Notes on the Web
Cardiovascular System: Blood Histology and Physiology

Bruce G. Stewart

Related Textbook Readings

Lecture Outlines

The following represent lecture/discussion materials. They will also give you a guide on topics to study thoroughly in your textbook. Use this outline as a guide, not your only source for study.

I. General Physical Characteristics of Blood Include the Following:

A. Viscous fluid - about 4.5-5.5 times as thick as water

B. Temperature - 38oC (100.4oF) (important for chemical reactions and proper enzyme function)

C. pH 7.35-7.45 (also critical for chemical reactions and proper enzyme function)

D. salty - 0.9% NaCl (important for normal physiological function)

E. about 8% of total body weight with a volume of about 5-6 liters/male and 4-5 l/female

II. Functions

A. Transport of: O2; from lungs --> cells; CO2; cells --> lungs; nutrients from gastrointestinal tract --> cells; waste from cells --> kidneys; hormones from endocrine glands --> cells; heat from internal areas --> skin

B. Regulates: pH with pH buffers; body temp since water is "heat buffer"; osmotic balance of cells through Na+ & protein function

C. Protects against: blood loss through clotting; foreign microbes & toxins with wbc's that phagocytize and specialized proteins (e.g. antibodies and interferon)

III. Components of Blood - formed elements

A. Formed elements- slightly over 45% of whole blood

1. Erythrocytes(RBC's)- represent most of the 45% of whole blood volume

a. % of RBC’s is termed the hematocrit

2. Leukocytes (WBC's) represents less than 1% of whole blood volume

a. Granular leukocytes (granulocyte): neutrophils, eosinophils, and basophils)

b. Agranular leukocytes (lymphocytes and monocytes)

3. Thrombocytes (platelets) (represent less than 1% of whole blood volume)

B. Origin of formed elements - hemopoiesis (=hematopoiesis) occurs in “hemopoiesis centers.”

1. Fetal & embryonic centers are found in the yolk sac, liver spleen, thymus gland, lymph nodes & bone marrow

2. Adult centers are found in the:

a. Red bone marrow (=myeloid tissue), especially in the epiphyses of the humerus & femur and flat bones of the sternum, cranium, ribs, vertebrae & pelvis

b. Lymphoid tissue of the spleen, tonsils, thymus, lymph nodes, etc.

3. Sources of specific cell types

a. RBC's, granular leukocytes & platelets primarily from myeloid tissue (red marrow)

b. Agranular leukocytes from myeloid and lymphoid tissue

4. Developmental origin of blood cells

a. hemocytoblasts: “stem” cells that develop from undifferentiated mesenchyme cells. Mesenchyme cells can develop into various precursors to cell types in muscular, connective and vascular tissues. Hemocytoblasts are the precursors to blood cells.

b. Cells that differentiate from hemocytoblasts:

  • proerythroblasts (=rubriblasts) which differentiate into RBC’s
  • myeloblasts which form neutrophils, eosinophils, basophils
  • megakaryoblasts which form thromboblasts (platelets)
  • lymphoblasts which form lymphocytes
  • monoblasts which form monocytes

c. Production of WBC's can be stimulated by colony stimulating factors CSF's (e.g. interleukin - 3) which may help treat AIDS, cancer & bone marrow suppression

C. Erythrocytes

1. Physical characteristics include biconcave shape, diameter of about 7-8 microns, the lack of nucleus (thus can't reproduce), lack of mitochondria, a selectively permeable plasma membrane is selective permeable and made of phospholipids, stromatin, lipids (lecithin & cholesterol) and other features described separately below.

2. The plasma membrane contains antigens that relate to blood type characteristics (e.g. ABO & Rh)

a. Study the textbook section, “Transfusion and Blood Replacement” in detail to understand this topic. Also, see links at end of these Notes on the Web.

3. Contain hemoglobin (heme + globin) – the molecule that can bind to and release respiratory gases

a. 33% by weight of cell and excluding water makes up 97% of contents

b. normal values in grams/100ml (a standard measurement): 14-20g/ml for infants; 14-20g/mil for adult males; 12-16g/ml for adult females.

