Chapter 1-8: Blood, Plasma, Hematopoiesis, and Erythrocytes
Blood: Structure, Functions, and Core Concepts
Blood serves as the body’s transport system and regulator of several critical processes. It carries oxygen from the lungs to tissues, distributing heat throughout the body as part of temperature regulation. Heat dissipation via sweating is also linked to blood flow and skin perfusion. Blood helps regulate pH, and proteins in the blood act as drivers of major physiological functions. Blood also contains buffers that resist pH changes, notably bicarbonate, which acts as a buffer to stabilize pH. The blood reservoir is essential for maintaining fluid volume and electrolyte balance, enabling constant exchange with cells in tissues. The blood is a vascular “pipeline” that must remain intact to preserve blood pressure and circulation. If the system were completely drained or the plasma volume collapsed, circulation would fail.
What is blood made of and how is it organized?
Blood is a unique connective tissue composed of a liquid extracellular matrix (plasma) and living cells (formed elements) suspended in plasma. When drawn and examined, whole blood appears red. If spun in a centrifuge, it separates into layers according to density: a dense bottom layer of erythrocytes (red blood cells), a thin middle layer called the buffy coat containing leukocytes (white blood cells) and platelets, and a top, pale plasma layer. The denser the components, the lower they settle. The bottom layer is erythrocytes, the middle layer (the buffy coat) is leukocytes and platelets, and the top layer is plasma.
Erythrocytes (RBCs) are the red, biconcave cells responsible for gas transport. They are the most numerous cellular component and are present in a dense bottom layer after centrifugation.
Leukocytes (WBCs) are the colorless white components involved in immunity; they and platelets occupy the buffy coat.
Platelets are small, disc-shaped cytoplasmic fragments essential for clotting.
Plasma is the pale yellow liquid component that bathes the formed elements; it is mostly water and contains dissolved solutes, electrolytes, gases, nutrients, hormones, nitrogenous wastes, and plasma proteins.
Hematocrit and blood layering
Hematocrit is the percentage of blood volume occupied by red blood cells. For a typical healthy adult, the hematocrit is about 45%. In a standard centrifuged sample, you see:
Erythrocytes (bottom) ~45% of the blood volume.
Buffy coat (1%) containing leukocytes and platelets.
Plasma (top) ~55% of the blood volume.
The hematocrit is a key clinical indicator. It reflects the proportion of red blood cells in the blood and is influenced by hydration status and disease states. The clinical interpretation can vary with age, sex, and racial background; a reference value is often reported as an average with ranges. The hematocrit is defined by:
\text{Hematocrit} = \frac{V{\text{RBC}}}{V{\text{Total}}} \times 100\%.
Blood volume is a significant fraction of body weight, with typical adults having about 8% of body weight as blood mass; this value can vary with body size, sex, and age.
Plasma: the liquid component and its solutes
Plasma is the liquid part of blood, constituting about 55% of blood volume. It is the solvent in which all other components are suspended or dissolved. Plasma is about 90% water, with the rest made up of solutes and proteins. The solutes include electrolytes (charged ions), nutrients, gases, hormones, nitrogenous wastes, and a large protein fraction. Plasma proteins account for roughly 8% of plasma weight and have diverse functions.
Plasma proteins: composition and functions
Albumin (≈60% of plasma proteins) is predominantly synthesized by the liver and plays a major role in maintaining osmotic (oncotic) pressure, helping to retain water within the vascular compartment.
Globulins are a family of transport and immune proteins. They include:
Alpha and beta globulins, which often function as transport proteins for lipophilic hormones and other molecules (e.g., thyroglobulin is an example tied to transport concepts).
Gamma globulins, which are antibodies produced by immune cells to fight pathogens.
Fibrinogen (a plasma protein produced by the liver) is essential for blood clotting.
Albumin maintains osmotic pressure in the plasma, helping to keep water within the vessels and thus maintaining blood volume and pressure. The osmotic effect of plasma proteins is a key contributor to plasma osmolarity, sometimes referred to as oncotic pressure in clinical contexts. Osmolarity is the measure of solute concentration and can be conceptually described by the van 't Hoff relationship
\pi = i M R T,
where $\pi$ is the osmotic (oncotic) pressure, $i$ is the van 't Hoff factor, $M$ is molar concentration, $R$ is the gas constant, and $T$ is temperature. Proteins, especially those that cannot cross the capillary wall, drive this pressure and therefore help retain water in the circulatory system.
