endocrinology Flashcards
what is defined as an acute hyponatremia?
develops in less than 48 hours
what is mild, moderate and severe hyponatremia?
mild- 130-135
moderate - 125-130
severe - <125
what are the clinical symptoms of hyponatremia?
mild confusion
coma
if severe can develop pseudo bulbar palsy and spastic paraparesis
what drugs can cause hyponatraemia?
Diuretics
- thiazide diuretics (indapamide, chlorothiazide)
- combination diuretics (amiloride/hydrochlorothiazide)
- loop diuretics - furosemide
ACE inhibitors - enalapril, ramipril
Anticonvulsants - carbamazepine
Hormonal analogues - desmopressin, oxytocin
Hypnotics - temazepam
Antidepressants
- SSRIS
- MAOI - moclobemide
ecstasy
what is cushing’s syndrome?
cushng’s syndrome is used to refer to the signs and symptoms that develop after prolonged abnormal elevation of cortisol in the blood.
what is cushing’s disease?
cushing diseases refers specifically to the condition where a pituitary adenoma secretes excessive ACTH.
Cushing disease causes cushing syndrome
what are the causes of Cushing disease?
NOTE: either endogenous or exogenous causes
ACTH dependant causes
- cushing’s disease,
- ectopic ACTH production e.. small cell lung cancer - also known as paraneoplastic cushings
ACTH independent causes
- iatrogenic - steroids
- adrenal adenomas
- adrenal carcinomas
- carney complex - syndrome including cardiac myxoma
Pseudo cushing’s - mimics cushing’s but is often due to alcohol excess or severe depression - causes false positive dexamethasone suppression test or 24 hour urinary free cortisol Insulin stress test may be used to differentiate.
what are the features of cushing’s syndrome?
- muscle wasting and thin extremities
- easily bruising
- abdominal striae
- facial redness
- fractures - premature osteoporosis
- full moon shaped face, buffalo hump and central obesity
- hyperglycaemia leading to glucose intolerance or diabetes mellitus
- menstrual irregularities
- psychotic symptoms - mood changes
- poor wound healing
- increased vulnerability to infections
what are the roles of cortisol in the body?
- part of the circadian rhythm - levels peak in the morning when we need to get up and drop off in the evening
- in stress cortisol increases gluconeogenesis, increases lipolysis and increased proteolysis
- cortisol maintains blood pressure by increasing sensitivity of peripheral blood vessels to catecholamine (epinephrine and norepinephrine) - which narrow the blood vessel lumen
- cortisol dampens inflammatory and immune response by decreasing the production and release of inflammatory mediators (prostaglandins and interleukins) and inhibits T-lymphocytes
- cortisol also has a rollin the brain
what investigations do you perform for cushing syndrome?
- serum glucose
- late night salivary cortisol
- dexamethasone suppression test
- 24 hour urinary free cortisol
- ACTH plasma levels
- imagining - pituitary MRI, adrenal CT, CT of chest, abdomen and pelvis
how does the dexamethasone test work?
This involves initially giving the patient the “low dose” test. If the low dose test is normal, Cushing’s can be excluded. If the low dose test is abnormal, then a high dose test is performed to differentiate between the underlying causes.
To perform the test the patient takes a dose of dexamethasone (a synthetic glucocorticoid steroid) at night (i.e. 10pm) and their cortisol and ACTH is measured in the morning (i.e. 9am). The intention is the find out whether the dexamethasone suppresses their normal morning spike of cortisol.
Low Dose Dexamethasone Suppression Test (1mg dexamethasone) - A normal response is for the dexamethasone to suppress the release of cortisol by effecting negative feedback on the hypothalamus and pituitary. The hypothalamus responds by reducing the CRH output. The pituitary response by reducing the ACTH output. The lower CRH and ACTH levels result in a low cortisol level. When the cortisol level is not suppressed, this is the abnormal result seen in Cushing’s Syndrome.
High Dose Dexamethasone Suppression Test (8mg dexamethasone)
The high dose dexamethasone suppression test is performed after an abnormal result on the low dose test.
