Liver and Nutritional Disease Flashcards
How much of the liver can be removed and still regenerate, assuming cirrhosis hasn’t taken hold? What percentage of the liver’s blood supply is arterial?
Up to 80%
25%
What are the functions the liver is responsible for?
- Storage and protein synthesis (e.g., vitamins, glucose, clotting factors)
- Secretion (e.g., bile salts)
- Excretion and synthesis of albumin and clotting factors
- Drug clearance and metabolism
What is the functioning unit of the liver called?
Hepatocyte
What structures do the portal tract join the hepatocytes to?
Blood supply and the bile duct
How long does liver failure have to persist to be considered chronic?
Over 6 months
What typically happens in the majority of acute liver failures once the cause is removed? What percentage of acute liver failures can be attributed to drugs?
They are self limiting and resolve
About 20-30%
What is chronic liver disease recognized by?
Permanent changes to the liver architecture
Which gender is at more risk of acute liver failure due to drugs?
Women
Why is the elimination of toxins and drugs essential for the liver?
To protect body systems
What is the primary function of CYP450 enzymes in Phase I liver metabolism? Which mechanisms do CYP450 enzymes use to cause this function?
To make the compound more hydrophilic
Oxidation, hydrolysis, and reduction
What happens in Phase II liver metabolism if Phase I doesn’t clear a compound? What type of enzymes are used in Phase II liver metabolism?
A larger polar group is conjugated
Transferase enzymes
What does the third phase of liver metabolism influence?
Effect, absorption, distribution, and elimination of the drug
What are the two main reasons for checking liver function tests (LFTs)? What two things does distinguishing between in LFTs help to confirm?
To confirm clinical suspicion and distinguish between types of jaundice
Acute hepatocellular injury and cholestasis
What are the tests of synthetic function?
Albumin and prothrombin time
What are the crude tests to distinguish liver damage?
Aspartate transaminase (AST) and alanine transaminase (ALT)
Alkaline phosphatase (ALP) and gamma glutaryltransferase (GGT)
Besides LFTs, what other tests can be done to assess the liver?
Ultrasounds and biopsies
Which marker is found in high concentrations in hepatocytes and is a primary marker of hepatocellular injury? What does this marker raised mean?
ALT
Liver cell damage
Which marker is found in hepatocytes, heart, muscle, and kidneys? What does this marker raised mean?
AST
Liver cell damage, but less specific than ALT
Where is ALP primarily derived from? What does a raised ALP indicate?
Biliary epithelial cells and bones
Bile flow obstruction
Where is GGT found? What does a raised GGT support?
Hepatocytes and biliary epithelial cells
Biliary obstruction
Where is bilirubin produced? What type of bilirubin is elevated in pre-hepatic jaundice? What does a decreased albumin level indicate? Where is albumin synthesized?
Haem breakdown in spleen, liver, and bone marrow
Predominantly unconjugated bilirubin
Severe hepatocellular damage
In liver
What does an AST:ALT ratio >2:1 suggest?
Alcoholic liver disease
What are some factors contributing to liver disease?
- Alcohol
- Viral infections (hepatitis A to E)
- Diet (obesity or anorexia)
- Diabetes (type 2)
- Drug abuse (prescription and recreation)
- Genetics (e.g., cystic fibrosis, hereditary hemochromatosis, Alpha-1 antitrypsin deficiency)
Which class of drugs can cause cholestatic jaundice with increased risk with age and in men?
Penicillin
What should you do if statins are causing continuous increases in liver function tests (LFTs)? What does paracetamol overdose typically lead to? What can methotrexate lead to if not stopped and regularly monitored? What should be done with methotrexate once the LFTs normalise?
Discontinue use
Hepatic necrosis
Hepatic cirrhosis
Restart at lower dose
What should be done with tuberculosis medication once LFTs normalize? What effect do tuberculosis drugs (rifampicin, isoniazid, and pyrazinamide) have on LFTs?
Restart
Increase transaminase or bilirubin
Which liver enzyme can phenytoin cause rises in? Why might dose adjustments be required for phenytoin when albumin is decreased?
GGT
Because it is hepatotoxic
What are some herbals & supplements that can cause liver disease?
- Iron or salt overload
- Arberry, black cohosh, chaparral
- Chinese ginseng, comfrey, creosote bush
- Germander, gordoloba yerba tea
- Greasewood, greater celandine
- False pennyroyal, Jamaican bush tea, Jin Bu Huan
- Kombucha tea (in excess/non-sterile, mistletoe, Sho-saiko-to
- Pennyroyal oil (squaw-mint oil), sassafras, Senna
- Skullcap and valerian combined and white chameleon
What is Cirrhosis classified as?
