Treatment and Therapy of Parkinson's Disease

Governance of Parkinson's disease
Parkinson's disease is a chronic disease that requires treatment in a holistic manner covering various fields. At this time there is no treatment to cure this disease, but treatment and surgery can overcome the symptoms that arise. Individualized treatment of Parkinson's disease and symptomatic, medication is usually given for the treatment of disease or to replace or mimic dopamine which will improve tremor, rigidity, and slowness.

 Treatment in patients with Parkinson's disease aims to slow and inhibit the progression of the disease. This treatment can be performed by administering medication and physical therapy such as walking therapy, sound therapy / speech and the patient is expected to keep doing daily activities.

1. Therapeutic Medicines
          Some medicines given to people with Parkinson's disease:
a. Anticholinergic Benzotropine (Cogentin), trihexyphenidyl (Artane).
Useful for controlling symptoms of Parkinson's disease. To smooth the movement.
b. Carbidopa / levodopa
Levodopa is the main treatment for Parkinson's disease.
In the brain levodopa is converted to dopamine. L-dopa is converted to dopamine in dopaminergic neurons by L-aromatic amino acid decarboxylase (dopadekarboksilase). However, only 1-5% of L-Dopa into dopaminergic neurons, the remainder is metabolized in any place, resulting in extensive side effects. Because the feedback mechanism, there would be inhibition of endogenous formation of L-Dopa. Carbidopa and benserazide are dopa-decarboxylase inhibitor, helps prevent the metabolism of L-Dopa before it reaches the dopaminergic neurons. Levodopa to reduce tremor, stiffness of muscles and improve movement. Patients with mild Parkinson's disease can return to normal activity medicine is administered with carbidopa to enhance their effectiveness and reduce side effects. Since its introduction late 1960s, levodopa is considered one of the most widely used medicines to date. Levodopa is considered the backbone of the treatment of Parkinson's disease. Thanks to levodopa, a Parkinson's patient can return to normal activities. Many physicians delay treatment with levodopa symptomatic until it is needed. If the patient's symptoms are mild and do not interfere, with levodopa therapy should not be done. It is given that the effectiveness of levodopa is associated with long time usage. Levodopa across the blood-brain-barrier and enters the central nervous system and enzymatic changes into dopamine. Inhibit the activity of dopamine neurons in the basal ganglia. Side effects of levodopa can be:
1) Nausea, vomiting, abdominal distress
2) Postural hypotension
3) Once in a while will get cardiac arrhythmias, especially in patients who are elderly. This effect is caused by beta-adrenergic effects of dopamine on the cardiac conduction system. This bias treated with beta blockers such as propranolol.
4) dyskinesia. Dyskinesias are most commonly found involving the limbs, neck or face. Dyskinesia often occur in patients who respond well to levodopa therapy. Some patients showing symptoms of an on-off which is very annoying because people do not know when a sudden movement to a standstill, frozen, hard. So the movement for a moment interrupted.
5) laboratory abnormalities. Granulocytopenia, abnormal liver function and increased blood urea is a rare complication of levodopa therapy. Side effects of levodopa on the use of many years is dyskinesia is not controlled motor movements in the limbs and body. Response of patients who take levodopa also progressively reduced. To eliminate the side effects of levodopa, the schedule of regulated and increased the dose, also by providing additional medicines that have different mechanisms such as dopamine agonists, COMT inhibitors or MAO-Binhibitor. If the combination of these medicines also not helping here considered the treatment of surgery.
Surgery is not a standard treatment for Parkinson's disease is also not as a replacement therapy to medication taken.
c. COMT inhibitors Entacapone (Comtan), tolcapone (Tasmar).
To control the motor fluctuations in patients taking the medicine levodopa. Tolcapone is a COMT enzyme inhibitor, prolonging the effects of L-Dopa. But because of excessive side effects such as liver toxic, it is rarely used. The same type, entacapone, does not cause decreased liver function.
d. Dopamine agonists.
Dopamine agonists such as bromocriptine (Parlodel), pergolid (Permax), pramipexol (Mirapex), ropinirol, cabergoline, and lisurid apomorfin considered effective enough to treat symptoms of Parkinson's. This medicine works by stimulating dopamine receptors, but this medicine also causes a progressive decrease in dopamine receptors which in turn will lead to increased symptoms of Parkinson's.
These medicines can be useful for treating patients who have experienced attacks and dyskinesia fluctuate as a result of high doses of levodopa. Apomorfin can be injected subcutaneously. Low dose is given every day can reduce the fluctuations in motor symptoms.
e. MAO-B inhibitors selegiline (Eldepryl), Rasagaline (Azilect).
MAO inhibitors are thought to be useful in Parkinson's disease because dopamine neuotransmisi can be improved by preventing damaging. Selegiline can also slow the worsening of Parkinson's syndrome, levodopa therapy thus may be deferred for some time. Useful for controlling symptoms of Parkinson's disease. That is to smooth the movement.
 Selegilin and rasagilin menginhibisi reduce symptoms with a monoamine oxidase B (MAO-B), thereby inhibiting dopamine released by the destruction of dopaminergic neurons. Metabolites contain L-L-amphetaminand methamphetamines. The side effects are insomnia. Combination with L-dopa can increase mortality, which until now has not explained clearly biased. Another effect of this combination is stomatitis.
 f.Amantadine (Symmetrel)
Useful for the treatment of akinesia, dyskinesia, rigidity, tremor.
g. Inhibitor of dopa and levodopa decarboxylation
To prevent the levodopa is changed into dopamine outside the brain, levodopa combined with dopa decarboxylase enzyme inhibitor. For this purpose can be used karbidopa or benserazide (madopar). Dopamine and karbidopa can not penetrate the blood-brain-barrier. Thus, more levodopa that can penetrate the blood-brain-barrier, and then converted into dopamine in the brain. The side effects generally similar to side effects caused by levodopa.

