Hypo-parathyroidism / Hypocalcaemia Flashcards

1
Q

What is the prevalence of hypoparathyroidism?

1 - 20-40 / 100
2 - 20-40 / 1000
3 - 20-40 / 10,000
4 - 20-40 / 100,000

A

4 - 20-40 / 100,000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

The parathyroid glands is the controller of Ca2+ in the body and is located on the posterior surface of the thyroid gland (4 in total). Ca2+is present in 3 key sights of the body:

  • bones = 85%
  • intracellular = 15%
  • extracellular (plasma) = 1%

The 1% extracellular Ca2+ comes in 3 separate forms, which of the following is NOT one of these?

1 - ionised Ca2+ (unbound Ca2+) = 50% at 1.2mmol/L
2 - plasma bound Ca2+, generally albumin = 41% at 1.0mmol/L
3 - Ca2+ complexes (phosphates and citrate) = 9% at 0.2mmol/L
4 - NaCa2+ rebasorbed from the renal tubules

A

4 - NaCa2+ rebasorbed from the renal tubules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Extracellular Ca2+ accounts for 1% of total body Ca2+, at a concentration of aprox 2.4mmol/L. It can be difficult to measure calcium in the blood as there are 3 different forms, evident in the image. When measuring Ca2+ in the blood we are really only interested in the ionised form, as this is unbound and biologically active . What must we correct for when measuring Ca2+?

1 - Hb
2 - albumin
3 - WCC
4 - platelets

A

2 - albumin
- high pH means Ca2+ can bind with albumin, so Ca2+ appears low
- patients may have hypo or hyperalbuminemia
- hypoalbuminemia may present as hypocalcaemia, but Ca2+ may be normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

There are the 3 main sites where calcium is present in the body:

  • bones = 85%
  • intracellular = 15%
  • extracellular (plasma) = 1%

Extracellular Ca2+ accounts for 1% of total body Ca2+, at a concentration of aprox 2.4mmol/L. It can be difficult to measure calcium in the blood as there are 3 different forms, evident in the image. When measuring Ca2+ in the blood we are really only interested in the ionised form, as this is unbound and clinically relevant. We must correct for albumin when measuring Ca2+. What are the 2 calculations for correcting this?

A

1 - adjusted (Ca2+) = ionised Ca2+ (mmol/L) + 0.02 (40 - (albumin in g/L)
2 - adjusted (Ca2+) = ionised Ca2+ (mg/dL) + 0.8 (40 - (albumin in g/dL)

MAJOR DIFFERENCE IS CONCENTRATION AND EXPECTS NORMAL ALBUMIN LEVELS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which vitamin promotes Ca2+ uptake?

1 - vitamin B12
2 - vitamin C
3 - vitamin B1
4 - vitamin D

A

4 - vitamin D
- aprox 35%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Is Ca2+ absorbed well in the intestines from the Ca2+ we consume in the diet?

A
  • no
  • divalent (+2) are poorly absorbed
  • aprox 90% is passed through faeces
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Ca2+ can be deposited or re-absorbed from all of the following sites, EXCEPT which one?

1 - bone
2 - cells
3 - kidneys
4 - skin
5 - GIT

A

4 - skin
- vitamin D is absorbed and this helps with Ca2+, but it is not absrobed by the skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Calcium levels in the blood are controlled by the parathyroid glands, located posteriorly on the thyroid gland. The chief cells in the parathyroid glands
play an important role in Ca2+ homeostasis. if the Ca2+ levels begin to drop, what do the chief cells secrete?

1 - Adrenocorticotropic hormone
2 - Thyrotropin releasing hormone
3 - Calcitonin
4 - Parathyroid hormone

A

4 - Parathyroid hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Chief cells secrete parathyroid hormones when Ca2+ levels are reduced. How long is the parathyroid hormone in terms of amino acids?

