Block 15 Flashcards
What is ulcerative colitis? (definition)
Severe ulcerating inflammatory disease that is limited to the colon and rectum and extends only into the mucosa and submucosa
What are the macroscopic features of Crohn’s disease?
Small and large intestine Skip lesions Strictures Thick walls Cobblestone Creeping fat
What are the macroscopic features of ulcerative colitis?
Colon only
Diffuse distribution - continuous
No strictures
Thin walls
What are the microscopic features of Crohn’s disease?
Transmural inflammation Deep, knife like ulcers Marked lymphoid reaction Marked serositis Granuloma Fistula Crypt abscesses Paneth cell metaplasia
What are the microscopic features of ulcerative colitis?
Inflammation limited to mucosa Marked pseudopolps Ulcers are superficial with a broad base No Granulomas No fistulas
What are the clinical features of chron’s disease?
Perianal fistula
Fat/vitamin absorption
Recurrence post op
Intermittent attacks of relatively mild bloody diarrhoea, fever and abdo pain (RLQ)
Periods of active disease with asymptomatic periods in between
Can be triggered by smoking and stress
Fistulae
What are some of the extra-intestinal manifestation of Crohn’s disease?
Uveitis
Migratory polyarthritis
Ankylosing spondylitis
Clubbing
What are the clinical features of ulcerative colitis?
Relapsing attacks of bloody diarrhoea with stringy mucoid material
Lower abdominal pain
Cramps (relieved by defaecation)
Can be relieved by smoking
What is gastroenteritis?
a syndrome characterised by GI symptoms including nausea, diarrhoea, vomiting and abdominal discomfort
Microbiology of E.Coli
4 different strains: ETEC, EIEC, EHEC, EPEC
Gram negative baccilus
Facultatively anaerobic
Microbiology of salmonella
Gram negative bacilli
Flagellated facultatively anaerobic
How does salmonella cause inflammation and diarrhoea?
Penetrates cells
Migrates to lamina propria of ileocecal region
Multiplies in lymphoid follicles – hyperplasia and hypertrophy
Leucocytes confine infection to GI tract
Stimulates cAMP and active fluid secretion
Diarrhoea
Epidemiology of Crohns and ulcerative colitis?
Females
Teens / early 20s
Caucasians
Incidence is increasing worldwide
Pathogenesis of inflammatory bowel disease?
Combination of defects in host interactions with intestinal microbiota, intestinal epithelial dysfunction and aberrant mucosal immune responses
Bacteria enter bowel (influx of bacterial components due to barrier defect)
Activated dendritic cells to commensals
T helper 1 cells - activate macrophages and secrete TNF gamma
T helper 2 cells - secrete IL13
T helper 17 cells - activate neutrophils
NOD2 gene believed to have a link
Microbiology of campylobacter jejuni
Gram negative bacilli
What does bile do?
Emulsifies dietary fats
Helps eliminate excess cholesterol, bilirubin and other waste products
Signalling molecules - activate MAPK pathway involved in gut signalling
Microbiology of cholera
Comma shaped gram negative
Vibrio cholerae
Need to be ingested in large numbers
Produces a toxin that causes a massive fluid and electrolyte loss with no damage to enterocytes
Microbiology of shigella
Gram negative bacilli
Faecal-oral, contaminated food and water
Non motile facultatively anaerobic
Different species, shigella dysentriae causes the most severe form
Rotavirus
Double stranded RNA
Causes diarrhoea by damaging transport mechanisms
What are the bacteria responsible for food poisoning?
Salmonella Norovirus Campylobacter E. Coli Listeria Clostridium perfringens
What are the 4 mechanisms of diarrhoea?
Osmotic
Secretory
Inflammatory
Abnormal motility
Describe osmotic diarrhoea
Fluid enters the bowel if there are large quantities of non-absorbed hypertonic substances in the lumen. It occurs because:
- patient ingested non absorbable substance
- patient has generalised malabsorption so high concentrations of solute e.g. Glucose remain in the lumen
- patient has specific absorptive defect e.g. Disaccharidase deficiency
Diarrhoea stops when you stop eating
Causes of secretory diarrhoea
Enterotoxins (cholera, E. coli, c diff) Hormones (VIP) Bile salts in colon Fatty acids in colon Some laxatives
Describe inflammatory diarrhoea
Occurs due to damage of the intestinal mucosal cells so loss of fluid and blood. Defective absorption of fluid and electrolytes
Dysentery due to shigella, inflammatory conditions like crohns and ulcerative colitis
Causes of abnormal motility diarrhoea
Diabetes
Post vagotomy
Hyperthyroid
Causes of gallstones
Chronic haemolytic Inflammation Infection Rapid weight reduction Stasis e.g. Pregnancy, spinal cord injuries Lithogenic bile
What are the complications of gall stones?
