What is Agranulocytosis?

It is otherwise known as granulopenia, granulocytopenia or agranulosis. It is sometimes interchanged with the medical term neutropenia. It is a medical condition or term, which is derived from a Greek word that means “without granulocyte”, that suggest a reduction in the production of granulocytes, which is a blood disorder, under this classification includes subtypes such as basophils, eosinophils and neutrophils.

Granulocytes are actually a kind of WBC or white blood cells. When a person has or is experiencing Agranulocytosis, he or she is at great risk to acquire infection as well as mucosal ulceration. Without these cells, the body is unable to fight off the infection.

Agranulocytosis Image

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Agranulocytosis Symptoms

Persons that have Agranulocytosis will experience the following symptoms:

• Weakness
• Ulcers in the person’ s stomach, bowels or mouth
• Chills
• Fever
• Rigors
• Fatigue
• headache
• Sore throat
• Opportunistic Infection to any organ such as the throat, rectum, mouth, vagina, or nose
• Septicemia (in the long run or as the condition worsens)

Although the symptoms mentioned above are associated with Agranulocytosis, still some of the persons who reportedly suffer from this kind of condition reports to have no symptoms or are asymptomatic during the illness period.

Agranulocytosis Causes

The etiological reason or cause of why Agranulocytosis occurs may be due to the following reasons or causes:

• Chemotherapy effect
• Diseases that affects the bone marrow
• Hereditary diseases
• Radiation therapy side effects
• Having autoimmune diseases
• Taking in prescriptions which have a side effect of Agranulocytosis such drugs like antineoplastic, sulfonamides, psychotropic and chloramphenicol.

Agranulocytosis Diagnosis

In diagnosing the patient with Agranulocytosis, the person will undergo examinations such as:

• Medical history
• Physical examination
• Complete blood count examination that includes differential which measures eosinophils, basophils and neutrophils
• Genetic examination
• Blood examinations may be done through bone marrow biopsy through the special procedure called FNAB or fine needle aspiration biopsy

The important and confirmative examination with regards to diagnosing the person disease is laboratory values. It is consider as the main indicative measure especially when person is experiencing Agranulocytosis. The laboratory values will depict a lower number of cell counts of the granulocytes, which is considered to be abnormal in nature and which are indicative of Agranulocytosis. The normal laboratory values will differ from one hospital to another it is advisable that the normal laboratory values in a particular hospital is to be followed to be accurate in diagnosing Agranulocytosis.

Bone Marrow Biopsy as a confirmative diagnosis for the presence of Agranulocytosis

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Agranulocytosis Treatment

In treating persons with Agranulocytosis, the causative or the reason must be established first and then the treatment will be based on the cause. If the cause is due to too much intake of medications which can lead to Agranulocytosis, thus, the treatment should be to change or to lessen the medications taken which will need consultation from the trusted physician. Other treatment includes:

• Isolation precaution
•  Antibiotics
• Bone marrow transplant
•  GMCSF or otherwise known as granulocyte colony stimulating factors
•  Stem cell transfusion

With regards to bone marrow transplantation, which is the primary effective treatment for persons that have Agranulocytosis, the criteria must be met prior to undergoing the transplant. The criteria includes matched donor, good health before undergoing the transplant procedure, the age is 40 years old and under.

Agranulocytosis Side Effects & Complications

There are no such thing as perfect treatment, hence we could not forego that there could be complications and side effects that are associated whenever we treat persons with Agranulocytosis. Such side effects and complications include the following:

• Allergic reaction
• High risk for infection
• Bleeding

Hence, by knowing such, we must be able to understand the risk of the treatment provided.

Define Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS) is a congenital rare syndrome appear due to genetic disorders. The primary characteristic of this syndrome is delayed physical development during fetal growth and continues to after birth. In other word, it can be described as a prenatal and postnatal growth retardation.

The signs and symptoms are associated with distinct physical appearance, including craniofacial (head and facial) abnormalities, defective upper limb (hands and arms) development; and mild to severe cognitive impairment due to mental retardation. The symptomatic variation seems with case to case. (1,2)

Sign and symptoms

The typical sign and symptoms of Cornelia de Lange syndrome is distinct, but some features are considered as secondary features. Therefore, the appeared signs and symptoms are divided into two categories, which include primary characteristics and secondary characteristics, though all the below mentioned sign and symptoms may not be prominent in every case.