2.Deep Brain Stimulation (DBS)
           In 1987, the treatment was introduced by inserting an electrode that emits a high frequency electrical impulses continuously into the brain. This therapy called deep brain stimulation (DBS). DBS is a minimally invasive disurgerykan actions through guidance computer with minimal damage to graft a medical device called a neurostimulator to generate electrical stimulation to targeted areas in the brain involved in controlling movement.
        This therapy provides a low electrical stimulation in the thalamus. This stimulation is driven by implantable medical devices that suppress tremor. This therapy offers the possibility of an emphasis on all the symptoms and side effects, doctors target areas subthalamic nucleus (STN) and globus pallidus (GP) as the electrical stimulation. Choice of target areas, depending on clinical assessment. DBS is now offering new hope for a better life with the latest surgical advances to patients with Parkinson's disease. DBS is recommended for patients with advanced Parkinson's disease (stage 3 or 4) that deliver the response to levodopa. Control of parkinsonism with DBS therapy showed 90% success. Based on research, as many as 8 or 9 out of 10 people using DBS therapy to achieve an increase in the ability to perform normal daily activities.
In addition to medicine therapy is given, feeding should really be considered, because it can cause muscle stiffness sufferers have difficulty swallowing so that it can happen malnutrition (malnutrition) in patients. Fiber foods will help reduce digestive disorders caused by lack of activity, fluids and some medications.

3. Physical Therapy
             The vast majority of people with Parkinson's will feel good effects of physical therapy. Patients will be motivated so that this therapy can be done at home, with examples given instructions or training in physical therapy clinics. Program of physical therapy in Parkinson's disease is a long-term program and the type of therapy tailored to the development or worsening of disease, such as changes in rigidity, tremor and other obstacles. Regular physical exercise, including yoga, tai chi, or dance can be beneficial in maintaining and improving mobility, flexibility, balance, and range of motion. Basic training is always recommended, such as carrying bags, wearing a tie, chewing hard and move the food in the mouth.

4. Sound therapy
        The greatest care for the sound mess caused by Parkinson's disease is the Lee Silverman Voice Treatment (LSVT). LSVT focus to increase the volume. One study found that electronic devices that provide sensory feedback listener or frequency auditory feedback (FAF) to improve the clarity of sound.

5. gene Therapy
          At this present time, investigations have been carried out up to the stage of gene therapy that involves using a harmless virus that is sent to the brain called the subthalamic nucleus (STN). Genes used for mempoduksi ordered an enzyme called glutamic acid decarboxylase (GAD), which accelerates the production of neurotransmitters (GABA). GABA acts as a direct inhibitor of cell that is too active in other STN.Terapi being developed is GDNF. Infusion of GDNF (glial-derived neurotrophic factor) in the basal ganglia using kathether implants through surgery. With a variety of biochemical reactions, GDNF stimulates the formation of L-dopa.

6. nerve grafting
           Stem cell grafts genetically to produce dopamine or stem cells turn into dopamine producing cells have begun to do. The first experiment was conducted randomized double-blind sham-placebo with dopaminergic transplants that failed to demonstrate improved quality of life for patients under age.

7. Surgery
           Surgery for Parkinson's sufferers rarely done since the discovery of levodopa. Surgery performed on patients with Parkinson's who have severe where medicine therapy is inadequate. Surgery performed thalamik thalatotomi and stimulation.

8. neuroprotective therapy
           Neuroprotective therapy may protect neurons from cell death induced disease progression. Which is being developed as a neuroprotective agent is apoptotic medicines (CEP 1347 and CTCT346), lazaroids, bioenergetics, anti-glutamatergic agents, and dopamine receptors. As for which is often used in clinics are monoamine oxidase inhibitors (selegiline and rasagiline), dopamine agonists, and complek I mitochondrial fortifier coenzyme Q10.

9.Nutrisi
         Some nutrients have been tested in a clinical study clinic to then widely used to treat Parkinson's patients. For example, L-tyrosine, which is an L-dopa perkusor mennjukkan effectiveness of about 70% dalammengurangi symptoms of this disease. Iron (Fe), an essential cofactor in the biosynthesis of L-dopa reduced 10% - 60% of symptoms in a study of 110 patients.
 THFA, NADH, and piridoxin perkusor which is a coenzyme and coenzyme in the biosynthesis of dopamine showed a lower efficacy than L-tyrosine and iron. Vitamin C and vitamin E high doses can theoretically reduce cell damage that occurs in Parkinson's patients. Both vitamins are required in the enzyme activity of superoxide dismutase and catalase to neutralize superoxide anions that can damage cells. Not long ago, Coenzyme Q10 has also been used in a manner similar to working with vitamin A and E. MitoQ is a new synthetic substance that has a similar structure and function of coenzyme Q10.

10. qigong
         There are two studies of qigong in Parkinson's disease. In experiments in Bonn, a study of 56 patients found an increase in non-motor symptoms and motor skills among patients who did qigong structured 1 time a week for 8 weeks.
  However, both studies showed no effective qigong in Parkinson's disease. In the study, researchers used a randomized cross-over trial comparing aerobic exercise with qigong in advanced stages of Parkinson's disease. two groups of PD patients were assessed, then do 20 sessions both aeronik and qigong exercises, graded again, then after a lapse of 2 months, exchanged with 20 other sessions, and then assessed again. Authors obtain an increase in motor skills and function cardiopulmonal after following aerobic exercise, but do not have the benefit after attending qigong.

11.Botox
         More recently, Botox injections are being investigated as one of the treatment of non-FDA in the future

Clinical Symptoms of Parkinson

Clinical symptoms

Although symptoms are presented below not only belong to people with Parkinson's disease, Parkinson's sufferers usually experience it.

