Normal EKG

Wave P Wave Atrial depolarization Upright in 1, 2, V 4-V 6, AVF Inverted in AVR If not inverted on the AVR lead, the depolarization is NOT coming from the SA node Variable in other leads P-R Interval From beginning of P wave to beginning of QRS complex Typical interval (time from SA node to ventricular fiber) 0.12-0.20 secs Through AV, purkinje If less: Pre-excitation, tachyrythmia If longer: AV blocks QRS comlex Ventricular depolartization 0.5-0.1 secs ST segment End of QRS complex to beginning of T wave Observe: Level 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 Shape Should be isoelectric T Wave Ventricular repolarization Upright in 1, 2, V 3-V 6 Inverted in AVR Variable in others Should not be greate than 5mm in standard leads Massive T waves can indicate MI QT Duration 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 Notes Everything is inverted in AVR Prominent T waves are found in African Americans Abnormal P Waves Notched P-mitrale Leads 1 & 3 Left atrial enlargement Flat in lead 1; tall in 2 & 3 P-pulmonale Right atrial enlargement Inverted in 2 & 3 AV nodal rhythm Not coming from SA node

Normal EKG

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

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Asthma & COPD

Asthma Chronic inflammatory disorder of the airways Wheezing Non-productive cough Chronic Bronchitis Chronic PRODUCTIVE cough for 3 months in each of 2 successive years Step Approach to Asthma Therapy Intermittent Step 1 Mild Step 2 Moderate Step 3 Severe Step 4 or 5 Step 1 SABA Step 2 Low dose inhaled glucocorticoids Step 3 Combine long-acting beta agonists with low dose inhaled glucocorticoids Step 4 or 5 Long-acting inhaled beta agonist combined with: Medium strength glucocorticoids (Step 4) High dose glucocorticoids (Step 5) Step 6 Addition of oral glucocorticoids daily or every other day

Emphysema Abnormal & permanent enlargement of the airspaces distal to the terminal bronchioles Destruction to airspace walls COPD results when actual airflow obstruction occurs Categorizing Asthma Lung function FEV 1 Steroid use over past year Exacerbations needing glucocorticoids Methacholine response Substance that causes bronchospasm Test used in suspected asthma patient >20% reduction in FEV 1 Categories Intermittent 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 Persistent Mild Daytime symptoms more than twice/week 3-4 nocturnal awakenings/month SABA's used more than twice/week Minor activity interference Moderate Daily symptoms More than 1 nocturnal awakenings/week Daily SABA use Significant activity limitation FEV 1 60-80% of normal Severe Asthma symptoms throughout the day Nightly nocturnal episodes SABA use several times a day Extreme activity limitation FEV 1 below 60% predicted value COPD Management SMOKING CESSATION Exercise Gentle OMM Oxygen therapy

Clinical Features of COPD 50+ years old (usually) Productive cough Dyspnea (shortness of breath) with exertion Risk Factors for COPD Chronic Obstructive Pulmonary Disease Smoking accounts for 80-90% COPD Diagnostics Spirometry Chest x-ray Lung volumes CO diffusing capacity ABGs

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Pneumonia
Definition/Etiology Infection of the bronchoalveolar unit that leads to inflammation & production of inflammatory exudate Causes: Bacteria, viruses, parasites & fungi Pathogenesis Normal Defenses Lower respiratory tract is sterile Reflex closure of the glottis & cough protect the lower respiratory tract Ciliary motion sweeps particles upwards to oropharynx Tobacco paralyzes this mechanism Alveolar macrophages ingest organisms Pathological entrance of organisms Aspiration Inhalation Hematogenous dissemination Direct inoculation Intubation Trauma

Epidemiology Most common Community-aquired Pneumoccus Nosocomial S. aureus Aspiration Anaerobes Lung abscess S. aureus Chronic lung disease H. influenzae HIV Pneumocystis Most common is Streptococcal pneumoniae Prison/health care TB Seasonal (fall/winter) Influenza (virus)

Signs & Symptoms Cough w/production of sputum Yellow or green Dyspnea Chest pain Fever Chills Signs Decreased breath sounds Dullness to percussion Wheezing
Community-Aquired Pneumonia (CAP) Low rate of established etiologic agent Empiric antibiotic therapy All patients should have CXR Inpatients should have sputum culture & gram stain

Clinical Features Pneumococcus (common) Sudden fever onset Productive cough Atypical (Mycoplasma) Gradual onset Nonproductive cough Prominent nonpulmonary symptoms Headache, muscle ache, etc. Anaerobic Putrid or feculent sputum Tissue necrosis Actinomyces sp. "sulfur granules"

Other Treatment Options Chest PT Hydration Increased activity OMM

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Antibiotic Treatment Start with empiric therapy Outpatients Doxycycline (for those under 40 y.o. Older or those with comorbidities Macrolide, doxycycline or fluoroquinolone Patients older than 60 y.o. or comorbidities 2nd gen. cephs, amoxicillin or amox/clav Inpatients 2nd or 3rd gen. cephs -lactam/-lactamase inhibitor Fluoroquinolone Critically ill patients Macrolide or fluoroquinolone should be included w/above therapies For MRSA Vanc or bactrim

Pleural Effusions Infection in pulmonary parenchyma Requires thoracentesis Studies to obtain: Gram stain Cultures Acid-fast (TB) Fungus smear & culture Characterizing effusions: Transudates Clear Protein <0.5 EX: CHF Exudates Clear or cloudy Protein >0.5 EX: empyema, pneumonia

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Interstitial Lung Disease (ILD)

General Anatomy Progressive disease which often Interstitium spans region between alveolar & vascular leads to pulmonary disability epithelium Therapy does NOT reverse fibrosis Space between air exchange in alveoli and blood in capillaries Irreversible High mortality ILD Classification Respiratory failure Histology Alveolitis, interstitial inflammation, fibrosis Clinical Approach to ILD Causes: Symptoms Asbestos Dsypnea Amiodarone Normal or on exertion Chemotherapy Non-productive cough Radiation Weight loss Unknown Fatigue IPF (idiopathic pulmonary fibrosis) Cyanosis CTD (connective tissue disorders) Smoking hx in 2/3 patients SLE, RA scleroderma Signs Goodpasture's "velcro crackles" bibasilar Granulomatosis response Expiratory wheeze Causes: Clubbing Hypersensitivity pneumonitis (HP) Cor pulmonale (RHF) Metals (silica etc.) Obese Unknown History Sarcoid, Wegener's Acute Hours-days Occupational History and Exposure Pneumonitis w/SLE Exposure: Associated lung disease Days-weeks Bird breeders: HP AIP (acute interstitial Farmers: HP pneumonitis) Woodworkers: HP Subacute Miners: Silicosis 2 weeks-month Coal miners: black lung (pneumoconiosis) Sarcoid Pipe fitters: Asbestosis Drug related Medications: pulmonary infiltrates COP, SLE History Chronic African americans 10-17x more likely to aquire Months-years sarcoid IPF, sarcoid & occupational Familiar pulmonary fibrosis is autosomal dominant Lab Nonspecific

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ILD with Alveolar Hemorrhage Goodpasture's Auto-Abs Granulomatosis vasculitis ILD Associated with Connective Tissue Disease Wegener's SLE Chest pain (pleurisy) effusion CT - ground glass, honeycombing Treatment Steroids, methotrexate, azathioprine RA Pleurisy w/ or w/o effusion Common in men

Interstitial Pulmonary Fibrosis (IPF) Most common Velcro crackles Poor response to therapy Mortality 75% CXR can show honeycombing CT scan May show ground glass Treatment Quit smoking Flu/pneumonia vaccine Remove enviornmental agent Oxygen Steroids Transplant (lung/heart)

Acute Interstitial Pneumonia (AIP) Presents like ARDS (Adult respiratory distress syndrome) Signs/symptoms SOB Fever Cough Hypoxic CT shows ground glass Biopsy shows diffuse alveolar damage Treatment Steroids Ventilator Mortality 60%

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Sarcoidosis NON-CASEATING GRANULOMAS Etiology Unknown Genetics, enviornment, infection Pathogenesis Increase in TH lymphocytes with macrophages & multinucleated giant cells form non-caseating granulomas Worldwide disease 10-17x more common in African Americans 20-40 y.o. Symptoms Cough Dyspnea Lab Nonspecific CXR Abnormal Classification 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 Stages I & II tend to be acute & reversible Stages III & IV are progressive Stage IV is irreversible Intrathoracic lymphadenopathy is most common finding in sarcoid "1, 2, 3 signs" Differential Other granulomas TB, fungal Cancer (metastasis) Diagnosis By exclusion Biopsy for NON CASEATING GRANULOMAS Therapy Steroids Prednisone Anti-TNF (Remicade) TNF-receptor antagonist (Enbrel)

"1, 2, 3 sign"

Progressive, "velcro crackles"

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Congestive Heart Failure (CHF)

General HF is the inablity of the heart to meet the metabolic demands of the body Etiology 60% of HF is due to coronary artery disease(CAD) Most common cause of LV systolic dysfunction is ischemic heart disease (IHD) 10% hypertensive heart disease Causes Myocardial damage CHD/IHD Ventricular overload Restriction/obstruction to ventricular filling No single diagnostic test Clinical diagnosis Classification of HF Systolic/diastolic High/low Acute/chronic Systolic HF 50% of cases Ejection fraction (EF) is less than 40% Hypoperfusion w/impaired ventricular emptying General HF symptoms Weak, fatigued, Dyspnea on exertion (DOE), paroxysmal nocturnal dyspnea (PND) Ventricular systole problem Mechanisms LV dysfunction results in decreased CO Results in activation of: Sympathetic nervous system (SNS) Increased Norepi Vasoconstriction Increase afterload & BP Increased HR & contractility Renin angiotensin aldosterone system (RAAS) Decreased renal perfussion Increased renin -> increased AG I & II Aldosterone release Further fluid retention Increased preload Vasopression system ADH Stimulation of thirst leads to increase in total body water and hyponatremia (dilutional) Increased preload As heart fails, fluid retention increases & CO decreases Diastolic HF General HF symptoms Problem is ventricles can't relax Increased resistance to vent. Filling Treatment blockers Diuretics

Acute/Chronic HF Acute Sudden injury/onset Acute MI, ruptured papillary muscle, mitral regurg., toxins Usually systolic HF Chronic Multivalvular disease or dilated cardiomyopathy Progresses slowly Edema

High/Low Output HF High output Hyperthyroidism, anemia, pregnancy, A-V fistula, High CO but low EF Low output Ischemic heart disease Hypertension Precipitating Causes of HF Top two: Non-compliance w/diet Too much Na+, calories and/or stimulants Non-compliance w/meds Any other stress on the heart From infection to stress -> lots

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Signs & Symptoms of HF General HF symptoms Weakness, fatigue Respiratory problems Dyspnea, SOB, DOE, PND etc. Hepatomegalia JVD Crackles in lungs Heart sounds S3 & S4 S3 is normal in athletes & children

NYHA Functional Classification of HF Class I No limitation of activity Class II Slight limitation of activity Ordinary activity causes symptoms Class III Marked limitation of activity Less than ordinary activity causes symptoms Class IV Inability to carry out physical activity Symptoms at rest

