When contemplating our sensations, we tend to focus on external stimuli and how we perceive them: sight, hearing, smell, touch, taste, vibration, pain and so forth. There are other sensations we perceive but these are internally derived. How our bodies process these central impulses is just as complicated as the means by which we analyze and resolve external constructs. In addition, when our internal urges increase, there must also be a means for turning them off–a feedback mechanism. On a biochemical level the complexity is almost overwhelming. Let’s run through some of these.
HUNGER
Large pelagic sharks never stop swimming- activity that requires large expenditures of energy and therefore large amounts of caloric replenishment. We all remember the scene in the 1975 movie Jaws during which actors Roy Scheider and Richard Dreyfuss open the stomach of a captured tiger shark to see if it contains human remains. Instead, an assortment of swallowed material is recovered–including a metal license plate. One would be inclined to consider this Hollywood exaggeration. That would be incorrect. In Thomas Helm’s book “Shark: Unpredictable Killer of the Sea” is a description of the gastric contents discovered in a captured blue shark that had followed a merchant ship and was caught and hauled on board. “Along with an assorted mass of partly digested garbage and small fish, a total of 27 different and completely indigestible articles spilled out on deck. In the collection we found two soft drink bottles, an aluminum soup kettle with a broken handle, a carpenter’s square, a plastic cigar box, a screw top jar partly filled with nails, a two-celled flashlight, several yards of 1/4 inch nylon line, a rubber rain coat, and a worn out tennis shoe. The largest and most improbable object was a 3 ft wide roll of tar paper with about 27 ft of the heavy black paper still wound on a spool.” Sharks are not concerned with digestibility, they are concerned with hunger. What their GI tract cannot absorb can be pooped out or thrown up. Needless to say, the sensation of hunger can be quite provocative.
Perhaps the most unique case of a shark’s ingestion involved an incident in Sydney, Australia. In April 1935 a recently captured tiger shark was publicly displayed at the Coogee Aquarium Baths, but a week after its introduction into the tank and in front of onlookers the shark vomited what remained of a human left upper extremity. The arm had been severed sharply-indicating it had been performed with a blade, not the shark’s teeth. Furthermore, the forearm displayed a distinct tattoo, unusual enough to be traced to James Smith-a small time criminal who had disappeared earlier that month. “Jimmy”, in addition to several questionable talents, turned out to also be a police informer, an occupation that apparently led to his demise. An associate named Reginald Holmes planned to cooperate with police investigating the murder and the trail led directly to Patrick Brady who was promptly arrested and charged with murder. Unfortunately for the prosecution the police neglected to provide protection for their star witness (Holmes) who was found shot to death in his car. Oops. The case was dropped due to lack of evidence, not to mention due to lack of the witness. Sadly, after vomiting the arm the captive shark died, outliving James Smith by only a brief duration. It is unknown if the local mob also silenced the fish .
Sharks get hungry. People get hungry. Virtually all of zoology relies on hunger to prompt ingestion of food stuff to provide energy. We are certainly aware of the sensation, and tend to consider hunger and eating as a single entity–but they are not. One provides impetus, the other fulfilment. Then what underlies this prompting and why does it shut off when surfeited? The answer lies in biochemistry and anatomic systems. The GI tract is not merely an extended tube that digests and absorbs food–it is the largest endocrine system in the body, capable of releasing over 50 different hormones. Many of these molecules are involved in the hunger/satiety balance. Ghrelin-sometimes labeled the hunger hormone-is primarily produced by the stomach but also from the brain, small intestine, and pancreas. Rising levels signal the brain’s hunger centers to consume, but we do not just want to eat. The system also produces a sensation of pleasure . This is why men ask ladies to dinner. And why they accept.
Once we have partaken of a meal, we need a mechanism to shut off the desire to eat. The stomach contains stretch fibers that send signals through the Vagus nerve to the brain: “I’m full”. In case the message is not fully received, the intestines also release Peptide YY: “Yes, I really am full.” And if needed, the small intestines finally have intragangliomic laminar endings (mercifully abbreviated IGLE) that finally tell the brain “OMG! STOP EATING!”
These are relatively short term mechanisms operating over minutes to a few hours, but longer duration appetite suppression is mediated by Leptin. This hormone is produced by fat cells and is slowly released. Think of the rapid acting mechanisms as “cash and carry” as compared to a 10 year bond that Leptin represents. The result of this biochemical frenzy (which amazingly seems to work quite well) is to initiate eating to provide caloric energy, but then subsequently tamps down the system to hopefully prevent over saturation. Throughout our body are multiple balancing systems with continuous feedback and control mechanisms to hopefully center our biologic see-saws on ideal health.
So why do people become obese? Leptin acts on biochemical receptors in the brain, but in some individuals Leptin resistance develops and the brain’s response is muted. The causes may be multiple- Inflammation, diet, genetic, psychiatric, medications-and worse, increasing obesity tends to result in even more Leptin resistance, a rolling snowball effect that ends up cancelling the “I’m full” signal.