Most are silent
In gall bladder or cystic duct
- acute/chronic cholecystitis
- empyema
- perforations
What stimulates gut motility?
Stretch
ACh
Parasympathetics
Define inanition
Exhaustion caused by lack of nourishment
Define anorexia
Lack or loss of appetite for food
Define cachexia
Wasting syndrome. Loss of weight, muscle atrophy, fatigue, weakness and significant loss of appetite in someone not actively trying to lose weight.
Loss do body mass than can’t be reversed nutritionally.
Describe the control of appetite
Hypothalamic arcuate nucleus is where various substances act.
Gherlin is released from the stomach and stimulates hunger. This increases neuropeptide Y which increases appetite and increases body weight
Leptin is released from adipose tissue and stimulates satiety. This decreases neuropeptide Y which decreases appetite and body weight
Name some methods to stop bacteria crossing the epithelial lining of the gut
Mechanical - tight junctions, longitudinal flow of fluid
Chemical - low pH, enzymes (pepsin)’ antibacterial peptides released from panneth cells, mucus
Biological - commensal bacterial flora
Causes of acute pancreatitis
Gallstones Alcohol Trauma, surgery, ERCP Viral infections e.g. Mumps Hypothermia Ischaemia Drugs Rare - hyperparathyroidism, hyperlipidaemia
Signs and symptoms of pancreatitis
Acute abdominal pain
Central and severe pain that often radiates to the back
Vomiting
History of alcohol excess, gall stones and certain drugs
Guarding and tenderness in upper abdomen
What would you expect to find on investigation of acute pancreatitis?
Raised serum amylase
Glucose intolerance
Hypocalcaemia
Raised CRP, WBC
Causes of chronic pancreatitis?
Alcohol, most common in males Biliary tract disease Hypercalcaemia Hyperlipidaemia Cystic fibrosis Idiopathic
Describe the mucosal immune system
MALT (mucosal associated lymphoid tissue)
3/4 of all lymphocytes are found in MALT
What are the effector cells formed from CD4+ cells?
TH1
TH2
TH17
What are the regulatory cells formed from CD4+ cells?
TR1
TH3
CD26
What substances are released from TH1 cells?
IFN gamma
Outline GALT
Gut associated lymphoid tissue
- Peyers patches
- Isolated lymphoid follicles
- Mesenteric lymph nodes
What is the dominant antibody in the mucosal immune system?
IgA
2 Y shaped antibodies connected end to end
Joined by a J chain
How are antigens detected by the gut immune system?
- Antigen presented at mucosal system
- Need to cross the epithelial barrier to stimulate the immune system
- Peyers patches are covered in M cells
- They take up the antigen via endocytosis
OR dendritic cells extend across epithelial layer to get to bacteria
What is the function of IgA in the immune system?
Binds to mucus Neutralises pathogens and toxins Prevents adherence of micro organisms Neutralise LPS and toxins Can't activate complement - no inflammation
What are the 2 different types of malnutrition?
Protein-energy metabolism
Physiological well, anorexia, suppression of appetite
Neglect
Specific malnutrition
Nutrient deficiency
What are the causes of bacterial overgrowth of the GI tract?
Jejunal diverticulosis
Obstruction
Motility disorders
Blind loop syndrome
What are the features of coeliac disease?
Gluten enteropathy Immune mediated Subtotal villous atrophy Crypt hyperplasia Intraepithelial lymphocytes Deficiency - iron, folate, vitamin D
What do you test in the blood for coeliac disease?
Anti-tissue tranglutaminase
What is the incidence of ulcerative colitis and Crohns?
UC - 11/ 100 000
Crohn’s - 7/ 100 000
What is the concordance in monozygotic twins for ulcerative colitis and Crohn’s?
