gastroenterology revision lecture

8/2/2019 Gastroenterology Revision Lecture

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Gastroenterology

Ammad Mahmood

GUMSA Revision Lectures



Contents

• Peptic ulcer disease

• Coeliac disease• Alcoholic liver disease

• Obstructive jaundice

• Hepatitis



Peptic Ulcer Disease



Gastric Acid Production

• Parietal cells produce hydrocholoric acid which: – Destroys microorganisms – Activates enzymes eg pepsinogen – Helps in digestion by breaking down and coagulating proteins

and by combining with calcium and iron to produce salts

• H+ ions are produced by dissociation of H2O andpumped into the stomach by H+ /K+ exchangers

• The OH-

ions combine with H2CO3 to produce H2O andHCO3- which is pumped into the blood by HCO3

- /Cl- exchangers

• The Cl- ions are pumped into the stomach with the K+

brought in by the H+

/K+

exchanger or move by diffusion



Control of Acid Secretion

• At rest the H+ /K+ exchangers are held in intracellularvesicles – stimulus to produce acid causes them to befused with the membrane which throws the membraneinto folds called secretory canaliculi increasing thesurface area for secretion

• Stimuli to produce acid include: – Acetylcholine – increases acid production – Histamine – increases acid production

– Gastrin – increases acid production

– Prostaglandin E2 – decreases acid production – Somatostatin – decreases gastrin release

• All of these function by having an effect on proteinkinases, through Ca2+ levels or G-proteins, which control

the activity of the H+

/K+

exchangers



Helicobacter Pylori

• Gram –ve rod bacteria, spread person to person, verycommon (90% in developing world, %=age in developedworld)

• Produces urease, an enzyme which produces ammoniafrom urea allowing it to survive in very acidicenvironments

• Using flagella it moves to the alkaline mucus layer in thestomach, irritating the gastric epithelium and causing aninflammatory reaction in this area (gastritis)



Peptic ulcers• A break in the epithelium of the stomach or duodenum caused by an

imbalance between gastric acid production and mucosal resistance

• Around 80% located in duodenum, 20% in stomach

• Causes

– H Pylori infection – NSAIDs – Zollinger Ellison syndrome – Post surgery – Smoking

• Ulcers are large (2-10cm), round, with perpindicular walls and asmooth base which can extend through to the muscularis externa orfurther

• They contain fibrin deposition and layers of granulation and scartissue



Peptic ulcers

• Duodenal ulcers – Ammonia released by H Pylori in the stomach causes increased

gastrin production which causes excessive acid production

– Excess acid causes damage to the duodenal mucosa and canlead to ulceration or gastric metaplasia

– Acid also precipitates the bile salts in the duodenum which wouldnormally have stopped infection

– The islands of gastric mucosa can be infected by H Pylori furtherworsening the problem

• Gastric ulcers – Epithelial damage and destruction of the protective alkaline

mucus barrier leads to ulceration



Clinical features

• Epigastric pain – worse at night and before meals

• Nausea, vomiting, dyspepsia

• Anorexia, weight loss

• Can be asymptomatic before complications

• Complications – Perforation – causes peritonitis

– Penetration – ulcer enters adjacent organ

– Haemorrhage – ulcer erodes into a blood vessel and bleeds – causes haemetemesis and melaena



Investigations

• Diagnosis of H Pylori infection – 14C urea breath test – 14C is ingested and if H Pylori is present it

will break urea down to ammonia and CO2. If 14C is detected ina breath test it is positive

– Serology for antibodies

– Stool test using immunoassays – Rapid urease/CLO test – Gastric biopsy added to solution

containing urea and pH indicator, if ammonia is produced pH willincrease

– Biopsy culture and histology

• Endoscopy – Carried out for over 55s or those with ‘alarm symptoms’

(dysphagia, weight loss, anorexia)

– Gastric ulcers are always biopsied



Treatment

• H Pylori infection is treated with eradication triple therapy – Proton pump inhibitor – omeprazole

– Antibiotics – clarithromycin + amoxicillin or metronidazole

• Drugs for treatment of dyspepsia

• Management of complications – Surgery for perforation or massive bleeds – may require partial

gastrectomy – Bleeding ulcers can be injected with adrenaline endoscopically



Management of Dyspepsia

• Dyspepsia refers to any disorder related togastric acid• Drugs used include:

– Proton pump inhibitors eg omeprazole – inhibit H+/K+pumps, effective as it works regardless of the stimulusfor acid secretion

– Antacids eg calcium carbonate – buffer acid andincrease pH

– H2 receptor antagonists eg ranitidine – antagonisehistamine to reduce acid production

– Anticholinergics eg atropine – reduce acid productionbut have too many side effects

– Synthetic prostaglandins eg misoprostol – reduceacid production and increase mucus and bicarbonateproduction



Coeliac Disease



Coeliac disease

• Abnormal reaction to gluten in the diet leading tomalabsorption

• 1 in 2000 prevalence in the UK, higher in Western

Ireland

• Aetiology not fully understood but a component of glutencalled gliadin is believed to stimulate enterocytes tomount an inflammatory reaction

• Other factors include: – Genetics – related to the HLA B8 antigen which is also involved

in the condition dermatitis herpetiformis – Environmental – a factor such as a viral infection may explain

the variable age of onset



Pathology

• Primarily affects the proximal SI around the jejunum

• Epithelial cell loss accelerates to the point where cellproliferation in the crypts is unable to maintain a normal

amount of functioning cells

• This leads to the classical histological findings of subtotalvillous atrophy and crypt hyperplasia

• The immature cells which populate the brush bordercannot absorb as efficiently and hormone secretion isalso impaired



Clinical Features

• Can present at any age but most commonis women in their 40s

• Symptoms are variable and non-specific: – Malnutrition and weight loss

– Anaemia

– Fatigue and malaise – GI symptoms – steatorrhoea, diarrhoea,

bloating, discomfort/pain



Investigations

• Jejunal biopsy – ‘Gold standard’, obtained by endoscopy

• Antibodies – IgA endomysial antibodies (IgA EMA)

– Tissue transglutaminase antibodies

• Blood tests – Macrocytic anaemia due to folate deficiency

– Iron deficiency



Management

• Gluten free diet – Substitute wheat, rye and barley for rice, maize, soya, some oats

• Vitamin and mineral supplementation

• Compliance to gluten free diet can be assessed bytesting antibodies at 4-6 weeks following start of diet



Obstructive Jaundice



Jaundice

• Caused by hyperbilirubinaemia• Symptoms

– Yellow discolouration of the skin and sclera due to cutaneousdeposition of bilirubin

– Pruritus

– Pale stools (absence of stercobilin) and dark urine (excretion ofconjugated bilirubin) in obstructive jaundice

• Causes divided into: – Pre-hepatic – unconjugated hyperbilirubinaemia usually due to

haemolysis

– Hepatic – mixed hyperbilirubinaemia, variety of causes, due tohepatocellular damage – Post-hepatic – conjugated hyperbilirubinaemia due to blockage

of the biliary tree – gallstones or pancreatic tumours



Gallstones (Cholelithiasis)

• Types of stones: – Cholestrol – large yellow stones – 20% – Bile Pigment – small black irregular – 5% – Mixed – 75%

• Typical patient – fair, fat, fertile

• Depending on anatomical site gallstones have differenteffects:

– Silent – Impaction in Hartmann’s pouch/cystic duct – biliary colic, acutecholecystitis

– Impaction in CBD – choledocholithiasis, ascending cholangitis – Gallstone ileus – Pancreatitis



Gallstones

• Biliary colic – Impaction at Hartmann’s pouch which the gallbladder tries to

contract against

– Causes RUQ colicky pain for 2-3 hours after eating which canradiate to right shoulder, patient characteristically lies still

– Not systemically unwell, not jaundiced

• Acute cholecystitis – Prolonged impaction at Hartmann’s pouch/cystic duct causing

the gallbladder to be irritated as it fills with concentrated bile.Becomes infected and fills with pus

– Persisting RUQ pain + fever

– Chronically can lead to a fibrosed gallbladder and chroniccholecystitis



Gallstones

• Choledocholithiasis – Impaction in the CBD

– Causes RUQ pain + jaundice

– If obstruction is not relieved the pressure can causeliver damage

• Ascending cholangitis

– Infection behind an impacted CBD stone – Causes RUQ pain + jaundice + fever (Charcot’s triad)

