PBL ILO’s Flashcards
Glucose metabolism
Glucose metabolism involves multiple processes, including glycolysis, gluconeogenesis, and glycogenolysis, and glycogenesis.
Glycolysis
Glycolysis is a series of reactions that extract energy from glucose by splitting it into two three-carbon molecules called pyruvates.
Each reaction in glycolysis is catalyzed by its own enzyme. The most important enzyme for regulation of glycolysis is phosphofructokinase, which catalyzes formation of the unstable, two-phosphate sugar molecule, fructose-1,6-bisphosphate44start superscript, 4, end superscript. Phosphofructokinase speeds up or slows down glycolysis in response to the energy needs of the cell.
Gluconeogenesis
Gluconeogenesis is the synthesis of glucose from nonsugar precursors, such as lactate, pyruvate, and the carbon skeleton of glucogenic amino acids.
Glycogenolysis
Glycogenolysis is the biochemical pathway in which glycogen breaks down into glucose-1-phosphate and glucose. The reaction takes place in the hepatocytes and the myocytes. The process is under the regulation of two key enzymes: phosphorylase kinase and glycogen phosphorylase.
Glycogenesis
Glycogenesis is the process of storing excess glucose for use by the body at a later time.
Micro vascular complications of diabetes
Microvascular complications:
• Long-term complications that affect small blood vessels.
• These typically include retinopathy, nephropathy and neuropathy.
Non proliferation retinopathy - diabetic complication
- Retinopathy
Nonproliferative retinopathy: development of microaneurysms, venous loops, retinal hemorrhages, exudates (fluid that leaks out of blood vessels into nearby tissues).
Pathophysiology
• Microaneurysms may form due to the release of vasoproliferative factors, weakness in the capillary wall or increased intra-luminal pressures.
• Microaneurysms can cause vascular permeability in the macula which can lead to macular oedema that threatens central vision.
• As capillary closure becomes extensive, intraretinal haemorrhages develop
Proliferative retinopathy- diabetic complication
Proliferative retinopathy: presence of new blood vessels, with or without vitreous hemorrhage. It is a progression of nonproliferative retinopathy.
Pathophysiology
• Develops due to retinal ischemia and release of vasoactive substances which stimulate new blood vessel formation.
• These may erupt through the surface of the retina and grow on the posterior surface of the vitreous humor -> vitrous hamorrhages which can contract and lead to retinal detachment.
• Can cause blindness.
Nephropathy- diabetic complication
- Nephropathy
Progressive deterioration in renal function resulting in end-stage renal disease, particularly glomerular sclerosis
Pathophysiology
• Increased glomerular capillary flow with urine containing high glucose levels results in increased extracellular matrix production and endothelial damage
• The vascular damage to the glomerulus causes increased permeability to macromolecules, results in proteinuria (excessive protein loss in the urine)
• Causes mesangial expansion and interstitial sclerosis which can cause glomerular sclerosis.
• Also nonaluminium renal impairment due to unresolved episodes of acute kidney injury
Tests
• ARC (albumin to creatine ratio)
• EGFR (glomerular filtration rate)
Neuropathy - diabetic complication
- Neuropathy
Heterogeneous condition associated with nerve pathology.
The condition is classified according to the nerves affected and includes focal, diffuse, sensory, motor, and autonomic neuropathy.
Pathophysiology
• Diabetes is associated with dyslipidemia, hyperglycemia, and low insulin and growth factor abnormalities.
• These abnormalities are associated with glycation of blood vessels and nerves which causes structural nerve damage including: segmental demyelination, axonal atrophy and loss, and progressive demyelination.
• These effects causes a decrease in nerve sensitisation and also affect ANS function -> neuropathy.
• In addition, autoimmunity may affect nerve structure.
• Poor blood supply and nerve damage can also lead to the formation of ulcers seen often on diabetic’s feet.
