KNOW Medicine, Knowledge Needed On the Wards

Part 2/2 WARFARIN ANTICOAGULATION PEARLS In terms of Oral anticoagulants, Direct Oral Anticoagulants−DOACs should be AVOIDED for: •WEIGHT EXTREMES: <50kg (112 lbs) or >120kg (260 lbs), as efficacy is uncertain, due to unpredictable pharmacokinetics, Warfarin being preferred •ANY VALVE DISEASE, Warfarin being preferred •ACUTE RENAL FAILURE INR monitoring is unreliable in patients w/ Cirrhosis & an ↑INR. The reason cirrhotics experience a GI hemorrhage is less due to coagulopathy, mainly being due to Portal hypertension. The INR should not prevent anticoagulation when indicated, albeit you cannot use Warfarin, as you cannot follow the INR All ANTIBIOTICS decrease the Intestinal bacterial burden. Being that intestinal bacteria continually synthesize Vitamin K, their loss INCREASES the effect of Warfarin. Consider reducing Warfarin dose during antibiotic treatment Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine #warfarin

Part 1/2 WARFARIN ANTICOAGULATION PEARLS Warfarin is a VITAMIN K BLOCKER, competing w/ it for binding sites on the HEPATOCYTE enzyme, Vitamin K epoxide reductase−VKOR. This binding effectively inhibits the action of Vitamin K in the formation of BOTH: •4 PRECURSOR COAGULATION FACTORS: 2 (Prothrombin), 7, 9 & 10 •Anticoagulant proteins C & S Initially, anticoagulant proteins C & S decrease relatively faster than the various coagulation factors, causing a transient HYPERCOAGULABLE STATE lasting several days Treatment requires ~1 WEEK (corresponding to 2 half lives or a 75% reduction of Prothrombin) to reach a true THERAPEUTIC LEVEL of an International normalized ratio (INR) of 2-3. Its effects also must await the metabolism of pre−existing plasma coagulation factors, w/ normal coagulation returning within several days of discontinuation Clotting factor half lives: •Factor 2 (Prothrombin): ~3days, being the longest half life •Factor 7: 6hours, being the shortest half life •Other factors: 6hours − 1day Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine #warfarin

Part 2/2 CORONARY ARTERY ANATOMIC TESTING COMPUTED TOMOGRAPHIC CORONARY CALCIUM SCORING •Non−contrast CT of the coronary arteries, looking for CALCIUM, INDICATING ATHEROSCLEROSIS. Due to its limitations (below), Calcium scoring is meant to assess the Cardiovascular risk of ASYMPTOMATIC patients who may have risk factors, to guide the implementation of preventive medical treatment & lifestyle changes •The score, adjusted for age, gender & race, reflects total coronary calcified plaque burden Findings/ Actions: •Significant disease (≥75th percentile) indicates the need for medical treatment ± intervention if symptomatic. There is no need for repeat testing, as Statins convert soft/ higher risk plaques to more stable/ calcified plaques, possibly worsening a subsequent score •Intermediate/ any disease indicates the need for consideration of medical treatment •No disease (Zero) is reassuring. Consider repeating @ 5 years Limitations: •Does not detect soft/ non−calcified plaques, (which are more vulnerable to rupture) or an associated acute thrombus (also being non−calcified). This limitation means that even a patient w/ a Calcium score of zero could have significant coronary artery disease or an acute thrombus. For this reason, it is not used to assess for suspected symptomatic disease/ acute pain, possibly underestimating the degree of luminal obstruction With that, what are its relative benefits? •It is NON−CONTRAST •it is NON−GATED, so doesn’t require pulse lowering medications to be tolerated Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine

