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Glossary of Block 6 PBL lectures

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NBTE
non-bacterial thrombotic endocarditis
infectious endocarditis pathogenesis
NBTE
Transient bacteremia
Interaction between the two
Infectious endocarditis: random facts
Continuous bacteremia
Embolic phenomenon (petechiae, strokes, TIA etc), abscesses, microscropic hematuria
CHF due to valve damage most common cause of death.
Osler's node vs
Janeway lesion vs
splinter hemorrhage
Finger/toe pad
Palms/soles
Fingernails
Duke's criteria
Positive blood cultures
Positive vegs on echo
New regurgitation
Valvular or endocardium involved.
Bacterial causes of SBE
Strept viridans group
Enterococcus
HAECK organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) Yikes.
Bacterial causes of ABE
Staph aureus
Beta-hemolytic strepts
Pneumococcus
Infectious endocarditis: treatment
Must be bacteriaCIDAL
Treat 4-6 weeks
If indicated, surgery NOW, don't wait. (CHF, PVE IE, abscess, large vegs).
Prophylaxis (amoxacillin) before dental procedures.
Arterial flow is directly proportional to:
Indirectly proportional to:
Pressure (diastolic pressure, most coronary flow during diastole)
Square of the radius (lumen size)

Length of the stenosis
Angina: pharacological treatment
One ASA, 80mg min
Reduce O2 consumption: B-blocker, Ca-channel blocker, Nitrates
Increase O2 supply: nitrates
Lipid management
Nitrates in angina: random facts
Nitric oxide donor -> activate cGMP -> VENULAR ONLY (nitroglycerin) smooth muscle dilatation -> reduced LV EDP (preload) -> reduced O2 consumption

TOLERANCE: must have nitrate free intervals (at night)

SubLing(give to all pts), Oral, topical available.
Beta blockers: examples
Atenolol
Metoprolol
Toprol XL (metoprolol) -- 2x more expensive
In order: 4 determinants of MVO2
Myocardial oxygen consumption!

Heart rate
Contractility
Afterload (BP)
Preload (LVEDP)
Calcium channel blocker names and relative effects on AV node, inotropy, BP?

.
Verapamil
L-Type Ca channel blocker
Contra: 2nd, 3rd AV block, hypotension,
Caution: CHF, MG, bradycardia
Adverse: AV block, CHF, hypotension, CONSTIPATION
Diltiazem
L-type Ca channel blocker
Contra: 2nd, 3rd AV block, WPW, acute MI
Caution: CHF, LVSD, liver/renal impairment
Adverse: brady, AV block, CHF, erythema multiforme.. but these are uncommon. Well tolerated.
Nifedipine
1st generation dihydro.

NO LONGER ANY ROLE FOR USE IN ANGINA! SERIOUS COMPLICATIONS.
Amlodipine
2nd generation dihydro
Contra: hypersensitivity to this drug
Caution: severe CAD, CHF, liver disease, aortic stenosis
Adverse: arrhythmia, syncope, EM, etc.
Ranolazine
Ranexa. Na channel inhibitor -> lower sodium decreases Ca overload via Na/Ca exchanger -> reduces stiffness of diastolic wall, relieving pressure on vessels. Cyclical. Basically the anti-digoxin.
VERY expensive.
ACE inhibitors in angina
No effect. May help lower high BP, reducing afterload.
Nonpharmacologic therapy in angina

And follow up.
Exercise
Weight reduction
SMOKING CESSATION (-25% risk in 1yr)

Monitor lipids, drug compliance, side effects, smoking cessation.
Characteristics of normal EKG
Sinus
+P wave axis in I,II,III, aVF
QRS 90 to -30
PR .12-.21, QRS < .10
QTc < .46 (QT/root(RR interval))
Precordial R wave progression (V3-V4 transition)
Baseline ST seg
T wave dir same as chest QRSs
Difference between ectopic atrial rhythm and wandering pacemaker?
Both have variable waves but wandering has 3+ P wave morphologies, with none of them appearing consistently sinus.
Early afterdepolarizations
Occur in Phase2/Phase3 of AP
Occur under conditions that prolong the action potential duration
May require concomitant “dispersion of refractoriness”
(eg, prolonged QT syndromes where disparity between epi-, mid- and endomycardial APD)
Stroke prevention in A.Fib
ASA 81 – 325 mg: age < 75 and < 1 risk factor
Warfarin INR 2-3: >1 risk factor, age > 75.
Warfarin INR 2.5-3.5: RHD, prosthetic valves etc.
Lidocaine
Class Ib, Na+ channel blocker
Treatment of ventricular arrhythmias in acute setting (V.Tach!!!!)
Amiodarone
Class III (and I,II,IV effects)
K+ channel blocker, blocks repolarization prolonging APD.
Great for A.fib and V.Tach.

Pulmonary toxicity, thyroid metabolism
Procainamide
Class Ia, Blocks Na (slow automaticity) and K (longer APD)
Great for WPW when presents with A.Fib. Slows accessory conduction.
Can cause lupus syndrome, long QT.
Adenosine
Opens outwards K+ channels, hyperpolarizing pacemakers. Slows sinus rate, depresses AV conduction.
Acute treatment (HL<8s) of SVT! NOT FOR WPW.
Beta blockers in arrhythmias
Slows HR, decreases DAD (triggered automaticity), decreases myocardial demand.
For long term SVT.
Can cause broncospasm.
Diltiazem and verapamil in arrhythmias
Ca channel blockers
Slows AV nodal conduction
NOT for WPW!!!
For long term SVT.
Can cause hypotension.
Digoxin
Vagotonic effect on AV node... slows HR. (in addition to use in CHF)
A.fib, especially in LV dysfunction when you cant use a Ca channel blocker!!
Narrow therapeutic range.
Phamacologic treatment of SVT: acute and preventive
Acute: adenosine, Ca channel blockers, B blockers, Digoxin
Prevention: B blockers, Digoxin, Type Ia, Ic, III.
Stages of HF
A: high risk
B: + structural
C: + symptoms
D: + refractory
NYHA functional class of HF
Symptoms with:
1: major exertion
2: normal exertion
3: minor exertion
4: at rest
Six general causes of heart failure:
Systemic HT
Pulmonary HT
Pericardial disease
Myocardial disease
Valvular disease
High output state
5 causes of high output HF:
Anemia
Hyperthyroidism
Paget's disease of bone
Beriberi disease
AV fistula
Pulsus paradoxus
Normally pulse weaker on inhalation and stronger on exhalation... exaggeration of this causes more beats on auscultation than periphreal pulses felt.
Pulsus alternans
Amplitude of normal pulse alternates between strong and weak.

