15 Flashcards

Question

Pathophysiology of ulcerative colitis

Answer 1

- Diffuse superficial inflammation - Relapsing-remitting Macroscopic appearance: - May affect whole large bowel - Bowel wall not thickened - Shallow ulceration with pseudopolyps, hyperaemia and haemorrhage - Diseased bowel is continuous Microscopic appearance: - Inflammation is limited to mucosa and submucosa with infiltration of both neutrophils and macrophages - Crypt abscesses with ulceration, crypt atrophy and paneth cell metaplasia

Answer 2

Malabsorption is the decreased absorption of nutrients which may be caused by a number of conditions including biochemical disorders Causes include: - Reduced small intestine SA - Infection - Loss of digestive enzymes - Drug induced mechanisms - Lymphatic obstruction - Rapid transit - Failure of nutrient to reach small bowel (fistula) - Surgical resection

Answer 3

- Abnormal reaction to gluten - Damage to enterocytes - Environmental factors allow gliadin to come into contact with transglutaminase in the lamina propria - Gliadin is the modified by TTG and recognised as an antigen by CD4+ T cells - Stem cells unable to keep up with rate of loss of enterocytes - Results in villous atrophy

Answer 4

- Frothy, greasy stools that are difficult to flush away - Anaemia - Diarrhoea - Weight loss - Abdominal distension - Vit K deficiency

Answer 5

- Lamina propria - where you find cells of immune system - Tight junctions - make cells stick together - Goblet cells secrete mucins - Paneth cells

Answer 6

Anti-microbial peptides

Answer 7

- Conc. increases | - Becomes more anaerobic

Answer 8

Pattern recognition receptors e.g. Toll-like receptors/NODs/CARDs They recognise patterns such as LPS, peptidoglycan and dsRNA Cannot distinguish specifically

Answer 9

Use antigen specific receptors B cell receptors is an antibody which can recognise 3D structures T cell receptors recognise MHC complex

Answer 10

Th1 - IFN-gamma - effective against intracellular pathogens e.g. toxoplasmosis Th2 - IL4 and IL-5 - effective against extracellular pathogens e.g. helminths Th17 - IL-17 - effective against extracellular bacteria and fungi especially at mucosal sites e.g. Klebsiella and Candida These help us fight pathogens

Answer 11

TR1 - IL-10 TR3 - TGF-beta CD25+ - IL-10 and TGF-beta These dampen the effectors - down-regulate

Answer 12

Chronic inflammation Autoimmunity Type 1 diabetes

Answer 13

Asthma | Allergy

Answer 14

Chronic inflammation Autoimmunity RA, MS, psoriasis and IBD

Answer 15

- Peyer's patches - Isolate lymphoid follicles - Mesenteric lymph nodes

Answer 16

- Lamina propria leukocytes | - Intraepithelial lymphocytes

Answer 17

- By endocytosis and phagocytosis - They then transport antigens to basal site where immune cells are - Dendritic cells pick up the antigen and are activated - Dendritic cells then migrate to the T-cell areas of peyer's patches - Then travel via lymphatics to mesenteric lymph nodes - activate T cells here

Answer 18

Poliovirus, Reovirus, Some retroviruses, Salmonella, Shigella Yersinia

Answer 19

Favour induction of Treg responses

Answer 20

Either too many effectors (Th1, Th2, Th17) or regulatory cell defect (Tr1, Tr3, CD25) In intestinal inflammation either too many effectors or not enough regulatory cells

Answer 21

Monomeric in blood Dimeric in mucosal immune system

Answer 22

- Mediated by poly-Ig receptor - J chain binds to receptor - IgA then transported across lumen - In the lumen, it is cleaved off with poly-Ig receptor still attached - It is now known as secretory IgA

Answer 23

- Binds to mucus layer, coating epithelium - Prevents adherence of microorganisms - Neutralises toxins and enzymes - Little capacity to activate classical pathway of complement or act as a opsonin

Answer 24

IgM - pentamer with J chain

Answer 25

Food antigens: - Default response to oral administration of protein antigen is oral tolerance - Oral tolerance means effecter T cells - Th1, Th2 and Th17 are switched off - Treg cells are generated which dampen immune response Commensal flora: - Induce IgA and Treg cells in intestine - Ignored by systemic immune system - some antigens won't get further than mesenteric lymph nodes

Answer 26

- DCs fully activated in presence of pathogens - Induce CD4+ cells to differentiate into effector cells - Innate immune system activated through pattern-recognition receptors (toll-like receptors) - TLR-2 - detects peptidoglycan - TLR-4 - detects LPS - TLR-5 - detects flagellin - You get up-regulation of MHC and co-stimulatory molecules as well as cytokine production

Answer 27

Localisation of PRRs - TLR-4 expression at crypt base - Basolateral TLR5 expression inside epithelial cells so pathogens invading tissues can trigger TLR activation Virulence factors in pathogens - Salmonella has type III secretion system so they can inject material into host cel to trigger activation from inside Commensals avoid PRR activation Changes in flagellating sequences - TLR5 hyporesponsive so TLR5 cannot be triggered

Answer 28

- Mutation in NOD2 (a PRR) - usually stimulated by muramyl dipeptide - IL-23 receptor - normally produced by innate cells following activation by PRR

Answer 29

Paneth cells (of SI) Paneth cells produce large amounts of α-defensins and other antimicrobial peptides, such as lysozymes and secretory phospholipase A2 (sPLA2). If you have mutation you therefore may not be able to mount immune response as they secrete antimicrobial peptides

Answer 30

- Helminth therapy - Faecal microbiotia transplant - Bacterial cocktails

Answer 31

Aminosalicylates - dampen inflammatory response e.g. sulphasalazine Corticosteroids Immunosuppressants

Answer 32

Mechanism - invasion of mucosa/production of cytokines Location - colon Organisms - shigella, salmonella, campylobacter and E. Coli

Answer 33

Mechanism - enterotoxin/mucosal adhesion Location - proximal small bowel Organism - vibrio cholerae, enterotoxigenic E. Coli and bacillus cereus

Answer 34

Mechanism - induced phagocytosis Location - distal small bowel Organism - salmonella, listeria monocytogenes, yersinia enterocolitis

Answer 35

Not advised Can make E. Coli 0157 worse Can cause diarrhoea

Answer 36

Lactose intolerance Intestinal hurry

Answer 37

- Sensory - taste and smell - Behavioural - programmed to avoid GI infection - Gastric acid pH 2 - Bile salts/acids - Peristalsis - Mucus - physical barrier and antimicrobial

Answer 38

Secretory IgA production

Answer 39

Where normal GI flora occupies space and produce antibiotic like substances End products of metabolism may also be toxic

Answer 40

Sum of all species in the bowel | 2-5kg

Answer 41

Cephalosporin Clindamycin Co-amoxiclav Ciprofloxacin

Answer 42

Metronidazole

Answer 43

Hydrogen breath test

Answer 44

Microcytic, hypochromic

Answer 45

Macrocytic, normochromic

Answer 46

Visual acuity

Answer 47

Dermatitis

Answer 48

- Autism - clostridium boltiae - Asthma/atopy - increased clostridia and decreased bifidobacteria - Obesity - increased actinobacteria and decreased bacterioids

Answer 49

- Cajal cells - Cells of the enteric nervous system - Adipose - Collagen

Answer 50

In the epithelium - goblet cells, absorptive colonocytes, endocrine and paneth cells (right colon only, metaplasia if found in the left) Lamina propria Basement membrane to support epithelium Muscularis mucosae - thin layer of muscle

Answer 51

Columnar - with goblet cells

Answer 52

Paneth - base of crypts Endocrine cells Intraepithelial lymphocytes Brunner's gland - alkaline mucous secretions and also rich in epidermal growth factor which encourages mucosal regeneration (duodenum) Lymphoid tissue

Answer 53

Obstruction by faecoliths Food residues Lymphoid hyperplasia Diverticulitis Neoplasia

Answer 54

- Abscess formation - Necrosis - Spread of suppurative inflammation - Perforation - Septicaemia

Answer 55

- Blunting and atrophy of mucosa - Increased intraepithelial lymphocytes - Crypt hyperplasia

Answer 56

- Mucosal damage = less SA for absorption - Immature enterocytes not capable of normal absorption - Decreases hormone production

Answer 57

- Caused by C. Difficile - Volcano like eruptions of neutrophils, fibrin, mucus and epithelial cells on the surface which creates a pseudomembrane - Causes infective diarrhoea and dehydration

Answer 58

- Inflammation limited to segment affected by diverticulum - Crypt architectural changes - Can be transmural with lymphoid aggregates and fistula formation

Answer 59

Coeliac trunk --> hepatic artery proper --? R and L hepatic arteries Right hepatic --> cystic artery (to gallbladder) Hepatic portal vein carries products of digestion from the GI tract to liver (partially oxygenated) Right and left hepatic ducts drain bile into the common hepatic duct which joins the cystic duct to form the bile duct

Answer 60

- Oxidation carried out mainly by cytochrome P450 in the hepatocyte SER - A number of drugs induce microsomal enzymes, affecting the metabolism of other drugs taken at the same time

Answer 61

- Number of chemical products are conjugates with drugs or their metabolites in the liver inc. glucuronyl, acetyl, methyl - Conjugation important with paracetamol - Paracetamol is inactivated by conjugation to form a glucuronide or sulphate

Answer 62

- Elimination of conjugated substances is via the blood, which then results in excretion through the kidneys or via bile through the intestines - ATPase pumps required to actively transport the substance out of the hepatocyte - The amount of active drug reaching the circulation is reduced and the drug is said to undergo significant first-pass metabolism

Answer 63

- Inflammation of the liver due to alcohol ingestion - Mallory bodies appear in the hepatocytes - Aggregation of neutrophils around damaged liver cells - Focal necrosis in zone 3 - Ballooning of hepatocytes can occur due to retention of proteins and water after injury to organelles - Alkaline phosphatase, alanine amino- transferase, aspartate aminotransferase, g-glutamyl transpeptidase, bilirubin and an increased prothrombin time

Answer 64

I GET SMASHED ``` Idiopathic Gallstones Ethanol (alcohol) Trauma Steroids Mumps Autoimmune Scorpion sting Hypothermia/hyperlipidaemia/hypercalcaemia ERCP Drugs ``` - Possible hyper stimulation of pancreas or pancreatic duct destruction leads to release of lytic enzymes which are then activated and cause damage - Trypsin, lipase and phospholipase A2 particularly digest pancreatic tissue, causing fat necrosis

Answer 65

Alcohol consumption main cause 4 key pathological features: - Continuous chronic inflammation - Fibrous scarring - Loss of pancreatic tissue - Duct strictures with formation of calculi

Answer 66

- ssRNA - Picornavirus - Does not cause chronic hepatitis - Endemic in countered with poor hygiene and sanitation - Faecal-oral transmission

Answer 67

- Contaminated blood products - ssRNA with several immunogenic subtypes - Fatigue and malaise common - Clinical jaundice in less than 20% of patients - 20% progress to cirrhosis

Answer 68

- partial dsDNA - Transmission through contaminated blood products - DNA virus that replicates i the liver where the core antigen incorporates itself into the host genome - Host DNA polymerase then transcribes the virus - Acute presentation - anorexia, abdominal discomfort - Chronic presentation - asymptomatic, majority discovered by accident

Answer 69

- Deltavirus - Incomplete RNA particle which is unable to replicate by itself - Co-infection with hep B - Activated in presence of hep B

Answer 70

- ssRNA - Faecal-oral transmission - Developing countries - No progression to chronic active hepatitis

Answer 71

- Covered by peritoneum except for bare area on the diaphragmatic surface - 4 lobes - Falciform ligament - remnant of the embryonic ventral mesentery

Answer 72

- Acute liver failure with massive hepatic necrosis - Chronic liver disease - Hepatic dysfunction without overt necrosis - hepatocytes viable but unable to perform their normal metabolic function

Answer 73

- End stage of any progressive liver disease - Caused by alcohol, viral hepatitis, drugs, autoimmune, cholestatic liver disease, metabolic liver disease etc. - Necrosis, fibrosis and regeneration

Answer 74

- Macronodular - regenerating nodules are generally large and of variable size - Micronodular - contains nodules that are <3mm - more commonly seen with alcohol abuse

Answer 75

- Portal hypertension - This increases portal vascular resistance due to collagen deposition and fibrosis and hence the formation of varices in the gastro-oesophageal junction

Answer 76

3 main types of liver damage: - Fatty change - ethanol metabolised in the liver, which results in hepatic fatty acid synthesis and reduced fatty acid oxidation = accumulation and fatty destruction of hepatic cells - Alcoholic hepatitis - infiltration with polymorphonuclear leucocytes and hyaline material (Mallory bodies) - Fibrosis - fibrosis with nodular regeneration implies previous or continuing liver damage

Answer 77

- Autoimmune disease - Associated with other autoimmune phenomena such as hypothyroidism and sicca syndrome - Antimitrochondrial antibodies - Sensitised T cells may account for damage

