GI/Liver Flashcards
List the layers of the bowel wall
4 layers
Mucosa
> Epithelium
> Lamina propria
> Muscularis mucosae
Submucosa
Muscularis propria (or externa)
> Inner circular layer
> Outer longitudinal layer
Subserosa
> Loose, fatty connective tissue
Describe the histological features of ulcerative colitis
Diffuse involvement of lower GIT
Predominantly affects left side of colon in a confluence pattern (diffuse)
Terminal ileum can be involved but generally only in severe cases where the whole bowel is involved (pancolitis)
No transmural changes, focused in mucosa
Crypt architectural changes are very marked
Little / no fibrosis
No granulomas
Describe the treatments for ulcerative colitis
Mesalazine
> Targets inflammation in GI tract
> 4.8g > 2.4g daily for induction of remission in moderate UC
> 2.4g daily as a maintenance dose
> Reduces frequency of flare ups and severity
Escalation of treatment
> Azathioprine (or mercaptopurine)
» With severe relapse / frequently relapsing disease
» Requiring 2 or more corticosteroid courses in a 12 month period
» Risks
»> Intolerance
»> Lymphoma, NMSC
Biologics
Surgery: cure
> Sub-total colectomy
Describe the complications associated with ulcerative colitis
Local
> Haemorrhage
> Toxic dilation aka toxic megacolon
Systemic
> Skin
>Erythema nodosum
> Pyoderma gangrenosum
> Liver
> Sclerosing cholangitis
> Cholangiocarcinoma
> Eyes
> Iritis
> Uveitis
> Episcleritis
> Ankylosing spondilitis
> Malignancy
> Colorectal cancer
» Screening colonoscopy after 10y of disease
» Intervals determined by risk – extent of disease
Describe the features of Crohn’s disease
Chronic inflammatory condition affecting anywhere from mouth to anus
Risk factors
> Smoking
» Stopping reduces relapse rate, need for immunosuppression and surgery
Peak incidence 15-25y
Features
> Abdominal pain
> Diarrhoea (watery > bloody)
> Commonly affects ileum and right sided colon
> Weight loss
> Fistulae, abscesses, oropharyngeal, gastroduodenal
Extra-intestinal symptoms
> Eyes – episcleritis, uveitis
> Joints – sacroilitis, inflammatory arthropathy
> Skin – erythema nodosum
Describe the pathological and histological features of Crohn’s disease
Granulomas – hallmark of Crohn’s
Differences between UC & Crohn’s
> Distribution of inflammation
> Small and large bowel inflammation
> Tends to involve proximal large bowel
> Patchy inflammation resulting in macroscopic “skip lesions”
Type of inflammation
> Transmural process
> Deep ulcerating inflammation
Perianal disease e.g. fistulas / sinus tracts
Macroscopic
> Small bowel strictures
> Narrowed areas with mucosal ulceration
Which investigations are used in the diagnosis of IBD?
Abdominal X-ray
> Exclude small bowel obstruction
Ileocolonoscopy
> Apthous ulcers in terminal ileum
> Active illeitis on biopsy
Faecal calprotectin
> Calcium-binding protein, predominantly derived from neutrophils
> Single 20g sample, stable for 5 days
> Useful test to differentiate between IBD / IBS and assess activity in IBD
> Sensitive but not disease specific
Stool cultures
MR / CT enterography
> Show ulceration and inflammation in terminal ileum
> Mucosal enhancement and luminal narrowing
Describe the staging of IBD
Montreal classification – staging of disease
What are risk factors for severe disease in IBD?