Indicates severe left ventricular dysfunction.
Framinghman criteria for CHF:
2/0 or 1/2
Major: PND or orthopnea, JVP, rales, cardiomegaly, S3, +HJR
Minor: ankle edema, night cough, DOE, hepatomegaly, pleural effusion, HR > 120/min
ANP & BNP: random facts
ANP: response to volume expansion... used to dx asymptomatic HF
BNP: response to increased ventricular filling pressures... used to dx acute decompensation
BNP values:
No HF: <100pg/mL
Non-cardiac dyspnea: 350pg/mL
Acute HF: 700pg/mL

Correlates with NYSA class:
FC I 244 to FC IV 817 pg/mL
Kussmaul's sign
JVP going up with inspiration rather than down as is normal. Due to impaired filling of RV.
Normal right sided pressures on Swan-Ganz:
RA: 5
RV: 30/5
PA: 30/10
PCWP: 8
Normal LV, aorta pressures
LV: 120/8
Aorta: 120/80
Equations for SVR and PVR:
SVR: (MAP-RAP)/CO * 80
PVR: (MPAP-PCWP)/CO * 80
Normal and abnormal O2 sats:
Arterial 95-100%
Mixed venous:
70% (CI = 3L/min) normal
50% (CI = 2L/min)
30% (CI = 1L/min)
3 hemodynamic pathologic states and pressures/resistance seen in them:
Volume loss: low pressures, high SVR
Septic shock: low pressures, low SVR
Cardiac shock: low pressures, high filling pressure (PCWP, LVEDP)
Murmurs heard during systole vs diastole?
Systole: AS, PS, MR, TR
Diastole: AR, PR, MS, TS
Causes of AS, AR, MS, MR, TR, PS
AS: bicuspid valve, calcific valve
AR: collagen disorder, degenerative, Marfan's, syphilis, dissection
MS: Rheumatic
MR: Cardiomyopathy, prolapse, ischemia
TR: left heart disease
PS: congenital
Auscultory signs of AS, AR, MS, MR, TR, PS
AS: systolic click, systolic murmur
AR: Early diastolic decresendo murmur
MS: Loud S1, opening snap, mid-diastolic murmur
MR: Holosystolic murmur in mitral area
TR: Holosystolic murmur, increases with inspiration
PS: Systolic ejection murmur
Balloon valvuloplasty effective in? not effective in?
effective in mitral stenosis, pulmonic stenosis

NOT for aortic stenosis in adults.
Spectrum of ischemic heart disease (4)
Chest discomfort on exertion: Angina
Increase in frequency/ at rest: Cardiac enzymes negative: Unstable angina
Chest discomfort at rest plus elevated enzymes: Non-ST elevation MI
Chest discomfort at rest plus ST elevation: ST elevation MI
WHO definition of MI
2 of 3
Chest pain
Q waves on EKG
Positive enzymes (troponin)
7 steps to take for acute STEMI:
Cardiac monitor
Aspirin
Oxygen
Nitroglycerin
Analgesia
Beta blocker
Reperfusion (cath or chem)
Thrombolytic agents:
Alteplase (rTPA)
Streptokinase
Reteplase
TNKase
Lanoteplase
Indications for PTCA (percutaneous coronary angioplasty)
Cardiogenic shock
Pt. recieved CPR (bleeding risk)
Contraindication to thrombolytic therapy (stroke?)
3 acute MI mechanical complications:
VSD
Myocardial rupture (tamponade)
mitral regurgitation
NSTEMI: treatment
Thrombolytic therapy NOT indicated
Immediate Revascularization (CABG, PTCA)
Size of infarct smaller
Future events higher
Unstable angina: treatment
Hospitalization
ASA
Heparin
Nitrates
Beta blockers
Coronary angiography
Thrombolytic therapy NOT indicated
Chronic stable angina: treatment

ABCDEs
Identification and treatment of associated diseases
Reduction of risk factors
Lifestyle adjustments
Pharmacologic management
Revascularization (PTCA, CABG)

Aspirin, B-blocker, cholesterol/cigs, diet/diabetes, education/exercise
Blood pressure levels and classifications
Normal: <120 / <80
PreHTN: 120-139 / 80-89
Stage 1: 140-159 / 90-99
Stage 2: >160 / >100
Pseudohypertension
Older pts have thick, hard arteries. More cuff pressure required to occlude vessel, hence higher BP readings.

Final diagnosis made by intra-aterial pressure measurement.

Suspect if antiHT therapy results in hypotensive symptoms (dizziness, syncope etc)
White coat hypertension
Hypotensive symptoms (weakness, dizziness) on a variety of different antihypertensive medications.

May develop sustained HT, higher risk of strokes!

Have patient take pressure outside of office.
Relationship between CVD and HTN:
Each inrease of 20/10 doubles risk of CVD, starting at 115/75.

