GI Flashcards
What is the normal oesophagus like
25cm long muscular tube mostly lined with squamous epithelium
Sphincter at upper end (cricopharyngeal) and lower end (gastro-oesophageal junction)
Distal 1.5-2 cm are situated below the diaphragm and lined by glandular columnar mucosa
The squamo-columnar junction is usually located at 40cm from the incisor teeth
What is oesophagitis
Inflammation of the oesophagus
Classified:
- acute
- chronic
Aetiology:
- Infectious (bacterial, viral (HSV1, CMV), fungal (candida))
- Chemical (ingestion of corrosive substances, reflux of gastric contents)
What are the risk factors for reflux oesophagitis
Defective lower oesophageal sphincter
Hiatus hernia
Increased intra-abdominal pressure
Increased gastric fluid volume due to gastric outflow stenosis
What is a hiatus hernia
Abnormal bulging of a portion of the stomach through the diaphragm
What are the complications of reflux oesophagitis
Ulceeration Haemorrhage Perforation Benign stricture (segmental narrowing) Barrett's oesophagus
What is Barretts oesophagus
Cause:
Longstanding gastro-oesophageal reflux
Risk factors:
Same as for reflux (male, Caucasian, overweight)
Macroscopy:
Proximal extension of the squamo-columnar junction
Histology:
Squamous mucosa replaced by columnar mucosa > “glandular metaplasia”
Premalignant condition with an increased risk of developing adenocarcinoma
Regular endoscopic surveillance is recommended for early detection of neoplasia
What are the two histological types of oesophageal carcinoma
Squamous cell carcinoma
Adenocarcinoma
What are the risk factors for squamous cell carcinoma of the oesophagus
Tobacco and alcohol Nutrition (potential sources of nitrosamines) Thermal injury (hot beverages) Human Papilloma Virus Male Ethnicity (black)
What usually causes acute gastritis
Chemical injury:
- drugs (NSAIDs)
- Alcohol
- Initial response to Helicobacter pylori infection
What are the causes of chronic gastritis
Autoimmune:
-anti-parietal and anti-intrinsic factor antibodies
Bacterial infection (Helicobacter pylori)
Chemical injury
What is Helicobacter pylori
Gram negative spiral shaped bacterium:
- 2.5-5.0 micrometres long
- 4 to 6 flagellae
- Lives on the epithelial surface protected by the overlying mucus barrier
Damages the epithelium leading to chronic inflammation of the mucosa
More common in antrum than body
Results in glandular atrophy, replacement fibrosis and intestinal metaplasia
What is peptic ulcer disease
Localised defect extending at least into submucosa
Major sites:
- First part of duodenum
- Junction of antral and body mucosa
- Distal oesophagus (GOJ)
Main aetiological factors:
- Hyperacidity
- H. pylori infection
- Duodeno-gastric reflux
- Drugs (NSAIDs)
- Smoking
What is the histology of an acute gastric ulcer
- Full-thickness coagulative necrosis of mucosa (or deeper layers)
- Covered with ulcer slough (necrotic debris + fibrin + neutrophils)
- Granulation tissue at ulcer floor
What is the histology of a chronic gastric ulcer
- Clear-cut edges overhanging the base
- Extensive granulation and scar tissue at ulcer floor
- Scarring often throughout the entire gastric wall with breaching of the muscularis propria
- Bleeding
What are the potential complications of peptic ulcers
Haemorrhage
Perforation -> peritonitis
Penetration into an adjacent organ (liver, pancreas)
Stricturing -> hour-glass deformity
What are the types of gastric cancer
Most frequently:
Adenocarcinoma
Less frequently:
Endocrine tumours
MALT lymphomas
Stromal tumours (GIST)
What is the aetiology of gastric adenocarcinoma
Diet (smoked/cured meat or fish, pickled veg) H. pylori infection Bile reflux Hypochlorhydia (allows bacterial growth) ~1% hereditary
What is coeliac disease
AKA coeliac sprue or gluten sensitive enteropathy
Immune mediated enteropathy (a disease of the intestine, especially the small intestine)
Reaction to ingestion of gluten containing cereals
~ 0.5% to 1% of population
Commonly those 30 to 60yo
What are gluten containing cereals
Wheat
Rye
Barley
Why is coeliac disease difficult to be diagnosed
- Atypical presentations / non specific symptoms
- Silentdisease: Positive serology / villous atrophy but no symptoms
- Latentdisease: Positive serology but no villous atrophy