1. Motor symptoms

a. tremor

Symptoms of Parkinson's disease often escape from the ordinary sight, and is regarded as an ordinary thing occurs in older people. One hallmark of Parkinson's disease is a hand tremors (shaking) if it is resting. However, if the person is asked to do something, the vibration was not seen again. That's called a resting tremor, which disappeared when sleep. Tremor also found on the fingers, tremors metacarpofalangis rough on the joints, sometimes tremors such as counting coins or scavenged (pill rolling). On the hand joints flexion-extension or pronation-supination in the foot flexion-extension, head flexion-extension or shook his head, mouth open to close, tongue lolling out-interested. This tremor disappeared breaks and intense emotions aroused time (resting / alternating tremor). Tremor not only occurs on the hands or feet, but can also occur on the eyelids and eyeballs, lips, tongue and fingers (such as people counting money). All this occurred during recess / unknowingly. In fact, the patient's head can be swayed if not doing the activity (unconsciously). That is, if realized, could stop tremors. At first tremor occurred only on one side, but the more severe the disease, tremors can occur on both sides.

b. Rigidity / stiffness

Another sign is the stiffness (rigidity). If the tremors fist is driven (by others) is slowly upwards resting on the wrist, there was such resistance through a toothed wheel so that the motion be broken / dotted. In addition to the hands and feet, stiffness it can also occur in the neck. Due to the stiffness, the movements become smooth again like break-dancing. Rigid motion makes the patient will walk with a hunched posture. To maintain its center of gravity to keep from falling, the pace is fast but shallow. Hipertoni presence on extensor and flexor muscles hipertoni whole movement, this is due to increased activity by alpha motorneuron, the phenomenon of toothed wheels (cogwheel phenomenon).

c.Akinesia / Bradykinesia

Both of the above symptoms are usually still less attention to signs of akinesia / bradykinesia appeared. Movement of people with a slow-paced. In the daily work can be seen in the Writings / signatures Become Smaller, harder wearing clothes, step into a short and dragged. Awareness still good, so people can Become depressed (stress) due to the disease. The face became expressionless. Wink and glance of the eye is reduced, a small voice, swallowing reflex is reduced, so often out of water liur.Gerakan volunteer to be slow so that the reduced associative movement, for example, difficult to wake up from a chair, difficulty starting to walk, slow retrieve an object, when speaking of motion of the tongue and lips become slow. Bradykinesia result in reduced expression of the face and expression and decreased spontaneous movement, such as face masks, eye blink is reduced, the reduced motion so that the saliva swallowed like out of the mouth.

d. Suddenly Stopped or Hesitate to Stepping

Another symptom is freezing, which stops in place when going to start moving, walking, or a U-turn; and start hesitation, that is hesitant to start moving. Can also occur frequent urination, and constipation. Patients with a slow thinking and depression.

e. Micrografia

Handwriting gradually became small and close together, in some cases this is an early symptom.

f. Step and gait (stance Parkinson)

Walking with small steps and getting a quick shift (marchea petit pas), locally advanced head flexed to chest, shoulders bent forward, her back arched when walking.

g. talk monotonous

This is due to bradykinesia and rigidity of respiratory muscles, vocal cords, laryngeal muscles, so when speaking or utter words that monotonous with subtle volume (whisper voice) is slow.

h. Dimentia

A change in mental status during the course of their illness with cognitive deficits.

i. behavioral disorders

Gradually become dependent (dependent on others), easily frightened, less assertive attitude, depression. This way of thinking and slow response to the question (bradifrenia) usually still be able to give correct answers, if given enough time.

j. Other symptoms

Both eyes blinking fiercely on palpation above the bridge of his nose (a sign of positive Myerson)

2. Non-motor symptoms

excessive Sweat

a. -Autonomous dysfunction, excessive saliva, sphincter disturbances and orthostatic hypotension. Especially incontinence, oily skin and seborrheic dermatitis-Spending a lot of urine, Altered sexual function disorders, characterized by the weakening of sexual desire, behavior, orgasm.

b. Mood disorders, Patients Often experience depression. Cognitive disturbances, slow response to stimuli

c. Sleep disorders, Patients have difficulty sleeping (insomnia)

Pathophysiology of Parkinson's Disease

pathophysiology

Two hypotheses are referred to as the mechanisms of neuronal degeneration in Parkinson's disease are: the free radical hypothesis and the hypothesis neurotoxins.

1. Free radical hypothesis. Alleged that the enzymatic oxidation of dopamine can damage neurons nigrotriatal, because this process produces hidrogren peroxide and other oxygen radicals. Although there is a protective mechanism to prevent damage from oxidative stress, but at the advanced age of this mechanism may fail.

2. Allegedly neurotoxin hypothesis of one or more kinds of neurotoxic substances play a role in the process of neurodegeneration in Parkinson's disease.

Current view, emphasizing the importance of the basal ganglia in neurophysiology plan required in performing the movement, and the part played by the cerebellum is to evaluate the information received as feedback on the implementation of the movement. Basal ganglia primary task is to collect the program for the movement, while the cerebellum monitor and rectification of errors that occur during movement of the program is implemented. One sign of extrapyramidal disorder is involuntary movement. Basic pathology included lesions in the basal ganglia (caudate, putamen, palidum, subtalamus nucleus) and brainstem (substantia nigra, nucleus rubra, locus ceruleus). Simply put, motor system disease or disorder can be divided as follows:

1.Piramidal; paralysis accompanied by an increased tendon reflexes and superficial reflexes are abnormal

