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.

Production of Hormones

The kidneys produce and interact with several hormones that are involved in the control of systems outside of the urinary system.

Calcitriol. Calcitriol is the active form of vitamin D in the human body. It is produced by the kidneys from precursor molecules produced by UV radiation striking the skin. Calcitriol works together with parathyroid hormone (PTH) to raise the level of calcium ions in the bloodstream. When the level of calcium ions in the blood drops below a threshold level, the parathyroid glands release PTH, which in turn stimulates the kidneys to release calcitriol. Calcitriol promotes the small intestine to absorb calcium from food and deposit it into the bloodstream. It also stimulates the osteoclasts of the skeletal system to break down bone matrix to release calcium ions into the blood.
 
Erythropoietin. Erythropoietin, also known as EPO, is a hormone that is produced by the kidneys to stimulate the production of red blood cells. The kidneys monitor the condition of the blood that passes through their capillaries, including the oxygen-carrying capacity of the blood. When the blood becomes hypoxic, meaning that it is carrying deficient levels of oxygen, cells lining the capillaries begin producing EPO and release it into the bloodstream. EPO travels through the blood to the red bone marrow, where it stimulates hematopoietic cells to increase their rate of red blood cell production. Red blood cells contain hemoglobin, which greatly increases the blood’s oxygen-carrying capacity and effectively ends the hypoxic conditions.
 
Renin. Renin is not a hormone itself, but an enzyme that the kidneys produce to start the renin-angiotensin system (RAS). The RAS increases blood volume and blood pressure in response to low blood pressure, blood loss, or dehydration. Renin is released into the blood where it catalyzes angiotensinogen from the liver into angiotensin I. Angiotensin I is further catalyzed by another enzyme into Angiotensin II.

Angiotensin II stimulates several processes, including stimulating the adrenal cortex to produce the hormone aldosterone. Aldosterone then changes the function of the kidneys to increase the reabsorption of water and sodium ions into the blood, increasing blood volume and raising blood pressure. Negative feedback from increased blood pressure finally turns off the RAS to maintain healthy blood pressure levels.

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

• The Autonomic Nervous System (ANS) Controls the Body's Internal Environment in a Coordinated Manner

• The ANS helps control the heart rate, blood pressure, digestion, respiration, blood pH and other bodily functions through a series of complex reflex actions
• These controls are done automatically, below the conscious level
• To exert this control the activities of many different organs must be coordinated so they work to accomplish the same goal
• In the ANS there are 2 nerves between the central nervous system (CNS) and the organ. The nerve cell bodies for the second nerve are organized into ganglia:
  • CNS -> Preganglionic nerve -> Ganglion -> Postganglionic nerve -> Organ
• At each junction neurotransmitters are released and carry the signal to the next nerve or organ.

• The ANS has 2 Divisions, Sympathetic and Parasympathetic

   

• Comparison of the 2 systems:

• 	Anatomical Location	Preganglionic Fibers	Postganglionic Fibers	Transmitter (Ganglia)	Transmitter (Organs)
  Sympathetic	Thoracic/ Lumbar	Short	Long	ACh	NE
  Parasympathetic	Cranial/ Sacral	Long	Short	ACh	ACh

   

  The Sympathetic is the "Fight or Flight" Branch of the ANS

• Emergency situations, where the body needs a sudden burst of energy, are handled by the sympathetic system
• The sympathetic system increases cardiac output and pulmonary ventilation, routes blood to the muscles, raises blood glucose and slows down digestion, kidney filtration and other functions not needed during emergencies
• Whole sympathetic system tends to "go off" together
• In a controlled environment the sympathetic system is not required for life, but it is essential for any stressful situation

• The Parasympathetic is the Rest and Digest Branch of the ANS

• The parasympathetic system promotes normal maintenance of the body- acquiring building blocks and energy from food and getting rid of the wastes
• It promotes secretions and mobility of different parts of the digestive tract.
• Also involved in urination, defecation.
• Does not "go off" together; activities initiated when appropriate
• The vagus nerve (cranial number 10) is the chief parasympathetic nerve
• Other cranial parasympathetic nerves are: III (oculomotor), VII (facial) and IX (glossopharyngeal)

• The Hypothalamus Has Central Control of the ANS

• The hypothalamus is involved in the coordination of ANS responses,
• One section of the hypothalamus seems to control many of the "fight or flight" responses; another section favors "rest and digest" activities

• The Adrenal Medulla is an Extension of the Sympathetic Nervous System

• The adrenal medulla behaves like a combined autonomic ganglion and postsynaptic sympathetic nerve (see diagram above)
• Releases both norepinephrine and epinephrine in emergency situations
  • Releases a mixture of epinephrine (E = 80%) and norepinephrine (NE = 20%)
  • Epinephrine = adrenaline
• This action is under control of the hypothalamus

• Sympathetic & Parasympathetic Systems

• Usually (but not always) both sympathetic and parasympathetic nerves go to an organ and have opposite effects
• You can predict about 90% of the sympathetic and parasympathetic responses using the 2 phrases: "Fight or Flight" and "Rest and Digest".
• Special cases:
  • Occasionally the 2 systems work together: in sexual intercourse the parasympathetic promotes erection and the sympathetic produces ejaculation
  • Eye: the sympathetic response is dilation and relaxation of the ciliary muscle for far vision (parasympathetic does the opposite)
  • Urination: the parasympathetic system relaxes the sphincter muscle and promotes contraction of muscles of the bladder wall -> urination (sympathetic blocks urination)
  • Defecation: the parasympathetic system causes relaxation of the anal sphincter and stimulates colon and rectum to contract -> defecation (sympathetic blocks defecation)

