BIO 301
Human Physiology


& Body Defenses I


Functions of Blood:


Components of Blood - average adult has about 5 liters (about 5 qts):

1 - Formed elements:

    • Red blood cells (or erythrocytes)
    • White blood cells (or leucocytes)
    • Platelets (or thrombocytes)

2 - Plasma = water + dissolved solutes

 
Red blood cell, platelet, and white blood cell



Red Blood Cells (or erythrocytes):




Determining the hematocrit

 
Erythropoiesis


Erythropoiesis = formation of erythrocytes



training.seer.cancer.gov


Three main classifications of blood cells derive from haematopoietic stem cells (HSCs) (Katsura 2002).


Hemoglobin


The binding and release of oxygen illustrates the structural differences between oxyhemoglobin and reduced (or deoxy-) hemoglobin. Only one of the four heme groups is shown
(Source: wikipedia).

 
Hemoglobin and oxygen transport


White blood cells (or leucocytes or leukocytes):

Granular white blood cells contains numerous granules in the cytoplasm, & their nuclei are lobed. Agranular white blood cells have few or no granules in the cytoplasm & have a large spherical nucleus. Granular white blood cells are produced in the bone marrow, while agranular white blood cells are produced in lymph tissue, e.g., Lymph nodes (specialized dilations of lymphatic tissue which are supported within by a meshwork of connective tissue called reticulin fibers and are populated by dense aggregates of lymphocytes and macrophages).

 
How white blood cells are formed

The primary functions of the various white blood cells are:

 
Neutrophils


Eosinophils respond to diverse stimuli, including tissue injury, infections, allografts, allergens, and tumors. Eosinophils can also release a variety of cytokines, chemokines, lipid mediators, and neuromodulators. Eosinophils directly communicate with T cells and mast cells. Eosinophils activate T cells by serving as antigen-presenting cells.

 


Release of histamine (that contributes to the 'symptoms' of allergies) by mast cells requires the production of antibodies (IgE) by B-cells and
that process is regulated, in part, by cytokines produced by basophils (Bischoff 2007).

Once distributed through the blood stream, monocytes enter other tissues of the body such as the liver (Kupffer cells), lungs (alveolar macrophages), skin (Langerhans cells), and central nervous system (microglia) (Gordon 2003).



Eosinophils (in green with red nucleus) catapult their mitochondrial DNA out of the cell, forming tangled traps (red) that ensnare foreign bacteria.
(Photo credit: Hans-Uwe Simon, Institute of Pharmacology, University of Bern, Switzerland)

Catapult-like release of mitochondrial DNA by eosinophils -- Although eosinophils are considered useful in defense mechanisms against parasites, their exact function in innate immunity remains unclear. Yousefi et al. (2008) found that eosinophils in the gastrointestinal tract release mitochondrial DNA in a rapid, catapult-like manner—in less than one second. The mitochondrial DNA and proteins released by the eosinophils bind to and kill bacteria. This is a previously undescribed mechanism of eosinophil-mediated innate immune responses that might be crucial for maintaining the intestinal barrier function after inflammation-associated epithelial cell damage, preventing the host from uncontrolled invasion of bacteria.


Some important characteristics of White Blood Cells (particularly neutrophils):


Phagocytosis


 
Lymph system


Chemotaxis & ameboid movement 

Platelets (or thrombocytes)


Platelet adhesion and aggregation  

Plasma:

1 - Water - serves as transport medium; carries heat

2 - Proteins


Twenty-two proteins constitute ~99% of the protein content of plasma (Tirumalai et al. 2003).

3 - Inorganic constituents (1% of plasma) - e.g., sodium, chloride, potassium, & calcium

4 - Nutrients - glucose, amino acids, lipids & vitamins

5 - Waste products - e.g., nitrogenous wastes like urea

6 - Dissolved gases - oxygen & carbon dioxide

7 - Hormones


Hemostasis - prevention of blood loss from broken vessel (check this Hemostasis animation and this one):

 
Blood coagulation

 

 1 - Vascular spasm - vasoconstriction of injured vessel due to contraction of smooth muscle in the wall of the vessel. This 'spasm' may reduce blood flow & blood loss but will not stop blood loss.

2 - Formation of a platelet plug - platelets aggregate at the point where a vessel ruptures. This occurs because platelets are exposed to collagen (a protein found in the connective tissure located just outside the blood vessel). Upon exposure to collagen, platelets release ADP (adenosine diphosphate) & thromboxane. These substances cause the surfaces of nearby platelets to become sticky and, as 'sticky' platelets accumulate, a 'plug' forms.