– High morbidity and mortality



Investigations

• Ultrasound – Gallstones – Thickened gallbladder surrounded by fluid – CBD dilation

• AXR – 10% of gallstones are radio-opaque

• MRCP – Specialised MRI scanner to image biliary tree and pancreas

• ERCP – Endoscopic retrograde cholangiopancreatography – An endoscope with a side view camera to visualise sphincter of Oddi – Diagnostic and therapeutic eg sphincterotomy, stone retrieval

• Bloods – LFTs, coagulation screen for procedures



Management

• Depends on which pathology is present

• Measures include – Analgesia eg morphine – Antibiotics (eg amoxicillin, gentamicin, metronidazole)

and rest – Removal of stone by ERCP or rarely using lithotripsy – Cholecystectomy either within 72h or after 6 weeks

after the inflammation has settled



Alcoholic Liver Disease



Alcohol Metabolism

• ADH – alcohol dehydrogenase• ALDH – aldehyde dehydrogenase

• CYP2E1 – an enzyme which is part of the microsomal ethanoloxidising system (MEOS)

• High levels of acetaldehyde and its derivatives in the geneticallysusceptible are hepatotoxic



Alcoholic Liver Disease

• Fatty liver – Excess fat deposition in the liver, reversible – Occurs in 50% of heavy drinkers – Causes derangement of LFTs but normal coagulation – Few symptoms, no encephalopathy – Also occurs without alcohol – non-alcohol steatohepatitis, occurs in

metabolic syndrome

• Acute hepatitis – Occurs in 40% of heavy drinkers – More deranged LFTs, prolonged clotting time

– Moderate symptoms, encephalopathy possible

• Cirrhosis – Severe alcohol abuse – Features of chronic liver disease eg encephalopathy, portal

hypertension



Clinical Features

• Some clinical features are common to chronic liverdisease due to any cause and some are specific toalcohol excess

• Chronic alcohol abuse leads to: – Neural damage due to the thiamine deficiency and alcohol

neurotoxicity. This leads to cortical and cerebellar atrophyresulting in reduced cognition and cerebellar ataxia

– Thiamine deficiency leads to Wernicke Korsakoff syndromewhich involves Wernicke’s encephalopathy in the early stagesand eventually causes Korsakoff psychosis

• Classically presents with confusion, gait ataxia and mild nystagmus• Immediate memory recall retained but have anterograde and

retrograde amnesia, display confabulation

– Peripheral neuropathy – Psychiatric problems



Chronic Liver Disease

• Ascites - Excess fluid in the peritoneal cavity due to: – Reduced albumin and oncotic pressure – Portal hypertension leading to transudation of fluid into

peritoneal cavity – Peripheral vasodilation leading to water retention by kidneys

• Portal hypertension – The normally low pressure in the portal system is elevated due

to back pressure caused by liver cirrhosis – Blood finds alternative pathways to the systemic circulation

which bypass the liver leading to portosystemic shunting anddistension of these vessels eg oesophageal varices – Thus the protective first pass metabolism of the liver is lost – Oesophageal varices have a tendency to rupture and with

concurrent coagulopathy this can be fatal



Chronic Liver Disease

• Hepatic encephalopathy – Portosystemic shunting leads to blood which has not been

detoxified reaching the brain

– Neurotoxins such as ammonia, FFA, excess GABA cause neuraldamage

– Patients are irritable, confused and disorientated, can lead tocoma

– Signs include fetor herpeticus and asterixis

• Other features: – Jaundice

– Coagulopathy

– Proximal muscle weakness

– Hepatorenal syndrome



Management

• Investigations – Bloods – FBC, U+E, LFTs, coagulation – Imaging – liver ultrasound, CT scan

• Detox – thiamine and benzodiazepines

• Alcohol abstinence – psychiatric input, antabuse drugseg disulfiram

• Liver cirrhosis is incurable and requires transplant



Viral Hepatitis



Hepatitis

• Hepatitis is inflammation of the liver and hasmany causes

• Viral causes include: –

Hepatitis A to E – EBV

– CMV

– Yellow fever

– Herpes Simplex



Hepatitis A

• Most common but least serious type• ssRNA hepatovirus• Spreads by faecal oral route, infects liver via gut, shed in faeces for

