Livros sobre o tema "Bone cells Metabolism"

Red blood cells, erythrocytes, are unique in that they do not contain a nucleus. This fact facilitates the study of their metabolism. Erythrocytes contain the protein pigment haemoglobin, which is in solution in the cells and consists of globin chains and iron. In this chapter, the development of the understanding of erythrocytes is linked to the blood conditions haemolytic anaemia and paroxysmal nocturnal haemoglobinuria. Premature destruction of erythrocytes, in the absence of blood loss, is termed haemolysis. If the bone marrow is unable to compensate adequately, then anaemia ensues and the condition is called haemolytic anaemia. The underlying defect is a deficiency in the activity of the enzyme glucose-6-phosphate dehydrogenase, termed G6PD deficiency.

Fibroblast growth factor 23 (FGF23) and Klotho have emerged as major hormonal regulators of phosphorus (P) and vitamin D metabolism. FGF23 is secreted by bone cells and acts in the kidneys to increase urinary P excretion and inhibit the synthesis of 1,25 dihydroxyvitamin D (1,25(OH)2D) and in the parathyroid glands to inhibit the synthesis and secretion of parathyroid hormone. Phosphorus excess stimulates FGF23 secretion, likely as an appropriate physiological adaptation to maintain normal P homeostasis by enhancing urinary P excretion and diminishing intestinal P absorption via lower 1,25(OH)2D. The FGF23 concentrations are elevated early in the course of chronic kidney disease (CKD) and may be a primary initiating factor for the development of secondary hyperparathyroidism in this setting. Klotho exists in two forms: a transmembrane form and a secreted form, each with distinct functions. The transmembrane form acts as the key co-factor needed for FGF23 to bind to and activate its cognate receptor in the kidneys and the parathyroid glands. The secreted form of Klotho has FGF23-independent effects on renal P and calcium handling, insulin sensitivity, and endothelial function. Disturbances in the expression of Klotho may play a role in the development of altered bone and mineral metabolism in early CKD. In addition, abnormal circulating concentrations of both FGF23 and Klotho have been linked to excess cardiovascular disease, suggesting that both play an important role in maintaining cardiovascular health.

Bone is metabolically active throughout life and metabolic disturbances may have wide-ranging consequences that are not restricted to altering its mechanics. The study of some genetic bone diseases has already provided remarkable insights into the normal regulation of bone metabolism. Skeletal dysplasias are developmental disorders of the chondro-osseous tissues commonly resulting in short stature, which is often disproportionate. The underlying mutations are often in the structural genes encoding components of the matrix but may also involve growth factors or cell signalling. In contrast, the dysostoses tend to affect single bones or groups of bones, reflecting the transient nature of the many different signalling factors to which they are responsive during development. Abnormalities of bone density (high or low) may be due to primary deficiency of bone matrix synthesis (e.g. osteogenesis imperfecta and hypophosphatasia) but may also reflect an imbalance between bone formation and resorption. This may be caused by abnormalities of bone formation (e.g. hyperostosis/sclerosteosis and osteoporosis pseudoglioma syndrome) or bone resorption (e.g. classic osteopetrosis and fibrous dysplasia).

