Of Medical Physiology - Fundamentals

In the beginning, there was a void. Not an empty one, but a bustling, hypoxic darkness deep within the spongy red marrow of a human femur. Here, in the hematopoietic niche, a humble hematopoietic stem cell received a signal: a whisper of the cytokine erythropoietin, released by the kidneys because the blood’s oxygen levels had dipped slightly below a set point.

In the lung’s alveolar capillaries, E-1173 experienced a transformation. It rolled to a stop, flattened against a thin endothelial wall. On the other side was a puff of inhaled air (partial pressure of O₂ ~100 mmHg). The air’s oxygen molecules, driven by the simple physics of , passed through the alveolar membrane, through the plasma, and into E-1173. There, oxygen bound cooperatively to the four heme groups of its hemoglobin. E-1173 turned from a dull maroon to a brilliant scarlet. It had been oxygenated . In return, it unloaded the waste product carbon dioxide (as bicarbonate, thanks to the enzyme carbonic anhydrase in its cytoplasm) back into the alveolus to be exhaled. The law of mass action was served. fundamentals of medical physiology

And E-1173 obeyed. The oxygen disassociated from its hemoglobin and diffused down its concentration gradient into a muscle cell. Inside that muscle cell, the oxygen was immediately consumed by the in the mitochondria, the final step of aerobic respiration, to produce ATP. The jogger’s leg contracted. Homeostasis, at this microscopic level, was being maintained. In the beginning, there was a void

But a crisis loomed.

Now bright and buoyant, E-1173 returned to the left heart and was launched into the systemic circulation. It traveled at breakneck speed through the aorta, then into arteries, then arterioles. The flow was not silent. It heard the faint, rhythmic thump-thump of each heartbeat—the —and felt the pressure wave that would be measured as 120/80 mmHg on a clinician’s cuff. In the lung’s alveolar capillaries, E-1173 experienced a

E-1173’s first challenge was to leave the marrow. It squeezed, deforming its flexible membrane (a property called ) through a tiny pore in the sinusoidal wall. It was now adrift in a raging river: the venous bloodstream. The current was driven by the right ventricle of the heart, a four-chambered marvel of hemodynamics . E-1173 was swept through the vena cava, into the right atrium, through the tricuspid valve, and into the right ventricle. With a coordinated electrical impulse from the sinoatrial node—a cardiac action potential —the ventricle contracted. Lub . E-1173 was shot through the pulmonary artery toward the lungs.

E-1173, however, was trapped and doomed. A macrophage, the tissue’s resident sentinel, engulfed it in a quiet act of . The heme group was broken down into biliverdin, then bilirubin, which the liver would eventually excrete in bile. The iron atom was carefully saved, bound to transferrin, and shipped back to the bone marrow to build a new red blood cell.