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Phase 2a Sam > HEPATOBILIARY > Flashcards

HEPATOBILIARY Flashcards

1
Q

Normal physiology - outline some of the basic roles of the liver

A
  • Storage(i.e. glycogen, iron, vitamins)
  • Breakdown(i.e. drugs, toxins, ammonia, bilirubin)
  • Synthesis(i.e. bile, cholesterol, coagulation factors, growth factors)
  • Immune function(i.e. innate immune protein production, resident immune cells)
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2
Q

Define what acute liver failure is.

A

Liver failure without an underlying chronic failure

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3
Q

What characterises acute liver failure?

A

Acute liver failure is a rare disease defined by jaundice, coagulopathy (derangement in clotting) , and hepatic encephalopathy.

coagulopathy (INR >1.5),
hepatic encephalopathy (HE) = altered level of consciousness as a result of liver failure.

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4
Q

What are the 3 ways acute liver failure can be categorised? What are these divisions based on?

A

ALF can be divided into hyperacute, acute and subacute based on the speed at which HE develops:

  • Hyperacute: HE within 7 days of noticing jaundice.
  • Acute: HE within 8-28 days of noticing jaundice
  • Subacute: HE within 5-12 weeks of noticing
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5
Q

What classification of Acute liver disease has the best prognosis

A

Hyperacute - Best prognosis as much better chance of survival and spontaneous recovery.

Subacute = Worst prognosis as usually associated with shrunken liver and limited chance of recovery.

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6
Q

Define acute on chronic liver failure

A

Acute-on-chronic = liver failure as a result of decompensation of chronic liver disease

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7
Q

Define Acute Liver Injury. How is it different to acute liver failure

A

acute liver injury from a primary liver aetiology. Characterised by impaired liver function but hepatic encephalopathy is absent, unlike in ALF.

It can lead to acute liver failure

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8
Q

What is the most common cause of acute liver failure in Europe/US?

A

Drug-induced liver injury - paracetamol and non-paracetamol (e.g. alcohol, anti-depressants, NSAIDs, ecstasy/cocaine, antibiotics).

Paracetamol most common

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9
Q

What is the most common cause of acute liver failure worldwide?

A

Viral (Hepatitis A, B and CMV)

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10
Q

What are some other causes of acute liver injury that can lead to acute liver failure?

A
  • Pregnancy-related(e.g. fatty liver of pregnancy, HELLP syndrome)
  • Autoimmune hepatitis
  • Wilson’s disease
    Other infections
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11
Q

What other infections have been known to cause Acute liver injury?

A

yellow fever, leptospirosis, EBV

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12
Q

What is a Secondary liver injury?
Give examples of it

A

similar to ALI but no evidence of a primary liver insult. Can also lead to acute liver failure

  • Ischaemic hepatitis
  • Severe infection(e.g. malaria)
  • Malignancy infiltration(e.g. lymphoma)
  • Heat stroke
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13
Q

Outline the general pathophysiology behind Acute liver failure

A

Damage due to the various causes leads to Massive hepatocyte necrosis/apoptosis, so liver cannot carry out normal function.

This leads to vasoconstriction and hepatic hypertension, to which the body responds to by trying to increase portal flow, by splanchnic vasodilation ==>
This leads to drop In BP, and poor peripheral perfusion leading to multi organ failure

Cerebral oedema can also occur

🡪 splanchnic vasodilation 🡪 drop in BP 🡪 increased CO to compensate for BP 🡪 salt and water retention to increase blood volume 🡪 hyperdynamic circulation (increased portal flow)

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14
Q

Pathophysiology behind acute liver injury - how can it lead to cerebral oedema?

A

Due to the liver failing to clear ammonia from the blood,

This can damage the cells in the brain, leading to inflammation and an increase in fluid in the brain, resulting in cerebral oedema.

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15
Q

What are some symptoms of Acute liver failure?

A

Jaundice

HE related:
Confusion
- Apraxia - difficulty with motor planning
- Asterixis:

  • Right upper quadrant pain(variable)
  • Hepatomegaly
    Nausea/vommitting
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16
Q

How can you grade Hepatic Encephalopathy?

A

The severity of HE can be graded using theWest Haven criteria, Grades I to IV

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17
Q

West Haven criteria - outline what a Grade I and Grade II patient with Hepatic encephalopathy would look like

A
  • Grade I: change in behaviour with minimal change in level of consciousness. May have mild asterixis or tremor.
  • Grade II: gross disorientation, drowsiness, asterixis and inappropriate behaviour
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18
Q

West Haven criteria - outline what a Grade III and Grade IV patient with Hepatic encephalopathy would look like

A
  • Grade III: marked confusion, incoherent speech, sleeping most of the time but rousable to verbal stimuli. Asterixis less noticeable, elements of rigidity.
  • Grade IV: coma that is unresponsive to verbal or painful stimuli. Evidence of decorticate or decerebrate posturing.
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19
Q

First line tests to order in suspected acute liver failure - what would you look for in blood tests?

A

Blood tests - can see hyperbilirubinaemia, elevated liver enzymes
U and Es - can be elevated due to renal failure secondary to ALF
FBC - can see leukocytosis, anaemia, thrombocytopenia
Prothrombin and International normalized ratio -INR <1.5

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20
Q

Other than blood tests, what other first line investigations should you do in acute liver failure?

A

Paracetamol levels
Arterial blood gas - can be acidotic in paracetamol overdose
Liver function tests - can see hyperbilirubinaemia, elevated liver enzymes

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21
Q

Acute liver failure - what viruses can you screen for in suspected acute liver failure?

A
  • Hepatitis A: anti-HAV IgM
  • Hepatitis B: HBsAg, anti-HBc IgM +/- HBV DNA levels
  • Hepatitis C: anti-HCV (unlikely to cause ALF - may be co-infected)
  • Hepatitis D: if positive for HBV
  • Hepatitis E: anti-HEV IgM +/- HEV RNA levels
  • Other: CMV, EBV, HSV, VZV, Parvovirus
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22
Q

What tests would you run to asses the cause of ALF?

A

Paracetamol serum level
Alpha-1 antitrypsin levels
Autoimmune markers: ANA, autoantibodies, immunoglobulins, ANCA
Toxicology screen: serum/urine
Viral screen:

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23
Q

How do you treat ALF?

A

Treat underlying causes
Liver transplant if damage is too bad

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24
Q

What key vitamins do you want to supplement patients with acute liver failure as you treat them?

A

Good nutrition - thiamine and folate supplementation

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25
Q

What are some complications of acute liver injury?

A
  • Acute kidney injury/ hepatorenal syndrome
  • Metabolic disturbance (electrolyte imbalance)
  • Hypoglycaemia
  • Haemorrhage (e.g. GI Bleeding)
  • Cerebral dysfunction (e.g. seizures, irreversible brain injury).
  • Patients are at risk of high output cardiac failure due to low vascular resistance from the widespread inflammatory response.
  • Sepsis
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26
Q

How can acute liver failure lead to renal failure?

A

because the liver is responsible for producing a number of proteins that help regulate blood pressure, and when the liver fails, these proteins are no longer produced.

This can lead to a decrease in blood pressure, causing the kidneys to not receive enough blood and oxygen, leading to renal failure.

Also Liver failure====> Leads to drop in BP - poor peripheral perfusion leading to multi organ failure

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27
Q

How can liver failure/liver cirrhosis lead to portal hypertension

A

Portal hypertension in cirrhosis is due to to a rise in intrahepatic vascular resistance because massive structural changes associated with fibrosis and increased vascular tone in the hepatic microcirculation.

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28
Q

How can liver cirrhosis lead to renal failure, known as hepatorenal syndrome?

A

Liver cirrhosis leads to portal hypertension

In response to this, portal blood vessels dilate, stretched by large amounts of blood pooling there.

This leads to a loss of blood volume elsewhere, including kidneys.

Leads to hypotension in the kidney and activation of the RAAS. This causes renal vasoconstriction, which combined with low circulation volume leads to starvation of blood to the kidney

Hepatorenal syndrome is fatal within a week or so unless liver transplant is performed

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29
Q

Define what chronic liver failure

A

Repeated damage to liver tha leads to inflammation, fibrosis and eventually cirrhosis.
CLD is generally defined as progressive liver dysfunction for six months or longer.

The end result of chronic liver disease is cirrhosis, which describes irreversible liver remodelling.

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30
Q

Name some common cause of chronic liver failure

A
  • Alcohol
  • Viral(Hepatitis B, C)
  • Inherited(Alpha-1-antitrypsin deficiency, Wilson’s disease, Hereditary haemochromatosis)
  • Metabolic(Non-alcohol fatty liver disease / Non-alcoholic steatohepatitis)
  • Autoimmune(Autoimmune hepatitis)
  • Biliary(Primary biliary cholangitis, primary sclerosing cholangitis)
  • Vascular(Ischaemic hepatitis, Budd-Chiari syndrome, congestive hepatopathy)
  • Medication(Drug-induced liver injury)
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31
Q

Outline the pathophysiology behind chronic liver failure.

A

Overtime, progressive insults to the liver leads toinflammation (hepatitis), fatty deposits (steatosis) and scarring (fibrosis).

The normal liver architecture is replaced by fibrotic tissue and regenerative nodules.

The end result of this process is cirrhosis, which describesirreversible liver remodelling

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32
Q

What are the two types of chronic liver failure?

A

Two types are Compensated - despite injury, liver can carry out normal function - aka asymptomatic

Decompensated - liver injury leads to inadequate function

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33
Q

What will you see in decompensated liver failure?

A
  • Coagulopathy(reducing clotting factor synthesis)
  • Jaundice(impaired breakdown of bilirubin)
  • Encephalopathy(poor detoxification of harmful substances)
  • Ascites(poor albumin synthesis and increased portal pressure due to scarring)
  • Gastrointestinal bleeding(increase portal pressure causing varices)
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34
Q

What are some signs of chronic liver failure?

A

Jaundice
Hepatomegaly
Spider Naevi
Palmar Erythema
Gynaecomastia
Bruising – due to abnormal clotting
Ascites
Caput Medusae –
Asterixis – “flapping tremor” in decompensated liver disease

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35
Q

Signs of chronic liver disease - what is
palmar Erythema
Spider Naevi
Caput Medusae

A

a) (redness of thenar and hypothenar eminences)
b) blanch on pressure and spider-like branches fill from a central arteriole
c) engorged superficial epigastric veins

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36
Q

What first line biochemical tests would you run in suspected chronic liver failure?

A

LFTs- Raised AST and ALT
FBC (thrombocytopenia)

Also could see Hyperbilirubinaemia, raised INR, low albumin - in decompensated liver disease.

ALT IS MORE SPECIFIC TO LIVER FAILIURE THAN AST, AS AST CAN BE FOUND IN OTHER ORGANS BESIDE LIVER

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37
Q

What is AST? Why is it useful in diagnosing Liver disease?

A

AST (aspartate aminotransferase) is an enzyme that is found mostly in the liver, but it’s also in muscles and other organs in your body. When cells that contain AST are damaged, they release the AST into your blood. An AST blood test measures the amount of AST in your blood.

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38
Q

What is ALT? Why is it useful in diagnosing Liver disease?

A

alanine transaminase. It is an enzyme found mostly in the liver. An ALT test measures the amount of ALT in the blood.