Criteria for Diagnosis of HF Major criteria PND, JVD, S3 , hepatojugular reflex (HJR), pulmonary edema, cardiomegalia, crackles Minor Other general HF symptoms EKG Ischemia, infarction or hypertrophy Lab Brain natriuretic peptide (BNP) Neurohormone made in the ventricles Sensitive to ventricular overstretching (excessive preload/afterload) BNP and severity of HF are directly proportional CXR Cardiomegalia Pulmonary edema

Pharmacologic Treatment of HF ABCs A. ACE inhibitors, ARBs, Aldactone B. blockers US Carvedilol HF Trial Reduced mortality by 65% & hospitalization by 29% Coreg C. CCBs D. Diuretics, digitoxin E. Eplerenone (aldosterone antagonist) F. Fluid restriction I. Inotropes (Dobutamine, dopamine) N. Nitrates, Na+ restriction H. Hydralazine OMM Lymphatic treatments for optimal fluid drainage

Treatment of HF Five basic principles 1. Make correct diagnosis 2. Determine etiology 3. Determine precipitating factors 4. Understand pathophysiology 5. Understand MOA of pharmacologic therapy Non-pharmacologic Quit smoking If overweight: Decrease caloric intake 2g Na+ diet Avoid isometric activity Encourage isotonic (walking etc.) Stool softener Avoid alcohol

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Mitral Regurgitation (MR) Valve leaks back into atria during systole History of Rheumatic fever contributes to MR Mitral Stenosis (MS) Etiology Thick, fibrous valve leaflets Chronic Ca++ deposits Mitral valve prolapse (MVP) Narrow "fish mouth" valve Acute Increased left A-V pressure gradient Something broke Often seen in patients w/history of rheumatic Chondral/papillary muscle rupture fever Something is on valve to inhibit Symptoms closure General HF symptoms Symptoms Hemoptysis General cardiac symptoms Coughing up blood RHF/LHF Hoarseness Edema Left atria enlargement compresses Physical exam left recurrent laryngeal nerve Decreased S1 Physical exam Systolic murmur Malar flush (plum colored cheeks) Prominent at apex, radiating into Increased S1 left axilla Opening snap after S 2 Echo "Rumbling" diastolic murmur P. mitrale Use bell Treatment EKG Afterload reduction Shows P. mitrale signs Vasodilator Echo Diuretics "hockey stick" deformity in mitral valve ACE inhibitor Treatment Useful for chronic MR Prophylaxis for hemolytic strep Surgery Warfarin Sever MR Mitral valve replacement If pulmonary HT and/or systemic Aortic Stenosis (AS) embolization Pathophysiology Obstruction to LV outflow produces a pressure MVP overload Redundant mitral leaflet tissue LVH Thickened Peak systolic gradient Inappropriate closure Symptoms Can be inherited Dyspnea, angina, syncope Marfan's Ehlers-Danlos, Physical exam osteogenesis imperfecta Narrow pulse pressure Clinical features Close values of systolic/ diastolic BP Can be asymptomatic Peripheral pulses rise slowly Palpations, dizziness, syncope & Parvus -> decreased amplitude angina Tardus -> slow upstroke Auscultation PMI can be laterally displaced Systolic click after S1 Auscultation Due to tensing of slack Harsh systolic murmur chordae tendinae Base of the heart and radiates to carotids Systolic murmur Treatment EKG HF treatments Non-specific T wave changes Surgery Treatment Valve replacement blockers

Valvular Disease

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Aortic Regurgitation (AR) Etiology Rheumatic fever Endocarditis Pathophysiology AR leads to volume over load condition which increases LVED volume Leads to LVH Myocardial ischemia develops due to increased muscle oxygen requirements History Acute AR Pulmonary edema Cardiogenic shock Chronic AR DOE, PND, angina Physical exam De Musset sign Bobbing of head w/systole Corrigan's Pulse Rapid rising 'water hammer pulse' which collapses as pressure falls Quincke's Pulse Capillary pulsation w/flushing at root of nail Auscultation Diastolic crescendo Blowing murmur Treatment Medical LV failure treatments, ACE inhibitors Surgical Pulmonary Valve Disease Auscultation Graham Steell's murmur Disatolic, high pitched decrescendo blowing murmur

Tricuspid Stenosis (TS) Etiology Rheumatic fever Associated with mitral stenosis & tricupsid regurg. Pathophysiology Prominent "A" wave Ascites, edema Symptoms Pulmonary congestion Fatigue due to low CO RVF Physical findings Ascites Giant "A" waves Auscultation Diastolic murmur Treatment Na+ restriction Diuretics Surgery Tricuspid Regurgitation (TR) Etiology Functional patient Usually not pathologic History Prominent "V" waves in JVP Hepatomegaly Ascites Auscultation Lowing holosystolic murmur Severe TR Decreased CO Treatment If pulmonary HT is present Surgery for repair/ replacement

Murmurs Systolic murmurs MR, MVP, TR, AS, PS & aortopulmonary shunts Diastolic murmurs AR, PR, MS, TS, & atrial myxoma Continuous murmurs PDA (patent ductus arteriosus), AV fistula, ASD (atrial septal defect) with high LA pressure

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Infective Endocarditis (IE)

General Produces 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 Acute S. aureas occurs on normal valve Rapidly destructive, produces metastatic foci (infectious groups of bugs) Fatal in 6 weeks Subacute Does not produce metastatic foci Prolonged course (1 year) S. viridans Endo in IV drug abusers 50-60% of cases are due to S. aureas Onset usually acute Pulmonary emboli Septic pneumonia Lines Due to central IV lines, Swan lines, arterial lines

Prosthetic Valve Endocarditis Aortic more effected than mitral Arising within 2 months post surgery Coag. (-) staph & staph A Arising 2-12 months post surgery Coag. (-) staph Arising 12 months post surgery Viridans

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

Physical Signs of Endocarditis Diagnostic Criteria New or changing murmur Definitive infective endocarditis Especially diastolic Microorganisms Splenomegalia Demonstrated by culture (lots) Hepatomegalia Vegetation that has embolized Mucocutaneous petechiae Pathologic lesions Roth spots Vegetation or intracardiac abscess Flamed shaped hemorrhagic lesions present Confirmed by histology w/pale centers in the retina Osler's nodes showing active endocarditis Tender, painful erythematous lesions Clinical Palms & soles At least 2 major clinical criteria Janeway lesions Fever, anemia & murmur Non-tender/-painful , erythematous, Possible infective endocarditis Findings consistent, but not definite or papular lesions Clubbing rejected Linear hemorrhages Rejected Splinter hemorrhagic lesions in nails

Symptoms of IE

Complications of IE
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1. 2. 3. 4. 5. 6.

Symptoms of IE Complications of IE Fever Valve destruction with regurgitation/obstruction Weakness/fatigue CHF Night sweats Myocardial abscess/aortic root abscess Arthralgias Surgery required for optimal outcome Embolic manifestations HF Most Common Cause of Death in Treated IE Fever, Murmur & anemia! Emboli Echocardiogram Renal failure Vegetation visible Rupture of myocardial aneurysm

Endocarditis Treatment Prophylaxis only used for HIGH risk patients Porsthetic heart valves Prior bacterial endocarditis Surgical shunts Congenital heart disease Dental, oral or upper respiratory surgery

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Cardiomyopathies
General Cardiomyopathy is a disease that involves the myocardium with cardiac dysfunction Muscle problem

Etiologic Classification Primary myocardial involvement Idiopathic Dilated (D), Restricted (R), Hypertophic (H) Familial D& H Eosinophilic endomyocardial disease R Endomyocardial fibrosis R Secondary myocardial involvement Lots Clinical classification of cardiomyopathies Dilated L or RV enlargement Impaired systolic function CHF Arryhthmias Emboli Restricted Endomyocardial scarring or myocardial infiltration Results in restriction to filling (L or RV) Hypertrophic Disproportionate LV hypertrophy Typically septum

Alcoholic Cardiomyopathy Dilated cardiomyopathy Holiday heart syndrome & arrhythmias following binge drinking
Peripartum Cardiomyopathy CHF during last trimester of pregnancy or 6 months later

Drugs That Can Cause Dilated Cardiomyopathy Doxorubicin Cyclophosphamide Tricyclic antidepressents Cocaine

Dilated Cardiomyopathy Impaired systolic function Reduced EF & CO Dilated LV cavity Clinical manifestations Maybe asymptomatic Decreased exercise tolerance DOE CHF PND, fatigue & orthopnea Edema, palpations, arrhythmias & emboli Physical exam JVD, S3, S4, MR (mitral regurg.) & TR (tricuspid regurg) Narrow pulse pressure Tachycardia Displaced PMI Crackles, peripheral edema & hepatomegalia CXR Enlarged cardiac sillhouette Echo LV dilation Can lead to MR because papillary muscles are so far away that valves can't close Treatment Non-pharmacologic No alcohol Monitor weight Exercise Na+ & fluid restriction ACE inhibitors Treat as managed HF Defibrillator for malignant arrhythmias Cardiac transplant Prognosis 25% stabilize, rest is poor prognosis 50% die suddenly

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Hypertrophic Cardiomyopathy Hypertrophy of IVS (interventricular septum) Larger than free wall Disorganized cardiac muscle cells Herebitary disease (+) family history in 50% of cases Clinical manifestations Syncope/sudden death Probably from ventricular arrhythmias related to exertion Triad Syncope Angina Dyspnea Physical exam S2 paradoxically split Loud systolic murmur Indicates LV outflow tract obstruction Echo Septum 1.3 or more times the free wall Small LV cavity Treatment Limit strenuous activity Drugs to increase contractility and decrease LVOT obstruction blockers CCBs

Restrictive Cardiomyopathy Least common Diastolic dysfunction w/rigid walls that impede ventricular filling Often due to fibrosis Carcinoid syndrome Results in endocardial fibrosis with stenosis/regurg of tricuspid/pulmonic valves

Eosinophilic Endomyocardial Disease Large mural thrombi Fibroplastic endocarditis

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Work of Breathing
Inspiratory Expiratory Stretch elatic components Overcome resistance of air & tissue movement Overcome resistance or air & tissue movement Given off as heat Given off as heat Return lungs to original volume Quiet breathing stores a lot of energy in the Quiet expiration can proceed passively due to elastic components stored energy in elastic elements Vigorous breathing requires additional work
Types of Work Resistance Energy is entirely lost Elastic Stored during inspiration Work of Vigorous Breathing Resistance increases Turbulence increases Airways can collapse during expiration Expiration is shortened Stored energy from inspiration is NOT enough to return lungs to their original volume within time limit

Diseases Which Decrease Compliance Compliance (elasicity) Restrictive (constrictive) diseases Neonatal distress syndrome CHF TB All increase the inspiratory work
Extrathoracic Obstruction Typified by: Snoring Sleep apnea Soft tissue in oro/nasopharynx collapse Worse on inspiration CPAP can be helpful maintaining positive pressure & maintaining flow

Autonomic Stimulation Sympathetic Stimulate 2 receptors of smooth muscle of airways Causes dilation & decreases resistance Local Control Parasympathetic Histamine causes bronchiolar constriction Constricts airways & increases Hypocapnia causes smooth muscle contraction & constriction resistance Bronchial Sm. Muscle Pulmonary Vasculature Systemic Vasculature Major Adrenergic Receptors 2

Diseases Which Increase Resistance Obstructive diseases Emphysema Asthma Sleep apnea Most resistance occurs in the large airways Trachea Bronchi Smaller total cross sectional area Smaller airway diameter varies with breathing cycle Inspiration causes dilation Expiration causes constriction Irritation can cause bronchitis & accumulation of substances impeding airflow Obstruction makes it harder to exhale Requires a larger positive pressure to push air out This can collapse airways Bronchitis High intrathoracic pressure Bronchitis + emphysema Increase intrathoracic pressure + "strut" failure

Adrenergic Stimulation Parasympathetic Stimulation

Hypoxia

Dilation (circulating) Constriction

??

