Gastrointestinal Flashcards

Question

How is ascites managed?

Answer 1

``` Fluid and salt restriction Diuretics Spironolactone +/- Furosemide Large-volume paracentesis + albumin Trans-jugular intrahepatic portosystemic shunt (TIPS) ```

Answer 2

Main cause of liver death in UK However, only 10-20% of heavy alcohol drinkers drinkers get serious ALD Often not alcohol dependent (‘alcoholics’) 25% will stop drinking and 25% will reduce Poor outcome – 10 year survival 25%

Answer 3

An increase in the blood pressure within a system of veins called the portal venous system. Veins coming from the stomach, intestine, spleen, and pancreas merge into the portal vein, which then branches into smaller vessels and travels through the liver. Increased hepatic resistance Increased splanchnic blood flow

Answer 4

Cirrhosis, fibrosis, portal vein thrombosis

Answer 5

Varices (oesophageal, gastric) | Splenomegaly

Answer 6

100 of total of 700 transplants/year in UK -limited by supply of livers Negative public attitudes But: post transplant survival similar to that for other liver diseases Drinking relapse –variable; recurrent ALD uncommon

Answer 7

``` Constipation Drugs - sedatives, analgesics - NSAIDs, diuretics, ACE blockers Gastrointestinal bleed Infection (ascites, blood, skin, chest) HYPO: natraemia, kalaemia, glycaemia Alcohol withdrawal (not typically) Other problems (cardiac, intracranial) Malnutrition Coagulopathy Endocrine changes ```

Answer 8

Impaired reticulo-endothelial function Reduced opsonic activity Leucocyte function Permeable gut wall

Answer 9

Commonest serious infection in cirrhosis Vague symptoms Based on neutrophils in ascitic fluid Gram stain often neg; use blood culture bottles After 1 episode patients should have antibiotic prophylaxis and consider liver transplantation

Answer 10

``` Drugs: Diuretics, NSAIDS, ACE Inhibitors, Aminoglycosides Infection GI bleeding Myoglobinuria Renal tract obstruction ```

Answer 11

A decline in brain function that occurs as a result of severe liver disease. Consequences: infection, GI bleed, constipation, hypokalaemia, drug (sedatives, analgesics)

Answer 12

``` Serial 7’s WORLD backwards Animal counting in 1 minute Draw 5 point star Number connection test ```

Answer 13

If these nodules remain small the result is a micronodular cirrhosis. If they are able to regenerate, they may become large, giving a macronodular cirrhosis. The constant replication of hepatocytes in this condition make them liable to replication errors, which may result in neoplasia developing. Hepatocellular carcinoma is a risk in patients with long-standing cirrhosis.

Answer 14

Analgesia: sensitive to opiates, NSAIDs cause renal failure, paracetamol safest Sedation: use short-acting benzodiazepines Diuretics: excess weight loss, hyponatraemia, hyperkalaemia,renal failure Antihypertensives: avoid ACE inhibitors Aminoglycosides: avoid

Answer 15

Malnutrition: naso-gastric feeding Variceal bleeding: endoscopic banding, propranolol, terlipressin Encephalopathy: lactulose Ascites / oedema: salt / fluid restriction, diuretics, paracentesis Infections: antibiotics

Answer 16

Alcohol Non Alcoholic Steatohepatitis (NASH) Viral hepatitis (B, C) Immune: autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis Metabolic: haemochromatosis, Wilson’s, antitrypsin deficiency… Vascular: Budd-Chiari (rare condition that occludes the hepatic veins)

Answer 17

Viral serology - hepatitis B surface antigen, hepatitis C antibody Immunology - autoantibodies AMA, ANA, ASMA,coeliac antibodies, immunoglobulins Biochemistry - iron studies, copper studies, 1-antitrypsin level, lipids, glucose Radiological investigations - pelvic ultrasound / CT / MRI

Answer 18

Autoimmune hepatitis is liver inflammation that occurs when your body's immune system turns against liver cells. Can lead to cirrhosis and eventually liver failure. 70-75% women ANA, ASMA- positive in about 70% Aggressive disease, 30% have cirrhosis at presentation 90%: dramatic response to prednisolone and azathioprine

Answer 19

A chronic disease in which the bile ducts in your liver are slowly destroyed. 90% women Pathogenesis unknown +ve AMA in 95% of patients Many patients have progressive disease Mayo Clinic prognostic score: uses bilirubin albumin and prothrombin time

Answer 20

``` Asymptomatic lab abnormalities Itching and/or fatigue Dry eyes Joint pains Variceal bleeding Liver failure: ascites, jaundice ```

Answer 21

UDCA, antihistamines - little help Cholestyramine helps in 50% of cases Rifampicin effective; occasionally damages liver Opiate antagonists Also: ultraviolet light, plasmapheresis, liver transplantation

Answer 22

Improvement in liver enzymes and bilirubin Subtle reduction in inflammation; but not fibrosis Reduced portal pressure and rate of variceal development Modestly reduced rate of death or liver transplantation No improvement in itching (may worsen it)

Answer 23

Leads to strictures (areas of narrowing) ± gallstones Over 50% have inflammatory bowel disease Presents as itching, pain ± rigors, jaundice Raised Alk phos and gamma-glutamyl transpeptidase 10% develop cholangiocarcinoma (bile duct cancer) Ursodeoxycholic Acid: unclear benefits Good results from Liver Transplantation

Answer 24

Genetic disorder 90% have mutations in HFE gene: C282Y, H63D Autosomal recessive Uncontrolled intestinal iron absorption with deposition in liver, heart and pancreas Diagnosis suggested by raised ferritin and transferrin saturation, confirmed by HFE genotyping and liver biopsy When cirrhosis present, increased risk of hepatocellular carcinoma Iron removal may lead to regression of fibrosis

Answer 25

``` Chronic fatigue Diabetes mellitus Melanoderma Skin dryness Joint pain Osteoporosis White, flat nails Hepatomegaly Cirrhosis Heptaocellular carcinoma ```

Answer 26

Results in inability to export a1-antitrypsin from liver Can lead to liver disease (protein retention in liver), emphysema (protein deficiency in blood) Phenotypic expression is variable: neonatal jaundice, chronic liver disease in adults No medical treatment

Answer 27

Primary liver tumour Most occur in patients with cirrhosis Risk: highest for hepatitis B,C, haemochromatosis lower: cirrhosis from alcoholic, autoimmune disease Males >Females May present with decompensation of liver disease, wt loss ascites, or abdominal pain Treatment: Transplantation, resection or local ablative therapies, Sorafenib recently shown to prolong life

Answer 28

Risk factors: Obesity, diabetes, hyperlipidaemia Usually no symptoms; liver ache in 10% Commonest cause of mildly elevated LFTs Fat, sometimes with inflammation, fibrosis (NASH) Need biopsy to distinguish NAFL from Nonalcoholic steatohepatitis Still no effective drug treatments Weight loss works- the more the better

Answer 29

Thrombosis (Budd-Chiari syndrome) Membrane obstruction Veno-occlusive disease (irradiation, antineoplastic drugs)

Answer 30

Abnormal liver tests Ascites Acute liver failure

Answer 31

Anticoagulation | Transjugular intrahepatic portosystemic shunt

Answer 32

None or non-specific, e.g. malaise, lethargy, myalgia (muscle aching) Gastrointestinal upset, abdominal pain (right upper quadrant) Jaundice + pale stools / dark urine

Answer 33

Tender hepatomegaly ± jaundice ± signs of fulminant hepatitis (acute liver failure) e.g. bleeding, ascites, encephalopathy Raised transaminases (ALT/AST >> GGT/ALP) ± raised bilirubin

Answer 34

``` Viral: Hepatitis A, B ± D, C & E Human herpes viruses e.g. HSV, VZV, CMV, EBV Other viruses Non-viral: Spirochaetes, e.g. leptospirosis, syphilis Mycobacteria, e.g. M. tuberculosis Bacteria, e.g. bartonella Parasites, e.g. toxoplasma ```

Answer 35

``` Drugs Alcohol Other toxins / poisoning Non-alcoholic fatty liver disease Pregnancy Autoimmune hepatitis Hereditary metabolic causes ```

Answer 36

Can be asymptomatic or have non-specific symptoms only May have signs of chronic liver disease: clubbing, palmar erythema, Dupuytren’s contracture, spider naevi, etc. Transaminases (ALT/AST) can be normal

Answer 37

Compensated: liver function maintained Decompensated: coagulopathy; jaundice (↑bilirubin); low albumin; ascites (± bacterial peritonitis); encephalopathy Other complications: hepatocellular carcinoma (HCC); portal hypertension (varices, bleeding)

Answer 38

Hepatitis B ± D, C (& E)

Answer 39

``` Drugs Alcohol Other toxins / poisoning Non-alcoholic fatty liver disease Autoimmune hepatitis Hereditary metabolic causes ```

Answer 40

Short incubation period: 15 to 50 days (mean 28 days) Usually symptomatic in adults: Pre-icteric phase: constitutional symptoms + abdominal pain Icteric phase (few days to 1 week after pre-icteric phase) - jaundice Self-limiting: no chronic disease 100% immunity after infection

Answer 41

Supportive: Monitor liver function (INR, albumin, bilirubin, etc.) in the case of acute liver failure, liaise with hepatology / liver transplant centre Management of close contacts Primary prevention: vaccination

Answer 42

Faeco-oral transmission: Person-to-person contact Ingesting contaminated food or water ``` Risk factors: Travel Household contact Sexual contact Injecting drug use ```

Answer 43

