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Blood Physiology

Original Editor - Alaa Kora

Top Contributors - Lucinda hampton, Jess Bell, Mandy Roscher, Kim Jackson, Tony Lowe, Tarina van der Stockt, Stacy Schiurring, Vidya Acharya, Rucha Gadgil and Olajumoke Ogunleye  

Introduction

Blood is essential for the preservation of human life.[1][2] It is responsible for transporting nutrients, hormones, gases and waste products around the body, and plays an important role in immunological defence. Blood is also critical in the homeostatic regulation of pH, temperature and various other internal conditions. It is composed of plasma, platelets, leukocytes (white blood cells) and erythrocytes (red blood cells).[3]

The adult human has approximately 4 to 5 litres of blood circulating in the body within the blood vessels.[4][5] Total blood volume accounts for approximately 7-8% of total body weight in healthy adults.[6]

Blood Plasma

Blood plasma is a light yellowish liquid that makes up approximately 55% of the total blood volume.[6] It acts as the fluid base of the blood and is composed of 91% water and 9% solids, including coagulants, plasma proteins, electrolytes and immunoglobulins.[7]

During embryonic development, blood plasma is formed from the mesenchymal cells. Albumin is formed first, followed by globulin and then other plasma proteins. In adults, the reticuloendothelial cells in the liver are primarily responsible for plasma production; this process is aided by bone marrow and spleen.[7]

Functions of Blood Plasma

Blood plasma serves several vital functions. It contains fibrinogen and procoagulants, such as thrombin and factor X, which are essential for coagulation. Immunoglobulins (antibodies) within the plasma contribute to the body's immunological defence. Plasma proteins, particularly albumin, are vital for maintaining oncotic pressure (maintained at around 25 mmHg), which ensures an appropriate balance of fluid between the blood and surrounding tissues. Plasma proteins also contribute to acid-base balance through their buffering action. Plasma is the primary medium for transporting nutrients, such as glucose, amino acids, lipids, and vitamins, from the digestive system to tissues throughout the body. It also facilitates the transport of respiratory gases—carrying oxygen from the lungs to peripheral tissues and returning carbon dioxide to the lungs for excretion—as well as the transport of hormones. Waste products from cellular metabolism are carried within the plasma and excreted via the kidneys, lungs and skin. Plasma also plays a role in temperature regulation.[7][8][9]

The erythrocyte sedimentation rate (ESR) is used as a diagnostic test. As fibrinogen increases in acute inflammatory conditions, the ESR will also increase.

Erythrocytes (RBCs)

Erythrocytes, known as red blood cells (RBCs), are biconcave discoidal cells.[10] They lack a nucleus and contain haemoglobin, the iron-rich protein that carries oxygen. Each cell is surrounded by a membrane composed of lipids and proteins. The normal healthy adult produces approximately 2-3 million red blood cells per second.[11] Erythrocytes make up around 45% of the total blood volume, and a single cell measures approximately 7 micrometres in diameter. They are produced by the red bone marrow through a process called erythropoiesis.[12][13]

Functions of Erythrocytes

A single erythrocyte has a lifespan of approximately 120 days. During that time, it has several roles. Its primary function is to deliver oxygen from the lungs to the peripheral tissues and to collect and return carbon dioxide from the peripheral cells to the lungs for removal.[14]

Erythrocytes contain haemoglobin with ferrous haem groups (Fe²⁺) that have a high affinity for oxygen. When the cell reaches deoxygenated cells, this affinity decreases due to a lower partial pressure of oxygen and a reduced pH. This facilitates the release of oxygen to the surrounding cells.

Leucocytes (WBCs)

Leucocytes, also known as white blood cells (WBCs), are the nucleated cellular component of the blood that lack haemoglobin. They make up approximately 1% of the total blood volume in healthy adults and play an important role in the immune system.[6] Leucocytes are produced in the bone marrow through a process called leukopoiesis.[15] Normal WBC counts range from 4,000 to 10,000 cells/μL (microlitre).[16]

Types and Functions of Leucocytes

There are several types of leucocytes, including neutrophils, eosinophils, basophils, lymphocytes (B and T) and monocytes.[17]

Neutrophils

Neutrophils are released from the bone marrow. They make up approximately 50% of the total WBC count, with around 100 billion produced each day. As the primary responders of the innate immune system, they migrate to sites of infection where they identify and kill bacteria and viruses.[18] Beyond their immediate pathogen-fighting role, neutrophils also produce cytokines, help resolve inflammation, regulate longer-term immune responses and contribute to innate immune memory.[19]