Insignificant Insignificant
Constriction (alveolar hypoxia)

Constriction Insignificant
Dilation (interstitial hypoxia)

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Ventilatory Control
Normal Breathing Medullary Respiratory Centers Mainly through the diaphragm (phrenic nerve) DRG The brain controls both the frequency & the Dorsal respiratory group Relays info about breathing to neurons pattern of breathing 95% premotor to phrenic Receives lots of sensory info Chemoreceptors Determines breathing pattern A normal response of a neuron to VRG decreased O2 & increased CO2 is a decrease Ventral respiratory group in activity Also relays breathing info to neurons This would decrease ventilation, Rostral (cephalic) making the situation worse Premotor to phrenic & OTHER Chemoreceptors prevent this inspiratory muscles Chemoreceptors do opposite Caudal Activity INCREASES during decreased Premotor to upper airway O2 & increased CO2 Muscles of expiration Chemoreceptors activate respiratory Determines breathing pattern centers & increase respiration PRG Two sets of chemoreceptors: Pontine respiratory group Central (brain) Involved in respiratory timing Peripheral (carotid & aorta) Pre-Botzinger Complex Primary site which generates the timing (frequency) of the respiratory rythym Central Chemoreceptors Located in the medulla Peripheral Chemoreceptors Sensitive to CO2 in blood Aortic arch CO2 crosses BBB Carotid Body Reacts w/water (carbonic anhydrase) Dopamine is transmitter Produces bicarb & H+ Sensitive to: H+ acts on central chemoreceptors O2 inducing ventilation CO2 H+ directly from blood can't H+ cross BBB Hypoxic, acidic etc. increase firing rate of afferents Respiratory Control Slowly Adapting Pulmonary Stretch Receptors (mechanoreceptors) Located in airways Relates info to brain via Vagus N. Stretch inhibits inspiration and prolonged expiration Important in infants & during exercise Rapidly Adapting Pulmonary Stretch Receptors Located in airways Info travels via Vagus N. Effect: COUGH J Receptors & Retinoic Acid Receptors (RARs) Located near blood vessels in alveoli Sensitive to pulmonary edema Vagus N. Effect: cough & tachypnea (rapid breathing) J receptors & RARs are protective Override the normal respiratory control system Increases ventilation Quicker than central chemoreceptors

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Pulmonary Function
Volume vs. Capacity Volume Non-overlapping subunits of volume Tidal Normal volume used during regular breathing Inspiratory Reserve Volume Additional amount that can be inhaled immediately following normal inspiration Expiratory Reserve Volume Additional amount that can be exhaled immediately following normal expiration Residual Volume Volume that cannot be expired from the lungs Capacity 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

Lung Volumes

Ventilation Minute ventilation Total volume moved in/out of the lungs per minute Breaths/min x tidal volume Alveolar ventilation Similar to minute but subtracts physiological dead space Anatomical dead space Trachea, bronchi etc. Nonperfused but ventilated alveoli (tidal volume - physiological dead space) x rate

Obstructive Disease Restrictive Disease Expiratory problems Pulmonary Fibrosis Emphysema & asthma Inspiration problem Harder to expire than inspire Lungs are less capable of expanding Barrel chest
Flow/Volume Curve Obstructive disease Expiration flows are relatively high during the initial phase Airways close and rate decreases below normal as airways close Restrictive disease Not as much air can be inspired Expiratory peak flows are less than normal

NORMAL

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NORMAL

OBSTRUCTIVE

RESTRICTIVE
FEV How long it takes to blow out all the air possible following maximum inspiration FEV 1 is volume expired after 1 sec Obstructive disease Takes a longer time than normal to evacuate the lungs FEV 1 is reduced FEV 1 /FVC is reduced Restrictive disease Lungs are evacuated rapidly but the total volumes are less FEV 1 is less than normal FEV 1 /FVC is normal or above normal

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Compliance & Pressures

Pressure Definitions Pleural pressure Intrapleural pressure Pressure between thoracic cage and lungs Given in cm water Negative under normal conditions (-5cm H2O) Lungs stick to thoracic wall Collapsing force (counteracting pleural pressure) is due to: Elastic nature of parynchma Surface tension in alveoli Only time there is a positive pleural pressure is during forced expiration Alveolar pressure Pulmonary or intrapulmonary pressure Pressure inside the lungs Equals 0 at rest Actually 760mmHg (or atmosphereic pressure) Inspiration Lungs expand creating a negative alveolar pressure, sucking air in Expiration Alveolar pressure and air flow reverses Transpulmonary pressure Difference between pulmonary and pleural pressure Absolute value of pleural pressure at rest Lung Compliance How much volume change will occur with a given change in pressure Little effort means lung comliance is high & normal If greater effort is required for same volume change, compliance is low Surface Tension Accounts for 2/3 of the elasticity in normal lungs Surfactant Intermolecular attraction of surfactant is much less than water Prevents alveolar collapse Intermolecular attraction becomes even less as thickness increases (during expiration)

Thoracic Cage Adds 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

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Acid-Base Cases

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Physiological Adaptations
Alveolar Oxygen Equation Ventilation Perfussion Alveolar O2 (PaO2 ) = Inspired O2 (PiO2 ) - Consumed O2 V/Q ratio PaO2 = PiO2 - O2 consumed Ratio between the amount of air PiO2 = (Patm - 47mmHg)FiO2 getting to the alveoli and the O2 consumed = PaCO2 / RQ amount of blood being sent to the RQ = 0.8 lungs PaO2 = [(Patm - 47mmHg)FiO2 ] - [PaCO2 /RQ] V/Q = alveolar vent./CO Alveolar-arterial O2 gradient CO = Cardiac Output (A-a O2 gradient) Decreased V/Q A-a O2 gradient = PAO2 - PaO2 Produced by: A = Alveolar; a = arterial Decreasing ventilation OR Increasing blood flow Results in a decrease in alveolar O 2 Forms of Hypoxia and an increase in alveolar CO 2 Hypoxia Increased V/Q Inadequate O2 available for tissue use Produced by: Anoxia Increased ventilation Total absence of O2 delivered to the tissue Decreased perfussion Hypoxemia Effect: Low O2 content in the blood Increase in PAO2 Four forms of hypoxia: Decrease in PACO2 & PaCO2 1. Hypoxic hypoxia The body normalizes V/Q through: PaO2 is below normal because either: Hypoxic vasoconstriction Alveolar PO2 is reduced Blood shunted to Blood is unable to fully equilibrate oxygenated areas with the alveolar air Raises th V/Q 2. Anemic hypoxia Bronchoconstriction Lungs work fine but O2 carrying capacity Increases the resistance & of the blood has been reduced decreases the amount of Carbon monoxide poisoning ventilation to a non3. Circulatory hypoxia perfused area Lungs & blood are fine but heart cannot Limits alveolar dead space & pump the blood to the tissues wasted work Sickle cell anemia 4. Histotoxic hypoxia Central Chemoreceptors Cells have been poisoned Detect changes in the arterial CO 2 levels Tissue is unable to use the O2 delivered Measure changes in the H+ ion Cyanide concentration in the CSF Increased Barometric Pressure (Diving) For every 10m depth, barometric pressure increases 1 atm Also add 1 atm for air pressure EX: 40m = 5 atm Effects Nitrogen narcosis N2 exhibits an effect similar to alcohol at high concentrations Rapid ascent N2 bubbles form & block circulation Bends or decompression sickness Air embolism Rapid ascent with a closed glottis Pulmonary veins may rupture, air enters blood stream, creating embolus

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Adjusting to Decreased Barometric Pressure (Altitude) FiO2 remains the same (21%) Oxygen content = (O2 capacity) x (% saturation) Altitude changes (acute): Step 1 Immediate response Peripheral chemoreceptors Increase their firing rate Increases ventilation Step 2 Increase in alveolar ventilation will increase PaO2 PaCO2 decreases Step 3 Decrease PaCO2 causes a decrease in firing rate of chemoreceptors Modifies the increased firing rate from Step 1 Patient has an greater alveolar ventilation, but not as great as in Step 1 Altitude changes (chronic): Acclimatization CSF pH is higher than normal More H+ is pumped into CSF CSF pH falls within normal range, decreasing influence of central receptors Peripheral chemoreceptors drive ventilation Increased ventilation Central chemoreceptors maintain a lower PaCO2 Increased erythropoietin release Increased mitochondria number and size Increased glycolytic enzymes Altitude sickness Related to changes in cerebral circulation Hypoxia leads to cerebral vasculature dilation Increased perfusion pressure Increased filtration Cerebral edema Can be severe & life threatening Pulmonary edema Increased pulmonary vasculature permeability Pulmonary hypertension

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Cardiac Failure/Shock
1. 2. 3. Hormonal Response - TPR BP drops Renin production (kidney) increases Renin increases Angiotensin I (AG I) production (liver) AG I is converted to AG II (lungs) by Angiotensin Converting Enzyme (ACE) AG II causes vasoconstriction a. AG II causes ADH (Anti-diuretic Hormone, Vasopressin) release (posterior pituitary) b. ADH causes vasoconstriction TPR increases BP increases 1. 2. Hormonal Response - CO BP drops Renin production increases (kidney) a. Increases H2O retention b. Increases salt retention AG I production increases (liver) AG I is converted to AG II by ACE (lung) AG II a. Vasoconstriction (vasculature) i. Increases preload 1) Increases CO b. Increases salt retention (kidney) i. Increases blood volume 1) Increases CO c. Increases ADH release (posterior pituitary) i. Increases H2O retention (kidney) 1) Increases blood volume a) Increases CO d. Increases Aldosterone production (adrenal cortex) i. Increased salt retention (kidney) 1) Increases blood volume a) Increases CO

4. 5.

3. 4. 5.

6. 7.

