Hospital dos Lusíadas

Alterações do metabolismo cálcio fósforoHipocalcemiaHipercalcemia

Pós graduação - Emergências Médicas

João Albuquerque Gonçalves

Assistente Hospitalar de Nefrologia

3 de Fevereiro de 2018

CÁLCIO - FÓSFORO

Excess PTH production

Metabolismo fosfo-cálcico

• DRC:

– Agravamento de função renal associado ao hiperparatiroidismosecundário

– Aumento do FGF23

– Hipocalcémia

– Défice de vit D2

– Hiperfosfatémia

Aumento de síntese de PTH

Consequências da DRC-DMO

Se não se tratar devidamente o HPTS:– Osteodistrofia renal

• Alteração da renovação, mineralização, volume• Alteração do crescimento linear e robustez óssea

– Calcificações:• vasculares ou de tecidos moles• Extra-esqueléticas

– Alterações Laboratoriais• Alterações do metabolismo do cálcio• Hiperfosfatémia• Hipocalcemia• Alterações da PTH e Vit D

Consequências da DRC-DMO

– Consequências clínicas:

• Fraturas

• Dores ósseas e musculares

• Necrose avascular

• Aumento de risco de mortalidade e hospitalizações (eventos cardiovasculares)

• Hiperplasia da Paratiróide

• Paratiroidectomia

Objectivos na DRC/HD

• iPTH entre 150-300

(ou entre 2-9x o valor de base – 150-600)

• Fósforo – 3,5 – 5,5

• Cálcio – 8,2 – 10,2

Fósforo

BMC Nephrol. 2013 Apr 17;14:88. doi: 10.1186/1471-2369-14-88.Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis.

Cálcio

BMC Nephrol. 2013 Apr 17;14:88. doi: 10.1186/1471-2369-14-88.Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis.

PTHi

BMC Nephrol. 2013 Apr 17;14:88. doi: 10.1186/1471-2369-14-88.Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis.

HPTS - Como tratar?

• Quelantes de fósforo

(com ou sem cálcio)

• Calcitriol

• Análogos da Vit D

• Calcimiméticos• PTX

Terapêutica disponível

• Alfacalcidol 0,25; 0,5; 1 mcg até 3 mcg/dia

• Calcitriol per os 0,25 até 1 mcg/dia

• Calcitriol ev - Calcijex 1-2 mcg/sessão

• Colecalciferol (D3) – 0,5 mg/mL

• Paricalcitol oral 1-2 mcg/dia ou 2-4 mcg/dias alternados

• Paricalcitol EV 5 mcg/mL freq máxima dias alternados (HD)

• Ergocalciferol (D2)

• Cinacalcet 30-180/dia

• Hipocalcémia severa e sintomática requer tratamento urgente

• Sintomas na urgência: tetania (latente), papiledema, convulsões

• Ansiedade, status confusional agudo, depressão, alucinações, psicose franca

• Prolongamento no intervalo QT no ECG

Hipocalcemia

HIPOCALCÉMIA

• Paresthesias, usually of the fingers, toes, and circumoral regions, and is causedby increased neuromuscular irritability

• Chvostek's sign

• Trousseau's sign

• Seizures, carpopedal spasm,

• Bronchospasm, laryngospasm,

• Prolongation of the QT interval.

Hipocalcemia

• Falsa hipocalcemia…. Avaliar Cálcio ionizado e albuminemia

• Procurar causas: hipomagnesiemia, pancreatite, sepsis, DRC, LRA; hipoparatiroidismo, deficiência em Vit D; infusões de citrato, fostato ou albumina. Toma de fósforo ou bifosfonatos ou calcitonina, rabdomiólise, síndrome de necrose tumoral, sd malabsorção, terapia anti convulsivante

HIPOCALCÉMIA

Tratamento hipocalcemia

Considerar Teriparitide

HIPOCALCÉMIA

• TREATMENT

– calcium gluconate, 10 mL 10% wt/vol (90 mg or 2.2 mmol) intravenously

– calcium supplements (1000–1500 mg/d elemental calcium in divided doses)

– vitamin D2 or D3 (25,000–100,000 U daily) or calcitriol [1,25(OH)2D, 0.25–2 g/d]

HIPERCALCÉMIA

• Excess PTH production – Parathyroid adenomas, hyperplasia, or, rarely, carcinoma

• Calcium mobilization from bone– Hyperthyroidism or osteolytic metastases

• Calcium overload – Milk-alkali syndrome, total parenteral nutrition with excessive calcium supplementation.