Compensated or decompensated
What happens in compensated cirrhosis? What happens in decompensated cirrhosis?
The liver is coping with the damage
The liver is not able to perform functions
What are some serious symptoms and complications of decompensated cirrhosis?
Portal hypertension, bleeding varices, ascites, and encephalopathy
What are the clinical manifestations of liver disease in its early stages? What are common symptoms as liver disease progresses?
Vague non-specific symptoms like weakness or fatigue
Weight loss and anorexia
Where is abdominal discomfort typically localized with liver disease? What is a common symptom of liver disease that can be particularly distressing at night? What causes bleeding complications in liver disease? What is a classic sign of liver disease especially in the sclera?
Right upper quadrant
Pruritus (itching)
Defective hepatic synthesis
Jaundice
What causes cholestatic jaundice? What causes hepatocellular jaundice? What causes prehepatic jaundice?
Obstruction of the bile ducts
Drugs, hepatitis, or cancer
Haemolysis
What does increased pressure in the portal venous system lead to? What does portal hypertension contribute to?
Venous formation which shunts blood
Ascites formation and encephalopathy
What can oesophageal variceal bleeds lead to? Why are oesophageal variceal bleeds often asymptomatic until the bleed?
Can be fatal
The thin walls cannot cope with increased pressure
What is ascites? What does activation of the renin-angiotensin system cause in ascites? How does decreased aldosterone metabolism contribute to ascites?
Accumulation of fluid in the abdominal cavity
Retention of sodium and fluid
Increased fluid retention
What do portal hypertension and splanchnic artery vasodilation alter in ascites? What is the aim in the management of ascites?
Capillary pressure and permeability
To collect and prevent fluid accumulation
What dietary recommendation can help delay the re-accumulation of fluid in ascites? What is the recommended fluid restriction for ascites?
Low sodium diet
1-1.5 litres/day
What should be maintained in the absence of peripheral oedema for ascites management? Which class of diuretics is used to block sodium reabsorption in ascites?
Steady weight
Aldosterone antagonists
What does paracentesis do? What should you also replace when performing paracentesis?
Drains fluid from the cavity
Lost albumin
What is the lifetime risk of at least one bleed if you have cirrhosis or varices? What is the preferred choice of treatment for varices?
30%
Endoscopic banding
What does TIPS stand for?
Trans-jugular Intrahepatic Portosystemic Shunts
What are hepatic encephalopathy complications a result of? What are three factors implicated in hepatic encephalopathy?
Liver failure
Portosystemic shunting, metabolic dysfunction, altered blood-brain barrier
Why do neurotoxic compounds bypass the liver and cross the blood-brain barrier in hepatic encephalopathy? What is the therapeutic management of hepatic encephalopathy aimed at?
Because of the changes
Decreasing ammonia in the circulatory system
What effect does lactulose have in hepatic encephalopathy? How does lactulose trap ammonia?
Suppression of proteolytic bacteria
Acidification of the colonic contents
What is the starting dose for lactulose in hepatic encephalopathy? When is the lactulose dose adjusted in hepatic encephalopathy? What can be used to treat patients unable to take lactulose?
30-45 ml three to four times daily
Two or three soft stools each day
Phosphate enemas
What is rifamixin?
Antibiotic
What does MELD stand for? What is the MELD scoring system useful for?
Model of End-stage Liver Disease
Prognosis and prioritization of liver transplants
What does the MELD score use to predict mortality? What is the MELD score valid in?
Serum bilirubin, creatinine, and INR
Patients over 12 years
How much pure alcohol is in one unit? How long does it take an average adult to process one unit of alcohol? What is the recommended maximum alcohol intake for both men and women per week?
10ml or 8g
1 hour
14 units
Name two antibiotics that can manage HE, though they are expensive.
Metronidazole and rifamixin
What advice should be given about how to spread your units across the week? How is the number of units in a drink calculated?
Spread across 3+ days with alcohol-free days
Total volume (ml) x ABV (%) / 1000
What are the two enzymes involved in the metabolism of alcohol? What compound does the hydrogen released during alcohol metabolism bind to?
ADH & ALDH
NAD+ to form NADH
What toxic substance is alcohol metabolized into by ADH? What is this metabolised into? And is this a carcinogen?
Acetaldehyde
Acetate and hydrogen
Yes
What two compounds are alcohol metabolised into in the final conversion step?
