#Pathophys #Acute #LiverFailure #Elevated #ICP #IntracranialPressure

Etiology of Acute Liver Failure – bolded entities are most likely to cause AST/ALT in the 1000s #Diagnosis #Acute #LiverFailure #Transaminitis #Differential

Mechanical Ventilation in High Intracranial Pressure (ICP) - Maintain PEEP < ICP - Dealing with ICP - HOB effect on ICP - Post-intubation Management #Mechanical #Ventilation #High #Intracranial #Pressure #ICP #Elevated #management #pulmonary #criticalcare

Intracranial Hemorrhage (ICH) and Increased Intracranial Pressure (ICP) - Pathophysiology ICH Management: 1. Manage Blood Pressure • Spontaneous ICH and SAH BP target: < 140-160 • Avoid vasodilating agents (nitro-) because they increase cerebral blood volume and ICP 2. Neuroprotective Intubation • Before: +/- local lidocaine, +/- pre-treatment with Fentanyl 3mcg/kg then wait 3min, pre-ox (goal O2 >95%), paralysis + sedation • During: Minimize attempts, use glidescope • After: Minimize PEEP, EtCO2 35-40, Ensure adequate sedation 3. Address Coagulopathy • DOACs: Octaplex • Warfarin: Octaplex + Vitamin K • Heparin: Protamine Sulfate • If platelets < 100: consider platelet transfusion 4. Maintain Normals: Glucose, Temp 5. Manage ICP and Seizures if needed ICP Physiology: CO2: • Low CO2 = constricts BV = temporarily reduces ICP (but also reduces CPP) • High CO2 = dilated BV = raises ICP O2: • Hypoxia = dilated BV = raise ICP (dilates BV directly and via lactic acid formation) BP: • Hypotension = reactive dilated BV = raise ICP • Hypertension = potential expansion of bleed • CPP = MAP - ICP. Target MAP: 80. Why? Target CPP 60. High ICP: 20. Temp: • Increased metabolic demand = increased cerebral blood flow - raise ICP Osmotic Agents: • Osmotic agents = increase osmolarity of blood = water leaves brain cells Dr. Sarah Foohey @SarahFoohey #Intracranial #Hemorrhage #ICH #elevated #Intracranial #Pressure #ICP #Pathophysiology #neurology #neurosurgery #management

Commonly Observed Laboratory Findings in Hepatic / Liver Failure - Elevated conjugated and unconjugated bilirubin - Defects in conjugation and excretion of bilirubin - Hypoalbuminemia - Decreased albumin synthesis - Elevated ALT and AST - Elevations of —100-fold with acute liver failure; rapid decline to normal can indicate permanent loss of hepatocytes; in chronic liver disease, ALT and AST can be normal - Hyperammonemia - Impaired urea cycle - Hypoglycemia - Impaired gluconeogenesis in the fasting state after glycogenolysis has exhausted liver glycogen stores - Prolonged PT - Decreased production of clotting factors, malabsorption of vitamin K, and decreased clearance of fibrin-split products - Thrombocytopenia - As a result of DIC or thrombopoietin deficiency - Anemia - Bone marrow suppression leads to chronic anemia; blood loss from esophageal varices - Elevated creatinine and BUN - Decreased urine output; the hepatorenal syndrome may be present; elevated BUN and a normal creatinine can indicate a GI bleed #LiverFailure #Hepatic #Hepatology #Laboratory #Diagnosis #Testing

