CP I Final

Wave

Atrial depolarization○

Inverted in AVR

If not inverted on the AVR lead, the depolarization is NOT coming from the SA node

Upright in 1, 2, V4-V6, AVF○

Variable in other leads○

P Wave•

From beginning of P wave to beginning of QRS complex

○

Through AV, purkinje

Pre-excitation, tachyrythmia□

If less:

AV blocks□

If longer:

Typical interval (time from SA node to ventricular fiber) 0.12-0.20 secs

○

P-R Interval•

Ventricular depolartization○

0.5-0.1 secs○

QRS comlex•

End of QRS complex to beginning of T wave○

Shouldn't be elevated more than 1mm in standard leads and 2mm in chest leads

□

Should never be depressed more than 1/2mm relative to baseline

□

Level

Should be isoelectric□

Shape

Observe:○

ST segment•

Ventricular repolarization○

Upright in 1, 2, V3-V6○

Inverted in AVR○

Variable in others○

Should not be greate than 5mm in standard leads

○

Massive T waves can indicate MI○

T Wave•

Length of ventricular systole○

From beginning of QRS complex to end of T wave

○

Should be less than 1/2 the R to R interval○

QT Duration•

Normal EKG

NotesEverything is inverted in AVR•Prominent T waves are found in African Americans

•

P-mitrale

Leads 1 & 3

Left atrial enlargement

Notched○

P-pulmonale

Right atrial enlargement

Flat in lead 1; tall in 2 & 3○

AV nodal rhythm

Not coming from SA node

Inverted in 2 & 3○

Abnormal P Waves•

Normal EKG

Internal Med Page 1

Left: P-mitrale. Middle: P-pulmonale. Right: AV nodal rhythm.

Internal Med Page 2

AsthmaChronic inflammatory disorder of the airways•Wheezing•Non-productive cough•

Chronic BronchitisChronic PRODUCTIVE cough for 3 months in each of 2 successive years

•

EmphysemaAbnormal & permanent enlargement of the airspaces distal to the terminal bronchioles

•

Destruction to airspace walls•COPD results when actual airflow obstruction occurs•

Categorizing Asthma

FEV1○

Exacerbations needing glucocorticoids

Steroid use over past year○

Substance that causes bronchospasm

Test used in suspected asthma patient

>20% reduction in FEV1

Methacholine response○

Lung function•

2 or fewer days/week

2 or fewer nocturnal awakenings

SABA's (short acting beta agonists) used less than twice a week

No interference with normal activites

Intermittent○

Daytime symptoms more than twice/week

□

3-4 nocturnal awakenings/month□

SABA's used more than twice/week□

Minor activity interference□

Mild

Daily symptoms□

More than 1 nocturnal awakenings/week

□

Daily SABA use□

Significant activity limitation□

FEV1 60-80% of normal□

Moderate

Asthma symptoms throughout the day□

Nightly nocturnal episodes□

SABA use several times a day□

Extreme activity limitation□

FEV1 below 60% predicted value□

Severe

Persistent○

Categories•

Step Approach to Asthma Therapy

Step 1○

Intermittent•

Step 2○

Mild•

Step 3○

Moderate•

Step 4 or 5○

Severe•

SABA○

Step 1•

Low dose inhaled glucocorticoids

○

Step 2•

Combine long-acting beta agonists with low dose inhaled glucocorticoids

○

Step 3•

Medium strength glucocorticoids (Step 4)

High dose glucocorticoids (Step 5)

Long-acting inhaled beta agonist combined with:

○

Step 4 or 5•

Addition of oral glucocorticoids daily or every other day

○

Step 6•

Risk Factors for COPDChronic Obstructive Pulmonary Disease•Smoking accounts for 80-90%•

Clinical Features of COPD50+ years old (usually)•Productive cough•Dyspnea (shortness of breath) with exertion

•

COPD DiagnosticsSpirometry•Chest x-ray•Lung volumes•CO diffusing capacity•ABGs•

COPD ManagementSMOKING CESSATION•Exercise•Gentle OMM•Oxygen therapy•

Asthma & COPD

Internal Med Page 3

Definition/EtiologyInfection of the bronchoalveolar unit that leads to inflammation & production of inflammatory exudate

•

Bacteria, viruses, parasites & fungi○

Causes:•

Pathogenesis

Lower respiratory tract is sterile○

Reflex closure of the glottis & cough protect the lower respiratory tract

○

Tobacco paralyzes this mechanism

Alveolar macrophages ingest organisms

Ciliary motion sweeps particles upwards to oropharynx

○

Normal Defenses•

Aspiration○

Inhalation○

Hematogenous dissemination○

Intubation

Trauma

Direct inoculation○

Pathological entrance of organisms•Epidemiology

Community-aquired Pneumoccus○

Most common•

S. aureus○

Nosocomial•

Anaerobes○

Aspiration•

S. aureus○

Lung abscess•

H. influenzae○

Chronic lung disease•

Pneumocystis○

Most common is Streptococcal pneumoniae

○

HIV•

TB○

Prison/health care•

Influenza (virus)○

Seasonal (fall/winter)•

Signs & Symptoms

Yellow or green○

Cough w/production of sputum•

Dyspnea•Chest pain•Fever•Chills•

Decreased breath sounds○

Dullness to percussion○

Wheezing○

Signs•

Clinical Features

Sudden fever onset○

Productive cough○

Pneumococcus (common)•

Gradual onset○

Nonproductive cough○

Headache, muscle ache, etc.

Prominent nonpulmonary symptoms○

Atypical (Mycoplasma)•

Tissue necrosis

Putrid or feculent sputum○

"sulfur granules"

Actinomyces sp.○

Anaerobic•

Community-Aquired Pneumonia (CAP)

Empiric antibiotic therapy○

Low rate of established etiologic agent•

All patients should have CXR•Inpatients should have sputum culture & gram stain

•

Other Treatment OptionsChest PT•Hydration•Increased activity•OMM•

Pneumonia

Internal Med Page 4

Antibiotic TreatmentStart with empiric therapy•

Doxycycline (for those under 40 y.o.○

Macrolide, doxycycline or fluoroquinolone

Older or those with comorbidities○

2nd gen. cephs, amoxicillin or amox/clav

Patients older than 60 y.o. or comorbidities

○

Outpatients•

2nd or 3rd gen. cephs○

β-lactam/β-lactamase inhibitor○

Fluoroquinolone○

Macrolide or fluoroquinolone should be included w/above therapies

Critically ill patients○

Vanc or bactrim

For MRSA○

Inpatients•

Pleural EffusionsInfection in pulmonary parenchyma•

Gram stain

Cultures

Acid-fast (TB)

Fungus smear & culture

Studies to obtain:○

Requires thoracentesis•

Clear

Protein <0.5

EX: CHF

Transudates○

Clear or cloudy

Protein >0.5

EX: empyema, pneumonia

Exudates○

Characterizing effusions:•

Internal Med Page 5

GeneralProgressive disease which often leads to pulmonary disability

•

Irreversible○

Therapy does NOT reverse fibrosis•

Respiratory failure○

High mortality•

AnatomyInterstitium spans region between alveolar & vascular epithelium

•

Space between air exchange in alveoli and blood in capillaries•

ILD Classification

Asbestos□

Amiodarone□

Chemotherapy□

Radiation□

IPF (idiopathic pulmonary fibrosis)

SLE, RA scleroderma◊

CTD (connective tissue disorders)

Goodpasture's

Unknown□

Causes:

Alveolitis, interstitial inflammation, fibrosis○

Metals (silica etc.)

Hypersensitivity pneumonitis (HP)□

Sarcoid, Wegener's

Unknown□

Causes:

Granulomatosis response○

Histology•

Clinical Approach to ILD

Normal or on exertion

Dsypnea○

Non-productive cough○

Weight loss○

Fatigue○

Cyanosis○

Smoking hx in 2/3 patients○

Symptoms•

"velcro crackles" bibasilar○

Expiratory wheeze○

Clubbing○

Obese

Cor pulmonale (RHF)○

Signs•

Pneumonitis w/SLE□

Hours-days

AIP (acute interstitial pneumonitis)

□

Days-weeks

Acute○

2 weeks-month

Sarcoid

Drug related

COP, SLE

Subacute○

Months-years

IPF, sarcoid & occupational

Chronic○

History•

Occupational History and Exposure

Bird breeders: HP○

Farmers: HP○

Woodworkers: HP○

Miners: Silicosis○

Coal miners: black lung (pneumoconiosis)○

Pipe fitters: Asbestosis○

Medications: pulmonary infiltrates○

Exposure: Associated lung disease•

African americans 10-17x more likely to aquire sarcoid

○

Familiar pulmonary fibrosis is autosomal dominant

○

History•

Nonspecific○

Lab•

Interstitial Lung Disease (ILD)

Internal Med Page 6

Interstitial Pulmonary Fibrosis (IPF)Most common•Velcro crackles•Poor response to therapy•Mortality 75%•CXR can show honeycombing•

May show ground glass○

CT scan•

Quit smoking○

Flu/pneumonia vaccine○

Remove enviornmental agent

○

Oxygen○

Steroids○

Transplant (lung/heart)○

Treatment•

Acute Interstitial Pneumonia (AIP)Presents like ARDS (Adult respiratory distress syndrome)•

SOB○

Fever○

Cough○

Hypoxic○

CT shows ground glass○

Biopsy shows diffuse alveolar damage○

Signs/symptoms•

Steroids○

Ventilator○

Treatment•

Mortality 60%•

ILD Associated with Connective Tissue Disease

Chest pain (pleurisy) effusion○

CT - ground glass, honeycombing○

Steroids, methotrexate, azathioprine

Treatment○

SLE•

Pleurisy w/ or w/o effusion○

Common in men○

RA•

ILD with Alveolar Hemorrhage

Auto-Abs○

Goodpasture's•

Wegener's○

Granulomatosis vasculitis•

Internal Med Page 7

SarcoidosisNON-CASEATING GRANULOMAS•

Unknown○

Genetics, enviornment, infection○

Etiology•

Increase in TH lymphocytes with macrophages & multinucleated giant cells form non-caseating granulomas

○

Pathogenesis•

Worldwide disease•10-17x more common in African Americans•20-40 y.o.•

Cough○

Dyspnea○

Symptoms•

Nonspecific○

Lab•

Abnormal○

Stage 0 - Normal CXR

Stage I - Hilar & mediastinal lymphadenopathy (enlarged, visible nodes)

Stage II - Lymphadenopathy & parenchymal disease

Stage III - Parenchymal disease only

Stage IV - Pulmonary fibrosis

Classification○

Stages I & II tend to be acute & reversible○

Stages III & IV are progressive○

Stage IV is irreversible○

"1, 2, 3 signs"

Intrathoracic lymphadenopathy is most common finding in sarcoid

○

CXR•

TB, fungal

Other granulomas○

Cancer (metastasis)○

Differential•

By exclusion○

Biopsy for NON CASEATING GRANULOMAS○

Diagnosis•

Prednisone

Steroids○

Anti-TNF (Remicade)○

TNF-receptor antagonist (Enbrel)○

Therapy•

"1, 2, 3 sign"

1

Progressive, "velcro crackles"

Internal Med Page 8

GeneralHF is the inablity of the heart to meet the metabolic demands of the body

•

Most common cause of LV systolic dysfunction is ischemic heart disease (IHD)

60% of HF is due to coronary artery disease(CAD)

○

10% hypertensive heart disease○

Etiology•

CHD/IHD

Myocardial damage○

Ventricular overload○

Restriction/obstruction to ventricular filling○

Causes•

Clinical diagnosis○

No single diagnostic test•

Mechanisms

Results in activation of:○

Increased Norepi

Increase afterload & BP□

Vasoconstriction

Increased HR & contractility

Sympathetic nervous system (SNS)○

Decreased renal perfussion

Increased renin -> increased AG I & II

Further fluid retention□

Aldosterone release

Increased preload

Renin angiotensin aldosterone system (RAAS)

○

ADH

Stimulation of thirst leads to increase in total body water and hyponatremia (dilutional)

Increased preload

Vasopression system○

LV dysfunction results in decreased CO •

As heart fails, fluid retention increases & CO decreases

•

Classification of HFSystolic/diastolic•High/low•Acute/chronic•

Systolic HF50% of cases•Ejection fraction (EF) is less than 40%•Hypoperfusion w/impaired ventricular emptying•

Weak, fatigued, Dyspnea on exertion (DOE), paroxysmal nocturnal dyspnea (PND)

○

General HF symptoms•

Ventricular systole problem•

Diastolic HFGeneral HF symptoms•

Increased resistance to vent. Filling○

Problem is ventricles can't relax•

β blockers○

Diuretics○

Treatment•

High/Low Output HF

Hyperthyroidism, anemia, pregnancy, A-V fistula,○

High CO but low EF○

High output•

Ischemic heart disease○

Hypertension○

Low output•

Acute/Chronic HF

Sudden injury/onset○

Acute MI, ruptured papillary muscle, mitral regurg., toxins

○

Usually systolic HF○

Acute•

Multivalvular disease or dilated cardiomyopathy

○

Progresses slowly○

Edema○

Chronic•

Precipitating Causes of HF

Too much Na+, calories and/or stimulants

Non-compliance w/diet○

Non-compliance w/meds○

Top two:•

From infection to stress -> lots○

Any other stress on the heart•

Congestive Heart Failure (CHF)

Internal Med Page 9

Signs & Symptoms of HFGeneral HF symptoms•Weakness, fatigue•

Dyspnea, SOB, DOE, PND etc.○

Respiratory problems•

Hepatomegalia•JVD•Crackles in lungs•

S3 is normal in athletes & children

S3 & S4○

Heart sounds•

Criteria for Diagnosis of HF

PND, JVD, S3 , hepatojugular reflex (HJR), pulmonary edema, cardiomegalia, crackles

○

Major criteria•

Other general HF symptoms○

Ischemia, infarction or hypertrophy

EKG○

Minor•

Neurohormone made in the ventricles

Sensitive to ventricular overstretching (excessive preload/afterload)

BNP and severity of HF are directly proportional

Brain natriuretic peptide (BNP)○

Lab•

Cardiomegalia○

Pulmonary edema○

CXR•

NYHA Functional Classification of HF

No limitation of activity○

Class I•

Slight limitation of activity○

Ordinary activity causes symptoms

○

Class II•

Marked limitation of activity○

Less than ordinary activity causes symptoms

○

Class III•

Inability to carry out physical activity

○

Symptoms at rest○

Class IV•

Treatment of HF

Make correct diagnosis1.Determine etiology2.Determine precipitating factors3.Understand pathophysiology4.Understand MOA of pharmacologic therapy

5.