CO2 and H2O
Excess NADH promotes what condition by stimulating fatty acid synthesis? What is released by the pathway that generates free radicals, causing oxidative stress? What does chronic alcohol abuse inhibit due to enhanced NADH generation?
Steatosis
Excess NADH
Mitochondrial β-oxidation
How do high concentrations of free fatty acids injure membranes? What inflammatory marker is secreted due to alcohol-induced hepatocyte apoptosis?
By contributing to necrosis, inflammation, and fibrosis
Tumour necrosis factor alpha (TNFα)
What type of immune cells are attracted to the liver by inflammatory markers? What does chronic inflammation in the liver eventually cause?
NK and NKT cells
Cirrhosis
What medications are used for seizures during acute alcohol withdrawal (non-epileptic)? What medications are used for delirium during acute alcohol withdrawal?
Benzodiazepines or carbamazepine
Haloperidol or lorazepam
How long should IV thiamine be given for in acute alcohol withdrawal? What is the dose of Naltrexone Hydrochloride tablets used for alcohol withdrawal management? What type of drug is Naltrexone? Why is some residual liver function required when using Naltrexone?
Minimum of 5 days
50mg
Opioid antagonist
It undergoes first-pass metabolism in the liver
What three symptoms are characteristic of Wernicke’s encephalopathy?
Confusion, ataxia, and vision changes
What is the dose of Acamprosate tablets used for alcohol withdrawal management? What two neurotransmitter systems does Acamprosate affect? In what situation can Acamprosate be given to a patient with liver failure?
333mg
GABAergic and glutamate
It has no hepatic involvement
What is the typical daily dose of Disulfiram used in alcohol withdrawal management? What enzyme does Disulfiram inhibit?
200 mg daily, up to 500 mg
Aldehyde dehydrogenase
What is the cause of DISULFRAM REACTIONS? Name 4 symptoms of DISULFRAM REACTIONS.
Increased blood acetaldehyde concentrations
Vasodilation, respiratory difficulties, nausea, hypotension
What kind of products containing alcohol should patients avoid to prevent Disulfiram reactions? What symptoms should prompt a patient to discontinue Disulfiram treatment and seek medical attention?
Perfumes and aerosol sprays
Fever or jaundice
What are type of symptoms are there for alcoholic hepatitis (AH)? Name 3 symptoms of Alcoholic Hepatitis
Non specific
Change in appetite, fever, jaundice
What does MMDF stand for? What is the MMDF used for? What is the formula to calculate MMDF?
Modified Maddrey’s discriminant function
Evaluating severity and prognosis of alcoholic hepatitis
4.6 x (PT test – control) + bilirubin
What MMDF score indicates a poor outcome and mortality rate of 35-45%?
≥32
What diagnostic procedure is used to confirm suspicions of alcoholic hepatitis? According to NICE, what is the biggest factor for survival in alcoholic liver disease?
Liver biopsy
Abstinence
What type of psychological assessment is used to test for alcohol dependance? When should a liver transplant be considered?
AUDIT
Decompensated failure
What type of drug is offered in AH? What are the risks that need to be discussed before offering?
Corticosteroids
Controlled bleeding and renal impairment
What does NAFLD stand for? What conditions is NAFLD linked to? Name two risk factors for NAFLD.
- Non-alcohol related fatty liver disease
- Obesity, insulin resistance, type II diabetes
- Hepatitis B & C and poor diet
What does NASH stand for? What can NASH lead to? What is NASH the biggest cause of?
Non-alcoholic steatohepatitis
Fibrosis and then cirrhosis
Idiopathic cirrhosis and liver failure
Why is NAFLD hard to notice?
Mild NAFLD are unlikely to notice symptoms
What increased risk does NASH cause? Name 8 symptoms of NASH.
Hepatocellular carcinoma
Jaundice, bruising easily, dark urine, dark black tarry faeces, ascites, pruritus, vomiting blood and encephalopathy
What 2 tests can help with diagnosing NASH? What type of management is used for NASH? Name 3 of these managements. Name 2 co-morbidities to manage.
Ultrasound and liver biopsy
Lifestyle management
Weight loss, abstinence and healthy diet
Hypertension and dyslipidaemia
What is Hepatitis? What can hepatitis result from? What 2 infectious agents can cause hepatitis? What 2 non-infectious agents can cause hepatitis? What other instance can cause hepatitis?
Inflammation of the liver
A variety of causes, infectious and non-infectious
Viruses and parasites
Certain drugs and toxic agents
An autoimmune reaction directed against liver cells
What is the most common cause of hepatitis? Name 3 types of this that can give rise to liver inflammation.