1 - 8.4 residues (amino acids)
2 - 18 residues (amino acids)
3 - 44 residues (amino acids)
4 - 84 residues (amino acids)

A

4 - 84 residues (amino acids)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Chief cells secrete parathyroid hormone that is 84 residues (amino acids) long. Once this has been produced by the chief cells, what must happen to the hormone before it becomes active?

A
  • undergo proteolytic cleavage
  • amino acids 1-34 make up active parathyroid hormone
  • amino acids 25-84 make up inactive parathyroid hormone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Parathyroid glands are able to detect plasma Ca2+ concentrations through whioch receptor?

1 - iodine Ca2+ receptor
2 - calcium sensing receptor (CaSR)
3 - GPCR Gas Ca2+ receptor
4 - all of the above

A

2 - calcium sensing receptor (CaSR)
- GPCR
- specifically Gaq

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

GPCR receptors on parathyroid hormone are able to detect plasma Ca2+ concentrations. When extracellular Ca2+ is high Ca2+ binds with the GPCR Gaq. Organise what then happens intracellularly?

1 - PLc then splits PiP2 into IP3 and DAG
2 - IP3 binds with ER in chief cell and Ca2+ is released
3 - increased intracellular Ca2+ INHIBITS the binding of vesicles containing PTH to the membrane and thus the release of PTH
4 - Ca2+ binds with Gaq and activates phospholipase C (PLc)

A

4 - Ca2+ binds with Gaq and activates phospholipase C (PLc)
1- PLc then splits PiP2 into IP3 and DAG
2 - IP3 binds with ER in chief cell and Ca2+ is released
3- increased intracellular Ca2+ INHIBITS the binding of vesicles containing PTH to the membrane and thus the release of PTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

GPCR receptors on parathyroid hormone are able to detect plasma Ca2+ concentrations. When extracellular Ca2+ is low Ca2+ binds with the GPCR Gaq. Organise what then happens intracellularly?

1 - PLc does not split PiP2 into IP3 and DAG
2 - IP3 does not bind with ER in chief cell and Ca2+ is not released
3 - low intracellular Ca2+ allows binding of vesicles containing PTH to the membrane and thus the release of PTH
4 - less Ca2+ binds with Gaq and activates phospholipase C (PLc)

A

4 - less Ca2+ binds with Gaq and activates phospholipase C (PLc)
1 - PLc does not split PiP2 into IP3 and DAG
2 - IP3 does not bind with ER in chief cell and Ca2+ is not released
3 - low intracellular Ca2+ allows binding of vesicles containing PTH to the membrane and thus the release of PTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Parathyroid hormone binds with receptors at specific sites in the body, which of the following is NOT one of these?

1 - cells (specifically blood)
2 - kidneys (control filtration of Ca2+)
3 - GIT absorbative cells in small intestines
4 - bone (osteoblast/osteoclast activation)
5 - skeletal muscle ER

A

5 - skeletal muscle ER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

The calcium sensing receptor (CaSR), a GPCR, specifically Gaq on parathyroid glands is able to detect plasma Ca2+ concentrations through GPCR. What 2 things can happen to Ca2+ levels if there is mutations in CaSR?

1 - hypercalcaemic
2 - hypocalcaemic
3 - cushings sundrome
4 - graves disease

A

1 - hypercalcaemic
2 - hypocalcaemic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

If Ca2+ levels are low, parathyroid hormone (PTH) is released and binds to a specific cell to release and increase Ca2+ levels. What cell is this?

1 - keratinocytes
2 - osteoblasts
3 - osteoclasts
4 - small intestinal cells

A

2 - osteoblasts
- cells that normally build the bones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Parathyroid hormone (PTH) is able to bind with osteoblasts in bones and release C2+. To do this osteoblasts release which 2 key cytokines?

