The pancreas

The pancreas consists of clusters if endocrine cells (the islets of Langerhans) and exocrine cells whose secretions drain into the duodenum.

Pancreatic fluid contains:

• sodium bicarbonate (NaHCO₃). This neutralizes the acidity of the fluid arriving from the stomach raising its pH to about 8.
• pancreatic amylase. This enzyme hydrolyzes starch into a mixture of maltose and glucose.
• pancreatic lipase. The enzyme hydrolyzes ingested fats into a mixture of fatty acids and monoglycerides. Its action is enhanced by the detergent effect of bile.
• 4 zymogens— proteins that are precursors to active proteases. These are immediately converted into the active proteolytic enzymes:
  • trypsin. Trypsin cleaves peptide bonds on the C-terminal side of arginines and lysines.
  • chymotrypsin. Chymotrypsin cuts on the C-terminal side of tyrosine, phenylalanine, and tryptophan residues (the same bonds as pepsin, whose action ceases when the NaHCO₃ raises the pH of the intestinal contents).
  • elastase. Elastase cuts peptide bonds next to small, uncharged side chains such as those of alanine and serine.
  • carboxypeptidase. This enzyme removes, one by one, the amino acids at the C-terminal of peptides.
• nucleases. These hydrolyze ingested nucleic acids (RNA and DNA) into their component nucleotides.

The secretion of pancreatic fluid is controlled by two hormones:

• secretin, which mainly affects the release of sodium bicarbonate, and
• cholecystokinin (CCK), which stimulates the release of the digestive enzymes.

Hyperventilation

1. Treatments :Rebreath air, hold breath (Increase CO₂)
   Give oxygen for Hypoxemia

SPECIAL VISCERAL AFFERENT (SVA) PATHWAYS

Taste

Special visceral afferent (SVA) fibers of cranial nerves VII, IX, and X conduct signals into the solitary tract of the brainstem, ultimately terminating in the nucleus of the solitary tract on the ipsilateral side.

Second-order neurons cross over and ascend through the brainstem in the medial lemniscus to the VPM of the thalamus.

Thalamic projections to area 43 (the primary taste area) of the postcentral gyrus complete the relay.

SVA VII fibers conduct from the chemoreceptors of taste buds on the anterior twothirds of the tongue, while SVA IX fibers conduct taste information from buds on the posterior one-third of the tongue.

SVA X fibers conduct taste signals from those taste cells located throughout the fauces.

Smell

The smell-sensitive cells (olfactory cells) of the olfactory epithelium project their central processes through the cribiform plate of the ethmoid bone, where they synapse with mitral cells. The central processes of the mitral cells pass from the olfactory bulb through the olfactory tract, which divides into a medial and lateral portion The lateral olfactory tract terminates in the prepyriform cortex and parts of the amygdala of the temporal lobe.

These areas represent the primary olfactory cortex. Fibers then project from here to area 28, the secondary olfactory area, for sensory evaluation. The medial olfactory tract projects to the anterior perforated sub­stance, the septum pellucidum, the subcallosal area, and even the contralateral olfactory tract.

Both the medial and lateral olfactory tracts contribute to the visceral reflex pathways, causing the viscerosomatic and viscerovisceral responses.

Biological Functions are Extremely Sensitive to pH

• H+ and OH- ions get special attention because they are very reactive
• Substance which donates H+ ions to solution = acid
• Substance which donates OH- ions to solution = base
• Because we deal with H ions over a very wide range of concentration, physiologists have devised a logarithmic unit, pH, to deal with it
  • pH = - log [H⁺]
  • [H⁺] is the H ion concentration in moles/liter
  • Because of the way it is defined a high pH indicates low H ion and a low pH indicates high H ion- it takes a while to get used to the strange definition
  • Also because of the way it is defined, a change of 1 pH unit means a 10X change in the concentration of H ions
    • If pH changes by 2 units the H+ concentration changes by 10 X 10 = 100 times

• Human blood pH is 7.4
  • Blood pH above 7.4 = alkalosis
  • Blood pH below 7.4 = acidosis
• Body must get rid of ~15 moles of potential acid/day (mostly CO₂)
  • CO₂ reacts with water to form carbonic acid (H₂CO₃)
  • Done mostly by lungs & kidney
• In neutralization H⁺ and OH^- react to form water
• If the pH changes charges on molecules also change, especially charges on proteins
  • This changes the reactivity of proteins such as enzymes
• Large pH changes occur as food passes through the intestines.

The Posterior Lobe

The posterior lobe of the pituitary releases two hormones, both synthesized in the hypothalamus, into the circulation.

• Antidiuretic Hormone (ADH).
  ADH is a peptide of 9 amino acids. It is also known as arginine vasopressin. ADH acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood.
  • A deficiency of ADH
    • leads to excessive loss of urine, a condition known as diabetes  nsipidus.
• Oxytocin
  Oxytocin is a peptide of 9 amino acids. Its principal actions are:
  • stimulating contractions of the uterus at the time of birth
  • stimulating release of milk when the baby begins to suckle

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.