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Physiology

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

An anti-diruetic is a substance that decreases urine volume, and ADH is the primary example of it within the body. ADH is a hormone secreted from the posterior pituitary gland in response to increased plasma osmolarity (i.e., increased ion concentration in the blood), which is generally due to an increased concentration of ions relative to the volume of plasma, or decreased plasma volume.

The increased plasma osmolarity is sensed by osmoreceptors in the hypothalamus, which will stimulate the posterior pituitary gland to release ADH. ADH will then act on the nephrons of the kidneys to cause a decrease in plasma osmolarity and an increase in urine osmolarity.

ADH increases the permeability to water of the distal convoluted tubule and collecting duct, which are normally impermeable to water. This effect causes increased water reabsorption and retention and decreases the volume of urine produced relative to its ion content.

After ADH acts on the nephron to decrease plasma osmolarity (and leads to increased blood volume) and increase urine osmolarity, the osmoreceptors in the hypothalamus will inactivate, and ADH secretion will end. Due to this response, ADH secretion is considered to be a form of negative feedback.

  1. PATHOPHYSIOLOGY OF THE CONDUCTION SYSTEM

  2. Cardiac arrhythmias = deviation from normal rate, rhythm

     

    1. Heart block (types) = conduction system damage
      1. Complete Heart Block = 3rd degree block
        1. idioventricular beat (35-45/min)
        2. Atria at normal sinus rhythm
        3. Periods of asystole (dizziness, fainting)
        4. Causes = myocardial infarction of ventricular septum, surgical correction of interseptal defects, drugs
      2. Incomplete Heart Block = 2nd degree block
        1. Not all atrial beats reach ventricle
        2. Ventricular beat every 2nd, 3rd, etc. atrial beat, (2:1 block, 3:1 block)
      3. Incomplete Heart Block = 1st degree block
        1. All atrial beats reach ventricle
        2. PR interval abnormally long = slower conduction
      4. Bundle branch blocks (right or left)
        1. Impulses travel down one side and cross over
        2. Ventricular rate normal, QRS prolonged or abnormal
    2. Fibrillation
      1. Asynchronous contractions = twitching movements
      2. Loss of synchrony = little to No output
      3. Atrial Fibrillation
        1. Irregular ventricular beat & depressed pumping efficiency
        2. Atrial beat = 125 - 150/min, pulse feeble = 60 - 70/min
        3. Treatment = Digitalis - reduces rate of ventricular contraction, reduces pulse deficit
      4. Ventricular Fibrillation
        1. Almost no blood pumped to systemic system
        2. ECG = extremely bizarre
        3. Several minutes = fatal
        4. Treatment = defibrillation, cardiac massage can maintain some cardiac output

Platelets

Platelets are cell fragments produced from megakaryocytes.

Blood normally contains 150,000 to 350,000 per microliter (µl). If this value should drop much below 50,000/µl, there is a danger of uncontrolled bleeding. This is because of the essential role that platelets have in blood clotting.

When blood vessels are damaged, fibrils of collagen are exposed.

  • von Willebrand factor links the collagen to platelets forming a plug of platelets there.
  • The bound platelets release ADP and thromboxane A2 which recruit and activate still more platelets circulating in the blood.
  • (This role of thromboxane accounts for the beneficial effect of low doses of aspirin a cyclooxygenase inhibitor in avoiding heart attacks.)

ReoPro is a monoclonal antibody directed against platelet receptors. It inhibits platelet aggregation and appears to reduce the risk that "reamed out" coronary arteries (after coronary angioplasty) will plug up again.

Maintenance of Homeostasis


The kidneys maintain the homeostasis of several important internal conditions by controlling the excretion of substances out of the body. 

Ions. The kidney can control the excretion of potassium, sodium, calcium, magnesium, phosphate, and chloride ions into urine. In cases where these ions reach a higher than normal concentration, the kidneys can increase their excretion out of the body to return them to a normal level. Conversely, the kidneys can conserve these ions when they are present in lower than normal levels by allowing the ions to be reabsorbed into the blood during filtration. (See more about ions.)
 
pH. The kidneys monitor and regulate the levels of hydrogen ions (H+) and bicarbonate ions in the blood to control blood pH. H+ ions are produced as a natural byproduct of the metabolism of dietary proteins and accumulate in the blood over time. The kidneys excrete excess H+ ions into urine for elimination from the body. The kidneys also conserve bicarbonate ions, which act as important pH buffers in the blood.
 
Osmolarity. The cells of the body need to grow in an isotonic environment in order to maintain their fluid and electrolyte balance. The kidneys maintain the body’s osmotic balance by controlling the amount of water that is filtered out of the blood and excreted into urine. When a person consumes a large amount of water, the kidneys reduce their reabsorption of water to allow the excess water to be excreted in urine. This results in the production of dilute, watery urine. In the case of the body being dehydrated, the kidneys reabsorb as much water as possible back into the blood to produce highly concentrated urine full of excreted ions and wastes. The changes in excretion of water are controlled by antidiuretic hormone (ADH). ADH is produced in the hypothalamus and released by the posterior pituitary gland to help the body retain water.
 
Blood Pressure. The kidneys monitor the body’s blood pressure to help maintain homeostasis. When blood pressure is elevated, the kidneys can help to reduce blood pressure by reducing the volume of blood in the body. The kidneys are able to reduce blood volume by reducing the reabsorption of water into the blood and producing watery, dilute urine. When blood pressure becomes too low, the kidneys can produce the enzyme renin to constrict blood vessels and produce concentrated urine, which allows more water to remain in the blood.

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

Membrane Structure & Function

Cell Membranes

  • Cell membranes are phospholipid bilayers (2 layers)
  • Bilayer forms a barrier to passage of molecules in an out of cell
  • Phospholipids = glycerol + 2 fatty acids + polar molecule (i.e., choline) + phosphate
  • Cholesterol (another lipid) stabilizes cell membranes
  • the hydrophobic tails of the phospholipids (fatty acids) are together in the center of the bilayer. This keeps them out of the water

Membranes Also Contain Proteins

  • Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long
  • Hydrophobic = doesn't like water = likes lipids
  • Membrane proteins have many functions:
    • receptors for hormones
    • pumps for transporting materials across the membrane
    • ion channels
    • adhesion molecules for holding cells to extracellular matrix

cell recognition antigens

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