Anterior pituitary

From Wikipedia, the free encyclopedia

Anterior pituitary gland
Median sagittal through the hypophysis of an adult monkey. Semidiagrammatic.
Details
Precursor	oral mucosa (Rathke's pouch)
Artery	superior hypophyseal
Vein	hypophyseal
Identifiers
Latin	lobus anterior hypophysis
MeSH	D010903
NeuroNames	407
NeuroLex ID	birnlex_1581
TA	A11.1.00.002
FMA	74627

A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior), is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the pituitary gland (hypophysis). The anterior pituitary regulates several physiological processes including stress, growth, reproduction and lactation. Proper functioning of the anterior pituitary and of the organs it regulates can often be ascertained via blood tests that measure hormone levels.

Structure

The anterior pituitary complex

 

The pituitary gland is a pea-sized gland that sits in a protective bony enclosure called the sella turcica (Turkish chair/saddle). It is composed of three lobes: the anterior, intermediate, and posterior lobes. In many animals, these lobes are distinct. However, in humans, the intermediate lobe is but a few cell layers thick and indistinct; as a result, it is often considered as part of the anterior pituitary. In all animals, the fleshy, glandular anterior pituitary is distinct from the neural composition of the posterior pituitary. 

The anterior pituitary is composed of three regions:

Pars distalis

Microanatomy of the pars distalis showing chromophobes, basophils and acidophils

The pars distalis, (distal part), comprises the majority of the anterior pituitary and is where the bulk of pituitary hormone production occurs. The pars distalis contains two types of cells including chromophobe cells and chromophil cells. The chromophils can be further divided into acidophils (alpha cells) and basophils (beta cells). These cells all together produce hormones of the anterior pituitary, and release them into the blood stream.

Nota bene: The term "Basophil" and "Acidophil" is used by some books, whereas others prefer to not use these terms. This is due to the possible confusion with white blood cells, where one may also find Basophils and Acidophils.

Pars tuberalis

The pars tuberalis, (tubular part), forms a part of the sheath extending up from the pars distalis which joins with the pituitary stalk (also known as the infundibular stalk or infundibulum), arising from the posterior lobe. (The pituitary stalk does not connect the hypothalamus to the posterior pituitary). The function of the pars tuberalis is poorly understood. However it has been seen to be important in receiving the endocrine signal in the form of TSHB (a β subunit of TSH) informing the pars tuberalis of the photoperiod (length of day). The expression of this subunit is regulated by the secretion of melatonin in response to light information transmitted to the pineal gland. Earlier studies have shown a localisation of melatonin receptors in this region.

Pars intermedia

The pars intermedia, (intermediate part), sits between the pars distalis and the posterior pituitary, forming the boundary between the anterior and posterior pituitaries. It is very small and indistinct in humans.

Development

The anterior pituitary is derived from the ectoderm, more specifically from that of Rathke’s pouch, part of the developing hard palate in the embryo. 

The pouch eventually loses its connection with the pharynx, giving rise to the anterior pituitary. The anterior wall of Rathke's pouch proliferates, filling most of the pouch to form the pars distalis and the pars tuberalis. The posterior wall of the anterior pituitary forms the pars intermedia. Its formation from the soft tissues of the upper palate contrasts with the posterior pituitary, which originates from neuroectoderm.

Function

The anterior pituitary contains five types of endocrine cell, and they are defined by the hormones they secrete: somatotropes (GH); Lactotropes (PRL); gonadotropes (LH and FSH); corticotropes (ACTH) and thyrotropes (TSH). It also contains non-endocrine folliculostellate cells which are thought to stimulate and support the endocrine cell populations.

Hormones secreted by the anterior pituitary are trophic hormones (Greek: trophe, “nourishment”) and tropic hormones. Trophic hormones directly affect growth either as hyperplasia or hypertrophy on the tissue it is stimulating. Tropic hormones are named for their ability to act directly on target tissues or other endocrine glands to release hormones, causing numerous cascading physiological responses.

Role in the endocrine system

Hypothalamic control

Hormone secretion from the anterior pituitary gland is regulated by hormones secreted by the hypothalamus. Neuroendocrine cells in the hypothalamus project axons to the median eminence, at the base of the brain. At this site, these cells can release substances into small blood vessels that travel directly to the anterior pituitary gland (the hypothalamo-hypophyseal portal vessels).

Other Control Mechanisms

Aside from hypothalamic control of the anterior pituitary, other systems in the body have been shown to regulate the anterior pituitary’s function. GABA can either stimulate or inhibit the secretion of luteinizing hormone (LH) and growth hormone (GH) and can stimulate the secretion of thyroid-stimulating hormone (TSH). Prostaglandins are now known to inhibit adrenocorticotropic hormone (ACTH) and also to stimulate TSH, GH and LH release. GABA, through action with the hypothalamus, has been shown experimentally to influence the level of GH secretion. Clinical evidence supports the experimental findings of the excitatory and inhibitory effects GABA has on GH secretion, dependent on GABA’s site of action within the hypothalamic-pituitary unit.

