CBL

Question 1

Percentage calcium bound to plasma proteins?

Answer 1

40% bound to plasma protein (primarily albumin)

Question 2

Where is calcitonin released from?

Answer 2

Calcitonin is released from the parafollicular cells of the thyroid gland in response to high levels of ionized calcium, will decrease calcium resorption from bone.

Question 3

What stimulates parathyroid hormone release?

Answer 3

Low calcium concentration.

Question 4

Name the major two causes of secondary hyperparathyroidism?

Answer 4

Low vitamin D and chronic renal failure.

Question 5

Calcium and PTH levels in secondary hyperparathyroidism?

Answer 5

Low or normal calcium

Elevated PTH

Question 6

Cause of tertiary hyperparathyroidism?

Answer 6

Long term secondary hyperparathyroidism leading to parathyroid gland hyperplasia.

Question 7

Calcium and PTH levels in primary hyperparathyroidism?

Answer 7

Elevated calcium

Elevated PTH

Question 8

Calcium and PTH levels in tertiary hyperparathyroidism?

Answer 8

Elevated calcium

Elevated PTH

Question 9

Histology of parathyroid cells?

Answer 9

Consists mainly of chief cells and some oxyphil cells

Chief cells secrete PTH

Question 10

What is the trigger for increased PTH secretion?

Answer 10

Drop in calcium concentration (even a very small drop)

Question 11

By what mechanisms does PTH increase calcium?

Answer 11

1. ) Osteolysis: upregulates calcium pump in osteocyte membranes -> calcium pumped out of osteocytes into “bone fluid” -> gradient created -> calcium absorbed from bone into fluid -> ↑calcium in ECF
2. ) Activation of osteoclasts: ↑ expression of RANKL -> ↑binding of RANKL to RANK -> upregulation of existing osteoclasts and ↑ formation of new osteoclasts from precursors -> ↑ osteoclastic resorption of bone

3.) Increased calcium reabsorption in kidneys:
Occurs in DCT, collecting tubules Prevents calcium excretion from depleting bone stores

4.) Increased activation of vitamin D Therefore indirectly increases intestinal absorption of calcium

Question 12

What are the effects/functions of Vitamin D?

Answer 12

1. ) Increases intestinal calcium absorption: ↑ calbindin production in intestinal cells -> ↑transport of calcium at brush border -> ↑calcium absorption -> indirectly promotes new bone formation
2. )↑ renal reabsorption of calcium
3. ) Promotes intestinal phosphate absorption
4. ) In large quantities, promotes bone resorption via ↑ osteoclastic activity

Question 13

Where is calcitonin secreted from?

Answer 13

Secreted by C-cells of thyroid gland

Question 14

Function of calcitonin?

Answer 14

Weakly affects plasma calcium in adults but has opposite effects to PTH
Decreases plasma calcium concentration by ↓ absorptive activity of osteoclasts and ↓ formation of new osteoclasts, therefore promoting bone formation

Question 15

Function phosphorus?

Answer 15

Cell membranes (phospholipids)
Enzymatic reactions (phosphorylation)
Phosphate buffer system
Bony calcification
Glucose metabolism

Question 16

Acidosis effect on ionized calcium concentration?

Answer 16

Acidosis causes ↓ plasma protein binding  ↑ ionised calcium

Question 17

Alkalosis effect on ionized calcium concentration?

Answer 17

Alkalosis causes ↑ plasma protein binding  ↓ ionised calcium

Question 18

Effect of phosphorus on calcium levels?

Answer 18

↑phosphate -> increased calcium

phosphate binding -> ↓ ionized calcium

Question 19

Typical presentation of hypercalcaemia?

Answer 19

Easy fatigue, muscle weakness, anorexia, weight loss
Depression
Polyuria, polydipsia
Constipation

Renal stones
Pancreatitis
Osteoporotic fractures
Peptic ulcers

Severe hypercalcaemia: confusion, cognitive decline, coma

Question 20

Typical presentation depression

Answer 20

DIGSPACES

Question 21

Typical presentation chronic renal failure/impairment

Answer 21

Sx: ankle swelling, pruritus, rash, constitutional sx
Risk: hypertension, diabetes, obesity, smoking

Question 22

Typical presentation hypothyroidism

Answer 22

Sx: cold intolerance, psychomotor retardation, weight gain, oligomenorrhoea, constipation, goitre
Risk: female, FHx, other autoimmune diseases

Question 23

Typical presentation Diabetes mellitus

Answer 23

Sx: polyuria, nocturia, polydipsia, peripheral neuropathy,
ulcers, infections, blurred vision
Risk: obesity, FHx, older age, Cushing’s, sedentary, metabolic syndrome

Question 24

Typical presentation anaemia (iron deficiency)

Answer 24

Sx: SOB, blood loss (melaena, haematochezia, menorrhagia, etc.), nail changes
Risk: older age, FHx of bowel cancer, NSAIDs, alcohol use, pregnant, vegan, coeliac

Question 25

Acute management symptomatic hypercalcaemia

Answer 25

Diagnose and treat underlying cause (If serum calcium >3.5mmol/L and/or symptomatic) Aggressively rehydrate with IV saline Bisphosphonates: pamidronate or zoledronate Side effects: flu-like sx, myalgia, bone pain, n&v, headache Calcitonin Primary HPT: consider parathyroidectomy Indications: serum calcium >= 2.8 or complications present (renal calculi, osteoporosis, fragility fracture, renal impairment) Malignancy: chemo, radio or surgical excision Steroids in sarcoid or vitamin D excess Dialysis in resistant, life-threatening hypercalcaemia Frusemide diuresis

Question 26

Parathyroid surgery complications

Answer 26

- Recurrent laryngeal nerve. Supplies cricoarytenoid muscles for phonation. Injury -> hoarse voice - Superior laryngeal nerve. Supplies cricothyroid muscle of the larynx. Injury -> voice change - Hypocalcaemia - Chvostek’s sign (facial nerve twitch on tapping) - Trousseau’s sign (carpopedal spasm when BP cuff applied) - Infection, haemorrhage, haematoma

Question 27

Principal (Chief) Cells structure and secretory role?