When liver cells are damaged, they release ALT into the bloodstream. High levels of ALT in your blood may be a sign of a liver injury or disease.

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39
Q

Regarding chronic liver disease, what would thrombocytopaenia be indicative of?

A

portal hypertension and hypersplenism

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40
Q

What types of imaging would you use when investigating chronic liver failure?

A
  • Transabdominal Ultrasound - first,
    CT - more specifc
    MRI - most specific/the best
    USS:US is quick, inexpensive, and has a sensitivity of 65-95% for detection of CLD.
  • CT:Provides a more detailed view of the abdominal viscera and is good for secondary findings (e.g. features of portal hypertension).
  • MRI:Is emerging as a highly sensitive and specific modality for liver fibrosis.
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41
Q

What is the gold standard test for chronic liver failure?

A
  • Liver biopsy - invasive so usually reserved for specific cases:
    • Liver disease of unknown aetiology
    • Differentiating between acute and chronic disease
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42
Q

How do you treat CLD?

A

Treat underlying pathology e.g. alcohol cessation, removal of offending medications or use of anti-viral therapies in chronic hepatitis.
Transplantation based on patient’s ‘United Kingdom model for end-stage liver disease’ (UKELD) score

Correct any electrolyte/glucose imbalances

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43
Q

How can you treat hepatic encephalopathy?

A
  • . Constipation is the main driver of HE.
    • First line treatments:Involves laxatives (i.e. lactulose 15-20 mls QDS)to maintain bowel motions
      **Correct electrolytes.
    • Second-line treatments:Involves the long-term use of antibiotics

rifaximin:

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44
Q

What antibiotic would you give to help treat hepatic encephalopathy?

A

i.e. rifaximin), as this lowers the amount of nitrogen producing bacteria in the gut flora

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45
Q

How could you use the AST and ALT values to determine whether someone’s liver disease is alcoholic liver disease, or hepatitis/NAFLD?

A

In Alcoholic liver disease - AST higher than ALT 2:1 ratio
In Hepatitis and Non Alcoholic fatty liver disease , ALT is higher

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46
Q

Complications of chronic alcohol disease -
How would you treat ascites? How does Chronic liver disease cause it?

A

– Ascites - develops due to a combination of portal hypertension and loss of oncotic pressure (hypoalbuminaemia).
- Aldosterone antagonists:e.g. spironolactone (can be combined with loop diuretics i.e. furosemide).
- Paracentesis:percutaneous drainage of ascites

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47
Q

Complications of chronic alcohol disease -
How would you treat GI bleeding? How does Chronic liver disease cause it?

A
  • GI bleeding - due to oesophageal varices secondary to portal hypertension
    • Beta blockers to reduce portal hypertension
    • Endoscopic variceal band ligation - for variceal haemorrhage
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48
Q

What are the 3 stages of alcoholic liver disease?

A

fatty liver (steatosis), alcoholic hepatitis (inflammation and necrosis), and alcoholic liver cirrhosis.

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49
Q

A UK unit of alcohol is equivalent to how many grams and how many millilitres of pure alcohol?

A

A UK unit is 8 grams or 10ml of pure alcohol

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50
Q

How can you calculate the amount of units in a drink?

A

Strength of the drink (% ABV)
x
Amount of liquid (Litres)

1 Bottle wine = 0.75L x 13.5% ABV
= 10 units

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51
Q

What are some risk factors for developing alcoholic liver disease?

A
  • Prolonged and heavy alcohol consumption
  • Hepatitis C - increased risk of cirrhosis
  • Female sex - ALD develops more rapidly and occurs at lower drinking levels in women than in men. However, most patients with ALD are male.
  • Genetic predisposition - genes encoding enzymes that metabolise both alcohol and acetaldehyde, and pro-inflammatory (tumour necrosis factor [TNF]-alpha) and anti-inflammatory cytokines (interleukins 6 and 10), may influence the predisposition to ALD and cirrhosis.
  • Increasing age >65
  • Obesity
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52
Q

Normal physiology - outline basic alcohol metabolism.

A

2 ways:
Alcohol =Alcohol Dehydrogenase=> Acetaldehyde == Acetaldehyde Dehydrogenase=> Acetate ==> CO2 and H2O

Chronic alcohol use upregulates cytochrome P450 2E1 =

more free radicals produced as there is more oxidation of NADPH to NADP

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53
Q

What is the third way that alcohol can be metabolised by the liver, that is activated by chronic alcohol consumption?

A

hepatic macrophages, which produce tumour necrosis factor (TNF)-alpha and induce the production of reactive oxygen species in the mitochondria.

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54
Q

What are people with an alcohol use disorder often deficient in?

A

Alcoholic patients are often deficient in antioxidants like Gluthathione and Vitamin E, so oxidative stress caused can lead to further hepatocyte necrosis and apoptosis

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55
Q

Pathophysiology behind alcoholic liver disease - What does the formation of acetaldehyde lead to?

A

When acetaldehyde is bound to cellular proteins, it produces antigenic adducts which are recognised as foreign and can be attacked by the immune system, causing further damage.

At this point, the patient develops hepatitis.

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56
Q

Name some general signs of alcoholic liver disease - can be seen in alcoholic fatty liver, hepatitis, cirrhosis

A
  • Hepatomegaly
  • Abdominal pain
  • Haematemesis
    Venous collaterals - engorged para-umbilical veins (caput medusae),
  • Jaundice
  • Palmar erythema
  • Asterixis
  • Ascites
  • Weight loss
  • Fatigue
  • Confusion
  • Bruising - coagulopathy
  • Withdrawal symptoms - high pulse, low BP, tremor, confusion, fits, hallucinations
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57
Q

Name some signs you may see in a patient with liver cirrhosis

A
  • Patients can be very well with few symptoms
  • On examination there are usually signs of chronic liver disease - ascites, bruising, clubbing and Dupuytren’s contracture
    palmar erythema
    spider naevi,
  • There are features of alcohol dependency
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58
Q

What is Dupuytren’s contracture and why do you see it in liver disease?

A

Dupuytren’s contracture is a progressive hand condition, leads to tightening of the palmar fascia, so fingers pull inward, leading to a claw-like deformity.

It is often seen in individuals with liver disease, as it is thought that the accumulation of toxins in the liver may cause the fascia to become thicker, leading to the contracture.

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59
Q

What two questionnaires can be used to screen for alcohol abuse in suspected alcoholic liver disease patients?

A

CAGE QUESTIONAIRE
C – CUT DOWN? Ever thought you should?
A – ANNOYED? Do you get annoyed at others commenting on your drinking?
G – GUILTY? Ever feel guilty about drinking?
E – EYE OPENER? Ever drink in the morning to help your hangover/nerves?

AUDIT QUESTIONAIRE (Alcohol Use Disorders Identification Test)
10 MCQs, a score of 8 or more shows harmful alcohol use

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60
Q

What are some baseline investigations you would do in suspected alcoholic liver disease

A

Raised Serum Aspartate aminotransferase AST, and alanine aminotransferase ALT
The classic ratio of AST/ALT >2 is seen in about 70% of cases

Raised Billirubin, Lowered Serum albumin
reduced platelets,
raised prothrombin time/INR

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61
Q

Outline some general management of alcoholic liver disease

A

Alcohol Cessation - eg Alcoholic anonymous

Disulfiram - causes negative effects for patients due to acetaldehyde buildup - aversion therapy

Good Hydration
Good nutrition, diet high in vitamins and protein

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62
Q

How can you manage alcoholic withdrawal in patients with alcoholic liver disease?

A
  • Diazepam
  • IV Thiamine to prevent Wernicke-Korsakoff encephalopathy (presents with
    ataxia, confusion and nystagmus) which occurs from alcohol withdrawal,
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63
Q

How can you manage Alcoholic hepatitis seen in alcoholic liver disease patients?

A

-Good diet of proteins and minerals

Steroids eg Prednisolone can be beneficial short term,
- Screen for infections (ascitic fluid tap) and treat spontaneous bacterial peritonitis

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64
Q

How can you manage Alcoholic cirrhosis seen in alcoholic liver disease patients?

A
  • Reduce salt intake
  • Avoid aspirin and NSAIDs
  • Liver transplantation
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65
Q

What are some complications of alcoholic liver disease on the
a) Liver
b) CNS
c) Gut

A
  • Liver cirrhosis and related complications e.g. liver failure, hepatocellular carcinoma
  • CNS - self neglect, low memory and cognition, cortical atrophy, retrobulbar neuropathy, fits, falls, neuropathy, hepatic encephalopathy, Wernickes
  • Gut - obesity, diarrhoea and vomiting, gastric erosions, peptic ulcers, varices, pancreatitis, cancer, oesophageal rupture
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66
Q

Complications of alcoholic liver disease - what is delirium tremens? What can it present with?

A

Delirium tremens is a rapid onset of confusion usually caused by withdrawal from alcohol.

Acute confusion , severe agitation, delusions and hallucinations,
tremor, tachycardia, hypertensio, hyperthermia, ataxia,
arrhythmias

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67
Q

What are some complications of alcoholic liver disease on the
a) Blood
b) Heart
c) reproductive system

A
  • Blood - coagulopathy, thrombocytopenia, anaemia from: marrow depression, GI bleeding, alcoholism related folate deficiency, haemolysis, sideroblastic anaemia
  • Heart - arrhythmias, high BP, cardiomyopathy, sudden death
  • Reproduction - testicular atrophy, low testosterone and progesterone, high oestrogen, fetal alcohol syndrome
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68
Q

Define non alcoholic fatty liver disease. Outline its spectrum of disease.

A

A fatty liver that cannot be attributed to alcohol or viral causes

Spectrum of disease - steatosis, steatohepatitis, fibrosis, cirrhosis (least to most severe)

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69
Q

What are some causes/risk factors for developing non alcoholic fatty liver disease?

A
  • Older age
  • Obesity
  • Hypertension
  • Diabetes
  • Hypertriglyceridemia
  • Hyperlipidemia
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70
Q

Outline the initial pathophysiology behind non alcoholic fatty liver disease.

A

Insulin resistance plays a key role
Overtime, insulin receptors are less responsive to insulin so liver increases fat storage and decreases fatty acid oxidation

There is also increased synthesis and uptake of free fatty acids from the blood (known as steatosis).

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71
Q

Pathophysiology behind non alcoholic fatty liver disease - what happens to the excess fat stored in the liver, and how does this damage the liver?

A

The fat in the hepatocytes causes them to swell.
These fats, especially unsaturated fats, are vunverable to ROS and form fatty acid radicals, which can further react with other fatty acids and oxygen -

These reactions damage the lipid membrane, leads to cell death

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72
Q

Pathophysiology behind non alcoholic fatty liver disease - what does damaged lipid membrane and cell death lead to?

A

It generates inflammation - inflammation + steatosis = steathepatitis

Damage also attracts neutrophils to the liver. Chronic steatoheptitis can trigger stellate cells to lay down fibrotic tissue (fibrosis).

The architecture then changes to the point where disease is now classed as cirrhosis

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73
Q

What are some clinical manifestations of non alcoholic fatty liver disease?

A

Sometimes symptoms are vague:

  • Fatigue
  • Malaise

Sufficient damage presents with:

  • Hepatomegaly
  • Pain in RUQ
  • Jaundice
  • Ascites
  • Bruising
  • Pruritis - itchiness/irritation of skin
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74
Q

What investigations would you carry out in suspected non alcoholic fatty acid disease?

