The Adrenal Glands

The adrenal glands are two small structures situated one at top each kidney. Both in anatomy and in function, they consist of two distinct regions:

• an outer layer, the adrenal cortex, which surrounds
• the adrenal medulla.

The Adrenal Cortex

cells of the adrenal cortex secrete a variety of steroid hormones.

• glucocorticoids (e.g., cortisol)
• mineralocorticoids (e.g., aldosterone)
• androgens (e.g., testosterone)

• Production of all three classes is triggered by the secretion of ACTH from the anterior lobe of the pituitary.

Glucocorticoids

They Effect by raising the level of blood sugar (glucose). One way they do this is by stimulating gluconeogenesis in the liver: the conversion of fat and protein into intermediate metabolites that are ultimately converted into glucose.

The most abundant glucocorticoid is cortisol (also called hydrocortisone).

Cortisol and the other glucocorticoids also have a potent anti-inflammatory effect on the body. They depress the immune response, especially cell-mediated immune responses. 

Mineralocorticoids

The most important of them is the steroid aldosterone. Aldosterone acts on the kidney promoting the reabsorption of sodium ions (Na⁺) into the blood. Water follows the salt and this helps maintain normal blood pressure.

Aldosterone also

• acts on sweat glands to reduce the loss of sodium in perspiration;
• acts on taste cells to increase the sensitivity of the taste buds to sources of sodium.

The secretion of aldosterone is stimulated by:

• a drop in the level of sodium ions in the blood;
• a rise in the level of potassium ions in the blood;
• angiotensin II
• ACTH (as is that of cortisol)

Androgens

The adrenal cortex secretes precursors to androgens such as testosterone.

Excessive production of adrenal androgens can cause premature puberty in young boys.

In females, the adrenal cortex is a major source of androgens. Their hypersecretion may produce a masculine pattern of body hair and cessation of menstruation.

Addison's Disease: Hyposecretion of the adrenal cortices

Addison's disease has many causes, such as

• destruction of the adrenal glands by infection;
• their destruction by an autoimmune attack;
• an inherited mutation in the ACTH receptor on adrenal cells.

Cushing's Syndrome: Excessive levels of glucocorticoids

In Cushing's syndrome, the level of adrenal hormones, especially of the glucocorticoids, is too high.It can be caused by:

• excessive production of ACTH by the anterior lobe of the pituitary;
• excessive production of adrenal hormones themselves (e.g., because of a tumor), or (quite commonly)
• as a result of glucocorticoid therapy for some other disorder such as
  • rheumatoid arthritis or
  • preventing the rejection of an organ transplant.

The Adrenal Medulla

The adrenal medulla consists of masses of neurons that are part of the sympathetic branch of the autonomic nervous system. Instead of releasing their neurotransmitters at a synapse, these neurons release them into the blood. Thus, although part of the nervous system, the adrenal medulla functions as an endocrine gland.The adrenal medulla releases:

• adrenaline (also called epinephrine) and
• noradrenaline (also called norepinephrine)

Both are derived from the amino acid tyrosine.

Release of adrenaline and noradrenaline is triggered by nervous stimulation in response to physical or mental stress. The hormones bind to adrenergic receptors  transmembrane proteins in the plasma membrane of many cell types.

Some of the effects are:

• increase in the rate and strength of the heartbeat resulting in increased blood pressure;
• blood shunted from the skin and viscera to the skeletal muscles, coronary arteries, liver, and brain;
• rise in blood sugar;
• increased metabolic rate;
• bronchi dilate;
• pupils dilate;
• hair stands on end (gooseflesh in humans);
• clotting time of the blood is reduced;
• increased ACTH secretion from the anterior lobe of the pituitary.

All of these effects prepare the body to take immediate and vigorous action.

Neurophysiology

Transmission of an action potential. This occurs in two ways:

1) across the synapse - synaptic transmission. This is a chemical process, the result of a chemical neurotransmitter.

2) along the axon - membrane transmission. This is the propagation of the action potential itself along the membrane of the axon.

Synaptic transmission - What you learned about the neuromuscular junction is mostly applicable here as well. The major differences in our current discussion are:

1) Transmission across the synapse does not necessarily result in an action potential. Instead, small local potentials are produced which must add together in summation to produce an action potential.

2) Although ACh is a common neurotransmitter, there are many others and the exact effect at the synapse depends on the neurotransmitter involved.

3) Neurotransmitters can be excitatory or inhibitory. The result might be to turn off the next neuron rather than to produce an action potential

The basic steps of synaptic transmission are the same as described at the neuromuscular junction

1) Impulse arrives at the axon terminus causing opening of Ca²⁺ channels and allows Ca²⁺  to enter the axon. The calcium ions are in the extracellular fluid, pumped there much like sodium is pumped. Calcium is just an intermediate in both neuromuscular and synaptic transmission.

