OFC occurs in approximately 50% of patients with ESRD. ESRD occurs when the kidneys fail to produce calcitriol, a form of vitamin D, which assists in the absorption of calcium into the bones. When calcitriol levels decrease, parathyroid hormone levels increase, halting the storage of calcium, and instead triggering its removal from the bones. The concept of renal osteodystrophy is currently included into the broader term chronic kidney disease-mineral and bone disorder (CKD-MBD). Fluoride intoxicationOFC was noticed in the early years of community fluoridation to be at higher risk when water supplies were fluoridated. Indeed, death rates which in some cases were gruesomely dramatic during dialysis quickly brought attention to the fact that fluoride in water during dialysis was a health hazard. Modern dialysis takes pains to de-fluoridate water in order to minimize bone disease including OFC. The 2006 National Research Council confirmed kidney patients are a sub-population particularly susceptible to ill effects from fluoride exposure which manifest in bones.Fanconi syndrome: decrease amino acids, phosphate, glucose, bicarbonate and potassium salts. Pathophysiology
The effects of OFC on bone are largely dependent on the duration of the disease and the level of parathyroid hormone (PTH) produced. PTH is responsible for maintaining a homeostatic calcium concentration in the blood. It activates the parathyroid-hormone related protein receptor located on osteoclasts and osteocytes, both of which are responsible for the breakdown and maintaining of bone. Abnormalities affecting the parathyroid glands cause a surplus of PTH, which, in turn, increases the activity and frequency of osteoclasts and osteocytes.
ALK and ROS fusions offer opportunities for targeted therapies with tyrosine kinase inhibitors. Pathophysiology
The respiratory tract can be divided into two main components: the conducting airways and the gas exchange airways. The gas exchange airways are made of alveoli, small microscopic air sacs that are responsible for the exchange of oxygen and carbon dioxide during normal breathing. Alveoli are composed of two cell types, type I and type II pneumocytes. Type I pneumocytes cover 95% of alveolar surfaces, and are not able to regenerate. Type II pneumocytes are more common, making up 60% of the cells within alveolar epithelium, but constitute only 3% of the alveolar surface.There are several factors that contribute to the transformation of normal alveolar epithelium into dysplastic, or pre-cancerous, lesions. Adenocarcinoma of the lung develops in a step-wise progression as type II pneumocytes undergo consecutive molecular changes that disrupt normal cell regulation and turnover. Atypical adenomatous hyperplasia (AAH) is considered a pre-cancerous lesion, and is thought to further progress to adenocarcinoma in situ and invasive adenocarcinoma of the lung. The lesions of AAH are <5 mm, can be single or multiple, and have a ground glass appearance on CT imaging. As more genetic mutations and dysregulation of normal cell signaling pathways accumulate, AAH can progress to adenocarcinoma in situ (AIS). AIS lesions are classified as small tumors <3 cm with abnormal type II pneumocyte cell growth that is limited to the alveolar spaces i.e. without invasion into the stroma, pleura, or vasculature.