Answer 27

- Small, polygonal cells with a central nucleus - Pale staining, contains vesicles, glycogen and lipids - Secrete PTH

Question 28

Oxyphil Cells structure and secretory role?

Answer 28

- Single cells or clusters of cells - More rounded and larger than principal cells - The numbers of oxyphil cell increase with age, and the cells have - no secretory role

Question 29

The External Laryngeal Nerve follows the course of the...?

Answer 29

Superior Thyroid Artery — high risk in thyroid surgery

Question 30

Describe the course of the recurrent laryngeal artery?

Answer 30

The Recurrent Laryngeal nerve runs up the posterior aspect of the Thyroid Gland, running between the Gland itself and the inferior thyroid artery - R Curls around R Subclavian - L curls around Arch of aorta

Question 31

Clinical definition of hypercalcaemia?

Answer 31

Total plasma Calcium levels exceeding the normal range of 2 - 2.5 mmol/L - Mild: 2.5-3 mmol/L - Moderate: 3-3.5 mmol/L - Severe/Hypercalcemic Crisis: >3.5 mmol/L

Question 32

What does TRAP AT HORMONE stand for?

Answer 32

``` Causes of hypercalcaemia: Parathyroid Hormone Increases Amyloidosis (AND other granulomatous diseases) Renal failure Addison's disease TB nodes Toxoplasmosis Histoplasmosis OD on Vit D Reynauds associated disease (SLE) Muscle primaries (Leiomyosarcomas) Ossifying metastasis Nephrocalcinosis Endocrine tumors ```

Question 33

What does hypercalcaemia and elevated PTH indicated?

Answer 33

Primary Hyperparathyroidism, FHH

Question 34

What does hypercalcaemia and low/suppressed PTH indicated?

Answer 34

- Malignancy - d/t RANKL release, or PTHrP release from SCC of Head/Neck/Lung - Granulomatous disease - Hyperthyroidism (inc bone breakdown) - Adrenal Insufficiency (inc bone turnover, dec. renal Ca excretion) - Pheochromocytoma - Immobilisation - Meds (Lithium, Thiazides, Vit D Toxicity, Milk Alkali syndrome)

Question 35

Pathophysiology of FHH

Answer 35

Most cases of FHH are associated with loss of function mutations in the calcium-sensing receptor (CaSR) gene, expressed in parathyroid and kidney tissue. These mutations decrease the receptor's sensitivity to calcium, resulting in reduced receptor stimulation at normal serum calcium levels. As a result, inhibition of parathyroid hormone release does not occur until higher serum calcium levels are attained, creating a new equilibrium. This is the opposite of what happens with the CaSR sensitizer, cinacalcet. Functionally, parathyroid hormone (PTH) increases calcium resorption from the bone and increases phosphate excretion from the kidney which increases serum calcium and decreases serum phosphate. Individuals with FHH, however, typically have normal PTH levels, as normal calcium homeostasis is maintained, albeit at a higher equilibrium set point. As a consequence, these individuals are not at increased risk of the complications of hyperparathyroidism.

Question 36

ECG changes in hypercalcaemia?

Answer 36

Specific changes, such as a shortened QT interval and prolonged PR interval, may be seen on an electrocardiogram (ECG)

Question 37

There is a general mnemonic for remembering the effects of hypercalcaemia. Describe it:

Answer 37

"Stones, Bones, Groans, Moans, Thrones and Psychiatric Overtones" Stones (kidney or biliary) Bones (bone pain) Groans (abdominal pain, nausea and vomiting) Moans (other non-specific symptoms) Thrones (polyuria) resulting in dehydration due to nephrogenic diabetes insipidus from nephrocalcinosis Muscle tone (hypotonicity, muscle weakness, hyporeflexia) Psychiatric overtones (Depression 30–40%, anxiety, cognitive dysfunction, insomnia, coma)

Question 38

Mechanism for the neuromuscular effects of hypercalcaemia?

Answer 38

The neuromuscular symptoms of hypercalcaemia are caused by a negative bathmotropic effect due to the increased interaction of calcium with sodium channels. Since calcium blocks sodium channels and inhibits depolarization of nerve and muscle fibers, increased calcium raises the threshold for depolarization

Question 39

Results of primary hyperparathyroidsim?

Answer 39

Primary Hyperparathyroidism - Normal/Elevated PTH - Normal/Low PO4 (due to wasting)

Question 40

Results of humoral hypercalcaemia?

Answer 40

Humoral Hypercalcemia: - Low PTH - High PTHrP - Low PO4

Question 41

Results of osteolytic metastases?

Answer 41

Osteolytic Metastases: - Low PTH - Normal/Raised PO4 - Normal/Low Vit D

Question 42

Results Vit D Releasing Tumors (Lymphoma)?

Answer 42

Vit D Releasing Tumors (Lymphoma): - Low PTH - Normal PO4 - Raised CALCITRIOL

Question 43

Results Hyperparathyroidism 2º to Renal Disease?

Answer 43

Hyperparathyroidism 2º to Renal Disease - High PTH - Low/Normal Calcium - Variable PO4 - can be low or high

Question 44

Results Hypercalcemia of Granulomatous Disease same as Vit-D Releasing Tumors?

Answer 44

Hypercalcemia of Granulomatous Disease same as Vit-D Releasing Tumors: - Low PTH - Normal PO4 - Raised CALCITRIOL