Calcium Disorders & MEN Flashcards
Role of Calcium (normally) within the body
how is the amount of secum calcium regulated
within the blood (and therefore from the lab values we obtain) how is calcium stored and floating
- plays a role in muscle contraction and the ability to contract
- plays a role (majority) in bone mineral density
- contraction of cardiac muscles
- platelet aggregation
- synaptic transmission with the nervous system
Regulation
- PTH hormone, calcitonin (to a lesser extent)
- Vit D
Calcium within the Serum
- usually bound to a protein within the blood (50% of the time)
- 50% is ionized calcium; free -floating
- thus: when drawing labs you can get total serum calcium (bound and free) vs. just ionized calcium levels
- when you get a total calcium level, you need to account for the amount of the calcium that is bound to proteins (namel,y albumin, or phosphate too)
- because IONIZED calcium is the only form of which hormone regulation is responding to
falsely “low” calcium: (in states where you have low protein, because youll appear like you have less calcium – but the body is keeping it in equlibrium between bound and free) = malnourished, cirrhotic, nephortic pts.
Fasely “high” calcum: in those with seemlingly hihg levels of protein; thus itll “appear” like you ahve more calcium, but the body keeps it in check to ensure theres not too much= pregnant, OCps, estrogen/progesteron inc.
Anatomy of the Parathyroid Glands
- sitting posterior of the thyroid, 4 glands on the back
- they are responsible for secreting PTH when there is low levels of serum calcium
- risk of damanging this during thyroid surgery; thus can have post-op hypocalcemia
Role of PTH within the body
- where does it effect (organs)
PTH is a direct relation to the level of calcium within the serum = thus in times of LOW calcium, this will stimulate the parathyroid galnds to realease PTH
on the parathyroid glands, CaR (calcium receptors) is what is bound and initiates the release of PTH
PTH then goes and acts on….
- Bone: increased bone breakdown to increase serum calcium
- Kidenys: to increase level of 1-alpha hydrox. to increase the production of active Vit D (caicitriol)
- Gut: to increase intestinal absorbtion of calcium
Role of Calcitonin in the body
calcitonin is released by the THYROID - the parafollicular C cells NOT by the parathyroid
- calcitonin is released when there is HIGh levesl of serum calcium in order to decreased amounts
Calcitonin: inhibits osteoclastic activity (to stop the bone breakdown)
mild kidney and gut impacts
calcitonin is not essentail for humans and doesnt play abig role, PTH pays a HUGE role in comparison
Vitamin D
- how is it produced within the body
- what is its role in calcium levels
- role of VIt D with the bones and kidneys
Vitamin D
the primary effect of active Vitamin D is to increase calcium levels
skin-activated (7-dehydroxycholesterol) by the UV of the sun- becomes Vitamin D (pre vit. D3)
the preVit D3 goes to the liver; becomes 25OH vitamin D (calicidiol)
in the kidney: calciDIol (25-hydrox.) into calciTRIol (1-25 hydroxy) via the action of the enzyme 1-alpha hydroxylase
this calcitriol = the active form of Vit D is released in the presence of low calcium and elevated PTH
Vit D + bones
- thought to activate osteoclasts from the RANKL system (and therefore bone breakdown to increase calcium)
- role in Rickett’s becuase these kids dont have Vit D in adequate amounts to conver it to the active form, thus there needs to be other ways to increase calcium
Vit D + kidney
- thought to increase calcium reabsorbtion
Role of Phosphate and calcium
Phosphate and calcium have a NEGATIVE RELATIONSHIP: increase 1 will decrease other
except if they’re binding to bones and increasing bone formation (which requires both compounds)
What is Parathyroid Hormone Related Peptide/Protein (PTHRP)
- what is it assocaited with
PTHRP: a different role than PTH
- produced in fetal and adult tissue with some role in proliferation of the chondrocytes and development of mamillary glands and skin
PTHRP: associated with hypercalcemia malignancy = elevated PTHRP causes significant hypercalcemia
Hypercalcemia
Etiology
Etiology
- a high level of serum calcium (total protein and free)
- can be due to elevated PTH (which was triggered by low calcium) OR from a low PTH