Five basic principles•

Quit smoking○

Decrease caloric intake

If overweight:○

2g Na+ diet○

Non-pharmacologic•

Encourage isotonic (walking etc.)○

Avoid isometric activity•

Stool softener•Avoid alcohol•

Pharmacologic Treatment of HF

ACE inhibitors, ARBs, AldactoneA.

Reduced mortality by 65% & hospitalization by 29%

□

Coreg®□

US Carvedilol HF Trial

β blockersB.

CCBsC.Diuretics, digitoxinD.Eplerenone (aldosterone antagonist)E.Fluid restrictionF.Inotropes (Dobutamine, dopamine)I.Nitrates, Na+ restrictionN.HydralazineH.

ABCs•

Lymphatic treatments for optimal fluid drainage

○

OMM•

Internal Med Page 10

Mitral Stenosis (MS)Thick, fibrous valve leaflets•Ca++ deposits•

Increased left A-V pressure gradient○

Narrow "fish mouth" valve•

Often seen in patients w/history of rheumatic fever

•

General HF symptoms○

Coughing up blood

Hemoptysis○

Left atria enlargement compresses left recurrent laryngeal nerve

Hoarseness○

Symptoms•

Malar flush (plum colored cheeks)○

Increased S1○

Opening snap after S2 ○

Use bell

"Rumbling" diastolic murmur○

Physical exam•

Shows P. mitrale signs○

EKG•

"hockey stick" deformity in mitral valve○

Echo•

Prophylaxis for βhemolytic strep○

Warfarin○

If pulmonary HT and/or systemic embolization

Mitral valve replacement○

Treatment•

Mitral Regurgitation (MR)Valve leaks back into atria during systole•History of Rheumatic fever contributes to MR•

Mitral valve prolapse (MVP)

Chronic○

Something broke

Chondral/papillary muscle rupture

Something is on valve to inhibit closure

Acute○

Etiology•

General cardiac symptoms○

RHF/LHF○

Edema○

Symptoms•

Decreased S1○

Prominent at apex, radiating into left axilla

Systolic murmur○

Physical exam•

P. mitrale○

Echo•

Diuretics□

Vasodilator

Afterload reduction○

Useful for chronic MR

ACE inhibitor○

Sever MR

Surgery○

Treatment•

MVP

Thickened○

Inappropriate closure○

Redundant mitral leaflet tissue•

Marfan's Ehlers-Danlos, osteogenesis imperfecta

○

Can be inherited•

Can be asymptomatic○

Palpations, dizziness, syncope & angina

○

Clinical features•

Due to tensing of slack chordae tendinae

Systolic click after S1○

Systolic murmur○

Auscultation•

Non-specific T wave changes○

EKG •

βblockers○

Treatment•

Aortic Stenosis (AS)

Obstruction to LV outflow produces a pressure overload

○

LVH○

Peak systolic gradient○

Pathophysiology•

Dyspnea, angina, syncope○

Symptoms•

Close values of systolic/ diastolic BP

Narrow pulse pressure○

Parvus -> decreased amplitude

Tardus -> slow upstroke

Peripheral pulses rise slowly○

PMI can be laterally displaced○

Physical exam•

Base of the heart and radiates to carotids

Harsh systolic murmur○

Auscultation•

HF treatments○

Valve replacement

Surgery○

Treatment•

Valvular Disease


Aortic Regurgitation (AR)

Rheumatic fever○

Endocarditis○

Etiology•

Leads to LVH

AR leads to volume over load condition which increases LVED volume

○

Myocardial ischemia develops due to increased muscle oxygen requirements

○

Pathophysiology•

Pulmonary edema

Cardiogenic shock

Acute AR○

DOE, PND, angina

Chronic AR○

History•

Bobbing of head w/systole

De Musset sign○

Rapid rising 'water hammer pulse' which collapses as pressure falls

Corrigan's Pulse○

Capillary pulsation w/flushing at root of nail

Quincke's Pulse○

Physical exam•

Diastolic crescendo○

Blowing murmur○

Auscultation•

LV failure treatments, ACE inhibitors

Medical○

Surgical○

Treatment•

Tricuspid Stenosis (TS)

Rheumatic fever○

Associated with mitral stenosis & tricupsid regurg.

○

Etiology•

Prominent "A" wave○

Ascites, edema○

Pathophysiology•

Pulmonary congestion○

Fatigue due to low CO○

RVF○

Symptoms•

Ascites○

Giant "A" waves○

Physical findings•

Diastolic murmur○

Auscultation•

Na+ restriction○

Diuretics○

Surgery○

Treatment•

Tricuspid Regurgitation (TR)

Functional patient○

Usually not pathologic○

Etiology•

Prominent "V" waves in JVP○

Hepatomegaly○

Ascites○

History•

Lowing holosystolic murmur○

Auscultation•

Decreased CO○

Severe TR•

Surgery for repair/ replacement

If pulmonary HT is present○

Treatment•

Pulmonary Valve Disease

Disatolic, high pitched decrescendo blowing murmur

Graham Steell's murmur○

Auscultation•

Murmurs

MR, MVP, TR, AS, PS & aortopulmonary shunts○

Systolic murmurs•

AR, PR, MS, TS, & atrial myxoma○

Diastolic murmurs•

PDA (patent ductus arteriosus), AV fistula, ASD (atrial septal defect) with high LA pressure○

Continuous murmurs•


GeneralProduces vegetations on the endocardium or on a heart valve

•

Associated w/congenital heart disease or valvular disease

•

Virulent organisms can infect normal heart

•

Always fatal if untreated•

Classification

S. aureas occurs on normal valve○

Rapidly destructive, produces metastatic foci (infectious groups of bugs)

○

Fatal in 6 weeks○

Acute•

Does not produce metastatic foci○

Prolonged course (1 year)○

S. viridans○

Subacute•

50-60% of cases are due to S. aureas○

Onset usually acute○

Pulmonary emboli○

Septic pneumonia○

Endo in IV drug abusers•

Due to central IV lines, Swan lines, arterial lines

○

Lines•

Prosthetic Valve EndocarditisAortic more effected than mitral•

Coag. (-) staph & staph A○

Arising within 2 months post surgery•

Coag. (-) staph○

Arising 2-12 months post surgery•

Viridans○

Arising 12 months post surgery•

PathogenesisBacteremia causes infection on sterile vegetation and bacteria adhere to platelet, fibrin, and/or fibronectin

•

Physical Signs of Endocarditis

Especially diastolic○

New or changing murmur•

Splenomegalia•Hepatomegalia•Mucocutaneous petechiae•

Flamed shaped hemorrhagic lesions w/pale centers in the retina

○

Roth spots•

Tender, painful erythematous lesions○

Palms & soles○

Osler's nodes•

Non-tender/-painful , erythematous, papular lesions

○

Janeway lesions•

Clubbing•

Splinter hemorrhagic lesions in nails○

Linear hemorrhages •

Diagnostic Criteria

Demonstrated by culture (lots)

Vegetation that has embolized

Microorganisms○

Confirmed by histology showing active endocarditis

□

Vegetation or intracardiac abscess present

Pathologic lesions○

At least 2 major clinical criteria

Fever, anemia & murmur

Clinical○

Definitive infective endocarditis•

Findings consistent, but not definite or rejected

○

Possible infective endocarditis•

Rejected•

Symptoms of IE Complications of IE

Infective Endocarditis (IE)


Symptoms of IEFever1.Weakness/fatigue2.Night sweats3.Arthralgias4.Embolic manifestations5.HF6.Fever, Murmur & anemia!•

Vegetation visible○

Echocardiogram•

Complications of IEValve destruction with regurgitation/obstruction•CHF•Myocardial abscess/aortic root abscess•Surgery required for optimal outcome•

Most Common Cause of Death in Treated IEEmboli•Renal failure•Rupture of myocardial aneurysm•

Endocarditis Treatment

Porsthetic heart valves○

Prior bacterial endocarditis○

Surgical shunts○

Congenital heart disease○

Dental, oral or upper respiratory surgery○

Prophylaxis only used for HIGH risk patients•


General

Muscle problem○

Cardiomyopathy is a disease that involves the myocardium with cardiac dysfunction•

Etiologic Classification

Dilated (D), Restricted (R), Hypertophic (H)

Idiopathic ○

D & H

Familial○

R

Eosinophilic endomyocardial disease○

R

Endomyocardial fibrosis○

Primary myocardial involvement•

Lots○

Secondary myocardial involvement•

L or RV enlargement

Impaired systolic function

CHF

Arryhthmias

Emboli

Dilated○

Endomyocardial scarring or myocardial infiltration

Results in restriction to filling (L or RV)

Restricted○

Typically septum □

Disproportionate LV hypertrophy

Hypertrophic○

Clinical classification of cardiomyopathies•

Dilated CardiomyopathyImpaired systolic function•Reduced EF & CO•Dilated LV cavity•

Maybe asymptomatic○

Decreased exercise tolerance○

DOE○

CHF○

PND, fatigue & orthopnea○

Edema, palpations, arrhythmias & emboli

○

Clinical manifestations•

JVD, S3, S4, MR (mitral regurg.) & TR (tricuspid regurg)

○

Narrow pulse pressure○

Tachycardia○

Displaced PMI○

Crackles, peripheral edema & hepatomegalia

○

Physical exam•

Enlarged cardiac sillhouette○

CXR•

LV dilation○

Can lead to MR because papillary muscles are so far away that valves can't close

○

Echo•

No alcohol

Monitor weight

Exercise

Na+ & fluid restriction

Non-pharmacologic○

ACE inhibitors○

Treat as managed HF○

Defibrillator for malignant arrhythmias

○

Cardiac transplant○

Treatment•

25% stabilize, rest is poor prognosis

○

50% die suddenly○

Prognosis•

Alcoholic Cardiomyopathy

Holiday heart syndrome & arrhythmias following binge drinking

○

Dilated cardiomyopathy•

Peripartum CardiomyopathyCHF during last trimester of pregnancy or 6 months later•

Drugs That Can Cause Dilated CardiomyopathyDoxorubicin•Cyclophosphamide•Tricyclic antidepressents•Cocaine•

Cardiomyopathies


Hypertrophic Cardiomyopathy

Larger than free wall○

Hypertrophy of IVS (interventricular septum)•

Disorganized cardiac muscle cells•

(+) family history in 50% of cases○

Herebitary disease•

Probably from ventricular arrhythmias related to exertion

Syncope/sudden death○

Syncope

Angina

Dyspnea

Triad○

Clinical manifestations•

S2 paradoxically split○

Indicates LV outflow tract obstruction

Loud systolic murmur○

Physical exam•

Septum 1.3 or more times the free wall○

Small LV cavity○

Echo•

Limit strenuous activity○

βblockers

CCBs

Drugs to increase contractility and decrease LVOT obstruction

○

Treatment•

Restrictive CardiomyopathyLeast common•Diastolic dysfunction w/rigid walls that impede ventricular filling

•

Often due to fibrosis•

Results in endocardial fibrosis with stenosis/regurg of tricuspid/pulmonic valves

○

Carcinoid syndrome•

Eosinophilic Endomyocardial DiseaseLarge mural thrombi•Fibroplastic endocarditis•


InspiratoryStretch elatic components•

Given off as heat○

Overcome resistance or air & tissue movement•

Quiet breathing stores a lot of energy in the elastic components

•

Expiratory

Given off as heat○

Overcome resistance of air & tissue movement•

Return lungs to original volume•

Vigorous breathing requires additional work○

Quiet expiration can proceed passively due to stored energy in elastic elements

•

Types of Work

Energy is entirely lost○

Resistance•

Stored during inspiration○

Elastic•

Work of Vigorous Breathing

Turbulence increases○

Airways can collapse during expiration○

Resistance increases•

Expiration is shortened•Stored energy from inspiration is NOT enough to return lungs to their original volume within time limit