Lower BP can reduce risk of stroke ~40%, MI 25%, HF 50%

Even pre-hypertension has these risks (minus stroke)!
Good prognostic indicators for HTN:
microalbuminuria (Bad)
LVH (bad)
reduced GFR (bad)
HTN therapy goals:
<140/90
or <130/80 if DM, chronic kidney disease
Lifestyle steps to reduce HTN
Weight reduction
Reduce sodium intake
Physical activity
Moderation of alcohol
DASH eating plan (low sat fat/cholesterol)
Stop smoking
Combined alpha/beta blockers in HTN, drug names and benefits:L
Carvedilol, labetalol
Alpha 1 blockade reduces SVR by vasodilation.
Benefits of ARBs over ACEi
No cough, reduces aldosterone output, can be used in pts with a history of angioedema.
HTN in African americans
More prevalent, severe.
Resistant to BBs, ACEi, ARBs

Use CCBs, diuretics.
General principles of HTN therapy
Goal – BP < 140/90
Most drugs are equally effective
Start with low doses, slowly titrating BP down
Use formulations that provide 24-hour efficacy... one dose increases compliance
Fewer side effects – combination of drugs with low dose – excellent control
Gradual reduction of BP except in people with severe target organ damage

Start with thiazide, if +20/10 over normal with thiazide, add 2nd agent.
Light's criteria + albumin addon
Total protein < .5 serum
LDH < .6 serum
LDH < 2/3 max serum LDH (200)

NOTE: if unsure, add albumin gradient, if serum > 1.2g over pleural fluid, transudate.
Criteria and 3 underlying causes for hemothorax
Pleural fluid Hct > 50%

Malignancy, Trauma, pulmonary embolism
Neutrophilic pleural fluid suggests:
PE
Subphrenic abscess
Early TB
Pancreatitis
Parapneumonic effusion
Eosinophilic (>10%) pleural fluid suggests:
Air
Blood 2ndary to trauma
Asbestos
Drug rx (nitrofurantoin!)
Parasite
Churg-Strauss
Basophilic pleural fluid suggests:
Leukemic involvement of pleural space
Lymphocytosis (>50%)pleural fluid suggests:
TB
Malignancy

Get a biopsy!
Low glucose in pleural fluid suggests:
Malignancy
Parapneumonic effusion
and other rare causes
High amylase in pleural fluid suggests:
Pancreatic disease
Malignancy
Esophageal rupture
Low pH in pleural fluid suggests:

<7 vs 7-7.2 vs >7.2 ?
Esophageal rupture
TB
Malignancy
Systemic acidosis
Urinothorax
Complicated parapneumonic effusion

Tube thoracostomy vs repeat eval looking for falling pH vs no tube necessary.
Top 6 causes of pleural effusion in order:
CHF
Pneumonia
Malignancy
PE
viral disease
Cirrhosis with ascites
CHF and pleural effusion treatment:
If no chest pain, fever etc, diuresis and observe. Should go away within 3 days. If not, thoracentesis.
4 types of acute respiratory failure
Type 1: acute hypoxemic (normocapnic)
Type 2: ventilatory (hypercapnic)
Type 3: perioperative
Type 4: shock
Acute Hypoxemic Respiratory Failure
Due to airspace filling

Pneumonia, ARDS, puledema

See dyspnea, anxiety
Ventilatory Respiratory failure
Alveolar hypoventilation, high dead space

COPD, CVA, ALS

See somnolence
Perioperative respiratory failure
Atelectasis due to reduction in FRC with increased closing volume.
pCO2 formula, normal values of VCO2, alveolar ventilation, pC02
CO2 production * .863
--------------------
alveolar ventilation

200ml/min, 4.2L/min, 40mmHg
A-a gradient calculation, normal value
AaDO2 = 150 - PaCO2/.8 - PaO2

Normal Age/4 + 4 or less.
Change in A-a gradient with increase in Fi02
Increases 5-7mmHg for each 10%.
Expected PCO2 equation, in terms of bicarbonate:
1.5(HCO3) + 8 +-2

If PCO2 is higher than expected, consider SIRS, Sepsis, anxiety, pain etc.
Overall 5 year mortality of HF:
50%
Life prolonging medications in HF and who should be on them?
Ace inhibitors: all patients
B-blockers: all patients
Aldosterone antagonists: all patients with class HF 3-4 in the last 2 months.
Hydralazine-Isosorbide dinitrate: not specified

All of these imply no contraindications or intolerance!
ACE inhibitors in HF: treatment guidelines
All patients with asymptomatic LV dysfunction, HF class 1-4, or LVEF < 40%.
Contra: hyperkalemia, angioedema, pregnancy
Use ARB if ACEi not tolerated.
B-blockers in HF: treatment guidelines
All patients with asymptomatic LV dysfunction, HF class 1-4, or LVEF < 40%.
Contra: cardiogenic shock, severe reactive airway disease, 2/3rd degree HB
Monitor HR, BP
Aldosterone antagonists in HF: treatment guidelines
All patients with Class II to IV HF due to LV dysfunction (LVEF < 0.40).
Contra: hyperkalemia, Cr>2.5/2.0 men/women
MUST MONITOR POTASSIUM AND RENAL FUNCTIONS!
Role of ICD in heart failure?
Reduces mortality in patients with LVEF < 35, Class II or III symptoms.
Role of Resynchronization + ICD in heart failure?
Reduces mortality in patients with LVEF < 35, QRS > 120 ms, Class III or IV.
Treatment of stage A HF
Control risk: treat HT, DM, lipids, CAD, smoking, alcohol
Treatment of stage B HF
All stage A methods and...

ACEi + Beta blocker, valve replacement if necessary
Treatment of stage C HF
All stage A&B methods and...

Loop diuretic
aldosterone antagonist
hydralazine + isosorbide dinitrite
digoxin
ARBs
AICD, pacing if LBBB, valve repair, home oxygen, salt restriction.
Treatment of stage D HF
All stage A&B&C methods and...

