Pathophysiology Flashcards
Berlin criteria
measure of acute lung injury severity
- PaO2/FiO2 less than 300 (normal: 100/.21 = 476)
- no evidence of volume overload
- acute onset of respiratory failure
- bilateral infiltrates on CXR (WHITE OUT)
asthma
airway hyper responsiveness: OBSTRUCTION, inflammation, epithelial injusry, neural mechanisms, intrinsic airway smooth muscle function
CD4 T cells, TH2
eosinophils, basophils, mast cells, eosinophilic cationic protein, major basic protein, histamine, leukotrienes, PG, PAF
IgE, IL-5
inflammatory, episodic, reversible bronchospasm
exacerbation: neutrophilic
reduce: FEV1, FVC, and FEV1:FVC ratio (reverses with bronchodilators)
NORMAL TLC
REVERSIBLE
Dx: SOB, WHEEZE, diurnal variation of PEFR greater than 20%, reduction of FEV1/FVC that is reversible, hyperinflation
NORMAL DLCO
COPD
CD8 T cells IL-8, macrophages (CD68+), neutrophils exacerbation: eosinophilic reduced: FEV1, FVC, and FEV1: FVC ratio FEV1: FVC less than 70 PARTIALLY reversible Sx: cough, dyspnea, sputum risk: tobacco, pollution, occupational Dx: SPIROMETRY
emphysema
permanent abnormal enlargement of air spaces distal to the terminal bronchioles, occurs in the lung parenchyma in COPD
PINK puffer
V/Q mismatch, LOW DLCO
HYPERVENTILATION (maintain normal PCO2), tachypnea, thin
centriacinar emphysema
SMOKING
dilatation and destruction of respiratory bronchioles
UPPER lobe process
panacinar emphysema
alpha-1 antitrypsin deficiency
destruction of entire acinus
LOWER lobe
resorption atelectasis
airway obstruction by mucous plugs, tumor
resorption of trapped O2 in dependent alveoli
mediastinum shifts TOWARD affected lung
compression atelectasis
filling of pleural cavity by tumor, blood, air
compression of pulmonary tissue
mediastinum shits AWAY from affected lung
contraction atelectasis
fibrotic lung or pleura
prevention of full expansion
NOT reversible
paraseptal emphysema
underlies spontaneous pneumothorax in young adults
A1 anti-trypsin deficiency
liver biopsy: pink PAS positive hyaline globules
misfolded protein accumulates in the ER
PiZZ homozygotes: liver cirrhosis and panacinar emphysema
PiMZ heterozygotes: ok unless smoker
chronic bronchitis
persistant cough with sputum at least 3 months in at least 2 consecutive years
Reid index > 50%
BLUE bloater, hypoxemia and hypercapnia
V/Q mismatch
long term hypoxemia: polycythemia, pull HTN, cor pulmonale (right heart failure causes edema)
HYPOVENTILATION
Charcot-Leyden crystals
disintegration of eosinophils
ASTHMA
Curschmann spirals
ASTHMA mucous forms tight coils
cystic fibrosis
chloride transport defect
immotile cilia syndrome
dynein arm defective
Tracheoesophageal (T-E) fistula
failure of fetal respiratory tract to separate from the GI tract
When do fetal lungs begin to make surfactant?
26-32 weeks
Allergic Bronchopulmonary Aspergillosis (ABPA) criteria
asthma due to Aspergillus type III IgE response 1. poorly controlled ASTHMA 2. EOSINOPHILIA 3. IgE > 1000ng/ml other 4. Aspergillus Fumigatus positive skin antigen test, IgG Ab 5. proximal bronchiectasis 6. fleeting chest infiltrates 7. peripheral eosinophilia with chest infiltrates Tx: PREDNISONE
positive end expiratory pressure (PEEP)
increase FRC and recruit atelectatic alveoli
improves oxygenation in patient with ARDS already on 100% O2
Why would increasing VT in a patient with ARDS increase mortality?
