GI and Liver Flashcards
1
Q
How long does hepatitis persist for to be deemed chronic?
A
6 months.
2
Q
Give 3 infective causes of acute hepatitis.
A
- Hepatitis A to E infection - VIRAL
- Herpes viruses (e.g. EBV, CMV, VZV) - VIRAL
- Coxiella (Q fever) - NON-VIRAL
- Toxoplasmosis - NON-VIRAL
3
Q
Give 4/5 non-infective causes of acute and chronic hepatitis.
A
- Alcohol.
- Drugs.
- Toxins.
- Autoimmune.
- Hereditary metabolic.
4
Q
Give 3 infective causes of chronic hepatitis.
A
- Hepatitis B (+/-D).
- Hepatits C.
- Hepatitis E.
5
Q
What is the presentation of symptomatic acute hepatitis?
A
- General malaise
- Myalgia
- GI upset
- Abdominal pain (upper right quadrant)
- ± cholestatic jaundice
- Tender hepatomegaly
- Raised AST, ALP ± bilirubin
6
Q
What are the signs of chronic liver disease?
A
- Clubbing
- Palmar erythema
- Dupuytren’s contracture
- Spider naevi
7
Q
What are the potential complications of chronic hepatitis?
A
Uncontrolled inflammation -> fibrosis -> cirrhosis -> HCC.
8
Q
Is HAV an RNA or DNA virus?
A
RNA virus
HAV = ACUTE HEPATITIS only
9
Q
How is HAV transmitted?
A
- Faeco-oral transmission
- Contaminated food and water
10
Q
Who could be at risk of HAV infection?
A
- Travellers
- Food handlers
- Children / young adults
11
Q
Is HAV acute or chronic?
A
Acute! There is 100% immunity after infection.
12
Q
Describe the pathophysiology of Hep A virus
A
- Picornavirus
- Replicates in liver, excreted in bile, then excreted in faeces for 2 weeks before clinical presentation, and 1 week after
- Maximally infectious just before onset of jaundice
- Incubation period = 2-6 weeks
- Self-limiting - rarely causes fulminant hepatitis
- 100% immunity after infection
13
Q
Describe the clinical presentation of HAV
A
- Viraemic symptoms (non-specific symptoms, e.g. nausea, fever)
- Jaundice (after 1-2 weeks, goes away within 3-6 weeks)
- Dark urine and pale stools - intrahepatic cholestasis
- Hepatosplenamegaly
- IgM production
14
Q
How might you diagnose someone with HAV infection?
A
LFT;
- Prodromal stage (between initial symptoms and jaundice)
- Bilirubinuria and raised urinary urobilinogen
- Raised serum AST / ALT
- Icteric stage (once jaundice is apparant)
- Serum bilirubin reflects level of jaundice
Viral serology: initially anti-HAV IgM and then anti-HAV IgG.
15
Q
Describe the management of HAV infection.
A
- Supportive.
- Monitor liver function to ensure no fulminant hepatic failure.
- Manage close contacts - give HNIG for Hep A to contacts
- NO ALCOHOL
16
Q
Describe the primary prevention of HAV.
A
- Good hygiene
- Chlorinated water
- Active immunisation - vaccination
17
Q
Is HEV a RNA or DNA virus?
A
Small RNA virus.
Only causes ACUTE hepatitis
18
Q
How is HEV transmitted?
A
Faeco-oral transmission
- Usually spread by contaminated water, rodents, dogs, and pigs
19
Q
Is HEV acute or chronic?
A
Usually acute but there is a risk of chronic disease in the immunocompromised.
20
Q
How might you diagnose someone with HEV infection?
A
Viral serology
- Initially anti-HEV IgM and then anti-HEV IgG.
21
Q
Describe the primary prevention of HEV.
A
- Good food hygiene.
- Vaccination.
22
Q
Is HBV a RNA or DNA virus?
A
DNA virus! It replicates in hepatocytes.
23
Q
How is HBV transmitted?
A
- Blood-borne transmission - IVDU, needle-stick, sexual
- Vertical transmission - MTCT
- Horizontal transmission - minor abrasions, survives on household items
HBV is highly infectious!
24
Q
Describe the pathophysiology of HBV infection
A
- Virus = inner core / nucleocapsid + outer envelope of surface protein (HBsAg - Hepatitis B surface antigen)
- HBsAg is produced in excess by infected hepatocytes
- HBsAg can exist independently in the serum and body fluid
- Following acute HBV infection, 1-5% will not clear the virus and will develop chronic Hep B
- Chronic Hep B can lead to cirrhosis or hepatocellular carcinoma (VERY BAD)
- Cirrhosis can lead to either HCC or decompensated cirrhosis
- Chronic Hep B results in ongoing hepatocellular damage
25
What HBV protein triggers the initial immune response?
The core proteins.
26
Describe the clinical presentation of a Hepatitis B infection
- Similar to Hep A
- Likely to be subclinical
- Incubation period = 1-6 months
- Viraemia
- Rashes (e.g urticaria)
- Polyarthritis
- Jaundice (after 1-2 weeks, rare in children)
- Intrahepatic cholestasis
- Hepatosplenomegaly
- Serology: HBsAg present
27
How might you diagnose someone with HBV?
**Viral serology:**
- HBsAg present 1-6 months after exposure
- HBsAg present 6m+ after exposure suggests Hepatitis carrier status
- Anti-HBV core IgM after 3 months
28
Describe the management of an acute HBV infection.
1. Supportive.
2. Monitor liver function.
3. Manage contacts - give HBIG
4. Follow up at 6 months to see if HBV surface Ag has cleared. If present -\> chronic hepatitis.
5. Avoid alcohol.
29
Describe the management for chronic Hepatitis B infection
1. Give SC pegylated interferon-alpha 2A.
- Immunomodulatory (stimulated an immune response
- Weekly SC injections
- Best long term treatment, but not always effective
- SFX; general malaise, lethargy, autoimmune disease, leukopenia, thrombocytopenia, anxiety, mental issues
2. Nucleos(t)ide analogues
- Inhibit viral replication
- One tablet a day
- High barrier to resistance
- Minimal side effects
- May be required life-long since no immune response stimulated
- e.g. oral tenofovir, oral entecavir
- Tenofovir requires renal monitoring
30
Is HDV a RNA or DNA virus?
It is a defective / incomplete RNA virus.
31
What does HDV rely on for successful host invasion?
HBV infection!
HDV can't exist without HBV as it needs HBsAg to protect it.
32
How is HDV transmitted?
Blood-borne transmission, particularly IVDU.
- All the same ways as HBV
33
What is HDV co-infection?
- Infection of HBV and HDV simultaneously
- Clinically indistinguishable from acute icteric HBV infection
- Distinguish by serum presence of IgM anti-HDV **and** IgM anti-HBV
- Co-infection increases severity of infection
34
What is HDV superinfection?
- When a person with chronic HBV gets HDV
- Chronic HBV is usually dormant (i.e. HBV DNA is low)
- Results in secondary acute infection
- Increases rate of liver fibrosis progression
- Rise in serum AST or ALT
- Can result in hepatocellular carcinoma
35
Is HCV a RNA or DNA virus?
HCV is a RNA virus.
36
Describe the epidemiology of HCV infection
- Very high incidence in Egypt due to failed public health initiative resulting in spread
- Blood borne transmission
- Common in haemophiliacs treated before blood products were screened
- Limited sexual transmission
- Vertical transmission is rare
37
What is the issue with a hepatitis C vaccination?
HCV mutates rapidly, so envelope proteins change all the time so a vaccine is difficult to develop
38
Describe the clinical presentation of HCV infection
- Most acute infections are asymptomatic
- 10% have mild flu-like illness with jaundice and rise in serum ALT / AST
- Most patients present years later with abnormal ALT / AST values or chronic liver disease
39
How might you diagnose someone with HCV infection?
HCV antibody
- Present within 4-6 weeks
- False negative in immunosuppresssed patients (no antibodies produced) and in acute infection (i.e. before 4 weeks)
HCV RNA
- Indicates current / acute infection
40
You want to find out if someone has previously been infected with HCV. How could you do this?
Viral serology - anti-HCV IgM/IgG indicates that someone has either a current infection or a previous infection.
41
Describe the treatment for HCV.
**SC pegylated interferon-alpha 2A + Oral ribavirin**
- Ribavarin causes haemolytic anaemia and anxiety
- Interferons cause lots of mental side effects so DAAs are better
**Triple therapy with direct acting antivirals (DAAs)**
- NS5A (initiates viral replication) inhibitor ending in 'asvir' (e.g. ledipasvir)
- NS5B (needed for viral replication) inhibitors ending in 'buvir' (.e.g sofosbuvir)
- Oral ribavirin
- EXTREMELY EXPENSIVE THERAPY
Lots of new drugs have been developed recently for HCV infection. Direct acting antivirals (DAA) are currently in use e.g. NS5A and NS5B.
42
What percentage of people with acute HCV infection will progress onto chronic infection?
Approximately 70%.
43
What percentage of people with acute HBV infection will progress onto chronic infection?
Approximately 5%.
44
How can HCV infection be prevented.
1. Screen blood products.
2. Lifestyle modification.
3. Needle exchange.
There is currently no vaccination and previous infection does not confer immunity.
45
What types of viral hepatitis are capable of causing chronic infection?
- B (+/-D)
- C
- E in the immunosuppressed.
46
What are the rhymes for summarising hepatitis?
**A** is Acquired by mouth from Anus, is Always cleared Acutely, and only Appears once
**E** is Even in England and can be Eaten (pigs), if not always beaten
**B** is Blood-Borne and if not Beaten can be Bad
**B** and **D** is a BastarD
**C** is usually Chronic but Can be Cured at a Cost
47
What is acute pancreatitis?
Process that occurs on the background of a previously normal pancreas, and can return to normal after resolution of the episode
It is caused by the destructive effect of **premature activation of pancreatic enzymes**, which causes **self-perpetuating pancreatic inflammation** by **enzyme-mediated auto-digestion**
48
What is the mortality rate of acute pancreatitis?
