PBL Topic 4 Case 3 Flashcards
Identify the two major types of tissues in the pancreas and what each secretes
- Acini: Digestive enzymes into duodenum
- Islets of Langerhans: Insulin and glucagon into blood
Identify the three main pancreatic enzyme(s) for digesting proteins
- Trypsin
- Chymotrypsin
- Carboxypolypeptidase
How does the splitting action of the pancreatic proteases differ?
- Trypsin and chymotrypsin split proteins into peptides
- Carboxypolypeptidase splits peptides into amino acids
Identify the main pancreatic enzyme(s) for digesting carbohydrates
- Pancreatic amylase
Identify two carbohydrates that are digested by pancreatic amylase and one that is not
- Starches, glycogen
- Cellulose
Identify the three main pancreatic enzymes involved in fat digestion
- Pancreatic lipase
- Cholesterol esterase
- Phospholipase
Identify the action of pancreatic lipase
- Hydrolyses neutral fats into fatty acids and monoglycerides
Identify the action of cholesterol lipase
- Hydrolysis of cholesterol esters
Identify the action of phospholipase
- Splits fatty acids from phospholipids
In what form are proteolytic pancreatic enzymes stored when they are first secreted?
- Inactive form (zymogens)
- Trypsinogen
- Chymotrypsinogen
- Procarboxypolypeptidase
When and how is trypsin activated?
- By the enzyme enterokinase
- Which is secreted by the intestinal mucosa
- When chyme comes into contact with the mucosa
- Also activated by active trypsin
How are chymotrypsinogen and procarboxypolypeptidase activated?
- By activated trypsin in the intestine
What is the role of trypsin inhibitor?
- Prevents activation of trypsin, chymotrypsin and procarboxypolypeptidase
- Both inside secretory cells and in acini and ducts of pancreas
From which region of the pancreas are bicarbonate ions secreted?
- Ductules and ducts that lead from acini
What is the importance of bicarbonate ions secreted by the pancreas?
- Neutralise the HCl of gastric acid
- That is emptied into the duodenum from the stomach
Outline the mechanism of bicarbonate secretion
- CO2 diffuses to interior of cell from blood
- Combines with water to form carbonic acid (catalysed by carbonic anhydrase)
- Which dissociates into bicarbonate and hydrogen ions
What happens to the bicarbonate ions that are formed by dissociation of carbonic acid?
- Transported in association with sodium ions through the luminal border of the cell into the lumen of the duct
What happens to the hydrogen ions that are formed by dissociation of carbonic acid?
- Exchanged for sodium ions through active transport
- Sodium ions are then transported through luminal border into pancreatic duct
- To provide electrical neutrality for the secreted bicarbonate ions
- Causing osmosis of water into pancreatic duct
Identify three stimuli that are involved in causing pancreatic secretion
- ACh, released from the parasympathetic vagus nerve endings
- CCK, secreted by I cells of the mucosa in the small intestine in response to proteins and fatty acids in chyme
- Secretin. secreted from S cells of the duodenum, when highly acidic food enters small intestine
Which cells do ACh and CCK stimulate?
- Acinar cells
- Producing large quantities of pancreatic enzymes
- And small quantities of water and electrolytes
Outline the process by which ACh and CCK cause enzyme release from acinar cells
- Bind to G-alpha-Q receptor protein on acinar cells
- Which activates phospholipase C
- Which causes breakdown of phosphatidylcholine and phosphoinositide
- Increasing calcium release from intracellular stores
- Which activates calmodulin
- Which causes activation of protein kinases and enzyme release
Which cell does Secretin stimulate?
- Ductal epithelial cells
- Secreting large amounts of water and bicarbonate
- To wash the enzymes into the duodenum
Outline the process by which secreting causes water and bicarbonate release from ductal cells
- Binds to G-alpha-S receptor on ductal cells
- Which stimulates adenylyl cyclase
- Leading to activation of protein kinase A
Identify the role of endocrine PP cells on pancreatic enzyme release?
- Secretes pancreatic polypeptide
- Which has an inhibitory on acinar cells
Identify hormones involved in regulating pancreatic secretion
- Somatostatin
- Peptide YY
- Glucagon-like peptide
- Leptin
- Ghrelin
Outline the cephalic phase of pancreatic secretion
- ACh released by vagal nerve acting on M3 receptors on pancreatic cells
- Accounting for 20% of pancreatic secretion
Outline the gastric phase of pancreatic secretion
- ACh released by vagal nerve acting on M3 receptors on pancreatic cells
- Accounting for 5-10% of pancreatic secretion
Outline the intestinal phase of pancreatic secretion
- Mainly in response to secretin from S cells (water)
- Accounting for 70% of pancreatic secretion
Outline the process that occurs in the duodenum to neutralise HCl
- Activation of secretin which causes copious amounts of pancreatic juice
- Which contains large amounts of NaHCO3
- Which reacts with HCl to form NaCl and H2CO3
What happens to the carbonic acid that is formed in the duodenum?