In Cushing’s Disease (pituitary adenoma) the pituitary still shows some response to negative feedback and 8mg of dexamethasone is enough to suppress cortisol.
Where there is an adrenal adenoma, cortisol production is independent from the pituitary. Therefore, cortisone is not suppressed however ACTH is suppressed due to negative feedback on the hypothalamus and pituitary gland.
Where there is ectopic ACTH (e.g. from a small cell lung cancer), neither cortisol or ACTH will be suppressed because the ACTH production is independent of the hypothalamus or pituitary gland.
how do you manage cushing’s disease?
first line is trans-sphenoidal removal of the pituitary adenoma
how do you manage cushing syndrome
resection of the cause
what is acromegaly?
it is the clinical manifestation of excessive growth hormone.
GH is produced by the anterior pituitary glad.
what are the causes of acromegaly?
most common cause is unregulated growth hormone secretion by a pituitary adenoma - this adenoma can be microscopic or can be a significant sized tumour that causes compression of local structures
rarely it can also be secondary to a cancer such as lung or pancreatic cancer that secretes ectopic growth hormone releasing hormone or growth hormone
what are the symptoms and signs of acromegaly?
if there is a space occupying lesion then they may develop teaches and visual field defects - bitemporal hemianopia
Overgrowth of tissues - prominent forehead and brow - frontal bossing, large nose, large tongue, large hands and feet, large protruding jaw - prognathism, arthritis from imbalanced growth of joint
GH can cause organ dysfunction - hypertrophic heart, hypertension, type 2 diabetes and colorectal cancer
they may also experience excessive sweating and oily skin - caused by sweat gland hypertrophy
what investigations would you perform fo acromegaly?
Serum insulin like growth factor 1 (IGF-1) - will be elevated
The oral glucose tolerance test is recommended to confirm the diagnosis if the IGF-1 levels are raised. If there is a lack of suppression of GH during OGTT it can confirm the diagnosis of acromegaly
MRI brain for the pituitary tumour
how do you manage acromegaly ?
trans-sphenoidal removal of the pituitary tumour
or surgical removal of cancer causing ectopic GH
There are medications that can be used to block GH
- Pegvisomant - GH antagonist give SC daily
- somatostatin analogues - block GH release
- dopamine agonists to block GH release - bromocriptine
what is hyperaldosteronism?
when there is too much aldosterone produced in the zona glomerulosa in the adrenal gland
what are the causes of hyperaldosteronism?
PRIMARY CAUSES:
where the adrenal glad itself is responsible for rise in aldosterone
- idiopathic hyperaldosteronism
- Conn’s syndrome - where an adenoma in the adrenal gland secretes too much aldosterone
- familial hyperaldosteronism - when the zona glomerulosa cells inappropriately make aldosterone in response to ACTH
- adrenal carcinoma
Secondary hyeraldosteronism - when the pathology lies outside the adrenal gland - there is excessive renin stimulating the adrenal glands to produce more aldosterone - causes of high renin are renal artery stenosis, renal artery obstruction, heart failure
how does aldosterone act on the kidneys?
Increase sodium reabsorption from the distal tubule
Increase potassium secretion from the distal tubule
Increase hydrogen secretion from the collecting ducts
what effects does hyeraldosteonism have on the body?
Lead to hypokalaemia (may present as muscle weakness, constipation and changes in heart rhythm)
leads to hypernatremia
leads to high blood volume and pressure
loss of hydrogen leads to a metabolic alkalosis
what investigations would you perform for hyperaldosteronism?
renin/aldosterone ratio
High aldosterone and low renin indicates primary hyperaldosteronism
High aldosterone and high renin indicates secondary hyperaldosteronism
BP
Serum electrolytes
Blood gas analysis - alkalosis
CT/MRI to look for adrenal tumour
renal doppler ultrasound, CT angiogram or MRA for renal artery stenosis or obstruction
how do you manage hyperaldosteonism?
treat underlying cause if possible : if they have adrenal adenoma - surgery
percutaneous renal artery angioplasty
if they have adrenocortical hyperplasia - give aldosterone antagonist - spironolactone or eplerenone or amiloride
what is adrenal insufficiency ?
where the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone.
what is primary adrenal insufficiency?
aka addisons diseases
refers to the specific condition where the adrenal glands have been damaged resulting in a reduction in the secretion of cortisol and aldosterone
most common cause is autoimmune but can also be caused by TB infection and metastatic carcinoma in the adrenal glands
what is secondary adrenal insufficiency?