In the most severe form of acute pancreatitis, mortality rate is 40-80%
Due to either necrosis or haemorrhage
49
List 11 causes of acute pancreatitis
**I GET SMASHED**
I - idiopathic
G - gallstones
E - ethanol
T - trauma
S - steroids
M - mumps
A - autoimmune
S - scorpion venom
H - hyperlipidaemia
E - ERCP (endoscopic retrograde cholangiopancreatography)
D - drugs (e.g. NSAIDs, ACE inhibitors)
50
Describe the pathophysiology of gallstone pancreatitis
1. Accumulation of enzyme-rich fluid within pancreas due to pancreatic duct obstruction
2. Intracellular Ca2+ increases -\> early activation of trypsinogen
3. Trypsinogen is cleaved to trypsin
4. Trypsin degradation is impaired, thus leading to overwhelming build-up of trypsin
5. Increased enzymatic digstion of pancreas
6. Extensive acinar damage
51
Describe the pathophysiology of alcohol-induced pancreatitis
1. Contraction of ampulla of Vater -\> increased stimulation of enzyme secretion and obstruction of duct
2. Alcohol then interferes with Ca2+ homeostasis, causing trypsinogen cleavage
52
What are the consequences of prematurely activated pancreatic enzymes on the body?
1. Enzymes digest vessel walls in pancreas -\> leakage of fluid into tissues -\> **oedema, inflammation,** and **hypovolaemia** (as fluid is trapped in gut, peritoneum, and retroperitoneum)
2. Digested blood vessels -\> **haemorrhage**
3. Destruction of adjacent islets of Langerhans -\> destroyed beta cells -\> less insulin -\> **hyperglycaemia**
4. Lipolytic enzymes -\> fat necrosis -\> **skin discolouration** (**Grey Turner's sign**) (if associated with anterior abdominal wall
5. Released fatty acids bind to Ca2+ -\> form white precipitates in necrotic fat -\> **hypocalcaemia** (if extensive) presenting with **tetany**
53
Describe the clinical presentation of acute pancreatitis
1. Gradual / sudden severe epigastric / umbilical pain which radiates to back (relieved by sitting forward)
2. Anorexia, nausea, vomiting
3. Tachycardia
4. Fever
5. Jaundice
6. Dehydration
7. Hypotension
8. Abdominal guarding / tenderness
9. Periumbilical ecchymosis - Cullen's sign (skin discolouration due to blood under skin)
10. Left flank bruising - Grey Turner's sign
54
How can acute pancreatitis be diagnosed?
**Blood tests**
- Raised serum **amylase** - 3-fold the normal upper limit - levels fall 3-5 days after acute event, and may be triggered by other things
- Raised urinary **amylase** - DIAGNOSTIC as remains raised for a long time
- Raised serum **lipase** - most sensitive / specific for pancreatitis
- **CRP** level for monitoring severity & prognosis
**Erect CXR** - essential for gastroduodenal perforation exclusion (which also raise serum amylase) and identifying gallstones / calcification
**Abdominal ultrasound** - gallstone pancreatitis diagnosis
**Contrast enhanced CT** - identify extent of necrosis
**MRI** - identify degree of damage, and can differentiate fluid and solid inflammatory masses
55
Name 2 pancreatic scoring systems and briefly describe them
**Glasgow & Ranson scoring system**
- Use various factors (e.g. age, neutrophils, calcium, etc.) to predict a severe attack (80% sensitive)
- Can only predict attack 48hrs after presentation
APACHE II score
- Used to assess severity
- Based on common physiological and laboratory values, age, and chronic conditions (e.g. obesity)
- High sensitivity
56
What 8 points make up the glasgow scoring system?
**PaO2** \< 8kPa.
**Age** \> 55 years.
**Neutrophils** \> 15x10^9.
**Calcium** \< 2mmol/L.
Raised **urea** \> 15mmol/L.
**Elevated enzymes.**
**Albumin** \< 32g/L.
**Sugar** - serum glucose \> 15mmol/L.
57
Describe the treatment for acute pancreatitis.
1. **ANALGESIA**! - IV morphine
2. **Catheterise** and ABC approach for shock patients.
3. **Drainage** of oedematous fluid collections.
4. Prophylactic **antibiotics** (e.g. beta-lactams) - reduce risk of infected pancreatic necrosis
5. **Nil by mouth**, nasogastric tube for **dietary supplements** (support patients nutritionally to decrease pancreatic stimulation)
6. Bowel rest.
7. **Severity** **assessment**
58
Give 2 potential complications of acute pancreatitis.
1. **Systemic inflammatory response syndrome.**
- Any two of;
1. Tachycardia \>90bpm
2. Tachypnoea \>20 breaths/pm
3. Pyrexia \> 38 degrees
4. High white cell count
2. **Multiple organ dysfunction.**
59
What is chronic pancreatitis?
Debilitating contuining inflammatory process resulting in progressive loss of exocrine pancreatic tissue, which is replaced by fibrosis
60
What are the main causes of chronic pancreatitis?
1. Long-term alcohol excess (~65%)
2. CKD
3. Inherited defects in trypsinogen gene
4. Cystic fibrosis
5. Autoimmune pancreatitis - raised IgG4 (seen in many autoimmune disorders) triggers pancreatitis
6. Trauma
7. Idiopathic
8. Recurrent acute pancreatitis
61
Describe the pathogenesis of chronic pancreatitis.
1. **Obstruction** / **reduction** in bicarbonate **secretion** (alkaline pH stabilises trypsinogen) -\> **activation** of **trypsinogen**
2. Trypsin causes pancreatic tissue **necrosis** -\> eventual **fibrosis**
3. Increased intrapancreatic enzyme activity causes **precipitation** of proteins within duct lumen -\> forms **plug** in duct
4. Plugs are **calcified** -\> further damage
62
Describe how alcohol can cause chronic pancreatitis.
Alcohol -\> proteins precipitate in the ductal structure of the pancreas (obstruction) -\> pancreatic fibrosis.
63
What immunoglobulin might be elevated in someone with autoimmune chronic pancreatitis?
IgG4.
64
How do you diagnose chronic pancreatitis?
Serum **amylase** and **lipase**
- May be elevated
- In advanced disease, there may not be sufficient residual acinar cells to produce elevation
Abnormal **feacal** **elastase** - in patients with moderate-severe disease
**Abdominal** **ultrasound** / **contrast enhanced CT** - detects pancreatic calcification and dilated pancreatic duct to CONFIRM DIAGNOSIS
**MRI** **with MRCP** to identify subtle abnormalities
65
Describe the clinical presentation of chronic pancreatitis
1. **Epigastric** pain which **radiates** to **back**
- Episodic or unremitting
- Relieved by sitting forward
2. **Nausea**, **vomiting**, **anorexia**
3. **Exocrine** dysfunction - **malabsorption**
- Weight loss
- Diarrhoea
- Steatorrhoea
- Protein deficiency
4. **Endocrine** dysfunction - **diabetes mellitus**
66
What is the treatment for chronic pancreatitis?
1. **Alcohol** cessation
2. **Opiates** (e.g. tramadol) for abdominal pain
3. Duct **drainage**
4. **Shock wave lithotripsy** to fragment gall stones in head of pancreas
5. **Pancreatic enzyme supplements** for steatorrhoea
- PPIs to help supplement pass stomach
6. **Insulin** if diabetic
67
How is autoimmune chronic pancreatitis treated?
It is very steroid responsive
Give oral prednisolone for 4-6 weeks
68
Give 4 functions of the liver.
1. Glucose and fat metabolism.
2. Detoxification and excretion.
3. Protein synthesis e.g. albumin, clotting factors.
4. Defence against infection.
69
Name 3 things that liver function tests measure.
1. Serum bilirubin.
2. Serum albumin - marker of synthetic function
3. Pro-thrombin time - marker of synthetic function
70
LFTs: What is useful about serum albumin levels?
- Marker of synthetic function
- Useful for gauging severity of chronic liver disease
- Falling serum albumin is a bad prognostic sign
- In acute disease, initial albumin levels may be normal
71
What information do you get from a liver biochemistry test?
1. Aminotransferases - enzymes within hepatocytes which leak into blood with liver cell damage
- **Aspartate aminotransferase (AST)**
* Present in heart, muscle, kidney, and brain
* High levels seen in hepatic necrosis, MI, muscle injury, and CCF
- **Alanine aminotransferases (ALT)**
* Specific to liver
* Only rises in liver disease
2. **Alkaline phosphatase**
- Raised in intrahepatic and extrahepatic cholestatic disease of any cause, due to increased synthesis
- Raised in hepatic infiltrations (e.g. metastasis) and cirrhosis
72
What enzymes increase in the serum in hepatocellular liver disease?
Transaminases e.g. AST and ALT.
73
Name a cholestatic enzyme.
Alkaline phosphatase.
74
Give 2 possible outcomes of acute liver disease.
1. Recovery.
2. Liver failure.
75
Give 5 causes of acute liver disease.
1. Viral hepatitis.
2. Drug induced hepatitis.
3. Alcohol induced hepatitis.
4. Vascular.
5. Obstruction.
76
Give 3 symptoms of acute liver disease.
1. Malaise.
2. Lethargy.
3. Nausea and anorexia.
4. Jaundice may develop later on.
77
Give 3 possible outcomes of chronic liver disease.
1. Cirrhosis.
2. Liver failure.
3. Recovery.
78
Give 5 causes of chronic liver disease.
1. Alcohol.
2. NAFLD.
3. Viral hepatitis (B, C, E).
4. Autoimmune diseases.
5. Metabolic e.g. haemochromatosis.
6. Vascular e.g. Budd-Chiari.
79
What is Budd-Chiari syndrome?
A vascular disease associated with occlusion of hepatic veins that drain the liver.
80
Give 10 signs of chronic liver disease.
1. Ascites.
2. Oedema.
3. Malaise.
4. Anorexia.
5. Bruising.
6. Itching.
7. Clubbing.
8. Palmar erythema.
9. Spider naevi.
10. Hepatomegaly
11. Abnormal LFTs
81
Drug induced liver injury is common. What question should you remember to ask in a patient history?