Electrolytes (ions such as Ca$^{2+}$, Mg$^{2+}$, K$^+$, Na$^+$, Cl$^-$, HCO$_3^-$) are the most abundant solutes by number, while plasma proteins are larger molecules that contribute to osmotic pressure but are present in smaller numbers. Plasma also contains nutrients, hormones, gases, nitrogenous wastes, and water (about 90% of plasma by mass).
The plasma-water balance and fluid exchange
Solutes that cannot cross the vessel wall, particularly large and charged proteins, help retain water within the vessels by keeping water from leaking out. This balance prevents fluid loss from the circulatory system and helps maintain blood pressure and volume. Solutes in the plasma also create gradients that drive exchange of nutrients, gases, and wastes between plasma and tissues. In short, plasma is the liquid matrix that supports transport, protection, and volume homeostasis.
The formed elements: erythrocytes, leukocytes, and platelets
The formed elements are the living cellular components of blood. They include:
Erythrocytes (RBCs): red blood cells, responsible for oxygen and carbon dioxide transport. They are disc-shaped with a biconcave surface, which increases surface area for gas exchange and allows flexible movement through small capillaries. RBCs are anucleate (they lack a nucleus) and lack most organelles, including mitochondria, to minimize oxygen consumption and maximize oxygen delivery to tissues.
Leukocytes (WBCs): white blood cells, the immune cells responsible for defense against pathogens. They are nucleated true cells and come in several types.
Thrombocytes (platelets): cell fragments essential for blood clotting. They are not true cells but fragments shed from certain bone marrow cells and are critical for hemostasis.
In blood, the cellular portion is described as formed elements, which originate from hematopoietic stem cells in the bone marrow and undergo a maturation process before appearing as mature red cells, white cells, or platelets.
Red blood cells and hemoglobin: structure and function
RBCs are remarkable for their oxygen-carrying capacity. They typically contain about $2.5 \times 10^8$ molecules of hemoglobin per cell, which is packed with water, antioxidants, and structural proteins. This high Hb content enables efficient oxygen transport from lungs to tissues.
Hemoglobin is a tetrameric protein composed of four globin chains (two alpha and two beta) and four heme groups. The globin portion forms two pairs of polypeptide chains, while each heme group contains an iron (Fe$^{2+}$) ion at its center. The four iron atoms together provide four oxygen-binding sites, allowing one hemoglobin molecule to bind up to four O$_2$ molecules reversibly:
Hb molecule composition: \text{Hb} = 2\,\alpha$-globin + 2\,\beta$-globin + 4\,\text{heme groups}.
Each heme contains one iron atom: \text{Fe}^{2+} \text{ per heme} \Rightarrow 4 \text{ Fe per Hb}.
Oxygen binding capacity: \text{O}_2\text{ binding sites per Hb} = 4.
The heme groups give hemoglobin its pigment and oxygen-carrying capacity. The iron in the center of each heme binds oxygen reversibly, allowing Hb to pick up oxygen in the lungs and release it in tissues with lower oxygen partial pressure.
Hemoglobin also functions as a buffer and helps resist pH changes in the blood. Although RBCs deliver most oxygen, they do not use the oxygen they transport; they lack mitochondria and rely on glycolytic energy pathways (anaerobic metabolism).
RBC shape, maturity, and life cycle
RBCs are biconcave discs, which increases their surface-to-volume ratio and facilitates gas exchange. They are not true cells: they lack a nucleus and most organelles. They arise from a developmental lineage starting as hematopoietic stem cells in the red bone marrow. Through hematopoiesis, they become erythrocyte precursors, accumulate hemoglobin, eject their nucleus and organelles during maturation, and are released as mature erythrocytes into the bloodstream. A reticulocyte index (an indirect measure of erythropoiesis) can be used clinically to assess RBC production.
Formation of erythrocytes (erythropoiesis)
Erythrocyte formation begins in red bone marrow and proceeds through committed progenitors. The kidney senses tissue hypoxia (low oxygen) and releases erythropoietin (EPO), which stimulates the marrow to increase RBC production. The marrow then produces more RBCs, which are released into the bloodstream as reticulocytes and mature into erythrocytes.