``` Zoonotic reservoir (pigs) Undercooked meat products ``` Contaminated food & water

Answer 44

>95% cases asymptomatic Usually self-limiting acute hepatitis Occasional acute-on-chronic liver failure (high mortality) Extra-hepatic manifestations, e.g. neurological Risk of chronic infection in immunosuppressed patients e.g. transplant recipients, HIV patients Rapid progression to cirrhosis

Answer 45

Acute infection: Supportive Monitor for fulminant hepatitis / acute-on-chronic liver failure: Liaise with hepatology / liver transplant centre Consider ribavirin Chronic infection : Reverse immunosuppression (if possible) If persists, treat with ribavirin

Answer 46

Avoid eating undercooked meats | Vaccines in development

Answer 47

``` Highly infectious blood-borne virus Blood Bodily fluids Transmission: Mother-to-child Sexual contacts Household contacts Iatrogenic Injecting drug use ```

Answer 48

Supportive management Monitor liver function (INR, albumin, bilirubin, etc.) Rarely fulminant hepatitic failure: 0.1 to 0.5% Oral nucleos(t)ide analogue (tenofovir, entecavir) Liaise with hepatology / liver transplant centre Management of close contacts - vaccinate!

Answer 49

Acute hepatitis B infection can spontaneously resolve (although may re-activate in immunosuppression) Can lead to Chronic hepatitis B which can cause hepatocellular carcinoma or cirrhosis.

Answer 50

Pegylated interferon-α 2a: immunomodulatory, weekly subcutaneous injection, 48 week long course, offers best chance of treatment-free control ``` Oral nucleos(t)ide analogues: Inhibit viral replication, One tablet once a day, High barrier to resistance, Minimal side effects, may be required lifelong ```

Answer 51

Antenatal screening (HBsAg testing) of pregnant mothers HBV vaccination administered to baby at birth and at 1, 2*, 3*, 4* and 12 months Screening ± immunisation of sexual and household contacts Universal childhood immunisation Universal screening of blood products Sterile equipment and universal precautions in healthcare Immunisation of healthcare workers + other risk groups (e.g. MSMs, PWIDs)

Answer 52

Defective RNA virus: requires HBsAg to replicate Transmitted via blood and body fluids Can be acquired simultaneously with HBV Alternatively acquired after HBV - acute on chronic hepatitis - accelerated progression to liver fibrosis Test: Hepatitis D antibody: if positive, test HDV RNA Treat: pegylated inteferon-α 48 to 96 weeks

Answer 53

Fixed dose combination of DAAs from 2 or 3 drug classes: NS5A (-asvir), NS5B (-buvir) and NS3/4A protease (-previr) inhibitors Sometimes co-administered with ribavirin (RBV) High cure rates: >95% in non-cirrhotic patients

Answer 54

No vaccine Previous infection does not confer immunity, can be re-infected Screening blood products Universal precautions handling bodily fluids Lifestyle modification, e.g. needle exchanges, etc. Treatment and cure of “transmitters”, e.g. active PWIDs

Answer 55

- Bacterial enzymes deconjugate certain compounds within the enterohepatic circulation aiding reabsorption back across the intestinal wall (bilirubin, bile acids, cholesterol, drugs) - Digestion of fibre - Metabolism of certain vitamins (Vitamin K) - Synthesis of Vitamin B12, folic acid & thiamine - Interfere and compete with exogenous pathogens preventing infection

Answer 56

The intestinal microflora is a complex ecosystem >400 species of bacteria Predominantly anaerobes Sparse microflora in the upper GI tract & luxuriant microflora in the lower GI tract.

Answer 57

Stable normal flora produces antimicrobial substances (bacteriocins and short chain fatty acids) which discourage infection by: Inhibiting overgrowth of endogenous pathogens Preventing colonisation by exogenous pathogens. Antibiotics can disrupt this balance increasing susceptibility to infections such as C.Difficile. If normal barriers are breached - Peritonitis

Answer 58

Gastric acid kills most swallowed pathogens The microbiome is protective against “alien invaders”, but is vulnerable to systemic antibiotics Less gastric acid & use of broad spectrum antibiotics leads to increased risk of intraluminal infection

Answer 59

Infective - Campylobacter, salmoella, HIV, bacterial or amoebic dysentry, cholera, systemic infections (sepsis, malaria..) Inflammatory - Crohn's disease, Ulcerative colitis Loss of absorptive area - coeliac disease, bowel resection Pancreatic disease - pancreatitis, cancer Drugs - anitbiotics, magnesium, digoxin Colon cancer Systemic disease - Thyrotoxicosis, uraemia, carcinoid Others - IBS, Gastrectomy

Answer 60

``` Onset/duration Characteristics of stool (blood, mucus, watery, fat content) Food/drink Travel/vaccinations Immunocompromised Occupation Hobbies (e.g fresh water swimming) Animal exposure Medications Unwell contacts ```

Answer 61

50-70% of cases of diarrhoea in the UK are caused by viruses Rotavirus (Children) Norovirus (All age groups, major epidemics) Rotavirus vaccine aged 8 & 12 weeks has led to a 70% reduction in cases! Other causes: Campylobacter, shigella, salmonella, c.perfringens, staph aureus, e.coli, c. diff, parasites

Answer 62

Damage mucosal architecture: Shortening & damage to villi Hyperplasia of crypts Inflammatory exudate

Answer 63

Enterotoxin-mediated (Vibrio cholera, Enterotoxigenic E.coli): Bacteria typically colonise the upper bowel Produce enterotoxins, increases intracellular AMP, mucosal cells secrete fluid, watery voluminous diarrhoea & dehydration Mucosal architecture remains intact Invasive:(Shigella and campylobacter) Typically affect the colon (shigella/campylobacter) or lower ilium (salmonella). Penetrate the intestinal mucosa causing bloody mucoid stools. Colitis marked by tenesmus (need to go but empty bowels)

Answer 64

Vibrio cholerae, gram negative bacteria Contaminated food and water (faecal-oral spread) Cholera toxin causes profuse watery ‘rice water’ diarrhoea, vomiting and rapid dehydration. 15-20L faecal output daily Tx: Doxycycline and fluids!

Answer 65

Escherichia coli 1% of local GI microbiota in humans Most serotypes harmless, some are pathogenic Classified based on O, H & K antigens in the outer membrane, flagella & capsule (e.g. O157:H7)

Answer 66

ETEC: EnteroToxigenic - LT and ST enterotoxin, Non invasive watery diarrhoea EHEC: EnteroHaemorrhagic - Shiga-like toxin Can cause Haemolytic Uraemic Syndrome (HUS) EIEC: EnteroInvasive - Dysentry like illness Similar to Shigella EPEC: EnteroPathogenic EAEC: EnteroAggregative DAEC: Diffusely Adherent LAST THREE: Watery diarrhoea due to adhesion to luminal wall, Non invasive

Answer 67

Most common travel related illness Bacteria (most common), viruses, protozoa High risk destinations: Asia, Middle east, Africa, Mexico, Central and South America (>20% travellers affected) 3 or more unformed stools in 24hrs +/- Fever/nausea/ vomiting/cramps/bloody stools (During or within 10 days of return from foreign travel)

Answer 68

``` Enterotoxigenic e.coli (30-70%) Campylobacter (5-20%) Shigella (5-20%) Non-typhoidal Salmonella (5%) V.parahaemolyticus (shellfish) Viral (10-20%) Protozoal (5-10% more chronic) Cholera ```

Answer 69

Bloods Inflammatory markers Blood cultures ``` Stool tests Microscopy Culture Ova, cysts, parasites Toxin detection ```

Answer 70

Barrier nursing: side room, gloves and apron Fluids Electrolyte monitoring and replacement Eg oral rehydration sachets, IV replacement (↓potassium, ↕sodium, ↓magnesium, ↓phosphate) Antiemetics

Answer 71

``` Dehydration Electrolyte imbalance Renal failure Immunocompromise Severe abdominal pain ``` ``` THINK OF CANCER Over 50 Chronic diarrhoea Weight loss Blood in stool FH cancer ```

Answer 72

A gram negative bacteria found in stomach of over half the worlds population. Transmission is faecal oral, gastro/oral and oral/oral. It lives within the mucus layer releasing virulence factors such as ureas which converts urea -> CO2 and ammonia which neutralizes stomach acid. Virulence factors released also damage the epithelial cells causing gastritis and ulceration. Acquisition usually asymptomatic (but can cause nausea, vomiting and fever) Ongoing symptoms – dyspepsia, epigastric pain, loss of appetite

Answer 73

Bacteria infection of the biliary tract due to obstruction Obstruction of common bile duct - stasis of bile - invasion of bacteria from duodenum eg e.coli - bacteraemia Can be obstructed by stone, cancer, stricture, parasite (ascaris). Also infection can be introduced through intervention eg ERCP Clinical diagnosis based on Charcot’s triad: jaundice, right upper quadrant pain, fever

Answer 74

Bacterial : Faecal flora eg E.coli, Klebsiella spp etc Amoebic: Entamoeba histolytica RUQ pain, fever, “PUO - pyrexia of unknown origin" Seen on ultrasound or CT Antibiotics and drainage Hydatid: Echinococcus granulosus (dog tapeworm) Insidious RUQ pain, eosinophilia Rupture - anaphylactic shock! Albendazole and PAIR (puncture-aspiration-injection-reaspiration)

Answer 75

Medical – SBP (spontaneous bacterial peritonitis), PID (pelvic inflammatory disease), dialysis related, TB Surgical – perforation of GIT eg trauma, appendicitis, cancer Intestinal flora are prime cause of infection in the perioneal cavity when intestinal wall breached Sterile – endometriosis, pancreatitis, FMF (familial Mediterranean fever), porphyria, hereditary angioedema

Answer 76

Systemic, potentially life threatening febrile illness common in areas of poor sanitation (faeco-oral spread). High incidence in South Asia Generalised/RLQ pain, high fever, bradycardia, headache, myalgia, rose spots, constipation or green diarrhoea. Diagnosis: Blood culture/bone marrow aspiration

Answer 77

GI bleed Perforation / peritonitis Myocarditis Abscesses

Answer 78

TYPHOIDAL: Causes Typhoid Fever & Paratyphoid Fever. Salmonella Typhi & Salmonella Paratyphi A, B & C NON-TYPHOIDAL: Causes Gastroenteritis and food poisoning. All other salmonella serotypes.

