Hepato Flashcards
(235 cards)
1
Q
A
2
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.
3
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
4
Q
Define acute on chronic liver failure
A
Acute-on-chronic = liver failure as a result of decompensation of chronic liver disease
5
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
6
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
7
Q
What is the most common cause of acute liver failure worldwide?
A
Viral (Hepatitis A, B and CMV)
8
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
9
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)
10
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.
11
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
12
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
13
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
14
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
15
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:
16
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
17
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
18
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)
19
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
20
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)
21
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
22
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
23
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.
24
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.
25
What types of imaging would you use when investigating chronic liver failure?
- 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.
26
What is the gold standard test for chronic liver failure?
- **Liver biopsy -** invasive so usually reserved for specific cases:
- Liver disease of unknown aetiology
- Differentiating between acute and chronic disease
27
How can you treat hepatic encephalopathy?
- . 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:***, abx that as this lowers the amount of *nitrogen producing bacteria in the gut flora*
28
Complications of chronic alcohol disease -
How would you treat ascites? How does Chronic liver disease cause it?
-- **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
29
Complications of chronic alcohol disease -
How would you treat GI bleeding? How does Chronic liver disease cause it?
- **GI bleeding -** due to oesophageal varices secondary to portal hypertension
- **Beta blockers** to reduce portal hypertension
- **Endoscopic variceal band ligation -** for variceal haemorrhage
30
What are some risk factors for developing alcoholic liver disease?
- **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
31
Normal physiology - outline basic alcohol metabolism.
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**
32
Pathophysiology behind alcoholic liver disease - What does the formation of acetaldehyde lead to?
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.
33
Name some general signs of alcoholic liver disease - can be seen in alcoholic fatty liver, hepatitis, cirrhosis
- 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
34
Name some signs you may see in a patient with liver cirrhosis
- 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
35
What is Dupuytren's contracture and why do you see it in liver disease?
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.
36
What two questionnaires can be used to screen for alcohol abuse in suspected alcoholic liver disease patients?
**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
37
What are some baseline investigations you would do in suspected alcoholic liver disease
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*
38
Outline some general management of alcoholic liver disease
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
39
How can you manage alcoholic withdrawal in patients with alcoholic liver disease?
- **Diazepam**
- **IV Thiamine** to prevent Wernicke-Korsakoff encephalopathy (presents with
ataxia, confusion and nystagmus) which occurs from alcohol withdrawal,
40
What are some complications of alcoholic liver disease on the
a) Liver
b) CNS
c) Gut
- 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
41
Define non alcoholic fatty liver disease. Outline its spectrum of disease.
A fatty liver that cannot be attributed to alcohol or viral causes
Spectrum of disease - steatosis, steatohepatitis, fibrosis, cirrhosis (least to most severe)
42
What are some causes/risk factors for developing non alcoholic fatty liver disease?
- Older age
- Obesity
- Hypertension
- Diabetes
- Hypertriglyceridemia
- Hyperlipidemia
43
Pathophysiology behind non alcoholic fatty liver disease - what happens to the excess fat stored in the liver, and how does this damage the liver?
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
44
What are some clinical manifestations of non alcoholic fatty liver disease?
Sometimes symptoms are vague:
- Fatigue
- Malaise
Sufficient damage presents with:
- Hepatomegaly
- Pain in RUQ
- Jaundice
- Ascites
- Bruising
- Pruritis - *itchiness/irritation of skin*
45
What investigations would you carry out in suspected non alcoholic fatty acid disease?
**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
46
name some general causes of hepatitis
Alcoholic hepatitis
Non alcoholic fatty liver disease
Viral hepatitis
Autoimmune hepatitis
Drug induced hepatitis (e.g. paracetamol overdose)
47
What are some non specfic symtoms of hepatitis?
Abdominal pain
Fatigue
Pruritis (itching)
Muscle and joint aches
Nausea and vomiting
Jaundice
Fever (viral hepatitis)
48
What type of Virus is Hep A? What family of viruses does it belong to?
The Hepatitis A virus is a non-enveloped single-stranded RNA virus, Belongs to the Picornaviridae family. **is a (picornavirus)**
49
How is Hepatitis A spread? Where is it endemic?
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
50
What are some risk factors for getting Hepatitis 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
51
Phases of Hep A - what happens in the
a) Incubation
b) Prodromal
Phases?
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
52
Phases of Hep A - what happens in the
a) Icteric
b) Convalescent
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.
