Calcium Metabolism & Bone Physiology Flashcards
1
Q
Which hormones increase blood calcium levels?
Where are they synthesised?
A
- PTH from the parathyroid glands
- Calcitriol (activated vitamin D) from the skin & UV light
2
Q
What hormones reduce calcium levels in the blood?
Where are they synthesised?
A
- calcitonin reduces serum calcium
- this is produced by parafollicular cells in the thryoid gland
3
Q
What are the stages involved in turning vitamin D from UV light / diet into calcitriol?
A
- vitamin D comes from the diet and UV light
- there is a first hydroxylation step in the liver
25-hydroxylase converts vitamin D into (25-(OH)D3)
- there is a second hydroxylation step in the kidneys
1a-hydroxylase coverts (25-(OH)D3) into calcitriol (activated vitamin D)
- PTH stimulates 1a-hydroxylase in the kidneys to increase the calcium levels
4
Q
What are the actions of PTH on the kidneys?
A
- stimulation of 1a-hydroxylase
- increased calcium reabsorption
- increased phosphate excretion
PTH is known as “Phosphate Trashing Hormone” as it lowers phosphate levels in the blood
5
Q
A
6
Q
What are the actions of PTH on the bone and small intestines?
A
- increased bone resorption
- increased calcium absorption in the small intestines
7
Q
What are the influence of calcitriol on the kidneys, bone and small intestines?
A
- increased calcium reabsorption in the kidneys
- increased bone formation
- increased calcium absorption and increased phosphate absorption in the small intestines
8
Q
Which hormone is better at increasing calcium levels?
A
- vitamin D (calcitriol) is better at increasing calcium levels than PTH
- calcitriol increases both calcium and phosphate levels
- PTH increases calcium levels but reduces phosphate levels
9
Q
What is the parathyroid axis and how does it work?
A
- when calcium levels fall, more PTH is released by the parathyroid glands
- this stimulates 1a-hydroxylase in the kidneys to produce more calcitriol (activated vitamin D)
- this leads to an increase in calcium levels
- both calcitriol and a rise in calcium levels feedback on the parathryroid glands to reduce secretion of PTH
10
Q
What happens in primary hyperparathyroidism?
How are calcium and phosphate levels affected?
A
- this is a disorder of the parathyroid glands, in which they become overactive
- the parathyroid glands secrete excess amounts of PTH
- this causes an increase in the level of calcium in the blood
- this also leads to a reduction in the level of phosphate in the blood
11
Q
What are examples of things that can cause primary hyperparathyroidism?
A
- parathyroid adenoma
- parathyroid hyperplasia
12
Q
What is another name for secondary hyperparathyroidism?
Why does this occur?
A
also known as osteomalacia
there is excessive secretion of PTH by the parathyroid glands in response to hypocalcaemia
this hypocalcaemia occurs as a result of low levels of calcitriol, due to renal or liver failure or vitamin D deficiency
13
Q
What are common causes of secondary hyperparathyroidism and how do they affect levels of calcium and phosphate?
A
Chronic kidney disease:
- this affects 1a-hydroxylase in the kidneys, reducing levels of calcitriol
- this leads to reduced levels of calcium
- there are increased levels of phosphate as the renal system cannot excrete it
Liver disease:
- this affects 25-hydroxylase in the liver, reducing levels of calcitriol
- there is reduced levels of calcium
Vitamin D deficiency:
- there are reduced levels of calcitriol
- levels of PTH are still high, so there are reduced levels of phosphate
14
Q
What causes tertiary hyperparathyroidism?
How are levels of calcium and phosphate affected?
A
it occurs as a result of secondary hyperparathyroidism in chronic kidney disease
there is autonomous PTH secretion
this leads to increased calcium and phosphate levels
(phosphate stays high as the kidneys cannot excrete it)
15
Q
What are the high PTH causes of hypercalcaemia?
A
- primary hyperparathyroidism
- tertiary hyperparathyroidism
16
Q
What are the low PTH causes of hypercalcaemia?
A
-
malignancy
- bone metastases
- haem e.g. multiple myeloma
- paraneoplastic syndromes e.g. lung squamous cell carcinoma
- sarcoidosis
- thiazide diuretics
17
Q
How can paraneoplastic syndromes, such as lung SCC, cause hypercalcaemia?
