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485 Cards in this Set

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Tell me all about Isoniacid
highly-effective
inexpensive
eliminated by acetylation
SE: liver, periph neuorpathy
Tell me all about Rifampin
highly-effective
BUT expensive
Eliminated by cytP450
SE: liver, inc. metabo of other drugs, like oral coags, contraceptives, skin rashes, and urine may go orange
Tell me all about Pyrazinamide
highly-effective INTRACELLULARLY
SE: Liver, hyperuricemia
Ethambutol
not active intracellularly
SE: RETROBULBAR NEURITIS
Streptomycin
parenteral admin, so rarely used
aminoglycoside, affects ribosomal protein syn

NOT active intracellularly

SE: oto- and nephrotoxicity- ALL AMINOGLYCOSIDES have this, and must check with audiograms to make sure people are not losing their hearing by taking this drug
What percent of patients will have active TB?
10%
Of the active TB patients seen, how many will progress within the first 2 years? (Progress means to see caseating nectrotic airways, very sick people with cough and malaise. Defined as going from INFECTION to DISEASE because of an inability to contain the infection.)
HALF will progress (50%)
If you're HIV+, what's your risk of TB going infection --> disease?
8-10% ANNUALLY
Up to 20% of positive TST are FALSE POSITIVES, what are the possible causes?
Ifx with mycobacteria other than TB

or

BCG vaccine
Up to 20% of individuals with active TB may be FALSELY NEGATIVE, what are the most common causes?
1) critically ill TB patient
2) Immunosuppressed person
3) Recent TB infection
What kind of testing do you want to do for TB?
targeted testing, based on the idea that the accuracy oft he test depends on the prevalence of the disease in the population you're testing
Goal of targeted testing in TB?
identify persons at high risk for TB who would benefit by treatment of LTBI
What are 2 things that put people at higher risk of TB disease?
1) recent ifx with Mycobacterium Tuberculosis

2) presence of clinical conditions that are associated with an inc. risk of progression of LTBI to active TB
TST in positive if you're in the Risk group, and your induration is...
>/= 5mm

-HIV+
-recent contacts of TB case
-fibrotic changes on chest radiograph consistent with old TB
-patients with organ transplanta and other immunosuppressed patients receiving equiv of >15mg/day prednisone >1 month (corticosteroid >1month treatment increases the risk).
What populations fall in the TST >/= 10mm induration as a positive test?
-recent arrivals- <5yrs- from high prevalence countries
-IVDUs
-residents and employees of high-risk congregate settings- i.e. prisons, jails, nursing homes, hospitals, residential facilities for AIDS patients, and homeless shelters

-mycobacterial personnel
-persons with clinical conditions increasing their risk
-children under 4 and adolescents exposed to adults that are at HIGH risk
What populations fall in the TST >/= 15mm induration as a positive test?
Persons with no risk factors for TB, but DO NOT TEST THIS POPULATION
STD of care for community in LTBI patient?
Isoniazid daily for 9 months.
Signs/Sx's of TB DISEASE:
fatigue
malaise
weight loss
fever
night sweats
cough
hemoptysis

"Patients say they had it for weeks/months/years"
CXR in Dx of TB:
-95% of cases have abnormalities in apical/posterior segments of upper lobe, OR superior segments of lower lobe

-poss. unusual appearance in HIV+ pt.

-CANNOT confirm Dx of TB
How many HIV+ patients have normal CXR?
30%!!!
How do you Dx TB?
-AFB smear
PROBLEM: not sensitive OR specific

Instead, do MTB test!
What do you do to TREAT TB Disease patients?
4 drugs:
INH
Rifampin
Pyrazinamide
Ethambutol
Summary of XDR-TB Conclusions:
1) HIGHLY lethal
2) resistance in most cases due to transmission of XDR
3) suspect nosocomial spread
3 key enzymes to HIV
1) integrase
2) reverse transcriptase
3) protease
Discuss the copathogenicity of TB and HIV
1) TB causes IFN-gamma release from T cells, TB-activated macrophages release TNF and IL-1, BOTH of which enhance viral replication (TB ACCELERATES HIV)

2) one year mortality rate for treated HIV-related TV: 20-35%, 4X higher than HIVnegative patients
How do you treat pulmonary complications of HIV, ideally?
via a DEFINITIVE microbio/patho diagnosis, over empiric therapy, whenever possible
What are the 4 Influences on Risk of Developed HIV-Assoc Pul Disorders?
1) severity of immunosuppression
-CD4 count
2) patient's demographic charac
-how you catch your HIV helps w/ prognosis of assoc disease
3) place of current/prior residence
-What bugs are THERE????
4) Wherther using prophylaxis against common HIV-associated infections and HAART
-MOST IMPORTANT
HIV-Assoc Pul Disorders:
Gay HIV+ men less likely to devo TB and bacterial pneumonia

-blacks, hispanics, and IVDUs more likely to get TB

-Whites more likely to get PCP, KS, CMV
Where do you most often see histoplasmosis?
Ohio and Mississippi River Valleys
Where do you most often see coccidiomycosis?
Southwest
Prophylaxis and HAART have helped to decrease what two HIV-Pul associated diseases?
PCP and TB

-NOTE: HAART reduces the incidence of ALL opportunistic infections
What is one indication of doing an HIV test because it might be the first presentation?
recurrence of bacterial pnemonias
Despite the availability of an effective prophylaxis and HAART this DISEASE is still the most common AIDS-indicator infection and an important cause of respiratory illness and death among HIV infected individuals?
PCP!!!
PCP Presentation
-insidious
-gradual progression of SOB, fever, dry cough over weeks, but could also be seen as a rapid development over days

-MOST COMMON CAUSE of ARDS in patients with HIV
What's the test used to rule out PCP, for the most part?
LDH test, if it's not high, it's UNlikely to be PCP
Agent of choice for Tx of PCP?
Bactrim

-may need to start steroids too to calm down inflammation they're seeing
HIV+, CD4 <200, what is something you do?
prophylaxis with Bactrim to hopefully prevent PCP
What is the key to a CMV diagnosis?
Owl-eye appearance of the cells
What would you like to see to Dx as CMV?
-it can be seen in a non-pathogenic situation, so to confirm it as the culprit, would prefer to see tissue invasion and inclusion bodies
How do you treat CMV?
-HAART to restore immune fucntion
-ganciclovir or foscarnet, too
Most common site of infx for cryptococcus neoformans?
meninges

-Dx est. by seeing organisms on lung specimens but HIGH cryptococcal Ag titer on BAL may be suggestive; thick-walled organisms on an india ink stain
Histoplasmosis
-endemic areas, so see people from those areas in order to consider this

-may see miliary pattern on CXR

TREAT: amphotercin B, if more localized seen, then you may use itraconazole
Aspergillosis
-VERY immunosupressed to see it there
-rare in AIDS, but it's dreaded

again, wanna see tissue invasion to Dx, and tissue inflammation as a result is as bad as, if not worse, than the fungus itself
Key to aspergillosus Dx?
45-degree branching hyphae on the slides
Where do you see blastomycosis endemic?
midwest US, sotuhwest US, and Canada

-Dx with organism isolation
-treat with Amphotercin B
-SAME AS coccidiomycosis
Kaposi's
-most ocmmon malignancy in patients with HIV

-skin most common presentation
What usually causes an ACUTE pneumonia?
bacterial in origin

manifests intraalveolar exudate
What usually causes a CHRONIC pneumonia?
-viral, "atypical", intracellular bacteria, nocardia, actinomyces

-manifests as interstitial or granulomatous
Pneumonitis, usually not infectious. What are they?
Usually toxins or sometimes "atypicals"
4 stages of pneumonia, assuming all goes well:
1) congestion
2) red hepatization
3) grey hepatization
4) resolution
CHARAC of Congestion Stage of Pneumonia
heavy- red and boggy, airless, with vascular congestion
-see proteinacious exudate, few neutrophils, and intraalveolar bacteria
CHARAC of Red Hepatization Stage of Pneumonia
-firm, red, airless
-feels like a liver
Define Bronchiectasis:
PERMANENT dilatation of bronchi and bronchioles due to destruction of muscular layer and supporting connective tissue resulting from CHRONIC NECROTIZING INFECTIONS

-Clinically presents as a severe persistent cough and production of copious amounts of purulent sputum
Define an abscess:
localized collection of supprative necrosis within pulmonary parenchyma--> 1 or more LARGE cavities
How does necrotizing pneumonia differ from an abscess?
-nectrotizing pneumonia is a SIMILAR PROCESS TO AN ABSCESS, with multiple small cavitations
Abscess is usually often a result of acute bacterial pneumonia, often caused by one of what 3 organisms?
1) K. pneumonia
2) P. aeruginosa
3) S. aureus
Atypical or Chronic Pneumonia CHARAC:
Bugs:
-MYCOPLASMA
-legionella
-viruses
-chlamydia
-fungi

Gross: red-blue AND congested, patchy OR lobar

Complications: Diffuse alveolar damage, which is also seen in ARDS

-see thickened/edematous interstitial infiltrates that are lymphocyte rich (VARIES from typical/acute because those are alveolar in nature)

-difficulty breathing because of very poor air exchange
What is is Histoplasmosis similar to clinically?
it mimics TB