Viral infection
Cytomegalovirus, yellow-fever virus, Epstein-Barr virus
What cases are usually applied only to those cases of liver disease caused by the hepatitis viruses?
Viral hepatitis
Where is Hep A common? Give 2 groups of people that are at a high risk of getting Hep A. What is the transmission route for Hep A?
In the developing world
Travellers and those with poor sanitation
Faecal-oral route
How long do Hep A symptoms take to develop? Give 3 groups of people that should get the Hep A vaccine. Give another group of people that should get the Hep A vaccine.
About 4 weeks
IVD users, high risk sex and sewage workers
Travelers to areas of poor sanitation
What is the best way to prevent a Hep A infection? How many doses does the Hep A vaccination consist of? Can pregnant women be vaccinated? How long after exposure must Immune globulin be administered?
Vaccination
2
Yes
Within 2 weeks
Give 3 groups of people that do NOT need routine vaccination against Hep A?
Food handlers, child-care staff and none patient facing healthcare staff
Is Hep B both acute and chronic? How many people in the UK are chronically infected with Hep B? What type of virus is Hep B?
Yes
180,000
Blood borne
Why is Hep B a public health matter? How long can Hep B survive on surfaces? Give 2 ways Hep B can be transmitted.
HIGHLY INFECTIOUS
Up to 1 week
Needle –stick injury and during child birth
What can chronic Hep B infection induce over the long term? Does a vaccine exist for Hep B? What year did babies start getting the Hep B vaccine as standard?
Liver disease or even hepatocellular carcinoma
Yes
August 1 2017
Is Hep B common in adults during the acute phase? How long does acute Hep B last? What is the incubation period for Hep B?
Yes
Up to 6 months
Over 6-24 weeks
How long does acute Hep B usually resolve itself in? How many people will develop severe Hep B during the acute phase? Why can severe Hep B be fatal?
Within 4-8 weeks
1%
It can induce extensive necrosis in the liver
How many people will be infected with Hep B during infancy in the chronic phase? How is chronic Hep B usually passed to a baby?
90%
From mother to baby during pregnancy
Give 3 phases of chronic Hep B development.
Do you always pass through the phases sequentially?
The “immune tolerant” phase
The “immune response” phase
The “immune control” phase
The “immune” phase
No
What should be offered to adults with Hbe-Ag-positive chronic hepatitis B and compensated liver disease, as a first line treatment?
48-week course of peginterferon alfa-2a
What is a potential fatal consequence of severe Hep-B?
Extensive necrosis in the liver
According to NICE CG165, what is offered as a second-line treatment for hepatitis B?
According to NICE CG165, what is offered as an alternative second-line treatment for hepatitis B if 2nd line is not tolerated or is contraindicated?
According to NICE CG165, what treatment is offered to pregnant women with HBV DNA greater than 10^7 IU/ml in the third trimester?
Tenofovir disoproxil
Entecavir
Tenofovir disoproxil
Why is tenofovir disoproxil given to pregnant women with high HBV DNA levels? According to NICE CG165, is breastfeeding considered a risk for transmitting HBV to babies if guidance is followed?
To reduce the risk of HBV transmission
No risk
According to NICE CG165, how should decompensated liver disease in adults with chronic hepatitis B be managed?
According to NICE CG165, which treatment should not be offered to people with chronic hepatitis B and decompensated liver disease?
In conjunction with a transplant centre
Peginterferon alfa-2a
According to NICE CG165, what is the first-line treatment for people with decompensated liver disease and no history of lamivudine resistance?
According to NICE CG165, what treatment is offered to people with a history of lamivudine resistance?
According to NICE CG165, what adjustment should be made to tenofovir disoproxil dosage for people with renal impairment?
Entecavir
Tenofovir disoproxil
Reduce the dose
How does hepatitis C affect people in terms of symptoms? What percentage of people infected with hepatitis C clear the virus in its acute form?
Many have no symptoms
1 in 5
What percentage of people infected with hepatitis C develop a chronic infection? What percentage of people with chronic hepatitis C will develop end-stage liver disease?
About 80%
About 20-30%
What are the most common hepatitis C genotypes in the UK, Europe, and USA?
1, 2 and 3
How is a diagnosis of active hepatitis C infection made? What people are at increased risk for hepatitis C infection?
Positive HCV antibodies and HCV RNA
People with HIV infection, current or former PWID, people on maintenance haemodialysis, recipients of blood before July 1992, healthcare workers after sharps exposures, children born to HCV-infected mothers
Is treatment always required for a new HCV infection? When is treatment necessary for HCV infection?