Have you started taking any new medication recently?
82
Name a drug that can cause drug induced liver injury.
1. Co-amoxiclav.
2. Flucloxacillin.
3. Erythromyocin.
4. TB drugs.
83
Name 3 drugs that are not known to cause drug induced liver injury.
1. Low dose aspirin.
2. NSAIDS.
3. Beta blockers.
4. HRT.
5. CCB.
84
What enzyme is responsible for 'mopping up' reactive intermediates of paracetamol and so prevents toxicity and liver failure?
Glutathione transferase.
85
What are the potential consequences of hepatocyte regeneration in someone with liver cirrhosis?
Neoplasia and therefore HCC.
Hepatocyte regeneration is liable to errors.
86
What is haemochromatosis?
Inherited disorder of iron metabolism, in which there is increased intestinal iron absorption, leading to deposition in joints, liver, heart, pancreas, pituitary, adrenals, and skin
87
Give 3 causes of iron overload.
1. Genetic disorders e.g. haemochromatosis.
2. Multiple blood transfusions.
3. Haemolysis.
4. Alcoholic liver disease.
88
What are the main causes of haemachromatosis?
1. HFE gene mutation - 90% of cases caused by this mutation
2. High intake of iron and chelating agents (e.g. ascorbic acid)
3. Alcoholism
89
Haemochromatosis is a genetic disorder. How is it inherited?
Autosomal recessive inheritance.
90
Describe the pathophysiology of haemochromatosis.
1. HFE gene protein interacts with **transferrin** receptor 1, which mediates intestinal iron absorption
2. **Hepcidin** (protein made in liver) **increases** when iron **deficient**, and **decreases** with iron **overload**
3. Mutated HFE genes mean hepcidin is **underproduced** -\> iron **overload**
4. Inappropriately high levels of iron are absorbed by **mucosal** **cells** in SI -\> **exceeds** **binding** **capacity** of transferrin
5. Excess iron **precipitates** **fibrosis** and **deposition**
Normal person's iron = 3-4mg
Symptomatic patient's iron = 20-40mg
91
What is the clinical presentation for haemochromatosis?
1. Male (women protected by menstruation / dietary intake)
2. Patient in 50s
3. Tiredness
4. Arthralgia
5. Hypogonadism - secondary to pituitary dysfunction
6. Slate-grey skin pigmentation
7. Signs of chronic liver disease (ascites, oedema, bruising)
8. Hepatomegaly, cirrhosis, dilated cardiomyopathy, osteoporosis, heart failure, arryhthmias
9. Bronze skin, hepatomegaly, DM - in GROSS iron overload
92
How might you diagnose someone with haemochromatosis?
1. Raised ferritin - non-specific
2. Raised iron - 20-40mg
3. HFE genotyping.
4. Liver biopsy - assess extent of damage / disease severity
93
How do you treat haemochromatosis?
1. Venesection
- Regular removal of blood allows body to use excess iron to make new RBCs
- Prolongs life and may reverse tissue damage
2. Chelation therapy, e.g. desferrioxamine
- For patients who can't tolerate venesection
- Chelating agent = substance whose molecules can form several bonds to a signle metal ion, thus preventing absorption
3. Treat diabetes
4. Treat hypogonadism
5. Low-iron diet
94
Name 3 metabolic disorders that can cause liver disease.
1. Haemochromatosis - iron overload.
2. Alpha 1 anti-trypsin deficiency.
3. Wilson's disease - disorder of copper metabolism.
95
Describe the pathophysiology of alpha-1-antitrypsin deficiency?
Alpha-1-antitrypsin inhibits the proteolytic enzyme (neutrophil elastase), and protects the lungs against tissue damage
Defiency results in emphysema, cirrhosis, and HCC
Protein retention in liver -\> cirrhosis
96
Describe the clinical presentation of alpha-1-antitrypsin deficiency
Presents as liver disease in children, and respiratory problems in adults
97
What is Wilson's disease?
An **autosomal** **recessive** disorder of copper metabolism; there is excessive deposition of copper in the liver. This can lead to fulminant hepatic failure and cirrhosis.
Defect within the gene coding for copper-transporting ATPase
98
What is the clinical presentation of Wilson's disease?
- Children present with hepatic problems (e.g. hepatitis, cirrhosis, fulminant liver failure)
- Adults present with CNS problems (e.g. tremor, dysarthria, dysphagia)
- Reduced memory
- Liver disease varies from acute hepatitis, to chronic hepatitis, to cirrhosis
- Kayser-Fleischer ring - copper deposition in cornea resulting in brownish pigment at corneoscleral junction
99
Describe the pathophysiology of Wilson's disease
- Dietary copper is absorbed in stomach / upper SI, and loosely bound to albumin for tranpsort to the liver
- In the liver, it is incorporated into glycoprotein caeruloplasmin
- The excess copper is excreted in the bile, and then in the faeces
- Wilson's disease results in copper deposition in the liver, basal ganglia, and cornea
- Basal ganglia shows cavitation, kidneys show tubular degeneration, and bones are eroded
100
How do you diagnose Wilson's disease?
- Reduced serum copper and caeruloplasmin (sometimes)
- High 24hr urinary copper excretion
- Liver biopsy - high hepatic copper, hepatitis, and cirrhosis
- MRI showing basal ganglia degeneration
101
How do you treat Wilson's disease?
1. Avoid high copper foods (e.g. liver, chocolate, etc.)
2. Lifelong chelating agents, e.g. penicillamine
3. Liver transplant if severe
4. Screen siblings as asymptomatic homozygotes need treating
102
What can cause raised unconjugated bilirubin?
PRE-HEPATIC JAUNDICE
- Haemolysis due to sickle cell disease, spherocytosis, hypersplenism etc.
- Gilbert's
103
Describe the presentation of pre-hepatic jaundice
**Pre-hepatic jaundice = raised unconjugated bilirubin**
Urine = normal
Stools = normal
Itching = No
LFTs = Normal
104
What can cause raised conjugated bilirubin?
**Raised conjugated bilirubin** = hepatic / post-hepatic jaundice (aka. cholestatic jaundice)
- Liver disease (hepatic)
- Bile-duct obstruction (post-hepatic)
105
Describe the presentation of cholestatic jaundice
## Footnote
*Cholestatic jaundice = hepatic or post-hepatic*
Urine = dark
Stools = pale (maybe)
Itching = maybe
LFTs = abnormal
106
Give 3 causes of duct obstruction.
1. Gallstones.
2. Stricture (narrowing) e.g. malignant, inflammatory.
3. Carcinoma.
4. Blocked stent.
107
Give 4 causes of hepatic jaundice.
1. Viral hepatitis / alcholic hepatitis
2. Congestive cardiac failure
3. Ischaemia.
4. Neoplasm.
108
Give 3 symptoms of jaundice.
1. Biliary pain - RUQ pain that radiates to shoulder
2. Rigors - indicate an obstructive cause.
3. Abdomen swelling.
4. Weight loss.
109
What is ascites?
An accumulation of free fluid in the peritoneal cavity that leads to abdominal distension.
110
Give 4 pathophysiological causes of ascites and an example for each.
1. Local inflammation e.g. peritonitis.
2. Leaky vessels e.g. imbalance between hydrostatic and oncotic pressures.
3. Low flow e.g. cirrhosis, thrombosis, cardiac failure.
4. Low protein e.g. hypoalbuminaemia.
111
Describe the pathogenesis of ascites.
**Inflammation**
- Local inflammation -\> fluid accumulation
**Low protein**
- Inability to pull fluid back into intravascular space
**Low flow**
- Fluid cannot move forwards through a system (e.g. due to a clot) -\> raises pressure in vessel -\> fluid leaks out
112
Describe the clinical presentation for ascites
- HISTORY!
- Length of swelling, drugs, weight loss, medical history
- Distended abdomen
- Fullness in flanks and SHIFTING DULLNESS!
- Mild abdominal pain
- Severe pain = query bacterial peritonitis?
- Respiratory distress
- Difficulty eating
- Peripheral oedema
113
How do you diagnose ascites?
- SHIFTING DULLNESS!
- Diagnostic aspiration of 10-20ml of fluid using ascitic tap
- Raised white cell count = bacterial peritonitis
- Gram stain and culture
- Cytology to identify malignancy
- Amylase to exclude pancreatic ascites
- Protein measurement of ascitic fluid
- Transudate = low protein (\<30g/L) - less bad
- portal hypertension, constrictive pericarditis, etc
- Exudate = high protein (\>30gL) - EXTREMELY BAD
- malignancy, peritoneal TB, peritonitis
114
How do you treat ascites?
1. Treat underlying cause
2. Reduce sodium to help liver and reduce fluid retention
3. Increase renal sodium excretion
- Aldosterone antagonist (e.g. oral spirolactone) since it spares K+
4. Drain fluid (paracentesis) - drain 5L at a time
5. Shunts - transjugular intrahepatic portosystemic shunt (TIPS)
115
What are the 3 phases of alcoholic liver disease.
1. Fatty change - hepatocytes contain triglycerides.
2. Alcoholic hepatitis.
3. Alcoholic cirrhosis - destruction of liver architecture and fibrosis.
116
What might be seen histologically that indicates a diagnosis of alcoholic liver disease?
Neutrophils and fat accumulation within hepatocytes.
117
What is non-alcoholic steato-hepatitis (NASH)?
An advanced form of non-alcoholic fatty liver disease.
118
Give 3 causes of non-alcoholic fatty liver disease.
