Week 13 Flashcards
Describe acute hepatitis, including causes and clinical and histological features:
Inflammatory disease with less marked bile stasis
Diffuse hepatocyte injury seen as swelling, with inflammatory cell infiltrate in all areas: especially in portal tracts and interface but also in parenchyma
Acute
HBV may look like acute hepatitis plus fibrosis (specific feature is ground glass cytoplasm in hepatocytes=accumulation of surface antigen)
Describe acute cholestasis/cholestatic hepatitis, including causes and clinical and histological features:
Inflammation with more marked acute bile stasis
Caused by extra hepatic biliary obstruction or drug injury (eg antibiotics)
Histology: brown bile (bilirubin) pigments +/- acute hepatitis
Describe fatty liver disease, including causes and clinical and histological features:
Potentially chronic and may develop fibrosis and progress to cirrhosis
Give examples of drug-induced liver disease:
Drugs can cause almost any pattern of liver disease
Most drug hepatotoxicity idiosyncratic (rare but usually single clinical pattern) thus difficult to investigate e.g. Augmentin (co-amoxiclav: may cause acute cholestatic hepatitis)
Occasional predictable liver damage e.g. paracetamol, methotrexate
Don’t forget non-prescribed drugs e.g. over internet or herbal
Describe the diagnostic path of space-occupying liver masses:
Focal liver lesions = space occupying lesions (SOLs)
Non-neoplastic are either developmental/degenerative (eg cysts) or inflammatory (eg abscess)
Neoplastic can be benign or malignant
List commonly encountered hepatic neoplasms including primary liver tumours
and metastases:
Benign: hepatocellular adenoma, bile duct adenoma, haemangioma
Malignant: hepatocellular carcinoma, cholangio-carcinoma, angiosarcoma and liver mets
Describe the common clinical manifestation of liver disease and explain the mechanisms by which liver disease leads to these:
Portal hypertension: cirrhosis increases resistance to blood flow through the liver, thus increasing pressure in the portal circulation
This causes; portal-systemic shunts and varices, ascites, and splenomegaly (hypersplenism)
Reduced effective circulatory volume (due to splanchnic vasodilation from porto-systemic shunting) causes compensatory vasopressors, leading to sodium retention causing ascites and renal vasoconstriction causing hepato-renal syndrome
Other complications include liver failure, hepatocellular carcinoma
Hepatic encephalopathy has precipitating factors leading to reduction of hepatic or cerebral function, stimulation of an inflammatory response and increasing ammonia levels
Common precipitating factors of hepatic encephalopathy:
- GI bleeding
- Infections
- Electrolyte imbalance
- Constipation
- Excess dietary (esp animal) protein
Discuss how to investigate a patient with liver disease:
Chronic liver disease:
- US
- FBC, liver screen, PCR for viral hepatitis
- Autoimmune liver disease: ANA/SMA/LKM; AMA (in PBC), immunoglobulins
- ferritin (haemochromatosis), caeruoplasmin (wilson’s), alpha1 anti-trypsin deficiency
Acute liver injury:
- US
- HAV, HBV, HEV, CMV antigens (PCR)
- ANA, SMA, LMK (AIH) and immunoglobulins
- paracetamol levels
AST/ALT ratio lower in NAFLD and higher in ALD
Describe the common management strategies for patients with liver disease:
Patients with NAFLD can see remission of condition with loss of 10% of their BMI
Describe basic gross and microscopic structure and anatomical relationships between the extrahepatic bile ducts, gallbladder and pancreas:
Right and left hepatic duct join to form the common hepatic duct
The cystic duct flows from the gallbladder joining the common hepatic duct to form the common bile duct
The pancreatic duct joins the common bile duct at the ampulla of vater which flows into the duodenum through the major duodenal papilla
List the different kinds of gallstones, their chief constituents, and risk factors or conditions
predisposing to their formation:
Bile becomes lithogenic if there is excessive secretion of cholesterol or decreased secretion of bile salts
