COPD and Cancer

A.    Chronic Obstructive Pulmonary Disease (COPD)

1.    Common features of COPD

a.    almost all have smoking history
b.    dyspnea - chronic "gasping" for air
c.    frequent coughing and infections
d.    often leads to respiratory failure

2.    obstructive emphysema - usually results from smoking

a.    enlargement & deterioration of alveoli
b.    loss of elasticity of the lungs
c.    "barrel chest" from bronchiole opening during inhalation & constriction during exhalation

3.    chronic bronchitis - mucus/inflammation of mucosa

B.    Lung Cancer

1.    squamous cell carcinoma (20-40%) - epithelium of the bronchi and bronchioles
2.    adenocarcinoma (25-35%) - cells of bronchiole glands and cells of the alveoli
3.    small cell carcinoma (10-20%) - special lymphocyte-like cells of the bronchi
4.    90% of all lung cancers are in people who smoke or have smoked 
 

SPECIAL SOMATIC AFFERENT (SSA) PATHWAYS

Hearing

The organ of Corti with its sound-sensitive hair cells and basilar membrane are important parts of the sound transducing system for hearing. Mechanical vibrations of the basilar membrane generate membrane potentials in the hair cells which produce impulse patterns in the cochlear portion of the vestibulocochlear nerve (VIII)

Special somatic nerve fibers of cranial nerve VIII relay impulses from the sound receptors (hair cells) in the cochlear nuclei of the brainstem

These are bipolar neurons with cell bodies located in the spiral ganglia of the cochlea.

Vestibular System

The vestibulocochlear nerve serves two quite different functions.

The cochlear portion, conducts sound information to the brain,

The vestibular portion conducts proprioceptive information.

It is the central neural pathways

Special somatic afferent fibers from the hair cells of the macula utriculi and macula sacculi conduct information into the vestibular nuclei on the ipsilateral side of the pons and medulla.

These are bipolar neurons with cell bodies located in the vestibular ganglion.

 Some of the fibers project directly into the ipsilateral cerebellum to terminate in the uvula, flocculus, and nodulus, but most enter the vestibular nuclei and synapse there.

Vision

The visual system receptors are the rods and cones of the retina.

Special somatic afferent fibers of the optic nerve (II) conduct visual signals into the brain

Fibers from the lateral (temporal) retina of either eye terminate in the lateral geniculate body on the same side of the brain as that eye.

SSA II fibers from the medial (nasal) retina of each eye cross over in the optic chiasm to terminate in the contralateral lateral geniculate body.

Area 17 is the primary visual area, which receives initial visual signals.

Neurons from this area project into the adjacent occipital cortex (areas 18 and 19) which is known as the secondary visual area. It is here that the visual signal is fully evaluated.

The visual reflex pathway involving the pupillary light reflex - in which the pupils constrict when a light is shined into the eyes and dilate when the light is removed.

Some SSA II fibers leave the optic tract before reaching the lateral geniculates, terminating in the superior colliculi instead.

From here, short neurons project to the Edinger­Westphal nucleus (an accessory nucleus of III) in the midbrain, which serves as the origin of the preganglionic parasympathetic fibers of the oculomotor nerve (GVE III).

The GVE III fibers in turn project to the ciliary ganglia, from which arise the postganglionic fibers to the sphincter muscles of the iris, which constrict the pupils.

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

Events in gastric function:

1) Signals from vagus nerve begin gastric secretion in cephalic phase.

2) Physical contact by food triggers release of pepsinogen and H⁺ in gastric phase.

3) Muscle contraction churns and liquefies chyme and builds pressure toward pyloric sphincter.

4) Gastrin is released into the blood by cells in the pylorus. Gastrin reinforces the other stimuli and acts as a positive feedback mechanism for secretion and motility.

5) The intestinal phase begins when acid chyme enters the duodenum. First more gastrin secretion causes more acid secretion and motility in the stomach.

6) Low pH inhibits gastrin secretion and causes the release of enterogastrones such as GIP into the blood, and causes the enterogastric reflex. These events stop stomach emptying and allow time for digestion in the duodenum before gastrin release again stimulates the stomach.