1. Type 2 diabetes mellitus.
2. Hypertension.
3. Obesity.
4. Hyperlipidaemia.
119
Describe the physiology of alcohol consumption
1. Ethanol is metabolised in liver, increasing NADH:NAD ratio
2. Altered redox potential causes increased hepatic fatty acid synthesis with decreased FA oxidation
3. Results in hepatic accumulation of FAs which are esterified into glycerides
4. Redox changes also impair carbohydrate & protein metabolism, are cause centrilobular necrosis of the hepatic acinus (typical of alcohol damage)
5. TNF-alpha released from Kupffer cells causes release of ROS -\> tissue damage and necrosis
120
Describe the pathophysiology of fatty liver
1. Alcohol metabolism produces fat in liver
- Minimal with small amounts of alcohol
- Larger amounts -\> swollen cells (steatosis)
2. Fat disappears when alcohol is removed
3. In some cases, collagen is laid down around central hepatic veins, sometimes progressing to cirrhosis without preceding hepatitis
4. Alcohol directly affects stellate cells, turning them into collagen-producing myofibroblast cells
121
Describe the pathophysiology of alcoholic hepatitis
1. In addition to fatty change, there is infiltration by polymorphonuclear leucocytes and hepatocyte necrosis
2. Dence cytoplasmic inclusions (Mallory bodies) are sometimes seen in hepatocytes
3. Giant mitochondria are also a feature of alcoholic hepatitis
122
Describe the pathophysiology of alcoholic cirrhosis
As well as fatty change, micronodular cirrhosis is seen
123
What is the clinical presentation of the various stages of alcoholic liver disease?
**Fatty liver**
* - Often asymptomatic*
* - Sometimes vague abdominal symptoms (e.g. nausea, vomiting)*
* - Hepatomegaly (maybe)*
* - Chronic liver disease symptoms (maybe)*
**Alcoholic hepatitis**
* - Possibly asymptomatic*
- Hepatitis only apparent on liver biopsy
- Mild-moderate symptoms of ill-health (e.g. mild jaundice)
* - Chronic liver disease (maybe)*
- Biochemistry & histology is deranged and diagnostic
**Alcoholic cirrhosis**
- *Can be well with few symptoms*
- Chronic licer disease (e.g. ascites, bruising, clubbing, Dupuytren's contracture)
- Alcohol dependency
124
How do you diagnose alcoholic liver disease?
Fatty liver
- Raised MCV (indicates heavy drinking)
- Raised ALT and AST
- Ultrasound / CT / histology will reveal fatty infiltration
Alcoholic hepatitis / cirrhosis
- Leucocytosis
- Raised serum bilirubin
- Raised AST / ALT
- Raised alkaline phosphate
- Decreased prothrombin time
125
How do you treat alcoholic liver disease?
**STOP DRINKING ALCOHOL!!!**
**-** Diazepam for delirium tremens
- IV thiamine to prevent Wernicke-Korsakoff encephalopathy (occurs from alcohol withdrawal 6-24hrs after last drink)
**Fatty liver** - stop alcohol
**Alcoholic hepatitis**
- Vitamins and protein diet
- Steroids for short-term benefit
- Prophylactic anti-fungals
**Alcoholic cirrhosis**
- Reduce salt intake
- Avoid NSAIDs and aspirin
- Liver transplant
126
What is cirrhosis?
A chronic disease of the liver resulting from necrosis of liver cells followed by fibrosis. The end result is irreversible impairment of hepatocyte function and distortion of liver architecture.
127
Give 3 causes of cirrhosis.
1. Alcohol!
2. Hepatitis B (±D) and C.
3. Any chronic liver disease e.g. autoimmune, metabolic, vascular etc.
128
What is the treatment of liver cirrhosis?
1. Deal with the underlying cause e.g. stop drinking alcohol.
2. Screening for HCC.
3. Consider transplant.
129
Approximately what percentage of blood flow to the liver is provided by the portal vein?
75%.
130
Portal hypertension can lead to varices. Explain why.
Obstruction to portal blood flow e.g. cirrhosis leads to portal hypertension. Blood is diverted into collaterals e.g. the gastro-oesophageal junction and so causes varices.
131
Give 3 causes of portal hypertension.
1. Cirrhosis and fibrosis (intra-hepatic causes). 2. Portal vein thrombosis (pre-hepatic). 3. Budd-Chiari (post-hepatic cause).
132
What are the potential consequences of varices?
If they rupture -\> haemorrhage.
133
What is the primary treatment for varices?
Endoscopic therapy - banding.
134
What is peritonitis?
Inflammation of the peritoneum often due to infection.
135
What can cause peritonitis?
1. Bacterial infection due to a perforated organ; spontaneous bacterial peritonitis; infection secondary to peritoneal dialysis. 2. Non-infective causes e.g. bile leak; blood from ruptured ecotopic pregnancy.
136
What is the commonest serious infection in those with cirrhosis?
Spontaneous bacterial peritonitis. It can also affect immunocompromised people and those undergoing peritoneal dialysis.
137
Name a bacteria that can cause spontaneous bacterial peritonitis.
1. E.coli. 2. S.pneumoniae.
138
How can spontaneous bacterial peritonitis be diagnosed?
By looking for the presence of neutrophils in ascitic fluid.
139
Give 3 symptoms of peritonitis.
1. Pain. 2. Tenderness. 3. Systemic symptoms e.g. nausea, chills, rigor.
140
Name a cause of pelvic inflammatory disease.
A complication of chlamydial infection.
141
Give 4 reasons why liver patients are vulnerable to infection.
1. They have impaired reticulo-endothelial function. 2. Reduced opsonic activity. 3. Leukocyte function is reduced. 4. Permeable gut wall.
142
What is primary biliary cirrhosis?
An autoimmune disease where there is progressive lymphocyte mediated destruction of intra-hepatic bile ducts -\> cholestasis -\> cirrhosis.
143
Describe 2 features of the epidemiology of primary biliary cirrhosis.
1. Females affected more than men. 2. Familial - 10 fold risk increase.
144
Describe the pathophysiology of primary biliary cirrhosis.
Lymphocyte mediated attack on bile duct epithelia -\> destruction of bile ducts -\> cholestasis -\> cirrhosis.
145
Give 3 diseases associated with primary biliary cirrhosis.
1. Thyroiditis. 2. RA. 3. Coeliac disease. 4. Lung disease. (Other autoimmune diseases).
146
Give 5 symptoms of primary biliary cirrhosis.
1. Itching. 2. Fatigue. 3. Dry eyes, 4. Joint pains. 5. Variceal bleeding.
147
What is the treatment for primary biliary cirrhosis?
Ursodeoxycholic acid; improves liver enzymes; reduces inflammation and portal pressure and therefore the rate of variceal development.
148
Give 3 risk factors for gallstone development.
1. Female. 2. Obese (fat). 3. Fertile.
149
How can gallstones be removed from the gall bladder?
Laproscopic cholecystectomy.
150
Give 4 potential complications of gallstones in the bile duct.
1. Biliary pain. 2. Obstructive jaundice. 3. Cholangitis (infection of the biliary tract). 4. Pancreatitis.
151
What is ascending cholangitis?
Obstruction of biliary tract causing bacterial infection. Regarded as a medical emergency.
152
Name the triad that describes 3 common symptoms of ascending cholangitis.
Charcot's triad: 1. Fever. 2. RUQ pain. 3. JAUNDICE (cholestatic)!
153
What is charcot's triad?
It describes 3 common symptoms of ascending cholangitis: 1. Fever. 2. RUQ pain. 3. Jaundice (cholestatic)!
154
What investigations might you do in someone who you suspect might have ascending cholangitis?
1. Ultrasound. 2. Blood tests - LFT's. 3. ERCP - definitive investigation.
155
Describe the management of ascending cholangitis.
- IV fluid. - IV antibiotics e.g. cefotaxime and metronidazole. - ERCP to remove stone. - Stenting.
156
What is the difference between ascending cholangitis and acute cholecystitis?
A patient with acute cholecystitis would not have signs of jaundice!
157
What is acute cholecystitis?
Inflammation of the gall bladder caused by blockage of the bile duct -\> obstruction to bile emptying.
158
Give 3 symptoms of acute cholecystitis.
1. RUQ pain. 2. Fever. 3. Raised inflammatory markers. - NO JAUNDICE!
159
Give 2 risk factors for acute cholecystitis.
1. Obesity. 2. Diabetes.
160
Describe the pathophysiology of primary sclerosing cholangitis.
Inflammation of the bile duct -\> strictures and hardening -\> progressive obliterating fibrosis of bile duct branches -\> cirrhosis -\> liver failure.
161
Give 3 symptoms of primary sclerorsing cholangitis.
1. Itching. 2. Rigor. 3. Pain. 4. Jaundice. 75% also have IBD.
162
What is biliary colic?
Gallbladder attack - RUQ pain due to a gall stone blocking the bile duct.
163
What can trigger biliary colic?
Eating a heavy meal especially one that is high in fat.
164
Give 5 causes of diarrhoeal infection.
1. Traveller's diarrhoea. 2. Viral e.g. rotavirus, norovirus. 3. Bacterial e.g. E.coli. 4. Parasites e.g. helminths. 5. Nosocomial e.g. c.diff.
165
Give 5 causes of non-diarrhoeal infection.
1. Gastritis/peptic ulcer disease e.g. h.pylori. 2. Acute cholecystitis. 3. Peritonitis. 4. Typhoid/paratyphoid. 5. Amoebic liver disease.
166
Give 3 ways in which diarrhoea can be prevented.
1. Access to clean water. 2. Good sanitation. 3. Hand hygiene.
167
What is the diagnostic criteria for traveller's diarrhoea?
\>3 unformed stools per day and at least one of: - Abdominal pain. - Cramps. - Nausea. - Vomiting. It occurs within 3 days of arrival in a new country.
168
Give 3 causes of traveller's diarrhoea.
1. Enterotoxigenic e.coli (ETEC). 2. Campylobacter. 3. Norovirus.
169
Describe the pathophysiology of traveller's diarrhoea.
Heat labile ETEC modifies Gs and it is in a permanent 'locked on' state. Adenylate cyclase is activated and there is increased production of cAMP. This leads to increased secretion of Cl- into the intestinal lumen, H2O follows down as osmotic gradient -\> diarrhoea.
170
Which type of e.coli can cause bloody diarrhoea and has a shiga like toxin?
Enterohaemorrhagic e.coli (EHEC) aka e.coli 0157.
171
What does EIEC stand for?
Enteroinvasive e.coli.
172
Which type of e.coli is responsible for causing large volumes of watery diarrhoea?
Enteropathogenic e.coli (EPEC).
173
What does EAEC stand for?
