Blood (Latin: sanguis, Greek: haima) is a suspension of cells in a saline solution containing protein. It makes up 6-8 % of the total body weight and has a pH value of 7.4. The blood carries out many essential functions and is the pivotal point of the whole organism. The following article provides, at a glance, the most important facts about this vital fluid called blood.

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Hematopoietic System of Bone Marrow

Picture: “Hematopoietic System of Bone Marrow” by Phil Schatz. License: CC BY 4.0


Blood Components

If a blood sample is centrifuged, a more or less turbid liquid (depending on the fat content of the blood) becomes visible with a red sediment set off against it. The liquid component represents the blood plasma; the sediment is the so-called blood clot made out of blood cells. The ratio of plasma to blood cells is indicated by the hematocrit. This is physiologically at 42% for women and 45% for men.

Blood Plasma

The plasma represents approximately 55% of the blood. It contains water, proteins, ions, hormones and physically dissolved gases. Serum free of coagulation factors can be obtained from the blood plasma.

Composition of Blood

Picture: “Composition of Blood” by Phil Schatz. License: CC BY 4.0

Normal values of plasma electrolytes:

  • Na140 mmol/l
  • K+ 4.5 mmol/l
  • Ca2+ 2.4 mmol/l
  • Cl105 mmol/l
  • HCO3– 24 mmol/l

This yields an osmotic pressure of 5,600 mmHg and an osmolarity of 290 mOsm/l for the plasma.The largest part of the plasma with 75 g/l are plasma proteins. They hardly contribute to osmolarity but do play an important role for the colloid osmotic (or oncotic) pressure, i.e., the osmotic pressure between plasma and interstitium. It comes to 25 mmHg and is thus significantly higher than that of the interstitium (5 mm Hg), which prevents too much plasma fluid from diffusing from the blood vessels into the tissue.

The most common protein is albumin (54-60 %). It is, therefore, essential for the oncotic pressure. Albumin is produced in the liver and is one of the smallest plasma proteins. It is used as a transporter of cations, bilirubin, fatty acids and cholate.

Other important plasma proteins are the globulins. These are divided into alpha, beta and gamma. Alpha and Beta globulins, like albumin, act as a vehicle. For example, the fat transporting LDL (low density lipoproteins) and HDL (high density lipoproteins) are important representative of the globulins.

Gamma globulins, by contrast, have an immunological function and contain immunoglobulin (Ig). They can be subdivided into five Ig classes according to their different chemical structures. In the plasma, there are primarily immunoglobulins IgG, IgA and IgM present.

Blood components in % Sub-components of the blood in % Type in % (if applicable) Production site
Main tasks
Plasma 43-63%  Water 92% Liquid Absorbed through the intestinal tract or produced during metabolism Transport medium
Plasma proteins 7% Albumin 54-60% Liver Maintains the osmotic concentration, transports lipid molecules
Globulins 35-38% Alpha globulins: liver Transport, maintain the osmotic concentration
Beta globulins: liver Transport, maintain the osmotic concentration
Gamma globulins (immunoglobulins): plasma cells Immune response
Fibrinogen 4-7% Liver Blood clotting during hemostasis
Regulatory proteins <1% Hormones and enzymes Various locations Regulate various body functions
Other dissolved substances 1% Nutrients, gases and waste Absorbed through the intestinal tract, replacement of cells in the respiratory tract or produced in cells Many different functions
Formed Elements 37-54 % Erythrocytes 99% Erythrocytes Red marrow Transports gases, primarily oxygen and some carbon dioxide
Leukocytes <1%, Platelets <1% Granular leukocytes: neutrophils, eosinophils and basophils Red marrow Non-specific immune response
Agranular leukocytes: lymphocytes, monocytes Lymphocytes: bone marrow and lymphoid tissue Lymphocytes: specific immune response
Monocytes: red marrow Monocytes: non-specific immune response
 Platelets <1% Megakaryocytes: red marrow Hemostasis

Blood Cells

Erythrocytes

The red blood cells are easily recognized by their biconcave shape. They have a diameter of 7.5 μm, and, with a count of 4.5 x 106 / μl in females and 5.2 x 106 / μl in males, they are the most common cells in the blood. Red blood cells contain hemoglobin. They have no cell nucleus or cell organelles and, therefore, have only a life span of approximately 120 days, before they are decomposed in the spleen.

The formation of erythrocytes takes place in the red bone marrow and is stimulated by the erythropoietin released in the kidneyThe last pre-stage of the red blood cells is the reticulocyte, which does not have a nucleus either and can be found in the blood smear in cases of increased new synthesis (for example, after severe loss of blood).

