Week 13 Flashcards
What are the broad causes of injury to the liver?
drugs and toxins including alcohol abnormal nutrition / metabolism infection obstruction to bile or blow flow autoimmune liver disease genetic/deposition disease neoplasia
What is meant by fulminant hepatitis?
severe acute, rapidly progressing towards liver failure
What is the definition of cirrhosis?
end stage liver disease
diffuse process with fibrosis and nodule formation
What is the clinical approach to liver disease?
History, symptoms and signs by examination
investigations - bloods, LFTS, haematology, viral and autoimmune serology, metabolic tests
radiology - ultrasound
What are some of the types of diffuse liver disease?
acute hepatitis acute cholestsis fatty liver disease chronic hepatitis chronic biliary disease hepatic vascular disease deposition / genetic disease
What is the appearance of acute hepatitis?
Diffuse hepatocyte injury seen as swelling, some cell death. spotty necrosis. There is an inflammatory cell infiltrate in all areas - portal tracts, interface and parenchyma
What are the causes of acute cholestasis or cholestatic hepatitis?
extrahepatic biliary obstruction
drug injury - antibiotics
What is the appearance of acute cholestasis in histology?
brown bile (bilirubin) pigment, +/- acute hepatitis
Describe hepatitis B on pathology
acute hepatitis plus fibrosis
ground glass cytoplasm in hepatocytes
What are the causes of chronic biliary / cholestatic disease?
primary biliary cholangitis
primary sclerosing cholangitis
What is the historical appearance of chronic biliary disease?
focal, portal predominant inflammation and fibrosis with bile duct injury
Granulomas in PBC
What are the causes of genetic/deposition liver disease?
haemochromatosis
wilson’s disease
alpha 1 antitrypsin
What are the non neoplastic space occupying lesions (focal liver lesions)?
developmental/degenertive cysts
inflammatory - abscess
What is the commonest form of liver cyst?
Von Meyenberg complex (simple biliary hamartoma)
can resemble metastases by naked eye operation
What are the benign and malignant names of liver cell neoplasms?
hepatocellular adenoma hepatocellular carcinoma (HCC)
What are the benign and malignant names of bile duct neoplasms?
bile duct adenoma (rare)
cholangio-carcinoma
What are the benign and malignant names of blood vessels neoplasms in liver?
haemangioma
angiosarcoma
Describe a haemangioma
benign blood vessel tumour
biopsy avoided because risk of bleeding
Describe a hepatic adenoma
rare
mainly 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 alpha feto-protein
screening available
What are the normal functions of the liver?
protein, carbohydrate and fat metabolism plasma protein and enzyme synthesis production of bile detoxification storage of protein, glycogen, vitamins and metals immune function
How is the actual function of the liver assessed?
albumin
bilirubin
prothrombin time
How should chronic liver disease be investigated?
ultrasound viral hepatitis serlogy AI - ANA/SMA/LKM (AIH), AMA (PBC) metabolic liver disease- ferritin (haemachromatosis) caeruloplasmin (wilsons) alpha 1 antitrypsin deficiency
How should acute liver injury be investigated?
ultrasound
acute viral hepatitis serology
autoimmune liver disease (ANA, AMA, LKM (AIH), immunoglobulins”
paracetamol levels
What are the most common causes of abnormal liver blood tests?
fatty liver - alcohol in non
chronic viral hepatitis - C
autoimmune liver disease - primary biliary cholangitis, autoimmune hepatitis
haemochromatosis
Describe the progression of alcoholic liver disease
alcoholic steatosis
alcoholic hepatitis
alcoholic cirrhosis
Describe the progression of non-alcoholic fatty disease
steatosis
non-alcoholic steatitic hepatitis
NAFLD cirrhosis
What are the main associations with NAFLD?
obesity, type 2 diabetes and hyperlipidaemia
How can ALD and NAFLD be differentiated with LFTs?