Enteroaggregative e.coli.
174
What does DAEC stand for?
Diffusely adherent e.coli.
175
What is the leading cause of diarrhoeal illness in young children?
Rotavirus. There is a vaccine - rotarix.
176
Name a helminth responsible for causing diarrhoeal infection.
Schistosomiasis.
177
Give 5 symptoms of helminth infection.
1. Fever. 2. Eosinophilia. 3. Diarrhoea. 4. Cough. 5. Wheeze.
178
Briefly describe the reproductive cycle of schistosomiasis.
1. Fluke matures in blood vessels and reproduces sexually in human host. 2. Eggs expelled in faeces and enter water source. 3. Asexual reproduction in an intermediate host. 4. Larvae expelled and penetrate back into human host.
179
Why is c.diff highly infectious?
It is a spore forming bacteria. (Gram positive).
180
Give 5 risk factors for c.diff infection.
1. Increasing age. 2. Co-morbidities. 3. Antibiotic use. 4. PPI. 5. Long hospital stays.
181
Describe the treatment for c.diff infection.
Metronidazole and vancomyocin (PO).
182
Name 5 antibiotics prone to causing c.diff infection.
1. Ciprofloxacin. 2. Co-amoxiclav. 3. Clindamycin. 4. Cephlasporins. 5. Carbapenems. RULE OF C's!
183
What can helicobacter pylori infection cause?
H.pylori produces urease -\> ammonia -\> damage to gastric mucosa -\> neutrophil recruitment and inflammation. This can cause gastritis; peptic ulcer disease and gastric cancer.
184
Describe h.pylori.
A gram negative bacilli with a flagellum.
185
Describe the treatment for H.pylori infection.
Triple therapy: 2 antibiotics and 1 PPI e.g. omeprazole, clarithromyocin and amoxicillin.
186
Who is most likely to be affected by diverticular disease?
Older patients and those with low fibre diets.
187
Describe the pathophysiology of diverticulitis.
Out-pouching of bowel mucosa -\> faeces can get trapped here and obstruct the diverticula -\> abscess and inflammation -\> diverticulitis.
188
What part of the bowel is most likely to be affected by diverticulitis?
The descending colon.
189
What is acute diverticulitis?
A sudden attack of swelling in the diverticula. Can be due to surgical causes.
190
Describe the signs of acute diverticulitis.
Similar to the signs of appendicitis but on the left side e.g. pain in the left iliac fossa region, fever, tachycardia.
191
Name the 3 broad categories that describe the causes of intestinal obstruction.
1. Blockage. 2. Contraction. 3. Pressure.
192
Intestinal obstruction: give 3 causes of blockage.
1. Tumour. 2. Diaphragm disease. 3. Gallstones in ileum (rare).
193
Intestinal obstruction: what is thought to cause diaphragm disease?
NSAIDS.
194
Intestinal obstruction: give 3 causes of contraction.
1. Inflammation. 2. Intramural tumours. 3. Hirschprung's disease.
195
Describe how Crohn's disease can cause intestinal obstruction.
Crohn's disease -\> fibrosis -\> contraction -\> obstruction.
196
Describe how Diverticular disease can cause intestinal obstruction.
Out-pouching of mucosa -\> faeces trapped -\> inflammation in bowel wall -\> contraction -\> obstruction.
197
What is Hirschprung's disease?
A congenital condition where there is a lack of nerves in the bowel and so motility is affected. This leads to obstruction and gross dilatation of the bowel.
198
Intestinal obstruction: give 3 causes of pressure.
1. Adhesions. 2. Volvulus. 3. Peritoneal tumour.
199
Intestinal obstruction: what are adhesions?
Adhesions often form secondary to abdominal surgery. Loops of bowel stick together and the bowel is pulled and distorted. 40% of intestinal obstructions are due to adhesions.
200
Intestinal obstruction: what causes adhesions?
Adhesions often form secondary to abdominal surgery.
201
Intestinal obstruction: what is volvulus?
Volvulus is a twist/rotation in the bowel; closed loop obstruction. There is a risk of necrosis.
202
Intestinal obstruction: which areas of the bowel are most likely to be affected by volvulus?
Volvulus occurs in free floating areas of the bowel e.g. bowel with mesentery. The sigmoid colon has a long mesentery and so can twist on itself.
203
Give 4 common causes of small bowel obstruction in adults.
1. Adhesions. 2. Hernias. 3. Crohn's disease. 4. Malignancy.
204
Which is more common: small bowel obstruction or large bowel obstruction?
Small bowel obstruction is more common; it makes up 75% of intestinal obstruction.
205
Give 3 common causes of small bowel obstruction in children.
1. Appendicitis. 2. Volvulus. 3. Intussusception.
206
Intestinal obstruction: what is intussusception?
Intussusception is when part of the intestine invaginates into another section of the intestine -\> telescoping. It is caused by force in-balances.
207
Define hernia.
The abnormal protrusion of an organ into a body cavity it doesn't normally belong.
208
What are the risks of hernia's if left untreated?
They can become strangulated and you may not be able to return them into their correct body cavity - irreducible.
209
Give 2 symptoms of hernia.
1. Pain. 2. Palpable lump.
210
Give 5 symptoms of small bowel obstruction.
1. Vomiting. 2. Pain. 3. Constipation. 4. Distension. 5. Tenderness.
211
Would dilatation, distension and increased secretions be seen proximal or distal to an intestinal obstruction?
Proximal.
212
Give 4 signs of small bowel obstruction.
1. Vital signs e.g. increased HR, hypotension, raised temperature. 2. Tenderness and swelling. 3. Resonance. 4. Bowel sounds.
213
What investigations might you do in someone who you suspect to have a small bowel obstruction?
1. Take a good history - ask about previous surgery (adhesions)! 2. FBC, U+E, lactate. 3. X-ray. 4. CT, ultrasound, MRI.
214
What is the management/treatment for small bowel obstruction?
1. Fluid resuscitation. 2. Bowel decompression. 3. Analgesia and anti-emetics. 4. Antibiotics. 5. Surgery e.g. laparotomy, bypass segment, resection.
215
Give 2 common causes of large bowel obstruction.
1. Colorectal malignancy. 2. Volvulus (especially in the developing world).
216
Give 5 symptoms of large bowel obstruction.
1. Tenesmus. 2. Constipation. 3. Abdominal discomfort. 4. Bloating. 5. Vomiting. 6. Weight loss.
217
What investigations might you do in someone who you suspect to have a large bowel obstruction?
1. Digital rectal examination. 2. Sigmoidoscopy. 3. Plain X-ray. 4. CT scan.
218
Describe the management for a large bowel obstruction.
1. Fast the patient. 2. Supplement O2. 3. IV fluids to replace losses and correct electrolyte imbalance. 4. Urinary catheterisation to monitor urine output.
219
Give 3 consequences of untreated intestinal obstructions.
1. Ischaemia. 2. Necrosis. 3. Perforation.
220
Describe the progression from normal epithelium to colorectal cancer.
1. Normal epithelium. 2. Adenoma. 3. Colorectal adenocarcinoma. 4. Metastatic colorectal adenocarcinoma.
221
Define adenocarcinoma.
A malignant tumour of glandular epithelium.
222
What is familial adenomatous polyposis?
Familial adenomatous polyposis is a genetic condition where you develop thousands of polyps in your teens.
223
Describe the pathophysiology of familial adenomatous polyposis.
There is a mutation in apc protein and so the apc/GSK complex isn't formed -\> beta catenin levels increase -\> up-regulation of adenomatous gene transcription.
224
Describe the pathophysiology of HNPCC.
There are no DNA repair proteins meaning there is a risk of colon cancer and endometrial cancers.
225
How can adenoma formation be prevented?
NSAIDS are believed to prevent adenoma formation.
226
What is the treatment for adenoma?
Endoscopic resection.
227
What is the treatment for colorectal adenocarcinoma?
Surgical resection can be done when there is no spread. Remember to balance risks v benefits. The patient has a pre-op assessment.
228
What is the treatment for metastatic colorectal adenocarcinoma?
Chemotherapy and palliative care.
229
Give 3 reasons why bowel cancer survival has increased over recent years.
1. Introduction of the bowel cancer screening programme. 2. Colonoscopic techniques. 3. Improvements in treatment options.
230
Give 5 risk factors for colorectal cancer.
1. Low fibre diet. 2. Diet high in red meat. 3. Alcohol. 4. Smoking. 5. A PMH of adenoma or ulcerative colitis. 6. A family history of colorectal cancer; FAP or HNPCC.
231
What can affect the clinical presentation of a colorectal cancer?
How close the cancer is to the rectum affects its clinical presentation.
232
Give 3 signs of rectal cancer.
1. PR bleeding. 2. Mucus. 3. Thin stools. 4. Tenesmus.
233
Give 2 signs of a left sided/sigmoid cancer.
1. Change of bowel habit e.g. diarrhoea, constipation. 2. PR bleeding.
234
Give 3 signs of a right sided cancer.
1. Anaemia. 2. Mass. 3. Diarrhoea that doesn't settle.
235
Describe the emergency presentation of a left sided colon cancer.
The LHS of the colon is narrow and so the patient is likely to present with signs of obstruction e.g. constipation; colicky abdominal pain; abdominal distension; vomiting.
236
Describe the emergency presentation of a right sided colon cancer.
The RHS of the colon is wide and so the patient is likely to present with signs of perforation.
237
What investigations might you do in someone who you suspect might have colorectal cancer?
Colonoscopy = gold standard! It permits biopsy and removal of small polyps. - Tumour markers are good for monitoring progress. - Faecal occult blood is used in screening but not diagnosis.
238
Give 5 non-infective causes of diarrhoea.
1. Neoplasm. 2. Inflammatory. 3. Irritable bowel. 4. Anatomical. 5. Chemical. 6. Hormonal. 7. Radiation.
239
Give 3 infective causes of dysentery.
1. Shigella. 2. Salmonella. 3. Campylobacter. 4. E.coli 0157.
240
Give 2 infective causes of non-bloody diarrhoea.
1. Rotavirus. 2. Norovirus.
241
Describe the chain of infection.