Red blood cells have a larger diameter than some capillaries. For this, the deformability of the red blood cells is extremely important. It is ensured through its distinctive membrane skeleton made out of ancyrin, spectrin and actin.

Thrombocytes

Platelets in their free form have a biconvex shape, and, with a diameter of only 2.5 μm, they are far smaller than erythrocytes. Healthy human blood contains 150,000–400,000 platelets/μl of blood. These nucleus-lacking cell fragments are formed by shedding off of the megakaryocytes of the bone marrow and circulate in the blood around ten days, if they do not become activated for blood coagulation.

Leukocytes

White blood cells are the immune cells of the blood. Their number varies between 4,000 and 10,000/μl of blood. They are divided into monocytes, granulocytes and lymphocytes.

  1. Monocytes stand out in the blood smear due to their size (15–20 μm). They usually have a kidney-shaped nucleus, and their cytoplasm appears pale grey under a light microscope. Monocytes are very rare (6% of the leukocytes) and circulate only one to three days in the blood. During this time, they mature to macrophages, which then migrate into the tissue. Accordingly, they are sparse in the blood smears.
  2. Granulocytes are 10–12 µm large; like all blood cells, they develop in the red bone marrow and are divided into three groups:
    • Neutrophils constitute the largest proportion of white blood cells and usually have a segmented nucleus. Those are called segmented neutrophils. 8% of the neutrophil granulocytes are banded neutrophils (or stab neutrophils) whose nucleus is not segmented but rather curved. In the Pappenheim stain, the granules of the neutrophils appear as a faint pink.
    • Eosinophil granulocytes make up only 3% of the white blood cells and have a nucleus that consists of two lobes. Their granules stand out in a blood smear by their brick-red coloration.
    • Basophil granulocytes are the least frequent in the blood smear. The granules usually cover the cell nucleus and are colored dark blue.
  3. Lymphocytes have a round, purple-colored cell nucleus which is surrounded by a thin, pale gray cytoplasmic border. They are classified as natural killer cells, B cells (bone marrow) and T cells (thymus). Under the light microscope, however, the three types cannot be distinguished.

Functions of the Blood

Erythrocytes: Transport of Gas

The oxygen content in the arterial blood of a healthy person is about 200 ml O2/l. Hemoglobin (Hb) binds 85% of the oxygen; the rest is physically dissolved in the plasma.

Hemoglobin is located in the erythrocytes. In an adult, Hb consists of 2 α- and 2 β-subunits. Each subunit has a Fe2+ ion, which binds O2. Thus, one Hb can transport four oxygen molecules. The Hb concentration in men is 16 g/dl and in women—14 g/dl.

In the periphery, Hb releases the oxygen into the tissue and also takes up a portion of the carbon dioxide. The majority of the CO2, however, is carried in the erythrocyte in the form of bicarbonate and is exhaled in the lungs.

Thrombocytes: Blood Clotting

Blood clotting is also called hemostasis and is divided into primary and secondary hemostasis.

Primary hemostasis occurs when the vascular endothelium is damaged and platelets come into contact with collagen located outside the vessel. The Von Willebrand factor in the collagen binds the glycoprotein lb of the platelets to its receptor, and the platelets anchor on the damaged endothelium.

At the same time, Ca2+ activates the blood platelets. This means that the tubules ring within the platelet contracts and pseudopods emerge. Together with adenosine diphosphate (ADP), released from the injured cells, thrombocytes thick together and a so-called platelet plug is formed. The activated platelets also secrete serotonin, fibrinogen and thromboxane A2. The latter causes, among other things, a vasoconstriction, thus supporting the closure of the vessel.

In order for the platelet plug not to block the whole vessel, the endothelium releases prostacyclin which inhibits platelet aggregation. This way, a targeted plug formation at the damaged endothelium is guaranteed.

The secondary hemostasis is divided into the extrinsic and intrinsic system.

The extrinsic system comes into action when tissue is destroyed. With a prothrombin time of about 14 seconds (Quick test), it acts very fast. The tissue factor from the vascular smooth muscles forms a complex with phospholipids. This is called tissue thromboplastin and binds the coagulation factor VII, which then activates factor X with Ca2+ present.

In the intrinsic system, factor XII comes into contact with negatively charged surfaces, such as collagen (or glass), and becomes activated. Subsequently, factor XI and then IX are activated. Factor IX along with phospholipids and Ca2+ ions form an enzymatic complex, which activates factor X (thrombokinase) by limited proteolysis. This process can be greatly accelerated with the thrombin activated factor VIII. The partial thromboplastin time comes to 40-50 seconds.