•

Diseases Which Decrease ComplianceCompliance (elasicity)•

Neonatal distress syndrome○

CHF○

TB○

All increase the inspiratory work○

Restrictive (constrictive) diseases•

Diseases Which Increase ResistanceObstructive diseases•Emphysema•Asthma•Sleep apnea•

Trachea○

Bronchi○

Smaller total cross sectional area○

Most resistance occurs in the large airways•

Inspiration causes dilation○

Expiration causes constriction○

Smaller airway diameter varies with breathing cycle•

Requires a larger positive pressure to push air out

This can collapse airways

Obstruction makes it harder to exhale○

High intrathoracic pressure

Bronchitis○

Increase intrathoracic pressure + "strut" failure

Bronchitis + emphysema○

Irritation can cause bronchitis & accumulation of substances impeding airflow

•

Extrathoracic Obstruction

Snoring○

Sleep apnea○

Soft tissue in oro/nasopharynx collapse

○

Typified by:•

Worse on inspiration•CPAP can be helpful maintaining positive pressure & maintaining flow

•

Autonomic Stimulation

Causes dilation & decreases resistance

Stimulate β2 receptors of smooth muscle of airways

○

Sympathetic•

Constricts airways & increases resistance

○

Parasympathetic•Local ControlHistamine causes bronchiolar constriction•Hypocapnia causes smooth muscle contraction & constriction•

Bronchial Sm. Muscle Pulmonary Vasculature Systemic Vasculature

Major Adrenergic Receptors β2 α α

Adrenergic Stimulation Dilation (circulating) Insignificant Constriction

Parasympathetic Stimulation

Constriction Insignificant Insignificant

Hypoxia ?? Constriction (alveolar hypoxia)

Dilation (interstitial hypoxia)

Work of Breathing

Physiology Page 17

Normal BreathingMainly through the diaphragm (phrenic nerve)•The brain controls both the frequency & the pattern of breathing

•

Medullary Respiratory Centers

Dorsal respiratory group○

Relays info about breathing to neurons○

95% premotor to phrenic○

Receives lots of sensory info○

Determines breathing pattern○

DRG•

Ventral respiratory group○

Also relays breathing info to neurons○

Premotor to phrenic & OTHER inspiratory muscles

Rostral (cephalic)○

Premotor to upper airway

Muscles of expiration

Caudal○

Determines breathing pattern○

VRG•

Pontine respiratory group○

Involved in respiratory timing○

PRG•

Primary site which generates the timing (frequency) of the respiratory rythym

○

Pre-Botzinger Complex•

Chemoreceptors

This would decrease ventilation, making the situation worse

○

Chemoreceptors prevent this○

A normal response of a neuron to decreased O2 & increased CO2 is a decrease in activity

•

Activity INCREASES during decreased O2 & increased CO2

○

Chemoreceptors activate respiratory centers & increase respiration

○

Chemoreceptors do opposite•

Central (brain)○

Peripheral (carotid & aorta)○

Two sets of chemoreceptors:•

Central ChemoreceptorsLocated in the medulla•

CO2 crosses BBB○

Reacts w/water (carbonic anhydrase)○

Produces bicarb & H+○

H+ directly from blood can't cross BBB

H+ acts on central chemoreceptors inducing ventilation

○

Sensitive to CO2 in blood•Peripheral ChemoreceptorsAortic arch•

Dopamine is transmitter○

O2

CO2

H+

Sensitive to:○

Carotid Body•

Increases ventilation○

Hypoxic, acidic etc. increase firing rate of afferents•

Quicker than central chemoreceptors•Respiratory Control

Located in airways○

Relates info to brain via Vagus N.○

Stretch inhibits inspiration and prolonged expiration○

Important in infants & during exercise○

Slowly Adapting Pulmonary Stretch Receptors (mechanoreceptors)•

Located in airways○

Info travels via Vagus N.○

Effect: COUGH○

Rapidly Adapting Pulmonary Stretch Receptors•

Located near blood vessels in alveoli○

Sensitive to pulmonary edema○

Vagus N.○

Effect: cough & tachypnea (rapid breathing)○

Override the normal respiratory control system

J receptors & RARs are protective○

J Receptors & Retinoic Acid Receptors (RARs)•

Ventilatory Control

Physiology Page 18

Volume vs. Capacity

Non-overlapping subunits of volume○

Normal volume used during regular breathing

Tidal○

Additional amount that can be inhaled immediately following normal inspiration

Inspiratory Reserve Volume○

Additional amount that can be exhaled immediately following normal expiration

Expiratory Reserve Volume○

Volume that cannot be expired from the lungs

Residual Volume○

Volume•

Total lung capacity = sum of all volumes○

Vital capacity = Total lung capacity - residual volume○

Inspiratory capacity = tidal volume + inspiratory reserve volume○

Functional residual capacity = expiratory reserve volume + residual volume○

Capacity•

Lung Volumes

Ventilation

Total volume moved in/out of the lungs per minute

○

Breaths/min x tidal volume○

Minute ventilation•

Trachea, bronchi etc.□

Anatomical dead space

Nonperfused but ventilated alveoli

Similar to minute but subtracts physiological dead space

○

(tidal volume - physiological dead space) x rate

○

Alveolar ventilation•

Obstructive DiseaseExpiratory problems•

Harder to expire than inspire○

Emphysema & asthma•

Barrel chest•

Restrictive DiseasePulmonary Fibrosis•

Lungs are less capable of expanding○

Inspiration problem•

Flow/Volume Curve

Expiration flows are relatively high during the initial phase

○

Airways close and rate decreases below normal as airways close

○

Obstructive disease•

Not as much air can be inspired○

Expiratory peak flows are less than normal○

Restrictive disease•

NORMAL

Pulmonary Function

Physiology Page 19

NORMAL

OBSTRUCTIVE

RESTRICTIVE

FEVHow long it takes to blow out all the air possible following maximum inspiration•FEV1 is volume expired after 1 sec•

Takes a longer time than normal to evacuate the lungs○

FEV1 is reduced○

FEV1 /FVC is reduced○

Obstructive disease•

Lungs are evacuated rapidly but the total volumes are less○

FEV1 is less than normal○

FEV1 /FVC is normal or above normal○

Restrictive disease•

Physiology Page 20

Pressure Definitions

Intrapleural pressure○

Pressure between thoracic cage and lungs○

Given in cm water○

Lungs stick to thoracic wall

Elastic nature of parynchma□

Surface tension in alveoli□

Collapsing force (counteracting pleural pressure) is due to:

Negative under normal conditions (-5cm H2O)○

Only time there is a positive pleural pressure is during forced expiration○

Pleural pressure•

Pulmonary or intrapulmonary pressure○

Pressure inside the lungs○

Actually 760mmHg (or atmosphereic pressure)

Equals 0 at rest○

Lungs expand creating a negative alveolar pressure, sucking air in

Inspiration○

Alveolar pressure and air flow reverses

Expiration○

Alveolar pressure•

Difference between pulmonary and pleural pressure○

Absolute value of pleural pressure at rest○

Transpulmonary pressure•

Lung Compliance

Little effort means lung comliance is high & normal

○

If greater effort is required for same volume change, compliance is low

○

How much volume change will occur with a given change in pressure

•Surface TensionAccounts for 2/3 of the elasticity in normal lungs•

Intermolecular attraction of surfactant is much less than water

○

Prevents alveolar collapse○

Intermolecular attraction becomes even less as thickness increases (during expiration)

○

Surfactant•

Thoracic CageAdds additional elastic resistance to inflation•Combining the elastic component of the thorax to that of the lungs effectively reduces the compliance of the system by 1/2

•

Compliance & Pressures

Physiology Page 21

Acid-Base Cases

Physiology Page 22

Alveolar Oxygen Equation

PiO2 = (Patm - 47mmHg)FiO2

RQ = 0.8□

O2 consumed = PaCO2 / RQ

PaO2 = PiO2 - O2 consumed○

PaO2 = [(Patm - 47mmHg)FiO2 ] - [PaCO2 /RQ]○

Alveolar O2 (PaO2 ) = Inspired O2 (PiO2 ) - Consumed O2•

(A-a O2 gradient)○

A-a O2 gradient = PAO2 - PaO2○

A = Alveolar; a = arterial○

Alveolar-arterial O2 gradient•

Ventilation Perfussion

Ratio between the amount of air getting to the alveoli and the amount of blood being sent to the lungs

○

CO = Cardiac Output

V/Q = alveolar vent./CO○

V/Q ratio•

Decreasing ventilation OR

Increasing blood flow

Produced by:○

Results in a decrease in alveolar O2 and an increase in alveolar CO2

○

Decreased V/Q•

Increased ventilation

Decreased perfussion

Produced by:○

Increase in PAO2

Decrease in PACO2 & PaCO2

Effect:○

Increased V/Q•

Blood shunted to oxygenated areas

Raises th V/Q

Hypoxic vasoconstriction○

Increases the resistance & decreases the amount of ventilation to a non-perfused area

Limits alveolar dead space & wasted work

Bronchoconstriction○

The body normalizes V/Q through:•

Forms of Hypoxia

Inadequate O2 available for tissue use○

Hypoxia•

Total absence of O2 delivered to the tissue○

Anoxia•

Low O2 content in the blood○

Hypoxemia•

Alveolar PO2 is reduced□

Blood is unable to fully equilibrate with the alveolar air

□

PaO2 is below normal because either:

Hypoxic hypoxia1.

Lungs work fine but O2 carrying capacity of the blood has been reduced

Carbon monoxide poisoning

Anemic hypoxia2.

Lungs & blood are fine but heart cannot pump the blood to the tissues

Sickle cell anemia

Circulatory hypoxia3.

Cells have been poisoned

Tissue is unable to use the O2 delivered

Cyanide

Histotoxic hypoxia4.

Four forms of hypoxia:•

Central Chemoreceptors

Measure changes in the H+ ion concentration in the CSF

○

Detect changes in the arterial CO2 levels•

Increased Barometric Pressure (Diving)

Also add 1 atm for air pressure○

EX: 40m = 5 atm○

For every 10m depth, barometric pressure increases 1 atm•

N2 exhibits an effect similar to alcohol at high concentrations

Nitrogen narcosis○

Bends or decompression sickness□

N2 bubbles form & block circulation

Rapid ascent○

Pulmonary veins may rupture, air enters blood stream, creating embolus□

Rapid ascent with a closed glottis

Air embolism○

Effects•

Physiological Adaptations

Physiology Page 23

Adjusting to Decreased Barometric Pressure (Altitude)FiO2 remains the same (21%)•Oxygen content = (O2 capacity) x (% saturation)•

Immediate response

Increases ventilation

Increase their firing rate□

Peripheral chemoreceptors

Step 1○

Increase in alveolar ventilation will increase PaO2

PaCO2 decreases

Step 2○

Modifies the increased firing rate from Step 1□

Patient has an greater alveolar ventilation, but not as great as in Step 1□

Decrease PaCO2 causes a decrease in firing rate of chemoreceptors

Step 3○

Altitude changes (acute):•

Acclimatization○

Increased ventilation◊

Peripheral chemoreceptors drive ventilation

CSF pH falls within normal range, decreasing influence of central receptors□

More H+ is pumped into CSF

Central chemoreceptors maintain a lower PaCO2

CSF pH is higher than normal○

Increased erythropoietin release○

Increased mitochondria number and size○

Increased glycolytic enzymes○

Altitude changes (chronic):•

Increased perfusion pressure□

Can be severe & life threatening◊

Cerebral edema

Increased filtration□

Hypoxia leads to cerebral vasculature dilation

Related to changes in cerebral circulation○

Increased pulmonary vasculature permeability

Pulmonary hypertension

Pulmonary edema○

Altitude sickness•

Physiology Page 24

Hormonal Response - TPRBP drops1.Renin production (kidney) increases2.Renin increases Angiotensin I (AG I) production (liver)

3.

AG I is converted to AG II (lungs) by Angiotensin Converting Enzyme (ACE)

4.

AG II causes ADH (Anti-diuretic Hormone, Vasopressin) release (posterior pituitary)

a.

ADH causes vasoconstrictionb.

AG II causes vasoconstriction5.

TPR increases6.BP increases7.

Hormonal Response - COBP drops1.

Increases H2O retentiona.Increases salt retentionb.

Renin production increases (kidney)2.

AG I production increases (liver)3.AG I is converted to AG II by ACE (lung)4.

Increases CO1)Increases preloadi.

Vasoconstriction (vasculature)a.

Increases CO1)Increases blood volumei.

Increases salt retention (kidney)b.

Increases COa)Increases blood volume1)

Increases H2O retention (kidney)i.Increases ADH release (posterior pituitary)c.

Increases COa)Increases blood volume1)

Increased salt retention (kidney)i.Increases Aldosterone production (adrenal cortex)d.

AG II 5.

