Gallstone Disease

Gallstone Disease
By:Tad Kim, M.D.

Overview
* Gallstone pathogenesis
* Definitions
* Differential Diagnosis of RUQ pain
* 7 Cases

Gallstone Pathogenesis
* Bile = bile salts, phospholipids, cholesterol
o Also bilirubin which is conjugated b4 excretion
* Gallstones due to imbalance rendering cholesterol & calcium salts insoluble
* Pathogenesis involves 3 stages:
o 1. cholesterol supersaturation in bile
o 2. crystal nucleation
o 3. stone growth

Definitions
Infection within bile ducts usu due to obstrux of CBD. Charcot triad: RUQ pain, jaundice, fever (seen in 70% of pts), can lead to septic shock

Cholangitis
Gallstone in the common bile duct (primary means originated there, secondary = from GB)

Choledocho-lithiasis
GB inflammation due to biliary stasis(5% of time) and not stones(95%). Seen in critically ill pts

Acalculous cholecystitis
Recurrent bouts of colic/acute chol’y leading to chronic GB wall inflamm/fibrosis. No fever/WBC.

Chronic cholecystitis
Acute GB inflammation due to cystic duct obstruction. Persistent RUQ pain +/- fever, ↑WBC, ↑LFT, +Murphy’s = inspiratory arrest

Acute cholecystitis
Wax/waning postprandial epigastric/RUQ pain due to transient cystic duct obstruction by stone, no fever/WBC, normal LFT

Symptomatic cholelithiasis
Differential Diagnosis of RUQ pain

* Biliary disease
o Acute chol’y, chronic chol’y, CBD stone, cholangitis
* Inflamed or perforated duodenal ulcer
* Hepatitis
* Also need to rule out:
o Appendicitis, renal colic, pneumonia or pleurisy, pancreatitis
Case 1

* 46yo F w RUQ pain x4hr, after a fatty meal, radiating to the R scapula, also w nausea. Pt is pain-free now.
* No prior episodes
* Minimal RUQ tenderness, no Murphy’s
* WBC 8, LFT normal
* RUQ U/S reveals cholelithiasis without GB wall thickening or pericholecystic fluid
* Diagnosis: ?

Symptomatic cholelithiasis

* aka “biliary colic”
* The pain occurs due to a stone obstructing the cystic duct, causing wall tension; pain resolves when stone passes
* Pain usually lasts 1-5 hrs, rarely > 24hrs
* Ultrasound reveals evidence at the crime scene of the likely etiology: gallstones
* Exam, WBC, and LFT normal in this case
* Treatment: Laparoscopic cholecystectomy

Spectrum of Gallstone Disease
Cholelithiasis
Asymptomatic
cholelithiasis
Symptomatic
cholelithiasis
Chronic
calculous
cholecystitis
Acute
calculous
cholecystitis
* Symptomatic cholelithiasis can be a herald to:
o an attack of acute cholecystitis
o or ongoing chronic cholecystitis
* May also resolve

Case 2
* Same case, except pt has had multiple prior attacks of similar RUQ pain
* No fever or WBC
* Ultrasound reveals gallstones, thickened GB wall, no pericholecystic fluid
* Diagnosis: ?
Chronic calculous cholecystitis

* Recurrent inflammatory process due to recurrent cystic duct obstruction, 90% of the time due to gallstones
* Overtime, leads to scarring/wall thickening
* Treatment: laparoscopic cholecystectomy

Case 3
* Same pt, now > 24hrs of RUQ pain radiating to the R scapula, started after fatty meal, a/w nausea, vomiting, fever
* Exam: Palpable, tender gallbladder, guarding, +Murphy’s = inspiratory arrest
* WBC 13, Mild LFT
* U/S: gallstones, wall thickening (>4mm), GB distension, pericholecystic fluid, sonographic Murphy’s sign (very specific)
* Diagnosis: ?
* Curved arrow
o Two small stones at GB neck
* Straight arrow
o Thickened GB wall
* GB also appears distended

Acute calculous cholecystitis
* Persistent cystic duct obstruction leads to GB distension, wall inflammation & edema
* Can lead to: empyema, gangrene, rupture
* Pain usu. persists >24hrs & a/w N/V/Fever
* Palpable/tender or even visible RUQ mass
* Nuclear HIDA scan shows nonfilling of GB
o If U/S non-diagnostic, obtain HIDA
* Tx: NPO, IVF, Abx (GNR & enterococcus)
* Sg: Cholecystectomy usu within 48hrs
* 87yo M critically ill, on long-term TPN w RUQ pain, fever, WBC
* Ultrasound: GB wall thickening, pericholecystic fluid, no gallstones

Acute acalculous cholecystitis
* In 5-10% of cases of acute cholecystitis
* Seen in critically ill pts or prolonged TPN
* More likely to progress to gangrene, empyema, perforation due to ischemia
* Caused by gallbladder stasis from lack of enteral stimulation by cholecystokinin
* Tx: Emergent cholecystectomy usu open
* If pt is too sick, perc cholecystostomy tube and interval cholecystectomy later on

Complications of acute cholecystitis
Less commonly, perforates into adjacent viscus = cholecystoenteric fistula & the stone can cause SBO (gallstone ileus)
Occurs in 10% of acute chol’y, usually becomes a contained abscess in RUQ
Perforated gallbladder
More commonly in men and diabetics. Severe RUQ pain, generalized sepsis. Imaging shows air in GB wall or lumen
Emphysematous cholecystitis
Pus-filled GB due to bacterial proliferation in obstructed GB. Usu. more toxic, high fever
Empyema of gallbladder

Case 5
* 46yo F p/w RUQ pain, jaundice, acholic stools, dark tea-colored urine, no fevers
* Known history of cholelithiasis
* Exam: unremarkable
* WBC 8, T.Bili 8, AST/ALT NL, HepB/C neg
* Ultrasound: Gallstones, CBD stone, dilated CBD > 1cm

Choledocholithiasis
* Can present similarly to cholelithiasis, except with the addition of jaundice
* DDx: cholelithiasis, hepatitis, sclerosing cholangitis, less likely CA with pain
* Tx: Endoscopic retrograde cholangiopancreatography (ERCP)
o Stone extraction and sphincterotomy
* Interval cholecystectomy after recovery from ERCP

Case 6
* 46yo F p/w fever, RUQ pain, jaundice (Charcot’s triad)
* If also altered mental status and signs of shock = Raynaud’s pentad
* VS tachycardic, hypotensive
* ABC’s, Resuscitate
o 2 large bore IV, Foley, Continuous monitor
o 1-2L fluid bolus, repeat until resuscitated
* Diagnosis: ?

Cholangitis
* Infection of the bile ducts due to CBD obstruction 2ndary to stones, strictures
* Charcot’s triad seen in 70% of pts
* May lead to life-threatening sepsis and septic shock (Raynaud’s pentad)
* Tx: NPO, IVF, IV Abx
* Emergent decompression via ERCP or perc transhepatic cholangiogram (PTC)
* Used to require emergency laparotomy

Case 7
* 46yo F p/w persistent epigastric & back pain
* Known history of symptomatic gallstones
* No EtOH abuse
* Exam: Tender epigastrum
* Amylase 2000, ALT 150
* Ultrasound: Gallstones
* Diagnosis: ?

