Gastroenterology

Question 1

Excluding the hepatitis A-E viruses, what other viruses may commonly be associated with hepatitis?

Answer 1

EBV
CMV
Influenza
Measles

Question 2

Compare Hep A-E.
- Transmission
- Chronic Sequelae
- Infectious Period
- Person-to-Person Spread
- Genetic Material

Answer 2

RNA viruses can usually be cured, DNA ones not so much because they integrate with host DNA.

So Hep C is more curable than Hep B.

Question 3

Acute or recent Hep A virus infections are detected using what test?

Answer 3

Test the IgM anti-HAV titres.
IgM is elevated in acute / recent infections.

Raised ALT can also indicate acute damage during hepatitis, which is useful in Hep A which is usually a short lived disease, however, is conditions like Hep B or C which can be chronic, you make have raised ALT well beyond an initial acute rise.

IgG will slowly become elevated but will stay elevated long term so it cannot distinguish easily between acute / chronic / past infections.

Question 4

What are the treatment options for Hep B infections?

Answer 4

Pegylated interferons
Oral antivirals
- Lamivudine
- Adefovir
- Entecavir
- Tenofovir

Hepatitis B (HBV) infection can be treated using different antiviral strategies, including pegylated interferons and several types of oral antivirals. Each type of treatment works through unique mechanisms to combat the virus, manage symptoms, and slow disease progression. Here’s a detailed overview:

1. Pegylated Interferons
   Mechanism of Action:
   Immune Modulation: Interferons are naturally occurring proteins that play a crucial role in the body’s immune response to viral infections. Pegylated interferons (such as Peginterferon alfa-2a and Peginterferon alfa-2b) are a form of interferon that has been chemically modified by the addition of a polyethylene glycol (PEG) molecule. This modification increases the half-life of the interferon in the bloodstream, allowing for less frequent dosing (usually once a week) and providing a more sustained antiviral effect.
   Antiviral Effects: They work by enhancing the immune system’s ability to fight the virus, including increasing the activity of natural killer cells and cytotoxic T cells against infected liver cells.
   Inhibition of Viral Replication: Interferons also inhibit the replication of the virus within liver cells by interfering with viral RNA and protein synthesis.

Clinical Use:
Pegylated interferons are used for a finite duration (usually 48 weeks), and can lead to a sustained virological response (SVR), where the virus remains undetectable in the blood long after treatment has finished. They can also result in the loss of the hepatitis B e antigen (HBeAg) and potentially the hepatitis B surface antigen (HBsAg), marking significant disease remission.

2. Oral Antivirals
   Oral antivirals are key in managing chronic hepatitis B by directly inhibiting viral replication. Here’s how each one works:

Lamivudine (3TC):
Mechanism: Lamivudine is a nucleoside analog that inhibits the reverse transcriptase enzyme of HBV, which is crucial for the virus’s RNA to DNA transcription process. By incorporating itself into the viral DNA, lamivudine causes premature chain termination.
Resistance: It has a higher rate of resistance development compared to newer agents, limiting its long-term effectiveness.

Adefovir:
Mechanism: Adefovir dipivoxil is another nucleotide analog reverse transcriptase inhibitor. It works similarly to lamivudine but can be used in patients who have developed resistance to lamivudine.
Dosing and Toxicity: Lower doses are used for HBV than for HIV to reduce nephrotoxicity, which is a significant side effect at higher doses.

Entecavir:
Mechanism: Entecavir is a more potent nucleoside analog than lamivudine and is effective against both wild-type and lamivudine-resistant HBV. It inhibits all three functions of the viral polymerase: base priming, reverse transcription of the negative strand from the pregenomic messenger RNA, and synthesis of the positive strand of HBV DNA.
Effectiveness: It is highly effective in reducing viral load and improving liver histology with a lower resistance profile than lamivudine.

Tenofovir:
Mechanism: Tenofovir is a nucleotide analog reverse transcriptase inhibitor. It is one of the most potent and commonly prescribed antivirals for HBV, effective in long-term suppression of HBV replication.
Advantages: It has a high barrier to resistance and is recommended for both treatment-naïve patients and those with resistance to other antivirals. It also is effective in improving liver histology and preventing progression to cirrhosis.

