hyponatremia => central pontine myelinosis
endocarditis
substantita nigra
Parkinson's due to dopamine deficiency
basal ganglia
caudate
putamen
globus pallidus
in Huntington's disease(HD), caudate nucleus is damaged
--------------------------------------------------------------------------
Collagen is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about 25% of the total protein content. It is one of the long, fibrous structural proteins whose functions are quite different from those of globular proteins such as enzymes., tough bundles of collagen called collagen fibers are a major component of the extracellular matrix that supports most tissues and gives cells structure from the outside, but collagen is also found inside certain cells. Collagen has great tensile strength, and is the main component of cartilage, ligaments, tendons, bone and teeth. Along with soft keratin, it is responsible for skin strength and elasticity, and its degradation leads to wrinkles that accompany aging. It strengthens blood vessels and plays a role in tissue development. It is present in the cornea and lens of the eye in crystalline form. It is also used in cosmetic surgery and burns surgery.
A keloid is a special type of scar which results in an overgrowth of tissue at the site of a healed skin injury. Keloids are firm, rubbery lesions or shiny, fibrous nodules and can vary from pink to flesh-colored or red to dark brown in color. Keloid isn't lethal but a keloid scar exposed to the sun can increase the chance of getting skin cancer. A keloid is benign, noncontagious and usually painless (although sometimes can be accompanied by a sharp pain), but they can be a cosmetic problem. Keloids should not be confused with Hypertrophic scars, which are raised scars that do not grow beyond the boundaries of the original wound and may reduce over time.
Occurrence
Keloids expand in clawlike growths over normal skin. They have the capability to hurt with a needle-like pain or to itch without warning. Although these are temporary sensations, they can be vexing for the subject.
If the keloid becomes infected, it may ulcerate. The only treatment is to remove the scar completely. However, the probability that the resulting surgery scar will also become a keloid is high.
Keloids form within scar tissue. Collagen, used in wound repair, tends to overgrow in this area, sometimes producing a lump many times larger than that of the original scar. Although they usually occur at the site of an injury, keloids can also arise spontaneously. They can occur at the site of a piercing and have been found on the earlobes, eyebrows, chest and other sites of piercings. They can occur as a result of severe acne or chickenpox scarring, infection at a wound site, repeated trauma to an area, excessive skin tension during wound closure or a foreign body in a wound. Keloids can sometimes be sensitive to chlorine (consult your dermotalogist if faced with this problem).
They affect both sexes equally although the incidence in young female patients has been reported to be higher than in young males, probably reflecting the greater frequency of earlobe piercing among women. There is a fifteen times higher frequency of occurrence in highly pigmented people.It is speculated that people who possess any degree of African descent, regardless of skin color, may be especially susceptible to keloid occurrences.
--------------------------------------------------------------------------The electrolyte disturbance hyponatremia or hyponatraemia exists in humans when the sodium (Natrium in Latin) level in the plasma falls below 135 mmol/l. At lower levels water intoxication may result, an urgently dangerous condition. Hyponatremia is an abnormality that can occur in isolation or, as most often is the case, as a complication of other medical illnesses. In the case of other mammals, particularly agricultural animals, different indications are relevant. The following refers to humans; an introduction to sodium deficiency in cattle is appended.
Symptoms
Most patients with chronic water intoxication are asymptomatic, but may have symptoms related to the underlying cause.
Severe hyponatremia may cause osmotic shift of water from the plasma into the brain cells. Typical symptoms include nausea, vomiting, headache and malaise. As the hyponatremia worsens, confusion, diminished reflexes, convulsions, stupor or coma may occur. Since nausea is, itself, a stimulus for the release of ADH (the water retaining hormone), the potential for a vicious circle of hyponatremia and its symptoms exists.
[edit] Causes
An abnormally low plasma sodium level is best considered in conjunction with the person's plasma osmolarity and extracellular fluid volume status.
Most cases of hyponatremia are associated with reduced plasma osmolarity. In fact, the vast majority of adult cases are due to increased vasopressin i.e. anti-diuretic hormone (ADH). Vasopressin (ADH) is a hormone that causes retention of water, but not salt. Hence, the patient with hyponatremia can be viewed as the patient with increased ADH activity. It is the physician's task to identify the cause of the increased ADH activity in each case.
In patients who are volume depleted (i.e. their blood volume is too low), ADH secretion is increased (since volume depletion is a potent stimulus for ADH secretion). As a result, the kidneys of such patients hold on to water and produce a very concentrated urine. Treatment is simple (if not without risk) - simply restore the patient's blood volume thereby turning off the stimulus for ongoing ADH release and water retention.
Some patients with hyponatremia have normal blood volume. In those patients, the increased ADH activity and subsequent water retention may be due to "physiologic" causes of ADH release such as pain or nausea. Alternatively, they may have the Syndrome of Inappropriate ADH (SIADH). SIADH represents the sustained, non-physiologic release of ADH and most often occurs as a side effect of certain medicines, lung problems such as pneumonia or abscess, brain disease, or certain cancers (most often small cell lung carcinoma).
