Week 15 - Case One and Two

Question 1

in paracetamol, what is associated with higher risk of hepatotoxicity

Answer 1

delayed presentation

Question 2

what is it important to assess for in paracetamol overdose for hepatotoxicity

Answer 2

• Confusion due to hepatic encephalopathy
• Liver asterixis (flapping tremor)
• Yellow skin or sclera due to jaundice
• Bruising of the skin or bleeding of the gums or from anywhere due to clotting derangement
• Tenderness in the right upper quadrant due to liver inflammation
• Hepatomegaly

Question 3

in patients who present within 24 hours of an overdose and biochemical tests suggest ALI, even though the plasma paracetamol conc. is below the treatment line on the graph, what should be started

Answer 3

acetylcysteine

Question 4

what does a staggered overdose involve

Answer 4

A staggered overdose involves ingestion of a potentially toxic dose of paracetamol over more than 1 hour, with the possible intention of causing self-harm. All patients who have taken a staggered overdose should be referred to hospital for medical assessment. The MHRA advises that all patients who have ingested a staggered overdose should be treated with acetylcysteine without delay.

Question 5

what is the criteria for liver transplant following paracetamol overdose

Answer 5

King’s college criteria: Liver transplant in paracetamol induced acute liver failure is indicated if:
Arterial pH <7.3 or arterial lactate >3.0 after adequate fluid resuscitation,
OR
If all of the three following occur in 24-hour period:
Creatinine >300micromol/l
PT >100 seconds (INR >6.5)
Grade III/IV encephalopathy

Question 6

when does toxicity peak in paracetamol overdose

Answer 6

48-72 hours after ingestion

Question 7

what can be an early indictor of acute liver failure

Answer 7

acidosis

Question 8

what is the most concerning initial blood result in paracetamol overdose

Answer 8

Prothrombin Time (PT)

The biggest concern in the blood tests given is that he has developed a degree of coagulopathy indicating there is some degree of liver function impairment.

Question 9

what is the usual management plan alongside acetylcysteine in paracetamol overdose

Answer 9

Catheterisation and hourly recording of urine output
Hourly capillary blood glucose recording
10mg of vitamin K IV
Repeat coagulation panel in six hours

Question 10

why should you avoid giving fresh frozen plasma to correct the prothrombin time in paracetamol overdose

Answer 10

as this makes it impossible to interpret the prothrombin time and use it to guide management over the next few hours

Question 11

what clinical signs and bedside tests would you look for as an indication that the patient is developing liver failure

Answer 11

• Spontaneous bruising or bleeding at venepuncture sites as a sign of progressive coagulopathy
• Reduced urine output indicating possible acute kidney injury
• Hypoglycaemia (indicated hepatic necrosis)
• Metabolic acidosis despite hydration
• Hypotension despite hydration
• Encephalopathy, which in this case may present with agitation, confusion or aggression rather than drowsiness as seen in chronic liver disease

Question 12

what is acute liver failure defined as

Answer 12

liver injury with the presence of hepatic encephalopathy in a patient without related pre-existing liver disease.

Question 13

what does an isolated raised ALT level suggest

Answer 13

suggests a hepatitic type problem

inflammation within the liver

Question 14

which two components assess the actual function of the liver

Answer 14

bilirubin and albumin

Question 15

what are the most common causes of inflammatory liver processes

Answer 15

• Fatty liver related to alcohol
• A viral infection
• Non-alcohol related fatty liver (usually associated with metabolic syndrome)
• Autoimmune liver disease

Question 16

what should be checked for haemochromatosis

Answer 16

• Ferritin should be checked for haemochromatosis.

Question 17

what is haemochromatosis

Answer 17

Haemachromatosis is an autosomal recessive genetic condition affecting the HFE gene which causes deficiency of the iron-regulatory hormone hepcidin. Symptoms occur as a result of accumulation of iron in tissues. Early symptoms include fatigue, weakness, arthropathy, abdominal pain, erectile dysfunction and cardiac issues (arrhythmia or cardiomyopathy). Late symptoms include: bronzing of the skin, hepatomegaly / cirrhosis of the liver and mood / memory disturbance.