1 - receptor activator of nuclear factor kappa-B ligand (RANKL)
2 - macrophage colony-stimulating factor (M-CSF)
3 - TNF-a
4 - IL-6

A

1 - receptor activator of nuclear factor kappa-B ligand (RANKL)
2 - macrophage colony-stimulating factor (M-CSF)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Parathyroid hormone (PTH) is able to bind with osteoblasts in bones and release C2+. To do this osteoblasts release receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). What does this cause in the bone?

1 - signals inflammatory response that damages bones and releases Ca2+
2 - interact with a preosteoclast cell (breaking down bone) that form mature osteoclast
3 - interacts with cells in small intestines and increases Ca2+ absorption
4 - all of the above

A

2 - interact with a preosteoclast cell (breaking down bone) that form mature osteoclast

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Parathyroid hormone (PTH) is able to bind with osteoblasts in bones and release C2+. To do this osteoblasts release receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) that interact with a preosteoclast cell (breaking down bone) that form mature osteoclast. What then happens?

1 - osteoblasts are activates and start breaking down bone
2 - osteoocytes are acticvated that induce Ca2+ release into the blood
3 - osteoclasts secrete enzymes that degrade bone and release Ca2+ into the blood
4 - all of the above

A

3 - osteoclasts secrete enzymes that degrade bone and release Ca2+ into the blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Parathyroid hormone (PTH) is also able to bind with receptors in the kidneys, specifically in the proximal tubules. What other molecule does PTH reduce the reabsorption of in the proximla tubules of the kidneys?

1 - Na+
2 - Ca2+
3 - phosphate
4 - Mg2+

A

3 - phosphate
- phosphate binds Ca2+ in blood
- less phosphate means more biologically avaialble Ca2+

21
Q

In addition to the parathyroid hormone (PTH) binding with receptors in the kidneys to reduce phosphate reabsorption, thus increasing ionised (free Ca2), what other important molecule does PTH increase the reabsorption of in loop of henle, distal tubule and collecting ducts?

1 - Na+
2 - Ca2+
3 - K+
4 - Mg2+

A

2 - Ca2+
- PTH binds with receptors and increases Ca2+ reabsorption through Na+/Ca2+ co-transporter

22
Q

How does vitamin D that is absorbed by the skin through sunlight get turned into active vitamin D?

A
  • cholecalciferol (pre-cursor of vit D) absorbed by the skin
  • converted into 25-hydroxycholecalciferol in the liver
  • 25-hydroxycholecalciferol is converted into 1,25 dihydroxycholecalciferol in kidneys creating active vitamin D
23
Q

Vitamin D is absorbed by the skin through sunlight that then gets turned into active vitamin D, through the process below, and in the image.

  • cholecalciferol (pre-cursor of vit D) absorbed by the skin
  • converted into 25-hydroxycholecalciferol in the liver
  • 25-hydroxycholecalciferol is converted into 1,25 dihydroxycholecalciferol in kidneys creating active vitamin D

How does this active vitamin D then increase Ca2+ uptake in the GIT?

1 - active vitamin D enters the GIT, binding Ca2+ so it can be reabsorbed
2 - active vitamin D enters the GIT and forms emulsion with bile and Ca2+ and increases absorption
3 - active vitamin D enters the enterocytes, cells lining the GIT
4 - all of the above

A

3 - active vitamin D enters the enterocytes, cells lining the GIT
- binds with Ca2+ receptors and actively transports Ca2+ into plasma

24
Q

Once parathyroid hormone has signalled increased Ca2+ is required, PTH initiates the following 3 process to increase Ca2+:

  • Ca2+ release from bone
  • Ca2+ reabsorption and phosphate excretion from kidneys
  • Ca2+ uptake increased in GIT

How do the Ca2+ receptors in the parathyroid gland then reduce PTH if the plasma levels are at a normal level?

A
  • Ca2+ detected in the plasma that has been released from the 3 pathways above
  • Ca2+ in plasma is its own negative feedback loop to stop hypercalcemia
25
Q

Vitamin D is absorbed by the skin through sunlight that then gets turned into active vitamin D, through the process below, and in the image.

