary expansion
Define hemorrhagic pleuritis.
> can be from bleeding into the pleural space
> rickettsial diseases
> neoplastic involvement of the pleural space
What is hemothorax?
> blood accumulating in the pleural space
> can be complication of ruptured aortic aneurysm, vascular trauma
> identified by large clots that accompany blood
> serous fluid within the pleural space
What is the most common cause of hydrothorax?
> CHF w/ pulmonary congestion and edema
> can also see in renal failure, cirrhosis of the liver
What is a chylothorax?
> accumulation of milky fluid of lymphatic origin in the pleural space
> contains finely emulsified fats
What are causes of chylothorax?
> thoracic duct trauma
> obstruction causing rupture of major lymphatic ducts (malignancy, metastasis in lymphatics)