3. Examen de LÍQUIDO
Gradiente sero-ascítico de Albúmina
>1.1 g indica hipertensió n portal.
DD con otras causas
Numero polimorfonucleares:
> 250 mm3 indica infecció n (PBE)
Cultivo en frasco de hemocultivo (>sensibilidad)
Proteínas totales:
< 1g/dl factor de riesgo para PBE
Gradiente sero-ascítico de Albúmina
>1.1 g indica hipertensió n portal.
DD con otras causas
Numero polimorfonucleares:
> 250 mm3 indica infecció n (PBE)
Cultivo en frasco de hemocultivo (>sensibilidad)
Proteínas totales:
< 1g/dl factor de riesgo para PBE
21. Factors precipitating acute episodes of encephalopathyFactors precipitating acute episodes of encephalopathy
(diuréticos)(diuréticos)
22. Cirrosis
Hipertensió n portal
GPVH > 10 mmHg
Clínicamente significativa:
Valor Pronostico
Predice Desarrollo de Complicaciones
Ripoll Hepatology 2006
23. Cirrosis compensada Ascitis
tiempo
Circulación hiperdinámica (vasodilatación GastoCardiaco
Hipovolemia efectiva Retención de Na
S.ReninaAngAldosterona SNS
HAD Hiponatremia
SHR GastoCardiaco
DISFUNCIÓN CIRCULATORIA EN LA CIRROSIS
Vasodilatación
esplácnica
25. ASCITIS. TRATAMIENTO
Dieta hiposódica (60 a 90 mEq/día = 1,5 - 2 g/d)
• Único tratamiento en pacientes sin
hiperaldosteronismo y con excreción urinaria de Na
conservada (10%)
• Mejora respuesta a diuréticos
• Esencial en pacientes con pobre respuesta a
diuréticos
Objetivo: corregir balance de Na y disfunción circulatoria
27. TRATAMIENTO DIURÉTICO
• Espironolactona es elección
• Furosemida: uso asociado
• Dosis escalonadas o combinación inicial
• Dosis máximas: espironolactona 400 mg/d
furosemida 160 mg/d
28. Monitoreo de respuesta:
• Control de peso:
descenso <0,5 kg /d en pacientes sin edemas
descenso < 1 kg/d en pacientes con edemas
Respuesta insuficiente: descenso < 1 kg en 1º sem
< 2 kg en siguientes sem
• Na urinario
insuficiente respuesta natriurética vs
incumplimiento de dieta
DIURÉTICOS
29. • Complicaciones por diuréticos:
deterioro de la funció n renal 20% (Creatinina)
hiponatremia
encefalopatía (25% de ascitis severa y dosis
altas)
hipokalemia
hiperkalemia y acidosis metabó lica
ginecomastia
calambres
30. Ruiz del Arbol L, Gastroenterology
Incremento en la VASODILATACION arterial
Elevación de renina plasmática 71%
Insuficiencia renal e hiponatremia 25%
No revierte espontáneamente
Incremento en la VASODILATACION arterial
Elevación de renina plasmática 71%
Insuficiencia renal e hiponatremia 25%
No revierte espontáneamente
DISFUNCIÓN CIRCULATORIA POST-PARACENTESIS
Sin DCPP
Con DCPP
Debe Prevenirse: Albúmina 8 g/L ascitis evacuada
Probabilidad de
sobrevida post
DisfuncionCPP
32. TIPS (Transjugular Intrahepatic Portosystemic Shunt)
Funciona como shunt porto cava laterolateral quirurgico
Descompresión de sistema portal y de sinusoides hepáticos
Reduce GPVH
Mejora la natriuresis
Mejora la respuesta a diuréticos
Previene la recurrencia de la ascitis
VIGILAR Disfunción del stent, falla cardiaca, encefalopatía
Salerno, Hepatology 2004
33.