Gallstone pancreatitis
* 35% of acute pancreatitis 2ndary to stones
* Pathophysiology
o Reflux of bile into pancreatic duct and/or obstruction of ampulla by stone
* ALT > 150 (3-fold elevation) has 95% PPV for diagnosing gallstone pancreatitis
* Tx: ABC, resuscitate, NPO/IVF, pain meds
* Once pancreatitis resolving, ERCP w stone extraction/sphincterotomy
* Cholecystectomy before hospital discharge

Take Home Points
* As always, ABC & Resuscitate before Dx
* Understanding the definitions is key
* Is this acute cholecystitis? (fever, WBC, tender on exam with positive Murphy’s)
* Or simply cholelithiasis vs ongoing chronic cholecystitis? (no fever/WBC)
* Is patient sick or toxic-appearing, to suspect empyema, gangrene or even perforation?
* Elicit h/o jaundice, acholic stools, tea-colored urine
* Rule out cholangitis, because this will kill the patient unless dx & tx early

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Lower Respiratory Tract Infections

Lower Respiratory Tract Infections
By: Divya Ahuja, M.D.

Lower respiratory infections: anatomic classification
* Tracheitis; bronchitis; tracheobronchitis
* Bronchiolitis
* Bronchopneumonia
* Segmental pneumonia
* Lobar pneumonia
* Interstitial pneumonia

Case #1
* 40-year-old man
* no underlying lung disease
* 7-day history of mild shortness of breath with exertion, and a productive cough.
* Temperature = 37°C, pulse 84 beats/min, and his respiratory rate 17 breaths per minute.
* no rales are heard; scattered wheezes are heard in the lung bases.

Acute bronchitis (“chest cold”)
* Usually of viral etiology(influenza, rhinovirus, parainfluenza, RSV, human metapneumovirus)
* A common cause for overuse of antibiotics
* Bacteria implicated are
o Bordetella pertussis (whooping cough)
o Mycoplasma pneumoniae
o Chlamydia pneumoniae

Acute bronchitis
* Similar to URIs but more prolonged
* Cough persists > 5 days (upto 40 days)
* 40% will have reduction in pulmonary function
* Main differential includes
o Asthma/ bronchiolitis
o Bronchiectasis
o Chronic bronchitis (cough and sputum for 3 months during 2 years

Acute Bronchitis

* Cough in the absence of fever, tachycardia, and tachypnea suggests bronchitis, rather than pneumonia
* Antimicrobial agents are not recommended in most cases of acute bronchitis
* Antimicrobial therapy is indicated when a treatable pathogen is identified (influenza, Bordetella pertussis )

Acute exacerbations of chronic bronchitis

* Chronic bronchitis is associated with cigarette smoking and COPD
* Extent to which specific bacterial pathogens explain exacerbations is controversial.
* However, repeated bacterial infections (especially H. influenzae) contribute to deterioration of lung function.

Case # 2

* 54 year male, chronic cough x 1 year. no hemoptysis. Denies fevers, shakes, chills. No sick contacts

Bronchiectasis
* Abnormal dilatation of bronchi with chronic productive cough.
* Can be clue to cystic fibrosis in younger patients (associated with S. aureus and Pseudomonas species)
* Uncommon associations: immunodeficiency disorders, dyskinetic cilia syndrome

Case # 3
* 54 year old male
* Flu like illness 2 weeks ago
* 5 day history of chills, fever, difficulty breathing, right sided pleuritic chest pain, cough and yellow sputum

Pneumonia
* 6th leading cause of death in U.S.A.
* About 3 million cases per year; > 500,000 hospital admissions
* About 50% of cases and the majority of deaths are due to bacteria
* Precise diagnosis is usually desirable but difficult to obtain

Acute pneumonia

* History
* Symptoms-cough, sputum, fever, malaise
* Clinical setting-community acquired, nosocomial
* Defects in host defense- HIV, neutropenia
* Possible exposures

Organisms in community acquired pneumonia

Organisms:
S pneumoniae
H influenzae
o P aeruginosa
o S aureus
o Atypicals
+ Chlamydia, Legionella
+ Mycoplasma, Bordetella

Pneumonia (2)
* Streptococcus pneumoniae the most common cause of community-acquired pneumonia requiring hospitalization
* Haemophilus influenzae and Moraxella catarrhalis are increasing in frequency
* Legionella species and Chlamydia pneumoniae have emerged
* Pneumocystis carinii (HIV disease)

Pneumonia: pathogenesis
* Endogenous vs. exogenous (inhalation)
* Bronchogenous vs. lymphohematogenous
* “Pulmonary clearance”: mucociliary blanket, alveolar macrophages
* Factors that impair pulmonary clearance: viral URI; smoking; alcohol; uremia; bronchial obstruction; 100% oxygen; others

“Typical” versus “atypical” pneumonia

* “Typical” (virulent bacteria): abrupt onset; productive cough with purulent sputum; pleuritic chest pain; impressive physical findings; leukocytosis or leukopenia
* “Atypical” (viral, Mycoplasma pneumoniae, others): gradual onset, nonproductive cough; substernal chest pain; unimpressive physical exam; white blood count normal

Typical versus atypical pneumonia

Classic pneumococcal pneumonia

* Antecedent upper respiratory infection
* Sudden onset with single violent chill, then fever
* Pleuritic chest pain
* Signs of lobar consolidation on exam
* If untreated, terminates gradually by “lysis” or suddenly by “crisis”

Atypical pneumococcal pneumonia

* Caught early: signs of consolidation may be absent
* Elderly: fever, classic history may be absent
* COPD: CXR and physical findings are distorted
* Ethanolism: blunted history; prostration, leukopenia
* Epilepsy: lack of history; fever and tachycardia may be attributed to seizures; anaerobes may co-exist
* Recurrent pneumonia: In same area, suggests obstruction or bronchiectasis

Some current problems with pneumococcal disease

* Failure of antibiotic therapy to improve survival during first 3 days
* Vaccine efficacy and distribution
* Resistance to penicillin G
* Overwhelming sepsis in asplenic persons
* Need for developing better diagnostic techniques

Group A streptococcal pneumonia

* Rare, except during influenza epidemics
* Large empyema (“pus in the chest”) is characteristic

Hemophilus influenzae pneumonia

* 2% to 18% of community-acquired pneumonias;
* Predisposition: underlying lung disease, alcoholism, recent URI, advanced age
* Often a patchy segmental pneumonia or bronchopneumonia
* Virtually-diagnostic Gram’s stain: small, pleomorphic gram-negative coccobacilli

Moraxella catarrhalis pneumonia

* AKA: Neisseria catarrhalis; Branhamella catarrhalis
* A large gram-negative diplococcus
* Causes pneumonia and bronchitis especially in persons with chronic lung disease
* Often a patchy bronchopneumonia

Mycoplasma pneumoniae pneumonia

* The classic “primary atypical pneumonia”
* Typically occurs in younger adults, often the parents of young children
* Subtle presentation
* Favors lower lobes
* Pleural effusion may occur (up to 20%)

Some nonrespiratory manifestations of Mycoplasma pneumoniae pneumonia

* Myringitis (sometimes bullous)
* Hemolytic anemia
* Arthritis, arthralgias, myalgias
* Pericarditis, myocarditis
* Hepatitis (mild)
* Erythema multiforme, other rashes
* Meningitis, meningoencephalitis, neuropathy

Chlamydia pneumoniae pneumonia

* Accounts for <5% of community-acquired pneumonias
* C. pneumoniae more commonly causes pharyngitis and hoarseness
* Bronchitis is often insidious
* Pneumonia usually mild and localized but difficult to eradicate