Answer 79

Emergency surgery Antibiotics! (IV Ceftriaxone) Mortality reduced from 20% to less than 1% with antibiotics! Typhoid Vaccine!

Answer 80

In the lumen In the wall of the bowel - contracting down on itself Outside the wall of the gut - squashing it

Answer 81

``` Tumour – carcinoma – lymphoma Diaphragm disease Meconium ileus Gallstone ileus ```

Answer 82

Some can stay in the wall, others invade into the lumen. Tumours on the right side of the colon = faeces is more liquidy, less likely to obstruct Tumours on the left side of the colon = faeces is more solid, more likely to obstruct

Answer 83

An uncommon gastrointestinal abnormality typical of nonsteroidal anti-inflammatory drug (NSAID)-induced injury. The disease is characterized by circumferential lesions of short length (<5 mm), located most commonly in the small intestine, causing multiple stenosis of the lumen.

Answer 84

Gallstone in the small bowel causing obstruction | Gallbladder is inflamed and erodes through, allowing gallstones to pass into the bowel (not through the bile duct)

Answer 85

``` Inflammatory – Crohn’s disease – Diverticulitis Tumours Neural – Hirschsprung’s disease ```

Answer 86

Can affect anywhere from the mouth to the anus Distinct granulomas Fibrosis and squeezing down of the bowel which causes the obstruction

Answer 87

Causes lots of inflammation and fibrosis Barium enema can be used to visualise Diverticula can go into the fat and cause obstruction With a low fibre diet, increased pressure, weaknesses in the mucosa mean that they push through. Faeces can get stuck there. They can get inflamed and rupture. If it ruptures you can get faecal peritonitis.

Answer 88

Adhesions Volvulus Tumour – peritoneal deposits

Answer 89

Developmental disorder is a neurocristopathy (abnormal migration, differentiation, division or survival of neural crest cells) and is characterised by the absence of the enteric ganglia along a variable length of the intestine. Causes obstruction as the stool cannot move through the bowel as it normally would.

Answer 90

Bowel adhesions are irregular bands of scar tissue that form between two structures that are normally not bound together. The bands of tissue can develop when the body is healing from any disturbance of the tissue that occurs secondary to surgery, infection, trauma, or radiation. Can cause adhesive small bowel obstruction. Can be surgically cut.

Answer 91

Volvulus occurs when a loop of intestine twists around itself and the mesentery that supports it, causing a bowel obstruction. Due to the high risk of recurrence, a bowel resection within two days is generally recommended. If the bowel is severely twisted or the blood supply is cut off, emergent surgery is required.

Answer 92

Optimal conditions for tumour growth and spread across the peritoneum. Can cause extrinsic intestinal compression, endoluminal obstruction, intramural infiltration, or extensive mesenteric infiltration.

Answer 93

``` Anorexia Nausea Vomiting Distension Abdominal Pain Altered Bowel Habits - Constipation - Obstipation ```

Answer 94

Proximal dilatation: Increased secretions and swallowed air (small bowel) or bacterial fermentation (large bowel). More dilatation leads to decreased absorption and therefore mucosal wall oedema. Increased pressure means that intramural vessels compressed leading to ischaemia

Answer 95

The colon proximal to obstruction dilates Increased colonic pressure leads to decreased mesenteric blood flow Mucosal oedema - transudation of fluid and electrolytes - lumen. The arterial blood supply compromised which can lead to mucosal ulceration and full thickness necrosis Bacterial translocation – sepsis If ileocaecal valve competent – The caecum - usual site of perforation If ileocaecal valve incompetent –faeculent vomiting

Answer 96

Increased secretions and distension Anorexia, nausea, vomiting / distension with pain Fluid and electrolyte imbalance- hypovolemia Bacterial overgrowth faeculent vomiting Untreated obstruction leads * Ischaemia * Necrosis * Perforation

Answer 97

Axial rotation – at mesenteric attachments: A 360° twist -a closed loop obstruction is produced. Fluid and electrolyte shifts into the closed loop Increase in pressure and tension - impaired colonic blood flow Ischaemia, necrosis, and perforation of the loop of bowel

Answer 98

``` Site Onset Character Radiation Association Time Course Exacerbation / Relieving factors Severity ```

Answer 99

``` NATURE Forceful Regurgitation CONTENT Bilious Faeculent Coffee Ground / Altered Blood ```

Answer 100

``` Less common -25% Intestinal obstruction - Functional obstruction (due to abnormal intestinal physiology) - Mechanical can be partial or complete Acute presentation (5 days of symptoms) - abdominal pain and obstipation, Chronic - a progressive change in bowel habits. ```

Answer 101

60 to 75% of Intestinal Obstruction 0.1 to 5% - No previous surgery 60% - previous surgery Inflammatory bowel disease – Crohns -25% 0.5% in first 2 year of life

Answer 102

``` Age and Race dependent - US/Europe – 90% colorectal malignancy - Age 70y ; Men and women equal 30% colorectal malignancy 5% Volvulus 3% strictures 2% rare causes – foreign bodies, hernia, abscess ``` African countries – 50% Volvulus Children: Anatomical development, Imperforate anus, Hirshsprung disease

Answer 103

abscess, Foreign Bodies

Answer 104

Peaks in incidence around 50/60 years of age Predominantly in Europe/North America Increasing in incidence in the UK Decreased mortality rates - better detection at an earlier age Those with polyps have an increased risk of colorectal cancer More common in rectum/anus (38%)

Answer 105

Develop thousands of polyps in teenage years APC gene produces a protein, it’s normal function is to regulate the levels of beta catenin, along with GSK. When it is mutated, you can get a misfolded protein or no protein at all. Beta catenin is then free to bind to the DNA, which can cause the development of epithelial proliferation and then an adenoma. Severity depends on the type of mutation in APC. 1% of colorectal cancers.

Answer 106

Damage to the DNA is repaired with 2 DNA repair protein genes Born with a mutation in 1 and may lose the second in life. Cells accumulate DNA damage.

Answer 107

Risk of further cancers (ureters, endometrium) in index patient and relatives Possible implication for therapy - tolerance of 5-FU, do not recognise DNA damage, apoptosis not activated

Answer 108

R0 - tumour completely excised locally R1 - microscopic involvement of margin by tumour R2 - macroscopic involvement of margin by tumour

Answer 109

Normal epithelium - prevention Adenoma - endoscopic resection Colorectal adenocarcinoma - surgical resection Colorectal adenocarcinoma - metastatic colorectal adenocarcinoma (chemotherapy, palliative care)

Answer 110

Stage A: limited to mucosa Stage B1: extending into muscularis propria but not penetrating through it; nodes not involved Stage B2: penetrating through muscularis propria; nodes not involved Stage C1: extending into muscularis propria but not penetrating through it; nodes involved Stage C2: penetrating through muscularis propria; nodes involved Stage D: distant metastatic spread

Answer 111

3 or more loose stools in 24 hours

Answer 112

``` NON INFECTIVE Neoplasm Inflammatory Irritable bowel - caused by stress Anatomical - born with a short gut/surgery, lack of water absorption in large bowel Hormonal - hyperthyroidism Radiation - radiotherapy Chemical ``` INFECTIVE Non-bloody - cholera, norovirus Bloody (Dysentery) - salmonella

Answer 113

RESERVOIR: Pathogen exists in the environment, potentially within a reservoir, portal of exit AGENT: mode of transmission, portal of entry HOST: Enter susceptible host, spread to a new host

Answer 114

Direct - direct route (STIs, scabies) faeco-oral route (viral) Indirect - vector-borne (malaria), vehicle-borne (hepatitis B) Airborne - respiratory (TB, legionella)

Answer 115

Norovirus is very common in care homes, hospitals, schools, cruise ships, families. Major cause of winter vomiting Vomiting, diarrhoea, nausea, cramps, headache, fever, chills, myalgia Last 1-3 days Immunity is short lived Can be dangerous in the elderly or immunocompromised

Answer 116

Widely distributed in soil and digestive tract Spores resistant to heat, drying and chemicals Associated with antibiotic use - especially broad-spectrum In hospitalized patients cause - antibiotic-associated diarrhoea, colitis, pseudomembranous colitis Morality high - patients tend to be elderly and ill Asymptomatic carriage occurs in 2-3% healthy adults, ⅔ of babies, 36% of hospital patients Spread by faeco-oral or through spores in the environment.