Effects of the anterior pituitary

Thermal homeostasis

The homeostatic maintenance of the anterior pituitary is crucial to our physiological well being. Increased plasma levels of TSH induce hyperthermia through a mechanism involving increased metabolism and cutaneous vasodilation. Increased levels of LH also result in hypothermia but through a decreased metabolism action. ACTH increase metabolism and induce cutaneous vasoconstriction, increased plasma levels also result in hyperthermia and prolactin decreases with decreasing temperature values. follicle-stimulating hormone (FSH) also may cause hypothermia if increased beyond homeostatic levels through an increased metabolic mechanism only.

Gonadal function

Gonadotropes, primarily luteinising hormone (LH) secreted from the anterior pituitary stimulates the ovulation cycle in female mammals, whilst in the males, LH stimulates the synthesis of androgen which drives the ongoing will to mate together with a constant production of sperm.

HPA axis

The anterior pituitary plays a role in stress response. Corticotropin releasing hormone (CRH) from the hypothalamus stimulates ACTH release in a cascading effect that ends with the production of glucocorticoids from the adrenal cortex.

Behavioral effects

Development

The release of GH, LH, and FSH are required for correct human development, including gonadal development.

Breast-feeding

Release of the hormone prolactin is essential for lactation.

Stress

Operating through the hypothalamic-pituitary-adrenal axis (HPA), the anterior pituitary gland has a large role in the neuroendocrine system’s stress response. Stress induces a release of corticotropin-releasing hormone (CRH) and vasopressin from the hypothalamus, which activates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. Then, this acts on the adrenal cortex to produce glucocorticoids such as cortisol. These glucocorticoids act back on the anterior pituitary gland and the hypothalamus with negative feedback to slow the production of CRH and ACTH. Increased cortisol under stress conditions can cause the following: metabolic effects (mobilization of glucose, fatty acids, and amino acids), bone re-absorption (calcium mobilization), activation of the sympathetic nervous system response (fight or flight), anti-inflammatory effects, and inhibition of reproduction/growth. When the anterior pituitary gland is removed (hypophysectomy) in rats, their avoidance learning mechanisms were slowed down, but injections of ACTH restored their performance. In addition, stress may delay the release of reproductive hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This shows that the anterior pituitary gland is involved in behavioral functions as well as being part of a larger pathway for stress responses. It is also known that (HPA) hormones are related to certain skin diseases and skin homeostasis. There is evidence linking hyperactivity of HPA hormones to stress-related skin diseases and skin tumors.

Aging

Operating through the hypothalamic-pituitary-gonadal axis, the anterior pituitary gland also affects the reproductive system. The hypothalamus releases gonadotropin-releasing hormone (GnRH), which stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone. Then the gonads produce estrogen and testosterone. The decrease in release of gonadotropins (LH and FSH) caused by normal aging may be responsible for impotence and frailty in elderly men because of the eventual decrease in production of testosterone. This lower level of testosterone can have other effects, such as reduced libido, well-being and mood, muscle and bone strength, and metabolism.

Tactile responding

It has been shown that infant mice who were stroked with a paintbrush (simulating motherly care) had more release and binding of growth hormone (GH) from the anterior pituitary gland.

Circadian rhythms

Light information received by the eyes is transmitted to the pineal gland via the circadian pacemaker (the suprachiasmatic nucleus). Diminishing light stimulates the release of melatonin from the pineal gland which can also affect the secretion levels in the hypothalamic-pituitary-gonadal axis. Melatonin can lower levels of LH and FSH, which will decrease levels of estrogen and testosterone. In addition, melatonin may affect production of prolactin.

Clinical significance

Increased activity

Hyperpituitarism is the condition where the pituitary secretes excessive amounts of hormones. This hypersecretion often results in the formation of a pituitary adenoma (tumour), which are benign apart from a tiny fraction. There are mainly three types of anterior pituitary tumors and their associated disorders. For example, acromegaly results from excessive secretion of growth hormone (GH) often being released by a pituitary adenoma. This disorder can cause disfigurement and possibly death and can lead to gigantism, a hormone disorder shown in “giants” such as André the Giant, where it occurs before the epiphyseal plates in bones close in puberty. The most common type of pituitary tumour is a prolactinoma which hypersecretes prolactin. A third type of pituitary adenoma secretes excess ACTH, which in turn, causes an excess of cortisol to be secreted and is the cause of Cushing's disease.

