Growth & Bone PDF

1 Understand the control of growth. Learn about the hypothalamic-pituitary-growth (liver) axis ¡ Understand the hormones that regulate growth ¡ Learn about bone growth and its regulation. ¡ Pathophysiology of the growth axis. ¡ ¡ 2 ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ Osteoblasts: bone building cells, deposi...

1 Understand the control of growth. Learn about the hypothalamic-pituitary-growth (liver) axis ¡ Understand the hormones that regulate growth ¡ Learn about bone growth and its regulation. ¡ Pathophysiology of the growth axis. ¡ ¡ 2 ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ Osteoblasts: bone building cells, deposit new bone Osteoclasts: bone dissolving cells Osteoid: the organic extracellular matrix that makes up bone Cartilage: similar to bone but not calcified. Epiphysis: knob at the end of long bone Diaphysis: cylindrical shaft Epiphyseal plate: layer of cartilage separating the epiphysis from the diaphysis in growing bone Osteocytes: osteoblast derived cells, the most abundant cell type in bone, important for calcium homeostasis Chondrocytes: cartilage cells in the outer edge of the epiphyseal plate that divide and multiply during bone growth Periosteum: connective tissue sheath covering the outer bone Cortical (compact) bone: outer bone compartment Trabecular (cancellous) bone: inner bone compartment Ossification: process of bone being laid down during growth or remodeling Bone marrow: site of blood cell production ACG: You need to know these terms for this unit as well as another, so start learning them! 3 ¡ Growth depends on § Hormones that directly affect growth, and other § § § § permissive hormones Peripheral and central neurotransmitters Genetics An adequate diet (especially protein) and normal metabolic processes Freedom from chronic disease and stress; adequate sleep ▪ clinical relevance: glucocorticoids to children stunt growth 4 ¡ Not continuous § Postnatal growth spurt § Pubertal growth spurt § Requires GH, IGF-1 ¡ Fetal growth requires placental hormones, especially IGF-2 (but not growth hormone) 5 Hypothalamus – 2 neuropeptides GHRH: 44 amino-acid peptide Somatostatin: 14 & 28-aa peptide Receptors are GPCRs Pituitary GH (growth hormone, somatotropin): 191 aa protein Receptor is a member of the cytokine family GH binds to a GH binding protein in circulation Liver: Insulin-like growth factor-1 (IGF-1), 70 aa peptide IGF-1 receptor is in the tyrosine kinase family IGF-1 binding proteins transport IGF-1 in circulation IGF-1 is also made in kidney, brain, gonads, where it has other functions. 6 ¡ ¡ ¡ Both GH, IGF-1, and their receptors are required for normal growth. GH is released in pulses, associated with sleep, enhanced during adolescence, sexually dimorphic (male > female). Direct (anabolic) effects on growth. § Stimulates protein synthesis, cell division, cartilage and bone growth. ¡ Other metabolic effects not related to growth. § Increases fatty acid levels in blood by enhancing breakdown of triglyceride fat stored in adipose tissue – i.e., mobilization of fat stores. § Increases blood glucose levels by decreasing glucose uptake by muscles – i.e., muscles use the fatty acids as their fuel source (this conserves glucose for the brain) 7 § Thyroid hormone § Ghrelin (gut hormone – stimulates appetite, as well as GH) § Insulin (Deficiency often blocks growth; Hyperinsulinism may spur excessive growth) § Androgens ▪ Males - play role in pubertal growth spurt, stimulate protein synthesis in many organs ▪ Initially stimulate but then terminate epiphyseal plate closure. § Estrogens ▪ Effects of estrogens on growth prior to bone maturation are not well understood. Estrogens close epiphyseal plates in both sexes. If levels of these hormones are disrupted during childhood, full growth will not be attained. 8 Bone is living tissue made of connective tissue consisting of cells and an extracellular organic matrix. ¡ Osteoblasts: “bone formers” - make the organic matrix from collagen. ¡ § Derive from mesenchymal precursors in bone marrow ¡ Osteoclasts: “bone breakers” § Derive from hematopoietic precursors in the bone marrow. Calcium phosphate crystals in the matrix make the bone hard. ¡ Cartilage is similar to bone but not calcified. ¡ 9 Epiphysis – knob at the end of long bones Cortical (compact) bone – Outer compartment Epiphyseal plate – layer of cartilage separating epiphysis from diaphysis in growing bone Trabecular (cancellous) bone – inner compartment Diaphysis – cylindrical shaft Bone marrow – site of blood cell production 10 § GH and IGF-1 act together to stimulate growth of bone thickness and length. § They stimulate osteoblast activity, and stimulate proliferation of epiphyseal cartilage. § Bone growth only happens when the epiphyseal plate is “open.” When the epiphysis closes, the plates ossify and bones cannot lengthen. 11 Cartilage cells (chondrocytes) in the outer edge of the epiphyseal plate divide and multiply. Older cartilage cells near diaphyseal border enlarge. This temporarily widens the epiphyseal plate. The epiphysis is now farther from the diaphysis causing the oldest cartilage to calcify. These cells are deprived of O2, and die. Osteoclasts clear the cells. Osteoblasts swarm up and lay down bone around the cartilage remnants. This is called ossification. As a result of this process, the bone has lengthened and the epiphyseal plate thickness is maintained. 12 § Addition of new bone to outer surface of existing bone. § Occurs in the periosteum, a connective tissue sheath covering the outer bone. § Osteoblasts deposit new bone on external surface. § Osteoclasts dissolve bony tissue next to the marrow cavity (allows cavity to increase in proportion to the bone shaft circumference). 13 § Due to pituitary defect or hypothalamic § § § § dysfunction Hyposecretion of GH in child is one cause of dwarfism Hyposecretion of IGF-1 (African pygmy) Mutated or defective GH receptor (Laron dwarfism) ▪ GH-resistant, cannot be “rescued” by GH replacement; may even have high [GH]. Deficiency in adults produces relatively few symptoms; associated with reduced skeletal muscle mass and strength; decreased bone density. 14 www.westeros.org § Most often caused by GH- secreting pituitary adenoma § Symptoms depend on age when abnormal secretion begins ▪ Gigantism ▪ Caused by overproduction of GH in childhood before epiphyseal plates close ▪ Acromegaly ▪ Occurs when GH hypersecretion occurs after adolescence 15 Understand the control of growth. Learn about the hypothalamic-pituitary-growth (liver) axis ¡ Understand the hormones that regulate growth ¡ Learn about bone growth and its regulation. ¡ Pathophysiology of the growth axis. ¡ ¡ 16