Secondary Adrenal Insufficiency is a result of inadequate ACTH stimulating the adrenal glands, resulting in low cortisol release. This is the result of loss or damage to the pituitary gland. This can be due to surgery to remove a pituitary tumour, infection, loss of blood flow or radiotherapy. There is also a condition called Sheehan’s syndrome where massive blood loss during childbirth leads to pituitary gland necrosis.
what is tertiary adrenal insufficiency?
Tertiary Adrenal Insufficiency is the result of inadequate CRH release by the hypothalamus. This is usually the result of patients being on long term oral steroids (for more than 3 weeks) causing suppression of the hypothalamus. When the exogenous steroids are suddenly withdrawn the hypothalamus does not “wake up” fast enough and endogenous steroids are not adequately produced. Therefore long term steroids should be tapered slowly to allow time for the adrenal axis to regain normal function.
what are the symptoms and signs of adrenal insufficiency?
low aldosterone leads to hyperkalaemia, hyonatraemia, hypovolaemia and metabolic acidosis - causing patients to crave salty foods, nausea, vomiting, fatigue, dizziness, cramps
low cortisol - leads to low blood glucose during times of stress - makes patients weak tired and disorientated
low androgens leads to loss of armpit and pubic hair and reduced libido but only in woman because men have the testis which also produce androgens
hypotension - particularly postural hypotension
Hyprerpigmentation to the skin because ACTH stimulated melanocytes to produce melanin
why do patients usually present late on in the disease process in primary adrenal insufficiency?
because the adrenal cortex has a high functional reserve meaning that a small amount of functional tissue can secrete enough hormones to meet the needs of the body
it is only when around 90% of the tissue is destroyed will symptoms present
what investigations would you perform for adrenal insufficiency ?
U&E
- hyponatraemia
- hyperkalaemia
hypoglycaemia
ABG
- metabolic acidosis
ACTH stimulation test - give synthetic ACTH and measure cortisol and aldosterone levels 30 to 60 mins after administration
ACTH. In primary adrenal failure the ACTH level is high as the pituitary is trying very hard to stimulate the adrenal glands without any negative feedback in the absence of cortisol. In secondary adrenal failure the ACTH level is low as the reason the adrenal glands are not producing cortisol is that they are not being stimulated by ACTH.
test for adrenal autoantibodies
CT/MRI of adrenal
MRI pituitary
how do you treat adrenal insufficiency?
replacement steroids titrated to signs, symptoms and electrolytes
- hydrocortisone is a glucocorticoid used to replace cortisol
- Fludrocortisone is a mineralocorticoid hormone and is used to replace aldosterone
doses are doubled during acute illness until they have recovered
what is adrenal crisis ?
aka addison ian crisis
acute presentation of severe addisons - where the absence of steroid hormones leads to a life threatening presentation
how does adrenal crisis present?
sudden pain in back abdomen or legs
severe vomiting and diarrhoea which leads to dehydration
low BP which leads to loss of consciousness
what can trigger addison ian crisis?
major stress
injury/trauma
surgery
infection/sepsis
adrenal haemorrhage e.g. waterhouse friderichsen syndrome - sudden rise in BP causes blood vessels in adrenal cortex to rupture - fills up adrenal cortex with blood and leads to tissue ischaemia and adrenal gland failure - fulminant meningococcemia
how do you manage adrenal crisis?
Do not wait to perform investigations and establish a definitive diagnosis before treating someone with suspected Addisonian Crisis as this is life threatening and they need immediate treatment.
Hydrocortisone 100mg IM or IV stat then 100mg every 6 hours until patient is stable - no fludrocortisone is required because high cortisol exerts a weak mineralocorticoid action
IV fluid resuscitation
correct hypoglycaemia
careful monitoring of electrolytes and fluid balance
what is diabetes insupidus?