- Dissociates into CO2 and H2O
- CO2 is absorbed into blood and expired through lungs
- Leaving a neutral solution of NaCl
What is the optimum pH for pancreatic digestive enzymes?
- pH = 7.0 - 8.0
- Provided by bicarbonate ion secretion
Why is fat malabsorption considered a late manifestation of pancreatic disease?
- It does not occur until there has been a reduction of 90% of pancreatic lipase
Outline a direct test of pancreatic function
- Intravenous infusion of secretin and cholecystokinin
- Aspiration is assessed for pancreatic enzymes and bicarbonate production
- In response to the these hormones
Outline the faecal test of pancreatic function
- Faecal elastase is present in faeces and diminished levels may suggest pancreatic insufficiency
- Increased fat in faeces also suggests insufficiency
Outline the pancreolauryl test
- Fluorescein dilaurate is hydrolysed by cholesterol esterase
- With the release of fluorescein which is conjugated in the liver and excreted in the urine
Outline the NBT-PABA test
- NBT-PABA is hydrolysed by pancreatic chymotrypsin to PABA
- Which is then is absorbed and excreted in the urine.
What is the role of plain abdominal radiography in pancreatic investigations?
- Shows calcification
- Associated with chronic pancreatitis
- Particularly when alcohol is the aetiology
What is the role of CT scanning in pancreatic investigations?
- Gold standard for investigation of pancreatic disease
What is the role of MRI scanning in pancreatic investigations?
- Alternative to CT
- Can be used to identify gallstones (magnetic resonance cholangiopancreatography)
What is the role of ultrasound in pancreatic investigations?
- Investigation of neoplasia and inflammation
- Endoscopic ultrasound provides fine-needle aspiration and biopsy of targeted lesions
What is the most common cause of acute pancreatitis? Identify three other causes
- Alcohol
- Infections
- Tumours
- Drugs
Identify four causes of activation of proenzymes in acute pancreatitis
- Defective transport and secretion of pancreatic zymogens
- Pancreatic duct obstruction
- Hyper-stimulation by alcohol or fat
- Reflux of infected bile or duodenal contents into pancreatic duct
Identify the clinical features of acute pancreatitis
- Epigastric abdominal pain
- That becomes more tense and leads to back pain
- Nausea and vomiting
- Tachycardia and hypotension
What do palpation and auscultation show in acute pancreatitis?
- Tenderness with guarding
- Absent bowel sounds
What are Cullen’s sign and Grey Turner’s sign?
- Cullen’s sign: bruising in periumbilical area
- Grey Turner’s sign: bruising in flanks
Identify two features of acute pancreatitis that are more likely to occur with gallstone aetiology
- Jaundice
- Cholangitis
Identify the investigations involved in the diagnosis of acute pancreatitis
- Urinary amylase (remains elevated longer than serum amylase)
- CXR to exclude GI perforation (which also causes serum amylase to rise)
- Contrast enhanced CT to detect complications (fluid collections, abscess or cyst development)
Why is IV access important in the treatment of acute pancreatitis?
- Early fluid loss may be large
What is the importance of nasogastric suction in the treatment of acute pancreatitis?
- Prevents abdominal distension and vomitus
- To reduce risk of aspiration pneumonia
What is imipenem and its role in the treatment of acute pancreatitis?
- Beta lactam
- Reduces incidence of infected pancreatic necrosis
What is the purpose of fentanyl in the treatment of acute pancreatitis?
- Patient-controlled system of pain control
Why is enteral nutrition preferred over parenteral nutrition in the treatment of acute pancreatitis?
- Lower risk of infection
Why is LMWH used in the treatment of acute pancreatitis?
- DVT prophylaxis
Which patients require positive pressure ventilation?
- Small proportion of patients who develop multi-organ failure
What is a sphincterotomy and when is it performed in acute pancreatitis?
- Incision made into the sphincter of ampulla
- In patients with gallstone related pancreatitis
What does the morbidity in acute pancreatitis reflect?
- First 7 days: systemic inflammatory response
- Thereafter: extent of pancreatic necrosis
What is considered excessive necrosis?
