Pathophysiology of the Human Stress Response Explained

Introduction

Stress may be defined as the physiological reaction of the human body that acts as a mediation mechanism, connecting a particular stressor with its associated target-organ effect. In this paper, the physiological and anatomical bases of the body's stress response are described within the bounds of historical analysis, theory, and the latest research outcomes. This is accomplished by (1) tracing psychophysiological effector processes that represent the stress response defined above, and (2) examining fundamental neuroanatomical structures (Everly & Lating, 2012).

Neurological Foundations

An understanding of the stress response requires a discussion of its bases in the nervous system's function and structure. The nervous system's fundamental functional units are called neurons. Neurons conduct motor, regulatory, and sensory signals throughout the body and possess the following basic units: (1) dendrites and postsynaptic dendritic membranes; (2) axon presynaptic membranes (the end points of the telodendria) and telodendria (the branching projections of the axon); and (3) the neuron's cell body, which contains the cell's nucleus (Everly & Lating, 2012).

Incoming signals first reach postsynaptic dendritic membranes. When these membranes are stimulated, ionotropic (electrical) and metabotropic (chemical) processes begin, with the neuron conducting incoming signals via the cell body and the dendrites. An impulse is then transmitted to presynaptic membranes via the axon and telodendria. From there, the signal is conducted to the next neuron's postsynaptic membrane — a complex task, as neurons are not in actual physical contact with one another (Everly & Lating, 2012).

Neurons are separated by a synaptic cleft, which may be traversed with the help of neurotransmitters. These chemicals reside in the storage vesicles of the telodendria and await the appropriate cue before moving toward presynaptic membranes. Once there, they discharge into synaptic clefts in order to inhibit or stimulate the postsynaptic membrane of the succeeding neuron.

The human body has two basic nervous systems — peripheral and central — which are functional structures housing several million neurons (Everly & Lating, 2012). The central nervous system comprises a "triune" brain with three functional levels and the spinal cord. The neocortex constitutes the brain's highest and most complex level. In addition to communication, interpreting and decoding sensory signals, and controlling overall musculoskeletal and motor behavior, the neocortex — especially its frontal lobe — controls imagination, memory, logic, planning, apprehension, decision making, and problem solving (Everly & Lating, 2012).

The next functional level's key element is the limbic brain, whose discussion is vital to the subject of stress because it serves as the brain's affective and emotional control center. This system comprises several neural structures, including the hippocampus, hypothalamus, septum, amygdala, and cingulate gyrus. The pituitary (endocrine) gland plays a key role in the limbic system (Everly & Lating, 2012).

The peripheral nervous system (PNS) comprises all neurons outside the central nervous system (CNS) and includes two networks: the autonomic and somatic nervous systems. The somatic system transfers motor and sensory signals between the PNS and CNS, innervating both the skeletal and striate musculature and the sensory organs. Anatomically, the PNS may be considered an extension of the CNS, as the former's functional control bases reside in the latter (Everly & Lating, 2012).

The human stress response is best understood by analyzing its dynamic "process," which can be defined from a systems standpoint — that is, from the perspective of interlinked multidimensionality. This systems perspective has undergone significant evolution and bears directly upon the phenomenology of human stress reaction. The model serves as a unifying theme, facilitating better insights into human stress phenomenology as well as its treatment and measurement. According to this model, the epiphenomenology of human stress reaction consists of complex interactive processes with several major elements:

1. Perceived or actual stressor events.
2. Activation of a target organ.
3. Affective integration and cognitive evaluation.
4. Coping behavior.
5. Neurological stimulating mechanisms (for instance, locus ceruleus, hypothalamic nuclei, and limbic nuclei).
6. The stress reaction — a physiological mediation mechanism (Everly & Lating, 2012).

Stressor events may be categorized as (1) biogenic and (2) psychosocial stressors (Girdano, Dusek, & Everly, 2009). Psychosocial stressors represent perceived or actual environmental events that set the stage for stress reaction production. They cannot cause stress reactions directly; rather, they require cognitive evaluation mechanisms. In fact, the majority of stressors are psychosocial in nature. Biogenic stressors, by contrast, are the actual causative elements of stress reaction production. These stimuli bypass higher cognitive evaluation processes and work directly on the neurological and affective stimulating nuclei. Owing to their biochemical characteristics, they trigger the stress reaction directly without the customary affective-cognitive processing (Everly & Lating, 2012). Biogenic stimuli include nicotine, ginseng, caffeine, and extreme cold or heat, pain-causing stimuli, and other physical factors.

Cognitive-Affective Domain and Neurological Triggering Mechanisms

Realistically, "reality" does not exist independent of the human perception that bears upon it. The systems model incorporates an affective-cognitive domain to capture this concept. Cognitive evaluation denotes the process of cognitive interpretation — the meanings assigned to events as they unfold. Affective integration denotes the blending of experienced emotions into cognitive interpretation, producing an affective-cognitive complex that reflects the way stressors are ultimately felt. This integrated view essentially determines whether psychosocial stimuli are converted into stressors. However, this perceptual process is uniquely personalized and susceptible to personality trends, biological dispositions, available coping resources, and learning history. While the model depicts a mutuality between affective and cognitive mechanisms, considerable evidence supports the cognitive primacy theory, which holds that cognition governs perceived emotion or affect and therefore assumes a superordinate role in restructuring human behavioral patterns (Everly & Lating, 2012).

As noted above, appraisal is a function of available coping resources, biological dispositions, personality trends, and learning history. After evaluation is carried out, efferent impulses project to the following structures for potentiating stimulation of key effector systems:

1. The limbic system's highly sensitive affective anatomy — particularly the hippocampus region — for experiencing stimulus-specific sensed emotion, as well as triggering visceral effector processes.
2. Neocortex regions related to neuromuscular behavior, where increased muscle tension or tone via the extrapyramidal and pyramidal systems may translate the intent to act into overt motor activity (Everly & Lating, 2012).

After being perceived, psychosocial stimuli stimulate general arousal and cognitive evaluation mechanisms. Stimuli evaluated as threatening, challenging, or aversive will likely produce emotional arousal. In most individuals, activation of limbic centers for emotional stimulation results in the expression of sensed emotions as neuromuscular and visceral activity. This neuromuscular and visceral activation constitutes the multi-axial physiological mediation mechanisms known as the "stress response." Before discussing the nature of the stress reaction, it is necessary to examine the mechanism that precedes stress reaction axes activation — what prior studies have labeled "neurological triggering mechanisms" (NTMs) (Everly & Lating, 2012).

NTMs comprise the locus ceruleus, the hypothalamic efferent stimulating complex, and the limbic system. Connected via serotonergic and dorsal and ventral adrenergic projections, this complex appears to include the hippocampus, locus ceruleus, posterior and anterior hypothalamic nuclei, and the septal-amygdaloid-hippocampal complexes. These structures appear to serve as the functional epicenters for somatic and visceral efferent secretions in response to emotional stimulation — in other words, they appear to produce the multi-axial stress reaction. These centers are also apparently capable of establishing a possibly self-perpetuating, endogenously governed neurological tone.

The terms "ego-tropic tuning," "charged arousal," and "limbic hypersensitivity" all indicate this tendency toward physiological stimulation and express a preferential sympathetic nervous system (SNS) pattern of reactiveness. Over time, this chronic tonic state may constitute the foundation for multiple psychophysiological and psychiatric disorders. The processes by which this neurological tone might impact a specific target organ form the focus of the model's next phase: the stress reaction as a physiological mediation mechanism (Everly & Lating, 2012).