-fibrotic granulomas, veyr lamellar lookings see epithelioid histiocytes to define it as a granuloma

-lamellar-ness is JUST A CLUE, need to find the bug!
ANYTHING GRANULOMATOUS, what tests do you definitely do?
AFB (acid-fast), GMS/PAS (fungi) stains
Aspergillous is highly invasive, especially in...
LUNGS
What is CHARAC of PCP on an H&E?
-see the fluffy, cotton-candy like intraalveolar eosinophilic exudate

-with silver stain, see TONS of organisms
CMV CHARAC on a slide...
-interstitial pneumonia, owl-like inclusions within the cell
Why are the upper part of the lower lobes OR the lower part of the upper lobes the main locales for TB ifx?
thought to be because of the oxygen tension in those areas
Ghon focus
area of caseating necrosis within the lung
Ghon complex
area of caseating necrosis PLUS hilar adenopathy
Secondary TB affects what part of the lungs?
usually the apices
HIGHLY-CONTAGIOUS now
If pneumonia is acute, what's its cause and what pathology do you see?
bacterial

AND

intraalveolar exudates
If pneumonia is chronic, what's its cause and what pathology do you see?
viral, "atypical", fungal, intracellular bacteria, Nocardia, Actinomyces

AND

interstitial OR granulomatous
Pnumonitis is caused by...
a toxin

OR

"Atypical"- interstitial findings; usually it's not infections though
Bronchopnemonia means
more than one lobe and it's patchy
Lovar pneumonia involves...
part of whole of one lobe, and that's how you see >90% of Strep. Pneumonia
What kind of pathology do you see with Histoplasmosis?
noncaseating/fibrotic granulomas with a lamellar arrangement
What stain is used on aspergillosis?
GMS or silver stain
What kind of histological finding do you see with PCP that is somewhat unique?
cotton-candy appearance
-using the GMS stain there to visualize the bugs
CMV has what unique histo finding?
owl-eye intranuclear inclusions
Ghon focus is a...
primary lesion caused by mycobacterium bacilli (tuberculosis) developed in the lung of a previously uninfected individual.
What do you use to stain for Mycobacterium Avium Intracellulare
Acid-Fast Stain

-it's uncommon if you're immunocompentent, BUT in AIDS patients it causes disseminated ifx's
What are the 5 causes of hypoxemia?
1) V/Q mismatch
2) low FiO2
3) diffusion barrier (almost never a cause at rest)
4) shunt
5) hypOventilation
If you are talking about a suspected COPD patient, but they lack obstructive disease, what do you make as the diagnosis?
chronic bronchitis SOLELY is the diagnosis.
What are the main drugs used in obstructive lung disease?
bronchodilators
anti-inflammatory agents, ESPECIALLY glucocorticosteroids
mucoavtive agents
and antimicrobials
Distinguish between Asthma AND COPD:
Obstruction:
Asthma- REVERSIBLE
COPD- Poorly reversible

Inflammation:
Asthma- CD4s and Eosinophils
COPD- CD8s, neutrophils, and macrophages
In COPD describe the mechanism of destruction of lung tissue:
inflammatory cells, mainly neutrophils and macrophages, act via proteases and ROS to:

1) destroy lung tissue
2) create mucus cell hyperplasia and hypersecretion
In asthma, what's the mechanistic basis of constriction?
ROS and eosinophils are acting on the epithelium and smooth muscle.
-vagus nerve is affected too
What do methylxanthines do for asthmatics?
they can help to improve diaphragmatic breathing functions
What do you use leukotriene antagonists?
the substances are very potent SM constrictors normally, so wanna BLOCK their action.
Why would you give anticholinergics to an asthmatic?
they act to decrease the mucous hypersecretion
-perhaps they may relax the smooth muscle as well
What are the major group of drugs used in COPD?
ANTICHOLINERGICS
What's the most important target of drug therapy in obstructive lung diseases?
Inflammatory cells and their products
What's bad about using GCsteroids in a patient?
-they are systemically active!
-lots of SEs
-want to avoid oral/systemic prolonged steroids
Major effects of GCsteroids:
-bronchial hyperreactivity (no direct dilation)
-increase airway caliber
-reduce freq. of asthma exacerbations
What is the major class of drugs used for asthmatics?
beta-agonists
What is the major class of drugs used for COPD?
anticholinergics!
How do we make the diagnosis of asthma?
it's a reversibility issue, so when you give bronchodilators, i.e. Beta-agonists, you see an increase in the %FEV, and that shows that it's an asthma patient because their exacerbation is reversible, as opposed to COPD which wouldn't respond very much to the Beta-agonists
What's a good chronic drug of choice for asthmatics?
salmeterol, it's a long-acting, with a slow onset and longer half-life, so don't use in acute exacerbation, but good for management of asthma
What is most commonly used to potently dilate the bronchi in a short-term scenario of asthma attack?
albuterol
Leukotrien receptor antagonists act on which subtypes?
C4
D4
E4

NOT B4, that's done by LOX inhibitors, but those drugs are much more toxic
Which drugs might you nebulize?
1) beta-agonists
2) anti-cholinergics
3) glucocorticosteroids
How do you diagnose BPD?
-positive pressure ventilation during the 1st 2 weeks of life for a minimum of 3 days
-clinical signs- abnormal resp. function
-KEY: requirements for supplemental O2 longer than 28 days of age to maintain pO2 above 50mmHg
-CXR w/ diffuse abnormal findings charac of BPD

"Chronic oxygen dependency with certain radiologic features at 28 days of age"
What radiologic findings do you see in BPD?
Stage I:
ground-glass appearance, similar to HMD

Stage II:
Whiteout BUT IT'S SELDOM SEEN

Stage III:
Same patient at 1 month of age shows the development of small cystic lucencies in the lungs.

Stage IV:
7 mo of age shows small cystic lucencies have coalesced into larger lucencies with interspersed fibrotic stranding. Hyperinflation.
Oxygen facts in a BPD baby:
-O2 sat needs to be >/=90-92%
-wean daytime b4 nighttime- need O2 at night due to underventilation
-hypoxia associated with failure to gain weight
-chronic hypoxia will lead to pul HTN
What can you say about fluids in BPD babies?
fluid intake and calories are related, they need 110-140 CC/KG/day necessary to get the needed calories, but you have to monitor closely so you're not giving them too much fluid and causing that now rarely-seen Stage II whiteout due to pulmonary edema
What are 2 electrolyte imbalances you must consider in a BPD baby?
hyponatremia

AND

hypokalemia

-also think of volume depletion with alkalosis
-lasix could cause some issues, too
Would you use bronchodilators in a BPD baby?
-quite possibly, YES
-Tx occurs with inhaled albuterol and atrovent, and they've shown beneficial short-term effects in lung mechanics
What charac. an exacerbation of Chronic Lung disease?
rales
retractions
tachypnea
desaturations
CO2 retention
increasing oxygen requirement
How do you manage an exacerbation of CLD?
oxygen
bronchodilators
diuretics
MAY need vent. support
What is the most common cause of hospital admission in the 1st year of life?
RSV-based bronchiolitis
Define & describe bronchiolitis:
-acute LRI w/ inflamm of small airways of infants
-in winter see SPIKE in RSV ifxs
-may also be caused by parainfluenza and influenza virus
Risk factors of an RSV ifx
LBW
prematurity
Low SES
crodwed living coniditions
parental smoking
day care
absence of breast feeding
RSV infectivity CHARAC:
-incubation of 2-5 days
-nasal viral shedding of 6-21 days
-secondary ifxs from fam members 46% of the time, 98% due to other kids in day care and 42% hospital staff
RSV Presentation in infants/toddlers up to age 2
fever
cough
dyspnea
wheeze
cyanosis: bronchiolitis, pneumonia
RSV Presentation in children >2y/o
febrile rhinitis
pharyngitis
RSV Presentation in older children and adulta
COMMON COLD
With RSV, when greater than 2 years old, we don't get bronchiolitis, but...
we have it in our nose and can easily spread it.
RSV clinical features
-profuse coryza (cold in the head)
-congestion
-low-grade fever
40% go to be an LRI w/in 2-5 days
cough
dyspnea
wheezing
feeding difficulties
usually fever has resolved
severe: FLARING, retractions, cyanosis
RSV course is mild, and what do you see?
func recovery- 5-7days
cough usually <2 weeks
CXR clear w/in 9 days
temporary immunity for THAT SUBTYPE
What's the other virus, that's similar to RSV?
hMPV, aka Human Metapneumovirus
-no good test for it!
-usually mild RTI, perhaps slightly milder than those caused by RSV
-sevrere RTI not uncommon in young children and IC pts.
-risk groups: children, elderly, Immunocomp people
Babies in first 2-3 months of life with RSV are particularly at risk to develop...
apnea

-typically premie
-<44weeks postconceptual age
-central, but not obstructive
-may be presenting symptom
-lasts for a few days, as they get over the acute ifx, it tends to resolve
RSV Bronchiolitis has what indications for admission?
HYPOXIA IS THE MOST IMPORTANT ONE!!!