- Symptomatic patients: Anaemia, chronic diarrhoea, bloating, or chronic fatigue
How is coeliac disease diagnosed
Non-invasive serologic tests usually performed before biopsy
The most sensitive tests:
- IgA antibodies to tissue transglutaminase (TTG)
- IgA or IgG antibodies to deamidated gliadin
- Anti-endomysial antibodies - highly specific but less sensitive
Tissue biopsy is diagnostic (2nd biopsy after Gluten free diet)
What is the treatment of coeliac disease
Gluten free diet results in symptomatic improvement for majority of patients
Reduces risk of long-term complications including anaemia, female infertility, osteoporosis and cancer
What is the morphology in coeliac disease
Villous atrophy
Crypt elongation
Increased IELs
Increased lamina proprietary inflammation
What is diverticulosis of the colon
Protrusions of mucosa and submucosa through the bowel wall
Commonly sigmoid colon
Located between mesenteric and anti-mesenteric Tania coli
Less commonly extensors into proximal colon
What is the pathogenesis of diverticulosis of the colon
Increased intra-luminal pressure:
- irregular, uncoordinated peristalsis
- overlapping (valve like) semicircular arcs of bowel wall
Points of relative weakness in the bowel wall:
- penetration by nutrient arteries between mesenteric and anti mesenteric Tania coli
- age related changes in the connective tissue
What are the clinical features of diverticular disease
Asymptomatic 90-99%
Cramping abdominal pain
Alternating constipation and diarrhoea
Acute and chronic complications (10-30%)
What are the potential complications of diverticular disease
Acute:
- Diverticulitis/ peridiverticular abscess (20-25 % )
- Perforation
- Haemorrhage (5%)
Chronic:
-Intestinal obstruction (strictures: 5-10 % )
-Fistula (urinary bladder, vagina)
-Diverticular colitis (segmental and granulomatous)
Polypoid prolapsing mucosal folds
What is colitis
Inflammation of the colon
Acute (days to a few weeks)
Chronic (months to years)
What are the types of acute colitis
- Acute infective colitis eg. campylobacter, shigella, salmonella, CMV
- Antibiotic associated colitis (including PMC)
- Drug induced colitis
- Acute ischaemic colitis (transient or gangrenous)
- Acute radiation colitis
- Neutropenic colitis
- Phlegmonous colitis
What are the types of chronic colitis
- Chronic idiopathic inflammatory bowel disease
- Ischaemic colitis
- Diverticular colitis
- Microscopic colitis (collagenous & lymphocytic)
- Chronic infective colitis eg. amoebic colitis & TB
- Diversion colitis
- Eosinophilic colitis
- Chronic radiation colitis
What are the idiopathic inflammatory bowel diseases
Ulcerative colitis
Crohn’c disease
Unclassified and indeterminate colitis (10-15%)
What is the clinical presentation of ulcerative colitis
Diarrhoea (> 66%) with urgency/tenesmus Constipation (2%) Rectal bleeding (> 90%) Abdominal pain (30 – 60%) Anorexia Weight loss (15-40%) Anaemia
What are the potential complications of ulcerative colitis
Toxic megacolon and perforation
Haemorrhage
Stricture (rare)
Carcinoma
What is the clinical presentation of Crohn’s disease
- Chronic relapsing disease
- Affects all levels of GIT from mouth to anus
- Diarrhoea (may be bloody)
- Colicky abdominal pain
- Palpable abdominal mass
- Weight loss / failure to thrive
- Anorexia
- Fever
- Oral ulcers
- Peri-anal disease
- Anaemia
What are the potential complications of Crohn’s disease
Toxic megacolon Perforation Fistula Stricture (common) Haemorrhage Carcinoma Short bowel syndrome (repeated resection)
What is ischaemic colitis
Colonic injury secondary to an acute intermittent or chronic reduction in blood flow
May be occlusive or non-occlusive (NOMI)
Usually multifactorial and associated with other vascular diseases
What are colorectal polyps
Mucosal protrusion Solitary or multiple (polyposis) Can be pedunculated or sessile or flat Small or large Due to mucosal or submucosal pathology or a lesion deeper in the bowel wall
What are the risk factors for colorectal cancer
Diet: -Dietary fibre (protective) -Fat -Red meat -Folate (protective) -Calcium Obesity / Physical Activity Alcohol NSAIDs & Aspirin (protective) HRT and oral contraceptives Schistosomiasis Pelvic radiation Ulcerative colitis and Crohn's disease Inherited susceptibility
What cancers are patients with Lynch syndrome at increase risk of
