Gastrointestinal System

ContentsPage 5 Cardiovascular Anatomy

Pericardium Left/Right Atrium and Left/Right Ventricle Atrioventricular and Semilunar Valves

Page 7 Cardiac Muscle Sarcomeres

Page 8 Histology of Blood Vessels Arteries Veins

Page 10 Histology of Heart Muscle (Mitral Valve)

Page 11 Cholesterol and Lipoproteins Review

Page 12 Electrical and Contractile Function Pacemaker/Contractile Cell Action Potentials Intrinsic Conduction Network Extrinsic/Neural Control of the Heart

Page 14 Cardiac Cycle

Page 15 Heart Murmurs Normal Heart Sounds Systolic and Diastolic Murmurs S3 and S4 Heart Sounds

Page 17 Blood Pressure Definitions Regulation of CO / HR / Blood Flow / BP

Page 19 Electrocardiograms (ECG) Supraventricular Arrhythmias / Ventricular Arrhythmias Pulseless Electrical Activity (PEA) Cardiac Arrests Atrioventricular (AV) Heart Blocks 12 Lead ECG Myocardial Infarctions / Acute Coronary Syndrome Takotsubo Syndrome

Page 28 Atrial Fibrillation (AF)

Page 29 Hypertensive Heart Disease Primary / Secondary HTN Pulmonary HTN / Cor Pulmonale Benign / Accelerated Nephrosclerosis

Page 31 Peripheral Vascular Disease

Page 33 Congenital Heart Disease Left-to-Right Shunts Right-to-Left Shunts Obstructive Lesions

Page 33 Valvular Heart Disease Degenerative Valve Disease Non-Bacterial Thrombotic Endocarditis (NBTE)

Page 36 Ischaemic Heart Disease Acute Coronary Syndrome (ACS) Myocardial Infarction (MI)

Page 38 Congestive Heart Failure (CHF)

Page 40 Cardiomyopathy Dilated / Hypertrophic / Restricted Cardiomyopathy (DCM / HCM / RCM)

Myocarditis

Page 41 Cardiovascular Drugs Diuretics Angiotensin Converting Enzyme Inhibitor (ACEI) Angiotensin II Receptor Blocker (ARB) Calcium Channel Blocker (CCB) -Blockers Statins Nitrates Anti-arrhythmics Thrombolytics / Anticoagulants / Anti-platelets Nicorandil

Page 46 Triple Whammy – Drug Interactions

Page 47 Vaughan Williams Classification of Antiarrhythmic Agents Sodium Channel Blockers / -Blockers / Anti-Arrhythmics / CCBs

Page 48 Pharmacological Guidelines for Management of VCD Hypertension (HTN) Ischaemic Heart Disease (IHD) / Angina / Unstable Angina (UA) / NSTEMI / STEMI Arrhythmias Heart Failure Hypercholesterolaemia

Page 51 Cardiovascular History

Page 51 Cardiovascular Physical Examination

Histology of the Gastrointestinal TractClassification of Epithelia

Squamous: When the width of the cell is greater than the height

Cuboidal: When the width, depth and height are approximately the same

Columnar: When the height exceeds the width.

Pseudo-stratified: Epithelium appears stratified although some of the cells do not reach the free surface

Transitional: Epithelium (urothelium) lines lower urinary tract (urinary bladder, ureters and superior urethra + gland ducts of the prostate). It is a stratified epithelium which allows it to distend.

Functions of Epithelia

Secretion: Eg. Columnar epithelium – stomach and gastric glands

Absorption: Eg. Columnar epithelium in gut and proximal convoluted tubules in the kidney

Transport: of materials along surface by cilia or across the epithelium to and from the connective tissue

Protection: As in stratified squamous epithelium of skin or transitional epithelium of urinary bladder

Receptor function: To receive and interpret external stimuli as in taste buds, olfactory epithelium and the retina of the eye.

Oral Cavity

Hard Palate: Consists of keratinised and parakeratinised stratified squamous epithelium

Lining Mucosa: Eg. Lips, cheek, floor of mouth and inferior surface of tongue is non-keratinised. Stratum basale (resting on basal lamina) Stratum spinosum Stratum superficiale (surface layer of mucosa)

Tongue: Muscular organ with both intrinsic and extrinsic muscles. Dorsum of the tongue is divided by the sulcus terminalis.

Multiple lingual papillae cover the surface: Filiform (like lines on the surface) Fungiform (like mushrooms on the surface) Foliate (like gills on the side) Circumvallate (like toadstools at the back in a V shape)

Salivary Glands: Paired parotid, submandibular and sublingual glands Parotid gland is completely serous (watery) Parotid duct enters at the upper 2nd molar Submandibular glad is completely mucinous Sublingual gland is a mixture of mucous and serous fluid being

produced.

Structure of the Gastrointestinal Tract

The major layers include: Mucosa Submucosa

Muscularis externa Serosa (visceral peritoneum)

Oesophagus: Consists of non-keratinised stratified squamous epithelium Glads are present to lubricate the oesophagus The mucosa and submucosa are thrown into large folds that

extend the length of the oesophagus. These allow for expansion during the passage of large bolus.

Stomach: Gastric Pits:

o The muscous cells at the base, or neck of each pit actively divide replacing superficial cells that are shed into the chime.

These release a mucus gel layer to protect the stomach.

o Also contain chief cells (release pepsin) and parietal cells (HCl and intrinsic factor – for B12 digestion)

Parotid Gland

Small Intestine: Principal site of digestion and absorption Duodenum:

o Contains brunner’s glands which help to identify the duodenum Jejunum:

o Most absorption takes place hereo Note the plica are arrange perpendicular to the lumen

Ileum:o Plica are still apparent here, however they disappear in the distal ileum.o Note the presence of lymphoid tissue (L) aggregated in nodules called “Peyer’s patches”.

Large Intestine: Principal function is reabsorption of electrolytes and water and elimination of undigested food and waste.. Muscularis externa exhibits thickened band known as teniae coli. There are no villi or plica present, however the large intestine exhibits sacculations (bunching) known as

haustrations.

Rectum: Transition exists between simple columnar epithelium of the intestinal mucosa and stratified squamous epithelium. Also note the disappearance of the muscularis mucosae, replaced by the internal anal sphincter.

Pancreas

Exocrine Component: synthesises and secretes enzymes into the duodenum to assist in fat breakdown (acinar cells – characteristic acidophilic zymogen granules in the cytoplasm)

Endocrine Component: Synthesises and secretes insulin and glucagon into the blood (islets of Langerhans). It appears scattered throughout the pancreas and is pale compared to the rest of the organ. 3 Types of Cells:

Alpha – 15-20% make Glucagon Beta – 70% make insulin Delta – 5-10% make somatostatin

Liver

Characteristic Spoke-Wheel formation – hexagonal cross section

Typical liver lobule has 6 portal areas, or hepatic triads, one at each corner of the lobule.

The central veins ultimately merge to form the hepatic vein, which then empties into the inferior vena cava.

