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W. Crone (303 FTZ, 629-7439, cronewil@hvcc.edu, http://www.hvcc.edu/academ/faculty/crone/index.html)

Cormack: Chs. 1, 3; Guyton: Chs. 1-3, 32, 33; Michael and Rovick: Introduction; van Wysberghe and Cooley: Cases 8-11. Possible web sites:

http://www.med.virginia.edu/medicine/clinical/pathology/educ/innes/text/nh/hema.html (hematology)

http://esg-www.mit.edu:8001/esgbio/chapters.html (MIT hypertext resource for introductory biology)

http://human.physiol.arizona.edu/ (a useful resource for the semester, or what you can accomplish with > 3 lect/wk)

Physiology: study of the function of living organisms. Phrased differently, physiology can be considered to be the effort to maintain a constant environment around cells so that they function well. Phrased yet another way, physiology studies the physical and chemical factors underlying biological activities. Cells contain intracellular fluid (ICF), and are surrounded by extracellular fluid (ECF). Mechanisms monitor the temperature, osmotic pressure, pH, and composition of the ECF.1

Homeostasis: maintenance of an internal steady state by means of self-regulation. A homeostatic mechanism is a regulating mechanism that is triggered in some (physiological) way to produce a compensating change in the opposite direction. What are requirements for this?4

  1. receptors to detect the alteration
  2. effectors, e.g., circulatory, digestive, respiratory, renal systems
  3. coordinating and integrating mechanisms: nervous system for fast, targeted communication, and endocrine system for slower, more diffuse communication.

A general approach to stable regulation is negative feedback (example of a thermostat).

Positive feedback leads to progressive change in one direction (e.g., axon action potential).


  1. Plasma membrane, the outer bilayer of the cell, regulation of material movement, and cell-cell recognition. The plasma membrane helps to keep ICF separate and of different concentrations of materials from the ECF.
  2. Cytoplasm contains three main structural components: organelles, inclusions, and cytoskeleton. The fluid component is called the cytosol. In the cytosol occur such"favorite" biochemical activities as glycolysis, HMP shunt, and fatty acid synthesis.
  3. Nucleus, surrounded by nuclear envelope, and also containing nucleolus. DNA is usually not by itself, but often combined with protein in chromosomes. When not dividing, this combination is known as chromatin. Remember that certain cells, especially GI epithelium, hair follicles, and bone marrow, are dividing continuously, so that cytotoxic drugs will involve them in side effects. Think of the targets of cancer chemotherapy drugs that would affect different parts of mitosis as a result.
  4. Nucleolus, also in the nucleus, contains RNA and proteins, for ribosome prefabrication.
  5. Ribosome, site of protein synthesis. Contains both rRNA and proteins, can be free floating or attached to endoplasmic reticulum. They are usually grouped in clusters called polyribosomes, as they are linked with mRNA (messenger RNA).
  6. Endoplasmic reticulum (ER), a series of membrane tubes and sheets throughout the cytoplasm that functions in communication and storage. Can either be rER (rough) ribosomes attached or sER (smooth) without. sER--surface area for chemical reactions, e.g., cytochrome P-450 enzymes in liver cells can be enhanced by ethanol intake.2 Also, sER elaborated into sarcoplasmic reticulum (SR) for cardiac and skeletal muscle cells.
  7. Golgi apparatus, associated with ER in the cytoplasm, for packaging and export of materials. A stack of membranes that can package and secrete, among other things, glycoproteins for the plasma membrane and lysosomes. Significance: Golgi: can help formation of large carbohydrates with a bit of protein: proteoglycans in mucus and hyaluronic acid.
  8. Lysosomes, in the cytoplasm, are membrane-surrounded pockets of digestive enzymes. These enzymes (acid hydrolases) are synthesized into the ER, then get packaged up and made into lysosomes by the Golgi apparatus. Lysosomes can help break down food vesicles or can be used to recycle the cell's contents. Clinical significance: lysosomal storage diseases from inactivity of the hydrolases, e.g., Tay-Sach's disease.
  9. Mitochondria (-ion, singular), in cytoplasm, are the power sources for the cell. Mitochondria are double-membraned. The inner membrane is highly folded for more surface area for energy-producing reactions. Leber's hereditary optic neuropathy--mitochondrial disorder.3
  10. Cytoskeleton, or lattice-like network of filaments throughout the cell for support. Clinical significance: dystrophin of muscle cells in Duchenne muscular dystrophy, spectrin in rbc with hereditary spherocytosis.3,5
  11. Centrioles. Centrioles are microtubule structures that assist in cell division in animal cells.
  12. Flagella and cilia. Both are membrane-bound cylinders that contain sets of microtubules, and move as a result of microtubule doublets sliding along each other. significance: immotile cilia syndrome: loss of flagellar//ciliary function: lung disease and infertility as results.5



Hematopoesis occurs in the bone marrow, with stem cells that differentiate among different cell lines to blast cells and then mature cells. Erythropoietin (from kidneys) stimulates rbc production by stimulating erythroblast production.