Answer 117

Control antibiotic use especially ampicillin, amoxicillin and cephalosporins Standard infection control procedures Surveillance and case finding Any patient with diarrhoea: isolate, enteric precautions, test stool samples, environmental cleaning, treat cases with metronidazole or vancomycin

Answer 118

Test stool samples for the toxin Can also culture it (in order to identify which strain it is) Tissue samples (histology) obtained at sigmoidoscopy Don’t need to screen or treat asymptomatic carriers

Answer 119

1. Rotavirus and measles vaccinations 2. Promote early & exclusive breastfeeding + Vitamin A supplementation 3. Promote hand washing with soap 4. Improved water supply quantity & quality, including treatment & safe storage of household water 5. Community-wide sanitation promotion.

Answer 120

- Hand-washing with soap - Ensure availability of safe drinking water - Safe disposal of human waste - Breastfeeding of infants & young children - Safe handling and processing of food - Control of flies/vectors - Case management including exclusion - Vaccination

Answer 121

Persons of doubtful personal hygiene or with unsatisfactory hygiene facilities at home, work or school Children who attend pre school or nursery People whose work involves preparing or serving unwrapped/uncooked food HCW/Social care staff working with vulnerable people

Answer 122

Diseases, infections and conditions specifically listed as notifiable under the Public Health Legal obligation for any doctor that suspects a case to inform the Proper Officer of the Local Authority PHE also accepts notifications from nurses and other health professionals. Don’t have to wait for laboratory confirmation! HIV, bird flu, or vCJD are not notifiable

Answer 123

``` Anthrax Cholera Plague Rabies Severe acute respiratory syndrome Smallpox Viral haemorrhagic fever Yellow fever // Acute encephalitis Botulism - wound Brucellosis - contact with animals Enteric fever (Typhoid & Paratyphoid fever) Haemolytic Uraemic Syndrome - caused by E coli Legionnaires Disease Ophthalmia neonatorum Leprosy Leptospirosis - from rat’s urine Malaria Relapsing fever Typhus fever ```

Answer 124

``` Acute poliomyelitis Diphtheria Measles Mumps Rubella Tetanus Whooping cough Acute Meningitis/Meningococcal septicaemia ```

Answer 125

Acute infectious hepatitis Foodborne (Food poisoning, Botulism, Enteric fevers, Infectious bloody diarrhoea) Scarlet fever - warm rough ‘sandpaper’ rash, ‘strawberry’ tongue, caused by group A streptococcus (gram neg) Tuberculosis

Answer 126

Detection of any changes in a disease: Outbreak detection, Early warning, Forecasting Track changes in disease: Extent and severity of disease, Risk factors Allows development of interventions targeted at vulnerable groups

Answer 127

Investigate: contact tracing, partner notification, look back exercises, etc... Identify and protect vulnerable persons: e.g. chemoprophylaxis, immunisation, isolation Exclude high risk persons or from high risk settings Educate, inform, raise awareness, health promotion Coordinate multi-agency responses

Answer 128

Passive immunity provided by injection of human immunoglobulin containing antibodies to the target infection Temporarily increases person’s antibody level to that specific infection. Protection gained within a few days but lasts only a few weeks. Most commonly cross-placental transfer of antibodies from mother to child (e.g. measles, pertussis) Or, via transfusion of blood or blood products including immunoglobulin (e.g. Hep B) Protection is temporary – usually only a few weeks or months. Specific immunoglobulins available for tetanus, hepatitis B, rabies and varicella zoster.

Answer 129

Vaccination stimulates immune response and memory to a specific antigen/infection Vaccines made from – inactivated (killed) (e.g. pertussis, inactivated polio) – attenuated live organisms (e.g. yellow fever, MMR, polio, BCG) – secreted products (e.g. tetanus, diphtheria toxoids) – the constituents of cell walls/subunits (e.g. Hep B) or – recombinant components (experimental)

Answer 130

Polysaccharide antigens not as immunogenic as protein antigens. Protection is not long-lasting Response in infants and young children often poor. Conjugation helps improve immunogenicity (e.g. Hib, Men C)

Answer 131

``` Live attenuated organism must replicate in the vaccinated individual to produce an immune response. Takes time (days or weeks). Usually does not cause disease but some may cause a mild form of the disease. ```

Answer 132

No vaccine offers 100% protection Small proportion of individuals get infected despite vaccination. Primary vaccine failure – person doesn’t develop immunity from vaccine. Secondary vaccine failure – initially responds but protection wanes over time.

Answer 133

Meningococcal infection can present as meningitis or septicaemia. Caused by Neisseria meningitidis Infection is not easily spread Transmitted from person to person by inhaling respiratory secretions from the mouth and throat or by direct contact (kissing) Close prolonged contact is usually required They do not live long outside the body

Answer 134

Majority of infections occur in children <5 years of age Peak incidence in under 1s. Smaller secondary peak in young adults (age 15-19 years) Most cases sporadic <5% of cases occur in clusters. Outbreaks more common among teenagers and young adults (e.g. in schools and universities). Marked seasonal variation with peak in winter. The winter season coincides with that of influenza.

Answer 135

Distinct serogroups, according to their polysaccharide outer capsule. The most common pathogenic serogroups are groups B, C, A, Y and W135. Most disease in the UK is caused by serogroups B (59%) and C (36%). Significantly fewer cases caused by serogroup C since routine vaccination introduced

Answer 136

``` Brain abscess Brain damage Seizure disorders Hearing impairment Focal neurological disorders Organ failure Gangrene Auto-amputation Death ```

Answer 137

Antibiotic therapy: Cefotaxime or Ceftriaxone | Supportive treatment

Answer 138

Contact for meningitis is taken to be any person having close contact with a case in the past 7 days Close contact includes kissing, sleeping with, spending the night together or spending in excess of eight hours in the same room Once contacts identified they can be offered advice (warn about symptoms and signs, glass test, contact telephone number) or antibiotic chemoprophylaxis - Ciprofloxacin (older children & adults) or Rifampicin (not pregnant women) to reduce spread. If the serotype of meningococcus is vaccine preventable, vaccination may be offered.

Answer 139

Men C immunisations since 1999. Men B vaccine rolled out 2015 Quadrivalent (A, C, W135, Y) for Year 9s (preuniversity)

Answer 140

Secretion - Digestion and Defence Motility - Mixing and Movement Defence - Pathogen invasion, Toxins, Vomit/nausea Control system Absorption of Nutrients/water Nutrient distribution through the blood stream

Answer 141

Longitudinal muscle - modifies length | Circular muscle - modifies lumen diameter

Answer 142

``` Mesenchymal cells located within the muscle layers of the alimentary tract that mediate communication between the autonomic nervous system and smooth muscle. Cyclic changes in membrane potential - Slow wave currents Na+-mediated (NOT action potentials) Location-specific frequency Stomach – 3/min Terminal ileum 9/min ``` - High frequency Spike potentials (1-10/sec; 10-20msec duration) Ca2+-mediated (slow channels) Dynamic resting membrane potential

Answer 143

Enteric nervous system - complicated organisation, two plexi Submucosal (Meissner’s) plexus Superficial location Regulates gut secretion/local blood flow Myenteric (Auerbach’s) plexus Located deep in the gut muscle layer Between circular and longitudinal smooth muscle layers Governs gut motility

Answer 144

``` Linear neurone chain: Acetylcholine Excitation causes increased: - Gut tone - Contraction rate / intensity - Excitatory wave conduction speed Some inhibitory function - Vasoactive Intestinal Peptide (VIP) - Reduced sphincter tome - Pylorus/ileocaecal valve ```

Answer 145

``` Monitors inner wall of each gut segment Mediates local - Secretion - Absorption - Muscularis mucosae contraction ```

Answer 146

Cranio-sacral system: 2-4th sacral divisions and Vagus Net stimulatory effect: Depolarisation by Acetylcholine (ACh) Efferent motor fibres↑ smooth muscle activity Afferent sensory fibres inform CNS

Answer 147

``` Thoracolumbar system: Segments T5-L2. Net inhibitory effect: Hyperpolarisation by Noradrenaline Synapse prevertebral ganglia - Inhibits gut smooth muscle activity and enteric nerve function Excites - Muscularis mucosae - Blood flow - Profound vasoconstriction ```

Answer 148

Reflexes within gut wall enteric nervous system - Secretion, peristalsis Reflexes involving sympathetic prevertebral ganglia Gastrocolic reflex: from stomach to evacuate colon Enterogastric reflex: from colon/SI to inhibit gastric secretion/motility Colonileal reflex: from colon to inhibit ileal emptying Reflexes from gut to spinal cord/brain stem back to gut Vagovagal reflex initiating gastric secretion Pain reflexes - general inhibition of gut Defaecation reflexes

Answer 149

Chewing aids digestion of food further down GI tract by increasing SA for digestive enzymes to work. Digestion is highly dependant on total surface area. Chewing is largely a reflex. Presence of bolus of food in mouth causes lower jaw to drop , stretch reflex causes jaw to rebound….cycle repeats

Answer 150

Swallowing reflex regulated by cranial nerves V, IX, X and XII 3 PHASES Buccal (voluntary):: initiates swallowing. The voluntary action of the tongue forcing the bolus of food towards the pharynx at the back of the throat. Pharyngea (less than 1-2 sec): The pharynx is the passageway for food, fluid and air. Lots of mechanoreceptors are present. Presence of food intiates a wave of peristaltic contraction (the larynx rises so that the epiglottis covers the nasopharynx and trachea). Oesophageal: involuntary phase promotes passage of food from pharynx into stomach.