A

Serum AST and ALT: Increase in ALT and sometimes AST. (Different to alcoholic liver disease where AST>ALT)

LFT: raised bilirubin, ALP, GGT, prothrombin time, low serum albumin

FBC: anemia and thrombocytopenia due to hypersplenism

Imaging: US, CT, MRI to look for fatty infiltrates

Biopsy: used to diagnose and assess severity
*think non alcoholic fatty liver disease when patients don’t drink lots of alcohol

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75
Q

What is the management for non alcoholic fatty liver disease?

A

Steatosis and steatohepatitis is reversible if underlying cause is addressed. Cirrhosis is not reversible.

  • Avoid alcohol consumption
  • Reverse factors that contribute to insulin resistance
    • Healthy diet
    • Active lifestyle
    • Medication to control blood glucose
  • Control risk factors e.g. bariatric surgery for obesity
  • Address cardiovascular risk (commonest cause of death)
  • Vitamin E may improve histology of fibrosis
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76
Q

name some general causes of hepatitis

A

Alcoholic hepatitis
Non alcoholic fatty liver disease
Viral hepatitis
Autoimmune hepatitis
Drug induced hepatitis (e.g. paracetamol overdose)

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77
Q

What are some non specfic symtoms of hepatitis?

A

Abdominal pain
Fatigue
Pruritis (itching)
Muscle and joint aches
Nausea and vomiting
Jaundice
Fever (viral hepatitis)

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78
Q

Other than Hep A-E, what other viruses can cause hepatitis?

A

Herpes viruses e.g., EBV (Epstein-Barr virus) CMV (Cytomegalovirus), VZV (Varicella Zoster Virus)

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79
Q

What type of Virus is Hep A? What family of viruses does it belong to?

A

The Hepatitis A virus is a non-enveloped single-stranded RNA virus, Belongs to the Picornaviridaefamily.is a (picornavirus)

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80
Q

How is Hepatitis A spread? Where is it endemic?

A

Spread via the faeco-oral route (contaminated food and water)

Endemic in Africa and South America. It is uncommon in the UK.
Most infections are in children

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81
Q

What are some risk factors for getting Hepatitis A?

A
  • Travel: those travelling to endemic areas
  • Sexual:high risk activities, multiple partners
  • Occupational risks: for example laboratory or sewage workers
  • IV drug users:known to be at increased risk
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82
Q

What are the 4 phases of Hepatitis A?

A
  1. Incubation
  2. Prodromal
  3. Icteric
  4. Convalescent
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83
Q

Phases of Hep A - what happens in the
a) Incubation
b) Prodromal
Phases?

A

a) Hepatitis A incubation period, may last from 2 - 6 weeks
b) Prodromal: Early part of the disease, characterised by fever, joint pain and rash. Flu-like symptoms may be present

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84
Q

Phases of Hep A - what happens in the
a) Icteric
b) Convalescent

A

a) Phase with jaundice, as well as abdo pain, changes in bowel habit – MOST INFECTIOUS JUST BEFORE JAUNDICE ONSET
b) Convalescent:Recovery phase as the body returns to normal and symptoms subside.

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85
Q

What are some key symptoms/signs of hepatitis A?

A
  • Jaundice
  • RUQ tenderness
  • Hepatomegaly (85%)
  • Abdominal discomfort
  • Nausea
  • Arthralgia
  • Anorexia
  • Diarrhoea
  • Flu-like illness
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86
Q

What are the 1st line tests for suspected Hepatitis A?

A

SEROLOGY - Hepatitis A virus Antibodies, IgG and IgM

  • +ve HAV-IgM, +ve HAV-IgG:**Likely acute hepatitis A infection
  • +ve HAV-IgM, -ve HAV-IgG:**May indicate acute infection or false positive IgM
  • -ve HAV-IgM, +ve HAV-IgG:**Indicates previous infection or vaccine based immunity
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87
Q

What is the management of a Hep A viral infection?

A

Supportive management:

  • General points: advise good oral hydration and rest. Alcohol should be avoided.
    Antiemetics
  • Reduce transmission:**stay at home, good hygiene, avoid unnecessary contact and unprotected sex for 7 days after jaundice appears or symptoms began.
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88
Q

What are some complications of Hep A? What should you monitor in these patients?

A
  • Fulminant liver failure: is rare, if so then give interferon alfa given.
    Relapsing hepatitis(may occur in 5-15%)

Patients should be reviewed on a weekly basis for clinical review and repeat LFTs. Refer to specialist services if clinically worsening or persistently abnormal LFTs.

  • Hep A vaccineHepatitis A vaccine is recommended to those at risk of infection and at risk of complications of infection.
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89
Q

Is Hepatitis A a notifiable disease?

A

YES

Clinicians should contact their local Health Protection Unit to allow contact tracing and monitoring of outbreaks.

In England hepatitis A is a ‘notifiable disease’, meaning you must notify a Proper Officer of the local authority.

At risk contacts should be reviewed, if they have not been vaccinated, immunoglobulin should be considered. Typically the hepatitis vaccine will be offered.

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90
Q

What type of virus in the Hepatitis B virus?
Can it cause acute, chronic, or both types of hepatitis?

A

Hepatitis B is caused by the hepatitis B virus (HBV).

It is an enveloped DNA virus that belongs to the Hepadnaviridae family and can cause acute or chronic hepatitis:

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91
Q

How is Hepatitis B spread?

A

It is transmitted by direct contact with blood or bodily fluids, such as during sexual intercourse or sharing needles (i.e. IV drug users or tattoos). It can also be passed through sharing contaminated household products such as toothbrushes or contact between minor cuts or abrasion

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92
Q

What are the 3 types of antigens that would show up in Serology tests in Hep B, and what can they show

A
  1. Surface Antigen - HBsAg present in active infection, and 6 months after exposure
  2. E Antigen - HBeAg - released during replications, indicates acute infection
  3. Core Antigen - HBcAg - not in the blood but in the core of the virus. implies past or current infection
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93
Q

Hep B infection - being positive for what antigen, after how long indicates you are a carrier of Hep B? What % of infections lead to carriers?

A

HBsAg persisting for >6 months defines carrier status and occurs in 5–10% of infection

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94
Q

Hep B serology - what antibody can distinguish acute, chronic or past infections? Levels of IgM and IgG versions of the antibody can show either
a) acute infection
b) chronic infection

A

Hepatitis B c antibodies (HBcAb) can help distinguish acute, chronic and past infections.

measure IgM and IgG versions of the HBcAb.

a) Anti-Hbc IgM implies an active infection, so high in acute infection and low in chronic infection

b) Anti- HBc IgG indicates a past infection where the HBsAg (antigen) is negative.

taken from OHCM 9th edition

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95
Q

Hep B serology - presence of what would indicate previous infection

A

Positive HBcoreAntibody IgG, and a negative HB surface antigen

HB surface antigen - indicates active disease

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96
Q

Hep B serology - what antibody will be present in those who have received an Hep B vaccination, but have not been infected?

A

Anti-HBsAg

(Antibody to the surface antigen on Hep B virus)

Vaccinated patients are tested for HBsAb to confirm their response to the vaccine. The vaccine requires 3 doses at different intervals.

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97
Q

Hep B serology - What would present HBeAg show? What does an absent HBeAg but present HBeAB indicate?

A

Hepatitis B e antigen
Where present, implies the patient is in an acute phase of infection, where virus is actively replicating.

The level of HBeAg correlates with their infectivity. aka high HBeAg = highly infectious.

When they HBeAg is negative but the hepatitis B e antibody is positive = implies they have been through phase of viral replication, but it has stopped replicating now, aka less infectious

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98
Q

What is the management for acute Hep B?

A

Supportive, so Monitor liver function
Fulminant hepatic failure (0.1% - 0.5%)
Antiviral if severe
Liaise with hepatology/liver transplant centre
Management of contacts (HV vaccine ± HBIG)

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99
Q

Name some antivirals used in the management of severe Hep B.

A

Consider oral nucleoside analogue, like

Entecavir, tenofovir,

They are incorporated into the DNA chain, causing the chain to terminate when the virus attempts to replicate

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100
Q

What management options would you consider in chronic Hep B?

A

Pegylated interferon-α 2a
Liver Transplant

Do this along side your antivirals, like Tenofovir and entecavir

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101
Q

What type of Virus is Hep C? Can infection be acute, chronic or both?

A

It’s an RNA flavivirus
Infection may be acute and chronic.

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102
Q

How many Genotypes of Hep B are there, and what are the types most common in Europe?

A

7 genotypes; genotype 1a and 1b account for 70% cases in USA and 50% in Europe

Rapid mutations so envelope proteins change rapidly so its hard to develop a vaccine

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103
Q

What are some signs of Hep C infection, in the
a) acute stage
b) chronic stage

A

Acute - Most patients are asymptomatic
- 10% have mild influenza-like illness with jaundice and a rise in serum aminotransferases (ALT and AST)

b) Chronic - Signs of cirrhosis, liver failure and hepatocellular carcinoma

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104
Q

What are the first line investigations for investigating Hep C?

A

HCV antibodies - confirms prior exposure (remember there is no vaccine for Hep C)

HCV PCR - if this is positive, implies an active/current infection

Serum aminotransferases may be elevated

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105
Q

What is the management for Hep C?

A

Directly acting anti-virals (DAAs)
Combination of DAAs - eg Entecavir from two or more of three drug classes, usually combined with ribavirin (RBV)

so eg
Ledipasvir, Sofosbuvir, Grazoprevir, Ribavirin

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106
Q

What type of Virus is Hep D? When do you see it?

A

It is a unique RNA virus - Requires HBV for assembly

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107
Q

Outline the pathophysiology behind Hep D

A

Hep D virus is an incomplete RNA particle enclosed in a shell of HBsAg
Virus
is unable to replicate on its own but is activated by the presence of HBV

It attaches itself to the HBsAg to survive and cannot survive without this protein.

If acquired simultaneously with HBV (co-infection) causes increased severity of acute infection

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108
Q

Hep D pathophysiology - Define
Co - infection
Superinfection

A

Co infection - When you get HVD and HBV at same time - indistinguishable from normal Hep B infection

Superinfection When you have chronic Hep B infection, and get HDV on top of it.
== Speeds up scarring

It attaches itself to the HBsAg to survive and cannot survive without this protein.

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109
Q

What do you test for in suspected Hep D patients?

When would you ask for it?

A

Anti-HDV antibody (only ask for it if HBsAg +ve)

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110
Q

What is the treatment for Hep D? Where is it most common?

A

As interferon-a has limited success, liver transplantation may be needed

Most common in eastern Europe, eg Romania

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111
Q

What type of virus is Hep E? How is it spread/where is it found?

A

RNA virus and acute only (can be chronic in immunosuppressed)

Route of Transmission
Faeco-oral route – water or food-borne
Found in undercooked pork

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112
Q

Which of Hepatitis A,B,C,D,E do you not need to identify public health organisations about?

A

None!! All cases of Hepatitis A,B,C,D,E you need to notify public health for

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113
Q

What tests can you do for suspected Hep E infection?

A

Serology – HEV antibodies
Nucleic acid amplification test

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114
Q

What is the acute management for someone with HEV?

