MEDICAL EDUCATION TEACHING NOTE
Year : 2020 | Volume
: 5 | Issue : 2 | Page : 97--101
“PhysioLego:” Learning concepts, building, and applying physiology knowledge
Hwee-Ming Cheng, See-Ziau Hoe
Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur
When we talk about conceptual learning, we also think about certain principles in physiology that recur in various organ systems in the body. These global underlying themes are like the Lego building blocks when we look at the mechanics of physiological processes. One main?” PhysioLego” concept of building brick is the relationship between membrane selective permeability and effective osmotic pressure. This is expressed in laboratory class demonstration by saying that the tonicity of a solution is dependent on not just the osmotic concentration but also importantly on the membrane penetrability of the solute in solution. The “PhysioLego” osmotic bricks and its construction to build an integrated understanding of physiology and pathophysiology will be described in this article.
|How to cite this article:|
Cheng HM, Hoe SZ. “PhysioLego:” Learning concepts, building, and applying physiology knowledge.BLDE Univ J Health Sci 2020;5:97-101
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Cheng HM, Hoe SZ. “PhysioLego:” Learning concepts, building, and applying physiology knowledge. BLDE Univ J Health Sci [serial online] 2020 [cited 2021 Jan 16 ];5:97-101
Available from: https://www.bldeujournalhs.in/text.asp?2020/5/2/97/283090
PhysiologyImagine you walked into your tutorial session class with a box and your students are seated indifferently around the table in classroom. Then, you pour out the Lego bricks onto the table. You can imagine the looks of surprise and the smiles, and the class is brightened up for what is to come. The Lego bricks make the essential point that in learning physiology, foundational concepts underpinning physiology events in the body should be grasped. These key core knowledge when understood will be a springboard from where other normal and pathophysiology mechanisms will be more readily appreciated. In this article, we elaborate on the basic “PhysioLego” concepts of osmosis, osmotic pressure, and tonicity. Physiology is fun, and students should learn to play and enjoy immersing themselves in this cornerstone discipline of medicine.
Concept Knowledge Block of Osmosis, Osmotic Pressure, and Tonicity
There is an essential association between definitions and concepts. A concept is defined by words. And, a defined word in physiology can carry a spectrum of meaning depending on the scenario and the place the physiologic event occurs. Let us take the example of this question on sodium, “Is sodium penetrating or nonpenetrating solute?”
The natural answer could deceptively simple. Sodium is nonpenetrating and therefore, it is osmoactive and contributes to the tonicity of a solution of body fluid. The comprehensive definition of osmosis, osmotic pressure, and tonicity can be illustrated from this definition of an isotonic solution in Vander's Textbook of Human Physiology, “An isotonic solution contains 300 mOsm/L of nonpenetrating solutes regardless of the osmotic concentration of other penetrating solutes.” 
An isotonic solution will have an equal osmotic pressure as the cytoplasm. As such, in students' laboratory practical, red cells incubated in an isotonic solution, for example, 0.15 M sodium chloride will not change their cell volume. The equal osmotic pressure inside and outside the erythrocytes will mean that there will be no net transmembrane movement of water by osmosis.
” Nonpenetrating” in different contexts
Note that the term “nonpenetrating” applied to sodium and chloride ions in solution. These electrolytes are restricted to the outside of the cells and do not easily transverse the cell membrane into the cytoplasm. As such, their nonpenetrating nature makes the sodium and chloride ions osmoactive with a reflection coefficient close to one. Both sodium and chloride ionic particles together exert an osmotic pressure.
One of my students who ponder well on what he hears during class asked: “But doesn't sodium penetrate the cells, e.g., by the membrane sodium/potassium (N/K) ATPase active pump?” This query is instructive for teachers as it highlights that a definition can be applicable only in specific situations. In the consideration of tonicity, the nature of the solutes, whether they pass through the lipid-rich membrane in red cell osmotic laboratory analysis in test tubes, is described as penetrating or nonpenetrating.
However, in vivo, the understanding of sodium movement in a variety of sites requires different physiologic concepts. At the microcirculation, in contrast to the cell membrane where sodium cation is nonpenetrating, the sodium equilibrates between the endothelial cell layer of the capillary. The sodium concentration in the interstitial fluid space is similar to the plasma sodium concentration. There is then no osmotic pressure contributed by the penetrating sodium ions at the capillary.
