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).

Nucleic Acids:

• Two major types: DNA
• RNA (including mRNA, tRNA, & rRNA) 
  • Both types have code which specifies the sequence of amino acids in proteins
  • DNA = archival copy of genetic code, kept in nucleus, protected
  • RNA = working copy of code, used to translate a specific gene into a protein, goes into cytoplasm & to ribosomes, rapidly broken down
• Nucleic acids are made of 5 nucleotide bases, sugars and phosphate groups
• The bases make up the genetic code ; the phosphate and sugar make up the backbone
• RNA is a molecule with a single strand
• DNA is a double strand (a double helix) held together by hydrogen bonds between the bases
  • A = T; C= G because:
    • A must always hydrogen bond to T

C must always hydrogen bond to G

Respiration involves several components:

Ventilation - the exchange of respiratory gases (O₂ and CO₂) between the atmosphere and the lungs. This involves gas pressures and muscle contractions.

External respiration - the exchange of gases between the lungs and the blood. This involves partial pressures of gases, diffusion, and the chemical reactions involved in transport of O₂and CO₂.

Internal respiration - the exchange of gases between the blood and the systemic tissues. This involves the same processes as external respiration.

Cellular respiration - the includes the metabolic pathways which utilize oxygen and produce carbon dioxide, which will not be included in this unit.

Ventilation is composed of two parts: inspiration and expiration. Each of these can be described as being either quiet, the process at rest, or forced, the process when active such as when exercising.

Quiet inspiration:

The diaphragm contracts, this causes an increase in volume of the thorax and the lungs, which causes a decrease in pressure of the thorax and lungs, which causes air to enter the lungs, moving down its pressure gradient. Air moves into the lungs to fill the partial vacuum created by the increase in volume.

Forced inspiration:

Other muscles aid in the increase in thoracic and lung volumes.

The scalenes - pull up on the first and second ribs.

The sternocleidomastoid muscles pull up on the clavicle and sternum.

The pectoralis minor pulls forward on the ribs.

The external intercostals are especially important because they spread the ribs apart, thus increasing thoracic volume. It's these muscles whose contraction produces the "costal breathing" during rapid respirations.

Quiet expiration:

The diaphragm relaxes. The elasticity of the muscle tissue and of the lung stroma causes recoil which returns the lungs to their volume before inspiration. The reduced volume causes the pressure in the lungs to increase thus causing air to leave the lungs due to the pressure gradient.

Forced Expiration:

The following muscles aid in reducing the volume of the thorax and lungs:

The internal intercostals - these compress the ribs together

The abdominus rectus and abdominal obliques: internal obliques, external obliques- these muscles push the diaphragm up by compressing the abdomen.

Respiratory output is determined by the minute volume, calculated by multiplying the respiratory rate time the tidal volume.

Minute Volume = Rate (breaths per minute) X Tidal Volume (ml/breath)

Rate of respiration at rest varies from about 12 to 15 . Tidal volume averages 500 ml Assuming a rate of 12 breaths per minute and a tidal volume of 500, the restful minute volume is 6000 ml. Rates can, with strenuous exercise, increase to 30 to 40 and volumes can increase to around half the vital capacity.

Not all of this air ventilates the alveoli, even under maximal conditions. The conducting zone volume is about 150 ml and of each breath this amount does not extend into the respiratory zone. The Alveolar Ventilation Rate, AVR, is the volume per minute ventilating the alveoli and is calculated by multiplying the rate times the (tidal volume-less the conducting zone volume).

AVR = Rate X (Tidal Volume - 150 ml)

For a calculation using the same restful rate and volume as above this yields 4200 ml.

Since each breath sacrifices 150 ml to the conducting zone, more alveolar ventilation occurs when the volume is increased rather than the rate.

During inspiration the pressure inside the lungs (the intrapulmonary pressure) decreases to -1 to -3 mmHg compared to the atmosphere. The variation is related to the forcefulness and depth of inspiration. During expiration the intrapulmonary pressure increases to +1 to +3 mmHg compared to the atmosphere. The pressure oscillates around zero or atmospheric pressure.

The intrapleural pressure is always negative compared to the atmosphere. This is necessary in order to exert a pulling action on the lungs. The pressure varies from about -4 mmHg at the end of expiration, to -8 mmHg and the end of inspiration.