Answer 151

Peristalsis – travelling wave of contractions Contraction behind & relaxation ahead so that the mass propelled along. Primary peristalsis is the continuation of waves that began in the pharynx. Secondary peristalsis is initiated partly by reflexes transmitted through vagal afferent from oesophagus to medulla and back to oesophagus via vagal efferent fibres.

Answer 152

Buccal Phase: Food bolus compressed against hard palate Retraction of tongue elevates soft Palate (isolating nasopharynx) Forces bolus into pharynx Pharyngeal phase: Bolus touches palatal arches and posterior pharyngeal wall. Elevation of larynx and folding of epiglottis close glottis Bolus directed into oesophagus by pharyngeal muscles – so that it won’t go back up Oesophageal phase Upper oesophageal sphincter opens -bolus pushed through. Primary peristaltic wave occurs, bolus carried down oesophagus This movement triggers opening of lower oesophageal sphincter; bolus enters stomach

Answer 153

Stores ingested foods - Storage capacity ≈ 1.5 litres Breaks down food - Contractions mix with gastric juices (acid/enzymes) to make chyme Strong peristaltic contractions - Controlled delivery rate of chyme into duodenum Optimum digestion and absorption

Answer 154

Fundus - upper expandable portion of the stomach which functions as a reservoir for ingested food. Body - main site for acid secretion Antrum - most heavily muscularised portion of stomach….grinds food into smaller particles. Pylorus - sphincter aids the grinding process and acts as a sieve. The inner surface of the stomach has a series of folds known as rugae, these increase the surface area of the gastric mucosa. The surface is composed of mucus secreting and columnar epithelial cells interrupted by gastric pits, the site of gastric secretion.

Answer 155

Upper part are mucus secreting cells Parietal cells secrete acid (oxyntic cells) Peptic cells – secrete enzymes G cells that produce gastrin and histamine and have a paracrine action to control acid secretion in parietal cells.

Answer 156

As food pours in, initial relaxation of the fundus to take it in. Contraction rings from the top to the bottom to squeeze the food down. At the same time there is contraction in the pylorus region, pushing the food against the constriction, allowing for it to be mixed. Retropulsion – making sure that the digestion juices have been fully mixed with the incoming food, breaking it down.

Answer 157

Collective term describing hormonal and neural mechanisms mediating gastric emptying Food enters duodenum Initiates multiple reflexes from duodenal wall that pass back to stomach Slow/stop stomach emptying

Answer 158

STOMACH SIGNALS - Gastric distension by food - Presence of gastrin Stretching of the stomach wall elicits vagal and local myenteric reflex Signals from stomach increase pylorus pumping force and inhibit the pyloric sphincter DUODENAL SIGNALS Depress pyloric pump Increase pyloric sphincter tone Excess chyme depress the pyloric pump

Answer 159

Rate of gastric emptying dependent on various factors including the physical form of food Solid food empties more slowly than liquids Permits longer time for complete gastric digestion Full stomach empties more rapidly Half-life for liquids to leave stomach ~20mins vs. 2hours for solids

Answer 160

Distension of the duodenum Irritation of mucosa Acidity of chyme Presence of chyme constituents - fats appear to be especially important

Answer 161

Cholecystokinin (CCK) (I-cells of duodenum and Jejunum) in response to fat (competitive inhibitor of gastrin) Secretin (S-cells of duodenal mucosa) Decreased pH stimulates release into blood, inhibits stomach gastrin secretion

Answer 162

Mixing contractions (segmental) Distension of SI elicits concentric contractions at intervals along the intestine Propulsive contractions (peristaltic) - activity increases after a meal - relatively weak - net movement of chyme at about 1cm/min Chyme ~3-5 hours from pylorus to ileocaecal valve.

Answer 163

Segmented contractions in response to distension of the gut Regularly spaced – chopping up the bolus of chyme, segmented and mixed (as well as moved by a peristaltic contraction) Governed by the myenteric plexus “slow wave propagation” Directional (Mouth to anus) Initiated by intestinal distension Mixes/churns chyme

Answer 164

``` Governed by the myenteric plexus Directional (Mouth to anus) Local reflexes - Gastroenteric (stomach distension) - Gastroileal (gastrin-mediated by stomach distention) ``` Circular muscle contract behind the bolus “receptive relaxation” of muscle in front of bolus - facilitates bolus movement Longitudinal muscles contract – shorten adjacent segments Continues along gut

Answer 165

Large intestine processes chyme into faeces. Proximal part absorbs any remaining water and electrolytes Distal part stores solid waste Unidrectional - Pressure closes ileoceacal valve and prevents backflow from caecum Ileocaecal sphincter slight constriction slows ileal emptying Post-meal gastroileal reflex opens ICV to promote emptying into caecum Caecal irritants/distention inhibit ileal peristalsis and promote ileal sphincter spasm

Answer 166

``` SEGMENTAL Constriction of circular & longitudinal muscle Unstimulated part bulges - Haustrations PERISTATIC Less common MASS Large scale contraction of colon May last 30sec, subside then repeat. ``` Rectal distension following mass movement can trigger a reflex involving: i) contraction of the sigmoid colon & rectum – forcing faeces out ii) relaxation of the anal sphincter

Answer 167

Rectal distension following mass movement can trigger a reflex involving: i) contraction of the sigmoid colon & rectum – forcing faeces out ii) relaxation of the anal sphincter Voluntary control developed by ends of infancy to permit postponement of defecation.

Answer 168

``` Internal anal sphincter: Smooth muscle (Several cm length) External anal sphincter: Striated muscle Surrounds IAS Extends distal to IAS Controlled by pudendal nerve and somatic nerve; voluntary control ```

Answer 169

``` Weak, local enteric nerves in rectal wall Augmented by parasympathetic reflex Distension of rectum by faeces Myenteric plexus initiates: peristaltic wave in DC, SC and rectum; faeces pushed to anus Inhibition of IAS tone (relaxes IAS) EAS consciously relaxed Defaecation occurs ```

Answer 170

Sacral spinal cord segments Rectal stimulation initiates signal to spinal cord Parasympathetic fibres return reflex from spinal cord to descending colon, sigmoid, rectum and anus Intensifies myenteric peristalsis into strong defaecation process Can empty bowel from splenic flexure Can be consciously controlled

Answer 171

Activation of vomiting centre by sensory afferents Initiates anti-peristalsis in ileum Profound relaxation of proximal stomach Retrograde Giant Contraction (vagal control) – contraction from deep within the ileum Reversal speed 2-3cm/sec Clears contents into duodenum/stomach in ~5 mins. Duodenal distention triggers vomiting act - Strong contraction of duodenum/stomach/abdominal wall - Relaxation/opening of oesophageal sphincters

Answer 172

``` Motion sickness Drugs – opioids Activate chemoreceptor trigger zone In turn activate vomiting centre Treatment – anti-emetics e.g. Ondansetron (5HT receptor antagonist) ```

Answer 173

Mechanical - Chewing, gastric mixing Chemical - Enzymatic and Emulsification Both processes require mucosal secretions

Answer 174

Digestion of food starts in the mouth where food is mechanically broken down by chewing and amylase and lipase (breakdown of starch). Production of saliva - reflex salivation by 3 glands (Parotid, submandibular sublingual) Under basal conditions about 0.5ml/min. Saliva contains large quantities of potassium and bicarbonate ions. Sodium and chloride low. Lowest NaCl when juice is flowing slowly and increases when flow rate increases. Flow of saliva helps wash away pathogenic bacteria as well as food particles, also contains factors that destroy bacteria – defence system.

Answer 175

Cephalic - stimulated by chemoreceptors and mechanoreceptors in buccal and nasal cavities Gastric - stimulated by food in stomach and distension it causes Intestinal - only a small portion of secretion

Answer 176

Sight, smell, thought, taste Accounts for 1/5 secretion Stimulated by chemo- and mechano-receptors in buccal and nasal cavities Vagal activity stimulated by afferent inputs cause release of Ach and gastrin releasing peptide (GRP) from neurons of stomach which act on parietal and gastrin cells – prepares the gut for food. Short local reflex: Efferent signal from stomach via abdominal branches of vagus Releases Ach and gastrin releasing peptide

Answer 177

Accounts for 2/3 secretion Principally due to distension & chemical content of food Food entering stomach stimulates vagal reflex Gastrin released

Answer 178

``` Presence of food in upper SI Acid triggers release of secretin and CCK Inhibits gastrin activity Controls rate of gastric emptying Allows SI to perform optimally ```

Answer 179

Presence of food in SI initiates a reverse enterogastric reflex Utilises coordination of myenteric, sympathetic and vagal nerves Reflex initiated by: Bowel distention, Acid in upper SI, Digested protein, Mucosal irritation

Answer 180

Gastric mucosa lined by columnar epithelial cells interrupted by gastric glands Oxyntic (Gastric) glands – acid secreting Pyloric glands – gastrin secreting Both secrete protective mucus

Answer 181

Mucous is alkaline and about 1mm thick. Secreted from the superficial epithelial mucus cells and the cells around the neck of the gastric glands. Mucus secretion is stimulated by acetylcholine, mechanical stimulation, and some chemicals such as ethanol.

Answer 182

Pepsinogen is an inactive precursor to pepsin, which is converted to pepsin when pH<5 or by the action of pepsin itself. Pepsinogen is released by chief cells from the gastric glands by the action of acetylcholine.

Answer 183

Gastrin is secreted by G-cells in the antral glands of the stomach in response to distension of the stomach wall. It stimulates the submucosal plexus, releasing Gastrin Releasing Peptide (GRP)), and partially digested food e.g. amino acids. It is released into the blood where it tavels to the parietal cells to stimulate acid secretion, and to ECL cells to stimulate histamine secretion. The net result of gastrin secretion is increased acid production through two mechanisms 1. Direct stimulation of the parietal cells 2. Trophic action on parietal cells increasing their number.

