liver failure acute for clinical officers.pptx

Liver failure

1. Acute Liver Failure Tr. Ruva John Bosco

2. Acute Liver Failure Acute liver failure describes the clinical syndrome of severe impairment of liver function - Encephalopathy C oagulopathy jaundice W ithin 6 months of the onset of symptoms. Friday, January 30, 2015 2 RJB

3. DEFINITION This is the acute onset of liver disease associated with reduced physiological ability of the liver with no known evidence of chronic liver disease. Occurs when 80% to 90% of hepatic functional capacity is eroded. Intercurrent conditions like systemic infection, electrolyte disturbances, severe stress may tip the balance towards decompensation . Overall mortality from liver failure is 70% to 90% Friday, January 30, 2015 3 RJB

4. Morphologic alterations causing liver failure Massive hepatic necrosis e.g fulminant viral hepatitis Chronic liver disease e.g from chronic hepatitis Hepatic dysfunction without overt necrosis e.g acute fatty liver of pregnancy Friday, January 30, 2015 4 RJB

5. Classification Friday, January 30, 2015 5 RJB

6. An alternative classification fulminant ( < 2weeks) and sub- fulminant ( > 2weeks)- liver failure - time from jaundice to encephalopathy less or more than 2 weeks Late onset liver failure describes encephalopathy developing more than 8 weeks (but less than 24 weeks) after the first symptoms Friday, January 30, 2015 6 RJB

7. Causes Neonates Infectious Herpes Virus , Hepatitis B virus Inborn Error of Metabolism Hereditary Fructose Intolerance , Galactosemia (Common) Immune Mediated Neonatal Hemochromatosis Ischaemia CHD , Cardiac Surgery , Myocarditis Infants Infectious Hep A , Hep B , Herpes Virus , NANB Hepatitis / non-A, non-B hepatitis (Common) Drugs Valproate , Isoniazide , Paracetamol (Common) Inborn Error of metabolism Hereditary Fructose Intolerance Immune Mediated Autoimmune Hepatitis Friday, January 30, 2015 7 RJB

8. Causes cont’ 2-18 years old Infectious NANB Hepatitis ,Hep A , Hep B (common) Drugs Same As Infants Immune mediated Autoimmune Ischaemia Budd Chiari Syndrome Metabolic Wilson’s Disease Friday, January 30, 2015 8 RJB

9. Potential causes of acute liver failure include Acetaminophen overdose.  Taking too much acetaminophen is the most common cause of acute liver failure Prescription medications.  Some prescription medications, including antibiotics, nonsteroidal anti-inflammatory drugs and anticonvulsants, can cause acute liver failure. Herbal supplements.  Herbal drugs and supplements have been linked to acute liver failure. Hepatitis and other viruses.  Hepatitis A, hepatitis B and hepatitis E can cause acute liver failure. Other viruses that can cause acute liver failure include Epstein-Barr virus, cytomegalovirus and herpes simplex virus. Friday, January 30, 2015 9 RJB

10. Potential causes of acute liver failure include cont’ Toxins.  Toxins that can cause acute liver failure include the poisonous wild mushroom. Autoimmune disease.  Liver failure can be caused by autoimmune hepatitis. Diseases of the veins in the liver.  Vascular diseases, such as Budd- Chiari syndrome, can cause blockages in the veins of the liver, leading to acute liver failure. Metabolic disease.  Rare metabolic diseases, such as Wilson's disease and acute fatty liver of pregnancy, infrequently cause acute liver failure. Cancer.  Cancer that either begins in or spreads to your liver can cause your liver to fail. Friday, January 30, 2015 10 RJB

11. Pathogenesis Massive destruction of hepatocytes – direct cytotoxic effect or immune response to antigens Contributing factors to liver failure – impaired hepatocyte regeneration , altered parenchymal perfusion, endotoxemia Friday, January 30, 2015 11 RJB

12. Clinical features The patient, previously having been well, typically develops non-specific symptoms such as nausea and malaise. Progressive Jaundice. Vomiting is common Abdominal pain . Rapid decrease in liver size without clinical improvement is an omnious sign Ascites Tachycardia, hypotension , hyperventilation and fever are later features Later coma & encephalopathy features Friday, January 30, 2015 12 RJB