-sustained O2 sat less than 90 or 92% in room air
-<6 months of age ESPECIALLY
-cannot maintain oral hydration
-markedly elevated resp rate
-CLD Tx'ed with O2
-CongenHD with Pul HTN
Bronchiolitis hospitalization
-median stay is 3-5 days
-vent for 5 days, O2 for 7, and discharge by the 9th day
Bronchiolitis CXR
-bilat perihilar and patchy parenchymal infiltrates
-peribronchial cuffing
-hyperinflations with flattened diaphragms
-atelectasis esp RUL or RML
When does Bronchiolitis pt. get admitted to ICU?
-O2 sat less than 92% when 50$ FiO2
-pCO2 >50mmHg
-extrapul Sx's
-arrythmia
-Congen HF
-Apnea
SUPPORTIVE CARE/Tx of Bronchiolitis is treated how?
-admin humidified O2
-nasal suctioning to clear the upper airway
-monitor for apnea, hypoxemia, and impending resp. failute
-normalize the body temp
-rehydrate orally or by IV
-monitor hydration status
How do you treat the baby airway obstruction?
-trial bronchodilator, and if clinical response, then use to treat
Are steroids indicated in uncomplicated simple bronchiolitis?
NO
What is synagis?
-reduced hospitaliztions by 55% in high-risk groups
-monthly admin necessary during RSV season but costs $1,000/dose for 4 months
What are the JUSTIFIABLE RSV therapies:
-supportive Tx
-nebulized epi
-mech vent
-trial of Beta-adrenergics
What are the RCT-necessary RSV therapies:
-physiotherapy
heliox
exogenous surfactant
Apnea baby definitions
>15 secs for full-term
>20 secs for preterm
ALTEs CHARAC:
-high recurrence risk
-not predictive of SIDS
-most common cause is idiopathic

-see them in ER with relative frequency
Define SIDS:
-sudden death of an infant under one year of age which remains unexplained after a thorough case investigation, including review of clinical history, performance of complete autopsy, and examination of the death scene
NEED ALL OF THESE!!!
What's the big high-risk group for SIDS?
prematurity

-peak age range 2-4 months
-males
-expossure to cigarette smoke
-hyperthermia
Keys to Michael Light Infant Pul Death Lecture:
-incidence of SIDS has declined dramatically int he last 15 years since the intro of Back 2 Sleep campaign
-smoking and co-sleeping remain risk factors for SIDS
-home monitors should NOT be prescribed to prevent SIDS
Cystic Fibrosis lungs show..
-bronchitis
-bronchiectasis
-pulmonary abscesses arising in the bronchi
What's the incidence of CF?
Caucasians:
1/2500 get it, 1/25 carry gene

AfrAmer:
1/15000 get it, 1/61 carry gene

AsianAmer:
1/31000 get it, 1/88 carry gene
Major CF Sx's:
-respiratory are HALF of all

-FTT/malnutirion
-steatorrheal/abnl stool
-meconium ileus/intestinal obstruction
THOSE 3 together make up a lot of the GI and malnutrition problems

MAIN FEATURES:
malnutrition
failure to thrive
diarrhea-like disease
What's the basis of the CF defect?
There's a deficient Cl' channel, and so you don't have Cl- REABSORPTION, and thus Cl- is on the outside, and keeps Na+ with it

Normal Cl- is 10-30mequiv/L

Positive Test: 60+
Intermed: 30-60
Cl- Test is positive for CF when?
Positive Test: 60+
Intermed: 30-60
How many patients with CF present initially with meconium ileus?
10-15%

-but when they present this way, MUST DO SWEAT TEST ON ALL OF THEM
If you see rectal prolapse, what do you do next?
SWEAT TEST!

-even if basal polyposis and they have allergies, do the sweat test there too
What percent of infants with meconium ileus also have CF?
NINETY (90%) PERCENT!
If an infant has an intestinal obstruction or perforation in utero, do you do a sweat test?
YES!
Define Pancreatic insufficiency:
-severe exocrine pancreatic disease with documented nutrient maldigestion
-requires pancreatic enzymes with meals
-supplement food with those enzyme, and the disease can start very early and be progressive with time
Define Pancreatic Sufficiency:
-mild/moderate exocrine pancreatic disease
-not severe enough to produce nutrient maldigestion
-do not require pancreatic enzymes with meals
What's the basis of the pancreatic issues in a CF patient?
There is a concentrated acidic protein secretion that blocks the tubular region and prevents the enzymes from ever even having the chance to get out
DO a serum immunoreactive trypsinogen test in a patient with suspected CF, what do you look to see?
a HIGH serum-level
Describe height/weight of CF patients?
they're shorter and thinner than normal folks
If the CF patient has GI/pancreatic issues, what do you do to Tx?
-give pancreatic enzyme supplements
-vitamin supplments
-high-calorie diet
-emphasis on good bowel regimen
Newborn screening for CF follows what steps?
-Measures the IRT- immunoreactive trypsinogen
-elevated levels get sent for genetics
-follow-up with a sweat test
What disease is related to CF in 8-15% of patients?
CFRD- CF-related diabetes
What causes CFRD?
-acinar atrophy
-fatty infiltration
-fibrosis
-dec. in # of pancreatic islets

NOT an autoimmune process
-diabetic ketoacidosis is an exception
A small portion of CF patients see what other disease appear?
-cholestasis, duct obstruction in the liver, so it's an overt liver disease
CF liver disease accounts for how much mortality?
1-2% of CF mortality
Why do CF patients have airway problems?
the airway fluids are underhydrated and that creates constant cough, along with a gelatinous, tenacious fluid there, when you really need mucociliary clearance to be functioning, and it's just TOO thick
What is the major cause of morbidity and mortality in CF patients?
MAJOR PATHOGENS:

staph. aureus and haemophilus influenzae often lead to the ability to be Ifx'ed with pseudomonas which is the ultimate killer


-also see:
Burkholderia cepacia- can cause rapid and severe advanced disease, also even septicemia

-atypical myco- can lead to more aggressive disease

-aspergillus- and it's not the aspergillus that is so brutal, but RATHER the allergic response to it- called ABPA that causes all the damage, and the most common patient pop for ABPA is CF patients
Most common people to get ABPA?
CF patients
Do a lot of CF patients get pseudomonas disease?
YES! Up to 80% over the course of the disease!!!
What is the issue with CFTR in CF patients?
it prevents the OUTFLOW of Cl- ions into the extracellular space when the channel is mutated
How do you Tx CF:
bronchodilators- albuteral
chest physiotherapy
rhDNase
Abx- Staph aureus and p. aeruginosa ESPECIALLY
-inhaled ABX
-macrolide Abx as a protection for anti-inflammation
influenza vaccine
corticosteroids
ibuprofen
Classes of CFTR Mutation
Class 1: no synthesis
Class 2: no maturation
Class 3: blocked regulation
Class 4: decreased conductance
Class 5: decreased abundance

class 3 and 4 may see various other mutations, but having the same degree of function
Class 1,2, and 3 mutations give what grade of disease?
SEVERE
-PI
-meconium ileus
CFRD
severe hepatobiliary disease
Class 4 and 5 mutations give what grade of disease?
Mild
pancreatic sufficiency
risk of:
acute pancreatitis
-recurrent pancreatitis
-chronic pancreatitis
What Tx do you give to try and fix the truncated proteins of CF?
Gentomycin!
-can bridge truncation and correct the protein, intervenes on the stop codons!
What repro sys issues does CF deliver?
-obstructive azoospermia

-can't conduct through the vas deferens!
2 aspects of breathing volumes affected by a restrictive lung disease?
1) decreased Vital Capacity, leading to:
2) DEC TLC

Recall Vital Capacity = IRV + ERV + TV
What are all the extrinsic restrictive diseases?
-pneumothorax
-pleural effusion
-pleural thickening as in asbestosis
-scoliosis
-ankylosing spondylitis
-polimyelitis
-GBS
-ALS
-Myasthenia gravis
-muscular dystrophies
What are the disease of the lung parenchyma?
-idiopathic pulmonary fibrosis
-sarcoidosis
-hypersensitivty penumonitis- extrinsic allergic alveolitis
-radiation-induced fibrosis
-collagen vacular-related fibrosis
-lymphangitis carcinomatosis
Which type of collagen do you see in restrictive lung disorders?
Collagen Type III
An indication of restrictive lung disease is...
preservation of the FEV1/FVC ratio!!!
What is the test you would do with a suspected restrictive lung disease patient to show really strong indications of it being present? Think oxygen.
6 minute walking test

-RLD patients OFTEN desaturate very early on in disease because of the disease's patchiness
What do you see, in general, histologically with restrictive lung disease?
cast-like blue collagen and hyaline, which is a result of the chronic injury to the epithelial cells
Progressive fibrosis is seen in what part of the lungs?
it progresses at the BASES of the lungs

-see O2 saturation dropping
-pul vasc resist INC, with co-existing or even primary vasc disease AND destruction of pul artieroles and capillaries

-pul HTN develops leading to cor pulmonale
-starts in the bases of the lungs and with exercise you'll really exacerbate the disease
Where do you see honeycombing?
in Usual Interstitial Pneumonia
Distinguish the patterns of UIP and NSIP
UIP:
heterogeneous, patchy