Summary
Pegylated Interferons: Good for finite treatment duration, can clear the infection in a subset of patients, improves immune response against HBV.
Oral Antivirals: Effective in long-term suppression of HBV, prevent liver damage from chronic hepatitis, and have a low barrier to resistance (especially newer agents like entecavir and tenofovir).

These treatments are chosen based on the patient’s HBV DNA levels, liver enzyme levels, liver damage extent, and whether they are at risk for developing liver cancer. Treatment decisions also take into consideration the patient’s desire to achieve viral clearance versus managing the infection as a chronic condition.

Question 5

What are the targets for direct acting antivirals?

Answer 5

Direct-acting antivirals (DAAs) are medications that target specific steps in the viral life cycle of viruses, particularly those of hepatitis C (HCV) and, more recently, other viruses such as HIV. These drugs act directly on viral enzymes or proteins, inhibiting their function and preventing the virus from replicating and infecting new cells. Here’s a breakdown of the primary targets for DAAs:

1. NS3/4A Protease Inhibitors
   Target: These drugs inhibit the NS3/4A protease enzyme that HCV uses to cleave and process its polyprotein into mature protein components necessary for viral replication.
   Examples:
   Boceprevir
   Simeprevir
   Paritaprevir
   Grazoprevir
   This class of drugs prevents the maturation of viral proteins, effectively stopping the virus from assembling and releasing mature viral particles.
2. NS5A Inhibitors
   Target: NS5A is a multifunctional protein essential for HCV replication and assembly. Inhibiting NS5A disrupts both the replication of the viral genome and the assembly of the virus.
   Examples:
   Ledipasvir
   Daclatasvir
   Ombitasvir
   Elbasvir
   NS5A inhibitors are particularly effective because they target a protein involved in multiple steps of the viral life cycle, thus offering a potent blockade against viral proliferation.
3. NS5B Polymerase Inhibitors
   Target: These drugs inhibit NS5B, the RNA-dependent RNA polymerase that HCV uses to replicate its RNA genome. There are two main types: nucleoside/nucleotide analogues and non-nucleoside inhibitors.
   Nucleoside/Nucleotide Analogues mimic the natural substrates of the polymerase and get incorporated into the viral RNA, causing chain termination.
   Non-Nucleoside Inhibitors bind to the polymerase at sites other than the active site, altering its conformation and function.
   Examples:
   Sofosbuvir (nucleotide analogue)
   Dasabuvir (non-nucleoside)
4. Integrase Strand Transfer Inhibitors (INSTIs) for HIV
   Target: HIV integrase enzyme, which is required for the viral DNA to integrate into the host DNA, a critical step in the HIV life cycle.
   Examples:
   Raltegravir
   Elvitegravir
   Dolutegravir
   These drugs prevent HIV from incorporating its genetic material into the host’s genome, effectively stopping the virus from replicating within the host cells.
5. Entry Inhibitors
   Target: These drugs block the virus from entering the host cells by interfering with the virus’s ability to bind to or fuse with the host cell membrane.
   Examples:
   Maraviroc (blocks CCR5 co-receptor for HIV)
   Enfuvirtide (inhibits HIV fusion with the host cell)
6. Protease Inhibitors for HIV
   Target: HIV-1 protease, an enzyme used by the virus to cleave newly synthesized polyproteins into functional viral proteins.
   Examples:
   Saquinavir
   Lopinavir
   Ritonavir
   By inhibiting the protease, these drugs prevent the maturation of viral proteins, leading to the production of non-infectious viral particles.

Summary
Direct-acting antivirals specifically target viral components, making them highly effective at inhibiting viral replication with minimal effects on host cells. This specificity not only increases the efficacy of the drugs but also generally results in fewer side effects compared to older treatments that non-specifically targeted rapidly dividing cells. DAAs have revolutionized the treatment of chronic viral infections like HCV and HIV, offering the possibility of cure and highly effective control of the infection, respectively.

Question 6

What is the difference between a Hepatitis D superinfection and an acute infection?

Answer 6

Hep D superinfection occurs when a patient who already has hepatitis B is infected with hepatitis D.

An acute infections occurs when a naive patient is exposed to both HBV and HDV at the same time.

Question 7

What are the different types of lesions in the pancreas?

Answer 7

Question 8

What imaging is best for assessing the pancreas?

Answer 8

A CT can provide an initial idea of whether a lesion is solid or cystic, but MRI/US is necessary for more specific diagnosis of a lesion.