A

Management
Supportive, liver transplant eg Entecavir
Consider ribavirin – anti-viral medication
Most likely see chronic HEV in immunocompromised

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115
Q

What is the chronic management for someone with HEV, when are you most likely to see someone with chronic HEV?

A

Chronic infection (immunosuppressed)
Reverse immunosuppression (if possible)
If HEV RNA persists, treat with ribavirin

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116
Q

What would you do for someone who it pregnant who has Hepataitis?

A

An Ultrasound of the foetus and test for it - to make sure foetus doesn’t get fulminant Hepatitis

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117
Q

Which Hepatitis Viruses have been known to lead to Hepatocarcinoma?

A

Hep B and Hep C

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118
Q

Recap - Outline how each of Hep A - E is spread

A

Hep A - faeco-oral route (contaminated food and water)
Hep B - direct contact with **blood or bodily fluids, such as during sexual intercourse or sharing needles*
Hep C - contact with infected blood - sharing needles and razors
Hep D- only with Hep B so also blood/bodily fluids
Hep E - Faeco-oral route – water or food-borne
Found in undercooked pork

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119
Q

Rules of thumb for hepatitis medication - outline suitable medication for Hep A - E

A

Always can say supportive, and avoid alcohol

Hep A - INTERFERON ALPHA - Entercavir

Hep B - Entecavir, Tenofovir

Hep C - Entecavir,
combined with Ribavirin

Hep D - Interferon a, liver transplant

Hep E - transplant Entecavir, Consider ribavirin

basically if in doubt say Entecavir - its a Direct acting antiviral

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120
Q

What is the cause of Autoimmune hepatitis? How many types are there?

A

We are not sure of the exact cause, however it could be associated with a genetic predisposition and triggered by environmental factors such as a viral infection that causes a T cell-mediated response against the liver cells.

There are 2 types

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121
Q

Where is type 1 autoimmune hepatitis most likely to occur?

A

Adults
Type 1 typically affects women in their late forties or fifties. It presents around or after the menopause with fatigue and features of liver disease on examination. It takes a less acute course than type 2.

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122
Q

Where is type 2 autoimmune hepatitis most likely to occur?

A

In type 2, patients in their teenage or early twenties present with acute hepatitis with high transaminases and jaundice.

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123
Q

What antibodies are you likely to see with type 1 autoimmune hepatitis?

A

Anti-nuclear antibodies (ANA)
Anti-smooth muscle antibodies (anti-actin)
Anti-soluble liver antigen (anti-SLA/LP)

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124
Q

What antibodies are you likely to see with type 2 autoimmune hepatitis?

A

Anti-liver kidney microsomes-1 (anti-LKM1)
Anti-liver cytosol antigen type 1 (anti-LC1)

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125
Q

What is the management of autoimmune hepatitis?

A

High dose steroids (prednisolone) that are tapered over time, as other immunosuppressants, particularly azathioprine, are introduced.

Immunosuppressants are normally life long

Liver transplant may be required in end stage liver disease, however the autoimmune hepatitis can recur in transplanted livers.

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126
Q

Outline what liver cirrhosis is.

A

Change in normal liver architecture due to repeated insult to abnormal nodules, and fibrotic tissue

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127
Q

What are some causes of Cirrhosis

A

Chronic alcohol use

Chronic HBV or HCV

Genetic disorder like haemochromatosis, A1AT Deficiency

Autoimmune hepatitis

Non alcoholic fatty liver disease

Drugs eg Amiodarone (An anti-arrhythmic medicine)

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128
Q

Outline some of the pathophysiology behind liver Cirrhosis

A

Liver injury results in inflammation, necrosis which leads to the release of ROS

ROS activates Heptaic Stellate cells and Tissue macrophages (Kupffer cells)
Stellate cells release cytokines that attract neutrophils and macrophages to the liver 🡪 further inflammation and necrosis 🡪 fibrosis

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129
Q

Define what compensated and decompensated liver failure is.

A

Compensated – when the liver can still function effectively and there are no (or few) noticeable clinical symptoms

Decompensated – when the liver is damaged to the point that it cannot function adequately and overt clinical complications (such as jaundice, ascites, variceal haemorrhage and hepatic encephalopathy) are present

130
Q

Name some clinical manifestations of liver cirrhosis

A
  • Clubbing
  • Palmar erythema
  • Dupuytren’s contracture
  • Spider naevi
  • Xanthelasma - yellow fat deposits under skin usually around eyelids
  • Gynaecomastia
  • Loss of body hair
  • Hepatomegaly
  • Splenomegaly
  • Bruising
  • Ankle swelling and oedema
  • Abdominal pain due to ascites
131
Q

What are some initial tests you would order in investigating liver cirrhosis?

A

Liver Function tests - Alaine aminotransferase (ALT) and and Aspartate aminotransferase, (AST) Alkaline phosphatase (APT) and gamma-glutamyl transferase (GGT) will be raised

Serum Albumin will be lowered
Serum Sodium will be lowered
Serum Potassium will be raised

Prothrombin time prolonged

Platelet count low

132
Q

When in particular is gamma- Glutamyl transferase raised?

A

Gamma-GT indicates damage to the liver and bile ducts.

GGT is particularly associated with alcohol use.

133
Q

What are some other tests you could do in suspected liver cirrhosis, over than serology? What is the gold standard test?

A

Liver biopsy - gold standard

Abdominal ultrasound
Abdominal CT
Abdominal MRI

134
Q

What the management for liver cirrohsis?

A

Treat underlying cause!!
==> aka Antivirals Ledipasvir, Ribavirin
Good nutrition is vital.
Alcohol abstinence
Avoid NSAIDS, sedatives, and opiates.

Treat side effects - eg Treat ascites, Pruritus, (Cholestyramine)

Give Hep A and Hep B vaccination to those that are at risk!!

135
Q

Complications of cirrhosis - How would you treat
a) Asciets
b) Puritis

and prevent Infection and Cancer?.

A

Ascites - fluid restriction and reduced salt intake, spironolactone

Pruritus - Cholestyramine (Itchy skin is causes by failure to eliminate bile salts due to liver failure) Cholestyramine binds to bile acid in GI tract to prevent reabsorption

Spontaneous bacterial peritonitis - antibiotics

Hepatocellular carcinoma - need an ultrasound every 6 months to screen for it

136
Q

What types of hepatitis are there vaccinations for?

A

There are vaccines available for hepatitis A and hepatitis B. The hepatitis B vaccine is also available in combination with the hepatitis A vaccine.

137
Q

How does liver failure lead to thrombocytopaenia?

A

Because the liver produces Thrombopoietin, the hormone that stimulates bone marrow to make platelets.

When the liver is damaged less of this is made leading to a reduction in platelet production

138
Q

What are some complications of liver cirrhosis?

A

Coagulopathy – fall in clotting factors II, VII, IX and X
Encephalopathy – liver flap (flapping tremor with wrist extended) and confusion/coma
When toxins e.g. ammonia make it into the brain and cause mental deficits
Thrombocytopenia
Hepatocellular carcinoma - need an ultrasound every 6 months to screen for it
Hypoalbuminaemia
Portal hypertension - leads to Ascites, Oesophageal varices

139
Q

Normal physiology: Briefly outline Haem metabolism and bilirubin formation,
From haemoglobin to Unconjugated Billirubin

A

Haemoglobin= Haem =(Hemoxygenase)=> Biliverdin

Billverdin => Reduced to Unconjugated Bilirubin, travels In blood to bound to albumin to liver

140
Q

Normla physiology - outline billrubn metabolism form unconjugated billrubin to its waste products

A

Unconjugated Bilirubin undergoes Glucuronidation into Conjugated Bilirubin, (by enzyme glucuronosyltransferase)

Conjugated Billirubin is released in Bile and becomes Urobilinogen

90% of Urobilinogen becomes Stercobilin (faeces) and 10% becomes Urobilin (recycled back to bile or urinated out)

141
Q

What 2 main products can Haem be broken into?

A

Biliverdin and Fe2+

142
Q

What protein does unconjugated bilirubin bind to and why?

A

Albumin as it is not soluble it needs to travel to the liver

143
Q

What does conjugated bilirubin form?

A

Urobilinogen/Stercobilinogen

144
Q

What converts conjugated bilirubin to urobilinogen?

A

Intestinal bacteria

145
Q

What can urobilinogen form?

A

It can go back to the liver
It can go to the kidneys and form urinary urobilin, to be urinated out
Can form stercobilin which is secreted in faeces 90%

146
Q

What is pre-hepatic jaundice?

A

Problem before the liver

is caused by increased haemolysis. This results in the increased presence of unconjugated bilirubin in the blood as the liver is unable to conjugate it all at the same rate.

147
Q

What would stools and urine look like in pre-hepatic jaundice?
What are some disease that cause pre hepatic jaundice?

A

Pre hepatic jaundice:
high in blood, but normal in urine. (so stools brown and urine normal)
Enlarged Spleen, (due to excess breakdown)
Seen in: Malaria. Sickle Cell anaemia. Gilbert’s syndrome,

148
Q

What is intra-hepatic jaundice?

A

is caused by liver impairment. This causes the decreased ability of the liver to conjugate bilirubin, resulting in the presence of conjugated and unconjugated bilirubin in the blood.

149
Q

What can cause intra-hepatic jaundice?

A

Hepatitis/B/C, alcoholic liver disease, drug misuse.

150
Q

What is post-hepatic jaundice?

A

is caused by the blockage of bile ducts. This results in backflow of conjugated bilirubin into the blood as it cannot move past the obstruction.

151
Q

What causes post-hepatic jaundice?

A

Gall stones, pancreatitis, Gall/pancreatic cancer

152
Q

What compound causes dark urine?

A

Conjugated bilirubin

153
Q

A patient with jaundice has pale stools. What compound is absent?

A

Stercobilinogen

154
Q

Which type of bilirubin is raised in pre-hepatic jaundice?

A

Unconjugated bilirubin

155
Q

What is the affect on the urine and stools in a patient with post-hepatic jaundice

A

Dark urine and pale stools

156
Q

Which enzyme is deficient in Gilbert’s Syndrome?

A

UDP-gluconoryltransferase, due a fault in the UGT1A1 gene

157
Q

What does Gilbert’s Syndrome lead to?

A

This faulty gene results in slower conjugation of bilirubin in the liver, causing it to build up in the blood stream. ==> Prehepatic jaundice

158
Q

Define Wernicke’s Encephalopathy

A

is a neurological emergency resulting from thiamine deficiency with varied neurocognitive manifestations.

159
Q

What is Korsakoff’s Syndrome? How is it related to Wernickes?

A

Hypothalamic damage & cerebral atrophy due to thiamine
(vitamin B1) deficiency (eg in alcoholics).

Wernicke’s encephalopathy is the acute, reversible stage of the syndrome, and if left untreated it can later lead to Korsakoff syndrome, which is chronic and irreversible.

160
Q

Normal physiology - where is thiamine (vit B1) stored? Where is it absorbed?

What does it do in the brain?

A

Thiamine is typically stored in the liver and absorbed in the duodenum

in the brain thiamine helps maintain normal amino acid and neurotransmitter levels.

161
Q

What are some risk factors for developing Wernicke’s encephalopathy?