NSIP Fibrotic + Cellular:
-homogenous, all looks the same
-other samples of this would appear cellular and homogenous
IPF Chief Complaint:
shortness of breath and/or cough for several months
Onset of IPF
-variable
-usually age 50-70
-familial disease, SO ASK FAM Hx
Clinical Presentation of IPF:
-progressive dyspnea on exertion
-cough, usually nonproductive and dry
-Clubbing in HALF OF PATIENTS
-bibasilar end-inspiratory crackles
-bibasilar, subpleural reicular opacities on CXR and HRCT
-restrictive pul phys with reduced lung columes and DLCo and WIDENED AaPO2
What are the MAJOR criteria of IPF?
-no known other causes of interstitial lung disease
-abnorm pul func studies
-abnorm CXR/HRCT scan
-No histo or cytological features supporting another diagnosis- MOST COMMON: IFX!
When you hear "velcro" sounds, and the duration of illness is >/= 3 months, think what disease?
after having ALL the major criteria, think IPF!
What are the 2 parts to the path of UIP?
1) periph accentuation of disease
2) transition into uninvolved lung
In what part of the lung do you typically see UIP?
usually subpleural and more prominent in lower lobes
What does general anesthesia do to FRC?
DEC by about 16%/500ml

-also creates V/Q mismatch and hypoxemia
Why do you see hypoxemia due to V/Q mismatch?
2 things:
1) INC dead space ventilation: more vent to NON-dependent areas of the lung
2) INC shuntlike- INC perfusion to POORLY VENTILATED dependent areas of the lung
What happens to lung volumes after abdominal surgery?
DECREASES IN:
TLC
FRC
RV
Which affects lung volumes more, Upper or Lower Abdo surgery?
UPPER
What's the normal closing volume and what happens to it with surgery?
it's normally about 30% of TLC and it's the vol at which flow from the dependent parts of the lungs stops during expiration due to airway closure, so it INCREASES with surgery
How do you predict post-op FEV1?
FEV1ppo = Actual pre-op FEV1 x %perfusion of the lung to remain, determined by an isotope scan

Equation 2:
FEV1ppo as a % of the normal
When trying to determine whether a patient is a candidate for a pneumonectomy, what is the required FEV1ppo?
>80%

if 40-80 then look at symptoms, and if <40% predicted, don't do the surgery if their Blood Gases don't look good.
How do you treat post-cardiac injury syndrome?
NSAIDs and corticosteroids work well!
Esophageal surgery post-op pul complications:
25-50% incidence
BUT
40-60% of operative MORTALITY!!!

-there is recurrent laryngeal nerve injury
-pleural effusion is possible
What do you measure with an incentive spirometer?
IC = IRV + VT
How does the expiatory curve get shifted in restrictive disorders?
TO THE RIGHT
Why does respiratory failure in chest bellows disorders show hypercapnia?
see increased work of breathing
leading to
decreased Tidal Volume and thus INC dead space
leading to
alveolar hypOventilation
leading to
the Hypercapnia, and acidosis
What is one of the major presenting features of Guillen-bairre Syndrome?
-see a RAPID progressive parethesias and muscle weakness initially in the legs, and then later on the arms, followed by dyspnea and weak cough, with an inability to clear secretions
What's the main cause of hypoxemia in chest bellows disorder patients experiencing respiratory failure?
V/Q mismatch
If you dip below what level of respiratory muscle strength do you see problems, and what is the problem?
if you drop under 50% and it's an issue with hypercarbia
Why do a sniff test, and what does it show if positive?
have the patient "sniff" the air, and the diaphragm should go DOWN, but with a hemidiaphragmatic paralysis, see the paralyzed side GO UP!!!
DIP shows what?
numerous macrophages in the alveolar spaces in a diffuse and uniform manner
-see type II pneumocyte hyperplasia and desquamation into the air spaces

-mortality: <20%
-smokers: 90% OF THE PATIENTS WITH THIS DISEASE
Respiratory Bronchiolitis-Associated Interstitial Lung Disease is strongly associated with...
smoking cigarettes

-more affinity for airways
-not as diffuse as DIP
-see broncioles with a lymphocyte infiltrate extending into the interstitium creating the picture of an interstitial disease

PROGNOSIS is much better than DIP and UIP
Where do you see NSIP?
-patients suffering from connective tissue disease, hypersensitivity reactions, and even due to drug toxicity

-uniform pattern with mononuclear infiltrates and different grades of fibrosis
lymphoid interstitial pneumonia is...
considered a lymphoproliferative disorder associated occasionally with immunsuppression
giant cell interstitial pneumonia is...
a hard metal pneumoncniosis assoc with exposure to cobalt
Reaction to the inhalation of organic dusts or biologic aerosolized particles int he environment
hypersensitivty pneumonitis/extrinsic allergic alveolitis

APPEARS AS A RESTRICTIVE PATTERN
Farmer's lung is caused by...
thermophilic actinomycetes
bird fancier's lung is due to...
pigeon breeder's lung, Ag present in bird poop, feathers, or serum proteins
Chronic Hypersensitivty pneumonia presents with.,..
chronic bronchiolitis
NSIP pattern
scattered granulomas
What are the complications of asthma?
infection
bronchiectasis
cor pulmonale
emphysematous changes
status asthmaticus
Wegener's Granulomatosis
charac. by presence of nectrotizing granulomatous inflammation and vasculitis

-affects upper respiratory tract, causes:
sinusitis
otitis
nasal disease
ear pain
oral lesions

lower resp tract sees:
multiple lesions

kidneys get affected by glomerulonephritis

PATIENTS HAVE ANTRINEUTROPHIL ANTIBODIES- ANCA- in serum
lung hemorrhage, glomerulonephritis, antibodies against basement membrane, with Ag being collagen IV
Goodpasture's Syndrome
Rheumatoid Arthritis
Patient presents with pleuritis, pleural effusion, chronic interstitial pneumonia resembling UIP, bronchiolitis, vasculitis, and necrobiotic nodules
Charcot-Leyden Crystals and Eosinophils
Asthma!

-see basement membrane thickening, too
pleuritis with pleural effusion, interstitial pneumonitis, DAD, hemorrhage, and vasculitis
Sys Lupus Erythematous
hypersensitive vasculopathy, chronic interstitial pneumonia with prominent fibrosis being the usual findings
Systemic Sclerosis or a scleroderma

-also think PUL HTN when you see this
Histo findings of sarcoidosis:
presence of collections of histiocytes and multinucleated giant cells

-granulomas have a distribution along the bronchovascular bundles
-rare in ppl <15 or >65
-blacks > whites
-T-cells mediate the granulomatous inflamm and thought to be due to an inhaled Ag rxn
Irreversible increase in size of air spaces distal to the terminal bronchioles
emphysema
2 types of emphysema:
1) centrilobular- proximal portion of term bronchiole is affected
ASSOC WITH CIG SMOKING
-it's the func impairment that does, because of great damage to the alveolar-capillary wall and reduced elastic recoil

2) panacinar- ENTIRE resp bronchiole is effected
seen in elderly patients
also in A1A deficiency patients

NEITHER OF THESE IS RESPONS FOR CLINCAL COURSE THOUGH
What is the pathogenic basis of emphysema?
IMblanace of proteases and antiproteases like A1A

-the antiproteases are made in the liver and if there's low production that could lead to a problem, or if the oxidative effects of cig smoke affected them, the elastic arch of alveolar septae may be destroyed

-emphysema occurs in ~15% of smokers
What are the major clinical Sx's of acute interstitial pneumonia?
cyanosis and SEVERE hypoxemia

BUT there is no catasrophic event precipitating it, so it's called idiopathic ARDS
What is the histologic pattern of ARDS?
diffuse alveolar damage with:
-fibrinous exudates
-hyaline membranes
-interstitial edema
-type II pneumocyte hyperplasia

HOMOGENEOUS APPEARANC
What kind of ifx in an immunosuppressed person could lead to acute interstitial pneumonia?
VIRAL ifx
How does an IPF patient present?
insidious presentation and PROGRESSIVE course, which is fatal in 5-6years
What does HRCT shown in IPF?
a PERIPHERAL honeycombing pattern!
How do you treat UIP?
cyclophosphamide, if anything
-numerous macrophages in the air spaces in a diffuse and uniform manner
-thickening of the alveolar septae with mild pneumonitis
-type II pneumocyte hyperplasia

WHAT IS IT?
desquamative interstitial pneumonia

-disease of mainly cig smokers
-affects lung homogeneously
-more affinity for airways
-less diffuse than other interstitial diseases
-macrophages in alveoli and bronchioles
respiratory bronchiolitis, associated with interstitial lung disease

-could be the same as DIP but in different stages
-related to cig smoke, too!
Interstitial lung disease with good prognosis and responsive to steroids
non-specific interstitial pneumonitis/fibrosis
Histology pattern is uniform w/ mononuclear infiltrates and different grades of fibrosis
NSIP

-homogeneous appearance
Interstitial disease due to the exaggerated reaction to the inhalation of organic dusts or biologic aerosolized particles in the home or work environment
hypersensitivity pneuonitis

-may result in severe fibrosing disease with continuous chronic exposure to the antigens
#1 treatment for hypersensitivty pneumonitis?
REMOVE THE ALLERGEN
What immune rxn is seen in hypersensitivty pneumonitis?
type II, sometimes some type IV with granulomas present
Chronic hypersensitivty pneumonitis presents how?
-acute exacerbations less frequent
-progressive respiratory insufficiency
-dyspnea
-cyanosis
-hard to tell from other chronic interstitial pneumonitis because total pul capacity is reduced
-may see:
honeycombing, loss of volume, and ground-glass opacities
See Charcot-leyden crystals, who makes em' and why?
ASTHMA!
-made by eosinophils
Multisystemic disorder charac by:
-necrotizing granulomatous inflammation
-vasculitis
Wegener's granulomatosis