AST:ALT ratio
AST is much higher in ALD
What are the essential features on alcoholic hepatitis?
excess alcohol within 2 months bilirubin >80 for less than 2 months exclusion of other liver disease treatment of sepsis / GI bleeding AST >500 (AST:ALT ration >1.5)
What are the characteristic features of alcoholic hepatitis?
hepatomegaly, fever, leucocytosis and hepatic bruit
What are signs of chronic liver disease?
stigmata: spiders, foetor, encephalopathy
synthetic dysfunction - prolonged prothrombin time, hypoalbuminaemia
What are the signs of portal hypertension?
caput medusa
hypersplenisms
thrombocytopaenia
Describe the cell count in the assessment of ascites
> 500 WBC/cm3 and 250 neutrophils/cm3 suggests spontaneous bacterial peritonitis
inflammatory conditions can also increase WBC count
lymphocytosis suggests TB or peritoneal carcinomatosis
Describe the albumin in the diagnosis of ascites
serum ascites albumin gradient (SAAG) = serum albumin - ascitic albumin
if SAAG >11g/l = portal hypertension
What is the management of ascites?
low salt diet spironolactone furosemide paracentesis transjugular intrahepatic portosystemic shunt liver transplant
What are common precipitating factors for hepatic encephalopathy?
gastrointestinal bleeding infections constipation electrolyte inbalance excess dietary (especially animal) protein
how can hepatic encephalopathy be treated?
lactulose and rifaximin
Describe lithogenic bile
bile becomes lithogenic for cholesterol if there is excessive secretion of cholesterol or decreased secretion of bile salts
excessive secretion of bilirubin (haemolytic anaemia) can cause its precipitation in concentrated bile in the gallbladder
Describe acute cholecystitis
severe RUQ pain, tenderness and fever
leukocytosis and normal serum amylase
usually resolves spontaneously but can progress to empyema, gangrene and rupture
initiated by stone obstruction of cystic duct causing supersaturation of bile and chemical irritation
Describe chronic cholecystitis
may be a sequel to repeated attacks of acute cholecystitis
gallstones are virtually always present
inflammation secondary to chemical damage (supersaturated bile)
rather than bacterial infection
How does acute pancreatitis present?
severe RUQ pain
fever
leukocytosis
raised serum amylase
Describe pancreatic abscess
potential complication of acute pancreatitis
infected pancreatic necrosis
avascular haemorrhagic pancreas good culture medium
drainage or necrosectomy plus antibiotics
Describe a pancreatic pseudocyst
potential complication of acute pancreatic no epithelial lining commonly in lesser sac high concentration of pancreatic enzymes may resolve spontaneously may be drained into stomach
What are the differentials of pancreatic pseuodocysts
mucinous cystic neoplasm - ovarian type
intraductal papillary mucinuos neoplasm
serous cystadenoma
What are the risk factors for pancreatic cancer?
gremlin mutations (BRCA) account for small proportion smoking is by far the biggest risk factor
What are the signs and symptoms of pancreatic cancer?
painless obstructive jaundice
new onset diabetes
abdominal pain due to pancreatic insufficiency or nerve invasion
tumours in head may obstruct pancreatic duct and bile duct - double duct sign on radiology
Describe pancreatic endocrine tumours
rare
may secrete hormones
commonest functional tumour is insulinoma which presents with hypoglycaemia, mainly benign
malignant endocrine tumours have a much better prognosis than pancreatic carcinoma
Describe cholagniocarcinoma
classified as intrahepatic or extra hepatic depending on origin
intrahepatic has to be distinguished from metastatic adnenocarcinoma and HCC
Extrahepatic has similar morphology and prognosis to pancreatic carcinoma,.
Describe carcinoma of the gallbladder
rare
gallstones usually present
adenocarcinoma
dismal prognosis unless incidentally found in a gallbladder removal for chronic cholecystitis
local infiltration may make gallbladder seem abnormally stuck down at theatre
Describe the exocrine function of the pancreas
ductal cells release alkaline fluid in response to secretin
acinar cells secrete digestive enzymes in response to secreaogues (CCH, secretin, substance P, VIP, acetylcholine, bombesin)
starch and glycogen breakdown
triglycerides
protein and polypeptides
describe cholelithasis
gallstones
most common cause of RUQ pain
abdominal ultrasound /EUS, MRCP
Describe acute cholecystitis
mainly secondary to gallstones
risk factors -female, fat, increasing age, rapid weight loss, pregnancy, drugs
persistent gallbladder neck or cystic duct obstruction
pain may radiate to right shoulder
Murphy’s sign
associated with fever and nausea
LFTs often deranged - elevated transaminases, ALP, mild hyperbilirubinaemia, mild hypermylasaemia
Describe biliary sepsis
cholangitis
chacots triad - fever, jaundice and RUQ pain
causes - gallstones, biliary manipulation, hepatobiliary malignancy
obstructive LFTs
may have raised amylase
positive blood cultures 50%
broad spectrum antibiotics and ERCP/PTC
Describe the presentation of acute pancreatitis
acute severe upper abdominal pain
50% radiates to back
partially relieved by sitting or bending forward
severe pancreatico - multi-organ failure, pleural effusions, ascites
5-10% painless
jaundice may be present if gallstones disease
What are the two signs of AP?
