The Role of LOLA in HE

The Role of LOLA In Hepatic Encephalopathy

Hariadi M PIT XIV IPD Malang 17 Oktober 2014

Introduction • Hepatic Encephalopathy (HE) is a complex neuropsychiatric syndrome with disturbances in: -consciousness -behavior,personality changes -fluctuating neurologic signs,asterixis/flapping tremor -distinctive EEG changes

• 2 types : - Acute ,reversible - Chronic and progressive/severeirreversible, co madeath •The diagnosis of HE is usually one of exclusion.

Classification of Hepatic Encephalopathy World Conggres of Gastroenterology 1998 Hepatic Encephalo pathy

Type A(=acute) HE associated with Acute liver failure,typically with cerebral edema

Type B(=bypass) caused by portal systemic shunting without associated with intrinsic liver disease

Type C(=cirrhosis) Occur in cirrhosis, Subdivided in: Episodic,persistent, minimal HE(MHE)

MHE,doesnot lead clinically overt cognitive dysfunction, can be demonstrated by neuropsychological studies.

Pathogenesis • • • •

Endogenous Endotoxins Increased permeability of BBB Change in neurotransmitter and receptor Others.

Endotoxins • • • •

Ammonia (the main candidate of neurotoxin) Mercaptans Phenols Short-chain and Mid-chain fatty acids.

The Pathogenesis of HE • The primary source of amonia is the intestine,formed by protein breakdown NH3

Normal

Intestine

NH3

urea

Portal vein Liverdetoxi cation Urea cycle

NH3

NH3

Cirrhosis

Intestine

Portal vein

NH3 GI Bleeding

Porto sytemis shunt Fischer’s ratio

Kidney

BBB

NH3

Brain

Liverdetoxi cation incapable

Kidney

Pathogenesis

Precipitating Factors Increased Nitrogen Load

Electrolyte-Metab imbalance

• Gastrointestinal bleding • Excess dietary protein • Azotemia •Constipation

Others : • Infections,surgery • Superimposed liver disease • Portal systemic shunt

• Hypokalemia,alkalosisincre ased renal production of NH4 • Hypoxia • Hyponatremia • Hypervolemiareduced liver metabolisme of ammonia • Acidosisinhibition of urea synthesis.

Drugs • Narcotics,CNS depression • Tranguilizer • Sedative • Diureticselectrolyte imbalance and hypovolemia.

Ammonia • Healthy individuals have equilibrium between production and detoxications. •The main site of synthesis are : - Intestine,small and large intestine - Muscle - Kidney Ammonia Production • Small intestine,the gradation of glutamine • Large intestine,breakdown of urea and proteins by normal flora • Muscle,proportion to muscle work •Kidney,increased production when hypokalemia and diuretic therapy

Ammonia Production Small intestine, -the degradation of glutamine Large intestine, -breakdown of urea&proteins by normal flora Muscle, -proportion to muscle work -degradation of glutamine glutaminaseammonia. Kidney, increased production when: -hypokalemia -diuretic therapy

Detoxication Liver, -detoxified ammonia urea,glutamine Brain, -detoxified into glutamine and glutama te.

Protein and HE Considerations • No valid clinical evidence supporting protein restriction in pts with acute ALF • Protein intake < 40g/day contributes to malnutrition and worsening ALF – Increased endogenous protein breakdown NH3

• Susceptibiliy to infection increases under such catabolic conditions

How Much Protein: That is the Question?? • Grade III to IV hepatic encephalopathy – Usually no oral nutrition – Upon improvement, individual protein tolerance can be titrated by gradually increasing oral protein intake every three to five days from a baseline of 40 g/day – Oral protein not to exceed 70 g/day if pt has hx of hepatic encephalopathy – Below 70 g/day rarely necessary, minimum intake should not be lower than 40 g/day to avoid negative nitrogen balance. – 1.0g/kg/day protein, depending on degree of muscle wasting – BCAA-enriched solutions may benefit protein intolerant (