If CT is used, get 3 phase, fine cuts.

MRCP (Good for differentiating cystic vs solid)

Endoscopic US is the most accurate test. Helps identify lesions for resection.

Look for a double duct sign which is a dilation of both bile duct and pancreatic duct, usually indicating a cancer in the head of the pancreas.

Question 9

What lab tests are useful for assessing the pancreas?

Answer 9

LFTs (looking for biliary obstruction)
EUC, BGL, Amylase, Lipase

Tumour markers
- Ca 19.9, CEA (adenocarcinoma), Chromogranin A (neuroendocrine)
- IgG4 - good for assessing likelihood of autoimmune pancreatitis.

Question 10

What types of cystic pancreatic lesions should be resected?

Which ones should be drained?

Which ones observed?

Answer 10

Resected
- Main duct IPMN (Intraductal papillary mucinous neoplasm)
- Large, symptomatic or morphologically concerning side branch IPMN.
- Mucinous cystic neoplasms > 3cm
- Cystic neuro-endocrine tumours
- Solid pseudopapillary neoplasms

Drain
- Large/ symptomatic pseudocysts

Observe
- Small pseudocysts
- Small MCN (mucinous cystic neoplasm)
- Small side branch IPMN
- Serous Cystadenomata

Question 11

MEN1 (Multiple endocrine neoplasia’s type 1) is associated with pancreatic neuroendocrine tumours true or false?

Answer 11

True

Question 12

If you were to collect fluid from a pancreatic cyst and it showed a very high amylase, what type of cyst is most likely? What is a reasonable differential?

If mucin is detected, what lesions may be present?

If CEA / Ca 19.9 are elevated, what cystic lesions are more likely?

Answer 12

Very high amylase - think pseudocyst. The less likely differential is IPMN.

If mucin is present it is either IPMN or Mucinous cystic.

If CEA / Ca 19.9 are elevated it is more likely mucinous neoplasms.

Question 13

A pseudocyst above … cm and > …. weeks after acute pancreatitis is unlikely to resorb spontaneously.

Answer 13

> 5cm, or >6 weeks.

Question 14

What is the management of symptomatic pseudocysts?

Answer 14

Endoscopic drainage.
- Endoscopic cyst-gastrostomy
- Endoscopic pancreatic duct stenting

Surgery can be considered if endoscopic management is insufficient.
- Surgical cyst gastrostomy
- Surgical cyst-Roux en Y-jejunostomy

Question 15

Why is a pseudocyst called a pseudocyst?

Answer 15

Both cysts and pseudocysts are encapsulated fluid filled structures.

True cysts have an epithelial lining.

Pseudocysts have a lining made of scar tissue and granulation tissue.

Question 16

Do IPMS have malignant potential?

Answer 16

Yes

Question 17

If there is a main duct IPMN with a diameter of >10mm what is the minimum % likelihood of cancer?

Answer 17

50% chance of cancer minimum.

5-10 mm is concerning but does not necessarily require surgery.

Question 18

What is the general surgical approach to IPMN?

Answer 18

Resect all involved pancreatic tissue, or perform a total pancreatectomy.

Question 19

An ERCP of an IPMN may reveal what?

Answer 19

Patulous ampulla with mucous flow

Question 20

You find multiple small cysts towards the head of the pancreas with mucous flow, what is the likely diagnosis?

Answer 20

Side branch IPMN.
Side branch rather than main due to the number of small cysts.

Question 21

The risk of cancer is higher in main branch or side branch IPMN?

Answer 21

Main branch

Question 22

The international guidelines recommend resection of side branch IPMNs when?

Answer 22

When 1 or more worrying features are present.
- Size >3cm (worrisome but not absolute criteria)
- Symptomatic (usually pain or pancreatitis)
- Mural nodule (esp. with enhancement)
- Concerning features on EUS and aspiration (High grade dysplasia)

The issue is that side branch IPMN occurs in the elderly and usually requires a pancreaticoduodenectomy for a condition with a modest malignant potential.

Question 23

What is the most common presentation on CT imaging for a Mucinous Cystic Neoplasm?

Are they more common in men or women?

What is the cell type commonly identified on histology of these lesions?

What fraction have malignant potential?

Answer 23

Usually a solitary cystic lesion in the tail of the pancreas, with possibly a few septations and a solid component. Sometimes calcifications.

