Chapter 3: Anesthesia Effects on Cellular Function

INTRODUCTION

The medical cellular biology of living human cells in the context of anesthesia is an elaboration of Chapters 1 and 2, where we reviewed fundamental cellular function/metabolism as well as neuromuscular physiology. Cellular biology is based on the fundamental laws of nature embodied in chemistry and physics whereas anesthesia can be broadly defined as a drug-induced reversible depression of the CNS resulting in loss of response to and perception of all external stimuli.¹ Even more precise, clinical anesthesia can be depicted as a collection of five changes in perception—amnesia, analgesia, unconsciousness, attenuation of autonomic responses, and immobility. Hundreds of millions of patients receive anesthesia care each year, making this topic critical to sound patient care and clinical practice.

CELLULAR MEMBRANE ARCHITECTURE

Nearly all human cells have a plasma membrane, nucleus, lysosome, endoplasmic reticulum, Golgi apparatus, ribosomes, and mitochondria. Each organelle contributes to cellular communication and energy metabolism that form the principle cellular behaviors we observe microscopically and macroscopically. The cellular membrane is a dynamic envelope compartmentalizing intracellular milieu from the extracellular environment. At the most basic level, a phospholipid bilayer assembles from outer hydrophilic phosphorylated glycerol heads and inner hydrophobic fatty acid tails. Cholesterol is abundant in the membrane, functioning to maintain adequate membrane fluidity in the face of a rapidly shifting extracellular environment. The protein component of the cell membrane includes both integral membrane proteins (embedded in the membrane) and peripheral proteins (attached outside the membrane).² Integral membrane proteins serve a wide variety of roles in the cell including membrane ion channels, pores, adhesion anchors, and membrane receptors. On the other hand, peripheral membrane proteins perform roles such as signaling, recognition, cellular division, cellular structure, and membrane trafficking.³ Interestingly, membrane lipids function as a filter, permitting free passage of lipid-soluble particles (e.g., steroid hormones, oxygen, carbon dioxide) while prohibiting diffusion of any hydrophilic substances (e.g., water, glucose, ions). Transporting these molecules is the role of membrane proteins. Accordingly, the amount and type of membrane protein dictate cell identity and functionality.

Transportation of a molecular entity across the cell membrane can be categorized into one of the three mechanisms: simple diffusion, facilitated diffusion, and active transport. While simple diffusion is driven by way of concentration difference across the membrane (i.e., without any energy input), facilitated diffusion and active transport both require energy input.⁴ Simple passive diffusion transports very small, uncharged, and nonpolar particles with a lipophilic profile. Conversely, facilitated diffusion and active transport move large, charged, polar, and/or lipophobic particles with a membrane impermeable profile. The classic example of active transport is the Na/K-ATPase pump which restores the high extracellular Na concentration and high intracellular K concentration via exchange of three sodium ions and two potassium ions.

TWO COMPETING THEORIES OF GENERAL ANESTHESIA MECHANISMS

The role of an anesthetic agent is to interact with several possible molecular ...