Anatomy A – Z – Page 9

ByRx Harun

Blood – Types, Functions, Physiology

Blood is a constantly circulating fluid providing the body with nutrition, oxygen, and waste removal. Blood is mostly liquid, with numerous cells and proteins suspended in it, making blood “thicker” than pure water. The average person has about 5 liters (more than a gallon) of blood.

Components of Blood

Blood is composed of plasma and three types of cells: red blood cells, white blood cells, and platelets.

Red blood cells – look like discs that are thinner in the middle. They can easily change shape to “squeeze through” narrow blood vessels. Unlike many other cells, red blood cells have no nucleus (“information center”). All red blood cells contain a red pigment known as hemoglobin. Oxygen binds to hemoglobin and is transported around the body in that way. In tiny blood vessels in the lung, the red blood cells pick up oxygen from inhaled (breathed in) air and carry it through the bloodstream to all parts of the body. When they reach their goal, they release it again. The cells need oxygen for metabolism, which creates carbon dioxide as a waste product. The carbon dioxide is absorbed from the cells by the blood plasma (some of it binds to hemoglobin too) and is transported back to the lungs in the bloodstream. There it leaves the body when we breathe out. Red blood cells can also pick up or release hydrogen and nitrogen. By picking up or releasing hydrogen they help to keep the pH of the blood stable; when they release nitrogen the blood vessels expand, and blood pressure falls. Red blood cells live for about 120 days. When they’re too old or damaged, they’re broken down in the bone marrow, spleen, or liver.
White blood cells – (leukocytes) have a cell nucleus and don’t contain hemoglobin. There are different types of white blood cells. They are classified according to how their nucleus is shaped and what the inside of the cell looks like under a microscope. Granulocytes have small granules inside them. Monocytes and lymphocytes also contain granules, but their granules are extremely small and can’t be seen under a microscope. There are many more red blood cells than white blood cells in the blood. But white blood cells can leave the bloodstream and move into tissues in the body. White blood cells play an important role in the immune system. Some fight intruders such as bacteria, viruses, parasites or fungi themselves and render them harmless. Others make antibodies, which specifically target foreign objects or germs like viruses. Leukocytes also play a part in allergic reactions: For instance, they are the reason why people with a dust mite allergy get a runny nose when they come into contact with dust. Certain lymphocytes can also kill cancerous cells that have developed elsewhere in the body. Most white blood cells have a lifespan of only a few hours to several days. Some lymphocytes can stay in the body for many years, though.
Blood platelets – (thrombocytes) also look like little discs, as do red blood cells, and they also have no cell nucleus. But they are much smaller than red blood cells. They play an important role in blood clotting: If a blood vessel is damaged – for instance, if you accidentally cut yourself with a knife – the healing process begins with blood platelets gathering and clumping together on the inside of the damaged wall of the blood vessel. This quickly causes a plug to form and close the wound temporarily. At the same time, strong protein threads are made and they hold the clump in place, attached to the wound. Thrombocytes usually live only 5 to 9 days. Old thrombocytes are mainly broken down in the spleen.

Key Points

Red blood cells’ primary function is to transport oxygen between the lungs and tissues of the body.

White blood cells, the cells of the immune system, provide defense against pathogens.

Platelets are involved in clot formation during wound healing.

Blood is an extracellular matrix tissue in which various blood cells are suspended in the plasma matrix.

Blood is vital for normal metabolic function due to the transfer of oxygen, carbon dioxide, and glucose to and from the body’s tissues. It also transports a number of other cells and molecules throughout the body.

Key Terms

plasma: The straw-colored or pale yellow liquid component of blood in which blood cells are suspended.

hemoglobin: The iron-containing substance in red blood cells that binds to and transports oxygen from the alveoli of the lungs to the tissues of the body. It consists of a protein (globulin) and haem (a porphyrin ring with an atom of iron at its center).

Composition of Blood: Two tubes of EDTA-anticoagulated blood. Left tube: after standing, the RBCs have settled at the bottom of the tube.

Blood is a circulating tissue composed of fluid, plasma, and cells. The cellular components of blood are erythrocytes (red blood cells, or RBCs), leukocytes (white blood cells, or WBCs), and thrombocytes (platelets). By volume, the RBCs constitute about 45% of whole blood, the plasma about 54.3%, and white blood cells about 0.7%. Platelets make up less than 1%. Although it consists of cells suspended in fluid, blood is still considered a tissue as it is technically a type of extracellular matrix.

Blood enables the transport of cells and molecules between parts of the body. Oxygen, carbon dioxide, and glucose are among the most vital molecules transported in the blood. Blood cells are essential for normal metabolic and immune system function.

Erythrocytes (RBCs)

Erythrocytes are discs measuring about seven to eight micrometers in diameter. RBCs contain hemoglobin molecules that bind to oxygen so they can be transported to tissues. Mature RBCs lack a nucleus and organelles and have no nuclear DNA. RBCs, endothelial vessel cells, and other blood cells are also marked by glycoproteins that define the different blood types. The ratio of RBCs to blood plasma is referred to as the hematocrit and is normally about 45%. The combined surface area of all red blood cells of the human body would be roughly 2,000 times greater than the body’s exterior surface.

Leukocytes (WBCs)

Leukocytes are usually larger in size (10–14 micrometers in diameter) than red blood cells. They lack hemoglobin but contain organelles, a nucleus, and nuclear DNA. WBCs are the main functional component of the body’s immune system. They destroy and remove old or aberrant cells and cellular debris, as well as attack infectious agents (pathogens) and foreign substances. There are several different types of white blood cells: basophils, eosinophils, neutrophils, monocytes, natural killer cells, B- and T-cell lymphocytes, macrophages, and dendritic cells, all of which perform distinct functions.

Thrombocytes (Platelets)

Thrombocytes measure between one to two micrometers in diameter. These membrane-bound cell fragments lack nuclei and are responsible for blood clotting (coagulation). They result from the fragmentation of large cells called megakaryocytes, which are derived from stem cells in the bone marrow. Platelets are produced at a rate of 200 billion per day, a process regulated by the hormone thrombopoietin. Platelets contain mitochondrial DNA, but not nuclear DNA.

The sticky surface of platelets allows them to accumulate at the site of broken blood vessels to form a clot, due in part to the release of clotting factors that occurs during endothelial injury to blood vessels. This process is called hemostasis. Platelets secrete factors that increase local platelet aggregation (e.g., thromboxane A), enhance vasoconstriction (e.g., serotonin), and promote blood coagulation (e.g., thromboplastin, fibrinogen). Platelets are critically important for wound healing, which can only occur once the clot forms and bleeding ceases completely.

Physical Characteristics and Volume

Blood contains plasma and blood cells, some of which have hemoglobin that makes blood red. The average blood volume in adults is five liters.

Key Points

Blood accounts for 8% of human body weight. The average adult has a blood volume of roughly five liters (1.3 gal).

By volume, red blood cells constitute about 45% of whole blood, the plasma about 54.3%, and white blood cells about 0.7%. Platelets make up less than 1%. Blood also contains proteins such as albumins.

Hemoglobin is the principal determinant of blood color invertebrates. Each molecule has four heme groups, and their interaction with various molecules alters the exact color of blood.

Veins appear to be blue because blue light penetrates the skin better than other forms of light. Deoxygenated blood is not blue.

Blood volume is a regulated variable that is proportional to blood pressure and a component of homeostasis.

Injury can cause blood loss. A healthy adult can lose almost 20% of blood volume (1 L) before the first symptom (restlessness) begins, and 40% of volume (2 L) before hypovolemic shock sets in.

Key Terms

erythrocyte: An anucleate cell in the blood involved with the transport of oxygen. Also called a red blood cell because of the red coloring of hemoglobin.
hemoglobin: The iron-containing substance in red blood cells that transports oxygen from the lungs to the rest of the body. It consists of a protein (globulin) and haem (a porphyrin ring with an atom of iron at its center).
tissue perfusion: The amount of blood that can reach the tissues to supply them with oxygen and glucose.

Blood is a specialized bodily fluid in animals that delivers necessary substances, such as nutrients and oxygen, to the cells and transports metabolic waste products away from those same cells. Blood plays many roles in sustaining life and has physical characteristics that distinguish it from other body tissues.

Physical Characteristics

Blood is a fluid that is technically considered connective tissue. It is an extracellular matrix in which blood cells are suspended in plasma. It normally has a pH of about 7.4 and is slightly denser and more viscous than water. Blood contains red blood cells (RBCs), white blood cells (WBCs), platelets, and other cell fragments, molecules, and debris. Albumin is the main protein found in plasma, and it functions to regulate the colloidal osmotic pressure of blood.

Blood appears red because of the high amount of hemoglobin, a molecule found on RBCs. Each hemoglobin molecule has four heme groups that interact with various molecules, which alters the exact color. In oxygenated blood found in the arterial circulation, hemoglobin-bound oxygen creates a distinctive red color.

Deoxygenated blood is a darker shade of red. It is present in veins and can be seen during blood donation or lab tests. Carbon monoxide poisoning causes bright red blood due to the formation of carboxyhemoglobin. In cyanide poisoning, venous blood remains oxygenated, increasing the redness. Under normal conditions, blood can never truly be blue, although most visible veins appear blue because only blue light can penetrate deeply enough to illuminate veins beneath the skin.

Blood Volume

Blood generally accounts for 8% of the human body weight. The average adult has a blood volume of roughly five liters (1.3 gals). By volume, red blood cells constitute about 45% of whole blood, the plasma about 54.3%, and white cells about 0.7%, with platelets making up less than 1%.

Composition of blood: Two tubes of EDTA-anticoagulated blood. Left tube: After standing, the RBCs have settled at the bottom of the tube. Right tube: contains freshly drawn blood.

Blood volume is a regulated variable that is directly proportional to blood pressure through the output of the heart. In order to maintain homeostasis, blood volume and blood pressure must be high enough that blood can reach all of the body’s tissues, a process called tissue perfusion. Most tissues can survive without perfusion for a short amount of time, but the brain needs a continuous supply of oxygen and glucose to stay alive.

Many mechanisms exist to regulate blood volume and tissue perfusion, including renal water excretion in the kidney, the pumping activity of the heart, and the abilities of the arteries to constrict or dilate. When blood volume becomes too low, such as from an injury, dehydration, or internal bleeding, the body will enter into a state of hypovolemic shock, in which tissue perfusion decreases too much. A healthy adult can lose almost 20% of blood volume (1 L) before the first symptom, restlessness, begins, and 40% of volume (2 L) before hypovolemic shock sets in. Conversely, higher than normal blood volume may cause hypertension, heart failure, and aneurysms.

Functions of Blood

The main function of blood is to supply oxygen to tissues and remove carbon dioxide. Other functions include pH regulation and thermoregulation.

Key Points

The main function of blood is to carry oxygen from lungs and deliver it to the body, where it is released and carbon dioxide is consumed.

The tissues of the body cannot survive without blood perfusion. Without blood, tissues may undergo hypoxia, ischemia, or infarction depending on the severity of the deficiency.

The blood is involved in the homeostasis of variables such as temperature, blood volume, blood pressure, blood pH, and blood glucose levels.

Other important blood functions include carbon dioxide transport and hormone signaling.

The blood is involved in immune system functions such as white blood cell activity and blood clotting.

Key Terms

hypoxia: A condition in which tissues are deprived of an adequate supply of oxygen for metabolic purposes; anoxia.
coagulation: The process by which blood forms solid clots.

Blood performs many functions critical for sustaining metabolic physiological processes in complex organisms. Blood is involved in everything from gas exchange to nutrient transport to the immune system and homeostatic functions.

Oxygen and Glucose Transport

Blood’s primary function is to transport molecules around the body to support critical metabolic processes. All cells require oxygen and glucose to undergo cellular respiration. Tissues cannot survive very long without these two molecules. Disruption of this process is most dangerous to the brain, which can survive only about two minutes without oxygen and glucose. These terms are used to describe oxygen or blood deficiency to tissues in the body:

Hypoxia: a state in which the tissues do not receive adequate oxygen supply, generally due to decreased tissue perfusion or decreased oxygen intake.
Ischemia: a reversible condition in which tissue does not receive adequate blood supply, usually from an obstructed or ruptured blood vessel.
Infarction: a usually irreversible condition in which tissues die as a result of prolonged oxygen or blood supply.

Most tissues can survive in a hypoxic or ischemic state for a few hours before infarction sets in. Heart infarction, which often occurs during a heart attack, will cause infarction in other tissues as blood is no longer pumped.

In addition to oxygen and glucose, the blood transports several other important molecules. Carbon dioxide, which travels through the blood mostly as bicarbonate, is transported from tissues as a waste product of cellular respiration to the lungs during gas exchange. Many hormones (chemical messengers) also travel through the blood as a form of communication between interrelated organs, which are often involved in homeostatic control.

Immune System Functions

White blood cells and antibodies circulate through the blood and destroy any foreign invaders ( pathogens ) that they encounter. Inflammation occurs in blood vessels due to the release of inflammatory mediators in the blood. This causes vasodilation and redness as other white blood cells are drawn to the region through the bloodstream to destroy infectious pathogens. They may also find molecular markers of pathogens called antigens and take them to lymphatic organs to stimulate powerful adaptive immune system responses.

The blood also has the ability to undergo clotting in response to vascular injury such as bleeding. Normally a series of clotting and anti-clotting factors are kept in balance through the blood so that no clotting occurs, but when endothelial cells are injured, the clotting factors are increased and cause blood to clot. Circulating platelets in the blood arrive at the injury site and form a mesh and plug to coagulate the blood and stop the bleeding. Wound healing can only begin after this clotting response occurs.

Homeostatic Functions

Blood is involved in maintaining homeostasis in several ways. Temperature regulation occurs in part as a result of the dilation and constriction of vessels in the blood. Blood pH is a regulated variable of the respiratory system because the pH of blood is directly proportional to the amount of carbon dioxide dissolved in the blood. This makes blood pH an indicator of respiratory homeostasis. Blood glucose levels are regulated by insulin and glucagon secretion. Blood volume and blood pressure are directly proportional regulated variables that are tied to the activity of the heart and the fluid retention of the kidney. If any of these variables are too high or too low, severe problems can occur. For that reason, a number of complex negative feedback mechanisms exist to keep all variables within homeostatic range, despite influences from the internal and external environments.

Blood Plasma

Plasma comprises about 55% of total blood volume. It contains proteins and clotting factors, transports nutrients, and removes waste.

Key Points

The majority of blood volume consists of plasma. This aqueous solution is 92% water. It also contains blood plasma proteins, including serum albumin, blood-clotting factors, and immunoglobulins.

Plasma circulates respiratory gases, dissolved nutrients, and other materials. It also removes waste products.

Globulins are a diverse group of proteins that primarily transport other substances and inhibit certain enzymes.

Albumins maintain an osmotic balance between the blood and tissue fluids through the exertion of oncotic pressure.

Fibrinogen is the main clotting protein found in plasma. It is responsible for stopping blood flow during wound healing.

Key Terms

platelet: A small, colorless, disc-shaped particle found in the blood of mammals. It plays an important role in blood clot formation.
immunoglobulin: Any of the glycoproteins in the blood serum that respond to invasion by foreign antigens and that protect the host by removing pathogens; an antibody.
albumins: A plasma protein that exerts a high degree of oncotic pressure to pull water and other substances into tissues.

About 55% of blood is blood plasma, a straw-colored liquid matrix in which blood cells are suspended. It is an aqueous solution containing about 90% water, 8% soluble blood plasma proteins, 1% electrolytes, and 1% elements in transit. One percent of the plasma is salt, which helps with pH. Human blood plasma volume averages about 2.7–3.0 liters.

Molecular Contents of Plasma

Composition of Blood: Two tubes of EDTA-anticoagulated blood. Left tube: after standing, the RBCs have settled at the bottom of the tube.

Plasma contains molecules that are transported around the body. Respiratory gases, such as oxygen and carbon dioxide, may be dissolved directly in the plasma. However, most oxygen is hemoglobin bound, and most carbon dioxide is converted to bicarbonate ions in the plasma. Hormones and nutrients such as glucose, amino acids and proteins, lipids and fatty acids, and vitamins are also dissolved in the plasma. Waste products are carried through the plasma during their removal, including urea and ammonia.

Plasma Proteins

The largest group of solutes in plasma contains three important proteins: albumins, globulins, and clotting proteins.

Albumins

Albumins, produced in the liver, make up about two-thirds of the proteins in plasma. Albumins maintain the osmotic balance between the blood and tissue fluids. These proteins exert a force that pulls water towards them, which is called oncotic or osmotic pressure. During inflammation, albumins leave the vascular endothelium and enter the tissues, which transports water and some of the plasma into the interstitial fluid. This is the principal cause of exudate edema, which is the swelling that indicates inflammation.

Albumins also assist in the transport of different materials, such as vitamins and certain molecules and drugs (e.g. bilirubin, fatty acids, and penicillin) due to the force exerted by their oncotic pressure. The plasma that is pulled into the tissues by albumin-exerted oncotic pressure becomes interstitial fluid. This gradually drains into the lymphatic system which it turns recirculates back into the plasma of the circulatory system.

Globulins

Globulins are a diverse group of proteins designated into three groups, gamma, alpha, and beta, based on how far they move during electrophoresis tests. Their main function is to transport various substances in the blood. For example, the beta globulin transferrin can transport iron. Most gamma globulins are antibodies (immunoglobulin), which assist the body’s immune system in defense against infections and illness. Alpha globulins are notable for inhibiting certain proteases, while beta globulins often function as enzymes in the body.

Clotting Factors

Clotting proteins are mainly produced in the liver. Twelve proteins are known as “clotting factors” participate in the cascade clotting process during endothelial injury. One important clotting factor is fibrinogen. Fibrinogen generates fibrin when activated by the coagulant thrombin, which forms a mesh that clots blood with the assistance of a platelet plug. Normally, anticoagulants and fibrinolytic in the plasma, such as plasmin and heparin, break up fibrin clots and inactivate thrombin. However, during endothelial injury, damaged cells will release tissue factor, another type of clotting factor that causes a cascade of thrombin production that will overpower the anticoagulants and cause a clotting response.

The serum is a term used to describe plasma that has been removed from its clotting factors. Serum still contains albumin and globulins, which are often called serum proteins as a result.

Disorders

General medical

Disorders of volume

Injury can cause blood loss through bleeding.^[rx] A healthy adult can lose almost 20% of blood volume (1 L) before the first symptom, restlessness, begins, and 40% of volume (2 L) before shock sets in. Thrombocytes are important for blood coagulation and the formation of blood clots, which can stop bleeding. Trauma to the internal organs or bones can cause internal bleeding, which can sometimes be severe.
Dehydration can reduce the blood volume by reducing the water content of the blood. This would rarely result in shock (apart from the very severe cases) but may result in orthostatic hypotension and fainting.

Disorders of circulation

Shock is the ineffective perfusion of tissues and can be caused by a variety of conditions including blood loss, infection, poor cardiac output.
Atherosclerosis reduces the flow of blood through arteries because atheroma lines arteries and narrows them. Atheroma tends to increase with age, and its progression can be compounded by many causes including smoking, high blood pressure, excess circulating lipids (hyperlipidemia), and diabetes mellitus.
Coagulation can form a thrombosis, which can obstruct vessels.
Problems with blood composition, the pumping action of the heart, or narrowing of blood vessels can have many consequences including hypoxia (lack of oxygen) of the tissues supplied. The term ischemia refers to tissue that is inadequately perfused with blood, and infarction refers to tissue death (necrosis), which can occur when the blood supply has been blocked (or is very inadequate).

Hematological

Anemia

Insufficient red cell mass (anemia) can be the result of bleeding, blood disorders like thalassemia, or nutritional deficiencies, and may require one or more blood transfusions. Anemia can also be due to a genetic disorder in which the red blood cells simply do not function effectively. Anemia can be confirmed by a blood test if the hemoglobin value is less than 13.5 gm/dl in men or less than 12.0 gm/dl in women.^[34] Several countries have blood banks to fill the demand for transfusable blood. A person receiving a blood transfusion must have a blood type compatible with that of the donor.
Sickle-cell anemia

Disorders of cell proliferation

Leukemia is a group of cancers of the blood-forming tissues and cells.
Non-cancerous overproduction of red cells (polycythemia vera) or platelets (essential thrombocytosis) may be premalignant.
Myelodysplastic syndromes involve the ineffective production of one or more cell lines.

Disorders of coagulation

Hemophilia is a genetic illness that causes dysfunction in one of the blood’s clotting mechanisms. This can allow otherwise inconsequential wounds to be life-threatening, but more commonly results in hemarthrosis, or bleeding into joint spaces, which can be crippling.
Ineffective or insufficient platelets can also result in coagulopathy (bleeding disorders).
Hypercoagulable state (thrombophilia) results from defects in the regulation of platelet or clotting factor function and can cause thrombosis.

Infectious disorders of blood

Blood is an important vector of infection. HIV, the virus that causes AIDS, is transmitted through contact with blood, semen, or other body secretions of an infected person. Hepatitis B and C are transmitted primarily through blood contact. Owing to blood-borne infections, bloodstained objects are treated as a biohazard.
Bacterial infection of the blood is bacteremia or sepsis. Viral Infection is viremia. Malaria and trypanosomiasis are blood-borne parasitic infections.

References

ByRx Harun

Endocrine Tissues and Organs

In terms of name recognition, the pituitary, thyroid, and adrenal glands get a lion’s share of the glory. These organs have no significant function other than to produce hormones and were relatively easy to study years ago using “remove it and see what happens” type of experiments. There are however a number of other endocrine tissues and hormones that, while less well known, are just as important in controlling vital bodily functions. In fact, there is probably no tissue that is not, in some way, an endocrine tissue.

Several of the “other” endocrine cells and tissues discussed here are sometimes referred to as the diffuse endocrine system to reflect the concept that many organs house clusters of cells that secrete hormones. The kidney, for example, contains scattered cells that secrete erythropoietin, a hormone essential for the production of red blood cells. Even the heart contains cells that produce the atrial natriuretic hormone, which is important in sodium and water balance.

The endocrine system is the system in which a message is transmitted from endocrine tissues; for example, the pancreas and insulin, by circulating body fluids mainly the bloodstream. The specificity of the signal depends on the receptors on target tissues and cells. The signal is released in the form of a chemical messenger known as hormones. Each hormone can have different effects in similar tissues depending on the receptor present; an example being epinephrine and how in arterioles it can cause vasodilation and/or vasoconstriction depending on the specific receptors present. Endocrine cells within endocrine glands release hormones conveyed particularly by the bloodstream and can act on distant cells: examples of endocrine glands being the anterior pituitary, the thyroid gland, and the adrenal gland.

Eicosanoids

The eicosanoids are signaling molecules that exert complex control over many bodily systems, mainly in inflammation or immunity.

Key Points

Eicosanoids are signaling molecules made by the oxidation of 20-carbon essential fatty acids (EFAs).

Eicosanoids derive from either omega-3 or omega-6 EFAs.

Omega-6 eicosanoids are generally more pro-inflammatory than omega-3 eicosanoids.

Anti-inflammatory drugs such as aspirin act by down-regulating eicosanoid synthesis.

There are four families of eicosanoids: prostaglandins, prostacyclins, thromboxanes, and leukotrienes.

Key Terms

omega-6: Fatty acids (also called ω6 fatty acids or n−6 fatty acids) that are commonly found in poultry and plant oils.

omega-3: Fatty acids (also called ω3 fatty acids or n−3 fatty acids) that are commonly found in marine and plant oils.

essential fatty acid: Any fatty acid required for the human metabolism that cannot be synthesized by the body and that must be present in the diet; it was originally designated as vitamin F.

In biochemistry, eicosanoids are signaling molecules made by the oxidation of 20-carbon essential fatty acids (EFAs). The networks of controls that depend upon eicosanoids are among the most complex in the human body.

Eicosanoids are derived from either omega-3 (ω-3) or omega-6 (ω-6) EFAs. The ω-6 eicosanoids are generally pro-inflammatory; ω-3s are much less so. An excess of
ω-6 to ω-3 fatty acids is common in western diets and is thought to encourage certain inflammatory disorders such as arthritis, cardiovascular disease, and cancers of the digestive system.

There are four families of eicosanoids:

Prostaglandins
Prostacyclins
Thromboxanes
Leukotrienes

For each, there are two or three separate series, derived either from an ω-3 or ω-6 EFA. These series’ different activities largely explain the health effects of ω-3 and ω-6 fats.

Biosynthesis

Two families of enzymes catalyze EFA oxygenation to produce the eicosanoids:

Cyclooxygenase, or COX, which generates the prostanoids.
Lipoxygenase, or LOX, in several forms.

Eicosanoids are not stored within cells; they are synthesized as required. They derive from the EFAs that make up the cell and nuclear membranes. Biosynthesis is initiated when a cell is activated by mechanical trauma, cytokines, growth factors, or other stimuli.

Function and Pharmacology

Eicosanoids exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system. Eicosanoids typically act as local hormones, acting on the same cell or nearby cells and then are rapidly inactivated.

Anti-inflammatory drugs such as aspirin and other NSAIDs act by down-regulating eicosanoid synthesis to prevent local and systemic inflammation.

This is a diagram that shows the pathways in the biosynthesis of eicosanoids from arachidonic acid.

Biosynthesis of eicosanoids: Pathways in the biosynthesis of eicosanoids from arachidonic acid.

Growth Factors

A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation, and cellular differentiation.

Key Points

Growth factors, cytokines, and hormones are all chemical messengers that mediate intercellular communication.

A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation, and cellular differentiation.

A cytokine is a small protein involved in cell signaling.

A hormone is any member of a class of signaling molecules that is secreted by ductless glands and are transported by the circulatory system.

Cytokines and hormones are not always growth factors.

Growth factors, cytokines, and hormones are all chemical messengers that mediate intercellular communication. Confusion arises due to their overlaps in function and definition.

Growth Factors

A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation, and cellular differentiation. An example is granulocyte-macrophage colony-stimulating factor (GM-CSF), a growth factor that stimulates the production of white blood cells. Growth factors are typically cytokines or hormones, but not all cytokines and hormones are growth factors.

Cytokines

A cytokine is a small protein involved in cell signaling. Some cytokines are involved in growth, such as GM-CSF, and so are classed as growth factors, but many others are not. Confusingly, cytokine and growth factor are sometimes used as interchangeable terms.

A cytokine differs from a hormone in that it is not secreted from a gland.

Hormones

A hormone is any member of a class of signaling molecules secreted by ductless glands that are transported by the circulatory system. As with cytokines, some are involved with growth, such as the growth hormone produced by the anterior pituitary gland, and may be classed as growth factors, but others are not.

Hormones are secreted from specialized ductless glands into the circulatory system, differentiating them from cytokines.

This chart shows the complexity of interactions, and the multitude of growth factors that stimulate proliferation and differentiation of cells that is common to all cell types. The majority of growth factors shown above are cytokines such as GM-CSF, however the hormone EPO secreted by the kidney plays a key role in erythrocyte (red blood cell) proliferation.

Hematopoiesis as it occurs in humans, with important hemopoietic growth factors affecting differentiation: This chart shows the complexity of interactions and the multitude of growth factors that stimulate proliferation and differentiation of cells that is common to all cell types. The majority of growth factors shown above are cytokines such as GM-CSF, however, the hormone EPO secreted by the kidney plays a key role in erythrocyte (red blood cell) proliferation.

Other Hormone-Producing Structures

Many issues within the body release hormones including the placenta, kidneys, digestive system, and adipose tissue.

Key Points

There are several other organs in the body that secrete hormones although they are generally not thought of as being part of the endocrine system.

The kidneys secrete many hormones that help maintain blood pressure and volume, including erythropoietin, calcitriol, and atrial natriuretic hormone, as well as several proteins and enzymes.

The heart secretes atrial natriuretic hormone to reduce blood pressure.

Many hormones are released in the digestive system to help in the absorption and breakdown of food, including gastrin, secretin, and cholecystokinin.

Adipose tissue, or fat, is a major endocrine organ and produces hormones such as leptin and estrogen.

The placenta secretes several important hormones in pregnancy, including human chorionic gonadotropin, human placental lactogen, estrogen, and progesterone.

There are several other organs in the body that secrete hormones although they are generally not thought of as being part of the endocrine system.