Monocytes

Monocytes make up 5 to 12% of the total WBC count. They function as phagocytes and play an important role in clearing dead cells and contributing to tissue regeneration.[20]

Eosinophils

Eosinophils represent less than 5% of the total WBC. They are found in large numbers within the digestive system. They play a key role in the immune response to bacteria and parasites.[21]

Basophils

Basophils make up approximately 1% of the total WBC count. They are involved in innate immunity and play a key role in allergic and hypersensitivity reactions, including anaphylaxis, through the release of histamine.[22]

Lymphocytes

Lymphocytes are necessary for adaptive immunity. There are two main types of lymphocytes: T cells, which have a direct cytotoxic function against infected/abnormal cells, and B cells, which are responsible for humoral immunity (i.e., immunity mediated by circulating antibodies).[23][24] Lymphocytes also play a role in immunological memory, enabling more rapid immune responses when a person is re-exposed to the same pathogen. This principle underpins the development of many vaccines.[25]

Pathophysiology of Leucocytes

An elevated WBC count (leucocytosis) can indicate a variety of conditions, including infection, inflammation, trauma, pregnancy, asthma, allergy, cancers, such as leukaemia, and even strenuous exercise.[26]

Conversely, a low WBC count (leucopenia) can indicate severe infections, bone marrow damage, autoimmune diseases, such as systemic lupus erythematosus (SLE), or splenic sequestration.[17]

Haematopoiesis

Haematopoiesis refers to the formation of blood cells. This process takes place in the red bone marrow (myeloid tissue).[27] Each blood cell type—erythrocyte, leucocyte and platelet—originates from a shared precursor: the haemocytoblast. These multipotent stem cells have a remarkable capacity for self-renewal and are located primarily in the bone marrow, although they can be released into the circulation in response to physiological demand. From this common origin, two lineages arise: 1) lymphoid stem cells, which produce lymphocytes, and 2) myeloid stem cells, which produce all other formed blood elements.[28]

Formation of Erythrocytes

During early foetal development, erythropoiesis (the production of red blood cells) takes place in the yolk sac. The liver and spleen take over this role between approximately 2 and 5 months of gestation, after which the bone marrow becomes the primary site and remains so throughout postnatal life.[29]

It takes approximately one week for a myeloid progenitor cell to develop into a mature erythrocyte. The progenitor cells first become normoblasts (or erythroblasts), a nucleated cell found within the bone marrow. As normoblasts mature, they accumulate haemoglobin and ultimately extrude their nucleus to become reticulocytes (or immature RBCs). At this point, they still retain some residual organelles. Some enter the peripheral circulation. Reticulocytes then shed their remaining organelles, becoming fully mature erythrocytes.[29]

Mature erythrocytes are anucleate (i.e., they lack a nucleus). This means that they cannot synthesise proteins, grow, or undergo further division. Over time, they become increasingly rigid and begin to break down, typically after 100 to 120 days. The bone marrow continuously replaces lost cells through ongoing haemocytoblast division.[29]

Erythrocyte production is regulated by erythropoietin, a hormone that circulates in small amounts at all times to maintain a steady rate of red blood cell formation.[29]

Formation of Leucocytes

In adults, leucocyte production and maturation primarily occur in the bone marrow. Granulocytes are produced entirely within the marrow. Lymphocytes also originate in the marrow, but undergo further development within lymphatic tissues, including the thymus, spleen and lymph nodes. Monocytes are also associated with the reticuloendothelial tissues of the spleen, liver and lymph nodes.

Formation of Platelets

Unlike other blood cells, platelets are not complete cells, but rather are small cytoplasmic fragments. They are derived from megakaryocytes, large cells found in the bone marrow. Platelet production is regulated by the hormone thrombopoietin.[30]

Blood Disorders

There are many conditions that affect the human haematologic system (i.e., the biological system that includes plasma, platelets, leukocytes, erythrocytes, and the bone marrow). Blood disorders are classified according to the blood component that is affected, and may involve dysfunction of platelets, erythrocytes, leucocytes, bone marrow, lymph nodes or blood vessels.[31][32]

Erythrocyte Disorders

Disorders of erythrocytes are characterised by impaired oxygen transport from the lungs to peripheral tissues. [33][34] They include a range of anaemias, such as iron-refractory iron deficiency anaemia (IRIDA), congenital sideroblastic anaemia, congenital dyserythropoietic anaemia, megaloblastic anaemia (including pernicious anaemia), iron deficiency anaemia, haemolytic anaemia and sickle cell anaemia. Other erythrocyte disorders include thalassaemia, haemolytic disease of the newborn, spherocytosis and haemochromatosis.[35]