Gallbladder

Hollow, pear-shaped organ that stores and concentrates bile prior to its excretion into the small intestine.

The gallbladder has two major functions:o Bile storageo Bile modification

Bile is secreted continuously, but it is released into the duodenum only under the stimulation of CCK

If bile becomes too concentrated, crystals of insoluble minerals and salts begin to appear (cholelithiasis)

If these are large and severe, the gallbladder may be surgically removed in a procedure called a cholecystectomy.

Embryology of the GIT

Basic Overview of Embryology

Day 1 – 7: Ferilisation

Week 1 – 8: Progression from a single cell to establishing organs – embryogenesis

Week 9 – delivery: Foetal period (total 38 weeks)

Week 3: trilaminar germ disc is formedEpiblast cells form all three embryonic layers:

Ectoderm:o CNS, PNS, sensory epithelium of ears, eye, nose, skin, glands, enamel

Mesoderm:o Vascular system, urogenital system (except bladder), spleen, skeleton

Endoderm:o GIT, respiratory tract, bladder, thyroid, parathyroids, liver, pancreas, tympanic cavity, auditory tube.

Note: mesoderm differentiates into a visceral and parietal mesoderm. The lateral mesoderm and endoderm go on to form the gut.

Formation of the Gastrointestinal Tract

As a result of folding, part of the yolk sac is incorporated into the primitive gut.

Endoderm forms the epithelial lining of the digestive tract and gives rise to specialised cells (hepatocytes, pancreas, etc.)

Mesentery

Ventral mesentery is derived from the septum transversum (mesoderm septum formed by the folding of the embryo.

Growth of the liver divides this into the lesser omentum and falciform ligament

Oesophagus normalities form around the same time as lung buds begin to form.

Atresia / Fistula

Oesophageal atresia results in accumulation of fluid in the amniotic sac

Stomach

Appears as a dilation of the foregut. Due to rotation and differering growth

rates, the stomach forms it’s shape and the omental bursa

Liver and Gallbladder

Liver appears as an endodermal epithelium outgrowth at week 3. The bud proliferates and penetrates the septum transversum (plate between the pericardial cavity and stalk of the

yolk sac) The outpouching between the liver and foregut narrows to form the bile duct

o Further outpouching of this duct gives rise to the gallbladder.

Pancreas

Formed from the uniting of the ventral and dorsal buds After rotation, the ventral bud lies below the dorsal bud. Further development fuses the two parts together with uniting of the pancreatic

ducts. An annular pancreas can occur when the ventral pancreas splits and forms a ring.

Caecum and Appendix

The loops rotate 270 degrees in total, causing the caecum to move from the upper right quadrant to the right iliac fossa.

A small bud appears on the caecum – the primate appendix.

Note: malrotation can occur, where the colon does not rotate properly, forming a volvulus.

Hindgut

Hindgut forms the distal third of the transverse colon, the descending colon, the sigmoid, the rectum and the upper part of the anal canal.

The cloaca is an endoderm lined cavity, covered ventrally by ectoderm – this forms the cloacal membraneAt the 7th week, the membrane ruptures, creating the anal opening.

The urorectal septum separates the allantois from the hindgut

Failure to Thrive: Chronic Disease and Diarrhoea

Influences on Growth Nutrition Absorption of food Metabolism of food – fat, protein and carbohydrates Energy utilisation and chronic disease Hormones – growth hormone, steroids, thyroid hormone, insulin Diarrhoea

Fats and Diet

Fat malabsorption can be due to pancreatic, hepatic and small intestinal mucosal reasons. This leads to pale stools or steatorrhoea.

Breast Feeding – Benefits

More Fat and CHO than formula – hence about 10% more calorie dense and breast fed infants grow more quickly. Lower protein and may lower/defer incidence of allergies in childhood Omega-3 fats help with CNS development – may enhance IQ IgA antibodies that help infants recover from gastroenteritis and respiratory infection. Bonding and helps mothers return to pre-pregnancy weight. Is free and is hygienic.

Infant Feeding

6 Months: Introduction of solids

12 Months: Family food introduced

No cow’s milk until 12 monthsMaximum 500ml/day cow’s milk at any age

Failure to Thrive

< 3rd centile or crossing two percentile chart lines Organic causes:

o Malabsorption – coeliac diseaseo Increase energy utilisation – chronic infection, cardiac failure

Non-organic causeso neglect

Detection: Weight centile low relative to length and head circumference centile Crossing centiles Appear physically malnourished – poor fat and muscle stores, loose skin folds in groin and axilla.

Gastrointestinal Disease

Acute vs. Chronic Diarrhoea (more than 4 loose motions a day for > 2 weeks) Infectious diarrhoea

o Commonest worldwide cause of morbidity and mortality in children < 5 yrs old. Villous atrophy / partial villous atrophy

o Coeliac diseaseo CMPIo Giardia

Dehydration

Moderate vs Severe Dehydration

Moderate Severe5-10% dehydrated 10%+Sunken eyes Moderate plus hypotensionDefinite loss of skin tugor Poor peripheral perfusionTachycardia Poor peripheral perfusionReduced urine output No urine output

Differential Diagnosis

Causes of serious bacterial infectiono UTIo Bacteraemiao Pneumoniao Meningitis

Acute Surgical Causes:o Appendicitiso Intussusception (inversion of one portion of the intestine within anothero Acute obstructiono Torsion of the testiso Inguinal herniao Refluxo Pyloric stenosis

Gastroenteritis Causes

Rotavirus: Less than 10% of cases since introduction of the vaccine 33% of patients will have fevers of 39C Illness last 3-7 days Most clinically significant infections occur in the 3-36month age group

Norovirus: Responsible for more than 50% of non-bacterial gastroenteritis Milder than rotovirus Lasts 1-2 days Spread by fecal oral route

Oral vs. IV

Oral works faster than IVo In mild-moderate dehydration at 2hours (better rehydrated on oral)

Clinical Aspects of Liver DiseaseLiver Tests

AST: Aspartate aminotransferase Liver, heart, skeletal muscle, kidney, brain

ALT: Alanine aminotransferase Primarily in the liver

GGT: Gamma-Glutamyl Transpeptidase In hepatobiliary system, kidneys, pancreas, intestine and prostate

ALP: Alkaline Phosphatase In liver, bone, placenta and intestine

Patterns of Abnormalities

Hepatocellular / Hepatic AST, ALT > GGT, ALP

Cholestatic / Infiltrative GGT, ALP > AST, ALT

Can be mixed!