A
  • Alcohol abuse
  • Malnutrition
  • Anorexia
  • Malabsorption due to stomach cancer and IBD
  • Prolonged vomiting e.g. due to chemotherapy, hyperemesis
162
Q

How can chronic alcoholism lead to a thiamine deficiency?

A

It block the phosphorylation of thiamine, stopping it from being converted into its active form

Ethanol reduces gene expression of Thiamine transporter, so can stop it getting absorbed in the duodenum.

Alcoholic tend to have a poor diet, relying on alcohol for calories so will not get enough Thiamine (b1) anyway

163
Q

How can a lack of thiamine (vit B1) affect the brain?

A
  • Thiamine deficiency impairs glucose metabolism and this leads to a decrease in cellular energy.
  • The brain is particularly vulnerable to impaired glucose metabolism since it utilises so much energy.
164
Q

What is the classical triad seen in Wernicke’s encephalopathy?

A

1 confusion
2 ataxia (wide-based gait; fig 2)

3 ophthalmoplegia (nystagmus,
lateral rectus or conjugate gaze palsies).

165
Q

What does Wernicke - Korsakoff syndrome predominantly target? What symptoms does this cause?

A
  • Mainly targets the limbic system, causing severe memory impairment:
    • Anterograde amnesia: inability to create new memories
    • Retrograde amnesia: inability to recall previous memories.
    • Confabulation: creating stories to fill in the gaps in their memory which they believe to be true.
    • Behavioural changes
166
Q

What investigations would you do in suspected Wernicke’s encephalopathy?

A
  • Diagnosis is typically made based on clinical presentation
  • Bloods including LFTs: measure thiamine levels, measure blood alcohol levels, liver function may be deranged in alcoholism
  • Red cell transketolase test: rarely done, thiamine is a co-enzyme to transketolases so transketolase activity will be low
  • MRI/CT: can confirm diagnosis by showing degeneration of the mammillary bodies

Lumbar puncture to rule out other causes of the symptoms of wernickes

167
Q

What is the management for Wernicke’s encephalopathy?

A

Urgent replacement to prevent irreversible Korsakoff’s syndrome (p718). Give thiamine (Pabrinex®)

Oral supplementation (100mg OD) should continue until no longer ‘at risk’, give other B vitamins as well

Correct Magnesium deficiency as well
If there is coexisting hypoglycaemia, correct it

168
Q

Why do you need to give Thiamine before you give glucose in a patient with Wernicke’s?

A

it’s important to normalise the thiamine levels first, because without thiamine pyrophosphate, most of the glucose will become lactic acid and that can lead to metabolic acidosis. (often the case in
this group of patients),

make sure thiamine is given before glucose, as Wernicke’s can be caused by glucose administration to a thiamine-deficient patient -

NOT GIVING THIAMINE AS YOU JUST THINK ITS HYPOGLYCAEMIA IS A COMMON MISTAKE DOCTORS MAKE

169
Q

What is biliary colic?

A

Biliary Colic is the name given to the pain experienced from gallstones, it is not a condition itself. Gallstones are often described as biliary colic though so this can be confusing.

170
Q

Describe the nature of the stone - induced ductular obstruction pain that is biliary colic

A

sudden onset, severe but constant and has a crescendo characteristic
Pain is temporary and stops when gallstone dislodges

171
Q

Outline some of the epidemiology of biliary colic

A

May be present at any age but unusual <30
Increasing prevalence with age
More common in females
More common in Scandinavians, S. Americans and Native North Americans

172
Q

Normal anatomy - what does the common hepatic duct and the cystic duct join to form?

A

The common bile duct

credit - teach me anatomy

173
Q

Normal anatomy - what does the common bile duct go on to join with? Where does the join happen?

A

The common bile duct goes onto to join the pancreatic duct. they meet at the major duodenal papilla (known as the ampulla of vater) , just as they enter the duodenum

picture credit - unknown

174
Q

Normal anatomy - where in the duodenum is the major duodenal papilla? What controls its opening and closing?

A

In the descending part of the duodenum. The Spinchter of Oddi controls its opening and closing

175
Q

Define Cholestasis

A

blockage to the flow of bile

176
Q

Define Cholelithiasis

A

the preasence of gall stones

177
Q

Define Choledocholithiasis

A

gallstone(s) in the common bile duct

178
Q

Normal physiology - what is bile made from

A
  • Bile salts
    • Cholesterol
    • Electrolytes
    • Phospholipids
    • Bilirubin
      It is Amphipathic - has both Hydrophobic and hydrophilic parts
179
Q

Normal physiology - name some functions of bile

A

Digestion of Dietary fats, Facilitates Protein absorption, Has anti-microbial properties, Prevents Calcium Gallstones

180
Q

How can stones in the gall bladder form?

A

Stones form from supersaturation of bile - 2 ways

  1. From build up of excess cholesterol, and cholesterol crystals
  2. From build up of pigment from excess bilirubin - seen in patients with chronic haemolysis (e.g. hereditary spherocytosis and sickle cell disease)

Reduced stasis and motility of Gall bladder.

181
Q

What are some risk factors for devloping gall stones/ experiencing biliary colic?

A

The 5Fs: Fat, Fertile, Forty, Female, Fair, (Caucasian) FHx

rapid weight loss

CROHN’S DISEASE can result in terminal ileitis, the part of the bowel where gall stones are absorbed - leads to bile salts not being absorbed - so Crohns can be a risk factor for galls stones

182
Q

What is the classic presentation of biliary colic?

A

Classically ‘colicky’ RUQ pain that is worse after eating large or fatty meals (triggers gallbladder to contract against the blockage).
May also radiate to epigastrium and back

Murphys sign negative

May have no symptoms!

183
Q

What is murphys sign?

When is it present?

A

Murphy’s sign is a maneuver used by physicians to diagnose the presence of gallstones.

Seen by patient inhaling while the physician palpates the right upper quadrant of the abdomen.

Pain in this area indicates the presence of gallstones.

Present in Cholecystitis, but not biliary colic

184
Q

What are some investigations you would do in biliary colic/suspected Cholelithiasis (gallstones)

A

Abdominal ultrasound
Liver function tests
Billirubin levels
Raised Alkaline Phosphatase - raised in biliary obstruction - !!!!!!!!!!!!!!!!!!!!!!
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels

185
Q

What would levels of Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and Alkaline Phosphatase be in an obstructive issue in in the bile duct?

A

In patients with cholestasis (e.g., due to gallstones), ALT and AST can increase slightly, with a higher rise in ALP (“an obstructive picture”).

186
Q

What would levels of Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and Alkaline Phosphatase be in problem inside the liver, aka hepatocellular injury/hepatic problem?

A

High ALT and AST, comapred with level of ALP

187
Q

What is the management for biliary colic/ Cholelithiasis?

A

Analgesia
An anti-spasmodic (e.g., hyoscine)
Ursodeoxycholic acid – decreases cholesterol

If the patient has symptomatic gallbladder stones but does not have features of cholecystitis, offer the patient elective laparoscopic cholecystectomy

188
Q

Define Cholecystitis

A

Inflammation of the gallbladder

189
Q

Outline the pathophysiology that causes cholecystitis.

A

When the GB has a gallstone in it, the squeezing of the GB can get it lodged in the cystic duct (aka when you have meal) –Therefore bile gets stuck

Bile stasis becomes a chemical irritant so causes mucosa to release mucus and inflammatory enzymes
🡪 inflammation, distension and pressure build up

Bacteria can start to grow e.g. E. coli and invade into gallbladder wall 🡪 peritonitis

190
Q

Name some common bacteria that can cause cholecysitis

A

E.Coli -ve rod
Enterococci - +ve Coci
Klebseilla - -ve Rod
Clostridium +ve rod

191
Q

What is the main difference between cholecystitis and biliary colic?

A

The main difference from biliary colic is the inflammatory component (local peritonism, fever, raised White Cell count)

Murphy’s sign is present in Cholecystitis, absent in biliary colic!!

192
Q

What are some signs and symptoms seen in cholecystitis?

A

RUQ pain
Fever
Nausea and vomiting

Murphy’s sign – tenderness that is worse on inspiration
Muscle guarding

193
Q

What are some investigations to do for cholecystitis?

A

CT/MRI of abdomen
Ultrasound: Thicc gallstone walls from inflammation
Inflammatory markers - FBCs, CRP - raised white blood cells, raised billirubin, elevated Alkaline Phosphatase

Positive Murphy’s Sign = Severe pain on deep inhalation with examiners hand pressed into the RUQ.

194
Q

What is the management for Cholecystitis?

A

Antibiotics IV, heavy analgesia, IV fluids and an eventual Cholecystectomy if needed.

Antibiotic should have anaerobic cover, such as cefuroxime (cephlasporin) and metronidazole (DNA)

195
Q

Define what cholangitis is.

A

Acute SAAG refers to infection of the biliary tree characteristically resulting in pain, jaundice and fevers

196
Q

Outline the pathophysiology behind acute ascending cholangitis.

What is the most common pathogen seen causing it?

A

Obstruction of common bile duct 🡪 stasis of bile 🡪 invasion of bacteria from duodenum

High pressure on the CBD (due to the obstruction) can cause spaces between the cells do widen which allows the bacteria and the bile access to the blood stream 🡪 bacteraemia and jaundice

E.Coli is the most common pathgogenic cause

(aerobic, gram negative, bacilli, lactose fermenting)

197
Q

What are some causes of acute ascending cholangitis? What is the most common pathogen seen causing it?

A

Choledocholithiasis, stones in the bile duct, is the most common cause of acute cholangitis

A Benign structure - - Chronic pancreatitis, Iatrogenic injury(during cholecystectomy), Radio / chemo-therapy, Idiopathic

  • Malignant stricture: e.g. cholangiocarcinoma, pancreatic cancer and gallbladder cancer.
  • Other:
    • Post-ERCP(normally related to inadequate drainage)
    • Blocked biliary stent

Parasites(e.g.Ascaris lumbricoides) can cause blockage

E.Coli is the most common pathgogenic cause

198
Q

What are some risk factors for acute ascending cholangitis?

A
  • Gallstones:the most common predisposing factor
  • Stricture of the biliary tree:benign or malignant
  • Post-procedure injuryof the bile ducts e.g. post-ERCP
199
Q

What are some key presentations of Acute Cholangitis?
What are the two eponymous groups of signs you need to remeber with acute cholangitis?

A

Charcots Triad
Jaundice (Dark urine, pale stools)
RUQ pain
Fever

Reynold’s Pentad - Those 3 and also Shock – (hypotension and tachycardia) and Confusion

200
Q

What are some investigations for suspected Acute cholangitis?

What is the gold standard?

A
  • FBC:leukocytosis with neutrophilia
  • LFTs:obstructive jaundice with raised ALP > ALT, and bilirubin
  • U&Es: pre-renal acute kidney injury in sepsis
  • CRP: acute-phase protein and marker of inflammation

Blood Cultures

  • MRCP:- Magnetic Resonance Cholangiopancreatographygold-standard for diagnosis and used for pre-intervention planning and has the highest sensitivity. However, not as readily available so CT tends to be performed first
  • ERCP:Endoscopic Retrograde Cholangiopancreatography) (basically a biliary tree contrast x-ray)
    Usually preceded by imaging
201
Q

What is the management for Acute ascending cholangtitis?

