PBL 9 diabetes

Question Answer
what percentage of the whole pancreas mass do islets make up? 1%
what is 99% of the pancreas dedicated to? exocrine function and acini
which has a better blood supply, islets or the acinar system? islets have a rich blood supply in comparison to the acinar system, this is because the islets need to release hormones directly into the bloodstream
what do the beta cells in the islets produce? insulin
what do the alpha cells in the islets produce? glucagon
what do the delta cells in the islets produce? somatostatin
what is insulin? a polypeptide hormone consisting of two short chains (A and B) linked by disulphide bonds
what do the ribosomes of the beta cells synthesise? pre-proinsulin from insulin mRNA
what happens to pre-proinsulin synthesised by the ribosomes of the beta cells? broken down into proinsulin by cleavage in the Golgi apparatus
what happens to proinsulin? it's converted to active insulin which are stored in secretory granules until needed for release
how does glucose enter B cells? via the GLUT-2 receptor
what does metabolism of glucose within the beta cells do? generates ATP, which closes the ATP-sensitive potassium (K+) channels in the cell membrane
what are the major sites of expression of GLUT-2? liver, pancreatic beta cell, small intestine, kidney
what does the GLUT-2 receptor do? transports glucose, galactose, and fructose. a low affinity, high capacity glucose transporter
what does closure of the K+ channels in the beta cell membrane do? causes a depolarisation in the membrane (since K+ is not moving out of the cell). Subsequently, calcium channels open, allowing calcium entry into the cell,
what does a build up of intracellular calcium ions lead to in the beta cell? fusion of insulin granules to fuse with the cell membrane, releasing insulin by exocytosis
what sort of effect does insulin have and what does this mean? insulin has an anabolic effect, it promotes the synthesis of larger molecules
how does insulin effect target tissues – what does it bind to? binds to insulin receptors (tyrosine kinase receptors) on the surface of target tissues
what's the tyrosine kinase receptor on the target tissues made up of and which part does insulin bind to? made up of 2 alpha and 2 beta units, with insulin binding to the alpha unit
What does insulin binding to the alpha unit on the tyrosine kinase receptor do? what does this eventually lead to? causes a conformational change in the beta units, causing auto-phosphorylation and an intracellular cascade of events. Eventually this leads to the translocation of GLUT-4 transporters in the cell membrane, which transports glucose molecules into cells
give five other anabolic effects insulin has increased uptake of metabolites, glycogen synthesis (liver, muscles), fatty acid synthesis (liver, adipocytes), increased amino acid production and protein synthesis, increased rate of glucose utilisation and ATP generation
what is GLUT4 responsive to? insulin (adipocytes and muscle only)
what are the major sites of expression of the GLUT 4 receptor? skeletal and cardiac muscle, adipocytes
give two characteristics of the GLUT 4 receptor? the insulin-responsive glucose transporter, high affinity for glucose
name three disaccharides maltose, sucrose, and lactose
what's type 1 diabetes mellitus? the autoimmune destruction of beta cells, leading to absolute insulin deficiency. This results in the inability to maintain blood glucose levels
what does untreated type 1 diabetes mellitus do – why do clinical problems arise? untreated diabetes mellitus disrupts metabolic activities through the body. Clinical problems arise because the tissues involved are experiencing an energy crisis, which results in the inability to maintain blood glucose levels
in type 1 diabetes mellitus how are most of the tissues responding? as they would in starvation, by breaking down (catabolic processes) lipids and proteins because they are unable to absorb glucose from the surroundings
what do cells do when they don't get the glucose they need to make energy? what happens when these are burned? they break down fats for energy. when these fats are burned, they release chemicals known as ketones which can buildup in the blood, making it more acidic
what occurs in type 1 diabetes mellitus as a result of a build up of ketones in the blood? respiratory compensation (hyperventilation) will occur, specifically Kussmaul's breathing (deep rapid breaths, 'air hunger')
what does increased production of acetic ketone bodies do? increases plasma pH
what's polyuria? excessive/an abnormally large production or passage of urine (greater than 2.5L or 3L over 24 hours in adults)
what causes polyuria? osmotic diuresis, glucose and ketones are freely filtered at the glomerulus and not all of it can be reabsorbed as it exceeds the renal threshold. An inc solute conc in the tubular lumen causes an osmotic gradient
what does the osmotic gradient in polyuria cause? results in increased water, sodium, and potassium loss in the urine
give three symptoms of diabetic ketoacidosis Polyuria, thirst, and weight loss
why do you get weight loss during diabetic ketoacidosis? due to fluid depletion and accelerated muscle/fat breakdown
what is thirst during diabetic ketoacidosis caused by? due to the resulting loss of fluid and electrolytes (dehydration, dry mouth)
what exacerbates renal potassium loss in diabetic ketoacidosis? what prevents potassium from moving into cells? hyperaldosteronism exacerbates renal potassium loss. lack of insulin prevents potassium from moving into cells.