Part 1/2 CORONARY ARTERY ANATOMIC TESTING Provides information on ATHEROSCLEROTIC PLAQUE BURDEN, but does not inform of a functional consequence (ischemia). The finding of significant disease can indicate the need for medical treatment (Aspirin/ Statin/ improved blood pressure control), & can be a powerful motivator for patient lifestyle change (weight management, aerobic exercise, smoking cessation, dietary changes, avoidance of excessive alcohol, stress management, regular health screenings) CORONARY COMPUTED TOMOGRAPHIC ANGIOGRAPHY−CCTA •CT w/ arterial phase contrast, being gated (synchronized to the ECG) •Standard catheter angiography simply shows the luminal anatomy, w/ possible obstruction. However, plaque growth is initially outward, into the vessel wall, w/ subsequent inward growth into the lumen. With that, the lumen can be unchanged/ minimally stenosed via catheter angiography, even w/ significant coronary atherosclerosis/ plaque burden. A CTA will detect all phases of plaque growth Findings/ Actions: •Significant disease (≥50% Left main stenosis or ≥70% major artery stenosis) indicates the need for medical treatment ± intervention if symptomatic •Intermediate/ any disease indicates the need for consideration of medical treatment •No disease is reassuring. Consider repeating @ 5 years Limitations: •Prior stents may create an imaging artifact, making interpretation difficult •Being that the images are obtained during coronary arterial filling (diastole), the patient must be able to tolerate a rate lowering medication used to extend diastole (β1 selective receptor blockers or non−dihydropyridine Calcium channel blockers) •Obesity may cause poor image quality due to tissue density Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine

LOW BACK PAIN The vast majority of non−traumatic low back pain complaints (>90%) are rarely serious & usually self−limited, being due to either: •Lumbosacral muscle, ligament or tendon injury •Radicular pain (ex: Sciatica) Although benign, there is associated significant pain and restriction of movement, being DIAGNOSES OF EXCLUSION, as life & limb threatening emergencies must first be ruled out EMERGENT ETIOLOGIES •INFECTION: Osteomyelitis, Spinal epidural abscess •FRACTURE, either traumatic or pathologic, causing Cord compression •CANCER, causing Cord compression •DISK HERNIATION, causing Cord compression •VASCULAR −Abdominal Aortic aneurysm, either due to distention, leak or rupture/ dissection −Retroperitoneal hemorrhage −Spinal epidural hematoma EMERGENT RISK FACTORS •History of CANCER •History of TRAUMA •Coagulopathy •Previous spinal intervention •Immunosuppression via any of the following: −Elderly (≥65y) −Diabetes mellitus −Alcoholism −Cirrhosis −Hematologic malignancy −HIV infection/ AIDS −Malnutrition/ hypoproteinemia −Medications: Chemotherapy, Chronic Glucocorticoid use, Immunomodulating medications −Neutropenia −Renal failure −Solid organ or Stem cell transplant EMERGENT FINDINGS •FEVER •AUTONOMIC DYSFUNCTION: ALWAYS consider Spinal cord compression/ disease with Autonomic dysfunction −BOWEL or BLADDER retention or incontinence. If the bowel & urinary bladder are spared, the Spinal cord is unlikely to be involved −Erectile dysfunction •UPPER MOTOR NEURON DYSFUNCTION via Lower extremity WEAKNESS or HYPERreflexia •Saddle area anesthesia (buttocks or anus) •Pain worsened on relaxation/ at rest •Percussion tenderness over the involved vertebra(e) Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine #lowbackpain