increasing tidal volume causes too much stretch and more inflammation
high peak pressure and high plateau pressure
compliance issue
high peak pressure and low plateau pressure
resistance issue
mechanisms underlying airway limitation in COPD
Irreversible vs Reversible
Irreversible
1. fibrosis and narrowing of airway
2. loss of elastic recoil
3. destruction of alveolar attachments that keep airway open
Reversible
1. inflammation, exudate, mucus accumulation
2. sm. muscle contraction of airway
3. hyperinflation (increased WOB and reduced exercise intolerance)
irreversible airflow limitation in COPD
- fibrosis
- loss of elastic recoil
- destruction of alveolar attachments
COPD Tx for each stage
I: mild: reduction of risk factors (pneumococcal and flu vaccine) and short acting bronchodilator when needed
II: moderate: ADD long acting bronchodilator and rehabilitation
III: ADD inhaled glucocorticoids if repeated exacerbations
IV: very severe: ADD longterm O2 if chronic respiratory failure; consider Sx
methacholine challenge test
high negative predictive value
Negative: you don’t have it
Positive: inconclusive
Pos: FEV1 decreased by 20% with 8 mg/dL dose
asthma Tx
- intermittent: as needed short acting beta2 agonist or short acting anticholinergic
- mild: add inhaled corticosteroid
- moderate: add long acting beta agonist
- severe: add leukotriene modifiers
other: systemic steroids, anti-IgE
IMPORTANT: LABA associated with increased mortality
extrinsic asthma
MOST COMMON IgE mediated response to allergen acute: minutes late: hours Family Hx
intrinsic asthma
triggered by respiratory infection
ADULT
NO IgE, Fam Hx doesn’t matter, skin antigen test neg.
drug-induced asthma
ADULT
ASPIRIN, NSAIDs
Samter’s syndrome
- asthma
- aspirin sensitivity
- nasal polyps
occupational asthma
ADULT
occurs after repeated exposure and sensitization
fumes, dusts, chemicals, gasses at work
IgE and non-IgE
exercise induced asthma
IMMEDIATELY after EXERCISE (5-10 min)
Cooling and drying of mucosal airways
Tx: pretreat with B agonist, slow warm up period
cough variant asthma
Sx: cough (possibly without wheezing); chronic cough with irritants
Dx: positive clinical response to treatment, methacholine inhalation challenge by aid in diagnosis
nocturnal asthma
Sx midnight to 8 am
decline of circulating catecholamines and cortisol
signs of life-threatening asthma
- accessory muscle use on
- presentation
- pulsus paradoxus
- right heart strain: P-pulmonale on EKG
- hypoxemia
- hypercapnia
death: usually DIFFUSE MUCOUS PLUGS
reversibility criteria for Dx of asthma
uses bronchodilator
12% improvement AND 200cc increase in FEV1 and/or FVC
OR
15% from basal FEV1
triggers of asthma
- humidity/ change in pressure
- allergens: dust mites, pollen, cockroach, food, NSAIDS
- occupation
- URI, sinusitis
- GERD
- hormonal
- psychological
- cigarettes
intrinsic restrictive lung disease
alterations in lung
- interstitial lung disease
- resection of lung tissue
extrinsic restrictive lung disease
alteration in the structures surrounding lung
- disease of pleura
- disease of chest wall
- neuromuscular disorder
interstitial lung disease
diffuse inflammatory process involving the lung parenchyma resulting in excess growth of connective tissue with dysfunction of lungs
drugs that induce interstitial lung disease
bleomycin
amiodarone
nitrofurantion
external radiation
granulomatous interstitial lung disease
berylliosis
hypersensitivity pneumonitis
sarcoidosis
list of interstitial lung diseases
berylliosis hypersensitivity pneumonitis asbestos, coal, silica drug induced sarcoidosis unknown etiology: idiopathic interstitial penumonias ILD with connective tissue diseases
Interstitial lung disease (ILD)
hypoxemia, HYPOcapnea, wide A-a gradient, exercise induced hypoxemia
Sx: DYSPNEA (most common), tachypnea, crackles, CLUBBING
late: cor-pulmonale, cyanosis
Dx: Hx, Sx, imaging, PFT, BAL (broncho-alveolar lavage) and lung biopsy
MACROPHAGES mostly, lymphocytes, few PMN
radiologic finding of end stage ILD
Honeycomb
radiologic finding of early stage ILD
ground glass
CFTR
What happens when it is mutated?
