3 Liver Flashcards
Roles of the liver (6)
Transformation of medicines to water-soluble metabolites
Protein synthesis
Storage and metabolism of fats and carbohydrates
Excretion of bilirubin
Metabolism of hormones
Detoxification of toxins including medicinal compounds
5 main changes in liver disease that affect the PK behaviour of a medicine
Hepatic blood flow Reduction in hepatic cell mass Portal system shunting Cholestasis Decrease in protein binding
PD changes in liver disease (in relation to specific drug class)
Increased sensitivity to medicines with sedative or hypnotic effects (BZ & opiates can percipitate encephalopathy)
FRAMES
approach for substance misuse related brief counselling interventions (NICE) Feedback, responsibility, advice, menu of options, empathy, self efficacy.
CAGE
Cut down on drinking, annoyed about criticism, guilty about drinking, eye opener
AUDIT Questionnaire
Alcohol Use Disorders Identification Test
Mild: <15
Moderate: 15-30
Severe: 31 +
Equations for units of alcohol
Strength (ABV) x volume (ml) / 1000
ABV - A measure of the amount of pure alcohol as a % of the total volume of liquid in a drink.
Units of alcohol in:
small (25ml) shot of spirit
pint of lower strength lager/beer/cider
750ml bottle of wine.
1
2
10
Max recommended number of units a day for a man or woman
3-4
2-3
Max recommended number of units a week (with at least 2 alcohol free days)
21 (man)
14 (woman)
Tools for drinking help 3
Alcohol unit calculator
alcohol self assessment
drinks tracker
Increasing risk drinkers
Drinking at the level increases the risk of damaging your health. (Drinking more that 3-4 units/day for a man, and more that 2-3 units/day for a woman).
Carbohydrate metabolism is primarily (2)
glucose and glycogen.
24 hours
How many hours worth of glycogen is stored in the liver?
Acute liver disease causes drug causes:
20-30%
eg.
paracetamol OD (intrinsic)
halothan (idiosyncratic)
Causes of chronic liver disease 5
Alcohol
Non-alcohol fatty liver
Autoimmune
Viral
Drugs
High risk drinkers
Have an even higher risk of damaging your health.
-more than 8 units/day or 50 units/week (man)
-more than 6 units/day or 35 units/week (woman)
3-5x more likely to get cancer of the mouth, neck and throat
3-10x more likely to develop liver cirrhosis
Increased risk of hypertension.
Alcohol accounts for what percentage of cirrhosis in the UK?
40-80%
Consequences of liver failure
Loss of glucose/lipid homeostasis
loss of protein synthesis (infections)
loss of bile synthesis and excretion (jaundice)
failure of bilirubin metabolism
4 Symptoms of acute alcoholic hepatitis
Raised WCC
fever
deterioration in clotting
large rise in ALT
Glucose
The liver can convert galactose to what for metabolism? (almost exclusive to the liver)
Clotting factor produced in the liver
2, 7, 9, 10
Mortality rate of people with ascites.
50% (2 years)
Acute liver disease involves….
Acute loss of synthetic function
(usually recoverable)
no long term structural change.
Chronic liver disease involves…
Progressive failure scarring/fibrosis ascites encephalopathy hepatorenal syndrome variceal bleeding
Treatment for acute alcoholic hepatitis
Prolonged course of steroids
&
Nutrition
(we don’t know why this works)
Discriminant function
Used for acute alcoholic hep:
(Prolongation in prothrombin time x 4.2) + (bilirubin/17)
>32 = severe disease = steroid treatment.
Discriminant function
(Prolongation in prothrombin time x 4.2) + (bilirubin/17)
>32 = severe disease = steroid treatment.
Signs of CLD 7
Jaundice bruising spider naevi dupuytren's contractures palmer erythema gyaecomastia ascites
Causes of death in alcohol liver disease
Hepatocellular carcinoma variceal haemorrhage liver failure hepatorenal syndrome infection/sepsis.
In-hospital mortality with first bleed of varices
and % of people who get infection from it
50%
20%
Child A/B/C - chance of one year mortality if survive haemorrhage
A 5%
B 25%
C 50%
Management of ascites 5
Exclude secondary causes. Salt restriction to lose water. Diuretics Paracentesis TIPSS
Glypressin
2mg stat then 1mg 6 hourly.
Controls bleeding.
Reduces failure to control bleeding.
May improve survival.
Features of SBP
Mild fever ascites deteriorating liver/renal function encephalopathy (asymptomatic?)
Diagnosis of SBP
Ascitic fluid white cell count of >250cell/mm3
Culture into block culture bottles doubles chance of detecting.
Clinical suspicion.
Treatment of SBP
Cefotaxime 2g bd IV 5 days
OR
ciproxin 750mg bd orally.