Legionella pneumophila pneumonia

* Up to 23% of community-acquired pneumonias but with wide geographic distribution
* L. pneumophila is not part of the normal flora; a true inhalation disorder
* CXR: patchy or nodular infiltrates that may progress rapidly; up to 50% are bilateral

Legionella pneumophila pneumonia (2)

* Relative bradycardia in 65%
* Neurologic findings in 26%
* Gram’s stain may show purulence without a predominant microorganism
* Laboratory: may have hyponatremia; elevations of AST (SGOT), alkaline phosphatase, and bilirubin; proteinuria, hematuria, and renal failure

Treatment

* S. pneumoniae resistance is increasing
* Options are cephalosporins, amox/clvulanic acid, macrolides, doxycycline, a respiratory fluoroquinolone
* All atypicals are covered by the macrolides , doxycycline and the fuoroquinolones
* Judge the severity to see if outpatient treatment will suffice

Aspiration (“mouth flora”) pneumonia

* usually presents as a subacute illness in patients with some combination of alcoholism, malnutrition, homelessness, and poor dentition
* sputum often has foul odor
* Necrotizing pneumonia; lung abscess(es) with air-fluid levels; empyema

Pneumonia: some clues
* Tularemia: rabbits and hares; ticks and fleas; inhalation (e.g., after mowing over carcasses)
* Psittacosis: birds
* Plague: ground squirrels, chipmunks, rabbits, prairie dogs, rats
* Legionnaire’s disease: contaminated aerosols (air coolers; hospital water supplies)
* Histoplasmosis: dust from soil enriched with bird or bat droppings; Mississippi and Ohio River valleys
* Coccidiodomycosis: southern California (esp.. San Joachin Valley); southwest Texas, Arizona, N Mexico
* Pneumocystis carinii: HIV risk factors
* Relative bradycardia: viral infection; Mycoplasma pneumoniae; Psittacosis; Tularemia; Legionella
* Q fever (Coxiella burnetii): goats, cattle, sheep
* Meliodosis: travel to S.E. Asia, East Indies, Australia, Guam, South or Central America
* Brucellosis: cattle; goats; pigs; abattoir works and veterinarians
* Anthrax: cattle, swine, horses; goat hair, wool, or hides

Pneumococcal pneumonia: Predisposing factors
* Sickle cell disease
* Asplenia
* IgG disorders: agammaglobulinemia, myeloma, chronic lymphocytic leukemia
* Nephrotic syndrome
* Cirrhosis
* Alcoholism

Case # 4
* RA 57 year Caucasian male
* Cough , dyspnea, diarrhea for weeks
* No response to cephalexin
* CT sinuses - normal
* Progressive malaise and presented to ER
* pO2 on 100% NRB- 90, Creatinine 1.8, WBC: 12
* CXR-read as normal, HIV positive

Pneumonia in AIDS patients
* When in doubt, respiratory isolation for Tb
* S. pneumoniae is the number 1 cause
* Investigations
o Obtain sputum for gram stain and culture
o Other serology and antigen testing as indicated (histoplasma, cryptococcus, PCP, coccidio, etc.
o AFB stain if indicated(sensitivity with 3 specimens is about 60%)

PCP: Diagnosis (Imaging)
Chest x ray: PCP pneumonia with bilateral, diffuse granular opacities.
Credit: L, Huang, MD, HIV InSite

Chest x ray: PCP pneumonia with bilateral perihilar opacities, interstitial prominence, hyperlucent cystic lesions. Credit: HIV Web Study, www.hivwebstudy. org, © 2006 University of Washington

PCP
* PCP is a SUBACUTE pneumonia, CD4 usually <200
* Dyspnea, dry cough, chest discomfort
* In 30% patients
o CD4 > 200
o CXR normal
* TMP/SMX and steroids if hypoxic

Tuberculosis in HIV patients
* Occurs at any CD4 count
* Primary TB
o Occurs especially in people with advanced HIV infection
o Comprises about 1/3 of TB cases in HIV patients
* Reactivation of latent TB
o More likely in HIV-infected patients
o 7-10% annual risk in HIV-infected patients with positive tuberculin skin test (TST)
+ In HIV uninfected, 5-10% lifetime risk
* Patients with TB have HIV viral loads and faster progression of HIV

Case # 5
* 45 year female
* Intubated in the ICU for 7 days
* Now has worsening fever, leukocytosis and increased oxygen requirement

Nosocomial pneumonia
* Role of oropharyngeal colonization, especially of gram-negative rods (Pseudomonas, acinetobacter, etc.) : by end of one week, 45% of ICU patients are colonized; pneumonia develops in 23% of colonized patients versus 3.3% of non-colonized patients
* Risk factors to colonization: more advanced illness, longer duration in the hospital, antibiotics, intubation, azotemia, underlying pulmonary disease

Case # 6
* 23 year male, acute leukemia and bone marrow transplant
* Is severely neutropenic due to chemotherapy

Cavitary pneumonia
* Tuberculosis
Actinomyces
Nocardia
Klebsiella
Staphylococcus aureus
Anaerobic organisms
* Fungal infection Histoplasmosis
Coccidiomycosis, aspergillus

Complications of pneumonia
* Pleuropulmonary: lung abscess; adult respiratory distress syndrome (ARDS); pleural effusion; empyema; bronchopleural fistula; bronchiectasis; fibrosis; slow resolution
* Extrapulmonary: meningitis; brain abscess; endocarditis; pericarditis; arthritis; osteomyelitis

Lung Abscess
* Lung abscesses are usually caused by mouth flora(viridans strep, anaerobes, etc.)
* They need prolonged courses of antibiotics
* Options are the clindamycin, amox/clavulanic acid, pip/tazo, carbapenems

Pneumonia: Summary
* 6th leading cause of death and most common nosocomial infection causing death
* Precise diagnosis desirable but all-too-often not obtained
* Bronchoalveolar lavage and endobronchial sampling are now standard in nosocomial or difficult to diagnose pneumonia


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Tube Thoracostomy: Complications and the Role of Prophylactic Antibiotics

Tube Thoracostomy: Complications and the Role of Prophylactic Antibiotics
By Ashley Laird

Indications for Tube Thoracostomy
* PTX (spontaneous, iatrogenic, traumatic)
* Hemothorax
* Chylothorax
* Decreased breath sounds in unstable patient after blunt or penetrating trauma
* Multiple rib fractures, sucking chest wound, subcutaneous air in intubated trauma patient
* Complicated pleural effusion, empyema, lung abscess
* Thoracotomy, decortication
* Pleural lavage for active rewarming for hypothermia

Complications
* Undrained PTX, hemothorax, or effusion despite TT clotted hemothorax, empyema, fibrothorax
* Improper placement +/- iatrogenic injuries (lung, diaphragm, subclavian, right atrium)
* Recurrent PTX after tube removal
* Intrapleural collections following tube removal
* Thoracic empyema

Factors Influencing Complications: Louisville study
* Prior studies report TT complication rates of 3-36%
* Etoch SW, Bar-Natan MF, Miller FB, Richardson JD. Tube Thoracostomy: Factors related to complications. Arch Surg. 1995; 130:521-525.
o Retrospective chart review (U of Louisville)
o 379 trauma pts, 599 tubes

Factors Influencing Complications: Louisville study
* Complications:
o Empyema
o Undrained PTX or effusion
o Improper tube placement (+/- iatrogenic injury)
o Post-tube PTX
o Other
* Measures:
o Rate of complications in association w/ TT setting, operator, patient characteristics, MOI, and severity of injury