53
What are some key symptoms/signs of hepatitis A?
- **Jaundice**
- **RUQ tenderness**
- **Hepatomegaly (85%)**
- **Abdominal discomfort**
- **Nausea**
- **Arthralgia**
- **Anorexia**
- **Diarrhoea**
- **Flu-like illness**
54
What are the 1st line tests for suspected Hepatitis 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
55
What is the management of a Hep A viral infection?
**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.
56
Is Hepatitis A a notifiable disease?
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.
57
What type of virus in the Hepatitis B virus?
Can it cause acute, chronic, or both types of hepatitis?
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:
58
How is Hepatitis B spread?
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
59
What are the 3 types of antigens that would show up in Serology tests in Hep B, and what can they show
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*
60
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
**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*
61
Hep B serology - what antibody will be present in those who have received an Hep B vaccination, but have not been infected?
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.
62
Hep B serology - What would present HBeAg show? What does an absent HBeAg but present HBeAB indicate?
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**
63
What is the management for acute Hep B?
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)
64
Name some antivirals used in the management of severe Hep B.
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
65
What management options would you consider in chronic Hep B?
Pegylated **interferon-α 2a**
Liver Transplant
Do this along side your antivirals, like Tenofovir and entecavir
66
What type of Virus is Hep C? Can infection be acute, chronic or both?
It's an RNA flavivirus
Infection may be acute and chronic.
67
What are the first line investigations for investigating Hep C?
**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
68
What is the management for Hep C?
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
69
What type of Virus is Hep D? When do you see it?
It is a unique RNA virus - **Requires HBV for assembly**
70
Outline the pathophysiology behind Hep D
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
71
Hep D pathophysiology - Define
Co - infection
Superinfection
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.
72
What do you test for in suspected Hep D patients?
When would you ask for it?
**Anti-HDV antibody** (only ask for it if HBsAg +ve)
73
What is the treatment for Hep D? Where is it most common?
As interferon-a has limited success, liver transplantation may be needed
Most common in eastern Europe, eg Romania
74
What type of virus is Hep E? How is it spread/where is it found?
RNA virus and acute only (can be chronic in immunosuppressed)
Route of Transmission
Faeco-oral route – water or food-borne
Found in undercooked pork
75
Which of Hepatitis A,B,C,D,E do you not need to identify public health organisations about?
None!! All cases of Hepatitis A,B,C,D,E you need to notify public health for
76
What tests can you do for suspected Hep E infection?
Serology – HEV antibodies
Nucleic acid amplification test
77
What is the acute management for someone with HEV?
Management
Supportive, liver transplant eg **Entecavir**
**Consider ribavirin – anti-viral medication**
Most likely see chronic HEV in immunocompromised
78
What are some causes of Cirrhosis
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)*
79
Where is type 1 autoimmune hepatitis most likely to occur?
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.
80
Where is type 2 autoimmune hepatitis most likely to occur?
In type 2, patients in their teenage or early twenties present with acute hepatitis with high transaminases and jaundice.
81
What antibodies are you likely to see with type 1 autoimmune hepatitis?
Anti-nuclear antibodies (ANA)
Anti-smooth muscle antibodies (anti-actin)
Anti-soluble liver antigen (anti-SLA/LP)
82
What antibodies are you likely to see with type 2 autoimmune hepatitis?
Anti-liver kidney microsomes-1 (anti-LKM1)
Anti-liver cytosol antigen type 1 (anti-LC1)
83
What is the management of autoimmune hepatitis?
**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.
84
Name some clinical manifestations of liver cirrhosis
- 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
85
What are some initial tests you would order in investigating liver cirrhosis?
**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
86
What are some other tests you could do in suspected liver cirrhosis, over than serology? What is the gold standard test?
Liver biopsy - *gold standard*
Abdominal ultrasound
Abdominal CT
Abdominal MRI
87
What the management for liver cirrohsis?
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!!***
88
What types of hepatitis are there vaccinations for?
There are vaccines available for hepatitis A and hepatitis B. The hepatitis B vaccine is also available in combination with the hepatitis A vaccine.
89
What are some complications of liver cirrhosis?
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
90
Normal physiology: Briefly outline Haem metabolism and bilirubin formation,
From haemoglobin to Unconjugated Billirubin
Haemoglobin= Haem *=(Hemoxygenase)=>* Biliverdin
Billverdin => Reduced to Unconjugated Bilirubin, **travels In blood to bound to albumin to liver**
91
What protein does unconjugated bilirubin bind to and why?