2 weeks before and 1 week after onset of symptoms• 90% of children in developing countries infected by 5 years

• Clinical features – Non specific symptoms eg nausea, malaise – Some may develop jaundice – Severe disease leading to liver failure rare

• Investigations – LFTs – marked increase in transaminases

– IgM indicates acute infection (IgG indicates previous infection)• No specific treatment, most recover by 3-6 weeks• Vaccine recommended for travellers etc, inactivated virus which

gives immunity for 1 year or 10 years with a booster. IgG treatmentprovides protection quickly for 3-4 months



Hepatitis B

• dsDNA virus with three important antigens: – HBsAg – surface antigen surrounding virus core – HBcAg – core antigen surrounding DNA – HBe – secreted by core, appears on hepatocyte surface, targetted by

immune system

• Spread by blood (eg blood products, needles, tattoos), sexualintercourse and vertical transmission from mother to child

• Infected 2bn people worldwide with 300m carriers – low prevalencein the Western world

• The majority of cases involve a mild or subclinical transient infectionhence which requires no treatment



Acute HBV Infection

Acute hepatitis Subclinical Infection

RecoveryDeath

Chronic HBV infection

CarrierChronic Hepatitis

Cirrhosis Hepatocellular Carcinoma

1%

99%

10-30% 70-90%

25% 65%

1-10%



Reaction to HBV infection

• The immune response is made by cytotoxic T cells – thetype of response depends on the type of T cell

• Th1 responses (IL-2, gamma interferon) lead toclearance of the virus

• Th2 reponses (IL-4,5,6,10,13) lead to chronic infection• A poor cell mediated response eg in children is more

likely to lead to carrier status but adults are more likely tosuffer liver damage

• Chronic infection goes through two stages: – Replicative stage – virus is replicated, patient is highly infectious

– Integrative phase – viral DNA is integrated into host DNA andtranscribed with it, inflammation decreases but cirrhosis andcancer more likely



Investigations• A number of viral antigens and host antibodies can be

detected to monitor the state and course of HBVinfection: – HBsAg – surface antigen is present in acute infection but rapidly

cleared, persistence beyond 6 months indicates chronic infection – Anti-HBs – appears a few weeks after clearance of HBsAg,

indicates immunity

– Anti-HBc – appears in symptomatic infection, persists followingany infection

– Anti-HBc IgM – appears in symptomatic acute or highly infectivechronic infection, disappears over 6-9 months

– HBeAg – appears in acute infection but generally cleared,persists in highly infective carriers

– Anti-HBe – only detected in low infectivity carriers

• LFTs would show hepatitis

• Imaging eg US or CT and biopsy in chronic infection



Treatment

• Interferon – Bind to host ribosomes and prevent translation of viral mRNA – Pegylated interferon α2a (pegylated means it is conjugated and stays in

circulation longer) – Clear HBeAg in 40% of patients – Severe side effects eg fever, headache, malaise, depression, diarrhoea,

hair loss, infection

• Antivirals – Nucleoside or nucleotide analogues which inhibit enzymes involved in

viral replication eg reverse transcriptase or DNA polymerase – Lamivudine used – reverse transcriptase inhibitor

• Vaccination – Active immunisation using the HBsAg antigen – In the UK it is administered to high risk groups – Passive immunisation can be given using HBV antibodies – Post exposure prophylaxis with both active and passive immunisation

should be given to people exposed to HBV eg needle stick injuries



Hepatitis C

• ssRNA flavivirus spread through blood, blood products,needles, tattooing etc

• Sexual or vertical transmission is less likely than HBV

• Identified in 1989, has infected around 240m peopleworldwide

• The course of illness also depends the immuneresponse mounted but progression to chronic illness ismuch more likely than HBV



Acute HCV Infection Acute hepatitis

Chronic HCV infection

Recovery

Chronic Hepatitis

CirrhosisHepatocellular Carcinoma

70%

20-30%

70-80%

20%1-4% per year

DecompensatedLiver Failure

4-5% per year



Management

• Investigations – Anti-HCV antibodies, HCV DNA and viral load – LFTs – Imaging and biopsy in chronic infection

• Treatment (similar to HBV) – Pegylated interferon α2b – Ribavirin – viral DNA polymerase inhibitor

– No vaccine



Questions?

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