Leukocyte Disorders

Leucocyte disorders are conditions that affect the WBCs and may result in increased or decreased cell counts or impaired WBC function. Neutrophils and lymphocytes are most commonly affected. Disorders involving monocytes and eosinophils are less common, and basophil disorders are considered rare.[36] Low WBC counts are seen in conditions such as neutropenia, Shwachman-Diamond syndrome,[37] and Kostmann syndrome.[38] Elevated WBC counts occur in conditions like eosinophilia and neutrophilia.[36] Clinically, leucocyte disorders often lead to recurrent infections, particularly of the sinuses, lungs and ears, as well as skin abscesses, mouth sores, periodontal disease and invasive fungal infections.[36]

Bleeding Disorders

Bleeding disorders occur when coagulation factors within the plasma are deficient or dysfunctional. Common examples include haemophilia and von Willebrand disease, both of which result in impaired haemostasis and prolonged/excessive bleeding.[39][40][41]

Summary

Blood is a complex fluid that is fundamental to sustaining life. Erythrocytes are responsible for gas exchange, leucocytes form the cellular basis of the immune system, and platelets are essential for haemostasis. Together with plasma (the transport medium for nutrients, hormones, gases and waste products), these components support a wide range of physiological processes.

References

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  2. ↑ Mathew J, Sankar P, Varacallo M. Physiology, blood plasma. InStatPearls [Internet] 2021 Apr 28. StatPearls Publishing.
  3. ↑ Basu D, Kulkarni R. Overview of blood components and their preparation. Indian journal of anaesthesia. 2014 Sep;58(5):529.
  4. ↑ Hamdan B, Diabat A. A two-stage multi-echelon stochastic blood supply chain problem. Computers & Operations Research. 2019 Jan 1;101:130-43.
  5. ↑ Sharma R, Sharma S. Physiology, Blood Volume. InStatPearls [Internet] 2018 Oct 27. StatPearls Publishing.
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  7. ↑ 7.0 7.1 7.2 Mathew J, Varacallo M. Physiology, blood plasma. InStatPearls [Internet] 2019 Jan 20. StatPearls Publishing.
  8. ↑ Heim MU, Meyer B, Hellstern P. Recommendations for the use of therapeutic plasma. Current Vascular Pharmacology. 2009 Apr 1;7(2):110-9.
  9. ↑ Nieuwland R, Siljander PR. A beginner's guide to study extracellular vesicles in human blood plasma and serum. Journal of Extracellular Vesicles. 2024 Jan;13(1):e12400.
  10. ↑ Smith JE. Erythrocyte membrane: structure, function, and pathophysiology. Veterinary Pathology. 1987 Nov;24(6):471-6.
  11. ↑ Jang Y, Eom YJ, Gwak SH, Koh Y, Han J, Rim YA, Nam Y, Ju JH. Advances in the characterization of in vitro-generated red blood cells: from biophysical properties to functional applications. Stem Cell Res Ther. 2025 Nov 28;17(1):3.
  12. ↑ Vasković J. Erythrocytes.Kenhub. https://www.kenhub.com/en/library/anatomy/erythrocytes. 2020. Accessed June 6, 2020.
  13. ↑ Chatzinikolaou PN, Margaritelis NV, Paschalis V, Theodorou AA, Vrabas IS, Kyparos A, D'Alessandro A, Nikolaidis MG. Erythrocyte metabolism. Acta Physiologica. 2024 Mar;240(3):e14081.
  14. ↑ Kuhn V, Diederich L, Keller IV TS, Kramer CM, Lückstädt W, Panknin C, Suvorava T, Isakson BE, Kelm M, Cortese-Krott MM. Red blood cell function and dysfunction: redox regulation, nitric oxide metabolism, anemia. Antioxidants & redox signaling. 2017 May 1;26(13):718-42.
  15. ↑ Jagannathan-Bogdan M, Zon LI. Hematopoiesis. Development. 2013 Jun 15;140(12):2463-7.
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  17. ↑ 17.0 17.1 Eldridge L. Types and Function of White Blood Cells (WBCs). Verywell Health. https://www.verywellhealth.com/understanding-white-blood-cells-and-counts-2249217. Published 2020. Accessed June 6, 2020.