34. ALTERACIONES RENALES EN CIRROSIS
↓Excreción Na ↓Clearence H2O libre ↓FGlomerular
mEq/día ml/min ml/min
ASCITIS HIPONATREMIA SINDROME
DILUCIONAL HEPATORENAL
36. INSUFICIENCIA RENAL EN LA
CIRROSIS
• Es una complicación frecuente en cirrosis avanzada
• Asociación con otras complicaciones de cirrosis:
- hemorragia gastrointestinal: 11% (Child C 29% )
- peritonitis bacteriana espontánea: 30%
- sepsis (no PBE): 25%
• Impacto negativo en evolución / mortalidad
• Es una complicación frecuente en cirrosis avanzada
• Asociación con otras complicaciones de cirrosis:
- hemorragia gastrointestinal: 11% (Child C 29% )
- peritonitis bacteriana espontánea: 30%
- sepsis (no PBE): 25%
• Impacto negativo en evolución / mortalidad
Cardenas, Hepatology 2001, de Franchis, J Hepatol 2005 Sort P , NEJM1999
37. CAUSAS DE INSUFICIENCIA RENAL EN CIRROSIS
INFECCIÓN
BACTERIANA
38%
27%
HIPOVOLEMIA
13%
ENF INTRÍNSECA
RENAL
SHR
12%
FARMACOS
3%
OTRAS
7%
Ginés P, Baveno 2005
Moreau, Hepatology 2003
38. IMPORTANCIA PRONOSTICA DE LA CAUSA
DE FALLA RENAL EN PACIENTES CON
CIRROSISCausas * Frecuencia Sobrevida 3m
Infecciones 213(46%) 31%
Hipovolemia 149 (32%) 46%
SHR 60(13%) 15%
Nefropatías 41( 9%) 73%
* En otros 99 pacientes las causas fueron varias
Martin Llahi, Gastro 2011
39. SINDROME HEPATORENAL
Insuficiencia renal funcional
Caracterizado por
- marcada disfunción circulatoria
- sobreactivación de sistemas vasoactivos endógenos
- vasoconstricción renal
Potencialmente reversible
Gran impacto negativo en el pronóstico
Insuficiencia renal funcional
Caracterizado por
- marcada disfunción circulatoria
- sobreactivación de sistemas vasoactivos endógenos
- vasoconstricción renal
Potencialmente reversible
Gran impacto negativo en el pronóstico
40. Cirrosis con HTP:
•Exagerada VASODILATACION ESPLACNICA
con VASOCONSTRICCION RENAL
•Subgrupo con caida relativa del gasto cardíaco (i.e., gasto cardiaco
elevado pero inferior al correspondiente a la caida de postcarga)
•Falla CARDIO-HEPATO-RENAL ≡
Insuficiencia Cardíaca de alto débito
Ruiz del Arbol
Riñ on y corazonRiñ on y corazon
42. Probabilidad de sobrevida
20% a 1 año
Arroyo V, J Hepatol 2003 Ginés P, y col, Gastroenterology 1993
Sobrevida media 2 semanas
SHR tipo 2 SHR tipo 1
Insuficiencia renal moderada y estable
creatinina 1.5 – 2.5 mg/dl
Insuficiencia renal rápidamente
progresiva duplicación de creatinina a
> 2.5 mg/dl en < 2 sem
Factor precipitante
INDICACIÓN DE TRASPLANTE HEPÁTICO
Progresión de disfunción circulatoria
Asociado a ascitis refractaria
43. SHR 1: TERLIPRESINA ASOCIADA A
ALBÚMINA (Consenso IAC-Gut 2007)
• Terlipresina 0.5 – 1 mg c/4h , ev
• Albúmina 1 g/kg en 1º día (hasta 100g), luego 20 – 40
g/d
• Terlipresina 0.5 – 1 mg c/4h , ev
• Albúmina 1 g/kg en 1º día (hasta 100g), luego 20 – 40
g/d
44. Vasoconstrictores
• Se recomienda administrarlos con albúmina
1. Análogos de Vasopresina
– Ornipresina
– Terlipresina
1. Análogos de Somatostatina
– Octreótido
1. Agonistas alfa-adrenérgicos
– Midrodine
– Noradrenalina
45. Terlipresina
• En SHR- 1: reduce creatinina por debajo de
1,5 mg/dl en 60- 75% de los pacientes
• Menos del 5% tiene efectos isquémicos
• Recurrencia: 17- 64%
• Cochrane tiene un metaanálisis en curso
(volúmen 2, 2005)
46. Agonistas alfa-adrenérgicos
Duvoux C, Hepatology 36: 274- 80, 2002
• Estudio: serie de casos
• Población: SHR- 1
• Intervención: Noradrenalina más Albúmina
durante 7 días
• Resultado:
– Incremento de presión arterial media
– Reducción en renina activa y aldosterona
47. Asociación de vasoconstrictores
Wong F, Hepatology 40: 55- 64, 2004
• Estudio: serie de casos
• Población: cirrosis con SHR- 1
• Intervención: Midrodine, Octreótido y Albúmina durante
14 días
• Resultado:
–Reduce creatinina sérica
–Incrementa excreción renal de sodio
48. Agonistas alfa-adrenérgicos
Restuccia T, J Hepatol 40: 140- 6, 2004
• Estudio: casos y controles
• Población: SHR tratado con análogos de
vasopresina vs falla hepática sin SHR
• Resultado:
– No diferencia en la incidencia de falla renal
después del trasplante hepático
49. Trasplante hepático
• Aplicable en SHR-2