Macro vascular complications of diabetes
Macrovascular complications
• Primarily diseases of the coronary arteries, peripheral arteries and cerebrovascular.
• Early macrovascular disease is associated with atherosclerotic plaque in the vasculature supplying blood to the heart, brain, limbs and other organs.
• Late stages of macrovascular disease involve complete obstruction of these vessels, which can increase the risk of MI, stroke, claudication and gangrene.
• Peripheral ischaemia causes poor skin healing and diabetic foot ulcers
Pathophysiology
Result from hyperglycemia, excess free fatty acid and insulin resistance -> increases oxidative stress, protein kinase activation and activation of glycine end products which act on the endothelium to cause:
• Increased vasoconstriction which causes hypertension and vascular smooth muscle cell growth
• Increased inflammation
• Thrombosis, hypercoagulation and platelet activation and decreased fibrinolysis
These pathways ultimately lead to atherosclerosis and the cause of macro-vascular complications of diabetes
T1 diabetes
T1DM is a condition where the pancreas stops being able to produce adequate insulin
Without insulin, the cells of the body cannot absorb glucose from the blood as use it as fuel.
The glucose levels in the blood keep rising, causing hyperglycaemia
Genetic susceptibility to Type 1 diabetes
Genetic susceptibility
• One trigger → cold weather
○ Develops more often in winter than summer and is more common in places with cold climates.
• Another trigger → viruses
○ Possible that a virus that has only mild effects on most people triggers T1DM in others
○ Enterovirus infections have been shown to be associated with T1DM
○ Coxsackie B may also trigger it
• Early diet may also play a role
○ T1DM is less common in people who were breastfed and in those who first ate solid foods at later ages
• Researchers are learning how to predict a person’s odds of getting diabetes
○ e.g. most white people with T1DM have genes called HLA-DR3 or HLA-DR4 which are linked to an autoimmune disease
Aetiology and risk factors of Type 1 diabetes
Aetiology and risk factors
• T1DM develops when the immune system mistakenly attacks and destroys cells in the pancreas that makes insulin
• This results in a deficiency of insulin → causing excess blood glucose levels
T1DM is caused by an immune reaction. Risk factors aren’t clear, but known risk factors include:
• Family history → having a parent, brother or sister with T1DM
• Age → you can get T1DM at any age, but it usually develops in children, teens or young adults
Presenting symptoms of Type 1 diabetes
Presenting symptoms
• T1DM may present with the classic triad of symptoms of hyperglycaemia:
○ Polyuria (excessive urine)
○ Polydipsia (excessive thirst)
○ Weight loss (mainly through dehydration
○ May also present with diabetic ketoacidosis
Diabetic ketoacidosis
Diabetic ketoacidosis
• Occurs as a consequence of inadequate insulin
• Three key features are:
○ Ketoacidosis
○ Dehydration
○ Potassium imbalance
Ketoacidosis
• Liver produces ketones to use as fuel as body cannot recognise glucose
• Over time, there are high glucose and ketone levels
• Initially the kidneys produce bicarbonate to counteract the ketone acids in the blood and maintain normal Ph
• Overtime, ketone acids use up the bicarbonate and blood becomes acidic → ketoacidosis
Dehydration
• High blood glucose (hyperglycaemia) overwhelm the kidneys, glucose leaks into urine
• Glucose in urine draws out water by osmotic diuresis
• Causes increased urine production (polyuria) → severe dehydration
• Dehydration = excessive thirst (polydipsia)
Potassium imbalance
• Insulin normally drives potassium into cells
• Without insulin, potassium is not added to and stored in cells
• Serum potassium can be high/normal
• However, total body potassium is low because no potassium is stored in cells