Real Liver Function Tests

Bilirubino End product of hemeo Elevated in jaundice from all causes

Albumino Synthesised by liver; half-life 14-20dayso Levels influenced by non-hepatic factorso Indicator of severity of chronic liver disease (CLD)

Prothrombin time / INRo Dependent on hepatic synthesis of clotting factors and uptake of Vit Ko Shorter half-life than albumino Earlier indicator of severe liver injury than albumin

Causes of Elevated Liver Function Tests

Viral Hepatitis Drug reactions / toxicity Alcoholic liver disease Biliary disease

o Stoneso Malignancy

Hepatic infiltration Haemochromatosis Others

Hepatitis A RNA virus Transmission: Faecal-oral Incubation 4wks Causes: Acute icteric (jaundiced) illness, rarely fulminant (sudden and severe) Anti-HAV IgM , elevated ALT, AST

o Anti-HAV IgM – recent infectiono Anti-HAV IgG – past infection and immunity

Progression to chronicity – NONE Symptoms:

o Prodromal illness including RUQ paino Jaundice 1-4weekso Palpable liver in 70% and spleen in 20%

Drugs Paracetamol – direct toxicity Antibiotics – flucloxacillin, augmentin Anticonvulsants – phenytoin, carbamazepine NSAIDs Amiodarone Allopurinol (Anti-gout) Isoniazid (anti-tb) Zidovudine (anti-retroviral)

Biliary Obstruction: Gallstones Strictures Cholangiocarcinoma Pancreatic cancer ^ bilirubin, GGT, ALP

Causes of Chronic Liver Disease

Alcoholic liver disease Hepatitis B Hepatitis C Haemochromatosis Non-alcoholic fatty liver disease / non-alcoholic steatohepatitis

Hepatitis B

DNA virus Transmission: blood borne, sexual, vertical (mother -> child), saliva Incubation 1- 4 months, may be asymptomatic Acute icteric illness, 1% become fulminant Diagnosis:

o Acute infection – HbsAg and anti-HBc IgMo Recovery – anti-HBc IgG and anti-HBs IgMo Chronic infection – HBsAG, anti-HBc IgG

IF ACTIVE: also have HBV DNA pos Progression to chronicity

o Adults <5%o Infants 90%

Symptoms:o Cirrhosis, liver failure, hepatocellular cancer

Treatment:o Acute – supportiveo Chronic:

Pegylated interferon Antivirals (entecavir, tenofovir)

Prevention:o Vaccinationo Immune globulin

Hepatitis C

RNA virus Common ~ 1% population

Transmission blood borne, vertical Incubation 6-8wks, often asymptomatic Anti-HCV, HCV RNA N or elevated ALT, AST Progression to chronicity: 70% Symptoms:

o Cirrhosis, liver failure, hepatocellular cancer Treatment:

o Pegylated interferon, ribavirin.

Chronic Liver Disease

Symptoms:o Lethargy, pruritus, RUQ discomfort

Progresses to cirrhosis over years – decades Eventually develops complications

o Decompensated cirrhosis Liver transplantation for decompensated disease

Physical Signs: Spider naevi Leuconychia (white nails) Palmar erythema Scratch marks, bruising Oedema Scleral or generalised jaundice Hepato- and splenomegaly asterixis

Cirrhosis

Diffuse process with fibrosis and nodule formation Follows ongoing inflammation and hepatocellular necrosis And be micronodular or macronodular Complications:

o Portal HTNo Ascites (inc. oedema)o Hepatorenal syndromeo Hepatic dysfunctiono Hepatic encephalopathyo Hepatocellular carcinoma

Mild jaundice: serum bilirubin 51 mol/l

Portal Hypertension

Obstruction of portal circulation results in development of a collateral circulation Oesophageal and gastric (fundal) varices

These correlate with severity of liver disease 40% of compensated cirrhosis patients will show varices 85% of decompensated cirrhosis patients will show varices

Ascites

Portal hypertension splanchinic dilatation decreased effective arterial blood volume vasoconstrictor and antinatruiretic factors secondary hyperaldosteronism sodium and water retention increased lymph production

Ascites develops in 30% of cirrhotics over 5 years. Once it develops, 5 yr survival = 30-40% Management:

o Salt restrictiono Diuretics

Spironolactone and possibly addition of frusemide

Spontaneous Bacterial Peritonitis

Bacterial translocation from intestinal lumen to lymph nodes with bacteraemia and ascetic infection. Prevalence 10-30% of hospitalised patients In-hospital mortality 20% Median survival after episode is 9 months Symptoms:

o Pain, vomitingo Fever, hepatic encephalopathy

Management:o Ascetic tap for diagnosiso Antibiotics (triple therapy – ciprofloxacin, ampicillim, metronidazole), and albumin for acute episodeo Prophylaxis reduces recurrence

Hepatobiliary Disorders and Clinical Approach to Jaundice

Bilirubin Metabolism

Haemoglobin released from destruction of RBCsIn the liver: haemoglobin haeme biliverdin bilirubin bilirubin glucuronide urobillinogens fecal excretion

Pathophysiology of Jaundice

Arises in 4 different ways:o Increased bilirubin loado Disturbance in uptake and transporto Defects in conjugationo Failure of excretion

Prehepatic:o Haemolysis

Hepatocelluar (hepatitis)o Acuteo Chronic

Cholestatico Undilated ducts (intrahepatic)o Dilated ducts (obstructive)

Differential Diagnosis of Jaundice

Acute:o Viral hepatitis: A, B, C, E or EBV, CMV, HSVo Drug reactionso Alcoholic hepatitiso Immune: autoimmune hepatitiso Other toxinso Biliary disease

Gall stones Malignancy

o Pregnancy relatedo Hepatic infiltration

Chronic:o Chronic cholestasiso Biliary disease

PBC (primary biliary cirrhosis) PSC (primary sclerosis cholangitis) Biliary strictures

o cirrhosis

Clinical Approach to Jaundice

lab tests:o lftso bilirubino albumino INRo FBC o Urine

Introduction to Abdominal Imaging

Abdominal X-Ray

3 films: supine, erect and CXRo CXR to check for air under diaphragm, or lung pathology that might cause abdominal symptoms.

Method of looking: Follow the densities – black to white Gas first, then fat, soft tissue, calcifications, bones, metal Soft tissues – liver, spleen, kidneys. Note: small bowel obstruction: small bowel >3cm = dilated

o Causes: Adhesions, Herniae Nalignancy Intraperitoneal inflammation Gallstone ileus Crohn’s disease

Large bowel obstruction:o Causes:

Carcinoma Volvulus Diverticulitis Colonic pseudo-obstruction Herniae Faecal impaction

Calcifications:

Fluoroscopic Studies – Barium Meal and Enema

Bariumo Suspension of inert powder particleso High density – good imageso Viscosity – can use double contrasto AE: dries out in lumen constipation or obstruction

Barium Enema:

Abdominal Ultrasound

Most organs are quite accessible except if covered by gas filled bowel. Focal tenderness can be quite well judged. Dynamic and interactive element of study No radiation – especially important in paediatrics. Used to view:

o Liver parenchyma, hepatic and portal veins

o Gallbladder and bile duct o Pancreas and ducto Spleeno Kidneyso Aortao Bladdero ascites