The Kidneys

The kidneys secrete a variety of hormones, including erythropoietin, and the enzyme renin. Erythropoietin is released in response to hypoxia in the renal circulation. It stimulates erythropoiesis (production of red blood cells ) in the bone marrow. Part of the renin-angiotensin-aldosterone system, renin is an enzyme involved in the regulation of aldosterone levels.

The Heart

Atrial natriuretic hormone (ANH) is a powerful vasodilator and a protein hormone secreted by heart muscle cells. It is involved in the homeostatic control of body water, sodium, potassium, and fat.

ANH is released by muscle cells in the upper chambers (atria) of the heart in response to high blood pressure. ANH acts to reduce the water, sodium, and adipose loads on the circulatory system to reduce blood pressure.

Stomach and Small Intestine

There are at least five hormones that aid and regulate the digestive system in mammals.

Gastrin is in the stomach and stimulates the gastric glands to secrete pepsinogen (an inactive form of the enzyme pepsin) and hydrochloric acid. Secretion of gastrin is stimulated by food arriving in the stomach. The secretion is inhibited by low pH.
Secretin is in the duodenum and signals the secretion of sodium bicarbonate in the pancreas and it stimulates the secretion of bile in the liver. This hormone responds to the acidity of the chyme.
Cholecystokinin (CCK) is in the duodenum and stimulates the release of digestive enzymes in the pancreas and stimulates the emptying of bile in the gall bladder. This hormone is secreted in response to fat in chyme.
Gastric inhibitory peptide (GIP) is in the duodenum and decreases the stomach churning, which in turn slows the emptying in the stomach. Another function is to induce insulin secretion.
Motilin is in the duodenum and increases the migrating myoelectric complex component of gastrointestinal motility and stimulates the production of pepsin.

Adipose Tissue

Adipose, or fat, tissue is loose connective tissue composed of adipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body.

Adipose tissue has in recent years been recognized as a major endocrine organ, as it produces hormones such as:

Leptin, which targets the hypothalamus and is important in regulating food intake.
Estrogen, which plays a key role in sexual function.
Resistin, which targets several tissues with unknown function.

The Placenta

The placenta endocrine function in humans, aside from serving as the conduit for oxygen and nutrients for the fetus, secretes hormones that are important during pregnancy, such as human chorionic gonadotropin, human placental lactogen, estrogen, and progesterone.

Male and Female Gonads

The gonads in males are the testes and the gonads in females are the ovaries.

Key Points

The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system.

Ovaries secrete both estrogen and progesterone, and also androgens such as testosterone.

The testicle is the male reproductive gonad in humans.

The primary functions of the testes are to produce sperm ( spermatogenesis ) and to produce androgens, primarily testosterone.

The functions of the testicle are influenced by gonadotropic hormones that are produced by the anterior pituitary.

Both testosterone and follicle-stimulating hormone are needed to support spermatogenesis.

Key Terms

gonad: A sex organ that produces gametes; specifically, the testes or ovaries.

testes: The male gonads responsible for the production of sperm and the secretion of testosterone.

ovaries: The female gonads responsible for the production of ova and the secretion of the key hormones
estrogen and progesterone.

The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. Both gonads in males and females are endocrine glands.

The Ovaries

The ovary is a paired, ovum-producing, reproductive organ located in the lateral wall of the pelvis in a region called the ovarian fossa. The fossa usually lies beneath the external iliac artery and in front of the ureter and the internal iliac artery.

This is a cut-away illustration of a female (human) ovary. The blood supply for the human female reproductive organs is highlighted.

Ovary: Blood supply of the human female reproductive organs. The left ovary is visible above the label ovarian arteries.

The ovaries are not attached to the fallopian tubes but to the outer layer of the uterus via the ovarian ligaments. Usually each ovary takes turns releasing eggs every month; however, if there was a case where one ovary was absent or dysfunctional then the other ovary would continue providing eggs to be released.

Ovaries secrete both estrogen and progesterone. Estrogen is responsible for the development of the secondary sex characteristics of human females at puberty and for the maturation and maintenance of the reproductive organs in their mature functional state. Progesterone functions with estrogen by promoting menstrual cycle changes in the endometrium. The ovaries also secrete testosterone, although at a much lower level than in males.

Progesterone and estrogen are secreted by granulosal cells, whereas testosterone is produced by thecal cells. Prior to ovulation, follicle-stimulating hormone is secreted by the granulosal cells that convert testosterone into
estradiol.

The Testes

The testes are the male reproductive gonads in humans. Like the ovaries, to which they are homologous, testes are components of both the reproductive system and the endocrine system. The primary functions of the testes are to produce sperm (spermatogenesis) and androgens, primarily testosterone.

This is a schematic diagram of male (human) testicles.

Testicles: Diagram of male (human) testicles.

The functions of the testicles are influenced by gonadotropic hormones, that are produced by the anterior pituitary. Luteinizing hormone results in testosterone release. The presence of both testosterone and follicle-stimulating hormone is needed to support spermatogenesis. Testosterone is secreted by
Leydig cells, which are located between the
seminiferous tubules.

The testes are located in the scrotum (a sac of skin between the upper thighs). In the male fetus, the testes develop near the kidneys, then descend into the scrotum just before birth. Each testis is about 1 1/2 inches long by 1 inch wide.

Placenta

The placenta is an organ that connects the developing fetus to the mother’s blood supply.

Key Points

The placenta functions as a fetomaternal organ with two components: the fetal placenta and the maternal placenta.

The placenta connects to the fetus by an umbilical cord, which contains two arteries and one vein.

The perfusion of the intervillous spaces of the placenta with maternal blood allows the transfer of nutrients and oxygen from the mother to the fetus and the transfer of waste products and carbon dioxide back from the fetus to the maternal blood supply.

Waste products excreted from the fetus include: urea, uric acid, and creatinine, which are transferred to the maternal blood by diffusion across the placenta.

In humans, the placenta also secretes hormones ( human chorionic gonadotropin, human placental lactogen, estrogen, and progesterone ) that are important during pregnancy.

Key Terms

placenta: A vascular organ present only in the female during gestation. It supplies food and oxygen from the mother to the fetus, and passes back waste. It is implanted in the wall of the uterus and links to the fetus through the umbilical cord. It is expelled after birth.

umbilical cord: The flexible structure connecting a fetus with the placenta that transports nourishment to the fetus and removes waste.

human chorionic gonadotropin: A hormone produced during pregnancy that is made by the developing placenta after conception, and later by the placental component.

The placenta is an organ connecting the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother’s blood supply.

The placenta functions as a feto-maternal organ with two components:

The fetal placenta, which develops from the same sperm and egg cells that form the fetus.
The maternal placenta, which develops from the maternal uterine tissue.

In humans, the placenta averages 22 cm in length and 2–2.5 cm in thickness; it typically weights 500g and is a dark-reddish color due to the large quantities of blood contained within.

This is a schematic of a mother's womb. The fetus is seen connected to the placenta by the umbilical cord. The placenta is an organ connecting the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply.

Placenta: The placenta is an organ connecting the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother’s blood supply.

The placenta connects to the fetus by an umbilical cord of approximately 55–60 cm in length that contains two arteries and one vein. Unlike the majority of systemic vessels the arteries in the umbilical cord carry de-oxygenated blood and the vein carries oxygenated blood.

The umbilical cord inserts into the chorionic plate of the placenta. Vessels branch out over the surface of the placenta and further divide to form a network covered by a thin layer of cells. This results in the formation of villous tree structures that allow for the efficient exchange of gasses and nutrients.

Functions of the Placenta

The major functions of the placenta include:

Nutrition
Excretion
Immunity and protection
Endocrine function

The perfusion of the intervillous spaces of the placenta with maternal blood allows the transfer of nutrients and oxygen from the mother to the fetus and the transfer of waste products and carbon dioxide back from the fetus to the maternal blood supply.

Waste products excreted from the fetus—urea, uric acid, and creatinine—are transferred to the maternal blood by diffusion across the placenta.

IgG antibodies can pass through the human placenta, thereby providing protection to the fetus in utero. The placenta functions as a selective maternal–fetal barrier against the transmission of microbes to the fetus. However, deficiency in this function may cause mother-to-child transmission of infectious diseases.

Endocrine Functions

The placenta also secretes hormones that are important during pregnancy. These hormones include:

Human chorionic gonadotropin
Human placental lactogen
Estrogen
Progesterone

Human chorionic gonadotropin (hCG) is the first placental hormone produced, which can be found in maternal blood and urine as early as the first missed menstrual period (shortly after implantation has occurred) through about the hundredth day of pregnancy.

This is the hormone analyzed by a pregnancy test; a false-negative result from a pregnancy test may be obtained before or after this period. Women’s blood serum will be completely negative for hCG by one to two weeks after birth. hCG testing is proof that all placental tissue is delivered. hCG is present only during pregnancy because it is secreted by the placenta, which is present only during pregnancy.

hCG also ensures that the corpus luteum continues to secrete progesterone and estrogen. Progesterone is very important during pregnancy because, when its secretion decreases, the endometrial lining will slough off and pregnancy will be lost. hCG suppresses the maternal immunologic response so the placenta is not rejected.

Human placental lactogen is lactogenic and promotes mammary gland growth in preparation for lactation in the mother. It also regulates maternal glucose, protein, and fat levels so they are always available to the fetus.

Estrogen stimulates the development of secondary female sex characteristics. It contributes to the woman’s mammary gland development in preparation for lactation and stimulates uterine growth to accommodate the growing fetus.

Progesterone is necessary to maintain the endometrial lining of the uterus during pregnancy. This hormone prevents pre-term labor by reducing myometrial contractions. Levels of progesterone are high during pregnancy.

ByRx Harun

Pancreas – Anatomy, Types, Structure, Functions

The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas has both an endocrine and a digestive exocrine function. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin, and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins, and fats in food entering the duodenum from the stomach.

The pancreas is an extended, accessory digestive gland that is found retroperitoneally, crossing the bodies of the L1 and L2 vertebra on the posterior abdominal wall. The pancreas lies transversely in the upper abdomen between the duodenum on the right and the spleen on the left. It is divided into the head, neck, body, and tail. The head lies on the inferior vena cava and the renal vein and is surrounded by the C loop of the duodenum. The tail of the pancreas extends up to the splenic hilum. The pancreas produces an exocrine secretion (pancreatic juice from the acinar cells) which then enters the duodenum through the main and accessory pancreatic ducts and endocrine secretions (glucagon and insulin from the pancreatic islets of Langerhans) that enter the blood.

Structure

The Parts of the Pancreas

Your doctor may refer to the parts of the pancreas when discussing your disease. The tumor’s location in the pancreas is important since it affects the symptoms and treatment of your disease.

FOUR MAIN PARTS

Head – The head is the widest part of the pancreas. The head of the pancreas is found in the right side of abdomen, nestled in the curve of the duodenum (first part of the small intestine).
Neck – The neck is the thin section of the gland between the head and the body of the pancreas.
Body – The body is the middle part of the pancreas between the neck and the tail. The superior mesenteric artery and vein run behind this part of the pancreas.
Tail – The tail is the thin tip of the pancreas in the left side of the abdomen, in close proximity to the spleen.

[Uncinate process – The uncinate is the part of the head that hooks towards the back of the abdomen around two very important blood vessels—the superior mesenteric artery and the superior mesenteric vein.

The pancreas (shown here in pink) sits behind the stomach, with the body near the curvature of the duodenum, and the tail stretching to touch the spleen.

The pancreas is an organ that in humans lies in the abdomen, stretching from behind the stomach to the left upper abdomen near the spleen. In adults, it is about 12–15 centimeters (4.7–5.9 in) long, lobulated, and salmon-colored in appearance.

Anatomically, the pancreas is divided into the head, neck, body, and tail. The pancreas stretches from the inner curvature of the duodenum, where the head surrounds two blood vessels: the superior mesenteric artery, and vein. The longest part of the pancreas, the body, stretches across behind the stomach, and the tail of the pancreas ends adjacent to the spleen.^[rx]

Two ducts, the main pancreatic duct, and a smaller accessory pancreatic duct, run through the body of the pancreas, joining with the common bile duct near a small ballooning called the ampulla of Vater. Surrounded by a muscle, the sphincter of Oddi, this opens into the descending part of the duodenum.^[rx]

Parts

The head of the pancreas sits within the curvature of the duodenum and wraps around the superior mesenteric artery and vein. To the right sits the descending part of the duodenum and between these travel the superior and inferior pancreaticoduodenal arteries. Behind rests the inferior vena cava, and the common bile duct. In front sits the peritoneal membrane and the transverse colon.^[rx] A small uncinate process emerges from below the head, situated behind the superior mesenteric vein and sometimes the artery.^[rx]

The neck of the pancreas separates the head of the pancreas, located in the curvature of the duodenum, from the body. The neck is about 2 cm (0.79 in) wide and sits in front of where the portal vein is formed. The neck lies mostly behind the pylorus of the stomach and is covered with the peritoneum. The anterior superior pancreaticoduodenal artery travels in front of the neck of the pancreas.^[rx]

The body is the largest part of the pancreas and mostly lies behind the stomach, tapering along its length. The peritoneum sits on top of the body of the pancreas, and the transverse colon in front of the peritoneum.^[rx] Behind the pancreas are several blood vessels, including the aorta, the splenic vein, and the left renal vein, as well as the beginning of the superior mesenteric artery.^[rx] Below the body of the pancreas sits some of the small intestines, specifically the last part of the duodenum and the jejunum to which it connects, as well as the suspensory ligament of the duodenum which falls between these two. In front of the pancreas sits the transverse colon.^[rx]

The pancreas narrows towards the tail, which sits near to the spleen.^[rx] It is usually between 1.3–3.5 cm (0.51–1.38 in) long, and sits between the layers of the ligament between the spleen and the left kidney. The splenic artery and vein, which also passes behind the body of the pancreas, pass behind the tail of the pancreas.^[rx]

Blood supply

The pancreas has a rich blood supply, with vessels originating as branches of both the coeliac artery and the superior mesenteric artery.^[rx] The splenic artery runs along the top of the pancreas and supplies the left part of the body and the tail of the pancreas through its pancreatic branches, the largest of which is called the greater pancreatic artery.^[rx] The superior and inferior pancreaticoduodenal arteries run along the back and front surfaces of the head of the pancreas adjacent to the duodenum. These supply the head of the pancreas. These vessels join together (anastomose) in the middle.^[rx]

The body and neck of the pancreas drain into the splenic vein, which sits behind the pancreas.^[rx] The head drains into, and wraps around, the superior mesenteric and portal veins, via the pancreaticoduodenal veins.^[rx]

The pancreas drains into lymphatic vessels that travel alongside its arteries and has a rich lymphatic supply.^[rx] The lymphatic vessels of the body and tail drain into splenic lymph nodes, and eventually into lymph nodes that lie in front of the aorta, between the coeliac and superior mesenteric arteries. The lymphatic vessels of the head and neck drain into intermediate lymphatic vessels around the pancreaticoduodenal, mesenteric and hepatic arteries, and from there into the lymph nodes that lie in front of the aorta.^[rx]

Arterial Supply

Branches of the splenic artery (a branch of the celiac trunk), superior mesenteric artery (SMA), and the common hepatic artery provide blood supply to the pancreas [2][3].

Pancreatic head: The gastroduodenal artery (a branch of the common hepatic artery) supplies the head and the uncinate process of the pancreas in the form of the pancreaticoduodenal artery (PDA). Part of the inferior portion of the head is supplied by the inferior PDA which arises from the SMA.
Body and the tail: The splenic artery and its branches supply these.

Venous Supply

Pancreatic head: The head drains into the superior mesenteric vein (SMV).
Body and the neck: The splenic vein drains these.

The SMV and splenic vein merge to form the portal vein.

Nerves

The pancreas has a complex network of parasympathetic, sympathetic, and sensory innervations [4]. It also has an intrinsic nerve plexus. Sympathetic and parasympathetic fibers are dispersed to pancreatic acinar cells. The parasympathetic fibers arise from the posterior vagal trunk and are secretomotor, but the secretions from the pancreas are predominantly mediated by cholecystokinin and secretin, which are hormones produced by the epithelial cells of the duodenum and proximal intestinal mucosa regulated by acidic compounds from the stomach. Sympathetic innervation is via the T6-T10 thoracic splanchnic nerves and the celiac plexus.

Overview of Pancreatic Islets

Pancreatic islets, also called the islets of Langerhans, are regions of the pancreas that contain its hormone-producing endocrine cells.

Key Points

The pancreatic islets are small islands of cells that produce hormones that regulate blood glucose levels. Hormones produced in the pancreatic islets are secreted directly into the bloodstream by five different types of cells.

The alpha cells produce glucagon and makeup 15–20% of total islet cells. The beta cells produce insulin and amylin and makeup 65–80% of the total islet cells. The delta cells produce somatostatin and makeup 3–10% of the total islet cells.

The gamma cells produce pancreatic polypeptide and makeup 3–5% of the total islet cells. The epsilon cells produce ghrelin and make up less than 1% of the total islet cells.

The feedback system of the pancreatic islets is paracrine and is based on the activation and inhibition of the islet cells by the endocrine hormones produced in the islets.

Key Terms

endocrine: Produces internal secretions that are transported around the body by the bloodstream.

paracrine: Describes a hormone or other secretion released from endocrine cells into the surrounding tissue rather than into the bloodstream.

exocrine: Produces external secretions that are released through a duct.

The pancreas serves two functions, endocrine and exocrine. The exocrine function of the pancreas is involved in digestion, and these associated structures are known as the pancreatic acini.

The pancreatic acini are clusters of cells that produce digestive enzymes and secretions and make up the bulk of the pancreas. The endocrine function of the pancreas helps maintain blood glucose levels, and the structures involved are known as the pancreatic islets, or the islets of Langerhans.

This is an illustration of the pancreas with a detailed view of a pancreatic islet with endocrine cells. The islet is surround by the pancreatic acini and pancreatic duct.

Pancreatic islets or islets of Langerhans: The islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells.

The pancreatic islets are small islands of cells that produce hormones that regulate blood glucose levels. Hormones produced in the pancreatic islets are secreted directly into the blood flow by five different types of cells.

This is a photo taken through a microscope of pancreatic tissue. The small cells in the middle are beta cells, and the surrounding larger cells are alpha, delta, gamma, and epsilon cells.

Pancreatic tissue: The small cells in the middle are beta cells, and the surrounding larger cells are alpha, delta, gamma, and epsilon cells.

The endocrine cell subsets are:

Alpha cells produce glucagon and make up 15–20% of total islet cells. Glucagon is a hormone that raises blood glucose levels by stimulating the liver to convert its glycogen into glucose.
Beta cells produce insulin and amylin and makeup 65–80% of the total islet cells. Insulin lowers blood glucose levels by stimulating cells to take up glucose out of the bloodstream. Amylin slows gastric emptying, preventing spikes in blood glucose levels.
Delta cells produce somatostatin and makeup 3–10% of the total islet cells. Somatostatin is a hormone that suppresses the release of the other hormones made in the pancreas.
Gamma cells produce pancreatic polypeptide and makeup 3–5% of the total islet cells. Pancreatic polypeptide regulates both the endocrine and exocrine pancreatic secretions.
Epsilon cells produce ghrelin and make up less than 1% of the total islet cells. Ghrelin is a protein that stimulates hunger.

The feedback system of the pancreatic islets is paracrine—it is based on the activation and inhibition of the islet cells by the endocrine hormones produced in the islets. Insulin activates beta cells and inhibits alpha cells, while glucagon activates alpha cells, which activates beta cells and delta cells. Somatostatin inhibits the activity of alpha cells and beta cells.

Types of Cells in the Pancreas

The islets of Langerhans are the regions of the pancreas that contain many hormone-producing endocrine cells.

Key Points

The pancreas reveals two different types of parenchymal tissue: exocrine acini ducts and the endocrine islets of Langerhans.

The hormones produced in the islets of Langerhans are insulin, glucagon, somatostatin, pancreatic polypeptide, and ghrelin.

The pancreatic hormones are secreted by alpha, beta, delta, gamma, and epsilon cells.

Key Terms

somatostatin: A polypeptide hormone, secreted by the pancreas, that inhibits the production of certain other hormones.

insulin: A polypeptide hormone that regulates carbohydrate metabolism.

glucagon: A hormone, produced by the pancreas, that opposes the action of insulin by stimulating the production of sugar.

Pancreatic Cells

The pancreas is a glandular organ that belongs to both the digestive and the endocrine systems of vertebrates. It is an endocrine gland that produces several important hormones, including insulin, glucagon, somatostatin, and pancreatic polypeptide.

It is also a digestive, exocrine organ, that secretes pancreatic juice that contains digestive enzymes to assist with digestion and the absorption of nutrients in the small intestine. These enzymes help to further break down the carbohydrates, proteins, and lipids in the chyme.

Under a microscope, stained sections of the pancreas reveal two different types of parenchymal tissue. The light-stained clusters of cells are called islets of Langerhans, which produce hormones that underlie the endocrine functions of the pancreas.

The dark-stained cells form acini, connected to ducts. Acinar cells belong to the exocrine pancreas and secrete digestive enzymes into the gut via a system of ducts.

Islets of Langerhans

This is a microscope photograph of a porcine islet of Langerhans. On the left is a brightfield image created using hematoxylin stain; nuclei are dark circles and the acinar pancreatic tissue is darker than the islet tissue. The right image is the same section stained by immunofluorescence against insulin, indicating beta cells.

Islets of Langerhans: A porcine islet of Langerhans. On the left is a brightfield image created using hematoxylin stain; nuclei are dark circles and the acinar pancreatic tissue is darker than the islet tissue. The right image is the same section stained by immunofluorescence against insulin, indicating beta cells.

Alpha cells produce glucagon and make up 15–20% of total islet cells. Glucagon is a hormone that raises blood glucose levels by stimulating the liver to convert its glycogen into glucose.
Beta cells produce insulin and amylin, and makeup 65–80% of the total islet cells. Insulin lowers blood glucose levels by stimulating cells to take up glucose out of the bloodstream. Amylin slows gastric emptying, preventing spikes in blood glucose levels.
Delta cells produce somatostatin and makeup 3–10% of the total islet cells. Somatostatin is a hormone that suppresses the release of the other hormones made in the pancreas.
Gamma cells produce pancreatic polypeptide and makeup 3–5% of the total islet cells. Pancreatic polypeptide regulates both the endocrine and exocrine pancreatic secretions.
Epsilon cells that produce ghrelin, and make up less than 1% of the total islet cells. Ghrelin is a protein that stimulates hunger.

The islets of Langerhans can influence each other through paracrine and autocrine communication. The paracrine feedback system is based on the following correlations:

The insulin hormone activates beta cells and inhibits alpha cells.
The hormone glucagon activates alpha cells which then activate beta cells and delta cells.
Somatostatin hormone inhibits alpha cells and beta cells.

Insulin Secretion and Regulation of Glucagon

Glucagon is a peptide hormone that works in conjunction with insulin to maintain a stable blood glucose level.

Key Points

Glucagon and insulin are peptide hormones secreted by the pancreas that plays a key role in maintaining a stable blood glucose level.

Glucagon is produced by alpha cells in the pancreas and acts to raise blood sugar levels.

Insulin is produced by beta cells in the pancreas and acts to lower blood sugar levels.

Key Terms

insulin: A polypeptide hormone that regulates carbohydrate metabolism.

glycogen: A polysaccharide that is the main form of carbohydrate storage in animals and also converts to glucose as needed.

glucagon: A hormone, produced by the pancreas, that opposes the action of insulin by stimulating the production of sugar.

Glucagon and insulin are peptide hormones secreted by the pancreas that play a key role in maintaining a stable blood glucose level. The blood glucose level is carefully monitored by cells within the pancreas that respond by secreting key hormones.

Glucagon

This is an image from a microscope stained for glucagon.

Glucagon staining: This is an image from a microscope stained for glucagon.

Glucagon is produced by alpha cells in the pancreas and elevates the concentration of glucose in the blood by promoting gluconeogenesis and glycogenolysis. Glucose is stored in the liver in the form of the polysaccharide glycogen, which is a glucan.

Liver cells have glucagon receptors and when glucagon binds to the liver cells they convert glycogen into individual glucose molecules and release them into the bloodstream—this process is known as glycogenolysis. As these stores become depleted, glucagon then encourages the liver and kidney to synthesize additional glucose by gluconeogenesis. Glucagon also turns off glycolysis in the liver, causing glycolytic intermediates to be shuttled to gluconeogenesis that can induce lipolysis to produce glucose from fat.

Insulin

Insulin is produced by beta cells in the pancreas and acts to oppose the functions of glucagon. It’s main role is to promote the conversion of circulating glucose into glycogen via glycogenesis in the liver and muscle cells.

Insulin also inhibits
gluconeogenesis and promotes the storage of glucose in fat through lipid synthesis and also by inhibiting lipolysis.

In Disease

When control of insulin levels fails, diabetes mellitus can result. As a consequence, insulin is used medically to treat some forms of diabetes mellitus.

Patients with type 1 diabetes depend on external insulin (most commonly injected subcutaneously) for their survival because the hormone is no longer produced internally.

Patients with type 2 diabetes are often insulin resistant and, because of such resistance, they may suffer from a relative insulin deficiency. Some patients with type 2 diabetes may eventually require insulin if other medications fail to control blood glucose levels adequately.

Pancreatic enzymes

Your pancreas creates natural juices called pancreatic enzymes to break down foods. These juices travel through your pancreas via ducts. They empty into the upper part of your small intestine called the duodenum. Each day, your pancreas makes about 8 ounces of digestive juice filled with enzymes. These are the different enzymes:

Lipase. This enzyme works together with bile, which your liver produces, to break down fat in your diet. If you don’t have enough lipase, your body will have trouble absorbing fat and the important fat-soluble vitamins (A, D, E, K). Symptoms of poor fat absorption include diarrhea and fatty bowel movements.
Protease. This enzyme breaks down proteins in your diet. It also helps protect you from germs that may live in your intestines, like certain bacteria and yeast. Undigested proteins can cause allergic reactions in some people.
Amylase. This enzyme helps break down starches into sugar, which your body can use for energy. If you don’t have enough amylase, you may get diarrhea from undigested carbohydrates.

Pancreatic hormones

Many groups of cells produce hormones inside your pancreas. Unlike enzymes that are released into your digestive system, hormones are released into your blood and carry messages to other parts of your digestive system. Pancreatic hormones include:

Insulin. This hormone is made in cells of the pancreas known as beta cells. Beta cells make up about 75% of pancreatic hormone cells. Insulin is the hormone that helps your body use sugar for energy. Without enough insulin, your sugar levels rise in your blood and you develop diabetes.
Glucagon. Alpha cells make up about 20% of the cells in your pancreas that produce hormones. They produce glucagon. If your blood sugar gets too low, glucagon helps raise it by sending a message to your liver to release stored sugar.
Gastrin and amylin. Gastrin is primarily made in the G cells in your stomach, but some is made in the pancreas, too. It stimulates your stomach to make gastric acid. Amylin is made in beta cells and helps control appetite and stomach emptying.

Common pancreatic problems and digestion

Diabetes, pancreatitis, and pancreatic cancer are three common problems that affect the pancreas. Here is how they can affect digestion:

Diabetes. If your pancreatic beta cells do not produce enough insulin or your body can’t use the insulin your pancreas produces, you can develop diabetes. Diabetes can cause gastroparesis, a reduction in the motor function of the digestive system. Diabetes also affects what happens after digestion. If you don’t have enough insulin and you eat a meal high in carbohydrates, your sugar can go up and cause symptoms like hunger and weight loss. Over the long term, it can lead to heart and kidney disease among other problems.
Pancreatitis. Pancreatitis happens when the pancreas becomes inflamed. It is often very painful. In pancreatitis, the digestive enzymes your pancreas make attack your pancreas and cause severe abdominal pain. The main cause of acute pancreatitis is gall stones blocking the common bile duct. Too much alcohol can cause pancreatitis that does not clear up. This is known as chronic pancreatitis. Pancreatitis affects digestion because enzymes are not available. This leads to diarrhea, weight loss, and malnutrition. About 90% of the pancreas must stop working to cause these symptoms.
Pancreatic cancer. About 95% of pancreatic cancers begin in the cells that make enzymes for digestion. Not having enough pancreatic enzymes for normal digestion is very common in pancreatic cancer. Symptoms can include weight loss, loss of appetite, indigestion, and fatty stools.