why is serum potassium normally elevated during diabetic ketoacidosis? K+ is lost in large quantities during osmotic diuresis, so there' an extracellular migration of K+ from cells into the blood, therefore serum K+ is normally normal or elevated
what's hypovolaemia decreased blood volume
how can you treat hypovolaemia caused by diabetic ketoacidosis IV fluids
how can you treat insulin deficiency as a result of diabetic ketoacidosis? IV insulin – insulin is the most essential treatment for switching off ketogenesis, and blood sugar may return to normal quite quickly with IV insulin
what's hypokalaemia ? Low level of potassium in blood serum
how can you treat hypokalaemia as a result of diabetic ketoacidosis? IV potassium
what's glycosuria the excretion of glucose into the urine
give two asymptomatic features of diabetes glycosuria and mild hyperglycaemia
what should the fasting plasma glucose level be in a normal individual? less than 7.0mmol/L
what should the plasma glucose 2 hours after oral glucose be in a normal individual? less than 7.8mmol/L
what is the fasting plasma glucose level in diabetes mellitus? more than 7.0mmol/L
what should the plasma glucose be in diabetic mellitus after a glucose tolerance test (2hours after 75g oral glucose)? more than 11.1mmol/L
what should the fasting plasma glucose be in impaired glucose tolerance? less than 7.0mmol/L
what should the plasma glucose be 2 hours after you've given glucose in someone with impaired glucose tolerance? between 7.8-11.0mmol/L
what are the results for the fasting/glucose tolerance test from? venous plasma – whole blood values are lower
autoantibody tests for diabetes mellitus type 1? Tests for C-peptide deficiency can help determine the decline in beta cell function (during insulin production, the C-peptide is cleaved off from the pre-proinsulin, leaving A and B peptides (chains)
what's glycated haemoglobin and how long is it measured over a form of haemoglobin that is measured primarily to identify the three month average plasma glucose concentration. The test is limited to a three month average because the lifespan of a red blood cell is four months
what do they measure when they measure glycated haemoglobin? Haemoglobin A1c (HbA1c)
glycated haemoglobin test – what values suggest diabetes mellitus? HbA1c > 6.5% (48mmol/L) suggests diabetes mellitus. 5.7-6.4% suggests a high risk of developing diabetes mellitus
what sort of disease is type 1 diabetes? a T-cell mediated autoimmune disease involving destruction of the insulin-secreting Beta cells in the pancreatic islets of Langerhans
in type 1 diabetes when does marked hyperglycaemia occur? progressive loss of beta cell function takes place over a prolonged period (months-years), but marked hyperglycaemia only occurs when 80-90% of beta cell functionality is lost, by immune mediated mechanisms
genetic predisposition to diabetes genetic factors account for 1/3 susceptibility in type 1 diabetes, inheritance is polygenic (multiple genes bring susceptibility to diabetes). main gene identified – HLA region (DR3 or DR4) of MHC on short arm of chromosome 6
environmental factors for diabetes mellitus type 1 nature of environmental factors is unknown. it could be due to substances that cause direct toxicity to beta cells, or by stimulating an autoimmune reaction against beta cells.
