During hemorrhage, several important positive feedback mechanisms can be observed. These include cardiac failure, acidosis, central nervous system depression, aberrations in blood clotting, and depression of the mononuclear phagocytic system (MPS). Let's discuss these mechanisms in detail.

Ventricular function curves show shifts to the right, particularly in the later stages of hemorrhagic shock (Fig. 19.24), indicating a progressive depression in myocardial contractility during hemorrhage.

The MPS, also known as the reticuloendothelial system, consists of macrophages distributed throughout the body. These macrophages are derived from bone marrow and circulate as monocytes before migrating into tissues. In the tissues, they phagocytose foreign material and present antigens to lymphocytes, initiating the adaptive immune response. Some examples of MPS cells include Kupffer cells in the liver, alveolar macrophages, microglia, and Langerhans cells.

The hypotension caused by hemorrhage leads to a reduction in coronary blood flow, thereby depressing ventricular function. This reduction in cardiac output further decreases arterial pressure, creating a classic positive feedback mechanism. Additionally, reduced blood flow to peripheral tissues causes an accumulation of vasodilator metabolites, which decreases peripheral resistance and exacerbates the fall in arterial pressure.

Inadequate blood flow during hemorrhage affects the metabolism of all cells. The decreased delivery of oxygen to cells results in accelerated production of lactic acid and other acid metabolites. Impaired kidney function hinders the proper excretion of excess H+, leading to generalized metabolic acidosis. Acidosis has a depressant effect on the heart, further reducing tissue perfusion and intensifying the metabolic acidosis. Moreover, acidosis decreases the reactivity of the heart and resistance vessels to neurally released and circulating catecholamines, intensifying the hypotension.

Hypotension in shock reduces cerebral blood flow. Moderate degrees of cerebral ischemia trigger significant sympathetic nervous system stimulation of the heart, arterioles, and veins, as mentioned earlier. However, in severe hypotension, the cardiovascular centers in the brainstem eventually become depressed due to inadequate cerebral blood flow. Consequently, the loss of sympathetic tone reduces cardiac output and peripheral resistance, exacerbating inadequate cerebral perfusion.
Some of the more important positive feedback mechanisms that are evident during hemorrhage include (1) cardiac failure, (2) acidosis, (3) central nervous system depression, (4) aberrations in blood clotting, and (5) depression of the mononuclear phagocytic system (MPS).
These mechanisms are discussed next.
Shifts to the right in ventricular function curves, particularly in the later stages of hemorrhagic shock (
Fig. 19.24 ), provide evidence of a progressive depression in myocardial contractility during hemorrhage.
*The MPS (previously called the reticuloendothelial system) consists of macrophages that are distributed throughout the body. They are derived from bone marrow and exist for a short period in circulating blood as monocytes. They then migrate into tissues, where they phagocytose foreign material and present antigens to lymphocytes to initiate the adaptive immune response. Cells of the MPS include the Kupffer cells of the liver, alveolar macrophages, microglia, and Langerhans cells.
•Fig. 19.24 Ventricular Function Curves for the Left Ventricle During the Course of Hemorrhagic Shock. Curve A representsthecontrolfunctioncurve;curves B toF representtimeafterthehemor-rhage:117minutes(curve B), 247minutes(curve C), 280minutes(curve D), 295minutes(curve E), and310minutes(curve F). (RedrawnfromCrowellJW,GuytonAC.Am J Physiol. 1962;203:248.)–2 0 2 4 6 8 10 12 0 200 400 600 800 1000 1200 1400 1600 A E F C D B Left atrial pressure (mm Hg) Cardiac output (mL/min)
The hypotension induced by hemorrhage reduces coronary blood flow and therefore depresses ventricular function. The consequent reduction in cardiac output further reduces arterial pressure, a classic example of a positive feedback mechanism. Furthermore, reduced blood flow to peripheral tissues leads to an accumulation of vasodilator metabolites that decrease peripheral resistance and therefore aggravate the fall in arterial pressure.
The inadequate blood flow during hemorrhage affects the metabolism of all cells. The decreased O2 delivery to cells accelerates tissue production of lactic acid and other acid metabolites. Moreover, impaired kidney function prevents adequate excretion of the excess H+ , and generalized metabolic acidosis ensues. The resulting depressant effect of acidosis on the heart is a further reduction in tissue perfusion, which aggravates the metabolic acidosis. Acidosis also reduces the reactivity of the heart and resistance vessels to neurally released and circulating catecholamines and thereby intensifies the hypotension.
The hypotension in shock reduces cerebral blood flow. Moderate degrees of cerebral ischemia induce pronounced sympathetic nervous stimulation of the heart, arterioles, and veins, as noted earlier. In severe hypotension, however, the cardiovascular centers in the brainstem eventually become depressed because of inadequate cerebral blood flow. The resulting loss of sympathetic tone then reduces cardiac output and peripheral resistance. The consequent reduction in Pa intensifies the inadequate cerebral perfusion.