- Greater than 50%
- May require necrosectomy
Outline the prognosis of acute pancreatitis
- Most patients make a full recovery
- Recurrent episodes may occur
- Patients with more severe acute pancreatitis may develop malabsorption and or diabetes
What is chronic pancreatitis?
- Chronic inflammatory disease
- Characterised by fibrosis and destruction of exocrine pancreatic tissue
- Diabetes mellitus occurs in advanced cases because the islets of Langerhans are involved
What is the most common cause of chronic pancreatitis in the Western world?
- Alcohol misuse
In the pathogenesis of chronic pancreatitis, what is the role of cationic trypsin mutations? Give an example of one.
- Early activation of trypsinogen to trypsin
- PRSS1+
What is the effect of ethanol in the pathogenesis of chronic pancreatitis?
- Ethanol dysregulates calcium levels
- Which plays a role in controlling trypsin activation
- Dysregulation causes early activation of trypsinogen to trypsin
What is the affect of Chymotrypsin C on pancreatic secretion? What is found in patients with chronic pancreatitis with regards to Chymotrypsin C?
- Chymotrypsin C inactivates trypsin
- Loss of function mutations
What causes an acute inflammatory response in chronic pancreatitis?
- Active trypsin within the pancreas leading to pancreatic injury
What is the effect of AIR on Kazal 1 (SPINK1)? What is the role of Kazal 1 (SPINK1)?
- AIR upregulates Kazal 1
- Which is a serine protease inhibitor
- Which blocks active trypsin
- Preventing further activation of trypsinogens
- Limiting further tissue damage
What is the role of CFTR in the pathogenesis of chronic pancreatitis?
- Expressed on apical surface of acinar cells
- Responsible for maintaining a high volume bicarbonate rich pancreatic secretion
- Responsible for flushing the activated trypsin into the duodenum
- Mutations in CF (delta F508) result in exocrine failure
Identify five IgG4-related disroders
- Chronic pancreatitis
- Autoimmune cholangitis
- Reidel’s thyroiditis
- Aortitis
- Tubule-interstitial nephritis
Why is chronic pancreatitis considered an IgG4-related disorder?
- Raised IgG4 level
- IgG4-positive plasma cells
Identify the two types of autoimmune chronic pancreatitis
- Type 1: Typically affects middle aged men with raised serum and tissue levels of IgG4
- Type 2: Occurs in middle age with equal sex distribution and is seen in association with IBD
Outline the clinical features of chronic pancreatitis
- Epigastric pain which radiates through back
- Associated with anorexia and weight loss
- Steatorrhoea
- Malabsorption
- Diabetes
- Jaundice when there is obstruction of common bile duct
Outline the investigations involved in the diagnosis of chronic pancreatitis
- Physical exam: thin, malnourished patient with epigastric tenderness, erythema ab igne
- Elevated serum amylase (inflammation increased cell permeability allowing entry of amylase into blood) and faecal elastase
- Gene mutation analysis: PSRSS1, SPINK1, CFTR
- CT shows calcification and a dilated pancreatic duct
Outline the treatments involved in chronic pancreatitis
- Short term pain: NSAID and opiate (tramadol)
- Chronic pain: TCA (amitriptyline) and membrane stabilising agent (pregabalin)
- Steatorrhoea: Pancreatic enzyme supplementation and an acid suppressor
What is the most common complication of chronic pancreatitis? How is this compilation treated?
- Pancreatic pseudocyst surrounded by granulation tissue
- Treatment of which involves endoscopic drainage using a direct fistula between the pseudocyst lumen and the gastric lumen which is kept patent by insertion of stents
Outline the epidemiology of carcinoma of the pancreas
- Fifth most common cancer in Western world (with increasing incidence)
- Men are affected twice as often as women
Identify four modifiable risks in the development of carcinoma of the panceas
- Smoking (two-fold increase)
- Excess alcohol
- Coffee intake
- Asprin
Identify two conditions that increase the incidence of pancreatic cancer
- Diabetes
- Chronic pancreatitis
Outline the pathogenesis of pancreatic cancer
- Mutations to DNA repair genes such as BRCA2
- Activation of KRAS2 oncogene
- Inactivation of tumour-suppressor gene TP53
Outline the clinical features associated with pancreatic cancer of the head and ampulla
- Courvoisier’s Sign
- Obstructive jaundice and palpable gall bladder
- Is pancreatic cancer until proven otherwise
Outline the clinical features associated with pancreatic cancer of the body or tail
- Abdominal pain
- Weight loss and anorexia
- Thromboembolic phenomenon
- Polyarthritis and skin nodules
Outline the investigations used in the diagnosis of pancreatic cancer
- Ultrasound: Bile duct obstruction + head mass
- CT: Exclusion of tumour invasion and lymph node involvement
What is the differential diagnosis of pancreatic cancer?