3 - Blood coagulation (clotting):


Used with permission of Michael W. King, Ph.D / IU School of Medicine

 

The result of all of this is a clot - formed primarily of fibrin threads (or polymers), but also including blood cells & platelets.

 

Blood clots in the right places prevent the loss of blood from ruptured vessels, but in the wrong place can cause problems such as a stroke (see below under inappropriate clotting).
 

Clot retraction:

Over time (with the amount of time depending on the amount of damage), the clot is dissolved and replaced with normal tissue.

Fibrinolysis:


Blue arrows = stimulation; red arrows = inhibition. tPA is released by damaged endothelium
(Source: en.wikipedia.org/wiki/Fibrinolysis)


Inappropriate clotting:


Source: http://www.ors.od.nih.gov/medart/portfolio/Donny/embolus.html


Thrombus and embolus

Excessive bleeding:

Thrombocytopenia is a condition where platelet counts are lower than normal, potentially leading to mild to serious bleeding. This bleeding can happen inside the body (internal bleeding) or on the skin. A normal platelet count is 150,000 to 450,000 platelets per microliter of blood. A count of less than 150,000 platelets per microliter is lower than normal, but the risk for serious bleeding doesn't occur until the count becomes very low—less than 10,000 or 20,000 platelets per microliter. Milder bleeding sometimes occurs when the count is less than 50,000 platelets per microliter. Several factors can cause a low platelet count, such as:

  • The bone marrow doesn't make enough platelets.
  • The bone marrow makes enough platelets, but the body destroys them (autoimmunity) or uses them up.
  • The spleen holds onto too many platelets. The spleen is an organ that normally stores about one-third of the body's platelets. It also helps your body fight infection and remove unwanted cell material.
  • A combination of the above factors.

How long thrombocytopenia lasts depends on its cause. It can range from days to years. The treatment for this condition also depends on its cause and severity. Mild thrombocytopenia most often doesn't need treatment. If the condition is causing serious bleeding, or if you're at risk for serious bleeding, you may need medicines or blood or platelet transfusions. Rarely, the spleen may need to be removed. Thrombocytopenia can be fatal, especially if the bleeding is severe or occurs in the brain. However, the overall outlook is good, especially if the cause of the low platelet count is found and treated (Source: NHLBI).


Related links:

Lifeblood

Acute Inflammation

General Immunology

Introduction to Immunology

Cell Mediated and Humoral Immunity

Understanding the Immune System

Humoral Immunity

Blood Types Tutorial


Literature Cited

Battinelli, E., S. R. Willoughby, T. Foxall, C. R. Valeri, and J. Loscalzo. 2001. Induction of plalelet formation from megakaryocytoid cells by nitric oxide. Proceedings of the National Academy of Science USA 98: 14458-14463.

Bischoff, S. C. 2007. Role of mast cells in allergic and non-allergic immune respones: comparison of human and murine data. Nature Reviews Immunology 7: 93-104.

Gordon, S. 2003. Differentiation, distribution and activation of macrophages in vivo. Nature Reviews Immunology 3: 23-35.

Katsura, Y. 2002. Redefinition of lymphoid progenitors. Nature Reviews Immunology 2: 127-132.

Rothenberg, M. E., and S. P. Hogan. 2006. The eosinophil. Annual Review of Immunology 24: 147-174.

Tirumalai, R. S., K. C. Chan, D. A. Prieto, H. J. Issaq, T. P. Conrads and T. D. Veenstra.  2003. Characterization of the Low Molecular Weight Human Serum Proteome. Molecular & Cellular Proteomics 2:1096-1103.

Yousefi, S., J. A Gold, N. Andina, J. J. Lee, A. M. Kelly, E. Kozlowski, I. Schmid, A. Straumann, J. Reichenbach, G. J. Gleich, and H.-U. Simon. 2008. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nature Medicine, published online (10 August 2008).



Back to 301 syllabus

 

Lecture Notes 1 - Cell Structure & Metabolism

Lecture Notes 2 - Neurons & the Nervous System I

Lecture Notes 2b - Neurons & the Nervous System II

Lecture Notes 3 - Muscle

Lecture Notes 4b - Blood and Body Defenses II

Lecture Notes 5 - Cardiovascular System

Lecture Notes 6 - Respiratory System


Lymph system graphic used with permission of John Kimball