Gastrointestinal Flashcards
Zero to finals GI (complete)
1
Q
What is alcoholic liver disease? Describe the stages.
A
Liver disease due to alcohol.
Stage 1: Alcohol related fatty liver. Reversible in 2 weeks if stop drinking.
Stage 2: Alcoholic hepatitis. Reversible if mild with permanent abstinence.
Stage 3: Cirrhosis - irreversible.
2
Q
What is the weekly recommended alcohol consumption?
A
14 units. If 14, spread evenly over 3 or more days, no more than 5u a day.
There is no safe level - increases risk of cancer especially breast, mouth and throat. Avoid in pregnancy.
3
Q
What are the screening tools which can be used to screen for harmful alcohol use?
A
1. CAGE - ever thought you should cut down? do you get annoyed when people comment? ever feel guilty? Drink in the morning (eye opener?) AUDIT - 10 questions, score of 8 or more indicates harmful use.
4
Q
Give 5 complications of alcohol.
A
Alcoholic liver disease Cirrhosis and HCC alcohol dependence and withdrawal Wernicke-korsakoff syndrome Pancreatitis Alcoholic cardiomyopathy
5
Q
Give 5 signs of liver disease.
A
Jaundice Hepatomegaly Spider Naevi Palmer erythema Gynecomastia Bruising (clotting) ascites Caput medusae (engorged superficial epigastric veins) Asterixis - flapping tremor in decompensated liver disease.
6
Q
What bloods would you do for alcoholic liver disease and what would they show?
A
FBC - raised MCV
LFTs - elevated ALT and AST (transaminases) and raised y-GT. ALP elevated later in disease.
Low albumin due to reduced synthetic function of liver. elevated bilirubin in cirrhosis.
Clotting - elevated PTT due to reduced synthetic function of liver
U+Es deranged in hepatorenal syndrome.
7
Q
How is alcoholic liver disease managed?
A
Stop alcohol permanently
Detox
Nutritional support - vitamins esp thiamine, high protein
Steroids improve short term outcomes (over 1 month) in severe alcoholic hepatitis but infection and GI bleeding need to be treated first. Do not improve outcomes over long term.
Treat complications of cirrhosis (portal hypertension, varices, ascites, hepatic encephalopathy)
Liver transplant if abstained from alcohol for 3 months and severe disease.
8
Q
What is delirium tremens and why does it occur?
A
Medical emergency alcohol withdrawal. Mortality 35% if untreated.
Alcohol stimulates GABA receptors –> inhibitory. Also inhibits glutamate receptors (usually excitatory) –> inhibition of electrical activity.
Over time, GABA system becomes downregulated and glutamate upregulated. When alcohol removed, GABA under-functionals and glu over-functions –> excitability of brain, excess adrenergic activity.
9
Q
How does delirium tremens present?
A
Acute confusion Severe agitation Delusions and hallucinations Tremor Tachycardia Hypertension Hyperthermia Ataxia (difficulties with coordinated movements) Arrhythmias
10
Q
How is alcohol withdrawal managed?
A
CIWA-Ar (Clinical Institute Withdrawal Assessment – Alcohol revised) tool to score the patient on their withdrawal symptoms and guide treatment.
PO chlordiazepoxide (“Librium”)= bzd used. Diazepam is a less commonly used alternative. Reducing regime titrated to the required dose based on the local alcohol withdrawal protocol (e.g. 10 – 40 mg every 1 – 4 hours) for 5-7 days.
Intravenous high-dose B vitamins (pabrinex) followed by regular lower dose oral thiamine.
11
Q
What is Wernicke-Korsakoff Syndrome?
A
Thiamine (B1) deficiency –> Wernicke’s encephalopathy (confusion, oculomotor disturbance, ataxia) –> if untreated, Korsakoff’s syndrome (retro- and anterograde memory impairment, behavioural changes, irreversible).
12
Q
What investigations would you do for alcoholic liver disease and what would they show?
A
USS - fatty changes show as increased echogenicity, cirrhosis. FibroScan is a type of high frequency USS that checks the elasticity of liver, assess degree of cirrhosis.
Endoscopy - assess and treat oesophageal varices when portal hypertension is suspected.
CT/MRI - fatty infiltration, HCC, hepatosplenomegaly, abnormal blood vessel changes, ascites
13
Q
How is the diagnosis of alcohol related hepatitis/cirrhosis confirmed?
A
Liver biopsy. Consider before starting steroids.
14
Q
What are the first symptoms of alcohol withdrawal (<24h)?
A
6-16 hours: tremor, sweating, headache, craving, anxiety
12-24 hours: hallucinations
15
Q
What are the later symptoms of alcohol withdrawal (24-72 hours)?
A
24-48 hours: seizures
24-72 hours: delirium tremens
16
Q
What is liver cirrhosis?
A
Scar tissue (fibrosis) and nodules of scar tissue in the liver due to cell damage caused by chronic inflammation. This affects structure and blood flow in liver.
17
Q
What are the complications of liver cirrhosis?
A
Portal hypertension due to increased resistance in portal veins (leading in to liver).
18
Q
Give the 4 most common causes of liver cirrhosis and 1 rarer cause.
A
Common: Alcoholic liver disease +non alcoholic fatty liver disease Hep B and C (think in pairs) Rarer: Autoimmune hepatitis Primary biliary cirrhosis Haemochromatosis Wilsons Disease Alpha-1 antitrypsin deficiency Cystic fibrosis Drugs (e.g. amiodarone, methotrexate, sodium valproate)
19
Q
Give 5 signs of liver cirrhosis.