Answer 78

- Inflammation of bile ducts both inside and outside the liver - Impedes flow of bile to gut - Causes cholestasis, leading to cirrhosis of the liver - Fat soluble vitamin malabsorption and fat malabsorption - Signs: hepatomegaly, jaundice, portal hypertension and dark urine

Answer 79

- Error of copper metabolism - Autosomal recessive gene on chromosome 13 - Faulty transporter protein ATP7B which excretes copper from liver via golgi complex

Answer 80

- Hepatocellular carcinoma - Hepatoblastoma - tumour formed by immature liver cells that primarily develops in children - Cholangiocarcinoma - cancer of the bile duct - Secondary metastasis

Answer 81

EBV | - May cause mild hepatitis during the acute phase of infectious mononucleosis

Answer 82

CMV - Particularly in newborn or immunocompromised - Can cause typical cytomegalic changes of that virus in almost any cell in the liver

Answer 83

May infect hepatocytes in babies or immunocompromised and can lead to hepatic necrosis

Answer 84

Causes hepatocyte apoptosis

Answer 85

Cause - Increased haemolysis (e.g. haemolytic anaemia) - Ineffective erythropoiesis Signs - Increased concentrations of unconjugated bilirubin

Answer 86

Cause - Gilbert's syndrome - Viral infection - Cirrhosis - Drugs - Autoimmune disease - Weil's disease - Wilson's disease Signs - Increased clotting time - Increased ALT and AST - Hepatocellular damage

Answer 87

- Causes hepatic jaundice - Due to deficit of UDP glucuronyl transferase - Build up on unconjugated bilirubin in the blood

Answer 88

Insufficient dietary intake to meet metabolic requirements

Answer 89

Disorder of the digestive tract resulting in the inability to utilise dietary intake

Answer 90

Carbohydrates

Answer 91

Protein-energy malnutrition

Answer 92

A lack of protein: Kwashiorkor. | - Hypoalbuminia, ascites (starling's).

Answer 93

Marasmus (starvation). - Severe malnutrition. - Growth failure, apathy, diarrhoes, fatigue, hepatomegaly, muscle wasting, oedema, anaemia.

Answer 94

- Kwoshiorkor: protein-energy malnutrition. | - Marasmus: total dietary caloric lack.

Answer 95

1) Protein-energy malnutrition. | 2) Total dietary lack (caloric) malnutrition.

Answer 96

1) Anorexia. 2) Neglect. 3) Dysphagia. 4) Increased metabolic demand

Answer 97

Suppression of appetite. - Lack of or loss of wanting to eat. - Cachexia (loss of weight, muscle, bone).

Answer 98

Production of cytokines by malignant cells. - May result from chemotherapy drugs. - Impact upon appetite centres in brain and stomach.

Answer 99

1) Psychological, anorexia nervosa. 2) Malignancy, cytokines and chemotherapy drugs. 3) Infection/inflammation, AIDS, TB.

Answer 100

People who want to eat but are unable to do so. | i.e. elderly.

Answer 101

- Elderly (improper care or tea and toast diet). - Hospitalised patients, can't care for themselves. - Neurological disease i.e. alzheimer's/demetia.

Answer 102

Difficulty swallowing. | - Oesophagitis, cancer (primary or secondary).

Answer 103

Body requires more intake than usual and isn't getting it. | - I.e. thyrotoxicosis, pregnancy.

Answer 104

- Iron (Fe) deficiency. - Vitamin B complex. - Folic acid. - Vitamin D. - B12. - Vitamin C. - Vitamin K.

Answer 105

Iron deficiency (microcytic hypochromic) anaemia. - Heavy periods (menses). - People who are vegetarian (no red meat)

Answer 106

- Mean corpuscular volume, average size of a red blood cell. | - Mean corpuscular haemoglobin, average amount of haemoglobin per red blood cell.

Answer 107

Neuropathy, cardiopathy. Chronic alcohol intake causes B vitamin deficiencies

Answer 108

Megaloblastic anaemia Through malabsorption i.e. coeliac disease or increased metabolic demand.

Answer 109

Osteomalacia (inadequate Ca2+ in bone) - People of darker pigmented skin (especially in cold climates). - Can't make vitamin D as well. - Indian sub-continent diet. - Lack of UV light.

Answer 110

``` Megaloblastic anaemia (pernicious). - Alcoholism. ```

Answer 111

- Pernicious (megaloblastic) anaemia. - Ataxia. - Peripheral neuropathy. - Dementia. - SACD (subacute combined degeneration of spinal cord).

Answer 112

Scurvy. | - A lot of vitamin C in fast foods now, not just fruit and veg.

Answer 113

Coagulopathy (tendency to bleed). | - Used in the coagulation cascade (target of warfarin).

Answer 114

Protein converted to peptides. - Peptides to amino acids. - Enzymes in inactive state then become active i.e. trypsinogen to trypsin.

Answer 115

Lipids need to be emulsified by bile due to their phospholipid bilayer. - Pancreatic enzymes used (lipases). - Broken down into fatty acids and monoglycerides.

Answer 116

- Water soluble: B complex, C | - Fat soluble: A, D, E, K.

Answer 117

Deficiency of a specific mineral of vitamin may give indication to what the diagnosis might be.

Answer 118

- Mastication, food broken down. - Lubrication by saliva. - Taste (more saliva produced). - Digestion, breakdown of molecules (salivary amylases and lipases).

Answer 119

1) Parotid. 2) Submandibular. 3) Submaxillary. - Salivary amylases and lipases.

Answer 120

Rapid gastric emptying time. | - Food isn't being broken down properly.

Answer 121

Acid. | - pH 4 stomach acid activates enzymes.

Answer 122

Release of ACh and histamines. - Increase acid production from parietal cells. - Increase pepsinogen release from Chief cells.

Answer 123

When it is expelled from the stomach into the duodenum.

Answer 124

Release of bicarbonate from the exocrine pancreas. | - Pancreatic enzymes would struggle to digest acidic chyme.

Answer 125

- Contracts the gallbladder, bile released into duodenum for emulsification. - Triggers pancreatic enzyme secretion. Secreted from I-cells in the duodenum.

Answer 126

1) Lipids. | 2) Proteins.

Answer 127

Emulsifies fat into micelles so that they can be easily digested by lipases

Answer 128

1) Large SA for absorption (including villi and microvilli). | 2) Brush border enzymes i.e. lactase.

Answer 129

- Infections (pain, diarrhoea, vomiting). | - Bacterial overgrowth.

Answer 130

Loss of the absorptive SA (Crohn's, surgery). Degradation of the absorptive SA (viili etc.) (Coeliac disease).

Answer 131

Disordered development of the lymphatic system. | - Post mucosal disease of the SI

Answer 132

Gluten sensitivity (gliadin protein). - Immune mediated attack of SI villi, SA reduced. - Subtotal villous atrophy - Mucosal disease.

Answer 133

Anti-tissue transglutaminase.

Answer 134

1) Fe deficiency. 2) Folate deficiency. 3) Vit D deficiency (osteomalacia).

Answer 135

Disorders of the lymphatic system.

Answer 136

- Giardiasis (G. lamblia). - TB. - Whipple's disease. - Ancylostoma (iron deficiency, parasitic). - AIDS associated OI's such as cryptosporidium.

Answer 137

- High folate, low B12. - Jejunal diverticulosis (structural abnormality). - Motility disorders. - Bowel obstruction. - Fistulation.

Answer 138

The presence of lots of fats in stool. - Inability to flush stool away. - Indicative of a malabsorptive state. Giardiasis (G. lamblia).

Answer 139

Bound to intrinsic factor from parietal cells. | - Loss of intrinsic factor = pernicious anaemia (aka B12 deficiency).

Answer 140

Obstructed biliary drainage. - Intrahepatic OR extrahepatic cause. - A, D, E, K (fat soluble vitamin) malabsorption.

Answer 141

- Pancreatic cancers | - Tumours blocking the pancreatic duct

Answer 142

Small intestine - it absorbed about 80-90%

Answer 143

Large intestine

Answer 144

You do not get the water being reabsorbed so there is an increase in the liquidity and quantity of faeces

Answer 145

SI - Brush border which increases SA = increased absorption capability LI - No brush border but still have secretory glands such as crypt of Lieberkuhn

Answer 146

- Sodium transporters - Sodium moved from the luminal side across the membrane of the LI creating a gradient - Aldosterone

Answer 147

Crypts of Lieberkuhn

Answer 148

Mucous for protection

Answer 149

Peristalsis | Segmentation

Answer 150

Constipation

Answer 151

Diarrhoea and urgency

Answer 152

Position when storing faecal material

Answer 153

- Puborectalis | - External sphincter

Answer 154

- Reverse peristalsis | - Consistently doing this causes the material to become compacted

Answer 155

- Puborectalis muscle and external sphincter relax - Opens up anal canal, correcting the ano-rectal angle - Allows the movement or contraction of muscle wall and gravity to work together to push faecal material out

Answer 156

A sulphonamide antibiotic used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease. It is often considered as a first line treatment in rheumatoid arthritis. - Broken down in gut to release 5-ASA which is the active metabolite - Contains sulphur which is not necessarily tolerated by patients

Answer 157

Aluminium silicate Absorbs material and acts as binding agent in diarrhoea Often sold with morphine as an anti-diarrhoeal

Answer 158

Stomach, spleen and intestines

Answer 159

- Protein synthesis - albumin and coagulation factors - Lipoprotein synthesis - Bile coagulation and excretion - Storage of glycogen, release of glucose and gluconeogenesis

Answer 160

CMV, EBV, HSV, varicella, mumps, yellow fever, rubella

Answer 161

- Overproduction of lymph - Hypoalbuminaemia - Portal venous hypertension

Answer 162

- Less sensitive than colonoscopy - Can't biopsy - Not tolerated by some patients - Patient needs to be mobile

Answer 163

Barium swallow

Answer 164

Barium swallow +/- CT

Answer 165

Capable of reaching caecum and terminal ileum

Answer 166

Shorter, more flexible instrument able to reach transverse colon

Answer 167

Covered with perinephric fat and enclosed in renal fascia

Answer 168

Zona glomerulosa - mainly mineralocorticoids (aldosterone) Zona fasiculata - mainly glucocorticoids (cortisol) Zona reticularis - mainly androgens and glucocorticoids

Answer 169

Para-aortic lymph nodes

Answer 170

- Left - adrenal vein travels inferior to enter left renal vein - Right - shorter --> straight into IVC

Answer 171

- AngII - High plasma K+ - ACTH

Answer 172

- Acts mainly on DCT and collecting ducts | - Causes reabsorption of Na+ and excretion of K+

Answer 173

Regulate metabolism of carbohydrate, protein and fat

Answer 174

Hypothalamus - CRH Anterior pituitary - POMC --> ACTH Adrenal cortex - cortisol

Answer 175

- Reduction in chronic inflammation | - Decreases uptake and utilisation of glucose

Answer 176

Fludrocortisone

Answer 177

- Primary hyperaldosteronism - Adenoma of the zona glomerulosa - Triad of hypertension, hypokalaemia and alkalosis

Answer 178

- Excess renin stimulation of zona glomerulosa | - Common causes of secondary are accelerated hypertension and renal artery stenosis

Answer 179

- Chronic excess of glucocorticoids

Answer 180

``` Centripetal obesity Facial plethora Glucose intolerance Weakness Hypertension ```

Answer 181

Due to action melanocyte-stimulating action of ACTH on the receptors for the structurally similar melanocyte-stimulating hormone

Answer 182

Pain (headache), pallor, perspiration, palpitations, pressure, paroxysms - Rare tumour in the adrenal medulla which secrete noradrenaline and adrenaline

Answer 183

- Deficiency of cortisol and possibly aldosterone - Primary insufficiency of the adrenal cortex - Can be caused by autoimmune adrenalitis, infection (TB) or tumour - High levels of circulating ACTH can cause skin pigmentation too Addison's disease arises from problems with the adrenal gland - not enough cortisol and possibly aldosterone are produced

Answer 184

An adrenal crisis

Answer 185

- Enlarged adrenal cortex secretes excess androgens - Early pseudo puberty - Early bone epiphyseal fusion

Answer 186

- Masculisation - Masculine body shape - Balding of temporal skull - Increased muscle bulk - Deepening of the voice - Enlargement of the clitoris

Answer 187

Situation where insufficiency blood flow is reaching the body's tissues

Answer 188

Fall in circulating blood volume caused by either: - External fluid loss e.g. vomiting, diarrhoea - Internal fluid loss e.g. pancreatitis, internal bleeding

Answer 189

Caused by impairment of cardiac function such that the heart is unable to maintain adequate cardiac output

Answer 190

Direct obstruction to blood entering or leaving the heart or great vessels

Answer 191

- Caused by toxins e.g. endotoxin - Systemic inflammatory response with production of cytokines - Causes widespread vasodilation and increase in capillary permeability - Total peripheral resistance falls and leakage of plasma proteins in interstitial fluid causes movement of fluid from vascular compartment into interstitial area, decreasing circulating volume - Reduces venous return and stroke volume

