GASTROENTEROLOGY

Jan 20, 2022

Gabriela Mineva, Y4 UL GEMS

Learning Objectives

Gabriela Mineva Y4 UL GEMS

January 20, 2022

• Anatomy and Histology of the GI tract
• Oesophageal Pathology
• Gastric pathology
• Congenital GI pathology
• Coeliac Disease
• Gallbladder pathology
• Diverticular Disease
• Inflammatory Bowel Disease
• LFTs +Jaundice – Classification and Differentials
• Pancreatitis
• Questions Time

Gross Anatomy

Gabriela Mineva, Doctorials 21/22

Q: At which part of the duodenum does the foregut become the midgut?

A: At the entry of the hepatopancreatic duct at the major duodenal papilla

Gross anatomy, Blood Supply and Innervation

Reference: Anthony Rowan Doctorials 20

Gabriela Mineva, Doctorials 21/22

FOREGUT: esophagus to proximal duodenum; liver, gallbladder, pancreas, spleen

• Celiac artery (T11-T12)
• PS-innervation: Vagus
• S-innervation:
• Preganglionic: thoracic splanchnic nerves (T5-T9)
• Postganglionic: celiac ganglion
• Referred Pain: Epigastrum

MIDGUT: Distal duodenum prox 2/3 transverse colon)

• Superior Mesenteric artery (L1)
• PS-innervation: Vagus
• S-innervation:
• Preganglionic: thoracic splanchnic nerves (T9-T12)
• Postganglionic cell bodies: superior mesenteric ganglion
• Referred pain: Umbilical

HINDGUT: (distal 1/3 transverse colon to upper half anal canal)

- Inferior Mesenteric artery (L3)

• PS-innervation: Pelvic splanchnic
• S-innervation:
• Preganglionic: lumbar splanchnic nerves (L1-L2)
• Postganglionic: inferior mesenteric ganglion
• Referred pain: Hypogastrium

Embryological Origins

Gabriela Mineva Doctorials 21/22

Reference: Anthony Rowan Doctorials 20

Histology- Overview

FA USMLE 2017, page 347

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Histology- Key features

Key Features:

• Esophagus: non-keratinized stratified squamous epithelium
• Stomach: gastric glands with specialized cells
• Duodenum: Paneth cells (base of crypts), Brunner’s glands, plicae circularis (distal), Peyer’s patches (few),
• Jejunum: plicae, Peyer’s patches (increasing), crypts of Lieberkuhn
• Ileum: plicae, Peyer’s patches (many), crypts of Lieberkuhn

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Q: Where in the GIT can you find submucosal glands?

A: ONLY in the esophagus and duodenum

Key Features:

• Colon: crypts, no villi, haustra, tenia coli (longitudinal smooth muscle), many goblet cells

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• Rectum: no tenia
• Anus: above dentate/pectinate- columnar cells and portal circulation, below-squamous cells and systemic circulation

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crypts of Lieberkuhn (contains stem cells)

Gabriela Mineva, Doctorials 21/22

Esophagus

• 25-30 cm long, posterior to trachea
• 1/3 skeletal muscle, 2/3 smooth
• Originates at C6
• Enters the abdomen at:
• T10
• I ate (8) 10 Eggs At noon (12)
• IVC T8, Esophagus T10, Aorta T12
• Cricopharyngeus= Upper esophageal sphincter- anatomical
• Lower esophageal sphincter- physiological
• Z-line (gastroesophageal junction): squamocolumnar junction

Clinical Quip:

The lower esophagus venous drainage is both systemic (azygous) and portal (left gastric vein)

Gabriela Mineva, Doctorials 21/22

Esophageal Motility

• What is peristalsis?
• The rhythmic contraction and relaxation of smooth muscle of the GIT to propel a bolus along
• Swallowing:
1. Arrival of bolus at the upper esophageal sphincter causes relaxation and peristalsis begins
2. Swallowing becomes involuntary once the bolus reaches the distal 2/3 smooth muscle
3. Lower esophageal sphincter relaxes and stays relaxed until bolus passes into stomach

