Endo3 Flashcards
Calcium and Bone
What is secreted when there is a calcium deficiency?
PTH
What organs does PTH directly and indirectly act upon?
Bones (directly)
Kidneys (directly)
SI (indirectly)
How does PTH act on the bones?
Increases osteoclast activity
Induces bonre resportion
Plasma Ca concentration increases
How does PTH act on the kidneys?
Increases Ca resorption and PO4 excretion
Increases 1 alpha hydroxylase activity
How does PTH act on the SI?
Increases 1 alpha hydroxylase activity in the kidneys
Converts 25-OH D3 into 1,25-(OH)2 D3 aka calcitriol
Calcitriol acts upon the SI
increases Ca resorption and PO4 resorption
What is the pathway of vitamin D?
Vitamin D is converted to 5-OH D3 in the liver
5-OH D3 is converted into 1,25-(OH)2 D3 in the kidneys
1,25-(OH)2 D3 increases Ca and PO4 resorption
What are some causes of hypercalcaemia?
Endocrine: -1 hyperPTH, 3 hyperPTH (renal failure) Malignancy: -PTHrp from SSC/breast Ca High bone turnover: -Paget's, MM, hyperthyroidism Other: -MEN 1/2a, sarcoidosis
What are some causes of hypocalcaemia?
Endocrine: -Vit D3 deficiency, hypoPTH Electrolyte: -Hyperphosphataemia, hypomagnesaemia Other: -Acute renal failure, pancreatitis, iatrogenic, drugs (eg. lithium)
What is the normal range of serum calcium?
2.2-2.6mmol/L
What are the signs and symptoms of hypercalcaemia?
Stones
-polyuria, thirst, nephrocalcinosis, renal colic, chronic renal failure
Bones
-bony pain
Abdominal groans
-anorexia, nausea, dyspepsia, pancreatitis
Psychic moans
-fatigue, depression, impaired consciousness, coma (if >3)
What are the signs and symptoms of hypocalcaemia?
CATs go numb: Convulsions Arrhythmia Tetany Paraesthesia
Trousseau’s sign
Chvostek’s sign
What is Trousseau’s sign?
Carpopedal spasm
Triggers due to ishaemia
eg. applying a BP cuff
What is Chvostek’s sign?
Twitch of the face
Triggered by tapping a facial nerve
What are the investigations for hyper/hypocalcaemia?
Plasma Ca Plasma Vit D3 Plasma PTH Plasma PO4 ALP Radiology ECG Bone biopsy
What is the treatment for hypercalcaemia?
Fluids
IV bisphosphonates
Haemodialysis
Treat underlying cause eg surgery for Ca
What is the treatment for hypocalcaemia?
IV calcium gluconate 10%
Calcium chloride
Vit D/Ca supplements
Treat underlying cause
What is primary hyperparathyroidism?
Abnormal secretion of PTH
What is secondary hyperparathyroidism?
Abnormal secretion of PTH secondary to hypocalcaemia
What is tertiary hyperparathyroidism?
PTH secretion due to long term 2 hyperPTH
What are the common causes of 1 hyperPTH?
Adenoma
Parathyroid carcinoma
MEN, radiation
What are the common causes of 2 hyperPTH?
Chronic renal failure
Vit D3 deficiency
What are the common causes of 3 hyperPTH?
Chronic renal failure
What are the symptoms of hyperPTH?
Insidious onset
Many are asymptomatic
Features of hypercalcaemia
What are the investigations for hyperPTH?
U+E:
- Ca raised in 1+3, normal/low in 2
- ALP slightly raised
- Vit D low in 2
- PTH raised
- PO4 low in 1+3, high in 2
What is the treatment for hyperPTH?
Treat acute hypercalcaemia with fluids Surgical is definitive treatment If surgery is contraindicated: -bisphosphonates -oestrogen -cinacalcet (PTH carcinoma, 3 hyperPTH)
What are the complications of hyperPTH?
Inflammation Organ deposition Arrhythmia Death Osteitis fibrosa cystica Surgical complications
What is osteomalacia?
Vit D deficiency leading to a disorder of bone matrix mineralisation in adults
What is Ricket’s?
Vi D deficiency leading to a disorder of bone matrix mineralisation in children
What are the risk factors for Vit D def?
Dietary Lack of sunlight exposure Malabsorption Liver/kidney disease Vit D resistance Renal phosphate wasting eg. Fanconi's syndrome
What are the signs and symptoms of osteomalacia?
Bone pain Weakness Malaise Waddling gait Proximal muscle weakness Signs of hypocalcaemia
What are the signs and symptoms of Ricket’s?
Hypotonia Growth retardation Skeletal deformities Frontal/parietal bossing Rickety rosary Bowed legs Knocked knees Short stature
What are the investigations for Vit D def?
Bloods: -low/normal Ca -low PO4 -slightly raised ALP -high PTH (2 hyperPTH) ABG- for acidosis XR -may show Looser's zone and osteopenia Bone biopsy after double tetracycline labelling
What is the management for Vit D def?
