CASE 3 Flashcards
what is the HARK questionnaire?
= framework for helping identify people who have suffered domestic abuse
= once point is given for every yes answer. a score of >1 is positive for IPV (intimate partner violence)
H - humiliation — within the last year, have you been humiliated or emotionally abused in other ways by your (ex) partner?
A - afraid — within the last year, have you been afraid of your (ex) partner?
R - rape — within the last year, have you been raped or forced to have any kind of sexual activity by your (ex) partner?
K - kick — within the last year, have you been kicked, hit, slapped, or otherwise physically hurt by your (ex) partner?
what are the 3 psychological theories of addiction?
- Moral Model : addiction as a result of weakness and a lack of moral fibre
- Biomedical Model : addiction as a disease
- Social Learning Theories : behaviours that are learned according to the rules of learning theory
describe the moral model (criminal justice model) of addiciton
• addicts are ‘weak’ and can overcome a compulsion to use with willpower
• drug abusers choose to use drugs
• drug abusers are anti-social and should be punished
• drugs are evil
describe the biomedical model of addiction
• addiction as a ‘brain disease’
• neurotransmitter imbalance
• disease model : agent = drug; vector = dealers; host = addict
• need to “stamp out” the disease by eliminating drugs
• drug antagonists medications = Welbutrin, naltrexone, antabuse
describe the social model of addiction
- addiction is a learned behaviour
- people use drugs because drug use is modelled by others
- peer pressure
- environmental effects lead to drug use (advertising, etc)
- drug use is a maladaptive relationship negotiation strategy
classical vs operant conditioning
• classical conditioning = associative behaviour (eg. associating drinking with feeling relaxed)
• operant conditioning = probability of behaviour occurring is increased if it is either positively reinforced by the presence of a positive event, or negatively reinforced by the absence or removal of a negative event (eg. probability of drinking increased by feeling of social acceptance, confidence and control and removal of withdrawal symptoms)
what affect does alcohol have on neurotransmitters?
• alcohol is a GABAA agonist (therefore body downregualtes GABAA receptors)
• causes upregulation of glutamatergic transmission - alcohol inhibits postsynaptic NMDA excitatory glutamate receptors
• causes activation of the dopaminergic reward pathway in the limbic system - increased dopamine in the mesolimbic pathway = VTA to limbic regions (inc ventral striatum (nucleus accumbens), amygdala, hippocampus and medial prefrontal cortex)
alcohol is absorbed from the upper small intestine via the __________ and is then transproted to the _____
- portal vein
- liver
describe alcohol metabolism
- ethanol is converted to acetaldehyde by alcohol dehydrogenase (in stomach and liver) and is then converted to acetate by aldehyde dehydrogenase
- acetate is broken into H2O and CO2 (in citric acid cycle) for easier elimination
what enzyme is involved in the metabolism of alcohol in the liver?
cytochrome P4502E1
what is the rate of metabolism of alcohol?
1 unit per hour
describe alcohol withdrawal in terms of neurotransmitters and that kind of thing
• decreased GABAa receptor function
• increased AMPA receptor function
• increased voltage gated Ca++ channel function
what can alcohol withdrawal lead to?
neuropsychiatric disorders such as seizures, delirium tremendous (delirium with hallucinations and autonomic disturbances), Wernicke’s encephalopathy etc
describe the progression of alcohol liver disease
- acute fatty change (reversible)
- acute alcohol hepatitis (reversible)
- hepatic fibrosis (reversible)
- cirrhosis (irreversible)
- hepatic decompression (fatal)
what are the 3 liver zones?
Zone 1 encircles the portal tracts where the oxygenated blood from hepatic arteries enters. Zone 3 is located around central veins, where oxygenation is poor. Zone 2 is located in between.
in which zone does the acute fatty change in alcohol disease occur?