Diabetes insipidus is a lack of antidiuretic hormone (ADH) or a lack of response to ADH. This prevents the kidneys from being able to concentrate the urine leading to polyuria (excessive amounts of urine) and polydipsia (excessive thirst).
how can diabetes insipidus be classified?
Nephrogenic diabetes insipidus - where the collecting ducts of the kidneys do not respond to ADH
cranial diabetes Insupidus is when the hypothalamus does not produce enough ADH for the pituitary gland to secrete
what are the causes of Nephrogenic Diabetes Insipidus?
Drugs, particularly lithium used in bipolar affective disorder
Mutations in the AVPR2 gene on the X chromosome that codes for the ADH receptor
Intrinsic kidney disease
Electrolyte disturbance (hypokalaemia and hypercalcaemia)
what are the causes of Cranial Diabetes Insipidus
can be idiopathic Brain tumours - craniopharygngiomas Head injury Brain malformations Brain infections (meningitis, encephalitis and tuberculosis) Brain surgery or radiotherapy haemochromatosis
DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram’s syndrome)
what is the presentation of diabetes insipidus?
Polyuria (excessive urine production) Polydipsia (excessive thirst) Dehydration Postural hypotension Hypernatraemia
what investigations would you perform for diabetes insipidus?
high plasma osmolality, low urine osmolality
a urine osmolality of >700 mOsm/kg excludes diabetes insipidus
water deprivation test
what do the results of a water deprivation test show in diabetes insipidus?
Initially the patient should avoid taking in any fluids for 8 hours. This is referred to as fluid deprivation. Then, urine osmolality is measured and synthetic ADH (desmopressin) is administered. 8 hours later urine osmolality is measured again.
In cranial diabetes insipidus the patient lacks ADH. The kidneys are still capable of responding to ADH. Therefore initially the urine osmolality remains low as it continues to be diluted by excessive water secretion in the kidneys. Then when synthetic ADH is given the kidneys respond by reabsorbing water and concentrating the urine so the urine osmolality will be high.
In nephrogenic diabetes insipidus the patient is unable to respond to ADH. They are diluting their urine with the excessive water secretion by the kidneys. Therefore the urine osmolality will be low initially and remain low even after the synthetic ADH is given.
In primary polydipsia the 8 hours of water deprivation will cause the urine osmolality to be high even before the synthetic ADH is given. A high urine osmolality after 8 hours of water deprivation indicates no diabetes insipidus. - Primary polydipsia is when the patient has a normally functioning ADH system but they are drinking excessive quantities of water leading to excessive urine production. They don’t have diabetes insipidus.
how do you manage diabetes insipidus?
nephrogenic diabetes insipidus: thiazides, low salt/protein diet (Desmopressin can be used in high doses but with careful monitoring)
central diabetes insipidus can be treated with desmopressin
what is SIADH?
Anti-diurectic hormone (ADH) is produced in the hypothalamus and secreted by the posterior pituitary gland. It is also known as “vasopressin”. ADH stimulates water reabsorption from the collecting ducts in the kidneys. SIADH is a condition where there is inappropriately large amounts of ADH.
This may be the result of the posterior pituitary secreting too much ADH or the ADH may be coming from somewhere else, for example a small cell lung cancer.
The excessive ADH results in excessive water reabsorption in the collecting ducts. This water dilutes the sodium in the blood so you end up with a low sodium concentration (hyponatraemia). The excessive water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a “euvolaemic hyponatraemia”. The urine becomes more concentrated as less water is excreted by the kidneys therefore patients with SIADH have a “high urine osmolality” and “high urine sodium”.
what are the symptoms of SIADH?
symptoms are similar to those of dehydration - headaches, nausea, muscle cramps and tremors
as sodium continues to decrease it can cause cerebral oedema leading to confusion, mood swings, hallucinations, seizures and coma
what are the causes of SIADH?
malignancy - small cell lung cancer, also pancreas an prostate
neurological - stoke, SAH, SDH, meningitis/encephalitis/anscess
Infections - TB, pneumonia
Drugs - sulfonylureas, SSRIs, tricyclics, carbamazepine, vincristine, cyclophosphamide
head injury
post operative from major surgery
when you suspect SIADH what other causes of hyponatraemia should be excluded?