Reservoir -\> agent -\> transmission -\> host -\> person to person spread.
242
Give 3 ways in which infection can be transmitted.
1. Direct e.g. faeco-oral. 2. Indirect e.g. vectorborne (malaria). 3. Airborne e.g. respiratory route.
243
What is the treatment for vibrio cholerae infection?
HYDRATE e.g. ORS. What goes out must be replaced.
244
Describe the management of c.diff infection.
1. Control antibiotic use. 2. Infection control measures. 3. Isolate the case. 4. Case finding. 5. Test stool samples for toxin.
245
Give 4 groups at risk of diarrhoeal infection.
1. Food handlers. 2. Health care workers. 3. Children who attend nursery. 4. Persons of doubtful personal hygiene.
246
Give 3 causes of peptic ulcers.
1. Prolonged NSAID use -\> decreased mucin production. 2. H.pylori infection. 3. Hyper-acidity. 4. Delayed gastric emptying. 5. Blood group O
247
Give 3 symptoms of peptic ulcers.
1. Burning epigastric pain - VERY SPECIFIC, worse at night and when hungry 2. Nausea 3. Anorexia / weight loss
248
What investigations might you do in someone who you suspect to have peptic ulcers?
1. H.pylori test e.g. urease breath test and faecal antigen test. 2. Gastroscopy. 3. Barium meal.
249
Give 5 treatments for peptic ulcers.
1. Stop NSAIDs. 2. PPIs e.g. omeprazole. 3. H2 antagonists 4. Lifestyle changes 5. H.pylori eradication - IF POSITIVE
250
Give 2 potential complications of oesophago-gastroduodenoscopy (OGD).
1. Cardiopulmonary. 2. Small risk of bleeding or perforation.
251
Give 3 indications for OGD.
1. Dyspepsia. 2. Dysphagia. 3. Anaemia. 4. Suspected coeliac disease.
252
Give 3 indications for colonoscopy.
1. Altered bowel habit. 2. Diarrhoea +/- dysentery. 3. Anaemia.
253
Give 8/9 symptoms of GORD.
OESOPHAGEAL 1. Heart burn. 2. Acid reflux. 3. Odynophagia. 4. Belching 5. Water brash. EXTRA-OESOPHAGEAL 6. Nocturnal asthma 7. Chronic cough 8. Laryngitis 9. Sinusitis
254
Describe the pathophysiology of coeliac disease.
\> Gliadin is resistant to digestion by pepsin and chymotrypsin, thus remains in intestinal lumen \> Gliadin peptides pass through epithelium and are deaminated by TG2 -\> INCREASES IMMUNOGENICITY \> Peptides bind to APC which interact with CD4+ T cells in lamina proprietary via HLA class II DQ2 or DQ8 \> HLA class II molecules activate gluten-sensitive T cells \> T cells produce pro-inflammatory cytokines and initiate inflammatory response \> Response produces metaloproteinases which cause villous atrophy, crypt hyperplasia, and intraepithelial lymphocytes \> Proximal small bowel mucosa is most affected \> Mucosal damage means B12, folate, and iron cannot be absorbed -\> ANAEMIA
255
Describe the clinical presentation of Coeliac disease
1. Diarrhoea / steatorrhoea 2. Weight loss. 3. Irritable bowel. 4. Iron deficiency ANAEMIA. 5. Mouth ulcers. 6. Abnormal liver function. 7. Abdominal pain 8. Bloating 9. Nausea and vomiting 10. Angular stomatitis 11. Fatigue 12. Osteomalacia
256
What investigations might you do in someone who you suspect to have coeliac disease?
1. Serology - look for auto-antibodies - TTG and EMA. 2. Gastroscopy - duodenal biopsies.
257
What part of the bowel is commonly affected by Crohn's disease?
Can affect anywhere from the mouth to anus.
258
What part of the bowel is commonly affected by ulcerative colitis?
It only affects the rectum. It spreads proximally but only affects the colon.
259
Give 5 complications of Crohn's disease.
1. Malabsorption. 2. Fistula. 3. Obstruction. 4. Perforation. 5. Anal fissures. 6. Neoplasia. 7. Amyloidosis (rare).
260
Give 5 complications of ulcerative colitis.
1. Colon: blood loss and colorectal cancer. 2. Arthritis. 3. Iritis and episcleritis. 4. Fatty liver and primary sclerosing cholangitis. 5. Erythema nodosum.
261
Give an example of a functional bowel disorder.
IBS.
262
Describe the multi-factorial pathophysiology of IBS.
The following factors can all contribute to IBS: - Psychological morbidity e.g. trauma in early life. - Abnormal gut motility. - Genetics. - Altered gut signalling (visceral hypersensitivity).
263
Give 3 symptoms of IBS.
1. ABDOMINAL PAIN! 2. Pain is relieved on defecation. 3. Bloating. 4. Change in bowel habit. 5. Mucus. 6. Fatigue.
264
Give an example of a differential diagnosis for IBS.
1. Coeliac disease. 2. Lactose intolerance. 3. Bile acid malabsorption. 4. IBD. 5. Colorectal cancer.
265
What investigations might you do in someone who you suspect has IBS?
1. Bloods - FBC, U+E, LFT. 2. CRP. 3. Coeliac serology.
266
Describe the treatment for mild IBS.
Education, reassurance, dietary modification e.g. FODMAP.
267
Describe the treatment for moderate IBS.
Pharmacotherapy and psychological treatments: - Antispasmodics for pain. - Laxatives for constipation. - Anti-motility agents for diarrhoea. - CBT and hypnotherapy.
268
Describe the treatment for severe IBS.
MDT approach, referral to specialist pain treatment centres. - Tri-cyclic anti-depressants.
269
Why are all gastric ulcers re-scoped 6-8 weeks after treatment?
All peptic ulcers are re-scoped to ensure they've healed. If they haven't healed it could be a sign of malignancy.
270
What is the criteria for dyspepsia?
\>1 of the following: - Postprandial fullness. - Early satiation. - Epigastric pain/burning.
271
Give 5 causes of dyspepsia.
1. Excess acid. 2. Prolonged NSAIDS. 3. Large volume meals. 4. Obesity. 5. Smoking/alcohol. 6. Pregnancy.
272
Give 5 red flag symptoms that you might detect when taking a history from someone with dyspepsia.
1. Unexplained weight loss. 2. Anaemia. 3. Dysphagia. 4. Upper abdominal mass. 5. Persistent vomiting.
273
What investigations might you do in someone with dyspepsia?
1. Endoscopy. 2. Gastroscopy. 3. Barium swallow. 4. Capsule endoscopy.
274
What is the management for dyspepsia if the red flag criteria has been met?
1. Suspend NSAID use and review medication. 2. Endoscopy. 3. Refer malignancy to specialist.
275
What is the management for dyspepsia without red flag symptoms?
1. Review medication. 2. Lifestyle advice. 3. Full dose PPI for 1 month. 4. Test and treat h.pylori infection.
276
What kind of lifestyle advice might you give to someone with dyspepsia?
1. Lose weight. 2. Stop smoking. 3. Cut down alcohol. 4. Dietary modification.
277
Describe the treatment for GORD.
1. PPI. 2. Lifestyle modification. 3. Anti-reflux surgery.
278
Give a potential consequence of anterior ulcer haemorrhage.
Acute peritonitis.
279
Give a potential consequence of posterior ulcer haemorrhage.
Pancreatitis.
280
Name 5 things that can break down the mucin layer in the stomach and cause gastritis.
1. Not enough blood - mucosal ischaemia. 2. H.pylori. 3. Aspirin, NSAIDS. 4. Increased acid - stress. 5. Bile reflux - direct irritant. 6. Alcohol.
281
Describe the treatment for gastritis.
1. Reduced mucosal ischaemia. 2. PPI. 3. H2RA. 4. Enteric coated aspirin.
282
Give 5 broad causes of malabsorption.
1. Defective intra-luminal digestion. 2. Insufficient absorptive area. 3. Lack of digestive enzymes. 4. Defective epithelial transport. 5. Lymphatic obstruction.
283
Malabsorption: what can cause defective intra-luminal digestion?
1. Pancreatic insufficiency due to pancreatitis, CF. There is a lack of digestive enzymes. 2. Defective bile secretion due to biliary obstruction or ileal resection. 3. Bacterial overgrowth.
284
Why can pancreatitis cause malabsorption?
Pancreatitis results in pancreatic insufficiency and so a lack of pancreatic digestive enzymes. There is defective intra-luminal digestion which leads to malabsorption.
285
Malabsorption: what can cause insufficient absorptive area?
1. Coeliac disease. 2. Crohn's disease. 3. Extensive parasitisation. 4. Small intestine resection.
286
Malabsorption: give an example of when there is a lack of digestive enzymes.
Lactose intolerance - disaccharide enzyme deficiency.
287
Malabsorption: what can cause lymphatic obstruction?
1. Lymphoma. 2. TB.
288
Describe the distribution of inflammation seen in Crohn's disease.
Patchy, granulomatous, transmural inflammation (can affect just the mucosa or go through the bowel wall).
289
Describe the distribution of inflammation seen in ulcerative colitis.
Continuous inflammation affecting only the mucosa.
290
Histologically, what part of the bowel wall is affected in ulcerative colitis?
Just the mucosa.
291
Histologically, what part of the bowel wall is affected in crohn's disease?
Can affect just the mucosa or can go all the way through to the bowel wall -\> transmural inflammation.
292
What is the treatment for crohn's disease and ulcerative colitis?
Anti-inflammatories.
293
Name the break down product of gluten that can trigger coeliac disease.
Gliadin.
294
What part of the small intestine is mainly affected by coeliac disease?
Duodenum.
295
What disorders might be associated with coeliac disease?
Other autoimmune disorders: 1. T1 diabetes. 2. Thyroxoicosis. 3. Hypothyroidism. 4. Addisons disease. Osteoporosis is also commonly seen in people with coeliac disease.
296
What is the prevalence of coeliac disease?
1%.
297
What cells normally line the oesophagus?
Stratified squamous non-keratinising cells.