Answer 192

- Severe type I hypersensitivity reaction - IgE immune response consists of the activation of basophils and mast cells, leading to release of histamine and other factors

Answer 193

- Sudden loss of sympathetic nervous system signals - Results in hypotension and bradycardia - Mechanism is that disruption of autonomic pathways leads to loss of sympathetic tone and vasodilation

Answer 194

Failure of the circulation that results in adequate perfusion of tissues and end organ

Answer 195

1. Humoral control - RAAS | 2. Neural control - baroreceptors

Answer 196

1. Decrease in BP detected by baroreceptors 2. Decrease in Na+ levels in the nephron measured by macula densa cells of JGA 3. Sympathetic nervous system

Answer 197

- Adrenal cortex to produce aldosterone - Hypothalamus to secrete ADH - increased water reabsorption in the CD and DCT - translocation of aquaporin water channels into CD plasma membrane and increases thirst - Acts on arteries - SM to activate and constrict

Answer 198

- Macula densa in DCT - JG cells - smooth muscle cells of the afferent arteriole - Extraglomerular mesangial cells found outside the glomerulus

Answer 199

- Cartoid sinus | - Aortic arch

Answer 200

- Increased BP detected - Sensed by baroreceptors in the aortic arch and carotid sinuses - Vagus nerve stimulate - HR is slowed - Reduction of sympathetic outflow - BP drops

Answer 201

- Increase in BP detected - Baroreceptors increase their firing rate - Positive firing of baroreceptors is inhibitory on catecholamine hormones - Vasodilation occurs - BP drops

Answer 202

- Forcible expiration against closed glottis - Increases intrathoracic pressure - Venous return is reduced - BP should drop - Baroreceptors detect this and should decrease firing, causing inhibition of the vagus nerve - Leads to increased HR and vasoconstriction - This is corrected once the epiglottis is opened

Answer 203

Venous system

Answer 204

Resistance

Answer 205

Venous system is full | - Venous hypertension

Answer 206

CO = SV x HR

Answer 207

MAP = SVR x CO Mean arterial pressure = systemic vascular resistance x cardiac output

Answer 208

Force of contraction of the cardiac muscle is proportional to its initial length Filling the heart makes it contract more, increasing preload

Answer 209

PRIME - blood loss causes preload to be low and therefore CO is low COMPENSATION - increased resistance, tachycardia, hypotension CLINICALLY - cold/clammy, tachycardia, prolonged cap refill, empty veins

Answer 210

PRIME- reservoir increases COMPENSATION - tachycardia, CO rises, auto regulation CLINICALLY - warm/dry peripheries, tachycardia, short cap refill, bounding pulse

Answer 211

Poor tissue perfusion can result in oliguria, altered conscious levels due to lack of perfusion to the brain, tissues become acidotic due to lack of oxygen causing the production of lactic acid so lungs try to blow off more CO2

Answer 212

Intravascular - bleeding (revealed, concealed e.g. in femur or pelvic fracture) Extravascular - evaporation, GI losses (diarrhoea), polyuria

Answer 213

Intrinsic - muscle, conduction tissue, valves (aortic stenosis) Extrinsic - obstruction (PE), compensation (tamponade), blood supply

Answer 214

Systemic inflammatory response syndrome - Increased HR, RR, WCC - Fever

Answer 215

SIRS and confirmed infection

Answer 216

SIRS with refractory hypotension - Evidence of infection - End organ failure

Answer 217

Vasoconstriction

Answer 218

Inotropic Chronotropic Peripheral vasodilation

Answer 219

Vasoconstriction

Answer 220

B1, B2 agonist - Vasodilation (decrease BP) - Increase HR, - Increase SV Dobutamine is a sympathomimetic drug used in the treatment of heart failure and cardiogenic shock. Its primary mechanism is direct stimulation of β1 receptors of the sympathetic nervous system.

Answer 221

Alpha, B1, B2 agonist - Vasoconstriction (increase BP) - Increase HR - Increase SV Pharmacological doses of epinephrine stimulate α1, α2, β1, β2, and β3 adrenoceptors of the sympathetic nervous system.

Answer 222

B2, D1, D2 agonist - Splanchnic vasodilator - Increase HR Dopexamine is a synthetic analogue of dopamine that is administered intravenously in hospitals to reduce exacerbations of heart failure. It works by stimulating beta-2 adrenergic receptors and peripheral dopamine receptor D1 and dopamine receptor D2. It also inhibits of neuronal re-uptake of norepinephrine

Answer 223

Albumin - Absorbed into hepatocytes and made more water soluble (polar) - Excreted into the bile duct or back into the blood - Depends on size BIG = BLOOD

Answer 224

First pass metabolism

Answer 225

- Most of the drug is taken up by the liver on the first pass - Usually very lipid soluble

Answer 226

Hepatic enzymes

Answer 227

- Start with the lipophilic drug - Phase 1 - P450 and mono-oxygenases in the SER makes drug more polar by hydrolysis, oxidation or reduction and adds a small active group onto drug, ready for phase 2 - Phase 2 - conjugation with small endogenous molecules such as transferases, sulphatases - resulting compounds are highly water soluble and can be excreted in bile or urine

Answer 228

- Multiple drugs bind to the same subtype of cytochrome P450 - Highest affinity one will out compete the lower affinity one - Results in slowed metabolism of lower affinity drug

Answer 229

At least 50 different sub types of the enzyme - each with a unique binding site and some can metabolise several drugs

Answer 230

- This means individual features | - Happens through genetic variation

Answer 231

Pathways of elimination - Biliary excretion - directly into bile if highly polar after conjugation - Can be actively transported into bile duct - Biliary excretion important if molecular weight greater than 200 - As MW falls, urinary route more important

Answer 232

- Decreased albumin binding - Malnutrition - reduced availability of micronutrients to create liver enzymes - Decreased renal clearance

Answer 233

- Liver can form a prodrug | - Drug could be turned into toxic metabolite

Answer 234

- Electrophilic components added to drugs in liver | - If P450 doesn't stop it, it can cause the development of free radicals which cause lipid peroxidation and cell death

Answer 235

- Chronic alcohol use induces P450 and increases hepatotoxicity - Acute use inhibits P450 and stops you producing toxic metabolites

Answer 236

- Paracetamol metabolised in NAPQI - Leads to cell death around 3-4 days later - Normally glutathione binds to this NAPQI and inhibits it - In excess, glutathione cannot inhibit - Leads to hepatic necrosis and liver failure

Answer 237

- Severe prolongation of prothrombin time | - Presence of acidosis

Answer 238

- Administration of cysteine donors | - IV parvolex

Answer 239

- Blister packs - No bulk buying - Add methionine to tablets - an oral donator of glutathione

Answer 240

- 2nd commonest cause of cancer death | - 17,000 deaths

Answer 241

- Foregut - mouth to ampulla of vater in duodenum - coeliac - Midgut - ampulla of vater to splenic flexure - sup. mesenteric - Hindgut - splenic flexure - anus - inf. mesenteric