Volvulus

PET Scan

Alcohol AbuseNational Guidelines

No more than 2 standard drinks on any day No more than 4 standard drinks on a single occasion Standard drink:

o 10 grams of pure alcohol

Alcohol Treatment

Pharmacological Methods of Detoxification Benzodiazepines are the drugs of choice in managing alcohol withdrawal as they:

o Alleviate many withdrawal symptomso Are effective in preventing development of complex withdrawal features when given earlyo Have a wide margin of safetyo Have a low likelihood of cross-dependence

Naltrexone:o Opioid receptor antagonisto Used in both alcohol and opioid dependence

Topiramate:o Anti-epileptic drug which also assists in alcohol dependence

Ondansetron:o A serotonin antagonist, it may also be used in alcohol dependence

Post-Detoxification: Rehab centres Alcoholics Anonymous

Pharmacology of Lower Gastrointestinal TractOverview of the Small Intestine

Functions: Digestion and absorption Defence against antigen entry

Pathophysiology: Malabsorption:

o Coeliac disease Bleeding / Ulceration:

o Duodenal ulcer (Tx of PPI, H2 antagonist)

Structure: Extends from duodenum to ileum SA increased by mucosal folds. Innervation:

o Parasympathetic cholinergic (muscarinic and nicotinic receptors)o Sympathetic, adrenergic (alpha and beta receptors)

Large Intestine (Colon)

Functions: Stores waste Reclaims water, maintains water balance and absorbs some vitamins and electrolytes. Defence against antigen entry

Pathophysiology: Malabsorption:

o Diarrhoeao Inflammatory bowel diseases

Ulcerative colitis Crohn’s disease

May affect from mouth to anus Pseudomembranous colitis

o Irritable bowel diseases Diverticulitis

o Diarrhoeao Constipation

Megacolon

Antidiarrhoeal Agents

Antiperistaltic Agents: Opiods such as codeine Inhibit gastric motility and peristalsis

o Diphenoxylateo Loperamide

Adsorbents: Kaolin

o Acts as an adsorbant agento May prevent absorption of other drugs

Laxatives

Step 1:o Exercise,o Fluid intakeo Increased fibre

Step 2:o Bulk forming laxatives

Psyllium hydrophilic mucilloid (Metamucil) Ispaghula husk

Step 3:o Stool softeners

Coloxyl Step 4:

o Osmotic laxatives Sorbitol Magnesium sulphate Lactulose

Onset is dose dependant 2-6hrs Watch for griping, wind.

Step 5:o Stimulants

Sennoside granules Senna Bisacodyl

Step 6:o Suppositories / enemas

Suppositories – glycerine, bisacodyl Enemas – microlax

Step 7: o Colonic lavage

Golytely Glyo-prep Involves surgery

Step 8:o Manual evacuationo Surgical deimpactation

Antispasmodics

Hyoscine, hyoscyamine, atropine, propanthelineo Eg. Travacalm

All are anticholinergico Cause antimuscarinic side-effects (dry mouth, constipation, etc.)

Serotonin (5-HT) Modulators in the Intestine

Serotonin stimulates gut motility so agonists help constipation, while antagonists can help diarrhoea predominant IBS.

Agonists: Tegaserod

o Selective 5-HT4 agonist for constipation SSRIs

o Would believe this would help with constipation predominant IBS

Antagonists: Alosetron

o 5-HT3 antagonisto Only given to women on a very restricted program.

Motility Stimulants / Prokinetic Agents

Metoclopramide, domperidone, erythromycin MOA:

o Accelerate gut transit timeo Absorption of concomitant drugs may be affectedo Causes diarrhoea

Examples: metoclopramide (maxolon)Class: Dopamine antagonist with cholinergic activityMOA: enhances motility from the oesophagus through to the small bowel AND decreased relaxation of the upper stomach and increases antral contractionIndications: Nausea and vomiting, IBS, GORDAE: Hirsutism, drowsiness, confusion (elderly)

Pathologies of the GITOesophageal Cancer

The most common malignant tumour in the proximal 2/3 of the oesophagus is squamous cell carcinoma; adenocarcinoma is the most common in the distal 1/3. Symptoms are progressive dysphagia and weight loss. Diagnosis is by endoscopy, followed by CT and endoscopic ultrasound for staging. Treatment varies with stage and generally includes surgery with or without chemotherapy and radiation. Long-term survival is poor except for those with local disease.

Food Intoxication: Staphylococcus AureusAssociated with foods rich in protein salt and sugar (ham, creamy cakes, salads with mayonnaise). It induces diarrhoea and vimiting 1-6h after ingestion.

Food Intoxication: Bacillus CereusAssociated with rice dishes. Acute onset 1-6h of nausea, abdominal pain and vomiting w/o diarrhoea.

Campylobacter Spp.Most common cause of diarrhoea in developed countries. C. jejuni most common.

SalmonellosisSecond most common cause of diarrhoea in developed countries. Trasmitted via contaminated foods; especially poultry, eggs, meats and dairy products.

Enteric Fevers: Typhoid and ParatyphoidCaused by Salmonella typhi and S. paratyphi. Incubation period 10-14 days, early symptoms of fever, headache, dry cough, abdominal discomfort (diarrhoea or constipation), fever increases if untreated. Around 3% of patients become chronic carriers.

RotavirusCauses severe watery diarrhoea lasting 4-7days. Major cause of gastroenteritis in infants and children.

NorovirusesOften food borne; common in older children and adults. Usually presents as acute-onset vomiting, watery non-bloody diarrhoea with abdominal cramps and nausea. It is highly infections and can spread rapidly in confined areas (aged care, cruise liners, etc.)

Giardia IntestinalisEpidemic in developed countries and endemic in developing countries. Faecal-oral transmission in day-care setting most common. Many cases asymptomatic.

CholelithiasisCholelithiasis is the presence of one of more calculi (gallstones) in the gallbladder. It affects approximately 30% of the population, and is more common in females. It is generally asymptomatic, with the most common symptom being biliary colic; gallstones do not cause dyspepsia or fatty food intolerance. More serious complications include cholecystitis; biliary tract obstruction (stones in the bile ducts or choledocholithiasis), sometimes with infection (cholangitis); and gallstone pancreatitis. Diagnosis is usually by ultrasonography. If cholelithiasis causes sypmtoms or complications, cholecystectomy is necessary.

Acute Cholecystitis Acute cholecystitis is inflammation of the gallbladder that develops over hours, usually because a gallstone obstructs the cystic duct. Symptoms include right upper quadrant pain and tenderness, sometimes accompanied by fever, chills nausea and vomiting. Abdominal ultrasonography detects the gallstone and sometimes the associated inflammation. Treatment usually involves antibiotics and cholecystectomy.

Bile Duct Obstruction (Cholestasis)

Extrahepatic or Intrahepatic

Extrahepatic: Obstructs the flow of bile within the ducts or secondary to external compression Gallstones are the most common cause Other causes are inflammation of surrounding structions, malignancy infection or biliary cirrhosis.