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Gabriela Mineva, Doctorials 21/22

Oesophageal Pathology –Congenital

• Oesophageal Atresia +/- Tracheoesophageal Fistula
• Atresia 🡪 Orifice or Passage in the body is absent
• IN this case, Blind ending pouch or Stenosis
• Fistula 🡪 Abnormal connection between two epithelial lined surfaces
• In this case the Trachea and Oesophagus
• Clinical Features: Neonates Drool, Choke, Vomit with first feeding
• Diagnosis: Unable to pass NG tube into stomach, TOF 🡪 Air in Stomach 🡪 Can see on CXR

Gabriela Mineva, Doctorials 21/22

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Oesphageal Motility Disorders

• Achalasia
• High Lower Oesphageal Sphincter tone
• Failure of relaxation of the sphincter
• Unknown : Auerbach’s myenteric plexus axonal degeneration
• Barium Swallow
• “Bird peak” : Narrow gastro-oesphageal junction
• Dilation of oesphagus
• Manometry
• Absence of peristaltic waves
• High resting intra-oesphageal pressure

Gabriela Mineva, Doctorials 21/22

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Esophageal Pathology- G(E/O)RD

• Gastro-esophageal reflux disease: reflux of stomach contents (acid) into the esophagus
• Decrease in LES tone
• Consequences: esophagitis, strictures, Barrett’s metaplasia, adenocarcinoma

Gabriela Mineva, Doctorials 21/22

Esophageal Pathology- Barrett’s

• Replacement of non-keratinized squamous epithelium to intestinal non-ciliated columnar epithelium with goblet cells
• Precursor to adenocarcinoma
• Endoscopy: shows Z-line as more proximal

FA USMLE 2017, page 361

Gabriela Mineva, Doctorials 21/22

Esophageal Pathology- Cancer

FA USMLE 2017, page 361

Gabriela Mineva, Doctorials 21/22

Esophageal Pathology- Other

• Esophageal varices
• Dilated submucosal veins in lower esophagus
• Secondary to portal hypertension- why?
• If ruptured🡪 hematemesis
• Mallory-Weiss syndrome
• Mucosal lacerations due to severe vomiting
• Presents with hematemesis
• Boerhaave syndrome
• Transmural rupture from violent retching
• Plummer-Vinson syndrome
• Triad of dysphagia, iron deficiency anemia, esophageal webs (thin protrusion of mucosa into upper esophagus)

FA USMLE 2017, page 360

Clinical Quip:

During portal hypertension, there is increased pressure at the level of the portal vein, thus the blood backflows through the left gastric vein, whish anastomose with the esophageal veins (azygous) and become dilated

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Stomach

• Cardia: mucous, no acid
• Corpus: H+, intrinsic factor
• Pylorus: gastrin and somatostatin

FA USMLE 2017, page 357

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Stomach- Physiology

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Stomach- Gastric Secretion

FA USMLE 2017, page 357

1. Parietal cells stimulated by:
• ACh (from vagus)
• Histamine (from ECL cells)
• Gastrin (from G cells)
2. Parietal cells secrete H+ generated by carbonic anhydrase (CA) into the gastric lumen via H+/K+ ATPase (primary active transport)
3. Net loss of cellular H+ balanced by HCO3- release into blood
• Alkaline tide
4. Inhibited by:
• Somatostatin (from D cells)
• Secretin (from presence of acid in duodenum)

Q: What classes of drugs act to decrease acid secretion?

A: H2 antagonists (-tidine), PPIs (-prazole)

Gabriela Mineva, Doctorials 21/22

Stomach Pathology- Pyloric Stenosis

• Presents in infancy (2-6 weeks) with nonbilious projectile vomiting
• Palpable olive shaped mass in epigastric region (due to the hypertrophy of the pyloric muscularis mucosa)
• Results in hypokalemic hypochloremic metabolic alkalosis
• Loss of acid in vomit as well as volume loss
• Infants fail to thrive

FA USMLE 2017, page 345

Q: Why is the vomit nonbilious?