zone 3 = this area is furthest away from blood supply
describe alcohol steatohepatitis
- fatty change, mainly large droplet (macrovesicular)
- Mallory’s hyaline (histological appearance)
- intracytoplasmic accumulation of cytoskeletal components (keratin)
- associated neutrophil polymorphs infiltration
- reversible on withdrawal of alcohol
mallorys hyaline = also known as “alcoholic” hyaline because it is most often seen in conjunction with chronic alcoholism. The globules are aggregates of intermediate filaments in the cytoplasm resulting from hepatocyte injury
describe non-alcoholic steatohepatitis
- identical features to alcohol hepatitis
- associated with obesity, diabetes mellitus, hyperlipidaemia, drug use esp corticosteroids and amiodarone
- may progress to fibrosis and cirrhosis
- reversible on correction of underlying factor
describe hepatic fibrosis
- starts in acinar zone 3
- initially pericellular fibrosis
- caused by activation of hepatic stellate (Ito) cell - facultative myofibroblast
hepatic stellate (Ito) cell = perisinusoidal in the space of Disse — regulate the proliferation of hepatoblast progenitor cells and hepatocytes by secreting growth factors (eg. Wnt, FGF)
albumin levels in liver failure?
low
what 3 things can portal hypertension cause?
- ascites
- varices
- splenomegaly
what blood tests can be used to identify heavy drinkers?
- gamma glutamyl transferase (GGT)
- mean corpuscular volume (MCV) (large in alcoholics)
We can divide the pancreas into an exocrine gland, containing the ________ and _______, and the endocrine gland containing the _____________
We can divide the pancreas into an exocrine gland, containing the acinar and duct tissue, and the endocrine gland containing the islets of Langerhans.
Digestive Enzyme Secretion — PANCREAS
The acinar cells produce digestive enzymes on the ______________. They are then moved to the ____________ where they form condensing vacuoles. These condensing vacuoles are then concentrated into inactive ______________ in pancreatic acinar cells and stored for secretion. They are secreted into the main pancreatic duct, which merges with the ___ duct at the _____ of the pancreas and forms the _______________. From here it enters the __________.
- rough endoplasmic reticulum
- golgi complex
- zymogen granules
- bile duct
- head
- Ampulla of Vater
- duodenum
what are the chemical reactions forming bicarbonate?
H2O + CO2 —> H2CO3 (catalysed by carbonic anhydrase)
H2CO3 —> H+ + HCO3- (carbonic acid dissociates into hydrogen ions and bicarbonate ions)
what are H+ ions transported out of the pancreatic ductal cells into the blood in exchange for? what happens to the exchanged ion?
Na+ ions by the H+/Na+ antiporter
the Na+ ions that enter the cell are then removed by the Na+/H+ ATPase
the HCO3- produced from the dissociation of carbonic acid is then transproted into the intercalated ducts of the pancreas in exchange for what? how is build up of this exchange ion avoided?
Cl-
An intracellular build up of Cl– is avoided by a chloride channel which allows chloride ions to return to the lumen of the intercalated ducts
what 3 things move through the intercalated ducts and end up at the main pancreatic duct ready for secretion into the duodenum upon an appropriate stimulus?
bicarbonate ions, Na+ and water
how does vagal innervation affect the pancreas?
stimulates the pancreas to secrete enzymes
what stimulates S cells to secrete secretin?
acid chyme entering the duodenum
what causes the pancreatic cells to secrete the alkaline parts of the pancreatic juices?
secretin — stimulates HCO3- secretion from duct cells
what do fatty acids and protein present in chyme, combined with the acidic pH, trigger?
trigger I cells in the duodenum to release cholecystokinin (CCK) — leads to secretion of digestive enzymes in the pancreatic juices and stimulates bile secretion via gall bladder contraction
how is cystic fibrosis relevant to the pancreas?
Bicarbonate secretion in ductal cells depends on the protein CFTR. This is both a chloride channel and a bicarbonate channel. When the CFTR protein is defective, as it is in Cystic Fibrosis, the secretion of bicarbonate by duct cells is affected. This leads to a blockage in the pancreatic ducts and inappropriate zymogen activation. This causes damage to acinar and duct cells.
Patients suffering from a complete lack of CFTR function are usually born with pancreatic insufficiency. This means their pancreas releases an inadequate amount of digestive enzymes. These patients require constant treatment with digestive enzyme supplements.
