Medicine

Medicine Teaching Resident Session: Cirrhosis Dr. Saji Abraham 4/8/04 Cirrhosis is classically categorized as micro or macronodular, though there is no clinical correlation, and micro becomes macronodular; alcohol is classically macronodular. Etiologies include alcoholism, the #1 cause in the U.S. EtOH is a mitochondrial poison and initiates a fibrotic process involving the peroxidase system. Hepatitis B and C, sclerosing cholangitis, Wilson‟s disease, in which patients have chorea, psychiatric disorders, Kaiser-Fleischer rings in the limbus of the cornea, low ceruloplasmin (though that isn‟t pathognomonic); treatment is penicillamine; alpha-1 antitrypsin deficiency, primary biliary cirrhosis, cardiac cirrhosis, CREST syndrome, hemochromatosis- hereditary or acquired- for which phlebotomy is the first line of treatment; SB; prolonged use of TPN; and Budd-Chiari syndrome, which is associated with HRT, causing portal vein thrombosis leading to cirrhosis. Hypervitaminosis A can give jaundice without scleral icterus. Presenting features include palmar erythema, ascites, asterixis, mental status change, fatigue, anemia; acute alcoholic hepatitis advances to cirrhosis, and presents with pain and jaundice, and a 2:1 AST to ALT ratio, since alcohol inhibits ALT and promotes AST release. Cirrhosis becomes the diagnosis when coagulation factors, testosterone drop and asterixis setts in. Usually, in cirrhosis, the PT is the first to change, then albumin, then later, testicular atrophy, gynecomastia, asterixis, ascites, etc. Complications include ascites, esophageal and gastic varices, caput medusae, retroperitoneal bleeds, leg swelling, hepatic encephalopathy, generalized constitutional symptoms, hepatoma, jaundice, low libido, heart failure, splenomegaly, hepatorenal syndromewhose etiology is not clearly defined but involves Na retention and intravascular depletion; treatment requires liver transplant, and it commonly sets in after use of NSAID, diuretic, vasoconstrictive agent; the patient has prerenal azotemia though he looks overloaded. Ascites is due to portal hypertension- high pressure and low oncotic pressure leads to fluid buildup in the peritoneum that exceeds lymphatic ability to resorb it. The serum:ascites albumin gradient, if >1.1, indicates portal hypertension as the etiology of the ascites; if less, leads us to suspect another cause such as TB or carcinomatosis. Spontaneous bacterial peritonitis is usually caused by e. coli and can be prophylaxed for with nitrofurantoin. Varices, encephalopathy- a patient may develop encephalopathy despite a relatively low ammonia level due to medications or a GI bleed and the concomitant hemolysis and protein release. Treatment is lactulose, which traps ammonia in the gut, and neomycin, which kills protein-digesting bacteria in the gut without being absorbed by gut mucosa. Ascites can be treated with beta blockers, which lower portal hypertension, and spironolactone is maintenance therapy; only 900 cc is handled by the liver, so care should be taken not to diurese more, since the patient is already in a state of reduced effective blood volume, and he may get dehydrated and prerenal. If ascites continues to worsen, options include paracentesis; albumin is a temporizing measure; lasix, but no more than 1L of diuresis per day; also, watch urine lytes. Paracentesis of 4-6 L 2-3x a week, send labs on the fluid- WBC, chemistry, albumin, cytology (if there is carcinomatosis- e.g. hepatoma, ovarian carcinoma), ADA (adenosine deaminase, which helps in TB diagnosis; gram stain and culture. Next stepTIPS, which relieves portal pressure, helping ascites and varices but accelerating encephalopathy. Varices treatment- a Blakemore balloon can be used to stabilize the patient if no gastroenterologist is available to do immediate banding; complication rates are high in the wrong hands. Banding is better than sclerotherapy for acutely bleeding varices. Grand Rounds Misconceptions in Opioid Management Dr. Robert R. Duarte 4/20/04 Top ten list- “I left my bottle upstate at the ski lodge (in chronic pain, yet can go to ski lodge?)”, “my sister stole my bottle (she is the addict)”, “The drug store computer broke down and...”; “someone stole my Percocet from my car (they left everything else, even the radio)”, “My dog ate it,” “my husband needs the prescription”, “the pills fell into the toilet”, “the druggist dropped nail polish remover on the prescription”, “I‟ve been throwing up and my pills...”, “my girlfriend put a gun to my head, said „I will only have sex with you if...‟”. Pain is the most common reason individuals seek medial attention. 75% of all advanced stage cancer patients, 85% of AIDS patients have moderate to severe pain, 50% of post-op patients undermedicated, women, minorities, substance abusers undertreated for pain. Pain is all in your head- true; to feel pain, you need a cortex; all pain has a psychological component, so there is a need for a multidisciplinary approach; includes psychiatrists, physiatrists, neurologists, and nurses. Acute pain- hurt arm, leg- comes and goes, is over, nothing left. Chronic pain- “affective and sensory component”- IASP- numbness, tingling, burning- but also frustration, anger, etc. McCaffrey- pain is “whatever the patient states hurts”- if you don‟t believe the patient, transfer to someone who willing to treat it. “Pain that has outlived its usefulness.” Pain diagnosis- acute vs. chronic, intensity, pathophysiology- neuropathic syndrome; i.e., Reflex Sympathetic Dystrophy (CRPS), diabetic neuropathy, trigeminal neuralgia, shingles thennociceptive- non-neuropathic- achy- arthritis, bone cancer; then- kvetch- don‟t know what‟s going on. Neuropathic agents- pain modulators- antidepressants, anticonvulsants- gabapentin, and even anti-arrhythmics- mexilitine; but rare, usually former two. Analgesic agents- for nociceptive pain- NSAIDs; which is the most effective? All are about the same; combination analgesics- Vicodin, Percocet, etc. Then- opioids- short-acting vs. long-acting; morphine, hydromorphone is short-acting, while oxycontin, duragesic, etc. are long-acting. Opioids- some evidence to show that IV fentanyl is effective in some neuropathic pain; TD fentanyl- peripheral neuropathic pain; oxycodone- PHN, tramadol- diabetic neuropathy. 1970- Controlled substances act- regulates controlled substances; before approval of any drug, must be approved by FDA and DDA; classified opioids, drugs into five schedules according to relative potential for abuse. Class I- high potential for abuse, no currently accepted medical use- heroin; class II- is high abuse potential but accepted medical use; class III-V- less abuse potential. Yet lower-end drugs are likelier to be abused, probably because easier to access them. Brand vs. generic- brand of vicodin makes more money on the street, should be no difference in effect, so why asking for it? Looking for quick onset, short duration of actionquick rush, intensity, whether a product can be injected or snorted successfully- has high street value if can be injected. Back in 1970‟s, drug abuse warning network to monitor what happened with these drugs. Drug-related deaths #1- cocaine; then heroin/morphine, then alcohol-in-combination, then codeine. Methadone was number 8; Propoxyphene- Darvocet- #11 drug cause of death; we consider it very mild- Tylenol with side effects! Meperidine was #32- oral form doesn‟t give quick rush. Fentanyl was lower down, as was hydromorphone, but latter has risen on the list. Joint commission- administer analgesics “around the clock” rather than PRN; administer drugs orally whenever possible; avoid intramuscular injections. Avoid using meperidine (for no more than 48 hours- metabolite- normeperidine- toxicity), never for chronic pain state. Addiction occurs very rarely in patient who receives opioids for pain control. Barriers to effective pain management- pain is under-recogized; health care providers lack knowledge about what is addiction, dependency, tolerance; fear of legal consequences, that DEA coming after you; patient, family, societal beliefs- „I don‟t want to get addicted.‟ Dependence simply means that if take drug, then decide to stop it, will go through withdrawal process, and are dependent upon the drug; if stop taking it, will have a problem; same with opioids. Tolerance- if tend to need more to get the same effect; in cancer patients- Kathleen Foley showed- if cancer worsens, tend to need more. In non-malignant pain, see it less often- if pathology doesn‟t change, tolerance doesn‟t change. Addiction- chronic problem- if taking on chronic basis- craving to get a high, altered sensation, use it despite harm- had patient taking 100 tramadol pills a day, had seizures and renal failure but still took them. “I feel like a king” syndrome- that‟s not what drug is supposed to do for you. Addiction is common- false; 0.034% in hospitalized patients. Behaviors more suggestive of addiction disorder- selling prescription drugs, prescription forgery, injection of oral/transdermal formulatons, multiple dose escalations despite harm, multiple episodes of prescription loss, seeking prescriptions from multiple doctors, stealing prescription pads, missing multiple appointments, the “out of towners.” Moderate to severe pain, put on occasional Darvocet or codeine, still complain of painmay be pseudo-addicted- may really be undertreated. Drug hoarding at times of reduced painvery common- patient may actually keep e.g. a 3-week extra supply that they keep when they don‟t need it as much; this doesn‟t mean they‟re addicted, just that using it as needed. If they come in, ask for specific drug- I want methadone, I want codeine, etc.- they allow you to evaluate record, etc., then they tell you “this is what works for me”- maybe that is the best thing to do, follow closely, be sure no other signs of aberrant behavior. If demand up front- show them the door. Obtaining strong analgesics for minor procedures- Ok. Unsanctioned dose escalations- if uncommon, episodic- 1-2 occasions- Ok. Resistance to change to another medicine- Ok. Call on weekends or after hours for prescription- I consider that aberrant behavior. Call from an anonymous informant- really can‟t go on that; can bring it up with patient the next time, but sometimes these are just trying to get the patient in trouble. Tolerance- to nausea, respiratory depression; sedation- usually goes away in 3-7 days. They never get tolerant to constipation, so give them prophylaxis. Opioids have no end organ toxicity- no effect on kidney or hepatic function, but does have constipation, decreased libido. We do recommend repeat LFT, renal function panels every few months. The DEA, State medical boards are watching- goal is to protect patients and society; exchanging prescriptions for sex, running a cash business, etc. DEA isn‟t out to get you- recognize legitimate use of these agents in treating pain for legitimate use of these agents in treating pain for legitimate medical purposes. Is the practice consistent with acceptable medical standards? They understand that all docs can be duped; as long as are documenting it, is Ok. In 1992 survey- 40% agreed that their prescribing of opioids for chronic pain was influenced by legal concerns. Total sanctions imposed- 4467, controlled-substance related- 337, 40 license revocations- so not very common. Just document. Ask self- is pain expected to be opioid responsive? Neuropathic, nociceptive, mixed? If neuropathic- try on anticonvulsants, etc. first; has patient tried other viable therapies? For severe pain, must start on opioid, but sometimes can try NSAIDs, etc. for more minor pain. Assess risk for addiction- ask about behaviors suggestive of abuse, prior history of addiction, records of prior docs, treatments; include pharmacists- but need to have understanding with patient that are allowed to speak with pharmacist- otherwise privacy violation. Contract- clarify expectations and goals, set limits, use drug screen, stress importance of using this drug appropriately. One and noone doctor, pharmacist, monthly visit, monthly prescription, report of my dog ate it; no weekend calls, etc. Follow-up visit- analgesia, ADL‟s, an adverse effects, aberrant behavior? Must get in any chronic pain patient. If no H&P- unlawful prescribing. Pharmacist is legally allowed to change directions on prescriptions if they call you; maximum daily dose, strength of dose if less, can be changed by pharmacist on phone; they can write in DAW; they can decrease quantity of drug only. Forged prescriptions- felony; telephone prescription is still a felony. Tell patients this. Also, write out „ten‟, because they can change number to 40, 70, etc. Rinsing prescriptions- can simply take nail polish remover, lift all the writing on a script if it‟s a simple white pad, except for your imprint, they can write whatever they want there, can take your penicillin prescription, write vicodin. Designate number of refills, even if non; consider duplicate prescriptions, consider tamper-resistant pads, don‟t pre-print your DEA number on prescription. Can by law give 3 month supply if write code D- relief of chronic pain. Post-dated prescription- illegal. Need to date it today, write „to be filled by‟ because can‟t write prescription if not see patient- is fraudulent. Emergency prescription- 3-day supply, document- for emergency dispensing; can give over phone. If you know patient is addicted, can‟t prescribe to maintain the addicted state. Want a written treatment objective and plan. In contract- can get in trouble- abide by contract, because patient can sue you for maintaining him in addicted state. Must document that saw patient at least every three months- on a regular basis. Should send him to someone else for second opinion if you have problems with it. Document. [Soma- red flag- I try to use other muscle relaxants.] [Don‟t put patient on antiinflammatory and acetaminophen on regular basis- hurts kidney function.] [Ultramacetaminophen and tramadol combination that is synergistic.] [How treat these patients when say no? Evaluate the patients, be up front with them from day one, set rules, parameters, that‟s it- if don‟t abide by it, are out the door; if want to go further, can send you to someone else. Once enter into relationship, are stuck, so set parameters from day one.] Coagulation Disorders Dr. Tu Tu Aung 4/14/04 Case- 35-y/o lady who came in with pulmonary emboli while on oral contraceptives, completed 3-6 months of coumadin, now see she‟s heterozygous for prothrombin gene mutationwhat to do? Not need long-term therapy, but d/c oral contraceptives. Homozygote- would treat with coumadin for life. PE 1 week after 16-hour airplane trip in 40-y/o Chinese woman- in Caucasian woman, would look for Factor V Leiden and prothrobin G20210A mutation; in Asian women, this is extremely low, so no testing required. Protein C assessment- is consumed at time of acute presentation, may produce false positive result. Once have started warfarin, can‟t assess, so wait 6 months, stop it, test. Lupus anticoagulant also isn‟t measured because patient is placed on heparin now. Screening for cancer- in older people, more malignancies can be suspected; this is relatively young person after flight, don‟t need whole body scan for one DVT. 67-y.o. with peripheral vascular surgery 2 months ago, now with myocardial ischemia, two days later- pain persists, platelet count drops- patient has heparin-induced thrombocytopenia, usually takes 5 days but he was exposed previously in his surgery; so stop the heparin immediately, use hirudin or argatroban, whichever thrombin-inhibitor you use. Platelets- if falling precipitously, even if not at 50,000, still assume HIT; also, anti-platelet antibodies. Lovenox also cannot be used if HIT. 50-y/o woman wants HRT for hot flashes, her daughter had DVT with OCP, heterozygous for factor V Leiden mutation- what do you do? Recommend against use of HRT; initiate anticoagulant prophylaxis at times of increased thrombotic risk- long flights, etc. 30 mg of Lovenox for prophylaxis. Even if get up and walk- low-pressure cabins, can still happen. If must give her HRT, don‟t give coumadin unless prior clot- risk/benefit ratio. 25-y/o at end of first trimester, had DVT on oral contraceptives three years ago- what to do? This patient did have one episode of thrombosis; although wasn‟t pregnant at that time, had one previous episode so still has risk; so- continue to monitor, after delivery, give enoxaparin for 6 weeks- usually get thrombi soon post-delivery. 65-y/o man with three-day history of swelling, warmth, erythema in left calf, DVT on ultrasound, heavy smoker. DRE, stool specimen- normal, CBC, PT, PTT, chemistry, PSA, SLE panel, CXR normal. Next best step- nothing- not cost effective to do full-body CT for every 65y/o with DVT. Upper, lower GI- if patient never had colonoscopy done, is recommended but not relates to DVT. 50-y/o with 3-day hx of low-grade fever, confusion, physical- pallor, ecchymoses, low Hb, WBC, platelets at 12K, peripheral smear- schistocytes, decreased platelets- TTP; add up clinical suspicion. Heparin-induced thrombocytopenia- platelets dropping after bypass surgery; no schistocytes in peripheral smear, PT/PTT normal so not DIC or TTP. HIT- serotonin-release assay for heparin-platelet factor 4; HIT causes arterial thrombosis. DVT treatment- lovenox 1 mg/kg, and warfarin 5 mg/d, adjusted to INR of 2 to 3. 40-y/o woman with DVT, PE 1 month post-partum, warfarin started, brother, father, she too- protein S deficiency; after 6-month coumadin for DVT- how treat? She developed DVT post-partum, had pre-eclampsia- want to consider giving her a chance- thrombosis risk is higher than others but DVT attack wasn‟t unprovoked- considerable risk factors- so give nothing, counsel about prophylactic anticoagulation in high-risk situation. Start with heparin, move to coumadin. Switching over from argatroban to warfarin- initate warfarin at 5 mg/d, and discontinue argatroban when INR is greater than 4; if INR is just 2, may be sole warfarin effect; need effects of both, so wait until INR is greater than 4. Low-molecular weight heparin post-DVT- 3-6 months. Unprovoked DVT, heterozygote for G20210A- test her whole family. Higher risk of recurrence is true of everyone who has had one DVT- always at risk for another DVT, prophylax for high-risk situations with lovenox. Coagulation pathway- natural anticoagulant- antithrombin III- to prevent clotting, protein C and S act on IX to X. Natural anticoagulant system- Protein C, S, ATIII, fibrinolytic system. All hereditary disorders associated with venous clots except for homocysteinemia; both arterial and venous- homocysteinemia, antiphospholipid antibody syndrome, HIT, myeloproliferative disorder- need phlebotomy, malignancy. Cost of transfusion- each bag is $500. Test informative in presence of anticoagulation agents- factor V Leiden, protrombin gene mutation, hexagonal phospholipids neutralization test, homocysteine levels. Thromboembolism association with OCP, HRT, pregnancy, puerperium but should still be tested for hereditary thrombotic disorders if one develops. Vena cava filters- higher recurrent DVT levels though sustained PE smaller, so place filter when anticoagulant therapy is contraindicated. Order D-dimer, if negative, clinical suspicion very low- can say „It‟s nor a DVT.” If D-dimer is positive, not necessarily PE or DVT. Negative does rule it out though. Morning Report 4/22/04 Pt with high blood pressure, one second of sharp pain, bingeing for four days, drinking 4 glasses of scotch a day, works as cab driver. Denies nausea, vomiting, diarrhea, any prior angina. Came to ER- 180/90. No caput medusae, asterixis, liver span normal, no spider angiomas, no scleral icterus or jaundice. Palmar erythema, dupuytren‟s contracture. Alcohol 41- probably drank 2-6 hours earlier. AST, ALT look normal- liver Ok. Alcohol syndrome- 8 million people in US are alcohol dependent. Some get more severe withdrawal syndromes than others. 7 to 34 days of drinking- minor withdrawal syndrome; 48-87 days- major withdrawal symptoms, but usually no withdrawal because drinking episodically. Gamma-aminobutyric acid, epinephrine, serotonin involved. Minor withdrawal symptoms- tremulousness, mild anxiety, headaches, diaphoresis, palpitations, anorexia, GI upsetetc. Withdrawal seizures- generalized tonic-clonic convulsions usually occurring within 48 hours after the last drink; alcoholic hallucinosis- 12-24 hours- usually visual, resolve in 24-48; global clouding of sensorium- no- specific hallucinations. Delirium tremens- delirium, tachycardia, hypertension, agitation, fever, diaphoresis; last 1 to 5 days; are associated with 5% death rate from arrhythmias, etc. Is diagnosis of exclusion. Risk factors- sustained drinking, previous DT‟s, etc. DT‟s- three days after abstinence, so must follow up patients. Ativan- use as maintenance- short-acting, can be used in cirrhotics, unlike valium. Librium not used as much because require conjugation in liver. Valium- has active metabolite. Fixed-dose, front-loading therapy, or symptom-trigger therapy- total amount needed is 5x less. Is option of lorazepam or oxezapam IV; surgical floors- like to give atenolol. Treatmentfrequent reevaluatiion- rule out infection ltrauma, metabolics, drug overdose, hepatic failure, etc. Fetal position- so if vomit, won‟t aspirate, and good for psancreatitis. Is situation in whch can get very hyponatremic very quickly- usually not. but must monitor, fix metabolic derangements. Give vitamins. May need LP, CT to rule out other causes. Now- JCAHO- mandated to offer alcohol counseling, rehabilitation, must be documented. How much drinking- suspect alcoholism? Screen with CAGE, if suspect risk, must offer some counseling, help. CPC Conference Dr. Slava Fuzaylov 4/22/04 55-y/o female who immigrated from Jamaica 12 years ago, nurse‟s aide at Elmhurst; one episode of hemoptysis, abnormal CXR but PPD negative. No recent travel. Pulmonologist sent after abnormal CXR. Right upper lobe- asymmetric density in right apex- fuzzy, nodular pleural thickening, doesn‟t completely go to apex; asymmetric infiltrate in right upper lobe. No obvious areas of cavitation, no obvious mediastinal, hilar lymphadenopathy. Apical lordotic view- tilt the ribcage, shows lung apex better. Patchy infiltrate again seen in right upper lobe. Makes us think about tuberculosis; really no lymphadenopathy, though, to indicate it. Intraparenchymal lesion could be present in mesothelioma, but usually marked pleural thickening throughout the chest. CT- densities we saw are much better characterized- is cavity in lung apex, little ball of soft tissue in the cavity; also see adjacent scarring, fibrosis. No adenopathy in chest; not typical for tuberculosis- no pleural effusion, no infiltrate, etc. Scarring, fibrosis, cavity- can get superimposed fungal infection; also must consider neoplastic process- cancer arising from scar. Mesothelioma would be very unlikely given this CT finding. We do thin slices with hemoptysis to look for bronchiectasis, none seen. Bronchoscopy was done, fungal, AFB, gram stain, etc.- all negative. Antibody tests- not particularly useful in fungal infection except urinary histoplasma antigen. Coccidiomycosisnever send for culture because is dangerous. Based on CT- admitted in 3/2004 for right thoracotomy with en block wedge resection of right upper lobe. due to possibility of malignancy. Physical exam- some wheezes. Differential diagnosis of hemoptysis with cavitary lesions- mycetoma in a cavitary lesion caused by TB, histoplasmosis, coccidiomycosis, sarcoidosis, bullous emphysema, and malignancy. Pathology- hyphae, majority detached from wall of cavity, sitting like foreign material. Some round because seeing them on cross-section, have septae- differentiates from mucor- no septae. Granulation tissue forms the wall of the cavity; plasma, lymphoid cells, then fibrotic wall of cavity- caused dense fibrous tissue; then- lung tissue which is approximately normal. Is it angioinvasive or not? I.e., does it just sit there or can it travel to other organs? No angioinvasion seen. Rest of the lung- bloody; if have invasive aspergillosis- can infarct lung tissue in wedge shape; here- lung parenchyma fine, not infarcted. Treatment algorithm is completely different. Fungus ball in cavity- resect for symptoms, not to treat; is no fungal therapy given to people with fungus in cavity. If is invasive, do need to provide antifungal therapy. If is angioinvasion, treat, duration depends upon underlying host risk factors. Frozen pathology specimen showed some aspergillus invading the tissue, since frozen section isn‟t as reliable, so patient was given Amphotericin B for one day, then continued on Cancidas for 5 days; discharged on Voriconazole 200 mg PO BID on the 5th day, for 2 weeks. In tissue, but not angioinvasive so 2 weeks, not 6-9 months. Aspergillus- genus of 200 fungi found worldwide; appear as round single cells like yeast, or chains- hyphae; filamentous fungus, can be easily made airborne. First known case- 1842; catalogued in 1729; caused allergic lung disease in wig combers. Some aspergillus makes mycotoxins, poisons in food; some are pathogenic, some make useful products. We normally breathe in 100-200 spores daily. Most common cause of invasive disease- aspergillus fumigatus, flavus; former and clavatus causes allergic disease most commonly. Fever, cough, chest pain, breathlessness, usually in immunocompromised or suffer other lung conditions. Three forms- Allergic bronchopulmonary aspergillosis, aspergilloma, or acute invasive aspergillosis- former to latter up with immune malfunction; other risk factors- diabetes; need tissue biopsy for diagnosis since it‟s an environmental pathogen- is all over. ABPA- hypersensitivity, often in asthmatics or cystic fibrosis patient; can show fleeting pulmonary infiltrates or impacted bronchial atelectasis. Aspergilloma- mycetoma fungus ball which develops in a preexisting cavity in lung; less commonly- can arise de novo in bronchi with subsequent erosion. Crescent of air partially outlining solid mass; may be free floating or attached to wall with stalk. Invasive aspergillosis- rapidly proghressive infection in patients with prolonged neutropenia or immunosuppression; interestingly, not seen very commonly in AIDS patients, but bone marrow or solid organ transplants, chemo, neutrophil dysfunction. Characterized by invasion of blood vessels and dissemination to other organs. Typically manifest with fever, dyspnea, pleuritic chest pain, hemoptysis. Variable CXR; CT may show Halo signground-glass area around cavitation. Allergic bronchopulmonary aspergillosis diagnosis- history of asthma/cystic fibrosis, fleeting pulmonary infiltrates, mucoid impaction, aspergillus in sputum, eosinophilia, etc. Definitive diagnosis- needle or open-lung biopsy. ABPA- mainstay of treatment- corticosteroids, and antifungal treatment decreases symptomatology, though unclear why since aspergillus isn‟t invasive. Aspergilloma- treatment is surgery; antifungal therapy is not required unless patient not fit for surgery or concurrent tissue invasion. Amphotericin B for IPA; but toxicity is high, so recent studies show that sequential treatment with caspofungin and the azoles comparable to Ampho B. Amphotericin- cidal, as is caspofungin, while azoles are static; in immunocompromised patients, is just your therapy, no immune system to help you out, so use combination therapy; animal studies- sequential therapy bad idea, if want to do it- ampho first, then azoles because latter decreases sterol production. Can give Ampho or cancidas with azoles. Diflucan- doesn‟t work for aspergillus, so use itraconazole or voriconazole- latter is better absorbed. Problem- significant CYP450 drug-drug interactions, must adjust for that, except with diflucan. So if choose azole, voriconazole with either amphotericin or cancidas. Why used latter- less nephrotoxic, and dose of amphotericin for aspergillus is highest possible, so give alternatives if they‟re as efficacious. If had been angioinvasive, would have given cancidas with voriconazole for one month, then latter alone for 6-9 months. We decided- she had TB cavity that became infected with minimal tissue invasion. Surgeon was concerned because was aspergillus at stump, feared stump would dehisce; otherwise, needs no treatment once resected. Resident Family Feud 4/23/04 Three clinical/serological differences of drug-induced SLE and idiopathic SLE: AntiDNA or anti-Histone antibodies; idiopathic can cause nephritis, cerebritis; drug-induced is reversible. Four top symptoms of Lyme disease- myalgias, arthralgias, headache, fatigue, erythema migrans. Four top causes of lower GI hemorrhage- hemorrhoids, arteriovenous malformation, diverticuli, carcinoma. Glucose > 200, LDH >350, Age > 55, AST > 250, WBC > 16,000. Four tumors that spread to bone- Prostate, Lung, Breast, Thyroid, Kidney. 3 common types of strokeshemorrhagic, ischemic, embolic. 5 common causes of CK elevation- MI, rhabdomyolysis, brain injury, myositis, renal injury, myocarditis, muscular dystrophy. Major modifiable CAD risk factors- tobacco, cholesterol, diabetes, hypertension. LDH elevation- 4 common causes- hemolysis, MI, hepatic injury, large PE, renal infarction, prosthetic heart valve. PCP, leukemia/lymphomas- less common. 5 diagnostic criteria for schizophreniahallucinations, delusions, disorganized speech, negative symptoms greater than 6 months. 3 top causes of community-acquired pneumonia- Pneumococcus, H. Influenza, M. Catarrhalis. Four kinds of thyroid cancer- Papillary, Follicular, Medullary, Anaplastic. Three hyperkalemia with metabolic acidosis- RTA 4, Addison‟s, hyperalimentation. Lab analysis of transudative pleural effusion vs. exudative- 10% of transudates are malignant. Primary Care Internal Medicine Dr. Cruz M. Fana 4/26/04 46-y/o little league coach pitched batting practice over the course of a 6 week season and his right shoulder became sore. Symptoms persisted for several weeks after the end of the little league season despite Ibuprofen self-treatment. Loss of PROM in external rotation and abduction, pain with elevation of his arm above horizontal, pain and weakness are present when his right shoulder is positioned at 90 degrees of abduction, elbow flexed and forearm pronated. Relief of symptoms with lidocaine. What would be appropriate management at this time? Subacromial injection of a long-acting anesthetic-corticosteroid followed by physical therapynot surgical candidate until goes for physical therapy, physical exam alone reveals rotator cuff tear. If not get better in six months, MRI- think rupture, not tear. 38-y/o man got inversion sprain of ankle, iced on and off, now can‟t bear weight, left ankle ecchymotic and swollen, tenderness on anterior, lateral aspects, painful inversion; ligamentous testing reveals third-degree (complete) tear of lateral ankle ligaments; no fractures. How treat him? Inversion sprain- most common type of ankle injury. Think of RICE- rest, ice, compression, elevation within 24-72 hours; use compression bandage to reduce swelling- need full leg cast but aircast, ice them down for 2-3 days, send to rehabilitation ASAP. 20-y/o woman dislocated glenohumeral joint of throwing arm for first time, anteriorly; dislocation reduced; no fractures, no neurologic impairment of axillary nerve. These- first-time80% chance of recurrence, can reduce rate with arthroscopy by orthopedic surgeon. 