Respiratory acidosis is a state in which decreased ventilation (hypoventilation) increases the concentration of carbon dioxide in the blood and decreases the bloods pH (a condition generally called acidosis). Carbon dioxide is produced continuously as the bodys cells respire, and this CO2 will accumulate rapidly if the lungs do not adequately expel it through alveolar ventilation. Alveolar hypoventilation thus leads to an increased PaCO2 (a condition called hypercapnia). The increase in PaCO2 in turn decreases the HCO3−/PaCO2 ratio and decreases pH. Types
Respiratory acidosis can be acute or chronic. In acute respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range (over 6.3 kPa or 45 mm Hg) with an accompanying acidemia (pH <7.36). In chronic respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range, with a normal blood pH (7.35 to 7.45) or near-normal pH secondary to renal compensation and an elevated serum bicarbonate (HCO3− >30 mEq/L). Causes
Acute
Acute respiratory acidosis occurs when an abrupt failure of ventilation occurs. This failure in ventilation may be caused by depression of the central respiratory center by cerebral disease or drugs, inability to ventilate adequately due to neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, Guillain–Barré syndrome, muscular dystrophy), or airway obstruction related to asthma or chronic obstructive pulmonary disease (COPD) exacerbation. Chronic
Chronic respiratory acidosis may be secondary to many disorders, including COPD.
Cause
This section discusses the tumorigenesis of neurofibroma in terms of genetics, cell signaling, histology and the cell cycle. Neurofibromin 1 gene
The NF1 gene is composed of 60 exons spanning 350kb of genomic data, and maps to chromosomal region 17qll.2. This gene codes for neurofibromin which is a large 220-250 KDa cytoplasmic protein that is composed of 2,818 amino acids with three alternatively spliced exons (9a, 23a and 48a) in the encoding gene. The functional part of neurofibromin is a GAP, or GTPase-activating protein. GAP accelerates the conversion of the active GTP-bound RAS to its inactive GDP-bound form, inactivating RAS and reducing RAS-mediated growth signaling. Loss of RAS control leads to increased activity of other signaling pathways including RAF, ERK1/2, PI3K, PAK and mTOR-S6 kinase. This increased activity of downstream RAS pathways might work together to increase cell growth and survival. Genes that code for proteins that regulate cell growth, such as NF1 and TP53, are referred to as tumor suppressor genes. Neurofibromin has other growth-regulatory properties besides its ability to regulate RAS activity, but these other functions are poorly understood at this time. Schwann cells
There are two kinds of Schwann cells, myelinating and nonmyelinating. While myelinating Schwann cells cover large diameter (>1 micrometer) peripheral nervous system (PNS) axons with myelin, nonmyelinating Schwann cells encapsulate small diameter PNS axons with their cytoplasmic processes. Nonmyelinating Schwann cells are the neoplastic element in neurofibromas. This conglomeration of nonmyelinating Schwann cells and axons is called a Remak bundle.