Diabetes insipidus and Hyperparathyroidism Flashcards
Diabetes insipidus
- caused by:
- what happens
- symptoms
- either a lack of ADH or a lack of response to ADH
- prevents the kidneys from concentration urine –> polyuria, polydipsia
- polyuria, polydipsia, nocturia, enuresis
Vasopressin secretion
- regulated by the osmotic pressure of body fluids
- control is mediated by osmoreceptors that are sensitive to small changes in plasma concentration of sodium and its anions
- osmoreceptors are insensitive to other solutes, ex: urea and glucose
below the threshold –> suppressed to levels that permit the development of a maximum water diuresis
above the threshold –> levels rises in direct proportion to plasma osmolarity, reaching levels sufficient to affect pa maximum antidiuresis
Vasopressin actions (2)
- reduce water excretion by promoting concentration of urine
- it does that by increasing the hydro osmotic permeability of cells that like the tubules and ducts of the kidney
What happens in the absence of vasopressin?
- cell are impermeable to water and reabsorb little
- lack of reabsorption results in the excretion of very large volumes of maximally dilute urine = water diuresis
Antidiuretic effect of vasopressin is mediated via…?
G protein coupled V2 receptors that increases intracellular cAMP –> inducing translocation of aquaporin 2 water channels into the apical membrane
The resultant increase in permeability permits an influx of water that diffuses out of the cell through AQP 3 and AQP 4 channels on the basal-lateral surface
Thirst (2)
- vasopressin cannot reduce water loss below a certain minimum level –> evaporation from skin and lungs is necessary to ensure adequate intake –> preventing dehydration
- regulated by an osmotat that is situated in the hypothalamus and is able to detect very small changes in the plasma concentration of sodium and its anions
Diabetes Insipidus (DI) (5)
- definition
- lab values
- will the patient present with clinical signs of dehydration?
- a decrease in 75% or more in the secretion or action of vasopressin
- production of abnormally large volumes of dilute urine
- 24h urine volume >40 ml/kg/ body
- osmolarity <300
-nope, it is uncommon –> unless thirst or compensatory increase of fluid intake is impaired
DI classification (4)
Pituitary - decreased production of ADH
-acquired, congenital malformations, genetic
Gestational
Nephrogenic - collecting ducts don’t respond to ADH
Primary polydipsia - normal ADH –> drink too much water –> too much urine –> patient doesn’t have DI
-psychogenic or dipsogenic
DI
-pathophysiology
Pituitary, gestational, nephrogenic
- polyuria –> decrease in body water –> increase in plasma osmolarity and sodium –> thirst and compensatory mechanisms
- hypernatremia and signs of dehydration do not develop
Primary polydipsia
- pathogenesis is the reverse
- abnormal cognition or thirst –> excessive fluid intake –> increase in body water –> reduces plasma osmolarity/sodium, vasopressin secretion and urine concentration
Nephrogenic DI
- vasopressin is normal or elevated
- urine osmolarity is low (<300)
Pituitary DI
- basal plasma vasopressin is low or undetectable (<1 pg/mL)
- MRI - T1 images - pituitary “bright spot” is always absent or abnormally small
Primary polydipsia
-MRI - T1 image - pituitary “bright spot” is present
Treatment of DI
-Uncomplicated pituitary DI
-desmopressin (synthetic analogue of vasopressin)
Desmopressin
-IV, subcutaneous injection, nasal inhalation or orally
Treatment of DI
- Primary polydipsia
- Nephrogenic
-not treated safely with desmopressin - because eliminating polyuria does not eliminate the urge to drink
- polyuria and polydipsia are not affected by desmopressin
- thiazide diuretic and/or amiloride + low sodium diet and a prostaglandin synthesis inhibitor
Factors involved in calcium and bone metabolism
- Parathyroid hormone - increases reabsorption of calcium from intestine and kidneys, increases osteoclast activity
- Vitamin D - increases intestinal calcium reabsorption, bone resorption and plasma calcium
- Calcitonin - decreases bone turnover and plasma calcium
- Sex steroids
- Growth hormone and insulin-like factors
- Thyroid hormone - increases bone resorption
- Prolactin - increases renal calcium reabsorption
- Glucocorticoids - increases bone resorption, decrease bone synthesis
- Inflammatory cytokines - increases bone resorption
Parathyroid hormone - effects
- decrease calcium levels
- PTH is released
- increased activation of vit. D
- increase absorption of calcium in intestines and kidneys, increase osteoclasts activity in bones, decreased the reabsorption of inorganic phosphate
***elevations of inorganic phosphate –> release of PTH
Hyperparathyroidism
- increase in PTH levels in the blood due to a disorder within the parathyroid glands or outside the parathyroid glands
- primary, secondary or tertiary
Primary Hyperparathyroidism
- Cause
- PTH level
- Calcium level
- Treatment
- Cause: tumor (parathyroid hormone secreting adenoma, parathyroid carcinoma, parathyroid glandular hyperplasia), genetic abnormalities (MEN)
- PTH levels: increase
- Calcium levels: increase
- Treatment: surgery - ensure patient is hydrates, control hormones levels, IV biphosphates if patient has hypercalcemia
Secondary Hyperparathyroidism
- cause
- PTH level
- Calcium level
- Treatment
- Cause: decrease vit.D or CKD
- PTH levels: increase
- Calcium levels: decrease or normal
- Treatment: increase vit. D, kidney transplant
Tertiary Hyperparathyroidism
- cause
- PTH level
- Calcium level
- Treatment
- Cause: hyperplasia after secondary hyperparathyroidism
