Metabolic, Endocrine, and Hematologic disease 주선영 가톨릭대학교인천성모병원

Transcription

1 Metabolic, Endocrine, and Hematologic disease 주선영 가톨릭대학교인천성모병원 1

2 Metabolic disease Ca, P metabolism Vit D metabolism Rickets Nutritional Hypophosphatemic Renal osteodystrophy Hypophosphatasia Hypervitaminosis A Vitamin C deficiency 2

3 Metabolic control of calcium metabolism 3

4 Vit D metabolism 4

5 Biochemical Consequences of Vitamin D Deficiency Vitamin D deficiency Reduced Ca absorption Secondary hyperparathyroidism Depressed extracellular Ca Depressed extracellular P Defective mineralization of the bone in formation Increased bone resorption demineralization of the existing bone 5

6 Rickets An Osteomalacic syndrome Failure of mineralization of chondroid and osteoid Lack of ionized calcium and/or phosphate Less mineralized bone per unit volume Bowing deformities Stress fractures with resultant deformities 6

7 Severe osteomalacia: marked increase in osteoid Bordering trabecular and endosteal bone Almost all (~100%) bone surfaces are covered by osteoid (surface osteoid is < 20% in normal bone) 7

8 Type of rickets Nutritional rickets Hypophosphatemic Renal osteodystrophy Hypophosphatasia Ca Phosphate ALP PTH 25(OH) VitD 1,25(OH) 2 VitD Nutritional N- N- Vit D resistant (XLH,RTA,Fanconi s,oncogeni c) N N N N Vit D dependent type I (inability to hydroxylate) Vit D dependent type II (receptor insensivity) N- Renal Osteodystrophy N- N 8

9 Classification of Rickets according to what is lacking at the osteoblast- bone interface a 9

10 Nutritional rickets Rare in developed countries Prolonged breast-feeding, vegetarian diet, TPN, anticonvulsant Generalized muscular weakness, lethargy, and irritability, developmental delay Thickening of the ankles, knees, and wrists Genu valgum, coxa vara, stress fractures Short stature 10

11 Nutritional rickets Elongation of the physis and a hazy appearance of the provisional zone of calcification Beading of the ribs (rachitic rosary)-enlargement of the costochondral junctions Harrison s groove horizontal line at the lower margin of the thorax Diaphragm, which is always in tension, pulls the softened bone inward 11

12 Structural changes in rickets Physeal widening concentrated in the middle part of the physis in severe rickets with less involvement at the periphery This translates radiographically into cupping of the metaphyseal regions 12

13 Nutritional rickets Treatment Administration of vitamin D ( IU/day) 6 to 10 weeks Within 2-4 weeks, detectable healing evidence Vitamin D-resistant rickets should be suspected if the child does not respond to vit D therapy 13

14 Nutritional rickets 14

15 Hypophosphatemic rickets Familial hypophosphatemic rickets X-linked dominant (m/c) Renal tubule s inability to retain phosphate Phosphate diabetes, hypophosphatemia 15

16 Hypophosphatemic rickets 1/100,000 ~ 1/1,000,000 Mutation in the PHEX genes sequence, chromosome Xp22.1 Laboratory findings Normal or nearly normal levels of calcium Normal PTH, Vit D Decreased serum phosphate Increased concentration of phosphate in urine 16

17 Hypophosphatemic rickets Clinical features Becomes apparent at a slightly older age than nutritional rickets (1-2 years of age) Delayed walking, angular deformities (genu varum/valgum) Periarticular enlargement, rachitic rosary Short stature (below 2SD) Fractures 17

18 Hypophosphatemic rickets Radiographic findings Same as those seen in nutritional rickets Physeal elongation and widening Indistinct osteopenis metaphyses Coxa vara Anterior and lateral bowing of the entire femur Tibia vara 18

19 Hypophosphatemic rickets 19

20 Hypophosphatemic rickets Medical treatment Oral replacement of phosphorus in large doses and the administration of vitamin D Longitudinal growth is greater in children who undergo Vit D treatment Nephrocalcinosis ~79% of treated children with hypophosphatemic rickets 20

21 Hypophosphatemic rickets GH GH and insulin-like growth factor I (IGF- I) Transiently stimulate phosphate reabsorption Increase height, bone density, phosphate retention Vit D 3 analogs 21