A

The sepsis 6 protocol should be implemented when indicated

  • Intravenous antibiotics: broad-spectrum antibiotics with gram-negative and anaerobic cover e.g. cefotaxime and metronidazole for 4-7 days
  • IV fluids: patients are often septic and require rehydration
  • Analgesia: if needed, and tailored to patients’ needs.

Srugery if needed

202
Q

What surgery interventions can be done for severe acute cholangitis?

A

ERCP Endoscopic Retrograde Cholangiopancreatography: first-line procedure usually performed within 24-48 hours. Allows for endoscopic exploration of the biliary tract with the removal of gallstones to facilitate drainage.

Elective cholecystectomy:

203
Q

Do you see RUQ pain, Fever/Raised WCC, Jaundice in
a) Biliary Colic
b) Acute Cholecystitis
c) Cholangitis

A

Biliary colic - YES RUQ, NO Fever/raised WCC, NO Jaundice

Acute Cholecystitis - YES RUQ, YES fever/raised WCC, NO jaundice

Cholangitis - YES RUQ, YES fever/raised WCC, YES jaundice

204
Q

Define what primary biliary cholangitis is.

A

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis,

Autoimmune condition, with granulomatous destruction of intrahepatic biliary ducts (the bile ducts that drain the liver) . ===> It can lead to fibrosis, cirrhosis, and portal hypertension

205
Q

What is the aetiology behind primary biliary cholangitis? What is the hallmark of PBC?

A

Unknown environmental triggers (?pollutants, xenobiotics,
non-pathogenic bacteria) + genetic predisposition (eg IL12A locus) leading to loss
of immune tolerance to self-mitochondrial protein

Antimitochondrial antibodies
(AMA) are the hallmark of PBC

206
Q

Outline the pathophysiology behind Primary biliary cholangitis.

A

The inflammatory process coupled with trapping of bile acids in the liver leads to progressive fibrosis, cirrhosis, and eventually liver failure.

207
Q

name some other autoimmune conditions that are commonly assassinated with Primary biliary cholangitis.

A

Up to 50% of PBC patients have at least oneassociated autoimmune condition, such as:
- Sjögren’s syndrome (25%)
- Raynaud’s phenomenon (25%)
- Autoimmune thyroid disease (25%)
- Rheumatoid arthritis (20%)
- Systemic sclerosis(10%

Far more common in women, middle aged!

208
Q

What are some main presenting features you’d see in a patient with Primary Biliary cholangitits?

A
  • Skin hyperpigmentation: due to increased melanin
  • Clubbing
  • Mild hepatosplenomegaly
  • Xanthelasma and xanthomata (late sign) - due to leakage of cholesterol
  • Jaundice in eyes
  • Pruritis (itchy skin) - leakage of bile salts
  • Fatigue and weight loss
  • Obstructive jaundice (late sign) - due to leakage of bile and conjugated bilirubin
    • Icteric (Jaundice)
    • Pale stool and dark urine

Far more common in women, middle aged!

209
Q

What are some key investigations you would do for primary biliary cholangitis?

A
  • Antimitochondrial antibodies (AMA):present in 95% of patients (highly specific)
  • Antinuclear antibodies (ANA):present in 50% of patients
  • Raised serum cholesterol
  • LFTs:an obstructive picture is seen with a raised ALP, GGT and bilirubin. AST and ALT may be mildly raised
  • Serum immunoglobulin:elevated IgM
  • Transabdominal ultrasound: excludes other extrahepatic causes of cholestasis e.g. gallstones

MRCP:if the above tests are inconclusive, an MRCP should be conducted to look for intrahepatic biliary duct stenosis

210
Q

What is the management for primary biliary cholangitits? What is the key first line treatment?

A
  • Ursodeoxycholic acid
    • First-line agent in all patients
    • A bile acid analogue which dampens the inflammatory response, acts as an anti-apoptotic agent, and improves cholestasis

This may be combined with Obeticholic acid,
As well as Cholestyramine: bile acid sequestrant for symptomatic relief ofpruritus (itching)

Fat-soluble vitamin supplementation: cholestasis impairs fat absorption; vitamins A, D, E and K must be supplemented

Codeine phosphate: for diarrhoea

Liver transplantation if V severe

211
Q

What is the second line treatment for patients with severe primary biliary cholangitis?

A

Liver transplantation: indicated in end-stage disease with liver cirrhosis

212
Q

What is primary sclerosing cholangitis?

A

It’s a condition where the intrahepatic or extrahepatic ducts become narrowed, stiffened and fibrotic. This causes an obstruction to the flow of bile out of the liver and into the intestines

213
Q

What are some differences between primary biliary cholangitis, and primary sclerosing cholangitis?

A

The main difference between primary biliary cholangitis and primary sclerosing cholangitis is the cause of the disease.

PBC is caused by an autoimmune disorder, while PSC is caused by inflammation, from a number of causes

Primary Bilialry cholangitis affects intrahepatic ducts only

Primary Sclerosing Cholangitis affects affects intrahepatic and extrahepatic ducts -

Additionally, PBC is more likely to affect women, while PSC is more likely to affect men. - PSC is associated with Ulcerative Collitis

214
Q

What are things that are thought to sometimes lead to Primary scleroisng cholangitis? What disease is it associated with?

A

The cause is mostly unclear although there is likely to be a combination of genetic, autoimmune, intestinal microbiome and environmental factors. There is an established association with ulcerative colitis, with around 70% of cases being alongside established ulcerative colitis.

215
Q

Irrespective of the cause, what does Primary Sclerosing Cholangitis do, and what does this lead to?

A

Irrespective of cause, the damage to bile ducts leads to:

  • Cholestasis
  • Bile and toxin build up in the liver
  • Bile duct strictures

All of the above contribute toliver fibrosis, cirrhosisand progression toend-stage liver disease.

PSC is associated with Ulcerative Collitis

216
Q

What are some signs of Primary sclerosing cholangitis?

A

PSC is often asymptomatic in the early stages and detected on routine blood tests.

  • Jaundice
  • Signs of complications:
    • Ascending Cholangitis: Charcot’s triad
    • Chronic liver disease:rare at first presentation, e.g. ascites or encephalopathy
217
Q

What are some symptoms of Primary sclerosing cholangitis?

A
  • Pruritis
  • Fatigue
  • RUQ/ epigastric abdominal pain
  • Symptoms of underlying bowel disease: bloody stools, tenesmus, diarrhoea, steatorrhoea
218
Q

Outline some investigations for Primary sclerosing cholangitis

A

LFTs - raised ALP (Alkaline phosphatase) and raised bilirubin, raised GGT (gamma-glutamyl transferase) , raised ALT and AST if liver damage present, decreased albumin.

Viral hepatitis screen:screen for HBsAg and anti-HCV in all patients

Antimitochondrial antibody, will be negative, but ANA, SMA,
and ANCA may be +ve;

GOLD STANDARD - ERCP (Endoscopic Retrograde Cholangio-Pancreatography)

219
Q

Treatment for Bile duct issues - outline what actually happens in ERCP (Endoscopic Retrograde Cholangio-Pancreatography)

A

You insert a small cameria in persons throat - goes through oesophagus, stomach and duodenum to the a point in the duodenum where the bile ducts empty into the GI tract.

Then goes through Ampulla of Vater where they can now enter the bile ducts and use X-rays and injecting contrast to identify different structures These structures can be Stented/widened using the same technique, to help relieve symptoms

So can be used to view and diagnose/investigate, and can also fit stents with it, so can be used for treatment too

220
Q

What is the first line management for primary sclerosing cholangitis?

A

Observation and lifestyle optimisation, healthy diet, reduce alcohol etc

Cholestyramine:a bile acid sequestrant that is the first-line treatment for relief of pruritus

Fat-soluble vitamin supplementation:cholestasis leads to impaired fat absorption; to ensure the absorption of fat-soluble vitamins (ADEK), supplementation

Supplent calcium/vit D to prevent hepatic osterporosis

endoscopic retrograde cholangiopancreatography (ERCP), if severe

Liver transplant if end stage liver disease

No set definite cure for PSC!

221
Q

What are the main causes of acute pancreatitis?

A

Main are
Gall Stones
Ethanol - aka alcohol abuse
Trauma

Steroids
Mumps/malignancy
Autoimmune e.g. SLE
Scorpion stings
Hyperlipidaemia and hypercalcaemia
Endoscopic Retrograde Cholangiopancreatography
Drugs – azathioprine, metronidazole, tetracycline, furosemide

GET SMASHED

222
Q

How can gall stones causes acute pancreatitis?

A

Gall stones can get stuck, and block the ampulla of vater - leading to back flow of Bile and Pancreatic enzymes up into the pancreas.

This leads to increased Intracellular Ca2+, causes the early activation of trypsinogen into trypsin

Trypsin causes increased enzymatic digestion of the pancreas and inflammation leading to extensive acinar damage

223
Q

How can alcohol cause acute pancreatitis?

A

Increases zymogen secretion, but also decreased fluid bicarbonate in duct
🡪 thick and viscous pancreatic juice which can obstruct the pancreatic duct

This backs up and leads to enzymatic degrading of pancreas cells.

Alcohol also stimulates cytokine release 🡪 immune response 🡪 neutrophils release superoxides and proteases

224
Q

What are some symptoms of acute pancreatitis?

A

Epigastric pain radiating to the back – relieved by sitting forwards
Nausea and vomiting

225
Q

What are some signs of acute pancreatits?

A

Cullen’s sign – bruising around periumbilical region
Grey Turner’s sign – bruising on flanks
Tachycardia
Abdominal guarding and tenderness
Distension

226
Q

What are some initial investigations you would do for acute pancreatitis, and what would you see?

A

Serum amylase/Lipase - >3 times the upper limit of the normal range - Lipase is more sensitive and specific for pancreatitis.
CRP >150mg/L at 36h after admission is a predictor of severe pancreatitis

Elevated alanine aminotransferase (ALT) levels strongly suggest gallstones as the cause.

Abdo xray - : No psoas shadow (retroperitoneal fluid is increased)
Chest Xray
Abdominal ultrasound

227
Q

Which of the following liver function tests is raised disproportionately in pancreatitis?

A

Amylase

Amylase is produced in the pancreas and is used to digest carbohydrates. It is released into the blood in large quantities in pancreatic disease.

228
Q

What is the first line management of acute pancreatitis?

A

Gauge severity - Using PANCREAS pneumonic
Supportive treatment

IV fluid and maintain electrolyte balance - Give lots of fluids!!
Pain relief
Insert a urinary catheter, monitor urine
Oxygen supplementation if needed
Treat complications
Regular CT or CRPs to gauge progress

ERCP + gallstone removal may be needed if there is progressive jaundice

229
Q

How can you gauge the severity of acute pancreatitis?

A

3 or more positive factors detected within 48h of onset suggest severe pancreatitis, and should prompt transfer to ITU/HDU. Mnemonic: PANCREAS

PaO2 <8kPa
Age >55yrs
Neutrophilia WBC >15 x 109/L
Calcium <2mmol/L
Renal function Urea >16mmol/L
Enzymes LDH >600iu/L; AST >200iu/L
Albumin <32g/L (serum)
Sugar blood glucose >10mmol/L

Severity can also be assessed with the
help of CT (Computed Tomography Severity Index).1 CRP can be a helpful marker.