Different cells (or cell fragments) have different life spans Table 3-4 Cormack):2

granulated white cells: neutrophils, eosinophils, and basophils circulate only a few hours and then last a few days in tissue.

platelets: 9-10 days.

agranulated white cells: lymphocytes, monocytes: 100-300+ days (monocytes only a few hours in circulation, and then enlarge as macrophages in tissue).

erthyrocytes: 120 days. In particular, older rbcs are removed by the spleen and other sites with phagocytic cells.

As seen in Fig. 3-16 of Cormack,2 there are two major lines of cell production from pluripotential stem cells: the myeloid and lymphoid lines (you can tell that an increasing understanding of growth factors is also occuring!). (Red) bone marrow: among the spicules of spongy (cancellous bone), with support from stromal cells (e.g., fibroblasts), reticular fibers, and sinusoids (for drainage).

lymphoid lineage: lymphocytes (T cells and B cells)

B cells will mature in the bone marrow, and are responsible for humoral immune response (antibodies).

T cells will need to mature in the thymus and are involved in cell-mediated immune response (e.g., antigens presented by macrophages).

myeloid lineage: separate lineages for erythrocytes (rbcs), megakaryocytes (will fragment into platelets), as well as for the different wbcs.

Hematopoetic cell populations consist of:2

  1. stem cells (which can self-renew)
  2. progenitor cells (undergoing progressive differentiation)
  3. precursors (committed to a particular pathway, not fully functional)
  4. blood cells and derivatives

The erythroid series for rbc development and maturation has its own terminology:2

The basic trend is to turn from a nucleated cell with active protein production (which protein?) to a mature enucleated mature erythrocyte.

  1. proerythroblasts (dividing)
  2. basophilic erythroblast
  3. polychromatic erythroblasts (with the cytoplasm full of ribosome clusters)
  4. the maturing normoblasts, at which point the nucleus is extruded
  5. the reticulocyte (with some staining ribosomes left)
  6. finally, an erythrocyte

Given this pattern of development, anemia or decrease in rbcs or hemoglobin (Hb) content falls into three general categories of causation:

1. impaired rbc or Hb production

2. increased rbc destruction

3. increased rbc loss

The stem cells are under the influence of a bewildering variety of hematopoetic growth factors:

CFU (colony-forming unit)-(tag depending on ultimate progeny)

For the granulocytic series of cells:2

  1. myeloblast: large, 15-20 m m, ungranulated, and large nucleoli (which represent what?)
  2. promyelocyte (even larger cells, with initial primary granules)
  3. myelocyte (a bit smaller, condensing to normal size)
  4. metamyelocyte (now loss of mitotic capacity, with nucleus morphology altering--now kidney shaped)
  5. band (nucleus a horseshoe)
  6. finally segmented nucleus of the adult neutrophils

Blast cells would be prominent in the peripheral blood with leukemia.

Platelets arise from polyploid megakaryocytes that form a single, large multilobed nucleus under the influence of TPO (thrombopoetin)

In summary, an understanding of the genesis of rbc and wbc will enhance your time with the hematology/oncology portions of Clinical Sessions II and Pharmacology.


  1. JJ Bray et al., eds., Lecture Notes on Human Physiology, 3rd ed. (Blackwell Scientific, Oxford, 1994), pp. 1, 2, 5, 7.
  2. DH Cormack, Clinically Integrated Histology (Lippincott-Raven, Philadelphia, 1998), pp. 39, 41-45, 209.
  3. MC Dalakas,"Diseases of muscle and the neuromuscular junction," Ch. 11-IIIin DC Dale, DD Federman, eds., Scientific American Medicine (Scientific American, Inc., NY, 1997), pp. 2, 7.
  4. SI Fox, Human Physiology, 6th ed. (WCB McGraw-Hill, Boston, 1999), pp. 5-7
  5. LP Gartner, et al., Board Review Series: Cell Biology and Histology, 2nd ed. (Harwal Publishing, Philadelphia, 1993), pp. 11, 75.

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Please send comments and questions to: cronewil@hvcc.edu


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