Hemorrhage Changes

Decreases BP○

Stimulates short & long term reflexes○

Baroreceptors (neural)

Short term:○

Hormonally (kidney)

Long term:○

Decreased preload & blood volume•

Fluid retention changes are slow, but progressive•TPR changes are fast•

Decreased urine production

Fluid retention

Decreased BP causes decreased perfussion pressure of glomeruli

○

Kidney filtration•

Net movement into vascular space

Decreased hematocrit

Reduced BP decreases capillary pressure○

Interstitial fluid•

Cerebral Ischemia

Vascular collapse

If cerebral tissue becomes to ischemic, sympathetic stimulation will fail

○

Stimulates pressor region & inhibits depressor region

•

ShockInadequate O2 delivery to the tissues•

Natural compensatory mechanisms will bring BP back up to a reasonable level

Compensated○

Compensatory mechanisms are inadequate & tissue death will ensure w/o clinical intervention

Decompensated○

Nothing can be done to save the system/patient

Irreversible ○

3 states of shock:•

Kidney Changes During Shock

Nephrotic necrosis○

Accumulation of cellular debris○

Inflammatory response○

Decreased blood flow due to reflex & decreased BP

•

Cardiac Failure/Shock

Physiology Page 25

Causes of Shock

Hemorrhage

Vomiting/diarrhea

Dehydration

Decreased blood volume○

Hypovolemic1.

Inability to deliver O2 to the tissue○

MI etc.○

Cardiogenic2.

Inflammatory cause○

Sepsis & anaphylaxis○

Massive vasodilation and tissue leakage○

Distributive3.

Extracardiac compression○

Obstructive4.

Spinal trauma etc.○

Loss of pressor output○

Neurogenic5.

Cardiac FailurePreload immediately increases partially offsetting the decreased contractility

•

Compensated1.Decompensated2.

2 types:•

Reflex mechanisms gradually increase BP until an equilibrium is reached

○

No further increase in fluid retention○

Preload stabilizes at a higher level○

Produced by atria in response to large preload stretch

Causes natriuresis (water & Na+ loss)

Limits effect of renin/AG & volume overload

Natriuretic factor○

Less ability to increase CO during strenuous activity

Cardiac reserve is decreased○

Compensated•

Enough preload CANNOT be generated to adequately increase CO & BP

○

Too much stretch actually reduces the effeciency of the heart

Positive feedback loop results in complete failure

Heart becomes TOO dilated/stretched○

Decompensated•

Physiology Page 26

Pulmonary Capillary Wedge PressureTaken by wedging a catheter into a pulmonary capillary bed through the pulmonary artery

•

The uninterrupted column of blood from the tip of the catheter to the left atrium allows direct measurement of the pressure in the left atrium

•

Ventricular Systole

"Stiffens" the interventricular septum○

The septum depolarizes first•

Blood reverberation in the atria○

Caused by AV valves closure○

1st heart sound•

Ventricular pressuremust exceed diastolicpressure on each side to open the semilunar valves

•

Ventricular Diastole

Begins before 2nd heart sound○

Ventricules relax•

Blood in the aorta/pulmonary artery reverberates against closed semilunar valves

○

Elasticity causes backflow along with loss of driving force (ventricles) pushing blood into the arteries

○

2nd heart sound•

Atria has been filling the entire time, increasing pressure

○

Atrial pressure exceeds ventricular pressure (which can fall to 0) and blood flows passively intothe ventricles

•

Mitral Valve StenosisBlood has a difficult time moving from the left atrium to the left ventricle

•

Increases pressure in the left atrium

○

Blood backs up in the left atrium•

No valves○

Pressure backs up all the way to the lungs

•

Fluid moves into the lungs○

Pulmonary edema○

Dyspnea○

Hydrostatic pressure increases within the pulmonary capillaries

•

COPD & Right Ventricular Failure (RVF)

Lung tissue is a combo of capillaries & cells holding them together○

Capillaries are lost○

Progressive lung tissue loss•

Increases the resistance within the pulmonary vasculature○

The loss of pulmonary capillaries reduces the overall radius of the capillaries•

Pulmonary hypertension○

An increase in resistance increases BP•

Increased work leads to right ventricle hypertrophy○

A higher pulmonary BP means the right ventricles has to generate a higher pressure to open pulmonic valve

•

Hypertrophy eventually leads to right ventricle failure•

Blood in the pulmonary artery reverberates with greater force○

Greater pulmonary pressure also leads to altered 2nd heart sound•

RVF can also lead to peripheral edema•

Hydrostatic PressureArterial BP•

Cardiopulmonary Interactions

Physiology Page 27

Normal Values

12 mEq/L (mean of 12)○

[Na+] - ([Cl-] + [HCO3])○

Anion gap•

7.4○

pH•

25 mEq/L (mM)○

Bicarbonate•

40mmHg○

PaCO2•

<10○

Measured osmolality -(2[Na+] + glucose + urea)

○

Osmolal Gap•

36 - 43 mM○

[H+]•

Maintenance of Body pHLungs control CO2 - O2 exchange•RBCs transport gases between lungs & tissues•

Also regulate RBC production○

Kidneys maintain HCO3- and secrete H+ in urine•

Acids & BasesA weak acid (HA)or conjugate aciddissociates into H+ and an conjugate base (A-)

•

EX: pH = 7; -log[H+] = 7; [H+] = 1x10-7 M

○

pH = -log[H+]•

Ka = [H+][A-]/[HA]a•

pH = pKa + log ([A-]/[HA])○

Henderson-Hasselbalch Equation•

Ionization State of AA

Amino & carboxyl terminal

Both groups protonated○

At low pH•

Zwitterionic form○

Creates a polar molecule○

One group protonated, the other deprotonated○

Middle pH•

Both groups deprotonated○

High pH•

Bicarbonate Buffer SystemOperates principally in extra-cellular fluid (blood)•

H2O + CO2 <==> H2CO3○

Carbonic Anhydrase (CA)

Reaction occurs spontaneously in plasma○

CO2 is the major source of metabolic acid•

H2CO3 <==> HCO3 - + H+•

Availability of CO2 can be modulated by adjusting the rate of respiration

○

Dissolved CO2 is in equilibrium with the CO2 in the alveoli

•

pH = pKa + log([HCO3 ]/PaCO2 x 0.03)•

Both contain CA○

Plasma [bicarb] is controlled by the kidneys & RBCs•

Buffers in the Human Body

RBCs○

Can become protonated etc.○

Hemoglobin•

Intracellular○

Can also become protonated○

Proteins•

Intracellular○

Phosphate buffer•

Extracellular (plasma)○

Bicarbonate•

Intracellular BuffersProteins, phosphates & K+ exchange•

High plasma [H+]○

Protonates proteins

H+ moves intracellularly○

K+ is exchanged○

Can lead to high plasma [K+]○

Acidemia•

Low plasma [H+]○

Proteins deprotonated

K+ is exchanged (pumped into the cell)

H+ move out of the cell○

Can lead to decreased plasma [K+]○

Alkalemia•

Basics of Acid-Base

Biochemistry Page 28

CO2 Handling & Transport

CO2 produced in the tissues enters the blood1.CO2 enters the RBCs2.CO2 is converted into carbonic acid by CA3.Carbonic acid dissociates into H+ & HCO3-4.H+ is buffered by hemoglobin & phosphate5.

A Cl- ion is exchanged across the RBC membrane (chloride shift)

i.

Bicarb is transported into the blood & buffers the H+ in the plasma

6.

Handling (from tissue to RBC)•

70% of CO2 is in the carbonic acid/bicarb system○

20% is carried as carbamino groups○

10% is dissolved in plasma○

Transport•

H+ & CO2 are released from Hb as it picks up O2

(Haldane effect)○

H+ combines w/bicarb forming carbonic acid○

Carbonic acid is converted to CO2 & H2O by CA○

As additional bicarb enters the RBC, Cl- is exchanged○

CO2 is expelled in the expired air○

Handling (from RBC to lung)•

Respiratory & Metabolic Compensation

Enhances CO2 excretion○

Lowers the PaCO2○

Hyperventilation•

Reduces CO2 excretion○

Raises the PaCO2○

Hypoventilation•

Biochemistry Page 29

Bacterial CausesTypical vs. Atypical•Community-aquired (CA) vs. Nosocomial

•

Typical Community-Aquired PneumoniaStreptococcus pneumoniae•Haemophilus influenzae•Staphylococcus aureus•

Atypical Community-Aquired Pneumonia

Mycoplasma pneumoniae○

Chlamydia pneumoniae○

Chlamydia psittaci○

Legionella sp○

Mycobacteria sp○

Bacteria•

Nonproductive cough•No organisms on smear•No response to B-lactam antibiotics•

Nosocomial Pneumonia in ImmunocompromisedPseudomonas aeruginosa•Staphylococcus aureus•Nocardia asteroides•Mycobacteria sp•

Typical Pneumonias

NAME TYPICAL ETIOLOGY CHARACTERISTICS PATHOGENESIS

Streptococcus pneumoniae

Most common CA pneumonia Large, polysaccharide capsule

Haemophilus influenzae

COPD patients are at risk Requires X factor (blood) & V factor (NAD) for culture growth

Capsule Ag is major virulence factor; endotoxin

Klebsiella pneumoniae

Common nosocomial infx; alcoholics are at risk

Staphylococcus aureus

Aspiration & hematogenous (IV) modes

Exotoxins; enzymes

Pseudomonas aeruginosa

Nosocomial; cystic fibrosis patients

Nocardia asteroides

Patients receiving immunosuppressive drugs

Partially acid-fast; Gram (+) Intracellular survival

Actinomyces israelii

Poor oral hygiene

Bacterial Causes of Pulmonary Infections

Microbiology Page 30

Atypical Pneumonias

NAME TYPICAL ETIOLOGY CHARACTERISTICS PATHOGENESIS

Mycoplasma pneumoniae

Absence of unique clinical findings; "walking pneumoniae"; common in crowded settings (prison/military)

No cell wall (no gram stain); grows on Eaton's culture

Not communicable person to person; reduced ciliary movement; cold agglutinin detected by type O Rh- RBCs

Legionella sp GI symptoms & headache; source of infx is usually water related (pool, air con,etc.); COPD patients have increased risk

Motile, flagellated rods; grows on charcoal yeast agar; obligate intracellular

No person-to-person transmission

Chlamydia psittaci

History of bird exposure Obligate intracellular

Chlamydia pnemoniae

Obligate intracellular

Coxiella History of domestic animal exposure

Mycobacterium tuberculosis

AIDS patients Acid-fast;

S. Susceptible; R. Resistant; Alpha -> Greenish tint; Beta -> clear hemolysis; Gamma -> no hemolysis; pyogenes is also called "Group A" strep; agalacticae is also called "Group B" strep


Upper Respiratory Tract Infections (URTIs)Common cold•Pharyngitis•Croup•

The Common Cold

Infection of the nasal mucosa○

Watery nasal discharge○

Cough and/or pharygitis○

Symptoms last 1 - 2 weeks○

Symptoms•

Bind via ICAM receptor

Infiltrate nasal epithelial cells○

Cell damage○

Clear outpouring of fluid from lamina propria

○

Possible bacterial superinfection○

Regeneration○

Pathogenesis•

Young children

Pain in both ears

Otitis media○

Potential Complications•

Most common isolates are rhinoviruses•

CroupInfection of the larynx, trachea & bronchi•

Bark-like cough○

Increased respiratory rate○

Stridor○

Fever○

Symptoms•

Occurs most common in children•Usually caused by parainfluenza & paramyxovirus•

Viral replication in the subglottic mucosal epithelial cells

○

Necrosis leading to edema○

Edema blocks narrow airways in children leading to bark-like cough

○

Pathogenesis•

Viral Upper Respiratory Tract Infections

NAME CHARACTERISTICS EPIDEMIOLOGY PATH CLINICAL CONTROL

Adenoviridae Nonenveloped; dsDNA

Respiratory droplets or fomite transmission; increased during winter

Rapid replication (in nucleus)

Pharyngeal conjunctional fever is associated w/under chlorinated pools

Hand washing

Parainfluenza Elderly & young at risk for pneumonia

Croup; virus spreads by cell fusion

IgA important in protection (but short lived)

No cross protection between serotypes; hand washing

Picornaviruses Rhinoviruses are members of this family; +ssRNA

Common cold; Replicate in cytoplasm

Enterovirus Cause infx in summer & fall

Transmitted fecal/oral route

Remain viable for a long time outside of body

Rhinovirus Common cold; droplet secretions & fomites

IgA important No cross protection

Coronavirus ssRNA; (+) polarity; enveloped

Large droplet secretion & fomites; common cold; SARS

Replicates in cytoplasm

Viral Causes of Pulmonary Infections


Viral LRTIsBronchiolitis•Pneumonia•Hantavirus Pulmonary Syndrome (HPS)•

BronchiolitisViral replication in epithelial cells liniing the LRT causes severe, necrotizing lesions in bronchi & bronchioles

•

Infants & young children•

Wheezing○

Dyspnea○

Hypoxia○

Expiratory prolongation○

Symptoms•

Respiratory syncytial virus is most common cause•

Pneumonia

Results in inflammatory response○

Infection of the lung parenchyma•

Infection & inflammation result in difficult gas exchange & hypoxia

•

Viral Lower Respiratory Tract Infections

NAME CHARACTERISTICS EPIDEMIOLOGY PATH CLINICAL CONTROL

Respiratory Syncytia Virus (RSV)

Major cause of bronchiolitis & pneumonia in children <1 y.o.