Answer 242

- Overt - visible | - Occult - not-visible

Answer 243

- Right sided cancer | - Iron deficiency anaemia

Answer 244

``` Oesophagus Stomach Pancreas Colon Rectum ```

Answer 245

Anus Small bowel Gallbladder

Answer 246

- Anus | - Oesophagus (upper 2/3rds, lower 1/3rd is adenocarcinoma)

Answer 247

- Used as suicidal agent | - 10g can produce hepatic necrosis

Answer 248

Methotrexate

Answer 249

Liver and possibly lungs

Answer 250

Stratified squamous epithelium --> simple columnar due to long term acid reflux

Answer 251

- Local invasion - Intramural (along the wall) - Nodal - Blood

Answer 252

- FAP - autosomal dominant - development of lots of polyps in the colon - HNPCC - mismatch repair defects

Answer 253

- Dysphagia - Associated with reflux - Weight loss (due to dysphagia) - Associated with elderly patients, smoking, alcohol and Barrett's oesophagus

Answer 254

Squamous cell

Answer 255

- Associated with H. pylori bacterial infection - Vague symptoms of weight loss, dyspepsia, abdominal pain - Common in Japan

Answer 256

Faecal-oral - Can get it as a small child - Better hygiene standard meaning this generation has less prevalence

Answer 257

- If it presents very late it can be pain - Typically painless jaundice - Courvoisier's sign (palpable gallbladder) - Poor survival rate

Answer 258

- Alteration in bowel habits - Abdo pain - Rectal bleeding with anaemia - Rapid weight loss - Begins as a benign polyps 3-5yrs before

Answer 259

- APC which causes hyperproliferative epithelium

Answer 260

K-RAS | - Causes it to go from a small adenoma to a large adenoma

Answer 261

Hepatocytes

Answer 262

Gallbladder

Answer 263

Eating stimulates CCK release from I cells of the small intestine

Answer 264

95% in the terminal ileum

Answer 265

1. Helps body absorb necessary fat - emulsifies fat which increases SA for lipoprotein lipase to work on 2. Helps eliminate waste products - e.g. bilirubin, excess cholesterol, non-water soluble xenobiotics 3. Involved in signalling - activates the iv pathway and TGR5

Answer 266

Breakdown of RBCs

Answer 267

Haem and globin Haem then broken down into iron + unconjugated bilirubin

Answer 268

Attached to albumin

Answer 269

When it is in unconjugated

Answer 270

When it is conjugated

Answer 271

Unconjugated bilirubin + glucuronic acid --> conjugated bilirubin

Answer 272

Glucuronic acid removed to form urobilinogen which then quickly becomes stercobilin Some is reabsorbed and becomes urobilinogen then urobilin and is excreted by the kidneys

Answer 273

High levels of bilirubin in the blood

Answer 274

1. Pre-hepatic - bilirubin unconjugated - producing lots of RBCs or breaking lots down - haemolysis (haemolytic anaemia) 2. Intrahepatic - enzyme defect - Gilbert's, drugs, hepatocellular damage (hepatitis, alcohol, cirrhosis) 3. Post-hepatic - duct obstruction outside the liver e.g. gallstones, fibrosis, extra hepatic biliary atresia

Answer 275

Itching of the skin

Answer 276

Conjugated bilirubin presents with pruritus. Unconjugated hyperbilirubinemia does not. Itch is present in 80%-100% of patients presenting with cholestasis and jaundice. Cholestatic pruritus is the sensation of itch due to nearly any liver disease, but the most commonly associated entities are primary biliary cirrhosis, primary sclerosing cholangitis, obstructive choledocholithiasis, carcinoma of bile duct, cholestasis, and chronic hepatitis C viral infection and other forms of viral hepatitis.

Answer 277

Congenital condition, the common bile duct is blocked, narrowed or absent. It causes post-hepatic jaundice

Answer 278

- Cholesterol - Pigment - Mixed

Answer 279

- Cholesterol reaching levels beyond solubilising capacity of bile - Hypersecretion of cholesterol - Decreased secretion of bile salts - Abnormal gallbladder function e.g. hypomobility

Answer 280

- Bile pigment (calcium bilirubinate) is the main component - Found in chronic haemolysis because of excess bilirubin - Typically black

Answer 281

Inflammation of the gallbladder which is associated with gallstones 90% of the time

Answer 282

- Chemical effects concentrated, static bile - Obstruction of outflow of gallbladder usually caused by gallstone - Exacerbated by secondary infection

Answer 283

No gallstones form the inflammation

Answer 284

Collection of mucus in the gallbladder

Answer 285

- Wall of gallbladder is thickened and rigid from fibrosis | - Chronic inflammation of mucosa and submucosa

Answer 286

- Acute/chronic cholecystitis - Mucocoele - Empyema - Perforation

Answer 287

- Partial/total obstruction - Pain - Cholangtitis - Gallstone ileus

Answer 288

Inflammation of the common bile duct Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is an infection of the bile duct (cholangitis), usually caused by bacteria ascending from its junction with the duodenum. It tends to occur if the bile duct is already partially obstructed by gallstones.

Answer 289

A collection of pus in a pre-existing cavity

Answer 290

Impaction of a gallstone in the lumen of the small intestine

Answer 291

Peptide hormone secreted by alpha cells of the pancreas

Answer 292

- Duct obstruction - reflux of bile up the pancreatic duct - toxic injury/increased intraductal pressure releasing enzymes - Direct acing injury e.g. trauma or viruses - Zymogens (proenzymes) inappropriately activated i.e. trypsin and digest pancreatic tissue

Answer 293

Increased intraductal pressure due to production of protein-rich fluid

Answer 294

Endoscopic retrograde cholangiopancreatography

Answer 295

- Acute abdominal pain - central, severe and radiates to the back, vomiting - Signs - guarding and tenderness in upper abdomen

Answer 296

Chronic alcoholism (most common), Biliary tract disease Hypercalcaemia Hyperlipidaemia CF Idiopathic

Answer 297

Chronic inflammation and fibrosis of the pancreas Relapsing-remitting pattern

Answer 298

- Recurrent bouts of severe abdominal pain - Malabsorption due to reduced endocrine function - Steatorrhea - Jaundice - Diabetes - due to destruction of endocrine pancreas

Answer 299

- Pseudocysts - contain fibrosis, organising blood clot, cholesterol crystals and debris - Pancreatic abscess - Cystic tumours - Carcinoma of the pancreas

Answer 300

- Middle aged/elderly - Smoking - Obesity

Answer 301

- Presents late

Answer 302

- Insulinoma - high insulin - Gastrinoma - Zollinger-Ellison syndrome - Glucagonoma - high glucagon - Somatostatinoma - high somatostatin - VIPoma - watery diarrhoea

Answer 303

Upper GI (70%) - Oesophagus - Stomach - Duodenum Rarest form of GI bleeding Small bowel GI bleeding ``` 2nd most common form of GI bleeding? Large bowel (30%) ```

Answer 304

- Oesophageal causes - Peptic ulcers - Gastroduodenal erosions - Varices rupture

Answer 305

- Angiodysplasia (vascular malformation) | - Diverticular disease

Answer 306

- Crohn's - UC - Carcinoma - Haemorrhoids - Fistula - Fissure

Answer 307

Iron deficiency

Answer 308

Testing for blood in the faeces - it may not always be visible

Answer 309

- Passage of fresh blood out of the anus, usually with stools - Lower GI bleeding

Answer 310

- Black, tarry faeces, foul smelling | - Upper GI bleeding

Answer 311

Rockall score

Answer 312

A system used to predict patient mortality and assess severity of GI bleed

Answer 313

- Age (50+, 60-79, 80+) - Shock - yes/no - Co-morbidity

Answer 314

Abnormally dilated veins

Answer 315

- Bleeding from tears in the mucosa at the junction between the stomach and the oesophagus - Caused by alcoholism, retching, coughing, vomiting

Answer 316

- Fresh melaena or haematochezia - Fall in BP - Rise in pulse - You would repeat endoscopic therapy

Answer 317

Small intestine

Answer 318

- SI does not absorb enough H2O - LI not designed to absorb large quantities - Big increase in faecal quantity and liquidity

Answer 319

Longitudinal muscle that runs along entirety of colon

Answer 320

Absorption of water

Answer 321

Storage of faeces

Answer 322

- Small intestine has a brush border surface (villi and microvilli) which produces a huge SA - Colon has no brush border but does have crypts of Lieberkuhn which are secretory glands (provides protection to LI from faeces)

Answer 323

- Absorption of water driven by sodium transporters - Sodium is moved from the luminal side across the membrane of the LI creating a gradient - Water follows Na+ from the lumen - Short chain fatty acid/Na symporter - Sodium channel regulated by aldosterone

Answer 324

1. Peristalsis - movement along the tract | 2. Segmentation - mixing and churning

Answer 325

- 75% water | - 25% solids (dead bacteria, fat, inorganic matter, protein, undigested roughage)

Answer 326

- Stercobilin - brown | - Urobilin - yellow

Answer 327

 Tight junctions  Goblet cells secrete mucins – forms a layer on top of epithelial cells  Paneth cells secrete anti-microbial peptides

Answer 328

* Nasal-associated lymphoid tissue (NALT) – lining nose * Bronchus-associated lymphoid tissue (BALT) – upper respiratory tract * Gut-associated lymphoid tissue (GALT)

Answer 329

MALT It produces the amjority of immuno globulin in healthy individuals

Answer 330

o Ignore harmless antigens | o Mount protective immune responses to pathogens

Answer 331

Celiac disease - response to the wheat protein gluten IBD - inappropriate response to intestinal bacteria

Answer 332

* Aminosalicylates – dampening the inflammatory process * Corticosteroids – block substances that trigger inflammation * Immunosuppressants – suppress the immune system * Biologicals – target a specific component of the immune system (e.g. anti-TNF-alpha monoclonal antibody)

Answer 333

* Helminth therapy (worms) * Faecal microbiota transplantation * Bacterial cocktails * Small-molecule approaches – molecules that modulate host response to bac

Answer 334

 Peyer’s patches – in small intestine  Isolated lymphoid follicles – in small intestine and large intestine  Mesenteric lymph nodes – largest lymph node in body, drain the intestinal tract

Answer 335

Lamina propria leukocytes • Immune cells of lamina propria • CD4,+ CD4+, DCs, plasma cells, macrophages, etc. Intraepithelial lymphocytes • Immune cells of the epithelial layer • Specialised types of T cells mainly found in the gut

Answer 336

M cells  M cells have characteristic membrane ruffles  M cells take up antigen by endocytosis and phagocytosis  Some pathogens target M cells to gain access to the subepithelial space • e.g. poliovirus, reovirus, some retroviruses, salmonella, shigella, yersinia  Antigen is transported across the M cells in vesicles + released at the basal surface

Answer 337

Serum IgA is monomeric Secretory IgA is polymeric ( mainly bimeric); monomers are linked by 2 chains, one is J chain (joining chain)

Answer 338

IgA o Dimeric secretory IgA is transported into the gut lumen through epithelial cells at the base of the crypts o IgA in the gut neutralises pathogens and their toxins

Answer 339

Poly-Ig receptor It has a high affinity for the J-chain found in IgA

Answer 340

 IgA is transported to luminal surface of epithelium, where it is released by proteolytic cleavage of the poly-Ig receptor  Part of the cleaved receptor remains associated with the IgA and is known as the secretory component  The resulting antibody is referred to as secretory IgA

Answer 341

 Bind to mucus layer coating the epithelial surface via carbohydrate determinants in secretory component  Prevents the adherence of microorganisms  Neutralises toxins, enzymes, and bacterial LPS that has penetrated the epithelial cells  Has little capacity to activate the classical pathway of complement or to act as an opsonin (cannot induce inflammation)  Main function – limit access of pathogens to mucosal surfaces, without risking inflammatory damage to tissue  Have important role in the symbiotic relationship between an individual and their commensal bacteria, helping to restrict these organisms to the gut lumen

Answer 342

secretory IgM IgM is pentameric, so it also contains a J-chain (which is the bit that the poly-Ig receptors bind)

Answer 343

o The default response to oral administration of a protein antigen is the development of specific peripheral unresponsiveness o Antigen-specific effector T cells are turned off or deleted o Antigen-specific Treg cells are generated

Answer 344

o Induce IgA and Treg cells in the intestine o Ignored by the systemic immune system – antigens normally don’t reach the rest of the body o Bacteria constitutes 60% of the cells in your body (weight 1-2 kg)

Answer 345

 Peptidoglycan  LPS  dsRNA

Answer 346

Dendritic cells Macrophages Monocytes Granulocytes (neutrophils, eosinophils, basophils)

Answer 347

Th1 – IFN-gamma o Beneficial against intracellular pathogens o Pathology: chronic inflammation, autoimmunity Th2 – IL-4, IL-5 o Beneficial against extracellular pathogens o Pathology: allergy, asthma Th17 – IL-17 o Beneficial against extracellular bacteria + fungi o Pathology: chronic inflammation, autoimmunity

Answer 348

* Tr1 – IL-10 * Tr3 – TGF-beta * CD25+ - IL-10, TGF-beta

Answer 349

o Beneficial against intracellular pathogens Pathology of Th1 cells cause chronic inflammation and autoimmunity

Answer 350

Extracellular pathogens Pathology of these leads to allerrgy and asthma

Answer 351

Extracellular bacteria + fungi

Answer 352

Dampening the inflammatory process in IBD treatment

Answer 353

Corticosteroids – block substances that trigger inflammation Used in IBD treatment

Answer 354

Immunosuppressants – suppress the immune system Used in. IBD treatment

Answer 355

 Infliximab – anti-TNF-a monoclonal antibody  Adalimumab – anti-TNF-a monoclonal antibod

Answer 356

 Columnar epithelium – goblet cells + enterocytes  Endocrine cells – amongst columnar epithelial cells (elaborate gut hormones and crypts – motility)  Paneth cells – base of crypts, contain eosinophilic lysozyme-rich granules, defensins, immunoglobulins (protection of stem cells + regulation of intestinal microbial levels)  Intraepithelial lymphocytes – less than 20 per 100 enterocytes; there are more at base than tip of villous  Brunner’s glands – duodenal submucosal glands producing alkaline mucous secretions, rich in epidermal growth factor, encouraging mucosal regeneration after injury  Lymphoid tissue (GALT) – dense aggregates in terminal ileum (Peyer’s patches), important in immunity, predominantly T suppressor cells maintaining tolerance to food antigens

Answer 357

 Enzymatic digestion and absorption of nutrients (90%)  Vast SA – plicae semicirculares villi, enterocytes with brush borders (harbour enzymes, barrier to microorganisms and luminal foreign material)

Answer 358

 Storage and elimination of food residues  10% of nutrients is absorbed here  Maintaining fluid and electrolyte balance by absorption of salt and water  Bacterial degradation of complex carbohydrates and other nutrients

Answer 359

 Mucosa  Smooth surface  Crypts – tubular, regular spacing  Intraepithelial lymphocytes – decreasing number from right colon to rectum  Epithelium  Basement membrane  Lamina propria – fibroblasts, myofibroblasts, inflammatory cells  Muscularis mucosae – thin layer of muscle transverse by various vessels, lymphatics and nerves  Submucosa – collagen, smooth muscle, adipose tissue, blood vessels, lymphatics, cells of enteric nervous system (Meissner’s + Henle’s) • Regulate gut motility via interstitial cells of Cajal and ganglia  Muscularis propria – 3rd plexus (Auerbach’s)  Subserosa – outside muscle coat, comprised of fat with blood vessels and lymph nodes  Serosa – shiny layer of peritoneum

Answer 360

Goblet cells – apical mucin for lubrication Absorptive colonocytes – principles cells; they are responsible for: o Ion + water transportation o Eosinophilic cytoplasm with minimal mucin o Striate border on apical surfaces o Mucosal immunity Endocrine cell – confined to crypts, inverse polarity, peptide hormones Paneth cells – eosinophilic apical granules, innate immunity, physiological features of midgut, pathological manifestation of metaplasia

Answer 361

 Coeliac disease is an immunologically mediated inflammatory disorder that is due to intolerance of gluten, in genetically susceptible individuals  Gliadin is thought to be toxic component – effects an immune response resulting in increased intraepithelial T-cells

Answer 362

 Strong association with HLA-DQ2 in 90% (remainder HAL-DQ8)  Combination of genetic susceptibility and sensitivity to gliadin may be triggered by other factors – e.g. viral infection

Answer 363

Malabsorption Classical (children) • Weight loss • Chronic diarrhoea • Failure to thrive (children) ``` Non-classical (adults) • IBS-type symptoms • Abdominal pain • Altered bowel habit • Anaemia (iron deficiency) ```

Answer 364

Coeliac disease - SI Crohn's disease - Most commonly occurs in SI + colon. Can affect any part of GIT. UC - LI only

Answer 365

Abdominal pain Diarrhoea mixed with blood Weight loss, fever, and anaemia may also occur.

Answer 366

 Patients are at an increased risk with another autoimmune condition and FHx of coeliac disease  Affects females more than males (2:1)  Commonly presents in childhood, but minority diagnosed in adults and elderly  Affects 1/2000 individuals in UK (but 1 in 300 in Ireland)  But increasingly recognised in east, possibly due to introduction of wheat into diet, and increasing trend of autoimmune disease

Answer 367

Tissue transglutaminase (tTG) antibody

Answer 368

 Constitutive (continuously stimulated by body)  Produces prostaglandin for basic house-keeping purposes, stimulate normal body functions such as stomach mucous production, regulation of gastric acid and kidney water excretion  Regulation of gastric acid and kidney water excretion

Answer 369

 Induced (not normally presented in cells)  Produces prostaglandins for inflammatory response  Used for signalling pain and inflammation

Answer 370

 65% of LT use develop ulcers + erosions – usually distal ileum and duodenum, sometimes in colon  Perforation + bleeding  Focal active colitis  Chronic NSAID enteropathy (diaphragm disease) – subacute obstruction • Thin diagram like projections that usually affects ileum that resembles perforated diaphragm  Suppositories – located proctitis, ulceration, strictures

Answer 371

o Many patients take broad spectrum antibiotics develop diarrhoea, usually not severe and resolves with withdrawal of antibiotic (antibiotic-associated colitis) o Iatrogenic disease caused by C. difficile + its associated toxins resulting in fulminant colitis o Produce diarrhoea, dehydration, and death in some debilitated patients

Answer 372

 Spore-forming gram-positive anaerobe  2 toxins (A and B) detected in faeces  25% antibiotic associated diarrhoea  Primarily colonic, but may be accompanying ileitis, in immunosuppressed individuals  Histologically ‘volcano-like’ eruptions of mucus, epithelial cells, neutrophils, fibrin on surface (pseudomembrane)

Answer 373

Fecalith, food residues, lymphoid hyperplasia, diverticulosis, neoplasia (carcinoid) Other aetiology – specific infections (yersinia, tuberculosis), inflammatory bowel disease

Answer 374

Herniation of mucosa into/through muscle wall at entry/exit point of blood vessels Common condition causing morbidity in western countries Can occur anywhere in intestinal tract – sigmoid commonest site

Answer 375

Abdominal pain, altered bowel habit, ulceration --> bleeding

Answer 376

 Diverticulitis  Pericolic abscess  Perforation  Fistula – communication between 2 organs

Answer 377

Diverticulitis - inflammation of a diverticulum, especially in the colon, causing pain and disturbance of bowel function. Diverticular disease - a condition in which muscle spasm in the colon in the presence of diverticula causes abdominal pain and disturbance of bowel function without inflammation.

Answer 378

o Mucosal inflammation limited to segment affected by diverticulosis o Mucosa proximal + distal (rectum) normal o Histologically – inflammation confined to mucosa with crypt architectural changes, but can be transmural with lymphoid aggregates + fistula formation, mimicking IB

Answer 379

o Acute GI infection = major cause of morbidity o Viruses play a leading role and small intestine is usually main site - Endoscopically and histologically mimics Crohn’s disease - Chronic granulomatous infection - TB and Yersinia - Terminal ileum and caecum

Answer 380

Mucosal inflammation limited to segment affected by diverticulosis

Answer 381

* Higher incidence in northern Europe + US * Proposed genetic defect that prevents a controlled and effective immune response to causative agent * HLA-DR1 and DQw5 haplotypes * Bimodal incidence – 20-30 years 60-70 years * Can occur in children (usually with FHx) * Becoming more prevalent that ulcerative colitis + incidence rising in Asia

Answer 382

* Cigarette smoking increases risk in genetically susceptible individuals of developing Crohn’s disease * Microvascular infarction – Oral contraceptive pill (procoagulant) * Triggers appear to be infective agents – mycobacteria, measles virus

Answer 383

SI is commonly affected, but any part of the intestinal tract may be affected: o Colon alone 20% o Small bowel alone 33% o Ileocolic 45% Presentation depends on disease location: o Colon – bloody diarrhoea o SI / Upper GI – severe abdo pain, vomiting, weight loss, strictures --> small intestinal obstruction o Perianal – ulcers, fissures, perianal abscess, fistula

Answer 384

o Serosal fat wrapping o Cobblestone – transverse ulcers intersecting oedematous mucosa seen on luminal surface o Serpiginous ulcers – longitudinal

Answer 385

o Flat surface o Crypt architecture often preserved o Ulcer, patchy activity – cryptitis + crypt abscess o Plasma cell rich infiltrate o Pyloric metaplasia – response to chronic inflammation/injury o Granuloma – collection of macrophages; not specific to Crohn’s disease

Answer 386

* Complications of disease process – fistula, strictures, intra-abdominal abscess, perforation, malabsorption * Main principle of surgery – preserve bowel length to avoid short bowel syndrome + intestinal failure

Answer 387

* Malabsorption – short loop/bowel syndrome due to repeated resection * Fistula formation * Anal lesions (60%) – fissures, fistula * Perforation, haemorrhage, toxic dilation not as frequent as ulcerative colitis * Increased risk of malignancy of SI but less frequent than ulcerative colitis

Answer 388

* 15–30 years or > 60 years * Anglo-Saxon individuals ~1/1000 Abdominal pain, diarrhoea mixed with blood, weight loss, fever, anemia

Answer 389

* Inappropriate immune response to an unknown environmental stimulus in the colon * Unknown cause – infection, diet, environmental factors, primary immunological defects, abnormalities in mucin, genetic disorders, psychomotor disorder * Appendicectomy may be protective – delay onset, producing a milder form * Smoking appears to be preventative – could be linked to increased glycoprotein synthesis maintaining protective mucosal barrier * NSAIDS known to reactivate CIBD

Answer 390

* Always begins in rectum * Can remain limited to rectum (ulcerative proctitis) * Extend proximally to a variable length, or involve the entire LI (pancolitis) in a continuous manner * Changes always most severe distally * Primarily affects mucosa, but in severe disease, deeper layers can be involved – fulminant colitis (toxic megacolon)

Answer 391

o Length may be shortened, reduction in transverse calibre – increase in sarcorectal distance radiologically o Normal serosa except in toxin megacolon o Granular/velvety friable surface o Ulcers – flask-shaped or undermining o Polyps – inflammatory – granulation tissue vs pseudopolyps (oedematous smucosal islands)

Answer 392

o Irregular surface o Diffuse crypt architectural distortion o Diffuse chronic inflammatory cell infiltrate, rich in plasma cells

Answer 393

* Resistance to medical therapy or dependence on unacceptable levels of therapy – immunosuppressants * Severe disease * Complications – dysplasia (unregulated cell proliferation and differentiation) and carcinoma

Answer 394

Incidence depends on severity + extent of colitis, but significant liver problems in 5-8%

Answer 395

 Pyoderma gangrenosum – tissue becomes necrotic causing deep ulcers; usually occur on the legs  Erythema nodosum – swollen fat under the skin causing red bumps and patches

Answer 396

Primary sclerosing cholangitis (PSC)  Disease of biliary tract  Most commonly seen with pancolitis (UC) • 1-5% of patients with IBD have PSC • 50-75% of patients with PSC have IBD

Answer 397

 Iritis – inflammation of the iris  Uveitis – inflammation of the uvea  Episcleritis – benign, self-limiting inflammatory disease affecting part of the eye between conjunctiva and sclera

Answer 398

Ankylosing spondylitis – form of arthritis that primarily affects the spine

Answer 399

o Incidence and prevalence is increasing, particularly in developing countries o This could be due to improved sanitation and health reducing exposure to enteric infections  immature immune system o There is an equal distribution between males and females

Answer 400

Colon – bloody diarrhoea

Answer 401

Severe abdo pain, Vomiting, Weight loss, Strictures --> small intestinal obstruction

Answer 402

Ulcers, fissures, perianal abscess, fistula

Answer 403

Coeliac disease

Answer 404

Weight loss Chronic diarrhoea Failure to thrive

Answer 405

* Irritable bowel syndrome-type symptoms * Abdominal pain * Altered bowel habit * Anaemia (iron deficiency)

Answer 406

Lymphoma Osteoporosis Hyposplenism Anaemia

Answer 407

Malnutrition

Answer 408

Malabsorption

Answer 409

In mouth with salivary amylase

Answer 410

In stomach with pepsin

Answer 411

o Begins in the mouth w/ salivary amylase o Acidic pH of stomach destroys salivary amylase o Starch not already broken down are cleaved by pancreatic amylase in pancreatic juice

Answer 412

o Brush-border enzymes (alpha-dextrinase) acts on resulting alpha-dextrin’s, clipping off one glucose at a time o Sucrose, lactose, and maltose aren’t acted on until they reach the SI

Answer 413

Via facilitated diffusion (fructose) or active transport coupled with Na+ (glucose + galactose)

Answer 414

Move out trough basolateral surfaces via facilitated diffusion + enters capillaries

Answer 415

Trypsin Chymotrypsin Carboxypeptidase Elastase

Answer 416

In the brush border into aa

Answer 417

By active transport in the duodenum + jejunum

Answer 418

o Begins in the mouth w/ salivary amylase o Acidic pH of stomach destroys salivary amylase o Starch not already broken down are cleaved by pancreatic amylase in pancreatic juice o Brush-border enzymes (a-dextrinase) acts on resulting a-dextrin’s, clipping off one glucose at a time o Sucrose, lactose, and maltose aren’t acted on until they reach the SI o Monosaccharides pass from the lumen of the SI through the apical membrane via facilitated diffusion (fructose) or active transport coupled with Na+ (glucose + galactose) o Move out trough basolateral surfaces via facilitated diffusion + enters capillaries

Answer 419

o Begins in the stomach with pepsin o Enzymes in pancreatic juice (trypsin, chymotrypsin, carboxypeptidase, elastase) continue to breakdown proteins into peptides o Protein digestion is completed by 2 peptidases in the brush border into aa o Amino acids are absorbed by active transport in the duodenum + jejunum

Answer 420

o Lipids combine w/ bile salts to form emulsification droplets o These are digested by lipase to form free fatty acids (monoglycerides) + bile salts o These combine to form micelles o Micelles transport poorly soluble monoglycerides to the surface of the enterocytes to be absorbed o Monoglycerides are absorbed once freely dissolved micelles are no absorbed - Vitamins + minerals

Answer 421

Emulsification droplets

Answer 422

Free fatty acids (monoglycerides) + bile salts These combine to form micelles

Answer 423

Poorly soluble monoglycerides to the surface of the enterocytes to be absorbed Monoglycerides are absorbed once freely dissolved micelles are no absorbed

Answer 424

Peristalsis, grinding, retropulsion

Answer 425

o Mucous neck cells – secrete mucous o Parietal cells – produce intrinsic factor + HCl o Chief cells – secrete pepsinogen + gastric lipase o G cells – secrete gastrin (stimulate gastric acid secretion) o Delta cell – secrete somatostatin

Answer 426