42-y/o man in-line skating fell on outstretched hand, treated for a comminuted fracture of his clavicle, abrasions, lacerations, mild concussion; gets better, but getting worsening wrist pain with active wrist flexion, extension and ulnar deviation. Pain localized to anatomical snuffbox. Problem with scaphoid fractures- often overlooked on X-ray, can get avascular necrosis, loss of function. So immobilize wrist in splint for 1 week; if symptoms persist, repeat X-ray, order bone scan if no fracture seen. 64-y/o woman has sudden onset of visual loss in left eye, recent history of headache, mild HTN treated with triamterene-hydrochlorothiazide; 20/30 in right, 20/70 in left next day; ophthalmoscopic exam- pale swollen optic disk of left eye with scattered flame-shaped hemorrhages near the disk- afferent papillary defect in left eye. So non-arteritic (not giant-cellpale optic disk) ischemic optic neuropathy. Occlusion of retinal artery- see cherry spot; cholesterol emboli look very different. 66-y/o black man with myopia, HTN, DM seen for his annual examination; no visual symptoms. Ophthalmoscopic findings that support diagnosis of glaucoma- not intraocular pressure itself; cup:disk ratio of greater than 0.5- enlarged optic nerve, asymmetric cup:disk ratios, flame hemorrhages at disk edge. Determine glaucoma with perimetry. Medicine, surgery for open-angle glaucoma; for closed-angle- red, painful eye, moderately dilated pupil, see halos, acutely nauseated, fix, mid-dilated pupil- emergency. Present over time with tunnel vision. 63 y/o obese man with left retro-orbital pain and diplopia for several hours, left eye cannot adduct on rightward gaze; mild left ptosis and normal bilateral pupillary reations are present. Gaze to left is normal. No nystagmus, ataxia or long-tract signs are present. This is diabetic optic disease- third nerve palsy but pupillary reactions intact. Most common causeposterior communicating artery aneurysm, suspect if >50. 45-y/o man present with history of fatigue for three months; flashlight shone into right eye, both pupils constrict equally; when the flashlight shone into left eye, left dilates without any consensual reaction in right pupil- MS; ask to abduct, see nystagmus. Optic neuritis- decrease in acuity; opthalmoplegia. 72-y/o woman with shoulder pain and mild drooping of left eyelid, anisocoria present with right pupil being 3 mm, left 2 mm, both react normally, EOMI- pancoast syndromehorner‟s. 64-y/o woman that straight objects look wavy- macular degeneration- most common blindness in elderly. 19-y/o female soccer player planted left foot, turned while running after ball, heard popping in left knee, difficulty walking from pain; left knee cas moderate effusion, anterior tibial translation with knee in 20 degrees of flexion while she is supine (Lachman test) is increased compared to the right knee- has ACL injury. Appropriate management includes aspiration of effusion, plain film radiographs, NSAIDs, ice, elevation 2-3 days, prompt evaluation by orthopedic surgeon. They say MRI is unnecessary. Popping sound in the area- don‟t forget Baker‟s cysts. 45-y/o woman with generalized pruritis for past 6 months in setting of increasing fatigue, recent cholesterol test is 310 mg/dl, not pregnant- concerned about primary biliary cirrhosis, get an alkaline phosphatase, if elevated- concerned; then look for antimitochondrial antibodies. 73-y/o has increasing pruritus for past 2 months, arms and especially legs itch, also has back itching, has HTN that is treated with HCTZ; no initial diagnostic testing needed- may be dry skin, xerosis. Might be reaction to HCTZ. 50-y/o woman noticed increased LUQ abdominal discomfort, annoyed by generalized itching, intensified after hot showers; describes itching as pins-and-needles prickling sensationno adenopathy but enlarged spleen- if not pins-and-needles, suspect lymphoma. Pins-andneedles- classic for polycythemia vera- get Hct. 20-y/o male competitive swimmer bothered by generalized pruritis over past 6 months, symptoms occur just after swimming, no adenopathy- dry skin- no need for diagnostic workupaquagenic pruritis. 27-y/o female grad student presents for evaluation of new right pelvic pain, began on routine training run, 2 miles into 18 mile run, unable to continue running after the pain began, pain with walking, weight bearing; point tenderness over right pubic ramus, can‟t stand on right foot alone without significant pain; plain radiograph- no fracture. Provide analgesia, put patient immediately on non-weight-bearing status- this is stress fracture of pelvis, X-rays don‟t become positive until callus formation weeks later. May present with amenorrhea due to decreased GnRH. 45-y/o man presents with bilateral foot pain, was mild, didn‟t interfere with running; prominent morning stiffness, mild pain in both feet, resolved with activity, sudden and severe increase in pain associated with running hills- plantar fasciitis is bilateral; other causes wouldn‟t be bilateral. Inflammation causes calcaneal spur, not vice-versa. If is severely painful, inject it; if patient doesn‟t respond, needs to go for repair- go for spur besides, but many spurs aren‟t causative. Is common in runners, people with flat feet, over-extended arch, lots of runningcommonly affected by this. Increased risk of running injury- weekly running mileage; age, sex, running on hard surface, BMI- not increase risk. 67-y/o man presents with muscle aches- eye doctor gave him new glaucoma med- is probably latanoprost- prostaglandin agonist. 81-y/o man with severe painful osteoarthritis of knee is in your waiting room for first appointment with you; also has cataract in left eye, mild-to-moderate high frequency hearing loss. Strong direct lighting in waiting room bad- glare; deep-cusioned chairs without armrestbad for osteoarthritis- don‟t want knees to be higher. All-talk radio station- can‟t distinguish from voice with sensorineural hearing loss. Office info printed in gray on black paper- contrast important. Straight-backed chairs with high seats and armrests will be better for them- sit without bending much. 73-y/o woman presents with 3 months of bilateral shoulder stiffness after cleaning overhead closets in kitchen; intermittent jaw pain, mild headache, unusual for her; she appears chronically ill, temporal arteries not palpable- nonetheless, think temporal arteritis, afraid of optic complications so high-dose steroids. Grand Rounds Colon Cancer: From Gene to Screen Dr. Steven Itzkowitz 4/27/04 We have capacity and manpower to screen every New Yorker above 50; question now is how to get them in for screening; payment may be an issue. First- magnitude of problem138,000 new cases per year, 1 new case diagnosed every 4 minutes. 55,000 deaths/year- fills yankee stadium; 150 deaths/day. We live in high-risk country for colon cancer, need to know about the condition. Our country- high-risk- 5% lifetime risk- 1/20 people of developing colon cancer. Why screen for colon cancer? Screening is proven effective. Must show not merely that finding more cancers but that more importantly, are saving lives. Is highly preventable, is welldefined premalignant phase- adenomatous polyp, and they take 5-10 years to become cancer. Molecular basis of carcinogenesis is best understood of all solid tumors. Why it‟s important to try to find colon cancer early- length of stay, costs of colon cancer admission are double that of average admission. Should be able to find colon ca before advanced enough to require surgery, chemotherapy. Risk factors for colon cancer- strongest factorsadvanced age, country of birth, FAP/HNPCC, long-standing ulcerative or Crohn‟s colitis. Moderately increasing risk- high red meat diet, previous adenoma or cancer, pelvic irradiation; modest risk- high fat diet, smoking and alcohol, obesity, cholecystectomy. Protective factorsmoderate- high physical activity, aspirin/NSAIDs use. Modest- high vegetable/fruit diet, high fiber diet, high folate/methionine intake, high calcium intake, postmenopausal hormone therapy. NSAIDs- very protective, but shouldn‟t put on aspirin if only goal is to prevent colon cancer because of downsides- GI bleeds, nephrotoxicity. Colon cancer- very common in US, Europe, see it increasing in areas of world that didn‟t used to have it. Incidence and mortality rate by gender and ethnicity- African-Americans are at higher incidence and mortality risk for colon cancer. With Hispanic Americans, data looks like they‟re relatively protected, but these rates may be falsely low because many are new immigrants from low-risk countries, but many studies show that within that generation, certainly in nextassume risk rate of surrounding population. So we really must be careful with everyone who lives in the US. Progression- normal colon to adenomatous polyp to cancer/ Pathways of carcinogenesisalong route from normal mucosa to carcinoma, two possible pathways. 85% develop via chromosomal instability, the way that cancers prefer in familial polyposis. Chromosomal instability- abnormal chromosomal segregation so in place of 2N in each daughter cell, abnormal DNA amount- aneuploidy; cell may then not carry normal tumor suppressor genes, APC, p53, 18q genes, and may carry K-ras oncogene. APC gene is critical; first to be lost, opens gates for all other abnormalities. 15% progress through microsatellite instability pathway- HNPCCthough normal ploidy. APC gene gives rise to protein that sits in cytoplasm; bad guy is beta-catenin; APC complexes with other proteins, phosphorylates and sends beta-catenin into destruction pathway so colonic cell proliferates, dies normally. APC mutation- can‟t bind beta-catenin, beta-catenin goes wild- binds to transcription factors, turn on C-myc, cyclin D1, and cox-2; cox-2 inhibitors or non-steroidals thus take over for APC function, thus prevent colon cancer. Microsatellite instability pathway- lose ability to repair DNA normally; every minute, cells dividing in body must faithfully transcribe their DNA, can be typographical errors, mismatches; system to recognize that- MSH2 protein recognizes, recruits MLH1, PMS2, helps to cut it out, replace. if have microsatellite instability- unable to effect this repair. 70% sporadic, 25% familial risk, FAP- 1%, HNPCC- 3%, hamartomatous polyposis syndromes- 1%. Will spend most time on sporadic colon cancer. Average risk- men and women over 50. High risk- hereditary syndromes, IBD, past or family history. Start screening at 50 because risk begins to rise at 50. Is elevated risk at 40 but not yet cost-effective. Is a list of tests that can offer patients; at age of 50- fecal occult blood test yearly, flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, or barium enema every 5 years. Effectiveness of annual fecal occult blood test- can reduce mortality by 33%. If do sigmoidoscopy, can reduce mortality by 60-75%. Even one sigmoidoscopy in last 10 years is protective, but only within reach of instrument. Can we do better? We think so. Colonoscopy- is becoming preferred technique for screening. Can look at whole colon, reduces risk of colon cancer by 76-90% in those who have already had adenoma; data about mortality not yet published, probably in next few years. Is therapeutic, not just diagnostic- can pull out polyp; if only need to do colonoscopy every 10 years- highly cost-effective. Downside- don‟t yet know if will save lives; higher up front costs, 0.2% perforation rate, need for sedation, 15-20% miss rate. If take average-risk, healthy people over 50- what find on colonoscopies? 0.6-1% will have a cancer, 37% will have adenoma, 7.9% over 1 cm, with dysplasia. When clear the colon of polyps- very little progression to cancer, when don‟t- considerable progression. Why aren‟t more people coming for colonoscopy if data is so good? Best statistics- 35% have had it, for many- doctor hasn‟t recommended it; must recommend to patients. If doctor recommends screening, very few- maybe 4%- will decline. New modalities- virtual colonoscopy (CT colonography), stool DNA testing. CT colonography- clean selves out, air is inflated via catheter, but not sedated, have CT, can go home, to work; is actually pretty good- has 2-D imaging, then 3-D construct of images- can reconstruct to 3-D structure. Sensitivity- if polyp is smaller than 6 mm- ½ of those are missed, so size is important. If >1 cm, pickup rate is pretty good. Mayo clinic study of higher than average risk patients- pickup rate even for big lesions not that good; if radiologist not have right training, can miss lesions; fairly labor intensive, needs lots of training. JAMA study- „real world‟ study- multicenter study- radiologists trained with 10 prior virtual colonoscopies- only slightly better than previous study, missed two cancers by virtual. So is it really ready for prime time? Hard to say. What put virtual colonoscopy on map- NEJM 2003- did so well because 3-D endoluminal display, and laced stool with barium/gastrograffin contrast- had to be willing to drink that stuff, and trained with over 100 VC beforehand; alsonormal-risk population; picked up even 1 more cancer than by regular colonoscopy. Soradiologist expertise, higher polyp prevalence, 3D fly-through use, use of oral contrast for fecal tagging seem to increase sensitivity. Stool DNA testing- need only 30 g; poop in bucket, put lid on it, freezer packs, fedex- tail pail mail approach. DNA is extracted in lab, analyzed for APC, k-ras, p53 mutations, Bat-26, long-DNA microsatellite markers. Mayo clinic- pulled stools from those with colonoscopic diagnosis of adenoma, cancer; 20/22 cancers picked up by marker combinations; negative colonoscopies- only 2 had K-ras false positives, 93% specificity, 100% if leave off K-ras. Stool DNA testing has potential as screening modality. Yearly fecal occult blood testing- will continue to be used. Sigmoidoscopy is disappearing, and barium enema isn‟t really used anymore for screening. Colonoscopy, virtual colonoscopy, stool DNA testing will increase; how will integrate them- no one knows yet. Familial risk, hereditary non-polyposis- If have a family history- 1-2 relatives- risk is shifted to left by 10 years; so recommendations- do same menu of options but start at 40 rather than 50 because of that curve. If more than 1 relative or young relatives affected- risk goes even higher. 1/20; 1/17- first degree; first and second- 1/12; if 1 under 45- 1 in 10- double risk of general population. 2 first-degree relatives- 1/6, etc. Screen at 40 or earlier- some recommend10 years younger than youngest case in family. Worst family history to have- HNPCC. Colon, endometrial, bladder, stomach, pancreas; 27, 28, 33, 37 y/o with colon cancer. HNPCCautosomal dominant condition, so each child has 50% chance of getting it; 80% lifetime risk, due to abnormal repair. Genetic testing- 1/3- MSH2, 1/3- MLH1; 1/3- don‟t really yet have genetic basis for, so may not find mutation that explains family syndrome, yet must watch very carefully. Few adenomas, proximal location, multiple simultaneous colon cancer, typical histology- signet ring cell, medullary; extra-intestinal cancers seen- colorectal, endometrial, stomach, biliary, urinary tracts, ovarian. Amsterdam criteria- 3-2-1 rule- 3+ HNPCC cancers, two of whom first degree relatives, 2 or more generations, 1 person affected below 50- test for gene mutation. Must do colonoscopy every year or two, start at 25 or younger if younger cancer in family, because grow very quickly, in 1-2 years. Colon cancer- the most preventable, but least prevented, cancer. Morning Report 4/29/04 CC- my finger is cold; HPI- 40-y/o male with no significant past medical history presents to ED with numbness, coldness, whitish discoloration of left index finger since 12 midnight; cyanotic at 9 AM, no trauma or similar episodes; has had fever, chills, nausea, vomiting for past week. Social history- 2 packs/day for 20 years, beers. Works as a cop. I/IV holosystolic murmur. Left index finger cool and dusky. With this presentation- if platelets were over 1 million- essential thrombocytosis, If H and H were very high- would be polycythemia vera. TEE- PFO. SLE- get venous and arterial thrombosis- ANA. Embolic occlusion of the distal ulnar and radial artery. Heparin works on antithrombin III, see in urine in hypercoagulable state. Neurologic, fever, renal problems, thrombocytopenia, anemia- FAT RN- in TTP. Nitropaste on finger, heparin, coumadin. Hypercoagulable states- in malignancy- migratory superficial thrombophlebitis, DVT, nonbacterial (marantic) thrombotic endocarditis, DIC, TTP, arterial thrombosis. Arterial thrombosis is much less common than venous. Marantic endocarditis- lesions from microscopic platelet aggregates to large vegetations, usually with advanced malignancy; most with adenocarcinoma; lung cancer- 7%. Initiating factor unknown; TNF or IL-1 circulating cytokines might trigger platelet deposition. Major clinical manifestations of MTBE- from systemic emboli rather than valvular dysfunction. Emboli seen in spleen, kidney, extremities, but most significant morbidity from CNS emboli, coronary arteries. Consider NBTE in all cancer patients with acute stroke syndrome or unknown etiology cerebral embolism. Pathogenesis- multiple variables; intact tumor cells may express procoagulant activity, or normal tissues may in response to tumor. Comorbid factors- bed rest, infection, surgery, drugs, may contribute. Early reports- many thrombotic-associated tumors were mucin-secreting, but also many non-mucin secreting, and no procoagulant moiety has been isolated from mucin. Tissue factor complexes with factor VII to activate IX and X; cancer procoagulantactivates X directly. Both implicated in hypercoagulable state in APL and to less extent AML. ATRA downregulates both. Monocytes express little procoagulant activity but can be induced to produce tissue factor and other direct factor X activators by host cells or tumor cells. Plateletsincreased reactivity secondary to either clonal abnormalities or tumor-platelet interactions can contribute to hypercoagulability. Tumor-induced thrombin generation, ADP production by tumor cells, etc. Endothelial cells can become procoagulant under influence of TNF and IL-1. TNF also suppresses endothelial fibrinolytic activity, increases endothelial cell IL-1 production, downregulated thrombomodulin expression, diminishes activation of the anticoagulant protein C. Other comorbid factors that may play a role- vascular stasis due to obstruction of blood flow by tumor or patient immobility, hepatic involvement and dysfunction, sepsis, advanced age, comorbidities, and many chemotherapeutics. So many factors play role in producing hypercoagulable state in malignancy, only therapies- anticoagulants and filtering devices. Are keeping this patient for 6 months, if find something else, will keep him on for longer. Papers- 3 months adequate, others- 6 months is comfort zone, but no definitive duration. In this patient- no cancer diagnosis, but if is- needs lifetime anticoagulation. Pregnant women with antiphospholipid syndrome- give heparin, not coumadin. Morning Report 4/30/04 68-y/o female Indian with hypertension, hypercholesterolemia, positive stress test, sent here for angioplasty. Complaints only general weakness, hoarse voice; EKG- left bundle branch block, old. 90% occluded LAD on day she came; CPK, troponin were elevated; very high cholesterol level- 550, LDL 326; triglycerides- 785. No family history of hypercholesterolemia or diabetes. Started zocor when she came. Cath result- single-vessel disease; LAD- 90% stenosis, one stent in place. Other vessels are good- no other problems. Echo- mild LVH, normal EF. Home- on toprol, vasotec, zocor. No baseline cardiomyopathy. Was walking, talking, good appetite, wanted to go home. CPKcontinued to have elevation. Hypothyroidism- CK-MB would be elevated. Troponin was 0.2; before, after stent- didn‟t change much. CPK- 623. Had been on Zocor for one year but no symptoms- no muscle cramps, itching, liver problems. Aches and pains- are medicines causing it? Stop for week, two weeks, three weeks, to see if causing it. Vitamin D-deficiency- many don‟t get sunlight during winter- 25-OH vitamin D is marker- can cause aches and pains. CXR- cardiomegaly, bilateral pleural effusion. Why does patient have persistent elevated enzymes, elevated LDH, no enlarged lymph nodes, multiple wall motion abnormalities on echo, moderate mitral regurgitation, mild LVH. Physical exam- only complaint was hoarseness of long duration, extremity reflexes diminished. Hypothyroid can give cardiomegaly, cause cardiac enzyme leak. So sent for TSH, and was >200; free T4- 0.003. Cortisol level- 24. Hypothyroidism- suspicions on lab findingshigh bicarbonate, hyponatremia, normocytic anemia. Myxedema coma- first manifestation is altered mental status; can have with no symptoms; infection, dehydration, medication; from medication list- amiodarone, beta blocker, diuretics, phenytoin, etc.; sepsis, UTI; hypothermia, etc. CPK elevation- MM is most of the time but can have MB, ST segment elevation; altered mentation, alopecia, bladder distention or dystonia, hypotension late, in early- diastolic hypertension. Systolic BP- 150-190. Delayed reflexes, dry cold, tough skin. Hypothermia, hypoventilation, generalized sweating, etc. Treatment of myxedema coma- still controversial; must do investigation. Should start on hydrocortisone; should be treatment like myxedema coma patient. Altered mental status. Takes about 4 weeks to treat; check TSH in 6 weeks. Surprised to pick it up- you never know. Explains isolated CPK elevation; still don‟t know why troponin is elevated, even as CPK declines. Any kind of carditis- elevates troponin. Issue- is it damage or decreased clearance? Always see elevated troponins in end-stage renal disease. Also saw high HbA1c, treated her for diabetes. NYPH 5/3/04 Dr. Bardes 52-y/o woman admitted for leg swelling; cut leg on barbed wire 3 days prior to admission; next day, area began getting warm; by day of admission, was red, warm, swollen, tender, so came to ER. PMH is unremarkable; takes no medicines; takes supplementsglucosamine chondroitin for sore knee, and calcium supplements. Physical exam- no acute distress, 38.9 T, BP 126/74. HR 80, exam normal except for left leg. So admitted to hospital with diagnosis of cellulites, treated with IV cefazolin. Day 3 of hospitalization, called to see her for chest pain. Now is Monday, you‟ve come on service, go see her; in room- what want to knowwhat kind of chest pain? Tight feeling across chest; started 10-15 minutes ago, never had it before; no shortness of breath, no radiating, stays about the same, doesn‟t change with inspiration; has been in bed, no venodynes, but subcutaneous heparin. Weighs 145 lbs. Never had this before. Family history of clotting disorders- father‟s brother had refractory anemia, then AML. No oral contraceptives. Had tetanus shot; gets heartburn but not same feeling; childhood asthma, 4/10 pain. No sense of incipient doom. O2 sat- 96% on room air. Breathing at 16. Physical exam- 142/86, HR 86, CTAB, cardiac exam- no JVD, PMI normal,RRR normal S1, S2, does have S4 gallop. Hypotheses- focusing on differential diagnoses of chest pain, zero in on most dangerous ones- MI, pulmonary embolism, aortic dissection, tension pneumothorax. How assess these- MIEKG, cardiac enzymes; PE- CXR, then spiral CT, V/Q. Spiral CT‟s have sort of caught on; sensitivity is only 65%, both about same- but V/Q- nuclear medicine treated as suspect by most physicians, except for thallium tests; also- isotope is short-lived, must order fresh each day, none left by 7 PM, so do spiral CT‟s a lot. Also- can pick up other things. Aortic dissection- check blood pressure in both arms, thigh, CXR, CT, TEE. Pneumothorax- CXR. EKG- shows NSR at 86 BPM, axis is +60 degrees, ST depression to 2 mm in V5-6; see some ischemia. What kind of ischemia having? In MI, see Q waves, but occur late in game; see ST elevation, T wave inversion. Non-MI ischemia- ST depression, inverted T-waves. In case of unstable angina- about ½ go on to have MI, other half doesn‟t; so ST depression can also be MI in half of those with unstable angina. Treatment- give oxygen, give nitroglycerin- trouble with sublingual nitroglycerin- in low dose available that way- can‟t dilate coronary arteries, but get peripheral vasodilation, decreases preload, leading to decreased work. Gets NTG sublingual, usual dose is 0.4 mg (don‟t care if remember as MSIII). Now- BP comes down to 130/82, HR 92, chest pain (CP) 2/10, headache. Now- sent off enzymes, waiting for CXR- give beta blockerdecreased left ventricular contractility, decreased BP and heart rate- lowers work- so now, BP down to 118/74, HR to 72, CP to zero, headache worse but tough noogies. Now- twin of this patient who cut right leg instead of left leg, has bronchial asthma, beta blockers all can cause bronchoconstriction- so use calcium-channel blocker; also causes decreased contractility, blood pressure, leads to decreased work. Balance of supply vs. demand. Giving her oxygen- may or may not be beneficial, because if plot O2 delivery against partial pressure of oxygen in blood- most of us live at top of curve, so that increasing blood pO2 increases SaO2 only a small amount. We tend to give oxygen to everyone- some live on steep part of curve, so will help them. To increase oxygen supply- also are antithrombotics- heparin, tPA- shorthand for streptokinase, urokinase; aspirin, and other antiplatelets- plavix, glycoprotein IIb/IIIa antagonists. Is chronic stable angina, and then, unstable angina- pain at rest, or change in their chronic exertional angina pattern; crescendo- getting worse- less exertion gives pain. Chronic stablefixed stenosis; unstable angina- thrombus which is being extended and shrunk moment to moment- war between body‟s clotbusters and prothrombotic forces. MI- thrombus, this time with total or near-total obstruction. Difference between unstable angina and MI is quantitative- get a little more thrombus, enough to cause downstream damage. Measured by CPK elevation, unstable troponins- but latter present even in unstable angina- may have downstream damage but not reflected in macro damage that cause elevated CPKs. Meds for CSA vs. UAP vs. MI; aspirin makes sense in MI- don‟t extend thrombus, unstable angina; aspirin has two roles in chronic stable angina- prevents clot formation and furthering of atherosclerotic process; same for plavix, etc. Heparin- may help in MI by giving the good guys a chance to win; in unstable angina- same logic; not in CSA- won‟t play tennis with IV pole. tPA- blows hole through clot- great for MI; in unstable angina- sort of makes senseexpect fewer MI‟s. All we‟ve said about this is based purely on pathophysiologic reasoning. But other way of looking at things- clinical studies. First and second year- focus on pathophysiology, science behind it, then- clinical studies- what actually happens. In clinical studies- get group of people with MI, randomize to the meds, look at endpoint like death. Aspirin is great- has been shown to work in clinical studies in CSA, UAP and MI. So we give aspirin at first moment with oxygen. Plavix, etc.- proven in UAP, increased side effects make CSA and MI equivocal. Heparin in MI- not very robust results- small benefit, increased side effects, but works in MI; in unstable angina- very robust death reduction. tPA- dramatic reductions in MI mortality35%; big news for several reasons. Overt clinical reason- first major pharmacologic progress in MI ever. Other thing- research project necessary to come up with thrombolytic therapyenormous research effort to elucidate thrombogenesis, come up with this new agent; first triumph of Big Science- NIH; Big Science, huge NIH approach, hadn‟t borne much fruit, e.g. for cancer; now- tPA validated Big Science approach to clinical medicine. Time constraint- earlier better; want to give to 4 hours, by 8 hours- must consider not giving at all; Italian study, thoughstreptokinase up to 24 hours showed benefit. Big MI, shock- may want to give thrombolytic therapy even late. tPA in UAP- mortality was from bleeding in head; 1% get hemorrhagic stroke with tPA, risk/benefit weighs for it in MI, with 20% mortality, but not with UAP. This weighing between pathophysiologic reasoning and clinical studies- what doctors do every day. Often agree but when disagree- bias is to weigh in with clinical studies. Allowed to use pathophysiologic reasoning but firmest ground is clinical studies. (Legal grounds- measure is what other doctors in your community do.) Another thing you can do to increase oxygen supply- PCI- percutaneous coronary intervention- embraces not merely PTCA- balloon, but also stent or rotational atherectomy- rotorooter. Done by interventional cardiologist. Don‟t do CABG in acute MI because high mortality rate- 10-20%. PCI data in MI just as good as tPA. Don‟t give thrombolytic therapy to fall patient if risk of hemorrhage; if too far out for tPA; need cardiac cath lab available 24/7 which can access quickly from ER, need CT surgery backup team in case rupture a coronary. In most places in US, no urgent access to catheterization. Raises some interesting public health ramifications. In Seattle, they give tPA in ambulance. Where have both- I choose PCI, because after tPA, have ratty plaque, undigested thrombus- unstable picture. So get 1% risk of hemorrhage, then risks of angioplasty that will need afterward anyway. Morphine- morpheus- god of sleep. Morphine does two things- is a good venous vasodilator, and is an anxiolytic and so on. Problem- may make pain go away while still ischemic. So- admitted, see Q waves, just want to take edge off, give them some rest- then appropriate. Now talk about some patients. 