Your pancreas is important for digesting food and managing your use of sugar for energy after digestion. If you have any symptoms of pancreatic digestion problems, like loss of appetite, abdominal pain, fatty stools, or weight loss, call your healthcare provider.

Function

Pancreatic Hormones and Their Function[1][2][3]

Insulin

Source: Beta cells of islets of the pancreas.

Synthesis: Insulin is a peptide hormone. The insulin mRNA is translated as a single-chain precursor called preproinsulin, and removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin. Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases, which excise the C peptide (one of three domains of proinsulin), thereby generating the mature form of insulin. Insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood. C-peptide is also secreted into the blood in a 1:1 molar ratio with insulin. Although C-peptide has no established biological action, it is used as a useful marker for insulin secretion.

Transport: insulin circulates entirely in unbound form (T1/2 = 6 min).

Main Target cells: hepatic, muscle and adipocyte cells (i.e., cells specialized for energy storage).

Mechanism of action: Insulin binds to a specific receptor tyrosine kinase on the plasma membrane and increases its activity to phosphorylate numerous regulatory enzymes and other protein substrates.

Regulation of its secretion: Plasma glucose level is the main regulator of insulin secretion. The change in the concentration of plasma glucose that occurs in response to feeding or fasting is the main determinant of insulin secretion. Modest increases in plasma glucose level provoke a marked increase in plasma insulin concentration. Glucose is taken up by beta cells via glucose transporters (GLUT2). The subsequent metabolism of glucose increases cellular adenosine triphosphate (ATP) concentrations and closes ATP-dependent potassium (KATP) channels in the beta cell membrane, causing membrane depolarization and an influx of calcium. Increased calcium intracellular concentration results in an increase of insulin secretion. Increased plasma amino acid and free fatty acid concentrations induce insulin secretion as well. Glucagon is also known to be a strong insulin secretagogue.

Physiological functions: Insulin plays an important role to keep plasma glucose values within a relatively narrow range throughout the day (glucose homeostasis). Insulin’s main actions are

(1) In the liver, insulin promotes glycolysis and storage of glucose as glycogen (glycogenesis), as well as the conversion of glucose to triglycerides,
(2) In muscle, insulin promotes the uptake of glucose and its storage as glycogen, and
(3) in adipose tissue, insulin promotes the uptake of glucose and its conversion to triglycerides for storage.

Amylin (diabetes-associated peptide)

Source: Beta cells of islets of the pancreas. It is co-secreted with insulin in response to caloric intake (feeding state).

Target cells: Alpha cells of islets of pancreas and hypothalamus.

Physiological functions: it suppresses glucagon secretion from the alpha cells of the islets in the pancreas via paracrine interaction between beta cells and alpha cells. Amylin also slows gastric emptying which delays the absorption of glucose from the small intestine into the circulation. Also, it stimulates the satiety center of the brain to limit food consumption.

Glucagon

Source: Alpha cells of islets of the pancreas.

Synthesis: The initial gene product is the mRNA encoding preproglucagon. A peptidase removes the signal sequence of preproglucagon during translation of the mRNA in the rough endoplasmic reticulum to yield proglucagon. Proteases in the alpha cells subsequently cleave the proglucagon into the mature glucagon molecule.

Target cells: Hepatic cells.

Mechanism of action: glucagon binds to a receptor that activates the heterotrimeric G protein Gas, which stimulates membrane-bound adenylyl cyclase. The cAMP formed by adenylyl cyclase, in turn, activates PKA, which phosphorylates numerous regulatory enzymes and other protein substrates.

Regulation of its secretion: The amino acids released by digestion of a protein meal appear to be the main determinant of glucagon secretion.

Physiological functions: Glucagon acts exclusively on the liver to antagonize insulin effects on hepatocytes. It enhances glycogenolysis and gluconeogenesis. It also promotes the oxidation of fat, which can lead to the formation of ketone bodies.

Somatostatin

Source: Delta cells of the islets of the pancreas, hypothalamus, and D cells of gastric glands.

Target cells: Beta cells of islets of the pancreas, somatotroph cells in the anterior pituitary gland, and the G cells of the gastric glands.

Mechanism of action: Somatostatin binds to a receptor that activates the heterotrimeric inhibitory G protein, which inhibits membrane-bound adenylyl cyclase and cAMP formation.

Regulation of its secretion: Glucagon stimulates somatostatin secretion via paracrine interaction between alpha cells and delta cells of the islets of the pancreas.

Physiological functions: Somatostatin inhibits the secretion of multiple hormones, including growth hormone, insulin, glucagon, gastrin, vasoactive intestinal peptide (VIP), and thyroid-stimulating hormone.

Ghrelin

Source: Epsilon cells of the islets of the pancreas, endocrine cells in the stomach and hypothalamus.

Target cells: Beta cells of the islets of the pancreas and somatotroph cells in the anterior pituitary gland.

Physiological functions: ghrelin inhibits the secretion of insulin from Beta cells of the islets of the pancreas via paracrine interaction between delta cells and beta cells of the islets of the pancreas. It also stimulates appetite and growth hormone secretion.

Pancreatic Polypeptide (PP)

Pancreatic polypeptide is secreted from upsilon (F) cells of the islets of the pancreas. Dietary intake of nutrients alters the secretion of the pancreatic polypeptide. Its function is not decidedly understood yet.

Paracrine Interaction Between Pancreatic Endocrine Cells

Insulin secreted by beta cells acts as a prime hormone of glucose homeostasis. Insulin and amylin inhibit glucagon secretion by alpha cells. Whereas glucagon activates insulin and somatostatin secretion, somatostatin secreted by delta cells and ghrelin by epsilon cells inhibits insulin secretion.

WHY IS THIS IMPORTANT?

Understanding the two functions of the pancreas is important because

Large tumors of the pancreas will interfere with both of these important bodily functions.

Exocrine: when tumors block the exocrine system, patients can develop pancreatitis and pain from the abnormal release of digestive enzymes into the substance of the pancreas instead of into the bowel, and they can develop digestive problems, such as diarrhea, from the incomplete digestion of food.
Endocrine: when tumors destroy the endocrine function of the pancreas, patients can develop sugar diabetes (abnormally high blood sugar levels).

Tumors can arise in either component, exocrine or endocrine.

Exocrine: the vast majority of tumors of the pancreas arise in the exocrine part and these cancers look like pancreatic ducts under the microscope. These tumors are therefore called ductal adenocarcinomas, or simply adenocarcinoma, or even more simply pancreatic cancer.
Endocrine: less commonly, tumors arise from the endocrine component of the pancreas and these endocrine tumors are called “pancreatic neuroendocrine tumors,” or “islet cell tumors” for short.

References

ByRx Harun

Adrenal Glands – Anatomy, Structure, Functions

The adrenal glands, also called the suprarenal glands, are a significant part of the endocrine system. The adrenal glands play a vital role in the body’s fight or flight response. They generate stress hormones that activate physiological adaptations that are necessary to counteract changes in the external environment. The adrenal glands also secrete several essential hormones that play a significant role in regulating the body’s immune system, body metabolism, and salt and water balance. The paired adrenal glands are triangular-shaped organs that measure approximately 5 cm by 2 cm, are located on the superior aspect of each kidney, and weigh 4 to 5 grams each.

Structure

The adrenal glands lie close to critical vessels and organs. Both adrenal glands rest on top of the kidneys on their respective side of the body. They are enclosed within the superior renal fascia and sit in the perirenal space. At birth, the adrenal glands are roughly one-third the size of the kidney, though, by adulthood, they are only one-thirtieth the size of the kidney. Each adrenal gland is found in the epigastrium at the top of the kidney opposite the 11th intercostal end of the vertebral space and the 12th rib. The right suprarenal gland is pyramidal in form, while the left suprarenal gland is crescentic in shape. Each gland measures 50 mm in height, 30 mm in breadth, and 10 mm in thickness. Each gland weighs roughly 5 grams.

Anatomical Relations

The right adrenal gland sits just below the liver, posterior to the inferior vena cava, and anterior to the diaphragm. The left adrenal gland sits medially to the spleen, superior to the splenic artery and vein, lateral to the abdominal aorta, and anterior to the diaphragm.

Internal Structure

The adrenal gland is composed of two distinct tissues: the outer cortex and the inner medulla. The adrenal cortex tends to be fattier and thus has a more yellow hue. The adrenal medulla is more of a reddish-brown color. A thick capsule consisting of connective tissue surrounds the entire adrenal gland.

The adrenal cortex is much larger than the smaller medulla, which only accounts for approximately 15% of the gland. It is composed of three distinct zones:

Zona Glomerulosa (outer layer)

The zona glomerulosa is responsible for the synthesis of mineralocorticoids, of which the most important is aldosterone. This hormone plays an important role in electrolyte balance and regulation of blood pressure.

Zona Fasciculata (middle layer)

The zona fasciculata produces glucocorticoids, of which the predominant hormone is cortisol. This hormone plays a role in the regulation of blood sugar via gluconeogenesis. Cortisol also modulates the immune system and modulates the metabolism of fat, protein, and carbohydrates. The secretion of cortisol is under the adrenocorticotropic hormone regulation, which is released from the pituitary gland.

Zona Reticularis (inner zone)

The zona reticularis produces androgens and plays a role in the development of secondary sexual characteristics. The primary androgen produced in the zona reticularis is dehydroepiandrosterone (DHEA), which is the most abundant hormone in the body. It serves as a precursor for the synthesis of many other hormones produced by the adrenal gland, such as progesterone, estrogen, cortisol, and testosterone.

The function of these three zones can be remembered by the mnemonic “Salt, Sugar, Sex,” as they correlate to the function of the hormones produced in each layer of the adrenal cortex. The names of these zones can also be recalled by remembering “GFR” for glomerulosa, fasciculata, and reticularis.

The adrenal medulla synthesizes catecholamines. Catecholamines are made from the precursor of dopamine and combined with tyrosine, thus resulting in norepinephrine. Once norepinephrine has been created, it is then methylated via phenylethanolamine N-methyltransferase (PNMT), which is only present in the adrenal medulla.[rx]

Overview of the Adrenal Glands

In mammals, the adrenal glands (also known as the suprarenal glands) are endocrine glands that sit atop the kidneys.

Key Points

The adrenal glands are are endocrine glands located atop the kidneys.
They are responsible for releasing three classes of hormones;
mineralocorticoids, glucocorticoids, and androgens along with
catecholamines.
Each adrenal gland is composed to two structures: the adrenal medulla and adrenal cortex.

Key Terms

adrenal cortex: The outer portion of the adrenal glands that produces
mineralocorticoids, glucocorticoids, and androgens.
Adrenal medulla: The innermost part of the adrenal gland, consisting of cells that secrete adrenaline and noradrenaline.

In mammals, the adrenal glands (also known as the suprarenal glands) are endocrine glands that sit atop the kidneys. They are chiefly responsible for releasing three classes of hormones:

Mineralocorticoids (aldosterone)
Glucocorticoids (cortisol)
Androgens (DHEA)

Along with catecholamines (adrenaline), these hormones control a variety of functions including kidney function, metabolism, fight-or-flight response, and sex hormone levels.

In humans, the adrenal glands are found at the level of the 12th thoracic vertebra sitting above and slightly medial to the kidneys, lying within the renal fascia, and separated from the kidneys by a thin layer of connective tissue. In humans, the right adrenal gland is triangular shaped, while the left adrenal gland is semilunar shaped.

Each adrenal gland has two distinct structures, the outer adrenal cortex and the inner medulla—both produce hormones. The cortex mainly produces mineralcorticoids, glucocorticoids, and androgens, while the medulla chiefly produces adrenaline and nor-adrenaline.

Adrenal Cortex

The adrenal cortex is devoted to the synthesis of corticosteroid and androgen hormones.

Key Points

Specific cortical cells produce particular hormones, including aldosterone, cortisol, and androgens such as androstenedione.

The adrenal cortex comprises three zones, or layers: Zona glomerulosa (outer), Zona fasciculata and Zona reticularis.

The outermost layer, the zona glomerulosa, is the main site for the production of mineralocorticoids, mainly aldosterone.

Zona fasciculata is the layer situated between the glomerulosa and reticularis. This layer is responsible for producing glucocorticoids, such as cortisol.

Zona reticularis is the innermost cortical layer; the zona reticularis produces androgens, mainly DHEA.

Key Terms

adrenal cortex: The outer portion of the adrenal glands that produces hormones essential to homeostasis.

zona glomerulosa: The outermost layer of the adrenal cortex, responsible for producing mineralocorticoids such as aldosterone.

zona fasciculata: The middle layer of the adrenal cortex, responsible for producing glucocorticoids such as cortisol.

zona reticularis: The inner most layer of the adrenal cortex, responsible for producing androgens such as DHEA.

Zones of the Adrenal Cortex

The cortex is regulated by neuroendocrine hormones secreted by the pituitary gland, which are under the control of the hypothalamus, as well as by the renin-angiotensin system. The adrenal cortex has three zones or layers:

Zona Glomerulosa – The outermost layer, the zona glomerulosa, is the main site for the production of mineralocorticoids, mainly aldosterone, that are largely responsible for the long-term regulation of blood pressure. Aldosterone exerts its effects on the distal convoluted tubule and collecting duct of the kidney, where it causes increased reabsorption of sodium and increased excretion of both potassium (by principal cells) and hydrogen ions (by intercalated cells of the collecting duct). The major stimulus to produce aldosterone is angiotensin II, as ACTH from the pituitary only produces a transient effect. Angiotensin is stimulated by the juxtaglomerular cells when renal blood pressure drops below 90 mmHg.
Zona fasciculata – Zona fasciculata is the layer situated between the glomerulosa and reticularis. This layer is responsible for producing glucocorticoids, such as 11-deoxycorticosterone, corticosterone, and cortisol in humans. Cortisol enhances the activity of other hormones including glucagon and catecholamines.
Zona Reticularis – The innermost cortical layer, the zona reticularis, lies directly adjacent to the medulla. It produces androgens, mainly dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione (the precursor to testosterone) in humans.^[19] Its small cells form irregular cords and clusters, separated by capillaries and connective tissue. The cells contain relatively small quantities of cytoplasm and lipid droplets and sometimes display brown lipofuscin pigment.^[rx]

Hormones of the Adrenal Cortex

The different zones of the adrenal cortex produce different hormones.

Mineralocorticoids

These are produced in the zona glomerulosa. The primary mineralocorticoid is aldosterone. Its secretion is regulated by the oligopeptide angiotensin II. Aldosterone is secreted in response to high extracellular potassium levels, low extracellular sodium levels, and low fluid levels and blood volume. Aldosterone secretion affects metabolism in different ways:

It increases urinary excretion of potassium ions
It increases interstitial levels of sodium ions
It increases water retention and blood volume.

Glucocorticoids

These are produced in the zona fasciculata. The primary glucocorticoid released by the adrenal gland in humans is cortisol. Its secretion is regulated by the hormone ACTH from the anterior pituitary gland. Upon binding to its target, cortisol enhances metabolism in several ways:

It stimulates the release of amino acids from the body
It stimulates lipolysis, the breakdown of fat
It stimulates gluconeogenesis, the production of glucose from newly-released amino acids and lipids
It increases blood glucose levels in response to stress, by inhibiting glucose uptake into muscle and fat cells
It strengthens cardiac muscle contractions
It increases water retention
It has anti-inflammatory and anti-allergic effects.

Androgens

The zona reticularis produces androgens, the most important of which is
DHEA. In general, these hormones do not have an overall effect in the male body and are converted to more potent androgens such as testosterone and DHT or to estrogens (female sex hormones) in the gonads, acting in this way as a metabolic intermediate.

Adrenal Medulla

The adrenal cortex is devoted to the synthesis of corticosteroid and androgen hormones.

Key Points

The adrenal medulla secretes two water-soluble hormones (norepinephrine and epinephrine) that underly the fight-or-flight response.

To carry out this responsibility, the adrenal medulla receives input from the sympathetic nervous system.

Key Terms

adrenal cortex: The outer portion of the adrenal glands that produces hormones essential to homeostasis.

chromaffin: The cells of the adrenal medulla that secrete adrenaline and noradrenaline in response to nervous stimulation.

The adrenal medulla is the core of the adrenal glands, and is surrounded by the adrenal cortex. The adrenal medulla is responsible for the production of catecholamines, derived from the amino acid tyrosine.

Chromaffin cells are the neuroendocrine cells found in the medulla; they are modified post-synaptic sympathetic neurons that receive sympathetic input. These water-soluble hormones are the major hormones underlying the fight-or-flight response. The adrenal medulla secretes approximately 20% noradrenaline (norepinephrine) and 80% adrenaline (epinephrine). To carry out this responsibility, the adrenal medulla receives input from the sympathetic nervous system through nerve fibers originating in the thoracic spinal cord from T5–T11.

When stimulated, chromaffin cells secrete adrenaline and noradrenaline along with enkephalin and enkephalin-containing peptides into the bloodstream. The secreted adrenaline and noradrenaline play an important role in the fight-or-flight response.

The enkephalins and enkephalin-containing peptides are related to, but also distinct from, the endogenous peptides named endorphins (secreted from the pituitary). All of these peptides bind to opioid receptors and produce analgesic (and other) responses.

Some notable effects of adrenaline and noradrenaline include:

Increased heart rate and blood pressure.
Blood vessel constriction in the skin and gastrointestinal tract.
Smooth muscle dilation.
Dilating bronchioles and capillaries.
Increased metabolism.

All of these effects are characteristic of the fight-or-flight response. Receptors for catecholamines are widely distributed throughout the body to allow for a systemic response following secretion.

Blood Supply and Lymphatics

As the adrenal glands produce various systemically important hormones, they require significant blood supply and are extremely well vascularized. The blood supply is tightly controlled by neuroendocrine and paracrine mechanisms, which is one method of regulating the systemic levels of adrenal hormones.[rx]

The three chief sources of blood supply to the adrenal glands include:

The superior adrenal arteries, which are small branches coming off the inferior phrenic artery
The middle adrenal artery comes directly off the abdominal aorta.
The inferior adrenal artery originates from the renal artery bilaterally[rx]

The adrenal glands have one of the greatest blood supply rates per gram of tissue of any organ: up to 60 small arteries may enter each gland.^[rx] Three arteries usually supply each adrenal gland:^[rx]

The superior suprarenal artery, a branch of the inferior phrenic artery
The middle suprarenal artery, a direct branch of the abdominal aorta
The inferior suprarenal artery, a branch of the renal artery

These blood vessels supply a network of small arteries within the capsule of the adrenal glands. Thin strands of the capsule enter the glands, carrying blood to them.^[rx]

Venous blood is drained from the glands by the suprarenal veins, usually one for each gland:^[rx]

The right suprarenal vein drains into the inferior vena cava
The left suprarenal vein drains into the left renal vein or the left inferior phrenic vein.

The central adrenomedullary vein, in the adrenal medulla, is an unusual type of blood vessel. Its structure is different from the other veins in that the smooth muscle in its tunica media (the middle layer of the vessel) is arranged in conspicuous, longitudinally oriented bundles.^[rx]

Variations in adrenal artery origin are very common. The superior adrenal artery can come off the abdominal aorta, celiac axis, or, more rarely, an intercostal artery. The superior adrenal artery is also commonly found as multiple arteries. The middle adrenal artery can come off the inferior phrenic, renal, or superior mesenteric arteries, or the celiac axis. The inferior adrenal arteries can also originate from the abdominal aorta or the inferior phrenic artery.[rx][rx][rx][rx]

The venous drainage from the adrenal glands is dependent on the side of the gland. The left adrenal gland is anatomically further away from the inferior vena cava, and therefore the left adrenal vein drains into the left renal vein. The right adrenal vein is much closer to the inferior vena cava and drains directly into this large vessel. Variations in adrenal venous drainage are common, particularly on the left side. There are reports of venous connections between the left adrenal vein and the left genital vein, and the inferior phrenic vein. Double left adrenal veins are also common.[rx]

Nerves

The function of the adrenal gland is mediated by both synaptic stimulation and hormonal stimulation. Adrenocorticotropic hormone (ACTH) secreted from the anterior pituitary gland activates the adrenal cortex. Subsequently, ACTH activates the respective cortical zones to generate corticosteroids.[rx][rx] However, the adrenal medulla is innervated by preganglionic nerve fibers (type B) arising from the intermediolateral cell column of the spinal cord’s lateral horn from the T5–T8 spinal cord segments. These nerve fibers form the greater splanchnic nerve without entering the paravertebral sympathetic ganglion chain. Some of the nerve fibers from the greater splanchnic nerve synapse at the celiac ganglion. The blood vessels supplying the adrenal glands will then receive their innervation from the celiac ganglion’s postsynaptic fibers.

On the other hand, some fibers of the greater splanchnic nerve circumvent the celiac ganglion and directly enter the adrenal gland to synapse at the chromaffin cells’ membranes. This is the reason why the adrenal medulla acts as a neuroendocrine junction between the two physiological segments. The chromaffin cells release their neurohormones directly into the bloodstream to produce a widespread sympathetic response and apparently act as a special type of postsynaptic neuron.[rx][rx]

Function

Mineralocorticoids

The mineralocorticoids, which include corticosterone, 11-deoxycorticosterone, and more importantly, aldosterone, act on the kidney to increase sodium reabsorption and potassium excretion. Water reabsorption follows increased sodium reabsorption, resulting in an increase in effective circulating volume and therefore increased blood pressure. Specifically, mineralocorticoids achieve this via increased synthesis of epithelial sodium channels (ENaC) and sodium-potassium ATPases on the principal cells of the distal nephron.[rx]

Mineralocorticoids also promote potassium ion secretion at the principal cells because of the gradients produced by the above channels. In high potassium states, aldosterone synthesis is increased to promote potassium excretion. Lastly, mineralocorticoids promote hydrogen ion secretion at the intercalated cells.[rx]

Interestingly, 11-deoxycorticosterone and corticosterone also have mineralocorticoid effects. These are weaker than aldosterone but can produce a strong mineralocorticoid effect when present in excess levels, as in some forms of congenital adrenal hyperplasia (CAH), for example, 11-beta-hydroxylase deficiency resulting in hypertension.[rx]

Glucocorticoids

Cortisol is the major glucocorticoid and increases in response to stress which activates the HPA axis. Therefore, all of its functions can be thought of as allowing the body to function with increased stress. Upon engaging glucocorticoid receptors, cortisol increases the expression of genes that will regulate metabolism, the immune system, cardiovascular function, growth, and reproduction. Cortisol is essential for maintaining blood pressure because it increases the sensitivity of vascular smooth muscle to vasoconstrictors like catecholamines and suppresses the release of vasodilators like nitrous oxide.[rx] Cortisol suppresses the immune system, which is the basis for immunosuppressive drug therapy with glucocorticoids. Regarding metabolism, cortisol increases gluconeogenesis and decreases peripheral glucose uptake. These oppose the actions of insulin, and the net effect is an increase in serum glucose. Cortisol also activates lipolysis and stimulates adipocyte growth, which leads to fat deposition. Generally, growth is inhibited, leading to muscle atrophy, increased bone resorption, and thinning of the skin. Of note, glucocorticoids can act on mineralocorticoid receptors. However, aldosterone effects predominate in the kidney because the renal enzyme, 11-beta-hydroxysteroid dehydrogenase-2 (11-beta-HSD-2) converts cortisol to cortisone.[rx] The 11-beta-HSD-1 converts cortisone into cortisol. Hence, these enzymes add another layer of regulation to cortisol. Licorice toxicity inhibits 11-beta-HSD-2, causing hypertension and hypokalemic alkalosis with normal aldosterone levels. Also, there can be a loss of function mutations in 11-beta-HSD-2, resulting in hypertension with low aldosterone.[rx]

Androgens

The adrenal androgens, primarily DHEA, require peripheral conversion to active sex steroids in the gonads and peripheral tissue. Circulating DHEA-sulfate is the best measure of adrenal androgen excess. Some DHEA is also converted to androstenedione. Ultimately, both are converted to testosterone in peripheral tissues, which is converted to 5-alpha-dihydrotestosterone (DHT), the most potent androgen.[rx] Adrenal androgens do not play a major role in the adult male because the testes are the major source of testosterone. However, adrenal androgens are important in puberty for both males and females and are the main source of circulating testosterone in females. The rise in adrenal gland androgen synthesis is responsible for adrenarche, which precedes gonadarche.[rx]

Catecholamines

Adrenal catecholamines, epinephrine, and norepinephrine are involved in executing the fight-or-flight response of the sympathetic nervous system. They increase blood pressure via alpha-1 receptors on vascular smooth muscle. They help increase serum glucose by activating glycogenolysis and increasing glucagon secretion via beta-2 receptors and decreasing insulin secretion via alpha-2 receptors.[rx]

Hormones of the Adrenal Glands

The role of the adrenal glands in your body is to release certain hormones directly into the bloodstream. Many of these hormones have to do with how the body responds to stress, and some are vital to existence. Both parts of the adrenal glands — the adrenal cortex and the adrenal medulla — perform distinct and separate functions.

Each zone of the adrenal cortex secretes a specific hormone. The key hormones produced by the adrenal cortex include:

Cortisol

Cortisol is a glucocorticoid hormone produced by the zona fasciculata that plays several important roles in the body. It helps control the body’s use of fats, proteins and carbohydrates; suppresses inflammation; regulates blood pressure; increases blood sugar; and can also decrease bone formation.

This hormone also controls the sleep/wake cycle. It is released during times of stress to help your body get an energy boost and better handle an emergency situation.

How Adrenal Glands Work to Produce Cortisol

Adrenal glands produce hormones in response to signals from the pituitary gland in the brain, which reacts to signaling from the hypothalamus, also located in the brain. This is referred to as the hypothalamic pituitary adrenal axis. As an example, for the adrenal gland to produce cortisol, the following occurs:

The hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to secrete adrenocorticotropin hormone (ACTH).
ACTH then stimulates the adrenal glands to make and release cortisol hormones into the blood.
Normally, both the hypothalamus and the pituitary gland can sense whether the blood has the appropriate amount of cortisol circulating. If there is too much or too little cortisol, these glands respectively change the amount of CRH and ACTH that gets released. This is referred to as a negative feedback loop.
Excess cortisol production can occur from nodules in the adrenal gland or excess production of ACTH from a tumor in the pituitary gland or other source.

Aldosterone

This mineralocorticoid hormone produced by the zona glomerulosa plays a central role in regulating blood pressure and certain electrolytes (sodium and potassium). Aldosterone sends signals to the kidneys, resulting in the kidneys absorbing more sodium into the bloodstream and releasing potassium into the urine. This means that aldosterone also helps regulate the blood pH by controlling the levels of electrolytes in the blood.

DHEA and Androgenic Steroids

These hormones produced by the zona reticularis are weak male hormones. They are precursor hormones that are converted in the ovaries into female hormones (estrogens) and in the testes into male hormones (androgens). However, estrogens and androgens are produced in much larger amounts by the ovaries and testes.

Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline)

The adrenal medulla, the inner part of an adrenal gland, controls hormones that initiate the flight or fight response. The main hormones secreted by the adrenal medulla include epinephrine (adrenaline) and norepinephrine (noradrenaline), which have similar functions.

Among other things, these hormones are capable of increasing the heart rate and force of heart contractions, increasing blood flow to the muscles and brain, relaxing airway smooth muscles, and assisting in glucose (sugar) metabolism. They also control the squeezing of the blood vessels (vasoconstriction), helping maintain blood pressure and increasing it in response to stress.

Like several other hormones produced by the adrenal glands, epinephrine and norepinephrine are often activated in physically and emotionally stressful situations when your body needs additional resources and energy to endure unusual strain.

Adrenal Gland Disorders

The two common ways in which adrenal glands cause health issues are by producing too little or too much of certain hormones, which leads to hormonal imbalances. These abnormalities of the adrenal function can be caused by various diseases of the adrenal glands or the pituitary gland.

Adrenal Insufficiency

Adrenal insufficiency is a rare disorder. It may be caused by disease of the adrenal glands (primary adrenal insufficiency, Addison’s disease) or by diseases in the hypothalamus or the pituitary (secondary adrenal insufficiency). It is the opposite of Cushing syndrome and is characterized by low levels of adrenal hormones. The symptoms include weight loss, poor appetite, nausea and vomiting, fatigue, darkening of skin (only in primary adrenal insufficiency), abdominal pain, among other.