Cerebral Ischemia Stimulates pressor region & inhibits depressor region If cerebral tissue becomes to ischemic, sympathetic stimulation will fail Vascular collapse

Hemorrhage Changes Decreased preload & blood volume Decreases BP Stimulates short & long term reflexes Short term: Baroreceptors (neural) Long term: Hormonally (kidney) Fluid retention changes are slow, but progressive TPR changes are fast Kidney filtration Decreased BP causes decreased perfussion pressure of glomeruli Decreased urine production Fluid retention Interstitial fluid Reduced BP decreases capillary pressure Net movement into vascular space Decreased hematocrit

Shock Inadequate O2 delivery to the tissues 3 states of shock: Compensated Natural compensatory mechanisms will bring BP back up to a reasonable level Decompensated Compensatory mechanisms are inadequate & tissue death will ensure w/o clinical intervention Irreversible Nothing can be done to save the system/patient

Kidney Changes During Shock Decreased blood flow due to reflex & decreased BP Nephrotic necrosis Accumulation of cellular debris Inflammatory response

Physiology Page 25

Cardiac Failure Preload immediately increases partially offsetting the decreased contractility 2 types: 1. Compensated 2. Decompensated Compensated Reflex mechanisms gradually increase BP until an equilibrium is reached No further increase in fluid retention Preload stabilizes at a higher level Natriuretic factor Produced by atria in response to large preload stretch Causes natriuresis (water & Na+ loss) Limits effect of renin/AG & volume overload Cardiac reserve is decreased Less ability to increase CO during strenuous activity Decompensated Enough preload CANNOT be generated to adequately increase CO & BP Heart becomes TOO dilated/stretched Too much stretch actually reduces the effeciency of the heart Positive feedback loop results in complete failure

Causes of Shock 1. Hypovolemic Decreased blood volume Hemorrhage Vomiting/diarrhea Dehydration 2. Cardiogenic Inability to deliver O2 to the tissue MI etc. 3. Distributive Inflammatory cause Sepsis & anaphylaxis Massive vasodilation and tissue leakage 4. Obstructive Extracardiac compression 5. Neurogenic Spinal trauma etc. Loss of pressor output

Physiology Page 26

Cardiopulmonary Interactions
Pulmonary Capillary Wedge Pressure Ventricular Systole Taken by wedging a catheter into a pulmonary The septum depolarizes first "Stiffens" the interventricular septum capillary bed through the pulmonary artery The uninterrupted column of blood from the 1st heart sound Blood reverberation in the atria tip of the catheter to the left atrium allows Caused by AV valves closure direct measurement of the pressure in the left Ventricular pressuremust exceed diastolic atrium pressure on each side to open the semilunar valves Hydrostatic Pressure Arterial BP Mitral Valve Stenosis Blood has a difficult time moving from the left atrium to the left ventricle Blood backs up in the left atrium Increases pressure in the left atrium Pressure backs up all the way to the lungs No valves Hydrostatic pressure increases within the pulmonary capillaries Fluid moves into the lungs Pulmonary edema Dyspnea Ventricular Diastole Ventricules relax Begins before 2nd heart sound 2nd heart sound 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 Atrial pressure exceeds ventricular pressure (which can fall to 0) and blood flows passively intothe ventricles Atria has been filling the entire time, increasing pressure

COPD & Right Ventricular Failure (RVF) Progressive lung tissue loss Lung tissue is a combo of capillaries & cells holding them together Capillaries are lost The loss of pulmonary capillaries reduces the overall radius of the capillaries Increases the resistance within the pulmonary vasculature An increase in resistance increases BP Pulmonary hypertension A higher pulmonary BP means the right ventricles has to generate a higher pressure to open pulmonic valve Increased work leads to right ventricle hypertrophy Hypertrophy eventually leads to right ventricle failure Greater pulmonary pressure also leads to altered 2nd heart sound Blood in the pulmonary artery reverberates with greater force RVF can also lead to peripheral edema

Physiology Page 27

Basics of Acid-Base
Normal Values Anion gap 12 mEq/L (mean of 12) [Na+] - ([Cl-] + [HCO3]) pH 7.4 Bicarbonate 25 mEq/L (mM) PaCO2 40mmHg Osmolal Gap <10 Measured osmolality (2[Na+] + glucose + urea) [H+] 36 - 43 mM Maintenance of Body pH Lungs control CO2 - O2 exchange RBCs transport gases between lungs & tissues Kidneys maintain HCO3- and secrete H+ in urine Also regulate RBC production Ionization State of AA At low pH Both groups protonated Amino & carboxyl terminal Middle pH Zwitterionic form Creates a polar molecule One group protonated, the other deprotonated High pH Both groups deprotonated

Acids & Bases A weak acid (HA)or conjugate acid dissociates into H+ and an conjugate base (A-) pH = -log[H+] EX: pH = 7; -log[H+] = 7; [H+] = 1x10-7 M Ka = [H+][A-]/[HA]a Henderson-Hasselbalch Equation pH = pKa + log ([A-]/[HA])
Buffers in the Human Body Hemoglobin RBCs Can become protonated etc. Proteins Intracellular Can also become protonated Phosphate buffer Intracellular Bicarbonate Extracellular (plasma)

Bicarbonate Buffer System Operates principally in extra-cellular fluid (blood) CO2 is the major source of metabolic acid H2O + CO2 <==> H2CO3 Reaction occurs spontaneously in plasma Carbonic Anhydrase (CA) H2CO3 <==> HCO3 - + H+ Dissolved CO2 is in equilibrium with the CO 2 in the alveoli Availability of CO2 can be modulated by adjusting the rate of respiration pH = pKa + log([HCO3 ]/PaCO2 x 0.03) Plasma [bicarb] is controlled by the kidneys & RBCs Both contain CA

Intracellular Buffers Proteins, phosphates & K+ exchange Acidemia High plasma [H+] H+ moves intracellularly Protonates proteins K+ is exchanged Can lead to high plasma [K+] Alkalemia Low plasma [H+] H+ move out of the cell Proteins deprotonated K+ is exchanged (pumped into the cell) Can lead to decreased plasma [K+]

Biochemistry Page 28

Respiratory & Metabolic Compensation Hyperventilation Enhances CO2 excretion Lowers the PaCO2 Hypoventilation Reduces CO2 excretion Raises the PaCO2

CO2 Handling & Transport Handling (from tissue to RBC) 1. CO2 produced in the tissues enters the blood 2. CO2 enters the RBCs 3. CO2 is converted into carbonic acid by CA 4. Carbonic acid dissociates into H+ & HCO 35. H+ is buffered by hemoglobin & phosphate 6. Bicarb is transported into the blood & buffers the H+ in the plasma i. A Cl- ion is exchanged across the RBC membrane (chloride shift) Transport 70% of CO2 is in the carbonic acid/bicarb system 20% is carried as carbamino groups 10% is dissolved in plasma Handling (from RBC to lung) H+ & CO2 are released from Hb as it picks up O 2 (Haldane effect) H+ combines w/bicarb forming carbonic acid Carbonic acid is converted to CO 2 & H2O by CA As additional bicarb enters the RBC, Cl- is exchanged CO2 is expelled in the expired air

Biochemistry Page 29

Bacterial Causes of Pulmonary Infections

Bacterial Causes Typical vs. Atypical Community-aquired (CA) vs. Nosocomial Typical Community-Aquired Pneumonia Streptococcus pneumoniae Haemophilus influenzae Staphylococcus aureus

Atypical Community-Aquired Pneumonia Bacteria Mycoplasma pneumoniae Chlamydia pneumoniae Chlamydia psittaci Legionella sp Mycobacteria sp Nonproductive cough No organisms on smear No response to B-lactam antibiotics

Nosocomial Pneumonia in Immunocompromised Pseudomonas aeruginosa Staphylococcus aureus Nocardia asteroides Mycobacteria sp

NAME Streptococcus pneumoniae

Haemophilus influenzae

TYPICAL ETIOLOGY Most common CA pneumonia

COPD patients are at risk

CHARACTERISTICS Large, polysaccharide capsule

Requires X factor (blood) & V factor (NAD) for culture growth

PATHOGENESIS

Capsule Ag is major virulence factor; endotoxin

Klebsiella pneumoniae

Common nosocomial infx; alcoholics are at risk

Staphylococcus aureus Pseudomonas aeruginosa

Nocardia asteroides Actinomyces israelii

Aspiration & hematogenous (IV) modes Nosocomial; cystic fibrosis patients

Patients receiving immunosuppressive drugs Poor oral hygiene Partially acid-fast; Gram (+)

Exotoxins; enzymes

Intracellular survival

Typical Pneumonias

Microbiology Page 30

NAME Mycoplasma pneumoniae

TYPICAL ETIOLOGY Absence of unique clinical findings; "walking pneumoniae"; common in crowded settings (prison/military)
GI symptoms & headache; source of infx is usually water related (pool, air con,etc.); COPD patients have increased risk History of bird exposure

CHARACTERISTICS

PATHOGENESIS

No cell wall (no gram Not communicable person stain); grows on to person; reduced ciliary Eaton's culture movement; cold agglutinin detected by type O Rh- RBCs
Motile, flagellated No person-to-person rods; grows on transmission charcoal yeast agar; obligate intracellular Obligate intracellular

Legionella sp

Chlamydia psittaci

Chlamydia pnemoniae
Coxiella History of domestic animal exposure

Obligate intracellular

Mycobacterium AIDS patients tuberculosis

Acid-fast;

Atypical Pneumonias

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

Microbiology Page 31

Viral Causes of Pulmonary Infections

Upper Respiratory Tract Infections (URTIs) Common cold Pharyngitis Croup The Common Cold Symptoms Infection of the nasal mucosa Watery nasal discharge Cough and/or pharygitis Symptoms last 1 - 2 weeks Pathogenesis Infiltrate nasal epithelial cells Bind via ICAM receptor Cell damage Clear outpouring of fluid from lamina propria Possible bacterial superinfection Regeneration Potential Complications Otitis media Young children Pain in both ears Most common isolates are rhinoviruses

Croup Infection of the larynx, trachea & bronchi Symptoms Bark-like cough Increased respiratory rate Stridor Fever Occurs most common in children Usually caused by parainfluenza & paramyxovirus Pathogenesis Viral replication in the subglottic mucosal epithelial cells Necrosis leading to edema Edema blocks narrow airways in children leading to bark-like cough NAME Adenoviridae CHARACTERISTICS EPIDEMIOLOGY Nonenveloped; dsDNA

PATH

CLINICAL

CONTROL

Respiratory Rapid droplets or fomite replication transmission; (in nucleus) increased during winter

Pharyngeal Hand conjunctional washing fever is associated w/under chlorinated pools

No cross protection between serotypes; hand washing

Parainfluenza

Elderly & young at Croup; virus IgA important in risk for spreads by protection (but pneumonia cell fusion short lived)

Picornaviruses Rhinoviruses are members of this family; +ssRNA

Common cold;

Replicate in cytoplasm

Enterovirus

Cause infx in summer & fall

Common cold; droplet secretions & fomites ssRNA; (+) polarity; enveloped

Transmitted Remain viable for fecal/oral a long time route outside of body
IgA important No cross protection

Rhinovirus

Coronavirus

Large droplet Replicates secretion & in fomites; common cytoplasm cold; SARS

Viral Upper Respiratory Tract Infections

Microbiology Page 32

Viral LRTIs Bronchiolitis Pneumonia Hantavirus Pulmonary Syndrome (HPS) Pneumonia Infection of the lung parenchyma Results in inflammatory response Infection & inflammation result in difficult gas exchange & hypoxia

Bronchiolitis Viral replication in epithelial cells liniing the LRT causes severe, necrotizing lesions in bronchi & bronchioles Infants & young children Symptoms Wheezing Dyspnea Hypoxia Expiratory prolongation Respiratory syncytial virus is most common cause
PATH Large droplet secretions & fomites; spreads through cellular fusion CLINICAL Suspect RSV in all infants w/LRT disease CONTROL Encourage breast feeding

NAME Respiratory Syncytia Virus (RSV)

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

Hantavirus

Inhalation of virus shed in rodent urine, feces & saliva

Hantavirus Pulmonary Syndrome (HPS)

Febrile illness; bilateral diffuse interstitial edema;

Control rodent populations etc.