Inotropic infusions
hBNP infusions for acute decompensation
Mechanical assist devices
Transplantation
Drugs to avoid in HF
CCBs, NSAIDS, alcohol, thiazolidinediones
Two most important things to get if suspect ILD:

Other critical points:
HISTORY!!! Detail is critical!
OLD CXR!!! Also critical!

Speed of onset, duration of symptoms.
Traction bronchiecstasis:
Dilation of the bronchi due to fibrosis. Fibrotic alveoli contract and pull on the walls of the bronchi, dilating them.
Drugs associated with ILD
amiodarone
nitrofurantoin
bleomycin
MTX
Conditions associated with UIP:
IPF, CVD, drug toxicity, asbestosis, hypersensitivity pneumonitis
IPF
Chronic fibrosing interstitial pneumonia
UIP histological pattern
NO MEDICAL THERAPY PROVEN TO WORK though cautiously try steroids + azathioprine.

Pattern?
NSIP. Fibrotic stage

Pattern?
NSIP cellular stage

Pattern?
UIP

Pattern?
UIP, normal elements to lowerleft.
Most common rheumatoid arthritis associated ILD?
NSIP

Others do occur though! UIP, etc.

Pattern?
Loose granulomas in hypersensitivity pneumonitis

Pattern?
Loose granulomas in hypersensitivity pneumonitis

Pattern?
Well formed NCGs in Sarcoidosis.
7 causes of lung cancer
Smoking
2ndhand smoke
air pollution
Radon exposure -- 10%!
Occupational (asbestos)
Heredity
COPD
Pan coast's syndrome
Usually due to NSLC compressing brachial plexus.

Pain in shoulder, scapula, fingers
Horner's syndrome
Bone destruction
Atrophy of hand muscles
Superior vena cava syndrome
Lung cancer causes 60-80% of cases, compression of SVC.

Patients commonly experience fullness in the head and dyspnea. Vein distention for collateral to IVC. Resolves with chemo/radiation.
Paraneoplastic syndromes in lung cancer:
Cachexia
Clubbing and Osteoarthropathy
Deep Vein Thrombosis
Nonbacterial Thrombotic Endocarditis
SIADH (small cell – antidiuretic hormone)
Hypercalcemia (squamous cell - parathyroid)
Cushing’s Syndrome (ACTH)
Neurologic Syndromes (Eaton-Lambert syndrome, retinal blindness, polymyositis, periph. neuropathy)
Frequent sites of mets in lung cancer?
Brain, Bone, Liver, Adrenals
Staging of lunc cancer, NSCLC vs SCLC?
<3cm
>3cm, nodal involvement
Local structures
Distant mets

Limited(one hemothorax--30%) or extensive (anything else 70%)
Palliative measures for stage IV NSCLC
Photodynamic therapy
Laser therapy
Placement of airway stents
Brachytherapy
Screening for lung cancer?
Not recommended. False elevation of 5-yr survival. No real mortality benefits.
Carcinoid Tumor
~1-4% of 1º lung neoplasms
From neuroendocrine cells
Low grade malignancy invade locally, mets uncommon
Mostly 4th decade of life
Commonly in major bronchi
Present with no symptoms, pneumonia, hemoptysis, or focal wheezing
Carcinoid syndrome is rare
Surgical removal gives 5-yr survival of >90%
Mucoepidermoid Carcinoma
Rare tumor
Derived from minor salivary gland tissue from proximal tracheobronchial tree
50% of patients aged <30 years
Generally central in location
Patients present with cough, pneumonia, or hemoptysis
Diagnosis by bronchoscopy
Treatment – surgical resection
Malignant Fibrous Histiocytoma
Most common sarcoma
Relatively slow growing
Metastasizes late
If surgically resectable, prognosis is good
Leiomyosarcoma
Rare
Present with symptoms of bronchial obstruction
If surgically resectable, prognosis is good
Mesothelioma
Rarely benign.
Asbestos exposure
Latent period 20-40 yrs
No assoc. with smoking!!!!!!
Present with dyspnea or chest pain
Pleural effusion or mass on CXR
Local invasion can occur
Diagnosis –pleural bx
Treatment – surgery, chemo, XRT
Poor prognosis
Clinical definition of chronic bronchitis:
After ruling out all other causes of productive cough...

Presence of productive cough for at least 3 consecutive months in two consecutive years.
Pathological definition of emphysema:
enlargement of airspaces distal to terminal bronchioles and destruction of their walls without obvious fibrosis.
Genetic risk factor to develop COPD?
alpha-1 antitrypsin deficency... not present to break down elastases that destroy alveoli.
Natural history of COPD via FEV1:

.
Pathogenesis of asthma vs COPD
Asthma:
sensitizing agent
CD4+ Ts
Eosinophils
Completely reversible

COPD:
noxious agent (cigs)
CD8+ Ts
Macrophages
Neutrophils
Not completely reversible
Pathology of chronic bronchitis?
Mucus and inflammation of large airways.
Repeated cycles of injury of small airways, remodeling, scar, and narrowing.
Destruction of bronchioles, pulmonary capillaries and loss of elastic recoil in parenchyma.
Smoking history necessary to get COPD symptoms?
~20 pack years or longer
Physical exam findings in COPD:
Prolonged expiration
Wheezing
Chest hyperinflation
Distant breath and heart sounds
Coarse crackles
Accessory muscle use
Pursed lip breathing
Cyanosis
Cor pulmonale signs (edema etc).
Radiographic signs of COPD
hyperinflation, flattened diaphragms.
Role of spirometery in COPD?
If normal rules out COPD.
Expect decreased FVC and FEV1, with decreased FEV1/FVC ratio.S
GOLD criteria for staging COPD by FVC and FEV1?
All require FEV1/FVC < 70%

I: FEV1 > 80% predicted
II: FEV1 50-80% predicted
III: FEV1 30-50% predicted
IV: FEV1 < 30% predicted
Treatment of COPD by stage?