Large droplet secretions & fomites; spreads through cellular fusion

Suspect RSV in all infants w/LRT disease

Encourage breast feeding

Hantavirus Inhalation of virus shed in rodent urine, feces & saliva

Hantavirus Pulmonary Syndrome (HPS)

Febrile illness; bilateral diffuse interstitial edema;

Control rodent populations etc.

Cytomegalovirus (CMV)Replication occurs in epithelial, endothelial cells & macrophages

•

Virus resides in latent state in organs•

ParamyxovirusFruit bat host•

InfluenzaBelong to family Orthomyxoviridae•

A infects humans & animals○

B is species specific○

C causes only minor URTIs○

Three types: A, B, & C•

Enveloped•

6-8 segments of RNA○

(-) ssRNA•

HA (hemagglutinin, binds sialic acid) ○

NA (neuraminidase, allows virus release)○

Enveloped glycoproteins: •

Fever○

Body ache○

Fatigue○

Sneezing & cough○

Symptoms•

Antigenic Drift & ShiftInvolved in influenza evolution•

Viruses pass between species○

Segments of RNA get repackaged in new combinations when one cell is infected with more than one strain of influenze

○

Shift•

Point mutations encoding HA or NA○

Drift•


Common Causes of Pharyngitis (Sore Throat)

70% of acute pharyngitis has viral cause

○

Viruses•

Most common bacterial cause

Group A Streptococci ○

N. gonorrhea○

C. diphtheriae○

H. influenzae○

Bacteria•

Fever

Headache

Abdominal pain

Bacterial○

Sneezing, rhinorrhea & cough

□

Involvement of mucus membranes

Viral○

Clinical spectrum of pharyngitis•

Group A Beta-Hemolytic Streptococci (GABHS)

Anti-phagocytic

Hyaluronic capsule○

Antigenic determinant

Important in rheumatic fever

M proteins○

Toxins & enzymes○

Inactivates C5a

C5a peptidase○

Useful for typing

T protein○

Pyrogenic exotoxins○

Virulence factors•

Person-to-person via respiratory droplets○

Occurs primarily in winter & early spring○

Transmission•

Fever□

Tonsillar exudates□

Absence of cough□

Tender anterior cervical lymphadenopathy

□

4 criteria:

Method used to quickly diagnose GABHS○

Centor criteria•

Rapid test (minutes) from throat swab using monoclonal Abs

Sensitivity is only 80% (negative rapid test does NOT rule out GABHS)

Good for conformation, bad for diagnosis

□

Specificity is 95%

Serologic○

Longer test (1 hr) with 97% sensitivity test

More expensive

DNA-based○

β-hemolytic (clear colonies)

Gram (+) cocci (chains)

Catalase (-)

Culture○

Testing methods•

Likely viral

Patients who have 1 or no Centor criteria should NOT be treated for GABHS

○

Rapid strep test

Antiobiotics ONLY for those with (+) test and/or all four Centor criteria

Patients with 2+ Centor criteria:○

Diagnosis•

DOC is Pen VK po qd for 10 days○

Treatment•

Complications of GABHSScarlet fever•Rheumatic fever•Post-streptococcal glomerulonephritis (PSGN)

•

Scarlet FeverFollows infx w/certain strains•

Function as superantigens○

Due to secretion of pyrogenic exotoxins (A, B, C)

•

Fever○

Starts on chest and spreads to trunk & extremities

Diffuse erythematous rash○

"Strawberry tongue"○

Symptoms•

Strawberry Tongue

Sore Throat


Acute Rheumatic FeverSecondary to GABHS infx•

Leads to autoimmunity○

Strain Ags mimic host cell Ags•

Produce a thick glycoprotein capsule○

Cardiac myosin

Sarcolemma membrane proteins

Cartilage/synovium of heart, kidney & joints

Epitopes of M protein mimic:○

Rheumatogenic strains of GABHS•

Onset is 1-5 weeks after strep infx○

Migrating large joint pain□

Polyarthritis

Carditis

Disorganized twitching□

Chorea

Pink rash on the trunk□

Erythema marginatum

Manifestations○

Complications•

PSGN

Ag-Ab complexes in kidneys

○

Due to Type III hypersensitivity•

Associated w/ certain strains•

Urine appears dark or tea colored

Hematuria○

Proteinuria○

Periorbital edema○

Hypertension with or without oliguria (decreased urine production)

○

Symptoms•

Viral Pharyngitis

Adenoviruses (dsDNA)○

Common cold

Rhinoviruses, coronaviruses○

Colds, croup

Parainfluenza○

High fever, malaise, myalgia, arthralgia, sore throat

Influenza○

Etiologies•

Large droplet secretions and/or fomites

○

Transmission•

Treat symptomatically (NO antibiotics!)

•

EpiglottitisRapidly progressive cellulitis of the epiglottis•Can lead to ACUTE airway obstruction & death•

Type B○

Gram (-) bacillus○

X and V factor

Culture on chocolate agar○

Usually caused by H. influenzae•

Capsule is major virulence factor○

Virulence factor of H. influenzae•

H. influenzae is normal floral of URT○

Transmission is endogenous○

Epidemiology•

Progressive dysphagia (difficulty swallowing)○

Odynophagia (pain during swallowing)○

Fever○

Barking cough○

Stridor○

Symptoms•

Mostly clinical○

Laryngoscopy only by experienced surgeon○

Swollen, round epiglottis

X-ray will show "thumb sign"○

Culture○

Diagnosis•

IV antibiotics (Cephs)○

Any respiratory distress indicates intubation○

Treatment•

Thumb Sign in Epiglottitis

Corynebacterium diphtheria


Mononucleosis

Also called Herpesvirus-4 (HHV-4)○

dsDNA○

Usually caused by EBV •

Sore throat○

Fever○

Fatigue○

Rash○

Posterior cervical lymphadenopathy○

Splenomegaly○

Symptoms•

Infects B cells○

Via saliva○

EBV transmission•

Symptomatic○

Recovery in 4-6 weeks○

EBV treatment•

Corynebacterium diphtheriaSeen in un-/under-vaccinated populations

•

Gram (+) bacilli•"Chinese letter" morphology•

Inhibits host protein synthesis

○

Causes severe inflammatory response

○

Toxin production•

Person-to-person via respiratory droplets

○

Epidemiology•

Sore throat○

Dysphagia○

Hoarseness○

Low grade fever○

Symptoms•


Group A Streptococci

Contains hyaluronic acid capsule

M proteins

T protein

Antigenic structure○

Cause cell lysis□

Streptolysin O & S

Increases permeability□

Hyaluronidase

Activates plasminogen, producing plasmin

□

Streptokinase

Delays accumulation of PMNs□

C5a peptidase

Fever, shock, erythrothemia□

Pyrogenic exotoxins

Toxins/enzymes○

S. pyogenes•HACEK GroupHaemophilus•Actinobacillus •Cardiobaterium hominus•Eikenella corrodens•Kingella kingas•

No strep or staph○

Consider in culture negative cases•

Slow growing organisms found in the mouth•Require CO2 for optimal growth•

Haemophilus influenzaeGram (-) bacilli•Encapsulated•

Hemin & NAD○

Requires X & V factor•

Actinobacillus actinomycetailausGram (-) coccobacillus•Normal flora in URT•

Cardiobacterium hominusGram (-) pleomorphic rod•Normal colon flora•

Eikenella corrodensGram (-) bacillus•Mouth flora•

Skin & bone infx associated w/human bites○

Sepsis & soft tissue infx of head & neck found in IV uses who lick their needles

○

Causes of infection•

Kingella KingaeGram (-) bacillus•Oropharynx flora•

Etiologies of IE (IV drug users)S. aureus is most common•

Pseudomonas aeruginosa○

Gram (-) aerobic bacilli are 2nd most common•

Candida•

Etiologies of IE (Prosthetic valves)

Coag. (-) Staphylococci○

Gram (-) aerobic bacilli○

Candida○

+ Streptococcus viridans○

S. aureus most common, followed by:•Fungal Causes of IE

IV drug users○

Patients w/recent cardiac surgery○

Prolonged antibiotic therapy○

Occurs in •

Most common is Candida followed by Aspergillus sp.•

Host Factors Contributing to IERheumatic heart disease•Congenital heart disease•Mitral valve prolapse•Prosthetic valve replacement•

Leads to platelet accumulation○

Fibrin accumulation on valve serves as ideal site to trap bacteria

○

Predisposing cardiac lesion•

Bacterial Factors in IEOrganisms are always "sticky"•

Express dextran & surface adhesion Fim A protein

○

S. viridans•

S. sanguis can bind to platelet receptors•S. bovis has high dextran levels•S. aureus has increased binding to fibronectin

•

Lab IdentificationObtain at least 3 blood cultures, 15 mins apart•

Infective Endocarditis (IE)


Infectious Etiologies of MyocarditisCoxsackie viruses•Corynebacterium diphtheria•Borrelia burgdorferi•Trypanosoma cruzi•Chlamydia•

Corynebacterium diphtheriaGram (+) bacilli•

Mucosal colonization○

Toxin elaboration○

Pathogenesis•

Abrupt arrest of protein synthesis○

Diphtheria toxin•

Mycoplasma

Resistant to penicillins○

Inhibited by tetracyclines & erythromycin○

Lack a cell wall•

Affinity for mammalian cell membranes•

Adhesion & fusion to membranes of epithelial cells

Generation of H2O2 & superoxide radicals

Cytolysis

Pathogenesis○

Mycoplasma pneumoniae•

ChlamydiaObligate intracellular organisms•Chlamydia pneumoniae

Coxsackie VirusesPicornavirus family•Small, nonenveloped ssRNA viruses•Transmitted by fecal/oral route•

Myocarditis Assoc. w/Lyme DiseaseBorrelia burgdorferi•Bacteria adhere to connective tissue of heart•Manifested as conductive defects or mild cardiomyopathy

•

Myocarditis Assoc. w/Chagas' DiseaseTrypanosoma cruzi•Parasites invade myocytes•Rupture of myocytes releases parasites and leads to mononuclear infiltrate in the heart

•

Microbial Role in Initial Lesions of AtherosclerosisChlamydia & CMV•

NO○

Macrophage chemotactic protein-1 (MCP-1)○

IL-1○

TNF○

TGF-β○

Inflammatory mediators are released from activated endothelial cells•


Dietary Cholesterol

Deliver dietary TAGs to adipose, muscle & liver

○

Chylomicrons•

From intestines via lymphatics○

In blood, aquires apoC-II & apoE from plasma HDL

○

Enters chylomicrons•

Lipoprotein lipase (LPL)

Fatty acids of chylomicrons removed○

Fatty acids absorbed

ApoC-II in chylomicrons activates LPL○

At adipose & muscle•

Chylomicron remnant is composed of cholesterol, apoE & apoB-48

•

Liver Synthesis & LDL/HDLCholesterol from the liver is transported via VLDLs

•

VLDLs are converted to LDLs in the plasma (LPL)•LDLs are primary plasma carriers of cholesterol delivery to the tissues

•

Long half life○

75% of LDL uptake is at the liver○

LDL•

Facilitates removal of cholesterol from cells

○

Transports cholesterol to liver for bile acid synthesis

○

HDL•

Heritability of Blood Lipid TraitsTotal cholesterol has the highest heritability for all blood lipid characteristics

•Classification of Lipoprotein Disorders

LDL elevated○

High cholesterol○

Type IIa•

LDL & VLDL elevated○

High cholesterol & triglycerides○

Type IIB•

Hyperlipidemias

Dominant inheritance○

Can also be a problem w/ApoB-100 (LDL binding protein) but this is rare

Defective LDLR on cells leads to increased circulating LDL

○

Glucocorticoids decreases binding□

In diabetes & hypothyroidism there is an increase in hypercholesterolemia

□

Insulin & T3 increase the binding of LDL to receptors

In the liver○

Benign fat deposits beneath the skin□

Xanthoma

Common in older patients but rare in young people

□

Corneal Arcus

Xanthomas on skin of eyelid□

Xanthelasma

Symptoms○

Two different mutations inherited two different mutations from seemingly normal parents

The combination of two heterozygote defects in different areas (LDLR, endocytosis failure, etc.) involving LDL intake mimics a homozygous FH patient

Compound heterozygotes possible○

Familial hypercholesterolemia (FH)•

Corneal Arcus

LDL Receptor Gene

Introns allow recombination to occur between exons and allow new proteins to evolve w/similar blocks of important information

○

Demonstrate exon shuffling•

Familial Hypercholesterolemia & Long QT Syndrome

Genetics Page 39

Long QT Syndromes1:3000•Prolonged QT interval•

"torsade de pointe"

Looks like twisted ribbon○

Hallmark arrythmia•

Syncope (loss of consciousness)○

Primary symptom•

Usually K+○

Decreased repolarization○

Cardiac ion channel defects•

Palpitations○

Syncope○

Seizures/sudden death○

Clinical•

Genetics Page 40

COPDChronic Obstructive Pulmonary Disease•

Chronic bronchitis1.Emphysema2.Asthma3.Bronchietasis4.