A
paraneoplastic phenomena can change hormone levels
lung squamous cell carcinoma leads to the release of PTH related peptides
these act like PTH, increasing the levels of calcium in the blood
18
Q
What are the symptoms and signs of hypercalcaemia?
How can these be remembered?
A
- renal stones
- fractures, bone pain
- polyuria , polydipsia
- abdominal signs - nausea, constipation, pancreatitis
- psychiatric conditions - depression, anxiety
“Stones, bones, thrones, abdominal moans, psychiatric overtones”
19
Q
How can thiazide diuretics influence levels of electrolytes in the blood?
A
- hyponatraemia
- hypokalaemia
- hypercalcaemia
20
Q
What are the high PTH causes of hypocalcaemia?
A
- secondary hyperparathyroidism (osteomalacia)
21
Q
What are the low PTH causes of hypocalcaemia?
A
-
surgical complications (iatrogenic)
- e.g. thyroidectomy due to Graves’ disease
- the PTH glands may be removed accidentally, resulting in reduced PTh secretion
- auto-immune hypoparathyroidism
22
Q
What are the symptoms and signs of hypocalcaemia?
How can these be remembered?
A
” CATs go numb”
- C - convulsions
- A - arrhythmias (e.g. prolonged QT interval)
- T - tetany
- paraesthesia (hands, mouth, feet, lips)
23
Q
What are the 2 clinical signs of hypocalcaemia and how are they performed?
A
Chvostek’s Sign:
- twitching of the facial muscles in response to tapping over the area of the facial nerve
Trousseau’s Sign:
- when a blood-pressure cuff is inflated to a level above systolic pressure for 3 minutes, there is spasm of the hand
24
Q
What is the relationship between hypercalcaemia and pancreatitis?
A
hypercalcaemia is one of the causes of pancreatitis
25
What is the relationship between hypocalcaemia and pancreatitis?
Why does this happen?
hypocalcaemia is likely to be **seen** in a patient with pancreatitis due to **_saponification_**
* digestive enzymes in the pancreas tend to **digest the pancreas itself** (**_autolysis_**)
* this forms a mess which **calcium then binds to** (saponification)
* **_serum calcium levels are reduced_** as the calcium has bound to the enzyme mess in the pancreas
26
What is the definition of primary hyperparathyroidism?
What are the risk factors?
this involves **_adenoma / hyperplasia_** of the parathyroid glands
**Risk factors:**
* MEN-1 or MEN-2
* hypertension
27
What are the characteristics of MEN-1 and MEN-2 disease?
* multiple endocrine neoplasia (MEN) involves **_tumours_** of the **_endocrine glands_**
**MEN - 1:**
* parathyroid hyperplasia
* pituitary tumours
* pancreatic tumours (islet cells)
**MEN - 2:**
* parathyroid hyperplasia
* medullary thyroid tumours
* pheochromocytomas
28
What are the signs and symptoms of primary hyperparathyroidism?
* it is often **_asymptomatic_** as calcium is slightly raised, but not massively high
* signs of **hypercalcaemia**
* *"stones, bones, thrones, abdominal moans, psychiatric overtones"*
29
What is the definition of secondary hyperparathyroidism?
What can cause this?
it is a **_disorder of bone mineralisation_** that can be caused by:
## Footnote
(aka osteomalacia / rickets in children)
* **vitamin D deficiency (1)**
* poor dietary intake
* poor exposure to sunlight
* malabsorption (e.g. in coeliac / Crohn's disease)
* **chronic kidney disease (2)**
* **liver disease (3)**
30
What are the signs and symptoms of secondary hyperparathyroidism in adults and children?
***_Adults:_***
* fractures / bone pain
* proximal myopathy
* symmetrical weakness of proximal upper and/or lower limbs
* fatigue
* hypocalaemia
* *"CATs go numb"*
***_Children:_***
* bowed legs
* knock knees
31
What are the endocrine causes of proximal myopathy?
remember COT:
* **Cushing's disease**
* could also be caused by taking a lot of steroids e.g. for myalgia
* **osteomalacia**
* **thryotoxicosis**
32
What are the investigations for primary and secondary hyperparathyroidism?