To a lesser degree, patients with less severe mutations in CFTR proteins with some limited channel function still have an increased risk of developing pancreatitis.
what 3 carbs are absorbed by the SI?
glucose, galactose and fructose
what bonds does pancreatic amylase digest?
alpha 1-4 glycosidic bonds
disaccharides produces are converted to glucose by what?
brush border enzymes
glucose and galactose are absorbed across the apical membrane by/through what?
by secondary active transport (along with Na+) throguh the sodium-glucose cotransporter SGLT1
via what do glucose and galactose exit the cell across the basolateral membrane into the blood?
GLUT2 receptors
via what does fructose enter and leave the cell?
enters via GLUT5 and leaves via GLUT2
what 3 enzymes (the major enzymes involved in lipid digestion) hydrolyse micelles?
Pancreatic lipase, phospholipase A2 and cholesterol ester hydrolase
lipids are packaged inside apportions to form what?
chylomicrons
chylomicrons are too large to enter circulation, so they enter lymphatic system via what?
lacteals
where does most absorption of water and electrolytes occur?
SI
the surface of the mucosa in the stomach os covered with gastric pits or crypts which are lined with which 4 types of cells?
- G cells which secrete gastrin (stimulates acid secretion)
- parietal cells (secrete HCl and instrinsic factor)
- chief cells (secrete pepsinogen)
- mucous cells (secrete the glycoprotein mucin) - this cells are found at the neck of the pit
what is the pH of gastric juice?
1
what is the pH of gastric contents?
3, increasing progressively to 5 within the strongly adherent mucus layer
what is the intracellular pH of the cells lining the crypt? how is this maintained?
neutral or slightly alkaline in the deepest parietal cells — this pH gradient is maintained by the directional secretion of H+ into the gastric lumen and formation of HCO3- which neutralises acid and so protects the mucosal cells
The flow of H+ out of the cells is matched by an influx of K+, whilst the outflow of HCO3– is balanced by theinflow of Cl– which will eventually be secreted with H+ as HCl
parietal cells carry receptors for what 3 agents that stimulate acid secretion?
ACh, gastrin and histamine
describe the pacemaker cells in the myenteric plexus
interstitial cells of Cajal — these cells not only play a role as gut pacemakers, but also facilitate excitatory (cholinergic) and inhibitor (nitric oxide) motor responses, and are distributed throughout the gastric and intestinal smooth muscle layers
what are the causes of acute pancreatitis?
I GET SMASHED
I — idiopathic
G – Gallstones
E – Ethanol (alcohol!)
T – Trauma
S – Steroids
M – Mumps
A – Autoimmune – e.g. SLE
S – Scorpion bites (rare!)
H – Hypercalcaemia, hypothermia, hyperlipiaemia
E – ERCP
D – Drugs – e.g. azathiaprin
what is the final common pathway in AP? how does this lead to amylase and lipase release, fat necrosis, skin discolouration, hyperglycaemia and type II diabetes?
increased intracellular calcium and inappropriate enzyme activation (of proteases)
there is evidence that alcohol interferes with calcium homeostasis in pancreatic acinar cells
Proteases digest the walls of blood vessel → blood extravasation; amylase is released into the blood (but is a non-specific diagnostic marker). Released lipases (better diagnostic marker) cause fat necrosis within abdomen and subcutaneous tissue, can → discolouration of skin (Grey Turner’s sign). The released fatty acids can bind Ca2+ can → hypocalcaemia.Concomitant destruction of adjacent islets can → hyperglycaemia and thus cause Type II diabetes.
what are the symptoms and presentations of chronic pancreatitis?
• epigastric pain that radiates to back
• relieved by sitting forward/hot water bottle applied to front
• anorexia
• nausea
• weight loss
• diarrhoea
• steatorrhoea
• diabetes
causes of CP
- idiopathic (20-30%)
- alcohol (60-70%) - but don’t assume
- genetic - eg CF
- autoimmune eg. IgG4
- hyperlipidaemia - hypertriglyceriaemia
can occur after AO
can occur without over preceding illness
can have acute flairs of CP
what effects does alcohol have on the pancreas?
- alcohol causes an individual to produce more viscous secretions
- alcohol increases the protein secretions (enzymes) from acinar cells
- alcohol reduces the secretion of bicarbonate ions and water from duct cells
- this prevents the enzymes from being carried away as part of ‘pancreatic juice’
- the enzymes accumulate in the acini (plugging of the pancreatic duct) and begin to digest the pancreas itself
alcohol increases ROS production by neutrophils - directly destroy acini cells
what are beta cells?