AFFECTS:
URT-sinusitis, otitis, nasal disease, oral lesions
LRT
Kidneys
What is the key finding that will tell you "IT'S WEGENER'S!!!"?
ANCA
antineutrophil cytoplasmic antibodies with either the cytoplasmic/classic or perinuclear presentation
Autoimmune disorder consisting of the triad of:
1) glomeulonephritis
2) lung hemorrhage
3) anti-basement membrane antibody formation.
Goodpasture's syndrome

Ab's are to collagen IV
Pleuritis
pleural effusion
chronic interstitial pneumonia
resembles UIP
bronchiolitis
vasculitis
and
necrobiotic nodules
Rheumatoid Arthritis
Sarcoidosis demographic
women > men
blacks > whites
granulomatous disease
world-wide dist.
T-cells mediate the inflamm, which is thought to be due to an inhaled Ag
What's a very possible diagnosis when seeing a presentation involving bilateral hilar adenopathy?
sarcoidosis, especially if a female and/or black ethnically.
What tumors are centrally located?
squamous cell

AND

small cell
Breath Sounds, Resonance, and Fremitus of:

Pleural Effusion
Breath Sounds: DEC
Resonance: DULLNESS
Fremitus : DEC
Breath Sounds, Resonance, and Fremitus of:

Pneumonia- lobar
Breath Sounds: might be bronchial
Resonance: DULLNESS
Fremitus : INC!!!
Breath Sounds, Resonance, and Fremitus of:

Pneumothorax
Breath Sounds: DED
Resonance: HYPERRESONANT
Fremitus : ABSENT
How does the trachea displace when there's a collapse?
TOWARDS the lesion
Tension pneumothorax, which was does the trachea deviate?
AWAY from the lesion, you've put pressure on one side, so trachea will be pushed by that pressure.
What parts of the lung are usually involved in bronchiectasis?
lower lobes, extending from hila to periphery
How do you Dx bronchiectasis?
CT! Most likely, HRCT to see honeycombing. See those signet rings, too.

Side note: Histologically, see a heterogeneous pattern.
3 bugs that are most common causes of acute sinusitis, otitis media, and chronic bronchitis?
S. pneumo
Morraxella Catarrhalis
H. Influenza
What's the leading causes of death in AIDS patients?
TB!
What are the more likely risk groups for HIV-associated TB?
blacks
hispanics
IVDUs

Gays are NOT more likely.
Where in the lungs do you see reactivation TB?
Apical areas

-like Dr. Goljan says, they're strict aerobes, so need to go to the place with the most air to grow, thus the apical regions!
Key findings to make you think TB:
-night sweats
-hemoptysis
-cough >3 weeks
-cough w/fever >3 days
-weight loss
Atypical pneumonia causes:
mycoplasma
viral
legionella
chlamydia, which presents more insidiuously
Nosocomial pneumonia implies...
gram negative and resistant
The bugs of bronchopneumonia
by definition, involving more than 1 lobe:

-staph
-strep
-H. influenza
-P. aeruginosa
Bugs of lobar pneumonia
>90% due to strep. pneumonia
-also can see Klebsiella
What are the physical exam findings of pneumonia?
INC:
fremitus
dullness
egophony
bronchial breath sounds
What's a key radiologic finding of atypical pneumonia?
widening of the interstitium
-interstitial infiltrate predominantly lymphocyte rich
with proteinaceous exudates in the alveolar spaces
-DON'T see many cells in the exudates
What are the findings of mycoplasma pneumonia clinically/radiologically?
bronchial wall inflamm w/ non-purulent patchy interstitial infiltrates

-assoc. with cold agglutinins- IgM
What are good drugs to treat mycoplasma pneumonia?
B-lactams DON'T work

fluroquinolones
macrolides- watch GI issues
tetracycline
Most common cause of lobar pneumonia?
strep pneumonia
Where does strep pneumonia proliferate?
in the alveoli, causing an influx of PMNs with minimal structural damage
How do you Dx Step. Pneumonia?
Gram+
a-hemolysis on agar
catalse negative
sensitive to optochin
How do you treat strep pneumonia?
B-Lactams
emergence of penicillin resistant strains is big probme, but use bigger doses, or different beta-lactams

ALSO combine with macrolides
What are macrolides used to treat?
mycoplasma
What is the empiric therapy of a pneumonia diagnosis?
B-lactam, possibly with a B-lactamase inhibirotr
OR
2nd-generation cephalosporin

AND macrolide (for mycoplasma, in case it's an atypical presentation)
What's special about 2nd-generation cephalosporins?
Have EXTENDED gram-NEGATIVE coverage
How do you treat MRSA staph?
vancomycin
Patient presents with acute onset of fever, chills, chest pain and rusty sputum?
strep. pneumonia!
-alveolar proliferation with purulent secretions and lobar consolidation
H. influenza CHARAC
-gram neg
-needs factors V and X to grow- so grows well on choco agar
Moraxella catarrhalis is charac as a
gram neg
diplococcus

makes oxidase, catalase, DNase
What is the 2nd most common cause of COPD exacerbations?
moraxella catarrhalis
Legionella can't be treated with which drugs?
Beta-lactams

it's a gram neg bacilli, hard to see in a gram stain, and easier to see in silver stain

DIFFICULT to grow, so especially consider it if you see lots of WBCs but no bacteria...but do also consider the other atypicals

MAY GIVE hyponatremia
-failure to respond to Beta-lactam may give the diagnosis
Chlamydia pneumonia components and Tx
elementary body is INFECTIOUS

Reticulate body is metabolically active, non-infectious.

Tx:
fluoroquinolones are good for it.
macrolides and tetracyclines could be used too.
Adenovirus is a common cause of...
pneumonia in AIDS patients.
-SMUDGE cell or ROUND-GLASS appearance histo-wise
What are the bugs that often cause abscesses and empyema, especially in LRI...
S. aureus
Klebsiella
Pseudomonas
anaerobes

also common in nosocomial pneumonia, as a side-note

SEE: alveolar prolif and necrosis, with lobar consolidation and CAVITATION!!
Most common causes of bacterial pneumonia in HIV (2)?
S. pneumonia

AND

H. Influenza
What prophylaxis do you deliver in an HIV+ pt. when worried about bacterial pneumonia?
trimethoprim (TMP)
What prophylaxis do you deliver in an HIV+ pt. when worried about PCP?
Bactrim, aka TMP-SMZ

use in HIV+ with CD4 <200
Where do you see a cotton candy appearance?
PCP histology, due to intraalveolar eosinophilic exudates

-lots of edema and eosin in the alveolar spaces, not much damage to the tissues

-helmet-like or cup-shaped organisms
What's the threshold for seeing CMV?
HIV+ with CD4 <50 typically

-IFX of alveolar macrophages, endo and epi cells
-SEE RETINITIS, along with other GI issues

-OWL-EYE INCLUSIONS are indicative of CMV
How do you treat CMV?
HAART with IV ganciclovir or foscarnet
Most common fungus-based life-threatnening HIV+ illness?
cryptoccous

-meninges are most common ifx site
-CD4<100 usually
-FOAMY CELLS with big thick capsule on india ink

Dx. by seeing via histo
TREAT WITH AMPHOTERCIN B
Treating with amphotercin B, what do I have?
HIV+, likely CD4<100, Cryptococcus neoformans
Mimics TB with peripheral pulmonary lesion and hilar adenopathy, certain parts of U.S. specific, what is the bug?
Histoplasmosis

-MILIARY infiltrates on CXR
-NON-CASEATING fibrotic granulomas

AMPHOTERCIN B treatment or Itraconazole in pts with milder disease
CD4<30
brancing, septate organisms with 40 degree angles
Aspergillosis!
How does aspergillosis present?
NECROTIZING pneumonia and propensity for blood vessels so CXR shows UL disease with CAVITATION AND HEMOPTYSIS

Tx with AMPHOTERCIN B
What all do you treat with Amphotercin B?
1) Cryptococcus
2) Histoplasmosis
3) Aspergillosis
4) Coccidiomycosis
5) Blastomycosis
Where do you see blastmycosis
patient is immunosuppressed and localized to Midwest US, Southwest US and Canada
What's the major mutation of CF and the associated complication?
Δf508
-associated with pancreatic insufficiency!
Explain the CF mutation
Cl- channel is blocked and Cl- can't leave the bronchial cells, so Na+ goes inside and creates and extra-thick mucous that gets stuck and can't be moved by the mucociliary elevator
Do you see clubbing in CF?
yes, true.
Meconium ileus
CYSTIC FIBROSIS
What's the means of diagnosis of CF?
Sweat test with Cl- >60, intermediate if 30-60
Common organisms colonizing CF pt. airways?
P. AERUGINOSA
S. aureus
H. Influenza
BPD is characterized by...
INC vasc perm
-lungs are leaky and inflamm cells go where they're not supposed to, creating a significant inflammatory response
Is RSV seasonal?
Yes, but in Florida it's not as pronounced in terms of spikes during certain months, but rather it's higher most of the time!
Clinical Sx's of bronchiolitis?
-profuse coryza, or runny nose
-low grade fever
-LRI w/in 2-5 days
-cough, dyspnea, wheezing, feeding issues, flaring, retractions, and cyanosis
CXR of Bronchiolitis shows...
-bilateral perihilar and patchy parenchymal infiltrates with peribronchial cuffing

hyperinflation with flattened diaphragm

atelectasis especially in the right upper and middle lobes
What's the prophylaxis of Bronchiolitis?
synagis
1X/month, but $1,000/Tx
What are the intrinsic restrictive lung diseases?
PARENCHYMAL RESTRICTIVE:
IPF
sarcoidosis
hypersensitivity pneumonitis
radiation-induced fibrosis
autiommune-related fibrosis
or
lymphangitic carcinomas

