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1
Q

Hormones that increase calcium + how are they made?

A

PTH (parathyroid glands)

Calcitriol = activated Vit D = 1,25-hydroxy vitamin D (skin + UV light)

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2
Q

Hormone that decrease calcium + how is it made?

A

Calcitonin

Produced in parafollicular cells within thyroid)

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3
Q

Explain the steps of active Vit D synthesis

A

SKIN, INTESTINES
diet + UV -> vit D

LIVER
25-hydroxylase converts to 25-hydroxy vit D

KIDNEYS
1a-hydroxylase converts to calcitriol

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4
Q

Causes of raised prolactin - the 6 p’s

A 
pregnancy
prolactinoma
physiological
polycystic ovarian syndrome
primary hypothyroidism
phenothiazines, metoclopramide, domperidone
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5
Q

Compare the effects of PTH and calcitriol on calcium and phosphate

A

PTH:
↑ Calcium
↓ ↓ Phosphate (phosphate trashing)

CALCITRIOL:
↑ ↑ Calcium
↑ Phosphate

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6
Q

State 3 organs affected by PTH and the outcome for each

A 
KIDNEYS- 
- 1α-hydroxylase stimulation
- ↑ calcium reabsorption 
- ↑ phosphate excretion
BONE- 
- ↑ bone reabsorption

SMALL INTESTINE

  • ↑ calcium absorption
  • (↑ phosphate absorption)
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7
Q

State 3 organs affected by calcitriol and the outcome for each

A 
KIDNEYS- 
- ↑ calcium reabsorption 
-(↑ phosphate reabsorption)
BONE- 
- ↑ bone reabsorption

SMALL INTESTINE

  • ↑ calcium absorption
  • ↑ phosphate absorption
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8
Q

Which hormone decreases blood calcium levels?

A

Calcitonin

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9
Q

Which hormone, out of PTH and calcitriol, raises blood calcium levels the most?

A

Calcitriol

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10
Q

Which enzyme does PTH activate in the kidneys?

A

1α-hydroxylase

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11
Q

Which hormone increases urinary phosphate excretion?

A

PTH (=phosphate trashing hormone)

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12
Q

briefly explain the parathyroid axis

A
  • decreased calcium
  • parathyroid glands produce PTH
  • PTH stimulates 1-a hydroxylase to produce more calcitriol
    calcitirol + PTH increase calcium
  • negative feedback on parathyroid glands
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13
Q

State 2 causes of primary hyperparathyroidism

A

Parathyroid adenoma

Parathyroid hyperplasia

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14
Q

State 2 causes of secondary hyperparathyroidism

A

Vitamin D deficiency
CKD
Liver disease

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15
Q

What is another term used for secondary hyperparathyroidism?

A

osteomalacia

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16
Q

What are calcium and phosphate levels in:

  • Primary hyperPTH
  • Secondary hyperPTH
  • Tertiary hyperPTH
A

Primary hyperPTH

  • ↑ calcium
  • ↓ phosphate

Secondary hyperPTH

  • ↓ calcium
  • ↓ phosphate (unless CKD = ↑ phosphate)

Tertiary hyperPTH (autonomous PTH secretion)

  • ↑ calcium
  • ↑ phosphate
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17
Q

Which two forms of hyperPTH show a high phosphate?

A

Chronic kidney disease:

  • Secondary hyperPTH
  • Tertiray hyperPTH

Kidneys cannot excrete phosphate

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18
Q

What causes tertiary hyperPTH?

A

CKD

develops from secondary hyperPTH

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19
Q

Causes of high calcium?

A

HIGH PTH CAUSES

  • Primary hyperPTH
  • Tertiary hyperPTH

LOW PTH CAUSES

Malignancy:
- Bone metastases
- Haem (multiple myeloma)
- Paraneoplastic e.g. lung
SCC

Sarcoidosis

Thiazide diuretics

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20
Q

Symptoms of hypercalcaemia

A

“stones, bones, thrones, abdominal groans and psychiatric moans”

  • Renal stones
  • Fractures, bones
  • Polyuria, polydipsia
  • Abdo- nausea, constipation, pancreatitis
  • Depression, anxiety
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21
Q

Causes of low calcium?