Excessive secretion of bilirubin (eg haemolytic anaemia) can cause its precipitation in concentrated bile in the gallbladder
Discuss the contribution of gallstones to acute and chronic cholecystitis, obstructive jaundice,
acute pancreatitis and ascending cholangitis; and outline the main features and consequences
of these conditions:
Acute cholecystitis is initiated by stone obstruction of cystic duct causing supersaturation of bile and chemical irritation
Chronic cholecystitis may be a sequel to repeated attacks of acute cholecystitis
Inflammation is secondary to chemical damage from supersaturated bile rather than bacterial infection
Mucocoele of gallbladder can form around gallstones caused by inappropriate secretion of mucus and decreased gallbladder motility
Describe pancreatic carcinoma:
66% in head of pancreas, ductal adenocarcinoma is most common subtype
Perineural invasion
Pre-malignant pancreatic intraepithelial neoplasia is asymptomatic
There is no standard effective therapy
RFs: smoking and germ-line mutations (BRCA)
Signs and symptoms: painless obstructive jaundice, new onset diabetes, abdo pain due to pancreatic insufficiency or nerve invasion
Double duct sign on radiology may indicate tumour in head of pancreas obstructing pancreatic duct and CBD
Describe common presentations of pancreatico-biliary disease:
Acute pancreatitis
2 of 3:
- pain in keeping with pancreatitis (severe pain in the centre of the abdomen, radiating to the back)
- amylase 3 times upper limit of normal
- characteristic CT appearance
Discuss how to assess and investigate the patients with pancreatico-biliary disease:
US to assess for gallstones
MRCP to assess for CBD stones
CT if diagnostic doubt or concern about complications
How are pancreatic-biliary disorders are managed and treated?
Initial:
ABCs, fluids, oxygen, organ support, (abx)
Further:
Treat cause
ERCP, lap cholecystectomy, alcohol addictions advice, stop medication (DMARDs)
Describe cirrhosis:
Definition is three-fold: diffuse process with fibrosis and nodule formation
End-stage liver disease, result of chronic inflammation over many years
- persistence of injury causing agent
- (fibrous) scarring and hepatocyte regeneration (leads to nodules)
- eventually irreversible and cirrhosis develops
Describe haemangioma:
Benign blood vessel tumour
Biopsy avoided because of risk of bleeding
Describe hepatic adenoma:
Rare
Mainly in young women, often associated with hormonal therapy
Risk of bleeding and rupture so excision if large
Describe hepatocellular carcinoma:
Most common primary liver tumour
Usually arises in cirrhosis and associated with elevated serum AFP (alpha feto-protein)
Screening available
What is the pathogenesis of cirrhosis?
Hepatocyte injury leads to progressive liver cell loss, which causes chronic inflammation, and hepatocyte regeneration
Chronic inflammation causes fibrosis, and hepatocyte regeneration causes hyperplastic nodules
Both of these cause architectural abnormality in the liver, leading to ischaemia which causes further liver cell loss.
What secretory protein production is impaired in liver failure?
Albumin, transport proteins, coagulation and fibrinolysis (e.g. factors II, V, VII-XIII), complement and protease inhibitors
How are hepatitis A and E transmitted?
Faeco-oral, contaminated food and water, person-person
What is the main determinant of severity of hepatitis A infection?
Age, mostly asymptomatic in children under 5 years old
Subsequently develop life-long immunity
What is a unique clinical feature of hepatitis E, and which genotype is it associated with?
Neurological symptoms (Guillaine Barre, encephalitis, ataxia and myopathy), GT 3
What are three differences between hepatitis A and E?
Hep E has a higer mortality rate (especially in pregnant women with GT 1), hep E has neurological symptoms, and hep E can be carried chronically
How are hepatitis B,C and D transmitted?
Bodily fluids (blood, semen), transfusion, organs and tissue transplantation, mother to baby (most common cause globally), contaminated needles and syringes and child to child (children playing together)
What determines the severity of acute illness, and the risk of chronic HBV infection?