More common in women (almost exclusively in women)

The cell type see is ovarian type stroma with columnar mucosal lining.

1/3 harbour malignant potential

Resect them all. Recurrence is rare with complete resection.

Question 24

What pancreatic lesion is associated with Von-Hippel-Lindau Syndrome?

Answer 24

Serous Cystic Neoplasm (Serous cystadenoma)
These are usually seen in older women, they tend to grow slowly but can grow very large.

Morphologically they present with numerous cysts surrounding a spongey central scar.

They are rarely malignant or symptomatic. So resect large or symptomatic ones, but watch the rest.

Question 25

You complete imaging on a young 20 year old woman, and decide to take a biopsy of a lesion you identify in the pancreas.

The lesion has epithelial cells forming solid and pseudopapillary structures with haemorrhagic and necrotic cystic areas.

What is the likely diagnosis?

Answer 25

This is likely a solid pseudopapillary neoplasm (Solid and cystic neoplasm, Frantz tumour)

Low risk. Can grow anywhere. Low grade malignancy.

Question 26

Which IPMNs should be resected?

Answer 26

Main duct IPMN or large / symptomatic side branch IPMN.

Small side branch IPMN can be watched.

Question 27

In general should solid/cystic pseudopapillary lesions be resected or watched?

Answer 27

Resected

Question 28

What is the most useful investigation for pancreatic lesions?

Answer 28

FNA + EUS

Question 29

Are ductal adenocarcinomas of the pancreas solid or cystic?

Answer 29

Solid.
They are aggressive tumours with poor outcomes.
Associated with smoking, drinking, chronic pancreatitis, MEN1 syndrome.

Most uncurable with max 20% being operable, with only 25% of those surviving 5 years.

Resectable cases often present with painless jaundice. Those that occlude bile drainage early (those growing at head of pancrease), they can be identified quicker.
Ones that grow at tail tend to cause back pain.

There are many differentials like gallstones, cholangiocarcinomas, other cancer.

Question 30

The Ca 19.9 tumour marker can be elevated by pancreatic cancers and what by what common (more) benign cause?

Answer 30

Obstructive jaundice will also raise it.

Question 31

When imaging Pancreatic Neuroendocrine tumours (e.g. insulinomas) what specific type of scan can be done?

Hint: it was previously an octreotide scan

Answer 31

It is the DOTATATE PET scan

Question 32

A neuroendocrine tumour is identified and is 1.5cm. It is non functions (i.e. does not produce hormones affecting the body). Should it be resected?

Answer 32

No, not necessarily. It is <2cm.
If it was bigger, or was functional then resect.

Palliate patients if needed with long acting octreotide analogues.

Question 33

What is the mortality and morbidity rate of a whipple?

Answer 33

Mortality = 3-6%
Morbidity = 20%
- Gastroparesis
- Leak
- Diabetes
- Bleeding
- Dumping syndrome
- Diarrhoea
- Vit 12 deficiency due to loss of intrinsic factor producing cells.

Question 34

Following a whipple surgery, radiotherapy and chemotherapy are used. True or false?

Answer 34

False, the evidence suggests that chemotherapy is better.

Radiotherapy is only added when a case involves a very close margin where there is no sign of disease after a period of chemotherapy.

Question 35

What criteria are required to diagnose acute pancreatitis?

Answer 35

You need 2 out of the following 3.
- Clinical (upper abdominal pain)
- Laboratory (serum amylase or lipase > 3x upper limit of normal)
- And / or imaging (CT, MRI, ultrasound) criteria

Question 36

What are the main causes of pancreatitis, and what are the two most common?

Answer 36

I GET SMASHED

Gallstones and alcohol most common

Idiopathic
Gallstones
Ethanol
Trauma
Steroids
Mumps
Autoimmune
Stings / scorpions
Hypertriglyceridemia / Hypercalcaemia
ERCP
Drugs

Question 37

What is the pathophysiological explanation for acute pancreatitis, irrespective of aetiology?

Answer 37

The critical features is the premature intracellular activation of trypsinogen.

This activation is described in the Steer theory of co-localisation:
The secretion of zymogen granules is blocked due to microtubular dysfunction. The granules accumulate and fuse (co-localise) with lysosomes (acid hydrolases). This results in the intracellular activation of ZG leading the activation of trypsinogen and the eventual damage of the pancreatic cells and surrounding tissue.