Decreased activity

Hypopituitarism is characterized by a decreased secretion of hormones released by the anterior pituitary. For example, hypo-secretion of GH prior to puberty can be a cause of dwarfism. In addition, secondary adrenal insufficiency can be caused by hypo-secretion of ACTH which, in turn, does not signal the adrenal cortex to produce a sufficient amount of cortisol. This is a life-threatening condition. Hypopituitarism could be caused by the destruction or removal of the anterior pituitary tissue through traumatic brain injury, tumor, tuberculosis, or syphilis, among other causes. This disorder used to be referred to as Simmonds' disease but now according to the Diseases Database it is called Sheehan syndrome. If the hypopituitarism is caused by the blood loss associated with childbirth, the disorder is referred to as Sheehan syndrome.

History

Etymology

The anterior pituitary is also known as the adenohypophysis, meaning "glandular undergrowth", from the Greek adeno- ("gland"), hypo ("under"), and physis ("growth").

Additional images

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  The anterior pituitary is the anterior, glandular lobe of the pituitary gland.
  
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Thiamine deficiency (beriberi)

From Wikipedia, the free encyclopedia

Thiamine deficiency
Other names	Beriberi, vitamin B1 deficiency, thiamine-deficiency syndrome
A person with beriberi during the early twentieth century in South-East Asia
Specialty	Neurology, cardiology, pediatrics
Symptoms	Wet: Fast heart rate, shortness of breath, leg swelling Dry: Numbness, confusion, trouble moving the legs, pain
Types	Wet, dry, gastrointestinal
Causes	Not enough thiamine
Risk factors	Diet of mostly white rice; alcoholism, dialysis, chronic diarrhea, diuretics
Prevention	Food fortification
Treatment	Thiamine supplementation
Frequency	Rare (US)

Thiamine deficiency is a medical condition of low levels of thiamine (vitamin B1). A severe and chronic form is known as beriberi. There are two main types in adults: wet beriberi, and dry beriberi. Wet beriberi affects the cardiovascular system resulting in a fast heart rate, shortness of breath, and leg swelling. Dry beriberi affects the nervous system resulting in numbness of the hands and feet, confusion, trouble moving the legs, and pain. A form with loss of appetite and constipation may also occur. Another type, acute beriberi, is found mostly in babies and presents with loss of appetite, vomiting, lactic acidosis, changes in heart rate, and enlargement of the heart.

Risk factors include a diet of mostly white rice, as well as alcoholism, dialysis, chronic diarrhea, and taking high doses of diuretics. Rarely it may be due to a genetic condition which results in difficulties absorbing thiamine found in food. Wernicke encephalopathy and Korsakoff syndrome are forms of dry beriberi. Diagnosis is based on symptoms, low levels of thiamine in the urine, high blood lactate, and improvement with treatment.

Treatment is by thiamine supplementation, either by mouth or by injection. With treatment symptoms generally resolve in a couple of weeks. The disease may be prevented at the population level through the fortification of food.

Thiamine deficiency is rare in the United States. It remains relatively common in sub-Saharan Africa. Outbreaks have been seen in refugee camps. Thiamine deficiency has been described for thousands of years in Asia and became more common in the late 1800s with the increased processing of rice.

Signs and symptoms

Beriberi

Symptoms of beriberi include weight loss, emotional disturbances, impaired sensory perception, weakness and pain in the limbs, and periods of irregular heart rate. Edema (swelling of bodily tissues) is common. It may increase the amount of lactic acid and pyruvic acid within the blood. In advanced cases, the disease may cause high-output cardiac failure and death. 

Symptoms may occur concurrently with those of Wernicke's encephalopathy, a primarily neurological thiamine-deficiency related condition.

Beriberi is divided into four categories as follows. The first three are historical and the fourth, gastrointestinal beriberi, was recognized in 2004:

• Dry beriberi specially affects the peripheral nervous system.
• Wet beriberi specially affects the cardiovascular system and other bodily systems.
• Infantile beriberi affects the babies of malnourished mothers.
• Gastrointestinal beriberi affects the digestive system and other bodily systems.

Dry beriberi

Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis. It is characterized by:

• Difficulty in walking
• Tingling or loss of sensation (numbness) in hands and feet
• Loss of tendon reflexes
• Loss of muscle function or paralysis of the lower legs
• Mental confusion/speech difficulties
• Pain
• Involuntary eye movements (nystagmus)
• Vomiting

A selective impairment of the large proprioceptive sensory fibers without motor impairment can occur and present as a prominent sensory ataxia, which is a loss of balance and coordination due to loss of the proprioceptive inputs from the periphery and loss of position sense.

