Pathophysiology
Cerebral perfusion pressure (CPP), the pressure of blood flowing to the brain, is normally fairly constant due to autoregulation, but for abnormal mean arterial pressure (MAP) or abnormal ICP the cerebral perfusion pressure is calculated by subtracting the intracranial pressure from the mean arterial pressure: CPP = MAP − ICP . One of the main dangers of increased ICP is that it can cause ischemia by decreasing CPP. Once the ICP approaches the level of the mean systemic pressure, cerebral perfusion falls. The bodys response to a fall in CPP is to raise systemic blood pressure and dilate cerebral blood vessels. This results in increased cerebral blood volume, which increases ICP, lowering CPP further and causing a vicious cycle. This results in widespread reduction in cerebral flow and perfusion, eventually leading to ischemia and brain infarction. Increased blood pressure can also make intracranial hemorrhages bleed faster, also increasing ICP.Severely raised ICP, if caused by a unilateral space-occupying lesion (e.g. a hematoma) can result in midline shift, a dangerous sequela in which the brain moves toward one side as the result of massive swelling in a cerebral hemisphere. Midline shift can compress the ventricles and lead to hydrocephalus. Monro–Kellie hypothesis
The pressure–volume relationship between ICP, volume of CSF, blood, and brain tissue, and cerebral perfusion pressure (CPP) is known as the Monro–Kellie doctrine or hypothesis.The Monro–Kellie hypothesis states that the cranial compartment is inelastic and that the volume inside the cranium is fixed.
This finding indicates that EBV is not the cause for the NK cell activation and excessive proliferation seen in NKCE and LG and distinguishes these diseases from malignant diseases they can mimic such as extranodal NK/T-cell lymphoma, nasal type. In isolated reports, LG has occurred in individuals with Helicobacter pylori infection of the stomach or a history of stomach cancer, while NKCE has been reported to occur in patients with gluten sensitivity or circulating anti-gliadin antibodies. Both of the latter conditions are associated with the development of GI tract lymphomas. However, the relationship of any of these findings to the etiology of LB and NKCE is unclear. Histology
Biopsies of NKCE tissues reveal atypical medium to large lymphocytes identified by immunohistochemistry to be NK cells that are multiplying at a moderately rapid rate and that lack evidence of being infected by the Epstein-Barr virus. These cells are located primarily in the lamina propria, i.e. loose connective tissue lying just below the epithelium lining the GI tract. There is generally little invasion of these cells into the epithelium, submucosa, or glands of the GI tract, and the lesions almost always show a complete absence of vascular injury due to invasion by these cells. The lesions in LG closely resemble those of NKCE.