The adaptive immune system is the “big gun”, later evolved, big brother of the innate immune system. The innate immune system acts a little like prejudice does in society. There is INSTANT RECOGNITION of a salient characteristic of many common disease-producing organisms, that are not present in the person being infected.
For instance, ENDOTOXIN is a lipopolysaccharide present in many bacteria, and is immediately recognized by Toll-like Receptors (TLR-4) on dendritic cells and macrophages. This triggers the Natural Killer (NK) cells to destroy the invader. The problem is that the innate immune system is indiscriminate, reacting against whole classes of molecules like a shotgun, and may produce unwanted damage. It also fails to recognize many genuine threats.
The ADAPTIVE immune system is more complex, discriminant, and SPECIFIC, but is SLOWER to gear up, and takes several days to be effective. Once engaged, however, it has a MEMORY for the infection that is SPECIFIC to the organism involved. This memory makes a SECOND EXPOSURE response much more rapid and comprehensive, AMPLIFIED as it is BY ANTIBODIES.
This first experience can be PROPHYLACTICALLY accomplished by VACCINES, so that the second, real exposure generates a RAPID PROTECTIVE RESPONSE. ATTENUATED vaccines are weakened, but LIVING ORGANISMS, and usually provide a more DURABLE immunity, but because they are living, they are more worrisome.
SPLIT-PRODUCT Vaccines are safer, but expose the immune system to a narrower range of pathogen markers, and may therefore be less Protective.. The FDA is very dedicated to SAFETY. Like all Bureaucracies, it is relatively independent of Political pressure, of which I am increasingly appreciative.
When the COVID-19 VACCINE, for example, is released to the general public, it WILL BE SAFE. The vaccine-deniers are mis-informed people who should not, in my opinion, be allowed to interfere with the HERD IMMUNITY that comes with having a supermajority of the population vaccinated.
INSECTS are mainly pests. Except for the very commercially valuable Pollinators, Honeybees, the other useful insects, like ladybugs, dragonflies and spiders are beneficial because they eat other insects. It is very exciting, then, to hear about a pleasantly-smelling insect repellent that is quite harmless to Humans.
NOOTKATONE, after you get used to its ugly spelling, has an aromatic, Grapefruit-like smell. It was discovered while researching the CEDAR family. We all know of the association between Cedar and storage. One of my prized possessions was a Cedar chest for storing our families ski clothes.
Whenever I hear of a non-toxic chemical that repels and sometimes kills mosquitos, ticks, bedbugs and fleas, and yet is so harmless as to be used in perfumes, I like to hear of a proposed MECHANISM OF ACTION.
Nootkatone is thought to work by stimulating octopamine receptors, which insects use to make their muscles work. The muscles just keep on contracting and the insects die. The only problem is that Nootkatone is mainly a repellant, and a weaker insecticide.
Another good quality of Nootkatone is that the effect lasts several hours, in contrast to citronella and the other plant oils. Interestingly, the substance was isolated from grapefruit some 25 years ago, while looking for a repellant for the tick of Lyme disease.
Anaplasmosis and Rocky mountain spotted fever are 2 other tick-transmitted diseases present in America. Nootkatone is particularly effective against ticks, and is now EPA-approved.
Sometimes I wake up in the morning with a feeling of RELAXED ENERGY. My mind is clear, I have no fatigue, and believe once more that the world is wonderful, and it’s great to be alive.
I St-re-tch, exercise my hands (I have Osteoarthritis, and they are stiff), take out my Nite guard ( I grind my teeth at night and would otherwise wear them away), take my beta blocker eye drops ( to lower my intraocular pressure) and wash down my Eliquis ( an anticoagulant to prevent stroke from my Atrial Fibrillation) with 16 oz. of water, while thinking about all of the delights awaiting me.
Yes, my body was in better shape 60 years ago; but I had much more responsibility then, and much less discretionary time. All things considered, I like to believe that I am happier now.
The KEY is to stay in GOOD HEALTH. GOOD SLEEP is critical, but it cannot be had by willpower alone. As I have discussed previously, you need a bedtime routine, good SLEEP HYGIENE.
You also need a…….. GOOD DIET. with lots of fruits, vegetables and whole grains. Fatty, spicy foods will stay in your stomach and bother you at night, particularly if you eat Late. I like to finish eating by 5 PM. Late dinner is also likely to produce GERD, and maybe Sleep Apnea.
GOOD EXERCISE is also critical. If you are not tired at the end of the day, it is hard to get good sleep. I always seem to sleep better on the day when I walk the hills for an hour, which is 3 days a week. Try not to exercise within 2 hours of bedtime. Assuming that you have a good base of SLEEP, DIET and EXERCISE, there are other mechanisms that can foul things up. INFLAMMATORY conditions often cause fatigue.