UC - 8%
Crohn’s - 67%
What are the presdisposing factors for GI infections?
Age - extremes of age Immunodeficiency - HIV Achlorhydria - absence of gastric acid Inoculum size Pathogen virulence factors
What are the 4 antibiotic causes of C.diff infection?
4 C’s
Cephalosporin
Co-amoxiclav
Clindamycin
Clarithromycin
What are the features of non-inflammatory GI bacterial infections?
No invasion of mucosa Enterotoxins Mucosal adherence Proximal small bowel Vibrio cholerae, enterotoxogenic E. Coli
What are the features of inflammatory GI bacterial infections?
Invasion of mucosa
Colon
Campylobacter, salmonella, shigella
What are the features of penetrating GI bacterial infections?
Induced phagocytosis
Distal small bowel
Salmonella typhi, listeria monocytogenes
What are the consequences of bacterial overgrowth syndrome?
Malabsorption Steatorrhoea Diarrhoea Macrocytic anaemia Deficiency of fat soluble vitamins >10^5 bacteria per ml
What are the methods for disease control?
Surveillence - notifiable under public health act Epidemiology Education Environmental change Immunisation Law
What are the methods for disease prevention?
Public education Staff training Food inspector Equipments well maintained Good raw materials - farm to fork
Define outbreak
When 2 or more people contract the same infection from a common source
What is the blood supply to the liver?
Coeliac trunk - common hepatic - hepatic artery proper
Hepatic artery proper - 20% volume, 80% oxygen
Hepatic portal vein - 80% volume, 20% oxygen
Anatomy of the liver?
4 lobes: right, left, caudate, quadrate Falciform ligament (anterior) Anterior and posterior ligament Triangular ligaments Ligamentum venosum (superior) Ligamentum teres (inferior)
What are the functions of the liver?
Storages of glycogen Gluconeogenesis Protein synthesis Catabolism of amino acids Lipoprotein synthesis Detoxification of nitrogenous molecules Drug metabolism Bilirubin conjugation
Describe the hepatic lobule
Triad - branch of portal vein, branch of hepatic artery, bile duct
Sinusoids surrounding by hepatocytes that drains into central vein
Bile canaliculous drains in opposite direction
Hepatitis A virus
ssRNA
Faecal - oral transmission
Incubation 2-4 weeks
Never causes chronic disease
What are the risk factors for hep A infection?
Personal contact Travel to high risk areas Male homosexuality Intravenous drug use Certain occupation (sewage workers)
What are the clinical features of a hep A infection?
Mild flu like symptoms Anorexia Nausea Fatigue Malaise Joint pain Preceding jaundice Potentially diarrhoea
Icteric phase - dark urine (appears first), pale stools (not always), jaundice (70-85%), abdominal pain, itch, skin rash, hepatomegaly, splenomegaly, lymphadenopathy
Hepatitis B virus
dsDNA
Paenteral, sexual, perinatal spread
Incubation 1-4 months
Chronic frequency 10%
What are the clinical syndromes that can be caused by hep B virus?
Acute hepatitis with recovery and clearance of virus
Fulminant hepatitis
Non progressive chronic hepatits
Progressive chronic disease ending in cirrhosis
Asymptomatic carrier state
How common are each of the consequences of hep B infection?
60-65% - sub clinical disease (100% recovery)
20-25% - acute hepatitis (99% recovery, 1% fulminant hepatitis –> death)
5-10% - carrier
4% - chronic hepatitis (20-30% cirrhosis, also recovery, hepatocellular carcinoma)
Hepatitis C virus
ssRNA
Transmission - parenteral, intranasal
Incubation - 7-8weeks
Chronic frequency - 80%
How common are each of the consequences of hep C infection?
15% resolution
85% chronic hepatitis (80% stable disease, 20% cirrhosis) Of the 20% that get cirrhosis (50% stable cirrhosis, 50% death)
Rare - fulminant hepatitis
What are the risk factors for progression from hep C to cirrhosis?
Male
over 40
Alcohol
Asian
What are the medical consequences of alcohol?