``` Gastric chief cells Paneth cells (SI) ```

Answer 427

Paneth cells Goblet cells Enterocytes Enteroendocrine cells

Answer 428

Brunner's glands Oesophageal glands Pyloric glands

Answer 429

Examples include the salivary glands: Parotid gland - is predominantly serous Sublingual gland - mainly mucous glandcck Submandibular gland - is a mixed, mainly serous gland

Answer 430

They secrete gastrin produced by their G cells.

Answer 431

HCl + IF Intrinsic factor is a glycoprotein essential for the absorption of vitamin B12 (in the terminal ileum)

Answer 432

Somatostatin-producing cells. They can be found in the stomach, intestine and the pancreatic islets.

Answer 433

Stomach and duodenum Secretes gastrin

Answer 434

Histamine when pH becomes too high

Answer 435

Mucous Found in stomach

Answer 436

Releases pepsinogen and gastric lipase and is the cell responsible for secretion of chymosin in ruminants.

Answer 437

Aka mucous neck cells in the stomach that produce mucous

Answer 438

A peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein

Answer 439

Synthesised and secreted by enteroendocrine cells in the duodenum. Its presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively, and also acts as a hunger suppressant

Answer 440

Suppressant

Answer 441

When the stomach is empty, ghrelin is absorbed. When the stomach is stretched, secretion stops.a It acts on hypothalamic brain cells both to increase hunger, and to increase gastric acid secretion and gastrointestinal motility to prepare the body for food intak

Answer 442

S cells in glands of SI It is a hormone released into the bloodstream by the duodenum (especially in response to acidity) to stimulate secretion by the liver and pancreas.

Answer 443

When gastric juice enters duodenum and it's too acidic Secretin stimulates flow of pancreatic juice rich in HCO3- to buffer acidic chyme

Answer 444

Rapid digestion and absorption of macronutrients Absorption of nutrients virtually complete in distal jejunum

Answer 445

Specialised transport systems for bile acids (90% reabsorbed) + vitamin B12 absorbed in distal ileum

Answer 446

* Large surface area for absorption * Enzyme production * ‘leaky’ mucous membrane * Specific transport mechanisms * Lymphatic channels

Answer 447

Polarised cell o Have apical + basolateral membranes o Electrochemical gradients allow passive transport Intercellular spaces/junctions Specific transport pathways

Answer 448

Infections, bacterial overgrowth

Answer 449

Loss of absorptive surface area • Crohn’s disease, surgery, lymphoma Degradation of absorptive surface area • Coeliac disease

Answer 450

 Giardiasis – bloating, steatorrhoea  TB  Ancylostoma (parasite) – can cause iron deficiency  Tropheryma whippelii – bacteria that causes subtotal villous atrophy  Cryptosporidium, microsporidium, isospora – opportunist infections in immunocompromised patients

Answer 451

 High folate (B9), low B12  Jejunal diverticulosis  Blind (closed) loop syndrome – surgical procedure, fistulation  Obstruction  GI motility disorders – autonomic neuropathy (diabetes), scleroderma (connective tissue disorder)  Hypochlorhydria in the elderly

Answer 452

Immune mediated subtotal villous atrophy Crypt hyperplasia + villi shorten Intraepithelial lymphocyte can be seen Loss of surface area + villus maturation Autoantibodies – anti-tissue transglutaminase enzyme Substrate deficiency

Answer 453

Iron Folate Vit D --> osteomalacia

Answer 454

Bile salt malabsorption • Bile salt catharsis ``` B12 malabsorption • Megaloblastic anaemia • Peripheral neuropathy • Optic atrophy • Dementia • SACD – Subacute combined degeneration of spinal cord, aka Lichtheim's disease ```

Answer 455

Night blindness, | Xerophthalmia (abnormal dryness of conjunctiva + cornea)

