CBL Flashcards
Percentage calcium bound to plasma proteins?
40% bound to plasma protein (primarily albumin)
Where is calcitonin released from?
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.
What stimulates parathyroid hormone release?
Low calcium concentration.
Name the major two causes of secondary hyperparathyroidism?
Low vitamin D and chronic renal failure.
Calcium and PTH levels in secondary hyperparathyroidism?
Low or normal calcium
Elevated PTH
Cause of tertiary hyperparathyroidism?
Long term secondary hyperparathyroidism leading to parathyroid gland hyperplasia.
Calcium and PTH levels in primary hyperparathyroidism?
Elevated calcium
Elevated PTH
Calcium and PTH levels in tertiary hyperparathyroidism?
Elevated calcium
Elevated PTH
Histology of parathyroid cells?
Consists mainly of chief cells and some oxyphil cells
Chief cells secrete PTH
What is the trigger for increased PTH secretion?
Drop in calcium concentration (even a very small drop)
By what mechanisms does PTH increase calcium?
- ) 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
- ) 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
What are the effects/functions of Vitamin D?
- ) Increases intestinal calcium absorption: ↑ calbindin production in intestinal cells -> ↑transport of calcium at brush border -> ↑calcium absorption -> indirectly promotes new bone formation
- )↑ renal reabsorption of calcium
- ) Promotes intestinal phosphate absorption
- ) In large quantities, promotes bone resorption via ↑ osteoclastic activity
Where is calcitonin secreted from?
Secreted by C-cells of thyroid gland
Function of calcitonin?
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
Function phosphorus?
Cell membranes (phospholipids) Enzymatic reactions (phosphorylation) Phosphate buffer system Bony calcification Glucose metabolism
Acidosis effect on ionized calcium concentration?
Acidosis causes ↓ plasma protein binding ↑ ionised calcium
Alkalosis effect on ionized calcium concentration?
Alkalosis causes ↑ plasma protein binding ↓ ionised calcium
Effect of phosphorus on calcium levels?
↑phosphate -> increased calcium
phosphate binding -> ↓ ionized calcium
Typical presentation of hypercalcaemia?
Easy fatigue, muscle weakness, anorexia, weight loss
Depression
Polyuria, polydipsia
Constipation
Renal stones
Pancreatitis
Osteoporotic fractures
Peptic ulcers
Severe hypercalcaemia: confusion, cognitive decline, coma
Typical presentation depression
DIGSPACES
Typical presentation chronic renal failure/impairment
Sx: ankle swelling, pruritus, rash, constitutional sx
Risk: hypertension, diabetes, obesity, smoking
Typical presentation hypothyroidism
Sx: cold intolerance, psychomotor retardation, weight gain, oligomenorrhoea, constipation, goitre
Risk: female, FHx, other autoimmune diseases
Typical presentation Diabetes mellitus
Sx: polyuria, nocturia, polydipsia, peripheral neuropathy,
ulcers, infections, blurred vision
Risk: obesity, FHx, older age, Cushing’s, sedentary, metabolic syndrome
Typical presentation anaemia (iron deficiency)
Sx: SOB, blood loss (melaena, haematochezia, menorrhagia, etc.), nail changes
Risk: older age, FHx of bowel cancer, NSAIDs, alcohol use, pregnant, vegan, coeliac
Acute management symptomatic hypercalcaemia
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
Parathyroid surgery complications
- 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
Principal (Chief) Cells structure and secretory role?
- Small, polygonal cells with a central nucleus
- Pale staining, contains vesicles, glycogen and lipids
- Secrete PTH
Oxyphil Cells structure and secretory role?
- 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
The External Laryngeal Nerve follows the course of the…?
Superior Thyroid Artery — high risk in thyroid surgery
Describe the course of the recurrent laryngeal artery?
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
Clinical definition of hypercalcaemia?
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
What does TRAP AT HORMONE stand for?
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
What does hypercalcaemia and elevated PTH indicated?
Primary Hyperparathyroidism, FHH
What does hypercalcaemia and low/suppressed PTH indicated?
- 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)
Pathophysiology of FHH
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.
ECG changes in hypercalcaemia?
Specific changes, such as a shortened QT interval and prolonged PR interval, may be seen on an electrocardiogram (ECG)
There is a general mnemonic for remembering the effects of hypercalcaemia. Describe it:
“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)
Mechanism for the neuromuscular effects of hypercalcaemia?
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
Results of primary hyperparathyroidsim?
Primary Hyperparathyroidism
- Normal/Elevated PTH
- Normal/Low PO4 (due to wasting)
Results of humoral hypercalcaemia?
Humoral Hypercalcemia:
- Low PTH
- High PTHrP
- Low PO4
Results of osteolytic metastases?
Osteolytic Metastases:
- Low PTH
- Normal/Raised PO4
- Normal/Low Vit D
Results Vit D Releasing Tumors (Lymphoma)?
Vit D Releasing Tumors (Lymphoma):
- Low PTH
- Normal PO4
- Raised CALCITRIOL
Results Hyperparathyroidism 2º to Renal Disease?
Hyperparathyroidism 2º to Renal Disease
- High PTH
- Low/Normal Calcium
- Variable PO4 - can be low or high
Results Hypercalcemia of Granulomatous Disease same as Vit-D Releasing Tumors?
Hypercalcemia of Granulomatous Disease same as Vit-D Releasing Tumors:
- Low PTH
- Normal PO4
- Raised CALCITRIOL
