CSIM 2.25 - ELECTROLYTE ABNORMALITIES Calcium and Bone Calcium Homeostasis and Bone structure 1. Parathyroid gland release parathyroid hormone (PTH) which activates osteoclasts brings up calcium blood levels from bone reserves and works with vitamin D to draw calcium through intestinal walls. (kuarkan Ca2+ dari bones into bloods and absorbed Ca2+ from intestinal walls with the help of vitamin D)2. PTH antagonist: Calcitonin from thyroid. 3. Vitamin D synthesis and activation

Hypercalcaemia1. Symptoms; stones, bones, groans and moansRenal & fluid balance Thirst, polyuria, renal stones MS Weakness, myalgia, bone pain

GI Anorexia, vomiting, constipation CNS Mood-change, depression, confusion

hypoparathyroidism4

2. 3. Epidemiology a. Prevalence b. Gender bias. F:M, 3:1c. Age peak 50-70 years old. 4. Causes a. Benign solitary parathyroid adenoma (85%)b. 4-gland PT hyperplasia 15%c. Parathyroid carcinoma treat symptoms and prevent complication b. Conservative management; if asymptomatic, with regular monitoring c. Calcimimetic drugs; calcium receptor agonists (cinacalcet) Humoral Hypercalcaemia of malignancy1. When a tumour secretes PTHrP, this can lead to hypercalcaemia. 2. This is the first sign of malignancy; paraneoplastic phenomenon. 3. Hyperparathyroidism is the most common cause of hypercalcemia, followed by malignancy; up to 58% of hospitalized patients with hypercalcemia have an associated cancer. 4. In my own words, H.Cal in this situation is a consequence of HyperPTH which was not the PT fault. The PTH is secreted by PTHrP on tumour. High PTH leads to H.Cal. 5. Aetiology a. squamous cell carcinomasi. lung, breast, oesophagus, cervix, ii. skin, renal, bladder, ovaryiii. clinically obvious tumour mass6. Pathophysiologya. excess production of PTHrP i. tumour cellsb. suppressed PTH & 1,25(OH)2D3c. no high risk of pathological fractureHypercalcaemia in Myeloma 1. Hypercalcaemia is a common complication in myeloma; another type of malignancy. A myeloma cells ca. is associated with excessive tumor-induced, osteoclast-mediated bone destruction.2. Prevalencea. 30% of patients with myeloma 3. Pathogenesisa. diffuse osteolysisb. local IL6 production4. Biochemical featuresa. phosphate may be elevatedb. alkaline phosphatase normal5. Managementa. emergencyb. hypercalcaemia is steroid responsive

Focal Osteolytic Metastases 1. A further mechanism of hypercalcaemia which caused by metastases of cancer to the bones; skeletal metastases. 2. Pathophysiology; Direct invasion of bone3. Clinical featuresa. local pain b. high risk of pathological fractureother causes of hypercalcaemia Drugs vitamin D intoxication milk-alkali syndrome Sarcoidosis Renal failure FHH familial hypocalciuric hypercalcaemia Immobility & high bone turnover Pagets disease astronauts Endocrine problems hyperthyroidism addisons disease phaeochromocytoma

management 1. 2. Investigationa. renal & liver function b. baseline PTH if first presentation3. Cause-independent treatmenta. IV n-saline 6L/24hrs4. Cause-specific treatmentsa. IV bisphosphonates b. pamidronatec. zolendonated. steroids

Hypocalcaemia1. Symptoms and signs a. Paraesthesia of mouth & fingersb. Muscular twitching & leg crampsc. Laryngeal stridord. Carpopedal spasm i. tetanye. Seizures2. Causes Vitamin D deficiency HYPOPARATHYROIDISM Drugs vitamin D metabolism Renal failure hyperphosphateamia PTH or vitamin D resistance pseudohypoparathyroidism Severe illness acute pancreatitis acute rhabdomyolysis