Answer 184

``` Water Inorganic salts K+, HCO3- (higher than plasma) Na+, Cl- (lower than plasma) Lowest NaCl when juice is flowing slowly Increases when flow rate increases ```

Answer 185

Upper part contains mucous secreting cells Lower part contains parietal cells that secrete acid (HCl), peptic cells (chief cells) which secrete pepsinogen, intrinsic factor and causes absorption of vitamin B12 in ileum. Also contains Enterochromaffin-like (ECL) cells that secrete histamine in response to gastrin.

Answer 186

Present in the antrum of stomach Upper aspect contains mucus secreting cells which protect pyloric mucosa Lower aspect contains G-cells which secrete gastrin Paracrine regulation of Parietal cell acid secretion and ECL-cell histamine secretion

Answer 187

Secreted from enterochromaffin-like (ECL) cells of gastric glands Release stimulated by gastrin and acetylcholine act on ECL cell Acts directly on parietal cells via histamine H2 receptors Acts synergistically with gastrin and acetylcholine to stimulate acid synthesis

Answer 188

Breakdown of meat Activation of inactive pepsinogen Optimal conditions for the activity of pepsin Combines with Fe & Ca to form soluble salts - acid aids the absorption of these minerals Defence mechanism

Answer 189

Ulcers - Too much acid due to stress, reflux or infection (H.pylori) Achlorhydria/Hypochlorhydria - Destruction of parietal cells. Failure of stomach to secrete acid Pernicious anaemia - no intrinsic factor, no ileal VitB12 absorption

Answer 190

Pancreas | Gall bladder - Enters duodenum at bile & pancreatic duct

Answer 191

Sucrase, maltase & lactase are the digestive enzymes present on brush border Hydrolyse various disaccharides Not secreted

Answer 192

Exocrine (enzymes, HCO3-) | Endocrine (Insulin/Glucagon)

Answer 193

Pancreas is parallel to and beneath the stomach In addition to secreting insulin via the alpha/beta cells, it also secretes digestive enzymes from the pancreatic acini and also bicarbonate. The combined product flows through the pancreatic duct, joins the hepatic duct & empties into the duodenum at the spincter of Oddi. Secretion occurs most abundantly in response to the presence of chyme.

Answer 194

Bicarbonate serves to neutralise the chyme – to ph7/8 which is optimal Contains enzymes for digesting all 3 major food types: Protein, carbohydrate & fats

Answer 195

Acetylcholine - Released from the PS (vagus nerve) Gastrin - From stomach CCK - From duodenum & upper jejunum Secretin - From duodenum & jejunum. ACh, Gastrin & CCK all stimulate pancreatic acinar cells Secretin causes endocrine release induced by acid in duodenum Responsive pancreatic secretion of bicarbonate Neutralisation of chyme

Answer 196

Presence of food in SI initiates a reverse enterogastric reflex Requires coordination of: - myenteric nervous system - symp. and vagus nerves - intestinal factors (VIP, GIP, secretin, somatostatin) Reflex initiated by: Bowel distention, Acid in upper SI, Digested protein, Mucosal irritation

Answer 197

Proteolytic enzymes (not active until →SI) – really potent proteases: Trypsin, Chymotrypsin, Carboxypeptidase Carbohydrate: Pancreatic amylase breaks down starch Fat digestion: Pancreatic lipase - Triglycerides: Free fatty acids, monoglycerides & some glycerol - Cholesterole esterase: Hydrolysis of cholesterol esters - Phospholipase: Hydrolysis of fatty acid from phospholipids

Answer 198

``` Present in the proximal duodenum Secrete copious alkaline mucus Protective function Stimulated by mucosal irritation, vagal stimulation, vagal hormones (secretin) Inhibited by sympathetic stimulation ```

Answer 199

``` Located throughout SI - crypts of each villus Secretes almost pure ECF ~1800ml/day Provides vehicle for absorption Secretion mediated by Na+,Cl-, HCO3- Causes osmotic drag ```

Answer 200

Liver secretes 600-1200ml/day bile into gall bladder Bile in liver canniculi empty into the bile ducts Closed sphincter of Oddi - dilute bile secreted into gall bladder CCK most potent stimulus for bile secretion Gall bladder contracts and sphincter of Oddi relaxes Bile released into duodenum

Answer 201

Complex mixture of: Bile acids Cholesterol Concentrated by gall bladder as water/ions reabsorbed ``` FUNCTION Essential for lipid digestion Emulsifies fat droplets Facilitates action of pancreatic lipase Micelles allow fatty acid absorption Major route for cholesterol and bilirubin excretion ```

Answer 202

Metabolite of Hb. Some excreted in the faeces. Other reabsorbed for excretion in the kidney Jaundice results when there is excessive bilirubin in the blood, this occurs if the biliary flow is obstructed by gall stones.

Answer 203

Too much intestinal secretion Enteritis – inflammation caused by bacterial/viral or mucosa irritated Cholera Psychogenic - Over active parasympathetic system, increased secretion/motility Ulcerative colitis - Chronic bowel inflammation, continuous mass movements

Answer 204

Absorptive surface area - ~ 250M2 Counter-current blood supply ``` Carbohydrates Protein Lipids Water & Na+ Vitamins & minerals ```

Answer 205

Duodenum - Extensive mucus glands (Brunner’s) Jejunum - Maximal absorption in proximal villi Plica extensive and prominent Chyme now pH ~7-8 Ileum - Less absorption, villi smaller, less numerous

Answer 206

Body must absorb 25-30g Na+/day Na+/K+ ATPase creates significant Na+ gradient Absorption of Na+ drives that of other nutrients - Na+:nutrient symporters - Na+/H+ exchanger - +ve charge drags Cl- and water Water-soluble nutrients absorbed into villus blood supply and join hepatic portal circulation HCO3- buffers bacterial acid in the large intestine Fats and lipids are dissolved in bile micelle Micelles fuses with apical membrane Fatty acids diffuse directly into cell and smooth endoplasmic reticulum Transported in lacteal to lymphatic system

Answer 207

``` Processes ~1,500 ml chyme into ~200 ml faeces Absorbs H20, electrolytes, Facilitates bacterial fermentation Stores solid waste Proximal colon: absorption Distal colon: storage ```

Answer 208

Metabolic regulation: Glucose/fats/proteins, Detoxification, Storage of fat-soluble vitamins (A,D,E, K), Fe Haematological Regulation: Receives ~25% cardiac output, largest blood reservoir, synthesis of coagulation factors Bile synthesis and secretion

Answer 209

Basic functional unit – liver lobule has portal area at each corner (branches of portal vein, hepatic artery, bile ductules) Hepatocytes arranged in one-cell thick plates with numerous short micro-villi. They cluster around central vein and the sinusoids (lined with Kupffer cells) are empty here. Heptatocytes continuously produce bile which is collected in canaliculi which merge on a bile ductule - hepatic duct and common bile duct.

Answer 210

Bile acid and cholesterol-rich Secreted directly OR stored via cystic duct in gall bladder. HCO3- -rich solution added during transit through bile ductules (secretin-mediated) Acid neutralisation

Answer 211

~94% of bile salts recycled via enterohepatic circulation Reabsorbed via small intestine and portal circulation Diffusion in proximal SI Active transport in distal ileum First pass returns majority of bile salts to hepatocytes for re-secretion in bile canaliculi