* physical examination (cardio / resp / abdo / neuro)
* basic observations
* blood test:
* (FBC, CRP)
* **U&Es**
* **LFTs - particularly ALP**
* **calcium**
* **phosphate**
* **PTH**
33
What blood test results would you expect to see in primary hyperparathyroidism?
* **calcium** is **_elevated_**
* **phosphate** is **_reduced_**
* **PTH** is **_elevated or normal_**
* **ALP** is **_normal_**
in a healthy person, there is a **negative feedback loop** that results in **lowering PTH levels** when there is hypercalcaemia
**_high PTH_** or **_inappropriately normal PTH_** suggests that the **negative feedback mechanism is not working properly**
34
What would blood test results look like in someone with secondary hyperparathyroidism (osteomalacia)?
* **calcium** levels are **_reduced_**
* **phosphate** levels are **_reduced in vitamin D deficiency_** and **_raised in CKD_**
* **PTH** levels are **_elevated_**
* **ALP** is **_elevated_**
ALP is high as it is released by osteoblasts in osteomalacia
35
How can LFTs be used to tell the difference between primary and secondary hyperparathyroidism?
* in **primary** hyperparathyroidism, there is **_no change in ALP_**
* in **secondary** hyperparathyroidism, **_ALP is elevated_**
36
What other tests might be done in primary and secondary hyperparathyroidism?
* X-rays are performed to see the extent of bone disease
* a cervical USS is done prior to surgery
37
What sign might be seen on X-ray of the hands in primary hyperparathyroidism?
**_*subperiosteal bone resorption* (radial aspects)_**
* this is a result of **_high calcium_** and **_low phosphate_**
* affects the **radial aspects of the fingers** and the radial & ulnar aspects of the thumb
* there is also **_acro-osteolysis_**
* this is **erosion at the fingertips** where the bones aren't clearly defined and appear fuzzy
38
What sign is visible on the skull in someone with hyperparathyroidism?
***_Pepper pot skull_***
the skull looks fuzzy due to high levels of PTH
39
what sign is visible on the ribs of someone with secondary hyperparathyroidism?
***_Rachitic rosary_***
this is prominent knobs of bone at the costochondral junctions
this creates the appearance of beads under the skin of the rib cage
40
What type of fractures are seen in someone with secondary hyperparathyroidism?
***_Looser's pseudofractures_***
these are half-fractures that are specific for secondary hyperPTH
shown as a **radioluscent line** with **sclerosis at the margins**
41
What are the treatments for acute hypercalcaemia in primary hyperparathyroidism?
acute hypercalcaemia is a **_medical emergency_**
* **_IV fluids_** are given to **dilute the calcium** in the short-term
* **_bisphosphonates_** are given if the calcium remains high
42
What are the treatments of primary hyperparathyroidism, after the acute hypercalcaemia has been resolved?
***_First line - Surgery:_***
* total parathyroidectomy
***_Second line - Medical:_***
* for patients unsuitable for surgery
* a **_calcimemetic drug_**, such as **_Cinacalcet_**, is given
* this **mimics the action of calcium** to try and lead to lowering of PTH via negative feedback loop
43
What are the risks associated with total parathyroidectomy?
there is a risk of **_recurrent laryngeal nerve damage_**
this results in **hoarseness** of the voice
44
What are the treatments for acute hypocalcaemia in osteomalacia?
What else is this used to treat?
* **IV calcium infusion** of **_calcium gluconate_**
* this is also used to treat **hyperkalaemia** to stabilise the myocardium so that it is **less susceptible to arrhythmias**
45
What are the treatments for osteomalacia after acute hypocalcaemia has been resolved?
treatments are medical:
* **calcium**
* **_ergocalciferol_** (inactive form of vitamin D)
46
How is the treatment different for osteomalacia due to CKD?
* ergocalciferol is not given
* **_alfacalcidol_** is given instead - this is an **active form of vitamin D**
* an **_active form_** of vitamin D needs to be given as the second hydroxylation step cannot occur in CKD to activate vit D
47
What is Paget's disease?
a **_disorder of bone remodelling_** (i.e. formation and resorption)
it is not entirely clear what causes it, but **genetic factors** play a role
48
What are the 3 stages involved in the development of Paget's disease?
