Calcium Homeostasis, Hyper and Hypocalcaemia Flashcards
Why is calcium important?
- For …cytosis
- Secretion of both … and …
- Physical properties of …
- For exocytosis
- Secretion of both hormones and neurotransmitters
- Physical properties of bone
Hypocalcaemia destablizes what?
neurones
If someone has their first fit, what should you check? (serum…)
check serum calcium
Hypocalcaemia can cause what?
seizures
Physical signs of Hypocalcaemia
- with the cuff on the arm for a period of time - the arm relatively ischaemic - what happens?
- … sign is present in 10% of normal calcium levels also
- carpopedeal spasm (trousseau’s sign)
- Chvostek’s sign
What is Chvostek’s sign?
- The Chvostek sign (/ˈkvɒstɪk/) is a clinical sign of hypocalcemia.
- It is evidenced by the twitching of muscles innervated by the facial nerve (CNVII). It refers to an abnormal reaction to stimulation of the facial nerve.
Low plasma calcium … the permeability of neuronal membranes to …
Low plasma calcium increases the permeability of neuronal membranes to sodium
Consequences of Hypercalcaemia
-
acute
- thirst and …
- … pain
-
chronic
- Renal …
- osteo…
- … symptoms
- … aches / weakness
- constipation or diarrhoea?
- acute
- thirst and polyuria
- abdominal pain
- chronic
- Renal calculi
- osteoporosis
- neurobehavioural symptoms
- musculoskeletal aches / weakness
- constipation or diarrhoea? - constipation
Measuring serum calcium
-
protein bound - …%
- … bound - 90% of this
- globulin bound - 10% of this
-
bound to cations - 10%
- phosphate and citrate
- ionised (free) - …%
- protein bound - 40%
- albumin bound - 90%
- globulin bound - 10%
- bound to cations - 10%
- phosphate and citrate
- ionised (free) - 50%
The lab reports total serum ca++ corrected for the … concentration, but the corrected ca++ may be inaccurate in situations such as:
- If … concentration is
- In severe … …
- What would you measure in these cases?
The lab reports total serum calcium corrected for the albumin concentration, but the corrected calcium may be inacurate in situations such as:
- If albumin concentration is <20g/l
- In severe acute illness
- measure ionised Ca++ directly
Calcium levels in the blood are controlled within a tight normal range, what is this? (mmoles/l)
2.15-2.55mmoles/l
What hormone is important in maintaining correct levels of calcium in blood?
parathyroid hormone
What cells in the parathyroid gland make parathyroid hormone?
Chief cells
Parathyroid hormone release is determined by the … … concentration
serum calcium
How does the parathyroid cells know when to make parathyroid hormone? (or how does it know when blood ca++ is abnormal?)
- there is a calcium sensing receptor in the parathyroid chief cells
Calcium and PTH secretion
- Calcium levels …
- altered calcium … receptor formation
- modified … cell processes
- … hormone secretion
- Calcium levels low
- altered calcium sensing receptor formation
- modified chief cell processes
- parathyroid hormone secretion
Low … prevents parathyroid hormone release
Magnesium
- Presentation with low serum calcium and low PTH may mean …
- How do you correct this?
- may mean low magnesium
- give magnesium to raise calcium levels and PTH secretion
proton pump inhibitors may result in some people having low levels of …
magnesium
there are calcium sensing receptors in the parathyroid chief cells and … …
renal tubules
How does Parathyroid Hormone work?
- PTH (… …) receptor
- recognises PTH
- causes changes inside cell when PTH latches on to receptor, how?
- PTH activates the receptor by changing it’s …
- … effect
- PTH (Type 1) receptor
- recognises PTH
- causes changes inside cell when PTH latches on to receptor, how?
- PTH activates the receptor by changing it’s shape
- biological effect
Where are the PTH1 receptors? (where is the biological effect?)
- 2 places in the body …
Bone and kidney
Bone - rapid action of PTH
- In bone, the PTH attaches to it’s receptor in the bone cells and you get an … effect
- bone has a network of cells known as … - these have … which contract - push fluid with … calcium out into general circulation
- In bone, the PTH attaches to it’s receptor in the bone cells and you get an immediate effect
- bone has a network of cells known as osteocytes - these have projections which contract - push fluid with high calcium out into general circulation
Calcium release from bone
- PTH has a receptor on the bone osteoblasts
- PTH binds to osteoblasts
- Oestoblasts makes a cytokine called … …
- this attaches to a receptor on the … cell
- they are activated - produces acids and enzymes
- these acids and enzymes … bone - releasing calcium into the circulation
- PTH has a receptor on the bone osteoblasts
- PTH binds to osteoblasts
- Oestoblasts makes a cytokine called rank ligand
- this attaches to a receptor on the osteoclast cell
- they are activated - produces acids and enzymes
- this dissolves bone - releasing calcium into the circulation
What are osteoclasts?
Osteoclasts are multinucleated cells responsible for bone resorption
What is this image showing?
Osteoclast breaking down bone to release calcium
Kidney - actions of PTH
1) rapid calcium reabsorption
- increases calcium reabsorption in 3 places - what are they?
- decreases … reabsorption (proximal tubule)
2) renal synthesis of active … …
1) rapid calcium reabsorption
- increases calcium reabsorption in loop of henle, distale tubule, collecting ducts
- decreases PO4 reabsorption (proximal tubule)
2) renal synthesis of active vitamin D
Renal synthesis of Active Vitamin D
- … light -> skin -> stimulates production of vitamin D in skin
- can also get vitamin D from our … - such as cod liver oil, oily fish (wild), mushrooms, fortified foods
- Vitamin D then goes to the …
- Vitamin D is actually a …
- ultraviolet light - skin - stimulates production of vitamin D in skin
- can also get vitamin D from our diet - such as cod liver oil, oily fish (wild), mushrooms, fortified foods
- goes to the liver
- actually a steroid
What do we measure in the blood to figure out vitamin D stores in the body?