cystic fibrosis gene
cell surface: regulated chloride channel
normal: inhibits ENaC
mutant: ENaC not inhibited: Na absorption increased and water follows: low airway fluid and Cl- not secreted
mucus is dehydrated: impairs mucociliary clearance
cystic fibrosis
white
autosomal recessive
chromosome 7
bacterial airway infections, nasal polyps, pancreatitis, elevated sweat electrolytes, hepatobiliary disease, meconium ileum, obstructive azoospermia, portal HTN, clubbing
suspect if see: non-TB mycobacterial infection, allergic bronchopulmonary aspergillosis
most infected with P. aeruginosa by 18
what is the most common CF mutation?
FD508
What is the sweat chloride level of a CF patient?
greater than 60 mmol/liter
complications of CF
osteoporosis, hypertrophic pulmonary osteoarthropathy, allergic aspergillus, hempoptysis, spontaneous pneumothorax
systemic inflammatory response syndrome (SIRS)
due to infection proven or suspected NOT a positive culture 1. Temp: greater than 38 or less than 36 2. heart rater greater than 90 bpm 3. tachypnea (RR greater than 20) 4. white blood count greater than 12,000 or less than 4000 with greater than 10% bands
sepsis
SIRS + infection
profound immune activation
inflammatory cytokines elevated, NEUTROPHILIC leukocytosis
lacks sensitivity and specificity
severe sepsis
sepsis + organ dysfunction (or evidence of hypoperfusion)
MENTAL status change, increases MINUTE VENTILATION, not tolerating feeds
other: fever, tachycardia, tachypnea, hypotension, N/V, loss of appetite
septic shock
sepsis + hypotension not responding to fluid resuscitation
Tx: VASOPRESSORS
crystalloids
saline/LR
resuscitation fluid of choice for septic shock
early goal directed therapy (EGDT)
improves mortality of sepsis
two or more of:
1. central venous pressure 8-12 mmHg
2. mean arterial pressure greater than 65 mmHG
3. urine output greater than O.5 mL/kg/hr
4. central venous O2 saturation greater than 70%
Tx: underlying cause
afebrile infections
- very young or old
- CKD
- DM
- steroid use/NSAIDS
- immunocompromised
- neurologic: stroke or brain malformation
preventative measures in sepsis
- DVT prophylaxis: early ambulation
- stress ulcer prophylaxis
- remove foley catheter and central lines
- target glucose less than 150 mg/dL
- chlorhexidine mouthwash
other: hand washing, head of bed elevation to prevent VAP/HAP
FASTHUG: feeds, analgesics, sedation, thromboembolism, head of bead, ulcer, glucose
GM-CSF
can cause SIRS
What lab work should be done before giving antibiotics to someone with sepsis?
GET antibiotics EARLY or DIE
- gram stain and culture of appropriate body fluids
- TWO blood cultures: vascular device and peripheral
- imaging
- good H&P
levophed
NE for septic shock
BETTER than dopamine
add vasopressin
then wean levophed first then vasopressin
Factors that play a role in pleural effusion
- hydrostatic pressure
- oncotic pressure
- tissue pressure
- lymphatic drainage
Which pleura has lymph drainage?
parietal
What condition is indicated if a pleural effusion is due to increased hydrostatic pressure? Transudate or exudate?