Brain disease

Wernicke's encephalopathy (WE), Korsakoff's syndrome (alcohol amnestic disorder), Wernicke–Korsakoff syndrome are forms of dry beriberi.

Wernicke's encephalopathy is the most frequently encountered manifestation of thiamine deficiency in Western society, though it may also occur in patients with impaired nutrition from other causes, such as gastrointestinal disease, those with HIV/AIDS, and with the injudicious administration of parenteral glucose or hyperalimentation without adequate B-vitamin supplementation. This is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function.

Korsakoff's syndrome is, in general, considered to occur with deterioration of brain function in patients initially diagnosed with WE. This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative.

Alcoholics may have thiamine deficiency because of the following:

• Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamine.
• Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is disturbed during acute alcohol exposure.
• Liver thiamine stores are reduced due to hepatic steatosis or fibrosis.
• Impaired thiamine utilization: Magnesium, which is required for the binding of thiamine to thiamine-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamine that does reach the cells will further exacerbate the thiamine deficiency.
• Ethanol per se inhibits thiamine transport in the gastrointestinal system and blocks phosphorylation of thiamine to its cofactor form (ThDP).

Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamine deficiency are reversed, in particular poor brain functionality, although in more severe cases, Wernicke–Korsakoff syndrome leaves permanent damage.

Wet beriberi

Wet beriberi affects the heart and circulatory system. It is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become edematous. Wet beriberi is characterized by:

• Increased heart rate
• Vasodilation leading to decreased systemic vascular resistance, and high output heart failure
• Elevated jugular venous pressure
• Dyspnea (shortness of breath) on exertion
• Paroxysmal nocturnal dyspnea
• Peripheral edema (swelling of lower legs)
• Dilated cardiomyopathy

Gastrointestinal beriberi

Gastrointestinal beriberi causes abdominal pain. Gastrointestinal beriberi is characterized by:

• Abdominal pain
• Nausea
• Vomiting
• Lactic acidosis

Infants

Infantile beriberi usually occurs between two and six months of age in children whose mothers have inadequate thiamine intake. It may present as either wet or dry beriberi.

In the acute form, the baby develops dyspnea and cyanosis and soon dies of heart failure. These symptoms may be described in infantile beriberi:

• Hoarseness, where the child makes moves to moan but emits no sound or just faint moans caused by nerve paralysis
• Weight loss, becoming thinner and then marasmic as the disease progresses
• Vomiting
• Diarrhea
• Pale skin
• Edema
• Ill temper
• Alterations of the cardiovascular system, especially tachycardia (rapid heart rate)
• Convulsions occasionally observed in the terminal stages

Cause

Beriberi may also be caused by shortcomings other than inadequate intake: diseases or operations on the digestive tract, alcoholism, dialysis, genetic deficiencies, etc. All these causes mainly affect the central nervous system, and provoke the development of what is known as Wernicke's disease or Wernicke's encephalopathy. 

Wernicke's disease is one of the most prevalent neurological or neuropsychiatric diseases. In autopsy series, features of Wernicke lesions are observed in approximately 2% of general cases. Medical record research shows that about 85% had not been diagnosed, although only 19% would be asymptomatic. In children, only 58% were diagnosed. In alcohol abusers, autopsy series showed neurological damages at rates of 12.5% or more. Mortality caused by Wernicke's disease reaches 17% of diseases, which means 3.4/1000 or about 25 million contemporaries. The number of people with Wernicke's disease may be even higher, considering that early stages may have dysfunctions prior to the production of observable lesions at necropsy. In addition, uncounted numbers of people can experience fetal damage and subsequent diseases.

Genetics

Genetic diseases of thiamine transport are rare but serious. Thiamine responsive megaloblastic anemia (TRMA) with diabetes mellitus and sensorineural deafness is an autosomal recessive disorder caused by mutations in the gene SLC19A2, a high affinity thiamine transporter. TRMA patients do not show signs of systemic thiamine deficiency, suggesting redundancy in the thiamine transport system. This has led to the discovery of a second high-affinity thiamine transporter, SLC19A3. Leigh disease (subacute necrotising encephalomyelopathy) is an inherited disorder that affects mostly infants in the first years of life and is invariably fatal. Pathological similarities between Leigh disease and WE led to the hypothesis that the cause was a defect in thiamine metabolism. One of the most consistent findings has been an abnormality of the activation of the pyruvate dehydrogenase complex.

Mutations in the SLC19A3 gene have been linked to biotin-thiamine responsive basal ganglia disease which is treated with pharmacological doses of thiamine and biotin, another B vitamin. 

Other disorders in which a putative role for thiamine has been implicated include subacute necrotising encephalomyelopathy, opsoclonic cerebellopathy (a paraneoplastic syndrome), and Nigerian seasonal ataxia. In addition, several inherited disorders of ThDP-dependent enzymes have been reported, which may respond to thiamine treatment.