63-y/o man comes to ER with 6/10 chest pain while playing racquetball; BP 110/76; HR 56; also has nausea, vomiting; chest clear, cardiac- no JVD, RRR, normal S1, S2, S4; EKG- sinus bradycardia at 55/min, axis +30, ST depression to 2 mm in II, III, aVF. Distinction between unstable angina and MI is still useful because of the tPA studies. Can‟t tell from this that having MI. II, III, aVF- inferior wall ischemia; vagus nerve irritated so gets nausea, vomiting. Give him aspirin, oxygen, nitroglycerin lowers BP to 102/68, HR 60, CP 4/10; Beta blocker lowers him to 96/60, HR 55, CP to 2/10. Now- too low BP to give calcium channel blockers; can try platelet blockers, but now- all have left- heparin. Once give heparin, have committed self to PCI. Will stabilize UAP thrombus but not fix it; gave enough to reduce work, won‟t let you do more, now try to fix supply; heparin and cath lab. Another case- 44 year old man with CP 6/10 that awoke him from sleep; BP is 96/62, HR 128, chest has moist crackles 1/3 of way up, cardiac- JVP is cm of water, RRR, normal S1, S2, has S3, S4 gallop; EKG- ST depression to 4 mm in V1-4- could be anterior wall ischemia. Has hypotension, left heart failure, pulmonary edema, right heart failure; is very ischemic in four leads- lot of his LV; so the anterior wall- most important part- is affected, is affected a lot to a lot of it. For him- aspirin, oxygen, not beta-blockers, nitroglycerin- low pressure. Way to get around it- nitropaste- ointment that can put on skin, local effects under occlusive dressing, can wipe it off if pressure drops. Might try nitropaste, but find pressure goes down, have to wipe off. Calcium blocker- no; what‟s left- heparin and cath lab. So ends up at that point for same reason as previous guy but here, disease itself, not meds have led to lowered blood pressure, but principle is the same. [Lincoln- put on heparin, send emergently to New York hospital- really can‟t give tPA without ST elevations.] Now- NSR at 85, ST elevations to 2 mm in V3, V4; still do ASA, oxygen, NTG, beta blocker, but now- tPA or PCI- will open that vessel by hook or by crook ASAP. Idea- decrease work, improve supply; when can go no further- in ischemia- heparin and cath lab; in MI- open vessel as quickly as can with tPA or PCI. [Once give tPA, can wait a few days before deciding to do further PCI.] Radiographic evidence of Stroke Dr. Zimmerman 5/5/04 Past- no effective treatment of stroke, no rush, identify location and extent of infarction but couldn‟t do anything anyway; used to be said that took 24 hours for things to turn positive on CT- poor attention as well as technology. Now, with tPA, need to identify presence and extent of infarction within therapeutic tissue, risk factors for hemorrhage and tissue at risk for infarction. In future- neuroprotective agents, mechanical clot removal, etc. IV tPA- less than 3 hours, less than 1/3 MCA, no hemorrhage on CT, treatment criteria IA tPA- < 6 hours, to 24 if basilar, no evidence of hemorrhage on CT. tPA- 80% effective at opening up vessels; question not if will work but if it will help. Risk of hemorrhagic transformation, which leads to worse outcome. Treatment criteria reflect risk-benefit balance. If could exclude patients with no benefit- no salvageable brain, or most at risk for hemorrhage, therapeutic window might be extended. Key issue- time constraint- must be evaluated, treated within 3 hours of event- very constraining. Pathophys- hyperacute- vascular insufficiency- large vessel occlusions- thromboembolic; small vessel- lacunar- atherosclerosis or hypertension. Lacune- hole in brain surrounded by gliotic tissue. Decreased flow/arterial pressure- watershed infarct; at edge of circulation, perfusion is poorest. Imaging features of slow flow or occlusion may precede or occur in conjunction with changes in tissue density/intensity. Cytotoxic edema- circulatory collapse, within 5 minutes leads to inefficient anaerobic glyclolsis, water enters, NA pump isn‟t working, Na follows, intracellular space expandes, ECF space shrinks, Ca follows Na, Ca chews up protein, contents of cells become viscous, protein precipitate; excitatory amino acids Glu, vasocactive substances- further damage cells in region- ischemic cascade. Vasogenic edema- prolonged hypoxia- 30 min or more- endothelial damage opening tight junctions- BBB disruption; serum exudation leads to expansion of EC space, increased volumemass effect; begins in graw matter with later spread to subcortical; if no reperfusion, no edema, but typically do see reperfusion. Dense MCA sign- implies clot in the vessel. Also- loss of cortical ribbon- loss of normal cortical density. Insular cortex- usually dense, losses of density. These are signs of hyperacute infarction- very subtle changes. Need high index of suspicion to make diagnosis; negative CThighest indicator of acute infarct because symptoms but no bleed, no tumor. Can‟t call it reliably enough to decide treatment. By 8 hrs- normal gray matter density is lose, whole area looks dark. To see these subtle strokes- narrow the windows to 30-40, but even then becomes difficult. Two hours- TPA or not? Is this more or less than 1/3 the area of distribution? Large right hemispheric strokes- one approach to preserve life- if non-dominant hemisphere- take it out, or at least big chunk, to prevent herniation. Gyri swollen, dark- gyral swelling and edema, happening very quickly- rapid recanalization of vessels is bad- if recanalize after 3 hours- OK; if 6 hoursvascular tree no longer competent, will ooze, hemorrhage. Real cause of gray matter hypodensity- can‟t be “edema”- no net change in tissue waterdso can‟t cause hypodensity; not cytotoxic or vasogenic edema. So now thought is, cause is hypoperfusion- normal gray matter denser than normal white matter b/c has 2x the CBV of white matter. Blood is dense on CT. Earlier the hypodensity, therefore, the worse the occlusion. Hyperacute infarct- slow flow/no flow- can see on MR- diffusion abnormalities. Pt with cerebellar signs, developed acute field cuts- see vessels clearly, without contrast, on MRA. Can see slow flow with contrast. Acute clot- can look at flow-related enhancement; blood, acute clot is black; but white next to vessel- flow of blood- see with gradient echo- not seen if clot. FLAIRsuppresses CSF signal, on T2-weighted image. Diffusion-weighted image- signal intensities the same, but CSF is suppressed based on water-molecule motion. DWI- random motion of water molecules as they jostle each other. Mean free path is the distance the molecules move before they jostle with each other. Move depending on several factors- temperature, and what they bump into; in solids- can‟t move as far. In biology- two compartments in tissue- EC compartment- water can move pretty freely, inside cells, water can move less- in cells diffusion less than outside the cells. Old notion of cytotoxic edema- more water now intracellular then extracellular, now dominates over ICF; but no- already 80% in intracellular compartment! New notion- hypoxia leads to membrane ionic pump shutdown, internal organelle damage, so increased intracellular viscosity, more marked restricted motion. Allows you to see things more quickly. DWI- really robust so can make diagnosis. tPA study in Europe failed because misread CT scans. Flair- can see high or slow flow in vessel. On diffusion-weighted images- obvious that high signal. Much easier with MR than CT. T2-weighted image, then apply gradients that make image sensitive by subtracting signal based upon motion. If no longer bright on ADC- stays bright 4-6 days there, 2-6 weeks in DWIso can tell age of infact. Second phase- getting vasogenic edema- extracellular space expands, get diffusion returning to normal, increasing, lesions then no longer visible. To pick out new vs. old infarcts- DWI. 3-10% are false negatives. Can get stroke which turns positive later- 5 hours into event, case. Reversible DWI abnormalities- if cells poisoned, shouldn‟t be reversible. If quickly opened <2 hours, rare cases of TIA, post-icltal, hemiplegic migraine, transient global amnesioa. Initial ADC reduced <20%. Some damaged, some not. If occlude vessels in animals, resolution may be permanent or transient; a few days later, apoptotic. Where we stand- MR superior to CT, confirmed in study. DWI least sensitive in 12-16 hour period. Effects of expertise- much less with DWI than CT; Is one study that using source images from CT angiogram, could see same extent of disease as with DWI; but not looking at infarction, rather flow. But isn‟t DWI too late? So- have core area of infarction- unsalvageable- <10 ml/100 g/min. Around it, area of 10-20 ml/100/min- ischemic pernumbra- at acute risk for stroke growth. Beyond that- oligemic area- not at acute risk but may want to treat. If perfusion/diffusion mismatch- treat to save penumbra. If not- no reason to treat.. Perfusion imaging- on MR, can get relative perfusion parameters; CT- absolute perfusion values can be obtained, rCBF- same as infarct area on DWI- no advantage. Stroke wars- CT vs. MR- CT is easy, fat, available, more sensitive to hemorrhage, MR needs more time, patient monitoring more difficult. But now- with new technology, MR better on most counts. Flow, MTT more sensitive. Diagnosis remains complex, difficult; human strokes not so neat- some viable cells in core, dead cells in penumbra. Will never know arout cell viability with CT, do with MR. Hemorrhage- do see- now more sensitive than CT. 20% have punctuate hemorrhages, more prone to hemorrhagic infarction, CT will never show you, should not be anticoagulated. Resident Session Dr. Christopher Gabe Tutor Session Dr. Susan Wenderoth 5/5/04 Case- start off with brief sense of person‟s PMH first. Then HPI, include relevant lead-up story- Chest pain, fever, dark urine, watery diarrhea, diaphoresis, to ED. In surgery, this ends up in PMH. If you were assessing for diarrhea- anything like this before? Yes, but no CP. Recent travel- giardia, cholera, listeria- unpasteurized cheese and milk, ETEC; prior history- IBD, IBS; Antibiotics- erythromycin, clinda- predisposes to stool toxin. Other causes- Ova and parasitesamoebas, giardia, cryptosporidia, isosporidia, cyclospora; kid in daycare- Norwalk or rotavirus; wipes through everyone. Sprue, lactose intolerance; diabetic- glucophage; tons of medications do. Key to being good doctor- art of differential diagnosis. Most people‟s Ddx isn‟t very long, stop after 5 or 10, but every so often, get something weird, need to think of it. Incredibly useful task- practice in head making differential diagnoses in three different ways. Classic one- chest pain; think of something anatomic, outside in- is it zoster, musculoskeletal, costochondritis, MI, pleural effusion, lymphadenopathy? Another way- systems- cardiac- MI, aortic aneurysm? Pulmonary- pneumonia, PE? Infectious- rheumatologic, etc. Last one- physiology or pathologywhat is mechanism? Blood in urine- can say- anatomically- from kidney, ureter, bladder? Systems approach- infectious GN? Mass? Stone? Pathophys- what kind- membranous, MCD, etc? Diarrhea- natural starting place is infectious; then want to malabsorption; then to classic GI, meds, etc. Helps you not miss things. Really comes into play in areas in medicine that fall between these cracks- rheumatologic conditions, etc. that easy to miss. No blood- worry about E. Coli, Shigella, Salmonella, Campylobacter, Yersinia. Most common cause of bloody diarrhea is GI bleed- AVM, diverticulosis. With spicy food- alluded to fact that may have ulcer. Fever of 103, dark urine- could be blood; golden- dehydration, myoglobinuria; for myoglobin- will say blood, but no actual cells. Biliary issues. Also- every Ddx must have medications on the list. Incredibly common; rifampin, pyrazinamide, isoniazid turn the urine colors. If know nothing else about him- has history of diverticular disease, cardiac disease, has fever, etc.- 5 things on top of differential- diverticular disease; acute infectious diarrhea; most common missed GI diagnosis- mesenteric ischemia; two kinds- acute and chronic- pain is very severe, out of proportion to abdominal exam, periumbilical or diffuse, currant jelly stools; caused by thrombus, usually; can be embolic- cross-clamped aortas in bypass surgery- not subtle stuff. Chronic tends to be vasculopath- walk after they eat, watershed areas get hypoperfused- splenic flexure- classically LUQ pain. Can also get bloody diarrhea. Next- hemolytic process- HUS with e. coli- dark urine, malaria can give this. Last on differential- some kind of bleeding process. Comes to ER; five tests- vitals; guaiac should come near the top- is he bleeding or not? Abdominal palpation; visuals- did he look sick? Next- CBC, and finally lytes- with anion gap and creatinine clearance- same Cr can mean renal failure or normal. 140-age/72 x weight/Cr x 0.8. Do it once, that‟s it- need to renally adjust meds, or may have seizure- commonest cause of seizures in hospital. Rest of HPI- ER course- hypotensive (50/palp); 4 L of fluid brought BP to 110/70; found to be in acute renal failure; no ill contacts, no food sharing. PMH- history of liver abscess with pretovella loescheii, bile grew out bacteroides fragilis, no one knew from what. Allergic to sulfa, hx of tobacco, EtOH. Meds- ASA, Toprol, Lisinopril, Pravachol for cardiac disease. If only knew history of liver abscess, diarrhea- think entamoebas, echinococcus- hard to drain, common cause of seizure in Mexico. Abnormal labs- 13 WBC, AG 19, CrCl 44, etc. Differential for CBC- 8% monocytes. AST 45: ALT 22- alcoholic is 2:1; less than 20:1 BUN to Cr so not prerenal. CrCl of 44 is probably moderate. So moderate acute renal failure. Anion gap metabolic acidosis. Renal failure- prerenal- think about volume- gross volume- entire body volume, and then volume getting to kidney, what kidney is seeing- AAA, renal artery stenosis, clots; whole body volume- dehydration/diuretics, hemorrhage, diarrhea, burns, anaphylaxis, shock. Heart failure, sepsis, ascites, nephritic syndrome- third spacing; prerenal- BUN:Cr is 20:1; also FeNa- less than 1; urine Na- 10. Postrenal causes- renal/ureter- stones/stricture- retroperitoneal fibrosis, BPH, tumors; anatomic issues in younger people- vesicourethral reflux; mass; neurologic- spinal cord issues, MS, people on meds- anything you use to put people to sleep in hospital- benadryl, benzodiazepines- Ativan, Ambien, antipsychotics, narcotics- all cause urinary retention. Normal residual urine- 500 cc. Maximum bladder capacity is profound- if very chronic or slow. Renalvascular causes. How diagnose- percuss bladder, do KUB or renal sono, look for hydronephrosis; could percuss, put in foley. Renal- glomerular, tubulointerstitial, vascular- rheumatologic. Renal causes of renal failure- we learn path before diseases- minimal change, focal segmental, etc. Look at it- what info do you have? What does the urine look like- nephritic- blood; nephrotic- protein. That‟s one way to divide it. Another way- look in PMH- if have lupus- cross off some thing, suggests others. Casts- tubulointerstitial. So before differential- what urine look like? 17 WBC, 7 RBC, positive for protein, granular and hyaline casts. Hyaline casts- look like tubes; Granular- classic for acute tubular nephrosis. WBC casts only- pyelonephritis. Urinary eosinophils- acute interstitial nephritis; if greater than 12 weeks- chronic interstitial nephritis. One thing that will help you- if you need to tackle glomerular disease- start with urine- is it nephritic or nephrotic, is one of these Venn diagrams; ATN- can be caused by toxins; incredibly toxic- have sloughed off tubules; ischemia, meds, NSAIDs/diuretics, rhabdo, contrast. Interstitial disease- ATN, AIN, CIN- how distinguish AIN, CIN- big picture- AIN goes with allergy, therefore eosinophils- they got medication they have allergic response to; allergy, asthma, medications, parasites. CIN- bad kidneys, plus some kind of medication reaction- bad protoplasm at getgo. Diabetics, hypertensives, sickle cell, lupus, chemo, multiple myeloma- have stuff going on, then meds making it even worse. Meds for ATN, AIN, CIN same- NSAIDs, diuretics, antibiotics- all kinds. If you have to pigeonhole self about what abx- those to treat UTI; Cipro, amox, bactrim, nitrofurantoin, aminoglycosides; all NSAIDs- even cox-2 inhibitors. ACEI- all diabetic patients should be on it for renoprotection. So- you have diabetic on ACEI- efferent vasodilation- decreases GFR. NSAID addition- constricts- increases GFR- so gives DM patient with bad kidneys papillary necrosis. What causes ATN in this patient- hypotension; is on an ACEI, has high cholesterol, vasculopath- probably has cholesterol path- decreased lumen size on top of hypoperfusionseems to work. Aspirin can also do it. So- bad gastroenteritis made him dehydrated, hypotensive, became prerenal, hypotension sent him into ATN. Being treated with levoquin but got much better on fluid. Stool culturenegative but final results not back. Blood culture growing enterococcus, so now on levofloxacin. Urine cultures all negative. Missed endocarditis on differential; don‟t like to miss that- CABG in history. Levofloxacin covers E. faecium but not E. Faecalis, may switch to augmentin, which covers both. Normal values- think about how much time have to present. Bedside- 2 minutes; walk rounds- 5, attending rounds- 20 minutes. HEENT- in diabetic patient- dentition, facial pain, thrush; fatigue- no thyromegaly. [Turned out- gall bladder wall abscess, no pain.] Dr. Wenderoth Tutor Group 5/7/04 Transfer note is different from initial evaluation. Admitted for what, briefly describe course. Frustrating thing- big picture without missing details. PMH- before hospital, admission, in ER, then MICU, course- what had without telling how we determined it. Hypercapnic respiratory failure, with nephritic syndrome- task is to wean her, but has serious restrictive disease, pneumonia, nephritic syndrome. So all residents, attendings, fellows on 5W will care about the weaning, but big problem- has PNA, nephritic syndrome, morbidly obese. Sit down, talk to patients, see what they think. MICU- all will see intubated patients; weird thing- get better or worse, but often based on some will to live, or lack of will to live; people have to be strong enough to want to come off the vent. Sometimes cancer patients can muster the will to get off, and healthy die because of systemic disease they get on vent. Immunocompromised? Sedentary lifestyle, obesity; undiagnosed nephrotic syndrome at home, led to this- edema, hypoalbuminemia, hypercholesterolemia/hypertriglyceridemia, proteinuria >3g/d. Hypercoagulable- spill protein C, S, antithrombin III. Clots happen anywhere, but can have renal artery/vein thrombus with papillary necrosis; can get mesenteric edema leading to nausea, vomiting, diarrhea. Classic- periorbital edema. Hypercholesterolemia predisposes to CAD, PVD, CVA. Proteinuria- gives lowered oncotic pressure, get edema, lose protein C, S, ATIII, and lose complement and IgG, IgA. IgA protects in mucosa. Nystatincandidal infection- beginning of problem, but will get mucosal infection. See scurvy, malnourishment- thus repleting vitamin C. What causes nephrotic syndrome? How create useful differential? Nephrotic- no blood; white cell casts, bubbly, frothy- protein. IgA can do it; is the most common cause of glomerulonephritis in the world. Other differential system here- anatomic; in kids- minimal change disease- podocyte fusion, 90% remission with steroids. In adults- focal segmental, then membranous. Focal segmental- viruses- HIV, HBV, HCV; also rheumatic- SLE, etc., amyloid. Membranous- systemic causes- diabetes. When get down to etiologies- will look this up on up to date; will help you figure out what tests to order. Non-renal causes of nephrotic syndrome- Diabetes, SLE/RA, Hodgkin‟s, Myeloma/Amyloid, HIV, Hepatitis. Tests to order- 24-hour urine; in office, will never happenrandom microalbumin- measure spot urine protein, BUN and create a ratio; if that‟s really elevated, they do 24-hour urine to get 3 g/day. Now- steroids- great for MCD, good for FSGS, Ok for MGN; if leave nephrotic syndrome alone, get serious sequellae, so we treat right away, before gets clots, CAD, etc. Other tests beside urine protein, BUN/Cr- coag studies, though spot is variable; H&Hanemia of chronic disease doesn‟t happen in a month. MCV would be helpful with that. Cholesterol, albumin. Then run through other things. Is this new? I‟d say- less than a year. 5-year mortality for untreated nephritic syndrome90%, mostly from infection. Came in with RML pneumonia. Most likely bugs- when in doubt, say strep pneumonia. Is immunocompromised but comes from community; could have atypicals- 30% of all comersmycoplasma, Chlamydia- kids, mycoplasma- CXR looks much worse than physical examadolescents, legionella- water, old, immunocompromised, smokers; haemophilus influenza- kids, parents, unilobar, moraxella- DM, somewhat immunocompromised, chronic sinus infections. Klebsiella- smokers, drinkers, currant jelly; staph- multilobar abscesses after viral pneumonia. Top three tests to get- ABG, CXR- is she getting better, and want to know if getting something else- infection will be #1 killer for her. Are treating proteinuria, hypercoagulable state; cholesterol is normal- hasn‟t been going on for long time; then- lytes, CBC, etc. Morbidly obese- intertriginous rash can be very dangerous in morbidly obese, quickly get septicemic. 5/7/04 Dr. Bardes 43-y/o woman telephones with a UTI. Inpatient/outpatient distinction is arbitrary. She tells you she has a UTI; she‟s had them before, feels the same. Feels burning with urination, urgency, frequency, no fever, no flank pain, no blood, no discharge. Has had it once before, last1.5 years ago, had a urinalysis, culture showed E. coli, is single, lives with boyfriend, monogamous, he‟s had vasectomy, last sexually active with a week. Burning seems to be in urethra. Otherwise feels totally well, no odor. Choices- have her come in tomorrow, come to ERoffice not option. Past medical history- unremarkable, takes no medicines; smoked pack/day from 15-35, not since then, drinks wine on weekends, works, lives with boyfriend, NKDA. Part of question relates to level of confidence that she has UTI; cervicitis, STD‟s, severe UTI- pyelo, seemed not to have that, we‟re all pretty confident she has UTI, not very sick. Bladder cancer- wouldn‟t get better, often blood in urine- will let you know. We treat over the phone all the time; many times a day. Have elucidated many principles- simple case, very certain about diagnosis, not severewould treat cystitis, not pyelonephritis over phone, has to be reliable, not many comorbidities. Simple treatment, low in toxicity. Simple problem, confident about diagnosis, reliable, no comorbidities- confidently will call in prescription over phone- earaches, colds, ankle strainsperfectly Ok to treat over phone. Build in feedback loop- call/see me if not better. Treat with Bactrim- TMP-SMX bid x 3 days, call if not better. Next day- calls, complains she‟s weak- got medicine late, wake up to pee at night, felt really weak. Feels dizzy, pretty Ok when lying flat, was drinking cranberry juice but not while sleeping. Really hasn‟t peed- tried to get up, didn‟t make it. Has taken one dose thusfar. Can‟t tell whether she doesn‟t need to pee or can‟t pee. Send her where- office or ER? ER- worry that blood pressure so low that she could have very serious problem, not mentating well. On physical exam- looks sick- ill-appearing; BP is 86/palp; HR is 128. 86/palp- misleading; sounds like measuring by palpation, not auscultation; nurse means that Korotkoff sounds don‟t go away. Despite this- HEENT normal, neck supple- whole exam is normal. So now know why she‟s weak. Why does she have low BP? Possibilities- sepsis- decreased peripheral vascular resistance; also- neurogenic shockhypothalamic stroke, spinal cord, even peripheral neuropathy- if sympathetic nervous system is down- can‟t clamp down. Some drugs- calcium channel blockers, e.g.; anaphylaxis; and glucocorticoid insufficiency- addisonian crisis- will do this too- need cortisol present- arteriole can‟t squeeze without cortisol. Cardiogenic shock- CHF, arrhythmia, ischemia- MI now, or nonMI ischemia yet affecting such large part of LV that is in shock; tamponade; valvular problemsstenotic valvular disease. Also hypovolemia gives shock- decreased intake or increased outputno water present or can‟t get to water, or have lack of thirst- above 40, people less thirsty, above 70- blunted quite a bit; stroke could do it; or can‟t get to water- trauma, or doctor tied you downadmitted with ileus, NPO for days. Output- GI losses, hemorrhage, insensible losses, third spacing, renal loss- diuretics, diabetes mellitus- sweet; insipidus- bland- insipid- in saveur- no taste. Hypovolemic shock- extremities cool, pale; same for cardiogenic shock. Quality of pulseweak in hypovolemic shock- thready; in cardiogenic shock- also weak. So how tell the difference between the two? Everyone with shock is oliguric! So- cardiogenic- all will have JVD, may also have rales; neck veins in volume issues- flat. Peripheral vascular resistance decline- extremities are warm, flushed, pulses bounding. When ask resident about pulse, will give number; other medical traditions- qualitative pulse analysis- Chinese- three fingers- apply light vs. firm levels of pressures, valid diagnostic system that worked for their system. If pulses are weak, means person is vasoconstricted, hypovolemic or cardiogenic shock; if not- not constricting properly. Our patient- warm and flushed. If sepsis- what look for- fever, white count; bacteremia, though 48 hours to come back; tachypneic, story that hangs together, have metabolic lactic acidosis, could measure lactate level, but could assess with anion gap; normal for most- less than 15, don‟t skip alcoholic ketoacidosis though not in the mnemonics. Lactic acidosis- poor perfusion- poor pressure at capillary level. Oxygen present in TCA cycle- do oxidative phosphorylation; when not- lactic acidosis. So one theory- shunting from arterial to venous side, skips venous system, so despite lots of oxygen in blood, doesn‟t get to end target. Hypothesis 2endotoxin poisons oxidative phosphorylation so can‟t use it. Bottom line- sepsis typically develops lactic acidosis, manifest in elevated AG. Neurogenic, meds- obvious from history; anaphylaxis- rash- type I- IgE reaction. (Morbiliform rash is type IV); wheezing, stridor, edema, etc. Addisonian crisis- no aldosterone- low Na, high K, low glucose. Our patient- temperature on presentation was 38.8, CBC 12.6, 14.5, 300K; electrolytes133/4.9/105/20/8/0.7/100. Normal anion gap, high WBC; 85% PMN, 3% bands, 5% lymphs, 2% monocytes, 5% eosinophils. 5% of 12,000 is 600 and change- 630- eosinophilia- see with anaphylaxis and sepsis and addisonian crisis. If has sepsis- everyone gets fluids, give antibiotics, do blood and urine cultures first. Give epinephrine now if anaphylaxis; if Addison‟s- steroids. UTI‟s frequently cause sepsis, but not much white count fever. Anaphylaxis- she did start medicine, but have taken it before! No- it‟s the second exposure that you see the reaction- second bee sting, when have been primed. Absence of urticaria, wheezing, stridor argue against it. Na is a little low, K is a little high, glucose a little low- so not so suspicious for glucocorticoid. Would treat with antibiotics; epinephrine- won‟t hurt her. If has Addison‟s, give hydrocortisone- will get up like that, if septic, one dose won‟t hurt her. Sepsis- might have relative adrenal insufficiency. ER gave epi, hydrocortisone; neither worked; epi raises BP for few minutes, then comes back down. Fluid- LR or NS but must be isotonic crystalloid- so has her IV fluids, has her cefblastemall, hasn‟t responded to the other things, EKG shows sinus tachycardia; admitted to hospital Monday night; Tuesday- see her, not much better; come back the next day, still not much better, BP still in 90‟s, still not responding- get sono to look for perinephric abscess or obstructive pyelonephritis. UCx negative; UA- 20 per HPF; BCx negative. Changed antibiotics; sono- found foreign body in vagina- tampon; toxic shock- haven‟t thought about that; negative blood cultures with that. Transferred to ICU, got ischemia of fingertips, ultimately made complete recovery; toxic shock related to tampon, also had UTI that was treated. How went wrong here, didn‟t get what happened till day 3? Didn‟t have complete exam or history. If 20 year old woman comes in with any history at all- take complete history; didn‟t have complete history or physical. NYS law- all have to have gyn exam on admission, or can refuse. Regulation we commonly neglect, silly regulation. Can understand how error was madeall thought urosepsis all the way; when make assumptions, get burned. Third error- Ddx not as complete as could have been- forgivable if give feedback loop. Fourth error- neglected from 12-36 hour mark, no one pays attention that edematous, still in 90‟s. When someone not doing well, must challenge hypotheses; hypovolemia not problem, cardiogenic- did echo; but didn‟t think toxic shock until sono made diagnosis for them. Have seen with tonsillar abscess, IV catheters- staph is of strain that secretes exotoxin. So shock- schema of three basic areas- cardiogenic, hypovolemic shock- straightforward; peripheral vascular resistance- sepsis- but must think of specific diagnosis, sometimes takes sleuthwork. Is rational for complete H&P, give self feedback loop so continually re-evaluating, trying to figure out what problem is. Red herring led everyone down path of urosepsis. Had patient in hospital with multiple myeloma, tapering steroids, all thought was sepsis but really glucocorticoid insufficiency. Dr. Bardes 5/10/04 A 50-year old woman was short of breath, and she went to the local hospital and was told she had water on her lungs, and was treated with water pill and discharged- 3 months ago. One month ago, the same story happened, and she went back to the ER, was told she has „water‟ in the lungs again, off the water pill because it ran out. They said- you‟re supposed to keep taking the pill! Confusion created because all of us carry acute paradigm, not chronic paradigm, for how illness behaves; no plan for follow up; and people are better at compliance when educated about the problem. Also, she got better- acute/chronic model- thought she was Ok. Language may be a concern. People in pain are anxious, worried, scared, often don‟t get message under those circumstances. People don‟t want to look stupid. How you can make it better- write it down, keep instructions simple, etc.