Liver: alcoholic hepatitis, cirrhosis, liver cancer
GI: oral cavity cancer, oesophageal neoplasm and varices, pancreatitis
CV: AF, hypertension, stroke, cardiomyopathy
Neuro: loss of consciousness, withdrawal, seizures, subdural haemorrhage, peripheral neuropathy, cerebellar degeneration
What are the psychiatric consequences of alcohol?
Alcohol dependence syndrome
Suicidal ideation
Depression
Anxiety
What are the causes of pancreatitis?
Idiopathic Gall stones Ethanol (alcohol) Trauma Steroid Mumps/malignancy Autoimmune Scorpion bite Hyperlipidaemia/ Hypothermia ERCP Drugs
What genes are linked with pancreatitis?
PRSS1 trypsinogen gene
SPINK1 - pancreatic secretory trypsin inhibitor (prevents water digestion)
How does pancreatitis occur?
Pancreatic duct obstruction, increase in duct pressure, accumulation of enzyme fluid into interstitium
Acinar cell injury causing release of enzymes
Defective intracellular transport - proenzymes inappropriately delivered to intracelluar compartment containing lysosymes
What happens in pancreatitis?
Microvascular damage and leakage causing oedema
Necrosis of fat by lipolytic enzyme
Acute inflammation
Proteolytic destruction of pancreatic parenchyma
Destruction of blood vessels causing interstitial haemorrhage
What is the incidence of pancreatitis?
10-20 per 100,000
What are the clinical features of pancreatitis?
Abdominal pain - constant and intense Often referred to back and occasionally the left shoulder Severity from mild to incapacitating Anorexia Nausea Vomiting Elevated amylase and lipase
Medical emergency
Define chronic pancreatitis
Inflammation of the pancreas with irreversible destruction of exocrine parenchyma, fibrosis and in the late stages destruction of endocrine parenchyma
What are the causes of chronic pancreatitis?
Long term alcohol abuse
Long standing obstruction of pancreatic duct
Hereditary pancreatitis
What happens in chronic pancreatitis?
Parenchymal fibrosis
Decreased number and size of acini
Sparing of Langerhans cells
Variable dilation of pancreatic ducts
Chronic inflammatory infiltrate around lobules and ducts
Ductal epithelium = atrophied or hyperplastic or squamous metaplasia
What are the clinical features of chronic pancreatitis?
Can present in several ways:
- Repeated attacks of abdo pain or persistent back and abdo pain
- Entirely silent until pancreatic insufficiency and diabetes develop
- Recurrent attacks of jaundice
- Vague attacks of indigestion
Attacks can be precipitated by alcohol abuse, overeating, opiate use
Mild fever
Weight loss
Hypoalbuminaemic oedema
What is peritonitis?
Occurs when bacteria from GI lumen are released into abdo cavity
Usually E.Coli, streptococci, S. aureus or enterococci
What are the clinical features of peritonitis?
Acute abdo pain Abdo tenderness Abdominal guarding Exacerbated by moving peritoneum Rebound tenderness Fever Sinus tachycardia
What are the features of peritonitis?
Dull peritoneal surfaces
Turbid fluid accumulation
Volume of fluid can vary
Dense collection of neutrophils
What are the clinical features of severe hepatic dysfunction?
Jaundice and cholestasis Hyperammonaemia Palmar erythema Hypogonadism Weight loss Hypoalbuminaemia Hypoglycaemia Spider angiomas Gynaecomastia Muscle wasting
What are the main primary disease of the liver?
Viral hepatitis
Alcoholic liver disease
Non alcoholic fatty liver disease
Hepatocellular carcinoma
What is hepatic encephalopathy?
Can develop with acute or chronic liver disease
Occurs due to severe loss of hepatocellular function and shuntingof blood from portal to systemic circulation around a chronically diseased liver.
Patients show a spectrum of brain dysfunction from subtle abnormalities to coma
Rigidity, hyper relfexia, asterixis (flapping tremor)
What is cirrhosis?
Diffuse process characterised by fibrosis and conversion of normal liver architecture to structurally abnormal nodules
What processed are central to the pathogenesis of cirrhosis?
Death of hepatocytes
Extracellular matrix deposition
Vascular reorganisation
Pathogenesis of cirrhosis?