The most common inflammatory diseases are OBESITY, METABOLIC SYNDROME and DIABETES. OBESITY is the defining disease of our EXCESSIVE SOCIETY, where there is too much of everything, and excessive consumption is relentlessly advertised everywhere.
External correction is probably a pipe dream, since there is no will even to Tax Sugar-containing Beverages, the “low hanging fruit” of dietary excess. Internal correction is all that is left, and that takes WILL POWER, also in short supply.
INFECTIOUS DISEASES are a subset of inflammatory conditions. COVID 19 is the poster child of infection, and FATIGUE is one of the hallmarks of the disease. Interleukins, like TNF-alpha, IL-1, andIL-6 are some of the defense factors which cause the fatigue. AUTOIMMUNE Diseases like Rheumatoid Arthritis and Lupus are also associated with fatigue-producing interleukins.
Fatigue even has its own flagship disease, CHRONIC FATIGUE SYNDROME. Chronic viral disease has been suspected as the cause of this condition, and inflammatory cytokines may be elevated. This condition, and the similar GULF WAR SYNDROME are still poorly understood. Several CFS patients were sent to me when I was in practice, and I had some success in getting them to exercise regularly, which seemed to help. CANCER is another category of diseases where Fatigue is prominent.
Inflammation plays a role in these diseases, which also drain energy substrates from the Patients body; Cancer cells have a high metabolic requirement. MEDICATIONS, Cancer meds especially, but a variety of other Drugs are associated with FATIGUE. I went through MY MEDICATION LIST. Lo and behold, 3 of them are associated with fatigue.
Finasteride is a relic of my prostate operation, recommended to keep it from growing back. It causes fatigue, probably because of its ANTITESTOSTERONE effect. At least I can still pee, and am not bald. I take METFORMIN because of its fame in prolonging life. Its mechanism is that of interacting with the Sirtuin system, and increasing the inefficiency of mitochondria. Isn’t this surprising?
Like many other things in physiology, you place a stress on the body, and the body responds by improving its performance. If you are fatigued, you exercise. Respecting the body works with drugs as well. If you are drinking a ton of coffee and stop it, after a few weeks you will feel less fatigued.
And when you ARE FATIGUED, you drink a LITTLE coffee, and it wakes you right up. Caffeine works by displacing ADENOSINE, which causes Fatigue as it increases through the morning, peaking at SIESTA (or tea) time,at about 2 PM. OMEPRAZOLE, which I take to prevent HEARTBURN, also is related to fatigue especially if it blocks MAGNESIUM for long enough. DEPRESSION overlaps with fatigue, as does SLEEPINESS, to increase the complexity of the situation.
Many chronic LUNG, KIDNEY and LIVER diseases are associated with fatigue as a secondary concern. STAY HEALTHY!
Humans have a high energy requirement. Like a sports car we need to be turbosupercharged. We need an entirely separate Pulmonary circulation to handle our great oxygen demand.
Fish can get by on a single heart and circulation. They are “cold-blooded” and have no elevation of temperature above that in the environment. The water buoys them up, and they don’t need to constantly fight gravity.
Birds, and by extension, therapod dinosaurs, need more efficiency, and have a separate pulmonary circulation, just like we do. They share with us a DOUBLE CIRCULATION, a 4-chambered heart, with 2 entirely separate circuits.
In my residency, I saw a lot of congenital heart disease. In the process of development, the very early human embryo has a single circulation, just like “early” vertebrates, like fish.
In the process of development, the Systemic and Pulmonary circulations divide the previously unitary system into 2 separate systems, by a continuous spiral of partitions, or “septae”.
Ontogeny recapitulates Phylogeny: Development recaps Evolution. If this process of separation fails to happen in a given child, Congenital Heart Disease is the result:
IASD. Interatrial Septal Defect is failure to separate the Atria, the upper chambers of the heart;
IVSD, Interventricular Septal Defect, is failure to separate the Ventricles, the lower chambers of the heart;
AV Communis is both of the above, plus failure of Atria and Ventricles, the upper and lower chambers, to separate, giving one big inefficient chamber.
When you listen to the hearts of these children, there are prominent murmurs, or noises, which betray the presence of turbulence and inefficiency, the very thing that evolution “tried” to prevent.
In the normal Human Heart, the blood returns from it’s systemic circuit through the capillaries, depleted of oxygen, into the vena cava. It passes to the Right Atrium, through the tricuspid valves, to the right ventricle.
With the contraction of the heart, the blood goes through the pulmonary artery, into the pulmonary capillaries, into close contact with air-containing alveoli. The oxygen passes through the alveolar membrane into the capillary blood, which becomes red. The oxygenated blood then passes into the pulmonary veins and on into the left atrium, and the systemic circulation.