MOST COMMON heart failure transudate see cardiomegaly PWP greater than 24 mmHg visceral pleura shifts from fluid absorption to fluid formation Tx: diuretics
What condition is indicated if a pleural effusion is due to decreased hydrostatic pleural pressure? Transudate or exudate?
atelectasis
transudate
visceral and pleural formation of fluid
What condition is indicated if a pleural effusion is due to decreased systemic oncotic pressure? Transudate or exudate?
low albumin: malnutrition, renal loss, decreased production in liver
transudate
visceral and pleural formation of fluid
What condition is indicated if a pleural effusion is due to increased oncotic pressure in pleural space? Transudate or exudate?
inflammation (increased vascular permeability): infection, cancer
exudate
visceral and pleural formation of fluid
Sx of pleural effusion
dullness to percussion
decreased tactile remits
increased RR
decreased breath sounds
indication for thoracentesis of pleural fluid
greater than 10 mm on lateral decubitus Xray
How do you differentiate between transudate and exudate in pleural effusion?
exudate:
- pleural/serum protein ratio greater than 0.5
- pleural/srum LDH ratio more than 0.6
- serum LDH greater than 200 U/L
transudate: ABSENCE of all 3
What does a pleural fluid with greater than 5% mesothelial cells EXCLUDE?
TB pleurisy
What does a WBC of a. less than 1000/ ul b. greater than 5000 c. greater than 10,000 d. greater than 50,000 indicate?
a. transudate
b. Chronic: TB, CA
c. parapneumonic, pancreatitis, pulm. infarct
d. parapneumonic ONLY
What could low pleural fluid glucose be due to?
decreased transport: 1. rheumatiod 2. CA increased utilization: infection 1. empyema 2. TB 3. esophageal rupture
What can you suspect if pleural fluid is acidotic?
- esophageal rupture
2, empyema - rheumatoid
other: CA, TB, lupus
What can you suspect if pleural fluid amylase/serum amylase is greater than or equal to 1?
acute pancreatitis pancreatic pseudocyst esophageal rupture CA ruptured ectopic pregnancy
What is the most likely cause of lymphocytosis in pleural effusion?
TB
other: CA
primary pulmonary artery hypertension (PAH)
- mean PAP greater than 25 mmHg at rest (30 with exercise)
- mean PCWP and LVEDP less than 15 mmHG (rules out heart failure as a cause)
Sx: fatigue, exertion dyspnea, chest pain, syncope, edema
need HIGH INDEX of SUSPICION
Dx: apical impulse shifts OUT, parasternal HEAVE, accentuated and palpable P2, widely split S2, SEM L 2nd ICS
can have: RHF signs: JVD, bilateral leg edema, prominent central arteries on CXR, mild decreased DLCO, EKG: R axis deviation
POOR PROGNOSIS without Tx
causes of secondary PAH
- parenchymal lung disease
- chronic thromboembolic disease
- left sided valve disease
- myocardial disease
- systemic connective tissue disease
what are the 5 groups of PAH
- primary PAH
- heart disease
- lung disease
- CTEPH
- multifactorial
Factors that play a role in PAH pathogenesis
- prostacyclin, TXA2
- ET-1
- NO (reduced nitric oxide synthase)
- serotonin
- VEGF
- ANOREXIANTS (phenphen)
- CNS stimulant (COCAINE)
conditions associated with PAH
SCLERODERMA, HIV, SICKLE CELL
other: HHV-8, SLE, MCTD, RA, portal HTN, thrombocytsis (SEROTONIN), HHT (free heme and iron)
BMPR2 (bone morphogenetic protein receptor type II)
familial primary pulmonary HTN
NO role in PAH
PAH: reduced
vasodilation
inhibits sm. muscle growth
endothelin 1 role in PAH
potent vasoconstrictor
mitogen for Sm. muscle cells
VEGF role in PAH
speculative role in PAH
endothelial growth stimulate
expressed by endothelial cells in PLEXIFORM lesions
serotonin role in PAH
high levels in PPH
vasoconstriction and proliferation of sm. muscle cels
Kv (voltage gated potassium channels) role in PAH
control cell membrane potential and release of Ca
PPH: pulmonary artery sm. muscle has low mRNA for K channels and low channel curren: increase intracellular Ca
anorexiants role in PAH
appetite suppressant
blocks voltage gated potassium channels
What is the first test if PPH is suspected?
