Introduction to Clinical Cases

Homeostasis and disease

Homeostasis (from Greek: ὅμοιος, hómoios, "similar", and στάσις, stásis, "standing still") is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties such as temperature or pH. It can be either an open or closed system.

It was defined by Claude Bernard and later by Walter Bradford Cannon in 1926, 1929 and 1932.

Typically used to refer to a living organism, the concept came from that of milieu intérieur that was created by Claude Bernard and published in 1865. Multiple dynamic equilibrium adjustment and regulation mechanisms make homeostasis possible.

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Control mechanisms

All homeostatic control mechanisms have at least three interdependent components for the variable being regulated: The receptor is the sensing component that monitors and responds to changes in the environment. When the receptor senses a stimulus, it sends information to a "control center", the component that sets the range at which a variable is maintained. The control center determines an appropriate response to the stimulus. In most homeostatic mechanisms, the control center is the brain. The control center then sends signals to an effector, which can be muscles, organs or other structures that receive signals from the control center. After receiving the signal, a change occurs to correct the deviation by either enhancing it with positive feedback or depressing it with negative feedback.

Positive Feedback

Positive feedback is the body's mechanism to enhance a output needed to maintain homeostasis. Positive feedback mechanisms push levels out of normal ranges. Even thou this process can be beneficial, it is rarely used by body because of the risk of the increased stimuli becoming out of control. An example of positive feedback is the release of oxytocin to increase and keep the contractions of child birth happening as long as needed for the child's birth.Contractions of the uterus are stimulated by Oxytocin, produced in the pituitary gland, and the secretion of it is increased by positive feedback, increasing the strength of the contractions.

Negative Feedback

Negative feedback works in the opposite way that positive feedback does. With negative feedback, any change from the normal range of function,  causes the negative feedback mechanisms to resist or oppose the change, bringing the function back to normal ranges. Negative feedback requires a receptor, a control center, and a effector. The receptors are connected to the control center within the brain. When the brain receives information that there is a deviation in the body's internal condition, it sends out a signal along nerve lines that prompt the changes to bring the internal conditions back to normal ranges. A good example of a negative feedback loop is the body's internal thermometer. When the temperature drops or raises above the range of the set temperature, the body will initiate a homeostatic response. Some of these responses include sweating to cool down, and shiveringto warm up. 

Another good example, is the regulation of blood pressure. Blood vessels can sense resistance of blood against the walls when blood pressure increases. They in turn send a message to brain, which sends a message to the heart , which is an effector. The heart rate will decrease, changing the blood pressure back to its normal range. 

Another very important example of a negative feedback loop is the blood sugar regulation.

The body requires volumes of sugar to create ATP. ATP transports chemical energy within the cells. The body regulates the availability of glucose to maximize its energy potential. 

Hormones responsible for controlling the glucose in the blood are insulin and glucagon.The pancreas is responsible for monitoring glucose levels, and sending messages to the receptors of the liver that more insulin or glucagon is needed. The liver is the place for storage of glycogen, the storage form of glucose. When either of these hormones target the liver either insulin is released as a result of increased glucose levels, and promotes the conversion of glucose into glycogen, or glucagon is released as a result of a decrease in glucose, and therefore promotes the conversion of glycogen into glucose.

Homeostatic imbalance

Many diseases are a result of disturbance of homeostasis, a condition known as homeostatic imbalance. As it ages, every organism will lose efficiency in its control systems. The inefficiencies gradually result in an unstable internal environment that increases the risk for illness. In addition, homeostatic imbalance is also responsible for the physical changes associated with aging. Even more serious than illness and other characteristics of aging is death. Heart failure has been seen where nominal negative feedback mechanisms become overwhelmed, and destructive positive feedback mechanisms then take over.

Diseases that result from a homeostatic imbalance include diabetes, dehydration, hypoglycemia, hyperglycemia, gout, and any disease caused by a toxin present in the bloodstream. All of these conditions result from the presence of an increased amount of a particular substance. In ideal circumstances, homeostatic control mechanisms should prevent this imbalance from occurring, but, in some people, the mechanisms do not work efficiently enough or the quantity of the substance exceeds the levels at which it can be managed. In these cases, medical intervention is necessary to restore the balance, or permanent damage to the organs may result.

According to the following citation, every illness has aspects to it that are a result of lost homeostasis:

"Just as we live in a constantly changing world, so do the cells and tissues survive in a constantly changing microenvironment. The 'normal' or 'physiologic' state then is achieved by adaptive responses to the ebb and flow of various stimuli permitting the cells and tissues to adapt and to live in harmony within their microenvironment. Thus, homeostasis is preserved. It is only when the stimuli become more severe, or the response of the organism breaks down, that disease results - a generalization as true for the whole organism as it is for the individual cell." (Pathologic Basis of Disease, third edition, S.L. Robbins MD, R.S. Cotran MD, V.K. Kumar MD. 1984, W.P. Saunders Company)

Disease

Disease is a term for any condition that impairs the normal functioning of an organism or body. Although plants and animals also contract diseases, by far the most significant disease-related areas of interest are those conditions that afflict human beings. They can be divided into three categories: intrinsic, or coming from within the body; extrinsic, or emerging from outside it; and of unknown origin. Until the twentieth century brought changes in the living standards and health care of industrialized societies, extrinsic diseases were the greater threat; today, however, diseases of intrinsic origin are much more familiar. Among them are stress-related diseases, autoimmune disorders, cancers, hereditary diseases, glandular conditions, and conditions resulting from malnutrition. There are also illnesses, such as Alzheimer's disease, whose causes remain essentially unknown.

Signs and symptoms.