- all helps; all this was done on the second time around, all Ok until today, she feels short of breath again. She was sitting on rainy day inside bus, crowded and steamy; short of breath, figured because bus so crowded, in bus shelter- went away; walking home- again felt short of breath, had to stop in ice cream store; when cleaning up dinner- again felt short of breath, comes here. Past medical history- HTN treated with diet. We give drugs to people all day long; didn‟t anticipate before medical school that life would be applied pharmacology. Hippocratic times- didn‟t like pharmacon- drugs called „evil potion‟- Circe gave pharmacon to turn Odysseus‟s men to pigs; didn‟t like surgery- couldn‟t enter chest or abdomen; often took out bladder stones. Original Hippocratic oath- clause against taking out bladder stones- used to argue that oath meant for trainees only. What they did do- lifestyle modifications; spoke to patients a lot about exercise, diet, climate, etc. We don‟t do that much today, but should. For hypertension- hasn‟t been worked out if all benefit a little or some do, some don‟t on salt restriction. Cardiovascular exercise. Other issues on diet front- DASH diet- reducing animal fats, increasing low-fat sources of proteindairy, fish, soy; alcohol reduction- be careful- alcohol reduces ischemic heart disease at dose of 1/day for women, 2/day for men. But 3-4 or more increases blood pressure. Medicinesfurosemide is the „water pill‟; takes supplements- calcium, magnesium, glucosamine chondroitin for sore knees, coenzyme Q10, ginseng, prometabolic life formula, and selenium. On physical exam, she‟s visibly dyspneic; her blood pressure is 240/150, HR is 128, chest had moist crackles 1/3 of the way up bilaterally; JVP of 8 cm water- better to express as vertical distance from manubrium when is present. RRR, nl S1 S2, has S4 gallop, remainder of exam normal. Hypertensive crisis, pulmonary edema- confirm with chest X-ray. Had a patient that had CXR read as pneumonia but all else pointed to pulmonary edema, stuck to clinical impression, was right. Pulmonary edema- from left-sided heart failure. Can call it cardiogenic pulmonary edema, to distinguish from non-cardiogenic pulmonary edema- ARDS; some use ARDS to refer to all non-cardiogenic pulmonary edema; pancreatitis, vasculitis, burns, chemical- mustard gas, sepsis. Cardiogenic pulmonary edema- could be from LV failure due to decreased LV contractility- systolic, decreased LV compliance- diastolic- what happens in relaxation. Causes of systolic- ischemia- that having now, or that had before, part of heart dead; valvular diseasemostly in regurgitation, late in stenosis; dilated cardiomyopathy; arrhythmia- V-tach, V-fib, Afib; toxins; also some issues of milieu- electrolytes; myocarditis- coxsackie, lyme, trypanosomiasis. Decreased compliance- infiltrated LV- restrictive cardiomyopathy- amyloid can cause it, sarcoid, Gaucher‟s, etc. LV could be thick- hypertrophic cardiomyopathy- IHSS; also aortic stenosis, chronic hypertension, and coarctation; remember these from fact that within ventricleIHSS, in valve- AS, beyond valve- coarctation, periphery- HTN. Then- ischemia itself causes decreased compliance; cardiac relaxation is active process, so myocytes slide together, then latch, and for them to unlatch is ATP-requiring step; with ATP- do all this; without- can‟t unlatch- stuck in closed position. In acute ischemia- decreased LV compliance, so have diastolic heart failure. And acute severe hypertension does the same- is a matter of debate; either because are ischemic, or can‟t handle all that afterload. Echo is gold standard; EKG- may see ischemia, hypertrophy; on physical exam, may hear valvular disease- but atrial blood hitting against noncompliant LV. S3- “rapid ventricular filling”- like a slosh sound- means lowered compliance in LV. How can you tell which is which? S4 comes right before S1, S3 comes right after S2; when tachycardic, sounds like a gallop. This woman has an S4- so decreased LV compliance. Impulse- if to left- systolic; if in place but more forceful- diastolic dysfunction. (Tamponade- pressure is equally distributed throughout heart, affects low pressure more than high pressure- get shock, JVD but not pulmonary edema.) This woman- no infiltrated or dilated LV, clearly has lowered compliance- seems that problem is acute severe hypertension. Why should this woman have hypertension? Pheochromocytoma; drugs; renovascular- renal artery stenosis; saw woman with renin 5x normal at 25. Conn‟s syndrome- adrenal hyperplasia; could be Cushing‟s syndrome, hyperthyroidism, and finally renal insufficiency, irrespective of renovascular status. In renovascular hypertension, measure renin; pheo- catecholamines; Conn‟s- aldo, Cushing‟s- too much cortisol, thyroid- high T4, renin insufficiency- high creatinine. All normal; tox screen normal but for pot; marijuana use is on the rise, would need to smoke a lot to get this. Other drugs- prometabolic life formula- not in her reference book- all natural ingredients... etc. (Weight loss give reduced blood pressure.) Formula contained ephedra- alpha agonist- epinephrine analog; used in China under Ma Huang; helps dry up sniffles in cold, stimulant like caffeine, but can cause severe hypertension. Student‟s hypothesis- had pulmonary edema due to severe hypertension due to Ma Huang, stopped the Ma Huang, she had mild hypertension, treated her for that. [Caffeine- have found no health problems; in very high doses, caffeine protects against type II diabetes.] Systolic heart failure: Non-pharmacologic treatment for systolic heart failure- exercise. Usually these patients die of arrhythmia; exercise is potent stimulus of arrhythmia, so need to do monitored exercise; 63rd and York- NYH cardiac fitness center- exercise wearing monitors, at first sign of arrhythmia, stops the exercise, lets them recover. Weight loss is good but not particular. Valve replacement if bad valve. Decrease salt- these people are volume overloaded, so salt reduction helps; alcohol reduction- one of these toxins is alcohol; toxins include alcohol- can damage heart permanently or impair it temporarily; pregnancy can give dilated cardiomyopathy; adriamycin; beta-blockers impair cardiac function when present, contraindicated in systolic heart failure. Alcohol reduces ischemic heart disease in low dose but can be toxic to LV. Drug treatments for systolic heart failure- digoxin- inotrope- increases contractility; diuretics- decrease preload; ACE inhibitors- decrease afterload, and ARB‟s like losartan- same pathway- decrease afterload. Beta blockers are somewhat counterintuitive- impair LV contractility, but slow rate, allowing for increased filling; are antiarrhythmics, which is important- main cause of death in CHF is arrhythmia; also- decreased sympathetic tone is a good thing. Catecholamines cause myocardial fibrosis- thus cocaine toxic to heart- so can cause fibrosis and scarring. Nitrates reduce preload; another way to reduce afterload- hydralazine- old antihypertensive, decreases afterload. These will make you feel better. What will make you live longer? Not digoxin. Diureticslasix- no; spironolactone- yes. ACE inhibitors- dramatic decrease in mortality, have had tremendous benefit. ARB‟s- looks like answer is yes- CHF life expectancy is relatively low, acts on same pathway- so appears to be yes, even a little better with losartan than ACEI. Beta blockers do improve mortality but have to be careful- can make someone worse with beta blocker; if they can tolerate it, decrease mortality. ACEI, ARB‟s, beta-blocker- one by itself, two will improve mortality, three together won‟t. Nitrates and hydralazine- not alone, but yes in combination. Get tachycardia, headache, orthostatic hypertension, so hard combination to take. Temptation is to treat all CHF with lasix and digoxin, because feel much better, but won‟t help them live longer, so start with ACEI, add ARB if have to, then beta blocker, then spironolactone. Diastolic dysfunction- beta blocker, calcium channel blocker more important. Distinction between systolic and diastolic dysfunction in heart failure is really important. All need echo. If systolic- non-pharmacologic steps, then pharm; if diastolic- easy- beta-blocker, calcium channel blocker. On Friday- pediatrics conference room. Dr. Jonathan Bress 5/10/04 ABG- need to look at metabolic, acid-base status. Acidemia- strictly refers to pH below 7.36, alkalemia- pH above 7.44; acidosis is process causing acidemia, alkalosis- opposite. Get pH/pCO2/pO2; want to know- is CO2 consistent with metabolic panel bicarb? So- first want to know if are acidemic or alkalemic. Acidosis and alkalosis- metabolic and respiratory; within metabolic acidosis- is anion gap and non-gap. How come is maximum of three? Respiratory is either/or, but can have metabolic acidosis and alkalosis processes. If look at pH- get first disorder from looking at pCO2; if pH is low, pCO2 is uprespiratory acidosis; if pH high, pCO2 high- metabolic alkalosis. How do you get to secondary with calculations? Can‟t do ABG‟s in isolation- sometimes need story to go with it. If have primary respiratory acidosis, must first ask self- is it acute or chronic? Acute respiratory acidosis- hypoventilation- drug or CNS problem, e.g. Chronic respiratory acidosis- COPD. So need the story; in chronic respiratory acidosis, kidney compensates by keeping bicarb. So COPD patients have better pH. Normal pCO2 is 40; if PCO2 goes up by 10, pH in acute setting goes down by 0.08. Chronic will be better compensated, so less of a change- 0.03. So hypoventilating10 to 0.8, while COPDer will be 10 to 0.3; 7.32/50 vs. 7.37/50. Chronic conditions- kidneys compensate. Primary metabolic disorder- Winter‟s equation- 1.5 x [HCO3] + 8 +/- 2 = expected pCO2; if I have acidosis, will breathe off a little more, but how much? Look at bicarb on chemistry panel- is it internally consistent? So- if have bicarb of 12, anion gap is high, can expect pCO2 to be 26 +/- 2. That‟s how you can see if well-compensated in primary disorders. So- 7.32/26- primary metabolic anion gap acidosis, no alkalosis. Now- what if see 7.32/40? Primary metabolic acidosis with superimposed respiratory acidosis- PCO2 is too high- hypoventilating (pH should be lower). 7.15/60- If someone drank selves silly, no underlying lung disease- primary disorder is likely acute respiratory acidosis; if CO2 up by 20- expect pH in this case to be 7.24. Now- on lytes- expect there to be metabolic acidosis with anion gap. Now need to explain it. For anion gap acidosis- mud piles acronym. For metabolic alkalosis- hypokalemia, vomiting, volume contraction- can be from diuretics, dehydration, etc. Poor man‟s explanation- if you‟re volume depleted, kidney will retain Na at all costs; Na must go with anion- bicarb; so give chloride-containing solution- replete volume, while relieving alkalosis. Respiratory acidosis- acute- drugs, CNS, musculoskeletal, or chronic; respiratory alkalosis- pain, fever, anxiety. Haven‟t discussed non-anion gap acidosis. Anion gap acidosispresence of extra anion. Non-AG- losing bicarb or can‟t clear acid in kidney- HARD UPShyperalimentation, acetazolamide, RTA- renal tubular acidosis, Diarrhea, Ureterosigmoidostomy (bowel to urine), pancreatic fistula, and saline resuscitation. Hypercalcemia, multiple myeloma, lithium acidosis also do this. My big three- acetazolamide, RTA, diarrhea, saline resuscitation; others- know from history. Acetazolamide- prevents bicarb absorption so lose it, essentially create RTA I. RTA- types I, II, IV. Diarrhea- losing bicarb; saline resuscitation- switch to lactated ringer‟s. So check to ensure no wacko bladder fistulas, look at medex, look at chart- did they get liters upon liters of fluid? Are they stooling brains out? If not- RTA. Now have differential; should be picking apart ABG‟s. How get third disorder- third is either concurrent metabolic alkalosis, or non-anion gap acidosis. Calculate anion gap, then look at bicarb on chem panel. If anion gap is 20, should be 12, bicarb should go down by 8. So- CHF, COPD on diuretics- AG metabolic acidosis from lactate, metabolic alkalosis from diuretics, respiratory acidosis from COPD. So every time get patient with ABG‟s- ensure that is internally consistent, fits with disorders. Last point- we put sample on ice. If leave on room temperature- RBC will eat up O2 in sample- pCO2 goes up, pO2 goes down. 7.40/40/200- air bubble- pO2 will skyrocket spuriously. Try to take ABG radially. Ideal b/c has collateral. In groin, can cause retroperitineal hematoma. Usually numbers make sense.ABG‟s hurt- arteries are innervated. But skill that must have in middle of the night. Medicine clerkship website- 5-6 sample questions, topics Dr. Bardes expects you to know, etc. Resident Tutor Session Pneumonia Dr. Christopher Gade 5/10/04 Pneumonia- classic presentation of adult pneumonia- productive cough, fever, white count, focal infiltrate on CXR, usually pretty fulminant, see patient in a couple of days; rustcolored for s. pneumo, currant jelly for Klebsiella. Old person‟s friend- manifest in many waysjust mental status change- no cough, fever, CXR may not look right away like pneumonia. Any elderly patient who just doesn‟t look good- rule out pneumonia and UTI. Atypical bugsChlamydia pneumonia, Mycoplasma, Legionella- dry hacking cough, body aches, myalgias, no productive cough in first two; may not have WBC count, present like that. In immunocompromised- different organisms- could also present with dry hacking cough or shortness of breath. On exam, listen for two things- sensitive and reproducible- inspiratory crackles (also true for CHF, be careful) and egophony for consolidation. Dullness tells you about effusions, different category. Hard to differentiate between wet and dry crackles; IPF- Velcro crackles, but otherwise hard to tease it out. If O2 sat less than high 90‟s on room air, or less than 90- get gas, see pO2; are they febrile, what is RR? Then look at them- say- is this person sick; diaphoretic, leaning over, can‟t breathe? Can‟t speak in full sentences because in respiratory failure, using accessory muscles. What is volume status? Infected might be really dry. Both sides have crackles, equal- usually CHF. Rest of the exam is as usual. Then look at the labs. Also look- how old are they? Morbidity up with age. Other conditions- DM, renal failure, CHF, active malignancy- increases morbidity and mortality. Look at labs. PORT score- pulmonary outcome research- algorithm of whom to admit, who go to ICU as marker of outcomes; age and sex- men get -10; if 70, much different from 30. RR >30, PO2 <70, systolic BP <90- sepsis and old age. Then- comorbiditiesDM, CHF- +20 each; kidney failure- BUN >30; WBC- <5...; CXR- multilobar is marker for worse disease; points for effusion; then calculate the score, do you need admission, do you need ICU admission? Separate thing- look at four parameters- BUN >19.6, diastolic blood pressuremore marker for sepsis- <60; other two markers- probably O2 sat, etc. So look at patient, put together composite. Pneumonia- can look at it- what kind- community-acquired- did patient just come off street, or is it hospital-acquired? Ventilator-associated? Immune compromise- HIV or on prednisone- 15 mg/day for 1 month? Then- causative organisms. Most common- viral; most common bacterial- S. pneumonia- classically lobar infiltratecough, rust-colored sputum- never see, fevers, egophony with consolidations. Other organismstons of them. Gram negative rods- Klebsiella- alcoholics, people who aspirate- at risk for gram negative rods. Aspiration bugs can be gram negative rods, anaerobes from mouth- but for latter, must have teeth- peptostreptococcus, etc.; and can be staph. Most of the time, don‟t get the bug- sputum cultures- in community acquired pneumonia, what is value of sputum culture? Up to 85% sensitivity. We send for cultures only for recurrent pneumonias, patient who‟s vented or not getting better. GNB- any kind of head and neck problem, alcoholic, old- worried about aspiration; won‟t get mouth anaerobe if have false or no teeth. Peptostreptococcus, Strep mutans, fusobacterium. Try to figure out where fit in that spectrum. Community-acquired, not severe pneumoniaif admitted to hospital- atypical or typical organism? If walking pneumonia- give macrolide- Zpac- 5 days azithromycin, or tetracycline like doxy- will cover gram positives and atypicals very well. If admitted to hospital, severe enough to worry about broader coverage. [If gave augmentin- amoxicillin, clavulinic acid- doesn‟t cover atypicals.] If come to hospital- give thirdgeneration cephalosporin- ceftriaxone for 10 days, converted to PO augmentin, plus a macrolide. Ceftriaxone covers s. pneumo, GNB, though not anaerobes; macrolides cover atypicals. In the ICU, can still give them that if you think it‟s a CAP with other complicating factors- heart failure, renal disease in elderly- can treat with that cocktail, watch them closely. If fear other issues, may need to go to something stronger. If you think it‟s an aspiration pneumonia, can add clindamycin straight up, or give Zosyn- piperacillin-tazobactam- though probably overkill, or add flagyl; these cover anaerobes. If gave Zosyn, give macrolide too for atypicals. People with bronchiectasis- cystic fibrosis, in hospital for long time- pseudomonas; have piperacillin, ticarcillin, ceftazidine, and then huge guns like meropenem, imipenem. Quinolones have antipseudomonal activity but not great. Cipro- best activity against pseudomonas but worst for gram-positives. Zosyn, Timentin will cover pseudomonas. Gent used to be drug you could bank on covering pseudomonas, now resistance, here use Tobra but resistance now to that too. Hospital-acquired pneumonias- can use third-generation cephalosporin or penicillin plus quinolone- pseudomonas, GNB, aspiration bugs. HAP- aspiration, gram-negative rods, and worry about MRSA; if suspect that, throw Vanco on. Suspect if in same room or patient not responding to therapy, or culture it from blood or sputum. Viral pneumonias- usually influenza- A is epidemic, B is endemic; parainfluenza; December, January; usually older, immunocompromised. Fluffy midlung infiltrate, get really sick. Older people, health care workers, chronically ill should all get influenza vaccine. Antivirals- amantadine, etc. only work in first few days- won‟t eliminate organism but better outcome. In autumn, summer- Coxsackie- body aches, fever, etc. Fungi- look for findings on CXR- immune compromise, etc. Big three- Histo, Blasto, Coccidio. Mississippi valley, Puerto Rico; TB- might have focal infiltrate, lymphadenopathy on that side. Fungi- can have cavitary lesion, upper lobe infiltrate, pleural thickening, or lower lobe infiltrate; fungi can present like anything. In immune compromised patient- classic AIDS pneumonia- PCP; risk goes way up when CD4 count under 200, but possible at 240, etc. Also with immunocompromise otherwise; interstitial pattern, severe hypoxia with exertion- suggests PCP. A-a gradient of 35 or more, PO2 70 or less- IV bactrim or pentamidine or clinda- add prednisone, because part of picture is interstitial inflammation. HIV- 10% a year who are PPD positive convert to active TB. If get really immunocompromised- CMV can cause pneumonia-like picture; can also get MAI. Studies for these people- usually ends up coming to bronchoscopy, looking for PCP, CMV; can have CMV in washings yet have something else. Chicken pox, fulminant rash, pneumonia-like pictureworry about VZV pneumonia, but very uncommon. Common things will see- s. pneumo. So look at who they are, where come from, how sick they are. All should get two blood cultures peripherally before antibiotics; sputum culture for any question of diagnosis; then can go to bronchoscopy if they aren‟t getting better or question about other organisms not available from sputum. For TB- three sputums better than bronch. Effusion >1 cm should be tapped; worry about empyema- source of sepsis, lung trapping. Gram stains will be available right away, not culture results or special stains, so if suspect PCP, treat. Severe pneumonia- throw house at themvanc, imi and quinolone- if severely ill, afraid could have MRSA. If worry about resistant strep pneumonia- resistant to penicillins- transmits to cephalosporins; worry about people who got beta lactam antibiotics; people exposed to young children, have kids at home- worry about resistant strep pneumo. Worry about s. pneumo going to CSF, getting meningitis. Osler‟s triad- meningitis, endocarditis, pneumonia; so may be inclined to give levaquin up front- covers typicals and atypicals, one drug gets them all. Look for improvement with symptoms; should need less O2 to get sats up, fevers- if still spiking temps after 48 hours- treatment not working, or have effusion or loculated collection that must be taken care of. CXR- will lag behind clinical; if septic- other parameters. Generally 10-14 days of treatment. 7 days may be enough; have looked at levaquin at 750/day for 5 days rather than 500/d for 10, may have same efficacy. Vented patients- worry about pseudomonas, anything goes- gram-negatives, MRSA‟s. Specific patients- CF patient- worry about pseudomonas right off the bat; if really sickBurkholderia cepacia- bad bronchiectasis, poor prognosis- may not get lung transplant if have that, though treated with bactrim. COPD patients- anyone with underlying lung disease is already in the hole, as well as DM. [Kartagener‟s, as well.] Bread-and-butter pneumonia- strep pneumo, lobar infiltrate, cough, fever, WBC count, treat with 3rd generation cephalosporin and macrolide, or augmentin, unasyn, cover strep pneumo and gram negatives. Young person‟s pneumonia- like mycoplasma- macrolide deals with it well. Can look for other things- with mycoplasma- can have bullous myringitis in ear, cold agglutinins; with legionella- exposure to aerosolized water- showers, air conditioners, etc.; get really sick- GI symptoms as well- Legionnaires in Philadelphia- pneumonia, bad diarrhea, septic. Can see hyponatremia, hypophosphatemia, ALT elevation. Chlamydia psittaci- birdassociated disease, more serious than Chlamydia alone. Legionella clearly must be treated, others- unclear. Can send off urine for legionella, though not great sensitivity; PCR can detect. The other stuff- more esoteric. Any pulmonary process can cause SIADH, unclear why. PTHrP, ACTH, Eaton-Lambert, cerebellar toxicity, etc.- associated mainly with malignancies. Pleural effusions- 7 kinds of parapneumonic effusions from pleural effusions down to empyema; treatments range from tapping to thrombolytic agent to decortication. Book- try to read all of Fishman for clerkship- read cover to cover, gives good intro to basic stuff of Medicine. For patient- can read Cecil‟s, Harrison‟s for detail. Up to date- best search engine but patchy. Intro to Harrison‟s- approach to medicine- important for global view. Read Bardes‟s book because important for exam. Resident Tutor Session EKG I Dr. Christopher Madias 5/11/04 How start reading EKG? Rate. Normal rate is 60-100. Each big box is 0.2, so each little box is 0.04. Count down- 300, 150, 75, etc. from big boxes. Next- rhythm; normal sinus rhythmsinus- see P wave before every QRS; R to R intervals are equal; see QRS after every P. Other important thing to look at- axis; look at lead II and V1. Axis- I is 0 degrees, II, 60, aVF 90, III 120, aVR is -150, aVL is -30. Sinus node- right atrium- NSR comes from there, RA depolarizes, goes to AV node, purpose is to slow down conduction; purkinje system- left splits to anterior and posterior, right is branch. Lead reads voltage; when goes toward it- positive deflection. Look at lead II; upright P-wave in lead II is NSR; if upside-down P wave- going opposite way- could be a different origin of impulse, not NSR though could be regular. Axis- normal axis- -30 to 90; look at I, aVF; leads measure voltage. EKG is sum of vectors. If look at I and aVF, have positive deflection toward I and aVF, know normal axis if both upright; then- most isoelectric lead- 90 degrees away from that. Then- look at intervals. Care about PR, QRS, QT. Normal PR interval- 0.12-0.21. PRfrom beginning of P wave to beginning of QRS complex. When longer than 0.21- first degree heart block. Pause through AV node- amiodarone, lidocaine, beta blocker can cause it. Second degree heart block- Wenckebach- Mobitz type I- conduction disease- more at AV node or higher junctional area- increasing PR intervals, then dropped beat. Mobitz type II- lower down, at risk for complete heart block, ventricular arrhythmias- same intervals, then dropped beat. More worrisome. Third degree heart block- atrioventricular dissociation. That‟s dangerous- may not be enough to perfuse selves- bradycardic, and predisposed to ventricular arrhythmias. Shortness of breath, perhaps syncope, cold extremities secondary to heart failure- very fatigued, etc.; want to pace them. Overnight- until pacemaker lab opens- how temporize? Could use external pacemaker. Atropine not as effective in complete heart block. Temporary pacemaker- central line through neck, put wire through, ends up in RV, set rate, send little shocks through wire. Short PR interval- WPW- accessory pathway- bundle of Kent, tissue that acts as accessory pathway. Classic- delta wave on EKG- initial ventricular depolarization before going through AV node; His-purkinje system so effective at conduction that get normal-looking EKG but for this delta wave. QRS complexes in complete heart block- wide, because originating in ventricles- bundle of His. Normal QRS- <0.12. >0.12- call it wide QRS complex. Causes- ventricular rhythm, bundle branch block- left and right. Right- rsR‟ or „rabbit ears‟. True RBBB- need QRS to be >0.12. Get this morphology in V1, V2- V1 is very close to R ventricle in chest, will first see septal depolarization from R to L; then- depolarizes from left toward the right because RBB is cut off. LBBB- V6 and I, sometimes V5. Almost opposite of rsR‟; usually broad QRS in leads I, V6. Incomplete RBBB, LBBB possible. Left anterior fascicular block- usually look at axis. Often will see change in axis, will have very negative axis- > -30 without a reason for it- no LVH, etc. RAFB- >90. QTc is normalized for RR interval; divide by square root of RR interval. Cheater‟s way- look to see if QT is less than ½ of RR interval- normal. Borderline- have to calculate it; greater- long QT. QTc- <.45; greater than that- abnormal; electrolyte abnormalities or medications; dangertorsades de points, V-fib, V-tach. So- long QT- replete Mg, put on telemetry. After intervals- look at ST segments, T-wave inversions, Q waves, so forth; will discuss as go through EKG‟s. Hypertrophy- different criteria for hypertrophy. LV hypertrophyimportant leads to look at precordial leads. aVL criteria- R wave >11 small boxes; precordial leads- look at V2, V3, etc. RVH- look at V1, V2- see upward deflection where would normally see downward deflection- RV is much thinner than LV; vector usually away from V1; if severe hypertrophy- will go toward V1. R wave in V1 >7 small boxes is criteria. Poor R-wave progression- remains upgoing throughout V leads for longer than if normal; seen with RVH, COPD, MI with damaged ventricular tissue. L atrial enlargement- biphasic P-wave- look at V1 and II; in II- P mitrale, in V1- deeper than 1 mm. In right atrial enlargement- II- high P peak- P pulmonale- often associated with lung disease; V1- greater than 1.5 mm. Rate- normal. Rhythm- P before QRS, upright in lead II- NSR. Axis- bit more negative in III, but isoelectric- around 35- is between I and F because both upright. Now- intervals- PRsmall boxes. QRS- now wide. QT‟s- less than ½ RR interval. Any Q waves on this EKG- first downward deflection? III- definite Q wave; can represent old infarct. Isolated Q wave in one lead, no history of heart disease- insignificant. Wider than box, more than 3 mm down. Old infarct- three main arteries of heart- LAD, RCA, Circumflex. Distribution on EKGanterior, inferior, lateral infarcts. Classic anterior leads on EKG- V1-5- LAD. CCU- read EKG out loud, ST elevations in leads- what‟s going on? Lateral leads- V6, I, aVL, sometimes V5. Artery- Circ. Inferior leads- II, III, aVF. Think about where leads are actually placed on heart. RCA classically also gives off branches to sinus node and AV node, so see conduction abnormalities with inferior infarct- prolonged PR, see first, second degree heart blocks with MI. Put pacemaker in; usually other arteries give off collaterals to conduction system, will have normal P waves when reperfused; sometimes need permanent pacing. ST elevations? Not in this one. Inverted T wave- strain vs. ischemia- different morphology. Next- rate- 54- bradycardic. Rhythm- P before every QRS- sinus bradycardia. Axisaround 45. Intervals- PR interval- 3 boxes- normal; QRS- about box- normal. QT- less than ½ RR so normal. QRS morphology- micro-Q in III- probably not too significant, maybe aVF. ST segments, T waves; in I- inversion, and in V2, V3, V4, V5. If see this EKG, are worriedanterior. T-wave inversions not as sensitive as ST elevations/depressions in defining anatomy in ischemia but definitely concerned, want him to come to cath lab, probably will have anterior disease. Wellen‟s sign- bi-polar T-wave in V1, V2, more significant inversion in other leadsusually means proximal LAD injury or even left main disease. Rate- 90 to 100. Rhythm- sinus. Axis- isoelectric in AVF; 90 degrees, will be zero because up toward I; normal axis. P wave down in V1- could suggest atrial enlargement; fairly broad in II. Intervals- probably a little longer than 1 big box- PR interval- so first-degree block. QRS wider than 3 boxes; Rsr‟ seen in V3- not technically incomplete block because QRS is <100 ms. QT interval- is >1/2 of RR, might suggest long QT; measure RR, QT intervals, divide RR by square root of QT intervals. Bifascicular block- RBBB with extreme left axis, with no other reason- no inferior MI, no LVH. Q waves- III, aVF. Significant heart disease- may be inferior MI evidence. ST- elevated in II, III, aVF, V6; suppression of depression in V1, V2. If had to guess off the bat, would think lesion in RCA. Turns out not so- three-vessel CAD, stent in left circ, given thrombolytics- ST elevations have resolved; took to cath lab- think had in-stent restenosis- thrombus in stent, cleared with tPA. Window for tPA- 6 hours; people give it up to 12, but best data is under 6 hours. Over 12- no mortality advantage. Mechanisms of Perioperative Acute Renal Failure Dr. Saal 5/12/04 ATN- exaggerated vasoconstriction; get ischemia, damage to endothelium, small vessel plugging as a result- expression of adhesion factors, leading to more hypoperfusion. Proximal tubule is most at risk for more cellular damage. Constriction, cellular activity, hypoxia, cell injury. Ischemia translates into tubular damage. Series of overlapping mechanisms, pathways of injury. In ATN, one of first events- cytosolic calcium increase. Pumps disrupted, mitochondria disrupted; as result- more nitric oxide is produced, lipases, proteases, nucleases produced. So nitric oxide- vasoconstrictor before- now gives disruption in actin cytoskeleton- tubule cell polarity disrupted, no GFR. Diagnosis of ATN- FENa. Early on with exaggerated NO response- FENa may be low; only after pumps internalize into cell membrane- no electromotor force- no Na reabsorption, so FENa will become high. Tubules themselves can generate electromotor force, absorb Na by charge. No electromotor force generated- no Na absorption- high Na excretion. Finally- as Cl moves to macula densa- more renin, angiotensin production- GFR lost- because wasting Na. Finally- cast formation- tubular backleak, obstruction. In most human ATN- very little cell death, vs. animal models; many or most cells may be dysfunctional, but not cell death. Apoptosis- DNA destruction. Where do electrons come from for reperfusion injury? Hypoperfusion per se- many sources liberate electrons, which can convert oxygen to superoxide, lead to ROS creation. Acetylcysteine only works in one of those pathways. Most of the kidney damage that occurs with ATN is reversible; in most human forms of ATN- no irreversible cell death. Also- ischemia alone doesn‟t always lead to ATN- most high-risk don‟t get ARF. Sepsis data- 50% of hypotensives, but 25% of non-hypotensives! So- in cardiopulmonary bypassendotoxins released; occurs with exercise, as well- from gut bacteria. Contact activationcomplement protein cascade, intrinsic clotting cascade; as activate clotting system- lo and behold, PMN aggregation, etc.- mechanism of cell aggregation- complement activation per seleukocyte activation and chemotaxis, and C3 activation- get the same kind of thing, nothing to do with BP- clotting, but same sort of vascular ischemia. Bypass- longer on pump, more likely to get ATN. ½ of patients who go on bypass are endotoxin positive. Have natural ability to neutralize endotoxin- produce antibodies to endotoxin, Evolutionary purpose of lipoprotein particles- get rid of lipid-soluble wastes, like endotoxin. If look at endotoxin core antibodieshigher level of antibody, lower risk of adverse outcomes following cardiac surgery. Patients with same relative degree of illness- better outcome with endotoxin antibodies. We infused phospholipids emulsion in septic shock animal models, showed if raised ApoA- HDL-like molecules- protected animals from septic shock. Sold emulsion to glaxo, going to phase 2, phase 3 human trials now. All lipoprotein particles can bind endotoxin, didn‟t want to give LDL to patients. Other response- extrinsic clotting system activation by endotoxin; also- macrophage, mesangial cells bind- cytokines causing cellular, microvascular aggregation. CD14 receptor on macrophages can dislodge, circulate, interaction between LPS, receptor, LBP, endothelium. So if septic- analogous to going on bypass- clotting, cell activation, inflammatory response, cell aggregation Why does Xigris work? Doesn‟t just affect clotting system- affects complex of LPS, LBP, CD14 receptor and macrophage response, and where this complex binds epithelium, So not on works at clotting system but also on inflammatory response. Other agents haven‟t worked because deal with one mechanism in a redundant pathway (e.g. anti-TNF alpha, etc.) Same mechanisms over and over again. TNF-alpha, IL-1, IL-6, IL-8- huge inflammatory response affects microvascular circulation, causes ischemia regardless of blood pressure. Our approach- give them fluid- not all that successful, addresses only one pathway, not curing anything. Some will get shock, some won‟t, some get RF, some don‟t depending on their genetic polymorphisms. IL-10 is counter-regulatory- moderates upregulation of inflammatory response. Sort out mortality based on their ability to express cytokines; if more likely to make TNF alpha, IL-6, not IL-10- worse prognosis. Some growth factors- bone morphogenic protein, e.g., for CRF- insult propagation based on several mechanisms. If interfere with inflammatory response markers- can interfere with mechanisms. Concept of ATN, nothing else going on, bx normal, give fluids- leaves much to be desired- multiple mechanisms at once, will be interesting things on the horizon. Dr. Wenderoth Tutor Group 5/12/04 Next case- do all off the cuff except for labs. CC: Nausea, vomiting, diarrhea for four days. 25-year old female with history of endometriosis, PID; ate chicken wings, felt ill immediately; nausea, vomiting, diarrhea. Described abdominal pain as sharp, diffuse, non-localized, 6/10. Vomiting profuse- first food, then liquid substance, then dry heaves; diarrhea- green liquid with yellow mucus, no blood; would have diarrhea, vomiting together 10 or more times per day, for four days. When admitted10/10 pain, remained diffuse, non-localized; no medications, travel, ill contacts, no one else ate these chicken wings. LMP was 2 weeks ago, not particularly painful; longer, heavier than normal. No arthralgias, history of DM or polydipsia, polyuria. Nausea, vomiting, diarrhea- what want to know- could she eat at all? Not able to eat much at all despite being hungry. Appendicitis- if gave favorite meal, couldn‟t eat it- „hamburger sign.