The thyroid gland is a double-lobed structure located in the neck. Embedded in its rear surface are the four parathyroid glands.

The Thyroid Gland

The thyroid gland synthesizes and secretes:

• thyroxine (T₄) and
• calcitonin

T₄ and T₃

Thyroxine (T₄ ) is a derivative of the amino acid tyrosine with four atoms of iodine. In the liver, one atom of iodine is removed from T₄ converting it into triiodothyronine (T₃). T₃ is the active hormone. It has many effects on the body. Among the most prominent of these are:

• an increase in metabolic rate
• an increase in the rate and strength of the heart beat.

The thyroid cells responsible for the synthesis of T₄ take up circulating iodine from the blood. This action, as well as the synthesis of the hormones, is stimulated by the binding of TSH to transmembrane receptors at the cell surface.

Diseases of the thyroid

1. hypothyroid diseases; caused by inadequate production of T₃

• cretinism: hypothyroidism in infancy and childhood leads to stunted growth and intelligence. Can be corrected by giving thyroxine if started early enough.
• myxedema: hypothyroidism in adults leads to lowered metabolic rate and vigor. Corrected by giving thyroxine.
• goiter: enlargement of the thyroid gland. Can be caused by:
  • inadequate iodine in the diet with resulting low levels of T₄ and T₃;
  • an autoimmune attack against components of the thyroid gland (called Hashimoto's thyroiditis).

2. hyperthyroid diseases; caused by excessive secretion of thyroid hormones

Graves´ disease. Autoantibodies against the TSH receptor bind to the receptor mimicking the effect of TSH binding. Result: excessive production of thyroid hormones. Graves´ disease is an example of an autoimmune disease.

Osteoporosis. High levels of thyroid hormones suppress the production of TSH through the negative-feedback mechanism mentioned above. The resulting low level of TSH causes an increase in the numbers of bone-reabsorbing osteoclasts resulting in osteoporosis.

Calcitonin

Calcitonin is a polypeptide of 32 amino acids. The thyroid cells in which it is synthesized have receptors that bind calcium ions (Ca²⁺) circulating in the blood. These cells monitor the level of circulating Ca²⁺. A rise in its level stimulates the cells to release calcitonin.

• bone cells respond by removing Ca²⁺ from the blood and storing it in the bone
• kidney cells respond by increasing the excretion of Ca²⁺

Both types of cells have surface receptors for calcitonin.

Because it promotes the transfer of Ca²⁺ to bones, calcitonin has been examined as a possible treatment for osteoporosis

Membrane Potential

• Membrane potentials will occur across cell membranes if
  • 1) there is a concentration gradient of an ion
  • 2) there is an open channel in the membrane so the ion can move from one side to the other

The Sodium Pump Sets Up Gradients of Na and K Across Cell Membranes

• All cells have the Na pump in their membranes
  • Pumps 3 Nas out and 2 Ks in for each cycle
  • Requires energy from ATP
    • Uses about 30% of body's metabolic energy
  • This is a form of active transport- can pump ions "uphill", from a low to a high concentration
  • This produces concentration gradients of Na & K across the membrane
  • Typical concentration gradients:

•  
• The ion gradients represent stored electrical energy (batteries) that can be tapped to do useful work
• The Na pump is of ancient origin, probably originally designed to protect cell from osmotic swelling

Inhibited by the arrow poisons ouabain and digitalis

Control of processes in the stomach:

The stomach, like the rest of the GI tract, receives input from the autonomic nervous system. Positive stimuli come from the parasympathetic division through the vagus nerve. This stimulates normal secretion and motility of the stomach. Control occurs in several phases:

Cephalic phase stimulates secretion in anticipation of eating to prepare the stomach for reception of food. The secretions from cephalic stimulation are watery and contain little enzyme or acid.

Gastric phase of control begins with a direct response to the contact of food in the stomach and is due to stimulation of pressoreceptors in the stomach lining which result in ACh and histamine release triggered by the vagus nerve. The secretion and motility which result begin to churn and liquefy the chyme and build up pressure in the stomach. Chyme surges forward as a result of muscle contraction but is blocked from entering the duodenum by the pyloric sphincter. A phenomenon call retropulsion occurs in which the chyme surges backward only to be pushed forward once again into the pylorus. The presence of this acid chyme in the pylorus causes the release of a hormone called gastrin into the bloodstream. Gastrin has a positive feedback effect on the motility and acid secretion of the stomach. This causes more churning, more pressure, and eventually some chyme enters the duodenum.