4. Functions of and information about RBC's

a. Transport and release of respiratory gases

  • O2 + deoxyhemoglobin --> oxyhemoglobin
  • CO2 + hg --> carbaminohemoglobin (transport & release of only about 23% of CO2 in this manner; rest is carried in blood plasma as HCO3-)
  • One RBC --> 280 million hg molecules!
  • Shape increases surface area/volume ratio
  • Carries carbonic anhydrase which helps promote the following: CO2 + H2O --> H2CO3 --> H+ + HCO3-

5. Life span and fate of parts of RBC's: About 120 days before being removed by macrophages in spleen, liver, bone marrow

a. Hemoglobin is broken down to

  • Iron which forms hemosiderin or ferritin (iron/protein complexes). The iron can be recycled to make new hemoglobin molecules by erythroblasts and normoblasts.
  • bilirubin – remainder of the heme group (minus the iron) which secreted by liver into bile. Ultimately its components are excreted with the feces.
  • globin – protein with usable amino acids which are metabolized or recycled

6. Erythropoiesis: the production of RBC's

a. Normal number of rbc's is about 4.3-5.2 million/mm3 for females and 5.1 - 5.8 million/mm3 for males (2mil/sec must be produced to keep up!)

b. Low levels of O2 cause kidney to release the enzyme, renal erythropoietic factor which is a plasma protein converted to erythropoietin (a hormone) that causes red bone marrow to produce more RBC's [other sites (e.g. liver) also produce erythropoietin]

c. hypoxia - too little O2 is transported to cells

  • anemia can have multiple causes
    • Fe deficiency which leads to heme deficiency
    • amino acid deficiencies cause globin deficiency
    • deficiency of B-12 and folic acid which are needed for hemopoiesis in red bone marrow
    • diseases

d. Sickle-cell anemia - valine is substituted for glutamic acid (due to DNA gene code); low O2 causes crystallization in modified hemoglobin; results in tissue damage, etc.

D. Leukocytes or White Blood Cells (WBC)

1. structure & types – WBCs have no hemoglobin & do have nuclei; WBCs have various immune system functions

a. granular leukocytes - granules & lobed nuclei

  • neutrophils
    • 10-12 mm diameter
    • nuclei with 2-6 lobes connected by thin strands
    • fine, evenly distributed pale granules
  • eosinophils
    • 10-12 mm
    • bilobed nuclei (thick or thin connection)
    • large, uniform-sized granules that tend to be a red-orange color and they don't obscure nucleus
  • basophils
    • 8-10 mm
    • bilobed or irregular nucleus; often S-shaped
    • granules round, variably-sized, dark blue-black & often obscure nucleus

b. agranular leukocytes - no cytoplasmic granules under light microscope

  • lymphocytes
    • 7-15 mm
    • nuclei dark stained, & round or indented
    • cytoplasm sky-blue & rings around nucleus
  • monocytes
    • 14-19 mm
    • nuclei indented or kidney shaped

2. WBCs recognize certain membrane proteins of cells of the body

a. human leukocyte associated antigens (HLA ant.)

b. controlled by genes- major histo compatibility complex (MHC)

c. play a role in organ rejection

  • HLA antigen typing or tissue typing

3. Functions (of WBC's)

a. neutrophils and monocytes

  • neutrophils –phagocytize bacteria: produce lysozyme which is a powerful enzyme that can break down bacteria; often the first line of defense when bacteria enter the body
  • monocytes- delayed but significant phagocytizers of bacteria and other foreign materials and damaged tissues
    • migrate to infected tissues
    • differentiate into phagocytes
    • often called "wandering macrophages"
  • "chemotaxis" (orienting toward chemical gradients) both neutrophils and monocytes are attracted to toxins, damaged tissue, etc.
  • defensins - a neutrophil antibiotic defense against bacteria, fungi & viruses

b. eosinophils

  • combat effects of histamine & other mediators that increase the intensity in allergic reactions
  • perform diapedesis & phagocytize antigen-antibody complexes
  • fight parasitic worms such as in the tissues that line the small intestine

c. basophils

  • involved in allergic reactions but they help intensify the reactions
  • perform diapedesis and then liberate heparin (prevents clotting), histamine and serotonin all of which intensify allergic reactions
  • hypersensitivity in an individual can result from overactivity of basophils

d. lymphocytes – many important immune system functions including antibody production

