Blood disruption

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

State of deviation of plasma pH (systemic acidosis) or tissue extracellular pH (tissue or local acidosis) from normal (ca. pH 7.4) towards lower values. Deviation of 0.1 pH units is significant. Systemic acidosis can be caused by lung or kidney failure. Local acidosis can be the consequence of injury, inflammation, or tumor growth, due to disruption of blood supply. Local acidosis is normally associated with hypoxia. 

Acute coronary syndromes most often result from a physical disruption of the fibrous cap, either frank cap fracture or superficial endothelial erosion, allowing the blood to make contact with the thrombogenic material in the lipid core or the subendothelial region of the intima. This contact initiates the formation of a thrombus, which can lead to a sudden and dramatic blockade of blood flow through the affected artery. If the thrombus is nonocclusive or transient, it may either be clinically silent or manifest as symptoms characteristic of unstable angina. Importantly, if collateral vessels have previously formed, for example, due to chronic ischemia produced by multi vessel disease, even total occlusion of one coronary artery may not lead to an acute myocardial infarction. 

Amylase enters the blood largely via the lymphatics. An increase in hydrostatic pressure in the pancreatic ducts leads to a fairly prompt rise in the amylase concentration of the blood. Neither an increase in volume flow of pancreatic juice nor stimulation of pancreatic enzyme production will cause an increase in senm enzyme concentration. Elevation of intraductal pressure is the important determinant. Stimulation of flow in the face of obstruction can, however, augment the entry of amylase into the blood, as can disruption of acinar cells and ducts. A functional pancreas must be present for the serum amylase to rise. Serum amylase determination is indicated in acute pancreatitis in patients with acute abdominal pain where the clinical findings are not typical of other diseases such as appendicitis, cholecystitis, peptic ulcer, vascular disease or intestinal obstruction. In acute pancreatitis, the serum amylase starts to rise within a few hours simultaneously with the onset of symptoms and remains elevated for 2 to 3 days after which it returns to normal. The peak level is reached within 24 hours. Absence of increase in serum amylase in first 24 hours after the onset of symptoms is evidence against a diagnosis of acute pancreatitis (76). 

Dallasta LM, Pisarov LA, Esplen JE, Werley JV, Moses AV, Nelson JA, Achim CL (1999) Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. Am J Pathol 155 1915-1927... 

Latour LL, Kang DW, Ezzeddine MA, Chalela JA, Warach S. Early blood-brain barrier disruption in human focal brain ischemia. Ann Neurol 2004 56 468 77. 

Warach S, Latour LL. Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption. Stroke 2004 35 2659-2661. 

Rapid dermal absorption of trichloroethylene is evident from a study in which peak blood and exhaled air concentrations occurred within 5 minutes after a human subject immersed one hand in a solution of unspecified trichloroethylene concentration for 30 minutes (Sato and Nakajima 1978). Studies on dermal absorption of trichloroethylene in humans, as well as animals, are complicated by the fact that exposure in these studies is usually by direct contact of the skin with the undiluted chemical. Trichloroethylene is a lipophilic solvent that defats the skin and disrupts the stratum comeum, thereby enhancing its own absorption. Thus, the rate of absorption probably increases in a nonlinear fashion with greater epidermal disruption. Although the extent of absorption through the skin may be relatively modest with normal industrial use (Sato and Nakajima 1978 Stewart and Dodd 1964), there is insufficient information to evaluate the effects of chronic, low-level exposure in hiunans, especially when multiple routes may be involved. 

Traditional CNS stimulants have the potential to increase blood pressure and heart rate when used long term. In addition, excessive CNS stimulation can cause tremors and tics and can carry over into evening hours, where initiation of normal nighttime sleep can be disrupted. Caution should be used in patients with underlying cardiovascular or cerebrovascular disease and in patients with a history of seizures because stimulants may lower the seizure threshold. 

It is important to carefully document core ADHD symptoms at baseline to provide a reference point from which to evaluate effectiveness of treatment. Improvement in individualized patient outcomes are desired, such as (1) family and social relationships, (2) disruptive behavior, (3) completing required tasks, (4) self-motivation, (5) appearance, and (6) self-esteem. It is very important to elicit evaluations of the patient s behavior from family, school, and social environments in order to assess the preceding. Using standardized rating scales (e.g., Conners Rating Scales-Revised, Brown Attention-Deficit Disorder Scale, and IOWA Conners Scale) in both children and adults with ADHD helps to minimize variability in evaluation.29 After initiation of therapy, evaluations should be done every 2 to 4 weeks to determine efficacy of treatment, height, weight, pulse, and blood pressure. Physical examination or liver function tests may be used to monitor for adverse effects. 

Many areas of the human body are colonized with bacteria— this is known as normal flora. Infections often arise from one s own normal flora (also called an endogenous infection). Endogenous infection may occur when there are alterations in the normal flora (e.g., recent antimicrobial use may allow for overgrowth of other normal flora) or disruption of host defenses (e.g., a break or entry in the skin). Knowing what organisms reside where can help to guide empirical antimicrobial therapy (Fig. 66-1). In addition, it is beneficial to know what anatomic sites are normally sterile. These include the cerebrospinal fluid, blood, and urine. 

---