Activated stellate cells (myofibroblasts) - release chemokines and growth factor
Produce excess collagen
Dense extracellular matrix
Loss of fenestration in endothelial cells (increases pressure in sinusoids and decreases solute exchange)
Loss of microvilli on hepatocytes (decrease transport capability)
Activated Kupffer cells
What are the clinical features of cirrhosis?
Can be clinically silent Non specific symptoms Anorexia Weight loss Weakness Incipient or overt hepatic failure Complications related to portal hypertension
What are the causes of cirrhosis?
Hep B and C Alcoholic and non alcoholic steatohepatitis Autoimmune Biliary disease metabolic conditions (haemochromatosis)
What is portal hypertension?
Increased resistance to portal blood flow which can develop from prehepatic, intrahepatic or posthepatic causes
What is the pathogenesis of portal hypertension?
Increase resistnance to flow at level of sinusoids and compression of central veins by perivenular fibrosis and parenchymal nodules
Anastamoses between arterial and portal systems
Increase in portal blood flow from hyperdynamic circulation
Arterial vasodilation in splanchnic circulation
What are the clinical consequences of portal hypertension?
Ascites Hepatic encephalopathy Spider angioma Oesophageal varices Splenomegaly Periumbilical caput medusa Testicular atrophy Haemmorhoids
What is a portosystemic shunt?
With rises in portal venous pressure, shunts develop where systemic and portal circulations share capillary beds
Where are common locations to get portosystemic shunts?
Veins around rectum - haemmorhoids
Cardioesophageal junction - varices
Retroperitoneum
Falciform ligament of liver
What are the 3 liver alterations in fatty liver disease?
Steatosis
Hepatitis
Fibrosis
What are the microscopic changes in fatty liver disease?
hepatocyte ballooning Mallory-Denk bodies neutrophil infiltration central vein sclerosis chicken wire fence pattern - fibrosis
What does hepatocellular steatosis result from?
Shunting of substrates away from catabolism and toward lipid biosynthesis
Because of excess nicotinamide-adenine dinucleotide from metabolism of ethanol by alcohol dehydrogenase
Impaired assembly and secretion of lipoproteins
Increased peripheral catabolism of fat
What are the causes of alcoholic hepatitis?
Acetaldehyde (metabolite of ethanol) induces lipid peroxidation which may disrupt cytoskeleton and membrane function
Alcohol affects cytoskeleton organisation, mitochondrial function and decrease membrane fluidity
Reactive oxygen species
Cytokine mediated inflammation - TNF, IL1, IL6, IL8
What are the clinical features of hepatocellular steatosis?
Hepatomegaly
mild elevation of serum bilirubin and alkaline phosphatase
What are the clinical features of alcoholic hepatitis?
Acute onset after bout of heavy drinking Malaise Fever Anorexia Weight loss Upper abdominal discomfort Tender hepatomegaly
What are the investigation findings in alcoholic hepatitis?
Hyperbilirubinaemia
Increased alkaline phosphatase
Increased neutrophilic leukocytes
Increased serum ALT and aspartate aminotransferase
What is non alcoholic fatty liver disease commonly associated with?
Insulin resistance Metabolic syndrome Type 2 diabetes Obesity Dyslipidaemia Hypertension
What happens in non alcoholic fatty liver disease?
Steatosis, steatohepatitis, cirrhosis
Impaired oxidation of fatty acids
Increased synthesis and uptake of fatty acids
Decreased hepatic secretion of VLDL
Increased levels of TNF, IL6 which cause liver damage and inflammation
Describe Wilsons disease
autosomal recessive
Accumulation of toxic levels of copper in organs and tissues especially in the brain, liver and eye.
Mutations in ATP7B gene on chromosome 13
Without ATP7B copper can’t be passed onto apoceruloplasmin
Can’t be excreted into bile
Copper causes toxic injury
Red cell haemolysis and damage due to deposition
Mimics fatty liver disease - cirrhosis
What are the different tests included in the LFTs?
Bilirubin Albumin Transferases - ALT (alanine aminotransferase) - AST (aspartate aminotransferase) Gamma gutamyltransferase GGT Alkaline phosphatase ALP
What LFT changes would you expect in obstructive disease?
Increased ALP
Increased GGT
Small increase in AST and ALT
What LFT changes would you expect to see with intra-hepatic damage?