Pathophysiology

Thiamine in the human body has a half-life of 18 days and is quickly exhausted, particularly when metabolic demands exceed intake. A derivative of thiamine, thiamine pyrophosphate (TPP), is a cofactor involved in the citric acid cycle, as well as connecting the breakdown of sugars with the citric acid cycle. The citric acid cycle is a central metabolic pathway involved in the regulation of carbohydrate, lipid, and amino acid metabolism, and its disruption due to thiamine deficiency inhibits the production of many molecules including the neurotransmitters glutamic acid and GABA. Additionally thiamine may also be directly involved in neuromodulation.

Diagnosis

Oxidation of thiamine derivatives to fluorescent thiochromes by potassium ferricyanide under alkaline conditions

 

A positive diagnosis test for thiamine deficiency can be ascertained by measuring the activity of the enzyme transketolase in erythrocytes (Erythrocyte Transketolase Activation Assay). Thiamine, as well as its phosphate derivatives, can also be detected directly in whole blood, tissues, foods, animal feed, and pharmaceutical preparations following the conversion of thiamine to fluorescent thiochrome derivatives (Thiochrome Assay) and separation by high-performance liquid chromatography (HPLC). In recent reports, a number of Capillary Electrophoresis (CE) techniques and in-capillary enzyme reaction methods have emerged as potential alternative techniques for the determination and monitoring of thiamine in samples. The normal thiamine concentration in EDTA-blood is about 20-100 µg/l.

Treatment

Many people with beriberi can be treated with thiamine alone. Given thiamine intravenously (and later orally), rapid and dramatic recovery can occur within hours. In situations where concentrated thiamine supplements are unavailable, feeding the person with a thiamine-rich diet (e.g. whole grain brown bread) will lead to recovery, though at a much slower rate.

Following thiamine treatment, rapid improvement occurs, in general, within 24 hours. Improvements of peripheral neuropathy may require several months of thiamine treatment.

Epidemiology

Historically, beriberi was associated with a diet including much polished rice (white rice); when the relationship between polishing rice and the disease was discovered, it became possible to prevent and treat the deficiency condition, for example with inexpensive rice bran. Beriberi caused by inadequate nutritional intake is rare today in developed countries because of quality of food and the fact that many foods are fortified with vitamins. No reliable statistics are given for beriberi in developed countries in the 19th century or earlier; neither are statistics available before the last century in countries in extreme poverty.

Beriberi is a recurrent nutritional disease in detention houses, even in this century. In 1999, an outbreak of beriberi occurred in a detention center in Taiwan. High rates of illness and death in overcrowded Haitian jails were traced in 2007 to the traditional practice of washing rice before cooking. In the Ivory Coast, among a group of prisoners with heavy punishment, 64% were affected by beriberi. Before beginning treatment, prisoners exhibited symptoms of dry or wet beriberi with neurological signs (tingling: 41%), cardiovascular signs (dyspnoea: 42%, thoracic pain: 35%), and edemas of the lower limbs (51%). With treatment the rate of healing was about 97%.

Populations under extreme stress may be at higher risk for beriberi. Displaced populations, such as refugees from war, are susceptible to micronutritional deficiency, including beriberi. The severe nutritional deprivation caused by famine also can cause beriberis, although symptoms may be overlooked in clinical assessment or masked by other famine-related problems. An extreme weight-loss diet can, rarely, induce a famine-like state and the accompanying beriberi.

History

Earliest written descriptions of thiamine deficiency are from Ancient China in the context of chinese medicine. One of the earliest is by Ge Hong in his book Zhou hou bei ji fang (Emergency Formulas to Keep up Your Sleeve) written sometime during 3rd century. Hong called the illness by the name jiao qi, which can be intepreted as "foot qi". He described the symptoms to include swelling, weakness and numbness of the feet. He also acknowledged that the illness could be deadly, and claimed that it could be cured by eating certain foods like fermented soybeans in wine. Better known examples of early descriptions of "foot qi" are by Chao Yuanfang (who lived during 550–630) in his book Zhu bing yuan hou lun (Sources and Symptoms of All Diseases) and by Sun Simiao (581–682) in his book Bei ji qian jin yao fang (Essential Emergency Formulas Worth a Thousand in Gold).