some environmental factors identified viruses (mumps, coxsackie, retrovirus, rubella), chemicals
name the three types of insulin animal, human, analogues
human insulin recombinant insulin produced synthetically
analogues different chemical structure to insulin, in aim to achieve faster onset effects, or delayed effects. long-acting and short acting analogues can be used as a combination
what are short acting insulins used for? for pre meal injection in multiple dose regimens (continuous IV infusion or during medical emergencies)
how fast is human insulin absorbed? slowly, reaching a peak 60-90min after subcutaneous injection, and its action tends to persist after meals, predisposing to hypoglycaemia
why is absorption delayed because soluble insulin is in the form of stable hexamers and needs to dissociate more rapidly before it can enter the circulation
what can the action of human insulin be prolonged by? the addition of zinc or protamine. tend to be injected once or twice a day to provide background insulin lasting approximately 24 hours. They don't need to be taken with food since they don't have a peak action
when are intermediate insulins/combination taken? these are taken once or twice a day to provide background insulin mixed with short-acting insulins/rapid acting analogues
how is insulin mostly given? how long does this take for insulin levels to reach their peak? mostly insulin is given in the form of injections. subcutaneous injection takes 60-90 minutes for the plasma insulin levels to reach their peak
how do insulin pumps work? CSII (continuous subcutaneous insulin infusion) is delivered by a small pump strapped around the waist that infuses a constant trickle of insulin via a needle in the subcutaneous tissues
what's a basal bolus insulin regime? A basal-bolus routine involves taking a longer acting form of insulin to keep blood glucose levels stable through periods of fasting and separate injections of shorter acting insulin to prevent rises in blood glucose levels resulting from meals.
what's basal insulin for? The role of basal insulin, also known as background insulin, is to keep blood glucose levels at consistent levels during periods of fasting – usually taken once or twice a day depending on the insulin
what's bolus insulin and what type is used? A bolus dose is insulin that is specifically taken at meal times to keep blood glucose levels under control following a meal. Bolus insulin needs to act quickly and so short acting insulin or rapid acting insulin will be used.
what's the most common complication of insulin therapy? Hypoglycaemia
what does hypoglycaemia result from? an imbalance between injected insulin and a patients normal diet, activity, and basal insulin requirement
when are the times of greatest risk for hypoglycaemia? before meals, during night, and during exercise
when do hypoglycaemia symptoms develop? when blood glucose level falls below 3mmol/L with most patients experiencing 'adrenergic' features of sweating, tremor, and palpitations, hunger, and anxiety
give two physical signs of hypoglycaemia pallor and cold sweat
what can some patients slip rapidly into? a hypoglycaemic coma (neuroglycopenia which refers to the shortage of glucose in the brain)
what's nocturnal hypoglycaemia ? basal insulin requirement falls during the night but increases from about 4am onwards, at a time when levels of injected insulin are falling. As a result, many patients wake with high blood glucose levels
a patient wakes with high blood glucose levels – what does injecting more insulin at night cause? increases the risk of hypoglycaemia in the early hours of the morning
what should you do to treat hypoglycaemia? give glucose! 15-20g of a fast acting carb e.g. sugary fizzy drink, 3 or more glucose tablets, five sweets e,g, jelly beans
what do u need in severe hypoglycaemia help from another individual (patient may be unconscious)
hypoglycaemic patient is unconscious what do you do give intramuscular glucagon – glucagon will facilitate the release of stored glucose back into the bloodstream, raising the blood glucose level
what else can you give in severe hypoglycaemia intravenous dextrose (form of sugar), long acting carb may be required to prevent a further drop in blood sugar
driving with hypoglycaemia? DVLA must be informed. patient must wait at least 45 mins before the normalisation of blood sugar levels before driving

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