Risk factors for severe disease
Young onset
Smoking
Perianal disease
Stricturing SB disease
Describe the treatment of Crohn’s disease
Thiopurines
> Azathioprine and 6-mercaptourine
Biologics
> TNF-alpha antagonists
> Infliximab / adalimumab
Anti-integrins (alpha-4,beta-7)
> Vedolizumab
Anti-interleukin 12/23
> Ustekinumab
Methotrexate
Surgery
> 70% lifetime risk
> Aimed at removing the minimal amount of GI tract (fistulae, strictures, severe inflammation)
> Recurrence common – 50% further surgery
Describe the pathological changes associated with Crohn’s disease
Acute
> Acute inflammation
> Ulceration
> Loss of goblet cells
> Crypt abscess formation (neutrophils present)
Chronic
> Architectural changes
> Paneth cell metaplasia
> Chronic inflammatory infiltrates in lamina propria
> Neuronal hyperplasia
> Fibrosis
Describe the presentation, investigations, risk factors and treatment associated with infective colitis
Presentation
> Short history of diarrhoea and vomiting
> Abrupt onset and resolution of symptoms
> Systemic upset and fevers prominent
Risk factors
> Travel
> Unwell contacts
> Immunocompromised
Investigations
> Stool sample / CDT
» Need 4 for 90% sensitivity
Treatment
> Conservative if immunocompetent
> Even if bacterial gastroenteritis is confirmed
Describe the presentation and treatment of ischaemic colitis
Presentation
> Abrupt onset pain and bloody diarrhoea +/- SIRS
> Hypoperfusion > embolic
Risk factors
> Elderly
> CV disease
> Heart failure
> Constipation
> Female sex
> Smoker
More severe than IBD
Treatment
> Conservative
> IV fluids +/- antibiotics
Describe the assessment, investigations and treatment of severe ulcerative colitis
Assessment: Truelove and Witts’ classification
Stool frequency
>8/day
>3 & CRP >45 on day 3 predicts need for colectomy in 85%
Treatment
> IV steroids
> Methylprednisolone
> Hydrocortisone
> If non-responsive to steroids
> Surgery: colectomy
> Rescue medical treatment with
» Cyclosporin
» Infliximab (monoclonal antibody to TNF-alpha)
Investigations
> Stool culture
> Bloods
> Abdominal X-ray
» Essential in severe colitis
» Helps assess disease extent and severity
> > > Megacolon
> Transverse diameter of the colon (usually transverse colon >5.5cm or caecum >9cm)
> > > Toxic megacolon
> Megacolon and signs of systemic toxicity
> Emergency colectomy
> Risk of perforation and peritonitis
Other inpatient investigations
> Endoscopy
> Flexible sigmoidoscopy
> Colonoscopy
> CT scan
» Exclude signs of subclinical perforation
Describe the diagnosis and treatment of coeliac disease
Diagnosis
> Serology
> IgA anti-endomysial (immunofluorescence)
> > Anti tTG IgA (quantitative ELISA)
> Duodenal biopsy (second and first part of duodenum)
> Histology: crypt hyperplasia and villous atrophy
Treatments
> Gluten free diet
> Nutritional assessment
> Bone health (FRAX score/DEXA)
> Screen for osteoporosis due to malabsorption of calcium
> If anaemia (iron deficiency or B12/folate), supplementation
> Vaccination (due to increased risk of hyposplenism)
> Pneumococcus
> Meningococcus
Describe the complications associated with coeliac disease
Functional hyposplenism
Microcytic anaemia
Osteoporosis
Low BMI
Calcium/ vitamin D deficient
Dermatitis herpetiformis
Increased risk of cancer, specifically lymphoma (T cell) and small bowel adenocarcinoma
IgA deficiency
List the causes of acute hepatitis
Infections
> Hepatitis A, B, C, D, E
> EBV, CMV, toxoplasmosis
> Leptospirosis
> Q fever
> Syphilis
> Malaria
> Viral haemorrhagic fever
Toxins
Drugs
Alcohol
Autoimmune
Wilson’s: caeruloplasmin test
Haemochromatosis: assess ferritin & transferrin saturation
Describe the clinical features, diagnosis and treatment of hepatitis A
RNA virus
Transmission
> Faeco-oral
> Human reservoir
Virus can survive for months in contaminated water
Virus shed biliary tree into gut
No chronic carriage
Good immunity after infection or vaccination
Clinical features
> Incubation period 2-4 weeks
> Age is main determinant of severity
> Mostly asymptomatic in children <5 years
> Mortality rate 1.5% if >50 year
Diagnosis
> Acute hepatitis A – IgM positive or HAV RNA in blood or stool
> Previous Hep A or vaccinated – IgM positive
Treatments
> No specific treatments
> Maintain hydration, avoid alcohol
> Self-limiting illness
> No role for vaccine or immunoglobulin as treatment
Vaccination
> Hepatitis A vaccine
» Inactivated virus
» 95% efficacy after 4 weeks – 2nd dose gives life protection
» Pre-exposure: travellers, homosexual men, IVDU, chronic liver disease patients
» Post-exposure: outbreak cancer
Describe the clinical features and treatment of hepatitis E
RNA virus
Transmission
> Faeco-oral
> Pork products
> Minimal person-to-person
Incubation period - 40 days
Clinical features
> Similar to hepatitis A plus rare reports of neurological effects
> Guillain-Barré syndrome
> Encephalitis
> Ataxia
> Myopathy
> Case fatality rate 1-3%
Treatment – supportive
> No vaccine
Chronic hepatitis E is seen in very immunosuppressed patient e.g. bone marrow transplants
> Treatment – ribavirin
Describe the clinical features and treatments of hepatitis B
DNA virus
HBV vaccination in most countries
Transmission