If no improvement in 48hrs repeat tap (should be >25% reduction in wcc)
Hepato-renal syndrome
Functional renal impairment in someone with significant liver disease.
Type 1 hepato-renal syndrome
Doubling of creatinine over <6 weeks (reversible)
SBP
Spontaneous Bacterial Peritonitis
Type 2 hepato-renal syndrome
Doubling of creatinine over >6 weeks (irreversible)
Management of hepato-renal syndrome
Ensure fluid resuscitated.
Stop diuretics (and other nephrotoxins)
Look for SBP (or infection elsewhere)
Encephalopathy
Neurocognitive syndrome - affects ability to think and control emotion.
Often associated with acute GI bleed or infection.
Can be chronic and difficult to differentiate from dementia.
Nutritional treatment for LD
Pabrinex (thiamine - prophylaxis of Wernicke's) Potein-calorie supplements Thiamine No added salt diet Vitamin K
Encephalopathy treatment
Avoid sedating drugs Correct electrolytes Treat constipation - lactulose Actively seek infection, especially SBP Quiet room with same staff Consider intubation if reversible cause. Selective gut decontamination, e.g. using neomycin. Benzodiazepine antagonists. Transplantation
Gamma-glutamyl transpeptidase
ALP is found in liver and bone, but a concurrent increase in what confirms hepatic origin?
Albumin
Synthesised in the liver, levels reflect LF over the preceding months as it has a long half life, so is a good indicator of chronic LD.
Short term markers of liver synthetic function for acute and chronic disease
Prothrombin time and INR
Coagulation factors
Synthesised in the liver, have a short half life so only show LF from the preceding days.
spider naevi
Found in drainage area of the superior vena cave, commonly seen on face, neck, hands and arms.
Palmar erythema
Reddening on palms of hands
Dupuytren’s contracture
Thickening and shortening of the palmar fascia of hands causing flexion deformities.
Ascites
Accumulation of fluid within abdominal cavity.
Pruritis
Due to deposition of bile salts within the skin. Concentration doesn’t correlate with severity.
Antihistamines often don’t work
Colestyramine
Treatment for pruritus in LD
Transjugular intrahepatic portosystemic shunting
TIPSS. Invasive, used to manage refractory ascites or control variceal bleeding. An expandable intrahepatic stent is placed between one hepatic vein and the portal vein.
Hepatic encephalopathy
Occurs due to a build up of toxins. Features: liver flap to coma.
Treat with lactulose, 30-40ml/day, titrated to result in 2-3 bowel motions each day.
6 drug causes of concen
paracetamol halothane antiTB (isoniazid & rifampicin) psychotropics antibiotics cytotoxics NSAIDs (as polypharm with other hepatotoxics)
Hepatotoxicity is divided into
Choleostatic
Cytotoxic
Cytotoxic is divided into
Steatic (fatty degredation)
Necrotic (cellular breakdown)
Choleostatic means
impaired bile flow
Drugs in which LFT is advisable in first 6 months (5)
methyldopa antiTB methotrexate&sulfasalazine amiodarine sodium valproate
Reserve capacity of the liver
70-80%
How does alcohol kill you
Vit A containing hepatic stellate cells become matric secreting cells - produce perocellular fibroids.
-Network of callogen fibres around cells leads to cell death
LFT are used for…
monitoring progression
isolated increases in one are not indicative
Bilirubin
Increasing conc > jaundice
Reflects severity of disease
(Jaundice at <35-50micromol/l)
Name two transaminiases
ALT & AST
Transaminase elevation indicates
hepatic cell death (although not specific to liver?)
Alkaline phospatase
present in other tissues too
cocomitant levels of gamma-GT indicative of alcohol and enzyme inducers
Albumin
Marker of liver synthetic function
10-12g produced/day
PT & INR indicate
short term markers for synthetic capacity (3 day half life)
Withdrawal typically presents
6-12 hours after ingestion Peak at 48-72 hours
Chronic alcohol misused leads to what deficiency
vit B
Drug of choice for withdrawl
Chlordiazepoxide
Also:
• Diazepam
• Lorazepam for severe hepatically inpaired (unlicensed)
1-3days max per Rx
What might you average alcoholic be taking 7
- Thiamine
- BZ for withdrawal
- Liver disease
- GI problems
- Mood problems
- ‘Resolve’
- Painkillers
Withdrawl symptoms
palpitations, shakes, delirium tremens, sweaty, tachycardia. We medicate because we are worried about seizures and dreath.
Symptom triggered approach
patients are regularly assessed and when Clinical Institute Withdrawal Assessment of Alcohol Scale revised (CIWA-Ar) is elevated they receive a dose of BZ, continues until symptoms no longer present
Fixed-dose regimen
initial assessment of withdrawal placed on fixed BZ regimen which is reduced over 7-10 days. Patient receives treatment regardless of symptoms. Can lead to over or under treatment. Less specialist monitoring required. Treatment of choice in community and non-specialist hospital.