- 25 OH vitamin D (made in liver)
Vitamin D - from liver to kidney
- .. … vitamin D made in liver
- Gets to kidney - 1 hydroxylated into … …. Vitamin D
- What stimulates this?
- increases levels of vitamin D - in turn, this stimulates … transporters and binding, also protein in gut cells - overall effect = increased absorption of what?
- 25 OH vitamin D made in liver
- Gets to kidney - 1 hydroxylated into 1,25 OH Vitamin D
- What stimulates this? - parathyroid hormone
- increases levels of vitamin D - in turn, this stimulates calcium transporters and binding, also protein in gut cells - overall effect = increased absorption of what? - calcium
Increased 1,25 OH Vitamin D in the kidney increases absorption of
calcium
The Kidney and Phosphate Excretion
- … (hormone) produced by … (bone cells)
- One of it’s main roles is to increase renal … excretion
- FGF23 (hormone) produced by osteocytes (bone cells)
- One of it’s main roles is to increase renal phosphate excretion
The Kidney and Vitamin D
- 25 OH vitamin D converted to 1,25 OH vitamin D - via … hormone
- When 1,25 OH vitamin D is high - … recognise this and produce …23 which inhibits this conversion of 25 OH vitamin D to 1,25 OH vitamin D
- 25 OH vitamin D converted to 1,25 OH vitamin D - via parathyroid hormone
- When 1,25 OH vitamin D is high - osteocytes recognise this and produce FGF 23 which inhibits this conversion of 25 OH vitamin D to 1,25 OH vitamin D
Primary Hyperparathyroidism - Diagnosis
- Serum … increased
- Serum … reduced
- … hormone increased
- Serum calcium increased
- Serum phosphate reduced
- parathyroidhormone increased
parathyroid hormone increases renal … excretion
renal phosphate excretion
Complications of Hyperparathyroidism
- Osteo…
- Bone … (if severe)
- Osteoporosis
- Bone cysts (if severe) (shown in image)
What is Osteoporosis?
Osteoporosis is a skeletal disorder characterised by low bone density and microarchitectural deterioration of bony tissue. This results in an increase in fracture risk.
Complications of Hypercalcaemia
- what is shown in image?
- renal stones
Indications for Parathyroidectomy
- …porosis
- Renal …
- Age under ?
- Serum calcium over … mmol/l
- Consumer choice
- Osteoporosis
- Renal Calculi
- Age <50 years
- Serum calcium >2.8 mmol/l
- Consumer choice
Locating the … adenoma
- do a … ultrasound
- measure the hormone before and afterwards - concentration should have gone down if you have taken out the right thing
- If you cannot find on ultrasound - what scan?
- If you can’t find on either of these, what then?
Locating the parathyroid adenoma
- do a neck ultrasound
- if you cannot find - do a Sesta Mibi parathyroid scan
- 4D CT scan - parathyroid adenoma
What is a Sesta Mibi Parathyroid scan?
A sestamibi parathyroid scan is a procedure in nuclear medicine which is performed to localize parathyroid adenoma, which causes Hyperparathyroidism
What is a 4D CT scan of the parathroid used for?
- In recent years 4D-CT has emerged as a useful imaging technique in the work-up of patients with primary hyperparathyroidism to allow sensitive detection and localisation of parathyroid adenomas and parathyroid hyperplasia.
Hypoparathyroidism
- Serum … low
- PTH is … or …
- Serum calcium low
- PTH is low / normal
Hypoparathyroidism causes
- … causes such as:
- thyroidectomy
- radical neck surgery
- auto…
- hypo…
- … mutations
-
Iatrogenic
- thyroidectomy
- radical neck surgery
- autoimmune
- hypomagnesaemia
- genetic mutations
Secondary Hyperparathyroidism - common causes
- …. / … levels of serum Calcium and … parathyroid hormone
- low serum … vitamin D
- lack of … exposure
- GI problems such as … and extensive surgery (small bowel)
- … failure
- low serum … vitamin D
-
low / low normal levels of serum Calcium and high parathyroid hormone
- low serum 25 OH vitamin D
- lack of sun exposure
- GI problems such as malabsorption and extensive surgery (small bowel)
- renal failure
- low serum 25 OH vitamin D
Reduced Vitamin D concentration can cause … (in children)
Ricketts
Reduced Vitamin D concentration can cause … (in adults)
- Osteomalacia (Osteomalacia refers to a marked softening of your bones, most often caused by severe vitamin D deficiency.)
- Looser’s Zone (A pseudofracture, also called a Looser zone, is a diagnostic finding in osteomalacia.)
Vitamin D levels in the Elderly
- Low vitamin D levels as you get …
older
Elderly skin & Vitamin D production after UV light exposure vs younger people
- effect is a lot less than in … than … people
- Vitamin D deficiency increases … and …
- effect is a lot less than in elderly than younger people
- Vitamin D deficiency increases falls and fractures
Overview of calcium homeostasis
Chief cell makes PTH
PTH -> receptors in bone (efflux of calcium into bone) and kidney (decreased loss of calcium in urine)
production of 1,25 Vit D also increased - goes to bowel - enhanced absorption of calcium from intestine
maintains blood ca++ concentration and maintains bone mineral density