Endometrial Ovarian Gastric Small bowel Urinary tract Biliary tract
What are the sterile sites in the GI tract
Peritoneal space
Pancreas
Gall bladder
Liver
What are the non-sterile sites in the GI tract
Mouth Oesophagus Stomach Small bowel Large bowel
What is angular cheilitis
Acute or chronic inflammation of the skin and contiguous labial mucosa located at the lateral commissures of the mouth
Presents with erythema, maceration, scaling and fissuring at the corners of the mouth, with lesions usually bilateral and may be painful
Treated with topical antifungals/antibiotics
Which patients may present with hairy leukoplakia and why
HIV patients caused by Epstein Barr virus
What are peritonsillar abscesses
Unilateral swellings of tonsil
Normally streptococcus A
Symptoms: painful swallowing, unilateral sore throat and ear ache
Signs: muffled voice, trismus (lock jaw), unilateral deviation of the uvula towards the unaffected side and soft palate fullness or oedema
Oral airway may be compromised and drooling may occur
Surgical drainage and antibiotic management normally indicated
What is parotitis
Non mumps:
Occurs in patients with poor oral hygiene and dehydration
Staph aureus
Normally unilateral
Sudden swelling from cheek to angle of jaw and bacteraemia may result
Systemically unwell
Surgical drainage should be considered and antibiotics given
What is Ludwig’s angina
A bilateral infection of the submandibular space
Aggressive, rapidly spreading cellulitis without lymphadenopathy with potential for airway obstruction
Requires careful monitoring and rapid intervention for prevention of asphyxia and aspiration pneumonia
If abscesses form, surgical drainage is required
Antibiotics given
What are the deep neck space infections
- Peritonsillar abscess (quinsy)
- Acute suppurative parotitis
- Submandibular space infections (Ludwig’s angina)
- Pretracheal space infections
- Prevertebral space infections
- Parapharyngeal space infections
- -Carotid sheath involvement
- -Suppurative jugular thrombophlebitis (also known as Lemierre’s syndrome)
- Retropharyngeal and danger space infections
What is mucositis
Inflammation of the mucous membranes of the GI tract
Chemo induced
Lasts about 2 weeks after stopping chemo
What is the medical definition of trauma
An injury or wound to living tissue caused by an extrinsic agent
What is shock
Interruption to the supply of substrates to the cell:
oxygen, glucose, water, lipids, amino acids, micronutrients
Interruption to the removal of metabolites from the cell:
CO2, water, free radicals, toxic metabolites
What happens in phase 1 after trauma
Shock Develops within 2-6 hours after injury Lasts 24-48h Cytokines, catecholamines and cortisol secreted IncreasedHeart rate (tachycardia) Increased respiratory rate Peripheral vasoconstriction: (selective peripheral shut-down to preserve vital organs) Hypovolaemia Primary aims: -stop bleeding -prevent infection
What happens in phase 2 after trauma
Catabolic state Develops ~ 2 days after injury Necessary for survival but is persists/severe, increased mortality Catecholamines Glucagon ACTH ->Cortisol ^ Oxygen consumption ^ metabolic rate ^ Negative nitrogen balance ^ Glycolysis ^ Lipolysis Primary aims: -Avoid sepsis -provide adequate nutrition
What happens in phase 3after trauma
Occurs approx 3-8 days after uncomplicated surgery
May not occur for several weeks after severe trauma and sepsis
Coincides with beginning of diuresis and request for oral intake
Gradual restoration of:
-Body protein synthesis
-Normal nitrogen balance
-Fat stores
-Muscle strength
Primary aims:
Adequate nutrition supply is critical in this phase
Refeeding syndrome risk
May last a few weeks / a few months
Obesity paradox
What is the inflammatory response at a trauma site
Bacteria and pathogens enter wound
Platelets release clotting factors
Mast cells secrete factors that mediate vasodilation to increase blood delivery to the injured area
Neutrophils and macrophages recruited to phagocytose pathogens
Macrophages secrete cytokines to attract immune cells and proliferate inflammatory response
Inflammatory response continues until wound is healed
What are the catabolic and anabolic hormones
Catabolic:
ACTH (so also cortisol)
Glucagon
Catecholamines
Anabolic:
Growth hormone