Bones are multifunctional passive organs of movement that supports soft tissue and directly attached muscles. They also protect internal organs and are a reserve of calcium, phosphorus and magnesium. Each bone is covered with periosteum, and the adjacent bone surfaces are covered by articular cartilage. Histologically, the bone is an organ composed of many different tissues. The main component is bone tissue (cortical and spongy) composed of a set of bone cells and intercellular substance (mineral and organic), it also contains fat, hematopoietic (bone marrow) and cartilaginous tissue. Bones are a tissue that even in adult life retains the ability to change shape and structure depending on changes in their mechanical and hormonal environment, as well as self-renewal and repair capabilities. This process is called bone turnover. The basic processes of bone turnover are: • bone modeling (incessantly changes in bone shape during individual growth) following resorption and tissue formation at various locations (e.g. bone marrow formation) to increase mass and skeletal morphology. This process occurs in the bones of growing individuals and stops after reaching puberty • bone remodeling (processes involve in maintaining bone tissue by resorbing and replacing old bone tissue with new tissue in the same place, e.g. repairing micro fractures). It is a process involving the removal and internal remodeling of existing bone and is responsible for maintaining tissue mass and architecture of mature bones. Bone turnover is regulated by two types of transformation: • osteoclastogenesis, i.e. formation of cells responsible for bone resorption • osteoblastogenesis, i.e. formation of cells responsible for bone formation (bone matrix synthesis and mineralization) Bone maturity can be defined as the completion of basic structural development and mineralization leading to maximum mass and optimal mechanical strength. The highest rate of increase in pig bone mass is observed in the first twelve weeks after birth. This period of growth is considered crucial for optimizing the growth of the skeleton of pigs, because the degree of bone mineralization in later life stages (adulthood) depends largely on the amount of bone minerals accumulated in the early stages of their growth. The development of the technique allows to determine the condition of the skeletal system (or individual bones) in living animals by methods used in human medicine, or after their slaughter. For in vivo determination of bone properties, Abstract 10 double energy X-ray absorptiometry or computed tomography scanning techniques are used. Both methods allow the quantification of mineral content and bone mineral density. The most important property from a practical point of view is the bone’s bending strength, which is directly determined by the maximum bending force. The most important factors affecting bone strength are: • age (growth period), • gender and the associated hormonal balance, • genotype and modification of genes responsible for bone growth • chemical composition of the body (protein and fat content, and the proportion between these components), • physical activity and related bone load, • nutritional factors: – protein intake influencing synthesis of organic matrix of bone, – content of minerals in the feed (CA, P, Zn, Ca/P, Mg, Mn, Na, Cl, K, Cu ratio) influencing synthesis of the inorganic matrix of bone, – mineral/protein ratio in the diet (Ca/protein, P/protein, Zn/protein) – feed energy concentration, – energy source (content of saturated fatty acids - SFA, content of polyun saturated fatty acids - PUFA, in particular ALA, EPA, DPA, DHA), – feed additives, in particular: enzymes (e.g. phytase releasing of minerals bounded in phytin complexes), probiotics and prebiotics (e.g. inulin improving the function of the digestive tract by increasing absorption of nutrients), – vitamin content that regulate metabolism and biochemical changes occurring in bone tissue (e.g. vitamin D3, B6, C and K). This study was based on the results of research experiments from available literature, and studies on growing pigs carried out at the Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences. The tests were performed in total on 300 pigs of Duroc, Pietrain, Puławska breeds, line 990 and hybrids (Great White × Duroc, Great White × Landrace), PIC pigs, slaughtered at different body weight during the growth period from 15 to 130 kg. Bones for biomechanical tests were collected after slaughter from each pig. Their length, mass and volume were determined. Based on these measurements, the specific weight (density, g/cm3) was calculated. Then each bone was cut in the middle of the shaft and the outer and inner diameters were measured both horizontally and vertically. Based on these measurements, the following indicators were calculated: • cortical thickness, • cortical surface, • cortical index. Abstract 11 Bone strength was tested by a three-point bending test. The obtained data enabled the determination of: • bending force (the magnitude of the maximum force at which disintegration and disruption of bone structure occurs), • strength (the amount of maximum force needed to break/crack of bone), • stiffness (quotient of the force acting on the bone and the amount of displacement occurring under the influence of this force). Investigation of changes in physical and biomechanical features of bones during growth was performed on pigs of the synthetic 990 line growing from 15 to 130 kg body weight. The animals were slaughtered successively at a body weight of 15, 30, 40, 50, 70, 90, 110 and 130 kg. After slaughter, the following bones were separated from the right half-carcass: humerus, 3rd and 4th metatarsal bone, femur, tibia and fibula as well as 3rd and 4th metatarsal bone. The features of bones were determined using methods described in the methodology. Describing bone growth with the Gompertz equation, it was found that the earliest slowdown of bone growth curve was observed for metacarpal and metatarsal bones. This means that these bones matured the most quickly. The established data also indicate that the rib is the slowest maturing bone. The femur, humerus, tibia and fibula were between the