> Vertical transmission (most common) - at birth
> Sexual contact
> Blood transfusions
> Blood, semen
> Incubation: 2-6 months
Acute case fatality rate: 0.5-1%
> Age at time of infection determines severity of acute illness and risk of chronic HBV infection (CHB)
> Infection at birth / young child is usually asymptomatic but leads to chronic infection
> Infection as an adult is usually symptomatic but cleared
Chronic HBV
> Development of chronic liver disease in 25%
Results in
> Cirrhosis
> Decompensation
> Hepatocellular carcinoma (HCC)
> Death
Treatment
Acute HBV
> No treatment
> Usually resolves and infection is cleared
Chronic HBV
> Only treat those with liver inflammation
> Increased ALT or biopsy or fibrosis (on fibroscan or biopsy)
2 types
> Immunomodulatory – interferon
> Suppress viral replication – tenofovir or entecavir
Describe the diagnosis of hepatitis B
Lab tests – HBV DNA
Histology - cytoplasmic inclusion – ground glass cytoplasm in hepatocytes
Acute
> SAg – surface antigen
» Marker of infection
> SAb – surface antibody
> Marker of immunity
> Core IgM & IgG – recent infection
> E antigen (eAg) - suggests high infectivity
E antibody (eAb) - suggests low infectivity
Chronic HBV: sAg detectable for >6/12
> Carriers are broadly divided into 2 groups
> > eAg +ve (early disease)
> High viral load
> High risk of CLD and HCC
> Highly infectious
> > eAg –ve (late disease)
> Low viral load
> Lower risk of CLD and HCC
> Less infectious
Describe the clinical features and treatment of hepatitis D
ss RNA virus
> Requires HBV to replicate
Transmission same as hep B
Vertical transmission rare
Acquired by
> Co-infection with HBV
> Super-infection of chronic HBV carriers
> Infection only possible in persons who are HBV sAg+
Increases risk of chronic liver disease
Treatment
>Interferon only
> Bulevirtide – suppressive treatment
Describe the clinical features, diagnosis and treatment of hepatitis C
RNA virus
Incubation period 6-7 weeks
> 25% of newly infected are symptomatic
30% clear infection
70% chronic hep C
> Cirrhosis
> HCC
Diagnosis
> Screening of high risk groups
» Drug users
» Immigrant from high prevalence countries
> Anti HCV IgG positive = chronic or cleared infection
> PCR or antigen positive = current infection / viraemia
Transmission
> Injecting drugs
> Transfusion + transplant
> Sexual / vertical rare
No vaccine, no post exposure prophylaxis
No reliable immunity after infection
Treatment
> Directly acting antivirals (DAAs)
> Inhibit different stages of the replication cycle
> Cure rates >95% with 8-12 weeks of oral treatment
Describe the causes and histology of chronic biliary disease
Causes
> Primary biliary cirrhosis (PBC): anti mitochondrial antibody
> Primary sclerosing cholangitis (PSC): anti-neutrophil cytoplasmic antibody
Histology
Focal, portal predominant inflammation and fibrosis with bile duct injury
Granulomas in PBC
List the clinical features, investigations and treatments associated with autoimmune hepatitis
Clinical presentation
> Asymptomatic
> Non-specific symptoms
» Fatigue
» General ill health
» Lethargy
» Weight loss
>Mild right upper quadrant pain
> Acute jaundice arthralgia
> Unexplained fever
Chronic liver disease
Acute or even fulminant hepatic failure
Investigations
> Elevated AST and ALT
> Anti-nuclear antibody (ANA)
> Anti-smooth muscle antibody (SMA)
> Anti-liver kidney microsomal antibody (LKM)
> Raised IgG
Treatment
> Immunosuppressants
» Corticosteroids: prednisolone, budesonide
» Azathioprine / mycophenolate
Describe the clinical features and treatment of primary biliary cirrhosis
Most common chronic cholestatic liver disease
9:1 female to male
90% have anti-mitochondrial antibodies against pyruvate dehydrogenase complex (PDC-E2) in mitochondria
LFTs
> Elevated GGT & ALP in early disease
> Elevated bilirubin in advanced disease
Symptoms
> Tiredness
> Itching
> Jaundice
Treatment
> Ursodeoxycholic acid
Describe the clinical features, cause and treatment of haemochromatosis
Iron accumulation in tissues and organs including liver, adrenal glands, heart, skin, gonads, joints, pancreas
Presentation
> Abnormal LFTs
> Chronic liver disease
> Polyarthropathy
> Adrenal insufficiency
> Heart failure
> Diabetes
> Skin pigmentation – bronzed diabetes
Cause
> Mutation in HFE gene: autosomal recessive
> Homozygous for C282Y mutation
> Compound heterozygote for C282Y and H63D
Investigations
> Raised ferritin and transferrin saturation
> Not all hyperferritinaemia is iron (infection)
> Liver MRI for iron – liver biopsy
Treated with venesection
Describe the cause, presentation and treatment of Wilson’s disease
Mutation in ATP7B gene: autosomal recessive
Failure to transport excess copper into bile leading to copper accumulation
Presentation
Chronic liver disease <55 years old
5% develop fulminant acute liver failure (often with low ALP and haemolysis)
Neurological or psychiatric symptoms
Parkinsonism with or without hand tremor
Masked facial expressions
Slurred speech, ataxia or dystonia
Low caeruloplasmin
High copper levels
Kayser Fleischer rings
Treatment
Copper chelation – penicillamine or trientine
Oral zinc – reduces copper absorption
Which enzyme deficiency can result in liver disease?