Factors Influencing Complications: Louisville study
* Overall rate of complications: 21% per patient (16% per tube)
* 8.2% of complications required thoracotomy

Factors Influencing Complications: Setting
* 48% of tubes placed in ED, 23% in OR, 12% in ICU, 7% on floor, and 9% at OSH prior to transfer
* Significantly higher complication rate when TT performed in outside hospital prior to transfer (33%, p<.0001)
* No significant difference in complication rates between TT in ED (9%) vs. TT in other areas of study hospital (7%)

Factors influencing Complications: Operator
* 59% of tubes placed by surgeons, 26% by ED physicians, 8% by physicians prior to transfer
* Highest complication rate for tubes placed by physicians in outside hospitals, mostly nonsurgeon physicians (38%)
* Complication rates for TT’s in study hospital: 13% for ED physicians, 6% for surgeons (p<.0001)
* For TT’s in ED: 13% complication rate for ED physicians vs 5% complication rate for surgeons (p<.01)

Factors influencing Complications: Mechanism/Severity of Injury

* No difference in complication rate related to:
o Age and sex of patients
o Mechanism of injury (23% for blunt vs 18% for penetrating)
o ISS
* Significantly increased complication rate related to:
o ICU admission (29% vs 11%, p<.0001)
o Mechanical ventilation (29% vs 15%, p<.002)
o Presence of hypotension (SBP<90) on admission (31% vs 17%, p<.003)

Factors Influencing Complications: University Hospital study
* Deneuville M. Morbidity of percutaneous tube thoracostomy in trauma patients. Eur J CT Surg. 2002; 22:673-678.
o Prospective observational study (University Hospital, Guadeloupe)
o 128 trauma pts, 134 tubes
o ‘Non-thoracic’ operators vs. thoracic surgeons

Factors Influencing Complications: University Hospital study
* Overall complication rate 25% (29% per tube)
o 5 (12.8%) improper placement, no iatrogenic injury
o 4 (10.3%) improper placement w/ iatrogenic injury (lung x 2, diaphragm, subclavian artery)
o 4 (10.3%) undrained hemothorax/PTX
o 12 (30.8%) post-removal PTX
o 7 (18%) post-removal fluid collection
o 3 (2.3%) empyema
o 4 (10.3%) combined
* 18 (46.2%) of complications required surgery (thoracotomy or VATS)

Factors Influencing Complications: University Hospital study
* No difference in complication rate related to:
o Blunt trauma vs. penetrating wounds
o Indication for TT: hemothorax vs PTX
o Presence of pulmonary contusion, abdominal injury, or need for immediate abdominal surgery
* Significantly increased risk of complication related to:
o Polytrauma (RR 2.7, p<0.05)
o Need for assisted ventilation (RR 2.7, p<.003)
o TT by non-thoracic surgeons (RR 8.7, p<.0001 for blunt trauma and RR 12.5%, p<.0001 for penetrating trauma)

Thoracic Empyema
* Causes of post-traumatic empyema:
o Iatrogenic infection during TT
o Direct infection from penetrating injury
o Secondary infection from associated intra-abdominal injuries w/ diaphragmatic disruption or hematogenous or lymphatic spread to pleural space
o Secondary infection of undrained hemothoraces
o Parapneumonic empyema resulting from posttraumatic pneumonia, contusion, or ARDS

Thoracic Empyema
* Empyema occurred in 1.8% (Louisville study) and 2.3% (University Hospital study) of patients undergoing TT
* No difference in rate of empyema related to setting or operator
* No difference in rate of empyema related to administration of antibiotics within 24 hours of initial TT in Louisville study (2% vs 2%)


‘Prophylactic’ Antibiotics in TT: EAST Guidelines
* Does ‘prophylactic’ antibiotic use in injured patients requiring TT reduce the incidence of empyema and/or pneumonia?
* Paucity of literature, especially well-designed multi-institutional double-blinded trials that control for setting, operator, mechanism of injury, timing of antibiotic administration, choice and dose of antibiotic, and duration of prophylaxis

‘Prophylactic’ Antibiotics in TT: EAST Guidelines
* Luchette FA, Barrie PS, Oswanski MF, Spain DA, Mullins CD, Palumbo F, Pasquale MD. Practice Management Guidelines for Prophylactic Antibiotic Use in Tube Thoracostomy for Traumatic Hemopneumothorax: the EAST Practice Management Guidelines Work Group. J Trauma. 2000; 48(4):753-7.
o MEDLINE search (1977-1997) for references using query words: antibiotic prophylaxis, chest tubes, human, drainage, tube thoracostomy, infection, empyema, and bacterial infection-prevention and control.
o 11 articles reviewed: 9 prospective series, 2 meta-analyses

Prophylactic’ Antibiotics in TT: EAST Guidelines
* Articles classified by Agency for Health Care Policy and Research (AHCPR) methodology
o Class I: prospective, randomized, double-blinded, controlled trials
o Class II: prospective, randomized, non-blinded trial
o Class III: retrospective series of patients or meta-analysis
* Four class I articles, five class II, and two class III meta-analyses

Prophylactic’ Antibiotics in TT: Conclusions and Recommendations
* Incidence of empyema in placebo groups ranged from 0-18%, compared to 0-2.6% in antibiotic groups
* Two class I studies saw a reduced incidence of empyema w/ antibiotic Rx (Cant, 1993; Grover, 1977)
* Two class II studies saw no benefit w/ antibiotics (Mandal, 1985; Demetriades, 1991)
* Other studies didn’t control for MOI
* Insufficient evidence to support prophylactic antibiotics as a standard of care for reducing incidence of empyema or PNA in patients requiring TT

Prophylactic Antibiotics in TT: Conclusions and Recommendations
* Extreme variability in choice of antibiotic, dosing, and duration of therapy among studies
* One class I study reported no empyema in patients receiving cefazolin for 24hrs compared to 5% incidence in placebo group (Cant et al, 1993)
* Administration of antibiotics for >24hrs did not significantly reduce risk of empyema compared with shorter duration (Demetriades, 1991)

Prophylactic’ Antibiotics in TT: Conclusions and Recommendations

* Incidence of pneumonia in placebo groups ranged from 2.5-35.1%, compared to 0-12% in antibiotic groups
* In most reports, significant reduction in pneumonitis seen in patients receiving prolonged antibiotics (but also see increased cost and length of hospital stay)
* Presumptive, rather than prophylactic therapy, in setting of acute trauma

‘Prophylactic’ Antibiotics in TT: Conclusions and Recommendations

* Recommendations (for isolated chest trauma)
o Level I: insufficient data to support level I recommendation as standard of care
o Level II: insufficient data to suggest prophylactic antibiotics reduce incidence of empyema
o Level III: sufficient class I and II data to recommended prophylactic antibiotic use in patients receiving TT after chest trauma. A first generation cephalosporin should be used for no longer than 24hrs. There may be a reduction in incidence of PNA, but not empyema.


Recommendations
* Additional training of all trauma physicians
* Early thoracotomy or VATS in settings of persistent fluid collection or multiple chest tube placements as means to prevent against development of empyema
* First generation cephalosporin for no more than 24 hours
* Further research!