  18. ↑ Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annual Review of Pathology: Mechanisms of Disease. 2014 Jan 24;9:181-218.
  19. ↑ Rosales C. Neutrophil: a cell with many roles in inflammation or several cell types? Front Physiol. 2018 Feb 20;9:113.
  20. ↑ Karlmark K, Tacke F, Dunay I. Monocytes in health and disease—Minireview. European Journal of Microbiology and Immunology. 2012 Jun 1;2(2):97-102.
  21. ↑ McBrien CN, Menzies-Gow A. The biology of eosinophils and their role in asthma. Frontiers in Medicine. 2017 Jun 30;4:93.
  22. ↑ Cromheecke JL, Nguyen KT, Huston DP. Emerging role of human basophil biology in health and disease. Current allergy and asthma reports. 2014 Jan 1;14(1):408.
  23. ↑ Farlex Partner Medical Dictionary © Farlex 2012 Available from:https://medical-dictionary.thefreedictionary.com/humoral+immunity (last accessed 30.11.2020)
  24. ↑ Hoffman W, Lakkis FG, Chalasani G. B cells, antibodies, and more. Clinical Journal of the American Society of Nephrology. 2016 Jan 7;11(1):137-54.
  25. ↑ Lam N, Lee Y, Farber DL. A guide to adaptive immune memory. Nat Rev Immunol. 2024 Nov;24(11):810-829.
  26. ↑ Riley LK, Rupert J. Evaluation of patients with leukocytosis. American family physician. 2015 Dec 1;92(11):1004-11.
  27. ↑ Li H, Côté P, Kuoch M, Ezike J, Frenis K, Afanassiev A, Greenstreet L, Tanaka-Yano M, Tarantino G, Zhang S, Whangbo J. The dynamics of hematopoiesis over the human lifespan. Nature methods. 2025 Feb;22(2):422-34.
  28. ↑ Iwasaki H, Akashi K. Myeloid lineage commitment from the hematopoietic stem cell. Immunity. 2007 Jun;26(6):726-40.
  29. ↑ 29.0 29.1 29.2 29.3 Tang P, Wang H. Regulation of erythropoiesis: emerging concepts and therapeutic implications. Hematology. 2023 Dec;28(1):2250645.
  30. ↑ Sim X, Poncz M, Gadue P, French DL. Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets. Blood. 2016 Mar 10;127(10):1227-33.
  31. ↑ Peters M. AZ family medical encyclopedia. Dorling Kindersley; 2004.
  32. ↑ Rozenberg G. Guide to Paediatric Haematology Morphology. CRC Press; 2024 Aug 14.
  33. ↑ Boston’s Children Hospital. Red Blood Cell Disorders Symptoms & Causes. http://www.childrenshospital.org/conditions-and-treatments/conditions/r/red-blood-cell-disorders/symptoms-and-causes. Accessed June 7, 2020.
  34. ↑ Srinivasan A. Failure of Erythrocyte Production. InBenign Hematologic Disorders in Children 2021 (pp. 369-383). Springer, Cham.
  35. ↑ Types of Blood Disorders in Children and Teens. Dana farber Bosten Children. http://www.danafarberbostonchildrens.org/conditions/blood-disorders.aspx. Accessed June 7, 2020.
  36. ↑ 36.0 36.1 36.2 White  Blood  Cell  Disorders.  Dana  farber  Bosten  Children. http://www.danafarberbostonchildrens.org/conditions/blood-disorders/white-blood-cell-disorders.aspx.                 Published 2020. Accessed June 7, 2020.
  37. ↑ Thompson AS, Giri N, Gianferante DM, Jones K, Savage SA, Alter BP, McReynolds LJ. Shwachman Diamond syndrome: narrow genotypic spectrum and variable clinical features. Pediatric Research. 2022 Mar 23:1-0.
  38. ↑ Fadeel B, Garwicz D, Carlsson G, Sandstedt B, Nordenskjöld M. Kostmann disease and other forms of severe congenital neutropenia. Acta Paediatrica. 2021 Nov;110(11):2912-20.
  39. ↑ Tebo C, Gibson C, Mazer-Amirshahi M. Hemophilia and von Willebrand disease: a review of emergency department management. J Emerg Med. 2020 May;58(5):756-766.
  40. ↑ Kalot MA, Husainat N, El Alayli A, Abughanimeh O, Diab O, Tayiem S, Madoukh B, Dimassi AB, Qureini A, Ameer B, Eikenboom JC. von Willebrand factor levels in the diagnosis of von Willebrand disease: a systematic review and meta-analysis. Blood advances. 2022 Jan 11;6(1):62-71.
  41. ↑ Maneikis K, Krumb E, Hermans C. Normalization in hemophilia: conceptual foundations and clinical implications. Res Pract Thromb Haemost. 2025 Sep 30;9(7):103200.
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