Negative short synacthen test to exclude adrenal insufficiency
No history of diuretic use
No diarrhoea, vomiting, burns, fistula or excessive sweating
No excessive water intake
No chronic kidney disease or acute kidney injury
how do you diagnose SIADH?
In a way, SIADH is a diagnosis of exclusion as we do not have a reliable test to directly measure ADH activity. Clinical examination will show euvolaemia. U+Es will show a hyponatraemia. Urine sodium and osmolality will be high.
how do you manage SIADH?
the aim is to establish and treat the cause of SIADH
it is essential to correct the sodium slowly to prevent central pontine myelinolysis - aim for a change in sodium of less than 10mmol/l er 24 hours.
fluid restriction - restrict fluid intake to 500mls - 1 litre.
Tolvaptan - vaptans are ADH receptor blockers - they are very powerful and can cause rapid increase in sodium - therefore they are usually initiated by specialist endocrinologist and require close monitoring
Demeclocycline is a tetracycline antibiotic that inhibits ADH. It was used prior to the development of vaptans and is now rarely used for this purpose.
what is central pontine myelinolysis?
also known as osmotic demyelination syndrome.
It is a complication of long term severe hyponatraemia being treated to quickly
As blood sodium level falls water will move by osmosis across the blood-brain barrier into the cells of the brain from the area of low concentration of solutes (the blood) to the area of high concentration of solutes (the brain). This causes the brain to swell. The brain adapts to this by reducing the solutes in the brain cells so that water is balanced across the blood-brain barrier and the brain does not become oedematous. This adaptation takes a few days. Therefore, if the hyponatraemia has been present and severe for a long time the brain cells will also have a low osmolality. This is not a problem until the blood sodium levels rapidly rise. When this happens water will rapidly shift out of the brain cells and into the blood. This causes two phases of symptoms:
First phase: this is due to the electrolyte imbalance and the patient presents as encephalopathic and confused. They may have a headache or nausea and vomiting. These symptoms often resolve prior to the onset of the second phase.
Second phase: this is due to the demyelination of the neurones, particularly in the pons. This occurs a few days after the rapid correction of sodium. This may present as spastic quadriparesis, pseudobulbar palsy and cognitive and behavioural changes. There is a significant risk of death.
Prevention is essential as treatment is only supportive once CPM occurs. A proportion of patients make a clinical improvement but most are left with some neurological deficit.
where is parathyroid hormone secreted and what causes it to be excreted?
There are four parathyroid glands situated in four corners of the thyroid gland. The parathyroid glands, specifically the chief cells in the glands, produce parathyroid hormone in response to hypocalcaemia (low blood calcium).
how does parathyroid hormone act to increase blood calcium levels?
Increasing osteoclast activity in bones (reabsorbing calcium from bones)
Increasing calcium absorption from the gut
Increasing calcium absorption from the kidneys
Increasing vitamin D activity
Vitamin D acts to increase calcium absorption from the intestines. Parathyroid hormone acts on vitamin D to convert it into active forms. So vitamin D and parathyroid hormone act together to raise blood calcium levels.
what is primary hyperparathyroidism?
Primary hyperparathyroidism is caused by uncontrolled parathyroid hormone produced directly by a tumour of the parathyroid glands. This leads hypercalcaemia: an abnormally high level of calcium in the blood. This is treated by surgically removing the tumour.
what is secondary hyperparathyroidism?
This is where insufficient vitamin D or chronic renal failure leads to low absorption of calcium from the intestines, kidneys and bones. This causes hypocalcaemia: a low level of calcium in the blood.
The parathyroid glands reacts to the low serum calcium by excreting more parathyroid hormone. Over time the total number of cells in the parathyroid glands increase as they respond to the increased need to produce parathyroid hormone. This is called hyperplasia. The glands become more bulky. The serum calcium level will be low or normal but the parathyroid hormone will be high. This is treated by correcting the vitamin D deficiency or performing a renal transplant to treat renal failure.
what is tertiary hyperparathyroidism?