• Organ	Parasympathetic Response "Rest and Digest"	Sympathetic Response "Fight or Flight"
  Heart (baroreceptor reflex)	Decreased heart rate Cardiac output decreases	Increased rate and strength of contraction Cardiac output increases
  Lung Bronchioles	Constriction	Dilation
  Liver Glycogen	No effect	Glycogen breakdown Blood glucose increases
  Fat Tissue	No effect	Breakdown of fat Blood fatty acids increase
  Basal Metabolism	No effect	Increases ~ 2X
  Stomach	Increased secretion of HCl & digestive enzymes Increased motility	Decreased secretion Decreased motility
  Intestine	Increased secretion of HCl & digestive enzymes Increased motility	Decreased secretion Decreased motility
  Urinary bladder	Relaxes sphincter Detrusor muscle contracts Urination promoted	Constricts sphincter Relaxes detrusor Urination inhibited
  Rectum	Relaxes sphincter Contracts wall muscles Defecation promoted	Constricts sphincter Relaxes wall muscles Defecation inhibited
  Eye	Iris constricts Adjusts for near vision	Iris dilates Adjusts for far vision
  Male Sex Organs	Promotes erection	Promotes ejaculation

   

• Sensory:
  • Somatic (skin & muscle) Senses:
    Postcentral gyrus (parietal lobe). This area senses touch, pressure, pain, hot, cold, & muscle position. The arrangement is upside-down (head below, feet above) and is switched from left to right (sensations from the right side of the body are received on the left side of the cortex). Some areas (face, hands) have many more sensory and motor nerves than others. A drawing of the body parts represented in the postcentral gyrus, scaled to show area, is called a homunculus .
  • Vision:
    Occipital lobe, mostly medial, in calcarine sulcus. Sensations from the left visual field go to the right cortex and vice versa. Like other sensations they are upside down. The visual cortex is very complicated because the eye must take into account shape, color and intensity.
  • Taste:
    Postcentral gyrus, close to lateral sulcus. The taste area is near the area for tongue somatic senses.
  • Smell:
     The olfactory cortex is not as well known as some of the other areas. Nerves for smell go to the olfactory bulb of the frontal cortex, then to other frontal cortex centers- some nerve fibers go directly to these centers, but others come from the thalamus like most other sensory nerves
  • Hearing:
    Temporal lobe, near junction of the central and lateral sulci. Mostly within the lateral sulcus. There is the usual crossover and different tones go to different parts of the cortex. For complex patterns of sounds like speech and music other areas of the cortex become involved.
• Motor:
  • Primary Motor ( Muscle Control):
    Precentral gyrus (frontal lobe). Arranged like a piano keyboard: stimulation in this area will cause individual muscles to contract. Like the sensory cortex, the arrangement is in the form of an upside-down homunculus. The fibers are crossed- stimulation of the right cortex will cause contraction of a muscle on the left side of the body.
  • Premotor (Patterns of Muscle Contraction):
    Frontal lobe in front of precentral gyrus. This area helps set up learned patterns of muscle contraction (think of walking or running which involve many muscles contracting in just the right order).
  • Speech-Muscle Control:
    Broca's area, frontal lobe, usually in left hemisphere only. This area helps control the patterns of muscle contraction necessary for speech. Disorders in speaking are called aphasias.
• Perception:
  • Speech- Comprehension:
    Wernicke's area, posterior end of temporal lobe, usually left hemisphere only. Thinking about words also involves areas in the frontal lobe.
  • Speech- Sound/Vision Association:
    Angular gyrus, , makes connections between sounds and shapes of words

The small intestine

Digestion within the small intestine produces a mixture of disaccharides, peptides, fatty acids, and monoglycerides. The final digestion and absorption of these substances occurs in the villi, which line the inner surface of the small intestine.

This scanning electron micrograph (courtesy of Keith R. Porter) shows the villi carpeting the inner surface of the small intestine.

The crypts at the base of the villi contain stem cells that continuously divide by mitosis producing

• more stem cells
• cells that migrate up the surface of the villus while differentiating into
  1. columnar epithelial cells (the majority). They are responsible for digestion and absorption.
  2. goblet cells, which secrete mucus;
  3. endocrine cells, which secrete a variety of hormones;
• Paneth cells, which secrete antimicrobial peptides that sterilize the contents of the intestine.

All of these cells replace older cells that continuously die by apoptosis.

The villi increase the surface area of the small intestine to many times what it would be if it were simply a tube with smooth walls. In addition, the apical (exposed) surface of the epithelial cells of each villus is covered with microvilli (also known as a "brush border"). Thanks largely to these, the total surface area of the intestine is almost 200 square meters, about the size of the singles area of a tennis court and some 100 times the surface area of the exterior of the body.

Incorporated in the plasma membrane of the microvilli are a number of enzymes that complete digestion:

• aminopeptidases attack the amino terminal (N-terminal) of peptides producing amino acids.
• disaccharidasesThese enzymes convert disaccharides into their monosaccharide subunits.
  • maltase hydrolyzes maltose into glucose.
  • sucrase hydrolyzes sucrose (common table sugar) into glucose and fructose.
  • lactase hydrolyzes lactose (milk sugar) into glucose and galactose.

Fructose simply diffuses into the villi, but both glucose and galactose are absorbed by active transport.

• fatty acids and monoglycerides. These become resynthesized into fats as they enter the cells of the villus. The resulting small droplets of fat are then discharged by exocytosis into the lymph vessels, called lacteals, draining the villi.