OR

AIR-SPACE FILLING DEFECTS:
i.e. pneumonia, could result in diffusion problems
What are the extrinsic restrictive lung diseases?
Pleura:
-pneumothorax
-pleural effusion
-pleural thickening- asbestosis

Chest wall:
-scoliosis
-ankylosing spondylitis

Neurmuscular disease:
-polio
-GBS
-ALS
-Myasthenia Gravis
-Muscular dystrophies
In diseases of the lung parenchyma, where do you see the fibrosis?
starts at the bottom of the lung and works its way up.
Diseases that may lead to IPF:
scleroderma
asbestosis
amiodarone (lipid containing vesicles)
methotexate drug-use
Does IPF respond to steroids?
NO!
only tx if any is supplemental O2
How does IPF spread?
usually starts at the periphery and works its way inward, there is also scattered fibroblast foci, and representative areas of active fibrosis
How many IPF patients have clubbing?
HALF!
If you hear velcro crackles, think...
IPF
Clinical presentation of IPF shows 3 big things:
-clubbing in half of patients
-velcro crackles
-reticular opacities, i.e. ground-glass appearance
Clinical features of AIP?
diffuse infiltrates on CXR
hypoxemia
cyanosis
hyaline membranes
interstitial edema
type II hyperplasia

fluid in the alveolar space
organizing DAD
DIFFUSE PROLIFERATION OF INTERSTITIAL FIBROBLASTS
NSIP is what kind of process?
VERY CELLULAR, LOTS of inflammation
Does NSIP respond to steroids?
YES!
What 2 interstitial diseases are associated with smoking?
DIP and RB-ILD
What characterizes Wegener's Granulomatosis?
NECROTIZING granulomatous inflammation and vasculitis
Key diagnostic finding of Wegener's?
ANCA antibodies!!!
Key pathogenesis of Sarcoidosis?
T-cells mediate inflamm
bilat hilar lymphadenopathy
RESEMBLES TB
2 key clinical features of sarcoidosis?
skin nodules
eye irritation, i.e. uveitis
What do lab tests show for sarcoidosis?
hypergammaglobulinemia
hypercalcemia
INC ACE levels
How do you Tx sarcoidosis?
cortisone or prednisone
Where do you see the fibrotic nodules of silicosis?
upper lobes

egg shell calcification in the hilar LNs
NO CLUBBING
What part of the lungs do you see involved in asbestosis?
peribronchiolar fibrosis involving the LOWER lobes

-alveolar spaces may have asbestos bodies and inflamm cells
Coal workers pneumonia is seen in what part of the lungs?
usually UL zones, with nodular or rounded appearance
Rheumatoid arthritis has what finding similar to IPF, what is it?
Velcro crackles in the lower lobes
What organs does Sjorgen's syndrome affect?
eyes
salivary glands
Bleomycin toxicity causes...
PMNs alveolitis and eosinophil proliferation in hypersensitivity reactions

causes nodular lesions mimicking metastasis due to BOOP
Methotrexate toxicitiy shows...
T-cell alveolitis and eosinophil prolif
Patient presents with lamellar bodies on EM and lipid-containing vacuoles, what's the problem?
amiodarone toxicity
2 KEY histo findings of Squamous Cell Carcinoma?
1) Keratin pearls
2) Intracellular bridges via desmosomes
What is the triad of pulmonary embolism?
1) dyspnea
2) pleuritic chest pain
3) hemoptysis- occurs later on
Most common mutation leading to PE?
Factor V leiden
How do you treat PE?
heparin, then long-term use coumadin, elastic stokcings, pneumatic compression devices, an IVC filter, thrombolytics are RARE and so is a thromboendarterectomy
What is defined as Pul HTN?
mPAP >25mmHg at rest or >30mmHg during exercise
Define ARDS:
diffuse alveolar damage, specifically to th e alveolar capillary walls that results in the rapid onset of severe life-threatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia that is refractory to O2 therapy and may progress to extrapulm organ failure
Findings of ARDS
Profound dyspnea and tachypnea herald ARDS, but the CXR is initially normal. Subsequently, there are increasing cyanosis & hypoxemia, respiratory failure, and appearance of diffuse bilateral infiltrates on CXR.

Looks like bilateral lung opacity (“white out”). They’re heavy, stiff, non-compliant lungs.
Describe ARDS pathogenesis:
-Diffuse alveolar damage leads to:
-INC alveolar capillary perm leads to:
-protein-rich leakage into alveoli
leads to:
-formation of intra-alveolar HYALINE MEMB
leads to:
-neutrophilic substances toxic to alveolar wall, activaiton of coag cascade, or oxygen-derived free radicals
When does the incidence of lung cancer peak?
ages 55-65
#1 risk factor for lung cancer?
SMOKING
#2 risk factor for lung cancer?
Passive exposure to smoke
#3 risk factor for lung cancer?
Occupational exposures:
-asbestos ESPECIALLY
-roofers exposed to coal tars
-railroad workers
-others
Local tumor clinical Px:
-cough
-hemoptysis
-wheezing due to tumor obstructing airway
-atelectasis or postobstructive pneumonia--> dyspnea, signs of pneumonia
What are the Sx's of pancoast syndrome?
see Horner's syndrome, which is ptosis and myosis, along with anhydrosis

"a droopy-eyed, constricted people in someone NOT sweating."
What are all the paraneoplastic syndromes you could see:
-endocrine
-mskel: hypertrophic osteroarthropathy
-neurlogic- Lambert-Eaton, peripheral neuropathy, dementia, cerebellar degen
-hematologic: thrombophlebitis
What are the paraneoplastic issues seen with squamous cell carcinoma?
PTH-syndrome giving:
-HYPERcalcemia
-lethargy
-polyuria
-polydipsia (excessive thirst)
-constipation
-abdominal pain
-possible coma
Why do you typically see SVC syndrome?
due to mediastinal LN invasion of the tumor
SIADH Sx's
hyponatremia leading to:
-irritability
-confusion
-weakness
-poss. seizures
Cushing's Sx's:
-facial edema
-cachexia
-hypokalemia
-alkalosis
-
Hypertrophic osteoarthropathy Sx's:
overgrowth of cortical bone and presenting with pain in the lower joints
What are the 2 options for Dx of a Small-Cell lung cancer?
Limited (30%)

or

Extensive (70%)
What are the options for a Non-Small-Cell Lung CA:
Can the patient tolerate resection, determined by pul func test

and
is the tumor possibly resected for a cure?
When a tumor is more periperal, how do you resect it?
Use fluorscopy-assisted percutaneous needle aspiration
What are the levels needed to permit a pneumonectomy?
FEV1ppo and DLCO >/= 75% predicted

if less, do split pul func test to estimate post-resection FEV1 and DLCO...

If they're greater than 40% then you can still do the pneumonectomy
What are the steps of lung CA staging?
1) extent of Primary Tumor- T
2) presence and extent of regional metastasis to hilar and mediastinal LNs- N
3) presence/absence of distant mets- M
T of TNN:
T1 </= 3CM
T2 >3CM
T3 INVADES CHEST WALL
T4 invades VITAL intrathoracic strucs
N of TNM:
N0- no LNs
N1- ipsilateral peribronchial/hilar LNs
N2- ipsilateral mediastinal/subcarinal LNs
N3- CONTRAlateral mediastinal/hilar LNs and/or supraclav LNs
Small Cell Tx:
Limited disease:
-do radiation port to Tx, confined to one hemithorax, and only regional LNs, Tx is chemo and radiation!

Extensive disease:
tumor beyond limited limits, Tx is chemo
How to be sure a Solitary Pulmonary Nodule is benign?
1) No growth on X-ray for 2 years
2) pt. <35 yrs of age AND non-smoker
3) chest radiograph and/or CT shows it's calcified: through and through, target, laminar, or popcorn
Which tumor do you Tx with surgery and which is too bad already when Dx'ed?
try to treat Non-Small cell with surgery, but small cell is considered already spread by the time the Dx is made so you do chemo and radiation if it's a limited disease, and just chemo if it's an extensive small-cell diagnosis
Atypia, dysplasia, and DCIS of bronchial epi imply...
invasive squamous cell CA likely assoc with heavy cig smoking.
Scar carcinoma is...
when pul fibrosis, such as IPF is present and then a tumor arises at the site of prev fibrosis
Desmoplasia is when..
fibrosis 2ndary to presence of a carcinoma.
C-myc is a mutation found in...
small cell CA
K-ras is seen in...
adenocarcinomas
What 2 genes are often inactivated in lung CAs?
p53 and retinoblastoma
Adenocarcinoma definition:
malignant epi tumor with GLANDULAR DIFFERENTIATION

-see gland formation or see intracytu mucins!

