DISCUSSION:

Metabolic functions of Liver

 Carbohydrate metabolism
o Storage of large amounts of glycogen
 Removes excess glucose in blood  glycogen
 If defective, blood glucose may inc by 2x-3x after a meal compared to a normal person
o Converts galactose & fructose  glucose
o Gluconeogenesis
 Fat Metabolism
o Oxidation of fatty acids (gluconeogenesis)
o Synthesis of cholesterol ( bile salts  bile), phospholipids and lipoproteins
o Synthesis of fat
 Protein metabolism
o Deamination of amino acids (gluconeogenesis)
o Formation of urea for removal of ammonia from blood
 NH4+ comes from deamination of proteins and bacteria from gut
  NH4+ in blood  hepatic coma
o Formation of plasma proteins
 Storage for vitamins (Vit. A, Vit. D and B12)
 Storage for iron (ferritin)
 Formation of coagulation factors (1, 2, 5, 7)
 Removes excess drugs, hormones, and other subs

Effects of alcohol
 Alters neurochemical processes in the brain
o Depresses neuronal activity (similar w/ benzodiazepines and barbiturates)
o Impaired judgment and coordination
o Cause “hangover”  nausea, vomiting, headache, thirst, and fatigue
o Peripheral neuropathy
o Cerebellar degeneration/ atrophy
o Wernicke-Korsakoff syndrome (thiamine)
 Psychiatric Comorbidity
o Antisocial personality  impulsivity and disinhibition
o Sadness
o Anxiety (during withdrawal)
o Auditory hallucinations or paranoid delusions
o Seen temporarily during heavy drinking and subsequent withdrawal
 Affect metabolism of medications
 Pharmacology of ethanol
o 10-12g ethanol found in 340ml of beer / 43ml of whisky
o Absorbed mainly in proximal portion of small intestine
o Excreted directly through lungs, urine, sweat, but mostly metabolized to acetaldehyde by liver by
alcohol dehydrogenase (ADH)
 Impaired gluconeogenesis  hypoglycemia
DIFFERENTIALS
Alcohol use disorder

 Pathophysio
o Due to environmental influence (started early in life or raised by alcoholics)
o Due to low sensitivity to alcohol  heavy drinking
o National institute on alcohol abuse and alcoholism defines “at-risk drinking”
 >4 drinks/day or 14 drinks/week for men
 >3 drinks/day or 7 drinks/week for women
 Epidemiology
o 60% of risk for AUD is due to genes; 4x higher risk if child of an alcoholic (environmental influence)
o  heavy drinking and alcohol problems
 S/Sx
o 6-8 or more drinks per day
o Job problems
o Histories of accidents
 Labs/Diagnostics
o GGT > 35U
o Carbohydrate deficient transferrin (CDT) >20U/L
o MCVs ≥91 μm3
o Serum uric acid > 416mol/L or 7mg/dL
Alcohol Withdrawal (Delirium Tremens)
 Pathophysio
o Begin 5-10hrs of decreasing ethanol intake; peaks on day 2 or 3
o Begins within 8 hrs after last alcoholic drink
o Occurs if patient is an excessive and steady drinker, unable to drink due to circumstances
(hospitalizations or in our case, imprisonment), becomes delirious after 2-4 days
o Occurs as a single episode, lasting ≤72 hrs; may relapse.
o Short-lived, ends abruptly. May persist for 4-6 months
 Epidemiology
o 2% experience withdrawal seizure
o 24% of admitted alcoholics develop delirium tremens; of these, 8% died.
 S/Sx
o Mental confusion, Agitation, Fluctuating levels of consciousness
o Delusions, vivid hallucinations
o Increased autonomic nervous system activity
 Dilated pupils, fever, tachycardia, profuse perspiration
o Tremor of hands, Agitation and anxiety
o Autonomic NS overactivity
 pulse, RR, sweating, and temp
o Insomnia
o Generalized seizures in first 24-48 hours
o
 Labs/Diagnostics
o Variable results
o Glucose may be increased/decreased
o Sodium, Chloride, and phosphate levels are often increased
o Ca2+, Mg2+ and K+ are decreased in 25% of patients
o PCO2 and high pH
 o Enlargement of 3rd and 4th ventricle
o MRI is normal

Hepatic Encephalopathy
 Pathophysio
o neurotoxins due to vascular shunting (bypasses liver)
o Alteration in mental status and cognitive function occurring in the presence of liver failure
o Seen in chronic liver disease
o Failure of conversion of ammonia to urea w/c is supposed to be excreted via urine
o Ammonia is one toxin, but is not the only one
o  in number and size of astrocytes only
 Epidemiology
o Common in px with cirrhosis
o Precipitating events
 Hypokalemia, infection,
 increased protein load, electrolyte imbalance
 S/Sx
o Changes in mental status occur w/in weeks/months
 Confused and change in personality
 Violent and difficult to manage OR
 Very sleep and difficult to rouse
 Mental slowing + confusion w/ hyperactivity followed by progressive drowsiness, stupor and
coma
o Brain edema
o Swelling of gray matter
o Asterixis (“liver flap” or sudden forward movement of wrist when arms and wrists are extended;
sustained muscle contraction); prominent symptom
o Ataxia, rigidity of trunk and limbs, exaggerated or asymmetric tendon reflexes, (+) Babinski
o Lead to stupor or coma
o May present with or without seizures
 Labs/Diagnostics
o Solely clinical diagnosis
o EEG may indicate impending coma (triphasic waves)
o Blood tests
 ammonia (>200mg/dL) & protein

Uremic Encephalopathy
 Pathophysio
o Urea is not the sole inductive agent; May be due to retention of other toxins, organic acids, and
phosphate in CSF
o Affects every level of CNS
o Absent cerebral edema
 Epidemiology
 S/Sx
 o Episodic confusion, Stupor, Apathy, Fatigue, Inattentive, Irritable
o Psychosis w/ hallucinations, delusions, insomnia, catatonia.
o Lightning-quick twitching & jerking OR Seizures (uremic twitch-convulsive syndrome)
o Asterixis
o Acidosis  Kussmaul breathing
o May lead to coma
 Labs/Diagnostics
o EEG
 Diffuse and irregularly slow (for weeks)
o CSF analysis
 Normal opening pressure
 Normal – slightly elevated protein
o Electrolyte tests
 Hypocalcemia & Hypomagnesemia
o CT scan and MRI
 Cerebral shrinkage

GUYTON
HARRISONS
ADAM’S
CURRENT