13. Fetor hepaticus Sweetish, slightly faecal smell of the breath of intestinal origin Normal demethylating processes being inhibited by liver damage. Methyl mercaptans excreted through lungs Frequent in patients with an extensive portal-collateral circulation Often precedes coma Friday, January 30, 2015 13 RJB

14. Skin changes - Vascular spiders F ound in the vascular territory of the superior vena cava. Common sites are the necklace area, the face, forearms and dorsum of the hand An arterial spider consists of a central arteriole, radiating from which are numerous small vessels resembling a spider’s legs Friday, January 30, 2015 14 RJB

15. Skin changes - Vascular spiders cont’ Pressure on the central prominence with a pinhead causes blanching of the whole lesion Disappear with improving hepatic function, whereas the appearance of fresh spiders is suggestive of progression. A few spiders are not sufficient to diagnose liver disease, but many new ones, with increasing size of old ones, should arouse suspicion. Friday, January 30, 2015 15 RJB

16. Palmar erythema (liver palms) The hands are warm and the palms bright red in colour, especially the hypothenar and thenar eminences and pulps of the fingers The mottling blanches on pressure and the colour rapidly returns. Friday, January 30, 2015 16 RJB

17. Vascular spiders and palmar erythema (cause) It is attributed to oestrogen excess. Oestrogens have an enlarging, dilating effect on the spiral arterioles of the endometrium, and such a mechanism may explain the closely similar cutaneous spiders Liver inactivates oestrogen– in liver failure it leads to increase in oestrogen levels – leads to cutaneous manifestations of liver failure Friday, January 30, 2015 17 RJB

18. Endocrine changes - Hypogonadism Diminished libido and potency are frequent The testes are soft and small. Seminal fluid is abnormal in some cases. Secondary sexual hair is lost The female has ovulatory failure. Loses feminine characteristics, particularly breast and pelvic fat. Gynaecomastia - A lcoholic liver disease is the commonest association. Friday, January 30, 2015 18 RJB

19. Endocrine changes – Hypogonadism cont’ Steroid hormones are conjugated in the liver. Derivatives of oestrogens, cortisol and testosterone are conjugated as a glucuronide or sulphate S o excreted in the bile or urine. F ailure of hormone metabolism in liver failure results in a rise in blood hormone levels. This alters the normal homeostatic balance between secretion rates of hormones and their utilization. Friday, January 30, 2015 19 RJB

20. Investigations: Haematology The prothrombin time (together with the degree of encephalopathy ) refractory to vitamin K treatment - central to the assessment of the severity of the clinical situation, and its progress . Haemoglobin and white count are obtained. A falling platelet count may reflect disseminated intravascular coagulation . Friday, January 30, 2015 20 RJB

21. Investigation: Biochemistry – Blood analysis Blood Glucose Blood Urea Serum Electrolytes Serum Creatinine Serum bilirubin Serum Albumin – initially normal but later low albumin carries poor prognosis Transaminases – of little prognostic values as levels tends to fall as condition worsens Friday, January 30, 2015 21 RJB

22. Other serological test Virological markers – Serum HBsAg IgM Anti HBc IgM anti HAV Anti HCV HCV RNA Friday, January 30, 2015 22 RJB

23. EEG The Guidelines now used for decision on management no longer depend on EEG Continuous EEG has shown 50% of patients with subclinical seizure and epileptiform activities Recommended for Grade 3 and 4 Encephalopathy Friday, January 30, 2015 23 RJB

24. Liver Biopsy & CT Brain Hepatic Parenchymal necrosis more than 50% indicates poor prognosis Hepatic Regenerative changes on histology (<50% Necrosis ) indicates good Prognosis From Practical point of view – clinical & laboratory data rather than biopsy are used for decision making CT – unreliable in detecting early cerebral oedema so movement of patient to radiology carries the risk of deterioration Friday, January 30, 2015 24 RJB

25. General measures Volume resuscitation should be carried out aggressively Fluids should be glucose based with infusion rate at least 6-8 mg/kg/min Strict input-output charting Friday, January 30, 2015 25 RJB