Age at the time of infection: infection at birth- asymptomatic, but leads to chronic infection; infection as an adult is usually symptomatic but cleared
How is HBV infection diagnosed?
If sAg (surface antigen), or HBV DNA are detectable with PCR
What does HBV cAb + only indicate?
What does HBV cAb + only indicate?
How are acute and chronic HBV treated?
There is no treatment for acute HBV
Only patients with liver inflammation due to chronic HBV are treated with pegylated interferon alpha (enhances anti-viral immune components), or antiviral drugs to suppress viral replication (treatment for life)
What are the three interventions to prevent HBV transmission during pregnancy?
- HBV vaccination to all newborns
- HBV immunoglobulin if eAg + or high viral load (VL)
- Tenofovir during the last trimester if high VL
How does hep D compare to hep B?
Requires HBV to replicated; transmission is same as hep B, though vertical transmission is rare
Treatment is with peg interferon only
How is HCV transmitted?
Injecting drugs, transfusion and transplantation (sexual/vertical transmission rare)
Describe the natural history of HCV
Acute infection -> 70% develop chronic HCV, 30% clear infection. Of the 70% with chronic infection 25% develop cirrhosis, and 1-5% develop hepatocellular carcinoma
How is HCV treated (post-2012)?
Direct acting antiviral (DAAs) have substantially increased the chance of curing HCV- delivered with methadone at pharmacy for IVDUs
What must patients with hepatitis B,C and D also be screened for?
HIV
Describe cholangiocarcinoma:
Classified as intrahepatic / extrahepatic depending on origin
Intrahepatic cholangiocarcinoma needs to be distinguished from metastatic adenocarcinoma (which may have similar histology) and hepatocellular carcinoma
Extrahepatic cholangiocarcinoma has similar morpholopgy and prognosis to pancreatic carcinoma. Treatment is currently Whipple’s operation to remove common bile duct and involved pancreas/duodenum. Trials likely to start looking at value of neoadjuvant therapy
What are the complications of acute pancreatitis:
Pancreatic necrosis (with/out necrosis), progressing to bleeding
Fluid collection:
- peripancreatic fluid colleciton
- pseudocyst
- pancreatic fistula
Describe oral cancer:
Can present with pain, ulcers, earache, general malaise and problems eating and speaking
Dysplastic oral mucosa can progress to invasive squamous carcinoma
Pain can be caused by perineurial invasion
Treated with surgical removal of cancer
Head and neck cancers may spread to lymph nodes in the neck, usually on the same side
Smoking and alcohol are risk factors, HPV can be involved in some cases (mainly tonsil and oropharynx)
An ulcer which will not heal is classic presentation of cancer- if an ulcer persists without definite, identifiable cause think cancer
Describe Barrett’s oesophagus:
- A metaplastic response to mucosal injury (eg from long term GORD)
- Squamous epithelium becomes glandular, usually intestinal with goblet cells
- Associated with the development of benign strictures
- Also associated with the development of adenocarcinoma
Dysplasia occurring in Barrett’s can be describe as indefinite for dysplasia, low grade dysplasia and high grade dysplasia
Dysplasia can progress to carcinoma , low grade and high risk with similar risk of progression
Describe oesophageal cancer:
Squamous carcinoma:
- associated with smoking can drinking
Adenocarcinoma:
- associated with GORD and obesity
What are the different causes of acute and chronic gastritis?