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Tools of Prenatal Diagnosis

Tools of Prenatal Diagnosis
By:Julie Moldenhauer, MD
Reproductive Genetics
Maternal Fetal Medicine
Obstetrics and Gynecology

Objectives:
* Discuss various prenatal screening and testing tools
* Discuss the timing of the various tools in gestation
* Discuss benefits and risks of various options
* Review the difference between screening and testing
Baseline Risk for Birth Defects in the General Population is 3-5%
What Can We Diagnose in the Prenatal Setting?
* Structural Abnormalities
o Congenital heart disease
o Spina bifida
o Gastroschisis
* Chromosomal Abnormalities
o Trisomy 21
o Triploidy
* Infections
o Parvovirus
o Cytomegalovirus
o Toxoplasmosis
* Growth Abnormalities
* Hematologic Abnormalities
o Anemia
o Thrombocytopenia
* Functional Defects
o Arthrogryposis
o Renal dysfunction
* Syndromes
o Skeletal Dysplasia
o Diabetic embryopathy

Prenatal Diagnosis Tools

* History
o Personal History
o Family History
* Population Screening
* Serum Screening
* Ultrasound
* Fetal MRI
* Invasive Diagnosis
o Chorionic villus sampling
o Amniocentesis

History is a Screening Tool!
o Maternal Age
+ > 35 years at delivery
o Obstetric History
+ Prior baby born with Down syndrome
+ Prior stillbirth
o Medical History
+ Is mom diabetic? How well controlled is her sugar?
+ Does she have PKU?
+ Is she hypertensive?
o Medication Exposures
+ What medications?
+ When was the exposure?
o Environmental Exposures
+ Does she work in a preschool and was exposed to parvovirus?
+ Is she exposed to high doses of radiation?
o Family History
+ Brother with hemophilia
+ Uncle with cystic fibrosis
+ Ethnic background
+ Consanguinity

As maternal age increases, the risk for aneuploidy increases. This is due to maternal meiotic nondisjunction.
Maternal age > 35 at the time of delivery is considered “Advanced Maternal Age” or AMA
The risk for recurrence of chromosome abnormalities is dependent upon the genetic mechanism involved.
Trisomy: 1% or maternal age-related risk
Translocation:
Maternal carrier: 10-15%
Paternal carrier: 2%

Down syndrome phenotype caused by trisomy 21
Down syndrome phenotype caused by 14;21 translocation

Maternal Diabetes: Reproductive Risks
* Fetal and Neonatal
o Congenital anomalies: 6-12%
o Intrauterine fetal demise
o Macrosomia – Shoulder dystocia
o Growth restriction
o Hyperbilirubinemia
o Hypoglycemia
o RDS
o Polycythemia
o Organomegaly
o Long term – obesity and carbohydrate intolerance
* Obstetric
o Spontaneous preterm labor
o Polyhydramnios
o Preeclampsia (15-20%)
o Intrauterine growth restriction
o Shoulder dystocia
o Cesarean delivery

Caudal Regression Syndrome
Teratogen Exposure
Fetal growth
Organogenesis complete
Eyes, heart, lower limbs
Axial skeleton, limb buds, musculature
CNS
None, “ALL or NONE”
* Examples:
* Accutane
* ACE inhibitors
* Lithium
* Antiepileptic drugs (AEDs)
* Anticoagulants: warfarin
* Antidepressants
* Methotrexate
* Thalidomide

Teratogen Exposure
* Fetal effects are timing and dose dependent

* Each medication is assigned a pregnancy category based on available data; A-D, X
* www.Reprotox.org
* www.otispregnancy.org

Ultrasound images of fetal hydrops – abnormal collection of fluid in multiple body compartments.
Mom works at a daycare where there was a Parvovirus B19 or Fifth Disease outbreak 4 weeks ago. Parvovirus causes fetal aplastic anemia that can be life-threatening.

Suspicion of diagnosis by altered maternal serum titers of Parvo IgG and IgM and confirmed by amniotic fluid PCR for Parvo.
Confirmed Parvo infection in a fetus with hydrops can be treated with intrauterine blood transfusions.

Fetal Ultrasound Showing Cardiac Rhabdomyoma
Fetal MRI Showing Tubers
Prenatal Findings Consistent with Tuberous Sclerosis Confirmed as Neonate
Screening for Genetic Disease
Ethnic Group Disease
African American Sickle Cell Disease: 1/12
Mediterranean Beta-Thalassemia: 1/30
Southeast Asian Alpha-Thalassemia: 1/20
Caucasian Cystic Fibrosis: 1/25

ASHKENAZI JEWISH ANCESTRY
GENETIC CARRIER TESTING
Gaucher’s disease
Bloom syndrome
Mucolipidosis IV
Niemann-Pick disease type A
Fanconi Anemia Group C
Familial Dysautonomia
Cystic Fibrosis
Canavan disease
Tay-Sachs disease
Detection rate
Carrier Frequency
Disease Incidence
Testing and screening options should be made available to all pregnant women
Prenatal Screening & Testing
When Screening
(risk estimate)
Definitive
(Invasive)
First Trimester
FIRST screen*
Ultrasound
CVS

Second Trimester
Maternal Serum Screen*
Ultrasound
Amnio
Cordo
*First and Second Trimester Integrated and Sequential Screening

Test Performance
* Detection rate – the percentage of affected that are test “positive”
o (the higher, the better)
* False positive rate – the percentage of unaffected that are test “positive”
o (the lower, the better)

Goals in Prenatal Screening:
* High sensitivity - low false positive rate
* Wide availability
* Reproducibility and accuracy
o Human error, testing conditions

First Trimester Screening
o 11-13 6/7 weeks (CRL 39-79 mm)
o Maternal serum sample for PAPP-A and Free b-HCG
o Ultrasound for Nuchal translucency
o Detection Rates:
+ 80% for Trisomy 21
+ 90% for Trisomy 18
+ Does not screen for NTDs

PAPP-A
b-HCG
T21
T18

Increased NT vs Cystic Hygroma
* Increased NT > 95th%
o With or without septations
* Structural defects
o Heart defects most common
* Syndromic associations
* Chromosomal defects
o Exponential increase with increased NT
o 50% Down syndrome
o 25% Trisomy 13 or 18
o 10% Turner Syndrome
o 5% Triploidy
o 10% other

NT > 3 mm is ABNORMAL
Second Trimester Serum Screening: Chromosome Abnormalities

* Maternal Serum Screening
o 15-20 weeks
o Triple screen: 60% for T21
o Quad screen: 70% for T21
o Gestational Age Dependent**
* Targeted Ultrasound
o 50% aneuploid fetuses will have ultrasound markers
AGE +AFP +hCG +uE3 +InhA
DR at 5% FPR
2nd trimester
single double triple quadruple
Serum Screening Test Performance at a fixed 5% False Positive Rate (Dating by Ultrasound)

Prediction
SURUSS
FASTER
Second Trimester Serum Screening: Neural Tube Defects
* Neural Tube Defects
o Spina Bifida
o Anencephaly
* AFP increased in “open” defects
* Sensitivity
o 90% anencephaly
o 80-85% open spina bifida
* False positive – 3-4%
Interpreting a Quadruple Screen

Bottom Line: AFP is increased with NTDs and decreased with chromosome abnormalities

Elevated MSAFP
* Incorrect Dates – most common reason
* Multiples
* Congenital Nephrosis
* Ventral Wall Defects
* IUFD
* Adverse Pregnancy Outcomes
o Stillbirth
o Placental abruption
o Preterm labor
o Oligohydramnios
o IUGR