‟ Blood- after retching? Mallory Weiss tear? Blood- red- never hit acid; minute it hits acidcoffee ground- e.g. in PUD. Nosebleeds that swallow- also red; so red is esophageal. Diarrhea- smell- melena stinks; or steatorrhea. Color- any black? Watery? Pain- 10/10 but started at 6/10; movement at all exacerbates it; nonlocalized- irritation of omentum, not peritoneum. Movement- peritonitis, or retroperitoneal- e.g. pancreatitis. Differential- viral gastroenteritis usually doesn‟t make you this ill. In kids, Norwalk can make them pretty sick, not in adults. Gastroenteritis- E. Coli, Salmonella, Shigella, Campylobacter, Yersinia, B. Cereus in refried rice, Staph preformed toxin. Only need 10 particles of Shigella to get sick. All but last two can give blood. TB- way down on list but possible. Hep A; Pancreatitis- stones, alcohol, meds, viruses. Can have PID, Fitz-Hugh-Curtiscan inflame liver capsule, make you sick as stink. Frank peritonitis or not- what matters is when catch PID. Other gyn causes- abdominal ectopic- huge problem for internists- miss it a lot. Ovarian torsion- ischemia causes cascade of responses. Ovarian cyst- during ovulation- can fill with blood, get superinfected, dermoid cysts grow huge and predispose to torsion, but can fill with blood, give chemical peritonitis. PMH- asthma, endometriosis, laparoscopy, on lupron and antibiotic she couldn‟t name, PID in 2002, hospitalized on IV antibiotics, went away after several doses; under no medications at home, family history of CAD, social history- according to patient- no history of tobacco, alcohol, drugs, entertainer, she monogamous to boyfriend, HIV negative. Dr. Oliver Fein starts with social history before presentation- thinks it makes all the difference in the world. Known painkiller abuser, borderline splitter of staff, lots of issues. Important to establish- do they know that you know? All have to start with same assumption of honesty; say- who are you, who am I, what are we here to do, what you will do, what I will do- I won‟t talk to press, you will tell me the truth. Often trust medical student in a way that don‟t trust others. Tend to discount psych history but when setting off alarm bells, must pay attention to it. Rich and famous people come to NYH but outcomes often poor because demand private doctors, special care, don‟t let anyone touch them, lose the checks and balances system; Andy Warhol‟s private nurse reported vitals 12 hours after he was dead. PE- irritable, rolling back and forth holding abdomen, left eyelid pain, tachycardic, hypoactive bowel sounds, more pain on R than L, tense; guarding, rebound, CVAT, CMT with discharge, guaiac negative. Everyone uncomfortable with cervical motion, want to know if she‟s jumping off table. Want to know if is orthostatic. Pyelonephritis added to differential. No thrush; white discharge could be yeast- nice to know if systemic or not. Now that know social history- adds narcotic withdrawal- people have nausea, vomiting; think cocaine causing ischemic bowel, but lot of cocaine for that. Also narcotics. Amylase/lipase, lytes, LFTs, beta-hCG [urine tox- 12 days to come back.] Stool culture, ova and parasites. ER triages all abdominal patients to surgery because they image, lower perforation, mortality than medicine dickering with labs. CT showed L ovarian cyst, free fluid in abdomen, L pyelo, R colitis. Anion gap of 18- probably from lactic acidosis from her nausea, vomiting, diarrhea, etc. LFT‟s- LDH was high, as was Alk phos- makes you think of bowelanytime serosa irritated, stretched- those happen. Urine hCG in ER was negative. Ketones, protein, no LE, positive bacteria and WBC‟s; quick GC/Chlamydia is still negative. Is there one thing that ties them all together? Must think. Antibiotics- want to cover gram negatives, anaerobes, antibiotics. Safest- treat in conjuction, see how it resolves. Thickeningcolitis becomes stranding, then resolves. Could have abscess in conjunction with ovarian cystureaplasma, etc. that not GC/Chlamydia that can affect colon and kidney, may not see on CT until some of surrounding inflammation resolves. Hydration with glucose- she has ketones, gap, vomiting and diarrhea. So antibiotics, hydration, sent stool for C-diff, surgical consult, etc.; OB/gyn- PID was at top of her list; serum hCG was negative, OB/gyn not impressed with CMT. Pyelonephritisofficial read- probably artifact on CT; so probably ureteral irritation. Problem- colitis is on right, pyelo is on left. A lot has happened; exquisite pain complaints so looked for free air on upright AXR. New CT- cyst, they said, may have slightly increased in size; hard to evaluate colitis but looked less or unchanged, physical exam is improving slightly. Very med-seeking, tells you what she wants to take, may be appropriate for endometriosis patient but hard to tease out, is some graying of borders, emotional overlay. At first- said it was campylobacter; may yet be that. Ascites in pelvis looks more physiologic on the last scan. Almost certainly has adhesions. Patients like this are challenging; emotional overlay, pain, and history of narcotics; anyone who‟s been addicted has different pain threshold. CSS- HIV clinic- when getting bloods drawn- person who used to inject drugs into scariest, weirdest places are the ones in the most pain, strangest thing. Patient who‟s 30, ethnic, terrible endometriosis; went to local doc, excruciating painpain appeared out of proportion, lot of drama associated with it; was admitted to psychiatric hospital, put on thorazine, in hospital on and off for 10 years until OB/gyn diagnosed with endometriosis. So sometimes so many layers, hard to get at truth of what‟s going on. Drugseeking sickle cell patients- role-playing patients start off being logical, then act like are in more pain than they are to get treatment; hard to convince people that are in level of pain that they are in. Dr. Wenderoth 5/13/04 38-y/o female with beta-thal major DM 2 on insulin, hemochromatosis with cardiomyopathy, recurrent UTI and pyelo admitted for right flank pain, cloudy urine; dark pH 7 urine, trace nitate, bili; 500 mg levaquin, admitted to floor. PMH- CHF from cardiomyopathy from hemochromatosis from beta thalassemia major transfusions; hemorrhagic stroke in 2000; L perinephric abscess; osteoporosis, cholelithiasis, hypogonadotrophic hypogonadism; DM2. PSH: Splenectomy in 1975, L breast lumpectomy for benign fibrocystic breast disease, 1997; ORIF of L hip- 2003. Allergic to Ceftan- rash. Lives with mother, on disability but activevolunteers. Complications of beta thalassemia major- hemolytic anemia- hemolytic, microcytic; also poor erythropoiesis; hemochromatosis, cirrhosis, diabetes requiring insulin, high output from CHF in severe cases. Cholelithiasis and resulting high bilirubin- leads to pancreatitis, cholecystitis, choledocholithiasis, cholangitis, etc. Bone problems- extramedullary hematopoiesis, osteoporosis and fractures, renal damage- myoglobin, transfusion dependent; clots- PE, CVA, can get ischemia; chipmunk facies; transfusions- HCV, hepatitis, viruses. After transfusions- 10 day risk of Yersinia bacteremia, infection; splenomegaly or asplenic leading to strep pneumo, h. flu infections. Gyn: hypogonadotropic hypogonadism from iron. Differential for flank pain, cloudy urine- UTI, pyelonephritis, nephrolithiasis, cholecystitis if radiation to shoulder; remember pancreatitis- retroperitoneum gives back pain. Could have abscess. Not acute distress but looked ill, tired. CVAT on right side. Abdomen- hepatomegaly, felt liver edge to 2 cm below costal margin. No rebound or guarding, normoactive bowel sounds, no stigmata of portal hypertension or cirrhosis. Good rectal tone, no masses. Good pulses, no C/C/E, upgoing babinski‟s, hypoactive reflexes. No murphy‟s sign, no grey turner‟s, no S3 or S4, no JVD, jaundice or excoriations, no hepatojugular reflex. Labs- UA, urine Cx, urine dip. Yellow, cloudy, glc -, pH 6; trace blood, 1.071, nitrates +, 2 RBCs, 26 WBC‟s, marked bacteria- dirty urine. Sono of RUQ region- pending. CT (stone)- not yet ordered. Indium, Gallium-scan CT- both tagged cell scans; gallium is specific- tag white cells, lights up abscess pretty well. Indium- may cell lines, a bit more non-specific, light up new fractures. WBC count- CBC- 31.1 corrected (beta-thal have high levels of NRBC, need counter to correct for it). 10.2 Hb, 631. In beta thalassemia, CBC almost never helps you, but Hb lets you know if needs transfusion. 10.2- depends on baseline. WBC- Neutrophils- 82%; MCV 89, RDWabove 12- 14.5- know has some microcytes. Last test- I‟d argue blood culture- febrile, may have bacteremia. Lytes, LFT‟s- albumin is great prognostic indicator; under 3- associated with significant 5-year mortality- whether old, not eating enough, or anemic, or under stress- doubles likelihood of death. Liver function- synthetic- cholesterol, albumin, PT, PTT- helps you figure out where they stand because liver could be half-dead with normal LFT‟s. Hemochromatosisinflammatory and deposition disease- so liver tends to get bigger b/c depositing this stuff. Other things done- got CXR- normal sized heart, clear lung fields, and did EKG- now missing from chart, but pretty much normal. Now what order? Pyelonephritis- E. coli, Klebsiella, Proteus, Pseudomonas, Staph saprophyticus, serratia, enterococcus, enterobacter, yersinia. Culture came back E. coli positive, resistant to levaquin, etc. Aztreonam- most common problem is renal failure; at 60 CrClmoderate renal failure. Antibiotics, fluids, monitor ins and outs. In this lady- watch for CHF, and watch her anemia- hemolytic process here, and allergy to cephalosporins- transfusion patients create anti-RBC antibodies very easily, also must watch for heparin-induced thrombocytopenia, palpable purpuras from antibodies to antibiotics. Watching for sepsis, abscess- be sure not progressing. Beta-thal major- protective from malaria. Hypercoagulable so put on beta-thal major. Beta-thalassemia major- excess alpha globulin genes- precipitates out in RBC‟s, basophilic stippling, Heinz bodies- precipitated alpha-globulin; also inclusion bodies. If have spleen- get spherocytes, no spleen- Howell-Jolly bodies. In her- target cells, anisocytosis, poikilocytosis, hypochromasia. Desferoxamine- given IM; difficult to get compliance with it. Holding her desferoxamine because infection. Beta-thalassemia major- what eat, what not to eat? Folate- green leafy things. Real challenge- must take in iron but utilize it most efficiently. Can only absorb so much iron, then what absorb is no longer efficient. Tea in Mediterranean- after meals- consume amount of iron in food, reaches a certain level, feel nauseous- body can‟t utilize absorbed iron effectively- tannins in tea precipitate out iron. Ascorbic acid- fruit juices early on in meal- enhance iron absorption. If she wants to become pregnant- spouse must be checked; dangerous to have kid, because of clots; sister- 50% chance of being heterozygous; 25% chance of normal. Risk of death very high early on. Must be counseled, sister must be counseled. Epogen- increased RBC production, but part of the problem- because extramedullary hematopoiesis, not always effective, end up making more inefficient cells, so let process happen at physiologic rate; hydroxyurea used for a while to try to improve cell production, make membranes more stable, didn‟t work. Cut down risks, give splenectomy so don‟t sequester all its cells. Bone marrow spinning its wheels, invades into bone cortex, kids can actually grow out bone, mimics bone tumor. Resident Lecture Dr. Jonathan Bress Hyponatremia, DKA management, hyperglycemia. DKA vs. HONK- DKA is usually managed in the ICU. DKA- what might clue you in- if patient has diabetes, what might clue you in? Nauseous, stomach hurts diffusely, dyspneic- for compensation; might have fruity breath smell; may appear to be volume depleted- orthostatic, dry mucous membranes. Type I DM- more common to get DKA, but can get it with type II as well. In DKA, what can tip into DKAinfection, any other stresses; forgot/didn‟t use insulin. Other things could be MI or ischemia, and in young kids- partying- alcohol intoxication. Seen more than one case in which kid drinks self silly, alcohol gives insulin resistance as well, tipped into DKA. On labs- will find ketones in the urine; typical glucose- around 300. Will find high anion gap. Bicarb is very low- 11, e.g.- if seen with fever- sepsis- MICU. No gap- thinking RTA; with gap- lactate or ketones? Hx- diabetic, and no WBC count. He‟s hyponatremic- e.g. 128- artifact of high glucose- 1.6 for every 100 over 100 glucose; so for him- 131. Still hyponatremic; hypovolemic hyponatremia. To clinch diagnosis- anion gap, high glucose, and serum ketones- they‟ll want that as the diagnosis. Very formulaic treatment. For DKA- insulin IV, sugar, fluids, potassium- will become hypokalemic, so K+ supplementation. Bicarb only given in desperation, if pH is really low. Here- insulin will bring it back to normal. 11 bicarb- no lung pathology but pCO2 will be 23- breathing double time; pH- 7.2, 7.1 range. Now- comes into ER- establish IV access, first thing to do- hydrate. Open up 2L of NS right away, a little bit of K in bag, then 200 cc/hr. No sugar right away in bag; will help hypovolemia, hyponatremia, dilute down ketones, close gap a bit. Then- push 0.1 units insulin per kg, 0.1 unit/kg per hour. Then- check Q1h fingersticks. Nausea, etc. goes away once get a few liters in. Now- Q1h fingersticks- keep sugar around low 200‟s. Measure of success is ketones and gap, so get Q4 chem 7; don‟t turn down insulin just because sugar drops below 200; give q1 fingersticks, give sugar. For this time, can eat whatever they want- candy bar, etc.protected by insulin drip. On the outside- will go into DKA if do this. Now- chem 7 is good, serum ketones trace positive- looking for gap. Want good gap of 12-14- no serum ketones at all- before turn off insulin drip. Na goes up- not hypovolemic anymore, and K will drop- dilutional and also- K goes into cell with insulin. Now- gap down to 9- has to go back on insulin so can go home. Formulaic- 0.6 units/kg42 in 70 kg patient; split 2/3 to 1/3; 28 to 18; 28 to 18 and 10, 14 to 10 and 5 NPH and regularso give NPH an hour before dinner, continue through dinner, then turn off drip. That gets them out of the unit, discharge them straight home. HONK- hyperosmotic non-ketotic hyperglycemia- more the type II DM. These will come in with glucose of 700; highest have seen- 1200; clinically, will walk into room, will be volume depleted, dizzy/confused, may even go into “coma”- not really coma. Any glucose above 250 will spill into urine- is a diuretic. May well have a normal bicarb. On their chem panel- glc is 800; Na is about 151. May be hypovolemic, get 120 corrected to 150. Means he/she is volume depleted. Key here- giving lots of fluid- NS to hydrate them up. Then- want to bring sugar down, so IV push and SQ of insulin at the same time- also 0.6 u/kg, split between IV and SQ; these don‟t need to be in unit unless mental status is really bad. Can actually do insulin drip for these guys- but less than in DKA. Then get them back on insulin control at home, use sliding scale. Precipitants of HONK- relative state of insulin deficiency is type I- DKA; in type IImore insulin resistance- HONK. Burnt out type II‟s may be making very little insulin, closer to DKA. So- insulin deficiency vs. resistance, where you are on scale determines in which you‟ll end up. In DKA- no need for ABG to torture them; VBG is just as good; issue isn‟t the oxygen, just pH and pCO2. pH is just 3 hundredths less than ABG; point is just to get a gestalt. Know hydration, K, etc. Dr. Bardes 5/14/04 70-y/o woman comes to see you b/c of a cough. New cough; brings up a little white stuff. No fever- maybe a little low grade; smoked in college less than year, stopped. No choking, SOB, not particularly worse at any time. No chills. Whole office has the same cough. No blood. On HCTZ, nothing else. Gets heartburn if she eats pizza, etc. She tried Echinacea, didn‟t help; tried steam treatment with chamomile flowers; no coughing with cooler breeze. Is a little headachy. Friends at work taking Biaxin, thought she would too. Cleaned house two weeks ago. Doesn‟t remember having PPD. Born in Pittsburgh, lived in New York 40+ years. Labor-relations mediator. Tried pot in 70‟s. Has HTN, takes HCTZ; had arthroscopic surgery- glucosamine chondroitin. Has grandson in college who visited over break. On physical exam- temperature is 99.5 oral, BP is 126/72, HR 68, HEENT exam shows conjunctival injection without discharge, nose has coryza, oropharynx is mildly injected without discharge; lymph nodes are shotty- like buckshot in shotgun shell- anterior cervical LN chain, smooth, slightly tender; normal superior cervical LN. Chest is clear, remainder of exam is normal- viral URI- generalized; conjunctival, redness, runny nose- never bacterial; bacteria causes sinusitis- congestion and pressure. So they don‟t need antibiotics. „Call me if don‟t feel better.‟ She‟s happy with your explanation; fluids, rest. 3 days later- increased temperature, greenish brown sputum; 102 for day; tired. No chest pain. Physical exam- T 39.5 tympanic; good to record how take T because normals change from site to site. BP 146/90, HR 80. When listen to chest- brief exam- is completely clear. When listen to right upper field anteriorly, hear coarse breath sounds. Could have pneumonia; staph can happen after URI, but people with staph pneumonia are really sick; tissue proteases can eat through skin, when put in alveoli- goes through them really quickly. Hypoxic, toxic, septic, multilobar PNA, really sick. Bronchitis from pneumonia- CXR could distinguish, or on physical exam- pneumonia- consolidation, egophany- igos in Greek means goat- bleating of a goat. Coarse breath sounds could go either way, but more pneumonia-like because are in one place. Fever is significantly higher than would usually see in bronchitis. CXR- shows RML infiltrate- RML is anterior. Treat with antibiotics. As inpatient or outpatient? Is a PORT score- older age pushes toward admission, few comorbidities- away. Not toxic or sick, good O2 saturation. Respiratory distress- have to count it yourself- RR is 18; accessory muscles- sternocleidomastoids, intercostals, abdominals, nasal flaring; cyanosis. Other factors- reliable host? If homeless, would admit. WBC count. She‟s not having respiratory distress, not hypoxic, no comorbidities, is reliable, is 70- so she has some factors stacking against her, some for her. If try to quantify that- score is below cutoff for admission to hospital. I use principles, not score itself. So would be inclined to send her home on oral antibiotic. However, her husband is ill, has ALS, visiting nurse- they can‟t take care of her, he can‟t- she needs nursing, support services they can provide in hospital. This sounds like blasphemy to people in our era- only admit if can‟t survive elsewhere or needed some procedure here- but that was history of hospital admission. See hospitals rising along pilgrim routes, industrial routes. How will we treat her? First question to ask- what organisms are we worried about? S. pneumonia, H. flu, M. catarrhalis- less than you think in healthy individuals. Atypicalsmycoplasma, Chlamydia, legionella. Term atypical- unfortunate- from when 99% was pneumococcal, everything else- didn‟t know exactly what it was. Term is useful to retain because clinically behave similarly, respond to similar antibacterials, but nothing atypical about these. Strep pneumo- most still respond to penicillins; practically any cephalosporin; macrolides- erythromycin, azithro, clarithro; next breath- tetracycline family- same coverage as macrolides. Fluoroquinolones- all but Cipro. Sulfas; can use clindamycin, vancomycin, etc. Almost all you can think of works against S. pneumo. H. flu- 2-3 generation cephalosporin, macrolide, tetracyclines, fluoroquinolones, sulfas. Mycoplasma- macrolide, tetracycline, fluoroquinolone. So could use macrolide, tetracycline, fluoroquinolone for any of these. If host changes a bit- now talk about comorbidity- diabetes or asthma, or above 65- have to think about GNB; Moraxella, and E. coli- 25% of pneumonia in this group; can do betalactam- cephalosporin or extended spectrum penicillin- plus macrolide/tetracycline, or fluoroquinolone. Penicillin family- in beginning, was penicillin; used to be effective for broad spectrum; now is good only for a few things- streptococcus, t. pallidum (syphilis), and oral anaerobespeptostreptococcus, etc.; dentists use penicillin to good effect. Next step- semi-synthetic penicillin- ampicillin, amoxicillin- they also cover some simple GNB like E. coli, things that cause UTI‟s in young women, that‟s where situation stood in mid1960‟s. So kid with staph infection- by mid-1960‟s- no longer treatable by antibiotics, because penicillins, sulfas no longer worked, nor did tetracyclines; they‟d isolate you, couldn‟t see siblings; would bathe wound with caustic topicals, no systemic treatment; serious problem until mid-1960‟s- “staph-specific penicillins”- oxacillin, dicloxicillin, nafcillin, methcillin; are good against staph and strep but since are such important pathogens, very important. Can add betalactamase inhibitor- ampicillin- Unasyn; amoxicillin- augmentin. Extended-spectrum penicillins- piperacillin- broad-spectrum antibiotic, gets staph, strep, GNB- broad spectrum. Added beta-lactamase inhibitor- Zosyn; very broad coverage, can use these for pneumonia. Could they have pseudomonas? Recent antibiotic, bronchiectasis, any nosocomial event, cystic fibrosis, etc. Is above plus aminoglycoside- need double coverage for pseudomonas. As host gets sicker, must think of different kinds of bacteria, think differently. Aspiration- if healthy 25-y/o aspirates during seizure- small intestine, stomach is sterile; what do aspirate is whatever‟s in mouth- oral anaerobes- so treat with penicillin- is perfectly fine. On other hand. But when think about aspiration, think neuromuscular disease, lots of GNB, etc., treat accordingly. 1976- Legionnaire‟s- Philadelphia- at the time, celebrating bicentennial, but also trash strike. Initial outbreak- those men really sick; multilobar PNA, systemic systems- headache, GI, liver, etc. WWII vet in 1970‟s- now in 50‟s, 60‟s; mainly smokers then, many drank lots of alcohol. Not sickly- could travel to Philadelphia, but not in prime of health. So- older middle age or older, have some comorbidities- any can get but these get it the most. Gets better beautifully with macrolides, tetracycline, fluoroquinolones. TB- HIV, immunocompromised; from endemic areas- almost the whole world now; certain social situations- homeless, prisons, alcoholics. Features of illness- consumption- La Boheme- fever, sweats, hemoptysis, weight loss. Reactivation is in upper lobe. Lady in Bronxupper lobe PNA, felt better after day of antibiotics, hydration, begged to go home to take care of kids; sent home, came back 4 days later with florid tuberculosis, had to be intubated; only clue was upper lobe. Primary tuberculosis- typical pneumonia not getting better on antibacterials, leads to bronchoscopy. PCP- HIV, bilateral perihilar infiltrates; but patient might not tell you has HIV, or might have another reason to get PCP- steroid taper. Hepatitis, meningitis-type symptoms, fever, CXR infiltrate, 55-y/o man- worked up for everything until finally told medical student he has HIV. Another few words on personalities of bacteria- Mycoplasma- mostly under 40- hacking cough for few weeks, don‟t feel that terrible, CXR looks worse than patient. Chlamydia pneumoniae- same story; behaves like mycoplasma. Back up a bit- let me pose a rhetorical question. We thought on presumptive grounds that this 70-y/o woman has simple GNB, treated with cefuroxime, azithromycin; the next day, didn‟t get better, didn‟t expect to get better instantly- but at 36 hours, didn‟t get better, sputum culture came back for Klebsiella, resistant to 2nd, not 3rd generation cephalosporin, so switched to ceftazidime, did fine. Why not treat everyone with Zosyn and azithromycin? Resistance; select for resistant organisms, spill into hospital and community; but is a little bit abstract; many doctors and patients take view- my obligation is to you sitting in exam room, consequences downstreamsomeone else‟s problem. So have to come up for other reasons. Resistance within the host- bacteria are in me. UTI in healthy 25-y/o female- Bactrim or Cipro. 26- second round of Cipro, gets better. 28- doesn‟t get better- perineum colonized with Cipro-resistant bacteria, now not getting better, Cipro-resistant bug- bigger problem than Bactrim-resistant bug. Toxicity is almost always higher in broad-spectrum antibiotics. Aminoglycosides- really good for gram-negatives- Gentamicin, Tobramicin, Amikacin- all good, Amikacin covers pseudomonas. All toxic to ears and kidneys; goes up from gent to tobra to amik- deaf as post Ok if saved from sepsis, not sniffles. Finally- cost is much higher with broad-spectrum antibiotics. IV penicillin for one day67 cents. Zosyn for one day- $200. UTI- course of Bactrum- $5; Cipro- big difference. Other problem- opportunistic infections- C. diff, yeast in vagina, mouth, esophagus, skinalways more with broad spectrum antibiotics. So broad-spectrum antibiotics may be worse for you than narrow-spectrum. So approach to choosing antibiotic- think first about host, then about likeliest organisms in that host, what antibiotics cover the likeliest contenders, then go narrow to cover those. Many of us have seen patients on 4 or 5 antibiotics on the floor- accustomed to dealing with sepsis or leukemia patients with no reserve at all. Our patient- spent extra day in hospital, didn‟t crash, burn and die. So with reserve- go as narrow as possibly can; with no reserve- go broad. What if sputum grew S. pneumo penicillin-sensitive? Switch immediately to plain old penicillin. Priniciple which applies to pneumonia applies to UTI, etc. Think of host, likeliest organisms, and narrowest possible depending on reserve. Resident Lectures Pleural Effusions Dr. Christopher Gade 5/14/04 Pleural space- potential space between visceral and parietal pleura; pleura- visceral adheres to lung surfaces, goes into interlobar fissures, and parietal lines chest wall, mediastinum, mesothelial cells with its own lymphatic and blood supply. About 5-10 ml of fluid in there; glycoprotein, hyaluronic-rich fluid so surfaces glide, transmits pressure on the lungs. See throughout body- pericardium, joint spaces- a little fluid so can move nicely. Drains into microcirculation of parietal pleura; lymphatics, microcirculation so don‟t really have pleural space. People get problems that allow fluid to collect. Two major kinds of problems can occur, one more systemic, one more local inflammatory process. Systemic problem is transudate; fluid flow depends upon oncotic pressure- 25 cm H2O in pleural space- and hydrostatic; hydrostatic in parietal- 30, visceral- 10 because supplied by lower pressure pulmonary circulation. Usually fluid comes off the parietal pleura, drains into microcirculation. Systemic problems- increased hydrostatic pressure- CHF; or problem with oncotic pressure- hypoalbuminemia from nephrosis, cirrhosis; or translocating fluid- ascites that gets through diaphragm to pleural space. More local problems- malignancies- local process that obstructs lymphatics; and infections, in which have changes in microcirculation, irritation in space, causes local inflammatory reaction, get fluid in the space. Presentation- cough, chest pain that can be pleuritic, shortness of breath. Very important to evaluate the whole patient because so many causes. #1 cause- CHF in this country- #1 cause of transudate; 80% bilateral, 8% right, 4% left- latter can be tricky because shouldn‟t tap them, puts them at greater risk, respond to diuresis. Exam- can get a rub, decreased or absent breath sounds, get dullness to percussion. Decreased fremitus- no transmission. So get chest X-ray, look for blunting of costophrenic angles. Can hide 300 mL on PA without blunting; lateral decubitus can hide 150 mL. If subpulmonic, between lung and diaphragm- can see widening of space to stomach, could see elevated right hemidiaphragm. Then decide- do you want to tap effusion or not? If has CHF, all consistent with HF, bilateral effusion- don‟t tap it; otherwise- should want to tap it. Don‟t for severe coagulopathy- correct; on mechanical ventilator- relative; high clinical suspicion; 10 mm of thickness necessary to be able to tap; if not at bottom, may need to assess with ultrasound. examine, see context, but could be complicated- CHF with pneumonia, etc. Is it transudate- nephrosis, cirrhosis, heart failure; Light criteria is what they use to diagnose it- any of three criteria- pleural to total protein ratio >.5; pleural to serum LDH >.6; and LDH absolute in pleural fluid greater than 200. Sometimes one is positive, other two negative, may think it‟s CHF so last thing- check albumin serum to pleura; if less than 1.2- exudates, greater- transudate. Thoracentesis- take fluid out, look at it. Is it bloody- certain implications; serosanguinous? White- chylous? Is it smelly? If transudate- done- get echo, sono- know heart, kidney, liver function. If exudate- 18gauge angiocath only needed for diagnosis- look at it, smell it, send off- one little container for culture and stain; send off cytology- almost always yes; if very young guy, infiltrate on CXRdon‟t need to. Mix with 1:1 ratio cytolyte, run it down to lab so get the best yield. 70% yield for adenoca; 20% for lymphoma, SCC; poor for mesothelioma. Glucose; pH- ABG syringe- take it straight out of fluid, not collected bottle. Get hematocrit, cell count and differentiation; get amylase, triglycerides- if not look chylous, don‟t need to send it. Pancreatitis, perforated posterior ulcer, Boerhaave‟s, ovarian malignancies. Lupus- ANA titer greater than 1:60- Lupus pleurisy, can be real or drug-induced lupus- HIP drugs- hydralazine, isoniazid, procainamideanti-histone antibody. Send for rheumatoid factor, always stain for mycobacteria. CHF is transudate. Then- pneumonia, cancer- could come together in smoker; then- PE which can be either trans or exudates. Bacterial pneumonias can all do it. Seven classes of parapneumonic effusions from simple to empyema. For some- drainage; more- need fibrinolytics; more- need decortication. Complication- abscess- loculated, bronchocutaneous fistula. Other infections- much less likely to be fungus; Coccidio- more likely to give effusion. Aspergillus, Nocardia- look for sulfur, infections, TB. Cell count- >50% PMN- more acute bacterial infections. Lymphos- TB, malignancies, multiple other processes. Monocytes- slower process, very non-specific. ChurgStrauss, etc.- eosinophils. TB- adenosine deaminase >40, AFB culture and stain, but very lowyield- get very vigorous response to TB organism but not many organisms. Much higher sensitivity- pleural biopsy. Malignancy causes- 1/3 lung, ¼ breast, 1/5 is lymphomas. Any cancer can do it but those are major ones. Send off cytology but may be low yield, need to look elsewhere. Chylothorax- triglycerides- due to thoracic duct interruption- trauma, lymphangioleiomyomatosis- young women get; lymphoma; major causes. 