The Nerve Impulse

When a nerve is stimulated the resting potential changes. Examples of such stimuli are pressure, electricity, chemicals, etc. Different neurons are sensitive to different stimuli(although most can register pain). The stimulus causes sodium ion channels to open. The rapid change in polarity that moves along the nerve fiber is called the "action potential." In order for an action potential to occur, it must reach threshold. If threshold does not occur, then no action potential can occur. This moving change in polarity has several stages:

Depolarization

The upswing is caused when positively charged sodium ions (Na+) suddenly rush through open sodium gates into a nerve cell. The membrane potential of the stimulated cell undergoes a localized change from -55 millivolts to 0 in a limited area. As additional sodium rushes in, the membrane potential actually reverses its polarity so that the outside of the membrane is negative relative to the inside. During this change of polarity the membrane actually develops a positive value for a moment(+30 millivolts). The change in voltage stimulates the opening of additional sodium channels (called a voltage-gated ion channel). This is an example of a positive feedback loop.

Repolarization

The downswing is caused by the closing of sodium ion channels and the opening of potassium ion channels. Release of positively charged potassium ions (K+) from the nerve cell when potassium gates open. Again, these are opened in response to the positive voltage--they are voltage gated. This expulsion acts to restore the localized negative membrane potential of the cell (about -65 or -70 mV is typical for nerves).

Hyperpolarization

When the potassium ions are below resting potential (-90 mV). Since the cell is hyper polarized, it goes to a refractory phrase.

Refractory phase

The refractory period is a short period of time after the depolarization stage. Shortly after the sodium gates open, they close and go into an inactive conformation. The sodium gates cannot be opened again until the membrane is repolarized to its normal resting potential. The sodium-potassium pump returns sodium ions to the outside and potassium ions to the inside. During the refractory phase this particular area of the nerve cell membrane cannot be depolarized. This refractory area explains why action potentials can only move forward from the point of stimulation.

Factors that affect sensitivity and speed

Sensitivity

Increased permeability of the sodium channel occurs when there is a deficit of calcium ions. When there is a deficit of calcium ions (Ca+2) in the interstitial fluid, the sodium channels are activated (opened) by very little increase of the membrane potential above the normal resting level. The nerve fiber can therefore fire off action potentials spontaneously, resulting in tetany. This could be caused by the lack of hormone from parathyroid glands. It could also be caused by hyperventilation, which leads to a higher pH, which causes calcium to bind and become unavailable.

Speed of Conduction

This area of depolarization/repolarization/recovery moves along a nerve fiber like a very fast wave. In myelinated fibers, conduction is hundreds of times faster because the action potential only occurs at the nodes of Ranvier (pictured below in 'types of neurons') by jumping from node to node. This is called "saltatory" conduction. Damage to the myelin sheath by the disease can cause severe impairment of nerve cell function. Some poisons and drugs interfere with nerve impulses by blocking sodium channels in nerves. See discussion on drug at the end of this outline.

Cells, cytoplasm, and organelles:

• Cytoplasm consists of a gelatinous solution and contains microtubules (which serve as a cell's cytoskeleton) and organelles

• Cells also contain a nucleus within which is found DNA (deoxyribonucleic acid) in the form of chromosomes plus nucleoli (within which ribosomes are formed)

• Organelles include:

1. Endoplasmic reticulum : 2 forms: smooth and rough; the surface of rough ER is coated with ribosomes; the surface of smooth ER is not , Functions include: mechanical support, synthesis (especially proteins by rough ER), and transport
2. Golgi complex consists of a series of flattened sacs (or cisternae) functions include: synthesis (of substances likes phospholipids), packaging of materials for transport (in vesicles), and production of lysosomes
3. Lysosome : membrane-enclosed spheres that contain powerful digestive enzymes , functions include destruction of damaged cells & digestion of phagocytosed materials
4.  Mitochondria : have double-membrane: outer membrane & highly convoluted inner membrane
   1. inner membrane has folds or shelf-like structures called cristae that contain elementary particles; these particles contain enzymes important in ATP production
   2. primary function is production of adenosine triphosphate (ATP)
5. Ribosome-:composed of rRNA (ribosomal RNA) & protein , primary function is to produce proteins
6. Centrioles :paired cylindrical structures located near the nucleas , play an important role in cell division
7. Flagella & cilia - hair-like projections from some human cells
   1. cilia are relatively short & numerous (e.g., those lining trachea)
   2. a flagellum is relatively long and there's typically just one (e.g., sperm)

• • Villi  Projections of cell membrane that serve to increase surface area of a cell (which is important, for example, for cells that line the intestine)