The iron required to form hemoglobin is sourced from dietary iron and stored as ferritin when not needed immediately. Iron is transported in the bloodstream by transferrin. The body recycles iron from old RBCs: the iron is liberated from heme, stored as ferritin, and a portion is mobilized when needed. If iron is not properly recycled or absorbed, iron-deficiency anemia can result, characterized by microcytic (small) red blood cells due to insufficient Hb synthesis.
Iron, ferritin, transferrin, and bilirubin cycle
Most iron used for hemoglobin synthesis (~65%) is directed toward heme and Hb production. The remainder is stored as ferritin, an iron reserve. When iron is needed, ferritin releases iron that binds to transferrin for transport to the marrow or other tissues.
Iron absorption and recycling are tightly regulated. Excess iron is toxic if left free in the bloodstream, so it is stored as ferritin or transported by transferrin and delivered where needed. The breakdown of heme from old RBCs yields bilirubin, which is processed by the liver and excreted into the intestine. Intestinal bacteria convert bilirubin to stercobilin, giving feces their brown color. Iron handling and bilirubin metabolism are integrated parts of RBC turnover and iron homeostasis.
Oxygen delivery, blood color, and pH balance
The color of blood varies with oxygen content: arteries (oxygen-rich) appear brighter red, while veins (oxygen-poor) appear darker.
Blood pH is slightly basic, typically around a pH range of 7.35–7.45. It is not strictly neutral (7.0) but is maintained within a narrow window to support enzyme function and cellular activities.
Viscosity and volume considerations
Blood is more viscous than water. It is often described as approximately five times more viscous than water, reflecting the complex cellular components and plasma proteins that impede flow relative to pure water:
\eta{\text{blood}} \approx 5 \;\eta{\text{water}}.
This viscosity is essential for proper circulation but must remain within a physiological range; excessive viscosity thickens the blood and can impede flow, while too little viscosity compromises circulatory efficiency.
Blood also contains buffers to resist pH changes. Bicarbonate (HCO$_3^-$) and other buffers help stabilize pH, which is critical for enzyme activities and metabolic pathways.
Connective tissue perspective and clinical implications
Hematocrit, plasma protein levels (notably albumin), and plasma osmolarity are clinically informative. Deviations can reflect nutritional status, hydration, renal function, liver function, and hematologic diseases.
Disorders of RBC production or destruction include various anemias (e.g., iron-deficiency microcytic anemia, pernicious macrocytic anemia, renal anemia due to low EPO). Polycythemia (overproduction of RBCs) can lead to increased blood viscosity and impaired circulatory flow; hematocrit values can rise substantially in such conditions.
Common disorders like sickle cell disease (sickle cell anemia) and thalassemias reflect abnormal Hb structure or globin chain production and can lead to altered rheology and oxygen delivery.
Quick recall: key terms and concepts
Hematocrit: \text{Hct} = \frac{V{\text{RBC}}}{V{\text{Total}}} \times 100\%.
Plasma composition: ~55% of blood; ~90% water; 8% of plasma weight as plasma proteins (albumin ~60% of plasma proteins; globulins; fibrinogen).
Osmotic pressure and oncotic pressure: driven largely by plasma proteins (especially albumin) that cannot cross capillary walls, maintaining water within vessels.
Erythropoiesis: stem cells in red bone marrow; EPO from kidneys stimulates RBC production in response to hypoxia.
Hb structure: 4 globin chains (2 α, 2 β) and 4 heme groups; 4 Fe per Hb; up to 4 O$_2$ molecules bound per Hb reversibly.
Iron metabolism: ferritin (storage) and transferrin (transport); bilirubin metabolism leads to stercobilin in feces.
RBC morphology and function: biconcave shape enhances diffusion and flexibility; RBCs lack nuclei and mitochondria to optimize oxygen transport.
Clinical states: anemia (reduced RBCs), iron-deficiency microcytosis, pernicious macrocytosis, renal anemia (low EPO), polycythemia (high RBCs), and hemoglobinopathies (e.g., sickle cell disease, thalassemias).
Notes for exam context
You may be asked to identify the layers of centrifuged blood, define hematocrit, or explain the role of albumin in osmotic pressure.
Understand how RBC structure (biconcave shape, lack of mitochondria, Hb content) supports oxygen transport.
Be able to describe the iron cycle (ferritin storage, transferrin transport) and the bilirubin/stercobilin pathway in the context of RBC turnover.
Recognize clinical implications of hematocrit changes and how hypoxia stimulates erythropoiesis via EPO.