Restore Vit D: -ergocalciferol -cholecalciferol -Ca supplements If in renal failure: -alfacalciferol
What are the complications of Vit D def?
Bone deformities (permanent in children) Hypocalcaemia: -seizure -arrhythmia -tetany Depression
What is osteoporosis?
Reduced bone density, resulting in bone fragility and increased fracture risk.
How is osteoporosis diagnosed?
If a Pt’s DEXA is >2.5 S.D’s below the peak bone mass in healthy adults (ie. T score)
What is the epidemiology of osteoporosis?
> 50yrs
Caucasians > Afro-Caribbeans
What are the causes of primary osteoporosis?
Idiopathic
What are the causes of secondary osteoporosis?
Malignancy- myeloma, carcinoma mets Endo- Cushing's Dx, thyrotoxicosis, 1 hyperPTH, hypogonadism Drugs- corticosteroids, heparin Rheum- RhA, ankylosing spondylitis GI- malabsorption, liver Dx, anorexia
What are the risk factors for osteoporosis?
Age, ethnicity, FHx
Alcohol, low Vit D nutrition
Medication
What are the signs and symptoms of osteoporosis?
Asymptomatic
Usually present after a fracture
Which fractures are commonly associated with osteoporosis?
Neck of femur fracture
Vertebral fracture
Colles’ fracture (distal radius)
What are the investigations for osteoporosis?
Bloods- normal in primary
XR- diagnose fractures
Isotope bone scans
DEXA scan
What is Paget’s disease of bone?
Excessive bone remodelling leading to deformities
What is the aetiology of Paget’s?
Overactivity of osteoclasts break down bone
Lytic wedges form
Compensatory osteoblast activity lays down trabecular bone, not lamellar bone
Marrow becomes filled with fibrous tissue what is hypervascular
What is the presentation of Paget’s?
May be asymptomatic
May have insidious onset of bone pain
Headaches/dizziness
Increasing skull size
Bitemporal head enlargement with frontal bossing
Spinal kyphosis
Anterolateral bowing of femur/tibia/forearm
Skin over the affected bone may be warm
Sensorineural deafness (CN VIII compression)
What are the investigations for Paget’s?
ALP (very very high) Ca and PO4 normal Lytic and sclerotic bone lesions Skull changes Radioisotope bone scan- increased activity
A 39-year-old man presents with a three-month history of depression. The patient recently lost a family member and around the same period began to feel unwell with constipation and a depressed mood. He has started taking analgesia for a sharp pain in his right lower back that often radiates towards his front. The most appropriate investigation is:
A. Serum parathyroid hormone B. Serum thyroid stimulating hormone C. Colonoscopy D. Fasting serum calcium E. MRI scan
D. Fasting serum calcium
This patient appears to be suffering from symptoms of elevated calcium levels, these can include depression, constipation and renal stone formation causing abdominal pain.
A 50-year-old woman presents to accident and emergency complaining of excessive lethargy. In addition, she mentions that she has been constipated. On examination, there are clinical features of dehydration. Blood tests have revealed a corrected calcium of 3.3 mol/L. Her chest x-ray shows bilateral streaky shadowing throughout both lung fields. She is given 3L of saline in 24 hours after admission. The following day her blood tests are repeated and her corrected calcium level is now 3.0 mmol/L. Results of parathyroid hormone levels and thyroid function tests are still awaited. What is the most appropriate management?
A. Intravenous saline rehydration
B. Intravenous saline rehydration and pamidronate
C. Pamidronate
D. Calcitonin
E. Intravenous saline rehydration plus calcitonin
E. Intravenous saline rehydration
Acute hypercalcaemia is an emergency that requires prompt treatment. The treatment of acute hypercalcaemia is saline, saline and more saline! Bisphosphonates (B) and (C) should be reserved for hypercalcaemia of malignancy. The most common causes of hypercalcaemia are hyperparathyroidism and malignancy. In light of the raised calcium, the chest x-ray findings should raise the suspicion of sarcoid or possible lymphangitis carcinomatosis. While a diagnosis of sarcoid must be confirmed with histology, hypercalcaemia in sarcoidosis is an indication for corticosteroid therapy. Therefore, this patient can be given a steroid challenge. If the calcium levels fall following this, it is suggestive of sarcoid. Administering bisphosphonates, however, would complicate the process of making the diagnosis of sarcoid as any correction in calcium following steroid therapy may have been produced by the bisphosphonate. Calcitonin (D) and (E) is seldom used in hypercalcaemia as it has a short- lived action and is painful upon intravenous administration.
- A 67-year-old man presents to his GP with pain in his pelvis. During the consultation, he mentions that his friends have been commenting that his head appears larger than before. In addition, he has noticed deterioration in hearing in his left ear. On neurological examination, a left-sided sensorineural deafness in detected. Closer inspection of the legs reveals bowing of the tibia. What is the most likely diagnosis?
A. Osteomalacia B. Osteoporosis C. Acromegaly D. Ricket's E. Paget’s disease
E. Paget’s disease
