Endocrinology Flashcards
Why does diabetes insipidus (DI) occur?
there are 2 reasons
- Lack of ADH = cranial DI
- Lack of response to ADH = nephrogenic DI
What are causes of cranial DI?
- idiopathic
- post head injury
- pituitary surgery
- craniopharyngiomas (brain tumour)
- infiltrative = histiocytosis X, sarcoidosis
- Wolfram syndrome = genetic condition where you get DI, optic atrophy, DM and deafness
- haemochromatosis
- genetic mutation in ADH gene (which is autosomal dominant inheritance)
What are causes of nephrogenic DI?
- idiopathic
- medications - especially lithium –> it desensitises the kidney’s ability to respond to ADH in collecting ducts
- genetic mutations in ADH receptor gene (X linked recessive)
- hypercalcaemia
- hypokalaemia
- kidney diseases - PCKD, sickle cell, pyelonephritis
What is presentation of DI?
Polyuria
Polydipsia
Dehydration
Postural hypotension
In children - nocturia
In infants - failure to thrive, constipation, fever
- Where is ADH made?
- Where is it secreted from?
- What is the role of ADH?
- hypothalamus
- posterior pituitary gland
- stimulates water reabsorption from the collecting ducts in the kidney
- What is primary polydipsia?
- How does this differ to diabetes insipidus?
- Patiet has normal functioning ADH system but drinks excessive amounts of water, leading to excessive urine production (polyuria)
- PP is NOT the same as DI - in DI, there is an inability to reabsorb water and concentrate urine (as either there is a lack of ADH, or a lack of response to ADH), causing polyuria
Describe the water deprivation test carried out to help diagnose DI
- Patient avoids fluids for up to 8 hours before the test (water deprivation)
- After this time, measure urine osmolality. If low - give synthetic ADH (desmopressin). (Note: if urine osmolality is high after water deprivation, DI can be ruled out)
- Measure urine osomolality for next 2-4 hours after giving desmopressin
What investigations would you do for suspected DI?
U&E (rule out renal failure)
Blood glucose (rule out DM)
Assessment of 24h urinary volume and osmolality under conditions of ad libitum (as much as they want) fluid intake.
* would see low urine osmolality
* more than 3L of urine in 24 hours collection
Serum osmolality
* would be high or normal
Water deprivation test - diagnostic for DI
Cranial MRI - to determine underlying cause of DI
water deprivation test is in another BS card
For primary polydipsia:
1. what would urine osmolality be after water deprivation?
2. is desmopressin necessary?
- high (as the patient with primary polydipsia has normal functioning of ADH - so when they are deprived of water, the urine will automatically concentrate urine, leaving a high osmolality
- not necessary - a high urine osmolality after water depriivation will rule out DI
For cranial DI:
1. what would urine osmolality be after water deprivation?
2. what would urine osmolality be after desmopressin?
- low
- high - as kidneys can still respond to ADH, they just lack ADH - so water will be reabsorbed when desmopressin is given
For nephrogenic DI:
1. what would urine osmolality be after water deprivation?
2. what would urine osmolality be after desmopressin?
- Low
- Low - as kidneys are unable to respond to the desmopressin given.
How is cranial DI managed?
- Manage underlying cause by treating it.
- desmopressin can be given
- need to monitor serum sodium - as there is a risk of hyponatraemia with desmopressin
How is nephrogenic DI managed?
- ensure access to plenty of water
- high dose desmopressin
- thiazide diuretics
- NSAIDs
- low salt/protein diet
Who does diabetic ketoacidosis occur in?
T1DM patients
DKA is usually the first presentation of child with T1DM
What are the three main features characterising DKA?
TMPaeds, z2f, PM
- Acidosis = blood pH < 7.3, plasma bicarb < 15 mmol/L
- Ketosis/ketonaemia = blood ketones above 3 mmol/L
- Hyperglycaemia = blood glucose above 11 mmol/L
Describe the pathophysiology of DKA
- Patients with T1DM can not produce insulin. Blood glucose is raised as it can not be used for metabolism or stored as patients do not have insulin to do this. The body thinks it is starving.