- IgG4 related autoimmune pancreatitis
Outline the management of pancreatic cancer
- Resection if tumour is localised
- With adjunct chemotherapy
- Palliative measures include stents for duodenal obstruction
What happens when a portion of the small intestine becomes distended by chyme?
- Stretching of the intestinal wall elicits localised concentric contraction
- Which are spaced at intervals along the intestine
- Resulting in segmentation of the small intestine
Outline the process of segmentation of the small intestine
- Intestine is divided into spaced segments
- As one set relaxes, a new set begins at points between the previous two contractions
- These contractions chop the chyme 2-3 times per minute
What determines the maximum frequency of segmentation contractions?
- Slow waves in the intestinal wall
- Up to 12 per minute (only under extreme conditions)
Describe the propulsive movements that occur in the small intestine
- Move 0.5-2 centimetres per second
- Faster in proximal intestine and slower in terminal intestine
- Doe out after 5 centimetres
What is the gastroenteric reflex?
- Distension of stomach after ingestion
- Excites local myenteric reflexes
- Which increase peristaltic activity in small intestine
Identify five hormones that enhance intestinal motility
- Gastrin
- CCK
- Insulin
- Motilin
- Serotonin
Identify two hormones that enhance intestinal motility
- Secretin
- Glucagon
Aside from causing progression of chyme in the small, identify another cause of peristalsis in the small intestine
- Spreads the chyme out
What is the gastroileal reflex
- Following a meal
- Intensifies peristalsis in the ileum
- To force remaining chyme through the ileocecal valve into the cecum
What is peristaltic rush?
- Rapid and powerful peristalsis
- That occurs following intense irritation of the intestinal mucosa
- Sweeping contents into the colon and thereby relieving the small intestine of the irritative chyme
- As occurs in diarrhoea
What are Brunner’s glands and where are they located?
- Compound mucous glands
- Located in the proximal duodenum (between pylorus and hepatopancreatic ampulla)
What type of mucous do Brunner’s glands secrete? What is the function of this mucous?
- Alkaline mucus
- Owing to bicarbonate content
- Which protects duodenal wall from GI juice
- By neutralising HCl
Identify three stimuli that cause release of mucus from Brunner’s glands
- Tactile or irritating stimuli
- Vagal stimulation
- Hormones (especially secretin)
Why are emotional states associated with peptic ulcers?
- Excitable states cause sympathetic stimulation
- Which inhibits alkaline secretions from Brunner’s glands
- Duodenum is unprotected form HCl
- Resulting in inflammatory changes and ulceration
What are Crypts of Lieberkuhn?
- Small pits which lie between intestinal villi
- Composed of goblet cells or enterocytes
What is the rate of intestinal secretions by the enterocytes of the crypts?
- 1800 ml / day
What is the pH of intestinal secretions by the enterocytes of the cyrpts?
- pH = 7.5 - 8.0
What is the role of the intestinal secretions by the enterocytes of the crypts?
- Supplies a water vehicle for absorption of substances from chyme when it comes into contact with the villi
What is the role of peptidases
- Split small peptides into amino acids
Identify four enzymes lining the villi of the small intestines that split disaccharides in the small intestine
- Sucrase
- Maltase
- a-Dextrinase
- Lactase
What is the life cycle of an intestinal epithelial cell? What is the importance of mitosis?
- 5 days
- Allows rapid repair of excoriations that occurs in the mucosa
How does pancreatic alpha amylase differ to salivary alpha-amylase?
- Several times as powerful
- Digests all carbohydrates in chyme in duodenum with 30 minutes
- Converts carbohydrates mainly to maltose
Identify the role of lactase
- Splits lactose into a molecule of galactose and a molecule of glucose
Identify the role of sucrase
- Splits sucrose into a molecule of fructose and a molecule of gluocse
Identify the role of maltase
- Splits maltose into two molecules of glucose
What is the importance of the breakdown products of lactase, sucrase and maltase?
- All are monosaccharides
- Which are water soluble
- And are absorbed immediately into the blood
What is the role of elastase
- Major pancreatic proteolytic enzyme
- Which digests elastin fibres that partially hold meat together
Describe the structure of enterocytes in the small intestine
- Bush border that consists of hundreds of microvilli
- Which are composed of multiple peptidases that protrude to the exterior
Identify two proteolytic enzymes found in the brush border of enterocytes. What is their role?