A

HIGH PTH CAUSES

  • Secondary hyperPTH
  • aka osteomalacia
  • aka vit D deficiency

LOW PTH CAUSES

  • surgical complications- post thyroidectomy for Grave’s
  • autoimmune hypoparathyroidism (rare)
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22
Q

Symptoms of hypocalcaemia

‘Cats go numb’

A

Convulsions
Arrhythmias (eg prolonged QT)
Tetany
Parasthesia (hands, mouth, feet, lips)

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23
Q

2 clinical signs of hypocalcaemia

A

Trousseau’s sign (carpopedal spasm caused by inflating BP cuff above SBP)
Chvostek’s sign (twitching of the facial muscles in response to tapping over facial nerve)

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24
Q

Which is more likely to be found in a pancreatitis patient: hypercalcaemia or hypocalcaemia?

A

Hypocalcaemia- due to saponification

Damage to pancreas leads to autodigestion of pancreas (autolysis)

Calcium binds to digestive ‘gunk’ + this draws out of blood

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25
Will bone cancer cause high PTH or low PTH
Low PTH (due to negative feedback)
26
Risk factors for PT gland hyperplasia
MEN-1 or MEN-2 | Hypertension
27
Which conditions come up in: MEN-1 (PPP) MEN-2 (PTP)
MEN-1: - PT hyperplasia - Pituitary tumours - Pancreatic tumours MEN-2: - PT hyperplasia - medullary Thyroid cancer - Phaeochromocytoma
28
signs and symptoms of hyperPTH
Often asymptomatic Hypercalcaemia: ”Stones, bones, thrones, abdominal moans, psychiatric overtones”
29
Define secondary hyperPTN
disorder of bone mineralisation
30
Causes of secondary hyperPTH
``` Vitamin D deficiency - Poor dietary intake - Poor sunlight - Malabsorption Chronic kidney disease Liver disease ```
31
Signs and symptoms of secondary hyperPTH
``` ADULTS Fractures/bone pain Proximal myopathy Fatigue Hypocalcaemia:”CATs go numb” ``` CHILDREN (Rickets) Bowed legs Knock knees
32
3 endocrine causes of proximal myopathy (COT)
Cushing’s Osteomalacia Thyrotoxicosis
33
Investigations for hyperparathyroidism
``` Physical examination (cardio/resp/abdo/neuro) Basic observations ``` Bloods - (FBC, CRP) - U&E - LFTs - ALP - Calcium - Phosphate - PTH Imaging - X-rays/CT (extent of bone disease) - Cervical U/S (before surgery, adenoma)
34
``` State the level of: Calcium Phosphate PTH ALP in primary hyperPTH ```
Calcium ↑ Phosphate ↓ PTH ↑ (or ↔) ALP ↔
35
``` State the level of: Calcium Phosphate PTH ALP in secondary hyperPTH (osteomalacia) ```
Calcium ↓ Phosphate ↓ PTH ↑ (↓ in CKD) ALP ↑
36
What 3 signs might you see of primary hyperPTH on xray?
- Subperiosteal bone resorption (usually radial) - Acro-osteolysis (resorption of distal phalanges) - Pepper pot skull (resorption by PTH)
37
What do you see in x-rays of children with secondary hyperPTH?
Rachitic rosary = nodularity at costochondral junctions
38
What do you see in x-rays of adults with secondary hyperPTH?
Looser’s pseudofractures Wide, transverse lucencies with sclerotic borders traversing partway through a bone, usually perpendicular to the involved cortex
39
Management of acute hypercalcaemia
IV fluids | Bisphosphonates (if calcium remains high)
40
Management of primary hyperPTH (associated risk)
Total parathyroidectomy - risk of recurrent laryngeal nerve damage (hoarseness) If unsuitable for surgery - Cinacalcet - calcimemetic- acts to negatively feedback on PTH axis
41
Management of secondary hyperPTH
IV calcium infusion (calcium gluconate) | also used to treat hyperkalaemia
42
Management of acute hypocalcaemia
Medical: - Calcium - Inactive vitamin D (ergocalciferol) - Active vitamin D (alfacalcidol) in CKD as cannot complete second hydroxylation step
43
Which hyperPTH is ALP high?
secondary
44
Define Paget's
disorder of bone remodelling (i.e. formation and resorption) – genetic factors play a role
45
3 phases of Paget's