- This leads to a rise in other hormones - glucagon, cortisol, catecholamines and growth hormone.
- This raises blood glucose further. Also initiates breakdown of fatty acids to ketones (ketones can cross the BBB to be used as fuel by the brain). Kidneys produce bicarb to buffer ketone acids to maintain normal blood pH.
- All bicarb is used up by ketones - blood starts to become acidic because of ketones = ketoacidosis
- Hyperglycaemia overwhlems the kidneys - glucose is filtered into urine - leading to osmotic diuresis. This causes child to become polyuric and dehydrated so they become thirsty - polydipsia
- insulin normally drives potassium into cells however in T1DM, there is no insulin, so cells have low potassium, and potassium in blood is either high or is driven out through kidneys in urine - leading to a potassium inbalance
In DKA, what complications are children at risk of?
cerebral oedema
hypokalaemia
aspiration pneumonia
hypoglycaemia
How does DKA presentation and management cause cerebral odema?
- children in DKA have dehydration and hyperglycaemia
- this causes a shift in water from intracellular space of the brain to the extracellular space
- this causes brain cells to shrink and become dehydrated.
- in managing DKA, fluids and insulin are given - rapid correction of this causes water to move from extracellular space to intracellular space
- this can lead to odema in the brain - causing cell destruction and death
How does DKA present?
Patient will present with symptoms of underlying hyperglycaemia, dehydration and acidosis:
* polyuria
* polydipsia
* nausea and vomiting
* abdominal pain
* lethargy
* weight loss
* Kussmaul respiration - deep hyperventilation.
* acetone smell on breath - pear drop smell
* dehydration and hypotension
* altered conciousness
* symptoms of an underlying trigger (sepsis)
What signs may you see when examining a child with DKA?
Signs of respiratory compromise:
* Kaussmaul breathing = deep, sighing breathing
* tachypnoea
* subcostal and intercostal recessions
Signs of circulatory compromise:
* shock - tachycardia, hypotension, increased cap refill time, cool peripheries
* dehydration - dry mucous membranes, sunken eyes/fontanelles, reduced skin turgor
GI signs:
* abdo pain - can be severe
Signs of neuro compromise (usually late signs)
* reduced score on AVPU or GCS
* signs ofo cerebral odema - slow pulse, irritable, rising BP, reduced conc level
* papillodema - late sign
Other:
* ketotic breath - pear drop smell
Differentials for DKA?
- new presentation of T1DM
- Dehydration from another cause - e.g. gastroenteritis
- Sepsis
- Appendicitis, intussusception (due to abdo pain)
- Renal failure or substance ingestion causing acidosis
What investigations would you do in suspected DKA?
- bedside blood glucose and ketones - to help diagnose.
- blood gas - to look at acid-base balance and electrolyte values
- bloods - blood glucose, U+Es, FBC and creatinine - check for renal impairment
- 12 lead ECG - for any cardiac signs of hypo or hyperkalaemia
Other tests that can be done in addition to ones above:
* coeliac screen (usually presents with T1DM)
* blood cultures, urine M,C+S = check for infection trigger/sepsis
* CXR - if suspect pneumonia.
How is DKA in children managed?
- A-E assessment
- IV fluid replacement evenly over 48hrs -> this will help dehydration and dilute hyperglycaemia and the ketones.
- fixed rate insulin infusion (delayed 1-2hrs after fluids to reduce chance of cerebral odema) at dose 0.05-0.1 units/kg/hr. When blood glucose is < 14 mmol/L, start dextrose infusion.
- potassium replacement - add to IV fluids. Continue ECG monitoring to look for signs of hypo or hyperkalaemia.
- one to one nursing - for fluid balance monitoring and hourly obs with BP and GCS - to assess signs of cerebral odema, hypoglycaemia.
How is DKA resolution defined?
i.e. what should pH be? Ketones? Bicarb?
pH >7.3 and
blood ketones < 0.6 mmol/L and
bicarbonate > 15.0mmol/L
TMPaeds: Child is clinically well, drinking and tolerating food. Blood ketones are less than 1mmol/L, or pH is normal.
