Excerpts from the novel "Oxygen"

The entire complex human machine pivots on the pinnacle of oxygen. The bucket brigade of energy metabolism that keeps us all alive ends with oxygen as the final electron acceptor. Take it away, and the cascade clogs up in minutes, backing up the whole precisely tuned engine until it collapses, choked, cold and blue. 

Two portals connect us to oxygen—the mouth and the nose—appreciated more for all their other uses: tasting, smelling, smiling, whistling, blowing smoke and blowing kisses, supporting sunglasses and lipstick designers, perfumeries and plastic surgeons. Seal them for the duration of the morning weather report and everything you had planned for the rest of your life evaporates in a puff of imagination.



From the novel, Oxygen
By Carol Wiley Cassella, MD

Venn Diagrams for Medical Students

Step 1 Practice Questions

1. A 12-year-old male refugee from Haiti is being examined by a physician working for Médecins sans frontières.  Auscultation of the heart reveals no audible sounds but pulse exam in normal.  Electrocardiogram is normal except for an extreme axis deviation. Chest X-ray was obtained (see figure). Which of the following is a complication of this condition that the patient is most likely to develop?



A. Bronchiectasis
B. Heart failure
C. Mitral valve prolapse
D. Pneumothorax
E. Small bowel obstruction

History of Blood Pressure Measurement

Hall, W. D. (1987). "Stephen Hales: theologian, botanist, physiologist, discoverer of hemodynamics". Clinical Cardiology. 10 (8): 487–9.

Reverend Stephen Hales was the first person to measure blood pressure.  He did this in 1733 using a glass tube inserted in the carotid artery of a sedated horse.  The artist chose to depict the tube coming out of the horse's neck but it was actually in the groin:  “In December I caused a mare to be tied down alive on her back … having laid open the left crural artery about three inches from her belly, I inserted into a brass pipe whose bore was one-sixth of an inch in diameter and to that by means of another brass pipe which was fitly adapted to it, I fixed a glass tube of nearly the same diameter which was nine feet in length. Then , untying the ligature on the artery, the blood rose in the tube to eight feet in length, three inches perpendicular above the level of the left ventricle of the heart”.

8 feet 3 inches = 99 inches of blood = 185 mmHg blood pressure

Water Movement across Membranes

'Fluid Physiology' by Kerry Brandis -from http://www.anaesthesiaMCQ.com

Fluid Physiology

1.2 Water Movement across Membranes

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1.2.1 Pathways for Water Movement

Oil & water don't mix

Water and lipids are the two major types of solvent in the body. The lipid cell membrane separates the intracellular fluid from the extracellular fluid (as discussed in Section 2.1). Substances which are water soluble typically do not cross lipid membranes easily unless specific transport mechanisms are present. It might be expected that water would likewise not cross cell membranes easily. Indeed, in artificial lipid bilayers, water does not cross easily and this is consistent with our expectation.

. . . but paradoxically, water crosses nearly all the membranes in the body with ease!

Two questions spring immediately to mind:

• How can this be so?
• How does it happen? (ie. What is the route & mechanism by which water crosses membranes?)

The answer to this problem:

Water molecules cross cell membranes by 2 pathways which we can call the lipid pathway & the water channel pathway.

What is the 'lipid pathway'?

This refers to water crossing the lipid bilayer of the cell membrane by diffusion. This initially does not seem to be very credible based on the 'oil & water don't mix' idea BUT it is nonetheless extremely important because this pathway is available in ALL cells in the body.

To express this slightly differently: The 'oil & water don't mix' idea can be quantified as the partition coefficient (i.e., concentration of water in the lipid phase to the concentration in the aqueous phase). This partition coefficient is as expected, extremely low: about 10-6 which is 1 to a million.

Now there are a couple of other equally important facts to consider:

• the concentration of water in water is extremely high
• the surface area of the cell membrane is very large (relative to the contained volume)

These factors must be included when considering diffusion across the membrane (as quantified by Fick's law of Diffusion) and they significantly counteract the the very low permeability.

The lipid composition of different cell membranes varies so the rate of fluid flow across cell membranes does vary.

What is the 'water channel' pathway?

In some membranes the water flux is very high and cannot be accounted for by water diffusion across lipid barriers. A consideration of this fact lead to the hypothesis that membranes must contain protein which provide an aqueous channel through which water can pass. The water channels have now been found and are discussed below. Flow of water through these channels can occur as a result of diffusion or by filtration.

What other factors are important for the passage of water across membranes?

