Multiple Myeloma – Symptoms, Diagnosis, Prognosis And Treatment

Multiple myeloma represents a malignant proliferation of plasma white cells ( a special type of mature, antibody-secreting B white cells), which are derived from a single clone.

The body responds to tumor products by symptoms given by organ dysfunction:

1. Bone pain or fracture
2. Renal failure
3. Susceptibility to infection
4. Anemia 
5. Hypercalcemia
6. Abnormalities of blood coagulation
7. Neurologic symptoms

As in many other forms of neoplasia, the main cause of multiple myeloma is not known.

The incidence of multiple myeloma increases with age. The median age of diagnosis is 68 years and men are affected more often than women. It was observed that multiple myeloma occurred, with increased frequency, in people who were exposed to the radiation of nuclear warheads in World War II, after a 20-year latency.

The malignant plasma cells all belong to a single clone, and the excessive antibodies they produce are identical monoclonal antibodies. These accumulate in the bloodstream and can be detected by serum protein electrophoresis (normally serum antibodies are of many forms and show a varied distribution of size in the electrophoresis test). In plasma cell myeloma, there is a large amount of one type of antibody wich form a characteristic spike.

Gel Electrophoresis

Excessive production of light-chain antibody fragments by malignant plasma cells results in their accumulation in blood and urine. When are found in urine, these light-chain fragments are called Bence Jones proteins. Bence Jones  proteins accumulate in the kidneys and cause kidney damage, therefore this is an important aspect to the pathogenesis of multiple myeloma.

Malignant plasma cells tend to accumulate in bone where they enhance osteoclastic activity and produce bone lesions. Pathologic fractures, especially compression fractures of the vertebral collumn are common.

Bone destruction releases calcium into the bloodstream, the result of this process is hypercalcemia.

Multiple Myeloma Signs And Symptoms

Most of the clinical manifestations of multiple myeloma are caused by bone and renal damage.

• Bone pain is the most common symptom of multiple myeloma affecting nearly 70% of patients.The pain usually involves the back and  ribs and unlike of metastatic carcinoma, which is often worse at night,the pain of myeloma is precipitated by movement.  Persistent pain which appear in a patient with multiple myeloma usually signifies a pathological fracture ( fractures with no known trauma). Radiological studies of the ribs, spine, skull and pelvis showed a characteristic appearance of the bone, called “honeycomb appearance”, due to the aspect of lucid areas given by the demineralised bone.

• Renal failure is a complication experienced by approximately 50% of patients with plasma cell myeloma. Renal function may decline over time culminating in chronic renal failure especially in case of dehydration. Renal failure is due to a combination of factors: hyperproteinemia, Bence Jones proteinuria, hypercalcemia, hyperuricemia, recurrent infections and use of non-steroidal agents for pain control.

• Chronic complications of hypercalcinemia may dominate the clinical picture. Such manifestations may include neurologic symptoms : lethargy, weakness, depression and confusion.

• Susceptibility for chronic infections is the next most common problem in patients with multiple myeloma.The most common infections are pneumonia and pyelonephritis. This is due to diffuse hypogammaglobulinemia if the M component is excluded. The hypogammaglobulinemia is related to both decreased production and increased destruction of normal antibodies.

• Anemia occurs in 80% of multiple myeloma patients. It is usually normocytic and normochromic and related to the replacement of normal marrow by expanding tumor cells. Tumor cells also play a part in inhibiting hematopoiesis.

Multiple Myeloma Diagnosis

Multiple Myeloma Prognosis And Treatment

Antineoplasic agents may be used to induce and maintain a remission in plasma cell proliferation. The best chemotherapy regimen has not yet been determined.

High dose chemotherapy followed by allogeneic bone marrow transplantation is becoming the most common course of treatment. However the mortality rate associated with transplantation is high (app. 50%). autologous stem cell transplantation is considered to be optimal therapy for most patients. Pharmacological management of renal dysfunction is also necessary. Chronic bone pain may require narcotic and non-narcotic pain relievers. Localised application of radiation to bone lesions may reduce bone pain in some cases.

Depression – Symptoms, Causes And Treatment

Major depression is now understood to be a complex illness involving inherited genetic susceptibility and symptoms associated with specific alterations in brain functioning and structure. Major depression is defined as depressed mood on a daily basis for a minimum duration of 2 weeks.

The American Psychiatric Association states that a diagnosis of major depression requires the presence of multiple symptoms that are intense enough to cause distress(stressful in an uncomfortable way) and to persistently impair psychosocial functioning. It means that when we are depressed we are basically  incapable of going on with our  lives the way we usually do. Although taken lightly, major depression is a common cause of suicide.

Depression

The illness frequently occurs as a comorbid disorder with serious physical illness as well as other mental disorders. Major depression can also develop as a serious secondary illness or illness complication.As a result of the potentially serious disability, morbidity and mortality risks directly associated with the illness, The World Health Association (WHO) ranks major depression among the top five glob health problems.