  • cholecalciferol (pre-cursor of vit D) absorbed by the skin
  • converted into 25-hydroxycholecalciferol in the liver
  • 25-hydroxycholecalciferol is converted into 1,25 dihydroxycholecalciferol in kidneys creating active vitamin D

What can happen if a patient is taking a dose of vitamin D that is too high?

A
  • Ca2+ absorption pathway will be continually active
  • 25-hydroxycholecalciferol can be stored
  • overall this can lead to hypercalcaemia
26
Q

What is the additional cytokine that is released by osteocytes that can signal the excretion of phosphate in the kidneys?

1 - receptor activator of nuclear factor kappa-B ligand (RANKL)
2 - macrophage colony-stimulating factor (M-CSF)
3 - TNF-a
4 - fibroblast growth factor-23 (FGF-23)

A

4 - fibroblast growth factor-23 (FGF-23)

27
Q

There is an additional cytokine called fibroblast growth factor-23 (FGF-23) that osteocytes release that can signal the excretion of phosphate in the kidneys. What does this then cause to happen in the kidneys?

1 - increase phosphate and Ca2+ reabsorption
2 - inhibits Ca2= reabsorption in kidneys
3 - FGF-23 acts as a negative feedback loop, inhibiting vitamin D precursor, 25-hydroxycholecalciferol from being converted into 1,25 dihydroxycholecalciferol
4 - all of the above

A

3 - vitamin D precursor, 25-hydroxycholecalciferol is NOT converted into 1,25 dihydroxycholecalciferol

  • FGF-23 acts as a negative feedback loop on the conversion of active vitamin D
    25-hydroxycholecalciferol is NOT converted into 1,25 dihydroxycholecalciferol (active form of vitamin D) in kidneys
  • less Ca2+ is therefore reabsorbed in kidneys and absorbed by the GIT
28
Q

In a patient with primary hypoparathyroidism, which is essentially damage to the parathyroid gland, hypocalcaemia can be caused, decreased level of Ca2+ in the plasma. What would we expect to see in the levels of the following?

1 - Ca2+
2 - serum 25 OH vitamin D
3 - parathyroid hormone

A

1 - Ca2+ = decreased
2 - serum 25 OH vitamin D = decreased
3 - parathyroid hormone = decreased / normal

29
Q

In a patient with primary hypoparathyroidism (damage to the parathyroid gland), hypocalcaemia can be caused, decreased level of Ca2+ in the plasma. What are the 2 main causes of primary hypoparathyroidism that can then lead to hypocalcaemia?

A

1 - thyroidectomy or damage during neck surgery
2 - autoimmunity
3 - genetic mutations

30
Q

What is the role of magnesium (Mg2+) in calcium homeostasis?

A
  • involved in conversion of inactive vitamin D to active vitamin D
  • so converting 25-hydroxycholecalciferol to 1,25 dihydroxycholecalciferol in kidneys creating active vitamin D requires Mg2+
  • Mg2+ is also required for cAMP synthesis. cAMP allows PTH go be released, so low Mg2+ = low PTH
31
Q

What is the difference between primary and secondary hypoparathyroidism?

A
  • primary = damage or problem with parathyroid glands
  • secondary = damage or problem with hypothalamus or pituitary gland or not directly the parathyroid gland
32
Q

Which of the following can cause hypocalcaemia?

1 - Hypoparathyroidism
2 - Pseudohypoparathyrodism
3 - Hypomagnesaemia
4 - CKD
5 - Acute rhabdomyolysis
6 - Vitamin D deficiency
7 - all of the above

A

7 - all of the above

  • Hypoparathyroidism is the most common
  • can be caused by thyroid surgery, autoimmune, congenital disorders (DiGeorge syndrome or magnesium deficiency)
33
Q

What is the difference between hypoparathyroidism and pseudohypoparathyroidism?