Acute:
- alcohol
- medication (NSAIDs)
- severe trauma
- burns (Curling’s ulcers)
- surgery
Chronic:
- A autoimmune
- B bacterial (H pylori)
- C chemical
Describe gastric cancer:
Strongly associated with chronic gastritis: H pylori or autoimmune
Background atrophic mucosa, chronic inflammation, intestinal metaplasia, dysplasia
Morphologically classified as intestinal or diffuse
Diffuse:
- individual malignant cells with mucin vacuoles
- may invade extensively without being endoscopically obvious, so called linitis plastica
- weaker link with gastritis
- metastasis to ovaries, supraclavicular lymph node
- umbilical metastasis: Sister Joseph nodule
Give an account of causes of chronic gastritis:
Autoimmune:
- autoimmune destruction of parietal cells
- due to auto-antibodies against intrinsic factor and parietal cell antibodies in blood
- leads to; complete loss of pyloric and intestinal metaplasia
- achlorhydria -> bacterial overgrowth
- hypergastrinaemia -> endocrine cell hyperplasia/carcinoids
- persistent inflammation which can lead to epithelial dysplasia and may lead to cancer
Bacterial:
- consequences include: haemorrhage, perforation, fibrosis (leading to stenosis)
Chemical:
- few inflammatory cells
- surface congestion, oedema, elongation of gastric pits, tortuosity, reactive hyperplasia/atypia, ulceration
- seen in antrum more than body
- causes include bile reflux, NSAIDs, ethanal, oral iron
How do causes of upper GI bleeding arise?
Peptic ulcer: due to acid, H. pylori, NSAIDs
Oesophagitis:
Gastritis
Duodenitis
Varices
Malignancy
Mallory-weiss tear: tear in GOJ
Describe the presentation of upper GI bleeding?
Presentation: haematemesis, coffee ground vomiting or melaena
Describe the important steps in management of upper GI bleeding:
Initial management
- resuscitate if required
- pulse and BP
- IV access for fluids/blood
- lie flat and give oxygen
- risk assessment and timing of endoscopy
- high risk: emergency endoscopy
- moderate risk: admit and next day endoscopy
- low risk: out-patient management
- risk scores are ‘admission’ Rockall or Glasgow Blatchford
- drug therapy and transfusion
- IV PPI post-endoscopy to high risk pts
- continue low dose aspirin after upper GI bleeding once haemostats achieved
- stop NSAIDs
- assess risks vs benefits of clopidogrel, warfarin and DOACs once bleeding stopped, usually continued
- transfuse blood once Hb <7-8
Endoscopic therapy:
- adrenaline injection
- endoscopic clips
- haemostatic powders
Radiological embolisation of bleeding vessel
Describe the important steps in management of upper GI bleeding from varices:
Resuscitation:
- restore circulating volume
- transfuse once Hb >7
- consider airway protection
Diagnosis: endoscopy
Therapy:
- abx early
- vasopressors early
- endoscopic band ligation
- rescue TIPS (trans-jugular intrahepatic stent shunt)
Beta blocker and repeated band ligation as prevention of rebreeding, one or the other for primary prophylaxis
What is the basic structure of the small and large bowels?
Mucosa- with folds/crypts increasing surface area and allowing distension/peristalsis
Submucosa
Muscularis propria
Peritoneal surface
Where are mucosal stem cells, transit amplifying and differentiated cells located?
- Intestinal stem cells (ISC) found at the base of the villi
- Transit amplifying cells (TA- progenitor cells) are also found here
- Differentiated cells found all through the crypts
What are the major categories of neoplasia in the GI tract?
Adenomas:
- hyperplastic (metaplastic) polyps
- hatmartomartous polyps
- inflammatory polyps
- submucosal lesions (eg lipoma, leiomyoma
Adenocarcinoma (most common)
Neuroendocrine tumours, GI stromal tumours and lymphomas can occur as primary tumours in S or LIs
Other rarer cancers: types of carcinoma
Adenomas and carcinomas of small instines are rarer than in colorectum, but have similar histology
What is the role of chronic inflammation in development of GI cancer?
Crohn’s and UC are both associated with higher risk of colonic carcinoma than general pop
What is meant by the adenoma-carcinoma sequence?