Beta cells are cells that make insulin, a hormone that controls the level of glucose (a type of sugar) in the blood. Beta cells are found in the pancreas within clusters of cells known as islets. In type 1 diabetes, the body’s immune system mistakenly destroys the beta cells.
why do you get pain in CP?
- dilation of the pancreatic ducts can occur as a result of blockage (eg. gallstones) or from the viscous secretions (eg. alcohol)
- this will lead to increased pressure in the ducts and cause pressure pains
- these can also cause acute inflammation and pancreatic fibrosis
- patients with chronic pancreatitis don’t deal with pain well and so gave abnormal CNS pain processing
- reduced bicarbonate secretion can cause pain elsewhere (eg. stomach — gastritis) because of lack of neutralisation of stomach acid
what is pancreatin?
• a mixture of several digestive enzymes produced by the exocrine cells of the pancreas
• it is composed of amylase, lipase and protease (trypsin)
• used to treat conditions in which pancreatic secretions are deficient, such as pancreatitis
what is prescribed alongside pancreatin and why?
omeprazole — reduce acidity in the stomach to allow more effectiveness of pancreatin (so pancreatin enzymes dont denature)
how do you differentiate between pancreatic and gastric pain?
• stomach disorders lead to imbalances in acid secretion (usually in excess)
• therefore drugs that act on acids (antacids) or acid secretion (PPIs/H2 antagonists etc) would be effective in gastric dysfunction
• however if it is pancreatic dysfunction then such drugs have little effect
• in both cases, one of the most common symptoms will be pain
—> pancreatitis: pain is usually referred to the back
—> gastric : pain localised to epigastrium
—> NSAIDs and analgesics have little effect on visceral pain,
but are efficient for somatic pain
why does referred pain occur?
due to convergence of 2nd order neurones. the same spinothalamic pathways carry nerves from adjacent skin and muscles — “visceromotor convergence”
pancreatic juice is secreted most abundantly in response to what?
the presence of chyme in the duodenum
beta cells vs alpha cells of the islets of Langerhans
- insulin is secreted by beta-cells of the islets of Langerhans
- glucagon is secreted by alpha-cells of the islets of Langerhans
describe the order from the fundamental secretory unit to the main pancreatic duct
the fundamental secretory unit is composed of an acinus and an intercalated duct; the intercalated ducts merge to form intralobular ducts, which in turn, merge to form interlobular ducts, and then the main pancreatic duct
• ________ is released by the duodenum in response to the arrival of acid chyme (pH < 4.5), stimulates _______ secretion from duct cells
• ______, secreted from the duodenum in response to the arrival of fat and protein, stimulates secretions from the acini of a group of enzymes and pro enzymes
- secretin is released by the duodenum in response to the arrival of acid chyme (pH < 4.5), stimulates HCO3- secretion from duct cells
- CCK, secreted from the duodenum in response to the arrival of fat and protein, stimulates secretions from the acini of a group of enzymes and pro enzymes
name the enzymes and proenzymes released due to stimulation from CCK
enzymes = lipase, amylase, cholesterol esterase, ribonuclease and deoxyribonuclease
pro-enzymes = trypsinogen, chymotrypsinogen and procarboxypeptidase
what is trypsin activated by?
by a small intestinal brush border enteropeptidase and then it activates the other pro enzymes
name 4 water-soluble vitamins
thiamine, folic acid, vit B12 (cobalamin), vitamin C
name 4 fat-soluble vitamins
vitamin A, D, E, K
lipase vs amylase levels in pancreatitis
lipase is preferred test — prolonged elevation and wider diagnostic window
what cells secrete CCK?
I Cells
what increases bicarbonate secretions from pancreas?
Secretion - S cells
‘pain greater with meals’ is a symptom of what?
gastric ulcer
pernicious anaemia can occur due to the absence of what?
intrinsic factor
PGE2 works as part of what pathway to reduce acid secretion in the stomach?
Gi
what does H.pylori inhibit?
somatostatin
what is the best method for peptic ulcers diagnosis?
endoscopy
