Free to follow every thread. No paywall, no dead ends.
Red blood cell: the story on HearLore | HearLore
Red blood cell
In the year 1658, a young Dutch biologist named Jan Swammerdam peered through an early microscope and became the first human to describe the red blood cell, observing the blood of a frog. He could not have known that he was witnessing the most abundant cell in the vertebrate body, a microscopic workhorse that would eventually be found to number in the trillions within a single human adult. These cells, known scientifically as erythrocytes, are the principal means by which oxygen is delivered to body tissues, yet they remain largely invisible to the naked eye. They are flexible biconcave disks, lacking a nucleus and organelles, designed to be sacks of hemoglobin wrapped in a plasma membrane. Each human red blood cell contains approximately 270 million hemoglobin molecules, and there are roughly 20 to 30 trillion of these cells circulating in the body at any given time. They constitute approximately 84% of all cells in the human body and make up nearly half of the blood's volume, a staggering statistic for structures so small that 25,000 of them could fit on the head of a pin.
The Shape of Survival
The red blood cell is a master of deformation, capable of squeezing through capillaries that are less than half its own diameter. A typical human red blood cell has a disk diameter of approximately 6.2 to 8.2 micrometers and a maximum thickness of 2 to 2.5 micrometers, yet it can compress itself to pass through vessels as narrow as 3 micrometers. This unique biconcave shape provides a high surface-area-to-volume ratio, facilitating the rapid diffusion of gases. The cell membrane is a complex structure composed of proteins and lipids, with half the membrane mass consisting of proteins that provide flexibility and durability. These proteins form a skeletal network that allows the cell to recover its discoid shape immediately after exiting a capillary, much like an object made of rubber. While most mammals share this design, exceptions exist within the artiodactyl order, where species like llamas and camels possess small, highly ovaloid cells, and red deer exhibit cells that assume fusiform, lanceolate, or crescentic forms. This evolutionary diversity highlights the critical role of shape in oxygen transport efficiency.
The Iron Heart
At the core of the red blood cell lies hemoglobin, an iron-containing biomolecule that is responsible for the red color of the cells and the blood. Each hemoglobin molecule carries four heme groups, and the iron atoms within these groups temporarily bind to oxygen molecules in the lungs or gills. The blood plasma alone is straw-colored, but the presence of hemoglobin changes the color to scarlet when oxygenated and to a dark red burgundy when oxygen has been released. This color change is so distinct that pulse oximetry takes advantage of it to directly measure arterial blood oxygen saturation. However, the relationship between hemoglobin and oxygen is not always benign; hemoglobin has a very high affinity for carbon monoxide, forming carboxyhemoglobin which is bright red. This can lead to a dangerous situation where a patient appears flushed and confused with a saturation reading of 100% on a pulse oximeter, yet is actually suffering from carbon monoxide poisoning. The red blood cells of an average adult human male store collectively about 2.5 grams of iron, representing about 65% of the total iron contained in the body, making iron metabolism a central component of survival.
When was the red blood cell first discovered by Jan Swammerdam?
Jan Swammerdam first described the red blood cell in the year 1658 while observing the blood of a frog through an early microscope. He became the first human to document these cells, which are now known to be the most abundant cell type in the vertebrate body.
How many red blood cells are in the human body and what percentage of all cells do they represent?
There are roughly 20 to 30 trillion red blood cells circulating in the body at any given time, constituting approximately 84% of all cells in the human body. These cells make up nearly half of the blood's volume and contain approximately 270 million hemoglobin molecules each.
What is the functional lifetime of a red blood cell before it undergoes eryptosis?
A red blood cell has a functional lifetime of about 100 to 120 days in a healthy individual before it undergoes eryptosis or programmed death. The aging cell changes its plasma membrane and is subsequently phagocytosed by macrophages in the spleen, liver, and lymph nodes.
When were the main blood groups A, B, and O discovered by Karl Landsteiner?
Karl Landsteiner published his discovery of the three main blood groups A, B, and C in 1901, later renaming group C to O. A year later, Alfred von Decastello and Adriano Sturli identified the fourth blood group AB, laying the foundation for safe blood transfusions.
