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.

Gonadotropin-releasing hormone (GnRH)

GnRH is a peptide of 10 amino acids. Its secretion at the onset of puberty triggers sexual development.

Primary Effects

FSH and LH Relaese

Secondary Effects

Increases estrogen and progesterone (in females)

testosterone Relaese (in males)

Growth hormone-releasing hormone (GHRH)

GHRH is a mixture of two peptides, one containing 40 amino acids, the other 44.  GHRH stimulates cells in the anterior lobe of the pituitary to secrete growth hormone (GH).

Corticotropin-releasing hormone (CRH)

CRH is a peptide of 41 amino acids. Its acts on cells in the anterior lobe of the pituitary to release adrenocorticotropic hormone (ACTH) CRH is also synthesized by the placenta and seems to determine the duration of pregnancy.  It may also play a role in keeping the T cells of the mother from mounting an immune attack against the fetus

Somatostatin

Somatostatin is a mixture of two peptides, one of 14 amino acids, the other of 28. Somatostatin acts on the anterior lobe of the pituitary to

• inhibit the release of growth hormone (GH)
• inhibit the release of thyroid-stimulating hormone (TSH)

Somatostatin is also secreted by cells in the pancreas and in the intestine where it inhibits the secretion of a variety of other hormones.

Antidiuretic hormone (ADH) and Oxytocin

These peptides are released from the posterior lobe of the pituitary

PHYSIOLOGY OF THE BRAIN

• The Cerebrum (Telencephalon) Lobes of the cerebral cortex

   

  1. Frontal Lobe
     1. Precentral gyrus, Primary Motor Cortex, point to point motor neurons, pyramidal cells: control motor neurons of the brain and spinal cord. See Motor homunculus
     2. Secondary Motor Cortex repetitive patterns
     3. Broca's Motor Speech area
     4. Anterior - abstract thought, planning, decision making, Personality
  2. Parietal Lobe
     1. Post central gyrus, Sensory cortex, See Sensory homunculus, size proportional to sensory receptor density.
     2. Sensory Association area, memory of sensations
  3. Occipital Lobe
     1. Visual cortex, sight (conscious perception of vision)
     2. Visual Association area, correlates visual images with previous images, (memory of vision, )
  4. Temporal Lobe
     1. Auditory Cortex, sound
     2. Auditory Association area, memory of sounds
  5. Common Integratory Center - angular gyrus, Parietal, Temporal & Occipital lobes
     1. One side becomes dominent, integrats sensory (somesthetic, auditory, visual) information
  6. The Basal nuclei (ganglia)
     1. Grey matter (cell bodies) within the White matter of cerebrum, control voluntary movements
  7. Cauadate nucles - chorea (rapi, uncontrolled movements), Parkinsons: (dopamine neurons of substantia nigra to caudate nucles) jerky movements, spasticity, tremor, blank facial expression
  8. The limbic system - ring around the brain stem, emotions(w/hypothalamus), processing of olfactory information

• The Diencephalon

   

  1. The Thalamus - Sensory relay center to cortex (primitive brain!)
  2. The Hypothalamus
     1. core temperature control"thermostat", shivering and nonshivering thermogenesis
     2. hunger & satiety centers, wakefulness, sleep, sexual arousal,
     3. emotions (w/limbic-anger, fear, pain, pleasure), osmoregulation, (ADH secretion),
     4. Secretion of ADH, Oxytocin, Releasing Hormones for Anterior pitutary
     5. Linkage of nervous and endocrine systems

• The Mesencephalon or Midbrain -

   

  1. red nucleus, motor coordination (cerebellum/Motor cortex),
  2. substantia nigra
• The Metencephalon
  1. The Cerebellum -
     1. Performs automatic adjustments in complex motor activities
     2. Input from Proprioceptors (joint, tendon, muscles), position of body in Space
        1. Motor cortex, intended movements (changes in position of body in Space)
     3. Damping (breaking motor function), Balance, predicting, inhibitory function of Purkinji cells (GABA), speed, force, direction of movement
  2. The Pons - Respiratory control centers (apneustic, pneumotaxic)
     1. Nuclei of cranial nerves V, VI, VII, VIII

• Myelencephalon

   