The causes of primary adrenal insufficiency may include autoimmune disorders, fungal and other infections, cancer (rarely), and genetic factors.

Although adrenal insufficiency usually develops over time, it can also appear suddenly as an acute adrenal failure (adrenal crisis). It has similar symptoms, but the consequences are more serious, including life-threatening shock, seizures, and coma. These may develop if the condition is left untreated.

Congenital Adrenal Hyperplasia

Adrenal insufficiency can also result from a genetic disorder called congenital adrenal hyperplasia. Children who are born with this disorder are missing an essential enzyme necessary to produce cortisol, aldosterone, or both. At the same time, they often experience an excess of androgen, which may lead to male characteristics in girls and precocious puberty in boys.

Congenital adrenal hyperplasia can remain undiagnosed for years depending on the severity of the enzyme deficiency. In more severe cases, infants may suffer from ambiguous genitalia, dehydration, vomiting, and failure to thrive.

Overactive Adrenal Glands

Sometimes, adrenal glands may develop nodules that produce too many of certain hormones. Nodules 4 centimeters or larger and nodules that show certain features on imaging increase suspicion for malignancy. Both benign and cancerous nodules may produce excessive amounts of certain hormones, which is referred to as a functional nodule. Functional tumors, malignant tumors or nodules greater than 4 centimeters are recommended to be referred for surgical evaluation.

Excess of Cortisol: Cushing Syndrome

Cushing syndrome results from excessive production of cortisol from the adrenal glands. The symptoms may include weight gain and fatty deposits in certain areas of the body, such as the face, below the back of the neck called a buffalo hump and in the abdomen; thinning arms and legs; purple stretch marks on the abdomen; facial hair; fatigue; muscle weakness; easily bruised skin; high blood pressure; diabetes; and other health issues.

Excess cortisol production can also be triggered by overproduction of ACTH by a benign tumor in the pituitary gland or tumor elsewhere in the body. This is known as Cushing’s Disease. Another common cause of Cushing’s syndrome is excessive and prolonged consumption of external steroids, such as prednisone or dexamethasone, which are prescribed to treat many autoimmune or inflammatory diseases (e.g., lupus, rheumatoid arthritis, asthma, inflammatory bowel disease, multiple sclerosis, etc.)

Excess of Aldosterone: Hyperaldosteronism

Hyperaldosteronism results from the overproduction of aldosterone from one or both adrenal glands. This is characterized by an increase in blood pressure that often requires many medications to control. Some people can develop low potassium levels in the blood, which can cause muscle aches, weakness, and spasms. When the cause is adrenal oversecretion, the disease is called Conn syndrome.

Excess of Adrenaline or Noradrenaline: Pheochromocytoma

Pheochromocytoma is a tumor that results in excess production of adrenaline or noradrenaline by the adrenal medulla that often happens in bursts. Occasionally, neural crest tissue, which has similar tissue to the adrenal medulla, may be the cause of the overproduction of these hormones. This is known as a paraganglioma.

Pheochromocytomas may cause persistent or sporadic high blood pressure that may be difficult to control with regular medications. Other symptoms include headaches, sweating, tremors, anxiety, and rapid heartbeat. Some people are genetically predisposed to developing this type of tumor.

Adrenal Cancer

Malignant adrenal tumors (adrenal cancer), such as adrenocortical carcinoma, are rare and often have spread to other organs and tissues by the time they are diagnosed. These tumors tend to grow fairly large and can reach several inches in diameter.

Cancerous adrenal tumors can be functional and release an excess of one or more hormones accompanied by corresponding symptoms, as listed above. Patients may also experience abdominal pain, flank pain or a feeling of abdominal fullness, especially when the adrenal tumor gets very large.

Not all cancers found in adrenal glands originate from the gland itself. The majority of adrenal tumors are metastasis, or cancer spread, from another primary tumor elsewhere in the body.

References

ByRx Harun

Inferior Parathyroid Glands – Anatomy, Structure, Functions

Inferior Parathyroid Glands/Parathyroid glands are four small glands of the endocrine system which regulate the calcium in our bodies. Parathyroid glands are located in the neck behind the thyroid where they continuously monitor and regulate blood calcium levels.

Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes parathyroid hormone in response to low blood calcium, which plays a key role in regulating the amount of calcium in the blood and within the bones.

Types

Superior parathyroid glands – These glands derive from the fourth pharyngeal pouch. They are classically located near the posterolateral aspect of the superior pole of the thyroid, 1cm superior to the junction of the recurrent laryngeal nerve (RLN), and the inferior thyroid artery. They classically lie deep to the plane of the recurrent laryngeal nerve.

Inferior parathyroid glands – These glands derive from the third pharyngeal pouch. These glands are classically located near the inferior poles of the thyroid glands, within 1-2 cm of the insertion of the inferior thyroid artery into the inferior pole of the thyroid. They classically lie superficial to the plane of the RLN. Their location is much more variable than the superior parathyroids, and can be intra-thyroidal or within the thymus or other mediastinal structures, and can even be found along the aortic arch.[rx]

Overview of the Parathyroid Glands

The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone.

Key Points

The parathyroid glands are four or more small glands, about the size of a grain of rice, located on the posterior surface of the thyroid gland.

The major function of the parathyroid glands is to maintain the body’s calcium level within a very narrow range, so the nervous and muscular systems can function properly.

Key Terms

calcitonin: A hormone that is produced primarily by the parafollicular cells of the thyroid. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone.

parathyroid gland: One of four endocrine glands situated in the neck, usually on the posterior surface of the thyroid gland, that produce parathyroid hormone.

parathyroid hormone: A hormone produced by the parathyroid gland that acts to increase blood calcium levels by stimulating osteoclasts to release calcium from the bone.

The parathyroid glands are small endocrine glands —approximately the size of a grain of rice—in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the posterior surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest.

This is an illustration of the parathyroid gland in relation to the thyroid gland. They are located on the posterior surface of the lobes. The two parathyroid glands on each side of the thryoid gland that are positioned higher are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands.

Parathyroid gland: The parathyroid gland in relation to the thyroid gland. They are located on the posterior surface of the lobes.

The two parathyroid glands on each side that are positioned higher are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands. Occasionally, some individuals may have six, eight, or even more parathyroid glands.

Parathyroid glands control the amount of calcium in the blood and within the bones. The major function of the parathyroid glands is to maintain the body’s calcium level within a very narrow range, so that the nervous and muscular systems can function properly. When blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated to release
parathyroid hormone (PTH) into the blood.

PTH modulates calcium and phosphate homeostasis, as well as bone physiology. PTH has effects antagonistic to those of calcitonin by increasing blood calcium levels by stimulating osteoclasts to break down bone and release calcium. PTH also increases gastrointestinal calcium absorption by activating vitamin D, and promotes calcium conservation by re-absorption in the kidneys.

Parathyroid Hormone

Parathyroid hormone maintains the body’s calcium levels by increasing the absorption of calcium from the bones, kidneys, and GI tract.

Key Points

The parathyroid hormone works in concert with another hormone, calcitonin, that is produced by the thyroid to maintain blood calcium levels.

Parathyroid hormone acts to increase blood calcium levels, while calcitonin acts to decrease blood calcium levels.

When blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated, and the parathyroid glands release a parathyroid hormone into the blood.

PTH acts on the bone to increase blood calcium levels by stimulating osteoclasts to break down bone and release calcium into the bloodstream; on the GI tract to increase the activity of the enzyme in the intestines that activates vitamin D; and on the kidneys to promote calcium reabsorption.

Key Terms

vitamin D: A fat-soluble vitamin required for normal bone development and that prevents rickets; it can be manufactured in the skin on exposure to sunlight.

osteoclast: A large multinuclear cell associated with the breakdown and resorption of bone.

bone remodeling: The resorption by osteoclasts and replacement by osteoblasts in bones.

Parathyroid Glands

The parathyroid glands are small, pea-sized endocrine glands located on the rear side of the thyroid gland. The major function of the parathyroid glands is to maintain the body’s calcium level within a very narrow range, so that the nervous and muscular systems, which depend on calcium to transmit action potentials, can function properly.

When blood calcium levels drop below a certain point, the calcium-sensing receptors in the parathyroid gland are activated, and the parathyroid glands release parathyroid hormone (PTH) into the blood. PTH is a small protein hormone that is integral to the regulation of the level of calcium in the blood via the bone, kidneys, and intestines.

PTH works in concert with another hormone, calcitonin, that is produced by the thyroid to maintain calcium homoeostasis. Parathyroid hormone acts to increase blood calcium levels, while calcitonin acts to decrease blood calcium levels.

This interaction between parathyroid hormone and calcitonin is also an important part of bone remodeling. This is a lifelong process where mature bone tissue is removed from the skeleton and new bone tissue is formed.

This diagram shows the parathyroid glands in the neck sending parathyroid hormone into the bloodstream. This activates calcium reabsorption and vitamin D hydroxylation in the kidneys, calcium absorption from the intestines, and calcium reabsorption from bones. This increases calcium levels in the blood, which provides feedback to the parathyroid glands.

Calcium regulation: Parathyroid hormone regulates the levels of calcium in the blood. to the parathyroid glands.

Parathyroid Hormone Action

Parathyroid hormone acts on a bone to increase its blood calcium levels by stimulating osteoclasts to break down bone and release calcium into the bloodstream.
Parathyroid hormone acts on the gastrointestinal tract to increase blood calcium by increasing the activity of the enzyme in the intestines that activates vitamin D.
It acts on the kidneys to increase blood calcium levels by promoting calcium reabsorption in the nephrons.

The Role of Calcium in the Human Body… and how the Parathyroid Glands Control All Calcium Levels in our Bodies.

First a word about CALCIUM and what it does in our bodies. We use many elements in our bodies to perform all the different functions of life. Calcium is essential to life, and is used primarily for three things:

To provide the electrical energy for our nervous system. The most important thing that calcium does in the human body provides the means for electrical impulses to travel along nerves. Calcium is what the nervous system of our body uses to conduct electricity. This is why the most common symptoms of parathyroid disease and high calcium levels are related to the nervous system (depression, weakness, tiredness, etc, etc). Much more about symptoms of the parathyroid disease on another page.
To provide the electrical energy for our muscular system. Just like the nerves in our bodies, our muscles use changes in calcium levels inside the cells to provide the energy to contract. When the calcium levels are not correct, people can feel weak and have muscle cramps.
To provide strength to our skeletal system. Everyone knows that calcium is used to make our bones strong, but this is really only half the story. The bones themselves serve as the storage system that we use to make sure we will always have a good supply of calcium. Just like a bank vault where we constantly make deposits and withdrawals, we are constantly putting calcium into our bones, and constantly taking calcium out of our bones… all in small amounts… with the sole purpose of keeping our calcium levels in the blood at the correct level. Remember, the most important role of calcium is to provide for the proper functioning of our nervous system–not to provide strength to our bones–that is secondary.
Thus, calcium is the most closely regulated element in our bodies. In fact, calcium is the ONLY element/mineral that has its own regulatory system (the parathyroid glands). There are no other glands in our bodies that regulate any other element. Why? Because its the nervous system that separates us from all other plant and animal life–and calcium provides the electrical system for our nervous system. When our calcium levels get elevated (almost always due to a bad parathyroid gland), then we can have changes in our personality (typically noticed by our loved ones) and many other nervous-system symptoms (depression, etc). So, the parathyroid disease is not just about osteoporosis and kidney stones, it is primarily about us feeling “normal” and enjoying life.
The ONLY purpose of the parathyroid glands is to regulate the calcium level in our bodies within a very narrow range – so that the nervous and muscular systems can function properly. They measure the amount of calcium in the blood every minute of every day… and if the calcium levels go down a little bit, the parathyroid glands recognize it and make parathyroid hormone (PTH) which goes to the bones and takes some calcium out (makes a withdrawal from the calcium vault) and puts it into the blood. When the calcium in the blood is high enough, then the parathyroids shut down and stop making PTH.

The single major disease of parathyroid glands is over-activity of one or more of the parathyroids which make too much parathyroid hormone causing a potentially serious calcium imbalance (too high calcium in the blood). This is called hyperparathyroidism and this is the disease that this entire website is about.

Organ Systems Involved

Parathyroid hormone is directly involved in the bones, kidneys, and small intestine.

Effects of PTH on the Bones – In the bones, PTH stimulates the release of calcium in an indirect process through osteoclasts which ultimately leads to resorption of the bones. However, before osteoclast activity, PTH directly stimulates osteoblasts which increases their expression of RANKL, a receptor activator for nuclear factor kappa-B ligand, allowing for the differentiation of osteoblasts into osteoclasts. PTH also inhibits the secretion of osteoprotegerin, allowing for preferential differentiation into osteoclasts. Osteoprotegerin normally competitively binds with RANKL diminishing the ability to form osteoclasts. Osteoclasts possess the ability to remodel the bones (resorption) by dissolution and degradation of hydroxyapatite and other organic material, releasing calcium into the blood.
Effects of PTH on the Kidneys – At the kidneys, the parathyroid hormone has 3 functions in increasing serum calcium levels. Most of the physiologic calcium reabsorption in the nephron takes place in the proximal convoluted tubule and additionally at the ascending loop of Henle. Circulating parathyroid hormone targets the distal convoluted tubule and collecting duct, directly increasing calcium reabsorption. The parathyroid hormone decreases phosphate reabsorption at the proximal convoluted tubule. Phosphate ions in the serum form salts with calcium that are insoluble, resulting in a decreased plasma calcium. The reduction of phosphate ions, therefore, results in more ionized calcium in the blood.
PTH Indirect Effects on the Small Intestines and Reabsorption of Calcium – Starting at the kidneys, PTH stimulates the production of 1alpha-hydroxylase in the proximal convoluted tubule. This enzyme, 1alpha-hydroxylase, is required to catalyze the synthesis of active vitamin D – 1,25-dihydroxycholecalciferol from the inactive form 25-hydroxycholecalciferol. Active vitamin D plays a role in calcium reabsorption in the distal convoluted tubule via calbindin-D, a cytosolic vitamin D-dependent calcium-binding protein. In the small intestine, vitamin D allows the absorption of calcium through an active transcellular pathway and a passive paracellular pathway. The transcellular pathway requires energy, while the paracellular pathway allows for the passage of calcium through tight junctions.

Related Testing

Parathyroid gland dysfunctions will be characterized as under-activity or overactivity of the gland and will be evaluated in the context of serum calcium. Whenever there is a calcium imbalance suspected or found, the following pertinent labs are initially obtained: PTH, calcium, phosphate, albumin, vitamin D, and magnesium.[rx]

PTH in the Context of Hypercalcemia – If your blood is found to have high levels of calcium, you would expect to find suppressed levels of PTH in circulation, lower than the normal range of 10 to 65 ng/L. If serum PTH is found to be elevated in the context of hypercalcemia, further investigation of the parathyroid gland is warranted and will be initiated with imaging.
Parathyroid Pathology and Ultrasound – For suspected parathyroid gland pathology, ultrasound is the first imaging modality utilized due to its efficiency and cost-effectiveness. Ultrasound will usually be able to identify the presence of an adenoma as a hypoechoic mass-a a darker area representing a structure that isn’t bouncing back sound waves very well. The ultrasound can also be useful for anatomy orientation in a preoperative setting once surgery has been determined.
Parathyroid Pathology and Scintigraphy – Scintigraphy is another effective imaging modality that is gaining more favor in identifying parathyroid abnormalities. Scintigraphy utilizes a radioisotope tracer that gets taken up by local structures and allows for visualization of specific anatomy. The specific tracer utilized in this setting is sestamibi combined with 99mTC. In practice, it is found that adenomatous and hyperplastic parathyroid glands will take up a greater amount of tracer and will retain it longer than other adjacent benign structures.
Other Imaging Modalities – Other imaging such as enhanced contrast CT and MRI have their place in the clinical investigation of hyperparathyroidism.
PTH in the Context of Hypocalcemia – If hypocalcemia and low levels of PTH characterize the clinical scenario, then the concern is that the parathyroid glands are not producing enough PTH. Hypoparathyroidism can be caused by a variety of different conditions and can manifest in various ways. The underproduction of PTH can be chronic or transient, depending on the etiology. More common causes of hypoparathyroidism are the autoimmune destruction of the gland, damage during thyroid resections, or severe illnesses. Each of those conditions would need to be investigated further.

Parathyroid Quick Facts

There are 4 parathyroids glands. We all have 4 parathyroids glands.
Except in rare cases, parathyroid glands are in the neck behind the thyroid.
Parathyroids are NOT related to the thyroid (except they are neighbors in the neck).
The thyroid gland controls much of your body’s metabolism, but the parathyroid glands control body calcium. They have no relationship except they are neighbors.
Parathyroid glands make a hormone, called “Parathyroid Hormone”.
Doctors and labs abbreviate Parathyroid Hormone as “PTH”.
Just like calcium, PTH has a normal range in our blood…we can measure it to see how good or bad a job the parathyroid glands are doing.
All four parathyroid glands do the exact same thing.
Parathyroid glands control the amount of calcium in your blood.
Parathyroid glands control the amount of calcium in your bones.
You can easily live with one (or even 1/2) parathyroid gland.
Removing all 4 parathyroid glands will cause very bad symptoms of too little calcium (hypoparathyroidism). HypOparathyroidism is the opposite of hypERparathyroidism and it is very rare… only one page of this entire site is about hypoparathyroidism disease.
When parathyroid glands go bad, it is just one gland that goes bad about 91% of the time–it just grows big (develops a benign tumor) and makes too much hormone. About 8% of the time people with hyperparathyroidism will have two bad glands. It is quite uncommon for 3 or 4 glands to go bad.
When one of your parathyroid glands goes bad and makes too much hormone, the excess hormone goes to the bones and takes calcium out of the bones, and puts it in your blood. It’s the high calcium in the blood that makes you feel bad.
Everybody with a bad parathyroid gland will eventually develop bad osteoporosis–unless the bad gland is removed.
Parathyroids almost never develop cancer–so stop worrying about that!
However, not removing the parathyroid tumor and leaving the calcium high for a number of years will increase the chance of developing other cancers in your body (breast, colon, kidney, and prostate).
There is only ONE way to treat parathyroid problems–Surgery.
Mini-Surgery is now available that almost everyone can/should have. You should educate yourself about the new surgical treatments available. Do not have an “exploratory” operation to find the bad parathyroid tumor–this old-fashioned operation is too big and dangerous.

References

ByRx Harun

Superior Parathyroid Glands – Anatomy, Structure, Functions

Superior Parathyroid Glands/Parathyroid glands are four small glands of the endocrine system which regulate the calcium in our bodies. Parathyroid glands are located in the neck behind the thyroid where they continuously monitor and regulate blood calcium levels.

Types

Overview of the Parathyroid Glands

The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone.

Key Points

The parathyroid glands are four or more small glands, about the size of a grain of rice, located on the posterior surface of the thyroid gland.

The major function of the parathyroid glands is to maintain the body’s calcium level within a very narrow range, so the nervous and muscular systems can function properly.

Key Terms

calcitonin: A hormone that is produced primarily by the parafollicular cells of the thyroid. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone.

parathyroid gland: One of four endocrine glands situated in the neck, usually on the posterior surface of the thyroid gland, that produce parathyroid hormone.

parathyroid hormone: A hormone produced by the parathyroid gland that acts to increase blood calcium levels by stimulating osteoclasts to release calcium from the bone.

Parathyroid gland: The parathyroid gland in relation to the thyroid gland. They are located on the posterior surface of the lobes.

Parathyroid Hormone

Parathyroid hormone maintains the body’s calcium levels by increasing the absorption of calcium from the bones, kidneys, and GI tract.

Key Points

The parathyroid hormone works in concert with another hormone, calcitonin, that is produced by the thyroid to maintain blood calcium levels.

Parathyroid hormone acts to increase blood calcium levels, while calcitonin acts to decrease blood calcium levels.

When blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated, and the parathyroid glands release a parathyroid hormone into the blood.

PTH acts on the bone to increase blood calcium levels by stimulating osteoclasts to break down bone and release calcium into the bloodstream; on the GI tract to increase the activity of the enzyme in the intestines that activates vitamin D; and on the kidneys to promote calcium reabsorption.

Key Terms

vitamin D: A fat-soluble vitamin required for normal bone development and that prevents rickets; it can be manufactured in the skin on exposure to sunlight.

osteoclast: A large multinuclear cell associated with the breakdown and resorption of bone.

bone remodeling: The resorption by osteoclasts and replacement by osteoblasts in bones.

Parathyroid Glands

Calcium regulation: Parathyroid hormone regulates the levels of calcium in the blood. to the parathyroid glands.

Parathyroid Hormone Action

Parathyroid hormone acts on a bone to increase its blood calcium levels by stimulating osteoclasts to break down bone and release calcium into the bloodstream.
Parathyroid hormone acts on the gastrointestinal tract to increase blood calcium by increasing the activity of the enzyme in the intestines that activates vitamin D.
It acts on the kidneys to increase blood calcium levels by promoting calcium reabsorption in the nephrons.

The Role of Calcium in the Human Body… and how the Parathyroid Glands Control All Calcium Levels in our Bodies.

To provide the electrical energy for our nervous system. The most important thing that calcium does in the human body provides the means for electrical impulses to travel along nerves. Calcium is what the nervous system of our body uses to conduct electricity. This is why the most common symptoms of parathyroid disease and high calcium levels are related to the nervous system (depression, weakness, tiredness, etc, etc). Much more about symptoms of the parathyroid disease on another page.
To provide the electrical energy for our muscular system. Just like the nerves in our bodies, our muscles use changes in calcium levels inside the cells to provide the energy to contract. When the calcium levels are not correct, people can feel weak and have muscle cramps.
To provide strength to our skeletal system. Everyone knows that calcium is used to make our bones strong, but this is really only half the story. The bones themselves serve as the storage system that we use to make sure we will always have a good supply of calcium. Just like a bank vault where we constantly make deposits and withdrawals, we are constantly putting calcium into our bones, and constantly taking calcium out of our bones… all in small amounts… with the sole purpose of keeping our calcium levels in the blood at the correct level. Remember, the most important role of calcium is to provide for the proper functioning of our nervous system–not to provide strength to our bones–that is secondary.
Thus, calcium is the most closely regulated element in our bodies. In fact, calcium is the ONLY element/mineral that has its own regulatory system (the parathyroid glands). There are no other glands in our bodies that regulate any other element. Why? Because its the nervous system that separates us from all other plant and animal life–and calcium provides the electrical system for our nervous system. When our calcium levels get elevated (almost always due to a bad parathyroid gland), then we can have changes in our personality (typically noticed by our loved ones) and many other nervous-system symptoms (depression, etc). So, the parathyroid disease is not just about osteoporosis and kidney stones, it is primarily about us feeling “normal” and enjoying life.
The ONLY purpose of the parathyroid glands is to regulate the calcium level in our bodies within a very narrow range – so that the nervous and muscular systems can function properly. They measure the amount of calcium in the blood every minute of every day… and if the calcium levels go down a little bit, the parathyroid glands recognize it and make parathyroid hormone (PTH) which goes to the bones and takes some calcium out (makes a withdrawal from the calcium vault) and puts it into the blood. When the calcium in the blood is high enough, then the parathyroids shut down and stop making PTH.

Organ Systems Involved

Parathyroid hormone is directly involved in the bones, kidneys, and small intestine.

Effects of PTH on the Bones – In the bones, PTH stimulates the release of calcium in an indirect process through osteoclasts which ultimately leads to resorption of the bones. However, before osteoclast activity, PTH directly stimulates osteoblasts which increases their expression of RANKL, a receptor activator for nuclear factor kappa-B ligand, allowing for the differentiation of osteoblasts into osteoclasts. PTH also inhibits the secretion of osteoprotegerin, allowing for preferential differentiation into osteoclasts. Osteoprotegerin normally competitively binds with RANKL diminishing the ability to form osteoclasts. Osteoclasts possess the ability to remodel the bones (resorption) by dissolution and degradation of hydroxyapatite and other organic material, releasing calcium into the blood.
Effects of PTH on the Kidneys – At the kidneys, the parathyroid hormone has 3 functions in increasing serum calcium levels. Most of the physiologic calcium reabsorption in the nephron takes place in the proximal convoluted tubule and additionally at the ascending loop of Henle. Circulating parathyroid hormone targets the distal convoluted tubule and collecting duct, directly increasing calcium reabsorption. The parathyroid hormone decreases phosphate reabsorption at the proximal convoluted tubule. Phosphate ions in the serum form salts with calcium that are insoluble, resulting in a decreased plasma calcium. The reduction of phosphate ions, therefore, results in more ionized calcium in the blood.
PTH Indirect Effects on the Small Intestines and Reabsorption of Calcium – Starting at the kidneys, PTH stimulates the production of 1alpha-hydroxylase in the proximal convoluted tubule. This enzyme, 1alpha-hydroxylase, is required to catalyze the synthesis of active vitamin D – 1,25-dihydroxycholecalciferol from the inactive form 25-hydroxycholecalciferol. Active vitamin D plays a role in calcium reabsorption in the distal convoluted tubule via calbindin-D, a cytosolic vitamin D-dependent calcium-binding protein. In the small intestine, vitamin D allows the absorption of calcium through an active transcellular pathway and a passive paracellular pathway. The transcellular pathway requires energy, while the paracellular pathway allows for the passage of calcium through tight junctions.

Related Testing

PTH in the Context of Hypercalcemia – If your blood is found to have high levels of calcium, you would expect to find suppressed levels of PTH in circulation, lower than the normal range of 10 to 65 ng/L. If serum PTH is found to be elevated in the context of hypercalcemia, further investigation of the parathyroid gland is warranted and will be initiated with imaging.
Parathyroid Pathology and Ultrasound – For suspected parathyroid gland pathology, ultrasound is the first imaging modality utilized due to its efficiency and cost-effectiveness. Ultrasound will usually be able to identify the presence of an adenoma as a hypoechoic mass-a a darker area representing a structure that isn’t bouncing back sound waves very well. The ultrasound can also be useful for anatomy orientation in a preoperative setting once surgery has been determined.
Parathyroid Pathology and Scintigraphy – Scintigraphy is another effective imaging modality that is gaining more favor in identifying parathyroid abnormalities. Scintigraphy utilizes a radioisotope tracer that gets taken up by local structures and allows for visualization of specific anatomy. The specific tracer utilized in this setting is sestamibi combined with 99mTC. In practice, it is found that adenomatous and hyperplastic parathyroid glands will take up a greater amount of tracer and will retain it longer than other adjacent benign structures.
Other Imaging Modalities – Other imaging such as enhanced contrast CT and MRI have their place in the clinical investigation of hyperparathyroidism.
PTH in the Context of Hypocalcemia – If hypocalcemia and low levels of PTH characterize the clinical scenario, then the concern is that the parathyroid glands are not producing enough PTH. Hypoparathyroidism can be caused by a variety of different conditions and can manifest in various ways. The underproduction of PTH can be chronic or transient, depending on the etiology. More common causes of hypoparathyroidism are the autoimmune destruction of the gland, damage during thyroid resections, or severe illnesses. Each of those conditions would need to be investigated further.

Parathyroid Quick Facts

There are 4 parathyroids glands. We all have 4 parathyroids glands.
Except in rare cases, parathyroid glands are in the neck behind the thyroid.
Parathyroids are NOT related to the thyroid (except they are neighbors in the neck).
The thyroid gland controls much of your body’s metabolism, but the parathyroid glands control body calcium. They have no relationship except they are neighbors.
Parathyroid glands make a hormone, called “Parathyroid Hormone”.
Doctors and labs abbreviate Parathyroid Hormone as “PTH”.
Just like calcium, PTH has a normal range in our blood…we can measure it to see how good or bad a job the parathyroid glands are doing.
All four parathyroid glands do the exact same thing.
Parathyroid glands control the amount of calcium in your blood.
Parathyroid glands control the amount of calcium in your bones.
You can easily live with one (or even 1/2) parathyroid gland.
Removing all 4 parathyroid glands will cause very bad symptoms of too little calcium (hypoparathyroidism). HypOparathyroidism is the opposite of hypERparathyroidism and it is very rare… only one page of this entire site is about hypoparathyroidism disease.
When parathyroid glands go bad, it is just one gland that goes bad about 91% of the time–it just grows big (develops a benign tumor) and makes too much hormone. About 8% of the time people with hyperparathyroidism will have two bad glands. It is quite uncommon for 3 or 4 glands to go bad.
When one of your parathyroid glands goes bad and makes too much hormone, the excess hormone goes to the bones and takes calcium out of the bones, and puts it in your blood. It’s the high calcium in the blood that makes you feel bad.
Everybody with a bad parathyroid gland will eventually develop bad osteoporosis–unless the bad gland is removed.
Parathyroids almost never develop cancer–so stop worrying about that!
However, not removing the parathyroid tumor and leaving the calcium high for a number of years will increase the chance of developing other cancers in your body (breast, colon, kidney, and prostate).
There is only ONE way to treat parathyroid problems–Surgery.
Mini-Surgery is now available that almost everyone can/should have. You should educate yourself about the new surgical treatments available. Do not have an “exploratory” operation to find the bad parathyroid tumor–this old-fashioned operation is too big and dangerous.