Insulin
What are the five cardinal signs of inflammation
Heat Redness Swelling Pain Loss of function
How is lactate used as a prognostic marker in trauma
Failure of blood lactate to return to normal following trauma resuscitation carries a poor prognosis
What is primary malnutrition
Protein calorie undernutrition (starvation)
Dietary deficiency of specific nutrients (trace elements, water soluble vitamins, fat soluble vitamins)
What is secondary malnutrition
Nutrients present in adequate amounts but:
-appetite is suppressed
-absorption and utilisation are inadequate
Increased demand for specific nutrients to meet physiological needs
What are the consequences of malnutrition
Negative nitrogen balance Muscle wasting Widespread cellular dysfunction Associated with: -infection -poor wound healing -changes in drug metabolism -prolonged hospitalisation -increased mortality
What is the overall incidence of malnutrition in hospitalised patients
~50%
How many newborns are affected by cystic fibrosis
1 in 2,500 in UK
What is the function of cystic fibrosis transmembrane regulator protein
Facilitates production of thin, watery, free-flowing mucus to:
-lubricate airways and secretory ducts
-protect lining of airways, digestive system, reproductive system
So that macromolecules can be secreted smoothly out of secretory ducts
What are the functions of the pancreas
Exocrine:
Secrete digestive enzymes (trypsin, lipase, phospholipase, elastase, amylase) which require activation
Endocrine:
Secrete peptide hormones into blood (insulin and glucagon)
What is pancreatitis
Inflammation of the pancreas
Associated with injury to the exocrine parenchyma
Acute: gland reverts to normal if underlying cause removed
Chronic: irreversible loss of the pancreatic tissue
What are causes of acute pancreatitis
Gallstones (50%) Alcohol (25%) Rare causes(<5%): -vascular insufficiency -viral infection (mumps, coxsackie B) -hypercalcaemia -ERCP -Inherited causes Idiopathic (10%)
What is hereditary pancreatitis
Recurrent attacks of severe pancreatitis
Usually begins in childhood
PRSS1 inherited mutations- autosomal dominant
SPINK 1 gene- autosomal recessive
What do PRSS1 inherited mutations do
Alter a site on the cationic trypsinogen molecule that is essential for inactivation of trypsin by itself
Mutations result in trypsin being resistant to cleavage by another trypsin molecule
Small amounts of trypsin activation results in activation of other digestive enzymes resulting in pancreatitis
What does SPINK 1 gene code for
A trypsin inhibitor which helps prevent auto digestion of pancreas by activated trypsin
What are the clinical features of acute pancreatitis
Presents in emergency state
Sudden onset of severe abdominal pain radiating to back
Nausea and vomiting
May be mild (recovery within 5-7 days) but can be serious with high mortality
Raised serum amylase/lipase (>3x normal)
Persistent hypocalcaemia is a poor prognostic sign
What are the potential complications of acute pancreatitis
Shock
Intravascular coagulopathy
Haemorrhage
Pseudocysts (collections of pancreatic juice secondary to duct rupture)
What is chronic pancreatitis
Progressive inflammatory disorder in which parenchyma of pancreas is destroyed and replaced by fibrous tissue
Irreversible destruction of the exocrine tissue, followed by destruction of the endocrine tissue
Leads to malnutrition and diabetes
How does chronic pancreatitis present
Intermittent abdominal pain
Back pain
Weight loss
Fibrosis of exocrine tissue
What are the complications of chronic pancreatitis
Malabsorption of fat (lack of lipase):
- staetorrhoea
- impairment of var soluble vitamin absorption (A, D, E, and K)
- Diabetes (late feature)
- pseudocysts
- severe chronic pain
- Mortality rate 50% with 20-25 years of disease onset
What is a desmoplastic response
Intense non-neoplastic host reaction composed of fibroblasts, lymphocytes and extracellular matrix
What are the poor prognostic factors of pancreatic adenocarcinoma
Extension of tumour outside of the pancreas Metastatic spread to local lymph nodes Vascular and perineurial invasion Poor differentiation Positive margins on resection
What is cholangiocarcinoma
Malignant tumour of bile duct cells
What is angiosarcoma
Aggressive tumour of blood vessels