Intrahepatic: Cholestasis generally occurs at the level of the hepatocyte or biliary canalicular membrane. Causes include

hepatocellular disease (viral hepatitis, drug induced hepatitis), cirrhosis and alcoholic liver disease. Excretion is the rate limiting step and is usually impaired to the greatest extent.

o As a result, conjugated bilirubin predominates in the serum.o Raised conjugated bilirubin and raised ALP

Meckel’s Diverticulum

Meckel’s diverticulum is a congenital sacculation of the distal ileum occurring in 2-3% of people. It is usually located with 100cm of the ileocec al valve and often contains heterotopic gastric tissue, pancreatic tissue or both. Symptoms are uncommon but include bleeding, bowel obstruction and inflammation. Diagnosis is difficult and often involves radionuclide scanning and barium studies. Treatment is surgical resection.

Intussusception

An intussusception is a medical condition in which a part of the intestine has invaginated into another section of intestine, similar to the way in which the parts of a collapsible telescope slide into one another. It causes intestinal obstruction and sometimes intestinal ischaemia. It generally occurs between ages 3months and 3 years. 65% of cases are before age 1.

Acute Appendicitis

Obstruction of the appendix lumen is the primary cause of appendicitis. Obstruction of the lumen leads to distension of the appendix due to accumulated fluid. Ineffective lympatic and venous drainage allows bacterial invasion of the appendix wall and, in advanced cases, perforation and spillage of pus into the peritoneal cavity.

Alcoholic Liver Disease

Alcohol abusers often have disorders that occur in this sequence: Fatty liver (in >90%) Alcoholic hepatitis (in 10-35%) Cirrhosis (in 10-20%)

Hepatocellular carcinoma may also develop, especially in association with iron accumulation.

Risk Factors

Quantity and duration of alcohol use (>8years) Sex - women

Genetic and metabolic traits Nutritional status

Pathology

Steatosis (macrovesicular) Alcoholic hepatitis (steatohepatitis)

Fibrosis Cirrhosis (micronodular)

Signs and Symptoms

Symptoms usually become apparent in patients in their 30’s-40’s, with more severe problems appearing about a decade later.

Fatty Liver is often asymptomatic. In 1/3 of patients, the liver is enlarged and smooth, but it is not usually tender.

Alcoholic hepatitis ranges from mild and reversible to life threatening. Most patients with moderate disease are undernourished and present with fatigue, fever, jaundice, right upper quadrant pain, tender hepatomegaly, and sometimes a hepatic bruit. About 40% deteriorate soon after hospitalisation, with consequences ranging from mild (eg. Increasing jaundice) to severe (eg. Ascites, portal-systemic encephalopathy, variceal bleeding, liver failure with hypoglycaemia, coagulopathy). Other manifestations of cirrhosis may be present.

Cirrhosis, if compensated, may be asymptomatic. The liver is unusually small; when the liver is enlarged fatty liver or hepatoma should be considered. Symptoms range from those of alcoholic hepatitis to the complications of end-stage liver disease, such as portal hypertension (often with oesophageal varices and upper GI bleeding), splenomegaly, ascites and portal-systemic encephalopathy. Portal hypertension may lead to intrapulmonary arteriovenous shunting with hypoxemia (hepatopulmonary syndrome), which can cause cyanosis and nail clubbing. Acute renal failure secondary to progressively decreasing renal blood flow may develop. Hepatocellular carcinoma develops in 10-15% of patients with alcoholic cirrhosis.

Diagnosis

Confirmed history of alcohol use Liver function tests and CBC Sometimes liver biopsy

Acohol is suspected as the cause of liver disease in any patient who chronically consumes excess alcohol. History should be confirmed by family members.

There is no specific test for alcoholic liver disease, however liver function tests (PT; serum bilirubin, aminotransferase, and albumin levels) and FBC are done to change for severity of liver damage or anaemia.

Treatment Abstinence Supportive care – AA, etc. Corticosteroids and enteral nutrition for severe alcoholic hepatitis Sometimes liver transplant

Gastro-Oesophageal Reflux Disease (GORD)Incompetence of the lower oesophageal sphincter allows reflux of gastric contents into the oesophagus, causing burning pain. Prolonged reflux may lead to oesophagitis, stricture and rarely metaplasia or cancer. Diagnosis is clinical, sometimes with

endoscopy, with or without acid testing. Treatment involves lifestyle modification, acid suppression using PPIs and sometimes surgical repair.

Epidemiology

GORD is common, occurring in 30-40% of adults. It also occurs frequently in infants, typically beginning at birth

Aetiology

The prescence of reflux implies lower oesophageal sphincter (LOS) incompetence, which may result from a generalised loss of intrinsic sphincter tone or from recurrent inappropriate transient relaxations. Treansient LES relaxations are triggered by gastrict distention or subthreshold pharyngeal stimulation

Factors contributing to reflux include weight gain, fatty foods, caffeinated or carbonated beverages, alcohol, tobacco smoking and drugs. Drugs that lower LOS pressure include anticholinergics, antihistamines, TCAs and CCBs.

Complications:GORD may lead to oesphagitis, peptic oesophageal ulcer, oesophageal stricture, barrett’s oesophagus and oesophageal adenocarcinoma. Factors that contribute to the development of oesophagitis include the caustic nature of the reflux, the inability to clear the reflux from the oesophagus and the volume of gastric contents.

Signs and Symptoms

The most prominent symptom of GORD is heartburn, with or without regurgitation of gastric contents into the mouth. Infants present with vomiting, irritability, anorexia and sometimes symptoms of chronic aspiration.

Oesophagitis may cause odynophagia (a dysphagia in which swallowing causes pain) and even oesphageal haemorrhage, which is usually occult, but can be massive. Peptic stricture causes a gradually progressive dysphagia for solid foods. Peptic oesophageal ulcers cause the same pain as gastric or duodenal ulcers, but the pain is usually localised to the xiphoid or high substernal region. They generally heal slowly, tend to recur and usually leave a stricture on healing.

Diagnosis

Clinical diagnosis Endoscopy for those not responding to emperic treatment

A detailed history points to the diagnosis. Patients with typical symptoms of gORD may be given a trial of therapy. Patients who do not improve or have long-standing symptoms or symptoms of complications, should be studied. Endoscopy with cytologic washings and biopsy of abnormal areas, is the test of choice. Endoscopic biopsy is the only test that consistently detects the columnar musocsal changes of barrett’s oesophagus.

Treatment

Head of bed elevated Coffee, alcohol, fats and smoking avoided PPIs

Management of uncomplicated GORD consists of elevating the head of the bed about 15cm and avoiding the following: eating within 2-3h of bedtime, strong stimulants of acid secretion (coffee and alcohol), certain drugs (eg. Anticholinergics), specific foods and smoking.

Omeprazole or oesomeprazole may be given before breakfast or in some cases bid, and can be continued long-term.

GastritisGastritis is inflammation of the gastric mucosa caused by any of several conditions, including infection (helicobacter pylori), drugs (NSAIDs, alcohol), stress, and autoimmune phenomena (atrophic gastritis). Many cases are asymptomatic, but dyspepsia (indigestion) and GI bleeding sometimes occur. Diagnosis is by endoscopy. Treatment is directed at the cause but often includes acid suppression and, for H. pylori, antibiotics.