References

ByRx Harun

Parathyroid Glands – Anatomy, Types, Structure, Functions

Parathyroid glands are four small glands of the endocrine system which regulate the calcium in our bodies. Parathyroid glands are located in the neck behind the thyroid where they continuously monitor and regulate blood calcium levels.

Types

Overview of the Parathyroid Glands

The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone.

Key Points

The parathyroid glands are four or more small glands, about the size of a grain of rice, located on the posterior surface of the thyroid gland.

The major function of the parathyroid glands is to maintain the body’s calcium level within a very narrow range, so the nervous and muscular systems can function properly.

Key Terms

calcitonin: A hormone that is produced primarily by the parafollicular cells of the thyroid. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone.

parathyroid gland: One of four endocrine glands situated in the neck, usually on the posterior surface of the thyroid gland, that produce parathyroid hormone.

parathyroid hormone: A hormone produced by the parathyroid gland that acts to increase blood calcium levels by stimulating osteoclasts to release calcium from the bone.

This is an illustration of the parathyroid gland in relation to the thyroid gland. They are located on the posterior surface of the lobes. The two parathyroid glands on each side of the thryoid gland that are positioned higher are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands.

Parathyroid gland: The parathyroid gland in relation to the thyroid gland. They are located on the posterior surface of the lobes.

Parathyroid Hormone

Parathyroid hormone maintains the body’s calcium levels by increasing the absorption of calcium from the bones, kidneys, and GI tract.

Key Points

The parathyroid hormone works in concert with another hormone, calcitonin, that is produced by the thyroid to maintain blood calcium levels.

Parathyroid hormone acts to increase blood calcium levels, while calcitonin acts to decrease blood calcium levels.

When blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated, and the parathyroid glands release a parathyroid hormone into the blood.

PTH acts on the bone to increase blood calcium levels by stimulating osteoclasts to break down bone and release calcium into the bloodstream; on the GI tract to increase the activity of the enzyme in the intestines that activates vitamin D; and on the kidneys to promote calcium reabsorption.

Key Terms

vitamin D: A fat-soluble vitamin required for normal bone development and that prevents rickets; it can be manufactured in the skin on exposure to sunlight.

osteoclast: A large multinuclear cell associated with the breakdown and resorption of bone.

bone remodeling: The resorption by osteoclasts and replacement by osteoblasts in bones.

Parathyroid Glands

Calcium regulation: Parathyroid hormone regulates the levels of calcium in the blood. to the parathyroid glands.

Parathyroid Hormone Action

Parathyroid hormone acts on a bone to increase its blood calcium levels by stimulating osteoclasts to break down bone and release calcium into the bloodstream.
Parathyroid hormone acts on the gastrointestinal tract to increase blood calcium by increasing the activity of the enzyme in the intestines that activates vitamin D.
It acts on the kidneys to increase blood calcium levels by promoting calcium reabsorption in the nephrons.

The Role of Calcium in the Human Body… and how the Parathyroid Glands Control All Calcium Levels in our Bodies.

To provide the electrical energy for our nervous system. The most important thing that calcium does in the human body provides the means for electrical impulses to travel along nerves. Calcium is what the nervous system of our body uses to conduct electricity. This is why the most common symptoms of parathyroid disease and high calcium levels are related to the nervous system (depression, weakness, tiredness, etc, etc). Much more about symptoms of the parathyroid disease on another page.
To provide the electrical energy for our muscular system. Just like the nerves in our bodies, our muscles use changes in calcium levels inside the cells to provide the energy to contract. When the calcium levels are not correct, people can feel weak and have muscle cramps.
To provide strength to our skeletal system. Everyone knows that calcium is used to make our bones strong, but this is really only half the story. The bones themselves serve as the storage system that we use to make sure we will always have a good supply of calcium. Just like a bank vault where we constantly make deposits and withdrawals, we are constantly putting calcium into our bones, and constantly taking calcium out of our bones… all in small amounts… with the sole purpose of keeping our calcium levels in the blood at the correct level. Remember, the most important role of calcium is to provide for the proper functioning of our nervous system–not to provide strength to our bones–that is secondary.
Thus, calcium is the most closely regulated element in our bodies. In fact, calcium is the ONLY element/mineral that has its own regulatory system (the parathyroid glands). There are no other glands in our bodies that regulate any other element. Why? Because its the nervous system that separates us from all other plant and animal life–and calcium provides the electrical system for our nervous system. When our calcium levels get elevated (almost always due to a bad parathyroid gland), then we can have changes in our personality (typically noticed by our loved ones) and many other nervous-system symptoms (depression, etc). So, the parathyroid disease is not just about osteoporosis and kidney stones, it is primarily about us feeling “normal” and enjoying life.
The ONLY purpose of the parathyroid glands is to regulate the calcium level in our bodies within a very narrow range – so that the nervous and muscular systems can function properly. They measure the amount of calcium in the blood every minute of every day… and if the calcium levels go down a little bit, the parathyroid glands recognize it and make parathyroid hormone (PTH) which goes to the bones and takes some calcium out (makes a withdrawal from the calcium vault) and puts it into the blood. When the calcium in the blood is high enough, then the parathyroids shut down and stop making PTH.

Organ Systems Involved

Parathyroid hormone is directly involved in the bones, kidneys, and small intestine.

Effects of PTH on the Bones – In the bones, PTH stimulates the release of calcium in an indirect process through osteoclasts which ultimately leads to resorption of the bones. However, before osteoclast activity, PTH directly stimulates osteoblasts which increases their expression of RANKL, a receptor activator for nuclear factor kappa-B ligand, allowing for the differentiation of osteoblasts into osteoclasts. PTH also inhibits the secretion of osteoprotegerin, allowing for preferential differentiation into osteoclasts. Osteoprotegerin normally competitively binds with RANKL diminishing the ability to form osteoclasts. Osteoclasts possess the ability to remodel the bones (resorption) by dissolution and degradation of hydroxyapatite and other organic material, releasing calcium into the blood.
Effects of PTH on the Kidneys – At the kidneys, the parathyroid hormone has 3 functions in increasing serum calcium levels. Most of the physiologic calcium reabsorption in the nephron takes place in the proximal convoluted tubule and additionally at the ascending loop of Henle. Circulating parathyroid hormone targets the distal convoluted tubule and collecting duct, directly increasing calcium reabsorption. The parathyroid hormone decreases phosphate reabsorption at the proximal convoluted tubule. Phosphate ions in the serum form salts with calcium that are insoluble, resulting in a decreased plasma calcium. The reduction of phosphate ions, therefore, results in more ionized calcium in the blood.
PTH Indirect Effects on the Small Intestines and Reabsorption of Calcium – Starting at the kidneys, PTH stimulates the production of 1alpha-hydroxylase in the proximal convoluted tubule. This enzyme, 1alpha-hydroxylase, is required to catalyze the synthesis of active vitamin D – 1,25-dihydroxycholecalciferol from the inactive form 25-hydroxycholecalciferol. Active vitamin D plays a role in calcium reabsorption in the distal convoluted tubule via calbindin-D, a cytosolic vitamin D-dependent calcium-binding protein. In the small intestine, vitamin D allows the absorption of calcium through an active transcellular pathway and a passive paracellular pathway. The transcellular pathway requires energy, while the paracellular pathway allows for the passage of calcium through tight junctions.

Related Testing

PTH in the Context of Hypercalcemia – If your blood is found to have high levels of calcium, you would expect to find suppressed levels of PTH in circulation, lower than the normal range of 10 to 65 ng/L. If serum PTH is found to be elevated in the context of hypercalcemia, further investigation of the parathyroid gland is warranted and will be initiated with imaging.
Parathyroid Pathology and Ultrasound – For suspected parathyroid gland pathology, ultrasound is the first imaging modality utilized due to its efficiency and cost-effectiveness. Ultrasound will usually be able to identify the presence of an adenoma as a hypoechoic mass-a a darker area representing a structure that isn’t bouncing back sound waves very well. The ultrasound can also be useful for anatomy orientation in a preoperative setting once surgery has been determined.
Parathyroid Pathology and Scintigraphy – Scintigraphy is another effective imaging modality that is gaining more favor in identifying parathyroid abnormalities. Scintigraphy utilizes a radioisotope tracer that gets taken up by local structures and allows for visualization of specific anatomy. The specific tracer utilized in this setting is sestamibi combined with 99mTC. In practice, it is found that adenomatous and hyperplastic parathyroid glands will take up a greater amount of tracer and will retain it longer than other adjacent benign structures.
Other Imaging Modalities – Other imaging such as enhanced contrast CT and MRI have their place in the clinical investigation of hyperparathyroidism.
PTH in the Context of Hypocalcemia – If hypocalcemia and low levels of PTH characterize the clinical scenario, then the concern is that the parathyroid glands are not producing enough PTH. Hypoparathyroidism can be caused by a variety of different conditions and can manifest in various ways. The underproduction of PTH can be chronic or transient, depending on the etiology. More common causes of hypoparathyroidism are the autoimmune destruction of the gland, damage during thyroid resections, or severe illnesses. Each of those conditions would need to be investigated further.

Parathyroid Quick Facts

There are 4 parathyroids glands. We all have 4 parathyroids glands.
Except in rare cases, parathyroid glands are in the neck behind the thyroid.
Parathyroids are NOT related to the thyroid (except they are neighbors in the neck).
The thyroid gland controls much of your body’s metabolism, but the parathyroid glands control body calcium. They have no relationship except they are neighbors.
Parathyroid glands make a hormone, called “Parathyroid Hormone”.
Doctors and labs abbreviate Parathyroid Hormone as “PTH”.
Just like calcium, PTH has a normal range in our blood…we can measure it to see how good or bad a job the parathyroid glands are doing.
All four parathyroid glands do the exact same thing.
Parathyroid glands control the amount of calcium in your blood.
Parathyroid glands control the amount of calcium in your bones.
You can easily live with one (or even 1/2) parathyroid gland.
Removing all 4 parathyroid glands will cause very bad symptoms of too little calcium (hypoparathyroidism). HypOparathyroidism is the opposite of hypERparathyroidism and it is very rare… only one page of this entire site is about hypoparathyroidism disease.
When parathyroid glands go bad, it is just one gland that goes bad about 91% of the time–it just grows big (develops a benign tumor) and makes too much hormone. About 8% of the time people with hyperparathyroidism will have two bad glands. It is quite uncommon for 3 or 4 glands to go bad.
When one of your parathyroid glands goes bad and makes too much hormone, the excess hormone goes to the bones and takes calcium out of the bones, and puts it in your blood. It’s the high calcium in the blood that makes you feel bad.
Everybody with a bad parathyroid gland will eventually develop bad osteoporosis–unless the bad gland is removed.
Parathyroids almost never develop cancer–so stop worrying about that!
However, not removing the parathyroid tumor and leaving the calcium high for a number of years will increase the chance of developing other cancers in your body (breast, colon, kidney, and prostate).
There is only ONE way to treat parathyroid problems–Surgery.
Mini-Surgery is now available that almost everyone can/should have. You should educate yourself about the new surgical treatments available. Do not have an “exploratory” operation to find the bad parathyroid tumor–this old-fashioned operation is too big and dangerous.

References

ByRx Harun

Thyroid – Anatomy, Blood, Nerve Supply, Functions

The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is in the neck and consists of two connected lobes. The lower two-thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyroid is located at the front of the neck, below Adam’s apple. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid. The thyroid gland secretes three hormones: the two thyroid hormones – triiodothyronine (T₃) and thyroxine (T₄) – and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis, and in children, growth and development. Calcitonin plays a role in calcium homeostasis.^[1] Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the anterior pituitary gland. TSH is regulated by the thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus.^[rx]

The thyroid gland is a midline structure located in the anterior neck. The thyroid functions as an endocrine gland and is responsible for producing thyroid hormone and calcitonin, thus contributing to the regulation of metabolism, growth, and serum concentrations of electrolytes such as calcium.[rx][rx]

Many disease processes can involve the thyroid gland, and alterations in the production of hormones can result in hypothyroidism or hyperthyroidism. The thyroid gland is involved in inflammatory processes (e.g., thyroiditis), autoimmune processes (e.g., Graves disease), and cancers (e.g., papillary thyroid carcinoma, medullary thyroid carcinoma, and follicular carcinoma).

In addition to considering its role in metabolism, growth, regulation of certain electrolytes, and its involvement in many disease processes, the thyroid gland deserves consideration for its anatomical location and its close relationship to important structures including the parathyroid glands, recurrent laryngeal nerves, and certain vasculature.

Graves' disease

Anatomy of Thyroid

The thyroid gland is divided into two lobes that are connected by the isthmus, which crosses the midline of the upper trachea at the second and third tracheal rings. In its anatomic position, the thyroid gland lies posterior to the sternothyroid and sternohyoid muscles, wrapping around the cricoid cartilage and tracheal rings. It is located inferior to the laryngeal thyroid cartilage, typically corresponding to the vertebral levels C5-T1. The thyroid attaches to the trachea via consolidation of connective tissue, referred to as the lateral suspensory ligament or Berry’s ligament. This ligament connects each of the thyroid lobes to the trachea. The thyroid gland, along with the esophagus, pharynx, and trachea, is found within the visceral compartment of the neck which is bound by pretracheal fascia.

The “normal” thyroid gland has lateral lobes that are symmetrical with a well-marked centrally located isthmus. The thyroid gland typically contains a pyramidal extension on the posterior-most aspect of each lobe, referred to as the tubercle of Zuckerkandl. Despite these general characteristics, the thyroid gland is known to have many morphologic variations. The position of the thyroid gland and its close relationship with various structures brings about several surgical considerations with clinical relevance.

Blood Supply and Lymphatics of Thyroid

The thyroid gland has an extremely rich blood supply and is estimated to be six times as vascular as the kidney and relatively three to four times more vascular than the brain. It receives blood from the superior and inferior thyroid arteries. These paired vessels supply the superior and inferior aspects of the gland. The superior thyroid artery is the first branch of the external carotid artery as it arises near the level of the superior horn of the thyroid cartilage. The superior thyroid artery then moves anterior, inferior, and towards the midline behind the sternothyroid muscle to the superior pole of the lobe of the thyroid gland. From this point, the superior thyroid artery branches off. One branching point runs down the dorsal aspect of the thyroid gland. The other superficial branch runs along with the sternothyroid muscle and thyrohyoid muscles, supplying branches to these muscles as well as the sternohyoid. The superficial branch continues downward to further give off the cricothyroid branch and to supply the isthmus, inner sides of the lateral lobes, and when present, the pyramidal lobe.[rx]

The thyrocervical trunk arises from the anterosuperior surface of the subclavian artery and gives rise to three branches, one being the inferior thyroid artery. The inferior thyroid artery branches from the thyrocervical trunk at the inner border of the anterior scalene muscle and advances medially to the thyroid gland. The artery reaches the posterior surface of the lateral lobe of the thyroid gland at the level of the junction of the upper two thirds and lower third of the outer border. The largest branch of the inferior thyroid artery is the ascending cervical branch, and it is important not to mistake this branch for the inferior thyroid artery itself. [4]

In 10% of the population, there is an additional artery known as the thyroid ima artery. This artery has a variable origin including the brachiocephalic trunk, aortic arch, the right common carotid, the subclavian, the pericardiacophrenic artery, the thyrocervical trunk, transverse scapular, or internal thoracic artery. The thyroid ima most commonly originates from the brachiocephalic trunk and supplies the isthmus and anterior thyroid gland.

The thyroid gland is drained via the superior, middle, and inferior thyroid veins. The middle and superior thyroid veins follow a tortuous route and eventually drain into the internal jugular vein on either side of the neck. The drainage of the inferior thyroid vein may enter either the subclavian or brachiocephalic veins, located just posterior to the manubrium.

Lymphatic drainage of the thyroid gland involves the lower deep cervical, laryngeal, pretracheal, and paratracheal nodes. The paratracheal and lower deep cervical nodes, specifically, receive lymphatic drainage from the isthmus and the inferior lateral lobes. The superior portions of the thyroid gland drain into the superior paratracheal and cervical nodes.

Nerves Supply of Thyroid

The autonomic nervous system primarily innervates the thyroid gland. The vagus nerve provides the main parasympathetic fibers, while sympathetic fibers originate from the inferior, middle, and superior ganglia of the sympathetic trunk. These nerves do not play a role in the control of hormonal production or secretion but mostly influence vasculature. [rx]

Muscles attachment of Thyroid

Several muscles should be considered when discussing neck and thyroid surgical anatomy.

Platysma: The first muscle encountered during neck dissection, it is enveloped by the superficial cervical fascia. It sits in the anterior neck and extends from the superficial fascia of the deltoid, over the clavicle, reaching the mandible and superficial fascia of the face superiorly.
Sternocleidomastoid: This muscle forms the anterior portion of the posterior triangle of the neck. The muscle runs obliquely from the mastoid to the clavicle and sternum. The sternocleidomastoid is found anterolaterally relative to the thyroid gland.
Digastric muscle: This muscle extends from the mandibular tubercle, passes deep and inferior to the hyoid, and loops back up to attach to the mastoid tip.
Infrahyoid muscles: These are also referred to as “strap muscles.” They include four paired muscles found on the anterolateral surface of the thyroid gland. The strap muscles result in gross movement of the larynx during swallowing and also adjust the positioning of the larynx during vocalization.
Omohyoid muscle: The omohyoid muscle is found deep in the sternocleidomastoid. It extends from the hyoid bone to the lateral aspect of the clavicle.
Sternohyoid muscle: This muscle sits anterior the remaining strap muscles and the thyroid gland. The sternohyoid muscle extends from its superior attachment at the hyoid bone inferiorly to the sternum.
Sternothyroid muscle: This muscle extends from the oblique line of the thyroid cartilage to the sternum. This muscle contacts the anterior surface of the thyroid gland.
Thyrohyoid muscle: The thyrohyoid muscle extends from the oblique line of the thyroid cartilage to the hyoid bone superiorly.
Inferior pharyngeal constrictor: This muscle extends from its anterior attachment at the oblique line of the thyroid cartilage and lateral aspect of the cricoid cartilage to the pharyngeal raphe. This muscle contacts the superior pole of the lateral lobe of the thyroid gland medially.

Surgical Considerations

Due to its close relationship with several structures, the following must be considered during total thyroidectomy, thyroid lobectomy, or procedures involving the excision of a thyroglossal duct cyst.[rx][rx][rx]

A chest radiography or mediastinal computed tomography [CT] is performed preoperatively if anatomic abnormalities or substernal extension of the thyroid are suspected.
Due to the location of the thyroid gland, a slight neck extension of the patient on the operating table facilitates access to the neck.
The typical skin incision allowing proper access to the gland ranges from one to one and a half to two fingerbreadths above the clavicle. This incision is curvilinear and parallel or within a skin line.

More about Structure

Larynx – In re-operative cases, it is recommended to perform laryngoscopy regardless of voice symptomology asymptomatic vocal cord paralysis can occur in up to 30% of patients after anterior neck surgery.
Recurrent Laryngeal Nerve – The two nerves of importance that pass through the thyroid are the left and right recurrent laryngeal nerves [RLN]. They are often located on the lateral aspect of the thyroid gland near the vicinity of the inferior thyroid artery. When operating on the thyroid gland, it is vital to visualize these nerves and avoid trauma. The nerve can be exposed caudal to the inferior thyroid artery or following mobilization of the superior and inferior poles. The nerve is most likely to be injured in its distal portion [2-3cm]. This distal portion of the RLN is covered by either or both the tubercle of Zuckerkandl [a pyramidal extension on the most posterior aspect of each lobe] and the ligament of Berry. Most often, it is not until the tubercle of Zuckerkandl is medially retracted that the RLN is seen. The RLN most often traverses just medial to the tubercle and is hidden from view. The distal course of the RLN is more easily identified in total lobectomies as opposed to subtotal lobectomies, in which the distal course of the RLN may not always be visualized.
Superior laryngeal nerve – When the superior pole of the thyroid gland is dissected, one may visualize the superior laryngeal nerve [SLN] which often runs next to the superior thyroid artery. High ligation of the superior thyroid artery should be avoided as one can easily injure the superior laryngeal nerve. Approximately 20% of patients are at risk of injury to the external branch of the SLN when using a technique in which the superior thyroid vessels are clamped, divided, and ligated en masse. Dividing the superior thyroid vessels as they enter the capsule prevents injury to those nerves in close proximity to the artery. In practice, most surgeons do not insist on direct visualization of the superior laryngeal nerve.
Cervical sympathetic trunk – Rarely, the cervical sympathetic trunk may be injured. This is a consideration when the carotid sheath is mobilized in order to treat retro esophageal extension of a goiter or malignancy.
Esophagus – Altered anatomy and displacement of the trachea can result in the exposure of the anterior esophageal surface, creating the risk of potential injury.
Carotid artery – The carotid arteries, which course posterolateral to the thyroid gland, are rarely an issue during thyroidectomy. Excessive lateral traction in an individual with an enlarged thyroid gland may result in ocular or central nervous system damage from reduced blood flow. This is preventable with proper retraction and tissue handling.
Parathyroid glands – The parathyroid glands are in a close anatomic relationship to the thyroid gland, sitting on the posterior aspect of the thyroid gland. The parathyroid glands also share arterial supply with the thyroid gland, being supplied by an end-artery, typically the inferior thyroid artery. Due to its anatomic relationship and vascular supply, there a few considerations with regards to the parathyroid glands in thyroid surgeries. By dividing the branches of the inferior thyroid artery beyond the parathyroid gland on the thyroid gland capsule, disruption of the end-artery can best be avoided. However, transplantation to a “dry” pocket in the sternocleidomastoid muscle, a subcutaneous area or forearm can be performed if end-artery damage does occur.
Thyroglossal duct cyst procedure – Approximately 50% of thyroglossal duct cysts are close to or just inferior to the hyoid bone. Due to its relation to the hyoid bone and the rates of recurrence, surgical removal includes the cyst, the middle segment of the hyoid bone, and the track that leads to the base of the tongue. This procedure is referred to as the Sistrunk Procedure.
Post Operative Bleeding – Due to the location, hematomas may lead to acute respiratory problems. Insidious hemorrhage may also result in laryngeal edema and infrequently can lead to the need for tracheostomy.
Muscle Closure Following Thyroid Procedures – Surgical considerations for wound closure are under consideration of transversely divided muscles. One must consider a closure that would create space for blood to disperse if bleeding were to occur. When the strap muscles are separated from the midline and retracted laterally, reapproximation in the midline is performed, once again with consideration of space for possible bleeding. Additionally, some reapproximate the platysma muscle and its fascia.

Clinical Significance

Goiter – It is a condition where the thyroid gland shows an abnormal enlargement. Goiters broadly classify into uni-nodular, multinodular, and diffuse types. Each further includes many different types of goiters. Some of the commonest with some of their important features are described below.[rx][rx]
Colloid nodular goiter – This is the commonest of the non-neoplastic lesions of the thyroid.[rx] In these types of goiter, the thyroid follicles are filled with an abundant amount of colloid in their lumens and lined by squamous follicular cells.
Hyperthyroidism (Thyrotoxicosis) – It is a condition of hypermetabolic state and hyperfunctioning of the thyroid gland resulting in increased T3 and T4 levels. Some symptoms included palpitations, tachycardia, nervousness, etc.
Graves disease – This disease is a combination of thyrotoxicosis, exophthalmos, and dermopathy (myxedema). It is especially seen in women in the age group of 20 to 40 years, manifesting in the form of prolonged and violent palpitations.
Thyroid cancer – Thyroid carcinomas arise either from the follicular epithelium or parafollicular C-cells. They are painless nodules and compression, displaces the adjacent structures. The carcinomas of the thyroid can manifest in the form of papillary carcinoma, follicular carcinoma, anaplastic carcinoma, and medullary carcinoma.
Thyroiditis – Inflammation of the thyroid, usually from a viral infection or autoimmune condition. Thyroiditis can be painful or have no symptoms at all.
Thyroid cancer – An uncommon form of cancer, thyroid cancer is usually curable. Surgery, radiation, and hormone treatments may be used to treat thyroid cancer.
Thyroid nodule – A small abnormal mass or lump in the thyroid gland. Thyroid nodules are extremely common. Few are cancerous. They may secrete excess hormones, causing hyperthyroidism, or cause no problems.
Thyroid storm – A rare form of hyperthyroidism in which extremely high thyroid hormone levels cause severe illness.

Symptoms of Hypothyroidism

Generalized decreased basal metabolic rate can present as apathy, slowed cognition, skin dryness, alopecia, increased low-density lipoproteins, and increased triglycerides. Hypothyroidism must be ruled out in psychiatry patients presenting with apathy and slowed cognition. Hypothyroidism can decrease sympathetic activity leading to decreased sweating, bradycardia, and constipation. Patients can present with myopathy and decreased cardiac output because of decreased transcription of sarcolemmal genes.

Hyperprolactinemia can be caused by hypothyroidism. Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates prolactin and TSH release. Prolactin release can suppress testosterone, LH, FSH, and GnRH release. Prolactin can also cause breast tissue growth.

Patients with hypothyroidism may present with myxedema caused by decreased clearance of complex glycosaminoglycans and hyaluronic acids from the reticular layer of the dermis. Initially, the nonpitting edema is pretibial. As the state of hypothyroidism continues, patients can develop generalized edema.

Symptoms related to decreased metabolic rate

Bradycardia
Fatigue
Cold intolerance
Weight gain
Poor appetite
Hair loss
Cold and dry skin
Constipation
Myopathy, stiffness, cramps, entrapment syndromes
Delayed deep tendon reflex relaxation

Symptoms from generalized myxedema

Myxedematous heart disease
Puffy appearance with doughy skin texture
Hoarse voice with difficulty articulate words
Pretibial and periorbital edema

Symptoms of hyperprolactinemia

Amenorrhea or menorrhagia
Galactorrhea
Erectile dysfunction, infertility in men
Decreased libido

Other symptoms

Depression
Impaired concentration and memory
Goiter
Hypertension

Congenital hypothyroidism

Umbilical hernia
Hypotonia
Prolonged neonatal jaundice
Poor feeding, absence of thirst (adipsia)
Decreased activity
Pot-belly, puffy-face, protuberant tongue
Poor brain development

Symptoms of Hyperthyroidism

Generalized hypermetabolism from hyperthyroidism causes increased Na+/K+-ATPase to promote thermogenesis. There is increased catecholamine secretion and, beta-adrenergic receptors are also upregulated in various tissues. As a result of the hyperadrenergic state, peripheral vascular resistance is decreased. In the heart, hyperthyroidism causes a decreased amount of phospholamban, a protein that normally decreases the affinity of calcium-ATPase for calcium in the sarcoplasmic reticulum. As a result of decreased phospholamban, there is increased Ca+ movement between the sarcoplasmic reticulum and cytosol, leading to increased contractility. Increased beta-receptors on the heart also lead to increased cardiac output.