Primary characteristics of CdLS

Depending upon the genetic differences, the primary characteristics occur, which include:

Overall growth of a infants

The infant born by CdLS usually has low birth weight, that approximately 5 lbs. or 1oz., but this is not a fixed for every case, and it varies within a range of 1 lb., 2 oz. to 10 lbs. The length of the child is also low and calculated mean birth length is around 18 inches. The provided value can help to indicate that CdLS cause growth retardation during  fetal development in the womb. The head size of the infant is also small, which is termed as microcephaly.

Delayed mental development

The children with CdLS typically has delayed mental development and cause mild to severe intellectual incapacitance. The common features  include Learning disabilities, language delays, but some individual can have borderline of standard intelligence.

Gastro esophageal Reflux Disease (GERD)

Vast majority of the CdLS patient (almost 85%) complains discomfort after ingestion of food, like heartburn due to the high possibility of GERD. The unpleasant effect also has a negative impact on  behavior.

Behavioral Issues

Different types of annoying behaviors, which may cause self hurting issues like head-banging or  hand-biting are often associated. Repetitive compulsive behavior,  Obsessive Compulsive Disorder, Attention Deficit Hyperactivity Disorder, Anxiety and Attention Deficit Disorder are also noticeable with patients having  CdLS syndrome.

Secondary Characteristics of CdLS

Typical  facial appearance

Along with microcephaly, a peculiar vertically extended groove present between the upper lip and nose, a stumpy nasal bridge; upturned nostrils; and a obtrude upper jaw. In addition, distinctive facial defects may consist of skinny, downturned lips; ears are low-sited; vaulted, prominent eyebrows that raise jointly diagonally from the bottom of the nose; an oddly short hairline on the forehead and the backside of the neck; and atypical twisted, elongated eyelashes and cleft palate or high-arched palate.

Limb distinction

The typical distinction of limb is also associated with CdLS patients, for them, which include small sized hands and feet with curved little finger (clinodactyl), incompletely united the second and third toes,  abnormal positioning of the thumbs. Associated hand abnormalities may be single sided or both sided. Foot size is smaller than the normal size. Other than these, rarely missing of fingers, forearms  or hands are noticed.

Other System Abnormalities

Other included abnormal features include inflamed eyelid, drooping eyelids, myopia (nearsightedness), involuntary rapid eye movement etc. (2,3,4)

Cornelia De Lange Syndrome Causes

The Cornelia de Lange syndrome is a genetic disorder. The responsible genes associated with CdLS are NIPBL gene on chromosome 5 and the SMC1L1 gene on the X chromosome. In most of the cases, almost half of the incidence is related to the abnormal mutation NIPBL gene, though a very few cases are associated with the abnormal mutation of SMC1L1 gene. Other involved gene yet to discover.

The mutagenic abnormality of the involved gene may carry forward from either of the parental source or new genetic alteration also cause the onset of CdLS. (2)

Diagnosis

An ultrasound imaging system may help to assume the presence of Cornelia de Lange syndrome (CdLS) during fetal growth. The waves of the ultrasounds form an image, which can detect growth retardation, deformities of limb, facial abnormalities and/or defective organ formation.

The confirmation can be notable about the presence CdLS is possible after the birth of the infant by performing a thorough clinical evaluation and detection of typical physical features. The different scientific literature described that a confirmed diagnosis of the presence of Cornelia de Lange syndrome can be reported  after receiving the distinct facial features with the association of  limb abnormalities, before and after birth growth retardation, and intellectual retardation. Mild symptomatic features can cause confusion of the CdLS diagnosis and often difficult to provide conclusive result.

In confirmatory test, molecular genetic testing is performed in the NIPBL and SMC1L1 and finding of abnormal genetic mutations validate the detected physical abnormality is related to CdLS. This test usually recommended for mild characteristic features.

If a precise NIPBL or SMC1L1 gene mutation has been detected, then in the prenatal stage diagnosis of CdLs is possible. (2,4)

Treatment

Depending upon the notable symptomatic approach, a treatment plan is prepared by the clinical experts. In the Cornelia de Lange syndrome, multiple organ deformity is involved, therefore a team of expert clinicians needs to provide a proper therapeutic approach to the affected child. The included specialists are pediatricians; surgeons; geneticists; orthopedists; orthopedic surgeons; plastic surgeon; gastroenterologists, urologists, otolaryngologists (specialist of the ears, nose, and throat); pediatric cardiologists; dentist; speech pathologists; audiologists (specialists who assess and treat hearing problems); eye specialists; physical and occupational therapists; and/or other health care givers.