Viral Lower Respiratory Tract Infections

Cytomegalovirus (CMV) Replication occurs in epithelial, endothelial cells & macrophages Virus resides in latent state in organs Antigenic Drift & Shift Involved in influenza evolution Shift Viruses pass between species Segments of RNA get repackaged in new combinations when one cell is infected with more than one strain of influenze Drift Point mutations encoding HA or NA Paramyxovirus Fruit bat host
Influenza Belong to family Orthomyxoviridae Three types: A, B, & C A infects humans & animals B is species specific C causes only minor URTIs Enveloped (-) ssRNA 6-8 segments of RNA Enveloped glycoproteins: HA (hemagglutinin, binds sialic acid) NA (neuraminidase, allows virus release) Symptoms Fever Body ache Fatigue Sneezing & cough

Microbiology Page 33

Sore Throat
Common Causes of Pharyngitis (Sore Throat) Viruses 70% of acute pharyngitis has viral cause Bacteria Group A Streptococci Most common bacterial cause N. gonorrhea C. diphtheriae H. influenzae Clinical spectrum of pharyngitis Bacterial Fever Headache Abdominal pain Viral Involvement of mucus membranes Sneezing, rhinorrhea & cough Group A Beta-Hemolytic Streptococci (GABHS) Virulence factors Hyaluronic capsule Anti-phagocytic M proteins Antigenic determinant Important in rheumatic fever Toxins & enzymes C5a peptidase Inactivates C5a T protein Useful for typing Pyrogenic exotoxins Transmission Person-to-person via respiratory droplets Occurs primarily in winter & early spring Centor criteria Method used to quickly diagnose GABHS 4 criteria: Fever Tonsillar exudates Absence of cough Tender anterior cervical lymphadenopathy Testing methods Serologic Rapid test (minutes) from throat swab using monoclonal Abs Sensitivity is only 80% (negative rapid test does NOT rule out GABHS) Specificity is 95% Good for conformation, bad for diagnosis DNA-based Longer test (1 hr) with 97% sensitivity test More expensive Culture -hemolytic (clear colonies) Gram (+) cocci (chains) Catalase (-) Diagnosis Patients who have 1 or no Centor criteria should NOT be treated for GABHS Likely viral Patients with 2+ Centor criteria: Rapid strep test Antiobiotics ONLY for those with (+) test and/or all four Centor criteria Treatment DOC is Pen VK po qd for 10 days

Complications of GABHS Scarlet fever Rheumatic fever Post-streptococcal glomerulonephritis (PSGN) Scarlet Fever Follows infx w/certain strains Due to secretion of pyrogenic exotoxins (A, B, C) Function as superantigens Symptoms Fever Diffuse erythematous rash Starts on chest and spreads to trunk & extremities "Strawberry tongue"

Strawberry Tongue

Microbiology Page 34

PSGN Due to Type III hypersensitivity Ag-Ab complexes in kidneys Associated w/ certain strains Symptoms Hematuria Urine appears dark or tea colored Proteinuria Periorbital edema Hypertension with or without oliguria (decreased urine production)

Viral Pharyngitis Etiologies Adenoviruses (dsDNA) Rhinoviruses, coronaviruses Common cold Parainfluenza Colds, croup Influenza High fever, malaise, myalgia, arthralgia, sore throat Transmission Large droplet secretions and/or fomites Treat symptomatically (NO antibiotics!)

Acute Rheumatic Fever Secondary to GABHS infx Strain Ags mimic host cell Ags Leads to autoimmunity Rheumatogenic strains of GABHS Produce a thick glycoprotein capsule Epitopes of M protein mimic: Cardiac myosin Sarcolemma membrane proteins Cartilage/synovium of heart, kidney & joints Complications Onset is 1-5 weeks after strep infx Manifestations Polyarthritis Migrating large joint pain Carditis Chorea Disorganized twitching Erythema marginatum Pink rash on the trunk

Thumb Sign in Epiglottitis

Epiglottitis Rapidly progressive cellulitis of the epiglottis Can lead to ACUTE airway obstruction & death Usually caused by H. influenzae Type B Gram (-) bacillus Culture on chocolate agar X and V factor Virulence factor of H. influenzae Capsule is major virulence factor Epidemiology H. influenzae is normal floral of URT Transmission is endogenous Symptoms Progressive dysphagia (difficulty swallowing) Odynophagia (pain during swallowing) Fever Barking cough Stridor Diagnosis Mostly clinical Laryngoscopy only by experienced surgeon X-ray will show "thumb sign" Swollen, round epiglottis Culture Treatment IV antibiotics (Cephs) Any respiratory distress indicates intubation

Corynebacterium diphtheria
Microbiology Page 35

Corynebacterium diphtheria Seen in un-/under-vaccinated populations Gram (+) bacilli "Chinese letter" morphology Toxin production Inhibits host protein synthesis Causes severe inflammatory response Epidemiology Person-to-person via respiratory droplets Symptoms Sore throat Dysphagia Hoarseness Low grade fever

Mononucleosis Usually caused by EBV Also called Herpesvirus-4 (HHV-4) dsDNA Symptoms Sore throat Fever Fatigue Rash Posterior cervical lymphadenopathy Splenomegaly EBV transmission Infects B cells Via saliva EBV treatment Symptomatic Recovery in 4-6 weeks

Microbiology Page 36

Infective Endocarditis (IE)

Group A Streptococci S. pyogenes Antigenic structure Contains hyaluronic acid capsule M proteins T protein Toxins/enzymes Streptolysin O & S Cause cell lysis Hyaluronidase Increases permeability Streptokinase Activates plasminogen, producing plasmin C5a peptidase Delays accumulation of PMNs Pyrogenic exotoxins Fever, shock, erythrothemia HACEK Group Haemophilus Actinobacillus Cardiobaterium hominus Eikenella corrodens Kingella kingas Consider in culture negative cases No strep or staph Slow growing organisms found in the mouth Require CO2 for optimal growth

Haemophilus influenzae Gram (-) bacilli Encapsulated Requires X & V factor Hemin & NAD
Kingella Kingae Gram (-) bacillus Oropharynx flora

Actinobacillus actinomycetailaus Gram (-) coccobacillus Normal flora in URT

Cardiobacterium hominus Gram (-) pleomorphic rod Normal colon flora

Eikenella corrodens Gram (-) bacillus Mouth flora Causes of infection Skin & bone infx associated w/human bites Sepsis & soft tissue infx of head & neck found in IV uses who lick their needles

Etiologies of IE (IV drug users) S. aureus is most common Gram (-) aerobic bacilli are 2nd most common Pseudomonas aeruginosa Candida

Fungal Causes of IE Occurs in IV drug users Patients w/recent cardiac surgery Prolonged antibiotic therapy Most common is Candida followed by Aspergillus sp.

Etiologies of IE (Prosthetic valves) S. aureus most common, followed by: Coag. (-) Staphylococci Gram (-) aerobic bacilli Candida + Streptococcus viridans

Host Factors Contributing to IE Bacterial Factors in IE Rheumatic heart disease Organisms are always "sticky" Congenital heart disease S. viridans Mitral valve prolapse Express dextran & surface Prosthetic valve replacement adhesion Fim A protein Predisposing cardiac lesion S. sanguis can bind to platelet receptors Leads to platelet accumulation S. bovis has high dextran levels Fibrin accumulation on valve serves S. aureus has increased binding to as ideal site to trap bacteria fibronectin Lab Identification Obtain at least 3 blood cultures, 15 mins apart

Microbiology Page 37

Infectious Etiologies of Myocarditis Coxsackie viruses Corynebacterium diphtheria Borrelia burgdorferi Trypanosoma cruzi Chlamydia

Corynebacterium diphtheria Gram (+) bacilli Pathogenesis Mucosal colonization Toxin elaboration Diphtheria toxin Abrupt arrest of protein synthesis

Mycoplasma Chlamydia Lack a cell wall Obligate intracellular organisms Resistant to penicillins Chlamydia pneumoniae Inhibited by tetracyclines & erythromycin Affinity for mammalian cell membranes Mycoplasma pneumoniae Coxsackie Viruses Pathogenesis Picornavirus family Adhesion & fusion to membranes of Small, nonenveloped ssRNA viruses epithelial cells Transmitted by fecal/oral route Generation of H2O2 & superoxide radicals Cytolysis Myocarditis Assoc. w/Chagas' Disease Trypanosoma cruzi Myocarditis Assoc. w/Lyme Disease Parasites invade myocytes Borrelia burgdorferi Bacteria adhere to connective tissue of heart Rupture of myocytes releases parasites and leads to mononuclear infiltrate in the heart Manifested as conductive defects or mild
cardiomyopathy

Microbial Role in Initial Lesions of Atherosclerosis Chlamydia & CMV Inflammatory mediators are released from activated endothelial cells NO Macrophage chemotactic protein-1 (MCP-1) IL-1 TNF TGF-

Microbiology Page 38

Familial Hypercholesterolemia & Long QT Syndrome

Dietary Cholesterol Chylomicrons Deliver dietary TAGs to adipose, muscle & liver Enters chylomicrons From intestines via lymphatics In blood, aquires apoC-II & apoE from plasma HDL At adipose & muscle Fatty acids of chylomicrons removed Lipoprotein lipase (LPL) ApoC-II in chylomicrons activates LPL Fatty acids absorbed Chylomicron remnant is composed of cholesterol, apoE & apoB-48 Liver Synthesis & LDL/HDL Cholesterol 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 LDL Long half life 75% of LDL uptake is at the liver HDL Facilitates removal of cholesterol from cells Transports cholesterol to liver for bile acid synthesis

Classification of Lipoprotein Disorders Type IIa Hyperlipidemias LDL elevated Familial hypercholesterolemia (FH) High cholesterol Dominant inheritance Type IIB Defective LDLR on cells leads to increased circulating LDL & VLDL elevated LDL High cholesterol & triglycerides Can also be a problem w/ApoB-100 (LDL binding protein) but this is rare In the liver Insulin & T3 increase the binding of LDL to receptors Glucocorticoids decreases binding In diabetes & hypothyroidism there is an increase in hypercholesterolemia Symptoms Xanthoma Benign fat deposits beneath the skin Corneal Arcus Common in older patients but rare in Corneal Arcus young people LDL Receptor Gene Xanthelasma Demonstrate exon shuffling Xanthomas on skin of eyelid Introns allow recombination to Compound heterozygotes possible occur between exons and allow Two different mutations inherited two different new proteins to evolve w/similar mutations from seemingly normal parents blocks of important information The combination of two heterozygote defects in different areas (LDLR, endocytosis failure, etc.) involving LDL intake mimics a homozygous FH patient

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

Genetics Page 39

Long QT Syndromes 1:3000 Prolonged QT interval Hallmark arrythmia Looks like twisted ribbon "torsade de pointe" Primary symptom Syncope (loss of consciousness) Cardiac ion channel defects Usually K+ Decreased repolarization Clinical Palpitations Syncope Seizures/sudden death