50:110- sort of in between triglyceride level. So if chylomicrons on lipid profile- is chylothorax. If not or under 50, is probably TB. Resident Lecture Acute Renal Failure Dr. Carolyn Bauer Definition of acute renal failure- three definitions- increase of creatinine of >0.5 mg/dL over baseline, or decrease of CrCl of 50%. Creatinine is secreted and absorbed but net- good marker. Some things can influence creatinine other than RF- drugs- bactrim, cephalosporin. A third definition- decrease in creatinine, renal function acutely- BUN. Things that can raise your BUN falsely- upper GI bleed- digestion, absorption of blood; also steroids, and increased catabolism. Three categories- prerenal, renal, postrenal; how distinguish? FENa- urine Na over serum Na divided by Ucr over Scr. <1%- kidneys are healthy, trying to hold on to Na; when in prerenal state- NSAIDs- inhibit cyclooxygenase, thus prostaglandin synthesis, can cause afferent vasoconstriction by inhibiting prostacyclin vasodilation; volume depletion- dehydration, hemorrhage, third spacing- laxatives, overdiuresis, diarrhea, nausea/vomiting- don‟t have effective arterial volume- CHF, cirrhotics. Other drugs- ACEI vasodilate efferent- angiotensin inhibited, so more blood bypasses glomerulus. Occurs when have low circulating blood volume, or renal artery stenosis. Hypertension puts too much pressure, want to decrease bad effects on kidney by causing more blood to bypass the glomerulus. 60-70% of community-acquired acute renal failure are prerenal- is bulk, and is reversible. Elderly patients- increased risk- already have atherosclerosis. Occurs after surgery, anesthesia, etc. Other ways to help you diagnose- BUN:Cr of 20:1, except with cortisol, increased catabolism, GI bleed. Oliguric- <400 cc urine/day- then FENa most effective. Diuretics throws off FENa- excrete more Na by inhibiting loop. Two other things can look at. One- urine osmolality- expect it to be high because concentrated- would be >500. People with intrinsic renal disease- opposite- can‟t concentrate urine, so expect urine to be 250-300- isostouric. Third wayFEUrea- done the same way as FENa- urine urea/serum BUN x Serum Cr/Urine Cr. If are prerenal- should be under 30- should absorb as much as can. 30-50- hard to say- other influences (unlike inulin); >50- probably not. Prerenal- easy to fix- give fluid; in CHF, etc.- fluid overload- harder; need afterload reducers to decrease work of heart, or need inotropes, or can get Swan-Ganz catheter, tailordirected therapy- one point on Starling curve. These are very hard to manage when get RF. Hepatorenal syndrome- this is what have. Contrast-induced nephropathy also makes FENa under 1- because causes severe vasoconstriction and intrinsic damage. Post-renal- stones, BPH or prostate cancer, masses, neurogenic bladder, stricture- from previous abdominal surgeries. More you stay obstructed, more difficult to reverse. So- when patient presents with ARF- put in a foley; treats BPH and neurogenic bladder. Then- postobstructive diuresis- can put out urine that can‟t concentrate appropriately, takes a while to regain previous function. Foley also to send off new urine for the FENa tests; also will look at urine, see what‟s in there. Look for blood, casts, crystals, cells, and osmolality, specific gravitypoor man‟s sense of concentration. Put in for US- is collecting system dilated? Sonograms- 8090% sensitive; but miss volume depleted, early obstruction or retroperitoneal. Stones- lithotripsy, take stones out or stent them. Masses- surgery, can stent or do percutaneous nephrostomy. Stones- calcium oxalate, struvite, uric acid, calcium phosphate. Can get indinavir stones in HIV patients. Also- light chains in multiple myeloma; also some drugs- acyclovir, etc. can cause ureteric obstruction. Stones- may see stone, blood, crystal. Prerenal- shouldn‟t see much. Renal- 25-40%- intrinsic- most of the glomerular diseases cause CRF; poststreptococcal, endocarditis, post-pneumococcal- nephritic picture; rapid progressive- lupus, Wegener‟s, goodpasture‟s, Churg-Strauss. Other- HIV- crescentic FSGS, get rapid progressive GN- from direct infection of tubules with HIV, only treatment is treatment for HIV. ATN- myoglobin, drugs- amphotericin, aminoglycosides. Oxygen gradient in kidney gets lower and lower, if reaches medulla- sloughing, damage; cortex- irreversible damage, so restore patients to euvolemia- if overload with fluid, need dialysis. Lasix to make them pee- decrease need for dialysis. Remove offending agents, and prevent any indication for acute dialysis. Indications- acidemia, hyperkalemia/hypercalcemia- other ways to treat before dialysis, fluid overload- can‟t breath, e.g., uremia- encephalopathy, and pericarditis. Other things can cause ATN- sepsis; not clear exactly what it is in sepsis, but sepsis can cause ATN. Most of time- ATN is multifactorial- CHF and NSAIDs, contrast and ACEI, or on top of chronic renal insufficiency, or with DM. In unit- high morbidity, mortality with ATN. Very hard to dialyze hypertensive or septic. Sometimes- need CVVH-D, which is a continuous method of taking fluid off. Daily hemodialysis has been shown to do the best for ATN, until get better. 20-60% require dialysis, less than 25% need dialysis for long-term. Contrast-induced- how prevent contrast-induced ATN? CT‟s, angiograms- including coronary angiograms- dye; prevention- be sure patient is well-hydrated beforehand with NS. ½ NS is hypotonic, NS is hypertonic- 154:140 of Na; hydrate them. Volume depleted, CRF, DM are predisposed. Mucomyst- restores glutathione, which soaks up free radical electrons from reactive oxygen species. Study in NEJM July 2000- 600 of N-acetylcysteine for 48 hours, hydrated both; patients who got mucomyst- 1/43 had contrast-induced ATN; 9/42 of those who didn‟t get it- huge different. So 12% of all patients in study had it, only 1 from mucomyst group. Big effect. So in patients in whom worried about renal insufficiency, give mucomyst before contrast. Epithelial cells, brown granular casts, a little protein. Acute interstitial nephritis- get fever, rash, eosinophilia, WBC in urine; drugs- stop them, go away. NSAIDs, sulfonamides, cephalosporins, penicillins- antibiotics. Basically just remove drug and it goes away. Vascular- things that cause micro- or macro- emboli- AAA repair, e.g.- get cholesterol emboli- livedo reticularis- lacy pattern on lower extremities, ischemic toe, etc.; HUS or TTP can both cause ARF- microemboli; Henoch-Schoenlein purpura also cause this kind of picture. HELLP syndrome, and atherosclerosis. Mortality- 7% admitted with prerenal azotemia may die, because many are hypervolemic or septic or really old, over 80% post-op- coronary bypass, etc. Sepsis, CV or pulmonary dysfunction are commonest causes of death. Chronic renal failure- CrCl of 15 in diabetics, 10 in normal- indication for dialysis. Dosing medications- for toxicity- can cause toxicity of medications if give high dose. They usually dose medications with CrCl less than 50. Dr. Wenderoth 5/17/04 Tough to get head around. Pulmonary problems- baseline pulmonary problems- top 5asthma- severity- meds, frequency of exacerbations- try to quantify it- what are your day symptoms, night symptoms, ED, admissions, intubated? What‟s her best peak flow? Problem in states- people don‟t have, know how to use peak flow meters. I tell people to use at same time every day, do three vigorous exhalations, count the best. We always forget to tell people to stand up- lose 20% of diaphragmatic force from sitting; we forget to tell them to use 3 times; and every peak flow meter is different, depends how you hold it; also- they need to understand that they have to put everything into it. Normal peak flow based on age and height; women are about 400, men- about 600; more for African-American, less for Asian. In 1997- NIH created system for classifying asthma- said- depends on number of day, night symptoms, peak flow readings, feed into classes- intermittent, mild, moderate, severe persistent. In general- people have more night symptoms than they do day symptoms- increased vagal tone, increased bradykinin around, decreased tidal volume, increased mucous secretion- so often night symptoms worse than day symptoms. One way to look at it- be very strict about day/night symptoms- but think about medications they should be on. If using beta-agonist every day- already moved into persistent category. If using beta-agonist every day, need something else- at least are mild. Intermittent can be on beta-agonist only- albuterol or xopinex; albuterol can give tachycardia, diaphoresis; in heart disease- xopinex- doesn‟t give tachycardia. Longeracting- salmeterol- serevent. Foradil- formeterol- onset of albuterol, duration of salmeterol. NowSerevent is a component of Advair, plus a steroid. We think she‟s worse on baseline. On albuterol, not enough- add inhaled steroid- flovent, e.g.- comes in dry disc inhalernot water based so don‟t need spacer; comes in 3 different doses so can taper depending on how bad someone is; doesn‟t taste bad or make people cough. In the late 1990‟s, we used to think that the severity of asthma should be matched to the potency of the steroids; went from beclamethasone- mildest to flunisolide (aerobid). Problem- it turned out- nothing to do with steroid potency but inhaler technique; all water-based, if older, demented, bad hand-eye coordination- just not getting enough. Radiolabeled mock inhaler- only 20% of pulmonary fellows got enough inhaled; so decided to make uniform particle size. Second thing- study at urban ER‟s- took look at all comers to ER, number of canisters of albuterol they used, whether they got better or not, ultimate outcome- mortality; more canisters use- higher mortality rate; so said- beta-agonists still have potential for tachyphylaxis- so much bronchospasm that won‟t be able to dilate, will die. But actually is surrogate marker for asthma severity; poor ability to reach health care, get inhaled steroid added. We now realize you can use lots of albuterol without added risk of death. 6 puffs on inhaler equal nebulizer treatment in ER, in case patient is at home, no access. After added advair, which has serevent and inhaled steroidsalmeterol dose is 50 mcg, can go up on steroid. Then can add other things. This lady‟s on theophylline- why? Ancient drug, hardly use in asthma, do use in COPD; kind of bronchodilator, and increases mucociliary clearance- that one cilia left in smoker beats harder; also increases diaphragmatic force- is some smooth muscle in it; increases central respiratory drive, and helps to dilate the pulmonary vasculature; so it‟s pretty safe. Problem- uses P450 system, so shied away from it- smoking interacts with it. If have emphysema, will die anyway, won‟t stop smoking- I tell them- pick number, brand of cigarettes you‟ll smoke, smoke same number every day, I‟ll get them therapeutic in that window. Sometimes it works, sometimes won‟t. Leukotriene inhibitors, cromolyn- more for outpatient. Ipratropium- atrovent- great for blue bloaters, helps them cough up the junk. Bronchiectasis, airway remodeling- severe. Problems- asthma, pneumonia, scarring/ARDS/atelectasis, vocal cord paralysis, tobacco, retaining CO2. Key here- step back, look at big picture- can change pets, tobacco, can give antibiotics, try to optimize asthma meds, diet for aspiration. Leads to something else- if she needed surgery, needed to do pulmonary pre-operative evaluation- they care about inability to get off vent, and pneumonia. Top 5 risk factors that make it hard to get off vent, hard to surgically clear- tobacco/COPD; PFT‟s to evaluate that. 72 hours without tobacco is enough to change oral flora; with smoking, have H. flu, S. pneumo, M. catarrhalis in upper mouth, push down with ET tube; 8 weeks is enough to regrow cilia. Second thing that increases risk for poor pulmonary outcome after surgery. If obeseseems like would create restrictive disease, problems; but isn‟t- if ambulate, incentive spirometry- do the same. Age is deceiving- depends on respiratory strength; 80-year old athlete better than 30-year old smoker. So- pulmonary strength- measure with PFT‟s with an obstructive component- classically think of in asthma patients- can‟t be easily extubated, likelier to have local vocal cord spasm, creating global bronchospasm. Also kind of surgery- laparoscopic is easier because of the degree of scarring. Long-acting sedating drugs like pancuronium- worse outcome because microaspirations. Also- closer to diaphragm is worse- lap chole worse than open hip surgery. Bipolar- don‟t treat with benzos, but makes the patient go away. Dr. Bardes 5/17/04 25-year-old man, fever and cough for 3 weeks, presented to ER, CXR showed interstitial infiltrates in RML, LLL, suspected mycoplasma pneumonia, our plan was to discharge him on azithromycin. Any testing to do? PPD in ER- trouble- how will you read it? Can do CBC- what hope to learn from CBC- elevated WBC count? Sputum culture- will again take a while to come back, gram stain will be back sooner; SMA-infinity- including LFT‟s; blood cultures x2, UA because has a fever. PT/PTT; at NYH, often get amylase and lipase. A lot more we could think about- but let‟s look at these critically. If WBC is 5- would you change action plan, to send home on azithromycin? No; might worry about PCP but doesn‟t look like it clinically. If WBC 15mildly elevated, kind of what we expect. If WBC count is 25, yet looks and feels well- WBC is interesting but not important unless really high- if 50, r/o leukemia admit, but not very useful otherwise. Sputum gram stain- probably wouldn‟t help much, negative if mycoplasma. SMAvolume status- of interest, but healthy guy, can probably eat or drink. Blood cultures- predictors for positive blood cultures- cholecystitis does, but not strep pneumo commonly. Also acute pyelonephritis, endocarditis, severely ill with lines, or false positives- staph epidermidis. Things that predict positive blood cultures- severe debilitation, lines, severe illnesses- pyelo, acute chole, endocarditis; immune compromise, very high fever, very high white count, shaking chills; all other patients- low likelihood of positive blood cultures, so low that can safely not draw them. In my practice I see fever every other day, draw blood cultures 2-3 times a year tops. House staff gets cultures on everyone with fevers because often do have these features. Just understand in advance- don‟t need to do that; when you run the circus, needn‟t draw blood cultures for those who don‟t have fevers. Urinalysis- probably negative for this guy. PT/PTT- if ecchymoses, petechiae- signs of bleeding diathesis, if are on anticoagulation, and for surgical procedures pre-op; zero data to support pre-op PT/PTT unless clinical evidence of abnormal bleeding, personal history of abnormal bleeding, or disease like cirrhosis that causes bleeding disorder or about to anticoagulate them, draw PT/PTT; if not- don‟t draw it- doesn‟t predict perioperative bleeding or mortality, likely to get false positive and unnecessarily delay surgery. All get amylase and lipase in NYH ER- old habit- in old days- NYH didn‟t have ER, rather a pre-surgical holding area- if surgical emergency, held you, observed, sent to OR; abdominal pain common so got amylase and lipase on everyone. Cost- CBC- $50, sputum gram stain, culture- $150, SMA-infinity- $50, blood cultures x2- $200, UA- $30, PT/PTT- $100, amylase/lipase- $120. $900, and since sent STAT from ER$1800- costs double; just spent $1800 unnecessarily. Professional secret- if patient came to see doctor in office for fever, cough, treat with azithromycin for mycoplasma pneumonia- doctor gets about $50 for the visit, is fine. When contrast with $1800 that send to lab- disparity catches one‟s attention. All normal, except that in SMA-infinity, were some elevations. ALT or SGPT was 90 u/L, normal is 45. AST (SGOT) is 80. So has liver test abnormalities, need to figure that out. Could have infection- viral hepatitisABC- classic, D superinfects B, E- fecal/oral, catastrophic for pregnancy. EBV, CMV; HIV itself, and childhood exanthems, varicella, measles. Bacterium that causes hepatitis- grampositive cocci don‟t really do this, nor do gram-negatives. Spirochetes- leptospirosis can cause itlives in rodent urine- saw in plumber in New York. Group of world-class athletes doing triathlon in Malaysia- swimming portion- though rain-swollen livers, got pneumonitis, hepatitis, meningitis, gets better instantly with doxycycline. Salmonella typhi can give hepatitis too, but rare bacterium that causes hepatits. Mycobacterium- MAC gets into liver. Fungal hepatitis can occur, but then you‟re really sick- leukemia, in ICU, immunosuppression, last stop before eternal care unit. Parasites- protozoa- complex single-cell organisms, and helminths- none of those really cause hepatitis. [Clonorchis- biliary tree, Schistosomiasis- affects prehepatic sinusoid.] Malariagives hepatitis- don‟t see much here, but 3 cases of malaria in New Jersey, Long Island where never traveled; do have the mosquitoes here, not burden of disease for transmission, but collapse of infrastructure- can see malaria again. Toxins- alcohol, acetaminophen (APAP) and lots of drugs- one system to approach- start with heart- statins can give hepatitis; lung- leukotriene antagonists, etc.; lots of meds- antiinfectives, anti-epileptics. Other toxins that affect the liver- benzene- organic solvents- you don‟t see much industrial disease; in rest of world- carbon tetrachloride, benzene, toluene- use to make things, toxic to liver. Natural- amanita mushrooms; aflatoxin- mold that grows on peanuts- have on African peanuts. Metabolic- Alpha-1 antitrypsin deficiency, hemachromatosis- high in Caucasians; Wilson‟s disease; and autoimmune hepatitis. Fatty liver- two different things that go by same name. Acute fatty liver of pregnancy- severe, catastrophic illness- liver goes away, replaced by mush, get shock, DIC, goes away instantly when deliver them. Other kind- obesity, diabetes, lipid disorders- energy use problem- not so sick but have LFT abnormalities because fat is laid down in liver- like marbled steak. Last category- vascular- arterial, venous or capillary insufficiency. Arterial- hard in liver; have seen infarctions in all but liver, because liver has dual blood supply- portal vein. Need global hypoperfusion- shock liver; classic- V-tach episode, ALT/AST of 1000 in CCU, got better in week. Venous- passive congestion- if start closest to liver- Budd-Chiari- hepatic vein; but can go up- IVC, tricuspid, pulmonic stenosis, Right heart failure. Capillary obstruction- DIC, TTPshower liver with emboli. Get titers of viruses, culture for MAC, smear for malaria, history for toxins, hemochromatosis- transferring, wilson‟s- ceruloplasmin, measure alpha-1 antitrypsin, sono for fatty liver. Our patient- all normal. Other pattern- alk phos- bile canaliculi, bone, GI tract, placenta. Alk phos- can tell where coming from by GGTP- gamma-glutamyl transpeptidase- elevated in bile, not the others. So- if GGTP elevated- know are in bile system, if not- bone or placenta. If the problem is alk phos with GGTP- what might cause it- cholestasis; usually means biliary obstruction, can also occur when not obstructed, basically like ileus, in severe illness like MI; pregnancy can do it, and estrogen- women on birth control pills; Biliary obstruction- stone, stricture, neoplasms- of head of pancreas, ampulla, obliterative- primary biliary cirrhosis, primary sclerosing cholangitis- here, biliary tree is effaced from within, giving alk phos elevation. When see cancer of head of pancreas- nothing like it- someone walking, talking, all fine but brightly jaundiced- can‟t be anything but. Clonorchis sinensis- sits here. Mass lesion in liver- nothing to bust and leak- disrupts architecture, not bust cells; mass lesions- tumor; can be primary- hepatocellular carcinoma, metastases, or benign tumors, abscess, cysts, granulomas- TB, sarcoid, syphilis, etc. If has cholestasis- how can tell? Sono or CT will give the answer; sono or CT will show mass lesion, as well. So all with ALP and elevated GGTP will get sono, CT. If being more accurate, these are liver leak tests; function- PT/PTT, Bili, Albumin. All of these could be due to multiple causes but combination is good reflection of liver function. So I use the leak system to tell me what problem is, function tests to tell me how bad the problem is. ALT- if 5 times normal, ALP twice normal- are on intrahepatic side of the algorithm. Statin- woman admitted at another hospital with ALT in 1000‟s, Bili of 5; ALT and AST were coming down, bili and protime going up, failed to realize that transaminases coming down because burning out liver, died of fulminant liver failure. So- ALP with high GGTP- imaging will get answer in hurry; if ALT/AST- more work, but can get to bottom of it with the appropriate tests. Acid-Base Dr. Christian Cruz If gives you an ABG- anything above 7.4, alkalosis; below- acidosis. Then- look at PCO2- if high with low pH- respiratory acidosis; if high with high pH- metabolic alkalosis. Next- metabolic acidosis- go to anion gap next- Na-(Cl+Bicarb); don‟t include K, Mg, Ca- all balanced by serum proteins. Normal anion gap is 12. Can have as many as three disorders at once; can‟t have respiratory acidosis and alkalosis at same time. Last- check compensation. If have metabolic abnormality, anion gap acidosis- any overlying respiratory abnormality? This is where calculations come in. Main differentials for all of them- metabolic acidosis, alkalosis, respiratory acidosis, alkalosis. Metabolic acidosis- nongap vs. gap. Gap- main things- ketones, lactate, renal failure. All the other ones- won‟t see much. Ethylene glycol, methanol, aspirin- makes lactate and ketones; INH. Non-Gap- GI vs. renal; GIdiarrhea, hyperalimentation; renal- RTA, renal failure. Metabolic alkalosis- GI, Endo, Renalanything that causes prerenal state- volume contraction, and diuretics, then Cushing‟s, Conn‟s, Gittelman‟s, Bartter‟s. Respiratory acidosis- hypoventilation- drug- sedative, CNS- tumors; pulmonary- COPD, pleural, mucous plugging, tumors, PTX, neuromuscular restriction, etc. Respiratory alkalosishyperventilation, CNS tumors, anxiety, pulmonary- restrictive lung disease, PE, CHF, sepsis; and aspirin. Calculations used depend on primary abnormality. If have metabolic abnormalitiesbicarb will usually be low- calculate expected CO2; for respiratory abnormalities, calculate expected bicarb. Two formulas for metabolic acidosis- delta/delta- change in anion gap over change in bicarb from expected. Extra anions should combine with bicarb, lower it the same amount; if bicarb is lower than would expect for that anion gap- tells you another non-gap metabolic acidosis going on. If bicarb is higher than expected- have metabolic alkalosis on top of acidosis. Winter‟s formula- 1.5 x bicarb + 8 +/- 2. So if bicarb is 10, would expect CO2 to be 23 +/- 2. So if CO2 was 30, bicarb was 8- expect CO2 to be 20, but in fact is 30- so has overlying respiratory acidosis; if was 15- respiratory alkalosis. Metabolic alkalosis- only one formula I know- CO2 to bicarb changes- 0.7:1. For every change in Bicarb by 1, should change CO2 by 0.7; if bicarb is 34, CO2 is 47. In respiratory abnormalities- have acute and chronic changes, have to look at clinical scenario. For every change of 10 in CO2, change of 0.08 in pH; in chronic process- 10:0.03. Acute sudden process- PE, gets bad acidosis. Chronic- COPD, etc.- need to look at clinical scenario. So if CO2 of 70, acute process- 30 mmHg of change; 3 x 0.8 is 0.24- should decrease by 0.24 in acidosis, get 7.16. If has CO2 of 70, pH is 7.3- doesn‟t quite work out, unless chronic process- 7.31; but could be metabolic alkalosis pushing it up a bit. Must then look at clinical scenario. Some other formulas- in acidosis- acute and chronic- 10:1, 10:3.5 in acidosis; alkalosisacute- 10:2, chronic- 10:4. 7.49/48/120- is metabolic alkalosis because pCO2 is high. Then- 130-(85+35) = 10 AGso no gap- metabolic alkalosis, no underlying acidosis- no gap; can‟t have metabolic alkalosis and non-gap metabolic acidosis- losing plus retaining bicarb. (Anion gap acidosis- extraneous acid there.) Now- compensation- since has metabolic alkalosis, want to look at bicarb, see what expected CO2 is. Normally expect 24- so change in 11 in bicarb. Then we‟d multiply 11 by 0.7expected CO2 of 47.7, has simple metabolic alkalosis. 7.24/23/103, 130/3.2/100/10/30/1.7- has metabolic acidosis; anion gap is 20- so has anion gap metabolic acidosis. Any other metabolic abnormalities? Delta-delta- if doesn‟t have primary metabolic acidosis, who cares- but he does. Anion gap is 8, change in bicarb is 14; tells you he has too little bicarb- so has a non-gap metabolic acidosis on top of his anion gap acidosis. Now- respiratorily compensated? 15 + 8 = 23 +/- 2 = our pCO2; so is mixed metabolic acidosis only. Now- make up story- DKA with renal failure, e.g. Now- 7.5/42/120; anion gap of 24, bicarb of 34- so- use the 0.7:1 equation- would expect 47 pCO2, is lower than expected- so superimposed respiratory alkalosis- triple disordermetabolic alkalosis, anion-gap acidosis, respiratory alkalosis; story- diabetic with diarrhea who‟s septic on top of that. 7.27/70, anion gap of 12, bicarb of 31. Has respiratory acidosis, no AG acidosis; thencompensation- if came in with acute acidosis- would expect pH to be 7.16; if chronic- 7.31 by same calculations. 7.27 is somewhere in between. Possibilities- acute respiratory acidotic process but must have metabolic alkalosis to push pH back up; or chronic respiratory alkalosis with overlying non-gap metabolic acidosis, or- could have acute on chronic. Bicarb calculations- acidosis- acute- PCO2 of 10 up gives 1 up in bicarb- so bicarb should be 27 for him, but is 31; in respiratory acidosis- just look at last two numbers in pH. Dr. Wenderoth 5/18/04 57-y/o male with history of hypertension who presented to the ED after lightheadedness, clammy, feeling „not quite right‟, dizzy and faint. Asymptomatic by the time he was seen. 5 days prior- 48-hour trip to Switzerland, passed one very hard, dark bowel movement followed by red blood on the toilet paper, afterward- bright red blood with stools but not enough to fill bowl. PMH- anal fissures, allergy-induced asthma, basal cell carcinoma, torn L meniscus, seasonal allergies. No screening colonoscopy; last stress test 7 years ago was “normal.” Mother- angina at very early age, two pacemakers, defibrillator, died of MI at 62; brother- defibrillator placed at age 58, grandmother- died at age 65, triple vessel CAD. If start with dizziness, differential‟s huge; so start with stools. Dark bowel movement, BRBPR; so two things- melena, and BRBPR; BRBPR could be from anal fissure, but could be related to melena if brisk upper GI bleed. Dark bowel movement- could be melena, could be iron, could be pepto bismol, could be oreos- special food coloring in chocolate- those are the foods that cause dark stools. Melena- peptic ulcer disease- at risk- stress, alcohol; Mallory-weiss tear, varices, nosebleeds, gastric ca, MALT; BRBPR fissures may be surrogate marker for IBD, hemorrhoids, AVM, diverticulosis, colitis. Other issues- dead bowel, thrombus- ischemic bowelacute hypotension- if got cold, clammy, syncopized- could have killed off bowel; also- family history of CAD- is there chance that on top of it, threw a clot? No fever, pain- unusual. Could have an arrhythmia, clot. Now- if start from full picture- feels clammy but no abdominal pain, has sense of impending doom- correlates positively with MI or PE. Most common missed serious diagnosis in medicine- PE. I start with simplest stuff first, then back up, think of ancillary symptoms- pain, fever, etc. Then- PMH- anything that predisposes him to anything? PMH- fissures; meds- ASA, Aleve; FHarrhythmias, cardiac disease. He‟s stressed- ulcers correlate- anxiety. Hospitalized twice in pastchest pain so awful that couldn‟t move; in 1990- tingling in left hand, numbness in left leg; could be vascular disease- spasm, TIA, other things; CVA is >24 hours. Yells out at me- cocaine usevasospasm. Prinzmetal‟s angina? Three things forgot on list- vasovagal; can feel that way for various reasons- got up too quickly, e.g.; hypoglycemia- diet, circadian rhythm may be off. Anyone with anal fissurespenetrative sex of any kind? HIV? Chronic constipation can give anal fissures as well. Anytime put PUD on list- think of Zollinger-Ellison syndrome- doesn‟t get better with PPI. Alsopheochromocytoma can give adrenaline, then hypotension episode- especially with stressful joblike vasovagal response. Top three labs- CBC, lytes, EKG- making sure there‟s no arrhythmia, ischemia, other thing going on; EKG also tells you about electrolyte abnormalities, etc. Pertinents- 8.5/25.4 H and H. EKG- NSR. RDW for CBC- high- may have high level of reticulocytosis, trying to compensate; could be microcytic from iron deficiency and macrocytic from alcohol, etc.