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home - Liver - Liver Failure - Hepatic Encephalopathy Theories Written by Dr Sebastian Zeki
Knowledge


Assesses the severity of liver dysfunction and its prognostic
significance following haemorrhage

Knows importance of correcting hypovolaemia preventing
complications of GI bleeding and deterioration of liver function and
stopping bleeding

Knows the potential use of blood & clotting factors the role of
antibiotics the use of vasoconstrictors therapeutic endoscopy the
indication for transjugular intra-hepatic portosystemic shunt (TIPS) or
surgical shunt surgery

Aware of the specific complications of bleeding in cirrhotic patients –
including hepatic encephalopathy need for airway protection
nutrition identification of alcohol withdrawal

Skills
Shows proficiency in endoscopy – including emergency endoscopic
techniques of variceal band ligation endoscopic sclerotherapy
injection of cyanoacrylate glues for gastric varices

Can place safely and manage a Sengstaken tube in refractory
variceal bleeding

Can prevent and treat complications including hepatorenal failure
ascites spontaneous bacterial peritonitis and hepatic encephalopathy

Behaviours
Appreciates criteria for referral to specialist centre when appropriate –
such as with bleeding gastric or ectopic varices or consideration of
TIPS

Appreciates need to treat patients using a multi–disciplinary approach
Shows understanding of an empathic approach which may involve


Also....

Knowledge
Knows risks and prognosis of recurrent variceal bleeding in cirrhotic
patients

Aware of role of secondary prophylaxis with either non–selective ?-
blockers endoscopic ligation or both

Skills
Can select suitable endoscopic therapy and perform the appropriate
procedure competently

Behaviours
Appreciates the potential role of other specialists e g interventional
radiologists and nurse specialists

Also...

Knowledge


Understands the mechanisms of biliary metabolism the various
abnormalities that lead to hyperbilirubinaemia and knows and
recognises the causes of the various forms of jaundice

Skills
Selects and interprets appropriate investigations and formulate
management plans

Behaviours
Approaches patients presenting with jaundice in a logical and
methodical manner

Also...
Knowledge


Can define the different types (I and II) of hepatorenal
syndrome(HRS)

Knows the differential diagnosis of different types of renal
failure/impairment in liver disease

Understands the major and minor criteria in diagnosis of HRS and be
able to differentiate between HRS and acute kidney injury

Appreciates the prognostic significance of renal impairment in
patients with chronic liver disease

Knows the options for management and treatment of HRS the role of
colloids and vasoconstrictors as well as renal supportive treatment by
dialysis

Skills
Uses and interprets result of sometimes complex investigations
appropriately

Behaviours
Can judge when to involve other specialists especially nephrologists
radiologists and intensivists

Also...

Knowledge


Understands the pathogenesis of hepatic encephalopathy (HE)
Knows the differential diagnosis of HE including the existence of risk
factors for its causation including metabolic disorders and intracranial
structural disorders (such as subdural haematomas)

Knows factors that may precipitate HE including bleeding electrolyte
disturbance drugs or other organ failure

Knows the various treatment options appropriate for grade of severity

Skills
Can grade the mental state (Glasgow coma score and West Haven
Criteria)

Shows ability to differentiate between acute and acute on chronic liver
injury

Can identify the patient at risk of raised intracranial pressure and
cerebral oedema

Selects and use investigations appropriately and determine timing of
airway protection

Behaviours
Appreciates the role of other specialists and interacts in a
professional manner with intensivists neurologists
neurophysiologists radiologists and other specialists

Makes referral where appropriate to specialist centre for liver
transplantation

Also...

Knowledge


Understands the causes of acute hepatitis including viral druginduced alcohol-induced and auto-immune liver disease

Knows the appropriate plan of investigation and management of
specific diseases including the role of serological investigations and
liver biopsy

Skills
Takes an accurate history from patients with acute liver disease and
performs detailed clinical examination

Utilises investigation in a structured manner
Behaviours
Considers all therapeutic modalities and preparedness to refer to
specialist centre where diagnosis remains in doubt or appropriate
management cannot be performed

Also...

Knowledge
Assessment
Methods GMP
Recognises and knows how to diagnose acute and chronic drug
induced liver injury and dysfunction
SCE 1,2
Aware of methods of diagnosis, role of liver biopsy and therapy
including role of steroids in treatment in selected cases
SCE, CbD 1
Skills
Understands the role of both prescription and recreational drugs and
the aetiology of a wide variety of liver disease and dysfunction often
requiring prompt intervention or involvement of specialist services
SCE, CbD 1,2,3
Has awareness of the range of iatrogenic liver dysfunction SCE, CbD 1,2,3
Behaviours
Able to interact with specialist pharmacy services. Can use yellow
card reporting system of potential adverse effects of drugs.