Albumin as it is not soluble it needs to travel to the liver
92
What does conjugated bilirubin form?
Urobilinogen/Stercobilinogen
93
What converts conjugated bilirubin to urobilinogen?
Intestinal bacteria
94
What can urobilinogen form?
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%
95
What would stools and urine look like in pre-hepatic jaundice?
What are some disease that cause pre hepatic jaundice?
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,
96
What can cause intra-hepatic jaundice?
Hepatitis/B/C, alcoholic liver disease, drug misuse.
97
What causes post-hepatic jaundice?
Gall stones, pancreatitis, Gall/pancreatic cancer
98
What compound causes dark urine?
Conjugated bilirubin
99
A patient with jaundice has pale stools. What compound is absent?
Stercobilinogen
100
What is the affect on the urine and stools in a patient with post-hepatic jaundice
Dark urine and pale stools
101
Define Wernicke's Encephalopathy
is a neurological emergency resulting from thiamine deficiency with varied neurocognitive manifestations.
102
What is Korsakoff's Syndrome? How is it related to Wernickes?
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.
103
What are some risk factors for developing Wernicke's encephalopathy?
- **Alcohol abuse**
- **Malnutrition**
- **Anorexia**
- **Malabsorption due to stomach cancer and IBD**
- **Prolonged vomiting e.g. due to chemotherapy, hyperemesis**
104
How can chronic alcoholism lead to a thiamine deficiency?
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
105
How can a lack of thiamine (vit B1) affect the brain?
- 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.
106
What is the classical triad seen in Wernicke's encephalopathy?
1 confusion
2 ataxia (wide-based gait; fig 2)
3 **ophthalmoplegia** (nystagmus,
lateral rectus or conjugate gaze palsies).
107
What investigations would you do in suspected Wernicke's encephalopathy?
- 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
108
What is the management for Wernicke's encephalopathy?
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
109
Why do you need to give Thiamine before you give glucose in a patient with Wernicke's?
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***
110
Define Cholestasis
blockage to the flow of bile
111
Define Cholelithiasis
the preasence of gall stones
112
How can stones in the gall bladder form?
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.**
113
What are some risk factors for devloping gall stones/ experiencing biliary colic?
The 5Fs: Fat, Fertile, Forty, Female, Fair, (Caucasian) FHx
rapid weight loss - seen in ozempic/munjaro injections
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**
114
What is the classic presentation of biliary colic?
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!
115
What are some investigations you would do in biliary colic/suspected Cholelithiasis (gallstones)
**Abdominal ultrasound**
Liver function tests
Billirubin levels
**Raised Alkaline Phosphatase** - raised in biliary obstruction - ***!!!!!!!!!!!!!!!!!!!!!!***
**Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)** levels
116
What would levels of Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and Alkaline Phosphatase be in an obstructive issue in in the bile duct?
In patients with cholestasis (e.g., due to gallstones), ALT and AST can increase slightly, with a **higher rise in ALP (“an obstructive picture”).**
117
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?
High ALT and AST, comapred with level of ALP
118
What is the management for biliary colic/ Cholelithiasis?
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
119
Define Cholecystitis
Inflammation of the gallbladder
120
What is the main difference between cholecystitis and biliary colic?
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!!
121
What are some signs and symptoms seen in cholecystitis?
RUQ pain
Fever
Nausea and vomiting
**Murphy’s sign** – *tenderness that is worse on inspiration*
Muscle guarding
122
What is murphys sign?
When is it present?
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**
123
What are some investigations to do for cholecystitis?
**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.
124
Name some common bacteria that can cause cholecysitis
E.Coli -ve rod
Enterococci - +ve Coci
Klebseilla - -ve Rod
Clostridium +ve rod
125
What is the management for Cholecystitis?
Antibiotics IV, heavy analgesia, IV fluids and an eventual Cholecystectomy if needed.
Antibiotic should have anaerobic cover, such as **cefuroxime (cephlasporin) and metronidazole (DNA)**
126
Outline the pathophysiology behind acute ascending cholangitis.
What is the most common pathogen seen causing it?
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)*
127
What are some causes of acute ascending cholangitis? What is the most common pathogen seen causing it?
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
128
What are some risk factors for acute ascending cholangitis?