Answer 456

Osteomalacia

Answer 457

Ataxia Dysarthria Absent tendon reflexes

Answer 458

Coagulopathy

Answer 459

Gastrin-secreting tumour or hyperplasia of the islet cells causes overproduction of gastric acid, resulting in recurrent peptic ulcers

Answer 460

o Protein-energy malnutrition (PEM) - split into developing and developed world PEM o Specific nutrient malnutrition – vitamin + mineral deficiency

Answer 461

Predominately lack of protein (Kwashiorkor) Total caloric dietary lack (Marasmus)

Answer 462

Anorexia Neglect Dysphasia Increased metabolic demands

Answer 463

Kwashiorkor is a form of severe protein malnutrition characterised by oedema, enlarged liver with fatty infiltrates Sufficient calorie intake, but with insufficient protein consumption, distinguishes it from marasmus

Answer 464

```  Growth failure  Apathy  Diarrhoea  Hepatomegaly  Muscle wasting  Oedema  Anaemia  Stomatitis – inflammation of mouth + lips ```

Answer 465

 Malignancy – cytokines suppress appetite  Infection/inflammation – TB, AIDS  Anorexia nervosa – self-induced

Answer 466

o Non-inflammatory o Invasive o Penetrating

Answer 467

Mechanism - Enterotoxins/Mucosal adherence Location - Proximal small bowel Examples: - Vibrio cholerae - Bacillus cereus - Enterotoxigenic E. coli

Answer 468

They act on colon Shigella spp. Salmonella spp. Campylobacter jejuni Enterohaemorrhagic/Enteroinvasive E. coli

Answer 469

Salmonella typhi Yersinia enterocolitica Listeria monocytogenes

Answer 470

o Behavioural/sensory o Gastric pH o Bile salts/acids o Peristalsis o Mucus – physical barrier, antimicrobials (lysozyme) o Humoral immunity – secretory IgA, cellular o GALT o Regional (normal) flora of GIT excluding mouth

Answer 471

* Synergistic * Synthetic (folate, biotin) * Release of nutrients (Fe, Ca, aa) * Remove toxins * Compete w/ pathogens * Release energy

Answer 472

 Colonisation resistance – occupy space, antibiotic-like substance production, metabolic end products may be toxic  Stimulate local immune system  Small numbers in stomach, duodenum, jejunum  Very large numbers in colon (>400 known species, possible 1500)  Regional GI can cause infection in extra-intestinal locations – peritonitis, UTI

Answer 473

```  Bloating  Abdo pain  Flatulence  Steatorrhea  Weight loss  Diarrhoea ```

Answer 474

* Fe – microcytic anaemia * B12/B9 – macrocytic anaemia * Ca – tetany * A – night blindness * Selenium – dermatitis * Protein – weight loss/cachexia * Fats – haemorrhagic stroke

Answer 475

Treatment of underlying condition Rifaximin

Answer 476

 Hydrogen 14C-D-xylose breath test  105 bacteria/ml in proximal small bowel aspirate

Answer 477

 Malabsorption – steatorrhea + diarrhoea  Deficiency of fat soluble vitamins  Macrocytic anaemia

Answer 478

Chemicals that alter the microbiome

Answer 479

Microorganism (such as lactobacillus or bifidobacterium) that when consumed maintains or restores beneficial bacteria to the digestive tract; also

Answer 480

PREBIOTICS are a special form of dietary fiber that acts as a fertilizer for the good bacteria in your gut. PROBIOTICS are live bacteria that can be found in yogurt and other fermented foods.

Answer 481

A leading cause of death worldwide Antibiotics rarely help, make E. coli 0157 worse, cause diarrhoea Usually infectious Comes from somewhere – travel/contact history Can cause post infection syndromes e.g. lactose intolerance Causes of gastroenteritis: o Viral (70%) – rotavirus (most common in children), norovirus, adenovirus, astrovirus o Bacterial – Campylobacter jejuni, E. Coli, salmonella, shigella o Parasitic – Giardia lamblia, Entamoeba histolytica, Cryptosporidium spp.

Answer 482

Rotavirus (most common in children) Norovirus Adenovirus Astrovirus

Answer 483

 Campylobacter (jejuni)  E. Coli  Salmonella  Shigella

Answer 484

 Giardia lamblia  Entamoeba histolytica  Cryptosporidium spp.

Answer 485

Mild symptoms to severe Mild diarrhoea to perforation Toxic megacolon Malnutrition Fever No vomiting, not bloody

Answer 486

o Usually affects elderly/infirm patients | o Nearly all causes follow antibiotic therapy

Answer 487

 Clindamycin – 50s inhibitor  Cephalosporins – are a class of beta-lactam antibiotics  Ciprofloxacin – a quinolone antibiotic  Co-amoxiclav – amoxicillin/clavulanic acid (combination of beta-lactam antibiotic + beta-lactamase inhibitor)

Answer 488

o Imbalance of regional flora caused by antibiotic o Acquisition of C. difficile o Increase in number of C. difficile in patients already colonised o Production of mucosa-damaging toxins (A + B)

Answer 489

o Stop inciting antibiotics (if possible) o Isolate patients o Specific anti-C. difficile antimicrobials for 10-14 days o Other measures – probiotics (e.g. Saccharomyces cerevisiae) o Faecal flora transplant o Relapsing infection

Answer 490

``` o Appendicitis o Ovarian ‘accident’ o Ectopic pregnancy o Renal colic o Inguinal/femoral hernia o Crohn’s disease o Diverticulitis o Perforated caecal cancer o Small bowel ischaemia ```

Answer 491

GIT + digestive organs Renal tract gynaecological sources Vascular Abdominal wall Other – cardiac, hyperparathyroidism

Answer 492

```  Vomiting  Bowel changes  Bleeding  Weight loss  Fever ```

Answer 493

 Hiatus hernia – presents as chest pain |  Strangulated hernia – tender bowels in hernia sac

Answer 494

```  Infarct  Ruptured aneurysm (AAA)  Ruptured ectopic  Perforated duodenal ulcer  Stone disease  Gonadal torsions ```

Answer 495

 Obstructive as the hollow muscular structure contracts to unblock itself causing pain  Bowel colic, biliary colic, ureteric colic, labour  Late bowel obstructions may not have colicky pain due to over distension of bowels

Answer 496

 Usually inflammatory process  Acute cholecystitis, appendicitis, gastritis, pancreatitis, diverticulitis, colitis  May progress to infection and/or perforation

Answer 497

Epigastric

Answer 498

Right hypochondriac

Answer 499

Left hypochondriac

Answer 500

Right and left lumbar regions

Answer 501

Left iliac region

Answer 502

Hypogastric region

Answer 503

Right iliac

Answer 504

Visceral - C fibres Parietal - myelinated A delta

Answer 505

Oesophagus 2nd part of duodenum

Answer 506

Suprapubic region

Answer 507

2nd part of duodenum to splenic (left colic) flexure

Answer 508

Splenic flexure to rectum

Answer 509

o Somatic – specific | o Visceral – general

Answer 510

``` o 35% Non-specific abdominal pain (NSAP) o 17% Appendicitis o 15% Obstruction o 6% Urinary disease o 5% Biliary disease o 4% Diverticular disease o 3% Trauma o 3% Malignancy o 3% Perforated ulcer o 2% Pancreatitis ```

Answer 511

``` o Appendicitis o Pelvic inflammatory disease – from chlamydia o Cholecystitis o Pancreatitis o UTI o Ovarian cysts o Mesenteric ischaemia ```

Answer 512

o Peptic ulcer o Colonic diverticulum o Sterocoral perforation o Aortic aneurysm

Answer 513

o Pyloric stenosis o Small bowel – adhesions, hernia, tumour, bolus (food/stone), Crohn’s o Colonic – carcinoma, diverticular, volvulus, pseudo-obstruction o Drugs

Answer 514

``` o Sickle cell crisis o Acute leukaemia o Addisonian crisis o Lead toxicity o Tabes dorsalis o Parathyroid disease o Narcotic withdrawal ```

Answer 515

 Cachexic, bruising, posture, speech, gait  Asymmetry of abdomen  Liver signs: ascites, spider naevi, clubbing, jaundice, skin changes  Evidence of other autonomic effects: sweating, pale, nausea, restlessness

Answer 516

Light palpation • To elicit tenderness/guarding • All quadrants Deep palpation • Go palpate for masses or organs or aortic aneurysm • Elicit signs such as Murphy’s and rebound tenderness Other sites • Groin examination • Digital rectal examination

Answer 517

```  Tympanic = gaseous  Dull = solid or fluid  Percuss from resonant to dull preferably  Define borders of organs such as liver  Shifting dullness for ascites ```

Answer 518

 Borborygumus or gurgling bowel sounds  Increased = increased bowel movement - e.g. gastroenteritis, bowel obstruction  Tinkling bowel sound = bowel obstruction  Absent bowel sound = no bowel activity - e.g. ileus, infarcted  Bruits

Answer 519

```  Oesophagitis  Gastritis  Duodenitis  Cholecystitis  Pancreatitis  Hepatitis ```

Answer 520

```  Enteritis  Meckel  Appendicitis  Colitis  Diverticulitis ```

Answer 521

 Colitis |  Diverticulitis

Answer 522

 Rapid onset of – colicky abdominal pain  Vomiting  Absolute constipation  Abdominal distension

Answer 523

 Abdominal distension  Tympanic  Visible peristalsis (thin patients only)  Increased bowel sound

Answer 524

 Initially – persistent or colicky pain initially  Later – localising severe pain progressing to generalised abdominal pain  Pain on movement / cough

Answer 525

```  Patient lying still  Tender abdomen on light palpation  Unable to tolerate deep palpation  Rigid abdomen  Rebound tenderness positive ```

Answer 526

```  Ulcers  Cancers  Foreign bodies  Stercoral  Obstruction  Infarcted bowel ```

Answer 527

Made in hepatocytes and stored in gallbladder

Answer 528

Eating stimulates CCK

Answer 529

CCK stimulates bile release into bowel through ampulla of vater

Answer 530

The gallbladder is located on the visceral surface of the liver in a fossa between the right + quadrate lobules

Answer 531

Bile acids:  Cholic acid  Chenodeoxycholic acid  Glycine and taurine conjugates Secondary bile acids:  Deoxycholic acid  Lithocholic acid Cholesterol Phosphatidylcholine Bilirubin

Answer 532

By water + ion absorption by the gallbladder mucosa (simple an epithelium with rugae)

Answer 533

Helps the body absorbs the necessary fats:  Emulsification of dietary fat (vital for absorption) Helps eliminate waste products:  Excess cholesterol, bilirubin, non-water-soluble xenobiotics (conjugated by hepatocytes) Signalling molecules:  Active MAPK pathway  Ligands for receptor TGF5  Active hormone receptor, e.g. FXR Bile salts + reabsorbed by active transport + return by blood to the liver (enterohepatic circulation)

Answer 534

Excess cholesterol Bilirubin Non-water-soluble xenobiotics (conjugated by hepatocytes)

Answer 535

Old RBCs are phagocytosed in the liver, this liberated globin + bilirubin (derived from haeme)

Answer 536

Bile (with bilirubin) passes into the SI and then the LI In the LI, bacteria convert bilirubin into urobilinogen Some urobilinogen is absorbed back into the blood, converted to urobilin, and excreted in urine Most urobilinogen is excreted in the faeces in the form of stercobilin (given faeces its brown colous)

Answer 537

Jaundice High bilirubin in the blood

Answer 538

Un-congugated Causes include: • Haemolysis • Resorption from bleed – e.g. burst aortic aneurysm • Gilbert syndrome – congenital condition where unconjugated bilirubin struggles to enter liver • Ineffective erythropoiesis

Answer 539

Congenital condition where unconjugated bilirubin struggles to enter liver When stressed, patient can go jaundice

Answer 540

* Liver disease – cirrhosis, viral hepatitis, primary biliary cholangitis (PBC) * Drugs * Toxins * Cancer

Answer 541

* Gallstones * Pancreatic cancer * Cholangiocarcinoma of biliary tree * Strictures * Biliary atresia

Answer 542

Accumulation of cholesterol in macrophages within the lamina propria (from foam cells) of gallbladder "Strawberry gallbladder" - stippled mucosa of gallbladder where you get cholesterol esters in foam cells

Answer 543

Inflammation of gallbladder

Answer 544

Calculous most common (obstruction of cystic duct usually by gallstones or biliary sludge) Acalculous - much less common (inflammation of gallbladder without gallstones or cystic duct obstruction)

Answer 545

Female, fat, fertile, fair, fourty

Answer 546

```  Chronic haemolysis  Lithogenic bile  Inflammation/infection  Rapid weight loss  Stasis (e.g. pregnancy, spinal cord injuries) ``` o 80% are cholesterol stones o 80% of stone have no identifiable risk factor

Answer 547

* More than 80% are silent * Acute/chronic cholecystitis * Mucocele – a swelling like a sac that is due to distension of a hollow organ or cavity with mucus * Empyema – gallbladder fills with purulent material * Perforation * Gallstone ileus