A
Jaundice – caused by raised bilirubin
Hepatomegaly – however the liver can shrink as it becomes more cirrhotic
Splenomegaly – due to portal hypertension
Spider Naevi – these are telangiectasia with a central arteriole and small vessels radiating away
Palmar Erythema – caused by hyperdynamic circulation
Gynaecomastia and testicular atrophy in males due to endocrine dysfunction
Bruising – due to abnormal clotting
Ascites
Caput Medusae – distended paraumbilical veins due to portal hypertension
Asterixis – “flapping tremor” in decompensated liver disease
20
Q
What would bloods show in cirrhosis?
A
LFTs - can be normal until decompensated, when ALT, AST, ALP and bili will all be abnormal.
markers of synthetic function:
Albumin decreased
PTT increased.
U+Es - hyponatraemia = fluid retention
Urea/creatinine derangement in hepatorenal syndrome
Causes - viral markers, antibodies
A-FP tumour marker for HCC - check every 6 months.
ELF = enhanced liver fibrosis test for assessing fibrosis in NAFLD.
21
Q
Give 3 findings on USS for cirrhosis.
A
Nodularity of the surface of the liver A “corkscrew” appearance to the arteries with increased flow as they compensate for reduced portal flow Enlarged portal vein with reduced flow Ascites Splenomegaly
(test every 6 months to screen for HCC)
22
Q
What is a FibroScan? Who gets one?
A
Checks elasticity of liver using high frequency sound waves to assess degree of cirrhosis. (aka transient elastography).
Test every 2 years if at risk of cirrhosis:
Hepatitis C
Heavy alcohol drinkers (men drinking > 50 units or women drinking > 35 units per week)
Diagnosed alcoholic liver disease
Non alcoholic fatty liver disease and evidence of fibrosis on the ELF blood test
Chronic hepatitis B (although they suggest yearly for hep B)
23
Q
What is the Child-Pugh score?
A
Score for cirrhosis from 5-15, scoring 1-3 for bili, albumin, INR, ascites and encephalopathy.
24
Q
What is the MELD?
A
Model for end stage liver disease. Use every 6 months in patients with compensated cirrhosis to estimate 3 month mortality, determines dialysis/transplant decisions.
25
How is cirrhosis managed? Give the screening programme.
```
USS+ A-FP every 6 months for hcc
Endoscopy every 3 years in patients without known varices
High protein, low sodium diet
MELD score every 6 months
Consideration of a liver transplant
Manage complications
```
26
Give 5 complications of cirrhosis.
Malnutrition
Portal Hypertension, Varices and Variceal Bleeding
Ascites and Spontaneous Bacterial Peritonitis (SBP)
Hepato-renal Syndrome
Hepatic Encephalopathy
Hepatocellular Carcinoma
27
How does cirrhosis lead to weight loss and wasting?
Increases use of muscle tissue as fuel
Reduces the protein available in the body for muscle growth.
Affects the metabolism of proteins in the liver
Reduces protein production
Disrupts glycogenesis + glycogenolysis
28
What is the management of malnutrition in cirrhosis?
```
Regular meals (every 2-3 hours)
Low sodium (to minimise fluid retention)
High protein and high calorie (particularly if underweight)
Avoid alcohol
```
29
What are varices and why do they occur?
The portal vein comes from the superior mesenteric vein and the splenic vein and delivers blood to the liver. Liver cirrhosis --> resistance of blood flow --> back-pressure into the portal system (“portal hypertension”). --> vessels at the sites where the portal system anastomoses with the systemic venous system become swollen and tortuous (varices).
Common sites:
Gastro oesophageal junction
Ileocaecal junction
Rectum
Anterior abdominal wall via the umbilical vein (caput medusae)
Varices do not cause symptoms or problems until they start bleeding. Due to the high blood flow through varices, once they start bleeding patients can exsanguinate (bleed out) very quickly.
30
How are stable varices managed?
Propanolol to reduce hypertension, elastic band ligation, sclerosant injections
If fails --> TIPS: transjugular intrahepatic portosystemic shunt = stent from portal to hepatic vein to reduce pressure
31
How are bleeding oesophageal varices managed?
Resuscitation: Vasopressin analogues (i.e. terlipressin) cause vasoconstriction and slow bleeding in varices
Correct any coagulopathy with vitamin K and fresh frozen plasma (=clotting factors)
Prophylactic broad spectrum antibiotics reduce mortality
Consider intubation and intensive care as they can bleed very quickly and become life threateningly unwell
Urgent endoscopy
Injection of sclerosant into the varices can be used to cause “inflammatory obliteration” of the vessel
Elastic band ligation of varices
Sengstaken-Blakemore Tube is an inflatable tube inserted into the oesophagus to tamponade the bleeding varices. This is used when endoscopy fails.
32
What is ascites and why does it occur in cirrhosis?
Fluid in the peritoneal cavity.
Portal hypertension causes fluid to leak out of the capillaries in the liver and bowel into the peritoneal cavity --> drop in circulating volume --> reduction in blood pressure entering the kidneys --> kidneys release renin --> RAAS activated --> reabsorption of fluid and sodium.
33
Does cirrhosis cause a transudative or exudative ascites?
Cirrhosis causes a transudative, meaning low protein content, ascites. The fluid comes from liver capillaries.
34
How is ascites managed?
Low sodium diet
Anti-aldosterone diuretics (spironolactone)
Paracentesis (ascitic tap or ascitic drain)
Prophylactic antibiotics against SBP (ciprofloxacin or norfloxacin) if <15g/l of protein in the ascitic fluid
Refractory ascities - TIPS, transplantation
35
What is SBP?