The second stage following acinar cell damage is activation of inflammatory cells (e.g. neutrophils, macrophages/monocytes, T cells, and endothelial cells).
This leads to SIRS (systemic inflammatory response syndrome), and eventually can progress to MODS (Multiple organ dysfunction syndrome) and or sepsis.

Question 38

SIRS present at admission is advised to predict severe acute pancreatitis, and persistent SIRS at 48 hours.
What other test indicates a poor prognosis (pancreatic necrosis) for pancreatitis?

Answer 38

A CRP of 150mg/L or more at 48 hours.

Question 39

Is CT required to diagnose pancreatitis?

Answer 39

No. US can be used earlier and is often adequate if imaging is needed.
Otherwise only use a CT if the diagnosis is uncertain, to confirm the severity if other markers indicate severe pancreatitis, or if there is failure to respond to conservative treatment.

Optimal timing for an initial CT is 72-96 hours after onset of symptoms anyway.

Answer 40

Management of acute pancreatitis primarily focuses on supportive care to manage symptoms and complications. The approach can vary depending on the severity of the condition—mild acute pancreatitis often requires less intensive treatment compared to severe cases, which may necessitate more aggressive intervention. Here’s a detailed overview of the standard management strategies:

Initial Management and Assessment

Initial Assessment:
Clinical Evaluation: Assess the severity of symptoms and signs, including abdominal pain, nausea, vomiting, fever, and tachycardia.
Laboratory Tests: Include serum amylase and lipase, liver enzymes, triglycerides, glucose, and a complete blood count.
Imaging: An abdominal ultrasound is often performed to assess for gallstones, one of the common causes of acute pancreatitis. CT scan may be used for a more detailed assessment or if the diagnosis is uncertain.

Severity Assessment:
The severity of acute pancreatitis is typically assessed using criteria such as the Ranson criteria, BISAP score, or APACHE II to predict the prognosis and guide management. These assessments help identify patients at risk of severe complications who may require more intensive care.
Supportive Care

Fluid Resuscitation:
Hydration: Aggressive intravenous hydration, typically with lactated Ringer’s solution, is crucial, especially in the first 24-48 hours. The goal is to counteract hypovolemia caused by fluid shifts and systemic inflammation.
Monitoring: Careful monitoring of fluid status, urine output, and hemodynamic parameters is necessary to avoid complications from both under-resuscitation and fluid overload.
5-10ml/kg/hr is good. Continue until.
- Make sure urine output is >0.5 ml/kg/hr
- You can also assess the haematocrit (35-44%, and the HR <120 BPM)

Pain Management:
Analgesia: Pain control is a cornerstone of acute pancreatitis management. Non-opioid analgesics are first-line, but opioids may be needed for severe pain. Intravenous administration is often required due to vomiting and abdominal pain.

Nutritional Support:
Oral Intake: Initially, patients are often kept NPO (nothing by mouth) to rest the pancreas and reduce pancreatic enzyme stimulation. This approach has become more conservative, with earlier reintroduction of oral feeding in mild cases as tolerated.
Enteral Nutrition: Recommended if unable to eat within 72 hours, especially in severe pancreatitis. Nasogastric or nasojejunal feedings can be started, as enteral feeding is associated with lower complication rates compared to parenteral nutrition.

Management of Complications:
Necrotic Tissue: Antibiotics are not recommended routinely but may be used in cases of infected pancreatic necrosis.
Organ Failure: Monitor and support organ systems as needed, including respiratory, cardiovascular, and renal support.
Infections: High vigilance for signs of infection, with appropriate use of antibiotics for confirmed infections based on culture results.

Monitoring and Prognosis
Regular Assessments: Ongoing assessment of abdominal pain, fluid status, and general well-being.
Re-evaluation: Repeat imaging (CT scan) if the condition worsens or fails to improve, to check for complications like necrosis or abscess.

Long-Term Management
Address Underlying Causes: Treat underlying causes such as gallstones (e.g., cholecystectomy after recovery from pancreatitis if gallstones are the cause) or alcohol use.
Lifestyle Modifications: Dietary changes, alcohol abstinence, and smoking cessation to prevent recurrence.