A: The narrowing of the pylorus occurs before bile enters the GIT (bile enters the small intestine in the duodenum)

Gabriela Mineva, Doctorials 21/22

Stomach Pathology- Hiatal Hernias

• Protrusion of stomach through the esophageal hiatus into thorax
• Type 1: Sliding hiatal hernia
• Most common
• GEJ and proximal part of stomach slide up above level of diaphragm
• Type 2: Rolling/paraesophageal hiatal hernia
• GEJ normal and remains intra-abdominal
• Part of fundus protrudes into thorax
• At risk of strangulation, usually a surgical emergency

Gabriela Mineva, Doctorials 21/22

Stomach Pathology- Gastritis

• Acute gastritis- erosion caused by:
• NSAIDS (decreased prostaglandin production🡪 decreased mucosa protection)
• Burns (Curling ulcer🡪 mucosal ischemia)
• Brain injury (Cushing ulcer🡪 increase vagal stimulation, increased ACh, increased H+)
• Chronic gastritis- mucosal inflammation leading to atrophy. Increased risk of gastric Ca.
• H. pylori- most common cause
• Autoimmune- autoantibodies to parietal cells and intrinsic factor

FA USMLE 2017, page 362

Q: Where in the stomach is h.pylori found? How is it treated?

A: Antrum. Triple therapy (PPI, amoxicillin, clarithromycin)

Q: What are the consequences of decreased levels of intrinsic factor?

A: Vit B12 deficiency, macrocytic anemia, pernicious anemia

Gabriela Mineva, Doctorials 21/22

Stomach Pathology- Peptic Ulcer Disease

FA USMLE 2017, page 363

• Complications of PUD:
• Hemorrhage
• Obstruction
• Perforation

Gabriela Mineva, Doctorials 21/22

Stomach Pathology- Gastric Cancer

• Most commonly gastric adenocarcinoma (90%)
• Intestinal type- associated with H.pylori, chronic gastritis, smoking
• Diffuse type- not associated with H.pylori, signet ring cells on histology (mucin-filled cells with nucleus displaced to the side)

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• Others: lymphoma, GI stromal tumour and carcinoid (rare)
• Carcinoid tumours can be found throughout GI tract and cause carcinoid syndrome (release of serotonin):
• Facial flushing
• Diarrhea
• Wheezing
• Tachycardia

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FA USMLE 2017, page 362

Gabriela Mineva, Doctorials 21/22

Small Intestine- Digestion and Absorption

• Factors of absorption:
1. Degree of digestion
2. Time in transit
3. Intestinal mixing
4. Absorptive surface area
5. Effectiveness of transport mechanisms

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• What gets absorbed in the SI?
• Carbohydrates
• Proteins
• Fats
• Fluids and electrolytes
• Iron (mostly duodenum)
• Folate (B9) (duodenum and ileum)
• Vit B12, Bile salts (terminal ileum)
• Mechanisms of absorption
1. Transcellular- active transport
2. Paracellular- passive transport
3. Solvent drag- solutes coupled to fluid

Gabriela Mineva, Doctorials 21/22

Carbohydrate Absorption

• Pancreatic amylase digests polysaccharides into maltose, maltotriose and a-limit dextrins
• Only monosaccharides are absorbed by enterocytes
• Glucose, galactose, fructose
• Glucose and galactose are taken up by SGLT1 (Na+ dependent)
• Fructose is taken up by facilitated diffusion by GLUT5
• All transported to blood by GLUT2

Gabriela Mineva, Doctorials 21/22

Protein Digestion and Absorption

1. Stomach
• Pepsinogen (chief cells) enzymes require acidic conditions to activate into pepsin
• Denatures proteins to produce polypeptides
2. Small Intestine
• Pancreatic proteases (trypsin activated by enterokinase (duodenal cells) subsequently activate chymotrypsin, elastase and carboxypeptidases) to break down proteins
• Hydrolases on brush border
3. Intracellular hydrolysis
• Cleaving of dipeptides and tripeptides by cytosolic proteolysis
4. Absorption (limited endocytosis)
• Na+/AA co-transporter apical membrane
• Uses Na+ gradient generated by Na+/K+ATPases
• Na+ independent transport (facilitated) and diffusion on basolateral membrane
• Most protein products are absorbed as aa, but some are absorbed as di- and tri-peptides

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Thanks to Phil!