In the late 19th century, beriberi was studied by Takaki Kanehiro, a British-trained Japanese medical doctor of the Imperial Japanese Navy. Beriberi was a serious problem in the Japanese navy: Sailors fell ill an average of four times a year in the period 1878 to 1881, and 35% were cases of beriberi. In 1883, Takaki learned of a very high incidence of beriberi among cadets on a training mission from Japan to Hawaii, via New Zealand and South America. The voyage lasted more than nine months and resulted in 169 cases of sickness and 25 deaths on a ship of 376 men. With the support of the Japanese Navy, he conducted an experiment in which another ship was deployed on the same route, except that its crew was fed a diet of meat, fish, barley, rice, and beans. At the end of the voyage, this crew had only 14 cases of beriberi and no deaths. This convinced Takaki and the Japanese Navy that diet was the cause. In 1884, Takaki observed that beriberi was common among low-ranking crew who were often provided free rice and thus ate little else, but not among crews of Western navies, nor among Japanese officers who consumed a more varied diet. 

In 1897, Christiaan Eijkman, a Dutch physician and pathologist, demonstrated that beriberi is caused by poor diet, and discovered that feeding unpolished rice (instead of the polished variety) to chickens helped to prevent beriberi. The following year, Sir Frederick Hopkins postulated that some foods contained "accessory factors"—in addition to proteins, carbohydrates, fats, and salt—that were necessary for the functions of the human body. In 1901, Gerrit Grijns, a Dutch physician and assistant to Christiaan Eijkman in the Netherlands, correctly interpreted beriberi as a deficiency syndrome, and between 1910 and 1913, Edward Bright Vedder established that an extract of rice bran is a treatment for beriberi. In 1929, Eijkman and Hopkins were awarded the Nobel Prize for Physiology or Medicine for their discoveries.

Etymology

Although according to the Oxford English Dictionary, the term "beriberi" comes from a Sinhalese phrase meaning "weak, weak" or "I cannot, I cannot", the word being duplicated for emphasis, the origin of the phrase is questionable. It has also been suggested to come from Hindi, Arabic and few other languages, with many meanings like "weakness", "sailor" and even "sheep". Such suggested origins were listed by Heinrich Botho Scheube among others. Edward Vedder wrote in his book Beriberi (1913) that "it is impossible to definitely trace the origin of the word beriberi". Word berbere was used in writing at least as early as 1568 by Diogo do Couto, when he described the deficiency in India.

"Kakke", which is a Japanese synonym for thiamine deficiency, comes from the way "jiao qi" is pronounced in Japanese. "Jiao qi" is an old word used in Chinese medicine to describe thiamine deficiency. "Kakke" is supposed to have entered in the Japanese language sometime between the 6th and 8th centuries.

Other animals

Poultry

As most feedstuffs used in poultry diets contain enough quantities of vitamins to meet the requirements in this species, deficiencies in this vitamin do not occur with commercial diets. This was, at least, the opinion in the 1960s.

Mature chickens show signs 3 weeks after being fed a deficient diet. In young chicks, it can appear before 2 weeks of age.

Onset is sudden in young chicks. There is anorexia and an unsteady gait. Later on, there are locomotor signs, beginning with an apparent paralysis of the flexor of the toes. The characteristic position is called "stargazing", meaning a chick "sitting on its hocks and the head in opisthotonos".

Response to administration of the vitamin is rather quick, occurring a few hours later.

Differential diagnosis include riboflavin deficiency and avian encephalomyelitis. In riboflavin deficiency, the "curled toes" is a characteristic symptom. Muscle tremor is typical of avian encephalomyelitis. A therapeutic diagnosis can be tried by supplementing thiamine only in the affected bird. If the animals do not respond in a few hours, thiamine deficiency can be excluded.

Ruminants

Polioencephalomalacia (PEM) is the most common thiamine deficiency disorder in young ruminant and nonruminant animals. Symptoms of PEM include a profuse, but transient, diarrhea, listlessness, circling movements, star gazing or opisthotonus (head drawn back over neck), and muscle tremors. The most common cause is high-carbohydrate feeds, leading to the overgrowth of thiaminase-producing bacteria, but dietary ingestion of thiaminase (e.g., in bracken fern), or inhibition of thiamine absorption by high sulfur intake are also possible. Another cause of PEM is Clostridium sporogenes or Bacillus aneurinolyticus infection. These bacteria produce thiaminases that will cause an acute thiamine deficiency in the affected animal.

Snakes

Snakes that consume a diet largely composed of goldfish and feeder minnows are susceptible to developing thiamine deficiency. This is often a problem observed in captivity when keeping garter and ribbon snakes that are fed a goldfish-exclusive diet, as these fish contain thiaminase, an enzyme that breaks down thiamine.

Wild birds and fish

Thiamine deficiency has been identified as the cause of a paralytic disease affecting wild birds in the Baltic Sea area dating back to 1982. In this condition, there is difficulty in keeping the wings folded along the side of the body when resting, loss of the ability to fly and voice, with eventual paralysis of the wings and legs and death. It affects primarily 0.5–1 kg sized birds such as the herring gull (Larus argentatus), common starling (Sturnus vulgaris) and common eider (Somateria mollissima). Researches noted, "Because the investigated species occupy a wide range of ecological niches and positions in the food web, we are open to the possibility that other animal classes may suffer from thiamine deficiency as well."