26. Complications of liver failure Hepatic encephalopathy Porto-systemic encephalopathy Cerebral edema (intracranial hypertension) Metabolic , electrolyte and acid base disturbances The causes of death are: cerebral oedema, infection, bleeding, respiratory and circulatory failure, renal failure, hypoglycaemia and pancreatitis Friday, January 30, 2015 26 RJB

27. Hepatic encephalopathy The brain is exposed to increased levels of ammonia, neurotransmitters and their precursors because of failed hepatic clearance. Neurological and psychiatric components. Features of encephalopathy can be separated into changes in consciousness, personality, intellect and speech. Friday, January 30, 2015 27 RJB

28. Hepatic encephalopathy cont’ Disturbed consciousness with disorder of sleep is usual. Hypersomnia appears early and progresses to reversal of the normal sleep pattern. Reduction of spontaneous movement, a fixed stare, apathy, and slowness and brevity of response are early signs. Further deterioration results in reaction only to intense or noxious stimuli. Coma at first resembles normal sleep, but progresses to complete unresponsiveness. Friday, January 30, 2015 28 RJB

29. Personality & intellect changes I rritability and loss of concern for family. Intellectual deterioration varies from slight impairment of organic mental function to gross confusion. Isolated abnormalities appearing in a setting of clear consciousness relate to disturbances in visual spatial gnosis. Most easily elicited as constructional apraxia, shown by an inability to reproduce simple designs with blocks or matches Writing is oblivious of ruled lines and a daily writing chart is a good check of progress Failure to distinguish objects of similar size, shape, function and position Micturating and defaecating in inappropriate places Friday, January 30, 2015 29 RJB

30. Friday, January 30, 2015 30 RJB

31. Speech Speech is slow and slurred and the voice is monotonous. Friday, January 30, 2015 31 RJB

32. Asterixis The most characteristic neurological abnormality is the ‘flapping’ tremor ( asterixis ). This is due to impaired inflow of joint and other afferent information to the brainstem reticular formation resulting in lapses in posture. It is demonstrated with the patient’s arms outstretched and fingers separated or by hyperextending the wrists with the forearm fixed . The rapid flexion–extension movements at the metacarpophalangeal and wrist joints are often accompanied by lateral movements of the digits. Friday, January 30, 2015 32 RJB

33. Asterixis Friday, January 30, 2015 33 RJB

34. Asterixis ‘Flapping’ tremor is not specific for hepatic pre-coma. It can also be observed in uraemia, in respiratory failure and in severe heart failure Deep tendon reflexes are usually exaggerated. Increased muscle tone is present at some stage and sustained ankle clonus is often associated with rigidity. During coma , patients become flaccid and lose their reflexes. The clinical course fluctuates, and frequent observation of the patient is necessary. Clinical grading should be used as a part of the clinical record Friday, January 30, 2015 34 RJB

35. Staging Friday, January 30, 2015 35 RJB

36. Pathogenetic mechanisms The basic processes are failure of hepatic clearance of gut derived substances, either through hepato -cellular failure or shunting, and altered amino acid metabolism Result in changes in cerebral neurotransmission. Several neuroactive toxins, in particular ammonia, and neurotransmitter systems are thought to be involved and inter-relate. Friday, January 30, 2015 36 RJB

37. Portal systemic Encephalopathy In patients with poor hepato -cellular function, such as acute hepatitis, the shunt is through the liver itself. The damaged cells are unable to metabolize the contents of the portal venous blood completely so that they pass unaltered into the hepatic veins In patients with more chronic forms of liver disease the portal blood bypasses the liver through enlarged natural ‘collaterals’. The portal– hepatic vein anastomoses, developing around the damaged liver, act as shunt. Patients going into hepatic coma are suffering from cerebral intoxication by intestinal contents which have not been metabolized by the liver - portal-systemic encephalopathy Friday, January 30, 2015 37 RJB

