Module 3D Endocrine - LOs Flashcards
Glucose metabolism –> what is the basic process?
- include the action of insulin
- and the action of glucagon
- and where they are produced
What is the ideal blood glucose range?
- Eating carbohydrates causes a rise in blood glucose levels (BM), as carbohydrates are absorbed from the small intestine into the blood
- As the body uses these carbs for energy, there is a fall in blood glucose levels
- The body ideally wants to keep blood glucose conc. between 4.4-6.1 mmol/L
. - Insulin is an anabolic hormone (building hormone) produced by the beta cells in the pancreatic islets
- Insulin acts to reduced blood sugar levels, it does this in two ways
- Insulin can allow cells in the body to absorb glucose from the blood and use it as fuel
- Or insulin can cause muscle and liver cells to absorb glucose from the blood and store it as glycogen - this process is called glycogenesis
- Insulin is always present in small amounts, but lvls increase when blood sugar lvls rise
. - Glucagon is a catabolic hormone (breakdown hormone), it is released in response to low blood sugar levels and stress –> it works to increases blood sugar levels
- Glucagon can tell the liver to break down stored glycogen and release it into the blood as glucose –> this process is called glycogenesis
- It can also tell the liver to convert proteins and fats into glucose –> this process is called gluconeogenesis
Ketogenesis (production of ketones):
- when does it occur?
- What is the process?
- How can ketone lvls be measured
- Characteristic smell on breath?
- Why is ketogenesis bad in T1DM pts?
- Occurs when there is insufficient glucose supply and glycogen stores are exhausted –> eg. in prolonged fasting
- The liver takes fatty acids and converts them to ketones –> ketones are water-soluble fatty acids that can be used as fuel –> they can cross the blood-brain barrier and be used by the brain
- Producing ketones is normal and not harmful in healthy patients under fasting conditions or on very low-carb + high-fat diets (keto-diet)
- Ketone lvls can be measured in the urine with a dipstick test and in the blood using a ketone meter
- (people in ketosis have a characteristic acetone/sweet smell to their breath)
- In healthy people, the kidneys buffer ketone acids so the blood does not become acidotic –> T1DM can cause extreme hyperglycaemic ketosis –> resulting in a life-threatening metabolic acidosis (diabetic ketoacidosis)
What are the 3 key features of DKA and explain the pathophysiology behind each one
- what biochemical imbalance should you watch out for when starting a pt on insulin treatment?
Ketoacidosis:
- Without insulin, the body’s cells cannot recognise glucose, even when there is plenty in the blood, so the liver starts producing ketones to use as fuel
- Over time, there are higher and higher glucose and ketones levels
- Initially, the kidneys produce bicarbonate to counteract the ketone acids in the blood and maintain a normal pH
- Over time, the ketone acids use up the bicarbonate, and the blood becomes acidic –> this is called ketoacidosis
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Dehydration:
- hyperglycaemia overwhelms the kidneys, and glucose leaks into the urine
- the glucose in the urine draws water out by osmotic diuresis –> this causes increased urine production (polyuria) and results in severe dehydration –> dehydration then results in excessive thirst (polydipsia)
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Potassium imbalance:
- insulin normally drives potassium into cells –> without insulin, potassium is not added to and stored in ells
- the serum potassium can be high or normal st he kidneys balance blood potassium with the potassium excreted in the urine
- However, total body potassium is low because no potassium is stored in the cells
- when insulin treatment starts, patients can develop severe hypokalemia (low serum potassium) very quickly, leading to fatal arrhythmias
What are the 4 ways to monitor blood glucose levels in T1DM patients?
