Insuficiencia Hepática

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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”

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GOT/ASAT GPT/ALAT Bilirrubina total Bilirrubina directa Fosfatasas alcalinas GGT LDH

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Tests de función hepática

Albúmina Protrombina Colesterol total Amonemia

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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:

AmomioAumento transporte aa neutrales (BHE)Aumento osmolalidad astrocitosAlteración actividad electricaOxindole

ALTERACIÓN DE LA BHE ALTERACIÓN DE LA NEUROTRANSMISIÓN:

GABAGlutamatoCatecolaminasSerotoninaHistaminaMelatonina

ALTERACIÓN DEL METABOLISMO ENERGÉTICO CEREBRAL EDEMA CEREBRAL HIPOPERFUSIÓN CEREBRAL ATROFIA CORTICAL

Encefalopatía hepática

Amonio, Producido en:intestino Enterocitosflora comensal, H. pyloriDetoxificaciónHepáticaMuscular

Glutamina (interfiere fx mitocondrial del astrocito)

Aumenta porDisminución del aclaramiento hepáticoShunting (TIPS)

Encefalopatía hepática

Aumento transporte aa neutrales (BHE)Aumento actividad transportador de L-aminoácidosAumento transporte de triptófano, tirosina y fenilalaninaAlteración síntesis dopamina, norepinefrina y serotoninaAumento osmolalidad astrocitosAcumulación de glutamina en astrocitosEfecto sólo en ratas con shuntVasodilatación cerebral vía NOAlteración actividad electricaInhibición de potenciales postsinápticos excitatorios e inhibitoriosOxindole: Metabolito tóxico del triptófano

Encefalopatía hepática

ALTERACIÓN DE LA NEUROTRANSMISIÓN:

GABA: Producido por flora comensal del intestino y detoxificado en el hígadoComplejo neurotransmisor GABA-benzodiacepina: inhibidor SNCAnimales expuestos al amonio o manganeso aumentan

la expresión del gen del receptor de benzodiazepina del astrocito

GlutamatoDisminución del glutamato cerebral totalAumento del glutamato extracelularCatecolaminasDisminución 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