values of these features for the metatarsal, metacarpal and rib bones. The rate of increase in bone mass and length differed significantly between the examined bones, but in all cases it was lower (coefficient b <1) than the growth rate of the whole body of the animal. The fastest growth rate was estimated for the rib mass (coefficient b = 0.93). Among the long bones, the humerus (coefficient b = 0.81) was characterized by the fastest rate of weight gain, however femur the smallest (coefficient b = 0.71). The lowest rate of bone mass increase was observed in the foot bones, with the metacarpal bones having a slightly higher value of coefficient b than the metatarsal bones (0.67 vs 0.62). The third bone had a lower growth rate than the fourth bone, regardless of whether they were metatarsal or metacarpal. The value of the bending force increased as the animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. The rate of change in the value of this indicator increased at a similar rate as the body weight changes of the animals in the case of the fibula and the fourth metacarpal bone (b value = 0.98), and more slowly in the case of the metatarsal bone, the third metacarpal bone, and the tibia bone (values of the b ratio 0.81–0.85), and the slowest femur, humerus and rib (value of b = 0.60–0.66). Bone stiffness increased as animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. Abstract 12 The rate of change in the value of this indicator changed at a faster rate than the increase in weight of pigs in the case of metacarpal and metatarsal bones (coefficient b = 1.01–1.22), slightly slower in the case of fibula (coefficient b = 0.92), definitely slower in the case of the tibia (b = 0.73), ribs (b = 0.66), femur (b = 0.59) and humerus (b = 0.50). Bone strength increased as animals grew. Regardless of the growth point tested, bone strength was as follows femur > tibia > humerus > 4 metacarpal> 3 metacarpal> 3 metatarsal > 4 metatarsal > rib> fibula. The rate of increase in strength of all examined bones was greater than the rate of weight gain of pigs (value of the coefficient b = 2.04–3.26). As the animals grew, the bone density increased. However, the growth rate of this indicator for the majority of bones was slower than the rate of weight gain (the value of the coefficient b ranged from 0.37 – humerus to 0.84 – fibula). The exception was the rib, whose density increased at a similar pace increasing the body weight of animals (value of the coefficient b = 0.97). The study on the influence of the breed and the feeding intensity on bone characteristics (physical and biomechanical) was performed on pigs of the breeds Duroc, Pietrain, and synthetic 990 during a growth period of 15 to 70 kg body weight. Animals were fed ad libitum or dosed system. After slaughter at a body weight of 70 kg, three bones were taken from the right half-carcass: femur, three metatarsal, and three metacarpal and subjected to the determinations described in the methodology. The weight of bones of animals fed aa libitum was significantly lower than in pigs fed restrictively All bones of Duroc breed were significantly heavier and longer than Pietrain and 990 pig bones. The average values of bending force for the examined bones took the following order: III metatarsal bone (63.5 kg) <III metacarpal bone (77.9 kg) <femur (271.5 kg). The feeding system and breed of pigs had no significant effect on the value of this indicator. The average values of the bones strength took the following order: III metatarsal bone (92.6 kg) <III metacarpal (107.2 kg) <femur (353.1 kg). Feeding intensity and breed of animals had no significant effect on the value of this feature of the bones tested. The average bone density took the following order: femur (1.23 g/cm3) <III metatarsal bone (1.26 g/cm3) <III metacarpal bone (1.34 g / cm3). The density of bones of animals fed aa libitum was higher (P<0.01) than in animals fed with a dosing system. The density of examined bones within the breeds took the following order: Pietrain race> line 990> Duroc race. The differences between the “extreme” breeds were: 7.2% (III metatarsal bone), 8.3% (III metacarpal bone), 8.4% (femur). Abstract 13 The average bone stiffness took the following order: III metatarsal bone (35.1 kg/mm) <III metacarpus (41.5 kg/mm) <femur (60.5 kg/mm). This indicator did not differ between the groups of pigs fed at different intensity, except for the metacarpal bone, which was more stiffer in pigs fed aa libitum (P<0.05). The femur of animals fed ad libitum showed a tendency (P<0.09) to be more stiffer and a force of 4.5 kg required for its displacement by 1 mm. Breed differences in stiffness were found for the femur (P <0.05) and III metacarpal bone (P <0.05). For femur, the highest value of this indicator was found in Pietrain pigs (64.5 kg/mm), lower in pigs of 990 line (61.6 kg/mm) and the lowest in Duroc pigs (55.3 kg/mm). In turn, the 3rd metacarpal bone of Duroc and Pietrain pigs had similar stiffness (39.0 and 40.0 kg/mm respectively) and was smaller than that of line 990 pigs (45.4 kg/mm). The thickness of the cortical bone layer took the following order: III metatarsal bone (2.25 mm) <III metacarpal bone (2.41 mm) <femur (5.12 mm). The feeding system did not affect this indicator. Breed differences (P <0.05) for this trait were found only for the femur bone: Duroc (5.42 mm)> line 990 (5.13 mm)> Pietrain (4.81 mm). The cross sectional area of the examined bones was arranged in the following order: III metatarsal bone (84 mm2) <III metacarpal bone (90 mm2) <femur (286 mm2). The feeding system had no effect on the value of this bone trait, with the exception of the femur, which in animals fed the dosing system was 4.7% higher (P<0.05) than in pigs fed ad libitum. Breed differences (P<0.01) in the coross sectional area were found only in femur and III metatarsal bone. The value of this indicator was the highest in Duroc pigs, lower in 990 animals and the lowest in Pietrain pigs. The cortical index of individual bones was in the following order: III metatarsal bone (31.86) <III metacarpal bone (33.86) <femur (44.75). However, its value did not significantly depend on the intensity of feeding or the breed of pigs.

