Transcript Insuficiencia Hepática
Insuficiencia Hepática e Hipertensión Portal Dr. Michel Baró A
agudo necrosis Daño Hepático crónico
regeneración
Insuficiencia hepática encefalopatía hepática cirrosis hipertensión portal hepatocarcinoma
Funciones del hígado:
Digestión
Síntesis de la bilis
Detoxificación
hormonas y compuestos extraños
Biosíntesis
Síntesis factores de coagulación, albúmina
Energía del Metabolismo
Metabolismo de glúcidos, proteínas, grasas
Otras Funciones
Filtración y almacenamiento de sangre Almacenamiento de vitaminas y hierro
Tests de evaluación del hígado
“Pruebas (daño) hepáticas”
• • • • • • •
GOT/ASAT GPT/ALAT Bilirrubina total Bilirrubina directa Fosfatasas alcalinas GGT LDH
• • • •
Tests de función hepática
Albúmina Protrombina Colesterol total Amonemia
• •
Bromosulftaleína Verde indocianina
Insuficiencia hepática Disminución síntesis Disminución depuración hipoglicemia hemorragia edema ictericia encefalopatía hiperestrogenismo
Estimated prevalence of common causes of acute liver failure worldwide
Principal causes of acute liver failure
Table 7-2. Principal Causes of Acute-Liver Failure
Drug-related hepatotoxicity Acetaminophen Idiosyncratic drug reactions Indeterminate etiology Viral hepatitis Acute hepatitis B Acute hepatitis A Others (hepatitis E, others rare) Autoimmune hepatitis Ischemic liver injury Cardiogenic "shock" Other (
eg,
cocaine, methamphetamines, ephedrine) Miscellaneous causes Wilson disease Budd-Chiari syndrome Acute fatty liver of pregnancy Malignancy Veno-occlusive disease Toxinas (micetismo)
Reactivation of inactive hepatitis B after chemotherapy (A)
Acetaminophen metabolic pathway
N-acetyl-p-benzoquinoneimine
Acetaminophen toxicity nomogram
Drugs implicated in idiosyncratic liver injury leading to acute liver failure Table 7-6. Drugs Implicated in Idiosyncratic Liver Injur y Leading to Acute Liver Failure Infrequent But Not Rare Rare Combination Agents with Enhanced Toxicity
Isoniazid Sulfonamides Phenytoin "Statins" Propylthiouracil Halothane Disulfiram Valproate Amiodarone Dapsone Bromfenac * Troglitazone * Herbals † Didanosine Sustiva (efavirenz) Metformin Ofloxacin Ketoconazole Meth yldopa Allopurinol Nefazodone Quetiapine Isoflurane Lisinopril Nicotinic acid Imipramine Gemtuzumab Ecstasy (methylenedioxymethamphetamine) Labetalol Etoposide Flutamide Tolcapone Ethanol-acetaminophen Trimethoprim -sulfamethoxazole Rifampin-isoniazid *
Removed from the market.
†
Usually combinations of various herbal agents.
Acute liver failure caused by Wilson disease Table 7-7. Acute Liver Failure Caused by Wilson Disease
Most patients are younger than 30 y Non-immune hemolytic anemia is often present with high bilirubin levels (> 20 mg/dL) Kayser-Fleischer rings may be absent Alkaline phosphatase levels may be depressed Serum ceruloplasmin is typically decreased, but it may be normal in 15% of cases Serum uric acid is often very low secondary to a renal tubular defect Almost universally fatal without hepatic transplantation Female: male ratio, 2:1
Basic physical findings in acute liver failure
Cerebral edema on CT scanning in a patient with acute liver failure (A)
Physical findings in patients with advanced hepatic encephalopathy and cerebral edema
Oxygen delivery curve
Renal parameters in acute liver failure Table 7-13. Renal Parameters in Acute Liver Failure Hemodynamic changes
Hypotension High cardiac output Low systemic vascular resistance Tachycardia Possible lactic acidosis
Serum factors elevated
Renin Aldosterone Tumor necrosis factor α Prostaglandins
Urine findings
Low urine volume * Low urinary sodium Increased potassium Increased urinary urobilinogen *
Presence of high urinary volume suggests tubular necrosis.