Answer 548

* Partial, total, intermittent obstruction * Pain * Cholangitis – infection of bile duct (cholangitis), usually caused by bacteria ascending from the duodenum * Gallstone ileus – small bowel obstruction caused by an impaction of a gallstone within the lumen of SI

Answer 549

Gallstones + ethanol

Answer 550

* Acute abdominal pain * Central, severe, and often radiates to back * Vomiting * History of alcohol excess gallstones, and certain drugs

Answer 551

* Guarding + tenderness in upper abdomen | * Can be complicated by: shock, DIC, renal failure, haemolysis, ARDS

Answer 552

* Raised serum amylase * Glucose intolerance * Hypocalcaemia (fat sequestration) * Raised CRP, WCC * Haemorrhagic peritoneal effusion

Answer 553

* ALCOHOL * Biliary tract disease * Hypercalcaemia * Hyperlipidaemia * Hemochromatosis * Cystic fibrosis * Idiopathic

Answer 554

* Irregular gland with fibrosis, fatty infiltration, calcification * Appearance mimics carcinoma (difficult biopsy diagnosis) * Endocrine pancreas relatively spare

Answer 555

* Pain * Weight loss * Steatorrhea * Diabetes * Jaundice (fibrosis causes biliary obstruction) * Hypalbuminaemia * Pseudocysts * Splenic vein thrombosis

Answer 556

o Insulinoma – tumor of pancreas that is derived from beta cells (secretes insulin) o Gastrinoma (Zollinger-Ellison syndrome) – tumor in the pancreas or duodenum that secretes excess of gastrin leading to ulceration in duodenum, stomach, SI o Glucagonoma – rare tumor of the alpha cells of pancreas o Somatostatinoma – a malignant tumor of the delta cells of the endocrine pancreas o VIPoma – watery diarrhoea, hypokalaemia, achlorhydria

Answer 557

60% head, 25% body, 15% tail

Answer 558

* Frequently v. little * Weight loss * Back pain * Painless jaundice (all painless jaundice is pancreatic cancer until proven otherwise)

Answer 559

Preserved + red meat Alcohol (men) Height Obesity

Answer 560

Alcohol Maybe obesity and height as well

Answer 561

Obesity | Glycaemic load

Answer 562

o Arteriole – a branch of the hepatic artery entering the liver o Venule – a branch of the hepatic portal vein entering the liver o Bile duct – branch of the bile duct leaving the liver

Answer 563

Kupffer cells Hepatocytes Stellate cells (perisinusodial cells)

Answer 564

Macrophages that capture + break down old, worn out RBCs

Answer 565

Cuboidal epithelial cells that line sinusoids, perform most of liver’s functions (e.g. detoxification)

Answer 566

 In normal liver they are the quiescent state, they store vitamin A, APC  When liver damaged they become activated + secrete collagen scar tissue leading to cirrhosis

Answer 567

Hepatic artery proper (25%) Hepatic portal vein (75%)

Answer 568

 Supplies the non-parenchymal structures of the liver with arterial blood  It is derived from the coeliac trunk

Answer 569

 Supplies the liver with partially deoxygenated blood, carrying nutrients absorbed from the SI  This is the dominant blood supply to the liver parenchyma  Allows the liver to perform its gut-related functions, such as detoxification

Answer 570

Venous drainage of the liver is achieved through hepatic veins o The central veins of the hepatic lobule form collecting veins which then combine to form multiple hepatic veins o These hepatic veins then open into the inferior vena cava

Answer 571

o Storage of glycogen, release of glucose, gluconeogenesis o Protein synthesis – e.g. albumin, coagulation factors  Muscle wastage occurs in patients because the muscles are used as a reservoir for protein o Catabolism of aa, urea production o Detoxification of nitrogenous molecules form GIT  Toxins of ammonia metabolites in blood can cross BBB and patient presents with encephalopathy o Drug + steroid metabolism o Lipoprotein synthesis o Conjugation + excretion of bilirubin o Synthesis + secretion of bile salts o Participation in immune processes

Answer 572

 Hep B – common, sometimes becomes chronic disease  Hep C – uncommon – 85% become chronic liver disease + occasionally cirrhosis

Answer 573

* CMV, EBV, HSV, Varicella, Reovirus, Mumps, Yellow fever, Cocksackie B, Adenovirus, Rubella * Lassa fever virus, Marbourg virus, Echovirus, Rift Valley Fever

Answer 574

Faeco-oral route (household, intimate, institutional)

Answer 575

Increases in: - ALT, - Bilirubin, - Faecal HAV IgA - anti-HAV IgM

Answer 576

Body fluids (blood, sex, vertical) Needle, piercings, tattoos

Answer 577

```  Heterosexual activity (40%)  Unknown (27%)  Homosexual activity (10%)  IV drug use (20%)  Healthcare workers  Non-sexual household contact (3%) ```

Answer 578

Hep B The combo has the highest fatality rate of all the hepatitis infections (20%)

Answer 579

Wide range of conditions caused by a build-up of fat in the liver – called NAFLD • Non-alcoholic fatty liver disease! • Ranges from fatty liver (steatosis) to cirrhosis to morbidity/mortality NASH is the intermediate form of liver damage that sometimes progresses to cirrhosis Some individuals who become cirrhotic from NAFLD develop hepatocellular carcinoma

Answer 580

 Vaccination (primary prevention)  Antivirals (when chronic hepatitis)  Transplant (liver failure)

Answer 581

```  Blood (IV drugs, transfusion)  Unknown  Household  Sexual contact  Vertical (maternal-neonatal) ```

Answer 582

Hep E It is more common than Hep A Mortality  Standard (<1%)  Pregnant (25%)  Accompanied chronic liver disease (<70%)

Answer 583

Pig is primary host – avoid undercooked pork

Answer 584

``` o Development of fibrosis o Formation of nodules o Loss of hepatocyte microvilli o Activated stellate cells o Deposition of scar matrix o Loss of fenestrae o Kupffer cell activation ```

Answer 585

``` o Alcohol o Hepatitis B, B+D, C o Non-alcoholic steatohepatitis o Drugs o Autoimmune liver disease o Cholestatic liver disease o Metabolic liver disease o Hepatic venous congestion --> oesophageal varices due to back pressure --> upper GI bleed ```

Answer 586

o Portal hypertension – backup of blood down portal venous system leads to portal hypertension leads to anastomose o Hepatorenal syndrome – rapid deterioration in kidney function in individuals with cirrhosis/liver failure o Ascites + spontaneous bacterial peritonitis o Hepatic encephalopathy – confused, altered consciousness level, coma due to ammonia accumulation

Answer 587

Backup of blood down portal venous system leads to portal hypertension --> anastomose

Answer 588

Rapid deterioration in kidney function in individuals with cirrhosis/liver failure

Answer 589

Usually painless, until large Diagnosis – AFP + USS/CT Incidence is rising ``` Treatable with:  Chemoembolisation  RFA  Excision  Orthotopic liver transplantation (OLTx) ```

Answer 590

 Chemoembolisation  Radiofrequency ablation (RFA)  Excision  Orthotopic liver transplantation (OLTx)

Answer 591

``` o Cerebral oedema o Bleeding + bleeding disorders o Infections o Kidney failure o Jaundice o Ascites o Melena o Hypotension + tachycardia – due to reduced systemic vascular resistance ```

Answer 592

o Unable to filter toxins + drugs effectively o Metabolism of nutrients reduced o Reduced immunity – unable to help fight infection by removing bacteria from blood o Reduced production of clotting factors – increased risk of clotting o Unable to store nutrient so body may experience shortage o Reduced protein production e.g. albumin o Reduced bile production – reduced absorption of vitamins A,D,E,K

Answer 593

Insidious onset – oden discovered at advanced stage Bleeding – overt, occult, anaemia ``` Pain – tubular blockage, tumour invasion  Foregut – upper (epigastric) pain  Midgut – periumbilical pain  Hindgut – lower (suprapubic) pain  Visceral pain is poorly localised ``` Alteration of flow – constipation, diarrhoea, dysphagia Weight loss – at advanced stages

Answer 594

Most of the GIT is lined with columnar epithelium Most tumours are adenocarcinomas (glandular), except oesophagus + anus (squamous) ``` Spread via:  Local  Intramural  Nodal  Blood born (usually to liver/lungs) ```

Answer 595

``` o Usually multifactorial o Genetic o Dietary o Environmental o Chemical (smoking, alcohol) o Inflammation – oesophagus (Barrett oesophagus), stomach (H. pylori) o Usually middle/older age o Slight male predominance (except familial conditions like APC + HNPCC) ```

Answer 596

o Surgery is the mainstay o Increasingly other therapies such as radiotherapy, chemotherapy, biotherapy o Decisions made by MDT

Answer 597

o Based on stage at time of diagnosis o Localised + completely removable surgically --> good prospects o Spread outside of the local area --> survival decreased

Answer 598

Squamous cell carcinomas (middle 1/3 of oesophagus) Adenocarcinomas (lower 1/3 and into cardia)

Answer 599

o Alcohol + tobacco o Poverty o Caustic injury, very hot beverages, radiation to mediastinum o Diet deficient in fruit + veg o Higher rates in some countries – Iran, China, Brazil, South Africa

Answer 600

o Less frequent (but on the rise), higher rates in Western countries o Most arise from Barrett oesophagus

Answer 601

* Usually elderly patients (70+) * Insidious onset with dysphagia, odynophagia * Progressive weight loss * Haematemesis --> anaemia * Usually already spread when symptomatic * Requires major surgery (high risks) * RT + CT widely used * Very poor 5-year survival (20% or less)

Answer 602

Intestinal type Diffuse infiltrative type

Answer 603

o Bulky or ulcerative with glandular structure o Precursor lesions (adenoma) o Pathogenesis – increased Wnt signalling (decrease APC, increase beta-catenin)

Answer 604

o Permeates stomach wall o Causes desmoplastic reactions o No precursor lesions o Pathogenesis – key step is loss of E-cadherin (CDH1)

Answer 605

* Marked variation of incidence (eastern Europe > northern Europe), high frequency in Japan * More common in lower socioeconomic groups • Becoming less common in western countries due to: o Decreased H. pylori prevalence o Decreased salt + smoking for food conservation

Answer 606

* Infiltrating ductal adenocarcinoma * 4th leading cause of cancer death (after lung, colon, breast) * Primarily older adults (60-80) * Smoking is the strongest risk factor * Arises from precursor lesions (intraepithelial neoplasia) * Oncogene KRAS altered in 90-95% cases * Tumour suppressor CDKN2A inactivated in 95% cases

Answer 607

Pancreatic cancer (after lung, colon, breast)

Answer 608

Surgical excision of pancreas Only option for pancreatic cancer treatment but it's only possible in >10% of cases

Answer 609

* Silent until it invades adjacent structures * Highly invasive * Brief progressive clinical course * Pain usually the first symptom * Obstructive jaundice (Courvoisier’s sign) – painless jaundice is pancreatic cancer until proven otherwise * Anorexia + weight loss when advanced * Migratory thrombophlebitis (Trousseau’s sign of malignancy) * Surgery (Whipple’s procedure) is the only option but only possible in >10% of cases * Survival rates are dismal <5%

Answer 610

Courvoisier's sign states that in the presence of a palpable enlarged gallbladder which is non-tender and accompanied with mild painless jaundice, the cause is unlikely to be gallstones.