- Aminopolypeptidase
- Dipeptidases
- Split larger polypeptides into tripeptides and dipeptides (a few amino acids)
- Which are transported through the microvillar membrane to the interior of the enterocyte
What happens to the dipeptides and tripeptides in the cytosol of the enterocyte?
- Broken down by peptidases that are specific for the remaining types of linkages between amino acids
- To form single amino acids
Why is fat broken down into very small sizes?
- To allow water-soluble digestive enzymes to act on its surface (emulsification)
Outline the first stage of fat digestion that occurs in the stomach
- Agitation in stomach
- To mix fat with products of stomach digestion
Identify two components of bile that are involved in fat digestion
- Lecithin
- Bile salts
Outline the process of emulsification of fats by bile
- Polar parts of bile salts and lecithin dissolve in water
- Fat soluble part of bile salts and lecithin dissolve in surface layer of fat
- Which reduces interfacial tension of globule
- Allowing easily hydrolysis
- Increasing the surface area of the fat
Identify the main enzyme involved in digestion of triglycerides
- Pancreatic lipase
What are the main breakdown products of triglycerides by pancreatic lipase?
- 2-monoglycerides
- Free fatty acids
What is the role of bile salts in the removal of monoglycerides and fatty acids
- Formation of micelles
- Which act as a transport medium to carry these products to enterocytes
Why do micelles develop?
- Bile salt has a fat soluble sterol nucleus
- As well as a water soluble polar group
Outline the process of micelle formation
- Sterol nucleus encompasses fat digestate
- Polar groups project outward and dissolves in water
What happens to the bile salts once the monoglycerides and fatty acids have dissolved?
- Released back into chyme to be reused in formation of micelles and transport of fatty acids/monoglycerides
Which enzyme is responsible for digesting cholesterol esters?
- Cholesterol ester hydrolase
Which enzyme is responsible for digesting phospholipids?
- Phospholipase A2
What is the total quantity of fluid that must be absorbed each day?
- 8 to 9 litres
- Includes both that ingested and that secreted
What volume of fluid is absorbed by the small intestine?
- All but 1.5 litres
- Leaving 1.5 litres to pass through ileocecal valve into colon
Identify two reasons why absorption in the stomach is poor?
- Lack villi
- Tight junctions between epithelial cells
What are plicae circulares?
- Circular folds in the small intestine (mainly duodenum and jejunum)
- Which form the absorptive surfaces of the small intestine
Identify two other structures involved in the absorption of fluid from the small intestine
- Villi located on epithelial cell surface the entire length of small intestine
- Microvilli on brush border of each epithelial cell
What are pinocytic vesicles and what is their function?
- Small vesicles which are pinched off portions of unfolded enterocyte membrane
- Which absorbed small amounts of substance by pinocytosis
What is the role of actin filaments on the brush border?
- Contract to cause continual movement of microvilli
- Keeping them constantly exposed to new quantities of intestinal fluid
Describe the movement of water across the mucosa of the small intestine
- Diffusion by osmosis from through mucosa in blood
- Can diffuse in opposite direction from blood to chyme when chyme is hyper-osmotic
Describe the movement of sodium ions across the mucosa of the small intestine
- Diffusion into epithelial cell down a concentration gradient (142 - 50 mEq/L)
- Active transport into the blood
What is the role of aldosterone in sodium absorption? What is the role of aldosterone is dehydration?
- Increased activation of Na+K+-ATPase for sodium absorption
- Increased sodium transport increases absorption of chloride ions and water by diffusion. Preventing water loss in dehydration
Describe the process of active absorption of bicarbonate ions
- Sodium ions are absorbed
- Hydrogen ions are secreted into lumen in exchange
- Which combine with bicarbonate ions to form carbonic acid
- Which dissociated into water and carbon dioxide
- Water remains as part of chyme
- Carbon dioxide is readily absorbed into blood and subsequently expired through the lungs
What is the importance of bicarbonate secretion into the ileum and large intestine?
- Alkaline neutralises acid produced by bacteria in small intestine
Outline the process of calcium absorption
- Mainly from duodenum
- PTH activates Vitamin D
- Which greatly enhances calcium absorption
Identify how the two different types of iron are absorbed into the epithelial cells of the small intestine
- Haem iron: by a carrier protein called HCP1
- Non-haem iron, converted from ferric (Fe3+) to ferrous (Fe2+) by ferrireductase and absorbed by DMT1 or NRAMP2
Identify how the body’s iron status determines the fate of iron that has been absorbed
- Stored as ferritin
OR
- Transported across basolateral surface by ferroportin 1 (+hephaestin) through its iron responsive element
What is the role of hepcidin?
