L5/6 - Adrenals Flashcards
What are the layers of the adrenal gland?
G- Glomerulosa (outside)
F- fasciculata
R - reticularis
Medulla in middle
What the adrenal causes of hypertension?
Primary Hyperaldosteronism - problem with zona glomerulosa - may be due to adenoma, hyperplasia or rare genetic disorders
Phaeochromocytoma - Tumour of the adrenal medulla
Whom to screen for primary hyperaldosteronism ?
Hypokalaemia
Resistant hypertension (3 drugs)
younger people
What tests would you do for primary hyperaldosteronism ?
1 - Initial screening tests suppressed renin Normal/High aldosterone Confirmatory tests - oral or IV sodium supression test
Adrenal CT scan
Adrenal venous sampling
Metomidate PET CT
Treatment for Primary Hyperaldosteronism
Unilateral adenoma - laparoscopic adrenalectomy
and sometimes medical treatment
Bilateral hyperplasia - medical treatment (aldosterone antagonist) spironolactone or eplerinone
What are the products of the adrenal medulla?
catecholamines - dopamine, adrenaline noradrenaline - alpha 1/2 vasoconstriction, increased bp, pallor adrenaline - alpha 1 and beta 1+2 vasoconstriction, vasodilation in muscles, increased HR, sweating
How does phaeochromocytoma present?
Spells - headache, sweating, pallor, palpitation, anxiety
hypertension
family history
What 3 genetic conditions are associated with phaechromocytoma?
NF1 - neurofibromatosis type 1 - Tumour under skin or deeper. Tumour which grows on the nerves
Also get axillary freckling
MEN2 - Multiple endocrine neoplasia type 2 - medullary carcinoma of thyroid
Von Hippel - Lindau syndrome - retinal hemangioglioblastoma
How would you diagnose phaeochromocytoma?
24 hour urine - normetanephrines and metanephrines
Plasma - noradrenaline/adrenaline
metanephrines
What other things can elevate the measured catecholamines?
L-DOPA
Amphetamine like drugs
Obstructive sleep apnoea
Labetalol
Other tests
CT to identify it
Then MIBG - a nuclear medicine scan
Meta-iodobenzylguanidine
Management for Pheo
Alpha blockers - phenoxybenzamine
doxazocin
BB - propanalol
Laparacopic adrenalectomy
Post adrenalectomy care
consider genetic testing
annual metanephrines - plasma and 24 hour urines
Why is calcium important?
exocytosis
- neurotransmitter secretion
hormone secretion
physical properties of bone
How does hypocalcemia affect neurons?
destabilises them
so it is important to check - if someone has first fit - check their serum calcium as hypocalcemia can cause seizures
The reason hypocalcemia causes neuron excitation (contrary to the above logic) is because a decrease in extracellular calcium concentration increases the neuron membrane’s permeability to sodium and allows sodium to easily depolarize the neuron’s membrane and cause an action potential
What physical signs are there are of hypocalcemia/
1) Trousseaus sign of latent tetany (carpopedal spasm) In a patient with hypocalcemia, carpal spasm may be elicited by occluding the brachial artery. To perform the maneuver, a blood pressure cuff is placed around the arm and inflated to a pressure greater than the systolic blood pressure and held in place for 3 minutes. If carpal spasm occurs, manifested as flexion at the wrist and metacarpophalangeal joints, extension of the distal interphalangeal and proximal interphalangeal joints, and adduction of the thumb and fingers, the sign is said to be positive and the patient likely has hypocalcemia
2 - Chvostek’s sign - low plasma calcium increases permeability of neuronal membranes to sodium. . If the plasma Ca2+ decreases to less than 50% of the normal value action potentials may be spontaneously generated, causing contraction of peripheral skeletal muscle
What are consequences of hypercalcemia?
acute - thirst / polyuria/abdominal pain
chronic - constipation
osteoporosis
renal calculi
How are calcium levels controlled within a narrow range?
Chief cells in the parathyroid glands make parathyroid hormone. results in increased calcium in serum. PTH release is determined by serum calcium concentration
How does it know when the blood calcium is abnormal?
parathyroid chief cells have calcium sensing receptors
a part of GPCR family.
The calcium-sensing receptor (CaSR) is sensitive to an increase in serum calcium, and stimulates the uptake of calcium by the parathyroid chief cell. This mechanism is critically important, as it describes a physiological feed-back loop by which parathyroid hormone secretion is down-regulated in response to a restoration of serum calcium.
How does magnesium affect PTH?
Low magnesium prevents PTH release?
How does PTH work?
Binds PTH type 1 receptor which is a GPCR. activation of adenylyl cyclase. PTH activates the receptor by changing its shape
Where are PTH receptors?
bone and kidney
PTH and Bone
The first action is to increase renal calcium resorption and phosphate excretion. In the kidney, PTH blocks reabsorption of phosphate in the proximal tubule while promoting calcium reabsorption in the ascending loop of Henle, distal tubule, and collecting tubule. Calcium also may exert a direct effect on renal resorption.
PTH promotes absorption of calcium from the bone in 2 ways.
a. The rapid phase brings about a rise in serum calcium within minutes and appears to occur at the level of the osteoblasts and osteocytes. Although it may seem counterintuitive that the cells that promote deposition of bone are involved in resorption, these cells form an interconnected network known as the osteocytic membrane overlying the bone matrix, but with a small layer of interposed fluid termed bone fluid. When PTH binds to receptors on these cells, the osteocytic membrane pumps calcium ions from the bone fluid into the extracellular fluid.
How is calcium released from bone?
PTH stimulates osteoblasts - rank ligand produced by osteoblasts- rank - osteoclast activation -
excess RankL drives bone destruction
Osteoclasts break down bone. - bone resorption
Action of PTH on kidneys
Rapid calcium reabsorption in loop of henle, dt and cd.
reduced phosphate reabsorption in PT.
PTH important for Vitamin D. which is needed for calcium absorption
Kidneys regulate production of 1,25 (OH)2D. PTH stimulates and FGF23 inhibits the production.
In turn, 1,25(OH)2D inhibits PTH production and secretion of the PTH gland and stimulates FGF23 production from bone.
OSTEOCYTES MAKE FGF23 WHICH MAKES YOU PEE OUT LOADS OF PHOSPHATE - RENAL PHOSPHATE EXCRETION
problems with calcium metabolism
Primary hyperparathyroidism
diagnosis: serum calcium increased, serum phosphate reduced and PTH increased
What are complications of hyperparathyroidism?
osteoporosis
bone cysts
Complication of hypercalcemia
renal stones
Levels in hypoparathyroidism
serum calcium low
PTH can be low or normal
What are causes of hypoparathyroidism?
iatrogenic - thyroidectomy, radical neck surgery
autoimmune
hypomagnesaemia
genetic mutations
What are causes of secondary hyperparathyroidism?
low serum calcium and HIGH PTH
low serum 25 OH vit D
lack of sun exposure/GI problems
renal failure
What is rickets
A softening of the bones in children potentially leading to fractures and deformity.