This happen when secondary hyperparathyroidism continues for a long period of time. It leads to hyperplasia of the glands. The baseline level of parathyroid hormone increases dramatically. Then when the cause of the secondary hyperparathyroidism is treated the parathyroid hormone level remains inappropriately high. This high level of parathyroid hormone in the absence of the previous pathology leads to high absorption of calcium in the intestines, kidneys and bones and causes hypercalcaemia. This is treated by surgically removing part of the parathyroid tissue to return the parathyroid hormone to an appropriate level.
what is the hormonal profile and clinical features in primary hyperarathyroidism?
PTH (Elevated)
Ca2+ (Elevated)
Phosphate (Low)
Urine calcium : creatinine clearance ratio > 0.01
May be asymptomatic if mild
“bones, stones, abdominal groans and psychic moans’
Recurrent abdominal pain (pancreatitis, renal colic)
Changes to emotional or cognitive state
what is the hormonal profile and clinical features in secondary hyperarathyroidism?
PTH (Elevated)
Ca2+ (Low or normal)
Phosphate (Elevated)
Vitamin D levels (Low)
May have few symptoms
Eventually may develop bone disease, osteitis fibrosa cystica and soft tissue calcifications
what is the hormonal profile and clinical features in tertiary hyperarathyroidism?
Ca2+ (Normal or high) PTH (Elevated) Phosphate levels (Decreased or Normal) Vitamin D (Normal or decreased) Alkaline phosphatase (Elevated)
Metastatic calcification
Bone pain and / or fracture
Nephrolithiasis
Pancreatitis
what differential diagnosis should you consider for hyperparathyroidism?
It is important to consider the rare but relatively benign condition of benign familial hypocalciuric hypercalcaemia, caused by an autosomal dominant genetic disorder. Diagnosis is usually made by genetic testing and concordant biochemistry (urine calcium : creatinine clearance ratio <0.01-distinguished from primary hyperparathyroidism).
what are the causes of primary hyerparathyroidism?
80%: solitary adenoma
15%: hyperplasia
4%: multiple adenoma
1%: carcinoma
what is hypoparathyroidism?
Primary hypoparathyroidism decrease PTH secretion e.g. secondary to thyroid surgery* low calcium, high phosphate treated with alfacalcidol
what are the symptoms is hypoparathyroidism?
The main symptoms of hypoparathyroidism are secondary to hypocalcaemia:
tetany: muscle twitching, cramping and spasm
perioral paraesthesia
Trousseau’s sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
Chvostek’s sign: tapping over parotid causes facial muscles to twitch
if chronic: depression, cataracts
ECG: prolonged QT interval
what is pseudohypoparathyroidism?
target cells being insensitive to PTH
due to abnormality in a G protein
associated with low IQ, short stature, shortened 4th and 5th metacarpals
low calcium, high phosphate, high PTH
diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.
what is the ideal blood glucose concetration?
4.4-6.1 mmol/l
how does insulin reduce blood sugar?
it causes cells in the body to absorb glucose from the blood and use it as a fuel and it causes muscle and liver cells to absorb glucose from the blood and store it as glycogen
when is ketogenesis?
Ketogenesis occurs when there is insufficient glucose supply and glycogens stores are exhausted, such as 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 as fuel. Producing ketones is normal and not harmful in healthy patients when under fasting conditions or on very low carbohydrate, high fat diets. Ketones levels can be measured in the urine by “dip-stick” and in the blood using a ketone meter. People in ketosis have a characteristic acetone smell to their breath.