  1. The Medulla
     1. Visceral motor centers (vasomotor, cardioinhibtory, respiratory)
     2. Reticular Formation RAS system, alert cortex to incoming signals, maintenance of consciousness, arousal from sleep
     3. All Afferent & Efferent fibers pass through, crossing over of motor tracts
  2. Corpus Callosum: Permits communication between cerebralhemispheres
• Generalized Brain Avtivity
  1. Brain Activity and the Electroencephalogram(EEG)
     1. alpha waves: resting adults whose eyes are closed
     2. beta waves: adults concentrating on a specific task;
     3. theta waves: adults under stress;
     4. delta waves: during deep sleep and in clinical disorders
  2. Brain Seizures
     1. Grand Mal: generalized seizures, involvs gross motor activity, affects the individual for a matter or hours
     2. Petit mal: brief incidents, affect consciousness but may have no obvious motor abnormalities
  3. Chemical Effects on the Brain
     1. Sedatives: reduce CNS activity
     2. Analgesics: relieve pain by affecting pain pathways or peripheral sensations
     3. Psychotropics: alter mood and emotional states
     4. Anticonvulsants: control seizures
     5. Stimulants: facilitate CNS activity
  4. Memory and learning
     1. Short-term, or primary, memories last a short time, immediately accessible (phone number)
     2. Secondary memories fade with time (your address at age 5)
     3. Tertiary memories last a lifetime (your name)
     4. Memories are stored within specific regions of the cerebral cortex.
     5. Learning, a more complex process involving the integration of memories and their use to direct or modify behaviors
     6. Neural basis for memory and learning has yet to be determined.
• Fibers in CNS
  1. Association fibers: link portions of the cerebrum;
  2. Commissural fibers: link the two hemispheres;
  3. Projection fibers: link the cerebrum to the brain stem

Blood Pressure

Blood moves through the arteries, arterioles, and capillaries because of the force created by the contraction of the ventricles.

Blood pressure in the arteries.

The surge of blood that occurs at each contraction is transmitted through the elastic walls of the entire arterial system where it can be detected as the pulse. Even during the brief interval when the heart is relaxed — called diastole — there is still pressure in the arteries. When the heart contracts — called systole — the pressure increases.

Blood pressure is expressed as two numbers, e.g., 120/80.

Blood pressure in the capillaries

The pressure of arterial blood is largely dissipated when the blood enters the capillaries. Capillaries are tiny vessels with a diameter just about that of a red blood cell (7.5 µm). Although the diameter of a single capillary is quite small, the number of capillaries supplied by a single arteriole is so great that the total cross-sectional area available for the flow of blood is increased. Therefore, the pressure of the blood as it enters the capillaries decreases.

Blood pressure in the veins

When blood leaves the capillaries and enters the venules and veins, little pressure remains to force it along. Blood in the veins below the heart is helped back up to the heart by the muscle pump. This is simply the squeezing effect of contracting muscles on the veins running through them. One-way flow to the heart is achieved by valves within the veins

Exchanges Between Blood and Cells

With rare exceptions, our blood does not come into direct contact with the cells it nourishes. As blood enters the capillaries surrounding a tissue space, a large fraction of it is filtered into the tissue space. It is this interstitial or extracellular fluid (ECF) that brings to cells all of their requirements and takes away their products. The number and distribution of capillaries is such that probably no cell is ever farther away than 50 µm from a capillary.

When blood enters the arteriole end of a capillary, it is still under pressure produced by the contraction of the ventricle. As a result of this pressure, a substantial amount of water and some plasma proteins filter through the walls of the capillaries into the tissue space.

Thus fluid, called interstitial fluid, is simply blood plasma minus most of the proteins. (It has the same composition and is formed in the same way as the nephric filtrate in kidneys.)

Interstitial fluid bathes the cells in the tissue space and substances in it can enter the cells by diffusion or active transport. Substances, like carbon dioxide, can diffuse out of cells and into the interstitial fluid.

Near the venous end of a capillary, the blood pressure is greatly reduced .Here another force comes into play. Although the composition of interstitial fluid is similar to that of blood plasma, it contains a smaller concentration of proteins than plasma and thus a somewhat greater concentration of water. This difference sets up an osmotic pressure. Although the osmotic pressure is small, it is greater than the blood pressure at the venous end of the capillary. Consequently, the fluid reenters the capillary here.

Control of the Capillary Beds

An adult human has been estimated to have some 60,000 miles of capillaries with a total surface area of some 800–1000 m². The total volume of this system is roughly 5 liters, the same as the total volume of blood. However, if the heart and major vessels are to be kept filled, all the capillaries cannot be filled at once. So a continual redirection of blood from organ to organ takes place in response to the changing needs of the body. During vigorous exercise, for example, capillary beds in the skeletal muscles open at the expense of those in the viscera. The reverse occurs after a heavy meal.