Genetics Page 40

Obstructive & Interstitial Lung Disease

COPD Chronic Obstructive Pulmonary Disease Actually a grouping of four illnesses: 1. Chronic bronchitis 2. Emphysema 3. Asthma 4. Bronchietasis Two of these are a result of smoking Chronic bronchitis Causes obstruction of air flow due to edema, necrosis, fibrosis, & recurring infx Emphysema Causes obstruction of air flow due to loss of lung's elastic recoil Allows small airways to collapse at beginning of expiration Gross pathology resembles "cigarette burns" in the lung Consequences of Smoking Tobacco & 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 Increased alveolar macrophages Impaired macrophage function Increased neutrophil & macrophage elastase production Loss of elasticity/destruction of alveolar walls Squamous metaplasia of respiratory epithelium

Emphysema Strong hypercarbic drive "Pink Puffer" Struggles to breath Patient is often agitated etc. Lung tests show prolongation of a full forced expiration Two forms: Centrilobular More dilation of the respiratory bronchioles & their alveoli Early smoker's emphysema Panlobular (panacinar) Involves the acinus uniformly Caused by -1 protease inhibitor ("antitrypsin") deficiency Small airways collapse during forced expiration Patients will hyperinflate their chest "Barrel chest" Increased total lung volume 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 Small bronchi are abnormally responsive to various stimuli that cause constriction/inflammation Produces dyspnea, wheezing & cough Attacks are often triggered by: Type I hypersensitivity IgE-mediated mast cell degranulation Allergic Asthma When patients attacks are triggered by IgEmediated hypersensitivity Eosinophil proteins crystallized as "CharcotLeyden crystals" in sputum of allergic asthmatics Also form Curschmann's spirals Coily strigns of altered goo from the little airways

Pathology Page 41

Obliterative Bronchiolitis Constructive bronchiolitis Lesion found in a minority of smokers Dense fibrosis under the epithelium of bronchioles with serious-to-total compromise of the lumens Look for underlying: Autoimmune disease of the lung SLE, RA, Sjogren's Occupational disease Chemicals etc. Penicillamine Adenovirus infx Lung transplant rejection GVH disease Measles pneumonia Ciliary Dyskinesia Syndromes Huge group Includes Kartagener's (no dynein arms) Clinical Recurrent respiratory infx Infertility (in men) Situs inversus (50% of cases) Interstitial Restrictive Lung Disease Stiff lung / fibrosing alveolitis Longstanding inflammatory damage leading to fibrosis of the alveolar walls Pulmonary compliance decrease Ventilation & perfusion are mismatched Blood flows through unventilated scar tissue Diffusion barrier PulmonaryBP increases "Velcro crackles"

Bronchiectasis Ectasis ("pulling wide" of the bronchi Defined by the permanent cylindrical dilation & ulceration of part of the bronchial tree Clinical Chronic cough Sputum production (Lots, as in cup loads) Ectasis results from contraction of scar surrounding the bronchus and atelectasis (alveolar collapse & fluid consolidation) Complicates respiratory infx, asthma, etc. Proximate cause is a bacterial infx

Obstructive Sleep Apnea Many episodes of upper airway obstruction each night As patient enters deep sleep, upper airway closes Results in thrashing, snorts, and finally partially wakes up Cycle repeats every few minutes Patient is unable to enter deep sleep or sleep soundly Symptoms Morning headaches Narcolepsy Cognitive/behavioral changes Social issues Treatment Have the patient sleep on one side Uvulva flops out of the way Protriptyline Helps maintain a patent airway Surgery Uvulopalatophatyngoplasty Tonsillectomy PEEP machine "Ondine's Curse" Central hypoventilation Diminished respiratory drive from the brain

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 Pneumonitis Responds well to glucocorticoids Uniformity of histologic changes All septa involved equally No "honeycomb cysts" Lymphangioleiomyomatosis Rare 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

Organizing Pneumonia Lesion in which little pieces of loose connective tissue develop & plug the respiratory bronchioles, alveolar ducts & spaces Air flow is obstructed Lung expansion is restricted
Alveolar Proteinosis Surfactant & proteinaceous goop fills the alveoli Rarely includes fibrosis Symptoms Dyspnea Cough up "white jello" CT shows "crazy quilt" pattern of involved and uninvolved lobules Bronchial lavage is mainstay of therapy Sarcoidosis Non-caseating granulomas Rash Erytema nodosum Painful red bumps on the front of the legs

Idiopathic Pulmonary Fibrosis (IPF) Hamman-Rich syndrome Pulmonary fibrosis Often occurs in middle age and progresses to death Grossly, lung looks like a course sponge Feels firm Alveoli are thickened Show chronic inflammation Ongoing, unexplained, self-perpetuating inflammation Appears in many other syndromes
Goodpasture's Disease Antibodies against the basement membrane of lung & kidneys Type II immune injury

Pathology Page 43

Chest Infections
Lung Infections Pneumonia Inflammation in the alveolar air spaces Pneumonitis Inflammation limited to the interstitium Bronchopneumonia "Lobular pneumonia" Patchy lung infx Often nosocomial Causes of infx: Many hospital patients don't cough and clear their lungs Medications, old age etc. Poor mucociliary elevator function Poor alveolar macrophage function Pulmonary edema

Lobar Pneumonia Infx of an entire lobe produced by a virulent organism Most common cause is Streptococcus pneumoniae Gram (+) diplococcus Klebsiella pneumoniae Common cause in deteriorated alcoholics Gram (-) bacillus w/ capsule Victims cough up sticky slime Four succesive stages: 1. Hyperemia & edema Bugs divide like crazy Blood vessels dilate & leak 2. Red hepatization Inflammation progresses Vessels leak fibrinogen Forms fibrin in the alveoli RBCs leak also 3. Gray hepatization Fibrin dominates RBCs break down ("gray") 4. Resolution Plasmin clears fibrin Lung returns to normal Complications Pleural surfaces overlying infection are usually involved (painful) Necrosis & abscess formation Infection worsens in pleural space filling with pus ("empyema")

Legionnaire's Disease Legionella pneumophila Need silver stain Common in standing water Symptoms Bad "chest cold"

Pneumocystis Pneumonia Histologically resembles "crushed pingpong balls" Caused by Pneumocystic jirovecii (carinii) Common in AIDS patients

Lung Abscess PMLs plus necrosis in a confined space Mechanisms 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 Anaerobic bacteria are often present Abscess will eventually rupture into an airway

Pathology Page 44

Tuberculosis (TB) Caseous granulomas Body over-response wreaks havoc on surrounding tissues, forming the granulomas Primary TB Original infection Ghon focus (a single lesion) occurs just under the pleura in the midportion of one lung (bestventilation) Progressive TB Overwhelming primary infx Secondary TB Active TB Bacilli escape the original Ghon focus or more bacteria enter body from outside Arrested TB Secondary TB that has calcified and/or been largely replaced by collagen Progressive pulmonary TB Spreads throughout the lung & can produce empyema involving the pleural cavities Often see cavities in the lung after debris has been coughed up Miliary TB Results when many TB bacilli enter the blood but the granulomatous response is good

Viral & Mycoplasmal Pneumonia "Primary atypical pneumonia" All cause interstitial pneumonitis Respiratory synctial virus Multinucleated epithelial cells in the bronchioles Metapneumovirus Causes wheezing in young patients Tied w/RSV as most common viral infx in transplanted lung Lethal influenze w/o Staph superinfection presents primarily as necrosis along the epithelium of the bronchi & bronchioles Also may be diffuse alveolar damage The severe H5N1 strain owes its' deadliness to "cytokine storm" affecting the lungs Herpes simplex Ulcerative tracheobronchitis in immunocompromised hosts "Herpes cells" Single, intranuclear inclusion surrounded by a clear hal SARS Coronavirus Reproduce in & destroy type II pneumocytes Preponderance of macrophages in inflammatory infiltrate Diffuse alveolar damage

Pathology Page 45

Heart & Lungs: The Great Patterns

Pulmonary Congestion & Edema Pulmonary edema Results from same factors that produce edema in the rest of the body: Increased venous hydrostatic pressure (LHF) Fluid overload Decreased albumin Hydrostatic pressure pushes fluid out of capillaries Lymphatic obstruction Endothelial damage Pnuemonias, hantavirus, poisons (phosgene) Physical asphyxiation Acute CNS injury Opiate overdose High altitudes Viens & arteries participate in hypoxic pulmonary vasoconstriction response Pulmonary BP increases Forces fluid out of lung capillaries & causes some to burst Pulmonary Embolization & Infarction Pulmonary thromboemboli are common and often originate in the deep veins of the legs Vichow' Triad 1. Stasis RHF Sickle cell anemia Morbid obesity 2. Hypercoagulable states Cancer (especially pancreas) Burns, surgery & trauma Pregnancy Lupus anticoagulant Smokers 3. Damaged endothelium IV lines Pulmonary thromboembolism associated problems: Instant death Saddle embolus Acute cor pulmonale RHF Increased in non-perfused pulmonary dead space Ischemia w/ surfactant loss & alveolar collapse (atelectasis) Infarction May occur if bronchial circulation is inadequate due to LHF, shock etc. Pulmonary Hypertension Results/initiates a positive feedback cycle with ever increasing pressure, resistance & vascular thickening Initial insult increases one of the above three, then: 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 Causes: LHF (especially mitral stenosis) Increased blood flow into the pulmonary arteries L-to-R shunts or lung resections Increased pulmonary vascular resistance Alveolar hypooxygenation High altitude, ARDS, emphysema, etc. Causes pulmonary arteriole constriction Pulmonary emboli

ARDS
Pathology Page 46

ARDS Results from anything that severely injures the Type I pneumocytes & capillary endothelial cells throughout the lung Two types Pulmonary ARDS Caused by direct lung injury Extrapulmonary ARDS Remote effect of injury elsewhere Outcome depends on severity of illness, not the type Causes Sepsis, shock Oxygen toxicity Lung contusion Viral Infx Influenza, measles, herpes, hantavirus Burns, radiation Drugs, poison gas Silo-filler's disease Inhaled N 2 oxidizes into nitric/nitrous acid Near-drowning Heart-lung machine Aspiration of gastric juices Severe multiorgan injury Blood transfusion Abs against HLA and/or neutrophils in donor plasma IL-8 is often found in fluid from lungs w/ ARDS Results of ARDS Pulmonary edema Cell necrosis Fibrin is released into alveoli (produces hyaline membranes) Loss of surfactant Alveoli collapse As Type I pneumocytes are destroyed, Type II pneumocytes divide to replace them Type II pneumocytes are not as permeable to O2 Fibrosis Lung more prone to bacterial infx ARDS results in death 50% More conservative treatments improve outcome Less transfusions, lower tidal volumes, lower ventilation pressures, less fluid overloading
Atelectasis Collapse of alveoli Obstructive atelectasis "Absorption atelectasis" Resutls from non-ventilation of alveoli that are still perfused Seen distal to tumors, foreign bodies, etc. If airways is obstructed, alveoli will fill w/ surfactant Surfactant will be engulfed by macrophages "Golden pneumonia" First CXR sign of lung cancer Compressive atelectasis Results from something in the pleural cavity Blood, exudate, tumor, air