A third group of patients with hyponatremia are often said to be "hypervolemic". They are identified by the presence of peripheral edema. In fact, the term "hypervolemic" is misleading since their blood volume is actually low. The edema underscores the fact that fluid has left the circulation (i.e. the edema represents fluid that has exited the circulation and settled in dependent areas). Since such patients do, in fact, have reduced blood volume, and since reduced blood volume is a potent stimulus for ADH release, it is easy to see why they have retained water and become hyponatremic. Treatment of these patients involves treating the underlying disease that caused the fluid to leak out of the circulation in the first place. In many cases, this is easier said than done when one recognizes that the responsible underlying conditions are diseases such as liver cirrhosis or heart failure - conditions that are notoriously difficult to manage, let alone cure.
It is worth considering separately, the hyponatremia that occurs in the setting of diuretic use. Patients taking diuretic medications such as furosemide (Lasix), hydrochlorothiazide, chlorthalidone, etc., become volume depleted. That is to say that their diuretic medicine, by design, has caused their kidneys to produce more urine than they would otherwise make. This extra urine represents blood volume that is no longer there, that has been lost from the body. As a result, their blood volume is reduced. As mentioned above, lack of adequate blood volume is a potent stimulus for ADH secretion and thence water retention.
A recent surge in death from hyponatremia has been attributed to overintake of water while under the influence of MDMA. Also, Almond et al.[1] found hyponatremia in as many as 13% of runners in a recent Boston Marathon, with life-threatening hyponatremia (serum Na below 120 mmol/L) in 0.6%. The runners at greatest risk of serious water intoxication had moderate weight gain during the race due to excessive water consumption (see reference).
[edit] Pseudohyponatremia
A normal or high plasma osmolarity with hyponatremia is called pseudohyponatremia. Pseudohyponatremia may be caused if extraordinarily high lipid or protein levels in the plasma interfere with the sodium assay.
[edit] Hypoosmolar hyponatremia
When the plasma osmolarity is low, the extracellular fluid volume status may be in one of three states:
- Low volume. Loss of water is accompanied by loss of sodium.
- Excessive sweating
- Burns
- Vomiting
- Diarrhea
- Urinary loss
- Diuretic drugs (especially thiazides)
- Addison's disease
- Cerebral salt-wasting syndrome
- Other salt-wasting kidney diseases
Treat underlying cause and give IV isotonic saline. It is important to note that sudden restoration of blood volume to normal will turn off the stimulus for continued ADH secretion. Hence, a prompt water diuresis will occur. This can cause a sudden and dramatic increase the serum sodium concentration and place the patient at risk for so-called "central pontine myelinolysis" (CPM). That disorder is characterized by major neurologic damage, often of a permanent nature.
Because of the risk of CPM, patients with low volume hyponatremia may eventually require water infusion as well as volume replacement. Doing so lessens the chance of a too rapid increase of the serum sodium level as blood volume rises and ADH levels fall.
- Normal volume.
- SIADH (syndrome of inappropriate antidiuretic hormone)
- Some cases of psychogenic polydipsia
For SIADH, you can give demeclocycline, an ADH antagonist.
- High volume. There is retention of water.
Placing the patient on water restriction can help.
Severe hyponatremia may result from a few hours of heavy exercise in high temperature conditions, such as hiking in desert areas, or from endurance athletic events when electrolytes are not supplied. (Such an incident notably happened to long-distance athlete Craig Barrett in 1998).
--------------------------------------------------------------------------Central pontine myelinosis is a demyelinating lesion in the pons. It is a complication of treatment of patients with profound, life threatening hyponatraemia. It occurs as a consequence of a rapid rise in serum tonicity following treatment in individuals with chronic severe hyponatraemia who have made intracellular adaptations to the prevailing hypotonicity.
--------------------------------------------------------------------------
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. The most common structures involved are the heart valves.
Endocarditis can be classified by etiology as either infective or non-infective, depending on whether a microorganism is the source of the problem.
Infective endocarditis
As the valves of the heart do not actually receive any blood supply of their own, which may be surprising given their location, defense mechanisms (such as white blood cells) cannot enter. So if an organism (such as bacteria) establish hold on the valves, the body cannot get rid of them.
Normally, blood flows smoothly through these valves. If they have been damaged (for instance in rheumatic fever) bacteria have a chance to take hold.
[edit] Classification
Traditionally, infective endocarditis has been clinically divided into acute and subacute (between acute and chronic) endocarditis. This classifies both the tempo of progression and severity of disease. Thus subacute bacterial endocarditis (SBE) is often due to streptococci of low virulence and mild to moderate illness which progresses slowly over weeks and months, while acute bacterial endocarditis (ABE) is a fulminant illness over days to weeks, and is more likely due to Staphylococcus aureus which has much greater virulence, or disease-producing capacity.
This terminology is now discouraged. The terms short incubation (meaning less than about six weeks), and long incubation (greater than about six weeks) are preferred despite the lack of advantage in meaning.
Infective endocarditis may also be classified as culture-positive or culture-negative. Culture-negative endocarditis is due to micro-organisms that require a longer period of time to be identified in the laboratory. Such organisms are said to be fastidious because they have demanding growth requirements. Some pathogens responsible for culture-negative endocarditis include Aspergillus species, Brucella species, Coxiella burnetii, Chlamydia species, and HACEK bacteria.