• When treatment with insulin starts, patients can develop severe hypokalaemia (low serum potassium) very quickly, leading to fatal arrhythmias
Diagnosing DKA
Diagnosing DKA
• Diagnosis requires all three of:
○ Hyperglycaemia (e.g. blood glucose above 11 mmol/L)
○ Ketosis (e.g. blood glucose above 3 mmol/L)
○ Acidosis (e.g. pH below 7.3)
Treatment of DKA
Treatment of DKA
• Fluids - IV fluid resuscitation with normal saline (1 litre in first hour, followed by 1 litre every 2 hours)
• Insulin - fixed rate insulin infusion (e.g. Actrapid at 0.1 units/kg/hour)
• Glucose - closely monitor blood glucose and add a glucose infusion when it is less than 14 mmol/L
• Potassium - add potassium to IV fluids and monitor closely (e.g. every hour initially)
• Infection - treat underlying triggers
• Chart - chart fluid balance
• Ketones - monitor blood ketones, pH and bicarbonate
Short term complications of T1DM
Short-term complications of T1DM
• Hypoglycaemia:
○ Low blood sugar level
○ May be caused by too much insulin, not consuming enough carbohydrates or not processing carbohydrates correctly
○ Needs to be treated with rapid-acting glucose
• Hyperglycaemia:
○ High blood sugar level
○ May indicate that insulin dose needs to be increased
○ Insulin injections can take several hours to take effect and repeated doses could lead to hypoglycaemia
Long term complications of T1DM
Long term complications of T1DM
• Chronic high blood glucose levels cause damage to endothelial cells of blood vessels
• Leads to leaky, malfunctioning vessels that are unable to regenerate
• High glucose also cause immune system dysfunction and creat an optimal environment for infectious organisms to thrive
Macrovascular complications:
• Coronary artery disease
• Peripheral ischaemia
• Stroke
• Hypertension
Microvascular complications:
• Peripheral neuropathy
• Retinopathy
• Kidney disease, particularly glomerulosclerosis
Infection-related complications:
• Urinary tract infections
• Pneumonia
• Skin and soft tissue infections
• Fungal infections, particularly oral and vaginal candidiasis
Genetic susceptibility of type 2 diabetes
Type 2 diabetes has a stronger link to family history and lineage than type 1, and studies of twins have shown that genetics play a very strong role in the development of type 2 diabetes.
1) A genetic inability of the tissues to respond normally to insulin (insulin resitance) 2) A genetic inability of the insulin producing cells to secrete enough insulin to overcome the insulin resistance
Pro-diabetes factors
Obesity
Sedentary life style
Pro-diabetes medications
High carbohydrate diet
Smoking
Alcohol
Aging
Ethnicity (black African or Caribbean and South Asian)
Family history
Anti-diabetes factors
Balanced diet
Active lifestyle
Weight loss
Age of onset of type 2 diabetes
Age of onset
You can develop type 2 diabetes at any age, even during childhood.
You are more likely to develop type 2 diabetes if you are age 45 or older, have a family history of diabetes, or are overweight or have obesity.
Presenting features of type 2 diabetes
Presenting features of diabetes include:
• Tiredness • Polyuria and polydipsia (frequent urination and excessive thirst) • Unintentional weight loss • Opportunistic infections (e.g. oral thrush) • Slow wound healing • Glucose in urine (on a dipstick)
Complications of type 2 diabetes
• Infections (e.g., periodontitis, thrush and infected ulcers)
• Diabetic retinopathy
• Peripheral neuropathy
• Autonomic neuropathy
• Chronic kidney disease
• Diabetic foot
• Gastroparesis (slow emptying of the stomach)
• Hyperosmolar hyperglycaemic state
• Cardiovascular risk factors
Insulin resistance
Insulin resistance
Repeated exposure to glucose and insulin makes peripheral tissue resistant to the effects of insulin. More and more insulin is required to stimulate the cells to take up and use glucose (blood sugar).
Over time, the pancreas becomes fatigued and damaged by producing so much insulin, and the insulin output is reduced.