- PTH levels: increase
- Calcium levels: increase
- Treatment: surgery
Primary Hyperparathyroidism
-clinical presentation (4)
- Asymptomatic PHPT - mild hypercalcemia
- Normocalcemic PHPT - elevated PTH, absence of hypercalcemia, ionized calcium levels should be normal
- Parathyroid crisis - rare, severe hypercalcemia, severe abdominal pain, nausea, vomiting, peptic ulcer, pancreatitis, CNS dysfunction
- Classical PHPT - bone alterations (decreased bone mineral density), kidney alterations (renal insufficiency, nephrolithiasis, nephrocalcinosis), digestive disorders (constipation, nausea, peptic ulcers, pancreatitis), neuromuscular symptoms (decreased muscle strength, weakness), neuropsychiatric disturbances (lethargy, depressed mood)
Primary Hyperparathyroidism
-diagnosis (5)
- hypercalcemia - elevated 24h urinary calcium
- elevated PTH
- vit. D, creatinine and GFR –> differential diagnosis for secondary
- imagining - neck ultrasound (first choice)
- parathyroid scintigraphy - if ultrasound is not informative, if you suspect malignancy, if the adenoma is big, if patient has already been operated or in case of relapse
- abdominal US (to check the kidneys), densitometry for bone mineral density —> only show us possible complications - NOT DIAGNOSTIC
Primary Hyperparathyroidism
-differential diagnosis (4)
- hypercalcemia due to malignancy
- familial hypocalciuric hypercalcemia (FHH) - mild hypercalcemia, normal/slightly elevated PTH, low urine calcium excretion, Calcium to creatinine clearance ration (CCR) <0,01
- drugs - thiazide diuretics (reduce urinary calcium excretion), lithium (decreases parathyroid gland sensitivity to calcium and reduce urinary calcium excretion)
- secondary hyperparathyroidism
Primary Hyperparathyroidism
-treatment other than surgery (4)
- Bisphosphonates –> inhibitors of bone resorption
- Maintain vit. D intake - vit. D deficiency –> stimulates PTH secretion and bone resorption
- Calcimimetics - activate the calcium sensing receptor –> inhibits PTH secretion
- medications are NOT an alternative for surgery because they are not effective enough!
Secondary Hyperparathyroidism (3)
-result of alteration outside the parathyroid gland
- parathyroid appropriately responds to a reduced level of extracellular calcium –> PTH levels rise –> increasing intestinal absorption and by increasing bone resorption
- hyperplasia of the glands
- causes: renal failure, impaired calcium absorption (vit. D deficiency, celiac disease, Bariatric surgery), inadequate calcium intake, renal calcium loss
vit. d deficiency or renal failure –> reduced Ca2+ absorption –> hypocalcemia –> increase PTH
Secondary Hyperparathyroidism
-renal SHPT - pathogenesis
- most frequent cause
- occurs in patients with chronic renal failure
- early –> reduction of vit. D and decrease in ionized calcium –> greater synthesis and secretion of PTH
- later –> parathyroid expression of vit. D and calcium is reduced –> parathyroid gland becomes resistant –> for any particular plasma calcium concentration, secretion of PTH is enhanced
Secondary Hyperparathyroidism
- clinical presentation
- diagnosis (6)
-osteitis fibrosa, osteomalacia, bone fractures –> most patients with advances staged of chronic kidney disease
- elevated serum creatinine/urea
- low GFR
- hyperphosphatemia
- hypocalcemia
- elevated PTH
- radiological signs of osteopathy
Secondary Hyperparathyroidism
-treatment
- Treat hyperphosphatemia - dietary phosphate restriction, phosphate binders (sevelamer, ferric citrate)
- Treat hypocalcemia - vit. D derivatives (calcitriol)
* **treat underlying causes
Secondary Hyperparathyroidism
-due to vit. D deficiency
- common
- diagnosis: mild hypocalcemia or normal calcium concentration, elevated PTH, low vit. D
- differential diagnosis: renal SHPT –> normal kidney function, normal phosphate concentration
- treatment: vit. D supplements
Tertiary Hyperparathyroidism
- pathogenesis
- diagnosis
- complications
- treatment
- excessive secretion of parathyroid hormone after a long period of SHPT
- most often affects all 4 glands and it is found is patients undergoing dialysis
- high blood calcium level, phosphate levels are elevated, PTH elevated
- diffuse tissue calcinosis
- surgery - removal of the glands (hyperplastic)
Hungry bone syndrome
- prolonged hypocalcemia, hypophosphatemia and hypomagnesemia
- exacerbated by suppressed PTH levels which follows parathyroidectomy
-symptoms: proximal muscle weakness, fatigue, cramps
- treatment: oral calcium + vit. D
- if tetany develops –> calcium IV –> infusion is needed constantly because if we stop it –> calcium is eliminated in the urine
PTH action on:
- Kidneys
- Bone
- Intestine
- decrease phosphate reabsorption, increase calcium reabsorption, increase vit. D formation
- increase resorption –> increases osteoclasts activity
- increase calcium absorption
result: decrease plasma phosphate and increase plasma calcium
Calcitonin action on:
- Kidneys
- Bone
- decrease phosphate reabsorption, decrease calcium reabsorption
- decrease resorption –> decreases osteoclast activity
result: decrease plasma phosphate and decrease plasma calcium
Vit. D action on:
- Kidneys
- Bone
- Parathyroid gland
- Intestine
- increase calcium reabsorption
- increase bone mineralization
- decrease PTH secretion
- increase calcium and phosphate absorption
Diabetes insipidus
-differential diagnosis - test
- typical symptoms
- 24h urine volume and osmolarity on unrestricted fluid intake
- Volume >40 and osmolarity <300 –> measure plasma AVP –> >1 –> Nephrogenic
- if MRI –> differentiate between pituitary and primary polydipsia based on the “bright spot”