General

Heat intolerance
Weight loss
Increased appetite
Increased sweating from cutaneous blood flow increase
Weakness
Fatigue
Onycholysis (separation of nails from nail beds)
Pretibial myxedema

Eyes

Lid lag (when looking down, sclera visible above cornea)
Lid retraction (when looking straight, sclera visible above the cornea)
Graves ophthalmopathy

Goiter

Diffuse, smooth, non-tender goiter
The audible bruit can be heard at the superior poles

Cardiovascular

Tachycardia (can be masked by patients taking beta-blockers)
Palpitations
An irregular pulse from atrial fibrillation
Hypertension
Widened pulse pressure because systolic pressure increases and diastolic pressure decreases
Heart failure (elderly patients)
Chest pain
Abnormal heart rhythms

Musculoskeletal

Fine tremors of the outstretched fingers. Face, tongue, and head can also be involved. Tremors respond well to treatment with beta-blockers.
Myopathy affecting proximal muscles. Serum creatine kinase levels can be normal.
Osteoporosis, caused by the direct effects of T3. Elderly patients can present with fractures.

Neuropsychiatric system

Restlessness
Anxiety
Depression
Emotional instability
Insomnia
Tremoulousness
Hyperreflexia

Conditions associated with hypothyroidism

Iodine deficiency [rx]
Cretinism [rx]
Wolff-Chaikoff effect
Subacute thyroiditis [rx]
Postpartum thyroiditis [rx]
Riedel thyroiditis [rx]
Hashimoto thyroiditis [rx]
Drug-induced [rx]

Conditions associated with hyperthyroidism

Graves disease [rx]
Iodine excess [rx]
Struma ovarii [rx]
Thyrotropic pituitary adenoma [rx]
Jod-Basedow phenomenon [rx]
Drug-induced: amiodarone, lithium [rx]
Thyrotoxicosis and thyroid storm [rx]
Toxic multinodular goiter [rx]
Thyroid adenoma [rx]

Diagnosis

History and Physical

Subclinical hypothyroidism is asymptomatic most of the time. However, it can present with symptoms of hypothyroidism.[rx] It is essential to assess hypothyroid symptoms as it influences whether thyroid replacement therapy requires initiation. The clinical features of hypothyroidism are as follows:

Integumentary: Dry skin, hair loss, loss of outer 1/3rd of eyebrows, facial puffiness.
Gastrointestinal: Constipation, dysphagia, loss of appetite, weight gain, cholelithiasis
Cardiovascular: Diastolic hypertension, bradycardia, pericardial effusions.
Neurological: Decreased attention span, pseudodementia, mononeuropathies (most commonly carpal tunnel syndrome)
Musculoskeletal: Muscular weakness, cramps, stiffness, fatigue.
Reproductive: Irregular periods, decreased libido.[rx]

Hypothalamus releases thyrotropin-releasing hormone (TRH) that stimulates the secretion of TSH in the pituitary gland. Increased free T4 and T3 inhibit the release of TRH and TSH through a negative feedback loop. As a result, T3 and T4 secretion and iodine uptake are reduced. Other hormones, such as somatostatin, glucocorticoids, and dopamine, also inhibit TSH production. Cold, stress, and exercise increase TRH release.

The initial tests of choice to screen for any thyroid abnormality are a TSH and free thyroxine (free T4) test. These determine whether the abnormality arises centrally from the thyroid gland (primary), peripherally from the pituitary (secondary), or hypothalamus (tertiary). In primary hypothyroidism is suspected, the thyroid gland is not releasing enough thyroid hormones. Therefore, TSH levels will be appropriately elevated, while free T4 levels will be lower. In primary hyperthyroidism, free T4 levels abnormally increased, and TSH levels will be appropriately decreased. Other lab tests such as TSH receptor antibodies or antibodies to thyroid peroxidase can help aid in diagnosing Graves disease or Hashimoto thyroiditis, respectively.[rx]

In pregnant women, thyroid-binding globulin production is increased because of estrogen and beta-human chorionic gonadotropin (beta-HCG). More free T4 will be bound to TGB, leading to increased production of T4. TSH levels and free T4 levels will normalize, and total T4 will increase. Therefore, laboratory values will show normal TSH, normal free T4, and elevated total T4.[rx]

Thyroid Tests

Anti-TPO antibodies – In autoimmune thyroid disease, proteins mistakenly attack the thyroid peroxidase enzyme, which is used by the thyroid to make thyroid hormones.
Thyroid ultrasound – A probe is placed on the skin of the neck, and reflected sound waves can detect abnormal areas of thyroid tissue.
Thyroid scan – A small amount of radioactive iodine is given by mouth to get images of the thyroid gland. Radioactive iodine is concentrated within the thyroid gland.
Thyroid biopsy – A small amount of thyroid tissue is removed, usually to look for thyroid cancer. A thyroid biopsy is typically done with a needle.
Thyroid-stimulating hormone (TSH) – Secreted by the brain, TSH regulates thyroid hormone release. A blood test with high TSH indicates low levels of thyroid hormone (hypothyroidism), and low TSH suggests hyperthyroidism.
T3 and T4 (thyroxine) – The primary forms of thyroid hormone, checked with a blood test.
Thyroglobulins – A substance secreted by the thyroid that can be used as a marker of thyroid cancer. It is often measured during follow-up in patients with thyroid cancer. High levels indicate recurrence of cancer.
Other imaging tests – If thyroid cancer has spread (metastasized), tests such as CT scans, MRI scans, or PET scans can help identify the extent of spread.

Thyroid Treatments

Antithyroid drugs that work in the thyroid gland [rx]

Perchlorate – inhibits Na+/I- symporter – blocks iodide uptake
Thionamides – inhibits TPO – block thyroid hormone synthesis
Iodide > 5mg – inhibits Na+/I- symporter and TPO – blocks iodide uptake and thyroid hormone synthesis
Lithium – inhibits thyroid hormone release (off-label use for thyroid storm)
Thyroid surgery (thyroidectomy) – A surgeon removes all or part of the thyroid in an operation. Thyroidectomy is performed for thyroid cancer, goiter, or hyperthyroidism.
Antithyroid medications – Drugs can slow down the overproduction of thyroid hormone in hyperthyroidism. Two common antithyroid medicines are methimazole and propylthiouracil.
Radioactive iodine – Iodine with radioactivity that can be used in low doses to test the thyroid gland or destroy an overactive gland. Large doses can be used to destroy cancerous tissue.
External radiation – A beam of radiation is directed at the thyroid, on multiple appointments. The high-energy rays help kill thyroid cancer cells.
Thyroid hormone pills – Daily treatment that replaces the amount of thyroid hormone you can no longer make. Thyroid hormone pills treat hypothyroidism and are also used to help prevent thyroid cancer from coming back after treatment.
Recombinant human TSH – Injecting this thyroid-stimulating agent can make thyroid cancer show up more clearly on imaging tests.

Antithyroid drugs that work in peripheral tissue – all these drugs inhibit the deiodinase enzymes. Deiodinase enzymes normally convert T4 into the active form T3. These drugs inhibit the conversion of T4 to T3 and reduce its activity.

Propylthiouracil (thionamide)
Dexamethasone
Amiodarone
Propranolol

References

ByRx Harun

Thyroid Hormone – Anatomy, Types, Structure, Functions

The thyroid hormone is well known for controlling metabolism, growth, and many other bodily functions. The thyroid gland, anterior pituitary gland, and hypothalamus comprise a self-regulatory circuit called the hypothalamic-pituitary-thyroid axis. The main hormones produced by the thyroid gland are thyroxine or tetraiodothyronine (T4) and triiodothyronine (T3). Thyrotropin-releasing hormone (TRH) from the hypothalamus, thyroid-stimulating hormone (TSH) from the anterior pituitary gland, and T4 work in synchronous harmony to maintain proper feedback mechanism and homeostasis. Hypothyroidism, caused by an underactive thyroid gland, typically manifests as bradycardia, cold intolerance, constipation, fatigue, and weight gain. In contrast, hyperthyroidism caused by increased thyroid gland function manifests as weight loss, heat intolerance, diarrhea, fine tremor, and muscle weakness.

Thyroid hormones are two hormones produced and released by the thyroid gland, namely triiodothyronine (T₃) and thyroxine (T₄). They are tyrosine-based hormones that are primarily responsible for the regulation of metabolism. T₃ and T₄ are partially composed of iodine.

Iodine is an essential trace element absorbed in the small intestine. It is an integral part of T3 and T4. Sources of iodine include iodized table salt, seafood, seaweed, and vegetables. Decreased iodine intake can cause iodine deficiency and decreased thyroid hormone synthesis. Iodine deficiency can cause cretinism, goiter, myxedema coma, and hypothyroidism.[rx][rx][rx]

Cellular Mechanism of Thyroid Hormone

Regulation of thyroid hormone starts at the hypothalamus. The hypothalamus releases thyrotropin-releasing hormone (TRH) into the hypothalamic-hypophyseal portal system to the anterior pituitary gland. TRH stimulates thyrotropin cells in the anterior pituitary to release of thyroid-stimulating hormone (TSH). TRH is a peptide hormone created by the cell bodies in the periventricular nucleus (PVN) of the hypothalamus. These cell bodies project their neurosecretory neurons down to the hypophyseal portal circulation, where TRH can concentrate before reaching the anterior pituitary.

TRH is a tropic hormone, meaning that it indirectly affects cells by stimulating other endocrine glands first. It binds to the TRH receptors on the anterior pituitary gland, causing a signal cascade mediated by a G-protein coupled receptor. Activation of Gq protein leads to the activation of phosphoinositide-specific phospholipase C (PLC). PLC hydrolyzes phosphatidylinositol 4,5-P(PIP) into inositol 1,4,5-triphosphate (IP) and 1,2-diacylglycerol (DAG). These second messengers mobilize intracellular calcium stores and activate protein kinase C, leading to downstream gene activation and transcription of TSH. TRH also has a non-tropic effect on the pituitary gland through the hypothalamic-pituitary-prolactin axis. As a non-tropic hormone, TRH directly stimulates lactotropic cells in the anterior pituitary to produce prolactin. Other substances like serotonin, gonadotropin-releasing hormone, and estrogen can also stimulate prolactin release. Prolactin can cause breast tissue growth and lactation.[rx]

TSH is released into the blood and binds to the thyroid-releasing hormone receptor (TSH-R) on the basolateral aspect of the thyroid follicular cell. The TSH-R is a Gs-protein coupled receptor, and its activation leads to the activation of adenylyl cyclase and intracellular levels of cAMP. The increased cAMP activates protein kinase A (PKA). PKA phosphorylates different proteins to modify their functions. The five steps of thyroid synthesis are below:

Synthesis of Thyroglobulin – Thyrocytes in the thyroid follicles produce a protein called thyroglobulin (TG). TG does not contain any iodine, and it is a precursor protein stored in the lumen of follicles. It is produced in the rough endoplasmic reticulum. Golgi apparatus pack it into the vesicles, and then it enters the follicular lumen through exocytosis.
Iodide uptake – Protein kinase A phosphorylation causes increased activity of basolateral Na+-I- symporters, driven by Na+-K+-ATPase, to bring iodide from the circulation into the thyrocytes. Iodide then diffuses from the basolateral side to the apex of the cell, where it is transported into the colloid through the pendrin transporter.
Iodination of thyroglobulin – Protein kinase A also phosphorylates and activates the enzyme thyroid peroxidase (TPO). TPO has three functions: oxidation, organification, and coupling reaction.
- Oxidation – TPO uses hydrogen peroxide to oxidize iodide (I-) to iodine (I2). NADPH-oxidase, an apical enzyme, generates hydrogen peroxide for TPO.
- Organification – TPO links tyrosine residues of thyroglobulin protein with I2. It generates monoiodotyrosine (MIT) and diiodotyrosine (DIT). MIT has a single tyrosine residue with iodine, and DIT has two tyrosine residues with iodine.
- Coupling reaction – TPO combines iodinated tyrosine residues to make triiodothyronine (T3) and tetraiodothyronine (T4). MIT and DIT join to form T3, and two DIT molecules form T4.
Storage – thyroid hormones are bound to thyroglobulin for stored in the follicular lumen.
Release – thyroid hormones are released into the fenestrated capillary network by thyrocytes in the following steps:
- Thyrocytes uptake iodinated thyroglobulin via endocytosis
- Lysosome fuse with the endosome containing iodinated thyroglobulin
- Proteolytic enzymes in the endolysosome cleave thyroglobulin into MIT, DIT, T3, and T4.
- T3 (20%) and T4 (80%) are released into the fenestrated capillaries via MCT8 transporter.[rx]
- Deiodinase enzymes remove iodine molecules from DIT and MIT. Iodine can be salvaged and redistributed to an intracellular iodide pool.[rx][rx][rx]

Organ Systems Involved

Thyroid hormone affects virtually every organ system in the body, including the heart, CNS, autonomic nervous system, bone, GI, and metabolism. In general, when the thyroid hormone binds to its intranuclear receptor, it activates the genes for increasing metabolic rate and thermogenesis. Increasing metabolic rate involves increased oxygen and energy consumption.

Heart – thyroid hormones have a permissive effect on catecholamines. It increases the expression of beta-receptors to increase heart rate, stroke volume, cardiac output, and contractility.
Lungs – thyroid hormones stimulate the respiratory centers and lead to increased oxygenation because of increased perfusion.
Skeletal muscles – thyroid hormones cause increased development of type II muscle fibers. These are fast-twitch muscle fibers capable of fast and powerful contractions.
Metabolism – thyroid hormone increases the basal metabolic rate. It increases the gene expression of Na+/K+ ATPase in different tissues leading to increased oxygen consumption, respiration rate, and body temperature. Depending on the metabolic status, it can induce lipolysis or lipid synthesis. Thyroid hormones stimulate the metabolism of carbohydrates and anabolism of proteins. Thyroid hormones can also induce the catabolism of proteins in high doses. Thyroid hormones do not change the blood glucose level, but they can cause increased glucose reabsorption, gluconeogenesis, glycogen synthesis, and glucose oxidation.
Growth during childhood – In children, thyroid hormones act synergistically with growth hormones to stimulate bone growth. It induces chondrocytes, osteoblasts, and osteoclasts. Thyroid hormone also helps with brain maturation by axonal growth and the formation of the myelin sheath.[rx]

Production

Central

Synthesis of the thyroid hormones, as seen on an individual thyroid follicular cell^[rx]

Thyroglobulin is synthesized in the rough endoplasmic reticulum and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis.
Meanwhile, a sodium-iodide (Na/I) symporter pumps iodide (I⁻) actively into the cell, which previously has crossed the endothelium by largely unknown mechanisms.
This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner.
In the colloid, iodide (I⁻) is oxidized to iodine (I⁰) by an enzyme called thyroid peroxidase.
Iodine (I⁰) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (in total containing approximately 120 tyrosyl residues).
In conjugation, adjacent tyrosyl residues are paired together.
Thyroglobulin re-enters the follicular cell by endocytosis.
Proteolysis by various proteases liberates thyroxine and triiodothyronine molecules
Efflux of thyroxine and triiodothyronine from follicular cells, which appears to be largely through monocarboxylate transporter (MCT) 8 and 10,^[rx]^[rx] and entry into the blood.

Thyroid hormones (T₄ and T₃) are produced by the follicular cells of the thyroid gland and are regulated by TSH made by the thyrotropes of the anterior pituitary gland. The effects of T₄ in vivo are mediated via T₃ (T₄ is converted to T₃ in target tissues). T₃ is three to five times as active as T₄.

Thyroxine (3,5,3′,5′-tetraiodothyronine) is produced by follicular cells of the thyroid gland. It is produced as the precursor thyroglobulin (this is not the same as thyroxine-binding globulin (TBG)), which is cleaved by enzymes to produce active T₄.

The steps in this process are as follows:^[rx]

The Na⁺/I⁻ symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodide ion. This is a secondary active transporter that utilizes the concentration gradient of Na⁺ to move I⁻ against its concentration gradient.
I⁻ is moved across the apical membrane into the colloid of the follicle by pendrin.
Thyroperoxidase oxidizes two I⁻ to form I₂. Iodide is non-reactive, and only the more reactive iodine is required for the next step.
The thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the colloid. The thyroglobulin was synthesized in the ER of the follicular cell and secreted into the colloid.
Iodinated Thyroglobulin binds megalin for endocytosis back into cell.
Thyroid-stimulating hormone (TSH) released from the anterior pituitary (also known as the adenohypophysis) binds the TSH receptor (a G_s protein-coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid.
The endocytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave the T₄ from the iodinated thyroglobulin.
The thyroid hormones cross the follicular cell membrane towards the blood vessels by an unknown mechanism.^[rx] Textbooks have stated that diffusion is the main means of transport,^[rx] but recent studies indicate that monocarboxylate transporter (MCT) 8 and 10 play major roles in the efflux of the thyroid hormones from the thyroid cells.^[rx]^[rx]

The Function of Thyroid Hormone

Metabolic – The thyroid hormones increase the basal metabolic rate and have effects on almost all body tissues.^[rx] Appetite, the absorption of substances, and gut motility are all influenced by thyroid hormones.^[rx] They increase the absorption in the gut, generation, uptake by cells, and breakdown of glucose.^[rx] They stimulate the breakdown of fats, and increase the number of free fatty acids.^[rx] Despite increasing free fatty acids, thyroid hormones decrease cholesterol levels, perhaps by increasing the rate of secretion of cholesterol in bile.^[rx]
Cardiovascular – The hormones increase the rate and strength of the heartbeat. They increase the rate of breathing, intake and consumption of oxygen, and increase the activity of mitochondria.^[rx] Combined, these factors increase blood flow and the body’s temperature.^[rx]
Developmental – Thyroid hormones are important for normal development.^[rx] They increase the growth rate of young people,^[rx] and cells of the developing brain are a major target for the thyroid hormones T₃ and T₄. Thyroid hormones play a particularly crucial role in brain maturation during fetal development and the first few years of postnatal life^[rx]
The thyroid hormones also play a role in maintaining normal sexual function, sleep, and thought patterns. Increased levels are associated with increased speed of thought generation but decreased focus.^[rx] Sexual function, including libido and the maintenance of a normal menstrual cycle, is influenced by thyroid hormones.^[rx]

Some of the essential functions of the thyroid hormones are as follows

They help in the overall growth, development, and differentiation of all the cells of the body.[rx][rx]
They regulate the basal metabolic rate (BMR).
They play an important role in calcium metabolism
They help in the overall development and function of CNS in children.[rx]
They stimulate somatic and psychic growth.
They stimulate heart rate and contraction.[rx]
They help in the deposition of calcium and phosphate in bone and make the bones strong.
They decrease the level of calcium in the blood.
They regulate carbohydrate, fat, and protein metabolism.
They also help in the metabolism of vitamins.
They regulate the body temperature.
They help degrade cholesterol and triglycerides.
They maintain the electrolyte balance.
They support the process of RBC formation.
They enhance mitochondrial metabolism.
They increase the oxygen consumptions of the cells and tissues.
They influence the mood and behavior of a person.[rx]
They stimulate gut motility.[rx]
They also enhance the sensitivity of the beta-adrenergic receptors to catecholamines.

The physiological effects of thyroid hormones are listed below

Increases the basal metabolic rate
Depending on the metabolic status, it can induce lipolysis or lipid synthesis.
Stimulate the metabolism of carbohydrates
Anabolism of proteins. Thyroid hormones can also induce the catabolism of proteins in high doses.
Permissive effect on catecholamines
In children, thyroid hormones act synergistically with growth hormones to stimulate bone growth.
The impact of thyroid hormone in CNS is important. During the prenatal period, it is needed for the maturation of the brain. In adults, it can affect mood. Hyperthyroidism can lead to hyperexcitability and irritability. Hypothyroidism can cause impaired memory, slowed speech, and sleepiness.
Thyroid hormone affects fertility, ovulation, and menstruation.

Mechanism

Thyroid hormones are lipophilic and circulate bound to the transport proteins. Only a fraction (approximately 0.2%) of the thyroid hormone (free T4) is unbound and active. Transporter proteins include thyroxine-binding globulin (TBG), transthyretin, and albumin. TBG transports the majority (two-thirds) of the T4, and transthyretin transports thyroxine and retinol. When it reaches its target site, T3 and T4 can dissociate from their binding protein to enter cells either by diffusion or carrier-mediated transport. Receptors for T3 bind are already bound to the DNA in the nucleus before the ligand binding. T3 or T4 then bind to nuclear alpha or beta receptors in the respective tissue and cause activation of transcription factors leading to the activation of certain genes and cell-specific responses. Thyroid hormones are degraded in the liver via sulfation and glucuronidation and excreted in the bile.[rx]

Thyroid receptors are transcription factors that can bind to both T3 and T4. However, they have a much higher affinity for T3. As a result, T4 is relatively inactive. Deiodinases convert T4 to active T3 or inactive reverse T3 (rT3). There are three types of deiodinases: type I, II, and III. Type I (DIO1) and II (DIO2) are located in the liver, kidneys, muscles, and thyroid glands. Type III (DIO3) deiodinases are located in the CNS and placenta. DIO1 and DIO2 convert T4 to the active form T3, and DIO3 converts T4 into inactive form rT3.[rx]

Clinical Significance

Goiter – It is a condition where the thyroid gland shows an abnormal enlargement. Goiters broadly classify into uni-nodular, multinodular, and diffuse types. Each further includes many different types of goiters. Some of the commonest with some of their important features are described below.[rx][rx]
Colloid nodular goiter – This is the commonest of the non-neoplastic lesions of the thyroid.[rx] In these types of goiter, the thyroid follicles are filled with an abundant amount of colloid in their lumens and lined by squamous follicular cells.
Hyperthyroidism (Thyrotoxicosis) – It is a condition of hypermetabolic state and hyperfunctioning of the thyroid gland resulting in increased T3 and T4 levels. Some symptoms included palpitations, tachycardia, nervousness, etc.
Graves disease – This disease is a combination of thyrotoxicosis, exophthalmos, and dermopathy (myxedema). It is especially seen in women in the age group of 20 to 40 years, manifesting in the form of prolonged and violent palpitations.
Thyroid cancer – Thyroid carcinomas arise either from the follicular epithelium or parafollicular C-cells. They are painless nodules and compression, displaces the adjacent structures. The carcinomas of the thyroid can manifest in the form of papillary carcinoma, follicular carcinoma, anaplastic carcinoma, and medullary carcinoma.
Thyroiditis – Inflammation of the thyroid, usually from a viral infection or autoimmune condition. Thyroiditis can be painful or have no symptoms at all.
Thyroid cancer – An uncommon form of cancer, thyroid cancer is usually curable. Surgery, radiation, and hormone treatments may be used to treat thyroid cancer.
Thyroid nodule – A small abnormal mass or lump in the thyroid gland. Thyroid nodules are extremely common. Few are cancerous. They may secrete excess hormones, causing hyperthyroidism, or cause no problems.
Thyroid storm – A rare form of hyperthyroidism in which extremely high thyroid hormone levels cause severe illness.

Symptoms of Hypothyroidism

Symptoms related to decreased metabolic rate

Bradycardia
Fatigue
Cold intolerance
Weight gain
Poor appetite
Hair loss
Cold and dry skin
Constipation
Myopathy, stiffness, cramps, entrapment syndromes
Delayed deep tendon reflex relaxation

Symptoms from generalized myxedema

Myxedematous heart disease
Puffy appearance with doughy skin texture
Hoarse voice with difficulty articulate words
Pretibial and periorbital edema

Symptoms of hyperprolactinemia

Amenorrhea or menorrhagia
Galactorrhea
Erectile dysfunction, infertility in men
Decreased libido

Other symptoms

Depression
Impaired concentration and memory
Goiter
Hypertension

Congenital hypothyroidism

Umbilical hernia
Hypotonia
Prolonged neonatal jaundice
Poor feeding, absence of thirst (adipsia)
Decreased activity
Pot-belly, puffy-face, protuberant tongue
Poor brain development

Symptoms of Hyperthyroidism

General

Heat intolerance
Weight loss
Increased appetite
Increased sweating from cutaneous blood flow increase
Weakness
Fatigue
Onycholysis (separation of nails from nail beds)
Pretibial myxedema

Eyes

Lid lag (when looking down, sclera visible above cornea)
Lid retraction (when looking straight, sclera visible above the cornea)
Graves ophthalmopathy

Goiter

Diffuse, smooth, non-tender goiter
The audible bruit can be heard at the superior poles

Cardiovascular

Tachycardia (can be masked by patients taking beta-blockers)
Palpitations
An irregular pulse from atrial fibrillation
Hypertension
Widened pulse pressure because systolic pressure increases and diastolic pressure decreases
Heart failure (elderly patients)
Chest pain
Abnormal heart rhythms

Musculoskeletal

Fine tremors of the outstretched fingers. Face, tongue, and head can also be involved. Tremors respond well to treatment with beta-blockers.
Myopathy affecting proximal muscles. Serum creatine kinase levels can be normal.
Osteoporosis, caused by the direct effects of T3. Elderly patients can present with fractures.

Neuropsychiatric system

Restlessness
Anxiety
Depression
Emotional instability
Insomnia
Tremoulousness
Hyperreflexia

Conditions associated with hypothyroidism

Iodine deficiency [rx]
Cretinism [rx]
Wolff-Chaikoff effect
Subacute thyroiditis [rx]
Postpartum thyroiditis [rx]
Riedel thyroiditis [rx]
Hashimoto thyroiditis [rx]
Drug-induced [rx]

Conditions associated with hyperthyroidism

Graves disease [rx]
Iodine excess [rx]
Struma ovarii [rx]
Thyrotropic pituitary adenoma [rx]
Jod-Basedow phenomenon [rx]
Drug-induced: amiodarone, lithium [rx]
Thyrotoxicosis and thyroid storm [rx]
Toxic multinodular goiter [rx]
Thyroid adenoma [rx]

Diagnosis

History and Physical

Integumentary: Dry skin, hair loss, loss of outer 1/3rd of eyebrows, facial puffiness.
Gastrointestinal: Constipation, dysphagia, loss of appetite, weight gain, cholelithiasis
Cardiovascular: Diastolic hypertension, bradycardia, pericardial effusions.
Neurological: Decreased attention span, pseudodementia, mononeuropathies (most commonly carpal tunnel syndrome)
Musculoskeletal: Muscular weakness, cramps, stiffness, fatigue.
Reproductive: Irregular periods, decreased libido.[rx]

Thyroid Tests

Anti-TPO antibodies – In autoimmune thyroid disease, proteins mistakenly attack the thyroid peroxidase enzyme, which is used by the thyroid to make thyroid hormones.
Thyroid ultrasound – A probe is placed on the skin of the neck, and reflected sound waves can detect abnormal areas of thyroid tissue.
Thyroid scan – A small amount of radioactive iodine is given by mouth to get images of the thyroid gland. Radioactive iodine is concentrated within the thyroid gland.
Thyroid biopsy – A small amount of thyroid tissue is removed, usually to look for thyroid cancer. A thyroid biopsy is typically done with a needle.
Thyroid-stimulating hormone (TSH) – Secreted by the brain, TSH regulates thyroid hormone release. A blood test with high TSH indicates low levels of thyroid hormone (hypothyroidism), and low TSH suggests hyperthyroidism.
T3 and T4 (thyroxine) – The primary forms of thyroid hormone, checked with a blood test.
Thyroglobulins – A substance secreted by the thyroid that can be used as a marker of thyroid cancer. It is often measured during follow-up in patients with thyroid cancer. High levels indicate recurrence of cancer.
Other imaging tests – If thyroid cancer has spread (metastasized), tests such as CT scans, MRI scans, or PET scans can help identify the extent of spread.

Thyroid Treatments

Antithyroid drugs that work in the thyroid gland [rx]

Perchlorate – inhibits Na+/I- symporter – blocks iodide uptake
Thionamides – inhibits TPO – block thyroid hormone synthesis
Iodide > 5mg – inhibits Na+/I- symporter and TPO – blocks iodide uptake and thyroid hormone synthesis
Lithium – inhibits thyroid hormone release (off-label use for thyroid storm)
Thyroid surgery (thyroidectomy) – A surgeon removes all or part of the thyroid in an operation. Thyroidectomy is performed for thyroid cancer, goiter, or hyperthyroidism.
Antithyroid medications – Drugs can slow down the overproduction of thyroid hormone in hyperthyroidism. Two common antithyroid medicines are methimazole and propylthiouracil.
Radioactive iodine – Iodine with radioactivity that can be used in low doses to test the thyroid gland or destroy an overactive gland. Large doses can be used to destroy cancerous tissue.
External radiation – A beam of radiation is directed at the thyroid, on multiple appointments. The high-energy rays help kill thyroid cancer cells.
Thyroid hormone pills – Daily treatment that replaces the amount of thyroid hormone you can no longer make. Thyroid hormone pills treat hypothyroidism and are also used to help prevent thyroid cancer from coming back after treatment.
Recombinant human TSH – Injecting this thyroid-stimulating agent can make thyroid cancer show up more clearly on imaging tests.