hypoparathyroidism 1. Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone. The common cause for hypocalcaemia. 2. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary muscle contraction), and several other symptoms. 3. The condition can be inherited, but it is also encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes. 4. The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results5. The main symptoms of hypoparathyroidism are the result of the low blood calcium level, which interferes with normal muscle contraction and nerve conduction. 6. As a result, people with hypoparathyroidism can experience paresthesia, an unpleasant tingling sensation around the mouth and in the hands and feet, as well as muscle cramps and severe spasms known as "tetany" that affect the hands and feet. 7. Many also report a number of subjective symptoms such as fatigue, headaches, bone pain and insomnia. Crampy abdominal pain may occur. Physical examination of someone with hypocalcemia may show tetany, but it is also possible to provoke tetany of the facial muscles by tapping on the facial nerve (a phenomenon known as Chvostek's sign) or by using the cuff of a sphygmomanometer to temporarily obstruct the blood flow to the arm (a phenomenon known as Trousseau's sign of latent tetany). 8. A number of medical emergencies can arise in people with low calcium levels. These are seizures, severe irregularities in the normal heart beat, as well as spasm of the upper part of the airways or the smaller airways known as the bronchi (both potentially causing respiratory failure). 9. Causes; a. Post-surgical i. thyroidectomyb. Congenital absence of parathyroidsi. DiGeorge syndromec. Autoimmunei. with candidiasis & Addisons diseased. Reset PTH set-point i. calcium receptor mutatione. Tissue resistance to PTHi. pseudohypoparathyroidismii. G protein LOF mutationf. Infiltration i. Defective PTH molecule10. biochemistry findingsa. Low serum calciumb. High serum PO43-c. Low or undetectable PTHd. Normal renal functione. Low urine calcium excretion

Bone diseaseOsteoporosis1. It is common in elderly2. Clinically defined as low impact fracture at HIP, SPINE and WRIST3. Whereas, radiographic definition are low bone mineral density and reduced bone mass 4. BUT NORMAL calcium & PTHInvestigations DXA at hip and spine (g/cm2) 1. Z-score: Bone mineral density (BMD) compared to age and gender matched population 2. T-score: BMD compared to race and gender matcher peak adult BMD3. Expressed as standard deviation from population mean4. Risk factors Low weight 170 cms Smoking & Alcohol use Ethnic background Asian Family History Low calcium intake Medication steroids Premature menopause Hypogonadism 5. 6. Causes Co-morbid medical problems malabsorption chronic liver diease renal disease rheumatoid arthritis immobilisation osteogenesis imperfecta Endocrine disease hypogonadism thyrotoxicosis hyperparathyroidism Cushings disease Drugs steroids anticonvulsants heparin7. 8. Difference between osteopenia and osteoporosis OsteoporosisOsteopenia

fragility fracture defines established osteoporosisIt is considered to be a precursor to osteoporosis. However, not every person diagnosed with osteopenia will develop osteoporosis

T score of -2.5 or less T score of -1 to -2.5

9. The problem is, at 80 years of age 100% of the population has osteopenia by BMD. 50% have BMD defined osteoporosis.10. Risk assessment: two-step FRAX tool. a. Red: treat, Yellow: measure BMD, Green: lifestyle advice and measure11. Treatment Generic & preventativePharmacological

calcium intake; >1200 mg/day vitamin D intake; >400 u/day life-style interventions; weight-bearing exercise

hormone replacement therapy bisphosphonates parathyroid hormone; teriparatide denosumab; anti-RANK ligand mAb SERM; selective estrogen receptor modulators strontium ranelate

Osteomalacia & Rickets 1. Is the softening of the bones caused by defective bone mineralization secondary to inadequate levels of available phosphate and calcium, or because of overactive resorption of calcium from the bone which can be caused by hyperparathyroidism (which causes hypercalcemia) consequence of hypercalcaemia (HPTH)2. Osteomalacia in children is known as rickets, and because of this, use of the term "osteomalacia" is often restricted to the milder, adult form of the disease. 3. Signs and symptoms can include diffuse body pains, muscle weakness, and fragility of the bones. 4. Investigation: 25(OH)D level. 5. Biochemistry: BiochemistryRadiology

low serum 25-OH vitamin D elevated PTH compensatory elevated alkaline phosphatase increased bone turnover hypocalcaemia hypophosphataemia cupped epiphyses loosers zones rachitic rosary

6. Management: intake of vitamin D and calcium supplements. Since most of the consequences of vitamin D deficiency are a result of impaired mineral ion homeostasis 7. Most common CAUSE: vitamin D deficiency which is normally derived from sunlight exposure and, to a lesser extent, from the diet (calcium, phosphate). Phosphate deficiency; dietary or renal phosphate leak. Renal or hepatic dx: lack of activation of vitamin D precursors. 8. High risk population: a. Nursing home residents and the homebound elderly population, as they receive little sun exposure. In addition, both the efficiency of vitamin D synthesis in the skin and the absorption of vitamin D from the intestine decline with age, thus further increasing the risk in these populations. b. Bypass surgery and coeliac disease: malabsorption. c. Individuals who immigrate from warm climates to cold climates, especially women who wear traditional veils or dresses that prevent sun exposure 9. Symptoms and signs:a. Weakness, myalgia, bone pain, tetanus, bowing of legs, craniotabes (softening or thinning of the skull).