  • produce antibody proteins that inactivate antigens such as parts of bacteria, their products, and their toxins
  • antigen-antibody response involves lymphocytes. The process: antigens enter --> stimulate lymphocytes called B-cells to become plasma cells --> produce antibodies that can attach to antigen (covers it )
    • the antigen-antibody response helps protect our body but also causes transfusion reactions, organ rejections, and contributes to allergies
  • certain antigens activate special lymphocytes called cytotoxic T-cells that can destroy antigens directly or recruit other lymphocytes & macrophages to help
    • this is effective against bacteria, viruses, fungi, transplant cells, & cancer cells

4. differential WBC counts – clinical use of numbers and relative numbers can indicate likely health problems

a. the total WBC count normally ranges between 5000-10,000/mm3 of blood (thus RBCs out number WBCs about 700/1)

  • leucocytosis - a high WBC count (> 10,000/mm2)
  • leucopenia - a low WBC count (< 5,000/mm3)

b. the differential WBC count is based on the percentage each WBC type represents of the total number

Approximate Normal Values (Different Sources Vary Slightly)

Type of WBC

Percent of Total WBC Count

Neutrophils

60-70%

Eosinophils

2-4%

Basophils

0.5-1.0%

Lymphocytes

20-25%

Monocytes

3-8%

c. abnormalities in the differential WBC count can suggest possible health problems; here are a few examples

  • high neutrophil % --> infections, burns, stress, inflammation
  • low neutrophil --> radiation, drugs, B12 deficiency. systemic lupus erythematosus
  • high eosinophil --> allergic reaction, parasites, auto-immune disease
  • low eosinophil --> drugs, stress, a genetic syndrome (Cushing's)
  • high basophil --> allergic react., leukemias, cancers, hypothyroidism
  • low basophil --> pregnancy, ovulation, stress, hyperthyroidism
  • high lymphocyte --> virus, immune diseases, some leukemias
  • low lymphocyte --> prolonged severe illness, high steroid levels, immuno-suppression
  • high monocyte --> viral, fungal, tuberculosis, some leukemias & chronic diseases

5. life span of WBCs vary from months (healthy) to days or hours (due to illnesses)

E. Thrombocytes – membrane packets that block blood loss from damaged vessels & initiate chain reactions of clotting

1. 2-4 mm diameter & have no nucleus

2. produced from hemocytoblasts --> Megakaryoblasts--> mega karyocytes --> fragments of membrane-bound cytoplasm

3. short-lived (5-9 days)

4. occur in high densities (250,000 - 400,000/mm3)

Laboratory Exercise - Study of Blood Histology

Microscope slides of blood preparations will be covered in lab at this point. When you finish your study of these slides, you should be able to identify:

You do not have to find basophils on our slides (they are too rare); however, you should know them in photographs such as are found in your textbook. We will also learn to identify abnormal blood smears due to such things as malaria, sleeping sickness, mononucleosus, eosinophilia, and others as demonstrated in lab.

Here is are two excellent blood histology sites that I highly recommend:

Video Histology Series - Blood
Dr. David Moran - Colorado State University

At this point we will view an excellent video histology presentation by Dr. David Moran. You can consider him to be a "visiting lecturer" throughout the semester since we will view video histology presentations by him on almost all major tissue types found in the human body systems we cover. We will always view these after we have completed our own lab exercises so that you will be better prepared to understand the presentations. Do not take these lightly since they can add a useful perspective on tissue structure, and Dr. Moran presents images taken with types of microscopes we do not have (e.g. scanning electron, transmission electron, Nomarski interference contrast, and phase contrast microscopes). He also shows images of materials prepared with different histological stains and techniques that enhance the quality of images.