Ketone acids (ketones) are buffered in normal patients so the blood does not become acidotic. When underlying pathology (i.e. type 1 diabetes) causes extreme hyperglycaemic ketosis this results in a metabolic acidosis that is life threatening. This is called diabetic ketoacidosis.
what happens in ketoacidosis?
the cells in the body have no fuel and think that they are starving so they initiate the process of ketogenesis so they have a usable fuel. Over time the patiet gets higher and higher glucose and ketone levels. Initially the kidneys produce bicarbonate to counteract the ketone acids i the blood and maintin normal pH. Over time the ketone acids use up the bicarbonate and the blood starts to become more acidic.
whatt are the main problems if DKA?
ketoacidosis, dehydration and potassium imbalance
what causes dehydration in DKA?
Hyperglycaemia overwhelms the kidneys and glucose starts being filtered into the urine. The glucose in the urine draws water out with it in a process called osmotic diuresis. This causes the patient to urinate a lot (polyuria). This results in severe dehydration. The dehydration stimulates the thirst centre to tell the patient to drink lots of water. This excessive thirst is called polydipsia.
what causes potassium imbalance in DKA?
Insulin normally drives potassium into cells. Without insulin potassium is not added to and stored in cells. Serum potassium can be high or normal as the kidneys continue to 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 treatment with insulin starts patients can develop severe hypokalaemia (low serum potassium) very quickly and this can lead to fatal arrhythmias.
how does DKA present?
- polyuria
- polydipsia
- nausea and vomiting
- acetone smell to their breath
- dehydration and subsequent hypotension
- altered consciousness
- they may have symptoms of and underlying trigger (i.e. sepsis)
how do you diagnose DKA?
Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
Ketosis (i.e. blood ketones > 3 mmol/l)
Acidosis (i.e. pH < 7.3)
how do you manage DKA?
The most dangerous aspects of DKA are dehydration, potassium imbalance and acidosis. These are what will kill the patient. Therefore the priority is fluid resuscitation to correct the dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to get the cells to start taking up and using glucose and stop producing ketones.
FIG PICK
F – Fluids – IV fluid resuscitation with normal saline (e.g. 1 litre stat, then 4 litres with added potassium over the next 12 hours)
I – Insulin – Add an insulin infusion (e.g. Actrapid at 0.1 Unit/kg/hour)
G – Glucose – Closely monitor blood glucose and add a dextrose infusion if below a certain level (e.g. 14 mmol/l)
P – Potassium – Closely monitor serum potassium (e.g. 4 hourly) and correct as required
I – Infection – Treat underlying triggers such as infection
C – Chart fluid balance
K – Ketones – Monitor blood ketones (or bicarbonate if ketone monitoring is unavailable)
**Remember as a general rule potassium should not be infused at a rate of more than 10 mmol per hour.
what are the short term complications relate to insulinn and blood glucose management?
Hypoglycaaemia - tremor, sweating, irritability, dizziness and pallor, more severe hypoglycaemia will lead to reduced consciousnness, coma and death if left untreated.
treating hypos - give rapid acting glucose e.g. lucozade and a slower acting carb such as biscuits and toast for when rapid acting glucose is used up
for severe hypos give IV detrose and IM glucagon
Hyperglycaema - they may need their insulin dose to be increased
what are the long term complications of diabetes?
chronic exposure to hyperglycaemia causes damage to the endothelial cells of blood vessles - this leads to leaky, malfunctioing vessels that are unable to regenerate. High levels of sugar in the blood also causes supression of the immune system and provides optimal eniviroment for infectious organisms to thrive
Macrovascular complications - coronary artery disease, peripheral ischaemia - diabetic foot, strokes, hypertension
Microvascular complications - peripheral neuropathy, retinopathy, kidney disease particularly glomerulosclerosis
Infection related complications
UTI, pneumonia, skin and soft tissue infections particularly in the feet, fungal infections particularly oral and vagial candidiasis.
how is diabetes moitered ?