.
Classes of bronchodilators used in COPD
Short B2 agonists (alburerol)
Long B2 agonists (salmeterol)
Anticholinergics (ipratropium)
Methylxanthines (theophylline)
Long term corticosteroids in COPD?
NOT indicated. No benefits, possible harm.
Vaccines in COPD?
Influenza every Fall, lowers mortality by 50%.

Pneumococcal every 5 years. Less benefit than flu.
Oxygen therapy in COPD?
Long term administration increases survival! > 15hrs/day
Indications for O2 therapy
PaO2 < 55mmHg
SaO2 < 88%

55-60 or 89% if signs of pulmonary HTN, right HF, or PCV.
Goal of pulmonary rehab? Time length?
Dealing with non-pulmonary problems
Exercise deconditioning
Social isolation
Depression
Muscle wasting and weight loss

MUST be 2 months or longer... the longer the better.
Surgical treatments and requirements for transplantion in COPD?
Bullectomy, Lung volume reduction surgery, transplantation.

FEV1 < 35% predicted
PaO2 < 55-60 mm Hg
PaCO2 > 50 mm Hg
Secondary pulmonary hypertension

Stage IV!
Only COPD treatment that improves survival?
Oxygen therapy.

Drugs and surgery merely relieve symptoms.
Loratidine
Claritin
H1 blocker, competes with histamine.
Hay fever, allergic rhinitus.

Use with caution in asthma... may increase secretions (!cholinergic activity)
Purpose of COHB (HBCO) on PFts?
CO poisoning OR smoking!
Which two pulmonary diseases have increasing prevalence?
COPD, Asthma
Atopic vs nonatopic asthma
Genetic vs ???
Young vs old
IgE vs no IgE
Antigen exposure vs other triggers
positive vs negative skin prick
atopy
Genetically determined state of hypersensitivity to environmental allergens.

IgE mediated.

Includes rhinitis, asthma, hay fever and eczema.
Top 4 trigger factors for asthma
Infection
Air Pollution
Allergens
Exercise
The big 3 in asthma pathophysiology
Airway inflammation
Smooth muscle dysfunction
Airway remodelling
Asthma management A to F
A - Allergen avoidance & Environmental Control
B - Beta agonists
C - Corticosteroids
D - Other Drugs
E - Education
F - Functional Assessment
Asthma classification system?
Days/nights/peak flow?

.
Step up and Step down in asthma?
Find the minimum possible drug regimen needed. Step up if not enough, step down by removing the most toxic drug if controlled for several weeks to find threshold.
Benefits of inhaled corticosteroids in asthma?
Fewer symptoms
Improved pulmonary function
Decreased airway hyperresponsiveness
Reduced exacerbation frequency and severity
Reduced airway remodeling
Reduced mortality
Drugs used in asthma?
Short and long acting B agonists
Inhaled corticosteroids
Mast cell stabilizers (Cromolyn)
Leukotriene modifying agents (Zafirlukast)
Methylxanthines (Theophylline)
Omalizumab
Recombinant anti-IgE antibody

May help to control symptoms and reduce exacerbations in patients with elevated serum IgE levels
Immunotherapy in asthma
S.Q. injection of allergen extracts
Induce immunologic tolerance
Symptoms
related to exposure to an unavoidable allergen to which the patient is sensitive
occur all year or during a major portion of the year
are difficult to control with medication
Treatment requires regular injections for ≥3years
Symptoms improve in most patients
Risk of anaphylaxis
Peak flow color zone system

.
Top 4 causitive organisms for community acquired pneumonia?
S. pneumoniae (45%)
Atypicals (15%)
H. influenzae (10%)
Aspiration pneumonia (10%)
Aspiration pneumonia: % of CAP, risks, 3 syndromes
5-10% of CAP
Risks: Altered consciousness, seizures, dysphagia,age

Syndromes
1. Acid- chemical pneumonitis, sick quick
2.Neutral fluids or solids- mechanical obstruction
3.Infected secretions- pneumonia in 2-5 days
Bugs- oral flora, anaerobes and others
Chest X-rays- dependent segments
Legionella pneumonia: organism, reservoir, pathogenesis?
Gram negative rod, aerobic, fastidious
L. pneumophila and others
Water- aerosols, hot water systems, cooling towers
Alveolar macs ingest but can’t kill
Cell mediated immunity key
HIGH mortality 5-25%
Treat with macrolide, quinolone
Mycoplasma Pneumonia: % of CAP, signs & symptoms, treatment
2-30% of hospitalized CAP
Common in children and young adults
Incubation 2-4 weeks, only 3% get pneumonia
“Atypical”- prodrome, dry, persistent cough
Chest X-ray- looks worse than patient does
Complications- hemolysis, CNS, rash
Diagnosis- cold agglutinins, serology, culture
Treatment- macrolide, tetracycline, quinolone
Chlamydophilia Pneumoniae: % of CAP, signs & symptoms, treatment
5-15% of CAP
Mild in young healthy
Worse with reinfection, older, co-morbidity
Coinfection with pneumococcus
Viral URI prodrome, sore throat, then pneumonia
Diagnosis ?
Treatment- macrolide, tetracycline, quinolone
Inhalational anthrax: epidemiology, diagnostic studies, microbiology, pathology
Sudden, multiple cases flulike illness, high mortality
Widended mediastinum, gram+ bacilli on smear
Cultures out with large gram +bacilli
Hemorrhagic mediastinitis, meningitis
Nosocomial Pneumonia: usual organisms, risk factor.
Gram negatives, staph.