Ultrasound detection of aneuploidy
Nuchal Fold
CPC
Duodenal atresia
Pyelectasis
Clinodactyly
Second trimester sonographic markers of Down syndrome
AV Canal
Trisomy 18
Edward Syndrome
* Close to 90% detected by prenatal scan
* US:
o Growth restriction
o Clenched fists
o >90% with cardiac defects
o Multiple malformations
* Grim prognosis
o 50% Stillbirth
o 50% die within the first week
o 5-10% survive the first year

Trisomy 13
Patau Syndrome
Fetal Anatomy by Ultrasound
Ventral Wall Defect
Gastroschisis
NTDs
Lemon Sign
Banana Sign
Meningomyelocele Sac
Meningomyelocele Sac on Newborn
PGD: Preimplantation Genetic Diagosis
Pearls for Invasive Testing
* Risk for Sensitization
o Mom Rh negative – Rhogam
o Other antibodies may increase risk
* Risk for Infection transmission
o Hepatitis B
o Hepatitis C
o HIV
o Need to know familial mutations prior to performing invasive testing

Chorionic Villus Sampling
* Performed 10-14 weeks
* Does not test for ONTD
* Technique – “Placental biopsy”
o Transabdominal
o Transcervical
* Risk for limb reduction defects if performed < 9 weeks
* Loss rate 1/100-1/200
* Risk for mosaicism (~1%)

Transcervical
CVS
Transabdominal
Performed at 10-14 weeks
Amniocentesis
* > 15 weeks
* Loss rate 1/200 (probably closer to 1/300-1/500)
* Tests for ONTD
* Technique
o Fine gauge needle
o Ultrasound guidance
o Aspiration of 20-30 cc of fluid

PERFORMED ROUTINELY 15-20 WEEKS
Ultrasound Guided Procedure
AMNIOCENTESIS
Cordocentesis
* Percutaneous Umbilical Blood Sampling
* Loss rate 1/100-1/200
* Typically done after 18 weeks
* Ability for:
o Rapid karyotype
o Blood/platelet counts
o Direct fetal injections/transfusions

Fetal Blood Sampling
“PUBS”
Conclusions

* Many options for screening and testing.
* Prenatal screening should provide the most effective test to the greatest number of women.
* The best method of screening is yet to be determined.
* Patient preference should be considered.
* Testing and screening should be available to all women.

Tools of Prenatal Diagnosis.ppt

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Menopause

Menopause
Division of Urogynecology and Reconstructive Pelvic Surgery
Department of OB/GYN

Epidemiology
* Average age is 51.4 years
* 95% confidence interval of Bell Curve gives a range of 45-55 years. Less than 2% occur before age 40.
* Factors associated with early menopause
o Cigarette smoking (1.5 yrs earlier)
o History of short intermenstrual interval
o Family history
o Chemo / Radiation / Genetic factors
* Unrelated to number of prior ovulations, pregnancies, use of OCPs, height, weight, age at menarche, race, class or education

Elderly Population
* In 2000, life expectancy:
o Women 79.7 years
o Men 72.9 years
* Once you reach 65:
o Women expect to live until 84.3 years old
o Men expect to live until 80.5 years old
* Therefore, more than 1/4 of a woman’s life is spent in menopause

Peri-menopause
* Peri-menopause
o Transitional period
+ Hallmark is menstrual irregularities
# Shortened cycle length
# Skipped cycles
# 10% of women will have abrupt cessation of menses
+ Median length of 4-5 years
o Median age of onset is 47.5 years

Physiology
General feature is depletion of follicles with loss of granulosa and thecal cell function
* 6-7 million oocytes at 20 weeks fetal age
* 1 million oocytes at birth drop to 400,000 at puberty
* 300-400 ovulatory events over lifetime
* Accelerated follicular loss 2-8 yrs before menopause

Physiology
* Granulosa cells produce less inhibin, which provides negative feedback for FSH secretion by the pituitary gland.
* Increase in FSH levels
* After menopause, LH levels are also elevated.
* Would you check a FSH or LH level to diagnose menopause?

Symptoms
* Menstrual irregularities is the primary reason women seek medical attention
* Cycles shorten as increased FSH triggers early ovulation
* Skipped cycles due to anovulation
* Long periods of anovulation can lead to excessive estrogen states and irregular, unexpected menses
* Do you think the perimenopausal women can get pregnant?
o YES
o Guinness World Record = 57 yrs & 120 days
o So, remember to recommend contraception. Low does oral contraceptives may be used in women without contraindications (i.e. smoking).
* Hot Flushes
o Subjective feeling of intense heat followed by skin flushing and diaphoresis.
o Sudden dilation of peripheral vasculature secondary to abrupt estrogen withdrawal. Skin temperature increases and core temperature drops.
o Usually, occurs for a few seconds to minutes.
o Duration is about 1-2 years. 25% for > 5 years.
* Genitourinary atrophy
o A variety of symptoms
o Atrophic vaginitis, urethritis, recurrent UTIs, dyspareunia
o Pelvic organ prolapse is NOT caused by estrogen deficiency
* Urinary Incontinence
o Atrophy of estrogen-dependant tissues such as the urethra may contribute to existing causes for urinary incontinence
o Typically addressed with local application of estrogen cream
* Sexual Disturbances
o Decreased interest in sexual activity
+ May be related to decreased testosterone levels
+ May be related to psychosocial stressors
o Anatomic changes secondary to estrogen deficiency
+ Atrophy of vaginal mucosa and lower urethra
+ Thinning of vaginal mucosa with decreased lubrication and elasticity, leading to dyspareunia
* Sleep Disturbances
o Estrogen appears related to producing restful, deep-stage sleep
o Hot flushes more common at night
+ Wakening or disruption of deep-stage sleep
+ Contributes to feeling of overall fatigue
* Mood Swings / Irritability / Depression
o NOT associated with menopausal hormone changes alone
o Stage of life associated with multiple changes (e.g., children leaving home, parents aging, retirement)
o Hot flushes and fatigue can lead to emotional lability
* Cognitive Function
o Some types of memory and brain function may be influenced by estrogen
o Some evidence suggests that Alzheimer’s disease is less frequent in estrogen users and the effect was greater with increasing dose and duration of use.

Adverse Health Effects
* Cardiovascular Disease
o Leading cause of death in US women (f/b malignancies, cerebrovascular disease and MVAs)
o Death rate for CV disease is 3X the rate for breast cancer and lung cancer.
o Changes in lipid profile in menopause
+ Increased LDL
+ Decreased HDL
+ ? Decrease in triglycerides
* Osteoporosis
o Spinal bone density peaks at 20 years, while cortical bone density peaks in late 20s
o Rate of loss of 0.5%/year prior to age 40, then anywhere from 2-9%/year for first 10-15 years after menopause
o Primary loss is trabecular bone, leading to compression fractures, loss of height, kyphosis
o Osteopenia = BMD between -1 and -2.5 SD of a young, white adult woman.
o Osteoporosis = BMD -2.5 or greater SD
o 25-50% of women will have spinal compression fractures by age 70
o 20% of Caucasian women age 80 will have hip fractures, with 15-20% mortality.
o Annual incidence is 1.3% after age 65
o High risk:
+ Caucasian, Asian
+ Thin, inactive, smokers
+ High caffeine/alcohol intake, low dietary calcium, high dietary protein and phosphates
+ H/o oligomenorrhea, excessive exercise, eating disorder
+ Medical conditions – hyperthyroid, cancer, myeloproliferative disorders
o Low Risk:
+ African American
+ Obese, active
o Protection:
+ Ca supplements (1200mg, 1500mg)
+ Weight-bearing exercise
+ HRT: estrogen increases
# Intestinal calcium absorption
# Renal conservation of calcium
# Increases 1,25-dihydroxyvitamin D (active form)
+ Vitamin D (400-800IU)