When were the oldest intact red blood cells discovered in Ötzi the Iceman?
The oldest intact red blood cells ever discovered were found in Ötzi the Iceman, a natural mummy who died around 3255 BCE, and these cells were discovered in May 2012. This finding highlights the enduring importance of understanding the red blood cell from its microscopic structure to its role in human history.
Mature red blood cells in mammals are anucleate, meaning they lack a cell nucleus, which is expelled during development to accommodate maximum space for hemoglobin. This absence of a nucleus means the cells cannot synthesize new proteins or divide, and they have limited repair capabilities. Consequently, they have a functional lifetime of about 100 to 120 days in a healthy individual, after which they undergo a process called eryptosis, or red blood cell programmed death. The aging cell undergoes changes in its plasma membrane, making it susceptible to selective recognition by macrophages in the spleen, liver, and lymph nodes. These immune cells phagocytose the old and defective cells, recycling the heme constituent into iron and biliverdin, which is reduced to bilirubin and released into the plasma. This cycle of creation and destruction is balanced, with approximately 2.4 million new erythrocytes produced per second in human adults to replace those that are removed. The inability to carry out protein synthesis also means that no virus can evolve to target mammalian red blood cells directly, although parvoviruses can affect erythroid precursors while they still have DNA.
The Chemical Messenger
Beyond their primary role of oxygen transport, red blood cells act as sophisticated chemical messengers that regulate blood flow and vascular tone. When red blood cells undergo shear stress in constricted vessels, they release ATP, which causes the vessel walls to relax and dilate to promote normal blood flow. When their hemoglobin molecules are deoxygenated, they release S-Nitrosothiols, which also act to dilate blood vessels, directing more blood to areas of the body depleted of oxygen. Furthermore, red blood cells can synthesize nitric oxide enzymatically using L-arginine as a substrate, contributing to the regulation of vascular tonus. They can also produce hydrogen sulfide, a signaling gas that acts to relax vessel walls, a process believed to be the reason behind the cardioprotective effects of garlic. In addition to these signaling roles, red blood cells play a part in the body's immune response; when lysed by pathogens such as bacteria, their hemoglobin releases free radicals that break down the pathogen's cell wall and membrane, killing it.
The Genetic Code
The history of red blood cell research is punctuated by pivotal discoveries that transformed medicine. In 1901, Karl Landsteiner published his discovery of the three main blood groups, A, B, and C, which he later renamed to O, identifying compatible and conflicting combinations between these groups. A year later, Alfred von Decastello and Adriano Sturli identified a fourth blood group, AB. These discoveries laid the foundation for safe blood transfusions, which are now a cornerstone of modern medicine. In 1959, Max Perutz used X-ray crystallography to unravel the structure of hemoglobin, the red blood cell protein that carries oxygen. The oldest intact red blood cells ever discovered were found in Ötzi the Iceman, a natural mummy of a man who died around 3255 BCE, and these cells were discovered in May 2012. These historical milestones highlight the enduring importance of understanding the red blood cell, from its microscopic structure to its role in human history.
The Blood Doping Paradox
The unique properties of red blood cells have led to both life-saving medical interventions and controversial performance-enhancing practices. Blood doping involves extracting about 1 liter of an athlete's blood, isolating the red blood cells, freezing and storing them, and then reinjecting them shortly before a competition. Red blood cells can be conserved for 5 weeks at 4 degrees Celsius, or over 10 years using cryoprotectants. This practice is hard to detect but may endanger the human cardiovascular system, which is not equipped to deal with blood of the resulting higher viscosity. Another method of blood doping involves injection with erythropoietin to stimulate production of red blood cells. Both practices are banned by the World Anti-Doping Agency. In 2008, it was reported that human embryonic stem cells had been successfully coaxed into becoming red blood cells in the lab, and a human trial was conducted in 2022 using blood cultured from stem cells obtained from donor blood. These advancements offer hope for the future of blood transfusions and the treatment of blood diseases.