Aetiology

Acute: Aspirin and other NSAIDs Alcohol, cigarette smoking Stress, burns, surgery Trauma: NG tube Chemotherapy, irradiation Infection: salmonellosis, CMV,

Chronic: Helicobacter pylori: most common cause Autoimmune: pernicious anaemia Crohn’s disease Bile reflux

Signs and Symptoms

Can be asymptomatic, or present with dyspepsia, nausea or vomiting. Often, the first sign is haematemesis or melena.

Treatment

For bleeding: endoscopic haemostasis For acid suppression: h2 antagonist or PPI

Peptic Ulcer caused by H. PyloriA peptic ulcer is an erosion in a segment of the GI mucosa, typically in the stomach or first few cm of the duodenum. Nearly all ulcers are caused by helicobacter pylori infection or NSAID use. Symptoms typically include burning epigastric pain that is often relieved by food. Diagnosis is by endoscopy and testing for H. pylori. Treatment involves acid suppression, eradication of H. pylori (if present), and avoidance of NSAIDs.

Treatment

Eradication of H. pylori Acid suppressive drugs

Antibiotics plus a PPI are the mainstay of treatment for a H. pylori infection. Triple therapy is recommended with: Oral omeprazole (PPI) Clarithromycin Amoxicillin (or metronidazole)

Diverticular DiseaseDiverticula are saclike mucosal out-pouchings that protrude from a tubular structure. True diverticular contain all layers of the parent structure; while false or pseudodiverticula are mucosal prjections through the muscular later. Esophageal and meckel’s diverticula are true diverticula. Colonic diverticula are pseudodiverticula; they cause symptoms by trapping faeces and being inflamed or infected, bleeding or rupturing. This passage focuses on diverticulitis.

Diverticulitis is inflammation of a diverticulum, which can result in phlegmon (spreading, diffuse inflammation with formation of exudate or pus) of the bowel wall, peritonitis, perforation, fistula, or abscess. The primary symptom is abdominal pain. Diagnosis is by CT. Treatment is with antibiotics (ciprofloxacin, cephalosporin and metronidazole) and occasionally surgery.

Aetiology

Diverticulitis occurs when a micro or macro perforation develops in a diverticulum, releasing intestinal bacteria. The resultant inflammation remains localised in 75% of patients. The remaining 25% may develop abscess, free intraperitoneal perforation, bowel obstruction or fistulas.

Occurs in people > 35years old and increases with age.

Signs and Symptoms

Diverticulitis usually manifests with pain or tenderness in the lower left quadrant of the abdomen and fever. Peritoneal signs (eg. Rebound or guarding) may be present, especially if there is abscesses or perforation. Fistulas may manifest as pneumaturia, feculent vaginal discharge or a cutaneous or myofascial infection of the abdominal wall, perneum or upper leg. Patients with bowel obstruction have nausea, vomiting and abdominal distention.

Diagnosis

Abdominal CT Colonoscopy after resolution

Clinical suspicion is high in patients with known diverticulosis. However because other disorders can have similar symptoms (appendicitis, colon or avarian cancer), testing is required. Abdominal CT with oral and IV contrast is preferred, although findings in about 10% of patients cannot be distinguished from colon cancer. Colonoscopy after resolution of the acute infection, is necessary for definitive diagnosis.

Treatment

Liquid diet, oral antibiotics for mild disease IV antibiotics, npo for more severe disease CT-guided percutaneous drainage of abscess Sometimes surgery

A patient who is not very ill is treated at home with rest, a liquid diet and oral antibiotics (ciprofloxacin, metronidazole and amoxicillin). Symptoms usually subside rapidly.

Patients with more severe symptoms should be hospitalised, as should patients taking prednisone (who are at higher risk of perforation and general peritonitis). Treatment is bed rest, npo, IV fluids and IV antibiotics.

Surgery involves resection of the affect colon and this is indicated for patients with free perforation or general peritonitis.

Coeliac DiseaseCoeliac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption. Smptoms usually include diarrhoea and abdominal discomfort. Diagnosis is by small-bowel biopsies showing characterisitic though not specific pathologic changines of villous atrophy that resolve with a strict gluten-free diet.

Epidemiology

Affects 10-20% of first degree relatives. Female to male ratio is 2:1. Onset is generally in childhood although can vary drastically.

Aetiology

Coeliac disease is a hereditary disorder causes by sensitivity to the gliadin fraction of gluten, a protein found in wheat, rye and barley. In a genetically susceptible person, T cells are activated and cause an inflammatory response which causes characteristic mucosal villous atrophy in the small bowel.

Signs and Symptoms

The clinical presentation varies, from asymptomatic to significant GI symptoms.

It can manifest in infancy and childhood after introduction to cereals. The child has FTT, apathy, anorexia, pallor. Abdominal distention and muscle wasting. Stools are soft, bulky, clay-coloured and offensive.

In adults, lassitude, weakness and anorexia are most common. Steatorrhoea ranges from mild, to severe.

Diagnosis

Serologic markers Small-bowel biopsy

The diagnosis is suspected clinically and by laboratory abnormalities suggestive of malabsorption. Family incidence is a valuable clue. Celiac disease should be strongly considered in a patient with iron deficiency, without obvious GI bleeding.

Confirmation requires a small-bowel biopsy from the second portion of the duodenum. Findings include lack-of, or shortening of villi, increased intraepithelial cells, and crypt hyperplasia. However, such findings can also occur in tropical sprue, severe intestinal bacterial overgrowth, eosinophilic enteritis, lactose introlerance and lymphoma.

Because biopsy is not specific, serologic markers can aid diagnosis. Anti-tissue transglutaminase (AGA) and anti-endomysial antibody (EMA) tests are >90% sensitive and specific.

Treatment

Gluten-free diet Supplements to replace any serious deficiencies

On a gluten free diet, symptoms improve in as fast as 1-2 weeks.

If a patient responds poorly to gluten withdrawal, either the diagnosis is wrong, or the disease has become refractory, in which case corticosteroids, DMARDs or MAbs (eg. Infliximab – TNF inhibitor) may be used.

Irritable Bowel SyndromeIrritable bowel syndrome (IBS) is characterised by abdominal discomfort or pain that is accompanied by at least two of the following: relief by defecation, change in frequency of stool or change in consistency of stool. The cause is unknown and the pathophysiology is incompletely understood. Diagnosis is clinical. Treatment is symptomatic, consisting of dietary management and drugs, including anticholinergics and agents active at serotonin receptors.

Aetiology

The cause is unknown. It is believed to be a combination of psychosocial and physiological factors.

Signs and Symptoms

IBS tends to begin in the teens and 20s, causing bouts of symptoms that recur at irregular periods. Onset in late adult life is less common but not rare. Symptoms are often triggered by food, particularly fats, or by stress.