A
  • hypoparathyroidism = low PTH
  • parahypoparathyroidism = normal PTH levels but tissue is unresponsive
34
Q

Why does acute rhabdomyolysis cause hypocalcaemia?

1 - rhabdomyolysis damages the kidneys
2 - rhabdomyolysis increases pH and Ca2+ binds with albumin
3 - rhabdomyolysis causes cell death, releasing phosphate that binds Ca2+
4 - all of the above

A

3 - rhabdomyolysis causes cell death, releasing phosphate that binds Ca2+

35
Q

How can pancreatitis cause hypocalcaemia?

1 - FFA bind with Ca2+ which becomes insoluble and precipitates out called saponification
2 - Ca2+ becomes trapped in inflamed pancreas and is excreted into the GIT
3 - pancreas collects Ca2+ that becomes fat necrotic tissue
4 - all of the above

A

1 - FFA bind with Ca2+ which becomes insoluble and precipitates out called saponification

36
Q

In a patient with secondary hypoparathyroidism (damage to the hypothalamus and/or pituitary gland, or not directly the parathyroid gland), hypocalcaemia can be caused, decreased level of Ca2+ in the plasma. Which of the following is NOT a cause of secondary hypoparathyroidism that can then lead to hypocalcaemia?

1 - pernicous aneamia
2 - renal failure
3 - low vitamin D
4 - GIT disorder

A

1 - pernicous aneamia

  • renal failure is the most common cause
  • GIT disorder = malabsorption of Ca2+
  • renal failure = Ca2+ not reabsorbed, phosphate not excreated and 25-hydroxycholecalciferol not cnverted to to 1,25 dihydroxycholecalciferol
37
Q

Which of the following medications does NOT cause hypocalcaemia?

1 - furosemide
2 - antineoplastic agents (e.g. mithramycin)
3 - phosphate
4 - calcitonin
5 - ACE-I

A

5 - ACE-I

  • furosemide = blocks Na+/Cl-/K+ channel, and Ca2+ depends on this channel, so Ca2+ is not reabsorbed
  • phosphate = binds calcium making it insoluble
  • calcitonin = opposite effects of PTH, so lowering Ca2+ levels
38
Q

In a patient with secondary hypoparathyroidism (damage to the hypothalamus and/or pituitary gland, or not directly the parathyroid gland), hypocalcaemia can be caused, decreased level of Ca2+ in the plasma. What would we expect to see if we measured the 3 following plasma markers?

1 - Ca2+
2 - serum 25 OH vitamin D (precursor for active vitamin D)
3 - parathyroid hormone

A

1 - Ca2+ = decreased or normal (can be normal as bone releases Ca2+)
2 - serum 25 OH vitamin D = decreased (no sun, not absorbed in GIT or reabsorbed in kidneys)
3 - parathyroid hormone = high (goes into overdrive but low serum 25 OH vitamin D)

39
Q

If patients who have primary or secondary hypoparathyroidism, they can have low levels of Serum 25 OH vitamin D, which means it will not be converted into the active form of vitamin D. This can cause softening in bones, what is this condition called?

1 - osteomyelitis
2 - osteosarcoma
3 - osteomalacia
4 - pagets

A

3 - osteomalacia
- causes microfractures

40
Q

If patients have primary or secondary hypoparathyroidism, they can have low levels of Serum 25 OH vitamin D, which means it will not be converted into the active form of vitamin D. This can cause softening in bones, called osteomalacia. What is this condition called in children?

1 - osteomyelitis
2 - rickets
3 - osteomalacia
4 - pagets

A

2 - rickets
- causes bowing of bones

41
Q

Which of the following is NOT a typical acute sign of hypocalcaemia, which is common in patients with hypoparathyroidism?