No, not always required
When it becomes chronic
What is the goal of hepatitis C treatment? Is there an effective vaccine against hepatitis C?
Cure
No
What does prevention of HCV infection depend on?
Reducing risk of exposure
What does combination dual drug therapy for Hepatitis C usually consist of?
Weekly self-administered subcutaneous injections of pegylated interferon alpha
Daily oral doses of oral ribavirin (not for pregnancy)
What are the newer drugs used to treat hepatitis C?
Sofosbuvir–velpatasvir (Epclusa)
Glecaprevir–pibrentasvir (Maviret)
Elbasvir–grazoprevir (Zepatier)
Ledipasvir-sofosbuvir (Harvoni)
What hepatitis C treatment is not approved by NICE?
Tenofovir alafenamide
What percentage of people achieve a sustained viral repression response with HCV treatment?
More than 99%
What is the treatment of choice for people with end-stage liver disease?
Liver transplantation
What is required for hepatitis D virus (HDV) replication? What are the routes of HDV transmission?
HBV
Percutaneously or sexually
Why is HDV-HBV co-infection considered the most severe form of chronic viral hepatitis?
Rapid progression to liver death
What is the generally recommended treatment for Hepatitis D? What is a benefit of Hepatitis D treatment?
Pegylated interferon alpha
Lower likelihood of disease progression
What is the overall rate of sustained virological response to Hepatitis D treatment?
Low
Where is hepatitis E widespread? What is the typical outcome of HEV infection in most people? In whom can acute hepatitis E infection become chronic?
Developing world
Self-limited, acute illness
Solid-organ transplant recipients
What is a major contributing factor to the spread of hepatitis E? How is HEV usually spread? What is the most common source of HEV infection in developing countries?
Inadequate water supply
Faecal-oral route
Contaminated drinking water
What other organisms can hepatitis E infect? When should HEV infection be considered?
Certain mammals
Viral hepatitis symptoms, negative markers
How does hepatitis E typically resolve? What kind of therapy should physicians offer for hepatitis E?
On its own without treatment
Supportive therapy
Is there a specific antiviral therapy for acute hepatitis E? What is typically advised to patients with Hepatitis E? What medication should hepatitis E patients avoid?
No
Rest, nutrition, fluids, avoid alcohol
Acetaminophen
When is hospitalization required for hepatitis E?
Severe cases and pregnant women
Approximately how many individuals are estimated to be at risk of malnutrition in the UK? What is malnutrition?
More than 3 million
Too much or not enough nutrients
What is a consequence of not getting appropriate nutrition?
Adverse effects on the body
What deficiency causes anaemia? What hormone does iodine affect? What deficiency is related to vision problems? What process is zinc involved in?
Iron
Thyroid hormone
Vitamin A
Enzyme production
What deficiencies induce rickets? What deficiency induces Wernicke’s encephalopathy?
Vitamin D & calcium
Thiamine
According to the WHO, what are the 3 broad groups of conditions malnutrition addresses?
- Undernutrition
- Micronutrient-related malnutrition
- Overweight, obesity and diet-related noncommunicable diseases
According to the WHO, what conditions are included in micronutrient-related malnutrition?
- Micronutrient deficiencies (lack of vitamins and minerals)
- Micronutrient excess
According to the WHO, what conditions are included in undernutrition?
- Wasting (low weight-for-height)
- Stunting (low height-for-age)
- Underweight (low weight-for-age)
In 2014, approximately how many adults worldwide were underweight? In 2014, approximately how many adults worldwide were either overweight or obese?
462 million
1.9 billion
In 2016, approximately how many children under the age of 5 years were suffering from stunting? In 2016, approximately how many children under the age of 5 years were overweight or obese?
155 million
41 million
Approximately what percentage of deaths among children under 5 years of age are linked to undernutrition? What are the impacts of the global burden of malnutrition?
Around 45%
Developmental, economic, social, and medical
Which groups are at particular risk of malnutrition?
Women, infants, children, and adolescents
What is another name for Korsakoff syndrome? What is the primary symptom of Korsakoff syndrome? What is a common cause of Korsakoff syndrome?
Korsakoff psychosis
Severe amnesia
Severe chronic alcoholism
What are the three classic features of Wernicke encephalopathy?
Ophthalmoplegia
Ataxia
Confusion
What time period is critical for optimising nutrition early in life?
Conception to child’s second birthday
What can cause Korsakoff syndrome other than alcoholism? What is the typical memory impairment in patients with Korsakoff syndrome?