With the activation of factor X, intrinsic and extrinsic system converge. Factor X, in combination with factor V, phospholipids and Ca2+ ions, forms the prothrombin activator, which splits factor II (prothrombin) to thrombin. Thrombin, in turn, divides factor I (fibrinogen) to soluble fibrin, which by means of factor XIII and Ca2+ ions becomes solid, so that a red thrombus is formed.

The process of breaking down coagulation is called fibrinolysis. This activates plasminogen to plasmin by blood factors. The latter then splits fibrin into individual peptides. In addition, it splits the coagulation factors I, II, V, VIII, IX, XI and XII, thus lowering the clotting ability of the blood.

Leukocytes: Defense against Foreign Bodies

Neutrophils granulocytes act as rapid action force for inflammation and thus belong to the non-specific immune system. During an infection, the number of neutrophils increases quickly by using the reserves from the marginal pool (on the endothelium of large veins) or the bone marrow. They fight bacteria and can remove debris of endogenous cells. The suspension of dead neutrophils and tissue debris in tissue fluid is called pus.

Eosinophil granulocytes serve to defend against worm parasites.

Lymphocytes, except for natural killer cells, are part of the specific immune system. In the thymus, T-lymphocytes are trained to distinguish the body’s own antigens from foreign antigens and to respond accordingly. Hereby, T-helper cells and cytotoxic lymphocytes develop. The first support the mechanisms of the specific and non-specific defense; the latter recognize virus-infected or degenerated cells based on their antigens and kill them.

B-lymphocytes can be activated to plasma cells, which produce free antibodies that bind foreign antigens and neutralize them. This means that B-lymphocytes belong to the humoral component of the specific immune response. When activated, part of the B-lymphocytes differentiates to become memory cells that remain in the body for many years. When contact occurs with a known antigen, they already know which antibodies are required.

Natural killer cells are part of the non-specific immune system, and, through their cytolytic granules, they are able to trigger apoptosis in degenerated cells.

Formed Element
Main subtypes Number per micro liter and importance (scale) Appearance in the standard blood smear Summary of the functions Comment
 Erythrocytes (red blood cells)Erythrocytes (red blood cells)  5.2 million (4.4-6.0 million) Flattened biconcave disc; no nucleus; bright red color Transport oxygen and some carbon dioxide between tissues and lungs Life: approx. 120 days
Leukocytes (white blood cells) 7,000 (5,000 -10,000) Clearly dark colored nucleus All of the functions of the immune system Leave the capillaries and move into the tissue,
life: usually a couple of hours or days
Leukocytes Granulocytes  4,360 (1,800-9,950) Abundant granules in the cytoplasm; usually capped nucleus Non-specific disease resistance Classified according to membrane-bound granules in the cytoplasm
NeutrophilsNeutrophils 4,150 (1,800-7,300) Number of nucleus lobes increases with age Phagocyte; particularly effective against bacteria, releases cytotoxic chemicals of granules Most common leukocyte,
life: minutes and up to days
EosinophilsEosinophils 165 (0-700) Nucleus usually two-lobed; bright, red-orange granules Phagocytic cells; particularly effective with antigen-antibody-complex; release antihistamines; promote action against allergies and parasitic infections Life: minutes to up to days
BasophilsBasophils 44 (0-150) Nucleus usually two-lobed, but difficult to detect due to heavy, dense and dark purple granules Promote inflammation Least frequent leukocyte,
life span: unknown
Agranulocytes
2,640 (1,700-4,950) Lack of granules in the cytoplasm; has a simply shaped nucleus, which can be indented Immune response Group consists of two main cell types from a number of different origins
LymphocytesLymphocytes 2,185 (1,500-4,000) Sphere-shaped cell with a single, often large nucleus, which accounts for a large part of the cell volume; dark spots; appears as a large (natural killer cells) and small (B and T-cells) variant Primary specific (adaptive) immune response; T-cells directly attack other cells (boost cellular immunity); B-cells release antibodies (humoral immunity); natural killer cells are similar to the T-cells, but are non-specific Initial cells derived from the bone marrow, secondary production occurs in the lymphoid tissue; several different subtypes; memory cells are formed after contact with a pathogen and provide a faster reaction; lifetime: many years
MonocytesMonocytes 455 (200-950) Largest leukocyte with indented or horse shoe-shaped nucleus. Particularly effective phagocytes, swallow up pathogens or worn cells; also serve as antigen-presenting cells for the other components of the immune system Produced in the red bone marrow; after leaving the circuit, called macrophages
 Blood plateletsBlood platelets 350,000 (150,000 -500,000) Cell fragments surrounded by plasma membrane, contain granules; purple spot Hemostasis and release of growth factors to repair and heal tissue Formed from megakaryocytes that remain in the red bone marrow and release platelets into the bloodstream

Diseases of the Blood

Levels of Inflammation in the Blood

Inflammation values play an important role in diagnostics. They are obtained by the analysis of a blood sample. This usually includes the erythrocyte sedimentation rate, C-reactive protein and white blood cell count. In addition, there is a differential leukocyte count.