2. Extrapyramidal: dominated by the presence of involuntary movements

3. Cerebellar: normal propioseptif ataxia or sensation often accompanied by nystagmus

4. Neuromuscular: paralysis is often accompanied by muscle atrophy and reduced tendon reflexes. Pathophysiology of depression in Parkinson's disease until now has not known for sure. But this theoretical allegedly associated with deficiency of serotonin, nor-adrenaline and  dopamine. Degenerate in Parkinson's disease neuronal cells that includes a variety of subcortical nuclei including the substantia nigra, ventral tegmental area, nucleus basalis, hypothalamus, pedunkulus Pontin, the dorsal raphe nucleus, locus cereleus, nucleuscentral pontine and autonomic ganglia. Severity of damage to this structure varies. At autopsy found loss of substantia nigra cells and cereleus locus varies between 50% - 85%, whereas in the dorsal raphe nucleus ranged between 0% - 45%, and the nucleus of the basal ganglia between 32% - 87%. Subcortical nuclei are a major source of neurotransmitters.. Involvement of this structure result in reduced dopamine in the caudate nucleus (reduced to 75%), putamen (reduced to 90%), hypothalamus (reduced to 90%). Norepinephrine was reduced 43% in the locus sereleus, 52% in the substantia nigra, 68% in the posterior hypothalamus. Serotonin is reduced 40% in the caudate nucleus and hippocampus, 40% in the frontal lobes and 30% in the temporal lobes, and 50% in the basal ganglia. There was also a reduction in specific nuropeptid such as Met-enkephalin, leu-enkephalin, substance P and bombesin. Changes lead to changes in neurotransmitters and neuropeptid neurofisiologic associated with changes in the atmosphere of feeling. Transmitter systems involved in this process mediates reward, motivation mechanisms, and response to stress. Dopamine system plays a role in the process of reward and reinforcement.

There was a doctor named Febiger, he put forward the hypothesis that abnormalities in neurotransmitter systems in Parkinson's disease will reduce the effectiveness of the mechanism of reward and lead to anhedonia, loss of motivation and apathy. Meanwhile, another doctor called, he emphasized the importance of the role of forebrain dopamine systems in the behavioral functions of hope and anticipation. This system plays a role in motivation and encouragement to do, so this dysfunction will lead to excessive dependence on the environment by reducing the desire to do the activity, decreased sense of ability to control themselves. Decreased ability to control feelings can manifest themselves as feeling useless and lost self-esteem. Dependence on the environment and the inability to perform the activity will lead to feelings of helplessness and despair. Serotonergic system plays a role in the regulation of mood feelings, waking regulation, aggression and sexual activity. Dysfunction of this system will cause disruption in sleep patterns, loss of appetite, decreased libido, and decreased ability to concentrate. Merging dysfunction all the elements mentioned above is the picture of classic depression syndrome.

Causes of Parkinson's disease

Everybody know who Cassius Clay aka Mohammed Ali is. Yes he was heavyweight boxer champion. In his older age, he get Parkinson's disease. what is parkinson's disease and what are causes of this disease? Modern Shaman from Medical and Health Information will explain.










DEFINITION

Parkinson's disease (paralysis agitans) or Parkinson's syndrome (Parkinsonism) is a disease / syndrome, due to disturbances in the basal ganglia caused by a decrease or absence of delivery of dopamine from the substantia nigra to the globus palidus / neostriatum (striatal dopamine deficiency).

Parkinson's disease is a progressive neurodegenerative disease that is closely related to age. This disease has a characteristic degeneration of dopaminergic neurons of substantia nigra pars compact, coupled with the inclusion intraplasma consisting of a protein called Lewy Bodies. In neurodegenerative parkinsonism also occurs in other brain regions including the locus ceruleus, raphe nuclei, nucleus basalis Meynert, hypothalamus, cortex cerebri, the motor nuclei of cranial nerves, the autonomic nervous system.

ETIOLOGY

Primary etiology of Parkinson's is unknown, There are some allegations, among them are: infection by a virus that non-conventional (yet unknown), an abnormal reaction to a virus that is common, exposure to toxic substances are not known, the occurrence of a premature or accelerated aging.

Parkinson's is caused by damage to brain cells, precisely in the substance nigre. A group of cells that regulate the movements that are not desired (involuntary). As a result, patients are not able to set up / resist movements that are not aware of. The mechanism of how the damage was not clear. Some of the things that allegedly could cause Parkinson's is as follows:

1. age:

The incidence increased from 10 per 10,000 population at the age of 50 to 200dari 10,000 population at the age of 80 years. It is associated with microglial reaction that affects neuronal damage, particularly in the substantia nigra, in Parkinson's disease.

2. geography:

Risk factors that affect this geographic difference in the numbers include the presence of genetic differences, immunity to disease and exposure to environmental factors.

3. Period:
 Fluctuations in the number of people with Parkinson's disease may be associated with each period of episodic environmental exposure, such as the infection process, industrialization or lifestyle. Data from the Mayo Clinic in Minessota, no major changes in morbidity between tahun1935 until 1990. This may be due to environmental factors are relatively less effect on the incidence of Parkinson's disease.

4. genetic:

Studies suggest a genetic mutation that contributes to Parkinson's disease. Namely mutations in the gene asinuklein the long arm of chromosome 4 (PARK1) in patients with autosomal dominant Parkinsonism. In patients with autosome recessive parkinsonism, found deletions and point mutations in the parkinson gene (PARK2) on chromosome 6. It also found the existence of mitochondrial dysfunction. A history of Parkinson's disease in a family increases the risk factor of Parkinson's disease by 8.8 times in less than 70 years of age and 2.8 times at more than 70 years of age. Although very rare, if it is caused by heredity, symptoms of parkinsonism appear at a relatively young age. Cases of genetics in the USA very little, undiscovered genetic cases were examined in 100 patients. In Europe too. Research in Germany found zero results in 70patients. Classic example of a genetic cause has been found in families in Italy because of cases of the disease occurred at the age of 46 years.