THIRST
Like hunger, the underlying biochemistry of simple thirst is more complicated than would be expected. We tend to think thirst is a dryness in the mouth and throat-that’s all. Actually, the sensation of being thirsty involves the hypothalamus in the brain, our kidneys, adrenal glands, and the forebrain as well. When we develop a degree of dehydration, our cells physically shrink in size, sending nerve mediated signals to the brain. There are also receptors in the hypothalamus that respond to increased molecular and elemental concentrations, especially sodium. This area of the brain is also sensitive to decreased total blood volume and blood pressure. Meanwhile, the kidneys release the hormone Angiotensin II, which in turn instructs the brain to produce antidiuretic hormone (ADH). The kidneys also ramp up production of aldosterone with the net result that salt that would be urinated out is retained. Simultaneously, the hypothalamus is signaling the forebrain to activate its thirst circuits. Sound complicated? Actually, there are many moving parts as our body is multi tasking. After drinking, sensors in the mouth and throat signal thirst relief.
Perhaps we should not be surprised that the kidneys and our heart are tied together in this system. A class of drugs (SGLT2 inhibitors) which block glucose reabsorption in the renal tubules has been used for diabetic control and has also been found to improve overall kidney function and cardiac performance. Everything is synchronized, tied together. Almost as if it was designed.
ELIMINATION
In the absence of injury or illness, we are all aware of the need to urinate or defecate. Similar to the inner sensations of hunger and thirst, we tend to take for granted the urges for elimination. In certain medical conditions, these sensations are not present with resulting incontinence of urine or stool. Not surprisingly, the mechanisms by which we are made aware of these needs are complex. The bladder wall stretches as urine accumulates and when a volume of 240 mL (about 1 cup) is reached there is activation of proteins coded by the P1EZ02 gene– these alert sensory nerves to signal the brain of the reservoir filling. As the bladder continues to swell, the brain becomes aware of a possible overflow crisis and sends messages through returning nerves both to the bladder wall muscles and the urinary sphincter muscles to hold back the rising tide. Eventually, the urge to urinate overrides the ability to retain urine. At this point the bladder contracts, the urethral sphincters relax, and hopefully there is a receptacle as well as some privacy available. And maybe a change of clothes.
In a similar fashion there are stretch receptors in the rectal wall which provide feedback for defecation. When you eat, the food does not mechanically push fecal content out the anus. There is a gastrocolic reflex that signals waste material to move into the rectum. Digestive hormones are released and signal the colon to contract. Certain foods such as fats, dairy products, grains, and citrus tend to intensify the impulse to defecate. The brain receives neural input from the rectum and is able (fortunately for our social reputation) to exert some voluntary control over both fecal and urinary release. There is even a defecation area of the brain – DBA or Defecation Brain Area (no, I am not making this up). Without the brain’s participation and override capabilities we would accumulate far more ” Most Embarrassing Moment” stories, a library that most of us would prefer not to stockpile.
SLEEP
Sleep is another requirement of life–if not satisfied we can reach the point of dosing off even under precarious circumstances. Similar to the other internal needs the mechanism of sleep is the product of a complex amalgam of multiple different biomolecules, brainstem structures, biologic clock genes, even the physical properties of light. At different sleep stages there are mechanisms to provide feedback affecting respiratory and cardiac activity. Light striking the retina releases glutamate which stimulates receptors in the suprachiasmatic nuclei located in the hypothalamus. This photon induced input can reset our biologic clock and can switch around bio electrical pathways in the brain similar to traffic control grids.
The effect of sleep cycles is to coordinate the release of various hormones from multiple locations in the body: Cortisol, growth hormone, thyroid hormones, melatonin. In fact, the entire panoply of sleep effects on our biophysiology is overwhelmingly complex in not fully understood. One would at 1st glance not think that the central nervous system would be such a major player in the development and satisfaction of hunger, thirst, elimination, sleep–but it is.
SEXUAL
If we do not satisfy the urges of hunger, thirst, elimination, and sleep we cannot survive. Life span would be measured in days. Sexual urges are also internally generated prompts and while not affecting life span in an individual if not satisfied, the absence of such a demand would result in elimination of the population in due course. Your progeny should feel grateful that mom and dad’s biological impulses resulted in them having such an affinity for each other, but I doubt it crosses their mind much.
The process of sexual attraction–and this should not surprise anyone at this point–is quite complex involving our sex hormones (testosterone, estrogen) and multiple biochemical neurotransmitters acting on various centers in the brain. Dopamine production results in pleasure and a desire to act to achieve this. Testosterone (and both males and females produce this) turns the volume up on sexual desire. There are multiple areas in the brain that are involved in the sexual appetite, and signals are sent to the sexual organs which induce nitrous oxide release and responding venous engorgement. Climaxing orgasm is caused by a blast of multiple inputs from dopamine, oxytocin, and other bio molecules. Afterwards the entire system stands down with a rise in serum prolactin. After the excitement, both parties need a break. Specific genes are involved in regulating each step of the entire sexual experience. Who knew that such a complicated process could be such fun. As a bonus, occasionally kids show up and everyone’s life changes dramatically.