2) Ca²⁺  causes vesicles containing neurotransmitter to release the chemical into the synapse by exocytosis across the pre-synaptic membrane.

3) The neurotransmitter binds to the post-synaptic receptors. These receptors are linked to chemically gated ion channels and these channels may open or close as a result of binding to the receptors to cause a graded potential which can be either depolarization, or hyperpolarization depending on the transmitter. Depolarization results from opening of Na⁺ gates and is called an EPSP. Hyperpolarization could result from opening of K⁺ gates and is called IPSP. 

4) Graded potentials spread and overlap and can summate to produce a threshold depolarization and an action potential when they stimulate voltage gated ion channels in the neuron's trigger region.

5) The neurotransmitter is broken down or removed from the synapse in order for the receptors to receive the next stimulus. As we learned there are enzymes for some neurotransmitters such as the Ach-E which breaks down acetylcholine. Monoamine oxidase (MAO) is an enzyme which breaks down the catecholamines (epinephrine, nor-epinephrine, dopamine) and nor-epinephrine (which is an important autonomic neurotransmitter) is removed by the axon as well in a process known as reuptake. Other transmitters may just diffuse away.

Graded Potentials - these are small, local depolarizations or hyperpolarizations which can spread and summate to produce a threshold depolarization. Small because they are less than that needed for threshold in the case of the depolarizing variety. Local means they only spread a few mm on the membrane and decline in intensity with increased distance from the point of the stimulus. The depolarizations are called EPSPs, excitatory post-synaptic potentials, because they tend to lead to an action potential which excites or turns the post-synaptic neuron on. Hyperpolarizations are called IPSPs, inhibitory post-synaptic potentials, because they tend to inhibit an action potential and thus turn the neuron off.

Summation - the EPSPs and IPSPs will add together to produce a net depolarization (or hyperpolarization).

Temporal summation- this is analogous to the frequency (wave, tetany) summation discussed for muscle. Many EPSPs occurring in a short period of time (e.g. with high frequency) can summate to produce threshold depolarization. This occurs when high intensity stimulus results in a high frequency of EPSPs.

Spatial summation - this is analogous to quantal summation in a muscle. It means that there are many stimuli occurring simultaneously. Their depolarizations spread and overlap and can build on one another to sum and produce threshold depolarization.

Inhibition - When the brain causes an IPSP in advance of a reflex pathway being stimulated, it reduces the likelihood of the reflex occurring by increasing the depolarization required. The pathway can still work, but only with more than the usual number or degree of stimulation. We inhibit reflexes when allowing ourselves to be given an injection or blood test for instance.

Facilitation - When the brain causes an EPSP in advance of a reflex pathway being stimulated, it makes the reflex more likely to occur, requiring less additional stimulation. When we anticipate a stimulus we often facilitate the reflex.

Learned Reflexes - Many athletic and other routine activities involve learned reflexes. These are reflex pathways facilitated by the brain. We learn the pathways by performing them over and over again and they become facilitated. This is how we can perfect our athletic performance, but only if we learn and practice them correctly. It is difficult to "unlearn" improper techniques once they are established reflexes. Like "riding a bike" they may stay with you for your entire life!

Post-tetanic potentiation - This occurs when we perform a rote task or other repetitive action. At first we may be clumsy at it, but after continuous use (post-tetanic) we become more efficient at it (potentiation). These actions may eventually become learned reflexes

The Action Potential

The trigger region of a neuron is the region where the voltage gated channels begin. When summation results in threshold depolarization in the trigger region of a neuron, an action potential is produced. There are both sodium and potassium channels. Each sodium channel has an activation gate and an inactivation gate, while potassium channels have only one gate. 

A) At the resting state the sodium activation gates are closed, sodium inactivation gates are open, and potassium gates are closed. Resting membrane potential is at around -70 mv inside the cell. 

B) Depolarizing phase: The action potential begins with the activation gates of the sodium channels opening, allowing Na+ ions to enter the cell and causing a sudden depolarization which leads to the spike of the action potential. Excess Na+ ions enter the cell causing reversal of potential becoming briefly more positive on the inside of the cell membrane.

C) Repolarizing phase: The sodium inactivation gates close and potassium gates open. This causes Na+ ions to stop entering the cell and  K+ ions  to leave the cell, causing repolarization. Until the membrane is repolarized it cannot be stimulated, called the absolute refractory period.