Gabriela Mineva, Doctorials 21/22

Fat Digestion and Absorption

• Enzymes:
• Gastric lipase (chief cells) and pancreatic lipase

Gabriela Mineva, Doctorials 21/22

SI Pathology- Congenital

• Duodenal atresia
• Failure to recanalize at 8 to 10 weeks (embryo)
• Presents with bilious vomiting
• Associated with Down Syndrome
• Ventral wall defects
• 6^th week of embryological development= midgut herniates through umbilical ring
• 10^th week supposed to return to abdominal cavity
• Omphalocele: persistent herniation of abdominal contents into umbilical cord. Covered by peritoneum
• Gastroschisis: complete extrusion of abdominal contents NOT covered by peritoneum

Gabriela Mineva, Doctorials 21/22

SI Pathology

• Intussusception
• Telescoping of proximal bowel segment into distal segment
• Most often at ileocecal area
• Associated with Meckel diverticulum
• Mostly in children

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• Volvulus
• Twisting of portion of bowel around its mesentery
• Midgut more common in infants
• Sigmoid more common in elderly (“coffee bean”)

Gabriela Mineva, Doctorials 21/22

SI Pathology- Celiac Disease

• In general, malabsorption syndromes present with diarrhea, steatorrhea, weight loss, weakness, vitamin and mineral deficiencies
• Autoimmune-mediated intolerance of gluten protein gliadin
• Associated with HLA DQ2 and HLA DQ8
• Labs (antibodies): IgA antitissue transglutaminase (IgA tTG), antiendomysial, antigliadin
• Definitive diagnosis= duodenal biopsy showing:
• Villous atrophy
• Crypt hyperplasia
• Intraepithelial lymphocytosis
• Treat with gluten free diet!

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FA USMLE 2017, page 364

Q: What type of anemia is most common in celiac disease?

A: iron deficiency anemia (recall, iron mostly absorbed in duodenum)

Gabriela Mineva, Doctorials 21/22

SI Pathology- Diverticular disease

• Diverticulum= outpouching of gut wall
• True= all 3 gut layers
• False= only mucosa and submucosa

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• Zenker diverticulum (pharyngoesophageal)
• False diverticulum
• Meckel diverticulum (small intestine)
• True diverticulum
• May contain ectopic gastric mucosa or pancreatic tissue
• Diverticulosis (colon)
• Many false diverticula, common in elderly, caused by increased intraluminal pressure
• Diverticulitis= inflammation of diverticula

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Gabriela Mineva, Doctorials 21/22

Colon Pathology- Inflammatory Bowel Disease

Crohn Disease

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Ulcerative Colitis

• Usually terminal ileum
• Skip lesions
• Rectal sparing
• Transmural, cobblestone appearance
• Noncaseating granulomas
• Mouth ulcers, fistulas, perianal disease
• Smoking worsens

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• Colon only, starts with rectum, distal to proximal
• Mucosal and submucosal
• Crypt abscesses
• Pseudopolyps
• Toxic megacolon
• Increased risk colon cancer
• Smoking protective

Gabriela Mineva, Doctorials 21/22

IBD Extraintestinal Manifestations

A PIE SAC

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Aphthous Ulcers (CD)

Pyoderma Gangrenosum

I (Eye): iritis, uveitis, episcleritis, conjunctivitis (CD>UC)