38. Illustration of porto -hepatic shunt Friday, January 30, 2015 38 RJB

39. Pathogenesis Ammonia is produced from the breakdown of proteins, amino acids, purines and pyrimidines . Ammonia arising from the intestine is synthesized by bacteria, dietary protein and glutamine. The liver normally converts ammonia to urea and glutamine through the urea cycle. Liver failure causes disorder of the urea cycle lead to an encephalopathy. Blood ammonia levels & Brain levels are also increased Increase in the cerebral metabolic rate for ammonia and an increase in the blood–brain barrier permeability to ammonia Thus disturbed brain functions. Friday, January 30, 2015 39 RJB

40. Investigations Cerebrospinal fluid - usually clear and under normal pressure , cell count is normal Electroencephalogram(EEG) - bilateral synchronous slowing of the wave frequency . EEG changes occur very early even before psychological or biochemical disturbances. CT scan to show cerebral oedema and cortical atrophy even in those with subclinical portal-systemic encephalopathy. Friday, January 30, 2015 40 RJB

41. EEG changes Friday, January 30, 2015 41 RJB

42. Treatment of Hepatic Encephalopathy Treatment broadly divides into three areas: 1 Identification and treatment of the precipitating cause. 2 Intervention to reduce the production and absorption of gut-derived ammonia and other toxins. I nvolves reduction and modification of dietary protein, A lteration of enteric bacteria and the colonic environment -antibiotics, lactulose / lactilol S timulation of colonic emptying - enemas, lactulose / lactilol . 3 Agents to modify neurotransmitter balance directly- bromocriptine , flumazemil - limited clinical value at present. Friday, January 30, 2015 42 RJB

43. Diet Energy Allowed Comment Carbohydrates High carbohydrates Fats Moderate Protein (non- encephalopathic state) Moderate It promotes growth & maintain positive nitrogen balance Vegetable Proteins - preferred Protein (encephalopathy) Reduce Further protein restriction exacerbate HE by causing breakdown of endogenous proteins Friday, January 30, 2015 43 RJB

44. Antibiotics Neomycin, given orally, is very effective in decreasing gastrointestinal ammonium formation - used for the acute case for 5–7 days In acute hepatic coma, lactulose is given -- neomycin added if the response is slow or partial. Metronidazole seems to be as effective as neomycin. Rifaximin , a non-absorbed derivative of rifamycin , is effective for grade 1–3 hepatic encephalopathy Friday, January 30, 2015 44 RJB

45. Lactulose and lactilol G iven by mouth lactulose R eaches the caecum where it is broken down by bacteria predominantly to lactic acid . The faecal pH drops. Faecal acidity would reduce the ionization and hence absorption of ammonia The growth of lactose-fermenting organisms is favoured and organisms such as bacteroides , which are ammonia formers, are suppressed. Friday, January 30, 2015 45 RJB

46. Diagram showing the use of lactulose Friday, January 30, 2015 46 RJB

47. Sodium benzoate and L-ornithine -L-aspartate Sodium benzoate promotes urinary excretion of ammonia and is as effective as lactulose and is less expensive. L-ornithine-L-aspartate treatment promotes hepatic removal of ammonia by stimulating residual hepatic urea cycle activity and promoting glutamine synthesis, particularly in skeletal muscle Friday, January 30, 2015 47 RJB

48. Cerebral edema (intracranial hypertension) U ncommon in patients with grade 1 or 2 encephalopathy D evelops in the majority with grade 4. Raised intracerebral pressure can lead to brainstem herniation and is the most common cause of death, being found in 80% of fatal cases Two mechanisms have been proposed: cytotoxic and vasogenic . Friday, January 30, 2015 48 RJB

49. The cytotoxic hypothesis Accumulation of osmolytes such as glutamine, in astrocyte - subsequent osmotic uptake of water into the cells. In the brain astrocytes are the site of ammonia metabolism by amidation of glutamate to glutamine. In acute liver failure cerebral glutamine concentrations rise. Friday, January 30, 2015 49 RJB

50. The vasogenic hypothesis Changes in cerebral blood flow and the blood–brain barrier Cerebral blood flow autoregulation (maintained blood flow despite falling or rising blood pressure) is lost in patients with fulminant hepatic failure . Loss of this protective mechanism could exacerbate cerebral changes due to systemic hypotension (giving cerebral ischaemia ) and cerebral hyperperfusion- increasing cerebral blood volume and interstitial water If not controlled - progresses to loss of pupillary reflexes and respiratory arrest from brainstem herniation. Friday, January 30, 2015 50 RJB