Alpha 1 antitrypsin
Describe the clinical features of alcohol-related liver disease
Alcoholic hepatitis
> Excess alcohol within 2 months
> Bilirubin >80 micromol/L for less than 2 months
> Exclusion of other liver disease
> Treatment of sepsis / GI bleeding
> AST < 500 (AST:ALT ratio >1.5)
Features
> Hepatomegaly
> Fever
> Leucocytosis
> Hepatic bruit
Glasgow Alcoholic Hepatitis Score (GAHS)
Spectrum of alcohol-related liver disease
> Hepatitis: liver cell necrosis, inflammation, Mallory bodies, fatty changes
> Cirrhosis: fibrosis, hyperplastic nodules
> Steatosis: fatty change, perivenular fibrosis
Describe the associations of non-alcoholic fatty liver disease and the investigations used
Main associations
> Obesity
> Type 2 diabetes
> Hyperlipidaemia
Non-invasive tests of liver fibrosis
> APRI
> FIB-4
NAFLD Fibrosis score
> Takes into account age, BMI, IFG/diabetes, AST/ALT ratio, platelet
Fibroscan: transient elastography
> F0-F4
Blood tests
> Enhances liver fibrosis (ELF) test
> FibroTest
Describe the main features of liver cirrhosis
End-stage liver disease characterised by
Diffuse process
> Changes throughout the whole liver
Nodule formation
> Changes from smoothness to lumps of various sizes
Fibrosis
> White tissue
> Result of chronic inflammation (hepatitis) over many years
Persistence of injury-causing agent
Fibrous scarring and hepatocyte regeneration
Eventually irreversible and cirrhosis develops
Describe the consequences of liver failure
Altered intermediary metabolism
Impaired synthesis of urea and glycogen (higher risk of hypoglycaemia)
Reduced albumin and other transport proteins
Coagulation disorders
Reduced complement so prone to infection
Jaundice
Altered xenobiotic metabolism e.g. drugs
Circulatory and endocrine disturbances
Describe the complications associated with liver cirrhosis
Portal hypertension
> Cirrhosis increases resistance to blood flow through liver
> Increases pressure in portal circulation causing:
> > Portal-systemic shunts and varices
> There is a junction where portal and systemic circulation meet
> If pressure is high, portal circulation blood can go back to systemic circulation
> Varices (vein enlargement) may rupture to give massive haematemesis and precipitate hepatic failure and encephalopathy
> > Ascites
> Increased fluid in abdominal cavity
> > Splenomegaly
> Back pressure is exerted on spleen through portal circulation
> Spleen is distensible so can accumulate more blood and become enlarged
Hepatocellular cancer
Describe the pathogenesis of ascites in liver disease
Portal hypertension leads to pressure in splanchnic capillaries and fluid into the peritoneum
Portal hypertension also leads to an increase in nitric oxide
Results in hypovolaemia and renal artery vasoconstriction, resulting in the activation of RAAS and sodium and water retention
List LFTs and what they indicate
- AST: aspartate transaminase; hepatocyte enzyme
- ALT: alanine transaminase; hepatocyte enzyme
- ALP: alkaline phosphatase: bile duct enzyme (may also be elevated in bone pathology or pregnancy)
- GGT: gamma glutamyl transfer: bile duct enzyme
- Albumin: decreased albumin indicates chronic liver disease & reduced synthetic function
- INR: increased INR indicates decreased synthetic ability of the liver, which produces clotting factors
- Bilirubin
CRP also indicates inflammation