Erythema Nodosum

(Primary) Sclerosing cholangitis (UC?CD)/ Sacroiilitis

Arthritis (HLAB27 Ankylosing Spondylitis)

Clubbing of fingers (CD>UC)

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Gabriela Mineva, Doctorials 21/22

Liver Function

• What is the liver responsible for?
• Filter toxins
• Synthesize bile
• Conjugate bilirubin
• Make clotting factors
• Make cholesterol
• Glycogen storage and gluconeogenesis
• Makes plasma proteins
• What are liver function tests? (LFTs)
• Misnomer- ALP, AST, ALT, GGT are markers of liver injury
• BEST markers of liver function represent its synthetic ability: PT/INR, albumin, bilirubin

Gabriela Mineva, Doctorials 21/22

LFTs

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Bilirubin and Jaundice

Pre-Hepatic Jaundice

• Hemolysis
• 🡹 unconjugated
• Normal stool
• Normal urine

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Post-Hepatic Jaundice

• Obstruction
• 🡹 conjugated
• Pale stools
• Dark urine

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Intra-Hepatic Jaundice

• Liver injury
• 🡹 conjugated OR 🡹 unconjugated
• Pale stools
• Dark urine (if conjugated), pale urine (if unconjugated)

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Gabriela Mineva, Doctorials 21/22

Liver Pathology- Hepatitis B Serology

• HBsAg🡪 surface antigen
• Active disease
• HBsAb (anti HBsAg)🡪 surface antibody
• No active disease, recovered from active infection OR immunization
• HBcAb🡪 core antibody
• History of infection (IgM if acute, IgG if chronic or recovered)
• HBeAg🡪 envelope antigen
• Active viral replication (high transmissibility)
• HBeAb🡪 envelope antibody
• Low transmissibility

Q: HBsAg +, IgM HBcAb +, HBsAb -

A: acutely infected

Q: HBsAg -, IgG HBcAb - , HBsAb +

A: vaccinated

Gabriela Mineva, Doctorials 21/22

Liver Pathology

Alcoholic Liver Disease

• Steatosis↔︎hepatitis→ cirrhosis
• Mallory bodies (intracytoplasmic inclusions of keratin filaments)
• AST>ALT “all Signs point to (>) Liquor”

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Non-Alcoholic Fatty Liver Disease

• Fatty infiltration of hepatocytes
• ALT>AST “L for more Lipids”

Gabriela Mineva, Doctorials 21/22

Liver Pathology- Hemochromatosis and Wilson

Hemochromatosis

• Recessive mutation in C282Y >> H63D on chr. 6
• Excessive iron levels due to impaired absorption
• Iron deposits in organs:
• Liver
• Pancreas
• Skin
• Joints
• Heart
• “Bronze diabetes”
• Treat with phlebotomy

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Wilson Disease

• Recessive mutation in hepatocyte copper-transport gene (ATP7B)
• Copper accumulation in:
• Liver
• Brain (putamen)
• Cornea (Kayser-Fleischer rings)
• Kidney
• Parkinsonism
• Treat with penicillamine “copper pennies”

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Gabriela Mineva, Doctorials 21/22

Gall Bladder- Pathology

Cholelithiasis

• Stones in the gall bladder
• Risk factors: 4 F’s
• Fat
• Female
• Forty
• Fertile (pregnant)

Cholecystitis

• Inflammation of the gallbladder
• Usually from stone
• Murphy Sign:
• Inspiratory arrest on RUQ palpation due to pain

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Choledocholithiasis

• Stones in the common bile duct

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Cholangitis

• Ascending infection with stone in the common bile duct
• Charcot Triad:
• RUQ pain
• Fever
• Jaundice

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Gabriela Mineva, Doctorials 21/22