What are the potential complications of gallstones
Obstruction at neck (pain) Chronic cholecystitis Perforation Obstruction at pancreatic level (pancreatitis) Adenocarcinoma (rare)
What is chronic cholecystitis
Inflammation of the gallbladder
What can cause liver disease
Poisoning Drugs Infection Alcohol Inadequate perfusion Fatty liver Autoimmunity Metabolic Tumours and metastases
What are the systemic effects of liver disease
Jaundice Oestrogen (gynaecomastia, spider naevi, liver palms, testicular atrophy) Bruising Pigmentation Clubbing Dependent oedema ascites encephalopathy Osteomalacia/ osteoporosis
What are the available liver function tests, testing
Production of metabolites Clearance of endogenous substances Clearance of exogenous substances Hepatocellular damage Biliary tract damage Through Imaging and biopsy
What are the routine LFTs
Alkaline phosphatase ALT (alanine aminotransferase) Bilirubin Albumin Total protein GGT (gamma glutamyl transferase)
What are the three stages of alcoholic liver disease
Fatty liver
Alcoholic hepatitis
Cirrhosis
What is primary biliary cirrhosis
Chronic cholestatic condition with destruction of bile ducts
What is primary sclerosing cholangitis
Progressive disease characterised by diffuse inflammation and fibrosis of the biliary system
What do levels of bilirubin show
Excretory capacity of the liver and free flow of bile
When should LFTs be measured
Signs and symptoms: -Pain -itchy -jaundice -TATT -Bruising Lifestyle: -Alcohol -Obesity -Diabetes -recent travel -drug use Is liver disease present?: -hepatitis -haemochromatosis -liver cancer -drugs How sever?: -Chronic hepatitis vs acute onset
What are the disorders of the pancreas
Acute pancreatitis Chronic pancreatitis Pancreatic insufficiency Cystic fibrosis Carcinoma of the pancreas
What are the medical liver diseases
Jaundice Acute and chronic hepatitis: -viral -alcohol -obesity -drugs -inherited (haemochromatosis, Wilson's, Alpha-t antitrypsin deficiency) -Autoimmune Cirrhosis Hepatic failure
What is jaundice
Visible when bilirubin >40umol/l
Commonest sign of liver disease
Pre-hepatic:
- too much bilirubin produced (haemolytic anaemia)
- unconjugated (bound to albumin, insoluble, not excreted) showing symptoms of yellow eyes/skin only
Hepatic:
- too few functioning liver cells (acute diffuse liver cell injury, end stage chronic liver disease, inborn errors)
- mainly conjugated (soluble) patients symptoms of yellow eyes and dark urine
Post-hepatic:
- bile duct obstruction (stone, stricture, tumour in bile duct or pancreas)
- Conjugated (soluble, excreted but can’t get into gut) symptoms of yellow eyes, pale stool and darkurine
What is unconjugated bilirubin, how does it become conjugated and where does it then go
Bilirubin produced by red blood cell breakdown
Metabolised in liver (conjugated)
Excreted in bile with some being re-absorbed from the gut
What is hepatitis
Inflammation in the liver (any liver disease that is not neoplastic)
What is NAFLD
Non-alcoholic fatty liver disease
What is DILI
Drug induced liver injury
What is the commonest cause of acute liver failure in the UK
Paracetamol as at toxic levels it results in necrosis of a high proportion of hepatocytes in a predictable zonal distribution without any inflammation
What is Wilson’s disease
Inborn error of copper metabolism Copper accumulates in: -liver causing cirrhosis -Eyes causing Kayser-Fleischer rings -Brain causing ataxia etc Treatment to chelate copper and enhance its excretion
What is a potential complication of cirrhosis of the liver
Hepatocellular carcinoma
What is the definition of cirrhosis
Define histologically as a diffuse hepatic process characterised by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules
End stage of all chronic liver disease.
Liver is converted into a mass of regenerating nodules wrapped by fibrous scar tissue
What are the causes of cirrhosis
Alcohol
Non-alcoholic steatohepatitis (metabolic syndrome)
Chronic viral hepatitis (B orC)
Autoimmune liver disease (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosis cholangitis)
Metabolic (iron, copper, alpha 1 antitrypsin)
What is the role of liver biopsy in chronic liver disease
Information of:
- stage of disease
- cause of disease
- current activity
- response to treatment