- **Gallstones:** the most common predisposing factor
- **Stricture of the biliary tree:** benign or malignant
- **Post-procedure injury** of the bile ducts e.g. post-ERCP
129
What are some key presentations of Acute Cholangitis?
What are the two eponymous groups of signs you need to remeber with acute cholangitis?
Charcots Triad
Jaundice *(Dark urine, pale stools)*
RUQ pain
Fever
Reynold’s Pentad - Those 3 and also **Shock** – (hypotension and tachycardia) and **Confusion**
130
What are some investigations for suspected Acute cholangitis?
What is the gold standard?
- **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 Cholangiopancreatography** gold-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
131
What is the management for Acute ascending cholangtitis?
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
132
What surgery interventions can be done for severe acute cholangitis?
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:
133
Do you see RUQ pain, Fever/Raised WCC, Jaundice in
a) Biliary Colic
b) Acute Cholecystitis
c) Cholangitis
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
134
Define what primary biliary cholangitis is.
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
135
name some other autoimmune conditions that are commonly assassinated with Primary biliary cholangitis.
Up to 50% of PBC patients have at least one associated 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!
136
What are some main presenting features you'd see in a patient with Primary Biliary cholangitits?
- 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!**
137
What are some key investigations you would do for primary biliary cholangitis?
- **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
138
What is the management for primary biliary cholangitits? What is the key first line treatment?
- **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 of **pruritus (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
139
What is primary sclerosing cholangitis?
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
140
What are some differences between primary biliary cholangitis, and primary sclerosing cholangitis?
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
141
Irrespective of the cause, what does Primary Sclerosing Cholangitis do, and what does this lead to?
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 to **liver fibrosis, cirrhosis** and progression to **end-stage liver disease.**
PSC is associated with Ulcerative Collitis
142
What are some signs of Primary sclerosing cholangitis?
***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
143
What are some symptoms of Primary sclerosing cholangitis?
- Pruritis
- Fatigue
- RUQ/ epigastric abdominal pain
- Symptoms of underlying bowel disease: bloody stools, tenesmus, diarrhoea, steatorrhoea
144
Outline some investigations for Primary sclerosing cholangitis
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)**
145
Treatment for Bile duct issues - outline what actually happens in ERCP (Endoscopic Retrograde Cholangio-Pancreatography)
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**
146
What is the first line management for primary sclerosing cholangitis?
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!
147
What are the main causes of acute pancreatitis?
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**
148
What are some symptoms of acute pancreatitis?
**Epigastric pain radiating to the back – relieved by sitting forwards
Nausea and vomiting**
149
What are some signs of acute pancreatits?
Cullen’s sign – bruising around periumbilical region
Grey Turner’s sign – bruising on flanks
Tachycardia
Abdominal guarding and tenderness
Distension
150
What are some initial investigations you would do for acute pancreatitis, and what would you see?
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
151
What is the first line management of acute pancreatitis?
**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
152
How can you gauge the severity of acute pancreatitis?
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.*
153
What is the main cause of chronic pancreatitis? What are the symptoms
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*
154
What is the management for chronic pancreatitis?
Alcohol and smoking cesscation - **first line**
Pain relief
Pancreas enzymes **eg creon** and Proton Pump Inhibitor
Insulin for diabetes
155
What are some complications of chronic pancreatitis?
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
156
Define ascites. How much fluid should there normally be in the peritoneal cavity?
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
157
What are the two categories of ascties?
- Normal portal pressure
- Raised portal pressure
158
What are the causes of ascites?
Malignancy
Cirrhosis
Low albumin
Pancreatitis
Bowel obstruction
Portal hypertension
159
What test is used to determine the cause of ascites?
SAAG the serum ascites-albumin gradient
160
What causes transudative fluid? What do you see in it and whats the protein content?
Transudative fluid has low protein content (≤2.5 g/dL), a high SAAG (≥1.1 g/dL), and is caused by systemic conditions like cirrhosis or heart failure.
161
How would you manage ascites?
A shunt
Spironolactone to increase sodium excretion
Paracentesis
162
Give the main cause of
a) Pre hepatic portal hypertension
b) Intra hepatic portal hypertension
c) Post hepatic portal hypertension
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
163
What is the most common cause of portal hypertension worldwide? What is it?
**Schistosomiasis** a parasitic disease caused by tiny worms known as Schistosoma.
164
what are some signs and symptoms of portal hypertension?
