Chapter 13 - Pathophysiology: General Principles

Abstract

Hypoxic-ischemic encephalopathy in the perinatal period is a common disorder that has an impact throughout the perinatal period in both the preterm and term-born infant. Hypoxic-ischemic encephalopathy is characterized by neuropathological and clinical features that constitute an important portion of neonatal neurology. To understand those features, which are discussed extensively in this Unit IV, it is necessary to be cognizant of the pathophysiological underpinnings, including the biochemical and physiological derangements, that lead to the structural and functional manifestations of this encephalopathy. Hypoxia refers to deficiency in oxygen within the circulation and at the cellular level. Ischemia refers to insufficient perfusion or, more specific to this setting, cerebral blood flow. This will usually be associated with concurrent hypoxia at the cellular level. The term hypoxic-ischemic injury is often used because of the intimate nature of these two components in mediating cerebral injury in the newborn infant. Thus, key to all is hypoxia and energy deprivation (including glucose) at the cellular level, resulting in alterations in cellular metabolism, with interruption of typical cellular function and a series of aberrant cellular consequences. In this chapter, we first deal with the major modes of cell death in the setting of hypoxic-ischemic injury. We then review the fundamental derangements in energy and cerebral blood flow, on a background of the normal cerebral biochemistry and circulation, of the perinatal brain. Much of what we know is based on experimental data, but translational data in humans with neuroimaging support these concepts. The secondary effects of these derangements in energy and cerebral blood flow via excitatory, oxidative, and inflammatory pathways is discussed. This will form the foundation for reviewing approaches to neuroprotection in the term and premature brain in relation to hypoxic-ischemic injury. The applications of these principles and their related neuropathologies in the setting of the preterm and term infant’s brain is discussed in more detail in the later chapters within this unit.