endo middle tier Flashcards
types of diabetes insipidus
cranial diabetes insipidus
nephrogenic diabetes insipidus
cranial - lack of vasopressin produced
nephrogenic - enough vasopressin is produced but resistance to vasopressin action
symptoms for diabetes insipidus
both cranial and nephrogenic!
Similar appearance to diabetes mellitus (or primary polydipsia - has polydipsia and polyuria)
- Polyuria 3L+/day
- Polydipsia
- Dehydration
- Low BP
- Lethargy, weakness
Distinct from diabetes mellitus
- No glycosuria (sweet wee with sugar)
- No elevated blood glucose levels
diabetes insipidus osmolality
=high serum osmolality and low urine osmolality
lots of water lost and not reabsorbed in kidneys (no vasopressin action)
diabetes insipidus diagnosis
1) to tell it is diabetes insipiud
2) to distinguish between cranial and nephrogenic diabetes insipidus
1) - Measure urine output - to confirm polyuria
- To distinguish it from DM, do plasma and urine glucose levels (no glycosuria/ elevated blood levels)
- Hyponatremia - due to water loss
- MRI hypothalamus - looking for masses
- Water deprivation test
- – 8h fasting with no fluids
- – Measure urine and serum osmolality hourly
- – Normal response: serum osmolality remains same and urine osmolality increases. Kidneys can concentrate urine.
- – DI: serum osmolality rises, urine unable to be concentrated- remains low osmolality. Kidneys still produce dilute urine, despite dehydration.
2) Desmopressin given
No response over few hours = nephrogenic
Good response over few hours = cranial
causes of cranial diabetes insipidus
Acquired
- idiopathic
- Tumours (rare)- metastases, posterior pituitary
- Trauma
- Infections (TB, encephalitis, meningitis)
- Vascular (sickle cell, infection)
- Inflammation
- Sarcoidosis
Genetic (rare)
- Defect in ADH gene
cranial diabetes management
Treat underlying condition (eg surgery for tumour, treat infection)
Give desmopressin (tablets, nasal spray, injection) -- V2 receptor analogue (fits it, stimulates the action of vasopressin- that is not produced enough here)
Thiazide diureticsmild hypovolemia → kidneys will take up more Na+ and water in proximal tubule
causes of nephrogenic diabetes insipidus
Acquired
- Reduction in medullary concentrating gradient
- – Hypokalaemia
- – Hypercalcaemia
- – Meant to be low NaCl and Ca in blood so more moves back to blood from urine. Meant to be high K in blood so more can be used in the Na/K pumps.
- Antagonism to vasopressin effects
- – Drugs (precipitating drugs? -Lithium chloride, gilbenclamide
- – Renal impairment eg renal tubular acidosis
- – Post obstructive uropathy
- – Prolonged polyuria
Genetic (rare)
- Sickle cell
- Mutation of ADH receptor
nephrogenic diabetes insipidus management
Difficult to treat
Access to water, to rehydrate
Give high dose desmopressin (tablets, nasal spray, injection) (V2 receptor analogue (fits it, stimulates the action of vasopressin))
Thiazide diuretics → mild hypovolemia → kidneys will take up more Na+ and water in proximal tubule
NSAIDs → lower urine volume and plasma Na as it inhibits prostaglandin synthase - and prostaglandins inhibit ADH action so it prevents that
SIADH pathophysiology
too much vasopressin, inappropriate release (despite very dilute plasma)
Increased insertion of aquaporin 2 channels in the apical membrane of the collecting duct
(opposite to cranial diabetes insipidus)
SIADH osmolality
low (lots of water)
is SIADH hypo/eu/hypervolemic
retention of water –> intracellular volume increases (cells swell) but EUvolemic
- as volume rises, aldosterone is suppressed and ANP is released which increases renal excretion, so ps volume normal
SIADH causes
- Head injury/ haemorrhage , subdural hematoma
- Tumour (eg lung, prostate, pancreas, thymus, lymphoma, CNS)
- Meningitis
- Thrombosis
- Lupus