- but chronic; if he only had fissures- not enough blood loss to get to Hb of 8.5, and wouldn‟t get a chronic anemia. Top of differential- likelier to be colon cancer; then- peptic ulcer disease, then- IBD- bimodal curve- right about the right age for IBD. If it was diverticulosis- blood is a cathartic; if really bleeding that much, not having hard dark stools. Diverticular disease- diverticulosis- no fever, WBC count or pain. IBD- should have history, pain. AVM- wall becomes friable, bleeds; if small capillary, bleeds and stops, if artery- continues to bleed. Dieulafoy‟s ulcer- similar idea in stomach. Plan- IV protonix, closely monitored CBC, made him NPO with EGD plans for next AM, gave fluids; didn‟t require any transfusions; planned on working up anemia more- sent off iron studies, came back iron deficient. Anemia studies- what if he‟s thalassemic? Also- once transfuse- can‟t do anemia studies, if still problems, need to do a bone marrow study. If EGD negative, would advise colonoscopy. EGD- quite significant gastritis, PUD in antrum, etc. Forgot- steroids- is an asthmaticperhaps he‟s on prednisone. With vascular disease- what presents in odd way- cerebral vascular ischemia- carotid or vertebrobasilar disease; have seen many come from hairdresser, airplane with vertebrobasilar complaints because sit with head tilted back, kinking the vessel by weird position. Eventually, all these differentials become so obvious that only when get burned, go back and try to figure out what left out. EKG II Dr. Christopher Madias 5/19/04 EKG 3- 37-year-old male with palpitations. Rate, rhythm, intervals, etc. Rate- somewhere around 75, but a little bit irregular, slower than that. Rhythm- look at bottom strip, rhythm strip, for the rhythm; see dropped beat, looks like getting longer each time, so it‟s a Mobitz I, Wenckeback, second-degree AV block. Axis- is up in I, down in aVF so left axis deviation; almost isoelectric in 2- if were completely isoelectric in 2, would be -30 or +150. Since voltage is going toward I, know it‟s closer to I; so is -30. Is about in -40 range, so left axis deviation. PR interval is prolonged- should be .12 to .21; QRS- wider than 3 blocks, so is prolonged; think some sort of bundle branch block; this looks like right bundle branch block- V1- Rsr‟. FinallyQT- grossly prolonged- more than ½ R-R at some points. P waves- look in direction of depolarization of R atrium- lead II, V1; should have upright P wave in lead II. Biphasic with large negative component- left atrial enlargement- broad P wave, can be notched- P mitrale. Q waves? In V3, V4- not so sure are real- may just be from Rsr‟ from bundle branch block. ST-segments- no significant elevation. Mobitz I 2nd degree block, RAE, RBBB, LAD. Consider also left anterior fascicular block- he also has- bifascicular block. (RV enlargement, perhaps, due to high R waves in V1, V2, V3.) Inverted T-waves- if chest pain, worry about acute ischemia. NSR, regular rate, 75. I, aVF both mostly pointing up so normal axis; most isoelectric is lead 1, negative in aVL- falls between I and aVL, closest to 1, so is around 90 degrees. Intervals- PR is two boxes- .08- so small; perhaps accessory pathway- WPW. This is the delta wave- bundle of Kent- get depolarization through it; no AV node- will go through fast, start depolarizing the ventricle. If AV node were blocked- would expect APC-like wave. Impulse will go through faster than the myocardium can depolarize from bundle of Kent; so begin slow depolarization, then superimposed bundle of His depolarization. Early PR in precordial leads. No signs of atrial enlargement- not P greater than one box, no Rsr‟; no ST depressions. Rate- 62, rhythm- NSR. Positive- upright everywhere- is 45-degree range; I, aVF upright and aVL is isoelectric. Is 54. Interval- PR interval is between .12 and .21, others also Ok. Lead II, VI- no enlargement, biphasics. ST elevations all over the place. T waves- pretty tall, peakedthink about hyperkalemia or acute MI. Early repolarization syndrome, benign- elevated but curve is scooped, not humped. J-point elevation; benign variant. Next- rate- 68, Mobitz I, axis- -4. Q-waves- one in III but not a box wide, isolated to one lead. HIV+ lady, came in with history of falls, but never had this block again on EKG‟s, so our guess- she was drunk, high on coke; would get weirdly tachycardic sometimes. Tamponadepulsus paradoxicus- physical finding; pulsus alternans- finding on EKG- large, then small. Sinus arrhythmia- is sinus because P before every QRS, QRS after every P, P is up in II so not ectopic pacemaker. aVF is down, I is up, II is isoelectric- is -24. PR interval- between 3-4 boxes- .12-.21. QRS isn‟t wide. QT interval is less than ½. RAE- lead II. LAE- biphasic, 2nd part larger, downgoing part greater than .04 seconds. P wave in II is a bit high- maybe also RAE. So definitely LAE, maybe BAE. Cutoff for aVL height for LVH- 11 boxes. Any signs of ischemia? Micro-Q in 1, ignore aVR. ST elevations, minor in V3. T wave inversions in I, II, V4, V5, V6. Hypertension in LVH. Delayed repolarization of large, hypertrophied LV- strain pattern- one way to explain T waves; if had chest pain, might think MI, in LAD. Jagged QRSes- if prolonged, might think intraventricular conduction delay. Anemia Resident‟s Lecture Dr. Jhanelle Rhoden Anemia- can subdivide it into reticulocyte index of <2 or >2. RI is (retic count (patient‟s Hct/Nl Hct))/maturation factor. Will have clinical scenario, however, and won‟t necessarily go through all this; also, reticulocytes don‟t come back immediately anyway. Break down to under vs. overproduction; RI <2- break into microcytic, normocytic, macrocytic. RI >2- hemolysis- will know- mechanical valves, etc.- or big bleed. Microcytic anemia- defined by MCV <80. Think about iron deficiency; will check iron, TIBC, ferritin. TIBC- hunger for iron, ferritin- iron stores. In iron deficiency- iron, ferritin, iron sat down, TIBC up. Another thing to consider- thalassemia, check electrophoresis for that. Pearls- alpha thalassemia can often give normal electrophoresis; so can‟t rule it out that wayneed globulin studies. Microcytosis, MCV in 60‟s- Fe-deficiency alone shouldn‟t make it that low- may be combination of thalassemia and iron-deficiency. Another thing with microcytosisanemia of chronic disease; can present normocytically as well. Anemia of chronic disease- iron will be low, TIBC will be low. Macrocytosis- MCV >100. B12, folate deficiency; with folate deficiency- takes weeks to months. B12 deficiency takes years. With B12- posterior column deficits, ataxia causing dementia. Folate deficiency- pregnant women, alcoholics get it. B12- how work it up? Pernicious anemia or Crohn‟s- terminal ileum. Easiest test to rule it out- send intrinsic factor antibody; pernicious anemia- either due to antibody or stomach not making IF. If this comes back negative, still don‟t know what‟s going on- is GI tract not making IF or are you not absorbing? If negative, Schilling test- saturate with B12, then give radiolabeled B12 with intrinsic factor orally, look for it in urine. If in urine- problem is that body not making IF. If not in urine- malabsorption is problem. These- give polysegmented neutrophils (>5 lobes). Hemolysis- MCV will be also be high from reticulocytosis. If has MCV >100, not folate or B12 deficient- bone marrow biopsy to rule out myelodysplastic syndrome. Have heard liver disease, thyroid disease, get macrocytosis- but is arguable. Normocytic anemia- could be mixed micro, macrocytic; hemolysis; myeloid dysfunction; sideroblastic anemia- on peripheral blood smear- see basophilic stippling; BM- see sideroblasts. If see normocytic anemia, check blood smear; schistocytes send you down hemolysis path; RDW could guide you- large RDW could be mixed picture, should check iron, B12, folate, be sure they‟re ok. Myelodysplastic syndromes, myelophthisis- something infiltrating bone marrow- TB, fibrosis; peripheral blood smear shows tear drop cells. Hemolysis- high K, jaundiced, high bilirubin, low haptoglobin- protein that binds heme; in hemolysis- free heme floating around, binds it. LDH is high. Coombs- direct and indirect; direct Coombs- antibodies to RBC; indirect- antibodies floating around in blood. AIHA- Warm agglutinins and cold agglutinins; warm is IgG, cold is IgM. IgM- 4 degrees; IgG- 37 or greater. Cold agglutinins- mycoplasma; warm- HIV, cancers. Cold- usually transient, resolve; warmbad. Treat with steroids, warm may progress to needing splenectomy. Drugs to worry about- penicillin, quinines, procainamide, alpha-methyldopa; is regular method- drug makes antibodies that bind the red blood cells; innocent bystander- drug make antibodies, drug and antibody bind, these bind RBC; Hapten- drug makes hapten appear on RBC, antibody made to that- PCN. Other things to consider in hemolysis- sickle cell disease- clinical history tells you a lot; hereditary spherocytosis- see on smear, and osmotic fragility test; G6PD- must avoid sulfa, fava beans. Bactrim, e.g. can provoke. Paroxysmal nocturnal hemoglobinuria- Ham test. Pencil cells- iron-deficiency anemia. Howell-Jolly bodies- splenectomy. Target cells- any hemoglobinopathy. Heinz bodies- thalassemia. Burr cells- indicative of uremia. Acute bleeds- may not see any anemia immediately- Hb might look stable. 6-8 hours to see Hb change. If massive bleed, not tachycardic- may have taken beta blocker that day- must ask. Dr. Deirdre Cohen Thyroid 5/21/04 Hyperthyroidism- heat intolerance, diarrhea, tachycardia, proptosis, pretibial edema with Graves, tremor, irritability, psychosis. Hypothyroid- myxedema coma, constipation, weight gain, lethargy; hypothyroidism- delayed reflexes. Different thyroid hormone we check- T3 and T4; T4 and T3 is made in the thyroid, T4 is converted to T3 peripherally. Reverse T3- don‟t usually check anymore- not biologically active; when iodine atom is removed from inner ring of T4 instead of outer. Thyroid hormone- binds TBG- thyroid binding globulin, binds albumin, and transthoratin- TTR. TBG is #1- up to 75% of thyroid hormone is attached to that. Many drugs change thyroid hormone levels. Estrogen increases TBG. Lithium affects thyroid, amiodarone can increase or decrease; iodine- contrast dye for CT scans or with angioplasty, get transient alterations of thyroid hormone; different ways that meds can work- can increase TBG, TSH levels- dopamine, corticosteroids; amiodarone reduces conversion of T4 to T3 so decreases it that way.\ Hypothyroidism- most common cause of hypothyroidism- Hashimoto‟s- antithyroid antibodies. Then- ablation for Graves, goiters; DeQuervain‟s thyroiditis, depending upon where are in stage, can give hyper or hyperthyroidism. Iodine deficiency, depending upon where are in the world. Hyperthyroid- small distinction between thyrotoxicosis and hyperthyroidism; latter is increase in production, release, not just transient elevation of T3. Most common cause- Graves; can do TSH receptor antibodies but rarely done; just do thyroid peroxidase or globulin antibodies. Second most common cause- nodular thyroid disease; third- exogenous- taking too much of their synthroid. How we‟d treat Graves- Propylthiouracil- inhibits peripheral conversion, methimazolethyroid conversion. Surgery almost never done for hyperthyroidism- easier to supplement after ablation- easier to deal with. Nodular thyroid disease- radioactive ablation or surgery. Iodine suppression- not usually done. Subclinical hypothyroidism- normal T4 but TSH is a bit high- question how to treat it- if complaining of vague fatigue, CBC‟s, TFT‟s- get this result- do treat it because will usually become hypothyroidism; antibodies support this diagnosis, gives more evidence that will go on to be permanently hypothyroid. Subclinical hyperthyroidism- low TSH, normal T4- associated with decreased cardiac function, osteoporosis and fractures so do treat that too. If woman delivers baby, noted to have decreased thyroid function- could have Sheehan‟s syndrome. Sick euthyroid syndrome- TFT‟s during hospitalization generally not helpful; normally have normal TSH, any T4 level, low total or free T3. Is secondary to cytokines, inflammatory mediators affecting pituitary, thyroid and periphery. Don‟t treat this because will resolve once they get better from their insult. Many patients are concerned about their thyroid supplementation; isn‟t that emergentcan go up to two weeks before become clinically symptomatic; have so much in periphery that can tell them to relax. Scintigraphy- hot nodules are generally benign. Graves disease will light up, ectopic thyroid gland, struma ovarii, etc. Thyroid nodules- go to neck, feel nodule- first step- assess its function- get TFT‟s- hyper, hypo or euthyroid? If hyperthyroid- go on to get scintigraphy- hot or cold? If eu or hypothyroid- go do FNA. If trouble localizing nodule, can use ultrasound guidance. Majority of thyroid nodules are benign, minority are malignant but that‟s the worst fear. Stick needle in anything that isn‟t hyperfunctioning or those which are but doesn‟t respond. Higher-risk- Old and young, children, radiation to neck- e.g Hodgkin‟s treatment, MEN. Other warning signs- dysphagia, hoarseness, hard, fixed nodules, fixed cervical adenopathy, and previous history of thyroid cancer- as with every cancer. On FNA- will find either benign, papillary, medullary, or follicular neoplasm- but can‟t distinguish adenoma or carcinoma, so then go to surgery. Lymphoma, anaplastic or metaplastic disease- no surgery b/c won‟t help you. Ultrasound helps for looking for recurrence, following nodule size; can‟t differentiate between benign and malignant. Case- 57-y/o man- smokes, no meds; unintentional weight loss; all normal; TSH .01, T4 is 12.5- TSH is very low, T4 is high- hyperthyroid; has the weight loss but not really symptomatic- HR normal, etc. Why to treat asymptomatics- hypothyroid- high risk of hyperlipidemia, hypercholesterolemia. Hyperthyroid- cardiac dysfunction, osteoporosis, fractures. In kids- hypothyroid- cretinism. Exophthalmos- doesn‟t go away. 52-y/o woman with history of ablation, normal until free T4 found to be up- usually don‟t monitor TFT‟s once get patient on a regimen; hyperlipidemia, etc.- meds that can interactsucralfate, MVI with iron, AlOH, conjugated estrogens, increase thyroid binding hormone. Guy in clinic who had positive PPD, complained of night sweats, coughing- seemed clearly to be TB; sent TFT‟s, ended up having Graves disease. Didn‟t treat with ablation- just under cutoff for tracer pickup; chose to treat him with PTU. Had palpitations but people always come in with that, tend to be normal when send TFT‟s. Dr. Bardes 5/24/04 26-year-old man with fatigue of three months‟ duration- general categories of things that he could have- anemia could certainly do it, but must be fairly significant anemia; mild won‟t do it- must be below 10. Infection- mono, but 3 months is kind of pushing it; people often link mono with chronic fatigue syndrome but different- mono- fevers, swollen lymph nodes, etc. Is a true entity called CFS but differs from EBV. Chronic hepatitis, osteomyelitis, HIV. Depression, particularly if expand to dysthymia; stress, overwork. Fatigue is uncommonly the presenting syndrome in cancer. Lots of endocrine problems- adrenocorticoid insufficiency, diabetes- frequent presenting cause; hypo, hyperthyroidism. Type I diabetes can happen at any age though we conceptualize of it as juvenile. Lung problem will commonly present as dyspnea if fibrosis first. Any chronic disease. Sleepiness, sleep apnea. Lots of possibilities. Norm for sleep- goes to sleep around 11:30. getting up around 7:00, recently goes to bed earlier. What else going on- stresses? Exercises; stamina has decreased a bit. Fevers, night sweats, cough, diarrhea- none of the above; has actually gained a few pounds. Depression issuechange in sleep patterns? In depression- broken sleep pattern- fall asleep readily, wake up in middle of night, not refreshed by sleep; appetite could go either way but is often disturbed, energy is down, etc. So if think about candidate for depression- sleep, then appetite, then energy, then talk about mood and affect. Palpitations, weight gain or loss, tremor, new diarrhea or constipation- thyroid. Diabetes- polyuria, polydipsia. He says no to all of these; no change in bowel function, cough, chest pain, headache- none of the above. PMH is really unremarkable. Takes no medicines; takes multivitamins; took Ginseng, didn‟t make a difference, so stopped. Drinks 1-2 beers on weekend. Doesn‟t smoke cigarettes, pot in college but didn‟t really care for it. BP- 148/92, HR 80, rest of exam unrevealing. AC PC SC AX ING- anterior, posterior cervical, supraclavicular, axillary, inguinal LN palpated, all negative. Not much to figure out. Family history- had aunt with major depression- actually bipolar, hospitalized twice; another aunt with hypothyroidism; diabetes. Sexual history- no new partners; sexual function is down a little bit- everything works Ok, just a little tired. Is from the US, grew up in Greenwich, Connecticut. Muscles are a little achy, rash between fourth and fifth toe on each foot, has had for a long time. Anemia- CBC is more accurate way to assess than looking at palms. WBC- 7.6, Hb 12.2, Platelets 220K. Smear is normal. Hb is a little low for a guy. Supports our notion that this isn‟t depression. TSH normal, Lyme titers negative. HIV is negative, cortisol normal, VDRL, ANA are negative, ALT 30, Glc 90, Ca 10.0, Ferritin normal, B12, Folate normal, ESR 20, PPD is negative, bili, alk phos is normal. UA- RBC 20-30/HPF, 1+ proteinuria. Albumin 3.7, globulins normal. Na 132/3.6. BUN/Cr- 40/2.9- bingo- tired because has renal insufficiency; not part of our original differential diagnosis, though would have come up with it, fits high BP, anemia, other things in the picture. Sometimes need to draw blood tests because need more informationsometimes addressing hypothesis, sometimes just need more facts. This isn‟t meant as justification for total body CT- just need more data, that kind of approach popped out answer. Renal insufficiency- prerenal, renal, postrenal; but taught in med school by pathologists, so odd way to approach, but does work in this case. Prerenal- decreased volume, blood pressure, cardiac output- hypoperfusion; hypoperfusion also from renal artery stenosis; third spacingascites, etc. Post-renal azotemia- mechanical obstruction like prostate, stone or stricture, neurogenic causes anywhere along axis- stroke, spinal cord problem- transverse myelitisdiabetics get problems with long nerves- sympathetic neuropathy; pharmacologic causesanticholinergics- some designed to be anticholinergic- atropine- famous bella donna- beautiful women used to make pupils dilate. Atropos- fate who cut the thread of life. We use atropine very occasionally and just for a moment. Medicines used for hypermotility- urospas, detrol, bentol. Anticholinergic side effects- tricyclic antidepressants, older antipsychotics like phenothiazine, haloperidol, opioids, antihistamines like benadryl. Another class that can make you unable to void- revisit bladder anatomy- two muscles- detrusor is parasympathetic, under influence of acetylcholine, to void, must increase Ach. But sphincter is sympathetic, to void, must relax sphincter by decreasing epinephrine, norepinephrine; when can‟t void- alpha-agonistssympathomimetics- pseudephedrine, ephedra- early chemical to be isolated from plant sourcesfrom Ma Huang; alpha agonist, vasoconstricts little capillaries in nose, also constricting bladder sphincter; combination antihistamine and pseudephedrine can cause problems in older patients. Prerenal- Bun/Cr >20, FENa <1%, UNa <10. Post-renal- voiding trial. Normal bladder holds about 500 cc‟s; young- can nearly empty all of it. Young guy- just do a sono. Palpate bladder- below umbilicus- if distended- palpate, percuss bladder. Our patient didn‟t have elevated BUN:Cr ratio, UNa is 50, no obstructed bladder on sono; So- renal insufficiency causes- glomerulonephritis, collagen-vascular disease, nephrotic syndrome- can be entity in its own right. Diabetes, hypertension- give glomerulosclerosis- small shrunken kidneys; and etc. Tubular-interstitial- acute tubular necrosis, acute interstitial nephritis; pyelonephritis; and etc.- heavy metals, etc. Casts- in glomerulonephritis- RBC casts; in ATN- granular casts; WBC casts in pyelo; in interstitial nephritis- eosinophils in the urine. Nephrotic syndrome- urine protein >3.5 g/24 hours. How do you look at casts? Lab‟s failure to report them isn‟t entirely reliable; really need fresh specimen- very often sample can sit around for hours. Need to look at it yourself if really concerned. Cast- imprint of lumen of the tubule- tom horsefall protein- matrix of cast, secreted by normal healthy tubular cells. Albumin in urine is always abnormal, but other proteins can be in urine. Proteins glom together- hyaline cast- misnomer- looked like hyaline to early microscopists but just means slow flow; all have hyaline in urine on first morning sample- are a bit dry, don‟t drink much overnight- slow flow through nephron, gives hyaline cast. In addition, stuff can get stuck in matrix; if RBC‟s get stuck- red cell cast; that equals glomerulonephritis, no further discussion. WBC casts- is pyelo. To get WBC cast- must be up in tubules. Can tell difference by size- RBC casts- 4-5 microns, WBC- 7-8 microns. Granular casts- in ATN- necrosis- dead cells lyse, spill contents into lumen, protein cast speckled with cellular debris. Collect urine in plasticcapped tubes. Casts hang out at ends of the cover slips. Eos in urine- need to stain- Wright stainmachine does it, can look for them under oil immersion. So this patient has renal azotemia, though casts not reported by laboratory, see RBC casts under microscope. So he has glomerulonephritis, though didn‟t recall being sick, had positive ASO, so PSGN, got completely better. How bad was this man‟s kidney function? 26-y/o man, Cr was 2.9, say he is 70 kg. To quantify it- Creatinine clearance and interpretation- >80 ml/min normal, 50-70 mildly impaired, 30-50- moderately, 15-30 severely impaired, <15- failure. Is a calculation- 140 x age/serum creatinine. fudge factors- (wt/70), (0.8 if woman)- is about 35 ml/min- so he has moderate to severe renal insufficiency. 85-year old woman with creatinine of 1.5- normal at NYH; weight is 70 kg- CrCl is about 28; so NYH says she has normal kidney function, but really has severe renal insufficiency. If she comes in with pneumonia- overdoses on penicillin- gets a seizure. 80% of meds cleared by kidney so calculate the clearance for every patient. If normal size, decreased clearance- give same dose less frequently; if reversed- lower dose, same frequency. Calculations I use daily- creatinine clearance, A-a gradient, anion gap. Worthwhile to know them. Tutor Group Dr. Wenderoth 5/28/04 57-y/o male who presents with chief complaint of altered mental status. PMH significant for propionobacterial bacteremia, pneumonia in 2001. Comes in with altered MSE, comes in with social worker, mildly demented girlfriend. Stopped talking to people for two weeks, stopped talking to girlfriend the day before, she got mad, called police. He was functional, though odd and not so talkative, until 2 weeks ago, caregiver for girlfriend and mentally retarded brother. Is one thing to be able to do your own ADL‟s, another thing to be able to do others‟. So mutism for last two weeks. If this is all we know- questions- headache? Not answers, but neck is supple. Focal deficits? Movements intact, hyperreactive reflexes- appears alert, almost catatonic; volume status- moist mucous membranes. Febrile? No. No meds. Glucose- 120; increased ICP signspapilledema? No. Never had this before. Didn‟t respond to sternal rub, only to deep pain. Differential diagnoses? Several ways to do this. My favorite- start with what strikes youall things that occur to you, then use those as branch point. Possibilities- CNS infectionmeningitis, encephalitis; CNS processes- malignancy, e.g.; psychiatric- dissociation, autism; electrolyte- hyperosmolar coma, or other lyte imbalances; bacteremia- infection; stroke, UTI, psychosis, chronic disease- cirrhosis, ESRD, trauma, toxicity. That‟s what occurs to you. Encephalitis- brain is swollen, inflamed, infected, often people are delirious as well. Methodically- by systems- CNS infections- infectious disease; within that- can have bacteremia or pyelo, meningitis or encephalitis; other things he could have- syphilis, e.g.; doesn‟t have fever or rash, no murmurs. Bacteremia, UTI‟s, prostatitis, pneumonias, endocarditis- could have mycotic aneurysm or brain abscess. CNS processes- could have space-occupying lesion- malignancy, brain abscess, hemorrhage- CVA, hematoma/bleed; could have weird amyloidosis. Periventricular white-matter disease- lacunar infarcts. CNS infiltrating disease- amyloid, prion disease; dementia or delirium? Pretty quick for dementia. Could be prion, CVA, PML- if HIV; Pick‟s disease often presents with mutism. Acute or chronic? This is subacute- 2 weeks. Focal or systemic process? Seems systemic, though fulminant focal process- brain abscess- could have taken over. Psych- could have dissociation, autism, psychosis, fugue, post-traumatic stress disorder- acute stage often presents with “shell-shock”; depression- if this guy was 80, would say he‟s depressed. Endocrine problems? Diabetes, thyroid, hyperparathyroidism- can present this way, adenoma can grow in 2 weeks; electrolytes- about any of them; sodium, ESRD; potassium. He had serious skin infection, pneumonia- worry about his IgA levels; rheumatologic disease- Berger‟s disease, HIV or malignancy. Benzo‟s, benadryl, opiates, ketamine, neuroleptics, LSD/PCP; signs like this tend to be pill-related. Alcohol- must think of Wernicke‟s and Korsakoff‟s. Subacute, not febrile when comes in but becomes febrile, more demented than delirious. Top 4 on differential- psych, toxicity, infection, lytes. LP- consistent with viral meningitis; before got results back- Ceftriaxone, Ampicillin to cover Listeria, and acyclovir for HSV. Neurologist thinks it‟s psych- history of being odd; when rolled him over for LP- “what are you doing?” Not moaning, not just responding to pain- makes you think volitional. New York- pods of Orthodox Jewish communities with particular medical issues; White Plains- Listeria- Hasidic community who processes own dairy products; elderly Holocaust survivors- at risk for unusual psych things; Israelis with PTSD from battle, etc.; Ashkenazi Jews- predisposed to genetic diseases. Next patient- 63-year-old male; right-sided chest pain, SOB, edema, flew, left lower extremity pain. Chest pain- pulmonary embolism, aortic dissection/aneurysm, MI, pneumothorax, pneumonia, tamponade, pericarditis; GI, psych, musculoskeletal- lower on differential. Now- to be more systematic- things around PE- why clot in the lung? Flew- DVT; hypercoagulability- heme; other causes of PE- trauma, stasis, malignancy, vascular disease. Expand differentials off differentials b/c need to incorporate things such as vasculitis. Aortic dissection/aneurysm- hypertension causes it; pain he‟s having- stabbing pain, radiating to back, wax and wane, acute; this could be MI, aneurysm; ischemic colitis, cholelithiasis, metastatic disease to spine, pancreatitis, pseudocyst, pancreatic cancer. 27-year old man with testicular cancer could present just with retroperitoneal lymphadenopathy. Kidneysnephrolithiasis- peristaltic movement of ureters; duodenal ulcer is in retroperitoneal. MI- PE, dissection, tamponade. Pneumonia- pleurisy- most common cause is adenovirus. Infectious pleurisy- bacterial or viral pneumonia; pericarditis. Inflamed serosa- pericarditis- uremia, TB possible, rheumatologicif woman- SLE; sarcoid is pretty common; Dressler‟s post-MI. Pneumothorax- could be spontaneous- emphysema- doesn‟t smoke, could have alpha-1 antitrypsin disease but is old; body habitus- tall and thin. Toxins- asbestos- mesotheliomas, asbestosis, fungal infections. Trauma can give PTX. Could have chronic lung scarring disease leading to PTX; things that cause scarring- multiple PNA‟s, severe COPD, inhalation injury- workplace related or cocaine- scars lungs badly; not marijuana so much but pesticides in it- in high enough doses, causes pesticiderelated toxicity. Psychiatric- anxiety, panic attack. Musculoskeletal- costochondritis. Hb of 15.7hemoconcentrated, or smoker- hypoxic- bumps RBC. Saw Kawasaki‟s here that took long time to diagnose; important to run differential to get at these sorts of entities. Next patient- CC- Abdominal pain x 1 day; s/p cholecystectomy. Was in usual state of good health when had this pain. Went to work, didn‟t feel well, several episodes of watery diarrhea, vomited several times, food, then liquid; fever/chills/myalgias/diaphoresis; no new food; meds no help; sexually active, monogamous; worse abdominal pain with inspiration; LMP Ok. Physical exam- not orthostatic- 36.5, spiked to 39.5; PMH- similar pain two years ago, came to doctor, got some sort of shot; tubal ligation; social history- Ecuador, works as prep cook, no alcohol or drugs. Physical- ill-appearing, mid-epigastric tenderness to deep palpation; electrolytes normal; no CVA, normal lytes, CBC with bands; AST 1077, ALT 688; LDH over 1000. Would hone in on elevated LFT‟s- hepatitis; alcohol because of ratios, or viral- hep ABCE, EBV, CMV, fungal, autoimmune, hemachromatosis, Wilson‟s; s/p cholecystectomystricture- obstructive; alpha-1 antitrypsin; fungal, parasites- is from Ecuador- clonorchis, echinococcus, entamoeba; big cause of hepatitis- HIV. Other things- toxins, acetaminophen, carbon tetrachloride- chemicals of all sorts, pesticides; portal vein thrombi. Shock liver; vasculitis. 2 g of Tylenol + ½ pint of alcohol can cause hepatitis. Amanita mushrooms; aflatoxin; choledocholithiasis if a month earlier. Autoimmune; PBC, PSC; she has hepatocellular picture. Picture- has been going on a couple of weeks. Could be subacute or acute on chronic. We‟ll get to bottom of the acute reason. But why does this 42-y/o woman have acute on chronic? So- she has hepatitis, but why? If not had LFT‟s- could be gastroenteritis, could be toxin- staph, etc.; typhoid if everywhere she went, people got sick. Everything came back negative. Her LFT‟s went to the 4000‟s. Sent leptospira antibody, following up autoimmune idea. Albumin is 4.6- so not serious chronic disease. Could be fatty, cirrhotic, infiltrated with amyloid, TB. Resident Lecture Dr. Christopher Madias 5/28/04 MICU- first thing- events overnight that happened to the patient, and the day before. Some on the team will know the patient, some won‟t. Hypercarbic respiratory failure, yesterday we weaned down to..., etc. Vitals- must say Tmax and Tcurrent; they like to hear not only what vitals are right now but more importantly, what they‟ve been; if outlier- blood pressure has mostly been 150‟s, once in 80‟s. HR- range. Respiratory- if someone‟s not intubated- O2 sat on what- 40% face mask, 3L nasal cannula? If intubated- they want mode of ventilation- are they on CPAP- say spontaneous, which is pressure support, which is CPAP. Or are they on IMV, or CMV (assist/control)? Tidal volume is at- 500? FiO2- how much oxygen getting- 50%? Rate? Sometimes rate is different- if agitated, breathing over the vent- rate is at 12/24; PEEP- usually 5 mmHg; pressure support- how much getting- 10? I‟s and O‟s are extremely important in hospital, weights if can get them; fingersticks- very important in ICU- tight glucose control. Lines- what kind of access do they have- triple lumen and femoral line? Subclavian and vas cath for dialysis? What do the lines look like? On dialysis? If there for long period of time- no significant change from yesterday? Flow the labs; then plan for day- system by system basis; neuro- being sedated with propofol, will wean off, see what MSE is; pulmonary- ARDS, doing low-volume ventilation, diuresing him. Lot of grade in ICU is presentation; look things up- rounds is your time to shine in the ICU. Rest of day- with residents, fellows. Procedures- if interns already certified by this time, may let you do arterial lines, etc; learn to do IV‟s, ABG‟s; ICU‟s are where really learn pathophysiology. Diabetes- will basically talk about management today. 5 minutes on DKA. Patient walks in, blood glucose very high, anion gap acidosis- first step in management- give fluid- average are down at least 3 liters, sometimes even more- 3-6 L, so give them 2 liters wide open at 250 cc‟s/hour- flood with fluid. So access- get lots of IV‟s, fluid- use NS or LR to volume replete them. Are hyperglycemic, so osmotically diuresing water. Know are getting enough fluid- track I‟s and O‟s- put foley in, be sure are peeing. Insulin- 10 units for normal sized person by IV. Then- fingersticks every 1-2 hours to follow; run IV drip at 0.1 units/kg; if big person- 10 units/hour to start; if not- will calculateabout 8 units/hr to begin. Also follow electrolytes- low-insulin states, acidosis- K falsely normal, with correction- potassium shifts into cells, peeing it out- so keep K > 4.5; even 5 good for young people. Also follow P. After volume resuscitate- give ½NS. Follow electrolytes every 3 hours. Also follow anion gap, blood ketones. Will give 10 units, start drip, fairly quick control of hyperglycemia; AG, ketones slower to catch up. Aim for blood sugar in 200-250 range; when get to there, start D5- give sugar in fluid with K to keep blood sugar in 200-250 range until ketoacidosis subsides. If they can eat- get them to eat whatever they want- ice cream, cake, hamburgers, French fries. When resolves- down to 1-2 units/hr range, are eating- give them long-acting insulin subcutaneous- NPH or lantus; important thing- don‟t give lantus and shut off drip- will go back to ketoacidosis; keep drip going for 2-3 hours after subQ. Then switch to normal- before meals and bedtime. On MICU- be sure to go down with the consults. Type I diabetes- not making insulin because beta cells destroyed. Type II DM- resistance to insulin, decreased secretion, increased gluconeogenesis by the liver. Drugs for DM II are set up to fight those things. Names unfortunately are all complicated, always forget them, always have to look them up. DM type II- oral meds- class, drugs, trade names, where/how, effect on HbA1c, adverse effects- sulfonylureas- glyburide, glipizide- second generation ones; we tend to use these because are often shorter acting than first generation ones, associated with fewer hypoglycemic episodes; trade names- glucotrol, micronase, diabeta. Work on potassium channels in beta cells, cause insulin secretion. Need some functioning pancreas for this to work. Often good in new-onset type II diabetics. Effect on HbA1c- glycosylated hemoglobin- want it to be below 7, which is equivalent of 150; 9 is 210, 11 is 300, 13 is approximately 400. Vascular damagecardiovascular, peripheral vascular; neuropathy, retinopathy, nephropathy, etc. from elevated blood glucose. If patient is compliant- expect 1-2% decrease in HbA1c. One agent usually won‟t be enough if they‟re 13. Adverse effects- hypoglycemia is one of the major ones, must look out in elderly. Also interact with a number of drugs, need to be careful about drug interactions. Next- meglitinides; repaglinide, nateglinide; trade names- Prandin, Starlix; also work on pancreas- ups secretion; secretagogues. Hb1Ac up by 0.8-1.7%; adverse effects- hypoglycemia as well. Broken down by liver, kidney so be careful with liver, kidney patients. Biguanides- metformin; trade name- Glucophage; combined with glyburide- Glucovance. They work in liver to decrease glucose production. Also work at muscle, adipose tissue to increase glucose uptake. Hb1Ac decreased by 1-2%. Worry about lactic acidosis- can be associated; worry when give dye for CT scans b/c that can also cause lactic acidosis, so often stop metformin 1-2 days before scheduled CT scans. Contraindicated in renal failure. Creatinine >1.5 in men, 1.4 in women- should not be on metformin. Good thing about metformin- lose weight. One thing with these- can cause GI side effects- bloating, nausea, diarrhea; but longacting type is better tolerated, as is the Glucovance combo. Alpha-glucosidase inhibitors- work at intestine- decreased absorption of glucose. Acarbose; Precose is tradename. 