In the counties of Blekinge and Skåne (south-most Sweden), mass deaths of several bird species, especially the European herring gull, have been observed since the early 2000s. More recently, species of other classes seems to be affected. High mortality of salmon (Salmo salar) in the river Mörrumsån is reported, and mammals such as the Eurasian Elk (Alces alces) have died in unusually high numbers. Lack of thiamine is the common denominator where analysis is done. In April 2012, the County Administrative Board of Blekinge found the situation so alarming that they asked the Swedish government to set up a closer investigation.

Endocrine system

From Wikipedia, the free encyclopedia

Endocrine system
Main glands of the endocrine system. Note that the thymus is no longer considered part of the endocrine system, as it does not produce hormones.
Details
Identifiers
Latin	Systema endocrinum
MeSH	D004703
FMA	t6uk5iii8iu67i6i6ii78ii8 9584, t6uk5iii8iu67i6i6ii78ii8

The endocrine system is a chemical messenger system comprising feedback loops of hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In humans, the major endocrine glands are the thyroid gland and the adrenal glands. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. The study of the endocrine system and its disorders is known as endocrinology. Endocrinology is a branch of internal medicine.

A number of glands that signal each other in sequence are usually referred to as an axis, for example, the hypothalamic-pituitary-adrenal axis. In addition to the specialized endocrine organs mentioned above, many other organs that are part of other body systems, inluding bone, kidney, liver, heart and gonads, have secondary endocrine functions. For example, the kidney secretes endocrine hormones such as erythropoietin and renin. Hormones can consist of either amino acid complexes, steroids, eicosanoids, leukotrienes, or prostaglandins.

The endocrine system can be contrasted to both exocrine glands, which secrete hormones to the outside of the body using ducts and paracrine signalling between cells over a relatively short distance. Endocrince glands have no ducts, are vascular and commonly have intracellular vacuoles or granules that store their hormones. In contrast, exocrine glands, such as salivary glands, sweat glands, and glands within the gastrointestinal tract, tend to be much less vascular and have ducts or a hollow lumen.

The word endocrine derives via New Latin from the Greek words ἔνδον, endon, "inside, within," and "crine" from the κρίνω, krīnō, "to separate, distinguish".

Structure

Major endocrine systems

The human endocrine system consists of several systems that operate via feedback loops. Several important feedback systems are mediated via the hypothalamus and pituitary.

• TRH – TSH – T3/T4
• GnRH – LH/FSH – sex hormones
• CRH – ACTH – cortisol
• Renin – angiotensin – aldosterone
• leptin vs. insulin

Glands

Endocrine glands are glands of the endocrine system that secrete their products, hormones, directly into interstitial spaces and then absorbed into blood rather than through a duct. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary gland are neuroendocrine organs.

Cells

There are many types of cells that comprise the endocrine system and these cells typically make up larger tissues and organs that function within and outside of the endocrine system.

• Hypothalamus

• Anterior Pituitary Gland

• Pineal Gland

• Posterior Pituitary Gland

• Thyroid Gland
  • Follicular cells of the thyroid gland produce and secrete T₃ and T₄ in response to elevated levels of TRH, produced by the hypothalamus, and subsequent elevated levels of TSH, produced by the anterior pituitary gland, which further regulates the metabolic activity and rate of all cells, including cell growth and tissue differentiation.

• Parathyroid Gland
  • Epithelial cells of the parathyroid glands are richly supplied with blood from the inferior and superior thyroid arteries and secrete parathyroid hormone (PTH). PTH acts on bone, the kidneys, and the GI tract to increase calcium reabsorption and phosphate excretion. In addition, PTH stimulates the conversion of Vitamin D to its most active variant, 1,25-dihydroxyvitamin D₃, which further stimulates calcium absorption in the GI tract.

• Adrenal Glands
  • Adrenal Cortex
  • Adrenal Medulla

• Pancreas
  • Alpha Cells
  • Beta Cells
  • Delta Cells
  • F Cells

• Ovaries
  • Granulosa Cells
• Testis
  • Leydig Cells

Function

Hormones

A hormone is any of a class of signaling molecules produced by glands in multicellular organisms that are transported by the circulatory system to target distant organs to regulate physiology and behaviour. Hormones have diverse chemical structures, mainly of 3 classes: eicosanoids, steroids, and amino acid/protein derivatives (amines, peptides, and proteins). The glands that secrete hormones comprise the endocrine system. The term hormone is sometimes extended to include chemicals produced by cells that affect the same cell (autocrine or intracrine signalling) or nearby cells (paracrine signalling). 