22 Hypophosphatemic rickets Orthopaedic treatment Anterolateral bowing of the femur combined with tibia vara Increasing pain or difficulty walking Surgical correction of angular deformities Discontinuation of Vit D before surgery Calcium levels can suddenly climb 22

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24 17/F POD 9Yr after temporary epiphysiodesis 24

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26 23/ M 26

27 Renal Osteodystrophy Increasing tendency due to advances in the medical treatment of CRF and the incidence of renal transplantation Pathogenesis Phosphate retention 1,25 (OH) 2 VIT D gut absorption of Ca 2 hyperparaphyroidism End results Combination of rickets and 2 nd hyperparathyroidism Ectopic ossification possible d/t solubility of serum Ca and phosphorus is exceeded 27

28 Renal Osteodystrophy Rickets Proliferating and hypertrophic regions are widened Additional changes: Resorption of lower regions of physeal cartilage and their replacement with fibrous tissue and poorly organized and mineralized woven bone 28

29 Renal Osteodystrophy Radiographic findings Mixture of osteomalacia, osteitis fibrosa cystica, osteosclerosis, and osteoporosis Significant resorption of metaphyseal bone Patterns of bone absorption are variable 29

30 Hypophosphatasia Deficiency of alkaline phosphatase Tissue-nonspecific alkaline phosphatase gene (TNSALP) Autosomal recessive inheritance or AD Decreased ALP, normal Vit D, PTH, serum phosphorus, hypercalcemia may be present Currently no successful treatment is available Vit D can worsen the heterotopic calcification and nephrocalcinosis 30

31 Hypervitaminosis A Vit A Fat-soluble vitamin Skeletal growth, maintenance and regeneration of epithelial tissues, preservation of visual purple in the retina Inappropriate use of vitamin supplements Retinoids used for acne 31

32 Radiographic findings Periosteal hyperostosis Thickening of the cortex of the long bones Ulna, radius, metacarpals, and metatarsals Subperiosteal new bone formation Mandible is spared Distinguishes hypervitaminosis A from Caffey s disease DDx Caffey s disease, scurvy, congenital syphilis 32

33 Vitamin C deficiency (scurvy) Nutritional deficiency of vitamin C Impaired collagen synthesis Dysfunctional osteoblast Failure to produce osteoid tissue Chondroblasts continue to function normally Persistence of cartilage cells and calcified chondroid approaches the metaphysis 33

34 Radiographic findings Best seen at the knees, wrists, and proximal humeri Osteopenia, cortical thinning Frankle s line The zone of provisional calcification increases in width and opacity Failure of resorption of the calcified cartilaginous matrix Scurvy line Radiolucent transverse band adjacent to the dense provisional zone Epiphyseal separation 34

35 Endocrine disease Growth hormone deficiency Hypothyroidism Hyperparathyroidism 35

36 Growth Hormone deficiency 2/3 of cases of hypopituitarism In congenital forms The infant is of normal size Diminished growth is noted around 2-4 years of age Normal limb proportion in relation to the head and trunk Can be associated with hypogonadism Low or absent of GH Stimulation test (-) 36

37 Orthopaedic manifestation Delayed skeletal maturation The ossification centers are late in both appearance and closure Osteoporosis of the long bones and the skull Slipped femoral capital epiphysis 37

38 Hypothyroidism Thyroid Hormone Act on nearly every cell in the body Increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone), neuronal maturation and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness Essential to proper development and differentiation of all cells of the human body Also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds Stimulate vitamin metabolism 38

39 Hypothyroidism Incidence 1/4000 newborns Aplasia or hypoplasia of the thyroid Prolonged jaundice, lethargy, sleepiness, feeding difficulties, constipation Enlarged tongue, expressionless face 39

40 Orthopaedic considerations Enchondral bone formation is disturbed Delayed appearance of the epiphyses Resembles Perthes disease or MED Slipped femoral capital epiphysis Screening Younger than usual (less than 11 years old), family history of thyroid abnormalities, not of the typical obese body habitus Contralateral prophylactic pinning 40

41 Hyperparathyroidism Hyperplasia or adenoma of the parathyroid glands Increased secretion of PTH 1,25-(OH) 2 vitamin D Hypercalcemia, hypophosphatemia, elevated ALP Lethargy, bone pain, abdominal complaints Hypercalcemic crisis Ectopic calcification, renal calculi 41