298
What is Barrett's oesophagus?
When squamous cells undergo metaplastic changes and become columnar cells.
299
What can cause Barrett's oesophagus?
1. GORD. 2. Obesity.
300
Give a potential consequence of Barrett's oesophagus.
Adenocarcinoma.
301
Describe how Barrett's oesophagus can lead to oesophageal adenocarcinoma.
1. GORD damages normal oesophageal squamous cells. 2. Glandular columnar epithelial cells replace squamous cells (metaplasia). 3. Continuing reflux leads to dysplastic oesophageal glandular epithelium. 4. Continuing reflux leads to neoplastic oesophageal glandular epithelium - adenocarcinoma.
302
Give 5 symptoms of oesophageal carcinoma.
1. Dysphagia. 2. Odynophagia (painful swallowing). People often present very late. 3. Vomiting. 4. Weight loss. 5. Anaemia. 6. GI bleed. 7. Reflux.
303
Give 3 causes of squamous cell carcinoma.
1. Smoking. 2. Alcohol. 3. Poor diet.
304
What can cause oesophageal adenocarcinoma?
Barrett's oesophagus.
305
Give 3 causes of gastric cancer.
1. Smoked foods. 2. Pickles. 3. H.pylori infection. 4. Pernicious anaemia.
306
Describe how gastric cancer can develop from normal gastric mucosa.
Smoked/pickled food diet leads to intestinal metaplasia of the normal gastric mucosa. Several genetic changes lead to dysplasia and then eventually intra-mucosal and invasive carcinoma.
307
Give 3 causes of oesophageal carcinoma.
1. GORD -\> Barrett's. 2. Smoking. 3. Alcohol.
308
What investigations might you do in someone who you suspect to have oesophageal carcinoma?
1. Barium swallow. 2. Endoscopy.
309
Describe the 2 treatment options for oesophageal cancer.
1. Medically fit and no metastases = operate. The oesophagus is replaced with stomach or sometimes the colon. The patient often has 2/3 rounds of chemo before surgery. 2. Medically unfit and metastases = palliative care. Stents can help with dysphagia.
310
Give 3 signs of gastric cancer.
1. Weight loss. 2. Anaemia. 3. Vomiting blood. 4. Melaena. 5. Dyspepsia.
311
A mutation in what gene can cause familial diffuse gastric cancer?
CDH1 - 80% chance of gastric cancer. Prophylactic gastrectomy is done in these patients.
312
What investigations might you do in someone who you suspect has gastric cancer?
1. Endoscopy. 2. CT. 3. Laparoscopy.
313
What is the advantage of doing a laparoscopy in someone with gastric cancer?
It can detect metastatic disease that may not be detected on ultrasound/endoscopy.
314
What is the treatment for proximal gastric cancers that have no spread?
3 cycles of chemo and then a full gastrectomy. Lymph node removal too.
315
What is the treatment for distal gastric cancers that have no spread?
3 cycles of chemo and then a partial gastrectomy if the tumour is causing stenosis or bleeding. Lymph node removal too.
316
What vitamin supplement will a patient need following gastrectomy?
They will be deficient in intrinsic factor and so will need vitamin B12 supplements to prevent pernicious anaemia.
317
Give 3 symptoms of spontaneous bacterial peritonitis.
1. Dull to percussion. 2. Temperature. 3. Abdominal pain.
318
What investigations might you do in someone who you suspect could have peritonitis?
1. Blood tests: raised WCC, platelets, CRP, amylase. Reduced blood count. 2. CXR: look for air under the diaphragm. 3. Abdominal x-ray: look for bowel obstruction. 4. CT: can show inflammation, ischaemia or cancer. 5. ECG: epigastric pain could be related to the heart. 6. B-HCG: a hormone secreted by pregnant ladies.
319
Give 5 potential complications of peritonitis.
1. Hypovolaemia. 2. Kidney failure. 3. Systemic sepsis. 4. Paralytic ileus. 5. Pulmonary atelectasis (lung collapse). 6. Portal pyaemia (pus in the portal vein).
320
Explain how paralytic ileus can lead to respiratory problems.
Peristaltic waves stop -\> dilation of bowel -\> distended abdomen therefore increased pressure -\> pushes on diaphragm -\> respiration affected.
321
What is the management for peritonitis?
1. ABC. 2. Treat the underlying cause! 3. Call a surgeon. 4. Set up post-management support.
322
What can cause exudative ascites?
Increased vascular permeability secondary to infection; inflammation (peritonitis) or malignancy.
323
What can cause transudative ascites?
Increased venous pressure due to cirrhosis, cardiac failure or hypoalbuminaemia.
324
Give 2 signs of ascites.
1. Flank swelling. 2. Dull to percuss and shifting dullness.
325
What investigations might you do in someone who you suspect has ascites?
1. Ultrasound. 2. Ascitic tap.
326
Describe the treatment for ascites.
1. Restrict sodium. 2. Diuretics. 3. Drainage.
327
Where in the colon do the majority of colon cancers occur?
In the descending/sigmoid colon and rectum.
328
Why do proximal colon cancers have a worse prognosis?
They have fewer signs and so people often present with them at a very advanced and late stage.
329
What 3 histological features are needed in order to make a diagnosis of coeliac disease?
1. Raised intraepithelial lymphocytes. 2. Crypt hyperplasia. 3. Villous atrophy.
330
What investigation is it important to do in someone with chronic liver disease and ascites? Explain why it is important.
It is important to do an ascitic tap so you can rule out spontaneous bacterial peritonitis as soon as possible.
331
What would be raised in the blood tests taken from someone with primary biliary cirrhosis?
1. Raised IgM. 2. Raised ALP. 3. Positive AMA.
332
What 4 features would you expect to see in the blood test results taken from someone who has overdosed on paracetamol.
1. Metabolic acidosis. 2. Prolonged pro-thrombin time (due to coagulability). 3. Raised creatinine (renal failure). 4. Raised ALT.
333
What 3 symptoms make up the triad of Wernicke's encephalopathy?
1. Ataxia. 2. Opthalmoplegia. 3. Confusion.
334
How can Wernicke's encephalopathy be reversed?
Give IV thiamine.
335
What histological stain can be used for haemochromatosis?
Perl's stain.
336
Name 4 fat soluble vitamins.
A, D, E and K.
337
What is the main difference between biliary colic and acute cholecystitis?
Acute cholecystitis has an inflammatory component!
338
What is the treatment for acute cholecystitis?
Laparoscopic cholecystectomy.
339
Why might someone with primary biliary cirrhosis experience itching as a symptom?
Because there is a build up of bilirubin.
340
Give 3 components of gallstones.
1. Cholesterol. 2. Bile pigment. 3. Phospholipid.
341
What investigations might you do in someone who you suspect has gallstones?
Ultrasound! ERCP.
342
Are most liver cancers primary or secondary?
Secondary - they have metastasised to the liver from the GI tract, breast and bronchus.
343
Where have most secondary liver cancers arisen from?
1. The Gi tract. 2. Breast. 3. Bronchus.
344
Describe the aetiology of HCC.
Most HCC is in patients with cirrhosis. This is often due to HBV/HCV and alcohol.
345
Give 5 symptoms of HCC.
1. Weight loss. 2. Anorexia. 3. Fever. 4. Malaise. 5. Ascites.
346
What investigations might you do on someone who you suspect has HCC?
1. Bloods: serum AFP may be raised. 2. US or CT to identify lesions. 3. MRI. 4. Biopsy if diagnostic doubt.
347
Describe the treatment for HCC.
1. Surgical resection of solitary tumours. 2. Liver transplant. 3. Percutaneous ablation.
348
How long after infection with hepatitis B virus is HBsAg present in the serum for?
HBsAg will be present in the serum from 6 weeks - 3 months after infection.
349
How long after infection with hepatitis B virus is anti-HBV core (IgM) present in the serum for?
Anti-HBV core (IgM) slowly rises from 6 weeks after infection and its serum level peaks at about 4 months.
350
Give 3 symptoms of haemochromatosis.
1. Hepatomegaly. 2. Cardiomegaly. 3. Diabetes mellitus. 4. Hyperpigmentation of skin. 5. Lethargy.
351
Name 3 diseases that lead to heamolytic anaemia and so a raised unconjugated bilirubin and pre-hepatic jaundice.
Causes of haemolytic anaemia: 1. Sickle cell disease. 2. Hereditary spherocytosis/elliptocytosis. 3. GP6D deficiency. 4. Hypersplenism.
352
Give 3 causes of liver failure.
1. Infection e.g. viral hepatitis B, C. 2. Induced e.g. alcohol, drug toxicity. 3. Inherited e.g. autoimmune.
353
Hepatic encephalopathy is a complication of liver failure. Describe the pathophysiological mechanism behind this.
The liver can't get rid of ammonia and so ammonia crosses the BBB -\> cerebral oedema.
354
Give 4 complications of liver failure.
1. Hepatic encephalopathy. 2. Abnormal bleeding. 3. Jaundice. 4. Ascites.
355
Describe the treatment for liver failure.
1. Nutrition. 2. Supplements. 3. Treat complications. 4. Liver transplant.
356
You do an ascitic in someone with ascites. The neutrophil count comes back as - Neutrophils \> 250/mm3. What is the likely cause of the raised neutrophils?
Spontaneous bacterial peritonitis.
357
Describe the treatment for spontaneous bacterial peritonitis.
Cefotaxime and metronidazole.
358
Give 5 symptoms of ruptured varices.
1. Haematemesis. 2. Melaena. 3. Abdominal pain. 4. Dysphagia. 5. Anaemia.
359
How would you know if an individual had been vaccinated against hepatitis B?
They would have anti-HBVs IgG in their serum.
360
What type of anaemia do you associate with alcoholic liver disease?
Macrocytic anaemia.
361
Name a protozoa that can cause amoebic liver abscess?
Entemoeba histolytica.
362
What are the symptoms of entemoeba histolytica?
- RUQ pain. - Bloody diarrhoea. - Fever and malaise. Often the patient has a history of foreign/rural travel.
363
What is the treatment for entemoeba histolytica?
Metronidazole.