- primary hyperparathyroidism and malignancy are the two most common causes
Causes
- Primary hyperparathyroidism: an adenoma of the parathyroid glands which consistenlty secreted PTH: will will consistnelty increase serum calcium (hypercalcemia)
- Malignancy
- Familial (FHH)
- endocrinopathies
- Drug induced: Vit D toxicity, thiazides and Milk-Alkali Syndrome (too many tums)
Hypercalcemia
Symptoms
Symptoms: “stones, bones, abdominal moans and pshyc. groans”
- Stones: renal stones due to increase calcium
- Bones: oseoporosis, osteopenia, arthritis (becuase you took the calcium from there)
- Abd. : N/V/Constipation
- pancreatic: PUD
- Psych: fatigue, depression, memory loss, stupor, confusion
- cardiac concerns: high calcium can create a shortedn QT interval and bradycardia
Pathophys. of hypercalcemia
high v low PTH
priamry hyperparathyroidism
v
malignancy
in Primary Hyperparathyroidism
- there is an overworking parathyroid gland: thus increase PTH released to increase the amount of calcium within the serum
- HIGH PTH with HIGH CALCIUM
in Malignancy
- there is some other trigger to increase the aboutn of calcium within the serum; of which its not coming from the parathyroid its self: so tehre is no increase in PTH
- instead, there is supression of the PTH becuase it says “hey, theres high amount of serum calicum ,i dont need to work”
- instead: PTHRP & osteoclastic/blastic activity are driving the hypercalcemia
hypercalcemia can decreased GFR and cause additional issues of dehydration, N/V/D and poor mentation
Primary HyperParathyroidism (PHPT)
Etiology
Etiology
- one of the most common causes of hypercalcemia in the outpt. setting
- can be a result of the parathyroid gland or multiple of the glands (in MEN1/2 they will have hyperactivity of all of the glands)
the elevated PTH leads to chronic cycle of
- bone: increased osteoclastic activity & calcium resorbtion
- renal: increased resporbtion of calcium from PTH signals, excretion of phosphate and increased caictriol producition (by increasing 1-alpha hydrox.)
- intestinal: increase calcitriol increases resobrtion at the gut
PHPT
Symptoms
Labs
Imaging
Symptoms: the class hypercalcemia symtpoms (stones, bones, gi graons, psych. moans)
Labs
- hypophosphatemia
- hypercalcemia
- cehck PTH: will be high or high-end of normal
- check vit D, BMP and 24 urine calcium if unclear picture
Imaging
- will NOT make the dx. just helpful for surgical planning
- neck US
- majority of help is a SPECT: which is CT + SPECT
- can get DEXA scan for bone involvement
PHPT
Treatment
first line treatment is surgery with a parathyroidectomy
- if not a candidate for surgery: medical treatment (older age, CVD risk)
Must Treatm
- bone disorders
- CKD pts.
- nephrolithiasis pts.
- multiglandular/MEN pt.
- significant hypercalcemia
- young pt.
Medical Treament
- moderate their calcum intake (1,000 mg daily max)
- replace Vit D if low (could help to reduce Ca+ if the PTH is being stimulated because of low calcium because of Vit D issues as well)
- avoid thiazide (hypercalcemia risk)
- bisphosphinates to help with the OP
- cinacalet calcimimetic: wil go to the CaR on the parathyroid and bind: blocking the PTH release and helping to decrease calcium
PHPT
Follow - up and post-op
Post-op
- pts. should be followed clsoesl tiwht ionized calcium levels, PTH and BMP labs
ensure they are on cinacalet and thie vit D is controlled!!
wathc for post-op hypoparathyroidism
Hypercalcemia : Malignancy
Etiology
Patho
Etiology
- one of the most ocmmon causes of hypercalcemia (outside of PHPT) in the in-pt. setting
- associated with lots of malignancies
- at the time of understanding the lamignancy is causing hypercalcemia: prognosis is poor
Causes
- solid tumor cancers
- breast cancer
- renal cell carcinomas
- squamous cell carcinomas!!!!!!!!: especially SqCC of the lung!!!!
- Multiple Myeloma (liquid!)
- lymphoma (liquid!)
Pathology
- humoral effects: result in bone resobrtion
- local/autocrine/paracrine: effects by tumro cells trigger osteolysis
- the humoral effect the tumors secrete PTHRP: which elicts similar effects as PTH without stimulation of PTH (hence why PTH levels are low) so impact bone and kidney
- the paracrine effect: the lytic lesions and bone involvement