It is interesting, and essential that the systemic arteries contain red, oxygenated blood, and the Pulmonary artery contains blue, oxygen-depleted blood. The “tired” blood, returning from the body must be “pepped up” by passing through the pulmonary circuit, picking up oxygen in the process.
Similarly a clot, originating in a quiet vein, perhaps a dilated, or varicose vein, is pumped into the Pulmonary circuit, where it lodges in the tiny capillaries and produces a PULMONARY EMBOLISM.
The embolus clogs the pulmonary circuit, increasing resistance, raises the normally-low pulmonary artery pressure and produces PULMONARY HYPERTENSION, placing more load and strain on the Right Ventricle.
Pulmonary Hypertension is also caused by a variety of Lung, heart, inherited and kidney diseases, as well as by certain drugs, high altitude, and Obstructive Sleep Apnea.
Please check the Mayo Clinic discussion that follows.
BLOOD VESSELS; it is hard to overestimate their importance. They are literally our lifelines, delivering the oxygen and nutrition necessary for life. We are as old as our blood vessels.
I will divide blood vessels into 4 components with rather separate domains: The Systemic Arterial system, the Pulmonary circulation, the Venous system, and the Lymphatic system, and will discuss these separately.
SYSTEMIC ARTERIAL SYSTEM
The Boy Scouts taught me the pressure points; The radial, at the thumb-side of the wrist, the brachial, on the inside of the upper arm, and the inguinal in the groin area. Pressure on these sites will stop arterial bleeding distally.
You should be able to locate the radial artery pulse, and begin to appreciate its strength and regularity. Strength in case you encounter a person who isn’t moving, and regularity for yourself; many older people develop an irregularity called Atrial Fibrillation, and you might be the first to discover it..
ANEURISMS are swelling of the arteries, and the swelling may thin the arterial wall so that it can burst. A Cerebral aneurysm can burst and cause a stroke-like problem. If an aortic aneurism bursts, the internal blood loss can be fatal.
RAYNAUD’S Phenomenon is fairly common, and consists of an over-reaction to cold, where arteries of the hands constrict, and the fingers get white and cold. Burger’s disease involves small arteries, and often is associated with Raynaud’s. The arteries carry the blood distally (away from the heart), continuing to divide into ever smaller arterioles which terminate in capillaries, which branch out in such an arborization as to supply all cells except cartilage and parts of the eye.
HYPERTENSION develops when the arterioles, under hormonal or neural influence, constrict, increasing the resistance to blood flow, and so the pressure. Increase in sodium retention and therefore the blood volume can also increase pressure.
ATHEROSCLEROSIS is the common disease of western life style. Excessive calories and sedentary life style combined with genetic defects in fatty metabolism produce cholesterol plaques which narrow and stiffen the arteries, often leading to BLOCKAGE of blood flow. Blockage of flow to the HEART, BRAIN, KIDNEYS, BOWEL, or EXTREMITIES each produce their separate disorders of Myocardial Infarction, Stroke, Renal artery Disease. Intestinal ischemic syndrome, and Claudication.
These disorders will each be separately discussed. I have always thought of vascular disease as a special class of CAUSATIVE MECHANISMS when trying to develop a DIFFERENTIAL DIAGNOSIS of a patient’s problems. Blockage to an area results in PAIN or LOSS OF FUNCTION.
Stroke is usually painless with blockage, since the brain has no pain sensors. Blockage of the renal artery often causes complex difficulties including Hypertension, because the kidney is an endocrine organ in addition to its excretory function.
A good Friend and patient showed what careful self-care can accomplish. It all started with a myocardial infarction, the first sign of his blood vessel disease. He had a complication in his workup, and had to have emergency bypass surgery. There had been damage to the heart muscle, with a large reduction in his EJECTION FRACTION.
His cardiologist gave him at most 5 years to live. That was 25 years ago, before the development of the statin drugs. He was given a draconian low cholesterol diet, which he followed exactly. One one visit to the cardiologist, he inquired whether he could have other areas of arterial blockage. His doctor then listened to his neck and discovered a bruit (noise) in the carotid artery, after which he had a Carotid endarterectomy.
In an orthopedist office for back pain, the orthopedist left the room, and my friend noticed in the CT scan report mention of cysts in the kidneys.
The Orthopedist cared mainly about his bones, and had overlooked the “incidental finding”. His brother had died of mesenteric artery blockage from atherosclerosis, he had stomach symptoms, and sure enough he also had arterial blockage to the intestines.
Bottom line: it pays to be an ACTIVE PARTICIPANT in our medical treatment, and even though we all have genetic determinants, we can make our health BETTER with attention to our health, especially SLEEP, DIET and EXERCISE.
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