Naltrexone & Acamprostate
started once abstinence is achieved.
Medicines to reduce cravings
(• Disulfiram (in patients not suitable for the above) – unpleasant systemic reaction after alcohol ingestion due to accumulation of acetaldehyde in the body)
PT unsuitable for community detox
- Risk of delirium tremens. Level of dependence is critical, more likely to fit.
- Severe withdrawal symptoms, history or complicated withdrawl
- Likely vitamin B deficiency
- Multiple substance withdrawal
- History of epilepsy
- Vulnerable patients
- Elderly
- Cognitively impaired
- Under 18
- Poor social support
- Homeless
- History of self-harm, risk of suicide
- Liver disease
Nalmefene
opioid system modulator licensed for the reduction of alcohol consumption in adult patients with alcohol dependence that have a high drinking risk level without physical withdrawal symptoms who do not require immediate detoxification. How is this being used in practice?
Liver flap, drowsy and confused
hepatic encephalopathy
Ataxias & eye movement
Wernika’s encephalopathy
Hepatic encephalopathy
Reversible neuropsychiatric complication: Intestinal neurotoxins (nitrogenous waste products not broken down by the liver) such as ammonia pass through diseased liver or bypass liver on shunts and go directly to the brain. Increases permeability of the BBB, enabling neurotoxins to enter the brain (free fatty acids, GABA and glutamate)
Why lactulose?
Laxatives to reduce bowel transit time, increases nitrogen output in faeces
• Lactulose, non-absorbable disaccharide. Decreases ammonia production in the gut. Broken down by bacteria for form acids acidify gut content leading to ionization of nitrogenous products, reducing their absorption.
• 30-50ml tds. Titrated to result in 2-3 bowel motions/day
Alternatives to lactulose for hepatic encephalopathy
- Phosphate enemas for those unable to take oral medication
* Antibiotics such as metronidazole to reduce ammonia production from GI
Pabrinex
thiamine
2 doses:
prophylaxis OR treatment of Wernicke’s encephalopathy
Standard stuff for hospital alcoholic 4
Chlodiazepoxide - for safe withdrawl
Parinex (thiamine) - propylaxix and treatment of Wernicke’s
Lactulose - for hepactic enceph
Vit K - rule out dietry definecey & try to correct INR
High risk detox might need what vitamins?
K & B
also C & D
PHarmacological abstinance eg
Naltrexone 25mg od (increase to 50mg if tolerIated)
Opiate receptor antagonist - lessens the rewards.
If using invasive tap to drain asities what is albumin for
to prevent dihydration and kidney failuire
Puritus caused by
(itchiness) deposition of bile salts in the skin - antihisamines often ineffective.
Relieve biliary obstruction surgically?
Anoin exchange resins to bind bile salts (cholestyramine - caution dose timing)
Why avoid aspirin/NSAIDs/anticoagulants?
Bleeding risk with no clotting factors
Acities is caused by
Reduction of plasma albumin (reduced oncotic pressure)
Activation of reninangiotensin due to hypovolemia (and reduction in aldosterone metabolism)
Portal hypertension
Treatement of ascities
Diuretics (spirono and furosemide)
What to monitor with spironolactone?
K levels - (potassium sparing)
Why avoid opiates in liver failure?
percipitate constipation and sedation - hepatic encephalopathy
Caput medusae cuased by
scarring requireing blood divertion across sruface of the abdomen
Gynecomastia caused by
liver cannot metabolise oestrogen
Pentoxifylline
Alternative to steroid treatment to prevent hepato renal syndrom but no evidence that it is better
TIPSS
Transjugular intrahepatic portosystemic shunt
communication between the inflow portal vein and the outflow hepatic vein - reduces protal hypertension - reduces acities
PHarmacologyical varicies treatment
- glycopressin for bleed
- ciproxin to reduce infection
Endoscopic sclerotherapy
injection of sclerosiing agent into the varicies to stop bleeding - issue if the patient has not clotting factors - monitor for infection after
Band ligation
suction and application of band to varicies
Balloon tamponade
balloon in tummy to squash varicies
pharmacological prophylaxis of varicies
betablockers
Child Pugh Scores
A
B
C
A - 5-6 is class A (15-20y life expectancy)
B - 7-9 (4-14y)
C - 10-15 (1-3y).
Wernicke’s encephalopathy
Occurs due to reduced thiamine
treat with thiamine or vit B compound strong
Terlipressin
Drug treatment for oesophageal varices. Highly effective, once diagnosed should be started and continued for 2-5 days.