Cullen’s
Grey Turner
Describe the diagnosis of AP
elevated serum amylase >3 times ULN amylase rises within 6-12 hours has a short half life alcoholic and hypertriglyceride pancreatitis - amylase may be lower serum lipase - elevated for longer imaging -Ct
What is the aetiology of AP?
I GET SMASHED idiopathic gallstones ethanol trauma steroids mumps / malignancy autoimmune scorpion sting hyperlipidaemia, hypercalcaemia ERCP / EUS drugs (azathioprine)
How can AP be classified?
internal oedematous acute pancreatiis
necrotising acute pancreatitis
mild (no organ failure or complications)
moderately severe (organ failure <48 hours or local complications)
severe acute pancreatitis (persistent rogan failure >48 hours)
What is the management of acute pancreatitis?
supportive in mild cases - fluid replacement, pain control, PO/enteral nutriotion, antibiotics (only if sepsis)
treat underlying cause
persistant symptomatic fluid collections >4 weeks may need drainage
Describe chronic pancreatis
inflammatory condition parenchyma replaced with fibrous tissue pain malnutrition diabetes increased risk of pancreatic cancer
What are the the risk factors for CP?
TIGAR - O
Toxic/metabolic - alcohol tobacco, hyperlipidaemia, CKD
Idiopathic
genetic
Autoimune
RAP/SAP associated - post necrotic, vascular, post -irradiation
obstructive
Describe the diagnosis of CP
calcification on imagine
aspiration of duodenal secretions post secretin / CCK at ERCP
secretin enchanted MRCP
EUS
labelled carbon breath test
wedge biopsy or section of resected pancreas
What is the treatment of CP?
potent analgesia duct drainage address exocrine and endocrine needs smoking cessation alcohol cessation surgery -
What are the mechanisms of exocrine pancreas insufficiency?
reduced secretion due to pancreatic disease
low CCK released to duodenal disease
acidic duodenal pH due to gastric hyper secretion or low bicarb secretion
abnormal aboral transit due to surgery
What are the causes of PEI?
acute pancreatitis chronic pancreatitis cystic fibrosis pancreatic cancer diabetes myelitis pancreatectomy gastrectomy coeliac disease IBD Zollinger-Ellision syndromw
What are the clinical consequences of PEI?
malnutrition is main clinical consequence - more pain episodes, more hospitalisation, cardiovascular events, fracture risk, infection risk
How is PEI diagnosed?
confirmation with tests not always essential
direct, indirect, faecal
consider a trial off PERT in suspected PEI patients
What are the aims of PEI theraoy
to avoid
steatorrhoea
weight loss
maldigestion related symptoms
to ensure a normal nutritional status
What are the layers of the oesophagus?
mucosa (non-keratinised stratified squamous) muscularis mucosae submucosa muscularis proproa adventitia
What is the appearance of reflux oesophagitis?
acid and digestive enzymes injure squamous epithelium lining oesophagus. increased numbers of inflammatory cells and basal layer. proliferative zone of the squamous epithelium is hyperplastic
What can cause infections of the oesophagus?
candida albicans (fungus) herpes simplex virus
What chemicals can cause oesophagitis?
reflux of acid, bile
caustics - cleaning products (NaOH)
Pills: iron, bisphosphonates, tetracyclines
What are other causes of oesophagitis?