• En postrasplante requieren hemodiálisis:
– SHR: 35%
– No SHR: 5%
• Retardar 48-72 hr Ciclosporina/Tacrolimus
• Sobrevida a 3 años de SHR tratado con Terlipresina en
pretrasplante: 100%
Notes de l'éditeur
Figure 7-1. Estimated prevalence of common causes of acute liver failure worldwide. Great variation is observed between the United Kingdom (high prevalence of acetaminophen toxicity) and India (predominantly hepatitis B and others, including a large percentage of hepatitis E cases) [24]. An increasing proportion of acute liver failure in the United States is attributable to acetaminophen. Although generally with better outcomes, these cases may account for more than 50% of patient hospital admissions for acute liver failure in certain urban areas [2], [13]. Furthermore, significant numbers of unintentional acetaminophen poisoning cases are being recognized, in which the medication is taken to relieve pain, without suicidal intent. Whether ethanol abuse is a cofactor in these cases is not entirely clear.
References:
[24]. Lee WM, Schiodt FV, Fulminant hepatic failure. In Schiff&apos;s Textbook of Liver Diseases. Edited by Schiff ER, Sorrell MF, Maddrey WC. New York: Lippincott-Raven; 1999
[2]. Lee WM, Medical progress: acute liver failure. N Engl J Med 1993 329 1862-1874
[13]. Schiodt FV, Rochling FA, Casey DL, Lee WM, Acetaminophen toxicity in an urban county hospital. N Engl J Med 1997 337 1112-1117
Table 7-2. Principal causes of acute liver failure. Cause of acute liver failure is important because it determines prognosis. In some instances, initial management must be directed at the specific cause. Disease-specific treatments include antidotes to acetaminophen and mushroom poisoning that must be given immediately on patient admission to the hospital. Identification of severe heart failure as the cause indicates proper resuscitation and correction of any fluid balance disturbance. Likewise, recognition of acute fatty liver of pregnancy leads to consideration of delivery of the mother as the logical treatment for this condition. Patients with fulminant Wilson disease carry such a poor prognosis that urgent listing for transplantation must be immediately undertaken once this diagnosis is made, although therapy with trientine or penicillamine is often initiated.
Figure 7-4. Acetaminophen metabolic pathway. The main metabolic pathways for xenobiotic metabolism by the liver are divided into phase I (using cytochromes P-450), phase II (sulfation and glucuronidation), and the glutathione-S-transferase system. Acetaminophen is a prime example of a well-understood metabolic pathway that uses all three mechanisms. Acetaminophen in therapeutic doses undergoes sulfation and glucuronidation (phase II reactions) but is metabolized by cytochrome P-450 2E1 (phase I reaction) to the toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) if the capacity of the phase II reactions is exceeded or if the cytochrome is induced. Glutathione-S-transferase is capable of detoxifying NAPQI to mercapturic acid if glutathione is available; N-acetylcysteine is an excellent source of glutathione substrate. Acetaminophen serves as an example of a direct toxin, one in which toxicity occurs in all individuals and is dose related, and in which all animal models demonstrate similar reactions. In alcoholic patients or individuals who are malnourished, glutathione depletion accentuates the liver injury. In addition, induction of P-450 2E1 by ethanol and some other drugs may enhance formation of NAPQI. This metabolite may cause hepatocyte damage via covalent binding to intracellular proteins [26]. Derangements in the regulation of apoptosis may also contribute to hepatocyte destruction [27], and the xenobiotic receptor CAR (constitutive androstane receptor) has recently been identified as a key regulator of acetaminophen metabolism and hepatoxicity in mice, suggesting new possibilities for potential hepatoprotective therapies in humans [28].CAR—constitutive androstane receptor; NAPQI—N-acetyl-p-benzoquinoneimine.