42 Hyperparathyroidism Radiographic findings Resembles those of renal osteodystrophy Osteopenia Angular deformities Treatment Correcting the cause of the hyperparathyroidism 42

43 Hematologic disease Acute leukemia Hemophilia 43

44 Acute leukemia Most common form of cancer in children Peak age at diagnosis : 2-4 Yrs 80% of childhood acute leukemia is Acute lymphoblastic leukemia (ALL) 44

45 Clinical presentation Lethargy or malaise 36% Fever or infection 31% Extremity or joint pain 23% Bleeding manifestation 18% Anorexia 12% Abdominal pain 7 % CNS manifestation 2 % 45

46 Skeletal manifestation Musculoskeletal pain 40-62% of patients Gait abnormalities, refusal to walk Back pain Pain and swelling in the joints More than one joint is involved Knee, ankle, elbow Resembles JRA or septic arthritis 46

47 Radiographic findings Radiolucent metaphyseal band Abnormal mineralization of metaphyseal bone rather than infiltration of leukemia cells Periosteal new bone formation along the diaphyses of long bone Radiolucent lesions in cortical bone Bone destruction from leukemic infiltrates Small bones (hands, feet) or skull Prognostic significance of skeletal lesions in leukemia is unclear 47

48 Differential diagnoses Osteomyelitis Mimic ostoemyelitis with lytic lesions, osteopenia, periostitis Septic arthritis, JRA, growing pain Suspicion Routine lab May show normal in early stage Peripheral blood smear Bone marrow biopsy 48

49 4 / M C.C: both leg pain D: several days P.I: 평상시건강하였던환아로특별한외상력없이수일전부터양측하지통증으로내원 P/Ex Not so ill looking appearance Fever(-) Swelling(-), tenderness(-) Erythema(-), purpura (+)

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51 Hb 9.1 g/dl ( ) Hct 26.7% (35-45) Plt 20K/ul ( ) WBC 4260/ul ( ) Blast 20% ESR 61mm/hr (0-10) CRP 3.57 mg/l (0-5)

52 Hemophilia Disorder of hemostasis caused by a deficiency of clotting factor Genetically transmitted deficiency in coagulation factors Hemophilia A (VIII) X-linked recessive 1/10,000 live births in the US Hemophilia B (IX, Christmas disease) Von Willebrand s disease 52

53 Hemophilia Diagnosis Measuring the activity of the clotting factors; factor activity is less than 20%-50% of normal aptt - prolonged (deficient factors affect the intrinsic coagulation pathway) PT, plt count, and BT remain normal Severity (factor actibity) < 1%, severe: Frequent, spontaneous bleeds 1-5%, moderate: Bleeds following minor trauma > 5%, mild: Only bleeds after surgery or trauma 53

54 Hemophilic arthropathy Degeneration of joints following recurrent hemarthroses Weight bearing joint (knee>elbow>shoulder>ankle ) Treatment Joint aspiration and decompression following replacement therapy Splinting for hrs and rehabilitation starts Replacement continued through the next 5-7days for re-bleeding 54

55 Hemophilia Muscle hematomas Compartment syndrome Femoral neuropraxia (iliopsoas hematoma) Carpal tunnel syndrome Hemophilic pseudotumor (hemophilic blood cyst) 55

56 Hemophilia Raise to at least 30-70% for hemorrhage Raise to 100% for surgery One unit of Factor VIII concentrate 2% increase in the serum activity level per B.W(Kg) with dosing every 8 to 12 hrs One unit of Factor IX concentrate 1% increase in the serum activity level per B.W(Kg) with dosing every 18 to 24hrs 56

57 8 mo/m C.C: left leg swelling D: several days P.I: 특별한외상력없이수일전부터좌측대퇴부종창, 쓰려하지않음 P/Ex Fever(-) Irritability(-) Swelling(+) Erythema(-)

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59 Hb 8.9 g/dl ( ) Hct 26.3% (35-45) Plt 656K/ul ( ) CRP 9.74mg/L (0-5) PT 12.6 sec ( ) I.N.R ( ) aptt sec ( ) Factor VIII 20%(60-150) Factor IX 109%(60-150) Von-Willebrand factor 61.6%(44-158) 59

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