0.5-1% effect on Hb1Ac; GI side effects- diarrhea; not really absorbed. Patients don‟t like them, rarely used. Thiazolidinidiones- Avandia, Actos- rosiglitazone, pioglitazone; are insulin sensitizerswork mostly at muscle, fat, a little at liver. Effect- 1-2% reduction. Effects- must monitor LFT‟s with these guys- can be liver toxic. What else can do- nutrition, weight loss, exercise. Effect on HbA1c- 1-2%. Today- will need 2 agents with most patients, are combinations; think pathophysiologically; two angle combinations- sulfonylurea with glucophage or thiazolidinidione, etc. Sulfonylurea- good to give prior to meals; will often tell patients to take before meal, snack. Talk to them about exercise, losing weight, checking blood sugars; information is very important with this disease. Complications- vascular; worry about cardiovascular, renal as #1, 2. Also must monitor blood pressure in these patients- want them systolics below 125- really good, tight control of BP in diabetics, ACEI are the best agents; first line is ARB, but that‟s because they‟ve been studied. Other things- lipids- look at LDL, should be below 100- treated as if have cardiovascular disease in terms of guidelines for cholesterol control; statins, diet big for these; titrate statins aggressively to LDL >100, studies will probably knock it down to 80 or below. Aggressive statins, weight loss, exercise, BP control. Screening test for nephropathy- microalbumin; dipsticks; if showing signs of proteinuria, must definitely add on ARB, be sure not becoming nephrotic; will usually be end-stage then though. Also send to podiatrists- older, evidence of peripheral vascular disease; often don‟t feel what‟s going on in feet because of neuropathy, step on tack; wound healing terrible- need dressing changes frequently; and yearly eye exams. CCU/MICU block Pharmacology Dr. Marcus Reidenberg 6/1/04 Have you decide what general area of pharmacology you want us to cover, select a case to present to illustrate the problem, send e-mail on Monday before 5:00 to tell me what problem is. Patient with history of aspiration pneumonias, C. difficile, put him on Vanc and Flagyl for C. diff- why put on both? The carriage rate of C. diff in general population is about 5-10%. Are hundreds of different organisms in the bowel, live in constant ecological warfare trying to kill the others. When we give antibiotics, we kill off a whole group of organisms that are the mainstay of bowelE. Coli, Klebs, Bacteroides- and C. diff grows out, produces a toxin causing pseudomembranous colitis, can be granulomatous but rare. Oral vanc is the only FDA-approved drug; flagyl- doctors using it anyway, generic, and 90% effective, so though not cost-effective for companies to seek FDA approval, most doctors use it. Vanco must be given orally to get to the C. diff, while flagyl can be given systemically. Why are they using both drugs, not just one? Patient has chronic C. diff colitis. When flagyl fails, go to vancomycin. But using both- focus of C. diff colitis- will see colitis, and pseudomembrane; vancomycin has to get down to colon to work; if have ileus- need to give per rectum going up, or IV- must be flagyl; PO vanco won‟t do anything. Recurrence rate is very high- about 10%. Other way to treat this disease, conceivably- drug that bind the toxincholestyramine binds the toxin nonspecifically, not all that well- so are willing to spend $30 million on this. Also- probiotic- acidophilus, e.g.- to re-establish normal colonic flora. Study on feeding relatives‟ feces to re-establish flora. Are deaths despite adequate treatment, and nagging problem of recurrence. With toxins- botulinum- don‟t make antibody, can get recurrences. So current research- directed at antitoxin therapy. Vanco, cholestyramine are spaced so doesn‟t interfere with vanco action. Patients on contact isolation since C. diff is a real nosocomial problem. Last recommendations- treat with flagyl once, then first recurrence, then go to vancomycin. Tachycardia in sepsis- from sympathetic innervation; if beta blockade- no tachycardia. Cholestyramine- anion exchange resin, will bind any anion, including anionic drug. Many drugs with enterohepatic recirculation. Cholestyramine lowers cholesterol that way; giving cholestyramine an hour apart from vanco will let initial effect work but may interfere with enterohepatic recirculation. If putting someone on cholestyramine- look at full name of drug; if tetracycline chloride- drug is cation, Ok, while if sodium phenytoin- know it‟s an anion, could be problem. Pressors- up until relatively recently, the last thing you‟d give someone with borderline myocardial function is beta-blocker; then started giving them gingerly, and turned out that these people lived longer than those who didn‟t get them. When people started to study inotropes- first studies with amrinone, milrinone- phosphodiesterase inhibitors- idea that ATP important for energy for heart; if could block waste pathway with PDI‟s so all the ATP available for muscle contraction, would be better. In acute studies- gave much better hemodynamics; for chronic- died much quicker. Clear that with adrenergic drugs, can get both rapid downregulation of adrenergic receptors, and those that remain active give less of a response- desensitization. Around the time this was going on, high-potency long-acting inhaled beta-agonists were marketed for asthma, death rate for asthma went up, correlated; took off market, death rate for asthma in Australia rapidly dropped off, worldwide acceptance of that relationship. Inotropic drugs for chronic heart failure- studies to show that digoxin doesn‟t improve survival compared to those who don‟t get it in this era of diuretics, ace inhibitors. Downregulation of digoxin receptors in hours. So right now- standard treatment- hypotensive patient- give them adequate fluids, then may give dopamine, dobutamine or norepinephrine; dopamine- in very low dose doesn‟t activate adrenergic receptors, in pressor doses probably does; in next few years- question of how to use these in settings of low blood pressure, adequate fluid; helpful initially but as continue, need higher doses to maintain pressure. Have adrenergic agonists which all act on adrenergic system in heart, digoxin which has limited efficacy, phosphodiesterase inhibitors which acutely make hemodynamics better but over months, kill people, and I suspect that over the next few years, we‟ll see more and more of these metaanalyses of little studies, probably not RCT‟s because hard to do RCT‟s withholding standard care. So- acutely- standard care- hypotensive- give fluid, adrenergics; but may start modifying that, particularly with respect to duration- may acknowledge that after time, can‟t stop but not doing much good. Part of CHF- mainstay was use of diuretics; limiting factor clinically- hyponatremia- if really push it; in response to that- in JAMA, a few months ago, article about anti-receptor arginine vasopressins; arginine vasopressin 2- antidiuretic so reabsorb water; reabsorbing saltfree water is the last thing you want to do if hyponatremic due to diuretics, so are series of drugs that inhibit binding of arginine vasopressins in kidney. Studies look good. Can make a peptide that blocks, enhances free water clearance- pharmacologically is doable; problem- other factor involved in this is poor renal blood flow, intrinsic renal vasomotor responses to poor renal blood flow, so pharmacologically, works well, but don‟t know how much can be accomplished just by blocking renal vasopressin receptor, and how much is hemodynamic; don‟t know what renal ischemia does. One fear- drug may adversely affect vasopressin 1 receptor, cause hypotension; but heart has enough sympathetic outflow that isn‟t an issue. Other problem- foreign peptide being given, don‟t know how soon getting neutralizing antibodies to it. Inotropes- if look at range of alpha vs. beta- if pick noradrenaline as having equal alpha, beta effects- phenylephrine is pure alpha, will give vasoconstriction without cardiac inotrope effect- classic use- spinal anesthesia that went up too high. Pure beta- isoproterenol- cardiac stimulation without vasoconstriction. Epinephrine is somewhere in between the two; lots of conventional therapy you‟ll see, but these are the differences. Norepinephrine- generally the one used for hypotension rather than epinephrine. Is there drug that raise BP without being such a strong renal vasoconstrictor as norepinephrine? Dopamine was best- so can get some increase in BP without renal vasoconstriction at lower doses. PDI‟s- wouldn‟t choose those over adrenergics; marketed only for acute problems in coronary care unit. Is a “last rites” drug- give to someone under extreme conditions, rarely will save their lives. Question- what is precipitating event, outcome? If catastrophic event but if survive, can reverse it- different from someone who‟s been sick and deteriorated over last 3, days. Look for precipitating event for deterioration in chronic disease- that‟s treatable. Patients with cirrhosis, on lactulose- mechanism, why efficacious? Ammonia is a reasonable marker- if someone‟s encephalopathic, high ammonia, cirrhotic- can ascribe to that. Seem to be some „evil humors‟ in intestine that get absorbed, liver detoxifies; if liver is cirrhotic, these „evil humors‟ get in, make brain encephalopathic. Lactulose- pharmacologic effectdiarrhea; judge dose by just enough, not too much. Presumably does something to keep these compounds out. Ammonia is an amine; a lot of these protein metabolites, presumably from gut bacteria, are also bases- nitrogenous metabolites; if ferment sugar, end up with acidic fermentation broth; ethanol- wine, beer- acidic; presumably, acidic products bind these basic amines, so pass through intestine. Normally, stool contents are basic, amines will rapidly diffuse across intestine to get into bloodstream. So this is how lactulose works- non-ionic backdiffusionif nitrogenous base metabolites from protein form in GI tract from these hundreds of thousands of microorganism species- makes sense. In renal failure, some of these nitrogenous bases are what contribute to the uremic syndrome. Dr. Reidenberg 6/8/04 Case- 49-y/o. HBV, HCV positive, found by police lethargic, “under influence of drugs,” in ER, became very lethargic, responded immediately to Narcan, admitted to alcohol, heroin use; became lethargic, intubated with propofol, seen to aspirate moderate amounts of vomitus, etc. Chronic anemia possibilities for him- anemia of renal failure, folate and B12 deficiency, GI bleed, alcohol. If chronic bleeding- small RBC‟s; if B12/folate- will be large; if both, can get mix. Any of the opioids cause sedation reversible by Narcan. Injection; time course of onset of action of opioid following IV administration- seconds; if came in conscious, gave history, then deteriorated- strange to think the dope is the cause of this. Physical sign- breathing slowrespiratory depression; pupils are pinpoint. What would give this presentation reasonably in something like this, recognize early- took a little heroin, BP high, HR high, RR is 18- opiate caused high BP, tachycardia, RR higher than 16- cocaine can do this- so do urine tox screen; look in blood to measure something you already know is there, urine better for general screen. Cocaine is a sympathomimetic alkaloid; its use in medicine for a long time was as topical nasal mucosal vasoconstrictor in ENT surgery, still use. So he uses heroin and cocaine, then lapsed into CNS depression from heroin, got narcan, woke up, wore off- 30 minutes; time course for narcan- 30 minutes, for heroin- prodrug for morphine- acetylmorphine, converted by hydrolysis to morphine. Heroin is more lipid soluble than morphine so gets into brain a bit faster, faster rush with heroin. Heroin, other things in Brompton mixture- hospital in London that treated many lung cancer patients; but later shown to have same effectiveness of Morphine for coughing pain. Heroin- 3 hours‟ duration. If he‟s taken morphine for weeks, give ampule of narcan, looks better, then lapses, and again- so we think- let‟s give 3-4 ampules- bigger dose, higher peak, will last longer- what if give someone who‟s achieved dependence big dose of antagonist- acute withdrawal- abdominal pain, vomiting, diarrhea, sweating, tachycardia, agitation. Sometimes hard to tell if agitation is withdrawal. If on cocaine, amphetamine, abruptly stop- sedation, somnolence. Alcohol- if drinking, abruptly stop- DT‟s; Librium- long half-life, when stop it, still get a taper; better than previous treatments- barbiturates and paraldehyde, which have much smaller margins of safety. Here fashionable to use Ativan- if overdose with Librium, effect persists longer than with Ativan; if are watching the patient, though, no reason not to use Librium. They treat themselves- eyeopener- „hair of the dog.‟ Delirium tremens has high mortality of 10-15%, if get them too late, fry their brain, have seizures, elevated fevers- 105, 106, die of metabolic derangements. This is unhappy case because patient hasn‟t awakened yet. Give thiamine as early emergency treatment because worry about Wernicke‟s encephalopathy. All alcoholics get thiamine, folate, multivitamin. Thiamine needed before glucose because used in Kreb‟s cycle. If someone just stops opiates- get the flu; precipitated withdrawal can be fatal. Alcohol withdrawal can kill; barbiturate withdrawal, if severe, can kill with seizures. CNS stimulantscocaine, amphetamine- overdose can kill. Opiates can exacerbate alcohol craving by shared mechanisms. Narcan can be useful to perk up generally sick patients temporarily. Withdrawal response to benzodiazepines- anxiety, agitation, insomnia; can persist for months. So nightly benzodiazepine for insomnia- once take it for week, are hooked, on it for life. Lactulose and hepatic encephalopathy- Cochrane database series delves into evidencebased reviews of drugs; no placebo-controlled studies to show that lactulose works; just studies in which was run against neomycin, no difference, but effect of neomycin is also not proven, so mechanism of action isn‟t known. Experience treating cirrhotic patients- treated cirrhotic by withdrawing protein, gave neomycin, lactulose, ready to go home, next morning, made rounds, found him in coma again- didn‟t understand; treated for hepatic coma, ready to go home, a few days later- see him in coma again. Turned out- as soon as got better, ate food of neighbor, big dose of protein, back in hepatic coma again. Question- what counts as evidence? Is this an issue important enough that one feels really doesn‟t know if lactulose in hepatic encephalopathy is more effective than starch pills, must do trial to find out? Have been many trials historically, etc. in which placebo arm did much better despite theoretical underpinning for this drug. Don‟t assume lack of evidence is evidence of lack. When is definitive clinical trial justified by fact that really don‟t know that intervention A is better or worse than B? How do adverse compare to beneficial effects, both to no treatment? We‟re beginning to see the tyranny of the meta-analysis- have either prospective RCT or no evidence at all; but are questions can‟t answer with RCT‟s- e.g. overdose effects. If look at quality of evidence- single case at one end of spectrum, RCT on other- series of cases better than single case, then consecutive cases, then variety of observational studies- case-controlled, non- randomized, cohort; comparison of treated cases to historical, leading to randomized doubleblind controlled trial. Most of our RCT‟s have narrow enough inclusion, exclusion criteria that not match our patient anyway, so we‟re extrapolating. Relevant to question of your degree of assertiveness in pushing a particular intervention. 100% fatal disease that drug helps one patient- penicillin for pneumococcal meningitisdon‟t need RCT; insulin for IDDM- 2 consecutive patients, methotrexate for choriocarcinoma- 6 or 8 consecutive patients. Need huge trials when drug effect is marginal at best, or high toxicities. Radiology Lecture Introduction to Chest Radiographs 6/10/04 Some basic anatomy, tubes and lines stuff. Frontal view- PA (posterior-anterior) or APanterior-posterior. PA is preferred; AP isn‟t as good, for several reasons; some has t o do with patient positioning. PA- put hands on hips, shoulders out, brings scapulae out, so don‟t confuse its border with PTX. Also- on AP, heart looks bigger than really is- plate is on back, rays hit the heart, is magnification effect. So on AP view, can‟t comment on heart size, or great vessels. Normal PA view, then lateral view- can‟t do portable lateral view- have to hold arms up; but if have both PA and lateral view, can cross-reference the two, place the item. CXR is difficult because many structures of many different densities lying on top of each other. Should always be able to see trachea, two main bronchi; ICU- if someone pulls out ET tube, need repeat film each time it gets manipulated, must see if tube is in trachea or too high up or too low. First rib you see under clavicle usually the third rib. Want to look for lucency of the carina. Mediastinal compartments- not real compartments but certain structures always in them- superior, anterior, middle, posterior mediastinum. Anterior- if filled in- lymphadenopathy, thymus, thymoma, etc. If someone has a little pleural fluid, thickening- can sometimes catch fissures. Can make out heart, aortic arch. Upper, lower lobe overlap in middle of chest, can figure out which lobe infiltrate is in by lateral view; also- heart silhouetting. Another problem with AP chest X-ray- aren‟t taking full breath, are collapsed on self; chin may be low on chest, vessels look much more dense, crowded together, collapse up and in toward hilum, can look like pneumonia. Can see bronchi, right pulmonary artery on lateral. Two knobs- aorta and pulmonary artery. X-ray- median sternotomy wires, EKG leads, Swan-Ganz- RA, RV, pulmonary arterycurls around; ETT, central line. Swan-Ganz- this one- not wedged; when need to make measurements, wedge it; worry if goes too far. ETT- want it to be at base of clavicles. Right mainstem bronchus intubation is common, can kill, so always want to be careful; see partial or complete collapse of left lung if do. Central line- as people get older- veins get more ectatic, may look like central line is in lung. Can see central line curling up. Swan-Ganz- may not be real numbers, but when wedgedsee tip in lung. Too far- out in lung. Feeding tube can accidently go down trachea- call floor, say- do not feed the patient. When stick tube down someone‟s nose, reaction is to pull head back, exposes the trachea. Feeding tube- hunch the patient over, have them keep chin on chest, will hold your head, etc. In unit patients or trauma victims- are out of it. Usually with feeding tube, not NGT, because of tip. Pneumothorax- until have seen lots of them, will sneak up on you; happen with central line, chest tubes; surgery- look for them almost any day. Lung is a little darker, denser than pure air alone, at edge, becomes more dense. AP- don‟t mistake scapula for PTX. Can be flat on top, down at base; if think is one at the base, ask the radiologist. Skin folds can kind of simulate a pneumothorax. Lines going across- muscle- subcutaneous emphysema; lots of PTX patients also have subcutaneous emphysema. Pneumopericardium seen too. Pleural effusion- always get meniscus. On portable film, patient lying; if propped up- can see meniscus but will be a bit fainter- will layer up, see gradual opacity. Left lateral decubitus- idea is- if lay someone on side, fluid free-flowing, will find a different level. If can‟t tap pleural effusion- loculated or infection, can‟t get in there- want to have that side down; is really frontal, not lateral. Lateral decubitustechs aim up in pediatrics, down in adults. CHF is supposed to look like batwings. Pulmonary edema radiates out from hilum following vessels and bronchi, as it gets worse, tends to be at bases due to gravity; perihilar, basilar opacities seen; see right, not left diaphragm- silhouetting- has to be some consolidation, fluid at left base for it to be same density as abdomen. Losing a line is known as silhouetting. Denser around hilum- even on normal CXR. Pacer- goes to left subclavian. Curly B-lines- as get out to lung periphery, interstitial markings get very fine, lymphatics resorb everything; if see lines about 1 cm from edge, congestion- CHF. Pneumonia- lingula- see density in middle of left lung, not see left heart porder, clear on lateral. See whole left lung involved- upper and lower. If learn to window- will save self lots of trouble as intern- window down- keep lightening picture- will be able to visualize, e.g., NG tube. Right heart border can‟t be made out, but right hemidiaphragm seen easily so isn‟t RLL. Thickened diaphragm- differential for that- includes subpulmonic effusion. Diaphragm is thin sheet of muscle. Minor fissure drawn up, opaque above- RUL atelectasis. Minor fissure is usually not seen- is in plane of the beam- unless fluid tracks up in there. Mucus pluging- happens all the time. Reading CXR- look at heart, let eye come up pulmonary arteries, then look at lung fields right left right left. Here- heart border gone on right- must be RML pathology. Must see heart border all the way around. Diaphragm- if see outline going all the way acrosspneumoperitoneum. Normal if just had laparoscopy but not if had colonoscopy- perforation. Pharmacology Dr. Reidenberg 6/15/04 Tachyarrhythmias- scenarios- individual who has such severe stage fright that loses ability to function- severe sympathetic outflow- beta blockers are fine; question to decide- at what point is it severe enough to be considered a disease to treat with medication? We all have certain mild tremor that‟s sympathetically mediated; in sports, highly competitive matches, beta blockers to cut out this tremor is considered cheating. So won‟t discuss sinus tachycardia. So- paroxysmal atrial tachycardia- beta-blockers or Ca-channel blockers, not both; worry about slowing down the heart rate; beta blockers act on the Na channel; Calcium-blockers block the Ca channel, take out major ion influx involved in pacemaker function, if do that too much, not much pacemaker function. Calcium blockers, especially verapamil- only active for supraventricular tachycardias, while beta blockers useful in both cases. Other thing for atrial tachycardias- carotid massage, vigorous respiratory excursions, press on eyes, sometimes do nothing, let it go away. If is paroxysmal, paroxysms will go away on their own; young person with healthy heart- may be better to let it go away on its own than to mess with these poisons. Atrial fibrillation- probably most common cause of tachycardia, should try to find proximal cause, look how damaged the heart is- convert to sinus or leave in atrial fibrillation just with normal range of rhythm? Need to find cause of atrial fibrillation. 1/3- hypothyroidism. Then- ischemic or valvular disease. Then- ultrasound measurement of left atrium- if >4.5 cm, not worthwhile to cardiovert- will return. If have hypertrophic cardiomyopathy- left atrial function is hemodynamically important- will cardiovert anyway. Beta blocker, amiodarone, sotalol- major trend for prevention of recurrence of atrial fibrillation. All other drugs shown to reduce patient survival- can improve quality of life but not prolong it. Synchronized cardioversion- if unstable- going at 200- shock because patient is in danger. Then- if have time- think- is it sinus? At 200, can‟t tell. If narrow and fast- tends to be supraventricular, have a little more time; can give adenosine, blocks AV node quickly, wears off quickly. If is flutter, may slow down long enough to see flutter waves. Adenosine- so quick on and off that not worry that drop BP; but person can become asystolic, transiently, on adenosine; have atropine ready. Machine can externally pace patient who has no rhythm of their own. Before go to drugs- is it sinus or not? From above AV node- a-flutter or a-fib- can‟t tell at 200so give something to slow it down; when determine it‟s flutter- 143- not emergency but should try to slow down- heart is working too hard at 143, beta-blockers, calcium channel blockers helpful with pseudostable patients with supraventricular tachycardias. Sinus- do nothing but figure out why are tachycardic- intubated, uncomfortable, exposed to noises, septic, etc. Good studies that show that atrial fibrillation patients on anticoagulants at reasonable rate- as good outcome as cardioverted patients. My judgment- unless contraindication to warfarin, probably better in long run to let them stay in fibrillation than maintain cardioversion, which is only temporary. Young age, no thrombus- can use aspirin; older age, or thrombuswarfarin. Sotalol, Amiodarone- for recurrence, or digoxin to keep heart rate between 60‟s and 80‟s. Atrial fibrillation- for most patients, not first event, so just try to control rate, needn‟t run to get them to sinus rhythm. If no history- must anticoagulate them so if young, small atrium, option of cardioversion. If documented New patient- are they hypothyroid? Particularly with old people- presentation will be atrial fibrillation; once get them euthyroid, cardiovert and will stay verted. Wherever chronic disease deteriorates, look for precipitating event because is easier to fix than chronic disease itself. Nodal tachycardias- beta blockers, calcium channel blockers, digitalis. Ventricular tachycardias- many antiarrhythmics that increase rate of sudden deathincrease QT interval, cause torsades de points. Standard care had peen to take patient with coronary heart disease with frequent VPC‟s- higher risk of sudden death, finding dose of antarrhythmic that would suppress VPC‟s, putting them on that drug at that dose lifelong. Preliminary study done with Halter monitor to find out how much this antarrhythmic therapy improved outcome. Turned out that death rate higher than controls; rapidly changed arrhythmia treatment. Same pharmacology in tricyclic antidepressants- found highest psychiatric hospital death rate in patients on tricyclics. Ventricular tachycardia- three consecutive beats or more from ventricular pacemaker- what do about them? Non-sustained VT- depending on EF from echo, do nothing or call electrophysiology team- data that implantable defibrillators save lives in patients with EF >30%, >40 with some caveats, ischemic cardiomyopathy. If patient already has AICDdo nothing- is there for that purpose. Amiodarone- sometimes prevents shocks from the machinepreventive measure. Pharmacology of amiodarone- primary antarrhythmic used today aside from betablockers- has long half-life, takes a while of dosing to reach steady-state levels. Are variety of toxicities, are real, include thyroid, pulmonary, etc.- are real, of concern, and not rare; this is why thoughtful people ask- are benefits to be gained by suppression greater than long-term risks, if we can delay starting it- person will be older, will defer onset. Major complication- lung problems, and psychiatric- sees all as pink, can be forever, unpleasant. Don‟t like to use amiodarone chronically for more than 3 years. Lower doses- 100 mg/day, etc.- lots of toxicity seems to be from cumulative dose effect. Can be debilitating- diffusion capacity lowered in lungs, thyrotoxicity, skin turns blue, etc. But still probably best option. If episodes of symptomatic tachycardia- can try to relieve symptoms; if question of ventricular fibrillation- cardioversion. If <3- do nothing; if >3, non-sustained- treat, may ablate re-entrant focus or implant AICD. In case of sustained ventricular tachycardia- cardioversion. Beta blocker side effects- can mask hypoglycemia, block body‟s response of glycogenolysis- makes it worse, sexual dysfunction, bronchoconstriction, Reynaud‟svasoconstriction, fatigue, can cause depression, CNS adverse effects. Study comparing beta blockers and reserpine with regard to depression causes- equivalent. We must be aware that many of these drugs have additive CNS effects; when sum, can be substantial; if look at drugs with anticholinergic effects, beta blockers- think about what know about sympathomimetic amines and mood- reasonable that can get impaired mood from blocking them. If patient says this drug made them feel bad, believe them- it probably did; we can dispute interpretation but accept the observations. Calcium channel blockers- side effects- excessive blockade; primary effect- peripheral vasodilation; if have peripheral vasodilation, no beta blockade- reflex sympathetic outflow with tachycardia. If get really profound vasodilation- can get postural hypotension. This is nifedipine group- don‟t use to treat arrhythmias, rather for hypertension treatment; shouldn‟t be use to treat heart failure, except maybe in dilated cardiomyopathy- study of Norvasc- not harmful. But side effects- tachycardia, drop in blood pressure. Also can give ankle edema- not very pleasant. Verapamil- used to treat arrhythmias, sometimes in ischemic heart disease- constipation, bradycardia; a little closer to beta-blockers in mechanism of action; concern in acute heart failure due to negative inotropy, and sexual dysfunction. May see used in HOCM in chronic basisoutflow relaxation- only case in which combine beta blockers and verapamil. WPW- digoxin, verapamil shouldn‟t be used in WPW- explanation- will block AV node, accessory track takes over, might conduct the impulse. If have someone with atrial fibrillation who is in failure, treat with digitalis- can go into sinus rhythm contrary to digitalis‟s effect. Chemical cardioversion in atrial fibrillation- flecainide or amiodarone. Used to use digitalis to stabilize ventricular rate, then quinidine but causes problems if doesn‟t work. Code situation- will see large doses of amiodarone given for patients with ventricular tachycardia but stable, etc. before cardioversion, especially when the patient is awake, speaking to you; may have troponin leak, microdamage of heart from cardioversion, traumatic.