Integration Lecture 1 Claudia Stanescu Ph D Office hours Tue 10 12 Thurs 2 3 Final exam format 40 multiple choice questions 4 pts each 10 questions from the two integration lectures 30 questions from the rest of the course lectures focusing on the objectives listed in the study guide posted on D2L Integration lecture objectives 1 Apply knowledge gained in this course to physiological scenarios problems 2 Integrate information across organ systems Collagen Mineral Organization Collagen microfibril Hambli R and Barkaoui A Journal of Theoretical Biology 301 2012 28 41 Minerals deposited in spaces between collagen molecules Nair AK et al Molecular mechanisms of mineralized collagen fibrils in bone Nature communications 2013 Bone Remodeling 1 ACTIVATION preosteoclasts are stimulated and differentiate under the influence of cytokines and growth factors into mature active osteoclasts 2 RESORPTION osteoclasts digest mineral matrix old bone 5 QUIESCENCE osteoblasts become resting bone lining cells on the newly formed bone surface 4 months 3 REVERSAL end of resorption recruitment of osteoblasts 4 FORMATION osteoblasts synthesize new bone matrix www iofbonehealth org Major Bone Diseases Osteoporosis Decreased bone mass and density that causes thinning of bones and increased risk of fracture normal ratio of bone mineral to matrix usually not associated with pain unless fracture occurs diagnosed with bone scan and usually not detectable with blood tests Osteomalacia Decreased mineralization of newly formed bone matrix at sites of bone remodeling as a consequence of Ca2 deficiency due to Vit D deficiency associated with achy bone pain Osteogenesis Imperfecta Congenital disorder that affects production of type I collagen due to genetic mutation brittle bones that fracture easily often in childhood or adolescence pain associated with fractures Problem 1 Ms Lopez is a 47 year old woman experiencing hip pain She tripped and fell earlier today and landed on her buttocks She has a history of low bone density but never had a single bone fracture Based on the patient information which of the following diseases could you rule out and why 1 Osteoporosis 2 Osteomalacia 3 Osteogenesis imperfecta Please discuss this in groups of 3 4 Major Bone Diseases Osteoporosis Decreased bone mass and density that causes thinning of bones and increased risk of fracture normal ratio of bone mineral to matrix usually not associated with pain unless fracture occurs diagnosed with bone scan and usually not detectable with blood tests Osteomalacia Decreased mineralization of newly formed bone matrix at sites of bone remodeling as a consequence of Ca2 deficiency due to Vit D deficiency associated with achy bone pain Osteogenesis Imperfecta Congenital disorder that affects production of type I collagen due to genetic mutation brittle bones that fracture easily often in childhood or adolescence pain associated with fractures Based on the patient history which of the following diseases could you rule out A Osteoporosis B Osteomalacia C Osteogenesis imperfecta 54 21 A 25 B C More about Ms Lopez History celiac disease hip pain for months skin cancer fear Blood tests mostly normal except Calcium 7 1 mg dl 8 6 10 6 mg dl 25 hydroxy vitamin D 9 ng ml 30 80 ng ml Parathyroid hormone 120 pg ml 15 75 pg ml Imaging Low bone density DXA and pseudofracture present in femur neck Based on the patient history and the labs and imaging what is your diagnosis and why 1 Osteoporosis 2 Osteomalacia Please discuss in groups of 3 4 More about Ms Lopez History celiac disease hip pain for months skin cancer fear Blood tests mostly normal except Calcium 7 1 mg dl 8 6 10 6 mg dl 25 hydroxy vitamin D 9 ng ml 30 80 ng ml Parathyroid hormone 120 pg ml 15 75 pg ml Imaging Low bone density DXA and pseudofracture present in femur neck Based on the patient history and the labs and imaging what is your final diagnosis A Osteoporosis B Osteomalacia 91 9 A B More about Ms Lopez History celiac disease hip pain for months skin cancer fear Blood tests mostly normal except Calcium 7 1 mg dl 8 6 10 6 mg dl 25 hydroxy vitamin D 9 ng ml 30 80 ng ml Parathyroid hormone 120 pg ml 15 75 pg ml Imaging Low bone density DXA and pseudofracture present in femur neck Vitamin D pathway Skin Vitamin D precursor 7 dehydrocholesterol PTH UV Light Skin Kidney Liver Vitamin D3 Cholecalciferol Blood 25 hydroxyCholecalciferol Calcidiol Blood Active form Blood Intestine Dietary Vitamin D3 Cholecalciferol 1 25 dihydroxycholecalciferol Calcitriol Low Blood Calcium Fish oil Egg yolks Milk Vitamin D is converted to the active form only if PTH present or Ca is low in the blood Discussion Osteomalacia vitamin D is low because of poor absorption in the intestine and because the patient is afraid of the sun Low vitamin D leads to calcium deficiency leads to release of PTH in an effort to increase the calcium levels in the blood PTH can stimulate calcium release from bones hence low bone density everywhere but cannot stimulate absorption of calcium from intestine without vitamin D Despite PTH presence serum calcium is still low because there is an absolute requirement for calcium from the diet to maintain calcium levels Osteoporosis Why are the blood tests normal in osteoporosis Patients do not experience pain with osteoporosis usually asymptomatic With osteoporosis bone resorption is greater than bone formation However bone remodeling cycles last 4 months and the release of calcium from bone is slow This may increase the blood and urine calcium slightly but not fast enough to be detected in a blood test values may be on the high end of normal Pseudofractures are not seen in osteoporosis Problem 1 Take Home Message 1 Deficiency of collagen or minerals in bone can lead to decreased bone strength understanding the role of each component in bone strength can help you understand different bone disorders 2 Osteoporosis does not usually present with pain serum calcium vitamin D and parathyroid hormone are usually normal 3 Low bone density does not always mean osteoporosis patient history and lab work are needed to rule out other conditions Problem 2 Effect of exercise on muscle Muscle will change in response to the stresses it encounters Exercise requires 1 increased energy utilization aerobic activity 2 increased force production strength training Problem 2 Effect of exercise on muscle MRI shows increased cross sectional area CSA with strength training Coronal Axial Quadriceps VL Quadriceps VL What