D) Excess potassium leaves the cell causing a brief hyperpolarization. Sodium activation gates close and potassium gates begin closing. The sodium-potassium pump begins to re-establish the resting membrane potential. During hyperpolarization the membrane can be stimulated but only with a greater than normal depolarization, the relative refractory period.

Action potentials are self-propagated, and once started the action potential progresses along the axon membrane. It is all-or-none, that is there are not different degrees of action potentials. You either have one or you don't.

Phases of cardiac cycle :

1. Early diastole ( also called the atrial diastole , or complete heart diastole) : During this phase :

- Atria are  relaxed
- Ventricles are relaxed
- Semilunar valves are closed
- Atrioventricular valves are open
During this phase the blood moves passively from the venous system into the ventricles ( about 80 % of blood fills the ventricles during this phase.

2. Atrial systole : During this phase :

- Atria are contracting
- Ventricles are relaxed
- AV valves are open
- Semilunar valves are closed
- Atrial pressure increases.the a wave of atrial pressure appears here.
- P wave of ECG starts here
- intraventricular pressure increases due to the rush of blood then decrease due to continuous relaxation of ventricles.

The remaining 20% of blood is moved to fill the ventricles during this phase , due to atrial contraction.

3. Isovolumetric contraction : During this phase :

- Atria are relaxed
- Ventricles are contracting
- AV valves are closed
- Semilunar valves are closed
- First heart sound
- QRS complex.
The ventricular fibers start to contract during this phase , and the intraventricular pressure increases. This result in closing the AV valves , but the pressure is not yet enough to open the semilunar valves , so the blood volume remain unchanged , and the muscle fibers length also remain unchanged , so we call this phase as isovolumetric contraction ( iso : the same , volu= volume , metric= length).

4. Ejection phase : Blood is ejected from the ventricles into the aorta and pulmonary artery .

During this phase :

- Ventricles are contracting
- Atria are relaxed
- AV valves are closed
- Semilunar valves are open
- First heart sound
- Intraventricular pressure is increased , due to continuous contraction
- increased aortic pressure .
- T wave starts.

5. Isovolumetric relaxation:  This phase due to backflow of blood in aorta and pulmonary system after the ventricular contraction is up and the ventricles relax . This backflow closes the semilunar valves .

During this phase :

- Ventricles are relaxed
- Atrial are relaxed
- Semilunar valves are closed .
- AV valves are closed.
- Ventricular pressure fails rapidly
- Atrial pressure increases due to to continuous venous return. the v wave appears here. 
- Aortic pressure : initial sharp decrease due to sudden closure of the semilunar valve ( diacrotic notch) , followed by secondary rise in pressure , due to elastic recoil of the aorta ( diacrotic wave)  .
- T wave ends in this phase

Structural Divisions of the nervous system:

1) Central Nervous System (CNS) - the brain and spinal cord.

2) Peripheral Nervous System (PNS) - the nerves, ganglia, receptors, etc

1. Automatic control (sensory) of respiration is in - brainstem (midbrain) 

2. Behavioral/voluntary control is in - the cortex

3. Alveolar ventilation -the amount of atmospheric air that actually reaches the alveolar per breath and that can participate in the exchange of gasses between alveoli and blood

4. Only way to increase gas exchange in alveolar capillaries - perfusion-limited gas exchange 

5. Pulmonary ventiliation not effected by - concentration of bicarbonate ions

6. Central chemoreceptors - medulla -  CO2, O2 and H+ concentrations

7. Peripheral chemoreceptors - carotid and aortic bodies- PO2, PCO2 and pH 

8. Major stimulus for respiratory centers - arterial PCO2 

9. Rhythmic breathing depends on 
1. continuous (tonic) inspiratory drive from DRG (dorsal respiratory group)
2. intermittent (phasic) expiratory input from cerebrum, thalamus, cranial nerves and ascending spinal cord sensory tracts

10. Primary site for gas exchange - type I epithelial cells for alveoli

Carbohydrates:

• about 3% of the dry mass of a typical cell
• composed of carbon, hydrogen, & oxygen atoms (e.g., glucose is C₆H₁₂O₆)
• an important source of energy for cells
• types include:
  • monosaccharide (e.g., glucose) - most contain 5 or 6 carbon atoms
  • disaccharides
    • 2 monosaccharides linked together
    • Examples include sucrose (a common plant disaccharide is composed of the monosaccharides glucose and fructose) & lactose (or milk sugar; a disaccharide composed of glucose and the monosaccharide galactose)
  • polysaccharides
    • several monosaccharides linked together

Examples include starch (a common plant polysaccharide made up of many glucose molecules) and glycogen (commonly stored in the liver)