The importance of the ALVEOLAR − ARTERIAL O2 PRESSURE GRADIENT For use in patients w/ UNEXPLAINED HYPOXEMIA, allowing for determining the cause as being either INTRApulmonary (causing an increased O2 pressure gradient via a ventilation/ perfusion mismatch) or EXTRApulmonary (having a normal gradient, lacking a ventilation/ perfusion mismatch) The Alveolar−arterial O2 pressure difference, termed the A−a gradient (in mmHg) represents the MEASURED ARTERIAL partial pressure of O2 (PaO2) subtracted from the CALCULATED ALVEOLAR partial pressure of O2 via the following formula, thus expressing THE EFFICIENCY WITH WHICH A LUNG EXCHANGES OXYGEN from the Alveoli to the pulmonary capillary beds Alveolar O2 pressure on ROOM AIR: 150 − (PaCO2 ÷ 0.8 − PaO2 Alveolar O2 pressure on Supplemental O2: (713 X FiO2) − (PaCO2 ÷ 0.8 − PaO2 In a perfect lung, there should be no difference. However, the slight ventilation/ perfusion mismatch that occurs in a normal lung causes a mild difference to occur via the following formulas: AGE ADJUSTED NORMAL A−a gradient = (Age ÷ 4) + 4 Simplified normal gradient is UP TO 20 Supplemental O2: Every 10% is expected to increase the A−a gradient by 5mmHg A WIDENED GRADIENT in the presence of hypoxemia indicates ↑VENTILATION/ PERFUSION MISMATCH (impaired gas diffusion) from ANY CARDIOPULMONARY DISORDER (Asthma/ COPD, CHF, Pneumonia, Pulmonary embolism, Interstitial lung disease) A NORMAL GRADIENT in the presence of hypoxemia indicates SOLE HYPOVENTILATION (CNS disease, Neuromuscular disease, Obesity hypoventilation syndrome, Anesthetics/ Sedatives), as these can affect the ability to adequately ventilate without causing a ventilation/ perfusion mismatch Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine #aagradient

CONSIDERATIONS IN THE TREATMENT OF DIABETES MELLITUS TYPE 2 Most patients w/ Diabetes mellitus Type 2 eventually require multi−drug therapy to maintain target glycemic control If maximal doses of 1−2 medications do not achieve target goals, consider adding INSULIN INSULIN is the medication of choice during PREGNANCY because it does not cross the Placenta. Data on the safety of other antihyperglycemic medications during pregnancy remain insufficient to recommend their use Diabetic medications cause HYPOGLYCEMIA when Insulin level is increased via administration of either Insulin or its secretagogues (Sulfonylureas & Meglitinides). Otherwise, medications not increasing Insulin level RARELY cause HYPOGLYCEMIA when used as monotherapy Glycosylated Hemoglobin effects: •Diet & exercise: 0.5−2%↓ •Oral hypoglycemic medications: ~1%↓ •Insulin: ~2%↓ Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine #diabetes

Part 2/2 CARBON MONOXIDE POISONING DIAGNOSIS Standard Oxygen measurements (FiO2 & PaO2) will be FALSELY NORMAL Arterial blood gas analysis will show a normal PaO2, reflecting O2 dissolved in blood, not that being bound to Hemoglobin (dissolved O2 comprises only 2% of arterial O2) •However, ARTERIAL BLOOD GAS w/ CO−OXIMETRY enables the DIRECT MEASUREMENT of various forms of Hemoglobin (OxyHemoglobin, DeoxyHemoglobin, CarboxyHemoglobin, or MetHemoglobin) Pulse Oximetry, will show a falsely normal SaO2 as CarboxyHemoglobin has the same absorbance spectrum of OxyHemoglobin−HbO2 •However, CO−OXIMETRY, enables the measurement of the concentration of various forms of Hemoglobin (OxyHemoglobin, DeoxyHemoglobin, CarboxyHemoglobin, or MetHemoglobin) via their ABSORBANCE SPECTRUMS, being akin to OxyHemoglobin measurement via a Pulse oximeter. It however, does not require a pulsatile flow, able to measure both arterial or venous levels •VISUAL INDICATOR: BRIGHT, CHERRY RED colored blood due to the bright red color of CarboxyHemoglobin TREATMENT Involve a Toxicologist (Poison control) OXYGEN SUPPLEMENTATION, until the COHb level is <10%, w/ the half life of CarboxyHemoglobin being: •5 hours on room air •1.5 hours on a Non−rebreather mask (100% O2) •0.5 hours on HYPERBARIC OXYGEN TREATMENT-HBOT (100% O2 under supra−atmospheric conditions). The goal of hyperbaric treatment is to both avoid acute hypoxemic neuro-cardiac failure, as well as reduce the probability of chronic neurologic sequelae. It is usually utilized @: −Moderate or Severe toxicity (see Part 1/2) −COHb level >25% −Pregnancy w/ COHb level >15% or fetal distress, as the affinity of fetal Hemoglobin for Carbon monoxide is even greater than adult Hemoglobin Contraindications to Hyperbaric oxygen •Untreated Pneumothorax, as the increased pressure can worsen the lung collapse. Chest tube placement should be considered to allow for HBOT Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine #carbonmonoxide

