Oxygen Transport

In adult humans the hemoglobin (Hb) molecule

• consists of four polypeptides:
  • two alpha (α) chains of 141 amino acids and
  • two beta (β) chains of 146 amino acids
• Each of these is attached the prosthetic group heme.
• There is one atom of iron at the center of each heme.
• One molecule of oxygen can bind to each heme.

The reaction is reversible.

• Under the conditions of lower temperature, higher pH, and increased oxygen pressure in the capillaries of the lungs, the reaction proceeds to the right. The purple-red deoxygenated hemoglobin of the venous blood becomes the bright-red oxyhemoglobin of the arterial blood.
• Under the conditions of higher temperature, lower pH, and lower oxygen pressure in the tissues, the reverse reaction is promoted and oxyhemoglobin gives up its oxygen.

There are three types of muscle tissue, all of which share some common properties:

• Excitability or responsiveness - muscle tissue can be stimulated by electrical, physical, or chemical means.
• contractility - the response of muscle tissue to stimulation is contraction, or shortening.
• elasticity or recoil - muscles have elastic elements (later we will call these their series elastic elements) which cause them to recoil to their original size.
• stretchability or extensibility - muscles can also stretch and extend to a longer-than-resting length.

The three types of muscle: skeletal, cardiac, and visceral (smooth) muscle.

Skeletal muscle

It is found attached to the bones for movement.

cells are long multi-nucleated cylinders.

 The cells may be many inches long but vary in diameter, averaging between 100 and 150 microns.

 All the cells innervated by branches from the same neuron will contract at the same time and are referred to as a motor unit.

 Skeletal muscle is voluntary because the neurons which innervate it come from the somatic or voluntary branch of the nervous system.

That means you have willful control over your skeletal muscles.

 Skeletal muscles have distinct stripes or striations which identify them and are related to the organization of protein myofilaments inside the cell.

Cardiac muscle

This muscle found in the heart.

 It is composed of much shorter cells than skeletal muscle which branch to connect to one another.

 These connections are by means of gap junctions called intercalated disks which allow an electrochemical impulse to pass to all the connected cells.

 This causes the cells to form a functional network called a syncytium in which the cells work as a unit. Many cardiac muscle cells are myogenic which means that the impulse arises from the muscle, not from the nervous system. This causes the heart muscle and the heart itself to beat with its own natural rhythm.

But the autonomic nervous system controls the rate of the heart and allows it to respond to stress and other demands. As such the heart is said to be involuntary.

Visceral muscle is found in the body's internal organs and blood vessels.

 It is usually called smooth muscle because it has no striations and is therefore smooth in appearance. It is found as layers in the mucous membranes of the respiratory and digestive systems.

It is found as distinct bands in the walls of blood vessels and as sphincter muscles.

Single unit smooth muscle is also connected into a syncytium similar to cardiac muscle and is also partly myogenic. As such it causes continual rhythmic contractions in the stomach and intestine. There and in blood vessels smooth muscle also forms multiunit muscle which is stimulated by the autonomic nervous system. So smooth muscle is involuntary as well

The nephron of the kidney is involved in the regulation of water and soluble substances in blood.

A Nephron

A nephron is the basic structural and functional unit of the kidneys that regulates water and soluble substances in the blood by filtering the blood, reabsorbing what is needed, and excreting the rest as urine.

 Its function is vital for homeostasis of blood volume, blood pressure, and plasma osmolarity.

It is regulated by the neuroendocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.

The Glomerulus

The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. Here, fluid and solutes are filtered out of the blood and into the space made by Bowman's capsule.

A group of specialized cells known as juxtaglomerular apparatus (JGA) are located around the afferent arteriole where it enters the renal corpuscle. The JGA secretes an enzyme called renin, due to a variety of stimuli, and it is involved in the process of blood volume homeostasis.

The Bowman's capsule surrounds the glomerulus. It is composed of visceral (simple squamous epithelial cells; inner) and parietal (simple squamous epithelial cells; outer) layers.

Red blood cells and large proteins, such as serum albumins, cannot pass through the glomerulus under normal circumstances. However, in some injuries they may be able to pass through and can cause blood and protein content to enter the urine, which is a sign of problems in the kidney.

Proximal Convoluted Tubule

The proximal tubule is the first site of water reabsorption into the bloodstream, and the site where the majority of water and salt reabsorption takes place. Water reabsorption in the proximal convoluted tubule occurs due to both passive diffusion across the basolateral membrane, and active transport from Na+/K+/ATPase pumps that actively transports sodium across the basolateral membrane.

Water and glucose follow sodium through the basolateral membrane via an osmotic gradient, in a process called co-transport. Approximately 2/3rds of water in the nephron and 100% of the glucose in the nephron are reabsorbed by cotransport in the proximal convoluted tubule.

Fluid leaving this tubule generally is unchanged due to the equivalent water and ion reabsorption, with an osmolarity (ion concentration) of 300 mOSm/L, which is the same osmolarity as normal plasma.