***_1 - Lytic phase:_***
* **hyperactive _osteoclasts_** lead to excess **bone resorption**, causing bone lysis
***_2 - Mixed phase:_***
* **_osteoblasts_** try to compensate
* there is both **bone formation and resorption** occurring
***_3 - Sclerotic phase:_***
* **hyperactive _osteoblasts_** lead to excess **bone formation**
* this is **woven, immature bone**, opposed to lamellar bone
49
What are the symptoms of Paget's disease?
Who does it tend to affect?
* it tends to affect **elderly people** and there is usually a **family history**
* it is often **asymptomatic**
* **_fragility fractures_**
* **_bone pain_** in the **skull, pelvis** and **femur**
* this is an insidious onset (gradually gets worse over time)
50
What is a fragility fracture and wy does this occur in Paget's disease?
a fracture that occurs when **_pressures are low_** (low impact needed to cause it)
this occurs due to the **_weakened immature woven bone_** present in Paget's disease
the smallest movements or trauma can cause fractures
51
What can happen to nerves in Paget's disease?
What are the resulting symptoms?
the nerves can become **_compressed_**
this can lead to **_sensorineural hearing loss_** and **_sciatica_**
during the **sclerotic phase**, where the bones are enlarging, the **foramina** within the bones **becomes smaller**
this leads to **_impingement of the nerves_**
52
What are the clinical signs that might be present in Paget's disease?
* bone **enlargement / bossing**
* **warm skin** over painful area (due to high metabolic activity)
53
What are the investigations carried out in Paget's disease?
* physical examination (cardio / resp / abdo / neuro)
* basic observations
* blood tests
* (FBC, CRP)
* U&Es
* **LFTs - particularly ALP**
* **calcium**
* **phosphate**
* **PTH**
54
What will the results of a blood test for Paget's disease show?
* calcium, phosphate and PTH are normal
* **ALP will be _extremely raised_**
55
What types of scans are performed in investigations for Paget's disease?
* **serum CTX** - bone resorption marker
* **serum P1NP** - bone formation marker
* **X-rays** and **bone scan** using Tec99
56
What is involved in the bone scan to investigate Paget's disease?
* a tracer is given that is absorbed by the bone and picked up on scans
* **_dark areas_** show highly functioning areas where **Paget's disease is present**
57
What is the definition of osteoporosis?
**_reduced bone density_**
osteoporosis can be primary or secondary
58
What are the causes of primary osteoporosis?
Who does this tend to affect?
* **elderly people**
* **post-menopausal**
* this is due to **_reduced oestrogen levels_** as oestrogen is protective of bones
59
What are the causes of secondary osteoporosis?
Who is more likely to get this?
* **_drugs_** - ***steroids***, ***thyroxine***, ***alcohol***
* **_endocrine_** - ***Cushing's disease***, hyperparathyroidism, hyperthyroidism
* **_GI_** - coeliac disease, IBD
* secondary causes are more common in **younger people**
60
What are the signs and symptoms of osteoporosis?
* it is often **asymptomatic**
* there may be **_fragility fractures_** and **_back pain_**
61
What are the classic osteoporosis fracture types?
* hip - neck of femur (NOF)
* wrist - Colles' fracture
* lumbar spine - vertebral wedge fractures
* shoulder - neck of humerus
62
What investigations are carried out in osteoporosis?
* physical examination (cardio / resp / abdo / neuro)
* basic observations
* bloods
* (FBC, CRP)
* U&Es
* **LFTs - in particular ALP**
* **calcium**
* **phosphate**
* **PTH**
63
What will the blood tests show in osteoporosis?
on the blood tests, everything should be normal
64
What types of investigations are performed that are specific to osteoporosis?
**_DEXA scans_**
* **_T-score_** - patient's BMD compared to a **young, healthy adult**
* **_Z-score_** - patient's BMD compared to **age-matched BMD**
(BMD = bone mineral density)
65
What score is used to determine osteoporosis from the DEXA scan?
**_T scores_** are used to determine whether someone has osteoporosis
this is when T score is **_less than -2.5_**
it is **_osteopaenia_** when the T-score is **between -2.5 and -1**
there is **sclerosis** and bones are **thicker** than the average person if T-score is **greater than 1**
66
What score can the DEXA score be used to calculate?
the DEXA score is used to calculate the **_FRAX score_**
this is the **10 year risk** of developing **fragility fractures**
* this can help to decide **whether treatment is required**
67