5. Environmental factors

a. Xenobiotics is closely linked to exposure to pesticides that may cause damage to mitochondria.

b. job

More people with higher metal exposure and longer.

c. infection

Suspected influenza virus exposure intrautero predesposisi factors contributed to the damage Parkinson's disease substantia nigra. Animal studies indicate the presence of damage to the substantia nigra by Nocardiaastroides infection.

d. diet

High fat and calorie consumption increases oxidative stress, one of the mechanisms of neuronal damage in Parkinson's disease. In contrast, coffee is neuroprotective.

e. head trauma

Cranio cerebral injury could cause Parkinson's disease, although its role is still not clear

f. Stress and depression

Some research suggests depression may precede motor symptoms. Depression and stress associated with Parkinson's disease because of the stress

ENDOMETRIOSIS

Endometriosis is a condition in which endometrial tissue that is still functioning, are outside the uterine cavity. This tissue is composed of glands and stroma, myometrium contained in or outside the uterus.  When endometrial tissue present in the myometrium is called adenomyosis, and when outside of the uterus is called endometriosis. 

In endometriosis, endometrial tissue is found outside the uterine cavity and the outer myometrium. The areas most commonly affected are the pelvic organs and peritoneum, although other organs such as lungs also affected although rarely. The disease is evolving from a small lesions and a little on the pelvic organs are normal then a hard  mass infiltrates and cystic ovarian endometriosis (endometrioma). endometriosis is often accompanied by the formation of extensive fibrosis and adhesions cause pelvic anatomy.

ETIOLOGY

     The cause of endometriosis is still unknown. Several theories emerged regarding anatomical factors, immunological, hormonal, and genetic.

1. Retrograde menstruation.

According to Sampson, endometriosis occurs because of menstrual blood to flow back (regurgitation) through the tube into the pelvic cavity. Already proved that menstrual blood was found in endometrial cells are still alive. Endometrial cells surviving implantation can then be entered in the pelvis.

2. immunological factors

Specific immunological factors that play a role in the implantation of endometriosis such as VEGF (vascular endothelial growth factor), MIF (migration inhibitory factor), and inflammatory mediators (interleukins, TNF) is suspected to have increased at the site of endometriosis.

3. hormonal factors

Aromatase, an enzyme triggers the production of estrogen, has been found on the implantation of endometriosis, although not yet found data that aromatase is also found in normal endometrium. PGE2(prostaglandin E2) serves as the strongest induction of aromatase production in endometriosis implantation.

4. Celomic metaplasia 

Theory suggests the potential of cells in the ovary and peritoneum transformed into endometriosis lesions caused by hormonal stimulation of hormones and repeated exposure. Robert Meyer suggests that endometriosis occurs due to stimulation of the coelomic epithelial cells that can sustain life in the pelvic area. This stimulation causes metaplasia of epithelial cells, thus forming endometrial tissue.

5. deployment limphatic

A study of autopsy showed that endometriosis cells are found in the pelvic lymph glands in 29% of women. This may explain why endometriosis ever found in the lungs.

6. genetic factors

Women who have a family history of endometriosis, a seven-fold risk of suffering from endometriosis. Undiscovered genetic defects in endometriosis.

RISK FACTORS

Risk factors include age, increased number of peripheral body fat, and menstrual disorders (polimenore, menorrhagia, and reduced parity). Smoking habits, exercise, and oral contraceptive use may be protective. There has been no evidence to suggest that controlling the risk factors can prevent the appearance of endometriosis. Genetic factors play 6-9 times more with a history of immediate family suffer from endometriosis.

CLINICAL SYMPTOMS

The symptoms are often found in this disease are:

1) under a progressive abdominal pain and thigh that occurs close to and during menstruation (Dysmenorrhea);

2) disparenunia;

3) painful defecation time, especially at the time of defecation;

4) poly-and hypermenorrhea;

5) infertility.

       Dysmenorrhea in endometriosis menstrual pain usually is gradually increasing in intensity. Cause of dysmenorrhea is unknown, but probably something to do with vascularization and hemorrhage in the nests of endometriosis at the time before and during menstruation. Pain is not always obtained, although abnormalities in endometriosis is extensive, should be mild abnormalities can cause symptoms of severe pain. 

          Dyspareunia is a common symptom, caused by the presence of endometriosis in the pouch of Douglas. A difficult and painful defecation, especially at the time of menstruation, caused by the presence of endometriosis on the wall rectosigmoid. Sometimes it can happen stenosis of the lumen of the colon. Bladder endometriosis is rare, the symptoms are impaired micturition and hematuria at the time of menstruation. Menstrual disorders and the cycle may occur in endometriosis when abnormalities in the ovaries so extensive that impaired ovarian function. There is a real correlation between endometriosis and infertility. 30-40 percent of women with endometriosis suffer from infertility. likely to become pregnant in women with endometriosis is less than half of the ordinary woman. An important factor causing infertility in endometriosis is when the mobility impaired due to fibrosis and tubal adhesions surrounding tissue. On gynecologic examination, especially in the examination vagino-recto-abdominal, are found in mild endometriosis, solid objects of grains of rice to the grain of corn in the pouch of Douglas and the ligament of the uterus in retrofleksi sacrouterinum with and fixed. Ovary at first be felt as a small tumor, but can be enlarged to the size of a fist. Ovarian tumors are often bilateral and driven hard.

DIAGNOSIS

       The diagnosis is usually made on the basis of history and examination, confirmed by laparoscopy examination. Kuldoscopy less useful, especially if the pouch of Douglas participated in endometriosis. In endometriosis were found in locations such as the posterior vaginal fornix, perineum, laparotomy scars, and so forth, a biopsy can provide certainty about the diagnosis. Laboratory tests in endometriosis is not a typical signal, only when there is blood in the stool or urine at the time of menstruation is an indication of the existence of endometriosis in the rectosigmoid or bladder. Sigmoidoscopy and cystoscopy can show where bleeding during menstruation. Making plain by including barium in the colon can give a picture filling defect in rectosigmoid with clear boundaries and an intact mucosa. Laparoscopy is an examination that is very useful to distinguish endometriosis of abnormalities in the pelvis.