Symptom: Any subjective evidence of disease. A symptom is a phenomenon that is experienced by an individual. Anxiety, lower back pain, and fatigue are all symptoms. They are sensations only the patient can perceive. In contrast, a sign is objective evidence of disease. A bloody nose is a sign. It is evident to the patient, doctor, nurse, and other observers.

Sign: Any objective evidence of disease. A sign can be detected by a person other than the affected individual. Gross blood in the stool is a sign of disease. It can be recognized by the patient, doctor, nurse, or others. In contrast, a symptom is, by its nature, subjective. Abdominal pain is a symptom. It is something only the patient can know.

Medical symptoms

There are three main types of symptoms.

• Chronic symptoms - long lasting or recurrent symptoms. As may be the case with such diseases as diabetes, asthma, or cancer.


• Relapsing symptoms - when a person is affected by symptoms again; symptoms which had occurred in the past, disappeared, and then come back. As may be the case with depression, multiple sclerosis, and also cancer.


• Remitting symptoms - when symptoms improve, and sometimes go away completely.

Symptoms may also progressively get worse, or better. Diseases and conditions can also be described as:

• Asymptomatic diseases/conditions - this means the disease is present but there are no symptoms. For example, during the early stages of breast cancer the patient may feel or sense no symptoms at all. Often, the first a person knows about an asymptomatic disease or condition is during a routine health check. High blood pressure (hypertension) is often asymptomatic. 
  
  
  An asymptomatic infection is also called a subclinical infection. An infected individual may not develop symptoms during the incubation period - also known as the period of subclinical infection. This is often the case with sexually transmitted diseases such as AIDS and genital warts. 
  
  
  The danger of asymptomatic infections is that the infected individual may not experience any symptoms but might transmit the infection to other people. It is also hard for health authorities to know accurately what the incidence of infection is. Examples of asymptomatic infections during which individuals may spread the infection include, whooping cough (pertussis), chlamydia, clostridium difficile, dengue virus, Epstein-Barr virus, Group A streptococcal infection, HIV-1, Legionnaires' disease), measles, gonorrhea, meningitis,tuberculosis (TB), salmonellosis (salmonella infection), noroviruses, poliomyelitis (polio), common cold, pneumonia, and syphilis. 
  
  
  Another danger of asymptomatic (subclinical) infections is that they can cause complications which are unrelated to the infection itself. For example, untreated urinary tract infections may cause premature births. 
  
  
  Many cancers are asymptomatic during their early stages. Prostate cancer, for example, is mainly asymptomatic until it has advanced to a certain point. This is unfortunate, because early treatment is crucial for effective cancer therapy. This is why regular testing for higher risk groups for some cancers is so important.


• Symptomatic diseases/conditions - this means the disease is present and there are symptoms. Some diseases/conditions are always symptomatic, such as motion sickness - feeling nausea and being unwell when travelling by car, plane or boat.


• Constitutional symptoms - also known as general symptoms. These are symptoms which are related to the effects a condition/disease has on the whole body - the systemic effects, e.g. fever, weight loss, or altered appetite. A constitutional symptom relates to the whole body.


• Presenting symptom - also known as chief complaint or presenting complaint, is a term used by doctors which refers to the initial symptom(s) that brought the patient to see the doctor. A patient who is eventually diagnosed with prostate cancer may have first come to the doctor because he had to keep getting up during the night to urinate - the presenting symptom was frequent urination, or getting up at night to urinate.


• Cardinal symptom - this is a term used by medical professionals referring to the symptom that ultimately leads to a diagnosis.

Medical signs

A medical sign is an objective feature indicating some medical fact or characteristic that is detected by a physician, nurse or medical/laboratory device during a physical examination of a patient. 

Sometimes a sign may not be noticed by the patient, and have no meaning at all for the patient, but is meaningful for the physician. Signs can help the doctor in his/her diagnosis. Examples of signs include:

• High blood pressure - this may indicate a cardiovascular problem, a reaction to medication, an allergy, as well as many other possible conditions or diseases.


• Clubbing of the fingers - this may point to lung disease, as well as other diseases.

Lester S. King wrote that a sign must have a thing signified. He said a sign must convey information and can only be a sign if it has meaning. He added that "a sign ceases to be a sign when you cannot read it".

There are different types of signs

• Prognostic signs - these are signs that point to the future. Rather than indicating the name of the disease they predict the outcome for the patient - what is likely going to happen to him/her. Hippocrates, a physician in ancient Greece, described the following facial signs as a predictor of impending death (re-written in modern lay terms): 
  
  
  Pinched nose, sunken eyes, hollow temples, cold and retracted ears, the skin of the forehead tense and dry, the lips pendent (hanging), relaxed and cold, and a discolored (livid) complexion. (Known as the Hippocratic face. Latin: facies Hippocratica).


• Anamnestic signs - these signs always point to the past. Some skin scars may point to severe acne in the patient's past. An anamnestic sign of polio during childhood may be observed as a limp during adulthood, or a distorted limb.


• Diagnostic signs - these signs help the doctor recognize and identify what the patient has; the name of the condition or disease. For example, elevated levels of PSA (prostate-specific antigen) in a male patient's blood may be a sign of prostate cancer or a prostate problem.


• Pathognominic signs - this is step further from a diagnostic sign - it means "a sure sign". A pathognominic sign is one that leaves the physician certain, sure, without a doubt, that a particular disease is present. For example, thickened lion-like facial skin (leonine facies) is a sure sign (pathognominic sign) of leprosy. A pseudomembrane on the tonsils, pharynx and nasal cavity is a pathognominic sign of diphtheria. A prostate biopsy is when a sample of the prostate is taken and observed under the microscope - if cancerous cells are detected there is no doubt the patient has prostate cancer.