Intestinal phase of stomach control occurs. At first this involves more gastrin secretion from duodenal cells which acts as a "go" signal to enhance the stomach action already occurring. But as more acid chyme enters the duodenum the decreasing pH inhibits gastrin secretion and causes the release of negative or "stop" signals from the duodenum.

These take the form of chemicals called enterogastrones which include GIP (gastric inhibitory peptide). GIP inhibits stomach secretion and motility and allows time for the digestive process to proceed in the duodenum before it receives more chyme. The enterogastric reflex also reduces motility and forcefully closes the pyloric sphincter. Eventually as the chyme is removed, the pH increases and gastrin and the "go" signal resumes and the process occurs all over again. This series of "go" and "stop" signals continues until stomach emptying is complete.

Hormones are carried by the blood throughout the entire body, yet they affect only certain cells.  The specific cells that respond to a given hormone have receptor sites for that hormone.  

This is sort of a lock and key mechanism.  If the key fits the lock, then the door will open.  If a hormone fits the receptor site, then there will be an effect.  If a hormone and a receptor site do not match, then there is no reaction.  All of the cells that have receptor sites for a given hormone make up the target tissue for that hormone.  In some cases, the target tissue is localized in a single gland or organ.  In other cases, the target tissue is diffuse and scattered throughout the body so that many areas are affected.  

Hormones bring about their characteristic effects on target cells by modifying cellular activity.  Cells in a target tissue have receptor sites for specific hormones.  Receptor sites may be located on the surface of the cell membrane or in the interior of the cell.

In general those protein hormones are unable to diffuse through the cell membrane and react with receptor sites on the surface of the cell.  The hormone receptor reaction on the cell membrane activates an enzyme within the membrane, called adenyl cyclase, which diffuses into the cytoplasm.  Within the cell, adenyl cyclase catalyzes or starts the process of removal of phosphates from ATP to produce cyclic adenosine monophosphate or c AMP.  This c AMP activates enzymes within the cytoplasm that alter or change the cellular activity.  The protein hormone, which reacts at the cell membrane, is called the first messenger.  c Amp that brings about the action attributed to the hormone is called the second messenger.  This type of action is relatively rapid because the precursors are already present and they just needed to be activated in some way.  

Functional Divisions of the Nervous System:

1) The Voluntary Nervous System - (ie. somatic division) control of willful control of effectors (skeletal muscles) and conscious perception. Mediates voluntary reflexes.

2) The Autonomic Nervous System - control of autonomic effectors - smooth muscles, cardiac muscle, glands. Responsible for "visceral" reflexes

Water: comprises 60 - 90% of most living organisms (and cells) important because it serves as an excellent solvent & enters into many metabolic reactions

• Intracellular (inside cells) = ~ 34 liters
• Interstitial (outside cells) = ~ 13 liters
• Blood plasma = ~3 liters

40% of blood is red blood cells (RBCs)

plasma is similar to interstitial fluid, but contains plasma proteins

serum = plasma with clotting proteins removed

intracellular fluid is very different from interstitial fluid (high K concentration instead of high Na concentration, for example)

• Capillary walls (1 cell thick) separate blood from interstitial fluid
• Cell membranes separate intracellular and interstitial fluids

• Loss of about 30% of body water is fatal

Ions = atoms or molecules with unequal numbers of electrons and protons:

• found in both intra- & extracellular fluid
• examples of important ions include sodium, potassium, calcium, and chloride

Ions (Charged Atoms or Molecules) Can Conduct Electricity

• Giving up electron leaves a + charge (cation)
• Taking on electron produces a - charge (anion)
• Ions conduct electricity
• Without ions there can be no nerves or excitability
  • Na⁺ and K⁺ cations  
  • Ca²⁺ and Mg²⁺ cations  control metabolism and trigger muscle contraction and secretion of hormones and transmitters

Na+ & K+ are the Major Cations in Biological Fluids

• High K+ in cells, high Na+ outside
• Ion gradients maintained by Na pump (1/3 of basal metabolism)
• Think of Na+ gradient as a Na+ battery- stored electrical energy
• K+ gradient forms a K+ battery
• Energy stored in Na+ and K+ batteries can be tapped when ions flow

• Na+ and K+ produce action potential of excitable cells