012A - Liver.pdf

LIVER KHRISTINE S. OLITA, MD  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts...

LIVER KHRISTINE S. OLITA, MD  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION EVALUATION OF THE LIVER Liver function Hepatic injury Biliary obstruction Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. RADIOLOGIC EVALUATION OF THE LIVER ULTRASOUND Excellent for biliary pathology and Limitations: focal liver lesions Incomplete imaging of the liver (dome or beneath ribs) Incomplete visualization of lesion Useful initial imaging test of the liver boundaries Obesity and overlying bowel gas may Inexpensive interfere with image quality Widely available No radiation exposure Well-tolerated by patients Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. RADIOLOGIC EVALUATION OF THE LIVER ULTRASOUND q Doppler Ultrasound Visualization of blood vessels Velocity and direction of blood flow Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. RADIOLOGIC EVALUATION OF THE LIVER ULTRASOUND q Intraoperative ultrasound Gold-standard for detecting liver lesions Real-time accurate information for surgical planning ü Tumor staging ü Visualization of intrahepatic vascular structures ü Guidance of resection plane ü Image-guided procedures (e.g. biopsy, radiofrequency ablation) Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. RADIOLOGIC EVALUATION OF THE LIVER COMPUTED TOMOGRAPHY SCAN Detailed morphologic information on the number, size, distribution, and vascularity of liver lesions High sensitivity Arterial, venous, delayed phases Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. RADIOLOGIC EVALUATION OF THE LIVER COMPUTED TOMOGRAPHY SCAN Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. RADIOLOGIC EVALUATION OF THE LIVER MAGNETIC RESONANCE IMAGING Higher soft tissue contrast resolution Magnetic resonance Excellent depiction of fluid-containing cholangiopancreatography structures (MRCP) No ionizing radiation o Rapid, noninvasive o Visualization of the following: q Biliary tree Dilated ducts and level of occlusion q Pancreatic duct Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION INFECTIONS OF THE LIVER LIVER ABSCESS PYOGENIC AMOEBIC ETIOLOGY Acute appendicitis Entamoeba histolytica Diverticulitis Impaired biliary drainage Subacaute bacterial endocarditis Indwelling catheters, Dental works E. coli, S. faecalis, Klebsiella, Proteus vulgaris, Bacteroides fragilis LOCATION Right liver lobe Supero-anterior aspect of the right lobe, near the diaphragm Necrotic central portion Anchovy paste or chocolate sauce SYMPTOMS RUQ pain and fever RUQ pain, fever, hepatomegaly Jaundice (1/3) Jaundice (not common) Leukocytosis History of travel Elevated ESR, Alkaline phosphatase Mildly elevated Alkaline phosphatase Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. NFECTIONS OF THE LIVER LIVER ABSCESS PYOGENIC AMOEBIC ULTRASOUND Round or oval hypoechoic Non-specific lesions Well-defined borders Variable internal echoes CT SCAN Hypodense Well-defined low density round Peripheral enhancement lesions that have enhancement of the wall Air-fluid levels (gas- Ragged with peripheral zone of producing organism) edema Septated central cavity MRI High sensitivity Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. NFECTIONS OF THE LIVER LIVER ABSCESS PYOGENIC AMOEBIC CULTURE 50% will yield causative Fluorescent antibody test agents MANAGEMENT Empiric therapy (8 weeks) Metronidazole 750 mg (Antibiotics) three times a day for 7 to 10 days (Surgical options) Open or laparoscopic Aspiration and drainage drainage o Large abscess Hepatic resection of necrosis o Failure of medical therapy o Superinfection of left lobe Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION INFECTIONS OF THE LIVER HYDATID DISEASE Hydatid disease o RUQ dull pain or mass o Echinococcus granulosus o CT Scan: Hypodense lesion with distinct wall o Dogs (Hosts) à Ova-containing feces contaminate grass and farmlands o Sheep, cattle, pigs, humans o Management: (Intermediate hosts) ü Laparoscopic or open complete cyst removal with instillation of scolicidal agent o Enzyme-linked immunosorbent assay (ELISA) (85% positivity rate) ü Hepatic resection (if cystectomy not possible) ü Albendazole Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. INFECTIONS OF THE LIVER ASCARIASIS Ascaris lumbricoides Ultrasound and ERCP Retrograde locomotion of ova (GIT to bile o Linear filling defects in the bile ducts ducts) Clinical presentation: Management: ü CBD obstruction and intrahepatic o Endoscopic extraction of worms and stones Anti-parasitics ü Biliary colic o Piperazine citrate ü Acute cholecystitis o Mebendazole or Albendazole ü Acute pancreatitis ü Hepatic abscess o Surgical extraction (If failed