The above discussion refers to water moving from one side of a lipid barrier to the other and this is relevant to the cell membrane. Other 'membranes' need to be considered; in particular the capillary membrane & the lymphatic endothelial membrane. These are tubular sheets of very many endothelial cells, each with their own cell membrane, but also with a potential pathway for water & solutes existing at the junction of adjacent cells. Similarly all epithelial cell layers can be considered as 'membranes' through which water passes and these also have intercellular pathways.

1.2.2 Capillary Membranes

Water can cross capillary membranes via:

• the intercellular gaps between the endothelial cells
• pores in the endothelial cells special areas where the cytoplasm is so thinned out that it produces deficiencies known as fenestrations.
• diffusion across the lipid cell membranes of the endothelial cells

Intercellular slits in the capillary membrane have a diameter of about 7 nm which is much larger than the 0.12 nm radius of a water molecule. Because the total surface area of the body’s capillaries is huge (6,300 m2) and their walls are thin (1 mm), the total diffusional water flux across the capillaries in the body is very large indeed. (See Section 4.1). Normally this diffusional exchange does not represent any net flow in either direction because the water concentration on both sides of the capillary membrane is the same.

Fenestrations are found only in capillaries in special areas where a very high water permeability is necessary for the function of these areas. A high water permeability is clearly necessary in the glomerular capillaries and water permeability here is very much higher than in muscle capillaries. Other areas with fenestrations are the capillaries in the intestinal villi and in ductless glands.

Water also easily enters the lymphatic capillaries via gaps between the lymphatic endothelial cells. These gaps function also as flap valves and this also promotes forward lymph flow when the capillaries are compressed.

In other areas of the body the water permeability of capillary membranes is quite low. An example is the blood-brain barrier. The capillary endothelial cells here are joined by tight junctions which greatly limit water movement by the intercellular pathway.

1.2.3 Aquaporins: Cell Membrane Water Pores

The presence of specific pores (channels) in the cell membrane has long been predicted but the proteins involved in these water channels have only recently been characterised. At present at least 6 different water channel proteins (named aquaporins) have been found in various cell membranes in humans. These aquaporin proteins form complexes that span the membrane and water moves through these channels passively in response to osmotic gradients. These channel proteins are present in highest concentrations in tissues where rapid transmembrane water movement is important (eg in renal tubules).

Aquaporin 0 is found in the lens in the eye. It has a role in maintaining lens clarity. The gene for this protein is located on chromosome 12.

Aquaporin 1 (previously known as CHIP28) is present in the red cell membrane, the proximal convoluted tubule and the thin descending limb of the Loop of Henle in the kidney, secretory and absorptive tissues in the eye, choroid plexus, smooth muscle, unfenestrated capillary endothelium, eccrine sweat glands, hepatic bile ducts and gallbladder epithelium. The Colton blood group antigen is located on extracellular loop A of aquaporin 1 in red cells. The gene is located on chromosome 7.

Aquaporin 2 is the ADH-responsive water channel in the collecting duct in the inner medulla. Insertion of the channel into the apical membrane occurs following ADH stimulation. The gene is located on chromosome 12.

Aquaporins 3 and 4 are present in the basolateral membrane in the collecting duct. They are not altered by ADH levels. Recently, aquaporin 4 has been found in the ADH-secreting neurones of the supraoptic and paraventricular nuclei in the hypothalamus and it has been suggested that it may be involved in the hypothalamic osmoreceptor which regulates body water balance. (See Section 5.3). The gene for aquaporin 3 is located on chromosome 7.

Aquaporin 5 is found in lacrimal and salivary glands and in the lung. It may be the target antigen in Sjogren’s syndrome.

The aquaporins all have a similar topology consisting of 6 transmembrane domains

Aquaporin research is currently an active field. These proteins have been identified in all living organisms. New aquaporin inhibitors may prove to be useful diuretic agents. Mercurial compounds used to treat syphilis were noted in 1919 to have a diuretic action. More potent mercurial diuretics were subsequently developed and were once used widely until replaced by less toxic diuretics. These mercurial diuretics act by binding to a specific site on aquaporin 2 with blocking of renal water reabsorption. (See Section 5.6)

1.2.4 Effect on Cell Volume

The movement of water across cell membranes is essential for cellular integrity but can cause problems. A small difference in solute concentration results in a very large osmotic pressure gradient across the cell membrane and the cell membranes of animal cells cannot withstand any appreciable pressure gradient. Water movement can eliminate differences in osmolality across the cell membrane but this alone is itself a problem as it leads to alteration in cell volume. Consequently regulation of intracellular solute concentration is essential for control of cell volume.

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'Fluid Physiology' by Kerry Brandis -from http://www.anaesthesiaMCQ.com

Cardiovascular Study Questions

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