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Asthma & Allergic Rhinitis

Key Terms Allergen Have little or no intrinsic activity by themselves Allergy Clinically adverse reactions to enviornmental Ags mediated by: Allergen specific IgE Mast-cell & eosinophil TH2 type of response IL-4, IL-5 & IL-13 Atopy Propensity for developing immediate hypersensitivity reactions to common enviornmental allergens Allergens A very small group humans are routinely exposed to Proteins & glycoproteins Activate innate immunity by: Enzymatic activity Activation of PRRs Bias the immune system towards TH2 type response Properties Der p 1 Cysteine protease of dust mites Activates innate immunity via cleavage of complement components Ragweed pollen Intrinsic NADPH oxidase activity Rapidly increases the level of ROS in lung epithelium Allergens contain substances that are recognized by TLR2, TLR4 or mannose receptor Endotoxin Chitin -glycans Aeroallergens Airborne proteins or glycoproteins Pollinating trees/grasses Mold spores Animal dander Dust mite/cockroach secretions Indoor allergens are associated w/ asthma Outdorr allergens are associated w/ allergic rhinitis

Allergic Diseases Result from harmful immune responses Associated w/ generation of IgE Driven by non-infectious Ags Innate immune response

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Asthma Factors that influence atopy Genetic Specific HLA alleles Polymorphisms of IL-4 Defects in target organ Enviornmental Excessive hygiene Triggers Cytokine balance Factors favoring TH1 Presence of older siblings Early exposure to day care Rural enviornment Leads to protective immunity Factors favoring TH2 Widespread use of antibiotics Western lifestyle Urban enviornment Diet Sensitization to allergens Leads to allergic disease (including asthma) Development of asthma Predisposition factors Enhancers Viruses, allergens, pollutants Triggers All genes implicated in asthma development encode for some kind of immune response Infections & asthma 1st born children more likely to develop rhinitis & asthma Risk does not apply to children that attend daycare at an early age Increased exposure to respiratory viral infections is protective against development of allergy & asthma Once asthma is established, viruses are a general trigger

Allergic Rhinitis Rhinitis Inflammation of the nasal mucous Clinically Nasal congestion, Rhinorrhea, Nasal itching, Sneezing Allergic rhinitis Airborne Ags enter nasal tissues Acute allergic rhinitis Occurs within minutes IgE-mediated degranulation Histamine, Tryptase, Leukotrienes, PGD2 Leakage & dilation of vessels Edema & occlusion of nasal passages

Sensitization to Allergens
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1. 2. 3. 4. 5.
6.

Sensitization to Allergens Activated T cell differentiates into TH2 cell Clonal expansion of activated T cell TH2 cells produce IL-4 & IL-13 Nave B cell (Ag presenting) picks up allergen and processes it for T H cell presentation Activated TH2 cell recognizes allergen/MHC-II a. Secretes IL-4 & IL-13 B cell is fully activated and class switches to IgE production a. Becomes plasma cell Immediate phase FcERI bound to mast cells & basophils High affinity for Fc region of allergen-specific IgE Mast cells -> tissue Basophils -> circulation Crosslinking of FcERI leads to degranulation and release of inflammatory mediators Occur within the 1st hour after crosslinking of IgE-FcERI Tissue specific effects Airway constriction Wheal-and-flare reactions in the skin Generalized symptoms Edema and pruritis (itching) Systemic symptoms Anaphylaxis Chronic disease development Cytokines from mast cells lead to recruitment of macrophages, T H cells, & eosinophils IL-4, IL-5, IL-13, histamine, leukotrienes, eicosanoids (HETEs) TNF- secretion Further inflammatory response Eventually leads to airway damage& remodeling Smooth muscle hyperplasia/trophy Mucus gland hyperplasia Activation of fibroblasts Collagen deposition Can eventually lead to COPD Treg cells could suppress allergies by responding to specific clonal cells & supressing activation IL-10

Cause of Increasing Prevalence of Allergies Hygiene hypothesis Immune system at birth is TH2 skewed Helminthes or virus infx restore a healthy balance of T H2 / TH1 response In absence of these stimuli (West), TH2 cytokine production persists Resulting in allergies & asthma Environmental changes in indoor air quality Lifestyle changes

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Respiratory Distress in Kids

Cardiopulmonary Emergencies Anticipation of CP Arrest Absence of effective ventilation, Pediatric assessment triangle: 1. Appearance circulation or both Cardiopulmonary arrest 2. Breathing Three components: 3. Circulatory status Pump Appearance Lungs Patients muscle tone Circulatory volume Poor tone indicative of serious problems Clinical Interactiveness Sedated, ill-appearing child Lack of interaction w/ toys & parents is a bad Can progress to hypoventilation sign Consolability & death Classic signs Restlessness & agitation are signs of hypoxia Nasal flare Look/gaze Tracheal tug Unfocused gaze is idicative of altered mental Sternal retractions status Decreased breath sounds Speech/cry Stridor (high pitched sound Loud cry is good Hoarse/muffled cry indicates airway in upper airway) Wheeze obstruction Tripod position Weak cry is a sign of significant illness Differences from adults Breathing Arrests in pediatric population Retractions Inability to cry or talk generally due to lung & Tripod seating circulatory components Progressive shock Airway sounds Asthma, croup, pneumonia Stridor Wheezing Rales Causes of CP Emergencies Moist sounds heard through the Complete or severe upper airway stethoscope obstruction Rhonchi Foreign body Added sound with a musical pitch Angioedema from anaphylaxis occuring on inspiration or expiration Epiglottis Grunting Croup Guttural sound Injury Snoring Tension pneumothorax Air leaking into pleural cavity w/ Circulation Skin mediastinal structure shift to Good signs are pink & warm nail beds, contralateral side mucus membranes, palms & soles Cardiac tamponade Capillary refill Buildup of fluid in pericardial sac Normal refill (nail bed) will take less than 2 Pulmonary embolism seconds in limb held above heart level Seen in kids w/ central lines Heart rate changes Other causes Tachycardia followed by bradycardia Flail chest Cyanosis 3+ rib fx Significant loss of blood Massive blood loss CNS injury Metabolic disease

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Other Common Causes of Respiratory Distress Respiratory tract conditions Infx Often develop more gradually Patients are often febrile & ill in appearance Retropharyngeal &peritonsillar abscesses Typically cause sore throat, difficulty swallowing, & local pain & swelling Hoarse voice Croup & tracheitis Croup is the most common cause of infectious airway obstruction in kids <36 m.o. Often viral (parainfluenza) Tracheitis is often a secondary bacterial infx to croup Stridor -> THINK CROUP Bronchilitis RSV, influenza, parainfluenza & adenovirus Characterized by URI symptoms Progressive cough Wheezing/atelectasis Pneumonia Bacteria are more localized Higher fiver & ill appearance Asthma Inflammation, edema, bronchospasm & mucus Anaphylaxis Often due to food or medications Foreign body Causes compression leading to respiratory distress Stridor, drooling or choking Chest wall abnormalities Trauma Flail chest Expiration produces visible chest wall changes Cardiovascular conditions Pulmonary edema

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Influenza A
Characteristics Surface glycoproteins Neuraminidase (NA) Assists with budding & viral release 9 subtypes (N1-N9) Hemagglutinin (HA) 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 M2 Involved with penetration Levels of Virulence Highly pathogenic Immune system "overcompensates" Results in "purulent" pneumonia Ends up looking like respiratory distress Low pathogenic Contained within LRT

Epidemiologic Concerns Incubation is short (1-4 days) Reservoir Respiratory tract Range of viral shedding 7 days before & 4-7 days after onset of symptoms
Modes of Transmission Fomites Respiratory droplets Endogenous Vector borne

Pharmacological Treatments NA inhibitors Sialic acid analogs Effective against influenza A & B Oseltamivir Adverse effects: GI: nausea & emesis (vomiting) Sodium benzoate displaces bilrubin in children <1 y.o. (contraindicted) Pro-drug given orally Eliminated renally Zanamavir Delivered intranasally or inhaled Adverse effects: Wheezing & bronchospasms (pre dose w/-agonist) Renal elimination Poor bioavailability (<5%) Approved for treatment of patients >7 y.o.; approved for prophylaxis >5 y.o. M2 inhibitors Insignificant efficacy due to viral resistance Amantadine & Rimantadine

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Drugs for Treating Asthma & COPD

-Agonists MOA Stimulates adenylate cyclase (AC) Increases cAMP production Decreases bronchial tone Bronchodilation Can be long and short acting Long acting Not for acute symptoms Beneficial when added to inhaled corticosteroids Black Box Warning Salmeterol may increase risk of asthma related death Short acting For acute relief of bronchospasm Adverse effects Sympathomimetric effects Tachycardia Nervousness Increased BP Dizziness, headache GI Nausea, vomiting, bad taste Hypokalemia Clinical Use Acute therapy Exercise induced asthma Corticosteroids Anti-inflammatory agents Clinical Uses Inhaled Long term controller medication Asthma (long term control) COPD (only severe) Oral Help speed recovery from severe exacerbations AE Systemic Lots of AE but usually only w/long term and high doses Inhaled Oral candidiasis (thrush) Rinse and spit after puffs Benefits of daily inhaled corticosteroid use Fewer symptoms Fewer exacerbations Reduced use of quick relief meds Methylxanthines MOA Unknown Cellular actions Interference of uptake & storage of Ca++ by SR Adenosine receptor block Inhibits breakdown of cAMP Chemically similar to caffeine Relaxes bronchial smooth muscle May enhance mucociliary clearance Clinical Uses COPD Asthma (alternative to -agonist) Adverse effects Think caffeine

Anticholinergics (Antimuscarinic) MOA Inhibits Ach induced bronchoconstriction Muscarinic receptors Stabilizes mast cells Clinical Uses COPD Not very effective for asthma AE Vary by route Inhalation Sore throat, hoarseness Intranasal Nasal irritation

Mast Cell Stabilizers Inhibits mast cell degranulation Suppresses chemoattractant activity Reduces hyperreactivity of bronchi BUT has no effect on bronchial relaxation Prophylactic medication Clinical Uses Asthma maintenance therapy Allergic rhinitis

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Leukotriene Inhibitors 5-lipooxygenase inhibitors Prevent formation of leukotrienes Receptor antagonists Block leukotriene receptors Clinical use Long term control in mild asthma Adverse effects Liver toxicity Zafirlukast only Hypersensitivity Flu like shyndrome Chills, fever etc. Zafirlukast only

Anti-IgE Clinical Use Moderate to severe uncontrolled asthma Adverse effects Life-threatening anaphylaxis

Medications for COPD Same as asthma but no: Leukotriene antagonists Mast cell stabilizers Anti-IgE

Stepwise Approach for Managing Asthma 1. Step 1 Rapid acting -agonist as needed 2. Step 2 Reliever medication plus a single controller Add low-dose inhaled glucocorticosteroid 3. Step 3 Reliever medication plus one or two controllers Combine low-dose inhaled glucocorticosteroid w/inhaled long-acting -agonist 4. Step 4 Reliever medication plus 2+ controllers Medium or high dose inhaled glucocorticosteroid combined w/long acting inhaled -agonist 5. Step 5 Reliever medication plus additional controller options Additional oral glucocorticosteroids Addition of anti-IgE