The major osmotic pressure at the microcirculation is that of plasma proteins that are restricted in the vascular compartment. This is the oncotic or colloid osmotic pressure, which is dependent on the plasma protein concentration. At the glomerular capillary, the major Starling's force that is calculated in the net filtration pressure is the glomerular oncotic pressure [Table 1].
In the functionally polarized epithelial cells, the sodium ions do enter the cells, and this occurs by different transporter mechanism at the basolateral and the apical/luminal membranes. Sodium “penetrates” the cell at the basolateral side by the active Na/K ATPase.
Facing the lumen, in both the renal tubules and the intestinal enterocytes, sodium enters (” penetrates” ) the cell membrane by either cotransport with other solutes or counter-transport. Glucose and amino acids are reabsorbed at both the renal tubules and the enterocytes by secondary active sodium-coupled cotransport. At the proximal tubule, hydrogen ion secretion is linked to a secondary active, sodium-proton antiporter. Moreover, at the renal collecting ductal cells, sodium passively enters the cell through aldosterone-sensitive luminal membrane sodium channels.
No action potential, no life or vice versa
The ionic basis of action potential generation and transmission involves an acute influx of sodium ions that “penetrate” the membrane of excitable cells through voltage-gated channels.
So back to the initial question, “Is sodium a penetrating solute?” The overall in vivo picture gives us the broader conceptual understanding that sodium can be both nonpenetrating and also “penetrating,” with the latter transmembrane sodium movement essential for life as in action potentials and movement of solutes in and out of cells.
Building Normal and Pathophysiology Mechanisms on the Osmotic Concept
We engage our students when we help them to see the important relevance of osmotic forces in normal and abnormal physiology. We give our students a good framework or big picture when we give attention to integrated teaching on in vivo physiology of osmosis.
On fresh entry into medical school, students' excitement to learn medical physiology can be stifled when they sit through a basic lecture in the initial weeks on osmolarity, tonicity, and osmotic pressure. Giving the students an appreciation of the essential concept of water movement by osmosis in the body will help them to discover the basic physiologic mechanisms covering all of medicine.
Start with the concept that all transmembrane movement of water requires an osmotic gradient. The osmotic gradient is the main driving pressure for water movement across cell membrane. Moreover, this water flux principally moves through membrane aquaporins as water is a polar molecule.
Syndrome of inappropriate antidiuretic hormone secretion
So what's important about knowing this definition? The students might response with little interest.
You could reply by saying that “Have you heard of water intoxication? Too much water retention in the body can kill you and you can die from an abnormal osmotic gradient!” The concept of osmoregulation should be introduced, and this involves the brain at the level of the hypothalamus which produces the aquaporin-inducing antidiuretic hormone (ADH) and where the thirst center is also located.
Osmoregulation is a very sensitive, fast response control mechanism monitored by osmoreceptors in the hypothalamus. (For more keen students, you could ask them to read up on the interesting scientific journey of the discovery of hypothalamic osmoreceptors.) A good clinical example to illustrate the critical role of osmoregulation is the excessive hypotonic expansion of the extracellular fluid (ECF) in a patient with an ADH-secreting lung cancer. The hypoosmotic ECF leads to water flux into cells and the neuron swell. Abnormal water-stretched neurons precipitate the neurological symptoms seen in “water intoxication.”
Sweat is always wonderfully hypo-osmotic
I often say to the students, “Whether you believe in God or in Evolution, the design of the human body is marvelous.” Take the example of the osmotic compensation when you exercise and sweat. Sweating loses a hypotonic fluid, and the ECF becomes hypertonically contracted. Of the total body fluid volume, twice the volume is found in the intracellular space, and this large volume functions as a reservoir and can spare some water when the ECF volume is reduced as during sweating. As we just said, water only moves when there is an osmotic gradient. Thus, for the intracellular water to shift to lessen the decrease in ECF, the osmotic gradient for the water flux must be a driving force out of the cell. Indeed, this is precisely what occurs when a person is dehydrated after sweating. The hyperosmotic ECF draws fluid osmotically from the intracellular fluid. This osmotic compensation, acting by the osmoactive sodium and its accompanying anions (” CompAnions” ), helps to restore ECF and blood volume or prevent excessive ECF volume loss.