Propylthiouracil (thionamide)
Dexamethasone
Amiodarone
Propranolol

References

ByRx Harun

Thyroid Gland – Anatomy, Types, Structure, Functions

The thyroid gland is a vital butterfly-shaped endocrine gland situated in the lower part of the neck. It is present in front and sides of the trachea, inferior to the larynx. It plays an essential role in the regulation of the basal metabolic rate (BMR), and stimulates somatic and psychic growth, besides having a vital role in calcium metabolism.

The thyroid weighs between 20 and 60 grams on average. It is surrounded by two fibrous capsules. The outer capsule is connected to the voice box muscles and many important vessels and nerves. There is the loose connective tissue between the inner and the outer capsule, so the thyroid can move and change its position when we swallow.

It is a gland consisting of two lobes, the right and the left lobes joined together by an intermediate structure, the isthmus. Sometimes a third lobe called the pyramidal lobe projects from the isthmus. It has a fibrous/fibromuscular band, i.e., levator glandular thyroidal running from the body of the hyoid to the isthmus.[rx] The lobes are 5 x 2.5 x 2.5 cm in dimension and weigh around 25 gm. It extends from the fifth cervical to the first thoracic vertebrae. The lobes extend from the middle of the thyroid cartilage to the fifth tracheal ring. The isthmus is 1.2 x 1.2 cm in dimensions and extends from second to third tracheal rings. It grows larger in females during the period of menstruation and pregnancy.

The lobes are conical in shape and have an apex, a base, three surfaces – lateral, medial, and posterolateral, and two borders – the anterior and posterior. The isthmus, however, has two surfaces – anterior and posterior and two borders – superior and inferior.

The lobes are related anteriorly to the skin, superficial and deep fascia, and platysma. Posteriorly, the lobes are associated with the laminae of the thyroid cartilage and tracheal rings, and laterally to the external carotid artery and internal jugular vein.

The thyroid gland is a richly vascular organ supplied by the superior and inferior thyroid arteries and sometimes by an additional artery known as the thyroid ima artery.[rx] The venous drainage is by superior, middle, and inferior thyroid veins. Sometimes a fourth thyroid vein might be present called the vein of Kocher. The nerve supply is mainly from middle cervical ganglion, but also partly from superior and inferior cervical ganglions.

Two capsules completely cover the thyroid gland. The true capsule is made up of fibro-elastic connective tissue. The false capsule is made up of the pre-tracheal layer of the deep cervical fascia. It consists of deep capillary plexus deep to the true capsule. Hence, it is crucial to remove the plexus with capsule during thyroidectomy.

Organ Systems Involved

Thyroid hormone induces effects on practically all nucleated cells in the human body, generally increasing their function and metabolism.

Cardiac output, stroke volume, and resting heart rate increase through positive chronotropic and inotropic effects. Active thyroid hormone increases myocardial intracellular calcium to increase contraction force and speed. Concomitantly, vasculature in the skin, muscle, and heart dilate, resulting in decreased peripheral vascular resistance while blood volume increases through activation of the renin-angiotensin-aldosterone system.
Basal metabolic rate (BMR), heat production, and oxygen consumption elevate through thyroid hormone activation of mitochondrial uncoupling proteins. Glucose and fatty acid uptake and oxidation also increase, which results in increased thermogenesis and necessitates increased heat dissipation. Heat intolerance in hyperthyroidism is attributable to this increase in thermogenesis. Compensation for increased thermogenesis is also mediated by thyroid hormone through increases in blood flow, sweating, and ventilation.
Resting respiratory rate and minute ventilation undergo stimulation by active thyroid hormone, triiodothyronine (T3), to normalize arterial oxygen concentration in compensation for increased rates of oxidation. T3 also promotes oxygen delivery to the tissues by simulating erythropoietin and hemoglobin production and promoting folate and cobalamin absorption through the gastrointestinal tract.
T3 is responsible for the development of fetal growth centers and linear bone growth, endochondral ossification, and epiphyseal bone center maturation following birth. Additionally, T3 simulates adult bone remodeling and degradation of mucopolysaccharides and fibronectin in extracellular connective tissue.
T3 stimulates the nervous system resulting in increased wakefulness, alertness, and responsiveness to external stimuli. Thyroid hormone also stimulates the peripheral nervous system, resulting in increased peripheral reflexes and gastrointestinal tone, and motility.
Thyroid hormone also plays a role in reproductive health and other endocrine organ function. It allows for the regulation of normal reproductive function in both men and women by regulating both the ovulatory cycle and spermatogenesis. Thyroid hormone also regulates pituitary function; growth hormone production and release are stimulated by thyroid hormone while inhibiting prolactin production and release. Additionally, renal clearance of many substances, including some medications, can be increased due to activated thyroid hormone stimulation of renal blood flow and glomerular filtration rate.[2][3]

Overview of the Thyroid Gland

The thyroid gland, in the anterior neck, controls body metabolism, protein synthesis, and a body’s responsiveness to other hormones.

Key Points

The thyroid gland controls how quickly the body uses energy, makes proteins, and controls how sensitive the body is to other hormones. It participates in these processes by producing thyroid hormones, the principal ones being triiodothyronine (T3) and thyroxine (T4).

Hormones released from the thyroid regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body.

The thyroid also produces calcitonin, which plays a role in calcium homeostasis.

Hormonal output from the thyroid is regulated by thyroid-stimulating hormone (TSH) produced by the anterior pituitary, which itself is regulated by thyrotropin-releasing hormone (TRH) produced by the hypothalamus.

The thyroid gland (the thyroid in vertebrate anatomy ) is one of the largest endocrine glands.

Key Terms

thyroid-stimulating hormone: Also known as TSH or thyrotropin, this is a hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone, synthesized and secreted by thyrotrope cells in the anterior pituitary gland, that regulates the endocrine function of the thyroid gland.

thyroxine: A hormone (an iodine derivative of tyrosine), produced by the thyroid gland, that regulates cell metabolism and growth.

In invertebrates, the thyroid gland is one of the largest endocrine glands. It is found in the neck, below the thyroid cartilage that forms the laryngeal prominence, or Adam’s apple. The isthmus (the bridge between the two lobes of the thyroid) is located inferior to the cricoid cartilage.

The thyroid gland controls how quickly the body uses energy, makes proteins, and controls how sensitive the body is to other hormones. It participates in these processes by producing thyroid hormones, the principal ones being triiodothyronine (T3) and thyroxine (sometimes referred to as tetraiodothyronine (T4)).

These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. T3 and T4 are synthesized from both iodine and tyrosine.

The thyroid also produces calcitonin, which plays a role in calcium homeostasis. The hormonal output from the thyroid is regulated by thyroid-stimulating hormone (TSH) produced by the anterior pituitary, which itself is regulated by thyrotropin-releasing hormone (TRH) produced by the hypothalamus.

This is a diagram of the thyroid system. The hypothalamus is shown in the center of the brain. It secretes TRH that activates the anterior pituitary gland to release TSH that travels down the neck to they thyroid gland. There, T3 and T4 are activated and produce increased metabolism, growth and development, and increased catecholamine effect that flow down through the body. The thyroid glad is also depicted as having a negative mechanism that reports back to the anterior pituitary and hypothalamus.

Thyroid system: Thyroid function is regulated by the actions of the hypothalamus and pituitary gland.

Anatomy of the Thyroid Gland

The thyroid gland is a butterfly-shaped organ and is composed of two cone-like lobes or wings, lobus dexter (right lobe) and lobus sinister (left lobe), connected via the isthmus. The organ is situated on the anterior side of the neck, lying against and around the larynx and trachea, reaching posteriorly the oesophagus and carotid sheath.

It starts cranially at the oblique line on the thyroid cartilage (just below the laryngeal prominence, or Adam’s Apple), and extends inferiorly to approximately the fifth or sixth tracheal ring. It is difficult to demarcate the gland’s upper and lower border with vertebral levels because it moves in position in relation to these structures during swallowing.

Formation, Storage, and Release of Thyroid Hormones

Thyroid hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and regulated by thyroid-stimulating hormone (TSH).

Key Points

Because the effects of T4 in vivo are mediated via T3 (T4 is converted to T3 in target tissues ), T3 is three- to five-fold more active than T4.

Thyroxine is believed to be a pro-hormone and a reservoir for the most active and main thyroid hormone T3. T4 is converted as required in the tissues by iodothyronine deiodinase.

Thyroid hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and are regulated by a thyroid-stimulating hormone secreted by the anterior pituitary gland.

Key Terms

thyroid-stimulating hormone: A hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body.

triiodothyronine: A thyroid hormone also known as T3 that plays a key role in many physiological processes and is much more active than T4.

thyroxine: A thyroid hormone also known as T4, thought to be a prohormone and a reservoir for T3.

The thyroid hormones
thyroxine (T4) and triiodothyronine (T3) are produced from thyroid follicular cells within the thyroid gland, a process regulated by the thyroid-stimulating hormone secreted by the anterior pituitary gland.

Thyroglobulin, the pre-cursor of T4 and T3, is produced by the thyroid follicular cells before being secreted and stored in the follicular lumen. Iodide is actively absorbed from the bloodstream by a process called iodide trapping. In this process, sodium is co-transported with iodide from the basolateral side of the membrane into the cell, and then concentrated in the thyroid follicles to about thirty times its concentration in the blood.

Through a reaction with the enzyme thyroperoxidase, iodine is bound to tyrosine residues in the thyroglobulin molecules to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). Linking two moieties of DIT produces T4. Combining one particle of MIT and one particle of DIT produces T3.

Proteases digest iodinated thyroglobulin, releasing the hormones T4 and T3, the biologically-active agents central to metabolic regulation. T3 is identical to T4, but it has one less iodine atom per molecule.

T4 is believed to be a pro-hormone and a reservoir for the more active and main thyroid hormone T3. T4 is converted as required in the tissues by iodothyronine deiodinase.

This is a diagrammatic representation of thyroid hormone synthesis in a thyroid follicle. Sodium is co-transported with iodide from the basolateral side of the membrane into the cell, and then concentrated in the thyroid follicles to about thirty times its concentration in the blood.

Thyroid hormone: Diagrammatic representation of thyroid hormone synthesis in a thyroid follicle.

Effects of Iodine Deficiency

If there is a deficiency of dietary iodine, the thyroid will not be able to make thyroid hormone. A lack of thyroid hormone will lead to decreased negative feedback on the pituitary, which in turn, will lead to increased production of thyroid-stimulating hormone, which causes the thyroid to enlarge (goiter).

This enlarged endemic colloid goiter has the effect of increasing the thyroid’s ability to trap more iodide, compensating for the iodine deficiency and allowing it to produce adequate amounts of thyroid hormone.

Action of Thyroid Hormones

The primary function of the thyroid is to produce the hormones triiodothyronine (T3), thyroxine (T4), and calcitonin.

Key Points

T4 is converted to T3 by peripheral organs such as the liver, kidney, and spleen.

Triiodothyronine (T3) is several times more powerful than T4, which is largely a pro-hormone.

The regulation of actin polymerization by T4 is critical to cell migration in neurons and glial cells and is important for brain development.

Thyroid hormones play an important role in regulating metabolic rate and body temperature.

Key Terms

thyroxine: A hormone (an iodine derivative of tyrosine) produced by the thyroid gland that regulates cell metabolism and growth.

Triiodothyronine (T3) and thyroxine (T4) are enzymes produced by the thyroid gland. T4 is thought to be a pro-hormone to the more metabolically active T3. T4 is converted to T3 in tissues as required by deiodinase enzymes.

Calcitonin is another hormone released by the thyroid gland that is responsible for modulating blood calcium levels in conjunction with parathyroid hormone, which is released from the parathyroid.

Effect of Thyroid Hormones on Metabolism

The main activity of the thyroid hormones T3 and T4 is to boost the basal metabolic rates of proteins, fats, and carbohydrates as well as vitamins.

Thyroid system: An overview of the thyroid system.

Effect of Thyroid Hormones on Body Temperature

Thyroid hormones affect the dilation of blood vessels, which in turn affects the rate at which heat can escape the body. The more dilated blood vessels are, the faster heat can escape.

A person who suffers from hyperthyroidism (an over-active thyroid) will experience a fever; conversely, a person who suffers from hypothyroidism (a less active thyroid) will experience a decrease in body temperature.

Action of Thyroid Hormones on the Developing Fetus

The cells of the developing brain are a major target for T3 and T4. Thyroid hormones play a particularly crucial role in brain maturation during fetal development by regulating actin polymerization during neuronal development.

Action of Thyroid Hormones in Blood

In the blood, T4 and T3 are partially bound to thyroxine-binding globulin (TBG), transthyretin, and albumin. Only a very small fraction of the circulating hormone is free—T4 0.03% and T3 0.3%. Only the free fraction has hormonal activity.

As with the steroid hormones, thyroid hormones are lipophillic and can cross the cell membrane and bind to intracellular receptors, which act alone as transcription factors or in association with other factors to modulate DNA transcription.

Calcitonin Activity

Calcitonin acts to lower blood calcium levels in three ways:

Inhibiting the osteoclast-mediated breakdown of bones.
Stimulating osteoblastic activity to produce new bone tissue.
Inhibiting re-absorption of calcium in the kidneys.

Control of Thyroid Hormone Release

The production of thyroxine and triiodothyronine is regulated by thyroid-stimulating hormone (TSH) that is released from the anterior pituitary.

Key Points

Thyroid hormones are released from the thyroid under the control of thyroid stimulating hormone (TSH).

TSH is secreted by the anterior pituitary gland and is itself under the control of thyrotropin-releasing hormone (TRH).

TRH is secreted by the hypothalamus.

Both TSH and TRH secretion are inhibited when elevated thyroid hormone levels are detected in the blood and provide negative feedback to the hypothalamus and anterior pituitary gland.

Key Terms

thyroid-stimulating hormone: A hormone released from the anterior pituitary gland that stimulates the release of thyroid hormones.

thyrotropin-releasing hormone: A hormone released from the hypothalamus that stimulates thyroid-stimulating hormone production from the anterior pituitary gland.

The production of thyroxine (T4) and triiodothyronine (T3) is primarily regulated by thyroid-stimulating hormone (TSH) that is released from the anterior pituitary gland. TSH release, in turn, stimulates the hypothalamus to secrete thyrotropin-releasing hormone (TRH). This results in increased metabolism, growth, development and the activation of numerous other systems controlled by thyroid hormones.

Thyroid hormones also provide negative feedback to the hypothalamus and anterior pituitary gland. When thyroid levels in the blood are elevated TSH and TRH production is reduced. Excessive TRH can also inhibit the production of further TRH.

This is a diagram of the thyroid system. It shows how thyroid hormones are produced from the thyroid under the influence of thyroid-stimulating hormone (TSH) from the anterior pituitary gland, which is itself under the control of thyroptropin-releasing hormone (TRH) secreted by the hypothalamus. Thyroid hormones provide negative feedback, inhibiting secretion of TRH and TSH when blood levels are high.

The thyroid system: Thyroid hormones are produced from the thyroid under the influence of thyroid-stimulating hormone (TSH) from the anterior pituitary gland, which is itself under the control of thyrotropin-releasing hormone (TRH) secreted by the hypothalamus. Thyroid hormones provide negative feedback, inhibiting the secretion of TRH and TSH when blood levels are high.

Blood, lymph and nerve supply

The thyroid is supplied with arterial blood from the superior thyroid artery, a branch of the external carotid artery, and the inferior thyroid artery, a branch of the thyrocervical trunk, and sometimes by an anatomical variant the thyroid ima artery,^[rx] which has a variable origin.^[rx] The superior thyroid artery splits into anterior and posterior branches supplying the thyroid, and the inferior thyroid artery splits into superior and inferior branches.^[rx] The superior and inferior thyroid arteries join together behind the outer part of the thyroid lobes.^[rx] The venous blood is drained via superior and middle thyroid veins, which drain to the internal jugular vein, and via the inferior thyroid veins. The inferior thyroid veins originate in a network of veins and drain into the left and right brachiocephalic veins.^[rx] Both arteries and veins form a plexus between the two layers of the capsule of the thyroid gland.^[rx]

Lymphatic drainage frequently passes the laryngeal lymph nodes (located just above the isthmus), and the pretracheal and paratracheal lymph nodes.^[rx] The gland receives sympathetic nerve supply from the superior, middle and inferior cervical ganglion of the sympathetic trunk.^[rx] The gland receives parasympathetic nerve supply from the superior laryngeal nerve and the recurrent laryngeal nerve.^[rx]

Structure

The thyroid gland is divided into lobules by the septae dipping from the capsule. The thyroid lobules consist of a large number of typical units called thyroid follicles.[rx] The thyroid follicles are the structural and functional units of a thyroid gland. These are spherical, and the wall is made up of a large number of cuboidal cells, the follicular cells. These follicular cells are the derivates of the endoderm and secrete thyroid hormone. The circulating form of this hormone is thyroxine, which is tetraiodothyronine (T4) along with a small quantity of triiodothyronine (T3). Even though most of T4 later converts to the more active form T3, both affect the target cells with varying degrees of stimulation. These hormones help in regulating the BMR of the body. In between these thyroid follicles or within the wall of the thyroid follicles, we find the small C cells, also know as Parafollicular cells. These are derived from neural crest cells and secrete polypeptide hormone known as calcitonin. The calcitonin helps in depositing calcium and phosphate in skeletal and other tissues leading to hypocalcemia. This function is the opposite of the parathormone.

These thyroid follicles act as storage compartments, filled with a substance called the colloid. This colloid is thyroglobulin, which is nothing but acidophilic secretory glycoprotein that is PAS-positive. These follicles are held together tightly within a delicate network of reticular fibers with an extensive capillary bed.

Function

Metabolic. The thyroid hormones increase the basal metabolic rate and have effects on almost all body tissues.^[rx] Appetite, the absorption of substances, and gut motility are all influenced by thyroid hormones.^[rx] They increase the absorption in the gut, generation, uptake by cells, and breakdown of glucose.^[rx] They stimulate the breakdown of fats, and increase the number of free fatty acids.^[rx] Despite increasing free fatty acids, thyroid hormones decrease cholesterol levels, perhaps by increasing the rate of secretion of cholesterol in bile.^[rx]
Cardiovascular. The hormones increase the rate and strength of the heartbeat. They increase the rate of breathing, intake and consumption of oxygen, and increase the activity of mitochondria.^[rx] Combined, these factors increase blood flow and the body’s temperature.^[rx]
Developmental. Thyroid hormones are important for normal development.^[rx] They increase the growth rate of young people,^[rx] and cells of the developing brain are a major target for the thyroid hormones T₃ and T₄. Thyroid hormones play a particularly crucial role in brain maturation during fetal development and the first few years of postnatal life^[28]
The thyroid hormones also play a role in maintaining normal sexual function, sleep, and thought patterns. Increased levels are associated with increased speed of thought generation but decreased focus.^[rx] Sexual function, including libido and the maintenance of a normal menstrual cycle, is influenced by thyroid hormones.^[rx]

Some of the essential functions of the thyroid hormones are as follows:

They help in the overall growth, development, and differentiation of all the cells of the body.[rx][rx]
They regulate the basal metabolic rate (BMR).
They play an important role in calcium metabolism
They help in the overall development and function of CNS in children.[rx]
They stimulate somatic and psychic growth.
They stimulate heart rate and contraction.[rx]
They help in the deposition of calcium and phosphate in bone and make the bones strong.
They decrease the level of calcium in the blood.
They regulate carbohydrate, fat, and protein metabolism.
They also help in the metabolism of vitamins.
They regulate the body temperature.
They help degrade cholesterol and triglycerides.
They maintain the electrolyte balance.
They support the process of RBC formation.
They enhance mitochondrial metabolism.
They increase the oxygen consumptions by the cells and tissues.
They influence the mood and behavior of a person.[rx]
They stimulate gut motility.[rx]
They also enhance the sensitivity of the beta-adrenergic receptors to catecholamines.

Thus the thyroid hormones act on almost all the cells of the body. They also take up a key role in the development, growth, and function of most of the tissues and organs of the body. One can also say that thyroid hormones are mandatory for the normal metabolic activity of all the cells of the body.

References

ByRx Harun

Pituitary Gland – Anatomy, Types, Funtions

The pituitary gland or the hypophysis cerebri is a vital structure of the human body as it performs essential functions for sustaining life. It has the pseudonym of “the master gland.” The location of the gland is within the sella turcica of the sphenoid bone. It is made up of two distinct regions called the anterior lobe and posterior lobe, which are functionally active. There is an intermediate lobe in between them. The anterior lobe secretes the majority of hormones from the pituitary gland, which are under the regulation of the hormones secreted from the hypothalamus.

Structure and Function

GROSS ANATOMY OF THE PITUITARY GLAND

The pituitary gland undergoes rapid growth from birth to adult life to reach a weight of 500 mg. The adult gland has an anteroposterior diameter of 8 mm and a transverse diameter of 12 mm. There is a discrepancy between the size of the gland in males and females. During pregnancy, it almost doubles in size as the pars distalis enlarges. Pars distalis is a part of the anterior pituitary. It is bound superiorly by the diaphragm sellae, anteroinferior by the sphenoid sinus, and laterally by the cavernous sinus. The optic chiasm lies anterosuperior to the gland. The tuber cinereum and median eminence of the hypothalamus give origin to an infundibulum. The tubular infundibulum connects the hypophysis to the brain. Due to the dual origin of the gland, they have a unique histological appearance. They are made up of anatomically and functionally distinct lobes called the anterior lobe (adenohypophysis), posterior lobe (neurohypophysis), and intermediate lobe.[rx][rx]

The pituitary gland is within the sella turcica or the hypophyseal fossa. This structure is present near the center at the base of the cranium and is fibro-osseous. The anatomical boundaries of the gland have clinical and surgical significance. Sella turcica is a concave indentation in the sphenoid bone. The reflections of the dura bound the fossa laterally and superiorly.

Sellar Anatomy

The bony walls of the sella turcica surround the fossa in the anterior, posterior, and inferior margins. The pituitary gland, along with the sella turcica, constitutes the sellar region. Tuberculum sellae makes up the anterior wall, and dorsum sellae makes up the posterior bony wall. Anterosuperior to the tuberculum is the sulcus chiasmaticus. The margins of the dorsum sellae form rounded structures called the posterior clinoid process. The anterolateral margin of the sella turcica forms the anterior clinoid process. These two clinoid processes aids in the attachment of the dural folds. The roof of the sphenoid sinus forms the floor of the pituitary fossa. The diaphragm sellae is a dural fold with a central aperture, and it covers the sella turcica as a roof incompletely. The adenohypophysis is separated from the optic chiasm by the diaphragm. It is continuous with the dura. The pituitary stalk and the blood vessels travel via the central aperture.

Parasellar and Suprasellar Anatomy

The cavernous sinus and the suprasellar cistern encompasses the parasellar region. The lateral walls of the pituitary fossa are made up of dura mater, and it contains the cavernous sinus. The cavernous sinus consists of the internal carotid artery, sympathetic fibers, cranial nerves III, IV, V, and VI. The suprasellar cistern encompasses the optic chiasm, part of the third ventricle, hypothalamus, and the tuber cinereum. This tuber cinereum is a gray matter lamina. Researchers identified an increased concentration of type IV collagen in the pituitary gland and surrounding tissue, including the capsule. This tissue has clinical importance as it has implications in the adenoma progression and invasion of adjacent structures.[rx][rx]

ANTERIOR PITUITARY GLAND

MICROSCOPIC ANATOMY

The adenohypophyses constitute well-defined acini, consisting of cells that produce and secrete hormones. There are six cell lines, of which five are hormone-producing cell types called somatotrophs, lactotrophs, corticotrophs, thyrotrophin, and gonadotrophs. Also, a nonhormone producing sixth cell type in the anterior pituitary called the folliculostellate cells. The anterior pituitary gland encompasses the following structures:

Pars Distalis: This is located at the distal part of the gland, and most of the hormones get secreted from this region. It forms the major bulk of the anterior pituitary. It is composed of follicles of varied sizes. Based on the staining methods used, the hormone-producing cells are classified below:
Acidophils: They are composed of polypeptide hormones, and their cytoplasm stains red to orange in color. The somatotrophs and lactotrophs are the acidophils.
Basophils: They are composed of glycoprotein hormones and their cytoplasm stain blue to purple in color. The thyrotrophs, gonadotrophs, and corticotrophs are the basophils.
Chromophobes: They do not stain well. They may represent stem cells that are yet to differentiate into mature hormone-producing cells.
Pars Tuberalis: The tubular stalk is divided into pars tuberalis anteriorly and posteriorly. It extends from the pars distalis. The pars tuberalis encircles the infundibular stem, which is composed of unmyelinated axons from the hypothalamic nuclei. The hormones oxytocin and vasopressin accumulate in these axons, forming ovoid eosinophilic swellings along the infundibular stem. They make up the ‘herring bodies.’
Pars Intermedia: This is present between the pars distalis and the posterior pituitary gland. It is made up of follicles containing a colloidal matrix and includes the remainder of the Rathke’s pouch cleft. Though it is mostly nonfunctioning, they produce melanocyte-stimulating hormone, endorphins and have some pituitary stem cells.

The hypothalamus is where the initial primary signal hormones get synthesized to stimulate the pituitary gland. Their synthesis is in the cell body of the neurons following which the axons project to terminate at the gland in the fenestrated portal capillaries. Then they travel via the bloodstream to the pituitary gland to stimulate the specific cells or inhibit it.

FUNCTION

The following are the hormones produced and secreted from the anterior pituitary.

Adrenocorticotropic Hormone (ACTH) – The release of this hormone from the gland is in response to the corticotropin-releasing hormone (CRH) from the hypothalamus. The CRH reaches the target location via the portal system and cleaves the proopiomelanocortin (POMC) into three major substances that are the ACTH, melanocyte-stimulating hormone, beta-endorphins. They then travel to reach the adrenal cortex, via the bloodstream to facilitate the release of cortisol. The negative feedback from the cortisol regulates the CRH and ACTH. They aid in the secretion of glucocorticoids during stress.
Prolactin (PRL): This hormone is under the direct control of the hypothalamus. Dopamine inhibits the release of prolactin. The suckling of the baby in the postpartum period will inhibit the release of dopamine, thus disinhibiting prolactin release. When there is a drop in the dopamine levels due to disease or drugs, the patient will present with galactorrhea. Their primary function is to stimulate the growth of the mammary glands and participate in milk production.
Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH): The gonadotropin-releasing hormone (GnRH) that is secreted from the hypothalamus acts on the gonadotropin cells to secrete the LH and FSH. In males, the LH acts on the Leydig cells and secretes testosterone from the testes. The FSH acts on the Sertoli cells and secretes inhibin B for spermatogenesis. In females, the LH acts on the ovaries to initiate the production of the steroid hormone, and its surge causes ovulation. FSH acts on the granulosa cells and initiates follicular development for ovulation by the mature Graafian follicle. The steroid sex hormones regulate the LH and FSH through negative feedback.
Growth Hormone or Somatotropin (GH): The GH gets secreted from the somatotrophs in response to the growth hormone-releasing hormone released from the hypothalamus. GH has anabolic properties and stimulates the growth of the cells in the body. The GH release is under the regulation of the negative feedback from the increased blood levels of GH and IGF-1.
Thyroid Stimulating Hormone (TSH): TSH secretion from the gland thyrotropic occurs in response to the thyrotropin-releasing hormone from the hypothalamus. This TSH acts on the thyroid gland to stimulate the release of T3 and T4. The TSH gets regulated by the blood levels of T3 and T4.[rx][rx][rd][rx]

POSTERIOR PITUITARY GLAND

MICROSCOPIC ANATOMY

This portion of the gland is a specialized neuroendocrine structure. The posterior pituitary is a combination of pars nervosa and the infundibular stalk. They contain axons that have originated from hypothalamic neurons, specifically the axon terminals of the magnocellular neurons of the paraventricular and supraoptic nuclei. Glial cells called pituicytes encircle the axons. The pituicytes have elongated processes that run along with the axons; these are absent in a typical astrocyte and is due to the transcription factor expression TTF-1. The axons together form the hypothalamohypophyseal tract, which terminates near the posterior lobe sinusoids. The terminals of the axons are close to the blood vessels to aid in the secretion of the hormones. The precursor hormones are packed into secretory granules, called the herring bodies. These precursor hormones then get cleaved during transport to the posterior pituitary. Neurophysins are proteins that are essential for the posttranslational processing of hormones. The posterior pituitary is not glandular, like the anterior pituitary. Thus they do not synthesize hormones.