ERCP) Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. INFECTIONS OF THE LIVER SCHISTOSOMIASIS Hepatic schistosomiasis Fecalysis Emboli of the ova in the intestines reach Serologic tests the liver via the mesenteric venous system Mildly elevated alkaline phosphatase Decreased serum albumin (3) stages of clinical symptoms: 1. Itching after the entry of cercariae Management: through the skin Praziquantel 40 to 75 mg/kg as a single 2. Fever, urticaria, and eosinophilia dose (Treatment of choice) 3. Hepatic fibrosis followed by Endoscopic variceal ligation (GI presinusoidal portal hypertension Bleeding) Distal splenorenal shunt or gastric devascularization and splenectomy (Refractory) Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION  EVALUATION OF INCIDENTAL LIVER MASS Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION BENIGN LIVER LESIONS CLINICAL PRESENTATION CYST Most common Cystic disorders of the liver: o Congenital cyst o Biliary cysatdenoma o Polycystic liver disease o Caroli’s disease (Type V Choledochal Cyst) BILE DUCT HAMARTOMA Small lesions found at the surface of the liver (about 2-4mm) Firm, yellow, smooth Management: Excision biopsy Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION BENIGN LIVER LESIONS CLINICAL PRESENTATION FOCAL NODULAR HEMANGIOMA ADENOMA HYPERPLASIA Most common benign solid Usually solitary Hyperplastic response to liver mass Premenopausal women anomalous artery Most are incidental 3rd decade of life Premenopausal women F>M Prior estrogen (oral contraceptives) Does not rupture Significant risk for Does not rupture spontaneously spontaneous spontaneously intraperitoneal bleeding Risk for malignant No malignant transformation transformation to HCC Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  BENIGN LIVER LESIONS CT SCAN Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. BENIGN LIVER LESIONS CT SCAN FOCAL NODULAR HEMANGIOMA ADENOMA HYPERPLASIA Asymmetric nodular Sharply defined borders Well-circumscribed with peripheral enhancement central scar Centripetal enhancement Hypervascular Homogenous hypervascular fill-in over time enhancement (Arterial) enhancement (Arterial) Hypodense/ Isodense Hypodense/ Isodense (Venous) (Venous) Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. BENIGN LIVER LESIONS MANAGEMENT FOCAL NODULAR HEMANGIOMA ADENOMA HYPERPLASIA Most common benign solid Usually solitary Incomplete imaging (dome and liver mass Premenopausal women ribs) Most are incidental 3rd decade of life Obesity, underlying bowels F>M Prior estrogen (oral contraceptives) Does not rupture Significant risk for spontaneous Does not rupture spontaneously spontaneously intraperitoneal bleeding Risk for malignant No malignant transformation transformation to HCC Conservative Reassurance and observation Surgical resection (>4-5cm) Resection (if symptomatic) Resection (if symptomatic) Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer Hepatic Resections ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION MALIGNANT NEOPLASMS OF THE LIVER HEPATOCELLULAR CARCINOMA Mostly asymptomatic Recommended for screening: Advanced HCC o Liver cirrhosis o Jaundice, weight loss, malaise, o Viral (Hepatitis B and C) upper abdominal pain o Non-viral (e.g. Alcoholic cirrhosis, NAFLD, NASH) Screening: o Hepatitis B carrier without cirrhosis o Liver ultrasound o Stage IV primary biliary cholangitis § Sensitivity 58-89%, Specificity >90%) o Alpha 1 antitrypsin deficiency o AFP § 100ng/mL (cut-off) § (Specificity 99%, Sensitivity 31%) § Not frequently elevated in early-stage disease European Association for the Study of Liver (EASL) Clinical practice guidelines: Management of hepatocellular carcinoma. 2018 NCCN Guidelines for hepatobiliary cancers. 2019 MALIGNANT NEOPLASMS OF THE LIVER HEPATOCELLULAR CARCINOMA Ultrasound screening every 6 months AFP (optional) Abdominal multiphasic CT/MRI (Marrero, et al 2018) o Elevated AFP o >10mm nodule (US) European Association for the Study of Liver (EASL) Clinical practice guidelines: Management of hepatocellular carcinoma. 2018 NCCN Guidelines for hepatobiliary cancers. 2019 NCCN Guidelines for hepatobiliary cancers. 2019 MALIGNANT NEOPLASMS OF THE LIVER HEPATOCELLULAR CARCINOMA Multiphasic abdominal CT/MRI o For patient with incidental liver mass/nodule found on US o Characteristics: ü Intense arterial uptake or enhancement ü Contrast washout ü Hypointense (delayed venous phase) PET-CT o useful for predicting prognosis (Sun, et. al. 2016), but low sensitivity for HCC detection (Lin, et. al. 2012; Park, et. al. 2008) European Association for the Study of Liver (EASL) Clinical practice guidelines: Management of hepatocellular carcinoma. 2018 NCCN Guidelines for hepatobiliary cancers. 2019 NCCN Guidelines for hepatobiliary cancers. 