Any involvement of cardiac problems, GI tract defect, audibility complications, and/or propensity towards respiratory infections need early detection and prompt medical care to reduce the complications. The interventions include pharmacological, surgical depending upon the site and type of abnormality. For example, child susceptible towards respiratory infection can need to treat with antibiotic therapy, episodes of convulsion can be controlled by anticonvulsive therapy, whereas abnormality in heart or limb abnormality may rectify by surgical intervention.

Other supportive therapeutic approaches like hearing aids may recommend and provide a beneficial effect for  hearing impairment. Remedial education, speech therapy, vocational training,  and/or other medical and/or social services also provide positive outcomes for CdLS.

Genetic counseling is suggested for affected persons and their family members. (2)

References

1. Cornelia de Lange syndrome, (2016); Genetic Home References; Retrieve from: https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome
2. Cornelia de Lange Syndrome; National Organization for rare diseases; http://rarediseases.org/rare-diseases/cornelia-de-lange-syndrome/
3. Characteristics of CdLS; CdLS foundation; http://www.cdlsusa.org/what-is-cdls/characteristics-of-cdls.htm
4. Matthew A Deardorff, Sarah E Noon, andIan D Krantz, (2016); Cornelia de Lange Syndrome; http://www.ncbi.nlm.nih.gov/books/NBK1104/

What is the Adrenal gland?

The adrenal gland or the suprarenal gland is a part of the endocrine system responsible for secreting hormones for stress and other body functions. The adrenal glands have different shapes. The left adrenal gland is semilunar in shape while the right adrenal gland is triangular shaped. The adrenal gland is a small gland one-third the size of a normal kidney.

The adrenal gland is supplied by blood by the superior, middle and inferior renal arteries. The venous blood is drained into the right and left suprarenal veins. The adrenal glands together with the thyroid gland are the top two organs that receive the most blood per gram of tissue.

Adrenal Glands is located at the top of kidenys

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 Adrenal gland Location

The adrenal glands are located on the top of each kidney in the retroperitoneum. It is termed as suprarenal gland because it is situated on the top of each kidney. In humans, the adrenal glands are surrounded by the renal fascia and adipose tissues. The adrenal glands are found on the level of the 12th thoracic vertebrae.

The adrenal glands are divided into parts: the adrenal medulla and the adrenal cortex. Both structures in the adrenal gland have definite functions and hormones to produce.

Adrenal Gland Hormones and Functions

The adrenal gland secretes various hormones needed in the body such as:
Hormones secreted by the adrenal cortex

Glucocorticoid

The adrenal cortex secretes cortisol, corticosterone, and deoxycorticosterone responsible for the utilization of fats, proteins and carbohydrates in the body. It is also responsible for anti-inflammatory effects in the body.

Mineralocorticoid

Mineralocorticoid is secreted in the form of aldosterone. Aldosterone serves as a regulator in the body because it regulates salt and water in the kidneys. When aldosterone is increased, there is more sodium and water retention in the body. Because of sodium and water control, aldosterone is directly responsible for the regulation of blood pressure.

Androgens

The adrenal cortex also secretes androstenedione and dehydroepiandrosterone, which are precursors for the production of sex hormones especially testosterone.

Hormones secreted by the adrenal medulla

Epinephrine

Epinephrine or adrenaline is responsible for the fight and flight response of the body. It is responsible for adapting to stress. Epinephrine is responsible for the increase in the heart rate, respirations, metabolic rate and muscle contraction during stress. It also delays muscle fatigue to enable to face the stressor. When people are under stress, the bladder and the colon are less stimulated leading to urinary retention and constipation.

Norepinephrine

Norepinephrine or noradrenaline is also similar to epinephrine in action. It causes constriction of the blood vessels leading to an increase in blood pressure. It also increases the heart rate and improves coronary blood flow.