Patients have abdominal discomfort, which varies considerably but is often located in the lower quadrant, steady or cramping in nature and relieved by defacation. In addition, abdominal discomfort is temporally associated with alterations in stool frequency (increase in diarrhoea and decreased in constipation) and consistency (loose or lumpy and hard).

Although bowel patterns are relatively consistent in most patients, it is not unusual for patients to alternate between constipation and diarrhoea. Patients may also have symptoms of abnormal stool passage (straining, urgency, tenesmus), pass mucus or complain of bloating or abdominal distension. Many patients also have symptoms of dyspepsia.

Diagnosis

Clinical evaluation with Rome criteria Screening for organic causes with basic laboratory tests and sigmoidoscopy or colonoscopy. Patients with red flag findings must have other tests (rectal blood, weight loss, fever)

Diagnosis is based on characteristic bowel patterns, time and character of pain, and exclusion of other disease processes through physical examination and routine diagnostic tests. The rome criteria are at least 2 of the following: relief after defecation, change in stool frequency or change in stool consistency.

Treatment

Support and understanding Normal diet, avoiding gas-producing and diarrhoea-producing foods Increased fiber intake for constipation Anticholinergic drugs (hyoscine, propantheline) or serotonin receptor agonists Loperamide for diarrhoea Possibly TCAs

Anticholinergic drugs may be used for their anti-spasmodic effects.

Serotonin agonists may be of bene to stimulate motility and alleviate constipation.

Loperamide may be used for diarrhoea.

Crohn’s DiseaseCrohn’s disease is a chronic transmural inflammatory disease that usually affects the distal ileum and colon but may occur in any part of the GI tract. Symptoms include diarrhoea and abdominal pain. Abscesses, internal and external fistulas and bowel obstruction may arise. Extraintestinal symptoms, particularly arthritis may occur. Diagnosis is by colonoscopy and barium contrast studies. Treatment is with 5-ASA, corticosteroids, immunomodulators, anticytokines, antibiotics and often surgery.

Epidemiology

Occurs in 1-6 per 100,000 people.

Aetiology

There is no known cause of Crohn’s disease, however it is believed to be autoimmune.

Crohn’s disease begins with crypt inflammation and abscesses, which progress to tiny focal ulcers. These lesions may then develop into deep longitudinal and transverse ulcerswith invtervening mucosal oedema, creating a characteristic cobblestoned appearance to the bowel.

Inflammation spreads transmurally, leading to lymphedema and thickening of bowel wall and mesentery. This extensive inflammation may result in hypertrophy of various structures and possible strictures, leading to obstruction. Abscesses are common and fistulas often penetrate into adjoining structures, including other loops of bowel, the bladder or psoas muscle. Fistulas may even extend to the skin of the anterior abdomen or flanks.

Segments of diseased bowel are sharply demarcated from adjacent normal bowel (“skip areas”). About 35% of Crohn’s disease cases involve the ileum alone; 45% the ileum and colon; and about 20% involve the colon alone, most of which (unlike ulcerative colitis) spares the rectum.

Signs and Symptoms

The most common initial manifestation is chronic diarrhoea with abdominal pain, fever, anorexia and weight loss. The abdomen is tender and a mass or fullness may be palpable. Gross rectal bleeding isunusual except in isolated colonic disease, which may manifest similarly to UC.

About 33% of patients will have perianal disease (especially fistula’s and fissures), which is sometimes the most prominent or initial complaint.

Chronic disease causes a variety of systemic symptoms, including fever, weight loss, undernutrition and extraintestinal manifestations.

Diagnosis

Barium x-rays of the stomach, small bowel, and colon Abdominal CT Sometimes MR enterography, upper endoscopy and/or colonoscopy

Crohn’s disease should be suspected in a patient with inflammatory or obstructive symptoms or in a patient without prominent GI symptoms but with perianal fistulas or abscesses or with otherwise unexplained arthritis, fever, anaemia or stunted growth.

Differentiation from UC may be an issue in the 20% of cases in which Crohn’s disease is confined to the colon; however as treatment is similar, this is only important in the case of surgery.

If initial presentation is less acute, an upper GI series is preferred over CT. These imaging studies are virtually diagnostic if they show characteristic strictures or fistulas with accompanying separation of bowel loops. Barium enema x-ray may be used if symptoms seem predominatly colonic (eg. Diarrhoea) and may show reflux of barium into the terminal ileum with irregularity, nodularity, stiffness, wall thickening and a narrowed lumen.

Treatment

Loperamide (Imodium) or antispasmodics (atropine, dicycloverine) for relief 5-ASA or antibiotics Other drugs depending on symptoms and severity Sometimes surgery

Fistulas:Fistulas are treated initially with metronidazole (antibiotic) and ciprofloxacin (quinone). If no response in 3-4 weeks, may receive an immunomodulator.

Surgery:Even though about 70% of patients will require an operation, it is done reluctantly. Resection of the involved bowel may ameliorate symptoms but does not cure the disease. There is also a very high relapse rate of >70% at 1 year.

5-Aminosalycylic acid: Examples: olsalazine, sulphasalazine Class: anti-inflammatory (GI) MOA: breaks down into 5-ASA and sulfapyridine which has anti-inflammatory and free radical scavenging effects. Indications: Ulcerative colitis and Crohn’s disease AE: GIT, skin, malaise

Immunosuppressants Examples: azathioprine, methotrexate, infliximab, ciclosporin Class: Immunosuppressant - DMARD MOA: inhibits purine synthesis Indications: refractory Crohn’s disease, transplant rejection, rheumatoid arthritis AE: myelosuppression

Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterised most often by bloody diarrhoea. Extraintestinal symptoms include, anorexia, fatigue, arthritis. Long-term risk of colon cancer is high. Diagnosis is by colonoscopy. Treatment is with 5-aminosalicylic acid, corticosteroids, immunomodulators, anticytokines, antibiotics and occasionally surgery.

Epidemiology2 – 10 per 100000 people.

Aetiology

It has an unknown cause. It begins in the rectum and may remain localised (ulcerative proctitis) or extends proximally, sometimes involving the entire colon.

The inflammation caused by US affects the mucosa and submucosa and there is a sharp border between normal and affected tissue. In early cases the mucous membrane is erythematous, finely granular, and friable, with loss of the normal vascular pattern, and often with scattered haemorrhagic areas.

Islands of normal or hyperplastic inflammatory mucosa (pseudopolyps) project above areas of ulcerated mucosa.

Signs and Symptoms

Bloody diarrhoea of varied intensy and duration is interspersed with asymptomatic intervals. Usally an attack begins insidiously, with increased udgency to defecate, mild lower abdominal cramps, and blood and mucus in the stools. Some cases develop aftre an infection.

If confined to the rectosigmoid, stolls may be normal or hard and dry. If more proximal, stools become looser and the patient may have >10 bowel movements per day, often with severe cramps and distressing rectal tenesmus.

Systemic signs and symptoms, more common with extensive UC, include malaise, fever, anaemia, anorexia and weight loss. Extraintestinal manifestations (joint and skin complications) are most common when sstemic symptoms are present.