Brain disorders, head injury, thiamine deficiency
Inability to remember recent events
What causes the neurological symptoms of Wernicke encephalopathy? What vitamin deficiency is most commonly associated with Wernicke encephalopathy? What larger group of disorders does Wernicke encephalopathy belong to?
Thiam
Biochemical lesions in the CNS
Thiamine (vitamin B1)
Thiamine deficiency disorders
What is the name of the syndrome when Wernicke encephalopathy and Korsakoff syndrome occur simultaneously? What causes this? Which condition is worse, Wernicke’s disease or Korsakoff syndrome?
Wernicke–Korsakoff syndrome
Vitamin B1 deficiency
Korsakoff syndrome
What is the most common cause of Wernicke-Korsakoff syndrome? What other conditions can induce Wernicke-Korsakoff syndrome?
Alcoholism
Dialysis or cancer
What are the symptoms of Wernicke-Korsakoff syndrome?
Blurred vision
Confusion
Amnesia
Hallucinations
What are the treatments for Wernicke-Korsakoff syndrome?
Replace lost vitamin B
Assess nutrition status
Alcohol support
Where is ALT found in high concentrations? What does the presence of ALT in the blood indicate?
Within hepatocytes
Hepatocellular injury
Where is ALP particularly concentrated? Why is ALP often raised in liver pathology? What is ALP a useful marker of?
Liver, bile duct, and bone tissues
Increased synthesis in response to cholestasis
Cholestasis
Abnormal ALP levels most often indicate a problem with which organs? Besides these organs, what else might abnormal ALP levels indicate?
Liver, gallbladder, or bones
Malnutrition, kidney cancer, or intestinal issues
What does a greater than 10-fold increase in ALT and a less than 3-fold increase in ALP suggest? What does a less than 10-fold increase in ALT and a more than 3-fold increase in ALP suggest?
Predominantly hepatocellular injury
Cholestasis
Is it possible to have a mixed picture of both hepatocellular injury and cholestasis?
Yes
In what tissues is AST found in the highest concentrations? What does an abnormal ALT result more likely relate to compared to an abnormal AST result? If AST levels are abnormal and ALT levels are normal, what is the problem more likely due to?
Liver, muscles, heart, kidney, brain, red cells
Liver injury
Heart condition or muscle problem
Where is GGT mainly found? What does the concentration of GGT within the bloodstream rising indicate? What is GGT a useful marker for detecting?
Liver
Liver injury or bile duct obstruction
Bile duct problems
What do raised GGT concentrations generally indicate? What may elevated GGT concentrations be due to?
Something is going on with liver
Liver disease, congestive heart failure, alcohol
Which drugs may cause elevated GGT concentrations? Which drugs may decrease GGT concentrations?
NSAIDs, lipid-lowering drugs, antibiotics
Oral contraceptives and clofibrate
What is bilirubin? What condition does increased bilirubin concentrations in the blood lead to?
Orange-yellow pigment, waste product
Jaundice
Why do newborn babies often have high unconjugated bilirubin concentrations?
Liver is not fully mature
Is physiological jaundice in newborns abnormal?
No
What can bilirubin concentrations be used to identify or monitor in adults? What may increased total or unconjugated bilirubin be a result of? What may elevated conjugated bilirubin indicate?
Liver disease or jaundice progression
Haemolytic, sickle cell, or pernicious anaemias
Blockage of liver or bile ducts
What is albumin? What are the functions of albumin? What organ makes albumin?
Liver
Most abundant protein in blood plasma
Maintains fluid balance, nourishes, transports substances
What happens to albumin concentration in the blood when the liver is damaged? What happens to albumin concentration in the blood when a person is dehydrated?
Concentration drops
Concentration increases
Which drugs increase albumin in your blood? How may large amounts of intravenous fluids affect albumin test results?
Anabolic steroids, androgens, growth hormones
Results may be inaccurate
When is urine albumin significantly increased?
People with nephrotic syndrome
What does the prothrombin time (PT) test measure? What is prothrombin? What does it mean if the PT is one of the more sensitive tests?
How long it takes blood to clot
Plasma protein produced by the liver
It is able to detect changes
What happens to the liver’s ability to make essential proteins when liver disease becomes serious?
It loses ability
What is ammonia a by-product of? Which organ detoxifies ammonia? What is ammonia converted to during detoxification? Why are ammonia measurements limited?
Protein metabolism
Liver
Urea
Poorly correlate with situations
What is encephalopathy?
Ammonia toxins impair brain function
What was the Child-Turcotte classification system developed to do?
Risk-stratify patients undergoing shunt surgery
What are the limitations of the CTP score?