References:
[26]. Ostapowicz G, Lee WM, Management of acetaminophen toxicity. In Drugs and the Liver. Edited by Deleve L, Kaplowitz N. : ; 2002 327-344
[27]. Reed JC, Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med 2001 7 314-319
[28]. Zhang J, Huang W, Chua SS, et al. Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Science 2002 298 422-424
Table 7-6. Drugs implicated in idiosyncratic liver injury leading to acute liver failure. A wide variety of medications have been associated at one time or another with acute liver injury. Although some drugs have never been implicated, others are well known as occasional acute hepatotoxins. The frequency of such reactions may vary from one in 100 patients receiving isoniazid to one in 10,000 patients receiving halothane, or less with many other compounds. Implication of a given drug requires that the physician make a careful listing of all agents taken by the patient, the time period involved, and the quantity ingested. Most examples of hepatotoxicity occur within the first 4 to 8 weeks of drug initiation. Combination agents may have enhanced toxicity in comparison to that experienced with either ingredient alone. It is important to note that certain herbal preparations and other nutritional supplements have been implicated in causing liver injury, so that inquiry about such substances must be made during a complete medication history [30].
References:
[30]. Stedman C, Herbal hepatotoxicity. Semin Liver Dis 2002 22 195-206
Figure 7-8. Basic physical findings in acute liver failure. Typical features observed in the patient with acute liver failure include confusion, agitation, and possibly hallucination. Mental status may deteriorate quickly to coma, making history taking difficult. Most patients will be icteric, although some barely so. Spider angiomata as seen in cirrhotic patients should be absent. Tachycardia, tachypnea, and relative hypotension are common. Asterixis, so commonly observed in chronic hepatic encephalopathy, is rarely seen. Fetor hepaticus, a sweet but pungent odor caused by mercaptans excreted in the breath, is often noted. Percussion over the rib cage to detect hepatic dullness may reveal a considerably decreased liver span; at times no dullness may be appreciated as evidence of the loss of hepatic mass. At autopsy, the normal liver mass of approximately 1600 g may be reduced to as little as 600 g. Edema is not observed initially but may develop during the course. Although the extremities are often cold, after resuscitation &quot;warm shock&quot; is the rule.
Figure 11-40. Factors precipitating acute episodes of encephalopathy. Precipitants of hepatic encephalopathy in 100 consecutive patients with hepatic encephalopathy at the West Haven Veterans Administration Hospital, West Haven, Connecticut. The most common precipitant was azotemia, which occurred in one third of the patients [42]. In about half of them the azotemia had been precipitated by diuretic agents such as furosemide. Precipitation of hepatic encephalopathy by tranquilizers, sedatives, or analgesic agents appears to be primarily responsible for induction of impaired mental state in a quarter of the episodes. Ninety-seven episodes had occurred in cirrhotic patients, 13 of whom had portacaval anastomoses. The severity of the encephalopathy tended to be milder in the azotemic and drug-induced patients. Hypokalemic alkalosis, which had been caused by vomiting, diarrhea, or diuretic drugs, was seen in 10% of the patients. The most severe encephalopathy occurred in association with gastrointestinal bleeding, infection, or azotemia. (Adapted from Fessel and Conn [42].)
References:
[43]. Fessel JM, Conn HO, An analysis of the causes and prevention of hepatic coma [abstract]. Gastroenterology 1972 62 191