Answer 611

* 2nd commonest cause of cancer death in the UK * Higher incidence in western countries – lifestyle, diet poor in vegetable fibre, high in refined carbs + fats) * Usually starts as benign polyp 3-5 years earlier (suitable for screening, polyp-cancer sequence well characterised) * Classic symptoms – alteration in bowel habit, pain, bleeding

Answer 612

Alteration in bowel habit, pain, bleeding

Answer 613

Lifestyle o Diet poor in vegetable fibre o High in refined carbs + fats

Answer 614

* Sporadic * Familial – FAP (familial adenomatous polyposis), less frequently DNA mismatch repair genes * Present in 30% western adults >60 years * Most clinically silent (unless large) * Majority do not progress into adenocarcinoma * Size correlates with risk malignancy * Surveillance (colonoscopy) recommended >50 years, especially if there is a family history

Answer 615

Sporadic – 80% Wnt pathway, 20% DNA mismatch repair genes Familial – HNPC (hereditary non-polyposis colorectal cancer, Lynch syndrome): o Associated to DNA mismatch repair genes FAP and HNPC are rare autosomal dominant conditions and manifest at young age

Answer 616

Familial adenomatous polyposis Rare autosomal dominant conditions that manifest at young age

Answer 617

Hereditary non-polyposis colorectal cancer, Lynch syndrome Associated to DNA mismatch repair genes

Answer 618

``` 20% present as emergency intestinal obstruction o Colicky abdominal pain o Abdominal distension o Vomiting o Absolute constipation ``` Commonest with solid faeces passing through narrow bore lumen – sigmoid colon, ileocecal valve Less common with liquid faeces or side lumen (unless advanced) – ascending colon and rectum

Answer 619

``` Alteration in bowel habits o More frequent than usual o Sometimes constipation o Feeling incompletely evacuation (tenesmus) o Main point is a change that persists o May have associated abdominal cramps ``` Bleeding o Dark red, mixed with stool o Persists over weeks/months o May not be all the time o May present as silent anaemia (classically from R sided cancer) • Until proven otherwise underlying cause of Fe deficiency in older men or post-meno female is GI cancer

Answer 620

* Usually produces visible bleeding or mucous * Often palpable on digital rectal examination * Tenesmus is a classic symptoms * Pain --> poor prognosis * Reasons for no PR – no anus or no finger

Answer 621

Surgery is the only curative option RT + CT widely used – RT common in treating rectal cancer Antibody therapy now use Outcome Is totally stage dependent o Stage A – >95% cure o Stage D – <5% survival at 5-years o Overall 50% 5-year survival Main cause of death is tumour spread – liver is most common (liver secondaries can be treated)

Answer 622

Intrinsic clearance

Answer 623

Metabolism

Answer 624

Conjugation

Answer 625

Hydrolysis

Answer 626

 Iron  Copper  Vitamins A, D, B12

Answer 627

 Nearest to the entering vascular system  Receives the most oxygenated blood  Hepatocytes here are specialised for oxidative functions

Answer 628

 Poorest oxygenation because hepatocytes along the sinusoids have used up much of the available oxygen  This is exacerbated by excess alcohol consumption  Hepatocytes here are most important for glycolysis

Answer 629

o Most drugs are fat soluble or lipophilic to a variable extent o Fat solubility is important because an orally administered drug must generally diffuse across the lipid membrane of the enterocyte to reach systemic circulation o A drug with little or no lipophilic property is poorly absorbed and is excreted in the stool o A drug that is absorbed is then bound to protein, usually albumin, and distributes itself to various tissues, inc. fat  Unless rendered more polar or water soluble, such drugs tend to accumulate in the body over a prolonged period o Whether give orally or parenterally, drugs eventually pass through the liver o The degree of hepatic drug extraction depends on hepatic blood flow + activity of the drug metabolising enzymes o In the hepatic sinusoids the drugs bound to protein pass through openings (fenestrae) in the endothelium + gain access to space of Disse, from which they enter the hepatocytes, where enzymes convert them into more polar compounds o Some of these water-soluble molecules pass back to the sinusoids, whereas other enter the biliary canaliculi

Answer 630

 Efficiency of metabolising enzymes  Liver blood flow  Intrinsic clearance  Protein binding

Answer 631

 Drug rapidly cleared from the blood by the liver (e.g. in a single pass)  Clearance depends primarily on hepatic blood flow  Therefore, clearance is non-restrictive  E.g. verapamil, morphine, propanolol

Answer 632

Drugs not efficiently cleared by the liver and extracted incompletely from hepatic blood Clearance is: • Relatively independent of hepatic blood flow • Determined by the intrinsic metabolising capacity of the liver + by the free drug fraction

Answer 633

Hepatic clearance of these drugs depends on: • Hepatic blood flow • Intrinsic metabolising capacity • Free drug fraction E.g. aspirin, codeine

Answer 634

o Each human p450 isoenzyme appears to be expressed by a particular gene (distributed among different chromosomes) o One p450 isoenzyme may be involved in the metabolism of one or more drugs, a single drug may be acted upon by multiple o Many drugs, are largely metabolised by a single form of p450 o Drugs must bind to the p450 at the substrate binding site, which is located close the enzyme’s heme prosthetic group o The binding affinity between certain drugs and p450 may vary so that a single p450 may be largely responsible for the metabolism of some drugs

Answer 635

o Methotrexate is widely used o Significant damage rare o Associated with cumulative doses of ?2g o Excess alcohol, obesity, age, increase risk o Monitoring – LFT, serum markers of fibrosis o Liver biopsy

Answer 636

o Used as suicidal agent o 10g produces hepatic necrosis o Plasma levels affected by vomiting o Alcohol – chronic use induces enzymes + increases hepatoxicity, acute use inhibits enzymes o No signs of toxicity for 48 hours, then progressive liver failure o Severe prolongation of PT and presence of acidosis predicts poor survival o Liver transplantation

Answer 637

```  Cytotoxic injury  Cholestatic injury  Mixed cytotoxic + cholestatic injury  Fatty liver  Cirrhosis ```

Answer 638

 Liver tumours  Vascular lesions  Chronic active hepatitis  Subacute hepatic necrosis

Answer 639

``` CRAP TPS  Carbamazepine  Rifampicin  Alcohol (chronic)  Phenytoin  Tobacco  Phenobarbital  Sulfonyureas ```

Answer 640

Cardiac: Amiodarone Verapamil Quinidine ``` Antibiotics: Ciprofloxacin Erythromycin Metronidazole Trimethoprim Isoniazid ``` Antifungals: Fluconazole Terafine Antacids: Cimetidine Omeprazole ``` Psychiatric: TCA Haloperidol SSRIs (fluoxetine) Valporate ``` HIV antivirals Grapefruit juice

Answer 641

Hepatocellcular failure  Decreased hepatic blood flow  Decreased enzyme function  Decreased plasma protein binding (which increases volume of drug distribution) Reduced renal clearance is associated witth reduced renal function  Seen with liver disease Malnutrition  Reduced availability of micronutrients important in metabolism

Answer 642

* Diminished complement of enzymes (sick-cell hypothesis) | * Functionally impaired because of poor perfusion (intact hepatocyte hypothesis)

Answer 643

* Due to formation of collaterals * Attendant extrahepatic * Extrahepatic shunting * Intrahepatic shunting * Capillarisation (and resulting hypoxia)

Answer 644

* From intrahepatic inflammation or extrahepatic obstruction * Applies to drugs that are primarily excreted in bile wo/ undergoing biochemical changes * E.g. nafcillin, piperacillin, apalcillin

Answer 645

o Upper GI bleed (70%) – oesophagus, stomach, duodenum o Small bowel GI bleed (<1%) o Large bowel GI bleed (30%)

Answer 646

``` Acute:  Haematemesis  Melaena  Shock  PR bleeding ``` Chronic:  Anaemia  Positive FOB (faecal occult blood)

Answer 647

``` o Oesophageal 10% o Peptic ulcer 50% o Gastroduodenal erosions 10% o Varices 10% o Idiopathic 20% ```

Answer 648

Small bowel:  Jejunal/ileal diverticulae ``` Large bowel:  Angiodysplasia 40%  Diverticular disease 40%  Carcinoma/polyp <5%  UC/Crohn’s <5%  Haemorrhoids/fissures/fistula ```

Answer 649

``` o History o Clinical examination o Abdominal examination o PR o Rigid sigmoidoscopy o Blood test including RBC, U+E, haematinics o Endoscopy, colonoscopy, CT colonography o Capsule, CT, or MR small bowel ```

Answer 650

```  Age >65  Co-morbidities – IHD, chronic lung disease, cirrhosis  Pulse >100bpm, bp <100 systolic  Shock on admission  Ascites  Continued bleeding  Re-bleeding  HB <8% on admission ```

Answer 651

 Alcoholism  Previous peptic ulcers  NSAID usage  Hepatomegaly

Answer 652

Monitor on ITU  Central line  Urine output  Regular FBC, clotting, creatinine, electrolytes, blood gases Replace clotting factors – FFP, platelets, etc Vasopressin, glypressin Somatostatin, octreotide Endoscopy – sclerotherapy or banding

Answer 653

Food poisoning It is charcterised by diarrhoea and vomitng plus or minus pain

Answer 654

``` Microbial infection  Bacterial – e.g. Salmonella, Staphylococcus aureus, E. coli, Campylobacter,!!!! Clostridium perfinges  Viral – e.g. norovirus  Fungal – e.g. aspergillus  Protozoal – e.g. cryptosporidia ``` Toxins  Bacterial toxins – Clostridium perfringens, Staph aureus, Clostridium botulinum  Marine biotoxins – scombroid poisoning, shellfish, ciguatera Chemicals  Heavy metals  Pesticides  Herbicides - Campylobacter is the most common cause, norovirus is under represented - If something comes on very rapidly it is unlikely to be bacterial/viral due to incubation period required

Answer 655

Salmonella sp. Staphylococcus aureus E. coli Campylobacter Clostridium perfinges

Answer 656

Clostridium perfringens toxins Staphylococcus aureus toxins Clostridium botulinum toxins

Answer 657

Campylobacter

Answer 658

Infection of contaminated food, faecal contaminations, person-person, contact with infected animals o Secondary cases are common in outbreaks

Answer 659

Raw food or failure to achieve adequate cooking temperatures:  Enteric fever – S. typhi (causes typhoid fever) + S. paratyphi (causes paratyphoid fever)  Enterocolitis – S. enteritidis

Answer 660

o Symptoms – diarrhoea, vomiting, fever, headache, chills o Treatment – symptomatic

Answer 661

 Previously cooked food gets contaminated with someone’s skin/nasal flora  Organism grows and produces toxin – 30-40% of S. aureus isolated produce enterotoxins  Toxin is heat + acid stable, therefore not affected by reheating food

Answer 662

o Transmission – bacteria gets into food via contact o Incubation period – 2-4 hours o Symptoms – rapid onset + rapid resolution, projectile vomiting + diarrhoea

Answer 663

o Transmission – Animal-human, person-person, contaminated water or land, associated with foreign travel o Incubation period – 2-5 days o Symptoms – watery or mucoid diarrhoea, severe illness in immunocompromised patients

Answer 664

Norovirus (RNA virus) Named due to seasonality and symptoms

Answer 665

Outbreaks common in semi-closed environments – e.g. hospitals, nursing homes Extremely low infective dose hence quick spread + high rates

Answer 666

Incubation period – 24-48 hrs Symptoms – nausea, projective vomiting, low-grade fever, diarrhoea (usually lasts 1-2 days)

Answer 667

Transmission – person-person, food/water, environmental by faecal oral route

Answer 668

Widely distributed in the environment + foods Part of normal gut flora Slow cooling and unrefrigerated storage -> spores germinate to vegetative cells Food poisoning follows ingestion of food containing large no. of vegetative cells - C. perfringens enterotoxin is produced after ingestion, not in foods Can also case gas gangrene

Answer 669

o Symptoms – Diarrhoea + abdo pain o Transmission – contaminated cooked meat + poultry, inadequate temperature control during cooling + storage

Answer 670

GIT of farm animals, soil, dust

Answer 671

Conn's syndrome is a disease of the adrenal glands involving excess production aldosterone. Another name for the condition is primary hyperaldosteronism. Conn's syndrome is important because it is a potentially curable cause of high blood pressure (hypertension).

Answer 672

Multiple endocrine neoplasia type 2 (MEN2) (also known as "Pheochromocytoma and amyloid producing medullary thyroid carcinoma". It is a group of medical disorders associated with tumours of the endocrine system.

Answer 673

Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to carcinoid tumours. The syndrome includes flushing and diarrhoea, and less frequently, heart failure, emesis and bronchoconstriction. It is caused by endogenous secretion of mainly serotonin and kallikrein.

Answer 674

A slow growing type of neuroendocrine tumour in cells of neuroendocrine system. Metastasis may occur in some cases. Carcinoid tumours of the midgut (jejunum, ileum, appendix, and cecum) are associated with carcinoid syndrome. Carcinoid tumours are the most common malignant tumour of the appendix, but they are most commonly associated with the small intestine, and they can also be found in the rectum and stomach.

Answer 675

Visceral pain is caused when the nerves on an organ sense an acute stretching of that structure's wall. This pain isn't well localised and is commonly described as an ache or cramp. Hollow organs will present with an intermittent colicky type pain, which can range from a mild ache to a severe cramping sensation, while the pain created by the solid organs is more constant. Parietal pain, also known as somatic pain, is caused by irritation to the parietal peritoneal wall. This type of pain is commonly described as "sharp" and "pinpoint" pain.

Answer 676

Small bowel meal

Answer 677

Small bowel barium enema

Answer 678

Barium meal is double contrast Barium swallow is single contrast

Answer 679

Colon Colon distended with air or CO2 then barium run into coon via rectal tube Patient must be starved for 2 days and cleared out using a strong laxative (picomax)

Answer 680

* Mucosa coated with barium and lumen distended with air * There is better mucosal detail with double contrast due to mucosal coating * So, can see smaller lesions (e.g. adenocarcinomas) * Double contrast may be give as barium meal

Answer 681

Short, rigid endoscopy used to examine rectum only No preparation needed

Answer 682

* Sedation (cardiopulmonary problems) * Perforation * Haemorrhage * Infection * Slight mortality risk

Answer 683

o Methotrexate is widely used – anticancer/antiarthritic drug o Significant damage rare o Associated with cumulative doses of >2g o Excess alcohol, obesity, age, increase risk o Monitoring – LFT, serum markers of fibrosis o Liver biopsy