1 - mild cramps
2 - perioral numbness
3 - carpopedal spasm
4 - neuromuscular excitability and seizures
5 - constipation
6 - paresthesia (pins and needles in peripheries and lips)
7 - stridor due to laryngospasm

A

5 - constipation
- typically caused by hypercalcaemia

  • neuromuscular excitability = extracellular Ca2+ typically inhibits the opening of Na+ channels. So low Ca2+ means Na+ channels are more likely to open and cause depolarisation
42
Q

Which of the following is NOT a typical chronic sign of hypocalcaemia, which is common in patients with hypoparathyroidism?

1 - Skin changes (brittle, ridged nails, dry/scaly skin, enamel abnormalities, alopecia)
2 - Eyes (cataracts)
3 - Cardiovascular (reduced QT interval, CHF, hypotension)
4 - CNS (parkinsonian syndrome (due to basal ganglia calcification), pseudotumorcerebri, papilledema

A

3 - Cardiovascular (reduced QT interval, CHF, hypotension)
- HF and hypotension do occur but QT interval typically becomes prolonged

43
Q

When trying to diagnose a patient with hypocalcaemia we can try to elicit Chvosteks sign. What is this sign?

1 - toes dorsiflex when running a tip on sole of the foot
2 - inflation of a BP cuff elicits carpopedal spasm
3 - tap facial nerve over parotid gland causes the corner of the mouth to twitch
4 - pressing the back of hands together to elicit paraesthesia

A

3 - tap facial nerve over parotid gland causes the corner of the mouth to twitch

  • carpopedal spasm = flexion at the wrist, flexion at the metacarpophalangeal joints, extension of the interphalangeal joints and adduction of the thumbs and fingers.
44
Q

When trying to diagnose a patient with hypocalcaemia we can try to elicit Trosseaus sign. What is this sign?

1 - toes dorsiflex when running a tip on sole of the foot
2 - inflation of a BP cuff elicits carpopedal spasm
3 - tap facial nerve over parotid gland causes the corner of the mouth to twitch
4 - pressing the back of hands together to elicit paraesthesia

A

2 - inflation of a BP cuff elicits carpopedal spasm

  • carpopedal spasm = flexion at the wrist, flexion at the metacarpophalangeal joints, extension of the interphalangeal joints and adduction of the thumbs and fingers.
45
Q

In a patient with hypoparathyroidism, the are likley to have hypocalcaemia. What affect can low Ca2+ have on the heart, as detected by ECG?

1 - reduced PR interval
2 - reduced voltage
3 - LBBB
4 - QT prolongation

A

4 - QT prolongation
- the slow release of Ca2+ is what causes the prolongation
- increases risk of arrhythmias and torsade de points

46
Q

Which 2 of the following would be valid differentials for a patients with suspected hypo-parathyroidism?

1 - cushings disease
2 - CKD
3 - vitamin D deficiency
4 - graves disease

A

2 - CKD
3 - vitamin D deficiency

47
Q

In patients with hypo-parathyroidism, all of the following are typically given, EXCEPT which one?

1 - Ca2+
2 - vitamin D
3 - Mg2+
4 - synthetic PTH

A

3 - Mg2+
- can be beneficial as is important in converting vitamin D pre-cursor into active vitamin D and required to create cAMP, which is needed to release PTH

48
Q

In a patient with acute hypocalcaemia that is an emergency situation, which of the following is NOT routinely performed?

1 - correct pH and H+ levels in acidosis before correcting Ca2+
2 - monitor digoxin toxicity when administering Ca2+
3 - correct Mg2+ levels
4 - check PTH prior to treatment
5 - administer Sandocal

A

1 - correct pH and H+ levels in acidosis before correcting Ca2+

  • correct Ca2+ 1st
  • then correct H+ causing metabolic acidosis
49
Q

When trying to diagnose a patient with hypocalcaemia, which of the following would NOT be typically measured?

1 - LFTS
2 - Serum Ca.
3 - PTH—the presence of a low, or even normal
4 - U&E
5 - Total vitamin D
6 - PO4+
7 - Mg2+

A

1 - LFTS

  • U&E = to rule out CKD