Chronic hyperglycaemia
Chronic hyperglycaemia
A high carbohydrate diet combined with insulin resistance and reduced pancreatic function leads to chronic high blood glucose levels (hyperglycaemia).
Chronic hyperglycaemia damages microvascular and macrovascular blood vessels which can lead to heart attack, stroke, and problems with the kidneys, eyes, gums, feet and nerves. There are also infectious complications.
Treatment of hypoglycaemia
Hypoglycaemia
• Plasma glucose of <3.0mmol/L
• If patient is conscious:
○ Administer glucose gel by mouth (e.g. GlucoGel)
○ Repeat capillary blood glucose after 10-15 minutes and if the patient is still hypoglycaemic, repeat administration of glucose gel a further 2-3 times
○ When the patient is fully alert, provide a longer-acting carbohydrate for the patient to eat (e.g. toast)
• If patient is unconscious: ○ Administer intravenous glucose (e.g. 150-160 ml of 10% glucose) ○ If the patient then regains consciousness, switch to using oral glucose as above ○ If IV access is not able to be established rapidly, administer glucagon 1mg via the intramuscular or subcutaneous route. Glucagon stimulates the conversion of stored glycogen within the liver into glucose. As a result, glucagon is ineffective in patients with depleted glycogen stores (e.g. elderly patients with poor oral intake and patients with eating disorders)
Treatment of DKA (FIGPICK)
Treatment of DKA - FIGPICK
• Fluids - IV fluid resuscitation with normal saline (1 litre in first hour, followed by 1 litre every 2 hours)
• Insulin - fixed rate insulin infusion (e.g. Actrapid at 0.1 units/kg/hour)
• Glucose - closely monitor blood glucose and add a glucose infusion when it is less than 14 mmol/L
• Potassium - add potassium to IV fluids and monitor closely (e.g. every hour initially)
• Infection - treat underlying triggers
• Chart - chart fluid balance
• Ketones - monitor blood ketones, pH and bicarbonate
Treatment of hypovolaemic shock
Treatment of hypovolaemic shock
• Fluid resuscitation
○ 500ml bolus of Hartmann’s solution or 0.9% sodium chloride (warmed if available) over 15 mins
○ Administer 250ml boluses in pts at increased risk of fluid overload (e.g. heart failure)
○ After each fluid bolus, reassess for fluid overload (JVP, auscultation of lungs)
○ Repeat administration of fluid boluses up to 4 times reassessing each time
○ Senior response if patient has negative response - increased chest crackled or pt not responding adequately to repeated boluses i.e. persistent hypotension
Hyperglycaemic hyperosmolar non-ketotic HONK coma
Hyperglycaemic hyperosmolar non-ketotic (HONK) coma
• Characterised by hyperosmolality (water loss leads to very concentrated blood), high sugar levels (hyperglycaemia) and the absence of ketones, distinguishing it from ketoacidosis • It presents with polyuria, polydipsia, weight loss, dehydration, tachycardia, hypotension and confusion • Medical emergency with high mortality. Involve experienced seniors early. Treatment is with IV fluids and careful monitoring
Hyperglycaemic hyperosmolar non-ketotic (HONK) coma treatment
Normalise osmolarity (glucose and sodium)
Replace fluids (1 litre of sodium chloride 0.9%)
Monitor and replace electrolytes (replace potassium if below 5.5mmol/L
Normalise blood glucose
Minimise risk (minimise risk of further complications such as prophylactic dose of a low molecular weight heparin to prevent venous thromboembolism
HbA1c non fasting diabetic test
Non fasting blood tests:
HbA1c:
An HbA1c test is the main blood test used to diagnose diabetes. It tests your average blood sugar levels for the last two to three months
Diabetes = HbA1c level is 48mmol/mol or above (6.5% or above)
Pre-diabetes (T2)= HbA1c level is between 42 and 48mmol/mol (5.7 to 6.4%)
Random blood glucose test for diabetic diagnosis
Random blood glucose test:
If you have severe symptoms of diabetes, you may have a random blood test at any time of the day. This is a quick test, through a finger prick or a vein in your arm.
