Insuficiencia Hepática

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Insuficiencia Hepática e
Hipertensión Portal
Dr. Michel Baró A
agudo
Daño Hepático
necrosis
regeneración
Insuficiencia hepática
encefalopatía hepática
crónico
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
Tests de función hepática
•
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Albúmina
Protrombina
Colesterol total
Amonemia
• Bromosulftaleína
• Verde indocianina
hipoglicemia
hemorragia
Disminución síntesis
edema
Insuficiencia
hepática
ictericia
Disminución depuración
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
Didanosine
Ethanol-acetaminophen
Sulfonamides
Sustiva (efavirenz)
Trimethoprim-sulfamethoxazole
Phenytoin
Metformin
Rifampin-isoniazid
"Statins"
Ofloxacin
Propylthiouracil
Ketoconazole
Halothane
Meth yldopa
Disulfiram
Allopurinol
Valproate
Nefazodone
Amiodarone
Quetiapine
Dapsone
Isoflurane
*
Bromfenac
Troglitazone
Herbals †
Lisinopril
*
Nicotinic acid
Imipramine
Gemtuzumab
Ecstasy
(methylenedioxymethamphetamine)
Labetalol
Etoposide
Flutamide
Tolcapone
*
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
ALTERACIÓN DEL METABOLISMO
•Catecolaminas
ENERGÉTICO CEREBRAL
•Serotonina
•Histamina
•Melatonina
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
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