The Loop of Henle

The loop of Henle is a U-shaped tube that consists of a descending limb and ascending limb. It transfers fluid from the proximal to the distal tubule. The descending limb is highly permeable to water but completely impermeable to ions, causing a large amount of water to be reabsorbed, which increases fluid osmolarity to about 1200 mOSm/L. In contrast, the ascending limb of Henle's loop is impermeable to water but highly permeable to ions, which causes a large drop in the osmolarity of fluid passing through the loop, from 1200 mOSM/L to 100 mOSm/L.

Distal Convoluted Tubule and Collecting Duct

The distal convoluted tubule and collecting duct is the final site of reabsorption in the nephron. Unlike the other components of the nephron, its permeability to water is variable depending on a hormone stimulus to enable the complex regulation of blood osmolarity, volume, pressure, and pH.

Normally, it is impermeable to water and permeable to ions, driving the osmolarity of fluid even lower. However, anti-diuretic hormone (secreted from the pituitary gland as a part of homeostasis) will act on the distal convoluted tubule to increase the permeability of the tubule to water to increase water reabsorption. This example results in increased blood volume and increased blood pressure. Many other hormones will induce other important changes in the distal convoluted tubule that fulfill the other homeostatic functions of the kidney.

The collecting duct is similar in function to the distal convoluted tubule and generally responds the same way to the same hormone stimuli. It is, however, different in terms of histology. The osmolarity of fluid through the distal tubule and collecting duct is highly variable depending on hormone stimulus. After passage through the collecting duct, the fluid is brought into the ureter, where it leaves the kidney as urine.

Transport of Carbon Dioxide

A.    Dissolved in Blood Plasma (7-10%)

B.    Bound to Hemoglobin (20-30%)

1.    carbaminohemoglobin - Carb Dioxide binds to an amino acid on the polypeptide chains

2.    Haldane Effect - the less oxygenated blood is, the more Carb Diox it can carry

a.    tissues - as Oxygen is unloaded, affinity for Carb Dioxide increases
b.    lungs - as Oxygen is loaded, affinity for Carb Dioxide decreases, allowing it to be released

C.    Bicarbonate Ion Form in Plasma (60-70%)

1.    Carbon Dioxide combines with water to form Bicarbonate

CO₂ + H₂O <==> H₂CO₃ <==> H⁺ + HCO₃-

2.    carbonic anhydrase - enzyme in RBCs that catalyzes this reaction in both directions

a.    tissues - catalyzes formation of Bicarbonate
b.    lungs - catalyzes formation of Carb Dioxide

3.    Bohr Effect - formation of Bicarbonate (through Carbonic Acid) leads to LOWER pH (H+ increase), and more unloading of Oxygen to tissues

a.    since hemoglobin "buffers" to H⁺, the actual pH of blood does not change much

4.    Chloride Shift - chloride ions move in opposite direction of the entering/leaving Bicarbonate, to prevent osmotic problems with RBCs

D.    Carbon Dioxide Effects on Blood pH

1.    carbonic acid-bicarbonate buffer system
    
low pH       → HCO₃- binds to H⁺
high pH     →   H₂CO₃ releases H⁺
    
2.     low shallow breaths    → HIGH Carb Dioxide    → LOW pH (higher H⁺)
3.     rapid deep breaths     → LOW Carb Dioxide   → HIGH pH (lower H⁺)

Contractility : Means ability of cardiac muscle to convert electrical energy of action potential into mechanical energy ( work).
The excitation- contraction coupling of cardiac muscle is similar to that of skeletal muscle , except the lack of motor nerve stimulation. 

Cardiac muscle is a self-excited muscle , but the principles of contraction are the same . There are many rules that control the contractility of the cardiac muscles, which are:

1. All or none rule: due to the syncytial nature of the cardiac muscle.There are atrial syncytium and ventricular syncytium . This rule makes the heart an efficient pump.

2. Staircase phenomenon : means gradual increase in muscle contraction following rapidly repeated stimulation..

3. Starling`s law of the heart: The greater the initial length of cardiac muscle fiber , the greater the force of contraction. The initial length is determined by the degree of diastolic filling .The pericardium prevents overstretching of heart , and allows optimal increase in diastolic volume.

Thankful to this law , the heart is able to pump any amount of blood that it receives. But overstretching of cardiac muscle fibers may cause heart failure.

Factors affecting  contractility ( inotropism)

I. Positive inotropic factors:

1. sympathetic stimulation: by increasing the permeability of sarcolemma to calcium.
2. moderate increase in temperature . This due to increase metabolism to increase ATP , decrease viscosity of myocardial structures, and increasing calcium influx.
3. Catecholamines , thyroid hormone, and glucagon hormones.
4. mild alkalosis
5. digitalis
6. Xanthines ( caffeine and theophylline )

II. Negative inotropic factors:

1. Parasympathetic stimulation : ( limited to atrial contraction)
2. Acidosis
3. Severe alkalosis
4. excessive warming and cooling .
5. Drugs ;like : Quinidine , Procainamide , and barbiturates .
6. Diphtheria and typhoid toxins.

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.