- Pulmonary lesions (TB, pneumonia, asthma, CF, lung abscess)
- Alcohol withdrawal
- Drugs: (SSRIs, sulfonylurea (DMT2) , cyclophosphamide (immunosuppressant), carbamazepine (anti-convulsant), some chemo )
SIADH signs and symptoms
why do u/ why do u not get oedema
- concentrated urine
- due to brain cell swelling:
- – reduction in GCS
- – fits, coma, confusion, drowsy, irritable
- Weakness
- Aches
- Anorexia, Nausea
- Malaise
NO !! Oedema !! – oedema is ECF increase whereas SIADH is euvolemic, only the intracellular fluid increases
SIADH investigations
- Low serum Na+, high urine Na+
- Low plasma osmolality, high urine osmolality
- Euvolaemia
- Need to distinguish between frail elderly patients’ hyponatraemia from salt and water depletion
- – Give 1-2L of 0.9%saline
- – If sodium depleted, will respond well as will fill in their defecit
- – SIADH will have no response, as the Na will be excreted in order to balance the low osmolality
No hypokalemia (low aldosterone! aldosterone ), No hypotension, no hypovolemia Normal adrenal, renal, thyroid function
SIADH treatment
Treat underlying condition (eg stop causative drug)
Increase Na in serum (hospital visits)
Restrict fluids (used for general low Na)
- 500-1000mL /day
- This will increase Na+ concentration (less fluid excess so less excretion including Na excretion)
Vasopressin antagonist = tolvaptan (oral)
Blocks V2 receptor
Promotes water excretion (less absorbed), without affecting electrolytes
Demeclocycline
Inhibits the action of ADH on the kidneys - resistant to its action – induces nephrogenic DI
If severe and you are worried about circulatory overload – loop diuetic = furosemide
tolvaptan vs desmopressin vs demeclocyclin
desmopressin = V2 receptor analogue - stimulates action of vasopressin (Agonist)
- promotes water reabsorption
- diabetes insipidus treatment
tolvaptan = vasopresssin antagonist - blocks V2 receptors
- promotes water excretion, does not affect electrolytes
- SIADH treatment
demeclocycline = vasopressin inhibitor at kidneys
- induces nephrogenic DI
- SIADH treatment
is hyponatraemia common?
salt deficiency or water excess?
yes
either- more commonly water excess
hyponatraemia symptoms
mild
severe
can be asymptomatic
Mild (often chronic)
- Headache
- nausea/ vomiting
- Irritable
- confusion/ disorientation/ mental slowing
- Unstable gait
- oedema?
Severe (often acute- eg marathon)
- due to brain swelling (cerebral oedema) due to low osmolality. Then it adjusts to less swollen but often appears shrunk (chronic look)
- coma/ stupor
- Convulsions
- Respiratory arrest
hyponatraemia causes/ treatment
find out underlying cause
find out serum volume levels (hypo /eu/ hypervolemic) - treatment depends on this!
find out serum and urine osmolality
is asymptomatic= fluid restriction
hypovolemic = saline replacement
- bleeding
- burns
- pancreatitis
- vom/diar
euvolemic = fluid restrict
- SIADH
hypervolemic = fluid restrict
- liver failure
addisons =
pathophysiology
autoimmune adrenalitis - loss of adrenal cortex
may also be caused by TB (commonest cause worldwide)
so primary adrenal insufficiency . this results in deficiciency of mineralocorticoid (aldosterone), glucocorticoid (coirtisol) and sex steroid (androgens, sex hormone precursors)
as a result there is no negative feedback on the anterior pituitary and hypothalamus so high levels of CRH and ACTH
addisons
- gender
- how common
- female
- very rare
addisons causes
- autoimmune adrenalitis = HIC
- TB = LIC (commonest cause worldwide)
- adrenal metastases
- long term steroid use
- oppertunistic HIV infection
- adrenal haemorrhage/infarction
secondary adrenal insufficiency
pathophysiology
causes
lack of cortisol due to lack of ACTH
so cortisol levels are low , as well as ACTH
(but mineralocorticoid (aldosterone) and sex steroid (androgens, sex hormone precursors) are NOT lower!)