Diagnosis Stool cultures and microscopy (to exclude infection eg. Clostridium difficile) Sigmoidoscopy with biopsy

The diagnosis is suggested by typical symptoms and signs, particularly when accompanied by extraintestinal manifestations or a hitory of previous similar attacks. UC should be differentiated from Crohn’s Disease, and from other causes of acute colitis.

Sigmoidoscopy should be done; it allows visual confirmation of colitis and permits direct sampling of stool or mucus for culture and microscopic evaluation, as well as biopsy of affected areas. Visual inspection and biopsies may be nondiagnostic (because of much overlap between different types of collitis), however can tell apart infectious colitis from Crohn’s colitis.

Treatment Loperamide (Imodium – antidiarrhoeal) and dietary management for symptom relief 5-aminosalicylic acid (5-ASA) Corticosteroids and other drugs depending on symptoms and severity

Loperamide may be given bid to qid for mild diarrhoea, to higher oral doses for more intense diarrhoea.

5-ASA is given once or bid via enemas or suppositories.

In moderate or extensive disease, oral 5-ASA may be given in addition to the enemas. Also, corticosteroids and immunomodulators may be indicated.In the case of severe disease, patients will have to be hospitalised and placed on IV corticosteroids.

In 1/3rd of patients, surgery will be necessary which will involve a total proctocolectomy. This will return life expectancy and QoL to normal.

Colorectal Cancer

Colorectal cancer (CRC) is extremely common. Symptoms include blood in the stool or changes in bowel habits. Screening is with fecal occult blood testing. Diagnosis is by colonoscopy. Treatment is surgical resection and chemotherapy for nodal involvement.

EpidemiologyCRC accounts for more new cases than any anatomic site except the lung. Incidence begins to rise at age 40 and peaks at age 60-75. Overall, 70% of cases occur in the rectum and sigmoid, and 95% are adenocarcinomas. Colon cancer is more common among women; rectal cancer is more common among men.

AetiologyCRC most often occurs as transformation within adenomatous polyps. About 80% of cases are sporadic, and 20% have an inheritable component. Predisposing factors include chronic ulcerative colitis and granulomatous colitis; the risk of CRC increases with the duration of these disorders.

Signs and SymptomsColorectal adenocarcinoma grows slowly and a long interval elapses before it is large enough to cause symptoms. Symptoms depend on lesion location, type, extent and complications.

The right colon has a large caliber and a thin wall so obstruction is usually very late. Bleeding is usually occult (seen in faeces – generally microscopically). Fatigue and weakness caused by severe anaemia may by the only complaints. Tumours sometimes grow large enough to be palpable through the abdominal wall before other symptoms appear.

The left colon has a smaller lumen, the faeces are semi-solid and cancer tends to encircle the bowel, causing alternating constipation and increased stoll frequency or diarrhoea. Partial obstruction with colicky abdominal pain or complete obsturction may be the initial manifestation. The stool may be streaked or mixed with blood. Some patients present with symptoms of perforation, usually walled off (focal pain and tenderness), or rarely diffuse peritonitis.

In rectal cancer, the most common initial symptom is bleeding with defecation. Whenever rectal bleeding occurs, even with obvious haemorrhoids or known diverticular disease, coexisting cancer must be ruled out. Tenesmus or a sensation of incomplete evacuation may be present. Pain is common with perirectal involvement.

Diagnosis Colonoscopy

Screening Tests:For average-risk patients, FOB testing should be done annually after the age of 50, with flexible sigmoidoscopy every 5 years.

Diagnostic Tests:Patients with positive FOB tests require colonoscopy, as do those with lesions seen on sigmoidoscopy or imaging study. All lesions should be completely removed for histologic examination. If a lesion is sessile (attached directly to the wall) or not removable at colonoscopy, surgical excision should be strongly considered.Once cancer is diagnosed, patients should have an abdominal CT, chest x-ray and routine laboratory tests to seek metastatic disease and anaemia and to evaluate overall condition.

PrognosisPrognosis depends greatly on stage. The 10 yr survival rate for cancer limited to the mucosa approaches 90%; with extension through the bowel wall 70-80%; with positive lymph nodes 30-50%; and with metastatic disease, <20%.

Treatment Surgical resection, sometimes combined with chemotherapy, radiation or both.

Surgery for cure can be attempted in the 70% of patients presenting without metastatic disease. It consists of wide resection and its regional lymphatic drainage with reanastomosis of bowel segments.

Chemotherapy (5-flurouracil usually) improves survival by 10-30% in colon cancer patients with positive lymph nodes.

In the case of palliation, median survival is 7 months.

Myasthenia Gravis

Myasthenia gravis involves episodic muscle weakness and easy fatigability caused by autoantibody and cell-mediated destruction of acetylcholine receptors. It is more common among young women but may occur in men or women at any age. Symptoms worsen with muscle activity and lessen with rest. Diagnosis is by measurement of serum acetylcholine receptor (AChR) antibody levels, electromyography and sometimes IV edrophonium challenge, which briefly lessens the weakness. Treatment includes anticholinesterase drugs, immunosuppressants, corticosteroids, plasma exchange, IV immune globin, and possibly thymectomy.

Epidemiology

Myasthenia gravis most commonly affects young women aged 20 – 40 yrs.

Aetiology

It results from an autoimmune attack on the post synaptic Ach receptors, which disrupts neuromuscular transmission. The trigger is unknown, but the disorder is associated with abnormalities of the thymus, autoimmune hyperthyroidism and other autoimmune disorders.

65% of patients will have thymic hyperplasia, and 10% have a thymoma.

Uncommon forms: Ocular myasthenia gravis (15% of cases) – involves only extraocular muscles.

Signs and Symptoms

The most common symptoms are ptosis, diplopia and muscle weakness after using the affected muscle. Occular muscles are affected initially in 40% of patients and eventually 85%.

Handgrip may alternate between weak and normal. Neck muscles may become weak. If generalised myasthenia gravis is going to develop after ocular symptoms, it usually does so within the first 3 years.

Myasthenic Crisis may develop in 15-20% of patients over a lifetime. It is a severe generalised quadriparesis or life-threatening respiratory muscle weakness. It is often due to a supervening infection that reactivates the immune system.

Diagnosis

Bedside tests AChR antibody levels, electromyography or both.

The traditional anticholinesterase test, done at the bedside by using the short-acting (<5 min) drug edrophonium, is positive in most patients who have myasthenia with overt weakness. It should only be done in patients with obvious ptosis or ophthalmoparesis; as these deficits must be clearly apparent to clearly see the improvement to normal strength. To perform the test, fatigue the muscles, give 2mg of edrophonium. If no adverse event occurs, give another 8mg. Rapid (<2min) improvement should be seen for a positive test result.

Following this, a serum AChR antibody level test should be performed to confirm the diagnosis. These antibodies are present in 80%-90% of pts with generalised, but only 50% with the ocular form.

After confirmation of diagnosis, a x-ray of the thorax should be performed to check for a thymoma.