Being on a respirator.
3 endemic fungal infections
Histoplasmosis-
Blastomycosis-
Coccidioidomycosis-
Viral Bronchitis
Most respiratory viruses
Very common- Please hold the antibiotics
Viral pneumonia
lung parenchyma
Adults- influenza, Adenovirus types 4, 7
Kids- RSV, parainfluenza, influenza
Elderly, immunocompromised- all of the above
Influenza virus
Orthomyxovirus, ss-RNA, types A, B
Type A- H and N antigens- H3N2, H1N1, Bs
Avian H5, H7, H9, horse/dog-H3N8
Antigenic drift, shift(pandemic)
Yearly winter epidemics, varying severity
Affects all ages; M+M in elderly, illnesses
Influenza clinical presentation
Incubation 1-2 days, abrupt onset of symptoms
Fever, malaise, myalgia, headache, eye ache
Dry cough, rhinitis, sore throat
Pneumonia- primary viral, secondary bacterial
COPD, Asthma, CHF exacerbation
Myositis/rhabdo, TSS, Reyes (ASA)
DX- clinical, antigens (respiratory), cultures
Influenza Vaccination
Prevents illness in ~70-90% of healthy persons <65yo
Elderly persons and persons with certain chronic diseases my develop lower post-vaccination antibody titers
In nursing homes, vaccination can be 60% effective in preventing hospitalization and pneumonia, and 80% in preventing death
Protection against influenza take 2 weeks to develop
Indications: >50 yo,< 2yo, high risk underlying illness, health care workers, household contacts of high risk
Give yearly in fall or before flu season
Respiratory Syncytial Virus
Paramyxovirus, ssRNA
Infects all ages, repeated infections
Pneumonia and tracheobronchitis in 6-24 month old
URI and tracheobronchitis in older kids, adults
LRI in elderly and immunocompromised adults

Can treat with Ribavirin...
Hantavirus Pulmonary Syndrome
Hantavirus- Bunyaviridae, RNA
Hemorrhagic fever with renal syndrome
Pulmonary- Sin nombre et al, rodent hosts
Zoonosis- inhaled rodent excreta
Since 1993- 234 US cases, 40-60% mortality
Febrile viral prodrome- then pulmonary capillary leak
Rapid hypoxemia, respiratory failure, hypotension
Increased WBC, Hct, atypical lymphs, LFTs
Severe Acute Respiratory Syndrome-SARS
Discovered 3/03 Hong Kong, Guangdong 11/02
Novel coronavirus-animal related- palm civets, et al
8437 cases, 813 deaths, adults, HCWs (65% in Canada)
Transmission-?droplets,aerosols,GI; “hyper spreader”
Viral prodrome, progressive pulmonary disease
Neutropenia, lymphopenia,thrombocytopenia,high LDH
Diagnosis- clinical, epidemiologic
Treatment-? Ribavirin, corticosteroids?, ?interferons
Control
Bronchiolitis
Predominantly infants- 2-10 months, seasonal
RSV- winter, parainfluenza- fall, spring
Viral infection of small bronchi, bronchioles
Epithelial damage, cuboidal non-ciliated cells
Viral URI prodrome, then cough dyspnea
Respiratory distress, wheezes, rales
Predisposes to asthma?
Bronchiectasis
Affects segmental or subsegmental bronchi
Damaged walls, permanent dilated, plugged
Results from infectious or toxic insult, immune
Cystic fibrosis
IgG deficiency
Ciliary problems- (Kartagener's)
Non-infectious
Signs, symptoms, X-rays
Criteria to diagnosis ACUTE vs CHRONIC leukemia
FAB: >30% blasts
WHO: >20% blasts
Acute leukemias vs chronic leukemias
immature vs mature cells
present vs absent nucleoli
rapidly vs slowly progressive
potentially curable vs incurable
ALL: WHO classification
Precursor B-lymphoblastic leukemia/lymphoma (85%)
OR
Precursor T-lymphoblastic leukemia/lymphoma (15%)

Choice between leukemia/lymphoma depends if marrow has > 25% malignant cells = leukemia

3 types: L1, L2, L3
ALL: T-cell CD patterns
CD2, CD5, CD7 positive
NOT yet CD3 usually.

Usually CD4/CD8 too...
ALL: FAB classification
ALL-L1: small uniform cells
ALL-L2: large varied cells
ALL-L3: large varied basophilic cells with vacuoles (Burkitt's type leukemia... t(8;14) effecting c-myc)
4 components of ALL therapy
remission induction, consolidation, continuation, and treatment of subclinical CNS leukemia
ALL: drug therapy
3-4 drugs, which may include a glucocorticoid, a vincristine, an asparaginase, and an anthracycline

AML subtype?
M0, undifferentiated AML
myeloblasts, little cytoplasm, CD13, CD33. Negative cytochemistries.

AML subtype?
M1, myeloblastic, without maturation.
Small blasts with high N/C ratio
Distinct nucleoli
Agranular cytoplasm
MPO, NASD, Sudan Black Pos.
CD13, CD33

AML subtype?
M2. Myeloblastic, with maturation.
More mature leukemic cell
Auer rods present
Good prognosis with t(8;21)
t(8;21) is 15% of AML
Cytochemisties strong positive

AML subtype?
M3. Promyelocytic.
Moderate N/C ratio
Round-to-oval nucleus
Prominent nucleoli
Prominent cytoplasmic granules
Treatment of AML M3.
All Trans Retinoic Acid (ATRA)
Vitamin A analog
Taken orally
Induces cell differentiation
Improved with demethylation

AML subtype?
M4, Myelomonocytic
Contains granulocytic and monocytic cells
7-10% of AML.
CD13, CD14
ANBE positive

AML subtype?
M4eo. Myelomonocytic together with bone marrow eosinophilia.
Inv(16) or t(16;16).
Breakpoint at 16q22.
Good prognosis.
Involves the CBFb gene (normally bound to AML1, the gene involved in M2 AML).

Subtype of AML
M5, Acute Monoblastic
Large cells
Moderate amount of cytoplasm
Very prominent nucleoli
Faint or no granules
M5a monoblastic, M5b promonocytic

AML subtype?
M6 Acute Erythroblastic
5% of AML.
Often associated with deletions in chromosomes 5 and 7.
Poorer prognosis, often preceded by myelodysplastic syndrome.
Seen in older patients.