Limited discriminatory capacity
Equal weight to each variable
Two parameters are subjective
Important factors are not included
What has studies involving patients with cirrhosis shown about CTP scores?
Estimate risk of death
Where is the principal site of biotransformation of phenytoin? Who may show early signs of toxicity when taking phenytoin? What is slow metabolism of phenytoin due to?
Liver
Impaired liver function, elderly
Limited enzyme availability
In whom is the rate of metabolism increased when taking Phenytoin? Which hepatic cytochrome P450 enzymes metabolize phenytoin?
Young children, pregnant women
CYP2C9 and CYP2C19
What can inhibition of metabolism produce when taking phenytoin? What does taking serum level determinations help determine when taking phenytoin?
Increases in circulating phenytoin
Possible drug interactions
Which drugs may increase serum levels of phenytoin? Which drugs may decrease serum levels of phenytoin?
Amiodarone, antifungal agents, chloramphenicol
Carbamazepine, reserpine, bleomycin
What type of antagonist is methotrexate? What enzyme is the major site of action for methotrexate? What is methotrexate’s main effect?
Folic acid antagonist
Dihydrofolate reductase
Inhibition of DNA synthesis
When does methotrexate have its main effect on cell division? What kinds of drugs should be avoided when taking methotrexate?
During the S-phase
Hepatic and nephrotoxic drugs
What can be the result of concomitant use of Acitretin and Methotrexate? What kind of hepatic toxicity can result from chronic administration of methotrexate?
Severe hepatitis
Liver atrophy, necrosis, fibrosis
What is the danger associated with high doses of green tea extract?
Can cause liver damage
What pyrrolizidine alkaloids are contained in comfrey? How do pyrrolizidine alkaloids damage the liver?
Intermedine, lycopsamine, symphtine, echnimidine
Toxic pyrrole metabolites cause sinusoidal obstruction
In which population is iron poisoning most common? What quantity of ferrous sulphate ingestion becomes toxic?
Toddlers
3g +
What level of elemental iron is considered toxic? What level of elemental iron is considered fatal?
More than 60 mg/kg
More than 180 mg/kg
What can CTP scores estimate in cirrhosis patients besides 3-month death risk?
1 to 2 year survival
What kind of inducer is phenytoin regarding hepatic drug-metabolizing enzymes?
Potent inducer
Chronic administration of certain substances may lead to what severe outcomes?
Osis, cirrhosis or death
By which enzymes are the pyrrolizidine alkaloids contained in comfrey metabolized? The pyrrole metabolites from comfrey have what kind of properties? What cells do pyrrole metabolites damage in the liver?
Cytochrome P450 enzymes
Alkylating properties
Hepatic endothelial cells
Damage to hepatic endothelial cells can cause what condition?
Sinusoidal obstruction
What is the typical sequence of symptoms of iron poisoning?
Nausea, vomiting, abdominal pain, diarrhoea, weakness, irritability, lethargy, stupor
Black cohosh is derived from what plant family? What is the scientific name of black cohosh? Black cohosh is primarily used for the relief of what symptoms?
Buttercup
Actaea racemosa
Symptoms of menopause
What kind of reaction is liver injury from black cohosh thought to be? What mediates the liver injury caused by black cohosh?
An idiosyncratic reaction
Immunological mechanisms
What part of the skullcap plant is used for medicinal purposes? What conditions is skullcap traditionally used to treat? Is hepatotoxicity from skullcap common?
Dried leaves and stems
Anxiety, stress, and insomnia
No, rare (usually mild to moderate and stops rapidly after the botanical is stopped)
What is the purpose of endoscopic sclerotherapy? Endoscopic sclerotherapy involves injecting what type of agent?
To treat bleeding oesophageal varices
Sclerosing agent
What does TIPS stand for? What kind of device is used to keep the connection open in a TIPS procedure? What vessels are connected during a TIPS procedure? What is the main benefit of a TIPS procedure?
Trans-jugular Intrahepatic Portosystemic Shunt
A stent
The portal vein to the hepatic vein
Reduce internal bleeding in stomach and oesophagus
What is used to tie off enlarged veins in endoscopic band ligation? What happens to the banded varices after endoscopic band ligation?
Tiny elastic bands
Eventually sloughed
Besides ADH and ALDH, what other enzymes can break down alcohol to acetaldehyde?
Cytochrome P450 2E1 (CYP2E1) and catalase
Under what conditions is CYP2E1 active? How are small amounts of alcohol removed from the body?
After consuming large amounts of alcohol
By interacting with fatty acids to form FAEEs
What effects do fatty acid ethyl esters (FAEEs) have on the body?