Also....

Knowledge


Understands the causes and pathophysiology of acute liver failure
Can plan appropriate investigation evaluate prognosis and construct
a detailed management plan

Identifies those potentially suitable for emergency liver transplantation
Skills
Develops ability to make accurate evaluation of patients with liver
failure at the stage of initial presentation

Can deliver management plan appropriately evaluate changes in
patient’s condition and react accordingly

Utilises the range of medical interventions necessary to support
critically ill patients

Behaviours
Demonstrates ability to identify patients at risk of developing acute
liver failure and understand the criteria for referral to specialist centres

Works collaboratively with nurses and all ITU staff as well as
colleagues in other clinical disciplines to deliver the highest standard
of clinical care

Communicates effectively and relates with empathy to family and
close friends of patients

Hepatic Encephalopathy Theories

Ammonia:-The intact liver clears almost all of the portal vein ammonia, converting it into glutamine and preventing entry into the systemic circulation.However, glutamine is metabolized in mitochondria yielding glutamate and ammonia, and glutamine-derived ammonia may interfere with mitochondrial function leading to astrocyte dysfunction.The arterial concentration of ammonia is increased in about 90% of patients with HE. Impaired blood to brain transport of amino acidsBranched chain amino acids are reduced; aromatic amino acids are inc. in brain and plasma.Amino acids compete for a common BBB transporter so if less branched chain AA around then more aromatic AA gets transported.Hyperammonemia may increase the cerebral uptake of neutral amino acids by enhancing the activity of the L-amino acid transporter at the blood-brain barrier.This effect may be the consequence of the brain to blood transport of glutamine, which is formed in excess for ammonia removal.The ensuing elevation in the cerebral concentration of neutral amino acids tyrosine, phenylalanine, and tryptophan may affect the synthesis of the neurotransmitters norepinephrine, and serotonin.Dopamine levels are usually normal. Altered neu-ronal electric activityAmmonia inhibits generation of both excitatory and inhibitory postsynaptic potentials. GABA-benzodiazepine neurotransmitter system Proabably plays a role. Receptors upregulated in HE Catecholamines —R educed noradrenaline in the brain due to overactivity of noradrenergic neurotransmission, possibly induced by hyperammonemia Serotonin — 5HT increases 2-4x in HE. Turnover also increased Histamine —Higher density and a lower affinity of histamine H1 receptors. The central histaminergic system is implicated in the control of arousal and circadian rhythmicity. Melatonin — Melatonin night time peaks occur in later hours. Furthermore, plasma melatonin levels are significantly higher during daylight hours, at a time when melatonin is normally very low or absent. Alteration Of Blood Brain Barrier:The cause of the nonspecific increase in blood-brain barrier permeability is unknown.There are also more specific changes in blood-brain barrier transport in HE. Altered Brain Energy Metabolism There is a 25% dec. in cerebral glucose utilization in HE rats.This is likely due to hyperammone-mia which reduces brain ATP Theories of Hepatic Encephalopathy Glutamine Overstimulation of NMDA receptors Triggers nitric oxide synthetase (n-NOS) via a calmodulin mediated mechanism Vasodilatation Increased ICP Ammonia Glutamine Changes intracellular osm therefore oedematous Moves into mitochondria and is metabolized yielding glutamate and ammonia. Ammonia makes mitochondria porous so get free radical damage in cell . Glutamate -Ammonia is produced by enterocytes from glutamine and by colonic bacterial catabolism of nitrogenous sources -Another source of ammonia may be urea digested by H. pylori in the stomach , although the role of H. pylori in HE is unclear. Impairment of Neurotransmission Citrulline Arginosuccinate L-Arginine Urea L-ornithine Carbamoyl phosphate L-Aspartate Fumarate H20 CO2+NH3 “Endog-enous” NH3 Systemic Circ. Portal Circ. Urea Urea Cycle Liver Urea Ureases Proteases NH3 NH4 Proteins:DietaryBacterialCellular Renal Excretion 25% 75% 85% 15% Colon Glucose Phosphophhe-nol Pyruvate Citrate Glutamine Alpha keto-glutarate Glutamate Proline GlutamateSemialdehyde Arginine Urea Cycle Ocaloacetate Glutathione Gamma aminobutyrate Written by Dr Sebastian Zeki

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