- HbA1c –> measures glycated haemoglobin (how much glucose is attached to the Hb molecule)
- This reflects the average glucose level over the previous 2-3 months (RBCs have a lifespan of about 4 months)
- It is measured every 3 to 6 months to track the average sugar levels –> it is a lab test
. - Capillary blood glucose (finger-prick test) can be measured using a blood glucose monitor, giving an immediate result
- Patients with type 1 and type 2 diabetes rely on these machines for self-monitoring their sugar levels
. - Flash glucose monitors (e.g., FreeStyle Libre 2) use a sensor on the skin that measures the glucose level of the interstitial fluid in the subcutaneous tissue
- There is a 5-minute lag behind blood glucose
- The sensor records the glucose readings at short intervals, so you get an excellent impression of what the glucose levels are doing over time
- The user needs to use their mobile phone to swipe over the sensor and collect the reading
- Sensors need replacing every 2 weeks for the FreeStyle Libre system
- The 5-minute delay means it is necessary to do capillary blood glucose testing if hypoglycaemia is suspected
. - Continuous glucose monitors (CGM) are similar the flash glucose monitors in that a sensor on the skin monitors the sugar level in the interstitial fluid
- However, continuous glucose monitors send the readings over bluetooth and do not require the patient to scan the sensor
T2DM management –> drugs
- First-line –> metformin
- Once settled on metformin, add an SGLT-2 inhibitor (eg. dapagliflozin) if pt has existing CVD or heart failure (Q-risk score > 10%)
- Second-line –> add a sulfonylurea, pioglitazone, DPP-4 inhibitor, or SGLT-2 inhibitor
- Third-line options –> Triple therapy with metformin and two 2nd-line drugs OR insulin therapy (initiated by specialist diabetic nurses)
- (If triple therapy fails and pt’s BMI > 35kg/m2 –> option to try GLP-1 mimetic)
Metformin –> class of drug + MOA + side effects
- Class of drug –> biguanide
- MOA –> increases insulin sensitivity and decreases glucose production
- Side effects –> GI symptoms (pain, nausea, diarrhoea), lactic acidosis (eg. secondary to AKI)
- (Note: if pt has GI side effects with standard-release metformin then can try modified-release metformin)
SGLT-2 inhibitors –> examples + MOA + side effects (2 main ones)
- Examples –> empagliflozin, canagliflozin, dapagliflozin and ertugliflozin
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MOA: - sodium-glucose co-transporter 2 protein is found in the proximal tubules of the kidneys –> it acts to reabsorb glucose from the urine back into the blood
- SGLT-2 inhibitors block the action of this protein, causing more glucose to be excreted in the urine
- Loss of glucose in the urine lowers the HbA1c, reduces the blood pressure, leads to weight loss and improves heart failure
(They can cause hypoglycaemia when used with insulin or sulfonylureas)
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Side effects: - increased frequency of UTIs and genital thrush –> due to lots of sugar passing through the urinary tract
- DKA –> all pts should be counselled about the features of DKA and when to seek help
Pioglitazone –> class of drug + MOA + side effects
- Class of drug –> thiazolidinedione
- MOA –> increases insulin sensitivity and decreases liver production of glucose (it does not typically cause hypoglycaemia)
- Side effects –> weight gain, heart failure, increased risk of bone fractures
Sulfonylureas –> example + MOA + side effects
- Eg. gliclazide
- MOA –> stimulates insulin release from pancreas
- Side effects –> weight gain, hypoglycaemia
What drug is used first-line to treat hypertension in patients with T2DM?
ACE-inhibitors
Neuropathic pain in diabetes –> management
- Amitriptyline –> tricyclic antidepressant
- Duloxetine –> SNRI antidepressant
- Gabapentin –> anticonvulsant
- Pregabalin –> anticonvulsant
Hypothyroidism refers to insufficient thyroid hormones, what are these two thyroid hormones?
triiodothyronine (T3) and thyroxine (T4)
Primary hypothyroidism VS secondary hpyothyrodism
- Primary hypothyroidism is where the thyroid behaves abnormally and produces inadequate thyroid hormones
–> negative feedback is absent, resulting in increased production of TSH
–> TSH is raised, and T3 and T4 are low
. - Secondary hypothyroidism, also called central hypothyroidism, is where the pituitary behaves abnormally and produces inadequate TSH
–> resulting in under-stimulation of the thyroid gland and insufficient thyroid hormones
–> TSH, T3 and T4 will all be low
What acute condition should be looked out for in a patient taking carbimazole for hyperthyroidism ?
Acute pancreatitis
–> e.g. severe epigastric pain radiating to the back
A patient on carbimazole or propylthiouracil has a sore throat, what should you be worried about?
- Agranulocytosis, with a dangerously low white blood cell counts
- Agranulocytosis makes patients vulnerable to severe infections
- A sore throat is a key presenting feature of agranulocytosis
- They need an urgent full blood count and aggressive treatment of any infections