Adrenal Gland Disorders

Deficiency and overproduction in the hormones secreted by the adrenal gland lead to problems in the body. Certain disorders in the adrenal gland may include:

Cushing’s syndrome

Cushing’s syndrome is a condition wherein there is an increase in the production of cortisol. Because of this, there is an excessive cortisol that the body doesn’t need leading to problems such as hypertension, edema, abnormal fat distribution, increased susceptibility to infection, poor wound healing, and decreased resistance to stress because of too much cortisol in the body. Cushing’s disease often results from adrenal hyperplasia, adrenal tumor or exogenous administration of steroids leading to increased in amounts in the body.

Cushing Syndrome as one of the disorders of adrenal glands

Adrenal gland tumors

Adrenal gland tumors may also arise as a result of primary or secondary malignancy. Primary tumors initially arise in the adrenal gland while secondary tumors may arise from metastasis from other areas in the body such as the lungs. The presence of adrenal tumors leads to hyperfunctioning similar to Cushing’s disease.

Adrenal Gland Failure

Adrenal gland failure is also termed as Addison’s disease. This leads to the hypofunctioning of the adrenal cortex. Because of this, there is limited secretion of mineralocorticoids, glucocorticoids and androgens. Addison’s disease is considered idiopathic or there is no known cause. Deficiency in the mineralocorticoids leads to poor regulation of salt and water leading to increase in water excretion. Glucocorticoid deficiency leads to decreased gluconeogenesis and increased in the production of melanocyte stimulating hormone by the pituitary gland.

Adrenal Failure Symptoms

Symptoms of adrenal failure result from the reduction in the secretion of the steroids in the body. These include:

• Fatigue – A reduction in the production of steroids may also affect the production of epinephrine. The reduced reaction to stress leads to fatigue.
• Weight loss – Low levels of aldosterone also promote water loss from the body leading to rapid weight loss.
• Hypoglycemia – Cortisol is responsible for gluconeogenesis. When the levels are low, it leads to poor metabolism of carbohydrates, fats and proteins that further leads to low blood sugar levels.
• Dehydration – As a result of water loss from the body, the extracellular volume is depleted leading to dehydration.
• Hyperkalemia – The potassium level also increases because of a decrease in the sodium levels in the body. Hyperkalemia further leads to cardiac arrhythmias.
• Postural hypotension – The volume depletion reduces the vascular tone leading to low blood pressure.
• Bronzed skin – The low levels of cortisol also fail to inhibit the adrenocorticotropic hormone produced by the pituitary gland, which increases the melanocyte stimulating hormone. As a result, there is increased production of melanin.
• Decreased resistance to stress – There will also be decreased resistance to stress because of reduced epinephrine and norepinephrine production.

Causes of Adrenal Failure

The exact cause of adrenal failure is unknown, but the presence of congenital hypoplasia of the adrenal gland, pituitary tumors and management of Cushing’s syndrome may cause the condition.

Treatment of Adrenal Failure

The main treatment of adrenal insufficiency is to replace the adrenal hormones that are lacking. Treatments include:

Corticosteroid Therapy

Exogenous corticosteroids are usually given to provide the body with the lacking cortisol in the body and reverse the symptoms. However, corticosteroid therapy should be carefully tapered to prevent life-threatening crisis when the treatment is stopped.

Intravenous Glucose Administration

Hypoglycemia may be treated with intravenous glucose therapy to prevent severe hypoxia of the brain cells.

Intravenous Infusions

Intravenous fluid infusions are also given to maintain vascular integrity and prevent severe dehydration. Increasing the fluids also reverses hypotension as a result of loss of intravascular volume.

What is Vasovagal Syncope?

It is a layman’s termed as fainting which can be experienced by anyone. It occurs due to various factors which may be discussed as we go along. When triggering factors are present, the patient will experience this kind of disease condition. It also activates the autonomic system before or after each attack. It may be otherwise known as neurocardiogenic kind of syncope or neutrally mediated hypotension or vasodepressor syncope. It can happen to anybody at anytime.

Aside from that, the most common etiological factor is a history of brief and acute episodes of losing consciousness that is sometimes happens momentarily. There are really no other  abnormalities associated to person’s both neurologic and cardiac aspects. Hence, it is totally harmless and does not really require treatment at all.

It deals with the vagus nerve, the nerve which crosses in the person’s larynx and throat and is responsible for heart rate as well as it supply the nerves of parasympathetic system such as esophagus, stomach or lungs and other organs in the abdominal region. When discussing about parasympathetic, it means that the system which controls the involuntary system of the person such as the lungs and heart and many other organs.