Spontaneous Bacterial Peritonitis - occurs in around 10% of patients with ascites secondary to cirrhosis and can have a mortality of 10-20%. It involves an infection developing in the ascitic fluid and peritoneal lining without any clear cause (e.g. not secondary to an ascitic drain or bowel perforation) - aka spontaneous.
36
How does SBP present?
Can be asymptomatic so have a low threshold for ascitic fluid culture
Fever
Abdominal pain
Deranged bloods (raised WBC, CRP, creatinine or metabolic acidosis)
Ileus
Hypotension
37
Give 3 common causative organisms of SBP.
Escherichia coli
Klebsiella pnuemoniae
Gram positive cocci (such as staphylococcus and enterococcus)
38
How is SBP managed?
Ascitic culture, then IV cephalosporin such as cefotaxime
39
What is hepatorenal syndrome?
Hepatorenal syndrome occurs in liver cirrhosis. Portal htn --> portal vessel dilation and pooling --> loss of blood volume in other areas of the circulation, including the kidneys. Kidneys think BP is low and activate RAAS which causes renal vasoconstriction, which combined with low circulation volume leads to renal ischemia. Hepatorenal syndrome is fatal within a week or so unless liver transplant is performed.
40
What is hepatic encephalopathy and why does it occur?
```
Aka portosystemic encephalopathy. Liver disease --> build up of toxins that affect the brain, eg ammonia produced by intestinal bacteria when they break down proteins and is absorbed in the gut. Functional impairment of the liver cells prevents them metabolising ammonia into harmless waste products, and collateral vessels between the portal and systemic circulation mean that the ammonia bypasses liver altogether and enters the systemic system directly.
Precipitating Factors:
Constipation
Electrolyte disturbance
Infection
GI bleed
High protein diet
Medications (particularly sedative medications)
```
41
How does hepatic encephalopathy present?
Acute - reduced consciousness and confusion.
| Chronic - changes to personality, memory and mood.
42
How is hepatic encephalopathy managed?
Laxatives (i.e. lactulose) promote the excretion of ammonia. The aim is 2-3 soft motions daily. They may require enemas initially.
Antibiotics (i.e. rifaximin) reduces the number of intestinal bacteria producing ammonia. Rifaximin is useful as it is poorly absorbed and so stays in the GI tract.
Nutritional support. They may need nasogastric feeding.
43
What is hepatitis?
Hepatitis describes inflammation in the liver. This can vary from a chronic low level inflammation to acute and severe inflammation that leads to large areas of necrosis and liver failure.
44
What causes hepatitis?
```
Alcoholic hepatitis
Non alcoholic fatty liver disease
Viral hepatitis
Autoimmune hepatitis
Drug induced hepatitis (e.g. paracetamol overdose)
```
45
How does hepatitis present?
```
Asymptomatic
Abdominal pain
Fatigue
Pruritis (itching)
Muscle and joint aches
Nausea and vomiting
Jaundice
Fever (viral hepatitis)
```
46
What is a hepatitic picture on LFTs?
LFTs show high AST/ALT with less of a rise in ALP. Suggests hepatitis.
Bilirubin may rise
47
What are transaminases?
Liver enzymes (AST, ALT) that are released into the blood as a result of inflammation of the liver cells.
48
How does hep A present?
Nausea, vomiting, anorexia and jaundice. It can cause cholestasis (slowing of bile flow through the biliary system) with dark urine and pale stools and moderate hepatomegaly. It resolves without treatment in around 1-3 months.
49
Which of the hepatitises are notifiable?
Hep A, B, C, D, E - all of them!
50
Which of the hepatitises are transmitted faeco-orally?
A and E
51
Which of the hepatitises are RNA viruses?
A, C, D, E
52
How is hep A managed?
Analgesia - should resolve in 1-3 months.
Vaccination preventable
Notifiable disease - inform public health.
53
Which of the hepatitises are transmitted through blood and bodily fluids?
B and C
54
Which of the hepatitises are DNA viruses?
B
55
What is the prognosis of hep B?
Most people fully recover from the infection within 2 months
10% go on to become chronic hepatitis B carriers. In these patients the virus DNA has integrated into their own DNA and so they will continue to produce the viral proteins.
56
How do you test for Hep B?
Antigen testing:
1. Core antigen (HBcAg) and Surface antigen (HBsAg) = active infection
2. E antigen (HBeAg) – marker of viral replication and implies high infectivity - correlates with infectivity.
3. Hepatitis B virus DNA (HBV DNA) – this is a direct count of the viral load
57
How do you diagnose previous infections/immunity for hep B?
Antibody testing:
1. Surface antibody (HBsAb) = vaccination or past or current infection. Used to confirm response to vaccination.
2. Core antibodies (HBcAb) – IgM and IgG versions.
IgM = active infection (at the Moment)
IgG (in context of negative HBsAg) = past infection (now Gone)
58
What does the vaccination for Hep B involve?
```
Inactive HBsAg (surface antigen). Testing for HBsAb confirms response to vaccine.
3 doses at different intervals
Part of the 6 in 1 vaccine
```
59
How is hep B managed?
Screening for hep B + other blood born viruses (hep A and C and HIV) and other STDs
Refer to gastroenterology, hepatology or infectious diseases for specialist management
Notify Public Health (it is a notifiable disease)
Stop smoking and alcohol
Education about reducing transmission and informing potential at risk contacts
Testing for complications: FibroScan for cirrhosis and ultrasound for hepatocellular carcinoma
Antiviral medication can be used to slow the progression of the disease and reduce infectivity
Liver transplantation for end-stage liver disease
60
Which of the hepatitises are vaccine-preventable?