Hormones are used to communicate between organs and tissues for physiological regulation and behavioral activities, such as digestion, metabolism, respiration, tissue function, sensory perception, sleep, excretion, lactation, stress, growth and development, movement, reproduction, and mood.

Hormones affect distant cells by binding to specific receptor proteins in the target cell resulting in a change in cell function. This may lead to cell type-specific responses that include rapid changes to the activity of existing proteins, or slower changes in the expression of target genes. Amino acid–based hormones (amines and peptide or protein hormones) are water-soluble and act on the surface of target cells via signal transduction pathways; steroid hormones, being lipid-soluble, move through the plasma membranes of target cells to act within their nuclei.

Cell signalling

The typical mode of cell signalling in the endocrine system is endocrine signaling, that is, using the circulatory system to reach distant target organs. However, there are also other modes, i.e., paracrine, autocrine, and neuroendocrine signaling. Purely neurocrine signaling between neurons, on the other hand, belongs completely to the nervous system.

Autocrine

Autocrine signaling is a form of signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on the same cell, leading to changes in the cells.

Paracrine

Some endocrinologists and clinicians include the paracrine system as part of the endocrine system, but there is not consensus. Paracrines are slower acting, targeting cells in the same tissue or organ. An example of this is somatostatin which is released by some pancreatic cells and targets other pancreatic cells.

Juxtacrine

Juxtacrine signaling is a type of intercellular communication that is transmitted via oligosaccharide, lipid, or protein components of a cell membrane, and may affect either the emitting cell or the immediately adjacent cells.

It occurs between adjacent cells that possess broad patches of closely opposed plasma membrane linked by transmembrane channels known as connexons. The gap between the cells can usually be between only 2 and 4 nm.

Clinical significance

Disease

Disability-adjusted life year for endocrine disorders per 100,000 inhabitants in 2002.

  no data

  less than 80

  80–160

  160–240

  240–320

  320–400

  400–480

  480–560

  560–640

  640–720

  720–800

  800–1000

  more than 1000

Diseases of the endocrine system are common, including conditions such as diabetes mellitus, thyroid disease, and obesity. Endocrine disease is characterized by misregulated hormone release (a productive pituitary adenoma), inappropriate response to signaling (hypothyroidism), lack of a gland (diabetes mellitus type 1, diminished erythropoiesis in chronic renal failure), or structural enlargement in a critical site such as the thyroid (toxic multinodular goitre). Hypofunction of endocrine glands can occur as a result of loss of reserve, hyposecretion, agenesis, atrophy, or active destruction. Hyperfunction can occur as a result of hypersecretion, loss of suppression, hyperplastic or neoplastic change, or hyperstimulation. 

Endocrinopathies are classified as primary, secondary, or tertiary. Primary endocrine disease inhibits the action of downstream glands. Secondary endocrine disease is indicative of a problem with the pituitary gland. Tertiary endocrine disease is associated with dysfunction of the hypothalamus and its releasing hormones.

As the thyroid, and hormones have been implicated in signaling distant tissues to proliferate, for example, the estrogen receptor has been shown to be involved in certain breast cancers. Endocrine, paracrine, and autocrine signaling have all been implicated in proliferation, one of the required steps of oncogenesis.

Other common diseases that result from endocrine dysfunction include Addison's disease, Cushing's disease and Graves' disease. Cushing's disease and Addison's disease are pathologies involving the dysfunction of the adrenal gland. Dysfunction in the adrenal gland could be due to primary or secondary factors and can result in hypercortisolism or hypocortisolism . Cushing's disease is characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. Some clinical signs of Cushing's disease include obesity, moon face, and hirsutism. Addison's disease is an endocrine disease that results from hypocortisolism caused by adrenal gland insufficiency. Adrenal insufficiency is significant because it is correlated with decreased ability to maintain blood pressure and blood sugar, a defect that can prove to be fatal.

Graves' disease involves the hyperactivity of the thyroid gland which produces the T3 and T4 hormones. Graves' disease effects range from excess sweating, fatigue, heat intolerance and high blood pressure to swelling of the eyes that causes redness, puffiness and in rare cases reduced or double vision.

Other animals

A neuroendocrine system has been observed in all animals with a nervous system and all vertebrates have an hypothalamus-pituitary axis. All vertebrates have a thyroid, which in amphibians is also crucial for transformation of larvae into adult form. All vertebrates have adrenal gland tissue, with mammals unique in having it organized into layers. All vertebrates have some form of a renin–angiotensin axis, and all tetrapods have aldosterone as a primary mineralocorticoid.

Additional images

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  Female endocrine system.
  
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  Male endocrine system