Actually a grouping of four illnesses:•

Causes obstruction of air flow due to edema, necrosis, fibrosis, & recurring infx

Chronic bronchitis○

Allows small airways to collapse at beginning of expiration

□

Causes obstruction of air flow due to loss of lung's elastic recoil

Gross pathology resembles "cigarette burns" in the lung

Emphysema○

Two of these are a result of smoking•

Consequences of SmokingTobacco & carbon pigment in lungs•Loss of ciliary motion•Goblet cell proliferation•Hypertrophy/plasia of mucous glands in the bronchi

•

Inflammation of the lamina propria•Thickening of respiratory epithelial basement membrane

•

Increased number of PMLs in the lungs

•

Impaired macrophage function○

Increased alveolar macrophages•

Increased neutrophil & macrophage elastase production

•

Loss of elasticity/destruction of alveolar walls

•

Squamous metaplasia of respiratory epithelium

•

EmphysemaStrong hypercarbic drive•"Pink Puffer"•Struggles to breath•Patient is often agitated etc.•Lung tests show prolongation of a full forced expiration

•

More dilation of the respiratory bronchioles & their alveoli

Early smoker's emphysema

Centrilobular○

Involves the acinus uniformly

Caused by α-1 protease inhibitor ("antitrypsin") deficiency

Panlobular (panacinar)○

Two forms:•

Small airways collapse during forced expiration

•

"Barrel chest"○

Increased total lung volume○

Patients will hyperinflate their chest•

Lung reduction surgery can improve exercise ability temporarily

•

Chronic Bronchitis"Blue bloater"•Lost hypercarbic drive•Doesn't stuggle to breath•CO2 causes narcosis•Increased PaCO2 , obese, edematous (cor pulmonale), happy (due to narcosis)

•

Bronchial Asthma

Produces dyspnea, wheezing & cough

○

Small bronchi are abnormally responsive to various stimuli that cause constriction/inflammation

•

IgE-mediated mast cell degranulation

Type I hypersensitivity○

Attacks are often triggered by:•

Allergic AsthmaWhen patients attacks are triggered by IgE-mediated hypersensitivity

•

Coily strigns of altered goo from the little airways

Also form Curschmann's spirals○

Eosinophil proteins crystallized as "Charcot-Leyden crystals" in sputum of allergic asthmatics

•

Obstructive & Interstitial Lung Disease

Pathology Page 41

Obliterative BronchiolitisConstructive bronchiolitis•

Dense fibrosis under the epithelium of bronchioles with serious-to-total compromise of the lumens

○

Lesion found in a minority of smokers•

SLE, RA, Sjogren's

Autoimmune disease of the lung○

Chemicals etc.

Occupational disease○

Penicillamine○

Adenovirus infx○

Lung transplant rejection○

GVH disease○

Measles pneumonia○

Look for underlying:•

BronchiectasisEctasis ("pulling wide" of the bronchi•Defined by the permanent cylindrical dilation & ulceration of part of the bronchial tree

•

Chronic cough○

Sputum production (Lots, as in cup loads)○

Ectasis results from contraction of scar surrounding the bronchus and atelectasis (alveolar collapse & fluid consolidation)

○

Clinical•

Complicates respiratory infx, asthma, etc.•Proximate cause is a bacterial infx•

Ciliary Dyskinesia Syndromes

Includes Kartagener's (no dynein arms)

○

Huge group•

Recurrent respiratory infx○

Infertility (in men)○

Situs inversus (50% of cases)○

Clinical•

Obstructive Sleep ApneaMany episodes of upper airway obstruction each night

•

Results in thrashing, snorts, and finally partially wakes up

○

Cycle repeats every few minutes○

Patient is unable to enter deep sleep or sleep soundly

○

As patient enters deep sleep, upper airway closes•

Morning headaches○

Narcolepsy○

Cognitive/behavioral changes○

Social issues○

Symptoms•

Uvulva flops out of the way

Have the patient sleep on one side○

Helps maintain a patent airway

Protriptyline○

Uvulopalatophatyngoplasty

Tonsillectomy

Surgery○

PEEP machine○

Treatment•

Central hypoventilation○

Diminished respiratory drive from the brain○

"Ondine's Curse" •

Interstitial Restrictive Lung DiseaseStiff lung / fibrosing alveolitis•Longstanding inflammatory damage leading to fibrosis of the alveolar walls

•

Pulmonary compliance decrease•

Blood flows through unventilated scar tissue

○

Diffusion barrier○

Ventilation & perfusion are mismatched

•

PulmonaryBP increases•"Velcro crackles"•

Pathology Page 42

Desquamative Interstital Pneumonitis (DIP)Fibrosis•Alveoli clog with lipid and mucin laden macrophages

•

Most patients are smokers•Treatment is steroids•

Non-Specific Interstitial PneumonitisResponds well to glucocorticoids•

All septa involved equally○

No "honeycomb cysts"○

Uniformity of histologic changes•

Organizing PneumoniaLesion in which little pieces of loose connective tissue develop & plug the respiratory bronchioles, alveolar ducts & spaces

•

Air flow is obstructed•Lung expansion is restricted•

LymphangioleiomyomatosisRare disease w/ marked proliferation of smooth muscle in the lung

•

Fibers sprout off main muscle bundles and grow into the septa

•

Lungs develp cysts•Pneumothorax is common•Obstruction of the thoracic duct produces chylous effusions

•

Alveolar ProteinosisSurfactant & proteinaceous goop fills the alveoli

•

Rarely includes fibrosis•

Dyspnea○

Cough up "white jello"○

CT shows "crazy quilt" pattern of involved and uninvolved lobules

○

Symptoms•

Bronchial lavage is mainstay of therapy

•

Idiopathic Pulmonary Fibrosis (IPF)Hamman-Rich syndrome•Pulmonary fibrosis•Often occurs in middle age and progresses to death

•

Feels firm○

Grossly, lung looks like a course sponge•

Show chronic inflammation○

Alveoli are thickened•

Ongoing, unexplained, self-perpetuating inflammation

•

Appears in many other syndromes•

SarcoidosisNon-caseating granulomas•Rash•

Painful red bumps on the front of the legs

○

Erytema nodosum•

Goodpasture's Disease

Type II immune injury○

Antibodies against the basement membrane of lung & kidneys

•

Pathology Page 43

Lung Infections

Inflammation in the alveolar air spaces○

Pneumonia•

Inflammation limited to the interstitium○

Pneumonitis•

Bronchopneumonia"Lobular pneumonia"•Patchy lung infx•Often nosocomial•

Medications, old age etc.

Many hospital patients don't cough and clear their lungs

○

Poor mucociliary elevator function○

Poor alveolar macrophage function○

Pulmonary edema○

Causes of infx:•

Lobar PneumoniaInfx of an entire lobe produced by a virulent organism•

Gram (+) diplococcus○

Most common cause is Streptococcus pneumoniae•

Common cause in deteriorated alcoholics○

Gram (-) bacillus w/ capsule○

Victims cough up sticky slime○

Klebsiella pneumoniae•

Bugs divide like crazy

Blood vessels dilate & leak

Hyperemia & edema1.

Inflammation progresses

Forms fibrin in the alveoli□

Vessels leak fibrinogen

RBCs leak also

Red hepatization2.

Fibrin dominates

RBCs break down ("gray")

Gray hepatization3.

Plasmin clears fibrin

Lung returns to normal

Resolution4.

Four succesive stages:•

Pleural surfaces overlying infection are usually involved (painful)

○

Necrosis & abscess formation○

Infection worsens in pleural space filling with pus ("empyema")

○

Complications•

Legionnaire's Disease

Need silver stain○

Legionella pneumophila•

Common in standing water•

Bad "chest cold"○

Symptoms•

Pneumocystis PneumoniaHistologically resembles "crushed ping-pong balls"

•

Caused by Pneumocystic jirovecii (carinii)•Common in AIDS patients•

Lung AbscessPMLs plus necrosis in a confined space•

Aspiration of bacteria when drunk or unconscious

○

Comlication of necrotizing pneumonia

○

Obstructed bronchus○

Infection within lung cancer○

Septic pulmonary embolus○

Infarction of a pre-existing infection○

Mechanisms•

Anaerobic bacteria are often present•Abscess will eventually rupture into an airway

•

Chest Infections

Pathology Page 44

Viral & Mycoplasmal Pneumonia"Primary atypical pneumonia"•All cause interstitial pneumonitis•

Multinucleated epithelial cells in the bronchioles

○

Respiratory synctial virus•

Causes wheezing in young patients○

Tied w/RSV as most common viral infx in transplanted lung

○

Metapneumovirus•

Also may be diffuse alveolar damage○

The severe H5N1 strain owes its' deadliness to "cytokine storm" affecting the lungs

○

Lethal influenze w/o Staph superinfection presents primarily as necrosis along the epithelium of the bronchi & bronchioles

•

Ulcerative tracheobronchitis in immunocompromised hosts

○

Single, intranuclear inclusion surrounded by a clear hal

"Herpes cells"○

Herpes simplex•

Coronavirus○

Reproduce in & destroy type II pneumocytes

○

Preponderance of macrophages in inflammatory infiltrate

○

Diffuse alveolar damage○

SARS•

Tuberculosis (TB)Caseous granulomas•Body over-response wreaks havoc on surrounding tissues, forming the granulomas

•

Original infection○

Ghon focus (a single lesion) occurs just under the pleura in the midportion of one lung (best-ventilation)

○

Overwhelming primary infx

Progressive TB○

Primary TB•

Active TB○

Bacilli escape the original Ghon focus or more bacteria enter body from outside

○

Secondary TB that has calcified and/or been largely replaced by collagen

Arrested TB○

Spreads throughout the lung & can produce empyema involving the pleural cavities

Progressive pulmonary TB○

Often see cavities in the lung after debris has been coughed up

○

Results when many TB bacilli enter the blood but the granulomatous response is good

Miliary TB○

Secondary TB•

Pathology Page 45

Pulmonary Congestion & Edema

Increased venous hydrostatic pressure (LHF)

Fluid overload

Hydrostatic pressure pushes fluid out of capillaries□

Decreased albumin

Lymphatic obstruction

Pnuemonias, hantavirus, poisons (phosgene)□

Endothelial damage

Physical asphyxiation

Acute CNS injury

Opiate overdose

Pulmonary BP increases

Forces fluid out of lung capillaries & causes some to burst

Viens & arteries participate in hypoxic pulmonary vasoconstriction response□

High altitudes

Results from same factors that produce edema in the rest of the body:○

Pulmonary edema•

Pulmonary Embolization & InfarctionPulmonary thromboemboli are common and often originate in the deep veins of the legs

•

RHF

Sickle cell anemia

Morbid obesity

Stasis1.

Cancer (especially pancreas)

Burns, surgery & trauma

Pregnancy

Lupus anticoagulant

Smokers

Hypercoagulable states2.

IV lines

Damaged endothelium3.

Vichow' Triad•

Saddle embolus

Instant death○

RHF

Acute cor pulmonale○

Increased in non-perfused pulmonary dead space

○

Ischemia w/ surfactant loss & alveolar collapse (atelectasis)

○

May occur if bronchial circulation is inadequate due to LHF, shock etc.

Infarction○

Pulmonary thromboembolism associated problems:•

Pulmonary Hypertension

Increased pressure leads to vascular thickening

Vascular thickening results in increased resistance

Increased resistance causes an in direct increase in pulmonary pressure through increased work of the heart

Cycle continues

Initial insult increases one of the above three, then:

○

Results/initiates a positive feedback cycle with ever increasing pressure, resistance & vascular thickening

•

LHF (especially mitral stenosis)○

L-to-R shunts or lung resections

Increased blood flow into the pulmonary arteries

○

High altitude, ARDS, emphysema, etc.