Symptoms
Often symptomatic
GI bleeding from oesophageal or gastric varices
Signs
Ascites
Hepatic encephalopathy
Splenomegaly
Oesophago-gastric varices
165
What are some investigations for portal hypertension?
- Abdominal ultrasound - dilated portal vein
- Doppler ultrasound - slow velocity and dilated portal vein
- Endoscopy - for presence of oesophageal varices
166
What is the management of portal hypertension?
- Treat underlying cause
- Salt reduction and diuretics
- Beta-blockers and nitrate to reduce blood pressure
167
What are oesophageal varices? What can they lead to
Oesophageal varices are abnormal, dilated veins that occur at the lower end of the oesophagus; they account for 10-20% of upper GI bleeds
168
How do oesophageal varices form?
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
169
What are some symptoms of oesophageal varices?
Haematemesis - *vomiting blood*
Abdominal pain
Rectal bleeding
170
What the management of acute bleeding in oesophageal varices?
**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
171
What is the management of non bleeding oesophageal varices?
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
172
What are the main bacteria that can cause primary peritontits?
Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae.
**Escherichia Coli is the most common**
173
Outline the main causes of peritonitis.
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
174
What anitbiotics would you use in an SPB
intravenous third-generation cephalosporin cefotaxime, ceftriaxone
Following an episode of SBP, patients require prophylactic oral antibiotics e.g. rifaximin.
175
What is hemochromatosis?
Is an iron storage disorder that results in excessive total iron and deposition of iron in tissues.
176
What are the symptoms of hemochromatosis?
Chronic tiredness
Joint pain
Bronze pigmentation of skin
Hair loss
Erectile dysfunction
Amenorrhoea
Cognetive symptoms
177
How would you initially test for hemochromatosis?
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
178
What are the gold standard tests for hemochromatosis?
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
179
What is the treatment for hemochromatosis?
venesection involves draining small amounts of blood around 500ml
Iron chelation can be used Deferoxamine
Patients should avoid alcohol
180
What mutation causes Wilson's disease?
Due to Mutation of the **ATP7B gene on chromosome 13,** resulting in dysfunction in ATP-mediated hepatocyte copper transport.
It is an autosomal recessive disease
181
What are some of the clinical manifestations of Wilson's disease?
Hepatic problems (40%)
Neurological problems (50%)
Psychiatric problems (10%
182
What are the hepatic problems of Wilson’s disease?
*In children/young adults*
Hepatosplenomegaly
Hepatitis and cirrhosis
Jaundice
Ascites
183
What are the neurological problems associated with wilson’s disease?
*In children/young adults*
Dysarthria (speech difficulties)
Dystonia
Parkinsonism (tremor, rigidity) - Similar presentation to Parkinson's
Awful handwriting
Motor symptoms often asymmetric
184
What are the psychiatric problems associated with Wilson’s?
Depression
Psychosis
Poor Memory; quick to anger; slow to solve problems; low IQ; delusions; mutism
185
What do you see in the eye of someone with Wilson’s disease?
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.
186
What are the first line investigations for Wilson’s disease?
Reduced ceruloplasmin and increased 24 hour urinary copper excretion is highly suggestive of Wilson’s disease.
187
What is the gold standard test for Wilson’s disease?
**Liver biopsy** to test for copper content.
- **Genetic testing:** ATP7B mutation; perform for all patients to confirm the diagnosis and facilitate family testing
188
What is the first line management for Wilson's Disease?
Copper chelation: usually the first-line treatment. Chelators bind copper and facilitate renal excretion;
**D-penicillamine** is most commonly used
189
Outline the pathophysiology behind Alpha 1 antitrypsin protein deficiency.
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
190
How does A1AD cause disease in the liver?
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***
191
What are the symptoms of A1AD?
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
192
How would you test for A1AD?
Serum A1AT levels:reduced with levels < 20 micromol/L
Genetic testing
193
What is some management available for A1AD?
Smoking cessation:
COPD treatment:
A1AT augmentation: **intravenous A1AT**
- **Alcohol avoidance**
- **Hepatitis A and B vaccinations**
- **Liver transplantation**: for end-stage, refractory liver disease
194
Classifications of hernias - Define
a) Irreducible
b) Obstructed
- Irreducible - contents cannot be pushed back into place
- Obstructed - bowel contents cannot pass as the intestine is obstructed
195
Classifications of hernias - Define
a) Strangulated
b) Incarceration
- 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
196
What is the most common type of hernia, and what is it?