Cancer produces endocrine and metabolic complications in two ways. Firstly, the primary tumour or its metastases may interfere with the function of endocrine glands, kidneys, or liver by invasion or obstruction. Secondly, tumours may give rise to remote effects without local spread and these actions are termed paraneoplastic manifestations of malignancy. Generally, these paraneoplastic syndromes arise from secretion by tumours of hormones, cytokines, and growth factors, but also occur when normal cells secrete products in response to the presence of tumour. This chapter reviews the pathogenesis, epidemiology, and management of the commonest paraneoplastic endocrinopathies including hypercalcaemia, Cushing’s syndrome, the syndrome of inappropriate antidiuresis, non-islet cell tumour hypoglycaemia, enteropancreatic hormone syndromes, Carcinoid syndrome, phaeochromocytoma, gonadotrophin secretion syndromes, prolactin and oxytocin secretion, and paraneoplastic pyrexia. The chapter concludes with a brief discussion of the management of metabolic disease in the context of advanced malignancy including hyperglycaemia, thyroid dysfunction, metabolic bone disease, renal failure, liver failure, and lactic acidosis.

Thyroid hormones act on most tissues via nuclear T3 receptors. Thyroid hormones stimulate oxygen consumption and heat production, influence cell growth and maturation (central nervous system, bone), and modulate metabolism (carbohydrates, lipids, proteins, drugs). Treatment for presumed thyroid disease frequently has to be initiated before the results of diagnostic tests are available. Treatment of hyperthyroidism should result in the reduction of serum thyroid hormone levels and their action on peripheral tissues with concurrent treatment of the precipitating event. In severe hypothyroidism the choice of thyroid hormone (thyroxine or tri-iodothyronine), optimal dosing, and the route of administration remain controversial

Normal serum magnesium levels are in the range of 0.7–1.0 mmol/l and, as for calcium, most of the total body magnesium is found in bone and soft tissues. Magnesium is essential for normal cell metabolism (as a cofactor for numerous enzymes) and for neuronal function, and regulates parathyroid hormone release. Alterations in serum magnesium levels are usually asymptomatic unless severe. As there are large tissue reserves of magnesium, hypomagnesaemia usually only develops with chronic gastrointestinal or renal losses, or prolonged dietary insufficiency. Hypermagnesaemia is almost always iatrogenic, due to excessive supplementation. This chapter reviews the causes and management of derangements of plasma magnesium.

Along with energy and protein, the body needs two further groups of nutrients in the diet, in relatively small amounts: mineral salts and vitamins. ‘Vitamins and minerals’ explains how these micro-nutrients are essential for maintenance of normal health, growth, and metabolic integrity. Vitamin D and niacin are the only vitamins that can be synthesized by the body; all other vitamins must be provided in the diet. The most important minerals are iron and calcium, but other trace elements are required in small amounts. Iron is needed for synthesis of the protein haemoglobin, which transports oxygen in red blood cells, and calcium is required for bone formation and regulating the activity of muscle.