Early Events in Acute GVHD #Pathophys #Honc #GVHD #GraftVersusHostDisease #NEJM

Liver Disease in Pregnancy Intrahepatic Cholestasis of Pregnancy (ICP) • Onset/Trimester: 25-32 weeks • Typical clinical features: Pruritus, Mild jaundice, Elevated bile acids, Vitamin K ↓ • Aminotransferases: Mild to 10-20-fold elevation, Bilirubin: <5 mg/dL • Hepatic imaging: Normal • Histology: Normal-mild cholestasis, no necrosis HELLP Syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelets) • Onset/Trimester: 3 or post-partum • Typical clinical features: Hemolysis, Thrombocytopenia(<50,000 often) • Aminotransferases: Mild to 10-20-fold elevation, Bilirubin: <5 mg/dL unless massive necrosis • Hepatic imaging: Hepatic infarcts, Hematomas, rupture • Histology: Patchy/extensive necrosis and hemorrhage Acute Fatty Liver of Pregnancy (AFLP) • Onset/Trimester: 3 or post-partum • Typical clinical features: Liver failure with coagulopathy, encephalopathy, hypoglycemia. DIC • Aminotransferases: 300-500 typical but variable ++, Bilirubin: often <5 mg/dL, higher if severe • Hepatic imaging: Fatty infiltration • Histology: Microvesicular fat in zone 3 BWH Medicine Chiefs @BrighamChiefs #Liver #Disease #Pregnancy #hepatology #obstetrics #hepatitis #comparison #differential #diagnosis #icp #HELLP #AFLP

Nebulized Tranexamic Acid for acute treatment of stable hemoptysis - Mike O'Brien @MikeEMPharmD #Pharmacology #EBM #Management #Dosing #Pathophys #NebulizedTXA #TranexamicAcid #Hemoptysis

Non-ACS Myocardial Injury - Elevated Troponin Differential Diagnosis and Workup Algorithm • Chronic Myocardial Injury: End Stage Renal Disease, Structural Heart Disease (ie HCM), Infiltrative Process (ie Sarcoid), Chronic Inflammation • Globally Abnormal or Normal - Impaired O2 Delivery (Pre-Coronarv): Shock, Hypoxemia, Anemia - Global Direct Iniury (Post-Coronarv): Stress (ie Sepsis-induced CM), Metabolic (ie acidosis), Tachycardia-induced HF, Severe Volume Overload/HTN • Focal, Non-Vascular Distribution: Acute Myocarditis, Catecholamines (Takutsubo), Toxins, Contusion/Trauma • No Obstruction (MINOCA): Transient Intra-Coronary Process (ie Spasm or Embolism), Microvascular CAD, Focal Direct Injury (Post-Coronary) • Acute Occlusion • Stable CAD Dr. Johnny Hourmozdi @JHourmozdi #Myocardial #Injury #Elevated #Troponin #Differential #Diagnosis #Algorithm

The protein complex mTORC1 is a convergence point for multiple signaling pathways that control cell growth and proliferation. These pathways sense the presence or absence of growth factors, hormones, and cytokines through cell-surface receptors, including receptor tyrosine kinases (e.g., INSR and EGFR) and G-protein–coupled receptors (GPCRs), or intracellular nutrients and energy (e.g., amino acids and ATP). Within the upstream signaling network are many oncogenes (orange) and tumor suppressors (pink) that are frequently mutated in sporadic cancers or that are associated with a variety of genetic overgrowth, tumor, and epilepsy syndromes (white boxes) characterized by elevated mTORC1 activation. #Pathophys #mTOR #oncogenes #TumorSuppressors #NEJM

Creatine Kinase - Causes of Elevated CK Levels Acute CK Elevation (Pain > Weakness): • RHABDOMYOLYSIS - Drugs: cocaine, amphetamines, alcohol - Medications: statins, fibrates, colchicine, daptomycin - Illness: viral (COVID19, CMV/EBV, HIV), clostridial spp, mycoplasma, staph, strep) - Seizures: Trauma, burns, hyperthermia, immobility • Critical Illness Myopathy (ICU, steroids, mechanical ventilation) • Myocardial infarction, Acute renal injury, Strenuous exercise Subacute to Chronic Causes (Weakness > Pain): • PROXIMAL MUSCLE WEAKNESS - Endocrine: Hypo/hyperthyroidism, acromegaly - Electrolytes: hypo- phos, kalemia, calcemia, natremia - Muscular dystrophy - Metabolic Myopathies - Neuromuscular disorders - Vit D/E deficiency - Medications- Statins, fibrates, colchicine, daptomycin - Chronic Illness: HIV, Trichinella, toxoplasmosis - Inflammatory myopathy: dermatomyositis, polymyositis, necrotizing myopathy - Autoimmune: mixed connective tissue disorder, SLE • PROXIMAL AND DISTA: Inclusion body myositis • ASYMPTOMATIC: Macro CK Ann Marie Kumfer @AnnKumfer #Creatine #Kinase #Elevated #CK #differential #diagnosis #rhabdomyolysis