Inguinal hernia
The protrusion of abdominal contents through the inguinal canal
- Account for 70% of all abdominal hernias
- M>F
197
What are the two different types of inguinal hernia?
**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%)
198
Tom Tip - what should you look at when assessing a hernia?
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.
199
What is a femoral hernia
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
200
What are umbilical hernias - in who do they most commonly occur
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
201
What are some symptoms of hiatus hernia?
Heartburn
Acid reflux
Reflux of food
Burping
Bloating
Halitosis (bad breath)
202
What is the treatment for hiatus hernia?
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
203
What types of tumours are the majority of pancreatic cancers? where do these tumours commonly metastise?
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
204
What are key presenting features of pancreatic cancer?
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
205
What is courvoisers law?
Courvoisier’s law states that a palpable gallbladder along with jaundice is unlikely to be gallstones. The cause is usually cholangiocarcinoma or pancreatic cancer.
206
Outline Trousseau's sign of malignancy, in relation to pancreatic cancer.
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)
207
What are the first investigations to order for suspected pancreatic cancer?
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,
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What is the management of pancreatic cancer?
surgical resection
PLUS –
pancreatic enzyme replacement
CONSIDER –
preoperative biliary stenting
CONSIDER –
neoadjuvant radiotherapy or chemoradiotherapy
pallitative support
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What is the main differential for pancreatic cancer?
Cholangiocarcinoma *accounts for 10% of liver cancer*
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What are some signs and symptoms for cholangiocarcinoma?
- 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
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What's the management of cholangiocarcinoma?
- **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**
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What are some risk factors for Hepatocellular carcinoma?
- HBV - leading cause worldwide especially, if high viral load
- HCV
- Autoimmune hepatitis
- Cirrhosis
- NAFLD
- Anabolic steroids
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What is the pathophysiology behind a paracetamol overdose?
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.
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What are some signs and symptoms of paracetamol overdose?
- 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
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What things to you do need to conisder/find out about in a paracetamol overdose?
- **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**
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What investigations do you do for suspected paracetamol overdose?
- **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
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What is the main first line management of paracetamol overdose?
- **Activated charcoal:** reduces intestinal absorption
- Administered if the patient presents **within 1 hour** of ingestion
- **N-acetylcysteine (NAC)**: *replenishes glutathione stores which bind NAPQI, the toxic metabolite*
218
How could you use the AST and ALT values to determine whether someone's liver disease is alcoholic liver disease, or hepatitis/NAFLD?
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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Hep B serology - presence of what would indicate previous infection
Positive HBcoreAntibody **IgG**, and a negative HB surface antigen
***HB surface antigen*** - indicates active disease
220
Which Hepatitis Viruses have been known to lead to Hepatocarcinoma?
Hep B and Hep C
221
How does liver failure lead to thrombocytopaenia?
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
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Normla physiology - outline billrubn metabolism form unconjugated billrubin to its waste products
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)**
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Which type of bilirubin is raised in pre-hepatic jaundice?
Unconjugated bilirubin
224
Which enzyme is deficient in Gilbert’s Syndrome?
UDP-gluconoryltransferase, due a fault in the UGT1A1 gene
225
Which of the following liver function tests is raised disproportionately in pancreatitis?
**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.
226
How can liver cirrhosis lead to renal failure, known as hepatorenal syndrome?
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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What is the key thing that is raised in the blood in a patients with Hepatocellularcarinoma
Alpha Fetoprotein is RIASED
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Recap - Outline how each of Hep A - E is spread
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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How can liver failure/liver cirrhosis lead to portal hypertension
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.
230
Rules of thumb for hepatitis medication - outline suitable medication for Hep A - E
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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What are some signs of ascites?
abdominal distention, Shifting dullness, flank dullness, Fluid thrill, Bulging flanks
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What is the key tumour marker you use to monitor pancreatic cancer?
**CA 19-9 (carbohydrate antigen)** - a tumour marker raised in pancreatic cancer, and also cholangiocarcinoma
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When in particular is gamma- Glutamyl transferase raised?
Gamma-GT indicates damage to the liver and bile ducts.
GGT is particularly associated with alcohol use.
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Complications of alcoholic liver disease - what is delirium tremens? What can it present with?
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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What causes exudative fluid? What do you see in it and whats the protein content?
Exudative fluid has high protein content (>2.5 g/dL), a low SAAG (<1.1 g/dL), and results from local pathology such as infection, malignancy, or inflammation.