Question 18

what is the mainstay of treatment for haemochromatosis

Answer 18

phlebotomy to lower iron levels in the blood

Question 19

A 24-year-old female presents 6 hours after an acute overdose of paracetamol. She weighs 61kg and took 12 x 500mg tablets within 10 minutes. She has no significant past medical history and reports feeling mildly nauseated but otherwise well. Her serum paracetamol levels are 24 at 6 hours and liver function / INR tests all return within normal range. Is treatment indicated?

Answer 19

No
.
The patient is otherwise well, took an acute overdose and paracetamol levels are below treatment line. Therefore, treatment with N-acetylcysteine is not indicated.

Question 20

A 29-year-old female is being monitored on an inpatient ward following an overdose of 24g of paracetamol. She is alert and orientated when you take bloods from her. When the bloods return, her ALT is 1930, Creatinine 196, INR 1.9. You take a venous blood gas which shows a pH of 7.36.

Does the patient meet criteria for consideration of liver transplant?

Answer 20

No

The King’s College criteria: liver transplant in paracetamol induced acute liver failure is indicated if:

Arterial pH <7.3 or arterial lactate >3.0 after adequate fluid resuscitation

OR

If all of the three following occur in 24-hour period
- Creatinine >300micromol/l
- PT >100 seconds (INR >6.5)
- Grade III/IV encephalopathy

Question 21

Which of the following are risk factors for hepatitis C?

Answer 21

IV drug use
Tattoos and piercings
Sexual contact
Blood transfusion prior to 1992

Question 22

Which of the following are potential complications of hepatitis C?

Answer 22

Hepatocellular carcinoma
Sjogren’s syndrome
Skin complications e.g., porphyria cutanea tarda
Liver cirrhosis

Question 23

What counselling should be given to a patient diagnosed with hepatitis C?

Answer 23

Abstain from alcohol
Avoid sharing razors with others
Aim for ideal body weight
Ensure you are fully vaccinated against other strains of hepatitis

Question 24

what is haemochromatosis

Answer 24

autosomal recessive genetic condition resulting in iron overload

it is an iron storage disorder

Question 25

what is the gene involved in haemochromatosis

Answer 25

The human haemochromatosis protein (HFE) gene is located on chromosome 6. The majority of cases of haemochromatosis relate to C282Y mutations in this gene. Mutations are required in both copies of the gene (homozygous) since it is an autosomal recessive condition. This gene is important in regulating iron metabolism.

Question 26

when does haemochromatosis usually present

Answer 26

after age 40 when the iron overload becomes symptomatic

Question 27

why does it present later in females

Answer 27

due to mentruation acting to eliminate iron from the body regularly

Question 28

what does haemochromatosis present with

Answer 28

Chronic tiredness
Joint pain
Pigmentation (bronze skin)
Testicular atrophy
Erectile dysfunction
Amenorrhoea (absence of periods in women)
Cognitive symptoms (memory and mood disturbance)
Hepatomegaly

Question 29

what is the initial investigation for haemochromatosis

Answer 29

serum ferritin

Question 30

what are the causes of a raised ferritin

Answer 30

Haemochromatosis
Infections (it is an acute phase reactant)
Chronic alcohol consumption
Non-alcoholic fatty liver disease
Hepatitis C
Cancer

Question 31

what helps to distinguish between high ferritin caused by iron overload and other causes

Answer 31

transferrin saturation

iron overload (transferrin saturation is high) and other causes (transferrin saturation is normal).

Question 32

what should be used to establish the iron concentration in the liver

Answer 32

Liver biopsy with Perl’s stain can be used to establish the iron concentration in the liver. Genetic testing means that a liver biopsy is not usually necessary for establishing a diagnosis. It may help stage the fibrosis and exclude other liver pathology.

Question 33

what are the complications associated with haemochromatosis

Answer 33

Secondary diabetes (iron affects the functioning of the pancreas)
Liver cirrhosis
Endocrine and sexual problems (hypogonadism, erectile dysfunction, amenorrhea and reduced fertility)
Cardiomyopathy (iron deposits in the heart)
Hepatocellular carcinoma
Hypothyroidism (iron deposits in the thyroid)
Chondrocalcinosis (calcium pyrophosphate deposits in joints) causes arthritis

Question 34

what is the management of Haemochromatosis

Answer 34

Venesection (regularly removing blood to remove excess iron – initially weekly)

Monitoring serum ferritin

Monitoring and treating complications