A, B
61
What is the disease course of hep C?
25% recover, 75% chronic.
| Complications: liver cirrhosis, hcc
62
How do you test for Hep C?
1. Hep C Ab (screening)
| 2. Hep C RNA testing (diagnosis, viral load, individual genotype)
63
How is hep C managed?
Screening for hep C, other blood born viruses (hepatitis A and B and HIV) and other STDs
Refer to gastroenterology, hepatology or infectious diseases for specialist management
Notify Public Health (it is a notifiable disease)
Stop smoking and alcohol
Education about reducing transmission and informing potential at risk contacts
Testing for complications: FibroScan for cirrhosis and ultrasound for hepatocellular carcinoma
Antiviral treatment with direct acting antivirals (DAAs) is tailored to the specific viral genotype. They successfully cure the infection in over 90% of patients. They are typically taken for 8 to 12 weeks
Liver transplantation for end-stage liver disease
64
What causes hep D?
Hep B. Attaches itself to HBsAG to survive.
65
What are the complications of hep D?
Increases complications and disease severity of hep B.
66
How do you manage hep D?
No treatment. Notify public health
67
What is the disease course of hep E?
Mild illness, self-limiting. Rarely, progresses to chronic hep and liver failure, esp in immunocompromised.
68
What is the most common hepatitis in the UK?
Hep C.
69
What is autoimmune hepatitis?
Rare cause of chronic hepatitis. May be associated with genetic predisposition and triggered by environmental factors - eg a viral infection that causes a T-cell mediated response against liver cells.
70
What is the difference between type 1 and 2 autoimmune hepatitis?
Type 1: occurs in adults, usually perimenopausal women with fatigue and liver disease.
Type 2: Occurs in young people/children with acute high transaminases and jaundice.
71
How is autoimmune hepatitis diagnosed?
LFTs - raised ALT+AST, IgG
Autoantibodies:
T1 - Anti-nuclear antibodies (ANA)
Anti-smooth muscle antibodies (anti-actin)
Anti-soluble liver antigen (anti-SLA/LP)
T2:Anti-liver kidney microsomes-1 (anti-LKM1)
Anti-liver cytosol antigen type 1 (anti-LC1)
Liver biopsy
72
How is autoimmune hepatitis managed?
High dose prednisolone at first, then taper and introduce other immunosuppressants (azathioprine). lifelong immunosuppressants required.
Liver transplant may be required but the AI hepatitis can recur in transplanted livers.
73
What is haemochromatosis?
Iron storage disorder that results in excessive total body iron and deposition of iron in tissues.
74
What causes haemochromatosis? (inheritance pattern?)
Usually a mutation in human haemochromatosis protein (HFE) gene on chromosome 6, which is important in iron metabolism regulation. Autosomal recessive inheritance.
75
How does haemochromatosis present?
Only becomes symptomatic after age of 40, later in females as menstruation gets rid of more iron.
Sx mainly due to iron deposition:
Fatigue, joint pain, bronze/slate grey discolouration, hair loss, erectile dysfunction, amenorrhea, cognitive symptoms eg memory and mood disturbance.
76
How is haemochromatosis diagnosed?
```
Serum ferritin (raised in inflammation and iron overload), transferrin saturation (raised in iron overload only, and genetic testing (confirms dx).
CT abdo shows increase in attenuation of liver
MRI shows liver and heart iron deposits more clearly.
```
77
What are the complications of haemochromatosis?
Type 1 Diabetes (iron affects the functioning of the pancreas)
Liver Cirrhosis
Iron deposits in the pituitary and gonads lead to endocrine and sexual problems (hypogonadism, impotence, amenorrhea, infertility)
Cardiomyopathy (iron deposits in the heart)
Hepatocellular Carcinoma
Hypothyroidism (iron deposits in the thyroid)
Chrondocalcinosis / pseudogout (calcium deposits in joints) causing arthritis
78
How is haemochromatosis managed?
Venesection (weekly blood removal), monitor ferritin and complications, avoid alcohol, genetic counselling.
79
What is Wilson disease?
Excessive accumulation of copper in the body and tissues
80
What causes Wilson disease? (inheritance pattern?)
Mutation in the “Wilson disease protein” on chromosome 13. The Wilson disease protein also has the catchy name “ATP7B copper-binding protein” and is responsible for various functions, including the removal of excess copper in the liver. Autosomal recessive (most metabolic things are).
81
How does Wilson disease manifest?
Most patients with Wilson disease present with one or more of:
Hepatic problems (40%) - hepatitis, cirrhosis
Neurological problems (50%) - cognition, co-ordination, dysarthria, dystonia, Parkinsons symptoms.
Psychiatric problems (10%) - depression, psychosis
Haemolytic anaemia
Renal tubular damage -> acidosis
Osteopenia
82
What is seen on examination of the eyes in Wilson disease?
Kayser-Fleischer rings in cornea (deposition of copper in Descemet’s corneal membrane) can be present in patients in Wilson disease. These are brownish circles surrounding the iris. They can usually be seen by the naked eye but proper assessment is made using slit lamp examination.
83
How is Wilson disease diagnosed?
Serum caeruloplasmin will be low. Can be falsely normal or elevated in cancer/inflammation.
Liver biopsy for copper content (gold standard).
24h urine copper assay (elevated)
Scoring systems
Low serum copper, kayser-fleischer rings, MRI brain
84
How is Wilson disease managed?
Copper chelation using penicillamine or trientene.
85
What is a-1-antitrypsin deficiency?
Abnormality in gene for alpha-1-antitrypsin which is a protease inhibitor, so its deficiency leads to excess protease formation.