- Regulates ferroportin by binding to it an causing its degradation
- Thereby decreasing iron efflux
Identify a cause of high levels of hepcidin and a cause of low levels of hepcidin?
- High levels: inflammatory cytokines (IL-6) e.g anaemia of chronic disease
- Low levels: iron-deficiency / hypoxia
Outline the process of glucose absorption from small intestine
- Via co-transport with glucose
- Active transport of sodium into blood causes facilitated diffusion of sodium into epithelial cell
- Via the sodium dependent glucose transport (SGLT)
- Which also carries a glucose molecule into the cell
- Facilitated diffusion of glucose into blood by transport protein e.g. GLUT-2
How is galactose absorbed?
- Same mechanism as glucose
How is fructose absorbed?
- Facilitated diffusion into cell but not coupled with sodium transport
- Where it becomes phosphorylated and converted into glucose
- Transported through basolateral surface by facilitated diffusion e..g GLUT-2
Outline process of protein absorption?
- Either by co-transport with glucose or by facilitated diffusion (like that of frucotse)
Outline the process of fat absoprtion
- Lipid diffusion into cell
- Taken up by ER and converted into new triglycerides
- Which are released in the form of chylomicrons through the basal surface
- Through thoracic duct to empty into circulating blood
How does the absorption of small and medium-chain fatty acids (e.g butterfat) differ to that of long-chain fatty acids?
- Absorbed directly into portal blood
- Since they are more water soluble
What is Coeliac disease?
- Immunologically mediated inflammatory disorder of the small intestine that results in malabsorption
Outline the epidemiology of Coeliac disease
- Most common in Northern Europe
- Prevalence of 1%
- Most patients are asymptomatic
What are prolamins?
- Plant storage found in proteins
- Mainly in cereals and grains
- That are resistance to digestion by pepsin
- Because of their high glutamine and proline content
What is gliadin?
- A type of prolamin present in wheat
- That is deaminated by transglutaminase
- Which increases its immunogenicity
Outline the pathology of Coeliac disease
- Gliadin is deaminated and binds to antigen presenting cells
- APCs interact with CD4 T cells via HLA class II molecules DQ2 or DQ8
- T cells interact with B cells to produce transglutaminase antibodies
- Release of inflammatory cytokines, particularly INF-Y
- Results in villous atrophy and crypt hyperplasia
Identify 3 environmental factors implicated in Coeliac disease
- Bread feeding at age of introduction of gluten into diet
- Rotavirus
- Adenovirus-12
Outline the clinical features of Coeliac disease
- Diarrhoea, steatorrhoea, abdominal pain, weight loss
- Mouth ulcers and angular stomatitis
- Abdominal distension, and growth delay in children
- Anxiety and depression
- Infertility
Outline the investigations used in Coeliac disease
- Endoscopic small bowel biopsy demonstrating blunting of villi and crypt hyperplasia
- IgA anti-endomysial antibodies
- tTg assay (tissue transglutaminase antibody)
- Full blood count shows anaemia
- Measurements of BMD
Identify the treatments used in Coeliac disease
- Vitamin and mineral replacement e.g. iron, folic acid, calcium, vitamin D
- Gluten free diet for life
Identify the complications of Coeliac disease
- Twofold increased risk of malignancy (small bowel carcinoma)
- Jejuna-ileitis (fever, pain, obstruction or perforation)
- Osteoporosis and osteomalacia in poorly controlled disease
Identify the cellular mechanisms postulated for the depressant effects of ethanol
- Enhancement of GABA and glycine action
- Inhibition of calcium channel opening
- Activation of potassium channels
- Inhibition of NMDA-type glutamate receptors
Behavioural impairment of ethanol increases in relation to what measurement?
- Blood alcohol concentration (BAC)
- Measured in mg/dL
Identify three peripheral effects of ethanol
- Self-limiting diuresis (reduced ADH secretion)
- Cutaneous vasodilation
- Delayed labour (reduced oxytocin secretion)
Identify adverse effects associated with ethanol consumption
- Dementia and peripheral neuropathy
- Cirrhosis and liver failure
- Impaired fetal development
- Psychological and physical dependence
Outline the process of ethanol metabolism
- Ethanol metabolised by liver
- First by alcohol dehydrogenase to acetaldehyde
- Then by aldehyde dehydrogenase to acetate
- Both processes involve reduction of NAD to NADH
What is the maximum rate of ethanol metabolism?