Conclusion
Acute pancreatitis requires a coordinated approach that includes intensive supportive care, careful monitoring, and treatment of underlying causes and complications. The severity of the disease often dictates the level of care, with mild cases possibly managed with simple supportive care and more severe cases requiring intensive care and potentially surgical interventions.

Question 41

Does pancreatitis always require antibiotics?

Answer 41

No, prophylactic antibiotics not needed.
Only use if there is a clear indication of infection.

Question 42

If a patient presents with pancreatitis, when is an urgent ERCP indicated?

Answer 42

An URGENT (<24hrs) ERCP is indicated in patients with biliary pancreatitis with acute cholangitis.

MRCP and EUS may prevent some ERCPs that would otherwise be performed for suspected common bile duct.

Question 43

A patient has a sterile necrotizing pancreatitis. No mass effect, or persistent symptoms. Does it need intervention?

Answer 43

No.

If there is mass effect, persistent symptoms, or full transection of the pancreatic duct in the presence of pancreatic necrosis. Then you can intervene.

In sick patients, usually delay in patients for at least 4 weeks to allow for the collection to become walled off. Then use radiological assistance to place a drain via the left retro-peritoneum.

Question 44

What are the two main inflammatory bowel diseases?

Answer 44

Crohn’s disease
Ulcerative colitis

Question 45

Describe the pathophysiology of Crohn’s disease and Ulcerative Colitis.

Answer 45

Crohn’s Disease:
Involvement: Can affect any part of the gastrointestinal tract from the mouth to the anus, with a predilection for the terminal ileum and colon. The inflammation is typically transmural, affecting the entire thickness of the bowel wall.
Granulomas: Characteristic feature, though not present in all cases.
Etiology: Thought to result from an inappropriate immune response to intestinal microbiota in genetically susceptible individuals, exacerbated by environmental factors.

Ulcerative Colitis:
Involvement: Limited to the colon and rectum, with continuous lesions starting from the rectum and extending proximally; inflammation is confined to the mucosal layer.
Etiology: As with CD, involves an abnormal immune response but is more confined to the colonic mucosa and submucosa.

Question 46

What genes are associated with Crohn’s disease and Ulcerative Colitis?

Answer 46

Crohn’s Disease:
NOD2 (Nucleotide-binding oligomerization domain-containing protein 2):
This was the first gene associated with increased susceptibility to Crohn’s disease. Variations in NOD2, located on chromosome 16, affect the bacterial recognition capabilities of immune cells, potentially leading to an inappropriate immune response.

ATG16L1 (Autophagy-related 16-like 1):
Mutations in this gene are involved in the autophagy pathway, which helps cells remove damaged organelles and pathogens. Impaired autophagy can lead to abnormal inflammatory responses.

IL23R (Interleukin 23 receptor):
Variants in the IL23R gene, which encodes a subunit of the IL-23 receptor, can influence the development of Crohn’s disease by affecting Th17 cell differentiation and inflammatory responses.

Ulcerative Colitis:
HLA (Human Leukocyte Antigen):
Certain HLA alleles are associated with an increased risk of ulcerative colitis. These genes play critical roles in immune system regulation and antigen presentation.

SMAD3 (SMAD family member 3):
This gene is involved in TGF-beta signalling, which is important for maintaining immune homeostasis and controlling inflammation.

PTPN22 (Protein tyrosine phosphatase, non-receptor type 22):
PTPN22 influences T cell receptor signalling, with certain variants potentially increasing the risk of UC by affecting immune regulation.

Common to Both Crohn’s and Ulcerative Colitis:
TNFSF15 (Tumour necrosis factor ligand superfamily member 15):
Also known as TL1A, this gene is involved in inflammatory signalling pathways and has been linked to both Crohn’s disease and ulcerative colitis.

IL10 (Interleukin 10):
IL10 is a crucial anti-inflammatory cytokine. Mutations that reduce IL-10 expression or function can lead to an unchecked inflammatory response, contributing to IBD.

IL12B and IL23R:
These genes encode components of the interleukin-12 and interleukin-23 pathways, which are critical in regulating the immune system’s inflammatory response. Variants can affect susceptibility to both forms of IBD.

Genetic Testing and Clinical Relevance
While these genes contribute to the risk of developing IBD, the presence of a risk allele in any of these genes is neither necessary nor sufficient alone to cause the disease. IBD is a polygenic disorder, meaning that multiple genetic factors combined with environmental triggers lead to the development of the disease.