Intraoperative photographs of related living-donor liver transplantation (A)
Intraoperative photographs of related living-donor liver transplantation (B)
Massive liver necrosis secondary to halothane anesthesia
Histologic findings in a selection of patients with acute liver failure (A)
Histologic findings in a selection of patients with acute liver failure (B). Acetoaminofeno
Histologic findings in a selection of patients with acute liver failure (C): Halotano
Histologic findings in a selection of patients with acute liver failure (D): Halotano
Histologic findings in a selection of patients with acute liver failure (E): sindrome de Reye
Histologic findings in a selection of patients with acute liver failure (F): Enfermedad de Wilson
Histologic findings in a selection of patients with acute liver failure (G): Melanoma
Histologic findings in a selection of patients with acute liver failure (H): Tuberculosis
Histologic findings in a selection of patients with acute liver failure (I): Amiloidosis
Histologic findings in a selection of patients with acute liver failure (J): Miocardiopatía
Encefalopatía hepática
NEUROTOXINAS:
•Amomio •Aumento transporte aa neutrales (BHE) •Aumento osmolalidad astrocitos •Alteración actividad electrica •Oxindole
ALTERACIÓN DE LA BHE ALTERACIÓN DE LA NEUROTRANSMISIÓN:
•GABA •Glutamato •Catecolaminas •Serotonina •Histamina •Melatonina
ALTERACIÓN DEL METABOLISMO ENERGÉTICO CEREBRAL EDEMA CEREBRAL HIPOPERFUSIÓN CEREBRAL ATROFIA CORTICAL
Encefalopatía hepática
•Amonio, Producido en: •intestino •Enterocitos •flora comensal, •H. pylori •Detoxificación •Hepática •Muscular
Glutamina (interfiere fx mitocondrial del astrocito)
•Aumenta por •Disminución del aclaramiento hepático •Shunting (TIPS)
Encefalopatía hepática
•Aumento transporte aa neutrales (BHE) •Aumento actividad transportador de L-aminoácidos •Aumento transporte de triptófano, tirosina y fenilalanina •Alteración síntesis dopamina, norepinefrina y serotonina •Aumento osmolalidad astrocitos •Acumulación de glutamina en astrocitos •Efecto sólo en ratas con shunt •Vasodilatación cerebral vía NO •Alteración actividad electrica •Inhibición de potenciales postsinápticos excitatorios e inhibitorios •Oxindole: Metabolito tóxico del triptófano
Encefalopatía hepática
ALTERACIÓN DE LA NEUROTRANSMISIÓN:
•GABA: •Producido por flora comensal del intestino y detoxificado en el hígado •Complejo neurotransmisor GABA-benzodiacepina: inhibidor SNC •Animales expuestos al amonio o manganeso aumentan
la expresión del gen del receptor de benzodiazepina del astrocito
•Glutamato •Disminución del glutamato cerebral total •Aumento del glutamato extracelular •Catecolaminas •Disminución de la norepinefrina cerebral
Ammonia and glutamate metabolism in the brain
Hepatic encephalopathy: assessment of mental status
Asterixis
Blood ammonia concentration in hepatic encephalopathy
Laennec’s cirrhosis and encephalopathy (A)
Laennec’s cirrhosis and encephalopathy (B)
Factors precipitating acute episodes of encephalopathy
(diuréticos)
Precipitants of hepatic encephalopathy in cirrhotic patients Drugs Benzodiazepines Narcotics Alcohol Increased ammonia production, absorption or entry into the brain Excess dietary intake of protein Gastrointestinal bleeding Infection Electrolyte disturbances such as hypokalemia Constipation Metabolic alkalosis Dehydration Vomiting Diarrhea Hemorrhage Diuretics Large volume paracentesis Portosystemic shunting Radiographic or surgically placed shunts Spontaneous shunts Vascular occlusion Portal vein thrombosis Hepatic vein thrombosis Primary hepatocellular carcinoma