Damage liver and pancreas
What is the primary cause of portal hypertension in cirrhosis? The development of portal hypertension leads to what? What circulatory syndrome can develop as a result of portal hypertension?
Increased intrahepatic vascular resistance
Formation of collateral vessels and arterial vasodilation
Hyperdynamic circulatory syndrome
What structural changes contribute to increased intrahepatic vascular resistance?
Fibrosis and increased vascular tone
What conditions can the hyperdynamic circulatory syndrome lead to?
Oesophageal varices or ascites
How does increased blood flow into the portal vein affect portal hypertension?
It exacerbates portal hypertension
What consequences could endothelial cell dysfunction have in the liver?
- Impaired vasomotor control (primarily vasoconstrictive)
- Inflammation
- Fibrosis
- Impaired liver regeneration
What happens to NO production/bioavailability in cirrhotic livers? What effect does decreased NO bioavailability have on intrahepatic vascular resistance? What do superoxide radicals react with to form peroxy-nitrite (ONOO-)?
It is significantly diminished
It contributes to increased resistance
Nitric oxide (NO)
What type of endogenous toxicant is peroxy-nitrite (ONOO-)? The activity of which enzyme increases in cirrhotic livers?
An endogenous toxicant
COX-1
Increased COX-1 activity results in greater quantities of what vasoconstrictor?
Thromboxane A2 (TXA2)
What role does angiogenesis play in portal hypertension? Where does blood from the digestive organs divert into in portal hypertension?
A crucial role in intrahepatic circulation
Porto-systemic collateral vessels
Where is an increased number of vessels observed in cirrhotic livers? What flow patterns contribute to increased intrahepatic vascular resistance?
In the fibrotic septa and surrounding regenerative nodules
Irregular flow patterns generated by splitting angiogenesis
How does increased portal blood flow affect portal hypertension?
Arterial vasodilation
What organ does hepatic encephalopathy primarily affect? In what kind of liver disease patients does hepatic encephalopathy occur?
The brain
Patients with advanced liver disease
What are some mild symptoms of hepatic encephalopathy? What are some severe symptoms of hepatic encephalopathy? What should you do if you notice worrying symptoms of hepatic encephalopathy?
Confusion, forgetfulness, personality changes
Unusual movements, seizures, severe confusion
Seek advice from your doctor
The “immune tolerant” phase of chronic Hepatitis B is characterized by what? In acutely infected individuals, what does the “immune tolerant” stage represent? How long may the immune-tolerant stage last in neonates with chronic Hepatitis B?
High HBV DNA, HBeAg positivity, normal transaminases
The incubation period before the immune response
Years to decades
What occurs during the “immune response” stage of chronic Hepatitis B? What is considered chronic HBV infection? What risk is highest during the immune response phase of chronic Hepatitis B?
Destruction of HBV-infected cells, elevating transaminases
Persistence of the immune response phase beyond six months
Progression to cirrhosis and hepatocellular carcinoma
What characterizes the “inactive carrier” state of chronic Hepatitis B? What is the conversion rate in chronically infected neonates in the inactive carrier state? What factors are associated with a higher conversion rate in the inactive carrier state?
HBeAg negativity, anti-HBe appearance, normal transaminases
5-15% per year
Increasing age and elevated ALT levels
What characterizes the “immune” stage of chronic Hepatitis B? What is the usual status of HBV DNA during the “immune” stage?
Clearance of HBsAg
Usually undetectable
Where is the sclerosing agent injected in endoscopic sclerotherapy?
Into or around oesophageal varices
Approximately how many ferrous sulphate tablets lead to toxicity in iron poisoning?
Approximately 10 tablets
What are the two main contributors to portal hypertension?
Increased hepatic resistance and increased portal blood inflow
What architectural disturbances contribute to increased hepatic resistance? What functional alterations contribute to increased hepatic resistance?
Fibrosis, scarring, and vascular thrombosis
Contraction of vascular smooth muscle and stellate cells
How does increased hepatic resistance lead to portal hypertension?
Obstruction of blood flow through the liver raises pressure in the portal vein
What happens to splanchnic circulation in response to portal hypertension? What effect does this have on blood volume?
Splanchnic vasodilation occurs
It causes effective hypovolemia (a relative decrease in circulating blood volume)
How does the body respond to effective hypovolemia?
Activation of endogenous vasoactive systems
What are the effects of activating endogenous vasoactive systems?
Sodium retention
Hypervolemia
Increased cardiac index
How does increased portal blood inflow exacerbate portal hypertension?
It adds more volume to an already congested system, worsening the pressure buildup