diverticula, achalasia, schatzki ring, systemic sclerosis, hiatus hernia
Describe eosinophilic oesophagitis
overlap with reflux oesophagitis
causes dysphasia
eosinophils infiltrate epithelium. Allergic aetiology. Responsive to steroids
may be possible to identify dietary sensitisers
fluticasone sometimes used in treatment
Describe oesophageal cancre
late presentation - high lethality
squamous carcinoma - associated with smoking and drinking
adenocarcinoma- associated with gastro-oesophageal reflux disease and obesity
Describe Barrett’s oesophagus
metaplastic response to mucosal injury - squamous becomes glandular
usually intestinal with goblet cells
associated with benign strictures but also with adenocarcinomas
Describe dysplasia
architecturally and cytologically abnormal
low grade - cells polarised, nuclei stratified
high grade - polarity lost, nuclei rounder, vesicular, prominent nucleoli, abnormal mitoses, necrosis
What are the causes of acute gastritis?
alcohol, NSAIDs, severe trauma
What are the causes of chronic gastritis?
Autoimmune
Bacterial (H. pylori)
Chemical
Describe the absorption of B12
B12 bound to salivary haptocorrin is protected from gastric acid
haptocorrin is digested in duodenum
B12 binds to Intrinsic factor secreted by gastric parietal cells. Absorbed in terminal ileum via specialised receptor
Describe autoimmune gastritis
autoimmune destruction of parietal cells
anti-parietal cell antibodies in blood
eventual complete loss of parietal cells with pyloric and intestinal metaplasia
achlorydia - bacterial overgrowth
hypergastrinaemia - endocrine cell hyperplasia / carcinoids
persistent inflammation can lead to dysplasia and to cancer
Describe Zollinger-Ellison syndrome
Hypersecretion of gastrin by an endocrine tumour (gastrinoma) in pancreas or duodenum leads to increased gastric acid output and severe peptic ulceration
Describe H.Pylori gastritis
potentially lifelong. colonises gastric mucosa and leads to chronic inflammation: IL8 attracts neutrophils
Describe antral-predominant gastritits
hypergastrinaemia and duodenal ulceration
Describe pangastriits
hypochlorhydria, multifocal atrophic gastritis, IM, cancer (intestinal type)
What are the causes of chemical gastritis?
bile reflux, NSAIDs, ethanol, oral iron
Describe gastric cancer
historically more distal than proximal
strongly associated with chronic gastritis - H.pylori or autoimmune
background atrophic mucosa, chronic inflammation, intestinal metaplasia, dysplasia
intestinal versus diffuse
proximal (reflux) vs distal (infectious)
Describe diffuse gastric cancer
individual malignant cells with mucin vacuoles: signet ring cells
may invade extensively without being endoscopically obvious - linitis plastica
weaker link with gastritis
metastasis to ovaries (Krukenberg tumour)
supraclavicular lymph node (Virchows)
Sister Joseph’s nodule - umbilical
Describe familial gastric cancer
CDH1 (E.cadherin) mutation
Penetrance - 70-80% lifelong
small intamucosal foci of diffuse gastric cancer may be numerous
prophylactic gastrectomy
increased risk lobular carcinoma of breast
Describe giardiasis
waterborne protozoal infection
rare in Glasgow
usually a chronic infection
diarrhoea, malabsorption, weight loss but often asymptomatic
associated with immunodeficiency - can then be very serious
treated with metronidazole
Describe cytomegalovirus infection in the GI tract
presents with severe pain, weight loss, weakness, remitting fever
gastrointestinal lesions are erosive ulcerous or ulceronephrotic
infection and viral replication, mostly occurs in ulcerative disease of the intestine - IBD
Describe Whipple’s disease
very rare affects middle aged men weight loss, arthralgia, diarrhoea, abdominal pain Diagnosed by biopsy tropheryma whipplei
Describe a tropical sprue
also called post-infectious sprue
affects people living in or visiting the tropics
endemic and epidemic features
may be due to E.coli or haemophilus.