Answer 212

``` Excess bilirubin in extracellular fluid Yellowish tinge to skin/eyes Normal range ~0.5 mg/dl plasma Jaundice up to 40 mg/dl Yellow skin tinge at ~1.5 mg/dl ```

Answer 213

Haemolytic jaundice Increased red blood cell destruction Obstructive Jaundice Bile duct obstruction Hepatocyte damage

Answer 214

Fe removed and recycled Haem converted to bilivirdin Bilivirdin reduced to unconjugated (free) bilirubin Unconjugated bilirubin released from macrophages Absorb by hepatic cells ~80% conjugated to glucuronide (conjugated bilirubin) Excreted from liver - bile Intestinal bacteria convert conjugated bilirubin to urobilinogen Hepatic/renal excretion Oxidised in faeces to stercobili

Answer 215

Gastritis is a general term for a group of conditions with one thing in common: inflammation of the lining of the stomach. The inflammation of gastritis is most often the result of infection.

Answer 216

In acutely ill patients, there is a reduction in blood flow to the stomach (mucosal ischaemia). In this case, the glandular gastric cells are unable to produce mucin so are not well protected from the acidic conditions of the stomach. This causes the cells to die and produces a micro-ulcer. This hole in the cells makes the cells that are at the side vulnerable to the acid too - risk of gastroduodenal ulceration.

Answer 217

Acid is corrosive and if there is increased acid in the stomach, it may be able to break down the mucin layer, and the cells will die. Stress can cause increased acid. Helicobacter can cause increased acid production. Aspirin can sit on the mucosa, release salicylic acid which inhibits COX2 (prostaglandin synthetase) and can cause ulceration.

Answer 218

Bile comes into the duodenum through the sphincter of Oddi but it is not good for the stomach. Bile reflux means that bile enters the stomach and can kill the cells. This may be because the patient has had a partial gastrectomy.

Answer 219

Helicobacter live in the mucin layer in the stomach (very niche environment). Ingested, a lot of them are killed by the acid, but some survive. They produce chemicals that attract acute inflammatory cells which move in and produce chemicals which cause gastric ulceration. If they are present for a long time, the stomach can undergo intestinal metaplasia, becoming intestinal tissue. Gives a small risk of gastric cancer. Can be treated with antibiotics.

Answer 220

There will be pain as soon as there is an ulcer present. There may be some bleeding from some vessels. But if the ulcer moves down deeper, it can hit an artery and cause a haemorrhage - vomiting up litres of blood. If it goes all the way through, you can get peritonitis or pancreatitis.

Answer 221

Can manifest itself as weight loss, pale floating faeces (because fat is not being absorbed), anaemia.

Answer 222

Small bowel is arranged in villi to maximise surface area for reabsorption. The crypts are full of proliferative cells to replace the epithelium cells higher up. The brush border around the villi also increases surface area.

Answer 223

Insufficient intake of the right nutrients Defective intraluminal digestion Insufficient absorptive area Lack of digestive enzymes Defective epithelial transport due to abetalipoproteinemia or primary bile acid malabsorption Lymphatic obstruction due to lymphoma or TB

Answer 224

The enzymes needed for digestion (e.g. amylase) are mostly produced by the pancreas. So if there is insufficient pancreas or blocked pancreatitis it can cause defective intraluminal digestion. This can occur in pancreatitis (pancreas destroyed by inflammation) and cystic fibrosis (secretions block off the ducts - pancreas atrophies). Can also be caused by defective bile secretion (lack of fat solubilisation) due to biliary obstruction or ileal resection (ileum circulates bile salts). Can also be caused by bacterial overgrowth.

Answer 225

Gluten-sensitive enteropathy - affects 1% of the population causes villous atrophy and crypt hyperplasia. Increased number of intraepithelial lymphocytes. Allergic reaction to gluten. Gliadin protein from gluten gets absorbed and processed by transglutaminase. It is presented to an antigen-presenting cell. CD patients make an allergic reaction to this gliadin and produce toxic T cells and the cells are killed, damaging the epithelium. Body cannot replace them quickly enough - villous atrophy.

Answer 226

Procedure for morbid obesity Crohn’s disease Infarcted small bowel Reduces surface area for absorption

Answer 227

``` Disaccharidase deficiency (lactose intolerance) - don’t absorb it, lactose goes undigested and bacteria live off it in the colon - abdominal distention and wind 80/90% in China are lactose intolerance Bacterial overgrowth - brush border damage ```

Answer 228

Chronic idiopathic inflammatory bowel disease - Crohn’s disease or Ulcerative Colitis Other inflammatory conditions - Diverticulitis, Ischaemic colitis, Infective colitis (bacterial or protozoal).

Answer 229

Patchy inflammation anyway from the mouth to the anus. Through the full thickness of the bowel wall (transmural) out into the fat. Granulomas present - patches of macrophages surrounded by lymphocytes.

Answer 230

Almost all in the bowel Malabsorption - disease extent or surgical resection Obstruction - acute swelling or chronic fibrosis Perforation - acute abdomen Fistula formation Anal - skin tags, fistula, fissure Neoplasia - colorectal cancer Systemic - amyloidosis (rare) - deposition of B-pleated proteins

Answer 231

Similar symptoms to Crohn’s disease Distinct in pathology Inflammation is all mucosal - starts in the rectum and is continuous No presence in the ileum Aetiology isn't known, could be bacterial

Answer 232

Liver - fatty change, chronic pericholangitis, sclerosing pericholangitis Colon - blood loss, toxic dilatation, colorectal cancer Skin - erythema nodosum, pyoderma gangrenosum Joints - ankylosing spondylitis (joints in the spine become fused), arthritis Eyes - iritis, uveitis, episcleritis

Answer 233

Chronic autoimmune enteropathy triggered by ingested gluten in genetically susceptible individual

Answer 234

Used to be considered as a pediatric disease Children were very malnourished, failure to thrive, distended abdomen Prevalence in Europe now is 1 in 100 Comments age for presentation is between 4-6th decade. More females than males For every paediatric case diagnosed there are 9 adult cases. People with undiagnosed adult coeliac disease generally have a normal BMI and may even be overweight. In a GI clinic, 3% prevalence.

Answer 235

``` A real increase Increased awareness of the spectrum of diversity in the presentation of coeliac disease Change in endoscopic techniques Antibody screening Reduced mortality rate ```

Answer 236

Viral infections? Dysbiosis? Gluten - gliadins (alcohol-soluble component of gluten) - glutenins (alcohol-insoluble component of gluten)

Answer 237

Genetic predisposition Association with HLA DQ2/DQ8 molecules Tissue transglutaminase

Answer 238

Gluten is a complex of proteins that are found in wheat, barley, rye, spelt and kamut. Viscoelastic and adhesive properties that give the dough it's typical elasticity. Essential for giving the bread the ability to rise properly during baking. Low cost, widely demanded by the food industry - gluten can be found in packaged food made from gluten-free components.

Answer 239

90-95% of coeliac patients express HLA-DQ2 molecules 5% of coeliac patients express HLA-DQ8 molecules Nearly 40% of caucausians express both DQ2 and DQ8. Negative predictive value is 100%

Answer 240

Classical - diarrhoea, steatorrhoea, weight loss, failure to thrive Non-classical - irritable bowel type symptoms, iron deficiency anaemia, osteoporosis, chronic fatigue, dermatitis herpetiformis, ataxia, peripheral neuropathy, hyposplenism, amenorrhoea, infertility, associated autoimmune disorders Silent - first degree relatives, screening of general population, ‘neglected’ coeliac disease

Answer 241

Central abnormality is that they are not able to fully digest gluten. Gluten peptides can pass across the enterocytes to the lamina propria. They initiate innate and adaptive immunity. Tissue transglutaminase is able to cause deamidation on the peptides.

Answer 242

Chronic autoimmune blistering skin condition Herpetiform clusters of intensely itchy urticated papules and small blisters distributed on the extensor aspects of the elbows and knees and over the buttocks and on the scalp. DH is a cutaneous manifestation of coeliac disease. Look for IgA deposits in the dermal papillae

Answer 243

``` - Serology: IgA tissue transglutaminase IgA anti-edomysial anitbody (EMA) Immunoglobulins - if IgA deficiency, test for class IgG antibodies - Upper GI endoscopy and duodenal biopsises - Histology: Villous atrophy Crypt hyperplasia ```

Answer 244

Testing is accurate only if performed while on a gluten-containing diet. When following a gluten containing diet they should eat some gluten in more than one meal every day for at least 6 weeks before testing.

Answer 245

``` Gluten free diet - strict and lifelong Dietitian review Coeliac UK information Prescription entitlement DEXA scan-osteoporosis risk Inform 10% risk in 1st degree relatives ```

Answer 246

``` Refractory coeliac disease type 1 Refractory coeliac disease type 2 Ulcerative jejunitis Enteropathy-associated T cell lymphoma (EATL) Abdominal B-cell lymphomas Small bowel adenocarcinoma ```

Answer 247

Gastro-oesophageal junction should be a clear junction between squamous epithelium of the oesophagus (needs to be resistant to abrasion) and glandular epithelium of the stomach. Mucin border to buffer acid.

Answer 248

Columnar lined lower oesophagus (CELLO) aka Barrett’s oesophagus: a precancerous condition where the normal cells lining the oesophagus have been replaced with glandular epithelium through metaplasia.

Answer 249

If there is a reflux of acid into the oesophagus, the squamous epithelial cells don’t have a protective layer of mucin so it kills them off very quickly. May cause pain, indigestion and ulceration. It could regrow, but if there is repeated reflux, metaplasia can occur - glandular epithelium in the oesophagus (now protective against other acid reflux).

Answer 250

Oesophageal squamous cancer - heavy smoking and alcohol (prognosis is bad) Adenocarcinoma of the oesophagus - obesity

Answer 251

Can protrude into the lumen and cause problems swallowing (dysphagia). Too much invasive outwards (outside mucosa) can be problematic for surrounding structures - trachea, brochii, aorta, vena cava etc. Can spread into the lymphatic or vascular system. Proportion that can be treated with curative therapy is very low.

Answer 252

Decreasing incidence, may be due to reclassification to ‘oesophageal cancers’. Common in eastern Asian and eastern european. A lot of smoked and pickled food may have an impact. Helicobacter pylori can also have an impact. Pernicious anaemia could also have an impact.

Answer 253

Early gastric cancer - only invades the submucosa (even if it’s spread to lymph nodes) - 90% 5 year survival rate Late gastric cancer - invades the muscular wall of the stomach - 60% 5 year survival rate (cannot be resected)

Answer 254

The peritoneal cavity is the largest cavity in the body, Two parts – the visceral peritoneum surrounding the viscera and the parietal peritoneum lining the other surfaces of the cavity. In health, only a few millilitres of peritoneal fluid are found in the peritoneal cavity. The fluid is pale and contains lymphocytes and other leukocytes; it lubricates the viscera allowing easy movement and peristalsis. The parietal portion is richly supplied with nerves and, when irritated, causes severe pain that is accurately localized to the affected area. The visceral peritoneum, in contrast, is poorly supplied with nerves (these being situated around blood vessels) and its irritation causes pain that is usually poorly localised to the midline.