Depression Ethiology and Neurobiology

There has been some progress made in determining the neurobiological mechanisms of major depression. Nevertheless, the specific cause of major depression remains unknown.

Neurobiological changes associated with major depression are thought to involve:

• neurotransmission dysregulation (serotonin)
• altered hippocampal and prefrontal cortex cell structure and functioning
• hypothalamic -pituitary-adrenal (HPA) system activation

based on observations of low central nervous system levels of SEROTONIN in persons with severe symptoms of depression, the basic neurobiology of depression has been said to be reduced brain serotonin neurotransmision activity.

The Serotonin Neuron

The fault is thought to be either through excessive presynaptic uptake or through stress-related downregulation of postsynaptic receptors.Serotonin is quite ay strange molecule for many reasons. First of all, it is formed from the amino acid L-tryptophan, which is one of the 20 standard amino acids required for life as we know it. Interestingly, it is also one of the few essential amino acids that the body does not synthesize itself, and have to get it from the diet. But we’ve usually got plenty. This image explains  the variations in the levels of postsynaptic serotonin:

Effects after Ecstasy is Gone

Chronic or persistent vulnerability to depression is thought to be related to decreased hippocampal volume or capacity and suppressed hippocampal neurogenesis.

HPA axis dysfunction has been associated with depression. Genetic susceptibility to depression seems to mediate the link between stress and depression.

Cognitive- behavioral models of depression particularly learned helplessness have been shown to correlate with the basic neurobiology of depression. Avoidant persons, when faced with a stressful situation avoid confronting the situation despite opportunities to do so. Persistent avoidance eventually conditions thee person to automatically respond to stressful situations with strong feelings of helplessness.

Stressful situation

Sleep studies of depression have shown significantly reduced slow-wave(stages 3 and 4) sleep and increased light sleep(stage 1). The periods of REM sleep latency are shortened. Sleep is restorative for brain cells.Severe reduction in serotonin activity have been associated with less restful sleep.Disturbed sleep is a hallmark symptom of depression. The classic sleep disturbances include difficulty falling asleep, early morning waking, and decreased total sleep time.

Sleep Disturbances

Circadian rhythms are closely associated with symptoms of major depression. The pineal gland in the brain produces the hormone melatonin.Brain melatonin levels can fluctuate significantly with annual and daily increases in light and dark periods. Depressed persons have been shown to suffer from low melatonin levels when their symptoms include disturbed sleep.

Low Melatonin Levels

Depression Signs And Symptoms 

Depressed mood and the loss of interest or pleasure are hallmark symptoms of major depression. Depressed mood is usually experienced as painful, numbing and bottomless. Loss of interest or pleasure can be more difficult to recognise. Others may notice this change before the depressed person does.

• Fatigue-or loss of energy is a common yet alarming symptom of depression. Fatigue associated with depression can make ordinarily daily activities once performed automatically nearly impossible, it is immobilising. Depressed people may associate their severe or sudden fatigue with serious physical illness such as cancer, diabetes, cardiovascular disease.

• Restless, irritable agitation– associated with depression can range from mild hyperactivity and sarcasm to aggression. Compulsive physical activities such as pacing are not uncommon.

• Impaired concentration-is experienced as a highly disturbing symptom of depression. Thoughts slow down and the process of thinking literally becomes difficult. Impaired decision making is one of many consequences.Minor choices and simple preferrences become difficult. The content of thought is typically dominated by highly depressive themes.

• Low self-esteem-is the psychological hallmark of depression.Negative appraisals range from pointless guilt to self- hate nearly every day.In some cases self guilt reaches delusional proportion or is markedly disproportionate to actual misdeeds or perceived failings. People generaly find ways to protect their self- esteem for the normal assaults of daily life.With severe depression, positive self -esteem can be absent and only rarely is the loss related to actual life events.

• Negative thinking-expressed as negative views of self, life and the future. This is a common symptom of severe depression often misunderstood. Severe depression is an empty experience that makes life itself seem futile.Negative thinking associated with depression can be mistaken as willful or so unpleasant that others avoid contact with the depressed person.

• Vegetative states-manifest as slow or reduced physical activity.Normal daily activities such as bathing and dressing may not be performed. These symptoms typically are described as feeling as though one is sleep walking, living in slow motion or has become a robot.

• Sleep disturbances-Insomnia is most common, but some people may sleep more (hypersomnia) or shift their sleep hours from night time to day time.Sleep symptoms include difficulty falling asleep, early morning awakening, frequent awakenings and waking tired. The cognitive activity generated by obsessive negative thinking disturbs sleep essentially by preventing it or by literally waking the person.

• Apetite disturbance-significant weight loss when not dieting or weight gain (a change of > 5% of body weight) or decreas/increase in appetite nearly every day. The person may experience marked change in food preferences. Severly depressed persons may become unaware of their hunger or thirst. Diminished salivary and gastric activity can dampen appetite.Overeating also occurs, but this disturbance seems to be more related to restlessness than to appetite. People who normally use food for emotional comfort may increase their consumption of high in fat, sugar,  and salt foods (comfort food).

• Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan or a suicide attempt or a specific plan for committing suicide.

A sign of worry is when five or more of these symptoms have been present during the same 2- week period and represent a change from the previous functioning.

Depression that lasts 2 years or more is commonly referred to as minor depression(dysthymia).

Depression Treatment

Most antidepressants currently available act by improving brain noreprinephrine and serotonin activity.

Brain Noreprinephrine

 Tricyclic antidepressants (TCAs) blocked the reuptake of norepinefrine and serotonin, thereby admitting more neurotransmiter activity.

Selective serotonin reuptake inhibitors (SSRIs) became widely available in the 1990s and were the first antidepressants with selective serotonin effects. SSRIs sucha as fluoxentine,paroxentine, sertaline have been shown to relieve depression symptoms three times faster than earlier medications with far fewer side effects. SSRIs became quickly the primary class of antidepressants. Altough they are improved they aren’t side effect free. Serotonin syndrome is a serious side effect that can result from excessive serotonin activity. Symptoms of serotonin syndrome include: altered mental status, restless agitation, myoclonus, hyperreflexia, sweating, shivering, tremor, gastrointestinal upset, ataxia, headache. Sexual dysfunction is also thought to result from SSRI-induced excessive serotonin activity. Onset can be immediate or gradual with effects ranging from loss of interest to anorgasmia. SSRI cellular and neurochemical mechanisms continue to be the subject of clinical research.

Serotonin and Dopamine

Psychological therapy

Psychological Therapy

Asking from outside help is not a shameful thing tot do when confronted to the suspicion of major depression. Psychiatric or psychological evaluation may confirm the diagnosis of major clinical depression and the patient can be helped accordingly.

Psychotherapy (“therapy” for short) actually involves a variety of treatment techniques. During therapy, a patient with depression talks to a  trained mental health care professional who helps him  identify and work through the problems that may be causing their episode of major depression. Taking care of the psychosocial and psychological aspects of major depression is not to be neglected.

Psychotherapy helps patients with major depression:

• Understand some of the behaviors, emotions, and ideas that contribute to his state
• Understand and identify the life problems or events — like a major illness, a death in the family, a loss of a job or a loved one that lead to their major depression and makes them understand which aspects of those issues they may be able to solve or improve.
• Regain a sense of control and pleasure

Sometimes psychotherapy can replace pharmacological therapy altogether but most of the times they complement each other in helping the depressive patient to gain his previous life back.

Stomach Pain After Meals

Stomach pain after meals is a common condition in case of large food intakes, in overweight persons or kids. The comsuntion of large quantities of food, a larger ones than the stomach capability to handle and digest, causes the fatigue sensation and the need to sleep. This particular habit – sleeping after eating is in many cases responsible for the stomach pain. Huge meals, unhealthy diets and the habit of sleeping after meals are responsible for altering the digestive process and can lead to many health problems.

Causes Of Stomach Pain After Meals

• Severe pain in the lower right area of the abdomen may be the cause of an inflamed appendix (appendicitis). Pain can be accompanied by nausea, vomiting or fever and demands the medical consult. Gallstones is another cause that can cause pain in this area, the pain can be diffuse towards the right portion of the back, right shoulder or chest.

• Severe pain in the superior region of the abdomen that occurs immediately after serving a big meal or pain that persists 6-12 hours after a big meal, can be the cause of pancreatitis. The pain sensation starts from the superior part of the abdomen and extends laterally in the back area, and can be followed by nausea, palpitations, or high fever. Sharp pain is a common symptom of a large number of diseases like: the pelvic inflammatory disease, the cardiac crisis, perforated ulcer, food poisoning or diabetes.

Stomach Pain

• Stomach cramps moderate or short and sharp that follow after eating are the probable result of an intestinal obstruction and can be followed by vomiting with a very nasty smell. Severe cramps accompanied by pain in the inferior left portion of the abdomen can be the cause of diverticulitis.

• Stomach pain accompanied by bloating is caused by intolerance to lactose. Short and sharp pain accompanied by bloating and less than 3 stools per week are signs of constipation. If the the daily menu does not include enough fibers or the liquid intake is not enough, serving meals can be accompanied by constipation and stomach pain.

• Fatigue sensation after meals, accompanied obviously by stomach pain and bloating can be a symptom of irritable bowl syndrome.

• Stomach problems can be caused also by abundant liquids consumption after meals, that dilutes the gastric acid. An adequate quantity of gastric acid helps kill “unhealthy” bacteria and fungus from food and maintains the health of the digestive system. By diluting the gastric acid, the digestion process slows down and bacteria survive, creating in many situation diarrhea.

• Infection with viruses and bacteria can be the cause of stomach pain after meal serving. When bacteria reach into your body, the organism reacts and tries to get rid of the infection through diarrhea and vomiting . Nausea after meals is also very common in these cases.