2019 European Association for the Study of Liver (EASL) Clinical practice guidelines: Management of hepatocellular carcinoma. 2018 MALIGNANT NEOPLASMS OF THE LIVER HEPATOCELLULAR CARCINOMA Criteria for resection: Adequate liver function o Child-Pugh A o Selected Child-Pugh B without portal hypertension Solitary mass without major vascular invasion Adequate liver remnant ü At least 20% without cirrhosis ü At least 30-40% in Child-Pugh A cirrhosis MALIGNANT NEOPLASMS OF THE LIVER HEPATOCELLULAR CARCINOMA Criteria for resection: Adequate liver function o Child-Pugh A o Selected Child-Pugh B without portal hypertension Solitary mass without major vascular invasion Adequate liver remnant ü At least 20% without cirrhosis ü At least 30-40% in Child-Pugh A cirrhosis Modified Barcelona Clinic Liver Cancer (BLCL) staging system and treatment strategy European Association for the Study of Liver (EASL) Clinical practice guidelines: Management of hepatocellular carcinoma. 2018 MALIGNANT NEOPLASMS OF THE LIVER HEPATOCELLULAR CARCINOMA Neoadjuvant or adjuvant therapies are not recommended following liver resection o No proven outcomes on improvement Follow-up after resection with curative intent is recommended o High rates of treatable recurrence  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION  Improved outcomes: MALIGNANT NEOPLASMS OF THE LIVER o Histologically negative margins CHOLANGIOCARCINOMA o Concomitant hepatic resection o Well-differentiated tumor histology 2nd most common primary malignancy of Prognostic factors affecting survival: the liver o Absence of mucobilia o Nonpapillary tumor type Adenocarcinoma of the bile ducts o Tumor of advanced stage Peripheral (Intrahepatic) and Central o Nonhepatectomy (Extrahepatic) o Lack of postoperative chemotherapy Klatskin Tumor o Hilar cholangiocarcinoma Factors denoting poor survival: o Painless, obstructive jaundice o Vascular invasion Management: o Positive margins Surgical resection (in the absence of o Multiple tumors primary sclerosing cholangitis) Chemoradiation Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  Improved outcomes: MALIGNANT NEOPLASMS OF THE LIVER o Histologically negative margins CHOLANGIOCARCINOMA o Concomitant hepatic resection o Well-differentiated tumor histology 2nd most common primary malignancy of Prognostic factors affecting survival: the liver o Absence of mucobilia o Nonpapillary tumor type Adenocarcinoma of the bile ducts o Tumor of advanced stage Peripheral (Intrahepatic) and Central o Nonhepatectomy (Extrahepatic) o Lack of postoperative chemotherapy Klatskin Tumor o Hilar cholangiocarcinoma Factors denoting poor survival: o Painless, obstructive jaundice o Vascular invasion Management: o Positive margins Surgical resection (in the absence of o Multiple tumors primary sclerosing cholangitis) Chemoradiation Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION MALIGNANT NEOPLASMS OF THE LIVER METASTATIC COLORECTAL CANCER 50-60% of colorectal cancer patients will Surgical options: develop liver metastases o Neoadjuvant chemotherapy o Portal vein embolization o Two-stage hepatectomy o Simultaneous ablation Resectability is no longer defined by o Resection of extrahepatic tumor what is actually removed, but indications for hepatic resection now Predictors of poor outcome: center on what will remain after o Node-positive primary resection o Disease-free interval 1 tumor o Tumor size >5 cm o CEA >200 ng/mL Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. TREATMENT OPTIONS FOR LIVER CANCER Hepatic resection Liver transplantation Radiofrequency ablation Ethanol ablation, cryosurgery, and microwave ablation Chemoembolization Yttrium-90 Microspheres Stereotactic radiosurgery Systemic chemotherapy Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION HEPATIC RESECTIONS Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York. Brunicardi, F., et.al. 2019. Schwartz’s Principles of Surgery, 11th edition. Mc-Graw Hill Education. New York.  EVALUATION OF INCIDENTAL LIVER MASS OUTLINE BENIGN LIVER LESIONS Hepatic Cysts Biliary Cystadenoma Hemangioma EVALUATION OF THE LIVER Adenoma INFECTIONS OF THE LIVER Focal Nodular Hyperplasia Pyogenic Liver Abscess Amoebic Liver Abscess MALIGNANT LIVER LESIONS Hydatid Disease Hepatocellular Carcinoma Ascariasis Cholangiocarcinoma Schistosomiasis Metastatic Colorectal Cancer HEPATIC RESECTIONS ACUTE LIVER FAILURE LIVER CIRRHOSIS PORTAL HYPERTENSION ACUTE LIVER FAILURE Etiology: Approach: o Viral hepatitis (B, A, E) o Admit and monitor at ICU o Drug-induced (Acetaminophen) o Liver biopsy Clinical presentation: o If acetaminophen overdose: o Jaundice o Discontinue acetaminophen o Encephalopathy o Activated charcoal o Hepatic coma o N-acetylcysteine o Creatinine >2mg/dL o Arterial pH