Presents in a similar fashion to coeliac disease
can be successfully treated with a long course of tetracycline
What are the intestinal diseases of entamoeba histolytica infection?
asymptomatic
dysentery
acute necrotising colitis with perforation
toxic megacolon
ameboma
perianal ulceration with fistula formation
Describe the histopathology of coeliac disease
villous atrophy
crypt hyperplasia
increased number of intraepithelial lymphocytes
increased number of plasma cells in lamina propria
What should prompt serological testing for coeliac disease?
persistent unexplained abdominal or GI symptoms
faltering growth
prolonged fatigue
unexplained weight loss
severe or persistent mouth ulcers
unexplained iron, vitamin B12 or folate deficiency
type 1 diabetes at diagnosis
autoimmune thyroid disease at diagnosis
irritable bowel syndrome
first degree relatives of people with coeliac disease
What can malabsorption lead to?
iron deficiency anaemia
fatty diarrhoea, bulky, pale, greasy, offensive
weight loss
reduced bone density with increased risk of fracture
What are the complications of acute appendicitis?
transmural gangrene leading to perforation
generalised peritonitis
right iliac fossa abscess
Describe the pathology of UC
chronic inflammation usually confined to large intestine rectum always involved inflammation confined to mucosa and submucosa no granulomas
Describe the pathology of Crohn’s disease
mouth - anus
commonly affects terminal ileum
inflammation commonly transmural
granulomas are diagnostic
What are the causes of ischaemic gut?
mesenteric artery or vein thrombosis mesenteric artery embolus hypotension stragulated hernia volvulus
Describe the history for IBD
stool frequency, constancy, urgency, blood
abdo pain, malaise, fever
weight loss
extra intestinal symptoms (joint, eyes, skin)
Travel
family history
smoking
Describe the examination for IBD
weight pulse temperature anaemia abdominal tenderness perineal examination
Describe erythema nodosum
perniculitis
usually on shins
exquisitely tender- associated with strep, sarcoid and IBD
Describe pyoderma gangrenosum
central ulceration surrounded by purple not painful does tend to heal without much scarring will respond to immunomodilatory therapy sometimes topical steroids
Describe the investigations for IBD
FBC, ESR U&E, LFTS CRP stool cultures + C.dif toxin faecal calprotectin AXR rigid sigmoidoscopy colonoscopy small bowel radiology labelled WCC scanning
Describe the categories of treatment for IBD
corticosteroids thiopurines biologics UC - 5ASAs Crohns - methotrexate, immune modulating diets
Describe the main roles of aminosalicylates
induction of remission in mild-moderate ulcerative colitis
maintenance of remission in UC
maintenance therapy may reduce cancer risk
renal impairment
Describe thiopurines
azothioprine and mercaptopurine are unliscenced in IBD therapy
effective as maintenance therapy for both
prevent T cell clonal expansion
need to checkTPMT
monitoring of FBC and LFT important
What are the side effects of thiopurines
leucopenia nausea, vomiting arthralgia pancreatitis hepatitis squamous skin cancres haematological malignancy
What are the side effects of methotrexate?
GI upset hepatotoxicity immunosuppression sepsis pulmonary fibrosis
What is the treatment for acute severe colitis?
prophylactic LMW heparin
IV hydrocortisone 100mg QDS or methylprednisalone 30mg BD
treat for 72 hours if no improvement - reduce therapy
What is the rescue therapy for acute severe colitis?
ciclosporin
infliximab
surgery
How does upper GI bleeding present?
haematemesis
coffee ground vomiting or malaena
What are the causes of upper GI bleeding?
peptic ulcer oesophagitis gastritis duodenitis varices malignancy mallory-weiss tear other
Describe the management of upper GI bleeding
resuscitate if required - pulse and BP, IV access - fluid /bloods, check hb, urea, lie flat, give oxygen
risk assessment and timing of endoscopy
drug therapy and transfusion
Describe endoscopic therapy of upper GI bleed
adrenaline injection
heater probe
endoscopic clips
Describe the use of blood products in upper GI bleedss
restrictive transfusion if Hb <7-8
transfuse platelets if actively bleeding and count <50
FFP if INR >1.5
prothrombin complex concentrate if on warfarin and active bleeding
Describe the management of acute variceal bleeding
resucitation - diagnosis - endoscopy therapy - antibiotics early vasopressors early endoscopic banding treatment
What is used to prevent rebreeding of varices?
beta blockers and banding