Lecture Outlines (continued)

F. Plasma – non-formed elements of the blood

1. plasma proteins

a. albumins

  • 55% of the plasma proteins
  • adds to viscosity and helps osmoregulate and control blood volume

b. globulins

  • 38%
  • includes antibody proteins (e.g. gamma globulin which forms antigen - antibody complex with such proteins from hepatitis, & measles viruses & tetanus bacteria)

c. fibrinogen

  • 7% of plasma proteins
  • blood clotting role as described later, but note now that this protein is water soluable and is available to form a precipatate modification called fibrin (which is not a plasma protein)

2. nitrogenous & phosphorous compounds

a. urea, uric acid, creatine, creatinine, & ammonia

3. foods such as amino acids, glucose, fatty acids, & glycerol

4. regulatory substances

a. enzymes

b. hormones from endocrine glands

5. respiratory gasses

a. CO2 more in plasma than O2

5. electrolytes

a. inorganic salts: cations Na+ K+ Ca2+ Mg2+1 & anions Cl- HPO42- HCO3-

  • help maintain osmotic pressure, pH, physiological balance cells/tissue

IV. Hemostasis

A. Defined - stoppage of bleeding

1. vascular spasm

2. platelet plug formation

3. blood coagulation (clotting)

B. Vascular Spasm

1. contraction response by smooth muscle to damage

2. occurs in vessels other than capillaries

C. Platelet Plug Formation and Triggering of Clotting Response

1. platelets contain many substances involved in various aspects of hemostasis and these substances contribute to three processes: vasoconstriction of blood vessels, platelet plug formation, and clotting (coagulation). Some of the platelet contents include:

a. ADP, ATP, serotonin, enzyme systems that produce prostaglandins, Ca2+, etc., etc.

b. PDGh (platelet derived growth factor); various clotting factors

2. upon touching damaged tissue, platelets become ‘sticky’ and adhere to the damaged site. This is followed by the release of three categories of substances from the platelets which in turn contribute to the processes shown in the following figure.


3. the platelet plug is formed as more and more ‘sticky’ platelets clog the damaged site. This alone can stop flow from very small tears in blood vessels. However, larger damage requires coagulation processes to continue to create a large clot to block the flow.

D. Physiology of Coagulation

1. first some useful terms

a. serum- plasma minus its clotting factors

b. clot - gel of insoluble proteins (fibrin) with trapped blood components

c. coagulation - process of clotting

d. thrombosis – clots are formed when not needed

e. hemorrhage – clots do not form when needed

f. coagulation factors - clotting chemicals

  • plasma - various
  • platelets – some as mentioned earlier
  • tissue factor – thromboplastin (released from damaged tissue)

2. the process of coagulation is an intricate a cascade of events

a. stages (extrinsic pathway is started by the release of thromboplastin from damaged tissue)

  • stage 1 - formation of prothrombin activator
  • stage 2 - conversion of prothrombin (a plasma protein made by liver) into thrombin by prothrombin activator
  • stage 3 - conversion of soluble fibrinogen (also plasma protein made in liver) into insoluble fibrin by thrombin.

b. details of many specific intermediate steps in the coagulation process should be reviewed in your text. Appreciate the large number of factors and substances involved.

Reminder about Textbook Study

As with other topics, your textbook has excellent presentations of the materials on the endocrine system. While you should focus on the specific material in the Notes on the Web, you should always use your textbook as a resource for illustrations and for understanding content that your notes cover. Also, your Notes on the Web sometimes refer you to specific materials to learn from your book.

As with all materials throughout the semester, you will have opportunities to ask questions or ask that any relevant material from your assignments be discussed in class. Please do not hesitate to seek help.

Related Internet Resources

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