230
Q

Outline the pathophysiology behind chronic pancreatitis

A

Each round of pancreatitis = increased chance of dilation of ducts and permanent damage.
- Stellate cells lay down fibrotic tissue - causes narrowing of ducts, acinar cell atrophy
- In Acute Alcohol PCT, Calcium deposits can plug ducts
Healthy tissue is replace by misshaped ducts, together with fibrosis and calcium plugs = chronic pancreatitis

It results in fibrosis and reduced function of the pancreatic tissue

231
Q

What is the main cause of chronic pancreatitis? What are the symptoms

A

Alcohol abuse

Also
Cystic Fibrosis – main cause in children
Tumours
Pancreatic trauma – knife wounds
Repeated bouts of acute pancreatitis

Epigastric pain that radiates to back – may be linked to eating meals
N+V ==> symptoms tend to be less intense and longer-lasting

232
Q

what would you see on a CT/MRCP, and Xray for chronic pancreatitis?

A

± CT (pancreatic calcifications confirm the diagnosis), MRCP + ERCP
(risks acute attack); AXR: speckled calcification; raised glucose

233
Q

What is the management for chronic pancreatitis?

A

Alcohol and smoking cesscation - first line

Pain relief
Pancreas enzymes eg creon and Proton Pump Inhibitor
Insulin for diabetes

234
Q

What are some complications of chronic pancreatitis?

A

Chronic epigastric pain
Loss of exocrine function, resulting in a lack of pancreatic enzymes (particularly lipase) secreted into the GI tract
Loss of endocrine function, resulting in a lack of insulin, leading to diabetes
Damage and strictures to the duct system, resulting in obstruction in the excretion of pancreatic juice and bile
Formation of pseudocysts or abscesses

235
Q

Define ascites. How much fluid should there normally be in the peritoneal cavity?

A

abnormal accumulation of fluid within the abdominal cavity

Physiologically, in men, no fluid should be present. In women, up to 20 mls may be considered normal depending on the timing of the menstrual cycle

236
Q

What are the two categories of ascties?

A
  • Normal portal pressure
  • Raised portal pressure
237
Q

What are the causes of ascites?

A

Malignancy
Cirrhosis
Low albumin
Pancreatitis
Bowel obstruction
Portal hypertension

238
Q

What are some signs of ascites?

A

abdominal distention, Shifting dullness, flank dullness, Fluid thrill, Bulging flanks

239
Q

What test is used to determine the cause of ascites?

A

SAAG the serum ascites-albumin gradient

240
Q

What do the different results of SAAG indicate?

measures the difference between the albumin level of serum and of ascitic fluid, may be used to assess the extent of ascites.

A

High SAAG >1.1g/dl or 11 g/l= raised portal pressure and cirrhosis (transudate)
Low SAAG <1.1g/dl or 11g/l= normal portal pressure (exudate)

241
Q

How would you manage ascites?

A

A shunt
Spironolactone to increase sodium excretion
Paracentesis

242
Q

What are the complications of ascites

A

Severe hypovolemia
Peritonitis

243
Q

What is portal hypertension defined as?

A

Elevated pressure in the portal venous system.

It is defined as pressure 5 mm Hg greater than the pressure in the inferior vena cava

(normal pressure 5-10)

244
Q

Give the main cause of
a) Pre hepatic portal hypertension
b) Intra hepatic portal hypertension
c) Post hepatic portal hypertension

A

THINK VENOUS BLOCKAGE!

Pre-hepatic – due to blockage of portal vein before liver
Portal vein thrombosis

Intra-hepatic – resulting from distortion of liver architecture
Cirrhosis – most common cause
Schistosomiasis

Post-hepatic – due to venous blockage outside of liver
Right HF

245
Q

What is the most common cause of portal hypertension worldwide? What is it?

A

Schistosomiasis a parasitic disease caused by tiny worms known as Schistosoma.

246
Q

Outline the pathophysiology that leads to portal hypertension.

A

Endothelin-1 production increased in cirrhosis 🡪 more vasoconstriction
NO production reduces in cirrhosis 🡪 less vasodilation
Reduced radius 🡪 increases resistance 🡪 higher pressure in portal system

247
Q

what are some signs and symptoms of portal hypertension?

A

Symptoms
Often symptomatic
GI bleeding from oesophageal or gastric varices

Signs
Ascites
Hepatic encephalopathy
Splenomegaly
Oesophago-gastric varices

248
Q

What are some investigations for portal hypertension?

A
  • Abdominal ultrasound - dilated portal vein
  • Doppler ultrasound - slow velocity and dilated portal vein
  • Endoscopy - for presence of oesophageal varices
249
Q

What is the management of portal hypertension?

A
  • Treat underlying cause
  • Salt reduction and diuretics
  • Beta-blockers and nitrate to reduce blood pressure
250
Q

What are some complications of portal hypertension?

A
  • Varices and variceal haemorrhage
  • Ascites
  • Hepatopulmonary syndrome
  • Liver failure
  • Hepatic encephalopathy
  • Cirrhotic cardiomyopathy
251
Q

What are oesophageal varices? What can they lead to

A

Oesophageal varices are abnormal, dilated veins that occur at the lower end of the oesophagus; they account for 10-20% of upper GI bleeds

252
Q

How do oesophageal varices form?

A

Veins of the oesophagus drain into the portal vein. Due to hypertension there is backflow from the portal vein causing the veins to enlarge and dilate

253
Q

What are some signs of oesophageal varices?

A

Hypotension
Tachycardia
Pallor
Signs of chronic liver damage – jaundice, easy bruising (liver not produced coagulation factors) and ascites
Splenomegaly
Ascites

254
Q

What are some symptoms of oesophageal varices?

A

Haematemesis - vomiting blood
Abdominal pain
Rectal bleeding

255
Q

What the management of acute bleeding in oesophageal varices?

A

ABCDE approach
Resuscitation and supportive care, IV fluids
Terlipressin:ADH analogue and causes splanchnic vasoconstriction
Blood Transfusion
Vitamin K, to correct bleeding abnormality
then surgery: endoscopic variceal band ligation within 24hr

256
Q

What is the management of non bleeding oesophageal varices?

A

diagnostic endoscopy + non-selective beta-blocker - propranolol
Nitrate to cause vasodilation 🡪 to reduce portal pressure
Terlipressin (ADH analogue) 🡪 reduce portal pressure

endoscopic variceal band ligation

257
Q

What are the main bacteria that can cause primary peritontits?

A

Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae.

Escherichia Coli is the most common

258
Q

Outline the main causes of peritonitis.

A

A – Appendicitis – umbilicus to RIF pain
E – Ectopic pregnancy – low abdominal pain, sudden onset, tachycardia, low BP
I – Infection (bacteria)
O – Obstruction – colicky pain, history of abdominal surgery
U – Ulcer – epigastric pain radiating to shoulder

VOWELS

259
Q

What anitbiotics would you use in an SPB

A

intravenous third-generation cephalosporin cefotaxime, ceftriaxone

Following an episode of SBP, patients require prophylactic oral antibiotics e.g. rifaximin.

260
Q

What is hemochromatosis?

A

Is an iron storage disorder that results in excessive total iron and deposition of iron in tissues.

261
Q

What is the most common mutation for hemochromatosis?

What chromosome is it found on?

A

The human haemochromatosis protein (HFE) gene is located on chromosome 6.

It is an autosomal recessive allele on this gene that causes disease

262
Q

What are risk factors for developing hemochromotosis?

A

Family history
Alcoholism
History of chronic transfusion: only relevant inacquiredhaemochromatosis, for example in patients with thalassaemia

263
Q

Describe the pathophysiology of hemochromatosis

A

There is unregulated absorption of iron from the gut causing iron overload
This results in iron deposition on multiple tissues most commonly affecting liver, pancreas, and the heart

264
Q

What are the symptoms of hemochromatosis?

A

Chronic tiredness
Joint pain
Bronze pigmentation of skin
Hair loss
Erectile dysfunction
Amenorrhoea
Cognetive symptoms

265
Q

How would you initially test for hemochromatosis?

A

Serum ferritin will be high but can also be high in other conditions
Serum transferrin if this is high as well then likely to be hemochromatosis

266
Q

What are the gold standard tests for hemochromatosis?

A

Liver biopsy with Perl’s stain can be used to establish the iron concentration in the parenchymal cells used to be the gold standard

Now genetic testing is gold standard

267
Q

What is the treatment for hemochromatosis?

A

venesection involves draining small amounts of blood around 500ml
Iron chelation can be used Deferoxamine
Patients should avoid alcohol

268
Q

What are some complications of haemochromatosis?

A

Endocrine - Diabetes Mellitus due to destruction of islet cells

Liver - cirrhosis, and hepatocellular carcinoma

Cardiac - Dilated cardiomyopathy, and congestive cardiac failure

MSK- Gout and pseudogout

Derma - Skin hyperpigmentation GREY SKIN

INFERTILITY

269
Q

What is wilson’s diseae?

A

An excessive accumulation of copper in the body and tissue.

270
Q

What mutation causes Wilson’s disease?

A

Due to Mutation of the ATP7Bgene on chromosome 13, resulting indysfunction in ATP-mediated hepatocyte copper transport.

It is an autosomal recessive disease

271
Q

Normal physiology - what is the total body copper content? What does the liver do to copper normally?

A

Total body copper content is ~125mg. Intake≈ 3mg/day (absorbed in
proximal small intestine).

In the liver, copper is incorporated into caeruloplasmin - the main copper carrying protein in the blood

272
Q

Outline the pathophysiology behind wilson’s disease

A

Wilson’s disease, intestinal copper absorption and transport into the liver are intact,
while copper incorporation into caeruloplasmin in hepatocytes and its excretion into
bile are impaired. Therefore, copper accumulates in liver, and later in other organs

273
Q

What are some of the clinical manifestations of Wilson’s disease?

A

Hepatic problems (40%)
Neurological problems (50%)
Psychiatric problems (10%

274
Q

What are the hepatic problems of Wilson’s disease?

A

In children/young adults

Hepatosplenomegaly
Hepatitis and cirrhosis
Jaundice
Ascites

275
Q

What are the neurological problems associated with wilson’s disease?

A

In children/young adults

Dysarthria (speech difficulties)
Dystonia
Parkinsonism (tremor, rigidity) - Similar presentation to Parkinson’s
Awful handwriting
Motor symptoms often asymmetric

276
Q

What are the psychiatric problems associated with Wilson’s?

A

Depression
Psychosis
Poor Memory; quick to anger; slow to solve problems; low IQ; delusions; mutism

277
Q

What do you see in the eye of someone with Wilson’s disease?

A

Kayser-Fleischer rings in cornea

yellow-brown deposits of copper in the cornea - They form a ring around the edge of the iris, the colored part of the eye.

278
Q

What are the first line investigations for Wilson’s disease?

A

Reduced ceruloplasmin and increased 24 hour urinary copper excretion is highly suggestive of Wilson’s disease.

279
Q

What is the gold standard test for Wilson’s disease?

A

Liver biopsy to test for copper content.

  • Genetic testing:ATP7B mutation; perform for all patients to confirm the diagnosis and facilitate family testing
280
Q

What is the first line management for Wilson’s Disease?

A

Copper chelation: usually the first-line treatment. Chelators bind copper and facilitate renal excretion;

D-penicillamine is most commonly used

281
Q

What is alpha 1 antitrypsin deficiency (A1AD)?