TREATMENT

         When the diagnosis of endometriosis was established, treatment options taken based on the extent of endometriosis and the patient's needs. Regimen of oral medication and surgery are determined by age, fertility status, severity of illness, previous treatment, cost, risks of treatment, and duration of treatment. The purpose of this treatment are:

  -What-treated (disease, symptoms, or both)?

- Why is administered therapy?

Provide therapeutic reasons: to restore fertility, as an alternative to surgery to relieve pain, relieve pain while waiting for surgery, prophylaxis to prevent recurrence of disease.

1.Terapi conservative

Endometriosis implantation has the same properties and reactions with the endometrium, especially in the production of estrogen. Conservative therapy aims to suppress the stimulation estrogenovarium to bypass the hypothalamic-pituitary-ovarian. Inhibition of ovulation with gonadotropins through a cycle of sex steroids can inhibit the formation of endometriosis.

a. inhibition of aromatase

Letrozole Anastrozole 1 mg or 2.5 md every day is a third generation aromatase inhibitor that inhibit the changes of androgens to estrogens by 50%. Side effects of this drug is a decrease in bone density, but this can be prevented with vitamin D and calcium intake.

b. pain control

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin released by endometriosis. NSAIDs are first-line drugs that are used when the diagnosis of endometriosis has not been enforced.

1. surgical therapy

Conservative therapy is a modality for patients who just want to relieve pain or to relieve pain in fertile conditions. For patients who are infertile, or patients who do not respond to conservative therapy, surgical therapy is an option. Surgery consists of definitive surgical therapy and conservatife.

1.Terapi definitive surgery includes total hysterectomy with bilateral salphyingo-ooferectomy. After definitive surgery performed, patients were given hormone replacement therapy

(Hormone Replacement Theraphy).

2.Terapi conservative surgery aims to restore the position of the pelvic anatomy and remove all visible endometriosis lesions.

COMPLICATIONS

           When implantation occurs in the intestine or ureter may lead to obstruction and impaired renal function. Pelvic distortion resulting in impaired fertility, oral contraceptive use resulted troboembolisme hipoetrogen effects of GnRH analogues and long-term result of osteoporosis.

PREVENTION

       Medical Shaman argues that pregnancy is the best way to prevent endometriosis. The symptoms of endometriosis are reduced or lost during and after pregnancy because endometrial regression in the nests of endometriosis. Therefore, marriage should not be delayed too long, and after marriage should be sought so that a desired children in the not too long. Such an attitude was not only a good prophylactic against endometriosis, but avoid the occurrence of infertility after endometriosis arise. Also do not perform inspections or conduct rough scrapings during menstruation, because it can cause the flow of menstrual blood from the uterus into the tube and into the pelvic cavity.

Chronic Kidney Disease (CKD) Evaluation and Management

EVALUATION and MANAGEMENT
What should we do if we have patient with Chronic Kidney Disease? Today, Mbah Dukun Bagong, modern shaman from medical and health information explains how to treat and give therapy for patient with chronic Kidney Disease (CKD). If someone has been established, there is an increased risk for Chronic Kidney Disease (CKD), but not yet exposed to CKD, it needs to be evaluated as below:

Clinical evaluation for all patients:
 Measurement of blood pressure
 serum creatinine to measure GFR
 The ratio of protein - creatinine ratio or albumin - creatinine morning, or when urine specimens (untimed spot urine specimen)
 Examination of urine sediment or disptik for detection of red blood cells and white blood cells
Clinical evaluation for a particular patient (depending on risk factors):
 ultrasound (eg for patients with symptoms of urinary tract obstruction; infection or stones, family history of polycystic kidney disease)
 serum electrolytes (Na, K, Cl, bicarbonate)
 Concentration of urine (specific gravity or osmolality)
 urine acidity (pH)

             It has been mentioned above (the definition of CKD) that markers of kidney damage is the presence of abnormalities in the composition of the blood or urine, or radiological abnormalities. Although there is some indication, but the NKF K / DOQI stresses the importance of proteinuria as a marker of kidney damage. The term proteinuria showed an increased excretion of urine for albumin, other specific proteins, or total protein. While the term specifically albumin showed an increase in urinary albumin excretion. Microalbuminuria indicates that the excretion of albumin above the normal value, but below levels that can be detected by tests for total protein. In adults with an increased risk of CKD is advisable to check with spot urine albuminuria, both with special disptik ratio for albumin or albumin / creatinine

Patients with CKD should be evaluated to determine:
a. Diagnosis (type of kidney disease)
b. comorbid conditions
c. Severity, through the determination of the degree of renal function
d. Complications, related to the degree of renal function
e. The risk of loss of kidney function
f. Risk of cardiovascular disease

For all patients that have been defined as CKD, the evaluation lab to do are:
 serum creatinine to determine GFR
 The ratio of protein / creatinine ratio or albumin / creatinine morning or when the spot urine
 Examination of urine sediment or dipstick for red blood cells and white blood cells
 radiological examination of kidney, usually ultrasound
 serum electrolytes (Na, K, Cl, bicarbonate)
Guidelines for K / DOQI 2002 recommends that interventions that are considered effective in inhibiting the progression are:
1. controlling blood sugar levels
2. control of blood pressure
3. RAA system activity control