- 10 ml / hour
Outline the effects associated with a BAC of 20-99 mg/dL (2)
- Impaired coordination
- Euphoria
Outline the effects associated with a BAC of 100-199 mg/dL (3)
- Ataxia
- Poor judgement
- Labile mood
Outline the effects associated with a BAC of 200-299 mg/dL (3)
- Slurred speech
- Nausea
- Vomiting
Outline the effects associated with a BAC of 300-399 mg/dL (2)
- Stage 1 anaesthesia
- Memory lapse
Outline the effects associated with a BAC of 400+ mg/dL
- Respiratory failure
- Coma
- Death
What is meant by alcohol misuse?
- Drinking in such a way that causes problems to partners or others
What is meant by a problem drinker?
- Drinker who experiences or causes harm as a consequence of drinking
What is meant by a heavy drinker?
- Drinking more than is safe to do so
What is meant by a binge drinker?
- Drink excessively in short bouts separated by periods of abstinence
What is meant by alcohol dependence?
- Physical dependence or an addiction to alcohol
Outline the epidemiology of alcohol misuse
- 20% of men and 10% of women drink more than recommended limits
- 4% of men and 2% of women report alcohol withdrawal symptoms suggesting dependence
- Two to three times increased risk of dying
What are the recommended limits of alcohol?
- 3 units a day in men (24 g of pure ethanol) (21 units per week)
- 2 units a day in women (14 g of pure ethanol) (14 units per week)
Outline CAGE questionnaire
- Have you ever felt you should CUT down?
- Have people ever ANNOYED you by criticising your drinking?
- Do you ever feel GUILTY about drinking?
- Have you EVER had a drink first thing in the morning
- Positive answer to two or more of these questions suggests a problem drinking
- Confirm by asking amount the maximum taken
What is alcohol dependence?
- Repeated self-administration
- That causes tolerance, withdrawal and compulsive drug taking
- Despite significant substance-related problems
Identify three genetic markers that are linked to alcohol dependence
- D2 receptor allele A1
- Alcohol dehydrogenase subtypes
- Monoamine oxidase B activity
Identify two other causes of alcohol dependence
- Grow up around parents who drink
- Psychiatric illness e..g depression and anxiety
Identify five symptoms of alcohol dependence
- Strong overpowering desire to drink
- Inability control starting or stopping drinking
- Increased tolerance
- Withdrawal state
- Continuing to drink despite being aware of harmful consequences
Identify the diagnostic criteria for alcohol withdrawal syndrome
- Any three of the following:
- Tremor of the hands, tongue or eyelids
- Sweating
- Nausea, retching, vomiting
- Anxiety
- Insomnia
- Tachycardia or hypertension
What percentage of cases of alcohol misuse lead to chronic alcohol dependence
- 25%
After how many years of drinking does alcohol dependence usually develop?
- 10 years in men
- 3-4 years in women
What name is given to most serious withdrawal state of alcohol dependence that occurs up to 3 days after alcohol cessation?
- Delirium tremens
What are the features of delirium tremens?
- Disorientated
- Agitated
- Tremor
- Visual hallucinations
- Signs include tachycardia, tachypnoea and pyrexia
Identify a complication of delirium tremens
- Wernicke-Korsakoff syndrome
- Damage to the mamillary bodies and dorsomedial nuclei of thalamus
- Due to a deficiency in thiamin (B1) caused by a heavy drinking
Identify non-pharmacological treatments for alcohol dependence syndrome
- Motivational therapy
- Cognitive behavioural therapy
- 12-step facilitation
- Group therapy (e.g. family, marital)
- Education
What is the mechanism of action of naltrexone?
- Opioid antagonist
- Reduces alcohol-induced reward
What is the mechanism of action of acamprosate?
- Weak NMDA antagonist
- Used to reduce craving
What is the mechanism of action of disulifram?
- Alcohol dehydrogenase inhibitor
- Which accentuates nausea and renders alcohol consumption unpleasant
Outline the treatment of delirium tremens
- Treat electrolyte abnormalities (e.g. Pabrinex)
- Sedate patient (chlordiazepoxide, a benzodiazepine)
- Prophylactic antiepileptics with a history of withdrawal fits (e.g. phenytoin, carbamazepine)
What is the cost of alcohol misuse for the NHS?
- £3.5 billion
- Accounts for 1 in 20 emergency admissions
- Accounts for 10% of UK burden of disease
Outline the Moral Modal of Addiction
- Person is choosing to behave excessively
- And is therefore deserving of punishment
Outline the First Disease Concept of Addiction
- Substance was the problem
- Individual succumbs to its addictive influence
Outline the Second Disease Concept of Addiction
- Individual has the problem
- Requiring support and treatment
How can classical conditioning explain alcohol addiction?
