Response to Hemorrhage

In another example of a part of an organism that changes its state in the face of brntal environmental conditions, we consider the effects of hemorrhage on the human body. A great loss of blood, even bleeding into internal tissnes, can lower cardiac output to the point where blood pres-snre falls dramatically. In response, the blood vessels constrict to increase resistance (and thus blood pressure), and to reduce blood stored in them. The veins, in particular, are normally blood storage vessels, and these constrict to move blood back to the heart faster. The contraction of the 

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Azar A, Trochimowicz HJ, Maxfield ME. 1973. Review of lead studies in animals carried out at Haskell Laboratory Two year feeding study and response to hemorrhage study. In Barth D, Berlin A, Engel R, et al., eds. Environmental health aspects of lead Proceedings, International Symposium, October 1972, Amsterdam, The Netherlands. Luxembourg Commission of the European Communities, 199-210. 

Sakai H, Takeoka S, Wettstein R, et al. Systemic and microvascular responses to hemorrhagic shock and resuscitation with Hb vesicles. Am J Physiol Heart Circ Physiol 2002 283 H1191. 

There is also experimental evidence that central DA neurons may be involved in inhibiting activated vasopressin secretion. In normal hydrated rats icv administration of DA suppresses anesthesia-induced vasopressin secretion (Forsling and Williams, 1984). Conversely, icv injection of a DA antagonist enhances vasopressin secretion in response to hemorrhage (Yamaguchi et al., 1990). No information is availability, however, regarding the identity of diencephalic neurons mediating the suppressive effects of DA on stimulated vasopressin release. 

Aldosterone secretion is under the control of the renin-angiotensin system and peripheral plasma renin levels have been found raised during laparotomy and in response to hemorrhage (CIO). 

Male rats given a single oral dose of 200 mg/kg of endosulfan had myocardial hemorrhages (Terziev et al. 1974). It is not clear whether this effect was due to a direct effect of endosulfan on the heart or secondary to other toxicity such as damage occurring in response to effects of endosulfan on neural control of the heart. 

Factor VIII and IX inhibitors are antibodies that develop in 20% and 12% of hemophilia A and hemophilia B patients, respectively, in response to replacement therapy. These antibodies bind to and neutralize the activity of infused factor concentrates. Although the inhibitors do not increase hemorrhage frequency, their existence challenges the treatment of bleeding episodes. Titers of inhibitors are measured and... 

This is not the only example. Recently, polymorphisms in the G protein p3-subunit gene have been shown to predict response to hydrochlorothiazide (Turner et al., 2001). Psaty et al. identified a subset of patients with a variant of the a-adducin gene that were associated with a lower risk of myocardial infarction and cerebral hemorrhage with diuretic therapy (Psaty et al., 2002). In addition, Genaissance has indicated that it has identified markers that predict the response to the statins, a class of drugs used to lower cholesterol. 

Nonimmune stresses can increase circulating proinflammatory cytokine concentrations. Hemorrhage, and certain psychological and physical stresses all increase HPA activity through mechanisms that may include catecholamines and peripheral CRH [reviewed in 29], However, in some experiments correlations between plasma ACTH and IL-6 levels in models of immune and nonimmune stresses are low. The role played by cytokines in the ACTH response to nonimmune stresses has not been established. 

The dorsal skin fold window model allows direct observation of tumor microvasculature (11). This model also permits longitudinal assessment of the tumor vascular response to therapy. An accurate systematic measurement of tumor blood vessels in the window model is the linear summation of blood vessels using Optimas software. This approach corrects for vascular dilation and hemorrhage. Quantification of red... 

Smyth et al. 1936). In some cases, moderate elevations in white cell counts are observed, perhaps in response to necrosis in the liver or kidneys. In a few cases, mild anemia is observed (Gray 1947), and occasionally this may become severe (Straus 1954). The mechanism underlying the blood dyscrasia is not known, but anemia might be secondary to internal hemorrhaging as a result of decreased synthesis of clotting factors by the liver (Guild et al. 1958 Stevens and Forster 1953 Straus 1954). 

Exposure of rats to carbon tetrachloride (up to 160 mg/kg/day for 10 days) by gavage did not alter the primary antibody response to sheep red blood cells, lymphoproliferative responses to mitogen or mixed leukocytes, natural killer cell activity, or cytotoxic T lymphocyte responses also, spleen and thymus weights were comparable to controls (Smialowicz et al. 1991). In rats exposed twice weekly for 4-12 weeks to 3,688 mg/kg/day, there was histologic evidence of hemorrhage, hemosiderin deposition, and lymphocyte depletion in the pancreaticoduodenal lymph node (Doi et al. 1991), an effect which may be secondary to induced hepatic damage. 

Eor many years the prevailing view was that p-blockers are contraindicated in CHE. The physiological rationale for not using 3-blockers in heart failure was certainly well founded. Heart failure patients have a decrease in cardiac output. Since cardiac output is a function of stroke volume times heart rate (CO = SV xHR), an increased heart rate would be necessary to maintain an adequate cardiac output in the presence of the relatively fixed decrease in stroke volume observed in CHE. A rapid increase in heart rate does play an important role in the physiological response to acute hemorrhage. Thus, a decrease in heart rate, along with a depression in contractility produced by p-blockers, would be expected to precipitate catastrophic decompensation and this certainly can happen in the acute setting. 

Indeed, your brain works so fast that you are always vulnerable to seizures in response to many different stimuli, such as a small head injury, a stroke, rapidly flashing lights, a tumor, vascular abnormalities, small hemorrhages, and so forth. Given the limitations of our brain physiology and chemistry, we are probably as smart as we possibly can be at this time in our species evolution. 

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