              The American Diabetes Association (ADA) recommends the use of ACE inhibitors in all patients with DM who proved existing kidney disorders (microalbuminuria or proteinuria), view or presence of hypertension, as long as the use of these drugs are contraindicated and not cause complications.
ACE inhibitors and angiotensin receptor antagonists (ARBs) have a special protective role in patients with diabetic kidney disease and non-diabetic, besides lowering systemic blood pressure also lowers blood pressure and capillary filtration glomeruler proteins thus slowing progression of kidney damage. In addition both drugs also reduced cell proliferation and fibrosis caused by angiotensin 2.
While interventions are still under evaluation and are not yet conclusive
1. Restriction of protein in the diet
2. Lipid-lowering drugs
3. correction of anemia

Some Practical Aspects Management of CKD Patients
In everyday practice management of CKD is as follows:
1. Basic treatment of the disease
2. Control of water and salt balance
3. Diets low in protein, high aklori
4. control of blood pressure
5. control of electrolyte imbalance and acid-base
6. prevention and treatment of renal osteodystrophy (ODR)
7. treatment of specific symptoms uremi
8. early detection and treatment of infections
9. adjustment of drug delivery
10. detection and treatment of complications
11. preparation for dialysis and transplantation.

1. Basic Medicine
Treatment that can still be corrected absolutely must be done. Including, control of blood pressure, blood sugar regulation in diabetic patients, correction if there is obstruction of the urinary tract, as well as the treatment of urinary tract infection (UTI).

2. Control of Water and Salt Balance
Fluid administration adjusted to the production of urine. Namely 24-hour urine output plus 500 ml. Salt intake depends efaluasi ekektrolit, generally in the limit 40-120 mEq (920-2760 mg). Normal diet contains an average of 150 mEq. High doses of furosemide can still be used in early CKD, but in the next phase is no longer useful and the obstruction is contraindicated. Weighing, monitoring urine output and fluid balance records will assist the management of fluid and salt balance.

3. And High Protein Diet Low Calorie
Restricted protein intake from 0.6 to 0.8 grams / kg / day. Average daily protein requirements in patients with Chronic Renal Failure is 20-40 grams. Caloric needs at least 35 kcal / kg / day. High protein low calorie diet will improve the complaints of nausea, lower BUN and will improve symptoms. Besides low-protein diet will inhibit progression of decline in renal physiology.

4. management of Hypertension
In contrast to the control of hypertension in general, the CKD problem of fluid restriction absolutely necessary. Target blood pressure 125/75 is required to inhibit the rate of progression of decline in renal physiology. -ACE inhibitors and ARBs are expected to inhibit the progression of CKD. Serial monitoring of renal physiology needs to be done in the early treatment of hypertension when used ACE-inhibitors and ARBs. If the suspected presence of renal artery stenosis, ACE inhibitors are contra-indications.

5. Control of Electrolyte Balance and Acid-Base
The main electrolyte balance disorders in CKD is hyperkalemia and asidosis.Hiperkalemia may remain asymptomatic despite life-threatening. EKG changes, sometimes only emerge after a life-threatening hyperkalemia. Prevention includes:
a) low-potassium diet
avoid fruit (bananas, oranges, tomatoes) and vegetables of excess
b) avoiding the use of K-sparring diuretics
Treatment of hyperkalemia depends on the degree of emergency:
Intensive - glukonase calcicus intravenous (10-20 ml of 10% Ca gluconate)
- Intravenous glucose (25-50 ml of glucose 50%)
- 10-20 units of insulin
- Intravenous sodium bicarbonate (25-100 ml 8.4% NaHCO3)
  can be used also fast-acting insulin 2 U are mixed into a 25 cc 40% dextrose, administered iv bolus.
Increases the expression of potassium
   • Furosemide
   • K-exchange resin
• Dialysis

Acidosis led to complaints of nausea, weakness, water-hunger and drowsiness. Intravenous treatment with NaHCO3 only given in severe acidosis, whereas if it is not life threatening can be administered either by mouth.

6. Prevention and Treatment of ROD
Included in this action is
a. control hiperphosphatemia
Serum P levels should be maintained less than 6 mg / dl.dengan way low phosphorus diet alone is not enough sometimes, so it should be given phosphate binder medication. 300-1800 mg of aluminum hydroxide is supplied with a meal. This method is now abandoned because of side effects of aluminum intoxication and constipation. As another option may be given 500-3000 mg of calcium carbonate with meals with a profit increase calcium intake and also for the correction of hypocalcemia. Foods that contain high phosphorus should be avoided such as milk, cheese, yogurt, ice cream, fish and nuts. Hiperphosphatemia control can also inhibit progression of decline in renal physiology.
b. Supplements of vitamin D3 active
1:25 dihydroxy vitamin D3 (calcitriol) is given only if the normal P levels. Limitation provision if the Ca × P <65. The dose given was 0:25 micrograms / day.
c. Paratiroidektomi
Done if the ODR process continues

7. Specific Treatment of Symptoms Uremi
Included here is the symptomatic treatment of pruritus, complaint handling gastrointestinaldan anemia. Diets low in protein, P-control as well as giving diphenhydramine may improve pruritus complaints. Low-protein diets also improve complaints of anorexia and nausea. Anemia that occurs in CKD mainly caused by a deficiency of the hormone erythropoietin. It also can be caused by defisisensi Fe, folic acid or B12. administration of recombinant erythropoietin in patients with CKD who underwent HD will improve the quality of life, can also be given to pre-HD patients with CKD. Before giving erythropoietin and iron supplementation is required evaluation undergraduate levels, TIBC, and ferritin. I.

8. Detection and Treatment of Infection
Patients with CKD is an patients with a low immune response, so the possibility of infection should always be considered. Febrile symptoms sometimes do not emerge because of this low immune response.