□

Causes pulmonary arteriole constriction

□

Alveolar hypooxygenation

Increased pulmonary vascular resistance

○

Pulmonary emboli○

Causes:•

ARDS

Heart & Lungs: The Great Patterns

Pathology Page 46

ARDSResults from anything that severely injures the Type I pneumocytes & capillary endothelial cells throughout the lung

•

Caused by direct lung injury

Pulmonary ARDS○

Remote effect of injury elsewhere

Extrapulmonary ARDS○

Outcome depends on severity of illness, not the type○

Two types•

Sepsis, shock○

Oxygen toxicity○

Lung contusion○

Influenza, measles, herpes, hantavirus

Viral Infx○

Burns, radiation○

Inhaled N2 oxidizes into nitric/nitrous acid□

Silo-filler's disease

Drugs, poison gas○

Near-drowning○

Heart-lung machine○

Aspiration of gastric juices○

Severe multiorgan injury○

Abs against HLA and/or neutrophils in donor plasma

Blood transfusion○

Causes•

IL-8 is often found in fluid from lungs w/ ARDS•

Pulmonary edema○

Cell necrosis○

Fibrin is released into alveoli (produces hyaline membranes)○

Loss of surfactant○

Alveoli collapse○

Type II pneumocytes are not as permeable to O2

As Type I pneumocytes are destroyed, Type II pneumocytes divide to replace them○

Lung more prone to bacterial infx

Fibrosis○

Results of ARDS•

ARDS results in death 50%•

Less transfusions, lower tidal volumes, lower ventilation pressures, less fluid overloading○

More conservative treatments improve outcome•

AtelectasisCollapse of alveoli•

"Absorption atelectasis"○

Resutls from non-ventilation of alveoli that are still perfused○

Seen distal to tumors, foreign bodies, etc.○

Surfactant will be engulfed by macrophages

"Golden pneumonia"

First CXR sign of lung cancer

If airways is obstructed, alveoli will fill w/ surfactant○

Obstructive atelectasis•

Blood, exudate, tumor, air

Results from something in the pleural cavity○

Compressive atelectasis•

Pathology Page 47

Key Terms

Have little or no intrinsic activity by themselves○

Allergen•

Allergen specific IgE

Mast-cell & eosinophil

IL-4, IL-5 & IL-13□

TH2 type of response

Clinically adverse reactions to enviornmental Ags mediated by:○

Allergy•

Propensity for developing immediate hypersensitivity reactions to common enviornmental allergens

○

Atopy•

Allergic Diseases

Associated w/ generation of IgE○

Driven by non-infectious Ags○

Result from harmful immune responses•

Innate immune response•

AllergensA very small group humans are routinely exposed to•Proteins & glycoproteins•

Enzymatic activity○

Activation of PRRs○

Activate innate immunity by:•

Bias the immune system towards TH2 type response•

Cysteine protease of dust mites

Activates innate immunity via cleavage of complement components

Der p 1○

Intrinsic NADPH oxidase activity

Rapidly increases the level of ROS in lung epithelium

Ragweed pollen○

Endotoxin

Chitin

β-glycans

Allergens contain substances that are recognized by TLR2, TLR4 or mannose receptor○

Properties•

Pollinating trees/grasses

Mold spores

Animal dander

Dust mite/cockroach secretions

Airborne proteins or glycoproteins○

Indoor allergens are associated w/ asthma○

Outdorr allergens are associated w/ allergic rhinitis○

Aeroallergens•

Asthma & Allergic Rhinitis

Immunology Page 48

Asthma

Specific HLA alleles

Polymorphisms of IL-4

Genetic○

Defects in target organ○

Excessive hygiene

Enviornmental○

Triggers○

Factors that influence atopy•

Presence of older siblings

Early exposure to day care

Rural enviornment

Leads to protective immunity

Factors favoring TH1 ○

Widespread use of antibiotics

Western lifestyle

Urban enviornment

Diet

Sensitization to allergens

Leads to allergic disease (including asthma)

Factors favoring TH2○

Cytokine balance•

Predisposition factors○

Viruses, allergens, pollutants

Enhancers○

Triggers○

Development of asthma•

All genes implicated in asthma development encode for some kind of immune response•

Risk does not apply to children that attend daycare at an early age

1st born children more likely to develop rhinitis & asthma○

Once asthma is established, viruses are a general trigger

Increased exposure to respiratory viral infections is protective against development of allergy & asthma

○

Infections & asthma•

Sensitization to Allergens

Allergic Rhinitis

Inflammation of the nasal mucous○

Nasal congestion, Rhinorrhea, Nasal itching, Sneezing

Clinically○

Rhinitis •

Airborne Ags enter nasal tissues○

Occurs within minutes

Histamine, Tryptase, Leukotrienes, PGD2□

IgE-mediated degranulation

Edema & occlusion of nasal passages□

Leakage & dilation of vessels

Acute allergic rhinitis○

Allergic rhinitis•

Immunology Page 49

Cause of Increasing Prevalence of Allergies

Immune system at birth is TH2 skewed○

Helminthes or virus infx restore a healthy balance of TH2 / TH1 response○

Resulting in allergies & asthma

In absence of these stimuli (West), TH2 cytokine production persists○

Hygiene hypothesis•

Environmental changes in indoor air quality•Lifestyle changes•

Sensitization to AllergensActivated T cell differentiates into TH2 cell1.Clonal expansion of activated T cell2.TH2 cells produce IL-4 & IL-133.Naïve B cell (Ag presenting) picks up allergen and processes it for TH cell presentation4.

Secretes IL-4 & IL-13a.Activated TH2 cell recognizes allergen/MHC-II5.

Becomes plasma cella.B cell is fully activated and class switches to IgE production6.

High affinity for Fc region of allergen-specific IgE

Mast cells -> tissue

Basophils -> circulation

FcERI bound to mast cells & basophils○

Crosslinking of FcERI leads to degranulation and release of inflammatory mediators○

Occur within the 1st hour after crosslinking of IgE-FcERI○

Airway constriction

Wheal-and-flare reactions in the skin

Tissue specific effects○

Edema and pruritis (itching)

Generalized symptoms○

Anaphylaxis

Systemic symptoms○

Immediate phase•

IL-4, IL-5, IL-13, histamine, leukotrienes, eicosanoids (HETEs)

Cytokines from mast cells lead to recruitment of macrophages, TH cells, & eosinophils○

Further inflammatory response

TNF-α secretion○

Smooth muscle hyperplasia/trophy

Mucus gland hyperplasia

Collagen deposition□

Activation of fibroblasts

Eventually leads to airway damage& remodeling○

Can eventually lead to COPD○

Chronic disease development•

IL-10○

Treg cells could suppress allergies by responding to specific clonal cells & supressing activation•

Immunology Page 50

Cardiopulmonary EmergenciesAbsence of effective ventilation, circulation or both

•

Pump

Lungs

Circulatory volume

Three components:○

Cardiopulmonary arrest•

Sedated, ill-appearing child○

Can progress to hypoventilation & death

○

Nasal flare

Tracheal tug

Sternal retractions

Decreased breath sounds

Stridor (high pitched sound in upper airway)

Wheeze

Tripod position

Classic signs○

Clinical •

Progressive shock

Asthma, croup, pneumonia

Arrests in pediatric population generally due to lung & circulatory components

○

Differences from adults•

Anticipation of CP Arrest

Appearance1.Breathing2.Circulatory status3.

Pediatric assessment triangle:•

Poor tone indicative of serious problems

Patients muscle tone○

Lack of interaction w/ toys & parents is a bad sign

Interactiveness○

Restlessness & agitation are signs of hypoxia

Consolability○

Unfocused gaze is idicative of altered mental status

Look/gaze○

Loud cry is good

Hoarse/muffled cry indicates airway obstruction

Weak cry is a sign of significant illness

Speech/cry○

Appearance•

Retractions○

Inability to cry or talk○

Tripod seating○

Stridor

Wheezing

Moist sounds heard through the stethoscope

□

Rales

Added sound with a musical pitch occuring on inspiration or expiration

□

Rhonchi

Guttural sound□

Grunting

Snoring

Airway sounds○

Breathing•

Good signs are pink & warm nail beds, mucus membranes, palms & soles

Skin○

Normal refill (nail bed) will take less than 2 seconds in limb held above heart level

Capillary refill○

Tachycardia followed by bradycardia

Heart rate changes○

Significant loss of blood

Cyanosis○

Circulation•

Causes of CP Emergencies

Foreign body○

Angioedema from anaphylaxis○

Epiglottis○

Croup○

Injury○

Complete or severe upper airway obstruction

•

Air leaking into pleural cavity w/ mediastinal structure shift to contralateral side

○

Tension pneumothorax•

Buildup of fluid in pericardial sac○

Cardiac tamponade •

Seen in kids w/ central lines○

Pulmonary embolism•

3+ rib fx

Massive blood loss

CNS injury

Metabolic disease

Flail chest○

Other causes•

Respiratory Distress in Kids

Pediatrics Page 51

Other Common Causes of Respiratory Distress

Often develop more gradually

Patients are often febrile & ill in appearance

Infx○

Typically cause sore throat, difficulty swallowing, & local pain & swelling

Hoarse voice

Retropharyngeal &peritonsillar abscesses○

Often viral (parainfluenza)□

Croup is the most common cause of infectious airway obstruction in kids <36 m.o.

Tracheitis is often a secondary bacterial infx to croup

Stridor -> THINK CROUP

Croup & tracheitis○

RSV, influenza, parainfluenza & adenovirus

Progressive cough□

Wheezing/atelectasis□

Characterized by URI symptoms

Bronchilitis○

Bacteria are more localized

Higher fiver & ill appearance

Pneumonia○

Inflammation, edema, bronchospasm & mucus

Asthma○

Often due to food or medications

Anaphylaxis○

Causes compression leading to respiratory distress

Stridor, drooling or choking

Foreign body○

Expiration produces visible chest wall changes

Flail chest□

Trauma

Chest wall abnormalities○

Cardiovascular conditions○

Pulmonary edema○

Respiratory tract conditions•

Pediatrics Page 52

Characteristics

Assists with budding & viral release

9 subtypes (N1-N9)

Neuraminidase (NA)○

Involved in attachment & penetration

16 subtypes (H1-H16)

Highly pathogenic strains tend to have HAs that are easily cleaved when they contact the cell surface

Hemagglutinin (HA)○

Involved with penetration

M2○

Surface glycoproteins•Levels of Virulence

Immune system "overcompensates"○

Results in "purulent" pneumonia○

Ends up looking like respiratory distress ○

Highly pathogenic•

Contained within LRT○

Low pathogenic•

Epidemiologic ConcernsIncubation is short (1-4 days)•

Respiratory tract○

7 days before & 4-7 days after onset of symptoms

Range of viral shedding ○

Reservoir •

Modes of TransmissionFomites•Respiratory droplets•Endogenous•Vector borne•

Pharmacological Treatments

Sialic acid analogs○

Effective against influenza A & B○

GI: nausea & emesis (vomiting)□

Sodium benzoate displaces bilrubin in children <1 y.o. (contraindicted)□

Adverse effects:

Pro-drug given orally

Eliminated renally

Oseltamivir○

Delivered intranasally or inhaled

Wheezing & bronchospasms (pre dose w/β-agonist)□

Adverse effects:

Renal elimination

Poor bioavailability (<5%)

Approved for treatment of patients >7 y.o.; approved for prophylaxis >5 y.o.

Zanamavir○

NA inhibitors•

Insignificant efficacy due to viral resistance○

Amantadine & Rimantadine○

M2 inhibitors•

Influenza A

Pharmacology Page 53

β-Agonists

Increases cAMP production

Decreases bronchial tone

Bronchodilation

Stimulates adenylate cyclase (AC)○

MOA•

Not for acute symptoms

Beneficial when added to inhaled corticosteroids

Salmeterol may increase risk of asthma related death

□

Black Box Warning

Long acting○

For acute relief of bronchospasm

Short acting○

Can be long and short acting•

Tachycardia

Nervousness

Increased BP

Dizziness, headache

Sympathomimetric effects○

Nausea, vomiting, bad taste

GI○

Hypokalemia○

Adverse effects•

Acute therapy○

Exercise induced asthma○

Clinical Use•

Methylxanthines

Unknown○

Interference of uptake & storage of Ca++ by SR

Adenosine receptor block

Inhibits breakdown of cAMP

Cellular actions○

MOA•

Chemically similar to caffeine•Relaxes bronchial smooth muscle•May enhance mucociliary clearance•

COPD○

Asthma (alternative to β-agonist)○

Clinical Uses•

Think caffeine○

Adverse effects•

Anticholinergics (Antimuscarinic)

Muscarinic receptors

Inhibits Ach induced bronchoconstriction○

Stabilizes mast cells○

MOA•

COPD○

Not very effective for asthma○

Clinical Uses•

Vary by route○

Sore throat, hoarseness

Inhalation○

Nasal irritation

Intranasal○

AE•

Mast Cell StabilizersInhibits mast cell degranulation•Suppresses chemoattractant activity•

BUT has no effect on bronchial relaxation

○

Reduces hyperreactivity of bronchi•

Prophylactic medication•

Asthma maintenance therapy○

Allergic rhinitis○

Clinical Uses•

CorticosteroidsAnti-inflammatory agents•

Long term controller medication

Asthma (long term control)

COPD (only severe)

Inhaled○

Help speed recovery from severe exacerbations

Oral ○

Clinical Uses•

Lots of AE but usually only w/long term and high doses

Systemic○

Rinse and spit after puffs□

Oral candidiasis (thrush)

Inhaled○

AE•

Fewer symptoms○

Fewer exacerbations○

Reduced use of quick relief meds○

Benefits of daily inhaled corticosteroid use•

Drugs for Treating Asthma & COPD


Leukotriene Inhibitors

Prevent formation of leukotrienes

○

5-lipooxygenase inhibitors•

Block leukotriene receptors○

Receptor antagonists•

Long term control in mild asthma

○

Clinical use•

Zafirlukast only

Liver toxicity○

Hypersensitivity○

Chills, fever etc.

Zafirlukast only

Flu like shyndrome○

Adverse effects•

Anti-IgE

Moderate to severe uncontrolled asthma○

Clinical Use•

Life-threatening anaphylaxis○

Adverse effects•

Stepwise Approach for Managing Asthma

Rapid acting β-agonist as needed○

Step 11.