Diverticulum

• What is a Diverticulum???
• Outpouchings of the GI tract
• False: Does not involve all layers of wall “Acquired/ Pseudodiverticulum”
• True: Dose involve all layers of wall
• Diverticulosis
• Condition where Diverticulum can be found within the colon especially Sigmoid
• False diverticulum
• Diverticular Disease
• Where Diverticulum in colon become symptomatic
• Diverticulitis
• Acute inflammation of Diverticulum e.g. infection
• Meckel’s Diverticulum
• Persistence of the Vitelline/Omphalomesenteric duct
• True Diverticulum
• Zenker’s Diverticulum
• Pharyngoesophageal false diverticulum/Pharyngeal pouch

Gabriela Mineva, Doctorials 21/22

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Bowel Obstruction

• Mechanical blockage arising from structural abnormality that presents a physical barrier to progression of gut content
• Key Features
• Abdominal Pain
• Constipation (Absolute)
• Vomiting (Bilious/Faeculent)
• Abdominal Distention
• Erect Chest X ray***(see image)
• PFA/CT Scan
• Dilated Loops of small or large bowel
• 3,6,9 Rule

Gabriela Mineva, Doctorials 21/22

Above image Showing Erect Chest X ray with Air underneath the hemi Diaphragm – Suggestive of Perforation

Pancreas Pathology

Acute Pancreatitis

“I GET SMASHED”

Idiopathic

Gallstones

Ethanol

Trauma

Steroids

Mumps

Autoimmune disease

Scorpion Sting

Hypercalcemia/Hypertriglyceridemia (>1000mg/dL)

ERCP (endoscopic retrograde cholangiopancreatography)

Drugs

Dx:

• Acute epigastric pain radiating to back
• ↑serum amylase and lipase
• Characteristic imaging findings

Gabriela Mineva, Doctorials 21/22

Question Time!!!

• A 40-year-old man was referred to the hepatology clinic by his GP due to concerns that he was developing chronic liver disease. The patient comments he has been feeling progressively more tired over the past couple of years. He attributes this to not sleeping well as low libido is causing him relationship difficulties with his wife. On examination he has gynaecomastia and palmar erythema. The hepatologist also notes that his skin pigmentation appears grey. Given the most likely diagnosis, what treatment would you give first?
• Liver Transplant
• Penicillamine
• Venesction
• Ursodeoxycholic acid
• Desferrioxamine

Gabriela Mineva, Doctorials 21/22

Question Time!!!

• You are reviewing a 55-year-old man who has recently been diagnosed with Barrett's oesophagus. This was diagnosed after the patient was referred due to difficult to control symptoms. No evidence of dysplasia was found on biopsies. In terms of risk factor modification, which one of the following has been shown to be most strongly linked to the development of Barrett's oesophagus?
• NSAIDS
• Eating smoked fish
• Alcohol
• Smoking
• GORD

Gabriela Mineva, Doctorials 21/22

Question Time!!!

• A 21-year-old woman presents to her GP complaining of mild diarrhoea, fatigue, and abdominal discomfort. She has been experiencing these symptoms for over a year. She has lost 4kg over the last 6 months. She has not passed any blood or mucus in her stool.��Her brother has coeliac disease and the patient stopped eating gluten 2 months ago, on his advice. Since then, the diarrhoea and abdominal discomfort have resolved but she still feels tired all the time.��The patient wants to be tested for coeliac disease. Which of the following options is the most appropriate for the GP do?
• Explain irritable bowel syndrome and reassure the patient
• Test only for tissue transglutaminase antibodies
• Test for tissue transglutaminase antibodies and IgA
• Advise her to start eating gluten again and to return in 6 weeks
• Arrange an abdominal x-ray

Gabriela Mineva, Doctorials 21/22

Question Time!!!

• A 45 year old gentlemen with a known history UC presents to ED with a 2 day Hx of right upper quadrant abdominal pain, fatigue and fever. On examination reveals a yellow tinge to his sclera. Bloods tests reveal deranged LFTs. A diagnosis of Primary Sclerosis Cholangitis is suspected. What auto-antibody is associated with this condition
• AMA
• P-ANCA
• Anti-dsDNA
• RF
• Anti-CCP

Gabriela Mineva, Doctorials 21/22