Hormone Replacement
* Types of hormone replacement
o Estrogen alone (for women without a uterus)
o Estrogen and progesterone
+ Sequential
+ Continuous
o Local estrogen
o SERM’s (Selective Estrogen Receptor Modulators)

HRT - Advantages
1. Relief of vasomotor symptoms
+ HRT is effective in reduces the number of hot flashes
+ 6-8 weeks to see maximal effect
+ Combination HRT (0.625mg estrogen/2.5mg MPA)
+ What about lower doses of HRT?
# For combination HRT, all doses resulted in similar relief of symptoms
# For estrogen alone, most relief with higher doses
2. Vaginal atrophy

# Menopause thins the vaginal epithelium and increases the vaginal pH (> 6.0).
# Estrogen decreases the vaginal pH, thickens the vaginal epithelium and reverses vaginal atrophy.
# Less atrophic changes with higher doses of HRT
3. Bone protection

+ Reduction of bone loss
+ Prevents OP-related hip fractures
+ Protects the spine and the small bones
+ WHI: 5 fewer hip fractures per 10,000 person-yrs
4. Colon cancer

o Some observational studies have suggested a reduced risk.
o WHI: 6 fewer cases / 10,000 person-yrs
1. Endometrial cancer
+ 8-10 fold increased risk with unopposed estrogen.
+ PEPI: unopposed estrogen x 3 yrs = 24% with atypical hyperplasia (vs 1% women on placebo)
+ Risk is increased with:
# Increased duration and dose
# Continuous versus cyclic therapy
# Absence of a progestin
2. Breast cancer

o Meta-analysis of 51 case-controlled & cohort studies showed no increased risk with short-term use.
o After 5 years of use, risk increased by 35%.
o WHI: 8 more invasive cases / 10,000 person-yrs
o Women diagnosed with breast cancer while using HRT have been shown to have better survival

HRT - Disadvantages

3. Thromboembolic disease

o Increases risk for DVT 2 – 3.5 fold
o Strokes: 8 more / 10,000 person-yrs
o PEs: 8 more / 10,000 person-yrs

HRT - Disadvantages

4. Cardiovascular disease:

o Traditionally, HRT was thought to provide protection against coronary heart disease (CHD)
o Observational studies found lower rates of CHD in postmenopausal women on HRT.
o The consensus was that CHD was about 35-50% lower in women using HRT.
o Many studies showed that HRT improved lipid profiles.

HRT - Disadvantages

4. Cardiovascular disease:

o What about secondary prevention? i.e. women who have a h/o coronary heart disease, does HRT help?
o Heart and Estrogen/Progestin Replacement Study (HERS) was a RCT, double-blinded study of 2,763 PM women with intact uteri and a h/o CHD
o 52% higher rate of major coronary events in the 1st year
o Then there was a reduction in the risk with longer use – i.e. 33% lower risk in the 4th and 5th years
o What about primary prevention? i.e. in healthy women, does HRT prevent CHD?
o Women’s Health Initiative (WHI)
o RCT of 16,608 postmenopausal women aged 50-79 years old with an intact uterus
o 40 different US centers
o Combination HRT – 0.625mg CEE and MPA 2.5mg vs placebo

Cardiovascular disease (WHI):
o 7 more CHD events
o 8 more strokes
o 8 more PEs
o 8 more invasive cancers
o Study stopped after 5.2 yrs (planned 8.5yrs) because of cases of breast cancer

SERMs
* Selective estrogen receptor modulators
* Work as agonists and antagonists depending on the tissue
* Raloxifene and tamoxifen

Estrogen Raloxifene Tamoxifen

Prevent OP
Risk Breast
Cancer
Hot Flashes
Endometrial
Cancer
Venous
Thrombosis
SERMs
* Overall, SERMs can help to prevent OP and breast cancer
* However, they aggravate hot flashes, the most common indication for estrogen therapy.
* Also, tamoxifen stimulates the endometrium.

Alternative Medicine
* Limited studies with relatively short duration of therapy and follow-up.
* Soy and isoflavones may be helpful in the short-term (< 2 yrs) for vasomotor sx and may protect against osteoporosis.
* 35-75mg qd isoflavones / day
* Black cohosh may be helpful in the short-term (< 6 mos) for vasomotor symptoms.

Summary
* Health Risks
o Osteoporosis
o Lipid abnormalities
o Cardiovascular disease
o Cancer
* Menopause is the natural course aging of the female reproductive system, driven by loss of oocytes
* Symptoms of menopause include:
o Menstrual irregularities
o Hot flushes
o Sleep disturbances
o Mood changes
o Sexual disturbances
o Urinary incontinence
o Cognitive function
o Hair growth

Hormone Replacement
Benefits
Detriments

* Vasomotor sx
* Vaginal atrophy
* Osteoporosis
* Colon cancer
* Endometrial ca
* Breast ca
* VTE
* CHD

Abnormal Bleeding
* A 44-year old woman presents for evaluation of abnormal menstrual bleeding. Her periods have been regular in the past but for the last 6 months she has had a period every 35-56 days, lasting 7-9 days. The bleeding is heavier than usual and she feels tired all the time. She has gained 15 lbs over the last 2 years, which she believes is due to lack of exercise and increased eating/sleeping. She complains that her skin is dry. Exam is unremarkable. What would your recommend next?
o Check pregnancy test
o Discuss exercise / eating patterns
o Check TSH, PRL
o Consider endometrial biopsy
o Expectant management versus hormonal management

Health Maintenance
* 58 year old postmenopausal woman referred to you by a friend. She has no known medical problems and is on no medications. Her social history is remarkable for an 80-pack/year history of tobacco use. Her physical exam is unremarkable. What are the important health maintenance aspects of the exam to focus on?
o Blood pressure
o Pelvic exam
o Breast exam / mammography
o Fecal occult blood
o Smoking cessation
o Flu shot
o Osteoporosis

Abnormal Bleeding
* A 47 year old woman, G2P2, presents with menstrual cycles varying in length from 20 to 40 days. Until 9 months ago she had regular 28 day cycles. She reports frequent hot flushes. She recently resumed sexual activity and uses no contraception, but she does not desire pregnancy. She does not smoke and has no other medical problems. Her physical exam is unremarkable. What are her options for cycle control?
o Low dose combination oral contraceptive
o Continuous low dose estrogen and progestin menopause regimen
o Cyclic progestin therapy for 12 days a month
o Continuous low dose estrogen (0.625mg conj EE)
o Estradiol vaginal ring

Osteoporosis

* A menopausal patient with osteoporosis has been reading information on the Internet about different treatment modalities for osteoporosis. She wishes to know more about what therapies are actually available and how they work?
o Estrogen: Reduces osteoclast activity
o SERMs: Reduces osteoclast activity
o Bisphosphonates: Reduces osteoclast activity
+ Take on empty stomach, first thing in AM with 8oz water and no food for 30 minutes
+ Take sitting up due to esophagitis risk
+ Calcium supplementation within 4 hours
o Calcium / Vitamin D supplements

Menopause.ppt

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Physiologic Changes in Pregnancy

Physiologic Changes in Pregnancy
By:Thomas S. Ivester, MD, MPH
Maternal-Fetal Medicine