HbA1c - glycated haemoglobin - average glucose over the last 3 months
capilary blood glucose
what can trigger the onset diabetes?
it may be triggered by certain viruses such as the coxsackie B virus and enterovirus
how does diabetes present?
some people will present in DKA the remaining of the patients present with the classic triad of symptoms of hyperglycaemia: - polyuria - polydipsia - weight loss
with a new diagnosis of diabetes what investigations h
when a new diagnosis is established the following bloods should be taken to exclude other associated pathology and get a baseling of the patients health:
- baseline bloods including FBC, renal profile and glucose
- blood cultures if there is a fever
-HbA1c
- TFT and TPO to test for associated autoimmune thyroid disease
antie TTG antibodies to test for associated coeliac disease
- insulin antibodies, anti GAD antibodies and islet cell antibodies to test for antibodies associated with the destruction of the pancreas and the development of type one diabetes
what can happen if insulin is injected in the same site repeatedly ?
lipodystrophy
what are the basal bolus regimes?
inslin regimes are initiated by a specialist in diabtes - patients are usally initiated on a basal bolus regime
the basal part refers to an injection of a long acting insulin such as lantus - typically in the evening - this gives a constant background insulin throughout the day
The bolus part refers to an injection of a short acting insulin such as actrapid usually three times a day before meals - this is also injected according to the number of carbohyrdrates consumed every time the patient has a snack
what are insulin pumps?
they are small devices that continuously infuse insulin at different rates to control blood sugar levels
not everybody qualifies to have these on the NHS - local criteria may vary
what are the four main ways of checking blood glucose?
a finger prick bedside glucose monitor
a one off blood glucose - fasted or non fasted
HbA1c
glucose tolerance test
what is the diagnostic criteria for diabetes?
fasting glucose greater than or equal to 7.0mmol/l
random glucose greater than or equal to 11.1 mmol/l
WHO also states that a HbA1c greater or equal to 6.5% is diagnostic of DM
for the above if the patient is asymptomatic the test must be repeated to confirm the diagnosis
what is classified as pre diabetes?
HbA1c 42-47 mmol/mol (6-6.4%)
fasting glucose 6.1-6.9 mmol/l
what are the main drugs used in the treatment of DM?
insulin metformin sufonylureas (glicazide and glimepiride) thiazolidinediones (pioglitazone) DPP-4 inhibitors (-gliptins) - vildagliptin, sitagliptin SGLT-2 inhibitors GLP-1 agonists (-tides) - exenatide
what are the main side effects of insulin?
hypoglycaemia
weight gain
Lipodystrophy
how does metformin work and what are the main side effects?
increases insulin sensitivity and decreases hepatic gluconeogenesis
SE:
GI upset
Lactic acidosis - common in exams but in real life not that common
can not be used in patients with an eGFR less than 30
what are the main side effects of sulfonylureas and how do they work??
they stmulate the pacreatic beta cells to secrete insulin
the main side effects are hyppoglycaemia
weight gain
hyponatraemia
what are the main side effects of thiazolidinediones and how do they work??
they activate the PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid utake
side effects
weight gain and fluid retention
what are the main side effects of gliptins and how do they work??
increase the incretin levels which inhibit glucagon secretion
they do not cause weight gain
side effects
- generally well tolerated but increase the risk of pancreatitits
what are the main side effects of SGLT-2 inhibotors (-gliflozins) and how do they work??
inhibits reabsorption of glucose in the kidney
SE:
UTI
what are the main side effects of GLP-1 agonists (-tides) and how do they work??
they increase insulin secretion and inhibit glucagon secretion - they are good becasue the result in weight loss
SE:
nausea and vomiting
pancreatitis
what conditions mean that HbA1c may not be used for diagnosis of diabetes?
the following conditions can cause increased red cell turnover which can cause misleading HbA1c results
- haemoglobinopathies
- haemolytic anaemia
- untreated iron deficiency anaemia
- suspected gestational diabetes
- children
- HIV
- CKD
- people taking medication whcih may cause hyperglycaemia e.g. corticosteroids
what is the aim for HbA1c for a patient who is on metformin?
you should aim for HbA1c of 48mmol/mol (6.5%) but should only add a second drug if the HbA1c rises to 58mmol/mol (7.5%)
what dietary advice do you give to a type 2 diabetic?
encourage high fibre, low glycaemic index sources of carbs
include low-fat diary products and oily fish
control the intake of foods containing saturated fats and trans fatty acids
limited substitution of sucrose-containing foods for other carbs is allowable, but care should be taken to avoid excess energy intake