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Asthma/COPD Drug Chart

CLASS 2 agonists
2 agonists

RESPONSE NAME(S) TIME Short acting

Long acting

Prefix/ Suffix

ASTHMA/ COPD Both

Both

Albuterol, Levalbuterol, Pirbuterol -rol

Salmeterol, Formoterol (rapid action), Bambuterol Theophylline, aminophylline Ipratropium (Short acting), Tiotropium (long acting) -rol

Methylxanthines Both Anticholinergics Both

-phylline Both -pium COPD (not very effective for asthma)

Bronchodilators

CLASS
Mast cell stabilizers

RESPONSE TIME

NAME(S)

PREFIX/ SUFFIX
NA

ASTHMA/COPD
Asthma

Long acting Cromolyn, Nedocromil

Corticosteroids Short acting Prednisone, Prednisolone, (systemic) Dexamethasone Corticosteroids Long acting Beclomethasone, Budesonide, (inhaled) Flunisolide, Fluticasone, Triamcinolone, Ciclesonide
Leukotriene Inhibitors Anti-IgE Long acting Zafirlukast & Montelukast (receptor antagonists), Zileuton (lipoxygenase inhibitor) NA Omalizumab

NA NA

Both Asthma & COPD (severe)

-kast Asthma (receptor only) NA Asthma

Anti-Inflammatory

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ACE Inhibitors & ARBs

ACE Inhibitors Angiotensin Converting Enzyme Inhibitor Drugs Suffix -> -pril MOA 1. Decreased formation of AG II Reduced vasoconstriction -> vasodilation 2. Decreased formation of AG II Decreased aldosterone release Decreased fluid volume 3. Reduced bradykinin breakdown Vasodilation Clinical considerations All ACE inhibitors have similar uses and AE No reason to favor one over the other Differ in potency, pharmacokinetic properties & active entity Captopril is the only active drug, all others are prodrugs Clinical uses Hypertension Do NOT have reflex sympathetic action 1st choice for patients w/diabetes, chronic kidney disease, & LVH HF Prevent or delay progression of heart failure Decreases incidence of death, MI & hospitalizations In patients with high risk of developing HF, structural abnormalities and/or those with a previous MI Diabetic nephropathy Prevent or delay kidney disease in type 1 & 2 diabetes Improved renal hemodynamics
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 Improved renal hemodynamics Proteinuria Stroke prophylaxis Post MI ACE inhibitors have NO significant effect on cholesterol levels Adverse effects Dry, hacking cough Angioedema & anaphylaxis Hyperkalemia Drug interactions w/K+ sparing diuretics Contraindicated in pregnancy & renal artery stenosis NSAIDs may blunt antihypertensive action ARBs Angiotensin Receptor Blockers Drugs Suffix -> -sartan Clinical uses Same as ACE inhibitors Do NOT differ significantly from ACE inhibitors for all causes of mortality & hospitalization due to heart failure ACE inhibitors are first line due to more data FDA approved HF ARBs Candesartan Losartan Valsartan Adverse effects Angioedema is less likely with ARBs than with ACE inhibitors Cross reactivity is possible 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 Renin Inhibitor Drug Aliskiren Blocks renin conversion of Angiotensinogen to AG I Approved for treatment of hypertension

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Vasopressors
Responses Elicited by Stimulation 1 Heart Increases rate & force of contraction Kidney Increases renin secretion 2 Lungs Bronchodilation Vascular smooth muscle Relaxation Responses Elicited by Stimulation 1 Vascular smooth muscle Contraction 2 Mixed responses 2 agonist (Clonidine) inhibits release of neurotransmitter of nerve terminal Reduces sympathetic output If drug effects both 2 and 1 , 1 will dominate response

Vasopressors All catecholamines are rapidly inactivated by monoamine oxidase (MAO) and catechol -Omethyltransferase (COMT) MAO and COMT are found in the gut and liver All catecholamines are given parenterally Also catecholamines have low bioavailability & short plasma half-lives

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Vasopressor Chart
NAME Epinephrine GROUP RECEPTOR TARGETS PHARM. ACTIONS Bronchial smooth muscle relaxation; increase HR, BP, contractility & CO Increase BP, vasoconstriction, vascular resistance, HR & contraction; barorecepter reflex can decrease HR at lower doses THERAPEUTIC USES Severe allergic rxns (anaphylaxis); cardiac arrest Acute hypotension; shock (cardiogenic or septic); Caution-> decreases renal blood flow

Direct-acting and ; dominates nonselective (low doses) catecholamines

Norepinephrine Direct-acting Powerful agonist nonselective catecholamines

Isoproterenol

Direct-acting nonselective catecholamines

Intense stimulation of Decreased CO HR & contraction force (increase CO); dilates arterioles of skeletal muscle (decreased vascular resistance) ( 2 action); Bronchodilation (2 action) Increase GFR & natriuresis; increase HR, contractility & systolic BP Treatment of decreased CO, hypotension (septic & cardiogenic shock)

Dopamine

Dopamine receptors > 1 > 1

Dose dependent: low dose-> dopamine receptors (vasodilation), medium dose-> dopamine receptors + 1 (increases CO), high dose-> 1 (increases BP)

Dobutamine

Selective 1

Increases CO & contractility

Severe HF (symptomatic benefits only) Alternative to epinephrine; supportive treatment of severe hypotension in shock

Vasopressin

Non-adrenergic Vasopressin receptors Contraction in (non(smooth muscle & capillaries, arterioles & catecholamine) renal tubules) venules peripheral vasoconstrictor

Catecholamines & Vasopressin

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Beta & Calcium Channel Blockers

Responses Elicited by Stimulation 1 Heart Increases rate & force of contraction Kidney Increases renin secretion 2 Lungs Bronchodilation Vascular smooth muscle Relaxation Blocker Properties Differentiate between drugs by: Cardioselectivity Lipophilicity Hydrophilic drugs tend to have fewer CNS adverse effects Partial agonist activity (intrinsic sympathomimetic activity; ISA) Blocker Drugs Suffix -> -olol Except Carvedilol 1 & nonselective antagonist 1 selectivity Acebutolol Atenolol Bisoprolol Betaxolol Metoprolol ISA Pindolol

Blockers MOA Antagonize the effects of catecholamines at the receptor through competition 1 receptors: Cardiac myocytes & conduction cells SA & AV nodes, Purkinje fibers 2 receptor: Bronchial and peripheral vascular smooth muscle Some blockers are partial agonists and can cause partial receptor activation if endogenous catecholamine levels are low
Blocker Effects Cardiovascular effects Decrease contractility, CO, renin release & AV nodal conduction (HR) Blunts sympathetic reflex w/exercise Adverse effects Respiratory tract Increase airway resistance Patients w/ashtma Cholesterol Lowers HDL & raises VLDL Blood glucose May inhibit recovery from hypoglycemia (caution in diabetic patients) Bradycardia, hypotension, heart block Sexual dysfunction Fatigue, depression & insomnia

Blocker Clinical Correlations Clinical uses Hypertension MI prevention Arrythmias HF 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 Use on the 3 agents: 1. Bisoprolol 2. Carvedilol 3. Metoprolol Stable angina Migraine headaches "stagefright" Clinical considerations Use 1 selective for patients with: Asthma Peripheral vascular disease Always start w/low dose and increase slowly Taper when drug is discontinued

Calcium Channel Blockers (CCBs)

CCB Effects
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Calcium Channel Blockers (CCBs) Intracellular Ca+: Triggers contraction Required for pacemaker activity Bind to specific Ca+ channels in the myocardium & vascular smooth muscle Agents Nondihydropyridines Verapamil Diltiazem Dihydropyridines Suffix -> -pine Properties Based on different binding sites Dihydropyridines Vascular (Nifedipine -> prototypical) Nondihydropyridines Diltiazem In-between, some vascular but mostly myocardial Verapamil Myocardial Clinical uses Hypertension Angina (including variant) Arrythmias Migraine prophylaxis

CCB Effects General Cardiac Reduced contractility Slowed conduction through AV & SA nodes Decreased HR Vascular Vasodilation Cardiac effects Strength of drug (for cardiac effects) Verapamil > Diltiazem > Nifedipine Reduces angina through reduced cardiac workload (result of decreased contractility and HR) Can cause serious cardiac depression and A-V block Vascular effects Nifedipine > Diltiazem > Verapamil Nifedipine reduces angina through coronary dilation Can cause tachycardia Adverse effects Nondihydropyridines AV block, sinus bradycardia Flushing, headache & hypotension Constipation (Verapamil) Dihydropyridines Vasodilation related Peripheral edema Flushing, headache, syncope, hypotension Dizziness Potential for lots of drug interactions!

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Infectious Endocarditis
Bacteremia & "Vegetations" Streptococcal Infections Always requires: Native valve Micrbiological test IV drug abuser Bacteriocidal antibiotics Obtain blood samples Lengthy treatment Isolate bacteria Via IV Susceptibility testing for Penicillin G Often requires combination treatments If yes, S. viridans Treatment is Pen G for 4 weeks Allergy influences: None -> Pen G Enterococcal Infections Mild -> Ceftriaxone (4 weeks) Partial penicillin resistance is common Severe/Anaphylaxis -> Vanc (4 Vanc is not always bacteriocidal weeks) Always add Gentamicin w/cell wall If No, Pen-resistant S. viridans inibitor Treatment is Vanc (4 weeks) Often prolong treatment Prosthetic valve Native valve Same drugs & principles Penicillin sensitive Prolong & intensify treatment Ampicillin (4 weeks) + Bacterial adhesion & dormancy is greater Gentamicin (4 weeks) 6 weeks of therapy Penicillin hypersensitivity

Vanco (4 weeks) + Gentamicin (4 weeks) Penicillin resistant Ampicillin + Sulbactam (4-6 weeks) + Gentamicin (4-6 weeks) OR: Vanc (4-6 weeks) + Gentamicin (4-6 weeks) Prosthetic valve Prolong treatment for 6 weeks Vanco Resistance Enterococcus Treat w/Linezolid (8 weeks) Bacteriostatic, but have no other choice Linezolid interacts w/MAOs

Vanco + Gentamicin Both can impair kidney function Renal clearance can result in nephrotoxicity

Sulbactam Inhibits -lactamase Irreversibly inactivates -lactamase Spares ampicillin Alone it has no intrinsic antibiotic effect

Pseudomonal Endocarditis Treatment is Ticarcillin & carbenicillin

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Staphylococcal Infections Penicillin resistance is likely Methicillin resistance is encountered Always test for methicillin susceptibility Native valve Pen G resistant, methicillin susceptible Nafcillin for S. aureus Chemical appendages make nafcillin a poor substrate for -lactamases No allergy -> Nafcillin (6 weeks) Mild -> Cefazolin ((6 weeks) Severe/anaphylaxis -> Vanc (6 weeks) MRSA Vanco (6 weeks) Prosthetic valve MRSA is common Always intensify treatment & add Gentamicin & rifampin Rifampin Unique ability to kill staphylococci adherent to foreign material Bacteriocidal Many drug interactions! Treatment Nafcillin (>6 weeks) + Rifampin ( >6 weeks) + Gentamicin (2 weeks)

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