Do they prove anything?

Dr.Vivek Nalgirkar

3/10/20224 min read

Exceptions…….do they prove any rule?”

Having a close look at the organ systems and their Physiology, one can sense that each one of them has a unique function or set of functions; for instance, cardiovascular system - primarily designed for supply of oxygen and nutrients to all tissues, digestive system – make the nutrients available to the body in usable forms, and so on.

In addition to their primary functions, each of these organ systems has some more functions that contribute to the homeostasis and survival.

There are non-respiratory functions of the lung (metabolic functions – synthesis of ACE, defence – alveolar macrophages; speech, pH regulation, etc). Heart and the digestive tract perform endocrine functions (e.g., ANP by heart; incretins for insulin secretion by digestive tract). Kidney has a long list of non-excretory functions (synthesis of Vit D & erythropoietin, pH regulation, osmoregulation, volume regulation, and so on).

However, it strikes me that Physiology of the organ systems has an uncanny knack of making exceptions at various places. Here are some of the exceptions –

-Sensory system: (Are we evolved to live in the dark??) The biological transducers, the receptors, have a resting membrane potential when no stimulus is being applied. When right kind of stimulus energy is applied, a receptor develops a depolarizing potential, the receptor potential. This receptor potential then generates impulses in the sensory neuron (which too was resting thus far). RODS IN THE RETINA MAKE AN EXCEPTION TO THIS. Rods respond to electromagnetic stimulus energy, that is, light, for our visual sense. However, in complete dark (when no light is striking retina), the rods already discharging the transmitter glutamate at their synaptic bodies (in other words, they don’t seem to have an RMP). Upon light falling on the retina, the visual cycle ensues that causes HYPERPOLARIZATION of rods. There is decrease in the transmitter release at their synaptic bodies, which is taken as the sense of light. May be the humans evolved to live in the dark, and light is an exception..!

-Hypoxia : (Lung, the supplier of oxygen, reacts differently) Hypoxia leads to vasodilation everywhere except in lungs. The hypoxia-induced vasodilation improves blood flow to a tissue, correcting the hypoxia. In lungs, though, hypoxia in a part means no ventilation to some of the alveoli. The constriction of vessels in this region would divert the blood flow to the better ventilated alveoli. O2-sensitive K+ channels in the vascular smooth muscle cells (VSMCs) are responsible for this hypoxic vasoconstriction.

-Nutrition to the organs: (Is heart asking for atherosclerosis?) Most organs utilize carbohydrates/glucose as their primary fuel for energy. Heart prefers fatty acids as the primary source. Double the source of energy? (Fats = 9 Cal/gm; carbs = 4 Cal/gm).

-Glucose entry: (GI and renal cells give away their sweets/sugar immediately) In most cells, glucose crosses the membranes, to enter cells, by using GLUTs as the transporter; the mechanism is facilitated diffusion. In all these cells, glucose enters and is metabolized or utilized. In GIT and kidney, glucose enters the lining cells via the SGLTs (the secondary active transporters). The reason is obvious – at these two places, it is the absorption of glucose, and it has to cross TWO membranes. It enters the cells of GIT & kidney by using SGLT (goes low-to-high concentration), and then it leaves the cells using GLUT-2 located on the other basolateral membrane (facing blood vessels).

-Adenosine: (increases blood flow everywhere; behaves differently in kidney) It causes vasodilation everywhere (Berne’s hypothesis). In kidney, it causes constriction of the afferent arteriole as a part of tubulo-glomerular feedback.

(By the way, kidney is the only organ where capillaries drain into arterioles; the glomerular capillaries drain into efferent arterioles. Everywhere else, the capillaries lead to venules/veins.)

-Oxygen utilization coefficient: (Why only heart suffers from heart attack??!!!) 20 mL of oxygen is carried by every 100 mL of arterial blood. Of this, the tissues extract 5 mL, making the utilization coefficient to be 25% (5 out of 20). The two organs that deviate from this are – heart and kidney. Heart has oxygen utilization coefficient of 75% (it extracts 15 out of the 20 mL). This is THE reason why heart is the worst sufferer of ischemia. Other tissues have a good reserve for oxygen; that is, they can extract more oxygen if the need be. Heart is already extracting maximum oxygen coming to it. Hence, in the case of increased demands, it can not increase oxygen extraction beyond a certain ceiling.

This coefficient is only 10-12% for the kidney. Kidney being a small organ with massive blood supply (25% of the cardiac output), whatever oxygen it extracts would make for a low utilization coefficient.

-Blood flow to organs: (Heart - the blood giver; the blood receiver) Most organs receive their blood flow during systole; heart itself receives its major share during diastole.

-ECF composition: (Hair cell – the most excitable cell, with largest transmembrane voltage gradient of 150 mV). Low potassium in the ECF is the rule (hardly 4 mEq/L). Endolymph has the exception. There is a high concentration of K+ in the endolymph, even though it is an ECF. It leads to many other exceptions. For all cells, RMP is – 10 mV or – 45 mV or – 90 mV, with exterior is taken to be zero (as all cells are surrounded by the same ECF). The cochlear hair cell has RMP of – 70 mV; however, this cell is bathed in the endolymph with high concentration of potassium (over and above the normal ECF composition). This creates the so-called endocochlear potential of + 80 mV (instead of zero, as is the case with ECF everywhere). Depolarization of the hair cell is brought about by entry of K+ from the top of the hair cell (elsewhere, the excitable cells are depolarized by entry of Na+ or Ca++, and repolarization by exit of K+).

-Thalamus: The obligate relay station: (Why don’t we feel the taste when smell is obliterated) All the general and special senses have their pathways having obligate relay in thalamus; olfactory sense is the only exception. In other words, all sensations meet in the thalamus, and move on to cortex. Does olfactory sense meet other sensations at all? Amygdala is where sense of smell gives collateral to potentiate some other pathways, especially the taste pathway. If this potentiation is dysfunctional (as occurs temporarily in common cold, with obliteration of smell), the taste can not be appreciated. There is nothing wrong with taste pathway in common cold.

-Nerve without a fiber? All nerves have at least a single axon that carries impulses over a certain distance. Two nerve cells make an exception. Amacrine cell in retina and postganglionic parasympathetic neurons are ANAXONAL neurons.

The list could still go on………….!

-Dr Vivek Nalgirkar