-usually periph location
-equally frequent in men and women, but most frequent type in the non-smoker population

-sometimes assoc with areas of scarring
4 sub-types of adenocarcinoma
tubular/acinar
papillary
solid
bronchioloaveolar
Squa cell CA definition:
-malignant epi tumor charac by presence of keratin prod AND/OR intracellular bridges

-closely assoc with smoking history
Large Cell CA is...
malignant epi neoplasm undifferentiated
-cells large/polygonal
-nucleolus is prominent and cell borders are well-defined

-see giant cell CA and clear cell CA in this group
Adenosquamous carcinoma is...
at least 10% of each of the two tumor types combined
Small cell definition
highly-defined neuroendocrine tumor strongly assoc with cig smoking

-usually close to hilum

-originated in the Kulchitsky cells

-composed of smallc ells with scant cytoplasm and ill-defined cellular borders
-salt and pepper chromatin
-nuclei molding is CHARACTERISTIC
Typical carcinoid tumors:
-low-grade neuroendocrine tumors
-great survival rate >90% at 10yrs
-salt and pepper chromatin appearance
-mitotic figures scant and necrosis absent

MOST COMMON LUNG TUMOR IN CHILDREN
Atypical Carcinoid tumors:
-10-yr survival around 55%
-more mitotic figures
-necrosis present
-nuclei tend to be more pleomorphic and nucleoli are conspicuous

slightly more agressive
What's the best way to Dx as an adenocarcinoma?
mucin-stains!
What's clearly indicative of a Squamous cell carcinoma diagnosis?
KERTAIN!!!

-also see intracellular bridges
Where do you see the Azzopardi effect?
in small cell carcinoma, it's a liberation of nucleic acids from the cells
Which tumors have APUD?
neuroendocrine tumors, which are Typical and Atypical Carcinoid and Small cell

APUD: Amine Precursor Uptake and Decarboxiylation
These cells take up amino acids and modify them into amines and peptides. APUD cells synthesize most of the hormones in the body.
Carcinoid tumor CHARAC:
Low grade malignant tumors demonstrating endocrine microscopic pattern admixed with abundant blood vessels
It usually involves large bronchi with an endobronchial growth pattern.
Affects patients under 45 years of age.
It is the most common lung tumor in children
Where do you see lamellar bodies in an interstitial lung disease?
amiodarone toxicity

"lipid-containing vacuoles"
What is amiodarone used for?
treat tachyarrhythmias
Bleomycin can cause...
BOOP
NSAIDs can cause...
pulmonary eosinophilia
Ara C and Aspirin can be associated with which disease?
ARDS
What's a key hallmark of cancer chem agent drug-induced lung disease?
-almost always assoc with fever, but they are a Dx of exclusion

-Tx limited to discontinuing the drug and considering ADDITION OF CORTICOSTEROIDS
Changes as a result of drug-induced lung disease?
-vascular damage- endo swelling with exudation of fluid
-type I destruction and type II prolif
What are some possible findings from a BALF?
-T-lymphocytes alveolitis- methtrxate
-PMNs alveolitis- bleomycin
-eosinophils in hypersensitivty rxns- MTX, Bleomycin, Procarbazine
Bleomycin toxicity increases with...
age

and

dosage
Bleomycin facts:
-DLCO predicted subsequent disease
-toxicity reversible if changes only minimal
-anticancer drug
-synergistic toxicity with cyclophosphamide
-if O2 and radiation included, plus the drug, mortality is 50-75%
-up to 20% mortality after cisplatin infusion
-see nodular lesions mimicking metastases due to BOOP
What's the cardinal symptom of radiation pneumonitis?
-2-3 months post-Tx
-see 93% dyspnea, but also dry cough and/or less-so fever
-due to local cytokine prod
-usually confined to field of irradiation
-generally self-limited, but may become progressive fibrosis

CAN ACCEL REPAIR PROCESS WITH CORTICOSTEROIDS
Malar rash, polyarthritis, rapid onset of a cough, fever, and some rapidly progressive dyspnea

-see also lung crackles and severe hypoxemia

Diagnosis?
Systemic Lupus, it was a black female, but I left that out.
What's a hallmark of diagnosing lung disease as a result of rheumatoid arthritis?
-pleurisy with effusion, an exudate that shows SUPER LOW SUGAR content, like less than 10
Rheumatoid arthritis lung effects may be seen as what in the bronchioles:
-bronchiolitis obliterans organizing pneumonia (BOOP)
-bronchiolitis obliterans
2 possible manifestations of rheum arthritis intrathoracically?
Poly/Dermatomyositis:
-fibrosing alveolitis or BOOP
-pul vasculitis or HTN
-aspiration pneumonia
-respiratory muscle weakness

Systemic Sclerosis
-fibrosing alveolitis
-BOOP
-pul HTN
aspiration pneumonia
CHEST WALL RESTRICTION

Sjorgen's Syndrome:
LYMPHOCYTIC infiltration, esp. in lungs

Pul Fibrosis and Autoimmune DIsease
-Myasthenia gravis
-chronic active hepatitis
-thrombocytopenic purpure
-hemolytic anemia
primary biliary cirrhosis
LNK- what disease?
Lungs, Nose, and Kidneys

Wegener's Granulomatosis
Saddle-nose deformity, what disease?
Wegener's!
What are 2 major presentations in blacks > whites for sarcoidosis?
skin sarcaoidosis

and

ocular Sx's, i.e. uveitis
Inherited coagulopathies involve...
Protein C and S
Factor V Leiden
antithrombin III deficiency
Where do you get the majority of PEs from?
DVTs
-with most coming from the popliteal fossa to the pelvis

-start as platelet aggs on valves in the venous sytem
If you see infarcts from PE, what type will they be?
red infarcts
What's the classic triad of Sx's in PE?
hemoptysis
pleuritic chest pain
dyspnea
What is in Virchow's triad?
1) stasis
2) hypercoaguability
3) venous injury
4 Signs of PE:
tachypnea
tachycardia
accentuated 2nd heart sound
fever- due to infarct
With a PE, what vent/perfusion do you expect to see?
It will create more deadspace, so if anything you would expect an elevated pCO2, but the person hyperventilates, so it's normal or low if anything
What happens to the pO2 in PE?
V/Q mismatch with hypoxemia due 2 bronchoconstriction
-DEC alveolar PCO2, and there's mediators giving clinical wheezing and bronchoconstriction
What are the expected pO2 and pCO2 VALUES in PE?
hypoxemia
AND
hypOcarbia
What would be an ECHO finding indicative of PE?
right vent dilation due to quick onset of INC press
Westermark's sign...
shows area of poor perfusion in a PE, but Salathe has never even seen one!
What happens on a V/Q scan when you have a PE?
see bronchoconstriction, so the radioisotopes have delayed washout in those areas, so there will be an area of no mottling, and an area of prolonged washout
What's diagnostic for PE when using a V/Q scan to examine the patient?
2 or more segmental deficits that are MISMATCHED, i.e. no perfusion, BUT ventilation
What 2 things can duplex measure?
1) compressibility, or in the case of a DVT, NON-compressibility


2) flow measurements can be done too
Cannot diagnose patients with Protein S and C deficiencies if they're on...
coumadin
What can cavitate in the lung?
1) squamous cell carcinoma
2) Wegener's
3) Aspergillosiss
What is the most common cavitator in the lung?
squamous cell carcinoma
Popcorn lung is associated with what disease?
BOOP
Where do you see the Golden S-sign?
-simple collapse of a lung/lobe would give a straight line

here, collapsing AROUND A MASS
-not a straight line b/c this mass is seeing lung drape over the mass
When do you see the air bronchgram sign?
When you have consolidation in the alveoli so it outlines the bronchi which are the only spots left with air in them
Where do 95% of pul thromboembo come from?
DVT from popliteal or larger
How many PEs affect the lower lobes?
75%

>50% are multiple
and
30% recurrence rate
Small emboli account for what % of PE?
70-95%

-60-80% are clinically silent.
-they're in a patient with adequate cardiorespiratory function

