Hypo-parathyroidism / Hypocalcaemia Flashcards
What is the prevalence of hypoparathyroidism?
1 - 20-40 / 100
2 - 20-40 / 1000
3 - 20-40 / 10,000
4 - 20-40 / 100,000
4 - 20-40 / 100,000
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
4 - NaCa2+ rebasorbed from the renal tubules
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
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
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?
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
Which vitamin promotes Ca2+ uptake?
1 - vitamin B12
2 - vitamin C
3 - vitamin B1
4 - vitamin D
4 - vitamin D
- aprox 35%
Is Ca2+ absorbed well in the intestines from the Ca2+ we consume in the diet?
- no
- divalent (+2) are poorly absorbed
- aprox 90% is passed through faeces
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
4 - skin
- vitamin D is absorbed and this helps with Ca2+, but it is not absrobed by the skin
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
4 - Parathyroid hormone
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)
4 - 84 residues (amino acids)
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?
- undergo proteolytic cleavage
- amino acids 1-34 make up active parathyroid hormone
- amino acids 25-84 make up inactive parathyroid hormone
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
2 - calcium sensing receptor (CaSR)
- GPCR
- specifically Gaq
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)
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
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)
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
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
5 - skeletal muscle ER
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
1 - hypercalcaemic
2 - hypocalcaemic
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
2 - osteoblasts
- cells that normally build the bones
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
1 - receptor activator of nuclear factor kappa-B ligand (RANKL)
2 - macrophage colony-stimulating factor (M-CSF)
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
2 - interact with a preosteoclast cell (breaking down bone) that form mature osteoclast
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
3 - osteoclasts secrete enzymes that degrade bone and release Ca2+ into the blood
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+
3 - phosphate
- phosphate binds Ca2+ in blood
- less phosphate means more biologically avaialble Ca2+
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+
2 - Ca2+
- PTH binds with receptors and increases Ca2+ reabsorption through Na+/Ca2+ co-transporter
How does vitamin D that is absorbed by the skin through sunlight get turned into active vitamin D?
- 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
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
3 - active vitamin D enters the enterocytes, cells lining the GIT
- binds with Ca2+ receptors and actively transports Ca2+ into plasma
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?
- 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
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?
- Ca2+ absorption pathway will be continually active
- 25-hydroxycholecalciferol can be stored
- overall this can lead to hypercalcaemia
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
3 - rhabdomyolysis causes cell death, releasing phosphate that binds Ca2+
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
1 - FFA bind with Ca2+ which becomes insoluble and precipitates out called saponification
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
2 - rickets
- causes bowing of bones
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
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.
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
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.