Finally, the distinction between native-valve endocarditis and prosthetic-valve endocarditis is clinically important.
The Russian classification includes "endocarditis in narcotic abusers" in addition to above given classification, as this disease is very common in narcotic drug users who inject with non-sterile injections/syringes.
[edit] Etiology and pathogenesis
As previously mentioned, altered blood flow around the valves is a risk factor in obtaining endocarditis. The valves may be damaged congenitally, from surgery, by auto-immune mechanisms, or simply as a consequence of old age. The damaged part of a heart valve becomes covered with a blood clot, a condition known as non-bacterial thrombotic endocarditis (NBTE).
In a healthy individual, a bacteraemia (where bacteria get into the blood stream through a minor cut or wound) would normally be cleared quickly with no adverse consequences. If a heart valve is damaged and covered with a piece of a blood clot, the valve provides a place for the bacteria to attach themselves and an infection can be established.
The bacteraemia is often caused by minor dental procedures, such as a tooth removal. It is important that a dentist is told of any heart problems before commencing.
Another group of causes result from a high number of bacteria getting into the bloodstream. Colorectal cancer, serious urinary tract infections, and IV drug use can all introduce large numbers of bacteria. With a large number of bacteria, even a normal heart valve may be infected. A more virulent organism (such as Staphylococcus aureus) is usually responsible for infecting a normal valve.
Intravenous drug users tend to get their right heart valves infected because the veins that are injected enter the right side of the heart. The injured valve is most commonly affected when there is a pre-existing disease. (In rheumatic heart disease this is the aortic and the mitral valves, on the left side of the heart.)
[edit] Clinical and pathological features
- Fever (often spiking)
- Continuous presence of micro-organisms in the bloodstream determined by serial collection of blood cultures
- Vegetations on valves on echocardiography
- Septic emboli, causing circulatory problems (stroke, gangrene of fingers)
- Chronic renal failure
- Osler's nodes (painful subcutaneous lesions in the distal fingers)
- Janeway lesions (painless hemorrhagic cutaneous lesions on the palms and soles)
- Roth spots on the retina
- Conjunctival petechiae
- A new or changing heart murmur, particularly murmurs suggestive of valvular incompetence
- Splinter haemorrhages
The substantia nigra, (Latin for "black substance", Soemering) or locus niger is a heterogeneous portion of the midbrain, separating the pes (foot) from the tegmentum (covering), and a major element of the basal ganglia system. It consists of two strongly contrasted ensembles, the pars compacta and adjacent dopaminergic groups, and another ensemble made up of the pars reticulata and the pars lateralis. The last two, along with the pallidal nuclei, are elements of the core of the basal ganglia. Although intricate and interconnected, the two ensembles must imperatively be clearly distinguished.
 | |
| Section through superior colliculus showing path of oculomotor nerve. | |
 | |
| Coronal slices of human brain showing the basal ganglia, globus pallidus: external segment (GPe), subthalamic nucleus (STN), globus pallidus: internal segment (GPi), and substantia nigra (SN). |
Function
The function of the dopamine neurons in the substantia nigra pars compacta is complex. Contrary to what was thought initially it is not directly linked to movements. "Dopamine neurons are activated by novel, unexpected stimuli, by primary rewards in the absence of predictive stimuli and during learning".[6] Dopamine neurons are thought to be involved in learning to predict which behaviours will lead to a reward (for example food or sex). In particular, it is suggested that dopamine neurons fire when a reward is greater than that previously expected; a key component of many reinforcement learning models. This signal can then be used to update the expected value of that action. Many drugs of abuse, such as cocaine, mimic this reward response—providing an explanation for their addictive nature.
[edit] Pathology
Degeneration of pigmented neurons in this region is the principal pathology that underlies Parkinson's disease. In a few people the cause of Parkison's disease is genetic, but in most cases the reason for the death of these dopamine neurons is unknown. Parkinsonism can also be produced by viral infections such as encephalitis or a number of toxins, such as MPTP, an industrial toxin which can be mistakenly produced during synthesis of the meperidine analog MPPP). Many such toxins appear to work by producing reactive oxygen species. Binding to neuromelanin by means of charge transfer complexes may concentrate radical-generating toxins in the substantia nigra. Pathological changes to the dopaminergic neurons of the pars compacta are also thought to be involved in schizophrenia (see the dopamine hypothesis of schizophrenia) and psychomotor retardation sometimes seen in clinical depression.
--------------------------------------------------------------------------The basal ganglia are a group of nuclei in the brain interconnected with the cerebral cortex, thalamus and brainstem. Mammalian basal ganglia are associated with a variety of functions: motor control, cognition, emotions and learning.
Basal Ganglia
Deep in the gray matter of the brain are the basal ganglia. The basal ganglia, along with the cerebral cortex and diencephalon, compose the region of the brain called the forebrain. The basal ganglia connect to the cortex and thalamus and organize muscle-driven “motor” movements of the body. They are the parts of the brain most affected by HD and many of the symptoms of HD result from damage to them.