Question 47

What are the clinical signs and symptoms of Crohn’s disease and Ulcerative colitis?

Answer 47

Clinical Signs and Symptoms
Crohn’s Disease:
Symptoms: Abdominal pain (often in the right lower quadrant), diarrhoea (which may be bloody), weight loss, fatigue, and fever. Symptoms can vary widely depending on the affected portion of the GI tract.
Complications: Strictures, fistulas, abscesses, malnutrition.

Ulcerative Colitis:
Symptoms: Bloody diarrhoea, abdominal pain and cramping, urgency to defecate, rectal pain, rectal bleeding, and tenesmus.
Complications: Toxic megacolon, increased risk of colorectal cancer, primary sclerosing cholangitis.

Question 48

What diagnostic tests can be done to assess for inflammatory bowel diseases?

Answer 48

Diagnostic Tests

Endoscopic Evaluation:
Crohn’s Disease: Colonoscopy with ileoscopy is standard; allows for visualization of patchy inflammation, skip lesions, and deeper ulcers.
Ulcerative Colitis: Colonoscopy is also used; shows continuous mucosal inflammation starting from the rectum.

Imaging:
Crohn’s Disease: MRI or CT enterography (MRE / CTE) to evaluate the small intestine and detect complications.
Ulcerative Colitis: Less frequently requires imaging, but may use them to assess severity or complications.
Imaging particularly used if patients have weight loss or other symptoms concerning of possible cancer.
Note: CTE is better for IBD than normal CT.

Laboratory Tests:
Both conditions: Complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), faecal calprotectin or lactoferrin (markers of inflammation).

Iron stores, Stool MCS + multiplex PCR +/- OCP (Ova, cysts, parasytes). LFTs, PT/APTT (patients with significant bleeding),
Nutritional workup can be done if patient has had this untreated for a long time (Ca/Mg, Phos, B12, Folate, Vit D)

Question 49

What histological features may be identified if you assess a piece of biopsied tissue from a patient with Crohn’s disease or Ulcerative Colitis?

Answer 49

Histology
Crohn’s Disease:
Histological Features: Transmural inflammation, granulomas (non-caseating), lymphoid aggregates, and fibrosis. Goblet cell depletion may occur in affected areas.

Ulcerative Colitis:
Histological Features: Mucosal inflammation, crypt abscesses, and ulceration. Goblet cell depletion and architectural distortion of crypts are typical.

Question 50

What is the general management of Inflammatory bowel disease?

Answer 50

Pharmacological Treatment: Includes aminosalicylates, corticosteroids, immunomodulators (e.g., thiopurines), and biologic therapies (e.g., TNF inhibitors, integrin inhibitors).

Surgical Treatment: May be necessary for complications or refractory disease. More common in Crohn’s disease (due to strictures, fistulae) but also significant in UC for curative intent (e.g., proctocolectomy).

Question 51

What are the common extra-intestinal manifestations of inflammatory bowel disease?

Answer 51

Joints
- 1) Oligoarticular large joint arthritis that parallels disease activity
- 2) Symmetrical polyarticular small joint arthritis that is independent of disease activity.
- 3) Axial spondyloarthropathy (1/4 patients)

Eyes
- Iritis / episcleritis / scleritis

Skin
- Pyoderma gangrenosum, erythema nodosum

Liver
- PSC, drug effects

Question 52

Antibiotics are ineffective in the management of IBDs, except for a small number of cases where they may be used short term,

What are the indications for short term used of antibiotics in IBD?

Answer 52

Pouchitis
Small intestinal bacterial overgrowth
Bacterial infective colitis
Perianal disease / abscess

Question 53

Which of these treatments is effective for IBD?
1. Long term opioids
2. Anti MAP therapy
3. Faecal transplant
4. Azathioprine
5. Diet

Answer 53

Only azathioprine is the only confirmed effective treatment from the options listed.

Faecal transplant - mixed results

Long term steroids do not work and they have many side effects that would make it worse.

Anti-MAP has not been shown to help cure Crohn’s.
Mycobacterium avium paratuberculosis (MAP) is an obligate intracellular organism that has frequently been associated with Crohn’s disease (CD).

Diet does not seem to change the course of the disease, but may help with symptoms as many patients also have irritable bowel syndrome.

Question 54

Which vaccines should not be given to patients on immune modulators or steroids?