What are ECG features of hypokalaemia?
U waves
small or absent T waves
prolonged PR interval
ST depression
long QT
‘In Hypokalaemia, U have no Pot and no T, but a long PR and a long QT’
What is target blood glucose concentration?
In a non-diabetic: 4-5.4mmol/L when fasting.
Up to 7.8 mmol/L 2 hours after eating
How does insulin reduce blood glucose?
- causes cells to absorb glucose from the blood and use it as fuel
- causes muscles and liver cells to absorb glucose and store it as glycogen.
if no insulin is present = cells can not take up and use glucose.
How does T1DM present?
- as DKA in 1st presentation - polyuria, polydipsia, dehydration, abdo pain, Kussmaul respiration, acetone breath
- as triad of symptoms - polydipsia, polyuria and weight loss
- secondary enuresis (bedwetting in a previously dry child)
- recurrent infections
What investigations should you do once T1DM is established in a child?
- FBC, U+Es, lab glucose
- Urine dip for glucose and ketones
- fasting glucose and random glucose
- blood cultures - for suspected infection if have a feve
- HbA1c - assess blood sugar over last 3 months (not that useful)
- TFTs and TPO - test for autoimmue thyroid disease
- anti-TTG - test for associated coeliac disease
- Insulin antibodies, anti-GAD antibodies and islet cell antibodies - test antibodies associated with destruction of the pancreas and development of T1DM.
What are diagnostic criteria for T1DM?
If child is symptomatic:
* fasting glucose greater or equal to 7 mmol/L
* random glucose greater than or equal to 11.1 mmol/L
If child is asymptomatic:
need the above criteria but demonstrated on two separate occassions.
What are major differences between T1DM and T2DM?
Mention differences in:
1. age of onset
2. speed of onset
3. weight of pt
4. features
5. presence of ketonuria
What does management of T1DM involve?
- pt and family education
- subcut insulin regimes
- monitoring dietary carb intake
- monitoing blood sugar on waking, at each meal and before bed
- monitoring for and managing complications ( short term ones and long term ones)
What type of insulin is prescribed to T1DM?
Long acting insulin - given once a day
short acting insulin - injected 30 mins before meals
This is called a basal bolus regime
Alternative to basla bolus = insulin administered by an insulin pump.
see Yr3 DM BS deck on insulin types
What are advantages and disadvantages to an insulin pump?
ADV:
* better blood glucose control
* more flexibility with eating
* less injections
DISADV:
* difficult to learn how to use pump
* having it attached to you all the time
* blockage in the infusion set
* small risk of infection
How does congenital hypothyroidism present?
- from newborn blood spot screening test
If not picked up at birth…
Symptoms:
* feeding difficulties
* lethargy and increased sleeping / reduced activity
* constipation
* prolonged neonatal jaundice
* slow growth and development
Signs on examination:
* poor growth on growth chart
* macroglossia
* myxedema
* large fontanelles
* hypotonia
* bradycardia
* distended abdomen with umbilical hernia
What is pathophysiology of rickets?
- vitamin D is created from cholestrol by the skin in response to UV radiation.
- vit D is essential in calcium and phosphate absorption from intestines and the kidneys
- vit D resposible for bone turnover and promoting bone reabsorption to boot serum calcium level.
- Low vit d = low calcium and phosphate in the blood.
- low calc and phosphate = defective bone mineralisation
- also leads to secondary hyperparathyroidism, where parathyroid gland secretes PTH = stimulates reabsorption of calcium from bones
- this leads to bone mineralisation
How does rickets present?
- lethargy
- bone pain
- swollen wrists
- bone deformity - bowed legs, knock knees, rachitic rosary (swelling at costochondrial junction), craniotabes,
- poor growth
- dental problems - delayed teeth with under-developed enamel
- muscle weakness
- pathological or abnormal fractures
What is the definition of thyrotoxicosis?
teach me paeds
the clinical manifestation of excess circulating thyroid hormones caused by hyperthyroidism or other causes (e.g. increased release of stored hormones from thyroiditis, increased ingestion of thyroid hormone medication)