86
What is the pathophysiology of a-1-AT def? (inheritance pattern?)
Neutrophils usually secrete elastase, which digests connective tissues. Alpha-1 antitrypsin inhibits this. When there is a deficiency,, there is excessive digestion of connective tissues. This mainly affects liver and lungs.
A1AT is on chromosome 14 and the defect is autosomal recessive.
87
How does alpha-1-AT def present?
Liver cirrhosis after 50 years old. Can lead to hcc.
| Bronchiectasis and emphysema after 30 years
88
How is alpha-1-AT def diagnosed?
Low serum-alpha 1-antitrypsin (screening test of choice)
Liver biopsy shows cirrhosis and acid-Schiff-positive staining globules (this stain highlights the mutant alpha-1-antitrypsin proteins) in hepatocytes
Genetic testing for the A1AT gene
High resolution CT thorax diagnoses bronchiectasis and emphysema
89
How is alpha-1-AT def managed?
Stop smoking (smoking dramatically accelerates emphysema)
Symptomatic management
NICE recommend against the use of replacement alpha-1-antitrypsin, however the research and debate is ongoing regarding the possible benefits
Organ transplant for end-stage liver or lung disease
Monitoring for complications (e.g. hepatocellular carcinoma)
90
What is primary biliary cirrhosis?
Immune system attacks small bile ducts within the liver --> obstruction of outflow of bile (cholestasis). Backpressure leads to fibrosis, cirrhosis and liver failure.
91
Why does PBC cause increased risk of CVD?
Bile ducts blocked --> build up of cholesterol --> cholesterol deposits in the skin called xanthelasma (xanthomas are larger nodular deposits in the skin or tendons) and blood vessels causing increased risk of cardiovascular disease.
92
Why do you get pruritus in PBC?
Obstruction of bile ducts -> buildup of bile acids.
| Bile acids cause itching
93
What would you see in the stool with PBC?
Bile acids are normally responsible for helping the gut digest fats. Having a lack bile acids in the stool cause gastrointestinal disturbance, malabsorption of fats and greasy stools (steatorrhoea).
Also pale due to lack of bilirubin in stool.
94
How does PBC present?
```
Fatigue
Pruritus
GI disturbance and abdominal pain
Jaundice
Pale stools
Xanthoma and xanthelasma
Signs of cirrhosis and failure (e.g. ascites, splenomegaly, spider naevi)
```
```
Usually in: Middle aged women with other autoimmune diseases (e.g. thyroid, coeliac),
Rheumatoid conditions (e.g. systemic sclerosis, Sjogrens and rheumatoid arthritis)
```
95
How is PBC diagnosed?
Liver Function Tests
Alkaline phososphatase is first liver enzyme to be raised (as with most obstructive pathology)
Other liver enzymes and bilirubin are raised in later disease
Autoantibodies
Anti-mitochondrial antibodies is the most specific to PBC and forms part of the diagnostic criteria
Anti-nuclear antibodies are present in about 35% of patients
Other blood tests:
ESR raised
IgM raised
Liver biopsy is used in diagnosing and staging the disease
96
How is PBC managed?
Ursodeoxycholic acid reduces the intestinal absorption of cholesterol
Colestyramine is a bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut and can help with pruritus due to raised bile acids
Liver transplant in end stage liver disease
Immunosuppression (e.g. with steroids) is considered in some patients
97
What are the complications of PBC?
```
Advanced liver cirrhosis, portal hypertension, hcc.
Pruritus
Fatigue
Steatorrhoea
Distal renal tubular acidosis
Hypothyroidism
Osteoporosis
```
98
What is the prognosis of PBC?
Variable from no symptoms to advanced liver cirrhosis.
99
What is primary sclerosing cholangitis?
Strictured and fibrotic bile ducts, in and outside of the liver. Causes obstruction to bile flow out of liver into intestines (cholangitis = bile duct inflammation). Leads to hepatitis, fibrosis and cirrhosis.
100
What causes PSC?
Unknown - genetic, AI, intestinal microbiome, environmental factors.
RFs: Male, age 30-40, FHx PSC, Ulcerative colitis (70% of pwPSC have UC)
101
How does PSC present?
```
Jaundice
Chronic right upper quadrant pain
Pruritus
Fatigue
Hepatomegaly
```
102
What is seen on LFTs in PSC?
Cholestatic picture - ALP raised most, bili and transaminases raised later as disease progresses.
103
How is PSC diagnosed?
LFTs - ALP raised
Autoantibodies - p-ANCA in <94%, ANA in 77%, aCL in 63%
Gold-standard is Magnetic Resonance Cholangiopancreatography (MRCP). May show bile duct lesions or strictures.
104
Give 5 complications of PSC.
```
Acute bacterial cholangitis
Cholangiocarcinoma develops in 10-20% of cases
Colorectal cancer
Cirrhosis and liver failure
Biliary strictures
Fat soluble vitamin deficiencies (ADEK)
```
105
How is PSC managed?
Liver transplant can be curative but is associated with its own problems (around 80% survival at 5 years).
ERCP can be used to dilate and stent any strictures
Colestyramine is a bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut and can help with pruritus due to raised bile acids
Monitoring for complications (such as cholangiocarcinoma, cirrhosis and oesophageal varices)
106
What is ERCP and how does it work?
ERCP (Endoscopic Retrograde Cholangio-Pancreatography) involves inserting a camera through the persons throat, oesophagus, stomach and duodenum to the a point in the duodenum where the bile ducts empty into the GI tract. They then go through the sphincter of Oddi and into the ampulla of Vater. From the ampulla of Vater they can enter into the bile ducts and use X-rays and injecting contrast to identify any strictures. These strictures can then be dilated and stented during the same procedure providing improved flow through those ducts and an improvement in symptoms.