Increased AST
Increased ALT
Small increase in ALP and GGT
In what condition would you expect ALT to be greater than AST?
Chronic liver disease
In what condition would you expect AST to be greater than ALT?
Cirrhosis
What would cause an increase in GGT and ALP?
Cholestasis
What would cause an increase in GGT with normal ALP?
Alcohol
Outline drug metabolism
2 reactions: phase 1 and phase 2, usually in liver
Phase 1 - catabolic and products are often more chemically reactive and can be more toxic than parent drug
Phase 2 - synthetic resulting in inactive produces
Describe phase 1 reactions
Involve the P450 mono oxygenase system
CYP…
Drug \+P450 enzyme \+molecular oxygen \+NADPH \+flavoprotein
Addition of an oxygen atom to form a hydroxyl group
Not all phase 1 reactions involve the P450 system
Describe phase 2 reactions
After phase 1 it is susceptible to conjugation = attachment of substituent groups
Resultant conjugate is almost always inactive
e.g. glucaronyl transfer - UDP glucuronyl transferase
Describe first pass metabolism
Some drugs are extracted so efficiently by liver or gut wall that the amount reaching the systemic circulation is considerably less than the amount absorbed
Much larger dose required when given orally and is unpredictable
Example of drugs that undergo first pass metabolism
Aspirin Metoprolol Morphine Propranolol Salbutamol Verapamil Lidocaine Levadopa GNT
What are the characteristics of preheaptic jaundice?
Inability to conjugate bilirubin fast Increased serum unconjugated bilirubin Decreased or no bilirubin in urine Increased urobilinogen in urine or faeces Dark brown faeces
Unconjugated hyperbilirubinaemia
What are the causes of prehepatic jaundice?
Sickle cell anaemia Thalassaemia Spherocytosis Incompatible blood transfusion Malaria Haemolytic anaemia
What are the characteristics of hepatic jaundice?
Increase in conjugated or unconjugated bilirubin Decreased faecal urobilinogen Increased urinary urobilinogen Pale stool Dark urine Increased ALT and AST
What are the causes of hepatic jaundice?
Gilberts Cirrhosis Viral hepatitis Alcoholic hepatitis Autoimmune hepatitis Drug induced hepatits
What are the characteristics of post hepatic jaundice?
Increased conjugated bilirubin Bilirubin in urine Decreased faecal urobilinogen No urobilinogen in urine Pale stools Dark urine Increased ALP, ALT, AST
What are the causes of post hepatic jaundice?
Gall stones Gall bladder carcinoma Pancreatic carcinoma Primary sclerosing cholangitis Pancreatitis Bile duct strictures
Epidemiology of bowel cancer
3rd most common UK cancer
2nd most common cause of cancer death
47/ 100 000
Higher in men than women
What are the risk factors for bowel cancer?
Family history of colorectal cancer under 60y IBD Crohns UC Polyposis syndromes Nulliparity Late age of first pregnancy Early menopause Diet: rich in meat and fat, low fibre Sedentary lifestyle Smoking Alcohol Obesity Diabetes
Presentation of left sided colon cancer
colicky pain rectal bleeding bowel obstruction tenesemus mass in left iliac fossa early change in bowel habit
Presentation of right sided colon cancer
weight loss anaemia occult bleeding mass in right iliac fossa more advanced on presentation
What is the prognosis (5 year survival rate) for bowel cancer?
Stage 1 = T1/2 M0 N0 = 75%
Stage 2 = nodal involvement = 60%
Stage 3 = T3/4 - 50%
Stage 4 = M1 6%
Describe hyperplastic polyps
Common epithelial proliferations in 60s and 70s
Results from decreased epithelial cell turnover and a pile up of goblet cells
Smooth nodular protrusions
<5mm in left colon
Describe hamartomatous polyps
Occur sporadically
Disorganised tumour like growths with mature cells
Increased risk of developing colorectal cancer
Pedunculated smooth surfaced red lesions
<3cm in diameter
Describe adenomas in the colon
Benign polyps that give rise to colorectal adenocarcinomas
Epithelial dysplasia
0.3-10cm can be pedunculated or sessile
Size correlates with risk of malignancy
Outline FAP
Familial adenomatous polyposis Autosomal dominant Mutations in APC gene Need at least 100 polyps on endoscopy Colorectal adenocarcinoma in 100% if untreated by 30
Describe hereditary nonpolyposis colorectal cancer
HNPCC - familial clustering of cancers at several sites
Colorectal, endometrium, stomach, brain
Occurs at a younger age often in right colon
Mutation in MSH2/1
Outline the pathogenesis of adenocarcinoma
Combination of genetic and epigenetic abnormalities
Mutations of APC tumour suppressor
APC/beta catenin pathway
Causes transcription of genes which promote proliferation
KRAS (late mutation) - promotes growth
TP53 mutation - 70% of cancers
BAX enhances survival of genetically abnormal clones
Describe the morphology of adenocarcinoma
Tumours in proximal colon
Rarely cause obstruction
Grow along wall
Tumours in distal colon
Annular lesions, napkin ring contrictions
Luminal narrowing
Tall columnar cells
Dysplastic epithelium
What methods are used to view the GI tract?