LYTIC PHASE- hyperactive osteoclasts > resorption SCLEROTIC PHASE- compensation by osteoblasts MIXED PHASE- hyperactive osteoblasts > formation (woven bone, not lamellar) So you get lots of immature bone leading to pain, fragility fractures
46
RF for Paget's
Elderly | FHx
47
Number of bones affected by Paget's
25% of cases: monostotic | 75% of cases: polyostotic
48
Symptoms of Paget's
Often asymptomatic - Fragility fractures - Bone pain (insidious onset)- skull, pelvis, femur Nerve compression- due to narrowing of foramina - Hearing loss (sensorineural- vestibulococular nerve) - Sciatica
49
Signs of Paget's
Bone enlargement/bossing | Warm skin over painful area (high metabolic activity)
50
Investigations for Paget's
Bloods - (FBC, CRP) - U&E - LFTs (ALP) - Calcium - Phosphate - PTH - Serum CTX (bone resorption marker) - Serum P1NP (bone formation marker) Imaging - X-rays - Bone scan- a type of nuclear medicine imaging test- using Tech99 tracer Looks at areas of increased metabolic activity
51
``` State the level of: Calcium Phosphate PTH ALP in Paget's ```
Calcium ↔ Phosphate ↔ PTH ↔ ALP ↑↑
52
define osteoporosis
low BMD
53
RF for osteoporosis (primary and secondary causes)
PRIMARY Post-menopausal Elderly SECONDARY Drugs – steroids, thyroxine, alcohol Endo – Cushing’s disease, hyperPTH, hyperT GI – coeliac disease, IBD (malabsorption > low vitD)
54
Signs and symptoms of osteoporosis
Often asymptomatic Fragility fractures Back pain
55
Classic fractures in osteoporosis
Hip – neck of femur (NOF) Wrist – Colles’ fractures Lumbar spine - vertebral wedge fractures (these can be asymptomatic- explain why older people 'shrink') Shoulder - neck of humerus
56
``` State the level of: Calcium Phosphate PTH ALP in osteoporosis ```
EVERYTHING NORMAL
57
Investigations for osteoporosis
``` Bloods (FBC, CRP) U&E LFTs (ALP) Calcium Phosphate PTH ``` Imaging - X-rays - DEXA scan
58
2 scores used to diagnose osteoporosis. Which one is more useful?
T-score: Patient’s BMD compared to young, healthy adult Z-score: Patient’s BMD compared to age-matched BMD T-score is used more often: >-1.0 = normal -1.0 and -2.5 = osteopaenia
59
What is T score used to calculate?
FRAX score: 10 year risk of developing fragility fractures Which can help decide if Tx is required
60
A 42 year old Pakistani woman attends her GP appointment. She has been experiencing non-specific pain in her legs alongside muscle weakness for a month. Her X-ray shows Looser's pseudofractures What is the most appropriate treatment option? ``` A  Increase calcium intake in diet B  Bisphosphonates C Calcium and vitamin D supplements D Total parathyroidectomy E  Recombinant PTH ```
Calcium and vitamin D supplements diagnosis = osteomalacia “Pakistani/Arabic women” is a common buzzword for vitamin D deficiency (due to the unfair generalisation that these women will be wearing hijabs and thus will not produce enough vitamin D from sunlight)
61
Treatment of osteoporosis/pagets
bisphosphonates (alendronic acid)
62
A 58 year old post-menopausal woman was diagnosed with a fragility fracture. Her past medical history includes a myocardial infarction at the age of 47, and rheumatoid arthritis for which she is taking prednisolone. Her blood results are normal What is the most likely underlying diagnosis? ``` A  Osteomalacia B  Primary hyperparathyroidism C  Paget’s disease D  Tertiary hyperparathyroidism E  Osteoporosis ```
osteoprosis- RF: Steroids can cause osteoporosis Menopause can cause osteoporosis (since oestrogen is protective of bones)
63
In which 2 bone conditions is calcium normal?
osteoporosis | Pagets
64
In which bone condition is calcium low?
osteomalacia / secondary hyperPTH
65
In which bone conditions is calcium high?
primary/tertiary hyperPTH, malignancy

Year 3 (38 decks)

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