107
What are the types of liver cancer and which is more common?
Primary
- hepatocellular carcinoma (HCC) 80%
- cholangiocarcinoma 20%
Secondary
108
What causes liver cancer?
HCC is caused by cirrhosis, which is caused by Hep B +C, alcoholic and non-alcoholic fatty liver disease.
Cholangiocarcinoma is associated with primary sclerosing cholangitis, and older age >50 years.
109
How does liver cancer present?
Often presents late by the times symptoms appear.
Wt loss, abdo pain, anorexia, N+V, jaundice, pruritus.
Cholangiocarcinoma = painless jaundice.
110
How is HCC diagnosed?
AFP is a tumour marker for HCC
Liver USS
CT and MRI for dx/staging
111
How is cholangiocarcinoma diagnosed?
CA19-9 is a tumour marker for cholangiocarcinoma.
| ERCP can be used to take biopsies or brushings to diagnose cholangiocarcinoma.
112
How is HCC treated?
Poor prognosis unless early dx
Surgery - curative resection
Liver transplant
Kinase inhibitors eg sorafenib, lenvatinib.
Chemo/radio therapy DONT work - may be used palliatively
113
How is cholangiocarcinoma treated?
Poor prognosis
Surgical resection if early
ERCP to stent bile duct and improve symptoms
Chemo/radio don't work
114
What is a haemangioma?
Common benign liver tumour, often found incidentally.
115
What is focal nodular hyperplasia?
Benign liver tumour of fibrotic tissue, often found incidentally. Often related to oestrogen (women, OCP).
116
What is orthotopic transplant?
Entire liver transplanted from a deceased patient into recipient.
117
What is a living donor transplant?
A portion of liver from a living donor transplanted into a patient, both regenerate into two fully functioning livers.
118
What is split donation?
Liver from a deceased patient is split and given to two patients where it regenerates.
119
What are the indications for liver tranplant?
1. Acute liver failure: usually immediate, acute viral hepatitis, paracetamol OD
2. Chronic liver failure: patients can wait longer, 5 months.
120
What are the contraindications for liver transplant?
Significant co-morbidities (e.g. severe kidney or heart disease)
Excessive weight loss and malnutrition
Active hepatitis B, hepatitis C or other infection
End-stage HIV
Active alcohol use (generally 6 months of abstinence is required)
121
What kind of scar do you get in liver transplant surgery?
Rooftop or Mercedes Benz incision (lower costal margin)
122
What does post liver transplant care involve?
Lifelong immunosuppressants eg steroids, azathioprine, tacrolimus
Lifestyle - avoid alcohol and smoking
Treat opportunistics
Monitor for disease recurrence and cancer (higher risk in immunosuppressed patients).
Monitor for evidence of transplant rejection - abnormal LFTs, fatigue, fever, jaundice.
123
What is GORD?
Acid from stomach refluxes (comes back up) through the lower esophageal sphincter and irritates the esophophageal lining (which lacks columnar epithelium that the stomach has to protect it)
124
How does GORD present?
'Dyspepsia' - heartburn, acid regurgitation (vomiting), retrosternal/epigastric pain, bloating, nocturnal cough, hoarse voice.
125
How is GORD investigated?
Endoscopy - assess for peptic ulcers, oesophageal or gastric malignancy if concerning features
R/o GI bleed eg melena, coffee ground vomit - admit, urgent endoscopy
H. Pylori testing. 2 weeks without using PPI for accurate result.
126
Give 5 red flags to ask about in a dyspepsia history.
```
*Dysphagia at any age*
Aged over 55 (this is generally the cut off for urgent versus routine referrals)
Weight loss
Upper abdominal pain / reflux
Treatment resistant dyspepsia
Nausea and vomiting
Low haemoglobin
Raised platelet count
--> 2 week wait for endoscopy.
```
127
How is GORD managed?
```
1. Lifestyle
Reduce tea, coffee and alcohol
Weight loss
Avoid smoking
Smaller, lighter meals
Avoid heavy meals before bed time
Stay upright after meals rather than lying flat
```
Medication:
Gaviscon, Rennie - neutralise acid
Proton pump inhibitors -reduce acid secretion in the stomach eg Omeprazole, Lansoprazole
Ranitidine - H2 receptor antagonist (antihistamine)
Reduces stomach acid
Surgery - laparoscopic fundoplication. This involves tying the fundus of the stomach around the lower oesophagus to narrow the lower oesophageal sphincter.
128
What is H. Pylori and how does it cause dyspepsia?
Gram -ve aerobic bacteria, in stomach, damages epithelial lining --> gastritis --> stomach cancer risk.
Goes into the mucosa to avoid acid --> epithelial cells exposed to acid.
Also produces ammonia which damages the epithelial cells.
129
How is H pylori tested for?
Urea breath test using radiolabelled carbon 13
Stool antigen test
Rapid urease test during endoscopy - aka CLO (Campylobacter-like organism) test. Biopsy of the stomach mucosa + Urea + H. pylori are present = ammonia. = pH increases. No H. Pylori = stays acidic.
130
How is H. Pylori treated?
PPI (e.g. omeprazole) plus 2 antibiotics (e.g. amoxicillin and clarithromycin) for 7 days.
131
What is Barretts Oesophagus?
Constant reflux of acid results in the lower oesophageal epithelium changing in a process known as metaplasia from a squamous to a columnar epithelium.
Patients typically get an improvement in reflux symptoms.