-10-15% lead to infarction, which means there was some sort of cardiorespiratory compromise
Steps of SMall Emboli in the Lungs:
1) ischemia of endothelial cells
-see pul hemorrhage with adequate cardioresp status and dual blood supply
2) Once there's compromised cardiorespiratory status, you'll get red infarct, which is coagulative necrosis of the parenchyma PLUS hemorrhage
3) RBCs will lyse and see red/brown hemosiderin deposits
-wedge shape formation, apex will be at the occluded vessel, the base will be at the pleural aspect
4) org of embolus, gray/white shrunken peripheral scar, so now it's FIBROTIC
What are the other conditions associated with having a PE?
pul HTN
chronic cor pulmonale
vascular sclerosis
3 Ways to get pul HTN
1) DEC cross-sectional area of pul vasc bed leading to inc vasc resistance
2) INC pul BFlow
3) INC in left heart resistance
How do you get secondary pul HTN?
-chronic obstructive or interstitial lung disease- destroying the parenchyma and there will be fewer alveolar capillaries
-recurrent pul emboli reduce the cross-sectional area
-heart disease with a Right --> Left shunt will INC flow across the lungs
What grades of pul HTN are reversible?
Grades 1-3
Grades IV/V of Pul HTN look like...
an organizing thrombus with re-canalization
-can't tell the diff b/n the 2!!
Grade VI Pul HTN presents as...
Necrotizing arteritis
AND
fibrinoid necrosis (vessel wall is now acellular, amorphous material)
Classic sign of pleural effusion?
meniscus sign
As you go down a lateral CXR, the spine should....
get DARKER, but if it gets lighter at all, then there is something there, some infiltrate is present.
How do distinguish between pleural effusion and pleural thickening on CT?
pleural thickening has an irregular border, whereas pleural effusion will appear pretty smooth. This was especially discussed in reference to a CT.
How distinguish a DDx of pleural effusion and pleural thickening?
POSITIONAL CHANGES
-put patient in the lateral decubitus position
Does the trachea deviate with pleural effusion?
if there's a large amount of fluid it'll get pushed away from the side with the effusion
What are 2 possible consequences of pleural effusion?
1) diaphragm can do gown
2) lung can get compressed even to point of atelectasis

-excess fluid in pleural space can compress lungs
If you see an opacity with a straight line, what do you think?
without the meniscus, think of a HYDROPNEUMOTHORAX, where the air-water interface ends up being a straight line!
If the pleural effusion is a transudate, what are the possible problems?
1) CHF
2) liver problem
3) renal problem

pleural fluid protein >3g/dl to be exudate
When is pneumothorax more apparent?
during expiration because the lung retracts more from the chest wall, so ORDER CXR at EXPIRATION
Bloody pleural effusion, think...
possible malignancy
What are the 3 most common causes of pleural effusion?
1) CHF
2) pneumonia- bacterial
3) malignant disease
Usually what gives only transudate will not give exudate, but...
what gives exudate may also give transudate
-part of why exudate is a more complicated DDx
Meig syndrome is the triad of...
1) right-sided hydrothorax
2) ascites
3) ovarian fibroma
What could cause serofibrinous pleuritis?
it's serous fluid plus fibrinous exudates

-inflamm in adjacent lung due to pneumonia, TB, an infarct, or abscess
-collagen vasc diseases like rheum arthritis or lupus
-uremia
-radiaiton
-systemic ifxs
Which is more common, metastases or primary PLEURAL TUMORS?
metastases
-coming from LUNG, BREAST, ovary, and GI tract
-see desquamated tumor cells in serosanguineous fluid
Solitary Fibrous Tumor, aka pleural fibroma:
CD34+Keratin-
-attached to pleural surface by a pedicle
-white, filmy mass
How often is malignant mesothelioma related to asbestos exposure?
90% of the time!
-25-45yr latency
-GROSS- diffuse grayish pink tumor, spreads widely in pleural space

CD34-Keratin+

-epithelial mesotheliomas may be difficult to DDx from mets of adenocarcinoma to the pleura
How to disting b/n Adenocarcinoma and mesothelioma
Adeno:
EMA + in CYTO, CEA+, Calretinin-

Mesothelioma:
EMA+membrane, CEA-, Calretinin-
How do you Dx diffuse pul interstitial fibrosis?
see "asbestos bodies"- golden brown rods containing asbestos fibers coated with iron-containing proteinaceous material
-pul macrophages attempt ti ingest asbestos fibers and are activated to release chemotactic factors and fibrogenic mediators that lead to a diffuse interstitial fibrosis
serpentine/chrysotile asbestos looks like...
curly and flexible

BOTH FORMS ARE FIBROGENIC
amphibole asbestos looks like...
straight and stiff

BOTH FORMS ARE FIBROGENIC
Asbestos inc. risk of bronchogenic CA...
5-fold
smoke too, see 55-fold increase in the risk of it!!!
How do you Tx mesothelioma?
pneumonectomy, radiation, and chemo
90% of mesotheliomas are related to asbestos exposure, BUT...
asbestos workers have GREATER chance of getting bronchogenic CA

-remember Goljan said Bronchogenic CA develops faster, so it's gonna come before mesothelioma has a chance to develop, that's why it's more prevalent
If see a malignant cytopathology, what's the DDx?
mesothelioma vs. adeno, so need IHC
If malignant cytopath, and determine by IHC it's adenocarcinoma...
use IHC cell markers like estrogen receptor for 70% of breast carcinomas, or TTF-1 for 70% of lung adenocarcinomas
Hypoxic respiratory failure:
Low paO2 (<50-60mmHg)
Normal/low pCO2
Hypercapnic hypoxic respiratory failure:
Low paO2 (<50-60mmHg)
PLUS
Elevated PaCO2 (>49mmHg)
Kussmaul breathing is...
very deep breathing that is used to correct for acidosis
paCO2 is NOT affected by...
age
OR
position
CO2 ventilation equation
VCO2 = paCO2 * Valv * k
What are the ALI criteria?
paO2/FiO2 < 300mmHg


only difference from ARDS is that ARDS is <200
ARDS is NOT a homogeneous disease. Giving PEEP will...
affect parts of the lung differently.
4 Causes of Type I Respiratory Failure:
This is hypoxic failure:

1) R-->L Shunt
2) V/Q MISMATCH
3) low piO2
4) diffusion problem, which almost never occurs at rest
Causes of Type II Respiratory Failure:
Alveolar ventilation insufficiency, leading to HYPOXIC-HYPERCAPNIC Resp Failure

-central resp drive is low
-INC work of breathing
-resp. muscle dysfunction
-hypOventilation
-can be combined with INC CO2 production
Does shunting respond to supplemental O2?
NO!
Shunting can be caused by...
-alveolar collapse- atelectasis
-intra-alveolar filling process, pneumonia or edema
-intracardiac- platypnea possible (Difficulty in breathing when erect, relieved by lying down.)

-vasc shunt w/in lung- AVmalformation

When seeing air bronchograms, MOST CONSISTENT with alevolar filling process and likely pneumonia
In a situation where you hypOventilate because of a drug overdose/neuro or muscle disease or injury/excessive load on resp. sys, then...
can see abnormal lungs WITH V/Q mismatch, and since patient can't INC alveolar vent sufficiently, then have hypoxia PLUS INC dead space, leading in total to HYPERCAPNIA
Hypoventilation is defined as...
HYPOXEMIA with a NORMAL A-a gradient.
Does hypoxemia respond to supplemental O2?
YES!
What happens to the body with an acute rise in acidosis?
1) DEC cardiac contractility
2) DEC resp muscle contractility
3) INC arterial vasodilation to compensate for cerebral BFlow
4) loss of conciousness
In a depressed drive patient, such as one with sedative and a prev. present resp. insufficiency, see that there is an increase...
in paCO2 with oxygen therapy
-due to V/Q mismatch
and
-depressed drive
Aminoglycoside SE leading to poss. resp. effects:
curare-like effects--> could paralyze resp. centers

also consider procainamide
Assist-Control Ventilation
-ventilator delivers set tidal volume when triggered by patient's inspiratory effort or independently if not patient effort occurs within a certain amount of time
Intermittent mandatory vent:
mandatory # of fixed volume breaths, pt. could also do own breaths in between
Pressure support:
graded assistance, physicians sets the level of pressure to augment every spontaneous resp effort
Controlled mech vent:
completely dependent upon rate and tidal volume set
-patients resp efforts have no effect
Peak Inspiratory pressure depends on...
compliance
Anosmia top 2 causes:
1) Viral URI
2) Trauma

RULE OUT: brain tumor/other neoplasm
Rhinosinusitis top 2 causes:
1) Viral URI
2) Allergic Rhinitis
Nodule
vs.
Polyp
vs.
Cyst
fix with speech therapy and it'll go away
vs.
so big it won't resorb
vs.
usually won't go away, esp. fluid-filled issues
Who gets pulmonary venous hypertension?
-left-sided atrial or vent. disease

-left-sided valvular heart disease
Definitive pul HTN dx?
Use right heart catheterization to measure right vent press
Idiopathic pul HTN typically seen in what age population?
age 30-50

progressive disease- survival is 2.8 years w/o therapy
What disorder is most commonly associated with pul HTN?
Systemic sclerosis
What's the other HTN assoc with pulmonary HTN?
PORTAL
When seeing PoPH, which presents first?
portal HTN
What happens to cardiac output when the pulHTN gets SEVERE?
starts dropping, a BIG problem
epoprostenol
IV med given through central line, and needs specialized pump and to be given on continuous basis due to a short half-life

-w/o the med see rebound and the pul art press shoots way up
What is Bosentan?
-aka tracleer
-oral endothelin dual receptor antagonist
-oral twice daily
metabo by liver
-teratogenic

DOES IMPROVE SURVIVALS
3 main pathways to impact in pul HTN?
1) endothelin pathway
2) NO pathway
3) prostacyclin pathway
Acute exacerbation of COPD, what do you do?
give ABx and Glucocorticosteroids (IV/oral) for FOURTEEN (14) days
Do you give steroids in hypersensitivity pneumonitis?
-DO NOT prevent the development of fibrosis
-they DO, however, reduce the time to recovery after exacerbation


MOST IMPT: Allergen Avoidance