Relevance of OB physiology
* 5-10 % of women in ER are pregnant
o Many don’t know or show
* Any female of reproductive age could be pregnant
o Should be assumed so!
* Virtually every organ system affected
* Can touch almost any specialty

Case history
Case 1

* 36 y.o. female presents to ER
* CC: Fatigue, dyspnea, chest pain
* HPI:
o Progressive SOB and dyspnea over several weeks.
o Poor exercise tolerance and easy fatigability
+ ‘get winded after 1 flight of stairs’
o Substernal chest pain, peaks in morning and night
o Nocturnal cough, semi-productive – clear
o Leg swelling
o polyuria
* PMH
o Mild obesity
* Ob/gyn – menses at age 12; irregular menses; no pregnancies
* Meds
o Oral contraceptives
o multivitamins
* Social
o Married for 2 years. No exposures

Case 1: PE
* Skin
o warm, clammy. Mild facial acne and increased hair – medium coarseness
* HEENT
o NC/AT. Nasal mucosa slightly hyperemic.
o Mild non-nodular thyromegaly
* CV
o Tachycardia (HR 107)
o + JVD
o 2/6 systolic murmurs over pulmonic and aortic v.
* Chest
o Clear bilaterally. Diaphragm elevated with decreased excursion
* Ext
o 1+ pretibial pitting edema
* Abd
o Skin – spider angiomata and striae. Medium course hair, infraumbilical.
o Distended, firm, non-tender.

Studies / labs
* EKG:
o Sinus rhythm; tachy; Left axis deviation
* CXR:
o Lungs clear. Cardiomegaly. Increased vascular markings
* Labs:
o Hct 32% (low); WBC 12 (high)
o Cholesterol 300 mg/dl
o D-dimer elevated
o Potassium and creatinine low

What does she have???
General Principles
* Most changes begin early
o Even before pregnancy recognized
* Most are hormonally driven
o Progesterone, estrogen, renin / aldosterone, cortisol, insulin
o Some ‘mechanically’ driven
* Designed to optimize conditions for fetus & prepare for delivery
o Delivery of oxygen & nutrients
Cardiovascular & Hematologic
* Vascular
o Decreased tone / vaso-relaxation
+ SVR decreased 20%
o Positional effects
o Placenta – low resistance shunt
* Hematologic
o Blood volume increases 50-100%
o RBC increases 25-40%
+ Relative anemia (“physiologic”)

Hematologic
* Hypercoagulable
o Estrogen & Vascular stasis
o Increased risk for thromboembolic disease
+ Increase in fibrinogen, all coag factors except II, V, XII
+ Fall in protein S and sensitivity to APC
* Fall in platelets and factor XI and XIII
* Increase in WBC

Changes in the Pump
* Cardiac axis displaced cephalad and left
o PMI lateral & elevated (not just due to baby!)
+ Altered thoracic dimensions
o Left axis deviation
* Murmurs > 96%
o Virtually all valves
+ Esp. Aortic and Pulmonary
+ Mammary Souffle
* Rate – increased (80’s typical)
* Ventricular distention – 25% increase
* Rhythm
o Non-specific ST & T changes
o Increase in dysrhythmias
+ Physiologic hypokalemia
* Anatomy
o LVH & Pericardial effusion
* Function
o Increased & markedly fluctuating output

Blood Pressure
Pregnancy Adaptations
Anatomical considerations
Uterine Position over Time
Cardiac Output – Positional Effects
* Aorto-caval Compression
Labor Changes
* SVR – Increased 10-25% with CTX
* Volume – autotransfusion 300-500cc
* Cardiac output -
o <3cm Increased 17%
o 4-7cm Increased 23%
o >8cm Increased 34%
The Fetus and Placenta
* Fetus (aka – “the parasite”)
o A sensitive survivor
o A window
* Placenta
o A veritable hormone factory
o Receives 20-25% of cardiac output*
+ 750-1000 ml/min
+ Refractory to vasoactive meds
o Uses as much O2 as fetus

Normal physiology or disease?
Signs & Symptoms of Normal Pregnancy that may Mimic Heart Disease
* Signs
o Peripheral edema
o JVD
* Symptoms
o Reduced exercise tolerance
o Dyspnea
* Auscultation
o S3 gallop
o Systolic ejection murmur
* Chest x-ray
o Change in heart position & size
o Increased vascular markings
* EKG
o Nonspecific ST-T wave changes
o Axis deviation
o LVH
Other systems
Changes in the Filter
* Renin – stimulated by progesterone
o Also made by placenta
o Angiotensinogen Angiotensin I Angiotensin II Aldosterone Distal tubule
+ Net absorption of Na+
+ Excretion of K+
+ Water retention: 6-8 liters
* Increased renal blood flow
o 50-75% increase
o GFR – 50% increase
o Decreased Albumin = lower colloid oncotic pressure

Other urinary tract changes
* Ureteral dilation / hydroureter
o Smooth muscle relaxation
o Later exacerbation by uterine obstruction
o Urinary stasis*
* Dilation of pelves and calyces
* Increased kidney size
Lungs and respiration
Respiratory Adaptations
o No change in rate or IRV
o Thorax
+ Tr. Diameter 2cm; circumference 5-7cm
o Increased minute ventilation
o Reduced FRC – 20%
o Increased Tidal Volume – 30-40%
o Compensated respiratory alkalosis
+ pH 7.4+
+ PaO2; PaCO2 (40 – 30)
+ Drives gradient b/w mom and fetus

Respiratory Changes
Gastrointestinal
* Slowed GI motility
o Constipation, early satiety
* Relaxation of LES
o GERD
* Nausea / vomiting
o Often proportional to HCG level
* Liver / gallbladder
o Biliary stasis, cholesterol saturation
+ More stones
o Coagulation factors
o Increased binding proteins (thyroid, steroid, vitamin D)
Other “Adaptations”

* “I can’t see my feet!!!”
o Altered center of gravity
o Altered gait
o Greater joint laxity
+ Widening of symphysis pubis
+ Affects other joints
+ Thorax; widened costovertebral angle
o Fatigue / somnolence

Integumentary Changes
* Spider angiomata and palmar erythema
* Hair growth (abdomen and face)
* Mucosal hyperemia
* Striae gravidarum
* Hyperpigmentation (esp. linea nigra)
o Rashes and acne relatively common
Other Endocrine
* Pancreas
o Carbohydrate metabolism -Insulin resistance
+ Human placental lactogen, cortisol
* Thyroid Function
o Increased TIBG (via liver)
o Increased total T4 and T3
+ free levels unchanged
+ HCG suppresses TSH
* Adrenal function
o Free plasma cortisol is elevated
+ CRH from placenta stimulates ACTH
Immunology

* Must adapt to accept ‘allograft’
* Immune response altered, but not deficient
* Modulates away from cell-mediated cytotoxic effects
o Progesterone effect
o NK cells decrease by 30%
o Enhanced humoral / innate immunity
+ Immunoglobulins still active
+ IgG crosses placenta
o More susceptible to CMV, HSV, Varicella, Malaria
o Decrease in symptoms of some autoimmune disorders

Pregnancy – not a disease

* Profound changes in physiology and anatomy
* Affects most organ systems
* Can dramatically impact disease states, susceptibility, and treatment
* Almost all will encounter and treat pregnant women
o Even if you don’t know it
* Under-appreciation of changes will lead to suboptimal treatment or outright mistakes

Physiologic Changes in Pregnancy.ppt

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