Reliever medication plus a single controller○

Add low-dose inhaled glucocorticosteroid○

Step 22.

Reliever medication plus one or two controllers○

Combine low-dose inhaled glucocorticosteroid w/inhaled long-acting β-agonist○

Step 33.

Reliever medication plus 2+ controllers○

Medium or high dose inhaled glucocorticosteroid combined w/long acting inhaled β-agonist○

Step 44.

Reliever medication plus additional controller options○

Additional oral glucocorticosteroids○

Addition of anti-IgE○

Step 55.

Medications for COPD

Leukotriene antagonists○

Mast cell stabilizers○

Anti-IgE○

Same as asthma but no:•


Bronchodilators

CLASS RESPONSE TIME

NAME(S) Prefix/ Suffix

ASTHMA/ COPD

Β2 agonists Short acting

Albuterol, Levalbuterol, Pirbuterol -rol Both

Β2 agonists Long acting

Salmeterol, Formoterol (rapid action), Bambuterol

-rol Both

Methylxanthines Both Theophylline, aminophylline -phylline Both

Anticholinergics Both Ipratropium (Short acting), Tiotropium (long acting)

-pium COPD (not very effective for asthma)

Anti-Inflammatory

CLASS RESPONSE TIME

NAME(S) PREFIX/ SUFFIX

ASTHMA/COPD

Mast cell stabilizers

Long acting Cromolyn, Nedocromil NA Asthma

Corticosteroids (systemic)

Short acting Prednisone, Prednisolone, Dexamethasone

NA Both

Corticosteroids (inhaled)

Long acting Beclomethasone, Budesonide, Flunisolide, Fluticasone, Triamcinolone, Ciclesonide

NA Asthma & COPD (severe)

Leukotriene Inhibitors

Long acting Zafirlukast & Montelukast (receptor antagonists), Zileuton (lipoxygenase inhibitor)

-kast (receptor only)

Asthma

Anti-IgE NA Omalizumab NA Asthma

Asthma/COPD Drug Chart


ACE InhibitorsAngiotensin Converting Enzyme Inhibitor•

Suffix -> -pril○

Drugs•

Reduced vasoconstriction -> vasodilation

Decreased formation of AG II1.

Decreased fluid volume□

Decreased aldosterone release

Decreased formation of AG II2.

Vasodilation

Reduced bradykinin breakdown3.

MOA•

No reason to favor one over the other

All ACE inhibitors have similar uses and AE○

Captopril is the only active drug, all others are prodrugs

Differ in potency, pharmacokinetic properties & active entity○

Clinical considerations•

Do NOT have reflex sympathetic action

1st choice for patients w/diabetes, chronic kidney disease, & LVH

Hypertension○

Prevent or delay progression of heart failure

In patients with high risk of developing HF, structural abnormalities and/or those with a previous MI

□

Decreases incidence of death, MI & hospitalizations

HF○

Prevent or delay kidney disease in type 1 & 2 diabetes

Improved renal hemodynamics

Diabetic nephropathy○

Clinical uses•

ACE Inhibitors & ARBs


Improved renal hemodynamics

Proteinuria○

Stroke prophylaxis○

Post MI○

ACE inhibitors have NO significant effect on cholesterol levels○

Dry, hacking cough○

Angioedema & anaphylaxis○

Drug interactions w/K+ sparing diuretics

Hyperkalemia○

Contraindicated in pregnancy & renal artery stenosis○

NSAIDs may blunt antihypertensive action○

Adverse effects•

ARBsAngiotensin Receptor Blockers •

Suffix -> -sartan○

Drugs•

Same as ACE inhibitors○

ACE inhibitors are first line due to more data

Do NOT differ significantly from ACE inhibitors for all causes of mortality & hospitalization due to heart failure

○

Candesartan

Losartan

Valsartan

FDA approved HF ARBs○

Clinical uses•

Cross reactivity is possible

Angioedema is less likely with ARBs than with ACE inhibitors○

Cough is much less likely than with ACE inhibitors○

Contraindications are same as ACE inhibitors○

Beware of increased risk of yperkalemia due to drug-drug interactions with ACE inhibitors and K+ sparing diuretics

○

Adverse effects•

Renin Inhibitor

Aliskiren○

Drug•

Blocks renin conversion of Angiotensinogen to AG I•Approved for treatment of hypertension•


Responses Elicited by β Stimulation

Increases rate & force of contraction

Heart ○

Increases renin secretion

Kidney○

β1 •

Bronchodilation

Lungs○

Relaxation

Vascular smooth muscle○

β2 •

Responses Elicited by α Stimulation

Contraction


α1•

Mixed responses○

Reduces sympathetic output

α2 agonist (Clonidine) inhibits release of neurotransmitter of nerve terminal

○

α2•

If drug effects both β2 and α1 , α1will dominate response

•

VasopressorsAll catecholamines are rapidly inactivated by monoamine oxidase (MAO) and catechol -O-methyltransferase (COMT)

•

All catecholamines are given parenterally○

Also catecholamines have low bioavailability & short plasma half-lives○

MAO and COMT are found in the gut and liver•

Vasopressors


Catecholamines & Vasopressin

NAME GROUP RECEPTOR TARGETS PHARM. ACTIONS THERAPEUTIC USES

Epinephrine Direct-acting nonselective catecholamines

α and β ; β dominates (low doses)

Bronchial smooth muscle relaxation; increase HR, BP, contractility & CO

Severe allergic rxns (anaphylaxis); cardiac arrest

Norepinephrine Direct-acting nonselective catecholamines

Powerful α agonist Increase BP, vasoconstriction, vascular resistance, HR & contraction; barorecepter reflex can decrease HR at lower doses

Acute hypotension; shock (cardiogenic or septic); Caution-> decreases renal blood flow

Isoproterenol Direct-acting nonselective catecholamines

β Intense stimulation of HR & contraction force (increase CO); dilates arterioles of skeletal muscle (decreased vascular resistance) ( β2

action); Bronchodilation (β2

action)

Decreased CO

Dopamine Dopamine receptors > β1 > α1

Dose dependent: low dose-> dopamine receptors (vasodilation), medium dose-> dopamine receptors + β1

(increases CO), high dose-> α1 (increases BP)

Increase GFR & natriuresis; increase HR, contractility & systolic BP

Treatment of decreased CO, hypotension (septic & cardiogenic shock)

Dobutamine Selective β1 β1 Increases CO & contractility

Severe HF (symptomatic benefits only)

Vasopressin Non-adrenergic (non-catecholamine) peripheral vasoconstrictor

Vasopressin receptors (smooth muscle & renal tubules)

Contraction in capillaries, arterioles & venules

Alternative to epinephrine; supportive treatment of severe hypotension in shock

Vasopressor Chart


Responses Elicited by β Stimulation

Increases rate & force of contraction

Heart ○

Increases renin secretion

Kidney○

β1 •

Bronchodilation

Lungs○

Relaxation


β2 •

βBlockers MOAAntagonize the effects of catecholamines at the β receptor through competition

•

SA & AV nodes, Purkinje fibers

Cardiac myocytes & conduction cells○

β1 receptors:•

Bronchial and peripheral vascular smooth muscle

○

β2 receptor:•

Some βblockers are partial agonists and can cause partial β receptor activation if endogenous catecholamine levels are low

•

Calcium Channel Blockers (CCBs)

βBlocker Properties

Cardioselectivity

Hydrophilic drugs tend to have fewer CNS adverse effects

□

Lipophilicity

Partial agonist activity (intrinsic sympathomimetic activity; ISA)

Differentiate between drugs by:•

βBlocker Drugs

α1 & nonselective βantagonist

Except Carvedilol○

Suffix -> -olol•

Acebutolol○

Atenolol○

Bisoprolol○

Betaxolol○

Metoprolol○

β1 selectivity•

Pindolol○

ISA•

βBlocker Effects

Decrease contractility, CO, renin release & AV nodal conduction (HR)

○

Blunts sympathetic reflex w/exercise○

Cardiovascular effects•

Patients w/ashtma□

Increase airway resistance

Respiratory tract○

Lowers HDL & raises VLDL

Cholesterol○

May inhibit recovery from hypoglycemia (caution in diabetic patients)

Blood glucose○

Bradycardia, hypotension, heart block○

Sexual dysfunction○

Fatigue, depression & insomnia○

Adverse effects•

βBlocker Clinical Correlations

Hypertension○

MI prevention○

Arrythmias○

Lessens symptoms

Reversal of cardiac remodeling, hypertrophy & cell death

Used in all patients with a history of MI, symptoms of HF and/or reduced LVEF

Bisoprolol1.Carvedilol2.Metoprolol3.

Use on the 3 agents:

HF○

Stable angina○

Migraine headaches○

"stagefright"○

Clinical uses•

Asthma

Peripheral vascular disease

Use β1 selective for patients with:○

Always start w/low dose and increase slowly

○

Taper when drug is discontinued○

Clinical considerations•

CCB Effects

Beta & Calcium Channel Blockers


Calcium Channel Blockers (CCBs)

Triggers contraction○

Required for pacemaker activity○

Intracellular Ca+:•

Bind to specific Ca+ channels in the myocardium & vascular smooth muscle

•

Verapamil

Diltiazem

Nondihydropyridines○

Suffix -> -pine

Dihydropyridines○

Agents•

Based on different binding sites○

Vascular (Nifedipine -> prototypical)

Dihydropyridines○

In-between, some vascular but mostly myocardial

□

Diltiazem

Myocardial□

Verapamil


Properties•

Hypertension○

Angina (including variant)○

Arrythmias○

Migraine prophylaxis○

Clinical uses•

CCB Effects

Reduced contractility

Decreased HR

Slowed conduction through AV & SA nodes

Cardiac○

Vasodilation

Vascular○

General•

Verapamil > Diltiazem > Nifedipine

Can cause serious cardiac depression and A-V block

□

Reduces angina through reduced cardiac workload (result of decreased contractility and HR)

Strength of drug (for cardiac effects)○

Cardiac effects•

Nifedipine > Diltiazem > Verapamil

Can cause tachycardia□

Nifedipine reduces angina through coronary dilation

Vascular effects•

AV block, sinus bradycardia

Flushing, headache & hypotension

Constipation (Verapamil)


Peripheral edema□

Flushing, headache, syncope, hypotension

□

Dizziness□

Vasodilation related

Dihydropyridines○

Adverse effects•

Potential for lots of drug interactions!•


Bacteremia & "Vegetations"

Micrbiological test○

Bacteriocidal antibiotics○

Via IV

Lengthy treatment○

Always requires:•

Often requires combination treatments•

Streptococcal Infections

IV drug abuser○

Isolate bacteria

Susceptibility testing for Penicillin G

Treatment is Pen G for 4 weeks□

None -> Pen G

Mild -> Ceftriaxone (4 weeks)

Severe/Anaphylaxis -> Vanc (4 weeks)

Allergy influences:□

If yes, S. viridans

Treatment is Vanc (4 weeks)□

If No, Pen-resistant S. viridans

Obtain blood samples○

Native valve•

Same drugs & principles○

Bacterial adhesion & dormancy is greater

6 weeks of therapy

Prolong & intensify treatment○

Prosthetic valve•

Enterococcal InfectionsPartial penicillin resistance is common•Vanc is not always bacteriocidal•Always add Gentamicin w/cell wall inibitor

•

Often prolong treatment•

Ampicillin (4 weeks) + Gentamicin (4 weeks)

Penicillin sensitive○

Vanco (4 weeks) + Gentamicin (4 weeks)

Penicillin hypersensitivity○

Ampicillin + Sulbactam (4-6 weeks) + Gentamicin (4-6 weeks)

OR: Vanc (4-6 weeks) + Gentamicin (4-6 weeks)

Penicillin resistant○

Native valve•

Prolong treatment for 6 weeks○

Prosthetic valve•

Vanco + GentamicinBoth can impair kidney function•Renal clearance can result in nephrotoxicity•

SulbactamInhibits β-lactamase•Irreversibly inactivates β-lactamase•Spares ampicillin•Alone it has no intrinsic antibiotic effect•

Vanco Resistance Enterococcus

Bacteriostatic, but have no other choice

○

Treat w/Linezolid (8 weeks)•

Linezolid interacts w/MAOs•

Pseudomonal EndocarditisTreatment is Ticarcillin & carbenicillin•

Infectious Endocarditis


Staphylococcal InfectionsPenicillin resistance is likely•Methicillin resistance is encountered•Always test for methicillin susceptibility•

Nafcillin for S. aureus

Chemical appendages make nafcillin a poor substrate for β-lactamases

No allergy -> Nafcillin (6 weeks)

Mild -> Cefazolin ((6 weeks)

Severe/anaphylaxis -> Vanc (6 weeks)

Pen G resistant, methicillin susceptible○

Vanco (6 weeks)

MRSA○

Native valve•

MRSA is common○

Always intensify treatment & add Gentamicin & rifampin○

Unique ability to kill staphylococci adherent to foreign material

Bacteriocidal

Many drug interactions!

Rifampin○

Nafcillin (>6 weeks) + Rifampin ( >6 weeks) + Gentamicin (2 weeks)

Treatment○

Prosthetic valve•


CP I Final

Documents