9. Dispensing Adjustment
Some drugs require dose adjustment due to excretion of metabolites through the kidneys. The use of nephrotoxic drugs such as aminoglycosides, co-trimoxazole, amphotericin should dihndari and diberika only on special circumstances. NSAIDs also decrease kidney function. Tetracycline also reduced protein catabolism. Nitrofurantoin should be avoided and the use of K-sparing diuretics should also be careful because it causes hyperkalemia.
10. Detection and Treatment of Complications
With more and continued PGK greater likelihood of complications arise. Some complications are indications for immediate commencement of hemodialysis (HD) even though the patient has not reached the stage of CKD stage 5.

Complications are an indication for HD action include:
a) uremic encephalopathy
b) Pericarditis or pleuritis
c) progressive peripheral neuropathy
d) progressive ODR
e) hyperkalemia that can not be controlled with medical treatment
f) overload syndrome
g) a life-threatening infections
h) Social conditions

11. Preparation of Dialysis and Transplantation
Patients with CKD and their families must be informed early on that at some point people will goes a HD or renal transplantation. Preparation of vascular access should've done before creatinine clearance below 15 ml / min. Vascular access creation is recommended if creatinine clearance was below 20 ml / min. Need to restrict blood vessel puncture area that will be used for limb-vascular access. Besides the preparation of medical terms is also important to non-medical preparation.



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How to know and diagnose CHRONIC KIDNEY DISEASE

CLINICAL MANIFESTATIONS

CKD patients with blood urea of less than 150 mg%, usually without any complaints or symptoms and are often found by chance on routine examination. Clinical picture more evident when the blood urea more than 200 mg%. At the initial level of CKD with a GFR less than 25% of normal, clinical picture is very minimal, only albuminuria, hyperuricaemia, and hypertension.

Clinical picture of severe CKD accompanied by azotemia extremely complex syndrome, including abnormalities of various organs such as:

a.    abnormalities hemopoeisis

Anemia nomokrom normositer (MCHC 32-36%) and normositer (MCV 78-94 CU).

b.    Gastrointestinal disorders

Nausea and vomiting are often a major complaint of most patients with chronic renal failure, especially in the terminal stage, Hiccup, azotemia stomatitis is characterized by dry mucous lesions accompanied by extensive ulceration stomatitis is called bright-red, parotid gland enlargement, and pancreatitis.

c.    eye disorders

Vision loss (amaurosis azotemia) in only a minority of patients. Optic nerve disorder that causes symptoms of nystagmus, miosis, and pupil asymmetry. Abnormalities of the retina (retinopathy), keratopathy.

d.    skin disorders

Itchy, dry and scaly skin.

e.    Serous membrane abnormalities

Pleuritis, pericarditis is often encountered in chronic renal failure, especially in the terminal stage.

f.    neuropsychiatric disorders

Mild mental disorders such as emotionally unstable, dilution, insomnia, depression. Severe mental disorders such as confusion, dilution, and not infrequently with symptoms of psychosis. Mild or severe mental disorders are often found in patients with or without hemodialysis, and depending on the basic personality (personality).

Neurological disorders such as muscular twitching or muscle spasms are often found in patients already heavy, plunging into a coma. The attack is accompanied grandma focal abnormalities often found in the terminal stage.

g.    Cardiopulmonal system disorders

Congestive heart failure, hypertension, peripheral vascular calcification, pericarditis, pulmonary azotemia (uremic lung)

DIAGNOSIS
a. History and physical examination diagnosis

History should be directed to collect all complaints relating to the retention or accumulation of toxins azotemia, Chronic Renal Failure etiology, course of disease, including all factors that can aggravate kidney physiology. It is also necessary data about the patient's disease history, and also data showing a gradual decline in renal physiology.

b.    laboratory tests

1)      Examination of renal physiology

Examination of urea & serum creatinine and serum uric acid is sufficient as screened for renal physiology. There was also the examination of creatinine clearance and radionuclide (gamma camera imaging) is almost close to the actual renal physiology.

2)      Routine Urinalysis

Albuminuria more than 3.5 grams per day and non-selective accompanied by abnormalities of sediment (erythrocytes Uriah, leukosituria and silinderuria) more often found in glomerulonefropati (primary or secondary).

3)      Microbiology urine (CFU per ml of urine)

Worsening of renal physiology that hard to explain UTI should be suspected as a cause by CFU per ml of urine more than 10⁵.

4)      Blood Chemistry

Hypercholesterolaemia are often found in idiopathic nephrotic syndrome (primary). Hyperuricaemia is not always associated with uric acid nephropathy due to chronic hyperuricaemia in parallel with a reduction in renal physiology. If found gaps serum urea and creatinine (without hiperkatabolisme factor), have suspected the possibility of obstructive nephropathy (lithiasis).

5)      Electrolytes

Examination of electrolytes (serum and urine) are essential for the diagnosis of CKD is associated with nephropathy (hypocalcaemia & hypokalemia) and nephrocalcinosis. examined serum  Na⁺, K⁺, HCO₃^2- , Ca²⁺ , PO₄^2-, Mg²⁺.

6)      Imunodiagnosis

Several checks imunodiagnosis to glomerulonephropathy include: ACB, ANA, HBsAg, Krioglobulin, CICx, examination of serum complement, imunofluoresen network

           7)  Additional ecamination

a) Plain abdominal: for identification of anatomical changes in renal

b) Ultrasonography (USG): accuracy higher than a plain photo abdomen. Useful to assess renal anatomy or identification.

c) Nephrotomogram: important for evaluation of obstructive nephropathy due mainly radiolucent stones or other causes.

d) Pielography retrograde: it is important for evaluation of obstructive nephropathy is difficult to determine why.

e) Pielography antegrade: for therapeutic and diagnosis of urinary tract obstruction.

f) Micturating cysto urography (MCU): indication of when the suspected possibility of vesicoureteric reflux.