51. Treatment Head should be elevated to 30 degrees High levels of PEEP should be avoided – it may increase hepatic venous pressure & intracranial pressure Mannitol bolus of 0.5 g/kg as 20 % solution over 15 minutes – can be repeated if serum osmolality less than 320 mOsm /L Other methods 3% hypertonic saline STEROIDS ARE NOT INDICATED IN TREATMENT OF INTRACRANIAL HYPERTENSION in ALF – as it may complicate infection & cause gastric erosions Friday, January 30, 2015 51 RJB

52. Coagulopathy The liver synthesizes all the coagulation factors (except factor VIII) inhibitors of coagulation and proteins involved in the fibrinolytic system. The coagulopathy of fulminant hepatic failure is complex Not only to factor deficiency, but also to enhanced fibrinolytic activity The platelet count may fall due to increased consumption or reduced production, and platelet function is also abnormal in hepatic failure. The resulting coagulopathy predisposes to bleeding- potential cause of death The prothrombin time is the most widely used test to assess coagulation. It is a guide to prognosis. Friday, January 30, 2015 52 RJB

53. Treatment Iv vitamin K to correct any reversible coagulopathy FFP – to be given in case of haemorrhage or if coagulopathy is severe (PT>60sec) Thrombocytopenia to be corrected Prophylaxis for GI bleed – administration of PPI , sucralfate , ranitidine Friday, January 30, 2015 53 RJB

54. Metabolic , electrolyte and acid base disturbances Hyponatremia Hypokalemia – decreased dietary intake , chronic illness , secondary hyperaldosteronism , frequent GI losses Hypophosphatemia – due to amount of regenerative liver mass as phosphate be a substrate for various kinase enzymes that phosphorylate proteins for liver regeneration Hypoglycemia – failure of hepatic gluconeogenesis , high plasma insulin levels due to decreased uptake Respiratory alkalosis – due to hyperventilation – direct stimulation of respiratory centre by toxic substances Friday, January 30, 2015 54 RJB

55. Treatment Hypokalemia 3 Meq (1.5 ml kcl ) if K+ >3 Meq 4 Meq (2 ml kcl ) if K+ is 2.5 - 3 Meq 5 Meq (2.5 ml kcl ) if K+ is 2 – 2.5 Meq 6 Meq (3 ml kcl ) if K+ is < 2 Meq Hyponatremia Restrict sodium infusion to < 2 Meq /kg/day Hypoglycemia Increase GIR ( glucose infusion rate ) Maintain blood sugar levels between 100 – 200 mg/dl Friday, January 30, 2015 55 RJB

56. Infections Ninety per cent of patients with acute liver failure and grade 2 or more encephalopathy have clinical or bacteriological evidence of infection The majority of infections are respiratory. The high rate of infection can be related to poor host defences with impaired Kupffer cell and polymorph function Friday, January 30, 2015 56 RJB

57. Renal Hepatorenal syndrome is the most common cause of renal insufficiency in ALF Secondary to renal vasoconstriction Type 1 – rapidly progressive in renal function, doubling of serum creatinine to a level > 2.5 mg/dl or 50 % reduction in Creatinine Clearance to < 20 ml/min in less than 2 weeks Type 2 – progression slow, > 2 weeks Friday, January 30, 2015 57 RJB

58. Treatment Primarily focussed on decreasing splanchic circulation – Vasoconstrictors – Terlipressin Alpha agonist- nor-epinephrine , medodrine Very effective in reversal of functional renal insufficiency Friday, January 30, 2015 58 RJB

59. Prognosis Overall survival for those reaching grade 3 or 4 encephalopathy is 20% without transplantation. If only grade 1 or 2 coma is reached, survival is around 65%. Aetiology is important - 66% for hepatitis A, 38.9% for hepatitis B and 50% for acetaminophen overdose Decerebrate rigidity, with loss of the oculovestibular reflex and respiratory failure are particularly ominous Prothrombin time is the best indicator of survival The association of a clotting factor V concentration of less than 15% with coma is also ominous Friday, January 30, 2015 59 RJB