Premalignant condition for adenocarcinoma of the oesophagus (3-5% lifetime risk with Barretts).
132
How is Barretts oesophagus managed?
Monitor for adenocarcinoma by regular endoscopy.
In some patients there is a progression from Barretts oesophagus (columnar epithelium) with no dysplasia to low grade dysplasia to high grade dysplasia and then to adenocarcinoma.
PPI
Regular aspirin may reduce rate of adenocarcinoma developing.
Ablation treatment during endoscopy using photodynamic therapy, laser therapy or cryotherapy is used to destroy the epithelium so that it is replaced with normal cells, used in low and high grade dysplasia in preventing progression to cancer.
133
What are peptic ulcers? Which type is the most common?
Peptic ulcers involve ulceration of the mucosa of the stomach (gastric ulcer) or the duodenum (duodenal ulcer). Duodenal ulcers are more common.
134
What causes peptic ulcers?
(1) breakdown of the protective mucus+bicarb layer of the stomach and duodenum by medications e.g. steroids or NSAIDs, and H pylori
(2) increase in stomach acid from stress, alcohol, caffeine, smoking, spicy foods
135
How do peptic ulcers present? Duodenal vs gastric?
Epigastric discomfort or pain
Nausea and vomiting
Dyspepsia
Bleeding causing haematemesis, “coffee ground” vomiting and melaena
Iron deficiency anaemia (due to constant bleeding)
Eating typically worsens the pain of gastric ulcers because it irritates the ulcer, and improves the pain of duodenal ulcers by mopping up the acid.
136
What investigation would you do to diagnose peptic ulcers?
Endoscopy +/- rapid urease test (CLO test) for H. pylori +/- Biopsy to exclude malignancy as cancers can look similar to ulcers during the procedure.
137
How are peptic ulcers treated?
Similar to GORD - high dose PPI, monitor with endoscopy to ensure healing and assess for more ulcers
138
What are the important complications of peptic ulcers?
1. Bleeding from the ulcer is a common and potentially life threatening complication.
2. Perforation (ulcer breaks through stomach/duodenal wall) resulting in an “acute abdomen” and peritonitis. This requires urgent surgical repair (usually laparoscopic).
3. Scarring and strictures of the muscle and mucosa. This can lead to pyloric stenosis which presents with upper abdominal pain, distention, nausea and vomiting, particularly after eating.
139
What's an upper GI bleed? Give 4 causes.
Common medical emergency. Bleeding from oesophagus, stomach, duodenum. This may be from an ulcer, mallory-weiss tear, varices, or cancer.
140
How does upper GI bleed present?
Haematemesis
“Coffee ground” vomit - digested blood
Melaena - tarry, black, greasy and offensive stools caused by digested blood
Haemodynamic instability occurs in large blood loss, causing a low blood pressure, tachycardia and other signs of shock. Bear in mind that young, fit patients may compensate well until they have lost a lot of blood.
Symptoms related to underlying pathology:
Epigastric pain and dyspepsia in peptic ulcers
Jaundice for ascites in liver disease with oesophageal varices
141
What does the glasgow blatchford score tell you and how is it calculated?
```
Estimates risk of uspected upper GI bleed based on clinical presentation. Score > 0 indicates high risk for an upper GI bleed. Takes into account:
Drop in Hb
Rise in urea (product of digested blood)
Blood pressure
Heart rate
Melaena
Syncope
```
142
What does the Rockall score tell you and how is it calculated?
The Rockall Score is used for patients that have had an endoscopy to calculate their risk of rebleeding and overall mortality. Uses:
Age
Shock (e.g. tachycardia or hypotension)
Co-morbidities
Cause of bleeding (e.g. Mallory-Weiss tear or malignancy)
Endoscopic stigmata of recent haemorrhage such as clots or visible bleeding vessels
143
How is upper GI bleed managed?
With BATED breath:
ABCDE approach to immediate resuscitation
B – Bloods (Hb, U+E, coag - INR, FBC - platelets, LFT, crossmatch)
A – Access (ideally 2 large bore cannula)
T – Transfuse
E – Endoscopy (arrange urgent endoscopy within 24 hours). Definitive treatment = banding/cauterisation.
D – Drugs (stop anticoagulants and NSAIDs)
If varices suspected (eg liver disease) also use terlipressin and prophylactic broad spec abx.
144
What is the difference between group and save and crossmatch?
“Group and save” is where the lab simply checks the patients blood group and keeps a sample of their blood saved in case they need to match blood to it. “Crossmatch” is where the lab actually finds blood, tests that it is compatible and keeps it ready in the fridge to be used if necessary.
145
What type of blood products would you give to a patient with a massive haemorrhage?
Blood, platelets and clotting factors (fresh frozen plasma)
146
When would you give platelets?
Active bleeding, thrombocytopaenia (plt <50), massive haemorrhage
147
When would you use prothrombin complex concentrate?
For patients taking warfarin that are actively bleeding.
148
What are the similarities between UC and Crohns?
Involve inflammation of the walls of the GI tract and are associated with periods of remission and exacerbation.
149
Give 5 differences between UC and Crohn's disease.
Crohns nest:
N – No blood or mucus (less common than in UC)
E – Entire GI tract
S – “Skip lesions” on endoscopy
T – Terminal ileum, Transmural (full thickness) inflammation
S – Smoking is a risk factor (don’t set the nest on fire)
Crohn’s is also associated with weight loss, strictures and fistulas.