Barium swallow/meal/follow through Barium enema Colonoscopy Endoscopy Abdominal ultrasound CT scan MRI
What should you think about when choosing a method of GI imaging?
Availability Patient tolerance Cost Risk of complications Most likely to answer clinical question
What are the single and double contrast used in barium radiology?
Single - lumen distended with barium
Double - mucosa coated with barium and lumen distended with air
What are the limitations of barium swallow/meal?
Limited senstivity for cancer and inflammation
Miss early lesions
Patients need to be fit and mobile
Need to retain stomach full of gas and barium
Poorly tolerated by elderly
What are the requirements for barium enema?
2 days starvation
Strong laxative
Barium into colon via rectal tube
Colon distended with air or CO2
What are the benefits of double contrast barium enema?
Safe with low complication rate
Well tolerated
Complete examination
Able to detect intrinsic and extrinsic disease
What are the limitations of DCBE?
Patients need to be mobile
Must be able to retain air and barium in colon
Less sensitive than colonoscopy
No scope for obtaining histology
What are the benefits of endoscopy?
Direct inspection of mucosa
Detects early pathology
Allows for biopsy or therapeutic procedure
Identifies conditions not seen at DCBE
What are the limitations of endoscopy (gastric)?
Less good at assessing motility and extrinsic disease Limited views of pharynx and cervical oesophagus Significant complication rate 0.1% Mortality rate 0.03% Cardiopulmonary problems if sedated Perforation Haemorrhage Transmission of infection
What are the common causes of upper GI bleeding?
Duodenal ulcers 20-30% Gastric or duodenal erosions 20-30% Varices 15-20% Gastric ulcer 10-20% Mallory-Weiss tear 5-10% Erosive oesophagitis 5-10% Angioma 5-10% Arteriovenous malformations <5%
What are the common causes of lower GI bleeding?
Anal fissures Angiodysplasia Colitis Colonic carcinoma Colonic polyps Diverticular disease IBD Internal haemorrhoids
What is the Rockall score and what does it take into account?
Used to determine risk for endoscopy
Age
Shock
Co-morbidity
Predicts mortality
Describe fluid absorption in the gut
80% in small intestine
80% of remaining 20% removed in large intestine
Describe the process of defaecation
Collection of faeces in sigmoid colon and rectum
Pressure on walls of large intestine
Involuntary - large peristaltic wave, distension of walls and opening of internal anal sphincter
Pelvic nerve
Voluntary - delay (reverse peristalsis, open external sphincter)
Pudendal nerve
Open sphincters
Levator ani contracts reducing anal-rectal angle
Anatomy of the adrenal glands
On top of each kidney
Inner medulla
Outer cortex
Surrounded by perinephric fat, enclosed in renal fasica
Cortex has 3 areas -
Zona glomerulos
Zona fasciculata
Zona reticularis
What is the blood supply to the adrenal glands?
Superior suprarenal (from inferior phrenic artery) Middle suprarenal (abdominal aorta) Inferior suprarenal (renal arteries)
What is secreted from each area of the adrenal cortex?
Zona glomerulosa - mineralocorticoids (aldosterone)
Zona fasciculata - glucocorticoids (cortisol)
Zona reticularis - gonadocorticoids (androgens)
Describe the adrenal medulla?
Chromaffin cells in clusters around blood vessels
Produce adrenaline and NA