AML subtype?
M7 Megakaryoblastic
Prominent nucleoli
Variably faint granules
“Cytoplasmic buds”
Trisomy 21, inversions or translocations of chromosome 3, t(9;22); t(1;22) in infants.
Also seen in Klinefelter’s syndrome XXY.
WHO AML classifications?
Acute Myeloid Leukemia with Recurrent Genetic Abnormalities
Acute Myeloid Leukemia with Multilineage Dysplasia
Acute Myeloid Leukemia and MDS, Therapy-Related
Acute Myeloid Leukemia, NOS
Rituximab
Rituxan® was the first monoclonal antibody found to be effective and safe for the treatment of lymphomas in the US. While it was aimed more at indolent lymphomas, it is now being used to treat aggressive CD20+ lymphomas and leukemias.
Zevalin
monoclonal antibody that targets the CD20 antigen and is linked to the radioisotope 90Yttrium
Survivorship issues in cancer and specifically leukemias.
fatigue; cognitive changes; body image; sexual health and functioning; infertility; fear of recurrence; PTSD and stress syndromes; family/caregiver distress; socioeconomic issues; and distress, anxiety, and depression
Composition of hemoglobins:
A
A2
F

% of each in an adult
alpha2, beta2 95%
alpha2, delta2 3.5%
alpha2, gamma2 1%
Macrocytic anemias?
Microcytic anemias?
Normocytic anemias?
MCV < 80: iron def, chronic blood loss, sideroblastic, thalassemias

MCV > 100: folate, B12, alcohol, hepatic disease

Norm: Chronic disease, hemolytic, hemoglobinopathies, early iron def, red cell membrane disorders
Retic Production Index:
retic count x (HCT/45)

times .5 if polychromatic??

Normally 2-3... < 2 suggests insufficent response to anemia
Warm vs cold hemolytic anemias
Warm (IgG): idiopathic (primary), drug-associated, systemic lupus erythematosus, malignant neoplasms

Cold (IgM): mycoplasmal infection, EBV infection
Total body iron amount and distribution:
3500mg
Functional pool: 60% Hg, 10%myoglobin
Storage pool: 29% ferritin, hemosiderin
Plasma: 1% bound to transferrin for transport
Red tongue, glossitis?
One amoung many symptoms of B12 or folate deficiency

B12/folate def leads to impaired DNA synthesis in RBC precursors. Due to lack of cofactors in converting dTMP to dUMP
Schilling test, 2 parts
part 1: oral radiolabeled B12, large B12 dose IM. Looking for excretion in urine to check absorption... (5-35% excreted)
Part 2: Same exact thing but give IF with oral dose. If urine B12 output corrects was pernicious anemia.
Sideroblastic anemia
Although adequate iron is present, a mitochondrial defect (decreased activity of D-ALA or ferrochelatase) prevents the incorporation of iron into hemoglobin.
Iron accumulates in mitochondria ringing the red cell nucleus forming "ringed sideroblasts".
Seen in myelodysplasia, alcohol, lead, drug ingestion.

How's the marrow look?
Normal.

How's the marrow look?
Aplastic
Pathology of WAIHA
Most common form of AIHA, active at 37 C
Half are idiopathic, half are secondary:
autoimmune conditions
drug-induced
Often IgG, rarely IgA that coats the RBC surfaces
Antibody Fc fragment get caught by monocytes/macrophages in spleen and liver
Partial phagocytosis leading to spherocyte formation
The spleen then clears the spherocytes
Presented as extravascular hemolysis
Pathology of CAIHA
IgM antibody, do not react at 37 C, most active at 0-4 C,
Not typically cause clinically significant hemolysis, but chronic low-grade hemolysis
RBC destruction by activating complement on the RBC surface (lysis); the C3b fragments on the surface lead to phagocytosis by monocytes/macrophages.
Positive DAT or agglutination on peripheral blood
Seen in mycoplasma pneumonia or infectious mononucleosis
Idiopathic condition or in association with lymphoproliferative disorders
Increase reticulocytes, RBC agglutinates

What's going on here?
WAIHA. Sphereocytes due to macrophates in spleen.

What's going on here?
CAIHA. RBC agglutination due to C3 and IgM
Direct and indirect Coombs test?

(ALSO CALLED DAT/IAT for direct antiglobulin test)
Direct: patients RBCs + anti-IgG. If it agglutinates, IgG must have been on the RBCs.
Indirect: patients serum + clean RBCs + anti-IgG. If it agglutinates, IgG must have been in patient's serum.
Different labs seen in intravascular vs extravascular hemolysis:
Intravascular has positive urine hemosiderin and hemoglobin, and a negative DAT. Extravascular is the opposite.

Findings and disease?
Bite cells, Heinz bodies.
G6PD
Alpha and beta thalassemias: genotypes
B-Thal major: B0/B0 or B+/B+
B-Thal inter: B0/B or B+/B+
B-Thal minor: B0/B or B+/B

Hydrops fetalis: -/- -/-
Hb H disease: A/- -/-
Trait: A/-/A/-
Silent carrier: A/A/A/-
Lipid disorders:
Familial hypertriglyceridemia: triGs
Familial combined hyperlipidemia: triGs, LDL, premature CAD
Familial hypercholesterolemia: LDLs, premature CAD
Low HDL: HDL duh. Diabetes and metabolic syndrome often present.
LDL response to diet?

What is a good diet for hyperlipidemia?
Drop by ~8%

Avoid trans-fatty acids -- increases LDL decrease HDL.
Add fiber, sterol ester margerines.
Add fish and omega 3 fatty acids.