The walls of arterioles are encased in smooth muscle. Constriction of arterioles decreases blood flow into the capillary beds they supply while dilation has the opposite effect. In time of danger or other stress, for example, the arterioles supplying the skeletal muscles will be dilated while the bore of those supplying the digestive organs will decrease. These actions are carried out by

• the autonomic nervous system.
• local controls in the capillary beds

The Stomach :

The wall of the stomach is lined with millions of gastric glands, which together secrete 400–800 ml of gastric juice at each meal. Three kinds of cells are found in the gastric glands

• parietal cells
• chief cells
• mucus-secreting cells

Parietal cells : secrete

Hydrochloric acid : Parietal cells contain a H⁺ ATPase. This transmembrane protein secretes H⁺ ions (protons) by active transport, using the energy of ATP.

Intrinsic factor: Intrinsic factor is a protein that binds ingested vitamin B₁₂ and enables it to be absorbed by the intestine. A deficiency of intrinsic factor  as a result of an autoimmune attack against parietal cells  causes pernicious anemia.

Chief Cells : The chief cells synthesize and secrete pepsinogen, the precursor to the proteolytic enzyme pepsin.

Secretion by the gastric glands is stimulated by the hormone gastrin. Gastrin is released by endocrine cells in the stomach in response to the arrival of food.

Excitability ( Bathmotropism ) : Excitability means the ability of cardiac muscle to respond to signals. Here we are talking about contractile muscle cells that are excited by the excitatory conductive system and generate an action potential.

Cardiac action potential is similar to action potential in nerve and skeletal muscle tissue , with one difference , which is the presence of plateau phase . Plateau phase is unique for cardiac muscle cells .
The  resting membrane potential for cardiac muscle is about -80 mV.
When the cardiac muscle is stimulated an action potential is generated . The action potential in cardiac muscle is composed of four phases , which are :

1. Depolarization phase (Phase 0 ) :

A result of opening of sodium channels , which increase the permeability to sodium , which will lead to a rapid sodium influx into the cardiac muscle cell.

2. Repolarization : Repolarization in cardiac muscle is slow and triphasic :

a. Phase 1 (early partial repolarization ) : A small fast repolarization , results from potassium eflux and chloride influx.
b. Phase 2 ( Plateau ) : After the early partial depolarization , the membrane remains  depolarized , exhibiting a plateau , which is a unique phase for the cardiac muscle cell. Plateau is due to opening of slow calcium-sodium channels , delay closure of sodium channels , and to decreased potassium eflux.
c. Phase 3  ( Rapid repolarization) :  opening of potassium channels and rapid eflux of potassium.
d. Phase 4 ( Returning to resting level) in other words : The phase of complete repolarization. This due to the work of sodium-potassium pump.

Absolute refractory period:

Coincides wit phase 0,phase1 , and phase 2 . During this period , excitability of the heart is totally abolished . This prevents tetanization of the cardiac muscle and enables the heart to contract and  relax to be filled by blood ..

Relative refractory period : 

Coincides with the rapid repolarization and allows the excitability to be gradually recovered .
Excitation contraction relationship : Contraction of cardiac muscle starts after depolarization and continues about 1.5 time as long as the duration of the action potential and reaches its maximum at the end of the plateau. Relaxation of the muscle starts with the early partial repolarization.

Factors , affecting excitability of cardiac muscle:

I. Positive bathmotropic effect :

1. Sympathetic stimulation : It increase the heart , and thus reduces the duration of the action potentia; . This will shorten the duration of the absolute refractory period , and thus increase the excitability .
2.  Drugs : Catecholamines and  xanthines derivatives .
3. Mild hypoxia and mild ischemia
4. Mild hyperkalemia as it decreases the K+ efflux and opens excess Na+ channels .
5. Hypocalcemia

II. Negative bathmotropic effect :

1. Parasympathetic stimulation: The negative bathmotropic effect is limited to the atrial muscle excitability , because there is no parasympathetic innervation for the ventricles. Parasympathetic stimulation decreases the heart rate , and thus increases the duration of cardiac action potential and thus increases the duration of the absolute refractory period.
2. moderate to severe hypoxia
3. hyponatremia , hypercalcemia , and severe hyperkalemia.

Clinical Physiology : Extrasystole is a pathological situation , due to abnormal impulses , arising from ectopic focus .It is expressed as an abnormal systole that occur during the early diastole .
Extrasystole  is due to a rising of excitability above the normal , which usually occurs after the end of the relative refractory period ( read about staircase phenomenon of Treppe)