```
Ulcerative Colitis (UC CLOSEUP)
C – Continuous inflammation
L – Limited to colon and rectum
O – Only superficial mucosa affected
S – Smoking is protective
E – Excrete blood and mucus
U – Use aminosalicylates
P – Primary Sclerosing Cholangitis
```
150
How does IBD present?
```
Diarrhoea
Abdominal pain
Passing blood (esp UC)
Weight loss (esp crohns)
```
151
What investigations would you do for IBD? How is it diagnosed?
Routine bloods for anaemia, infection, thyroid, kidney and liver function
CRP indicates inflammation and active disease
Faecal calprotectin (released by the intestines when inflamed) is a useful screening test (> 90% sensitive and specific to IBD in adults)
Endoscopy (OGD and colonoscopy) with biopsy is diagnostic
Imaging with ultrasound, CT and MRI can be used to look for complications such as fistulas, abscesses and strictures.
152
How is Crohn's disease managed?
1. Inducing Remission
First line: Steroids (e.g. oral prednisolone or IV hydrocortisone)
Others: Azathioprine, Mercaptopurine, Methotrexate, Infliximab, Adalimumab
2. Maintaining Remission
First line: Azathioprine, Mercaptopurine
Alternatives: Methotrexate, Infliximab, Adalimumab
3. Surgery
When the disease only affects the distal ileum it is possible to surgically resect this area and prevent further flares of the disease. Crohns typically involves the entire GI tract. Surgery can also be used to treat strictures and fistulas secondary to Crohns disease.
153
How is UC managed?
1. Inducing Remission:
a) Mild to moderate disease
First line: aminosalicylate (e.g. mesalazine oral or rectal)
Second line: corticosteroids (e.g. prednisolone)
b) Severe disease
First line: IV corticosteroids (e.g. hydrocortisone)
Second line: IV ciclosporin
2 Maintaining Remission
Aminosalicylate (e.g. mesalazine oral or rectal)
Azathioprine
Mercaptopurine
3. Surgery
Ulcerative colitis typically only affects the colon and rectum. Therefore, removing the colon and rectum (panproctocolectomy) will remove the disease. The patient is then left with either a permanent ileostomy or something called an ileo-anal anastomosis (J-pouch). This is where the ileum is folded back in itself and fashioned into a larger pouch that functions a bit like a rectum. This “J-pouch” which is then attached to the anus and collects stools prior to the person passing the motion.
154
What is irritable bowel syndrome (IBS)?
Functional bowel disorder in which bowel functions abnormally but is otherwise structurally normal. Affects 20% of population, mainly women, younger adults.
155
How does IBS present?
```
Diarrhoea
Constipation
Fluctuating bowel habit
Abdominal pain
Bloating
Worse after eating
Improved by opening bowels
```
156
How is IBS diagnosed?
```
Exclude other pathology:
Normal FBC, ESR and CRP
-ve Faecal calprotectin (IBD)
-ve coeliac disease serology (anti-TTG antibodies)
Exclude cancer
+
Abdominal pain relieved on opening bowels, or associated with a change in bowel habit
AND 2 of:
Abnormal stool passage
Bloating
Worse symptoms after eating
PR mucus
```
157
How is IBS managed first line?
Making a positive diagnosis and providing reassurance that there is no serious pathology present is important.
Healthy diet and exercise advice:
Adequate fluid intake
Regular small meals
Reduced processed foods
Limit caffeine and alcohol
Low “FODMAP” diet (ideally with dietician guidance)
Trial of probiotic supplements for 4 weeks
CBT
158
How is IBS managed if lifestyle modifications don't work?
1. Loperamide for diarrhoea
Laxatives for constipation. Avoid lactulose as it can cause bloating. Linaclotide is a specialist laxative for patients with IBS not responding to first-line laxatives
Antispasmodics for cramps e.g. hyoscine butylbromide (Buscopan)
2. TCA eg amitriptyline 5-10mg nocte
3. SSRI
CBT
159
What is coeliac disease? What is the usual demographic for diagnosis?
Coeliac disease is an autoimmune condition where exposure to gluten causes an autoimmune reaction that causes inflammation in the small bowel. It usually develops in early childhood but can start at any age.
160
Explain the pathophysiology of coeliac disease.
Gluten exposure --> auto-antibodies target epithelial cells of small intestine particularly the jejenum --> villous atrophy and crypt hypertrophy. Therefore malabsorption of nutrients.
161
How does coeliac disease present?
Often asymptomatic so have low threshold for testing if suspected.
Failure to thrive in young children
Diarrhoea
Fatigue
Wt loss
mouth ulcers
anaemia due to iron, B12 or folate def
Dermatitis herpetiformis (itching blistering abdo rash)
Neuro (rare) - peripheral neuropathy, ataxia, epilepsy.
162
Which genes and conditions are particularly associated with coeliac disease?
T1DM - all patients are tested for coeliac. Also asso thyroid, AI hepatitis, PBC, PSC
HLA-DQ2 (90%), HLA-DQ6
163
How is coeliac disease diagnosed and investigated?
Auto-antibodies - anti-TTG, EMA, anti-DGPs (rarer).
Test total IgA in case they have IgA deficiency.
Pt must still be eating gluten.
Endoscopy and intestinal biopsy - crypt hypertrophy and villous atrophy (ie flat bowel wall)
164
What can happen in untreated coeliac disease?
```
Vitamin deficiency
Anaemia
Osteoporosis
Ulcerative jejunitis
Enteropathy-associated T-cell lymphoma (EATL) of the intestine
Non-Hodgkin lymphoma (NHL)
Small bowel adenocarcinoma (rare)
```
165
How is coeliac disease managed?
Avoid gluten for life - this is essentially curative. Check coeliac antibodies to monitor disease.