Part 1/2 CARBON MONOXIDE POISONING Typically a disease of the Winter season, due to the increased use of heating systems. Toxicity ranges from constitutional symptoms to hypoxemic neurologic & cardiovascular collapse PATHOPHYSIOLOGY Carbon monoxide is a colorless, odorless, tasteless gas produced by the incomplete combustion of any Carbon product. Basically, Carbon monoxide is produced from burning anything or from any gas flame that is not completely efficient, highlighting the importance of proper ventilation & maintenance of combustion machinery/ appliances Most cases occur due to the indoor use of gas powered generators, faulty home heaters or campstoves, as these lead to the accumulation of Carbon monoxide in ENCLOSED SPACES where ventilation is inadequate Some occur due to suicide attempts using car exhaust It is the most common cause of death from a fire, especially closed space fires Intoxication causes Oxygen displacement from the Iron binding sites of Hemoglobin (having an affinity 250X that of O2), creating CarboxyHemoglobin−COHb→HYPOXEMIA, as it is deoxygenated hemoglobin Normal CarboxyHemoglobin level is <5%, but may be as high as 10% in smokers, or persons chronically exposed to vehicle/ gas machinery emission fumes MILD toxicity @ ~ 15−30%, mimicking a VIRAL ILLNESS •Headache •Lethargy •Lightheadedness •Abdominal pain/ Nausea/ Vomiting/ Diarrhea MODERATE toxicity @ ~ 30−50% •Delirium (acutely altered mental status) •Syncope •Seizure SEVERE toxicity @ > ~ 50%, approaching DEATH •Coma •Cardiac arrest Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine #carbonmonoxide

Part 2/2 SINUS TACHYCARDIA: A DYSRHYTHMIA of faster than normal heart rate (Atrial & ventricular rate of ≥100, typically ranging from 100−180bpm, w/ rates usually below 150bpm) SINUS (node) RHYTHM requires regularly appearing P waves of similar morphology & MUST have a positive/ upright deflection in leads 1, 2 & aVF ALL of the following are considered TACHYDYSRHYTHMOGENIC, meaning that they may incite or worsen an underlying tachydysrhythmia (ex: Atrial fibrillation) DIFFERENTIAL DIAGNOSIS: Based on an INCREASED Autonomic SYMPATHETIC TONE •FEVER, w/ the appropriate temperature−pulse relationship being 101°F → 100bpm. Thereafter, every 1°F ↑ causes an increase of 10bpm (ex: 102°F → 110bpm, 103°F → 120bpm, etc…). Keep in mind that this relationship does not account for rate controlling medications the patient may be taking •HEART FAILURE •HYPOVOLEMIA/ Dehydration •HYPOXEMIA •INFLAMMATION/ Infection/ Sepsis •PAIN •PULMONARY EMBOLISM •Postoperative, via tissue damage ± related fever &/or pain •Alcohol withdrawal •Anemia •Anxiety •Autonomic neuropathy causing ↓Parasympathetic tone •Excitement •Exercise •Hyperthyroidism •Pregnancy •Caffeine •Nicotine •Adrenergic medications: Catecholamines, β1 receptor agonists, Ephedrine, Methylxanthines (Aminophylline, Theophylline), Phenylpropanolamine, Yohimbine •Illicit drug use: Amphetamines, Cocaine, Ecstasy Visit our Website/ Medical wards app knowmedicine.net #medicalstudent #medicalresident #meded #medicalschool #internalmedicine #medicaleducation #medstudent #imresidency #medicalapp #foamed #hospitalist #hospitalmedicine #tachycardia