364
What is the treatment for mild/moderate UC?
Mesalazine.
365
A 4-year-old girl presents with diarrhoea and is hypotensive. What is the physiological reason that fluid moves from the interstitium to the vascular compartment in this case?
Reduced hydrostatic pressure. Fluid will move from the interstitium into the plasma if there is an increase in osmotic pressure or a decrease in hydrostatic pressure. As this patient is hypotensive it is more likely to be the latter.
366
What drug would you give to someone that has overdosed on paracetamol?
IV N-Acetyl-Cysteine.
367
With which disease would you associate Reynold's pentad?
Ascending cholangitis.
368
Describe Reynold's pentad.
- Charcot's triad (fever, RUQ pain and jaundice). - + hypotension. - + altered mental state.
369
What is a potential consequence of h.pylori infection in a person with decreased gastric acid?
Gastric cancer.
370
What is a potential consequence of h.pylori infection in a person with increased gastric acid?
Duodenal ulcer.
371
What might pain radiating to the back be a sign of?
Pancreatitis or AAA.
372
What blood test might show that someone has alcoholic liver disease?
Serum GGT (gamma-glutamyl transferase) will be elevated.
373
What distinctive feature is often seen on biopsy in people suffering from alcoholic liver disease?
Mallory bodies.
374
What feature seen on liver biopsy is diagnostic of cirrhosis?
Nodular regeneration.
375
A man has his ascites drained and is advised to restrict his diet. Which non-hormonal substance will promote re-accumulation of the ascites?
Salt.
376
What is the treatment for Wilson's disease.
Lifetime treatment with penicillamine.
377
Name the 2 main pathophysiological factors that contribute to the formation of ascites.
1. High portal venous pressure. 2. Low serum albumin.
378
Give 2 indications for the need of immediate surgical intervention in someone with a small bowel obstruction.
1. Signs of perforation (peritonitis). 2. Signs of strangulation.
379
Why is morphine contraindicated in acute pancreatitis?
Morphine increases sphincter of Oddi pressure and so aggravates pancreatitis.
380
What two enzymes, if raised, suggest pancreatitis?
LDH and AST.
381
Where is folate absorbed?
In the jejunum.
382
Where is vitamin B12 absorbed?
In the terminal ileum.
383
Where is iron absorbed?
In the duodenum.
384
In someone with coeliac disease, what are they most likely to be deficient in - iron, folate, or B12?
Iron. Coeliac disease mainly affects the duodenum and iron is absorbed in the duodenum. Folate is absorbed in the jejunum and B12 in the terminal ileum.
385
Give 5 histological features of a malignant neoplasm.
1. High mitotic activity. 2. Rapid growth. 3. Border irregularity. 4. Necrosis. 5. Poor resemblance to normal tissues.
386
What lymph nodes can oesophageal carcinoma commonly metastasise to?
Para-oesophageal lymph nodes.
387
What hormone is responsible for the production of gastric acid?
Gastrin.
388
State two pathological changes that occur in the liver with continued consumption of excessive amounts of alcohol.
1. Fatty liver. 2. Alcoholic hepatitis. 3. Cirrhosis.
389
A patient’s oedema is caused solely by their liver disease. State one possible pathophysiological mechanism for their oedema.
Hypoalbuminaemia.
390
List 5 important questions a GP should ask when taking a history to establish a cause of diarrhoea.
1. Blood or mucus in the stools. 2. Family history of bowel problems? 3. Abdominal pain. 4. Recent foreign travel history. 5. Bloating. 6. Weight loss.
391
List two blood tests a GP might perform to help differentiate between the different causes of diarrhoea.
1. FBC. 2. ESR/CRP.
392
List two stool tests a GP might request to help differentiate between the different causes of diarrhoea.
1. Stool culture. 2. Faecal calprotectin.
393
State one histological feature that will be seen in ulcerative colitis.
1. Crypt abscess. 2. Increase in plasma cells in the lamina propria.
394
What investigations might you do in someone with inflammatory bowel disease?
1. Bloods - FBC, ESR, CRP. 2. Faecal calprotectin - shows inflammation but is not specific for IBD. 3. Flexible sigmoidoscopy. 4. Colonoscopy.
395
Name 3 drugs or classes of drugs that can cause acute pancreatitis.
1. NSAIDs. 2. Diuretics. 3. Steroids.
396
What 2 products does haem break down in to?
Haem -\> Fe2+ and biliverdin.
397
What enzyme converts biliverdin to unconjugated bilirubin?
Biliverdin reductase.
398
What is the function of glucuronosyltransferase?
It transfers glucuronic acid to unconjugated bilirubin to form conjugated bilirubin.
399
What protein does unconjugated bilirubin bind to and why?
Albumin. It isn't H2O soluble therefore it binds to albumin so it can travel in the blood to the liver.
400
What does conjugated bilirubin form?
Urobilinogen.
401
What is responsible for the conversion of conjugated bilirubin into urobilinogen?
Intestinal bacteria.
402
What can urobilinogen form?
1. It can go back to the liver via the enterohepatic system. 2. It can go to the kidneys forming urinary urobilin. 3. It can form stercobilin which is excreted in the faeces.
403
What disease could be caused by a non-functioning mutation in NOD2?
Crohn's.
404
What are the differential diagnoses for GORD?
- CAD - Biliary colic - Peptic ulcer disease - Malignancy
405
What are the causes of GORD?
- Lower oesophageal sphincter hypotension - Hiatus hernia - Loss of oesophageal peristaltic function - Abdominal obesity - Gastric acid hypersecretion - Slow gastric emptying - Overating - Smoking - Alcohol - Pregnancy - Indigestion (fat, chocolate, coffee, alcohol) - Drugs (antimuscarinic, calcium channel blockers, nitrates) - Systemic sclerosis
406
What is the pathophysiology for GORD?
There is much more transient lower oesophageal sphincter relaxations than usual, due to reduced muscle tone of LOS which allows gastric acid to flow back into oesophagus
407
When do clinical features of GORD appear?
When the anti-reflux mechanisms fail, allowing prolonged contact between acid and lower oesophageal mucosa Hiatus hernias can impair anti-reflux mechanisms
408
What exacerbates and relieves heartburn pain caused by GORD?
Exacerbated by hot drinks, alcohol, bending, stooping, and lying down Relieved by antacids
409
What alarm bell signs result in a patient with symptoms of GORD requiring further investigations?
- Weight loss - Haematemesis - Dysphagia
410
If a patient with symptoms of GORD also has alarm bell signs, what investigations must be done?
Endoscopy - assess oesophagitis and hiatal hernia Barium swallow
411
Why do you do an endoscopy in a patient with GORD symptoms?
- Symptoms \>4w - Alarm bell signs - Persistent vomiting - GI bleeding - Palpable mass - 55+ - Symptoms despite treatment
412
What will a barium swallow reveal in a patient with symptoms of GORD?
Whether the GORD is due to a hiatal hernia
413
What is confirmation of reflux which is identified on an endoscopy?
- Oesophagitis - Barrett's oesophagus
414
If an endoscopy doesn't reveal anything abnormal, how else can you investigate reflux?
Intraluminal pH monitoring over 24hrs
415
What are the 4 lifestyle changes necessary to treating GORD?
1. Weight loss 2. Smoking cessation 3. Small, regular meals 4. Avoid hot drinks, alcohol, citrus fruit, and eating \<3hrs before bed
416
What are the 4 pharmacological treatments for GORD?
1. Antacids (e.g. magnesium trisilicate mixture) 2. Alginates (e.g. gaviscon) 3. Proton pump inhibitor (e.g. lansoprazole) 4. H2 receptor antagonists (e.g. cimetidine)
417
What is the surgical treatment for GORD?
Nissen fundoplication - laparoscopically increases the resting LOS pressure Only use when unresponsive to therapy
418
How do NSAIDs cause peptic ulcers?
\> Cyclo-oxygenase-1 is needed for prostaglandin synthesis \> Prostaglandins triggers inflammation and stimulates mucous secretion \> NSAIDs inhibit cycle-oxygenase-1 \> Less mucous production \> Decreased mucosal defence
419
How does H.pylori lead to peptic ulcers?
\> H.pylori exclusively inhabits mucous layer of gastric epithelium \> Causes major destruction to mucin layer that protects mucosa \> Decrease in duodenal HCO3-, thus increasing acidity of stomach as there is less alkali to buffer acid \> H.pylori also secretes urease, splitting urea into CO2 and ammonia \> Ammonia + H+ = ammonium \> Ammonium is toxic to gastric mucosa, resulting in less mucous production \> Secreted proteases, phosphlipases, and vacuolating cytotoxin A can also attack gastric epithelium \> Also increases gastrin release from G cells, increasing acid released from parietal cells
420
How does ischaemia of gastric cells lead to peptic ulcers?
\> Produces less mucin \> Less protection from acid \> Acid damages mucosa
421
How can stress lead to peptic ulceration?
Stress can result in increased gastric acid production, damaging mucosal surface
422
What is a complication of a duodenal ulcer?
- Ulcer can get deeper and deeper until it hits the gastroduodenal artery \> MASSIVE HAEMORRHAGE - Peritonitis as acid enters peritoneum - air under diaphragm on erect X-ray - Acute pancreatitis if ulcer reaches pancreas
423
Describe non-invasive H.pylori testing
C-urea breath test - quick and reliable test for H.pylori - measure CO2 in breath after ingestion of C-urea - used to monitor infection after eradication - highly sensitive and specific Stool antigen test - immunoassay using monoclonal antibodies for detection of H.pylori - monitors efficacy of eradication
424
Describe invasive H.pylori testing
Endoscopy - histology for direct visualisation - biopsy urease test
425
What are the lifestyle changes advised for treating peptic ulcer disease?
- Reduce stress - Avoid irritating food - Smoking cessation - Stop NSAIDS
426
How do you eradicate H.pylori?
Triple therapy - PPI for acid suppression (e.g. lansoprazole) - Plus two of; \> metronidazole \> clarithromycin (high resistance) \> amoxicillin (low resistance) \> tetracycline (low resistance) \> bismuth