FUNCTION

The following are the two hormones released from the posterior pituitary.

Oxytocin: They participate in the milk let-down or milk ejection reflex during lactation, myoepithelial, and smooth muscle contraction, uterine contraction. This hormone is available for exogenous administration to patients with postpartum hemorrhage. Five IU of oxytocin is the recommended intravenous injection dosage to prevent postpartum hemorrhage, and it is given following the delivery of the anterior shoulder of the fetus.[rx]
Arginine Vasopressin (AVP) or Antidiuretic Hormone (ADH): These hormones aid in the regulation of water content and prevents water depletion. It maintains the tonicity of the blood and blood pressure during an event of volume loss. The vascular smooth muscles express the V1 receptors, which, in response to the AVP, causes arteriolar contraction. The renal collecting duct and the tubular epithelium express V2 receptors, which in response to AVP, upregulate the aquaporin two channels and increases free water reuptake.[rx][rx][rx][rx]

Cellular

The hormones of the pituitary gland are protein or polypeptide in nature and vary in complexity.

Anterior Pituitary Hormones

Human Growth Hormone

Human growth hormone (HGH), also known as somatotropin, is a protein of 191 amino acid single chain polypeptides secreted by the acidophilic somatotropic cells of the anterior pituitary gland.[rx] Its levels in the body are under tight regulation by the hypothalamus mediators, growth hormone-releasing hormone (GHRH), and growth hormone-inhibiting hormone (GHIH or somatostatin).

Prolactin

Prolactin is a protein hormone secreted by the acidophilic lactotroph cells of the anterior pituitary gland. Chemically, prolactin is similar to a growth hormone composing of 199 amino acids, and forms after a 28-amino acid signal peptide are proteolytically cleaved from the prolactin prohormone (pre-prolactin).[rx] The secretion of prolactin by the anterior pituitary is tonically inhibited by dopamine from the tuberoinfundibular pathway of the hypothalamus and stimulated by thyrotropin-releasing hormone (TRH), estrogen, dopamine antagonist (antipsychotics), and multiple factors including suckling, stress, and sleep.

Follicle-stimulating Hormone (FSH) and Luteinizing Hormone (LH)

FSH and LH, also known as gonadotropins, are glycoprotein hormones secreted by the gonadotropin cells of the adenohypophysis. They are both glycoproteins made up of an alpha and beta subunit. The alpha subunits are identical between the two hormones, but the beta subunit of each is different and gives each hormone its biological specificity.[rx] Particularly, the alpha subunit of LH is made up of 92 amino acids, and the beta subunit contains 120 amino acids.[rx] The gonadotropic cells do not react well with acid or basic stains and thus appear either basophilic or chromophobic under the microscope.[rx] The secretion of these hormones is regulated by the release of gonadotropin-releasing hormone secreted by the hypothalamus.

Adrenocorticotrophic Hormone (ACTH)

The adrenocorticotrophic hormone is a polypeptide tropic hormone produced and secreted by the basophilic corticotropic cells of the anterior pituitary gland. ACTH is synthesized from Pro-opiomelanocortin (POMC) and consists of 39 amino acids. The hypothalamus-pituitary axis and secretion tightly regulate its production is in response to the corticotropin-releasing hormone.

Thyroid-stimulating Hormone (TSH)

Thyroid-stimulating hormone is a peptide hormone secreted by the basophilic thyrotropes of the anterior pituitary gland. It is composed of 1 alpha chain and one beta chain.[rx] The hypothalamus-pituitary axis regulates its release. The hypothalamus releases thyroid-releasing hormone (TRH), which stimulates thyrotrophs of the anterior pituitary to secrete TSH.

Posterior Pituitary Hormones

Vasopressin & Oxytocin

Vasopressin, also known as antidiuretic hormone (ADH), is synthesized in the supraoptic nuclei of the hypothalamus while oxytocin synthesis occurs in the paraventricular nuclei of the hypothalamus. Both the posterior pituitary hormones are packaged in secretory granules and move down the axon where they are stored in the Herring bodies. These bodies are neurosecretory granules that represent the terminal ends of the axons coming from the hypothalamus.

References

ByRx Harun

The Pituitary Gland – Anatomy, Structure, Functions

The Pituitary Gland/The pituitary endocrine gland, which is located in the bony sella turcica, is attached to the base of the brain and has a unique connection with the hypothalamus. The pituitary gland consists of two anatomically and functionally distinct regions, the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). Between these lobes lies a small region called the intermediate lobe. The hypothalamus regulates the pituitary gland secretion.[rx][rx][rx][rx][rx]

The Anterior Pituitary (Adenohypophysis)

The anterior pituitary is derived from the embryonic ectoderm. It secretes five endocrine hormones from five different types of epithelial endocrine cells. The release of anterior pituitary hormones is regulated by hypothalamic hormones (releasing or inhibitory), which are synthesized in the cell bodies of neurons located in several nuclei that surround the third ventricle. These include the arcuate, the paraventricular and ventromedial nuclei, and the medial preoptic and paraventricular regions. In response to neural activity, the hypothalamic hormones are released from the nerve endings into the hypophyseal portal blood and are then carried down to the anterior pituitary.[rx][rx][rx]

Anterior Pituitary (AP) Hormones

Growth hormone (GH)

Other names: somatotropic hormone or somatotropin

Precursor cells: somatotrophs in the AP
Target cells: almost all tissues of the body
Transport: 60% circulates free and 40% bound to specific GH-binding proteins (GHBPs)
Mechanism of action: GH binds to growth hormone receptors (GHRs) causing dimerization of GHR, activation of the GHR-associated JAK2 tyrosine kinase, and tyrosyl phosphorylation of both JAK2 and GHR. This causes recruitment and/or activation of a variety of signaling molecules, including MAP kinases, insulin receptor substrates, phosphatidylinositol 3′ phosphate kinase, diacylglycerol, protein kinase C, intracellular calcium, and Stat transcription factors. These signaling molecules contribute to GH-induced changes in enzymatic activity, transport function, and gene expression that ultimately culminate in changes to growth and metabolism.
Regulation of GH secretion: The release of GH is under dual control by the hypothalamus. GH secretion is stimulated by growth hormone-releasing hormone (GHRH) but suppressed by another hormone peptide, somatostatin (also known as growth hormone-inhibiting hormone (GHIH)). Insulin-like growth factor-1 (IGF-1) provides negative feedback for inhibiting GH release from somatotrophs. Thyroid hormones (T3 and T4) up-regulate GH gene expression in somatotrophs.
Physiological Functions: GH acts almost on every type of cell. Its principal targets are bones and skeletal muscles. It has direct metabolic effects on fats, proteins, and carbohydrates and indirect actions that result in skeletal growth.
Direct Metabolic Functions: GH is anabolic. It stimulates the growth of almost all tissues of the body that are capable of growing (increase in the number of cells). GH also increases the rate of protein synthesis in most cells of the body and decreases the rate of glucose utilization throughout the body (diabetogenic action). Also, it increases the mobilization of fatty acids from adipose tissue and increases levels of free fatty acids in the blood.
Indirect Actions on Skeletal Growth: GH stimulates the production of IGF-1 from hepatocytes. IGF-1 mediates the growth-promoting effects of GH on the skeleton. IGF-1 exerts direct actions on both cartilage and bone to stimulate growth and differentiation. These effects are crucial for growth from childhood to the end of adolescence.

Prolactin

Precursor cells: mainly from lactotrophs in the AP
Target cells: main target cells are mammary glands and gonads
Mechanism of action: binds to peptide hormone receptor (single transmembrane domain) to activate the JAK2-STAT intracellular signaling pathway similar to that of GH
Regulation: Like GH, dual hypothalamic inhibitory (from dopamine) and stimulatory hormones (PRH) regulate prolactin secretion. The predominant hypothalamic influence is inhibitory.
Physiological Functions: The main functions of prolactin are stimulating mammary gland growth and development (mammographic effect) and milk production (lactogenic effect). It also has effects on the hypothalamic-pituitary-gonadal axis and can inhibit pulsatile GnRH secretion from the hypothalamus.

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

Precursor cells: gonadotrophs in the AP
Target cells: gonads (ovaries and testes)
Mechanism of action: FSH and LH bind to G protein-coupled receptors to activate the adenylyl cyclase enzyme, which in turn increases intracellular cAMP. cAMP activates protein kinase A (PKA) that phosphorylates intracellular proteins. These phosphorylated proteins then accomplish the final physiologic actions.
Regulation: FSH and LH secretion are under the control of the hypothalamic gonadotropin-releasing hormone (GnRH).
Physiological Functions: FSH and LH regulate the functions of the ovaries and the testes. In females, FSH stimulates the growth and development of follicles in preparation for ovulation and secretion of estrogens by the mature Graafian follicle. LH triggers ovulation and stimulates the secretion of progesterone by the corpus luteum. In males, FSH is required for spermatogenesis, and LH stimulates testosterone secretion by Leydig cells.

Thyroid-stimulating hormone (TSH)

Precursor cells: thyrotropes in the AP
Target cells: thyroid follicular cells
Mechanism of action: TSH binds to the G-protein-coupled receptors on the basolateral membrane of the thyroid follicular cells. Similar to FSH and LH, it activates the adenylyl cyclase-PKA-cAMP system to phosphorylate several proteins, which in turn achieve the final physiologic actions
Regulation: TSH secretion is under the control of the hypothalamic thyrotropin-releasing hormone (TRH). Also, T4 feeds back to the anterior pituitary to inhibit TSH secretion.
Physiological functions: the main function of TSH is to stimulate the synthesis and secretion of thyroid hormones (tri-iodothyronine [T3] and thyroxine [T4]) from thyroid follicles. It also maintains the structural integrity of the thyroid glands.

Adrenocorticotrophic hormone (ACTH)

Precursor cells: corticotrophs in the AP
Target cells: cells in the cortex of the adrenal glands (adrenocortical cells)
Mechanism of Action: ACTH binds to its G-protein coupled receptors on the adrenocortical cells. Similar to TSH, FSH, and LH, it activates the adenylyl cyclase-PKA-cAMP system to phosphorylate several proteins, which in turn achieve the final physiologic functions.
Regulation: ACTH secretion is under the control of the hypothalamic corticotropin-releasing hormone (CRH). It is subject to negative feedback regulation.
Physiological functions: the main function of ACTH is to stimulate the secretion of adrenal cortex hormones (mainly glucocorticoids) during stress. [rx]

The Posterior Pituitary (Neurohypophysis)

The posterior pituitary is neural in origin. Unlike the anterior pituitary, the posterior pituitary is connected directly to the hypothalamus via a nerve tract (hypothalamohypophyseal nerve tract). It secretes two hormones: oxytocin and antidiuretic hormone (ADH) or vasopressin. The hormones are synthesized by the magnocellular neurons located in the supraoptic and paraventricular nuclei of the hypothalamus. The hormones are transported in association with neurophysins proteins along the axons of these neurons to end in nerve terminals within the posterior pituitary.[3]

Oxytocin

Precursor cells: paraventricular and supraoptic nuclei in the hypothalamus
Target cells: myoepithelial cells of the mammary glands and the uterine muscles (myometrium) in women and myofibroblast cells in the seminiferous tubules in men.
Mechanism of action: oxytocin acts on its target cells via a G-protein coupled receptor, which activates phospholipase C that in turn stimulates phosphoinositide turnover. This causes increased intracellular calcium concentration, which activates the contractile machinery of the cell.
Regulation: oxytocin is released in response to an afferent neural input to the hypothalamic neurons that synthesize the hormone. Suckling and uterine stimulation by the baby’s head during delivery are the major stimuli for oxytocin release. It is subject to positive feedback regulation.
Physiological Functions: oxytocin stimulates milk ejection from the breast in response to suckling (milk ejection reflex). It causes contraction of myoepithelial cells surrounding the ducts and alveoli of the gland and therefore milk ejection. Oxytocin also stimulates uterine contraction during labor to expel the fetus and placenta.

Antidiuretic Hormone (ADH) or Vasopressin

Precursor cells: paraventricular and supraoptic nuclei of the hypothalamus.
Target cells: renal distal convoluted tubules and collecting duct and vascular smooth muscle cells.
Mechanism of action: similar to oxytocin, it acts on its target cells via a G-protein coupled receptor, which activates phospholipase C that in turn stimulates phosphoinositide turnover and causes an increase in intracellular calcium concentration which in turn achieves the final physiologic actions.
Regulation: The main stimulus for ADH release is an increase in osmolality of circulating blood. Osmoreceptors located in the hypothalamus detect this increase and activate the paraventricular and supraoptic nuclei to release ADH. It also releases in response to hypovolemia.4Physiological Functions: ADH binds to V2 receptors on the distal tubule and collecting ducts of the kidney to up-regulate aquaporin channel expression on the basolateral membrane and increase water reabsorption. It, as its name suggests, also acts as a vasoconstrictor upon binding to V1 receptors on the arteriolar smooth muscle.

Overview of the Pituitary Gland

The pituitary gland is connected to the hypothalamus and secretes nine hormones that regulate body homeostasis.

Key Points

The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea. Although located at the base of the brain and often considered to be part of the brain, the pituitary gland is in fact a separate organ and is not part of the brain.

The pituitary gland is divided into two parts, the anterior pituitary, and the posterior pituitary. The anterior pituitary receives signaling molecules from the hypothalamus, and in response, synthesizes and secretes seven hormones.

The posterior pituitary does not produce any hormones of its own; instead, it stores and secretes two hormones made in the hypothalamus.

Key Terms

pituitary gland: An endocrine gland, about the size of a pea, that sits in a small, bony cavity at the base of the brain whose secretions control the other endocrine glands and influence growth, metabolism, and maturation.

hypothalamus: A region of the forebrain located below the thalamus, forming the basal portion of the diencephalon, and functioning to regulate body temperature, some metabolic processes, and governing the autonomic nervous system.

The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea. Although located at the base of the brain and often considered to be part of the brain, the pituitary gland is in fact a separate organ. It protrudes off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity.

This illustration shows where the pituitary gland is located in the brain. It protrudes off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity.

Pituitary location: The location of the pituitary gland in the human brain.

The pituitary is functionally connected to the hypothalamus by a small tube called the infundibular stem, or, pituitary stalk. The pituitary gland secretes hormones that regulate homeostasis.

The pituitary gland is divided into two parts, the anterior pituitary, and the posterior pituitary.

The anterior pituitary receives signaling molecules from the hypothalamus, and in response, synthesizes and secretes seven important hormones including thyroid-stimulating hormone and growth hormone.
The posterior pituitary does not produce any hormones of its own, rather, it stores and secretes two hormones made in the hypothalamus— oxytocin and
anti-diuretic hormone.

In this image that shows the location of the pituitary gland, it is referred to by its other name, the hypophysis.

The pituitary gland: In this image, the pituitary gland is referred to by its other name, the hypophysis.

Control of the Pituitary Gland by the Hypothalamus

The pituitary gland consists of the anterior pituitary and the posterior pituitary.

Key Points

While the pituitary gland is known as the master endocrine gland, both of its lobes are under the control of the hypothalamus: the anterior pituitary receives its signals from the parvocellular neurons, and the posterior pituitary receives its signals from the magnocellular neurons.

The pituitary gland is connected by a system of blood vessels to the hypothalamus. This system of blood vessels is known as the hypophyseal portal system, and it allows endocrine communication between the two structures.

The mechanism for hormone transport via hypothalamoportal vessels involves cells that are regulated by different nuclei in the hypothalamus; for instance, neurons that release neurotransmitters as hormones in the connective link between the pituitary and the brain.

Key Terms

pituitary gland: An endocrine gland, about the size of a pea, that sits in a small, bony cavity at the base of the brain whose secretions control the other endocrine glands and influence growth, metabolism, and maturation.

hypothalamus: A region of the forebrain located below the thalamus, forming the basal portion of the diencephalon, that regulates body temperature, some metabolic processes, and governs the autonomic nervous system.

hypophyseal portal system: The system of blood vessels that link the hypothalamus and the anterior pituitary in the brain.

The pituitary gland consists of two components: the anterior pituitary and the posterior pituitary, and is functionally linked to the hypothalamus by the pituitary stalk (also named the infundibular stem, or simply the infundibulum).

Whilst the pituitary gland is known as the master endocrine gland, both of the lobes are under the control of the hypothalamus: the anterior pituitary receives its signals from the parvocellular neurons, and the posterior pituitary receives its signals from magnocellular neurons.

The anterior lobe of the pituitary receives hypothalamic-releasing hormones from the hypothalamus that bind with receptors on endocrine cells in the anterior pituitary that regulate the release of adrenal hormones into the circulatory system. Hormones from the hypothalamus are rapidly degraded in the anterior pituitary, which prevents them from entering the circulatory system.

The posterior lobe of the pituitary gland develops as an extension of the hypothalamus. As such, it is not capable of producing its own hormones; instead, it stores hypothalamic hormones for later release into the systemic circulation.

This is a drawing of the skull with the parts of the brain identified. In particular, the anterior and posterior pituitary gland are called out. They are referred to as the anterieor and posterior hypophysis in the drawing.

Pituitary gland: The anterior and posterior lobes of the pituitary (hypophysis) gland are shown.

The Anterior Pituitary

The anterior pituitary secretes seven hormones that regulate several physiological processes, including stress, growth, and reproduction.

Key Points

A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland.

The anterior pituitary regulates several physiological processes, including stress, growth, reproduction, and lactation.

The anterior pituitary gland secretes 7 hormones: follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, thyroid-stimulating hormone, prolactin, endorphins, and growth hormone.

Key Terms

anterior pituitary gland: A major organ of the endocrine system that regulates several physiological processes including stress, growth, reproduction, and lactation.

A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis) is the glandular, anterior lobe of the pituitary gland. The anterior pituitary regulates several physiological processes including stress, growth, reproduction, and lactation.

Its regulatory functions are achieved through the secretion of various peptide hormones that act on target organs including the adrenal gland, liver, bone, thyroid gland, and gonads. The anterior pituitary itself is regulated by the hypothalamus and by negative feedback from these target organs.

Anatomy of the Anterior Pituitary Gland

The fleshy, glandular anterior pituitary is distinct from the neural composition of the posterior pituitary. The anterior pituitary is composed of multiple parts:

Pars distalis: This is the distal part that comprises the majority of the anterior pituitary; it is where most pituitary hormone production occurs.
Pars tuberalis: This is the tubular part that forms a sheath that extends up from the pars distalis and wraps around the pituitary stalk. Its function is poorly understood.
Pars intermedia: This is the intermediate part that sits between the pars distalis and the posterior pituitary and is often very small in humans.

Major Hormones Secreted by the Anterior Pituitary Gland

Adrenocorticotropic hormone (ACTH), is a polypeptide whose target is the adrenal gland. The effects of ACTH are upon the secretion of glucocorticoid, mineralocorticoids, and sex corticoids.
Beta-endorphin is a polypeptide that affects the opioid receptor, whose effects include the inhibition of the perception of pain.
Thyroid-stimulating hormone is a glycoprotein hormone that affects the thyroid gland and the secretion of thyroid hormones.
Follicle-stimulating hormone is a glycoprotein hormone that targets the gonads and affects the growth of the reproductive system.
Luteinizing hormone is a glycoprotein hormone that targets the gonads to effect sex hormone production.
Growth hormone is a polypeptide hormone that targets the liver and adipose tissue and promotes growth through lipid and carbohydrate metabolism.
Prolactin is a polypeptide hormone whose target is the ovaries and mammary glands. Prolactin influences the secretion of estrogen/progesterone and milk production.

Regulation

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

This is an illustration of the anterior pituitary, which is linked to the hypothalamus by a portal system. The hypothalamus releases signaling molecules that incite the anterior pituitary to produce hormones.

The anterior pituitary: The anterior pituitary, in yellow, is linked to the hypothalamus by a portal system. The hypothalamus releases signaling molecules that incite the anterior pituitary to produce hormones.

The Posterior Pituitary

The posterior pituitary secretes two important endocrine hormones—oxytocin and antidiuretic hormone.

Key Points

The posterior pituitary (or neurohypophysis) comprises the posterior lobe of the pituitary gland and is part of the endocrine system.

Hormones known as posterior pituitary hormones are synthesized by the hypothalamus, and include oxytocin and antidiuretic hormone.

The hormones are then stored in neurosecretory vesicles (Herring bodies) before being secreted by the posterior pituitary into the bloodstream.

Key Terms

oxytocin: A hormone that stimulates contractions during labor.

posterior pituitary: The posterior pituitary (or neurohypophysis) comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Despite its name, the posterior pituitary gland is not a true gland; rather, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior pituitary gland.

Antidiuretic hormone: A hormone that stimulates water reabsorption in the kidneys.

Posterior Pituitary Gland

This is an illustration of a pituitary gland that shows the anterior pituitary and the posterior pituitary, and the hypothalamus above them.

Pituitary: Pituitary gland representation.

The posterior pituitary (or neurohypophysis) comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Despite its name, the posterior pituitary gland is not a gland; rather, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior pituitary gland.

The posterior pituitary consists mainly of neuronal projections ( axons ) extending from the supraoptic and paraventricular nuclei of the hypothalamus. These axons release peptide hormones into the capillaries of the hypophyseal circulation. These are then stored in neurosecretory vesicles (Herring bodies) before being secreted by the posterior pituitary into the systemic bloodstream.

Anatomy of the Posterior Pituitary Gland

The posterior pituitary is derived from the hypothalamus and is distinct from the more fleshy, vascularized anterior lobe. The posterior pituitary is composed of two parts:

The pars nervosa also called the neural lobe or posterior lobe constitutes the majority of the posterior pituitary and is the storage site of oxytocin and vasopressin.
The infundibular stalk, also known as the infundibulum or pituitary stalk, bridges the hypothalamic and hypophyseal systems.

Major Hormones Secreted by the Posterior Pituitary Gland

The posterior pituitary stores two hormones secreted by the hypothalamus for later release:

Oxytocin, most of which is released from the paraventricular nucleus in the hypothalamus. Oxytocin is one of the few hormones that create a positive feedback loop.
Antidiuretic hormone (ADH, also known as vasopressin), the majority of which is released from the supraoptic nucleus in the hypothalamus. ADH acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood.

Clinical Significance

The following are some of the critical disease conditions associated with the pituitary gland.

Pituitary Adenoma – The most common pathology in the sellar region is the pituitary tumor. They classify into microadenomas (less than 10 mm) and macroadenomas (more than 10 mm). These macroadenomas can compress the adjacent structures. When it extends laterally, the cavernous sinus is compressed, producing ophthalmoplegia. The patients will present with diplopia due to cranial nerve compression. They may also present asymptomatically or with headaches. All the cell lines are capable of producing an adenoma.
Prolactinoma – This is the most common type of functioning secretory adenoma. They remain asymptomatic for an extended period until they cause compression or mass effect on the normal surrounding tissue causing hormonal dysfunction, visual changes, hydrocephalus, and hypogonadism.
Cushing Disease – This results from an ACTH secreting pituitary adenoma. They present with symptoms such as proximal myopathy, psychiatric disturbances, obesity, purple striae over the abdomen, extra fat around the neck termed buffalo hump, and hypertension. The standard method for resection of the tumor is transsphenoidal adenectomy. The route is via the posterior wall of the sphenoid sinus, which forms the inferior border of the pituitary gland.
GH Secreting Adenoma – This adenoma produces a lot of GH, which can cause acromegaly or gigantism. The patient may present with carpal tunnel syndrome, proximal myopathy, and rarely hypertension or diabetes mellitus.
Stalk Compression Syndrome – The patient presents with symptoms of hyperprolactinemia with raised prolactin concentration in the presence of a sellar or suprasellar mass compressing the stalk.
Pituitary Apoplexy – Pituitary adenomas that are often asymptomatic may enlarge in size and acquire additional arterial blood supply directly and undergo hemorrhagic infarction. The clinical presentation includes abrupt onset headache, visual symptoms like diplopia due to cavernous sinus compression, panhypopituitarism with low blood pressure, focal neurological deficits. The apoplexy triad includes headaches, visual changes, and vomiting. Clinicians can misdiagnose this condition as a subarachnoid hemorrhage. An emergency CT will show an enlarged pituitary fossa with some blood, and an MRI will confirm the diagnosis.
Sheehan Syndrome – This is due to the infarction and necrosis of the pituitary gland. It can be described as postpartum hypopituitarism, as postpartum hemorrhage is closely associated with its etiology. The gland enlarges during pregnancy, which causes the superior hypophyseal artery to get compressed. If the patient experiences a drop in her blood pressure during childbirth, this causes infarction and necrosis of the gland. The patient will commonly present with failure to lactate during the postpartum period, ultimately leading to a deficiency of the anterior pituitary hormones.
Lymphocytic Hypophysitis – This condition is commonly associated with pregnancy. It is an autoimmune condition with diffuse lymphocytic infiltration that destroys normal tissue with scaring. Imaging with an MRI shows homogenously enhancing and enlarged glands.
Granulomatous Hypophysitis – This is a non-caseating granuloma with Langerhans type giant cell. When it is present in the posterior lobe, it may be due to neurosarcoidosis.
Empty Sella Syndrome – There are two types of empty sella syndrome that are differentiated according to the cause. The primary empty sella syndrome is a defect in the diaphragm sellae that allows the contents above to herniate into the sella, thus compressing the gland. The secondary empty sella syndrome is due to causes such as tumors or surgery. This syndrome is associated with multiparous women, obesity, and benign intracranial hypertension. In multiparous women, this may be due to the repeated enlargement and involution of the gland leading to the gland becoming flattened. This condition must be differentiated from craniopharyngioma and Rathke’s cleft cyst as they may also present with a cyst within the same location.
Syndrome of Inappropriate Antidiuretic Hormone(SIADH) This is a condition with excessive production of antidiuretic hormone, which can result from various conditions such as nervous system disorders, neoplastic, ectopic sources such as paraneoplastic syndromes, head trauma, and drugs. The patients will present with altered mental status, seizures, or even more severe cases with coma. There will be hyponatremia due to dilution with free water. The urine analysis will show increased concentration and osmolality.
Craniopharyngiomas – Two variants are classified based on clinical and genetic features, which are the adamantinomatous (aCP) and papillary (pCP) craniopharyngiomas. The aCP occurs in children, and pCP is exclusive to adults. The embryonic theory proposed states that this develops from the ectopic embryonic remnants of Rathke’s pouch. The metaplastic theory states that the squamous epithelium that is part of the gland undergoes metaplasia and transforms.
Rathke’s Cleft Cyst – This is a benign cyst that originates from the mucinous substances in the remnants of Rathke’s pouch. The cyst contains the pink eosinophilic substance. Due to chronic inflammation, they may develop xanthogranulomas or cholesterol crystals.
Multiple Endocrine Neoplasia-1(MEN-1) – This is a genetic, endocrine neoplastic syndrome. There is an abnormal growth in the pituitary gland, parathyroid gland, and the pancreas.[rx][rx][rx]

References

Category Archive Anatomy A – Z

Blood – Types, Functions, Physiology

Components of Blood

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Erythrocytes (RBCs)

Leukocytes (WBCs)

Thrombocytes (Platelets)

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Physical Characteristics

Blood Volume

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Growth Factors

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The Kidneys

The Heart

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Adipose Tissue

The Placenta

Male and Female Gonads

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The Ovaries

The Testes

Placenta

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Functions of the Placenta

Endocrine Functions

Pancreas – Anatomy, Types, Structure, Functions

Structure

The Parts of the Pancreas

FOUR MAIN PARTS

Parts

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Nerves

Overview of Pancreatic Islets

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The endocrine cell subsets are:

Types of Cells in the Pancreas

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Pancreatic Cells

Islets of Langerhans

Insulin Secretion and Regulation of Glucagon

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Glucagon

Insulin

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