Answer 54

Live attenuated vaccines.

Question 54

What drugs are used in the treatment of IBD?

Answer 54

1. 5-ASA Drugs (5-Aminosalicylic Acid)
   Examples: Mesalamine, Sulfasalazine, Olsalazine, Balsalazide
   Mechanism of Action:
   Anti-inflammatory Properties: These drugs work at the level of the intestinal mucosa. They inhibit the production of prostaglandins and leukotrienes by blocking the activity of cyclooxygenase and lipoxygenase, enzymes involved in inflammation.
   Local Effect: They are delivered directly to the intestine, where they exert their effects topically rather than systemically, which reduces side effects.
   Clinical Use:
   Primarily used in UC for inducing and maintaining remission. Less effective in Crohn’s disease, especially for disease located in the small intestine.
   Side effects: N/V, headache, folate malabsorption, risk for haemolysis, agranulocytosis, hepatitis, pancreatitis, immotile sperm.
   Monitor FBC/EUC/LFTs - Fortnightly 1 month, then once every 6 months.
2. Corticosteroids
   Examples: Prednisone, Hydrocortisone, Budesonide
   Mechanism of Action:
   Broad Anti-inflammatory Action: Steroids inhibit multiple inflammatory pathways by inducing the synthesis of anti-inflammatory proteins and suppressing the expression of pro-inflammatory genes.
   Immune Suppression: They reduce the activity of the immune system broadly, decreasing the production of various cytokines and immune cells involved in the inflammatory process.
   Clinical Use:
   Effective for inducing remission in both UC and CD during flare-ups. However, due to significant side effects, they are not recommended for long-term use.
3. Immunomodulators
   Examples: Azathioprine, 6-Mercaptopurine, Methotrexate, Cyclosporine
   Mechanism of Action:
   Suppression of Immune Cell Proliferation: Azathioprine and 6-Mercaptopurine are purine analogues that interfere with DNA synthesis and repair, leading to reduced proliferation of lymphocytes and other cells critical for the inflammatory response.
   Anti-metabolite Activity: Methotrexate acts as a folic acid antagonist, inhibiting cell division and exerting anti-inflammatory effects.
   Clinical Use:
   Used for maintaining remission in both UC and CD. Often used when patients are either dependent on or refractory to steroids.
   Should monitor levels after at least 1 month of stable dosing. Also use a thiopurine methyltransferase (TPMT) test prior to starting the drugs to identify poor metabolisers and avoid myelosuppression. Monitor LFTs, FBC.
   Increased risk of hepatosplenic T cell lymphoma (rare).
4. Anti-TNF Drugs (Tumour Necrosis Factor Inhibitors)
   Examples: Infliximab, Adalimumab, Certolizumab pegol
   Mechanism of Action:
   TNF-α Inhibition: These biologics bind to tumour necrosis factor-alpha (TNF-α), a key cytokine involved in systemic inflammation, neutralizing its effect. This prevents TNF-α from interacting with its receptors on cell surfaces, inhibiting the cascade of inflammatory responses in the immune system.
   Clinical Use:
   Highly effective in reducing symptoms and inducing and maintaining remission in both UC and CD. They can also heal fistulas in CD.
5. Other Biologics
   Examples: Vedolizumab, Ustekinumab
   Mechanism of Action:
   Vedolizumab: Integrin receptor antagonist. It selectively blocks the migration of lymphocytes into the gut, reducing gut inflammation without affecting the rest of the immune system.
   Ustekinumab: Targets interleukin-12 and interleukin-23, cytokines involved in immune signalling and inflammation.
   Clinical Use:
   Used for both UC and CD, especially in patients who do not respond to or cannot tolerate anti-TNF therapy.
6. Surgery
   Mechanism of Action:
   Removal of Diseased Segments: Surgical interventions in IBD typically involve the removal of diseased portions of the gastrointestinal tract (resection), which can eliminate sources of severe symptoms.
   Restoration and Preservation of Gastrointestinal Function: Procedures may involve the creation of stoma (ostomy) or reconnection of different parts of the gastrointestinal tract (anastomosis).
   Clinical Use:
   Often considered for complications such as obstruction, perforation, abscess, or severe disease unresponsive to medical therapy. In UC, surgery can be curative (proctocolectomy with ileo-pouch anal anastomosis).