- Person associated drinking with feeling relaxed so is likely to repeat the behaviour
How can operant conditioning explain addiction?
- Drinking removes the negative withdrawal symptoms
- So individual is more likely to repeat behaviour
How can social learning theory explain addiction
- People learn from role models
- Parents / friends drinking influences people to drink
Outline the four stages of substance use
- Initiation
- Maintenance
- Cessation
- Abstinence
Identify psychological predictors of drinking
- Fun and pleasure
- Calming nerves
- Building confidence
Identify social predictors of drinking
- Parental drinking
- Peer group pressure
- Attitudes of school
What is meant by revolving door schema
- Cessation occurs in a dynamic manner across the five stages of cessation rather than a linear manner
Identify the five stages of cessation
- Pre-contemplation: not seriously considering quitting
- Contemplation: having some thoughts about quitting
- Preparation: seriously considering quitting
- Action: Initial behaviour change
- Maintenance: Maintaining behaviour change for a period of time
Identify three types of intervention that help to promote cessation
- Clinical interventions
- Self help movements: therapy: aversion therapy/contingency contracting/cue exposure
- Public health interventionsL government interventions, doctors advice, community-based programmes
Outline the relapse prevention model
- Addictive behaviours are learned and therefore can be unlearned,
- Addictions are not ‘all or nothing’ but exist as a continuum
- Lapses from abstinence are likely and acceptable, and are determined by good coping strategies and positive outcome expectancies.
What is a high risk situation?
- Situation that motivates individual to carry out addictive behaviour
- External cues include someone else drinking
- Internal cues include anxiety
Outline two types of coping strategies employed when an individual is exposed to a high risk situation
- Behavioural: avoiding situation, using a substitute behaviour
- Cognitive: remembering to abstain
What are positive and negative outcome expectancies?
- Positive: Expectancies that drinking will make the individual feel better
- Negative: Expectancies that drinking will be harmful to health
What is the HARK Questionnaire?
- Framework for helping identify people that have suffered domestic abuse in past year
- Humiliate: Make you feel bad about yourself, that you can’t do anything right
- Afraid: What is it that makes you scared of your partner
- Rape: Raped, forced into sexual activity
- Kicked: Physical abuse or threatened with physical abuse
What is IRIS?
- Support program to improve the general practice response to domestic violence
- Through interventions to help clinicians recognise and respond to patients affected by domestic violence
Outline the three components of the Theory of Planned Behaviour
- Attitude towards a behaviour (positive or negative)
- Subjective norm (perception of social norms and pressures to perform a behaviour)
- Perceived behavioural control, including internal control factors (skills, abilities) and external control factors (obstacles and opportunities)
Apply the Theory of Planned Behaviour to alcohol reducting
- Attitude to behaviour: reduction would be beneficial to health
- Subjective norms: family and friends would want them to cut down
- Perceived behaviour control: capable of drinking less due to past behaviour and evaluation of internal and external factors
What are odds?
- Likelihood of an event occuring
1 in 10 people develop pancreatitis. Calculate the odds of developing pancreatitis
- 1/(10-1) = 0.11
What are odds ratios?
- Used to compare whether the likelihood of an event differs between two groups
64 out of 256 people in the treatment group had the outcome. 45 out of 180 people in the control group had the outcome. Calculate the odds ratio
- 64/(256-65) / 45/180-45) = 1
What does an odds ratio of less than 1, 1 and greater than 1 mean?
- Less than 1: Event was less likely in treatment group
- 1: Event was equally likely in both groups
- More than 1: Event was more likely in control group
What does a Chi-square test test?
- A null hypothesis stating that
- Frequency distribution of observed findings
- Is consistent a particular theoretical distribution
Identify two types of Chi-square test
- Goodness of fit: whether observed frequency distribution differs from a theoretical distribution
- Independence: whether paired observation on two variables are independent of each other
What is a confounding variable?
- A variable that has an outcome on the effect and is also correlated to the exposure
- E.g. alcohol consumption has an effect on disease X and is correlated with smoking (the exposure) because smokers tend to drink more
Identify three common confuonders
- Age
- Socioeconomic status
- Gender
What is the purpose of multiple logistic regression?
- Control for many potential confounders at one time
How does simple logistic variation differ to multiple logistic variation?
- Simple: Explore associations between one outcome and one exposure variable (E.g. how does smoking affect likelihood of pancreatitis)
- Multiple: Explore associations between one outcome and two or more exposure variables (E.g. how does smoking affect likelihood of having pancreatitis, after accounting for alcohol smoking?’