The tendency of the lungs to expand, called compliance or distensibility, is due to the pulling action exerted by the pleural membranes. Expansion is also facilitated by the action of surfactant in preventing the collapse of the alveoli.

The opposite tendency is called elasticity or recoil, and is the process by which the lungs return to their original or resting volume. Recoil is due to the elastic stroma of the lungs and the series elastic elements of the respiratory muscles, particularly the diaphragm.

Conductivity :

 Means ability of cardiac muscle to propagate electrical impulses through the entire heart ( from one part of the heart to another)  by the excitatory -conductive system of the heart.
 
Excitatory conductive system of the heart involves:

1. Sinoatrial node ( SA node) : Here the initial impulses start and then conducted to the atria through  the anterior inter-atrial pathway ( to the left atrium) , to the atrial muscle mass through the gap junction, and to the Atrioventricular node ( AV node ) through anterior, middle , and posterior inter-nodal pathways.
The average conductive velocity in the atria is 1m/s.

2- AV node : The electrical impulses can not be conducted directly from the atria to the ventricles , because of the  fibrous skeleton , which is an electrical isolator , located between the atria and ventricles. So the only conductive way is the AV node . But there is a delay in the conduction occurs in the AV node .
This delay is due to:
- the smaller size of the nodal fiber.
- The less negative resting membrane potential
- fewer gap junctions.

There are three sites for delay:
- In the transitional fibers , that connect inter-nodal pathways with the AV node ( 0.03 ) .
- AV node itself ( 0.09 s) .
- In the penetrating portion of Bundle of Hiss ( 0.04 s)  .
This delay actually allows atria to empty blood in ventricles during the cardiac cycle before the beginning of ventricular contraction  , as it prevents the ventricles from the pathological high atrial rhythm.
The average velocity of conduction in the AV node is 0.02-0.05 m/s

3- Bundle of Hiss : A continuous with the AV node that passes to the ventricles through the inter-ventricular septum. It is subdivided into : Right and left bundle. The left bundle is also subdivided into two branches: anterior and posterior branches .

4- Purkinje`s fibers: large fibers with velocity of conduction 1.5-4 m/s.
the high velocity of these fibers is due to the abundant gap junctions , and to their nature as very large fibers as well.
The conduction from AV node is a one-way conduction . This prevents the re-entry of cardiac impulses from the ventricles to the atria.
Lastly: The conduction through the ventricular fibers has a velocity of 0.3-0.5 m/s.

Factors , affecting conductivity ( dromotropism)  :

I. Positive dromotropic factors :

1. Sympathetic stimulation : it accelerates conduction and decrease AV delay .
2. Mild warming
3. mild hyperkalemia
4. mild ischemia
5. alkalosis

II. Negative dromotropic factors :

1. Parasympathetic stimulation
2. severe warming
3. cooling
4. Severe hyperkalemia
5. hypokalemia
6. Severe ischemia
7. acidosis
8. digitalis drugs.

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 
 

The Parathyroid Glands

The parathyroid glands are 4 tiny structures embedded in the rear surface of the thyroid gland. They secrete parathyroid hormone (PTH) a polypeptide of 84 amino acids. PTH increases the concentration of Ca²⁺ in the blood in three ways. PTH promotes

• release of Ca²⁺ from the huge reservoir in the bones. (99% of the calcium in the body is incorporated in our bones.)
• reabsorption of Ca²⁺ from the fluid in the tubules in the kidneys
• absorption of Ca²⁺ from the contents of the intestine (this action is mediated by calcitriol, the active form of vitamin D.)

PTH also regulates the level of phosphate in the blood. Secretion of PTH reduces the efficiency with which phosphate is reclaimed in the proximal tubules of the kidney causing a drop in the phosphate concentration of the blood.

Hyperparathyroidism

Elevate the level of PTH causing a rise in the level of blood Ca²⁺ .Calcium may be withdrawn from the bones that they become brittle and break.

 Patients with this disorder have high levels of Ca²⁺ in their blood and excrete small amounts of Ca²⁺ in their urine. This causes hyperparathyroidism.

Hypoparathyroidism

This disorder have low levels of Ca²⁺ in their blood and excrete large amounts of Ca²⁺ in their urine.