For the determination of the erythrocyte sedimentation rate, blood is stored in a narrow tube for two hours in an upright position. After one hour, the distance the red cells have traveled downwards to settle at the bottom of the tube is measured. Normal values after an hour are less than 15 mm in men and under 20 mm in women. A change in these values can indicate anemia, inflammation and even cancer.

The C-reactive protein is part of the immune system and is considered a marker for acute inflammation. Its concentration in the blood in a healthy person is under 10 mg/l.

The number of white blood cells is determined automatically. A very high number is called leukocytosis. If the value is very low, in turn, this is called leukopenia.

For a differential blood count, the leukocytes in the blood smear are identified by subtypes. 100 leukocytes usually comprise four monocytes, 58 neutrophil granulocytes (of which only 3 are segmented), one eosin granulocyte, up to one basophil granulocyte and 35 lymphocytes. If the number of band neutrophils is significantly elevated, this is called a left shift. It is an indication for bacterial infection. If too many granulocytes are overly segmented, this is called a right shift. This can be due to a deficiency of vitamin B12.

Anemia

  • Iron deficiency anemia: erythrocytes are microcytic and hypochromic; cause: chronic blood loss, insufficient iron intake.
  • Megaloblastic anemia: erythrocytes are macrocytic and normochromic; cause: vitamin B12 deficiency, folic acid deficiency, alcoholism.
  • Renal anemia: insufficient erythropoietin production; cause: renal insufficiency.
  • Aplastic anemia: red blood cell deficiency; cause: damage to bone marrow.
  • Hemolytic anemia: abnormal destruction of red blood cells; cause: defective cytoskeleton (hereditary spherocytosis, sickle-cell disease, thalassemia), sepsis, malaria, poisoning.

Leukemia

Peripheral blood with chronic lymphocytic leukemia

Picture: “Peripheral blood with chronic lymphocytic leukemia” by Gabriel Caponetti. License: CC BY-SA 3.0

Leukemia is characterized by a greatly increased number of white blood cells (leukocytes), in particular their precursor cells. These leukocyte precursors (also called blast cells) have no immune function and spread into the bone marrow, the blood and the lymphoid organs, thereby reducing their functioning. This interferes with the formation of the other blood cells. Consequences are aplastic anemia, reduced blood clotting and a dramatically weakened immune defense.

Coagulation Disorders

Coagulation disorders are either inherited or acquired. Increased bleeding is mostly due to a disturbed functioning or the lack of one of the coagulation factors:

  • Hemophilia A: factor VIII deficiency;
  • Hemophilia B: factor IX deficiency;
  • Von Willebrand’s disease syndrome: Von-Willebrand factor deficiency;
  • Vitamin K deficiency: reduced synthesis of factors II, VII, IX and X.

Popular Exam Questions on Blood

Solutions can be found below the references.

1. Blood plasma refers to:

  1. The liquid left over after the coagulation of the blood.
  2. The ionized component of the blood.
  3. A saline solution isotonic to blood.
  4. The supernatant liquid after centrifugation of the blood.
  5. The cellular portion of the blood.

2. What substance is best used for platelet aggregation?

  1. Factor IX
  2. Factor XI
  3. Fibrinogen
  4. Factor X
  5. Plasmin

3. An iron-deficiency anemia is most often caused by:

  1. Chronic blood loss;
  2. Vitamin B12 deficiencies;
  3. Increased iron excretion due to renal insufficiency;
  4. Increased alcohol consumption;
  5. Damages to the hematopoietic bone marrow.
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References

Lüllmann-Rauch: Taschenlehrbuch Histologie, 4. Auflage – Thieme

Speckmann, Hescheler, Köhling: Physiologie, 6. Auflage – Urban & Fischer

Schmidt, Lang, Heckmann: Physiologie des Menschen mit Pathophysiologie, 31. Auflage – Springer

Correct answers: 1D, 2C, 3A

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