Adenomas of the colon are dysplastic and the majority are polyps
At some point during the development of a carcinoma, it will have features of dysplasia but has not yet full malignant potential
Identifying and removing adenomas removes the first stage in the sequence and stops it progressing
Describe colorectal screening:
Screening colonoscopy of U.C. Patients
Bowel Cancer Screening Programme faecal occult blood. testing of >50 -75 year old
(+ve -> colonoscopy)
Patient education of symptoms
PR bleeding
Change in bowel habit
What are the common investigations in GI inflammatory disorders?
History and exam
Bloods: FBC, ESR, U&Es, LFTs, CRP Stool cultures + C diff toxin Faecal calprotectin- indicates something is wrong not what is wrong AXR Colonoscopy Small bowel radiology Labelled WCC scanning
Describe commonly used maintenance treatments for inflammatory bowel disease:
Treatments common to UC and crohn’s:
- corticosteroids
- thiopurines
- purine anti-metabolites
- essentially prevent T cell clonal expansion in response to antigenic stimuli
- biologics
- infliximab: anti-TNF alpha MAB
- adalumimab: anti-TNF alpha MAB
- golimumab: same
Treatments for UC alone
- Aminosalicylates:
- mesalazine
Treatments for Crohn’s alone
- methotrexate
- has side effects
- immune modulating diets (work in children, not adults)
Describe commonly used treatments for acute exacerbations of inflammatory bowel disease:
Patients who fail to respond to optimal treatment with 5ASA/prednisolone or with severe disease warrant hospital admission
Intravenous steroid therapy required
Liaison with colorectal surgeon
Stool frequency >8/day / CRP >45 on day 3 predicts colectomy in 85%
Treatment
Prophylatic LMW heparin
IV hydrocortisone 100mg QDS or Methylprednisolone 30mg BD
Treat for 72 hours
Improving then oral prednisolone 40mg
No improvement – rescue therapy
Rescue therapy
Ciclosporin 2mg/kg/day IV
Infliximab 5mg/kg single dose
Surgery
If medical therapy doesn’t work then surgery indicated
What are the potential roles of surgical treatment for inflammatory bowel disease?
UC
Surgery “curative”
Ileo-anal pouch or ileostomy
Crohn’s
Indicated for stricturing, perforation, fistulizing disease
Sparing as will come back
What are the limitations of plain radiographs in imaging GI and liver?
Inflammation:
AXR useful for colitis
AXR signs not specific in other inflammatory conditions
US for cholecystitis (and appendicitis if young and slim)
CT first choice otherwise
Perforation:
CXR sensitive for free gas
AXR less so - can be very subtle
CT to confirm and look for cause
Obstruction: AXR useful look for: small and/or large bowel dilatation? how much gas in colon? any gas in rectum? any complications - ischaemia, perforation? CT to look for cause
Ischaemia:
AXR usually non-specific
positive signs usually mean advanced ischaemia
CT first choice test but <60% sensitive
Describe volvulus:
A volvulus is when a loop of intestine twists around itself and the mesentery that supports it, resulting in a bowel obstruction
Symptoms include abdominal pain, abdominal bloating, vomiting, constipation, and bloody stool
What is possible oesophageal pathology?
Infections:
- candida albicans (fungus)
- herpes simplex virus
Inflammation- chemicals:
- peptic oesophagitis/GORD; reflux of acid, bile
- caustics: lye (NAOH, caustic soda)
- pills: iron, bisphosphonates, tetracyclines, etc
Diverticula, achalasia, schatzki ring, systemic sclerosis, hiatus hernia
What are the CFs of candida oesophagitis?
- Active chronic inflammation with many neutrophils
- Especially near the luminal surface of the epithelium
- PAS stains confirm spores and hyphae of candida albicans
What are the extra-intestinal features of IBD:
Skin- most often on the shin and ankles
Erythema nodosum- red bumps/rash
Polyderma gangrenosum- deep ulcerations on the skin
Uveitis
Peri-anal disease; can cause faecal incontinence
What are the common investigations in acute severe colitis?
- Daily FBC, ESR, U+Es, CRP
- Stool cultures (including C.Difficile)
- Daily AXR
- ?Sigmoidoscopy