No evidence to support vitE or beta carotene as helping!!
Benefit of weight loss and exercise in hyperlipidemia:
Lowers TG, raises HDL-C, reduces risk of diabetes.
Diagnostic criteria for metabolic syndrome
3+
Abdominal obesity
TriGlyc > 150 mg/dL
HDL-C < 40mg/dL
BP > 130/85
Fasting glucose > 110 mg/dL
ATP risk categories, LDL treatment goals and when to use drugs?
HIGH RISK CHD history or risk: <100mg/dL >130mg/dL
MODERATE RISK 2+ risk factors: <130mg/dL, 160mg/dL
LOW RISK <2 risk factors: <160mg/dL, >190mg/dL
MOA of statins?
Reduce hepatic cholesterol synthesis by blocking HMG-CoA reductase, lowering intracellular cholesterol, which stimulates upregulation of LDL receptor and increases the uptake of non-HDL particles from the systemic circulation.
Adverse effects of statins?
Headache, GI intolerance
Elevated liver enzymes
Myopathy-- requires discontinuation in 0.4% of pts.
MOA of bile acid resins?
Bind bile acids in the intestine, which reduces the enterohepatic recirculation of bile acids. This promotes the upregulation of 7-alpha hydroxylase and the conversion of more cholesterol in the hepatocyte into bile acids. This decreases the cholesterol content in the hepatocyte, which enhances LDL-receptor expression, which in turn increases the removal of LDL and VLDL remnant particles from the circulation
Adverse effects of bile acid resins?
GI intolerance
Drug interactions: binds other negatively charged drugs... must give other drugs at least 1 hr before or 6 hrs after BARs.
MOA of nicotinic acid?
Niacin appears to exert its effects by inhibiting lipoprotein synthesis and decreasing the production of VLDL particles by the liver. It inhibits the peripheral mobilization of free fatty acids, thus reducing hepatic synthesis of triglycerides and the secretion of VLDL. LDL is made from VLDL so it is also decreased.
Adverse effects of nicotinic acid?
Flushing, itching, headache (immediate-release)
Hepatotoxicity, GI (sustained-release)
Activation of peptic ulcer
Hyperglycemia and reduced insulin sensitivity

DO NOT GIVE IN LIVER OR PEPTIC ULCER DISEASE.
Benefits of fish oils?
Lowers triGs 30-40%
BUT may increase LDLs.

Best in hypertriglyceridemia!
Churg-Strauss Syndrome
Allergic angiitis and granulomatosis
Infiltration of tissues by eosinophils
Lung involvement is predominant with a strong association with asthma
Severe asthma attacks and pulmonary infiltrates
Virchow's triad and other risk factors for PE?
Trauma, stasis and hypercoagulopathy.
Hormone replacement therapy.
Age, smoking, genetics, surgery.

NOT DIABETES, NOT hyperlipidemia!
EKG sign of PE (not always present!!)
S1Q3T3
Large S wave in lead I
Large Q wave in lead III
Inverted T wave in lead III
D-dimer in pulmonary embolism?
NEGATIVE test rules out PE.

Positive test requires MORE testing (V/Q scan or contrast CT, venous ultrasound, pulmonary angiograhy -- gold standard but .5% mortality so use only other tests don't rule in/out)
Therapy for pulmonary embolism?
Heparin: get PTT to 2 times normal within 24 hours
LMWH: as good as heparin, safer
Warfarin: !pregnancy, INR 2-3, overlap with heparin for 3 days.

Therapy for 3-6 months if first PE. 12 months if hypercoagulopathy. Lifelong if any recurrance of PE.
Role of thrombolytic therapy in PE?
Very little: does not change mortality.

Indicated only in MASSIVE PE with hemodynamic instability and hypoxemia.
IVC filters used when?
PE with contraindication to anticoag therapy. Patients with recurrant PE. Other recurrent thromboembolic problems.
Numerical definition of pulmonary hypertension
Mean PAP at rest > 25.
Mean PAP exercise > 30.

Normal is 10-20.
Conditions associated with primary pulmonary HTN?
Connective tissue disease (SLE, mixed connective tissue, Scl)
HIV
Portal hypertension & liver disease
Toxins (L-tryptophan, rapeseed oil)
Treatment of PPH?
Chronic anticoagulation
Vasodilators: calcium channel blockers, Epoprostenol infusion
Endothelin receptor antagonist (Bosentan)
Oxygen
Diuretic therapy
Digoxin
Transplantation
Proteins in the blood?

.
MGUS criteria?
Monoclonal gammopathy:
IgG < 35 g/L; IgA < 20 g/L
BJ Protein <1.0 g/L
<10% plasma cells in marrow.

No bone lesions, no anemia, renal failure, hypercalcemia. NO SYMPTOMS. But may develop into malignancies.
Risk factors for MGUS developing into malignancy?
Higher initial concentrations of Ig.
IgM or IgA riskier than IgG
Kappa MAY be riskier than lambda.
Polyclonal gammopathy... causes?
Liver, Lymphomas, Cancer, Infection, connective tissue diseases...
Smoldering Multiple Myeloma (SMM) criteria?
Monoclonal gammopathy:
IgG > 35 g/L; IgA >20 g/L
BJ Protein >1.0 g/L
10-20% plasma cells in marrow

No lytic lesions, no renal/anemia/hypercalcemia. Track, no treatment.
Solitary plasmacytoma of bone criteria?
Solitary bone lesion
Histologically proven plasmacytoma
Bone Marrow: normal <5%
No anemia, renal failure or hypercalcemia
M-Protein IgG < 35 g/L IgA <20 g/L*
BJP < 1g/24h*

Give RADIOTHERAPY to single lesion! Must MRI spine!
Extra-Medullary Plasmacytoma (EMP) criteria?
Solitary biopsy proven lesion
Bone Marrow (distant site) normal <5%
M-Protein same as SPB (normal or slightly elevated)
No anemia, renal failure or hypercalcemia

RADIOTHERAPY

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