Diabetes = blood glucose of 11.1mmol/l or more (200mg/dL or above) - regardless of how quickly you ate
Fasting blood test for diabetes diagnosis
Fasting blood tests:
Fasting blood sugar test (fasting plasma glucose FPG)
Fasting required for at least 8 hours
Diabetes = 7mmol/l or more (126mg/dL or above)
Pre-diabetes = 100 to 125 mg/dL
Oral glucose tolerance test for diabetes diagnosis
Oral Glucose Tolerance Test (OGTT):
This test is routinely done when diagnosing gestational diabetes.
The test is in two parts - a fasting glucose blood sample is taken and then a sugary drink is given. Two hours later another blood sample is taken.
If you are pregnant you have gestational diabetes if:
Fasting glucose is 5.6mmol/l or more
2 hour glucose is 7.8mmol/l or more
How to distinguish between type 1 and type 2 diabetes
Type 1 or Type 2:
If you’re diagnosed with diabetes, your provider may also run blood tests. These will check for autoantibodies that are common in type 1 diabetes. The tests help your provider decide between type 1 and type 2 diabetes when the diagnosis isn’t certain. The presence of ketones — byproducts from the breakdown of fat — in your urine also suggests type 1 diabetes, rather than type 2.
Dealing with a hypo as a diabetic patient
Dealing with Hypos
Px should be able to recognize a hypo from the following symptoms:
• Headache
• Anxiety
• Hunger
• Shaking
• Weakness or feeling faint
• Dizziness
• Sweating
• Dry mouth
Patients need to be aware to carry fast-acting sugar at all times in case they become hypoglycemic.
• Jelly Babies
• Dextrose tablets (Lucozade tablets)
• Sugar gel
If your sugar is low you may need to:
1. Take 3-6 dextrose tablets or Jelly Babies.
2. The effect of the fast-acting glucose will not last long, so take more substantial food within
½ an hour of having the dextrose tablets or Jelly Babies, such as a sandwich or toast and a
glass of milk.
3. Test your blood sugar regularly until normal.
4. You may not be able to help yourself so tell your family and friends when and how
they can help you.
Blood glucose targets for type 1 and type 2 children and adult diabetics
If you’re a child with type 1 diabetes
• when you wake up and before meals: 4 to 7mmol/l
• after meals: 5 to 9mmol/l
If you’re an adult with type 1 diabetes
• when you wake up and before meals: 5 to 7mmol/l
• before meals at other times of the day: 4 to 7mmol/l
If you have type 2 diabetes
• before meals: 4 to 7mmol/l
• two hours after meals: less than 8.5mmol/l
If you have gestational diabetes
• Fasting: below 5.3mmol/l
• One hour after meals: below 7.8mmol/l
Insulin regimens
Once Daily
• Suitable for those Type 2 diabetics taking insulin.
• Usually ultra long acting insulin with no peak of activity - mimicking the background levels in a healthy person.
Twice Daily
• Biphasic insulin taken
• In type 1 diabetes, a twice daily regimen is suitable in people who have a consistent day to day routine.
Basal Bolus/ multiple daily injection
• A basal-bolus regimen, also known as multiple daily injection therapy, involves taking a long acting or intermediate acting dose and separate injections of short or rapid acting insulin at each meal.
Insulin Pump
• Continuous subcutaneous insulin infusion (CSII), also known as insulin pump therapy, involves having an insulin pump connected to your body.
• The pump is not much larger than a mobile phone and delivers a constant feed of insulin into the body via a cannula which stays inserted into the fat under your skin. • At meal times, an increased burst (bolus) of insulin can be delivered to keep blood glucose levels under control.