A

Autosomal recessive genetic disorder, on A1AT gene on chromosome 14

282
Q

Normal physiology - what is the role of Alpha 1 Antitrypsin protein? Where is it produced?

A

Produced in liver

Function is to inhibit neutrophil elastase, which is a proteolytic enzyme (produced by neutrophils in the presence of inflammation, infection, smoking)

283
Q

Outline the pathophysiology behind Alpha 1 antitrypsin protein deficiency.

A

If there is A1AT deficiency, elastase from neutrophils can break down elastin unchecked
Deficiency affects lung (alveolar wall destruction) and liver

Without this there is destruction of cells leading to emphysema and lung dysfunction

284
Q

How does A1AD cause disease in the liver?

A

In the liver as the protein is misfolded it gets stuck in the hepatocyte. This causes cell death leading to liver damage (Jaundice, hepatitis, cirrhosis and hepatocellular carcinoma)

This only happens in certain genotypes of the disease

285
Q

What are the symptoms of A1AD?

A

Respiratory early onset COPD and SOB
Liver symptoms will only occur in certain subtypes but will be the symptoms of liver failure e.g., hepatic encephalopathy , Jaundice, coagulopathy, ascites

286
Q

How would you test for A1AD?

A

Serum A1AT levels:reduced with levels < 20 micromol/L
Genetic testing

287
Q

What is some management available for A1AD?

A

Smoking cessation:
COPD treatment:
A1AT augmentation: intravenous A1AT

  • Alcohol avoidance
  • Hepatitis A and B vaccinations
  • Liver transplantation: for end-stage, refractory liver disease
288
Q

What is a hernia

A

A hernia is a condition in which an organ or tissue pushes through a weak spot in a muscle or the surrounding tissue wall. In most cases, the hernia causes a bulge or lump in the abdomen.

289
Q

Classifications of hernias - Define
a) Irreducible
b) Obstructed

A
  • Irreducible - contents cannot be pushed back into place
  • Obstructed - bowel contents cannot pass as the intestine is obstructed
290
Q

Classifications of hernias - Define
a) Strangulated
b) Incarceration

A
  • Strangulated - ischaemia occurs as blood supply of the sac is cut off - this requires urgent surgery.
  • Incarceration - contents of the hernial sac are stuck inside by adhesions
291
Q

What is the most common type of hernia, and what is it?

A

Inguinal hernia
The protrusion of abdominal contents through the inguinal canal

  • Account for 70% of all abdominal hernias
  • M>F
292
Q

What are the two different types of inguinal hernia?

A

Direct hernia: hernia protrudes through the posterior wall of the inguinal canal.
- Less common (20%)

Indirect hernia: hernia protrudes through the deep inguinal ring and into the inguinal canal

  • More common (80%)
293
Q

Tom Tip - what should you look at when assessing a hernia?

A

When assessing a hernia, always comment on the size of the neck/defect (narrow or wide),

Hernias that have a wide neck, meaning that the size of the opening that allows abdominal contents through is large, are at lower risk of complications. While the contents can easily pass out of this opening, they can also easily be put back, which puts them at a lower risk of incarceration, obstruction and strangulation.

294
Q

What is a femoral hernia

A

herniation of the abdominal contents through the femoral canal. This occurs below the inguinal ligament, at the top of the thigh.

The opening between the peritoneal cavity and the femoral canal is the femoral ring. The femoral ring leaves only a narrow opening for femoral hernias, putting femoral hernias at high risk of:

Incarceration
Obstruction
Strangulation

295
Q

What are incisional hernias

A

Incisional hernias occur at the site of an incision from previous surgery. They are due to weakness where the muscles and tissues were closed after a surgical incision

296
Q

What are umbilical hernias - in who do they most commonly occur

A

Umbilical hernias occur around the umbilicus due to a defect in the muscle around the umbilicus.

Umbilical hernias are common in neonates and can resolve spontaneously. They can also occur in older adults

297
Q

If someone has a hernia in the epigastric area (upper abdomen), what is it called

What are some main causes of this

A

Epigastric hernia

Being overweight, being pregnant, ascites, straining due to constipation

298
Q

What is a hiatus hernia?

A

herniation of the stomach up through the diaphragm. The diaphragm opening should be at the level of the lower oesophageal sphincter and should be fixed in place.

299
Q

What are some symptoms of hiatus hernia?

A

Heartburn
Acid reflux
Reflux of food
Burping
Bloating
Halitosis (bad breath)

300
Q

What is the treatment for hiatus hernia?

A

Conservative (with medical treatment of gastro-oesophageal reflux)
Surgical repair if there is a high risk of complications or symptoms are resistant to medical treatment

301
Q

what is gilberts syndrome, and what can it cause?

A

mild inherited disorder of the liver. It is characterized by episodes of elevated levels of bilirubin in the bloodstream - its a common cause of unconjugated hyperbilirubinaemia

302
Q

What is Gilberts syndrome caused by

A

Gilbert’s Syndrome is caused by a genetic mutation affecting the UGT1A1 gene, which is responsible for encoding an enzyme involved in bilirubin metabolism.

This mutation results in reduced activity of this enzyme, leading to higher levels of bilirubin in the blood.

303
Q

What types of tumours are the majority of pancreatic cancers? where do these tumours commonly metastise?

A

The vast majority are adenocarcinomas, and most occur in the head of the pancreas (as opposed to the body and tail).

tend to spread and metastasise early, particularly to the liver, then to the peritoneum, lungs and bones

304
Q

What are key presenting features of pancreatic cancer?

A

Painless obstructive jaundice
Yellow skin and sclera
Pale stools
Dark urine
Generalised itching
New-onset diabetes or worsening of type 2 diabetes -think of PC in patients with this when they are trying to control it well
The presence of a palpable gallbladder and jaundice

305
Q

What is courvoisers law?

A

Courvoisier’s law states that a palpable gallbladder along with jaundice is unlikely to be gallstones. The cause is usually cholangiocarcinoma or pancreatic cancer.

306
Q

Outline Trousseau’s sign of malignancy, in relation to pancreatic cancer.

A

Trousseau’s sign of malignancy - that in pancreatic cancer (and other things) , can SEE MIGRATORY THROMBOPHLEBITIS - this is multiple venous thrombosis at different changing sites

(due to procoagulant factors made by cancer cells)

307
Q

What are the first investigations to order for suspected pancreatic cancer?

A

pancreatic protocol CT - indeed, suspected Pancreatic cancer is the only time a GP can directly refer for a CT

CA 19-9 (carbohydrate antigen) is a tumour marker that may be raised in pancreatic cancer. It is also raised in cholangiocarcinoma and a number of other malignant and non-malignant conditions.

Biopsy may be taken through the skin (percutaneous) under ultrasound or CT guidance,

308
Q

What is the management of pancreatic cancer?

A

surgical resection

PLUS –
pancreatic enzyme replacement

CONSIDER –
preoperative biliary stenting

CONSIDER –
neoadjuvant radiotherapy or chemoradiotherapy

pallitative support

309
Q

What is the key tumour marker you use to monitor pancreatic cancer?

A

CA 19-9 (carbohydrate antigen) - a tumour marker raised in pancreatic cancer, and also cholangiocarcinoma

310
Q

What is the main differential for pancreatic cancer?

A

Cholangiocarcinoma accounts for 10% of liver cancer

311
Q

What are some signs and symptoms for cholangiocarcinoma?

A
  • Palpation - enlarged, irregular, tender liver may be felt
  • Signs of chronic liver disease
  • Signs of decompensation - jaundice, ascites
  • Listen for bruit - murmur over the liver
  • Symptoms
    • Fever
    • Weight loss
    • Abdominal pain +/- ascites
    • Malaise
312
Q

What’s the management of cholangiocarcinoma?

A
  • Surgery (not possible in 70% of patients at presentation)
    • e.g. major hepatectomy, extrahepatic bile duct excision and caudate lobe resection
  • Purcutaneous stenting or ERCP - stenting of obstructed extrahepatic bililary tree improves QOL
  • Liver transplantation
313
Q

What are some risk factors for Hepatocellular carcinoma?

A
  • HBV - leading cause worldwide especially, if high viral load
  • HCV
  • Autoimmune hepatitis
  • Cirrhosis
  • NAFLD
  • Anabolic steroids
314
Q

What is the pathophysiology behind a paracetamol overdose?

A

A small amount of paracetamol is metabolised by the P450 system into toxic N-acetyl-p-benzoquinone imine (NAPQI), a mitochondrial poison.

Its normally detoxified by conjugation with glutathione

In Paracetamol OD - NAPQI increases, glutathione stores become depleted, leaving NAPQI to remain unconjugated and resulting in hepatocellular damage.

315
Q

What are some signs and symptoms of paracetamol overdose?

A
  • Signs
    • Jaundice
    • Encephalopathy - reduced GCS - consciousness
    • Tachycardia/ hypotension
    • Evidence of self-harm
  • Symptoms
    • Abdominal pain
    • Right upper quadrant pain
    • Nausea or vomiting
    • Confusion or coma
316
Q

What things to you do need to conisder/find out about in a paracetamol overdose?

A
  • Date of ingestion: is there a delay in presentation?
  • Timing of ingestion: single overdose or staggered
  • Time since last ingestion
  • Weight: if >110 kg, used 110 kg as the maximum weight for calculations.
  • Pregnancy: use pre-pregnancy weight to determine toxicity and current weight for treatment
  • Total amount ingested(mg/kg)
  • Current suicidal risk
317
Q

What investigations do you do for suspected paracetamol overdose?

A
  • Serum paracetamol:levels should be measured at 4 hours post-ingestion. If presenting after 4 hours of ingestion, take levels immediately
  • LFTs:deranged liver function and rising INR
  • Clotting screen:PT and APTT prolonged in hepatocellular damage
  • U&E:severe toxicity results in renal failure
  • Arterial blood gas:s
318
Q

What is the main first line management of paracetamol overdose?

A
  • Activated charcoal:reduces intestinal absorption
    • Administered if the patient presentswithin 1 hourof ingestion
  • N-acetylcysteine (NAC):replenishes glutathione stores which bind NAPQI, the toxic metabolite
319
Q

What are some complications of paracetamol overdose?

A
  • Acute liver failure:evidence of liver failure may warrant urgent liver transplantation, as per the King’s College Criteria
  • Acute kidney injury - due to acute tubular necrosis occurs in 25% of patients who have severe hepatic damage
  • Anaphylactoid reaction: NAC may cause ananaphylactoid reactiondue to non-IgE mediated mast cell degranulation (10-50% of patients).
320
Q

How does liver failure lead to thrombocytopaenia?

A

Because the liver produces Thrombopoietin, the hormone that stimulates bone marrow to make platelets.

When the liver is damaged less of this is made leading to a reduction in platelet production

321
Q

Normla physiology - outline billrubn metabolism form unconjugated billrubin to its waste products

A

Unconjugated Bilirubin undergoes Glucuronidation (conjugated with glucuronic acid )to form Conjugated bilirubin, (by enzyme glucuronosyltransferase)

Conjugated Billirubin is released in Bile and becomes Urobilinogen

90% of Urobilinogen becomes Stercobilin (faeces) and 10% becomes Urobilin (recycled back to bile or urinated out)

322
Q

What is the key thing that is raised in the blood in a patients with Hepatocellularcarinoma

A

Alpha Fetoprotein is RIASED

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