Transcapillary osmotic fluid shift in physiological compensation during hypovolemia
A similar osmotic compensation occurs at the microcirculation, and this is affected by the capillary oncotic pressure due to the nonpenetrating plasma proteins [Table 1]. When blood volume decreases either during trauma or after a blood donation, there will be a drop in arterial pressure and associated capillary hydrostatic pressure. The capillary oncotic pressure is unaffected during the reduction in blood volume. The balance of the Starling's forces at the capillary is thus tipped to favor less filtration and more reabsorption. This transcapillary shift of fluid from the interstitial space into the vascular compartment serves to maintain blood volume. This is a good example of osmosis in action in the cardiovascular system. It takes a little while before the actual blood volume is normalized by renal function.
Shared epithelial osmotic water transport in the intestines and the renal tubules
The kidneys and the intestines absorb water in the same osmotically way. Water absorption in the intestines/colon and by the renal nephrons at the proximal convoluted tubule, follows solute reabsorption. Upon solute reabsorption, there is an osmotic gradient set up between the interstitial space and the luminal fluid. Water then moves passively down its osmotic gradient transcellularly through aquaporins on both the luminal and basolateral membranes. There is also osmotic water flux paracellularly.
Duodenal osmotic regulation of optimal gastric emptying
The emptying of gastric chyme into the duodenum for further digestion is regulated, and one of the factors is osmolarity. Osmoreceptors are located at the duodenum, and gastric emptying is affected by changes in gastric chyme osmolarity. A hyperosmotic chyme tends to slow down the entry of gastric contents into the duodenum. The concept behind this osmotic control of gastric emptying through action on the pylorus is to prevent a hyperosmotic chyme in the duodenum interfering with water absorption. In the clinical scenario of dumping syndrome after gastrectomy when the gastric outflow is no longer regulated, the noncompliant patient who over eat may experience symptoms of hypovolemia due to the abnormal flux of water into the intestinal lumen along the abnormal osmotic gradient.
Abnormal osmotic excretion of water in diarrhea and diuresis
In persons with lactose intolerance, the cause of the watery stools is explained by what is termed osmotic diarrhea. Lactose that is not digested due to the absence of intestinal lactase remains unreabsorbed as only monosaccharides are absorbed. The lactose then behaves like “nonpenetrating” solute and suppresses the water reabsorption from the intestinal lumen.
A comparable clinical picture is seen in the kidneys in poorly controlled diabetes mellitus. The hyperglycemia exceeds the renal plasma threshold for glucose and glucosuria occurs. Unreabsorbed glucose at the proximal tube interferes with the iso-osmotic water reabsorption. The luminal fluid glucose behaves like “nonpenetrating” solute.
In normal kidneys, there is an unusual osmotic stratification of the renal medullary interstitium, the interstitial osmolarity increases progressively from 300 mOsm/L at the cortical/medullary border to 1300 mOsm/L at the inner medulla. This hyperosmotic interstitium, set up by the juxtamedullary nephrons, is essential for the kidneys to reabsorb and conserve more water during negative water balance or when the ECF becomes hyperosmotic.
Thus, even when we are dealing with osmosis in the initial weeks of the medical curriculum, we can briefly build on the essential concept of osmotic pressure and water osmotic movement and link them to essential normal physiology and adaptation to different scenario (sweating, blood donation, and water balance). We stimulate students' interest by citing the osmotic pathophysiology (syndrome of inappropriate antidiuretic hormone secretion, dumping syndrome, lactose intolerance, and diabetic polyuria) [Table 2].
We hope this description of “PhysioLego,” building and applying essential physiology concepts, will be useful for both students and teachers. As educators, it is for us to tease out the normal “PysioLego” in other organ systems and teach students to expand their understanding of related pathophysiology base on these “PhysioLego” foundation blocks. A previous published summary of essential in vivo osmosis is given in a modified humorous title after the Ten Commandments [Figure 1].
This “PhysioLego” approach to teaching is part of a list of reflective thoughts [Table 3] that was penned to remind and help educators to engage better in their students' learning process of physiology.
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