Fixed dose vs flexible
These will depend on the type of insulin taken and the patient. Some patients will take a varied amount of insulin depending on the meal they have eaten. Some patients will not take a variable amount post prandial, and instead are on a fixed dose. These will be incorporated into the above regime.
Metformin:
Clinical indication
Route dose frequency
Names
Metformin
Clinical indication
Gold standard for type 2 diabetes
• No weight gain.
• Has cardiovascular-protective effects= reduces risk of MI and death
• Does not usually cause hypoglycaemia.
• Cost-effective & long-term evidence
Route dose, frequency
Needs to be taken with meals
• Starting dose is 500mg daily & needs to be titrated up gradually over a period of weeks
Metformin basic pharmacology
Basic pharmacology
Has no direct effect on the pancreas and works by:
• reducing hepatic glucose production
• inhibiting intestinal absorption of glucose
• increasing glucose utilisation by enhancing the action of insulin at peripheral receptors
• increasing glucose uptake by muscles
Metformin:
Cautions
Contraindications
Side effects
Cautions
Risk factors for lactic acidosis
• Caution in chronic stable heart failure (monitor cardiac function)
• concomitant use of drugs that can acutely impair renal function.
• avoid in conditions that can acutely worsen renal function, or cause tissue hypoxia.
• Care if eGFR < 45, avoid if < 30 ml/min/1.72m
Contra-indications
Acute metabolic acidosis including lactic acidosis + diabetic ketoacidosis
Side effects
• Commonly - GI upset- abdominal pain; including nausea, vomiting, taste disturbance, anorexia and diarrhoea.
• Lactic acidosis – rare but metformin may be a contributory factor among patients who develop an intercurrent illness that causes metformin accumulation (e.g. renal impairment), increased lactate production (e.g. sepsis, hypoxia) or reduced lactate metabolism (e.g. liver failure).
Metformin monitoring
Monitoring
• Monitor renal function- once a year in normal people, twice a year in people with risk factors for renal function deteriorations.
• Assess blood glucose control by measuring HbA1c
• In treating type 2 diabetes with a single agent, the target HbA1c is usually <48 mmol/mol. Treatment is intensified by adding a second agent if the HbA1c is >58 mmol/mol, and a new target of <53 mmol/mol is then set (balancing the risks of hyperglycaemia against the risks of treatment, particularly hypoglycaemia).
Counselling points about Metformin
Counselling
• 3 meals a day recommended – to minimise fluctuations in blood glucose levels- extreme hyper and hypoglycaemia = shown to lead to poorer long-term outcomes.
• SICK day rules
Sulfonylureas:
Names
Clinical indications
Route, dosage & frequency
Names
Sulfonylureas
• Short acting: gliclazide
• Long acting: glimepiride, glibenclamide.
Clinical indication
• First line for patients who are not overweight or in whom metformin is contra-indicated or where a rapid response to therapy is required because of hyperglycaemic symptoms
• Steroid induced hyperglycaemia
In Type 2 diabetes:
• In combination with metformin (and/or other hypoglycaemic agents) where blood glucose is not adequately controlled on a single agent.
• As a single agent to control blood glucose and reduce complications where metformin is contraindicated or not tolerated.
✓Cost effective & long-term data
✓Better than metformin at bringing blood sugars down initially especially of the patient is symptomatic.
Route, dosage, frequency
• Gliclazide: easiest to use, particularly in elderly pts with impaired renal function
• Usually started at: 40-80mg od
• Dose gradually increased will blood glucose= controlled
• Mr form available
• To be taken with meals
Sulfonylureas basic pharmacology
Basic pharmacology
Work by:
• stimulating insulin secretion by acting directly on pancreatic beta cells
• increasing tissue sensitivity to insulin
• requires residual beta cell function
Cautions, contra indications and side effects of sulfonylureas
Cautions
Can encourage weight gain; elderly; G6PD deficiency, Elderly
Contra-indications
Severe renal/hepatic impairment
Side effects
• Weight gain
• Generally well tolerated, however can cause GI disturbances.