Causas de hipercalcémia

HIPERCALCÉMIA

Clinical Features

• Mild hypercalcemia (up to 11–11.5 mg/dL)

• Neuropsychiatric symptoms

– Trouble concentrating, personality changes, or depression

• Nephrolithiasis, and fracture risk may be increased

• Severe hypercalcemia (>12–13 mg/dL)

• Lethargy, stupor, or coma, as well as gastrointestinal symptoms

– nausea, anorexia, constipation, or pancreatitis

• Polyuria and polydipsia

• Bradycardia, AV block, and short QT interval

HIPERCALCÉMIA

Diagnostic

• Corrected calcium concentration is calculated by

– adding 0.8 mg/dL to the total calcium level

for every decrement in serum albumin of 1.0 g/dL

below the reference value of 4.1 g/dL for albumin

• PTH level using a two-site assay

• Serum creatinine

Tratamento de hipercalcemia sintomáticaTreatment of symptomatic hypercalcemia

• Volume expansion

• Loop diuretics

• Drugs that inhibit bone resorption

– as in malignancy or severe hyperparathyroidism

– bisphosphonates have replaced calcitonin or plicamycin

• Dialysis may be necessary

• Intravenous phosphate

– calcium-phosphate complexes may deposit in tissues

– In patients with 1,25(OH)2D-mediated hypercalcemia,

glucocorticoids are the preferred therapy

Tratamento hipercalcemia• Patients with asymptomatic or mildly symptomatic hypercalcemia (calcium <12 mg/dL [3

mmol/L]) do not require immediate treatment. However, they should be advised to avoid factors that can aggravate hypercalcemia, including thiazide diuretic and lithium carbonate therapy, volume depletion, prolonged bed rest or inactivity, and a high calcium diet (>1000 mg/day)

● Asymptomatic or mildly symptomatic individuals with chronic moderate hypercalcemia (calcium between 12 and 14 mg/dL [3 to 3.5 mmol/L]) may not require immediate therapy. However, an acute rise to these levels may cause gastrointestinal side effects and changes in sensorium, which requires treatment as described for severe hypercalcemia.

● Patients with more severe (calcium >14 mg/dL [3.5 mmol/L]) or symptomatic hypercalcemia are usually dehydrated and require saline hydration as initial therapy. A reasonable regimen is the administration of isotonic saline at an initial rate of 200 to 300 mL/hour that is then adjusted to maintain the urine output at 100 to 150 mL/hour.

● In patients with hypercalcemia receiving saline hydration, we suggest not routinely using a loop diuretic (Grade 2C). However, in individuals with renal insufficiency or heart failure, careful monitoring and judicious use of loop diuretics may be required to prevent fluid overload.

Tratamento de hipercalcemia

● For immediate, short-term management of hypercalcemia, we suggest administration of calcitonin (in addition to saline hydration) only in patients with calcium >14 mg/dL (3.5 mmol/L) who are also symptomatic (Grade 2B).

● For longer-term control of hypercalcemia in patients with more severe (calcium >14 mg/dL) or symptomatic hypercalcemia due to excessive bone resorption, we suggest the addition of a biphosphonate rather than denosumab (Grade 2B). Denosumab is an option for patients with hypercalcemia that is refractory to zoledronic acid (ZA) or in whom biphosphonates are contraindicated due to severe renal impairment.

● Among intravenous (IV) bisphosphonates, we suggest ZA (Grade 2B). Pamidronate is an alternative option when ZA is not available.

● Glucocorticoids are effective in treating hypercalcemia due to some lymphomas, sarcoid, or other granulomatous diseases

● Dialysis is generally reserved for those with severe hypercalcemia.

Caso clínico

ESC, sexo feminino,48 anos, caucasiana, casada, natural e residente no alentejo(Vidigueira)

Data internamento no Serviço Nefrologia HESE –21/12/2009

Antecedentes pessoais:

• Doença renal crónica por GlomeruloscleroseSegmentar e Focal

• Em HD desde 10/2004.

• Paratiroidectomia total com colocação de aloenxerto no MSE em 6/12/2006.

• Transferida para programa de DP (DPA) em 7/2009, por exaustão de acessos vasculares com estenose venosa central bilateral

• HTA desde 2004

• Obesidade mórbida (banda gástrica em 6/2006 (perdeu 40 Kg em 3 anos)

• Peritonite em 10/2009

Medicação habitual

• Ácido fólico 1 cp

• Complexo B 1 cp

• Sevelamer800 mg 2+3+2+3

• Paricalcitol2 mcg1 cp/dia

• Cinacalcet120 mg/d

• Darbepoetina80 mcgsc/sem (4ªf)

• Omeprazol20 mg/d

• Domperidona10 mg 1 cp3 x/dia

• A 21/12/2009 recorreu à consulta de urgência de DP por lesões na face interna das coxas com 6 semanas de evolução com ardor, dor e prurido intenso.

• Refere ligeiro alívio das queixas de dor com analgésicos e diminuição acentuada do apetite e anorexia.

• Negou toma de anticoncetivos, varfarina ou história de traumatismo.

História da doença atual

Análises

• Hg 8.7• Leuc 7740• Plaq 401• PCR 31.6• Ca 9.7• P 7.9• PTH 1344• Alb 1.6• CA X P = 76• Biopsia da pele - lesões de calcifilaxia

Calcifilaxia

• Produto cálcio-fósforo

Terapêutica e follow up

• Paratiroidectomia com melhoria da PTH e diminuição do Cálcio e Fósforo

Hg 10; Leuc 4500; Plaq 351

PCR <3

Ca 9.3; P 3.4; PTH 5.7; Alb 3.8

Obrigado pela atenção…