Vasovagal Syncope Symptoms

When a person undergoes vasovagal syncope, he or she will experience the following symptoms:

• Lightheadedness
• Tunnel vision
• Cold sweat
• Ringing in the ears
• Physical weakness
• Clammy sweat
• Nausea
• Diaphoresis or excessive sweating
• Dizziness
• Palpitations
• Paresthesia
• Chest pain
• Dyspnea
• Feeling of warmth or hot
• Pallor

Many of those who experienced Vasovagal syncope commonly reports that prior on experiencing attacks, they usually felt an aura such as being nervous without reason or perhaps having visual disturbances before the Vasovagal syncope.

Vasovagal Syncope Causes

There are a lots of factors that may trigger attacks of vasovagal syncope such as:

• Low blood pressure
• Blood flow towards the brain is reduced
• Emotional stress
• Undergone a shocking incident or accident
• Painful experience
• Anemia
• Fever
• Fasting episodes
• Prolonged bed rest
• Having organic heart disease
• Heat exposure
• Standing for long hours
• Having their blood drawn out
• At the sight of human blood or any blood for that matter
• Straining like during bowel movement
• The fear or anxiety upon injury of the body

These are just some of the common factors reportedly associated with vasovagal syncope.

Vasovagal Syncope Pathophysiology

The Vasovagal syncope occurs because of two factors: triggering factors and the activation of autonomic.

With regards to the triggering factor, there are actually two kinds: the central and the peripheral. The central triggers are those that deal with instrumentation, pain and emotion. Meanwhile, the peripheral triggers deals with being in a hot environment, dehydration, illness, exercise or perhaps excessive consumption of alcohol.

On the other hand, the activation of autonomic system will bring about the symptoms such as pallor, nausea and sweating, which are the most common symptoms.

Pathophysiologically speaking, what happens inside the person’s body during vasovagal syncope is that there is decrease venous return brought about by decrease blood flow which will in return result to decrease in the left ventricular filling and will then result to an increase in the person’s sympathetic tone as seen by the symptoms experienced such as palpitation and the like. When this happens, there will be vigorous ventricular contraction especially in the underfilled chamber which will trigger the increase in mechanoreceptor discharge which will eventually lead to the trigger of the central nervous system which results to vasodilation and bradycardia and hence the condition called as vasovagal syncope.

How to Treat Vasovagal Syncope?

Treating vasovagal syncope, in most cases, is not necessary. The condition will be gone in minutes even without treatment. If for instance you will encounter vasovagal syncope to the point that it interferes with your day to day activities, then you need to consult your physician so that you will be given diagnostic examination to know the condition that triggers you to have such condition. The physician may also recommend you the following treatment for such condition, such as:

Pharmacological treatment

The medications that are often prescribed to persons who encounter vasovagal syncope are as follows:

• Antidepressants

Antidepressants under the classification of SSRI or otherwise termed as selective serotonin reuptake inhibitors are good medications which will prevent the occurrence of Vasovagal syncope.

• Blood pressure medications

Drugs like metoprolol which treats persons with high blood pressure. This is given to patient who experiences vasovagal syncope because they act to block the signal which may lead to the said condition.

• Constriction for blood vessel

Medications for the treatment of asthma and low blood pressure helps in the prevention of vasovagal syncope.

Therapeutic Management Treatment

Therapeutic regimen such as the wearing of elastic stockings, increasing salt in diet which is done for patients who are not contraindicated or who have no heart problems, tensing your muscles of the leg especially during standing, foot exercises, and leg elevation during the syncope episodes are recommended. Aside from that, it is advisable that you avoid hot and crowded places and prolonged standing. You also need to combat dehydration by drinking lots of fluids particularly water.

Surgical treatment

Last and the certainly the least, some physician would suggest, especially to persons who have heart problems, that the patient undergoes surgery for the insertion of the pacemaker or electrical pacemaker for that matter which will help in the regulation of the blood, heartbeat and persons who encounter Vasovagal syncope.

The treatment for vasovagal syncope varies from one person to another. Prior to undergoing the treatment recommended, the patient should undergo series of diagnostic tests to rule out any possible health problems associated with this condition.