• Liver function impairment
• Increased risk of hypoglycaemia
Monitoring of Sulfonylureas
Monitoring
• HbA1c
• Measure renal and hepatic function before treatment: determine the need for caution/contraindications
Counselling for Sulfonylureas
Counselling
Driving considerations so only have to tell the DVLA if you’re on insulin or your on oral agents and have had 2 episodes of severe hypos in 12 months were you have required someone else to treat you, or you have had a disabling hypo whilst driving, or are unable to recognise a hypo when it starts.
Examination of a thyroid gland
General inspection:
Weight- gain or loss
Behaviour- anxiety, agitation, depression
Clothing- intolerance to heat or cold
Hoarse voice- compression of larynx due to thyroid enlargement
Mobility aids- indicating muscle weakness
Prescription/ charts
Hands
• Thyroid Acropachy - similar to clubbing but caused by phalangeal bone overgrowth as result of Graves disease.
• Onycholysis - Painless detachment of nail from nailbed
• Palmar erythema - redness of the palms
• Peripheral Tremor - indicative of overactive sympathetic nervous system
• Radial rate and rhythm - Tachycardic vs Bradycardic
Face
• Dry skin
• Excessive sweating
• Eyebrow loss - loss of the outer third of the eyebrows is a rare sign
Eyes
Lid retraction
Exophthalmos (bulging of the eye)
Eye inflammation
Pain or restriction during eye movement
Lid lag
Thyroid inspection
Scars, masses or changes
Thyroid should not be visible
Further Inspection of Mass
Swallow - ask the patient to swallow some water and observe the movement of the mass.
• Thyroid gland masses will move upward with swallowing.
• Lymph nodes will not move much during swallow
• Invasive thyroid malignancy may not move with swallow
Tongue protrusion
Thyroid palpation:
Size
Symmetry
Consistency
Masses
Palpable thrill
Palpation of the lymph nodes
Tracheal deviation
Percussion of the sternum
Auscultation of the thyroid gland
Reflexes:
Knee jerk reflex
Bicep reflex
Assess for promixal myopathy
The hypothalamic pituitary adrenal axis role in cortisol release
• Cortisol is secreted by the two adrenal glands, which sit above each kidney.
• The hypothalamus controls the release of cortisol. Cortisol is released in pulses throughout the day and in response to a stressful stimulus. It is a “stress hormone”. • It has diurnal variation, meaning it is high and low at different times of the day. Typically cortisol peaks in the early morning, triggering us to wake up and get going, and is at its lowest late in the evening, prompting us to relax and fall asleep. • The hypothalamus releases corticotropin-releasing hormone (CRH). CRH stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal glands to release cortisol. • The adrenal axis is also controlled by negative feedback. Cortisol is sensed by the hypothalamus and anterior pituitary, suppressing the release of CRH and ACTH. This results in lower amounts of cortisol. This way, cortisol is closely regulated to keep it within normal limits.
Actions of cortisol within the body
○ Increases alertness
○ Inhibits the immune system – inhibits the production of several inflammatory cytokines
○ Inhibits bone formation – chronically elevated cortisol can lead to osteoporosis)
○ Raises blood glucose – stimulating gluconeogenesis (synthesis of glucose from non-carbohydrate sources)
○ Increases metabolism – promoting breakdown of proteins which can result in muscle wasting in chronic states of cortisol elevation
○ An initial surge in cortisol levels triggers lipolysis, however, chronically elevated cortisol promotes lipogenesis.
What is cushing’s syndrome
Cushing’s syndrome refers to the features of prolonged high levels of glucocorticoids in the body.
There are two groups of corticosteroid hormones:
• Glucocorticoids (e.g., cortisol)
• Mineralocorticoids (e.g., aldosterone)
Cortisol is the primary natural glucocorticoid hormone produced by the adrenal glands.