echocardiograph: good screen
evidence of: right heart enlargement, paradoxical motion IVS, tricuspid insufficiency
What indicates a better prognosis in PPH?
vasoreactivity with NO: greater than 20 percent reduction in PAP and PVR
greater than 10 mmHg drop in MPAP (should drop to less than 40mmHg)
Drugs that improve survival in PAH
epoprostenol
bosentan
anticoagulation
S1Q3
EKG finding in a minority of pulmonary thromboembolism patients
pulmonary thromboembolism
LOWER extremities
Sx: bronchospasm, wheezing, dyspnea, pleuritic pain, tachypnea, tachycardia, LOUD P2
Tx: initiate as soon as suspected (DON’T wait to prove Dx)
Virchow’s Triad
predisposing factors for clot formation (PE)
- stasis
- hypercoagulable
- endothelial injury
congenital hyper-coagulability diseases
- factor V Leiden mutation
- antithrombin III deficinecy
- prothrombin G20210A
- protein C and S deficiency
- dysfibrinogenemia
- homocystinemia
acquired hypercoagulability
- estrogen use
- preganancy
- malignancy
- nephrotic syndrome
other: thrombocytosis, DIC, HIT (don’t give heparin), antiphospholipid Ab syndrome, PNH
physiologic consequences of PE
- increased PVR: obstruction, neurohumoral
- impaired gas exchange:
a. V/Q mismatch (WIDE A-a)
b. low DLCO
c. shunt (massive PE) - hyperventilation (HYPOCAPNIA)
- increased airway resistance (wheeze)
- decreased compliance
HYPOXEMIA
How does circulation compensate in PE?
- vasodilation of uninvolved vasculature
- helps decrease PVR
- improves V/Q in uninvolved areas
- improves overall oxygenation
EKG findings in PE
- nonspecific ST-T abnormalities
- tachycardia
- atrial arrhythmias
- MINORITY: S1Q3T3
Lab data seen in PE
ELEVATED D DIMER (> 500)
low: PaO2, PaCO2
wide: A-a
elevated: BNP, troponin, LDH, bilirubin
normal: WBC (can be elevated), transminases
V/Q lung scan meaning in PE
high clinical suspicion and high probability lung scan: confirms PE
both low: excludes PE
pitfalls: 15 sec hold breath, observer variability, most are indeterminate
GOLD standard for PE
pulmonary angiography
what is the primary diagnosis modality of choice for PE?
helical CT
if PE excluded: provides an alternate Dx in most patients
Signs of DVT
swelling in one leg
Homan’s only 50:50
Best diagnosis measure for DVT
real-time (B-mode) ultrasonography
Gold standard for Dx DVT and why isn’t it used
ascending contrast venography
can dislodge DVT and cause a pulmonary embolism
prevention of DVT
1. heparin 5000 units SQ every 8 hours OR low molecular weight heparin 2. early mobilization 3. T.E.D. hose stocking 4. intermittent external pneumatic compression of calf and thigh
aPTT
activate partial thromboplastin time
monitor heparin
PT
prothrombin time
monitor warfarin
Factor Xa
low molecular weight heparin
Tx of DVT
radiological: disrupt with catheter
surgical: RARE
SHOCK: t-PA for thrombolysis
fat embolism triad
long bone fractures in elderly
- mental status change
- thrombocytopenia
- petechiae in chest and neck