Answer 255

In health : Visceral lubrication Fluid and particulate absorption across the membrane In disease Pain perception Inflammatory and immune responses Fibrinolytic activity – responsible for adhesions

Answer 256

Inflammation of the peritoneum

Answer 257

Onset - Acute or chronic Source of origin - Primary or Secondary Location - generalised or localised Cause: Bacterial, gastrointestinal and non-gastrointestinal Chemical, e.g. bile, barium Traumatic, e.g. operative handling Ischaemia, e.g. strangulated bowel, vascular occlusion Miscellaneous, e.g. familial Mediterranean fever Peritonitis without qualification will be bacterial acute peritonitis.

Answer 258

Gastrointestinal perforation, e.g. perforated ulcer, appendix, diverticulum Transmural translocation (no perforation), e.g. pancreatitis, ischaemic bowel, primary bacterial peritonitis Exogenous contamination, e.g. drains, open surgery, trauma, peritoneal dialysis Female genital tract infection, e.g. pelvic inflammatory disease Haematogenous spread (rare), e.g. septicaemia

Answer 259

``` S&S of the underlying condition Pain Nausea and vomiting Fever Tachycardia Localised guarding Rebound tenderness Shoulder tip pain ( subphrenic) Tender rectal and / or vaginal examination (pelvic peritonitis). ```

Answer 260

Abdominal pain (worse by moving or breathing) Tenderness Generalised guarding Infrequent bowel sounds cease ( paralytic ileus) Fever Tachycardia

Answer 261

``` Generalised rigidity Destension Absent bowel sounds Circulatory failure Thready irregular pulse (Hippocratic face) – dry tongue, dry membranes Loss of consciousness ```

Answer 262

Urine dipstix for urinary tract infection. ECG if diagnostic doubt (as to cause of abdominal pain) or cardiac history. Bloods - U&Es - Full blood count (WCC) - Serum amylase (acute pancreatitis/ others like perf DU) - Group and save.

Answer 263

Correction of fluid loss and circulating volume Urinary catheterisation with potential gastrointestinal decompression Antibiotic therapy Analgesia ``` Specific treatment of the cause: Repair of perforated viscus – peptic ulcer Excision of perforated organ With or without drainage With or without restoring continuity ```

Answer 264

Bile peritonitis – due to perforation of the gallbladder Spontaneous bacterial peritonitis Primary pneumococcal peritonitis Tuberculous peritonitis Familial Mediterranean fever (periodic peritonitis)

Answer 265

An accumulation of excess serous fluid within the peritoneal cavity. Synonyms – Abdominal Dropsy, Peritoneal dropsy, hydrops abdomini

Answer 266

Stage 1 detectable only after careful examination/Ultrasound scan (Mild) Stage 2 easily detectable but of relatively small volume. Stage 3 obvious, not tense ascites. (moderate) Stage 4 tense ascites. (Large)

Answer 267

Transudates (protein <25 g/L) | Exudates (protein >25 g/L)

Answer 268

Low plasma protein concentrations: Malnutrition Nephrotic syndrome Protein-losing enteropathy High central venous pressure: Congestive cardiac failure Portal hypertension: Portal vein thrombosis /Cirrhosis

Answer 269

Peritoneal malignancy Tuberculous peritonitis Budd–Chiari syndrome (hepatic vein occlusion or thrombosis) Pancreatic ascites Others: Chylous ascites , Meigs’ syndrome

Answer 270

``` 75% Cirrhosis 10% Malignancy 9% Others Heart failure Pancreatitis TB ```

Answer 271

Abdominal distension - Clothes getting tighter Nausea, Loss of appetite Constipation Cachexia - wasting ? weight loss Pain / Discomfort (Present – malignant, Absent – non malignant) Associated symptoms of underlying cause

Answer 272

``` Abdominal distension (up to 1.5 to 2 l) Puddle sign (150ml) Shifting dullness (500ml) Flanks fullness 1500+ ml Fluid thrill Jaundice & Other Stigmata of liver disease (if cause is liver) ```

Answer 273

Underlying cause (LFTs, Cardiac function) Imaging: - X-Ray ( 500ml) - Ultra sound scan ( at least 20ml) - CT abdomen (< v small amt ) Ascitic aspiration (under imaging guidance) Fluid for microscopy, cytology, culture, including mycobacteria, and analysis of protein content and amylase.

Answer 274

Treatment of the specific cause Sodium restriction Diuretics Paracentesis (up to 4-6 L / day with colloid replacement) Indwelling drain (home paracentesis , smaller volumes) Peritoneovenous shunting (for rapidly accumulating ascites)

Answer 275

Make bile to absorb fat - breaks it down, enabling you to absorb fat-soluble vitamins (A, E, D, K) Stored in gallbladder and released through the Sphincter of Oddi During digestion bile acids are reabsorbed unconjugated In the terminal ileum bile salts are reabsorbed by specialised mucosa into portal circulation to be re-conjugated and secreted back into bile

Answer 276

Bile = bile acids + phospholipids + cholesterol Bile acids - cholic acid and chenodeoxycholic acid formed by cholesterol liver metabolism Secondary bile acids - bacterial metabolites of bile acid formed in the colon

Answer 277

``` Jaundice Itching Pain in the RUQ: intermittent (colic) Acute or chronic Painless Dark brown urine Pale/white stool (without bilirubin) Weight loss Lethargy - low appetite ```

Answer 278

Blood tests Obstructive - bilirubin >35 (clinical at >80), Alkaline phosphatase, ALT Isolated - slightly raised bilirubin (35-60)

Answer 279

Ultrasound - dilated common bile duct Strengths: can see gallbladder well, good for stones Poor: in overweight, difficult in distal CBD, difficult to exclude pancreas lesion in head ``` Magnetic resonance cholangiopancreatography Low radiation Complex number of imagine Takes times for reporting and scan Claustrophobia ``` ``` CT Good/sensitive for cancer Poor at stones unless >8mm and a non contract scan done first High radiation Picks up everything ``` Endoscopic ultrasound Pass a gastroscope into the duodenum with an ultrasound machine on the end of it Very sensitive Requires sedation

Answer 280

Increased cholesterol Cholesterol crystals precipitate and form stones 80% gallstones: cholesterol <20% gallstones: calcium bilirubinate Biliary sludge (mucus supersaturation) can also cause obstruction

Answer 281

``` Rapid weight loss - bariatric surgery Age OCP/pregnancy PBC Octreotide, fibrate, ceftriaxone NIDDM Crohn’s Pigment stones ```

Answer 282

``` Epigastric pain to RUQ RUQ to shoulder/scapula Pain 15-25% Colic - 30mins to 5 hours Post prandial Noctural OR can be completely asymptomatic (70%) ```

Answer 283

- Laparoscopic cholecystectomy: 3 or 4 small cuts are made in the abdomen. A laparoscope is inserted allowing the surgeon to view the operation on a video monitor. The gallbladder is then removed using surgical instruments. - Open cholecystectomy: If the patient is in their third trimester of pregnancy, extremely overweight, or have an unusual gallbladder/bile duct structure it is best that the patient has an open cholecystectomy. - Endoscopic retrograde cholangio-pancreatography - An endoscope is passed through the patient’s mouth into where the bile duct opens into the small intestine. During the ERCP, the bile duct is widened with a small incision or an electrically heated wire. The bile stones are then removed or left to pass into the intestine and out of the body. Sometimes a stent is placed in the bile duct to help the stones pass. - Bile salt therapy: Urodeoxycholic acid - dissolve over 2 years <50%. Rarely effective, they need to be taken for a long time to work (about 2 years) and the gallstones can reoccur once treatment is stopped.

Answer 284

``` Gallstones obstruction Biliary pain progressive Sepsis signs History of previous attacks MURPHY’S sign = AC no = BC Gall bladder palpable Jaundice in 25% ```

Answer 285

WBC, CRP Maybe Bil and Alk Phos USS - thick walled tender GB with stones CBD dilatation on MRI

Answer 286

``` Pancreatitis - Amylase Appendicitis Peptic Ulcer disease - ultrasound Liver abscess Pneumonia - chest X ray MI - ECG and troponin Perforated bowel - chest X ray ```

Answer 287

``` Common bile duct stone From gall bladder 1-25% of patient with GS have a CBD stone Can form without GB - dilated CBD Increase with age ‘Painful jaundice’ ```

Answer 288

``` Chronic diffuse inflammation Strictures are multiple and small Men > Women Age 20-50 Risks: UC in 80%, increased risk of colon cancer ``` Presents with fatigue, pruritus, anorexia, indigestion, jaundice, blood (increased Alk phos), P-ANCA 80% MRI good for differentials Risks of cholangiocarcinoma, gallstones

Answer 289

A disorder of some component of biliary part of the digestive system in which bile physically can not move normally in the proper direction through the tubular biliary tract. It most commonly involves abnormal biliary tract peristalsis muscular coordination within the gallbladder in response to dietary stimulation of that organ to squirt the liquid bile through the common bile duct into the duodenum.

Answer 290

Systemic inflammatory response syndrome (SIRS) is an exaggerated defense response of the body to a noxious stressor (infection, trauma, surgery, acute inflammation, ischemia or reperfusion, or malignancy to name a few) to localize and then eliminate the endogenous or exogenous source of the insult. SIRS with a suspected source of infection is termed sepsis.

Answer 291

``` Jaundice - head lesion Painless or vague abdominal pain New onset diabetes CT diagnostic test Ca19-9 marker - treatment response rather than diagnosis, raised with obstruction ```

Answer 292

``` Staging CT/PET CT Treat jaundice Surgery Biopsy - endoscopic ultrasound Palliative chemotherapy ``` Prognosis Operable - 2 years Inoperable - 5-12 months