Vascular calcification (VC) is a common feature of patients with advanced CKD and it could be, at least in part, the cause of increased cardiovascular mortality in these patients. From a morphologic point of view, there are at least two types of pathologic calcium phosphate deposition in the arterial wall—namely, intima calcification (mostly associated with atherosclerotic plaques) and media calcification (associated with stiffening of the vasculature, resulting in significantly adverse cardiovascular outcomes). Although VC was viewed initially as a passive phenomenon, it appears to be a cell-mediated, dynamic, and actively regulated process that closely resembles the formation of normal bone tissue, as discovered recently. VC seems to be the result of the dysregulation of the equilibrium between promoters and inhibitors. The determinants are mostly represented by altered calcium and phosphorus metabolism, secondary hyperparathyroidism, vitamin D excess, high fibroblast growth factor 23, and high levels of indoxyl sulphate or leptin; meanwhile, the inhibitors are vitamin K, fetuin A, matrix G1a protein, osteoprotegerin, and pyrophosphate. A number of non-invasive imaging techniques are available to investigate cardiac and vascular calcification: plain X-rays, to identify macroscopic calcifications of the aorta and peripheral arteries; two-dimensional ultrasound for investigating the calcification of carotid arteries, femoral arteries, and aorta; echocardiography, for assessment of valvular calcification; and, of course, computed tomography technologies, which constitute the gold standard for quantification of coronary artery and aorta calcification. All these methods have a series of advantages and limitations. The treatment/ prevention of VC is currently mostly around calcium-mineral bone disease interventions, and unproven. There are interesting hypotheses around vitamin K, Magnesium, sodium thiosulphate and other potential agents.

Paediatric Rheumatology, second edition is an indispensable resource for the identification and management of rheumatological diseases of children and young people. As well as covering common and rare musculoskeletal problems, there are also chapters on rheumatological emergencies designed for quick reference, and essential core clinical skills of relevance to the full spectrum of paediatric rheumatological disease. This second edition is fully updated, including state-of-the-art descriptions of new autoinflammatory diseases, advances in genetics in paediatric rheumatology, up-to-date guidance on the treatment of JIA, vasculitis, SLE, JDM, and other connective tissue diseases. Highlights of the second edition include alignment of management approaches for paediatric rheumatological diseases with recent evidence-based / consensus European guidelines; a description of North American treatment approaches to JIA; updated chapters on more specialist interventions including immunization in the immunosuppressed, and haematopoietic stem cell transplantation; and sections describing approaches to the management of rheumatological diseases in developing countries. Bone diseases are also described in detail including CRMO, skeletal dysplasias, and metabolic bone diseases. The second edition also includes a colour plate depicting rashes presenting in paediatric rheumatological conditions. This second edition is fully endorsed by the British Society for Paediatric and Adolescent Rheumatology (BSPAR), and many members of BSPAR have contributed most of the chapters. This second edition thus provides fully updated clinical guidelines and supporting information needed to successfully manage children and young people with rheumatological conditions.

Magnesium is critically important in the process of energy release. Although most magnesium is stored outside the extracellular fluid compartment, the regulated concentration appears in blood. Urinary magnesium excretion can decrease rapidly to low values when magnesium entry rate into the extracellular fluid volume is low, which has several important implications: cell and bone magnesium do not play a major role in the defence of blood magnesium concentration; while a major role is played by the kidney and especially the renal tubule, which adapts to match the urinary magnesium excretion and net entry of magnesium into extracellular fluid. In the kidney, magnesium is reabsorbed in the proximal tubule, the thick ascending limb of the loop of Henle (TALH), and the distal convoluted tubule (DCT). Magnesium absorption is mainly paracellular in the proximal tubule and TALH, whereas it is transcellular in the DCT. The hormone(s) regulating renal magnesium transport and blood magnesium concentration are not fully understood. Renal tubular magnesium transport is altered by a number of hormones, mainly in the TALH and DCT. Parathyroid hormone, calcitonin, arginine vasopressin, ß-adrenergic agonists, and epidermal growth factor, all increase renal tubular magnesium reabsorption; in contrast, prostaglandin E2 decreases magnesium reabsorption. Non-hormonal factors also influence magnesium reabsorption: it is decreased by high blood concentrations of calcium and magnesium, probably via the action of divalent cations on the calcium-sensing receptor; metabolic acidosis decreases, and metabolic alkalosis increases, renal magnesium reabsorption.