The Sliding Filament mechanism of muscle contraction.

When a muscle contracts the light I bands disappear and the dark A bands move closer together. This is due to the sliding of the actin and myosin myofilaments against one another. The Z-lines pull together and the sarcomere shortens

The thick myosin bands are not single myosin proteins but are made of multiple myosin molecules. Each myosin molecule is composed of two parts: the globular "head" and the elongated "tail". They are arranged to form the thick bands.

It is the myosin heads which form crossbridges that attach to binding sites on the actin molecules and then swivel to bring the Z-lines together

Likewise the thin bands are not single actin molecules. Actin is composed of globular proteins (G actin units) arranged to form a double coil (double alpha helix) which produces the thin filament. Each thin myofilament is wrapped by a tropomyosin protein, which in turn is connected to the troponin complex. 

The tropomyosin-troponin combination blocks the active sites on the actin molecules preventing crossbridge formation. The troponin complex consists of three components: TnT, the part which attaches to tropomyosin, TnI, an inhibitory portion which attaches to actin, and TnC which binds calcium ions. When excess calcium ions are released they bind to the TnC causing the troponin-tropomyosin complex to move, releasing the blockage on the active sites. As soon as this happens the myosin heads bind to these active sites.

Blood Transfusions

• Some of these units ("whole blood") were transfused directly into patients (e.g., to replace blood lost by trauma or during surgery).
• Most were further fractionated into components, including:
  • RBCs. When refrigerated these can be used for up to 42 days.
  • platelets. These must be stored at room temperature and thus can be saved for only 5 days.
  • plasma. This can be frozen and stored for up to a year.

safety of donated blood

A variety of infectious agents can be present in blood.

• viruses (e.g., HIV-1, hepatitis B and C, HTLV, West Nile virus
• bacteria like the spirochete of syphilis
• protozoans like the agents of malaria and babesiosis
• prions (e.g., the agent of variant Crueutzfeldt-Jakob disease)

and could be transmitted to recipients. To minimize these risks,

• donors are questioned about their possible exposure to these agents;
• each unit of blood is tested for a variety of infectious agents.

Most of these tests are performed with enzyme immunoassays (EIA) and detect antibodies against the agents. blood is now also checked for the presence of the RNA of these RNA viruses:

• HIV-1
• hepatitis C
• West Nile virus

• by the so-called nucleic acid-amplification test (NAT).

Oxygen Transport in Blood: Hemoglobin

A.    Association & Dissociation of Oxygen + Hemoglobin

1.    oxyhemoglobin (HbO₂) - oxygen molecule bound
2.    deoxyhemoglobin (HHb) - oxygen unbound
    
H-Hb     +    O₂  <= === => HbO₂ + H+

3.    binding gets more efficient as each O₂ binds
4.    release gets easier as each O₂ is released

5.    Several factors regulate AFFINITY of O₂

a.    Partial Pressure of O₂
b.    temperature
c.    blood pH (acidity)
d.    concentration of “diphosphoglycerate” (DPG)

B.    Effects of Partial Pressure of O₂

1.  oxygen-hemoglobin dissociation curve

a.    104 mm (lungs) - 100% saturation (20 ml/100 ml)
b.    40 mm (tissues) - 75% saturation (15 ml/100 ml)
c.    right shift - Decreased Affinity, more O2 unloaded
d.     left shift- Increased Affinity, less O₂ unloaded

C.    Effects of Temperature
    
1.    HIGHER Temperature    --> Decreased Affinity (right)
2.    LOWER Temperature        --> Increased Affinity (left)

D.    Effects of pH (Acidity) 

1.    HIGHER pH    --> Increased Affinity (left)
2.    LOWER pH    --> Decreased Affinity (right) "Bohr Effect"
a.    more Carbon Dioxide, lower pH (more H+), more O2 release

E.    Effects of Diphosphoglycerate (DPG)

1.    DPG - produced by anaerobic processes in RBCs
2.    HIGHER DPG    > Decreased Affinity (right)
3.    thyroxine, testosterone, epinephrine, NE - increase RBC metabolism and DPG production, cause RIGHT shift

F.    Oxygen Transport Problems

1.    hypoxia - below normal delivery of Oxygen

a.    anemic hypoxia - low RBC or hemoglobin
b.    stagnant hypoxia - impaired/blocked blood flow
c.    hypoxemic hypoxia - poor lung gas exchange

2.    carbon monoxide poisoning - CO has greater Affinity than Oxygen or Carbon Dioxide 
 

As the contents of the stomach become thoroughly liquefied, they pass into the duodenum, the first segment  of the small intestine. The duodenum is the first 10" of the small intestine

Two ducts enter the duodenum:

• one draining the gall bladder and hence the liver
• the other draining the exocrine portion of the pancreas.

From the intestinal mucosal cells, and from the liver and gallbladder. Secretions from the pancreas and bile from the gallbladder enter the duodenum through the hepatopancreatic ampulla and the sphincter of Oddi. These lie where the pancreatic duct and common bile duct join before entering the duodenum. The presence of fatty chyme in the duodenum causes release of the hormone CCK into the bloodstream. CCK is one of the enterogastrones and its main function, besides inhibiting the stomach, is to stimulate the release of enzymes by the pancreas, and the contraction of the gallbladder to release bile. It also stimulates the liver to produce bile. Consumption of excess fat results in excessive bile production by the liver, and this can lead to the formation of gallstones from precipitation of the bile salts. 

The acid in the chyme stimulates the release of secretin which causes the pancreas to release bicarbonate which neutralizes the acidity

• 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