- hypopituitarism
tumour
radiation
withdrawal from high dose steroid treatment (most common cause)
tertiary adrenal insufficiency
lack of CRH (hypothalamus) so suppression of HPA axis (hypothalamo- pituitary -adrenal)
due to withdrawal from high dose steroid treatment (most common cause)
effect of high ACTH and when is this seen
addisons (lack of cortisol negative feedback)
causes skin pigmentation - bronzing (alpha melanocortin)
addisons signs and symptoms
- Skin pigmentation, bronzing
- Vitiligo (white patches and loss of body hair due to loss of androgens)
- Lean
- hypotension/ Postural hypotension (Due to loss of aldosterone → hypovolaemia)
- Dehydrated (Loss of Na+ due to loss of aldosterone, which also causes high K+ (less renal excretion))
- Tachycardia -To compensate for low BP and low volume
- Lethargy, depression, low mood and self esteem
- Dizzy
- Anorexia, weight loss
- Nausea /vomiting / diarrhea/ constipation /abdominal pain
- hypogonadal (Amenorrhea
Impotence, loss of libido )
secondary adrenal insufficiency symptoms
No pigmentation (low ACTH) Malaise may have similar things to addisons (no gonadal symptoms though, and not dehydrated/ hypertension as adolsterone unaffected)
investigations into adrenal insufficiency
Bloods
- Low Na
- High K
- Hypoglycemia - due to low cortisol
- Hypoaldosteronism (aldosterone)
- Low cortisol
- Uraemia (high urea)
- Raised Ca2+ (due to low volume)
- Anaemia (low volume)
- Eosinophilia - high wbc as cortisol inhibits - anti-inflam
- ACTH levels - high in addisons, low in secondary
- Mineralocorticoid level- low in addisons, normal in secondary
Short ACTH test = Synacthen test
- Measure plasma cortisol
- Give synACTHen (ACTH analogue = tetracosactide)
- Measure plasma cortisol (30m)
- Addisons: cortisol should be low- not raised by the stimulant
- Secondary : cortisol rises
Adrenal antibodies - 21 hydroxylase antibody – high levels
Abdom/CXR
Looking for upper zone fibrosis or adrenal calcification → TB!
addisons managment
Immediate:
- IV hydrocortisone
- IV saline
- Glucose if hypoglycaemic
Later:
- Steroids 3x a day - mimic circadian rhythm - glucocorticoids (hydrocortisone), AND mineralocorticoids (fludrocortisone)
- Warn against abrupt steroid cessation
- Steroid card/ bracelet given
- steroid sick day rules: Mimic what the body would do. DOUBLE dose when infection/trauma/surgery and Increase dose in pregnancy/ before strenuous activity
Adrenal crisis (nausea, abdominal pain, muscle cramps, confusion) - IV hydrocortisone
secondary adrenal insufficiency treatment
If cause is long term steroid withdrawal:
Adrenals will recover eventually
Oral hydrocortisone
adrenal crisis
symtpoms
treatment
nausea,
abdominal pain,
muscle cramps,
Confusion
IV hydrocortisone
hyperkalemia causes
Renal impairment
- Acute kidney injury
Drugs:
- Potassium sparing diuretic - spironolactone (common)
- ACE i (decreases aldosterone so decreases K+ excretion) - (common)
- NSAIDs - (common)
- Heparin
T1DM
Redistribution of K+
- Intracellular → extracellular
- Diabetic ketoacidosis
- Metabolic acidosis
- Tissue necrosis/lysis
- – Severe burns
- – Rhabdomyolysis (death of muscle fibres by traumatic crush injury, releasing K+ into blood stream)
- –Tumour lysis syndrome
Addison’s
Increased load
- Blood transfusion
artefactually high K+ result
- Could be due to haemolysis (vigorous venepuncutre, abnormal rbc)
- FBC bottle anticoagulant contamination with k+
- Thrombocythaemia (increased platelets) - k+ leaks out during clotting
- potassium spikes after vigorous exercise
recheck if you get high K+
hyperkalemia pathophysiology
- Impaired neuromuscular transmission
- Reduced difference between electrical potential of cardiac myocytes and outside of cells.
- Threshold for action potentials is decreased, so more abnormal action potentials
- – Abnromal heart rhythyms
- – Muscle weakness,paralysis
hyperkalemia investigations
Blood test- serum potassium
- recheck if unusual
- > 5.5 = hyperk
- > 6.5 = emergency
ECG-
- tall tented T waves
- Widened QRS
- Prolonged PR interval
- Reduced P wave
- Fast, irregular pulse
hyperkalemia symptoms
- Not many
- Impaired neuromuscular transmission: Muscle weakness and paralysis
- Fatigue
- Light headed
- Chest pain, heart racing, palpitations
hyperkalemia treatment - if urgent
IV calcium gluconate – reduces excitability of cardiomyocytes
Drive k+ into cells
- Soluble insulin - IV actrapid (glucose takes K+ with it into the cell
- Give gkucose too- otherwise patient will become hypoglycaemic!
- IV salbutamol
hyperkalemia- if not urgent
Review medications : ACE i or NSAID or k+ sparing diuretic
Restrict potassium in diet
- Pinto beans, kidney beans
- Leafy greens eg spinach
- Dried fruit
- Banana, oranges, Apricot, Grapefruit
- Lentils
- Some meats, sea food
Polystyrene sulfonate resin binds to k+ in gut, reducing absorption
Loop diuretic (not k+ sparing)
hyperkalemia complications
Arrhythmias
MI
Muscle weakness
paralysis
