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

1.Rhythmicity ( Chronotropism ) :  means the ability of heart to beat regularly ( due to repetitive and stable depolarization and repolarization )  . Rhythmicity of heart is a myogenic in origin , because cardiac muscles are automatically excited muscles and does not depend on the nervous stimulus to initiate excitation and then contraction . The role of nerves is limited to the regulation of the heart rate and not to initiate the beat.

There are many evidences that approve the myogenic and not neurogenic origin of the rhythmicity of cardiac muscle . For example :
-  transplanted heart continues to beat regularly without any nerve supply.
-  Embryologically the heart starts to beat before reaching any nerves to them.
-  Some drugs that paralyze the nerves ( such as cocaine ) do not stop the heart in given doses.

Spontaneous rhythmicity of the cardiac muscle due to the existence of excitatory - conductive system , which is composed of self- exciting non-contractile cardiac muscle cells . The SA node of the mentioned system excites in a rate , that is the most rapid among the other components of the system ( 110 beats /minute ) , which makes it the controller or ( the pacemaker ) of the cardiac rhythm of the entire heart.

Mechanism , responsible for self- excitation in the SA node and the excitatory conductive system  is due to the following properties of the cell membrane of theses cells :
1- Non-gated sodium channels
2- Decreased permeability to potassium
3- existence of slow and fast calcium channels.

These properties enable the cations ( sodium through the none-gated sodium voltage channels , calcium through calcium slow channels) to enter the cell and depolarize the cell membrane without need for external stimulus.

The resting membrane potential of non-contractile cardiac cell is -55 - -60 millivolts ( less than that of excitable nerve cells (-70) ) . 

The threshold is also less negative than that of nerve cells ( -40 millivolts ).

The decreased permeability to potassium from its side decrease the eflux  of potassium during the repolarization phase of the pacemaker potential . All of these factors give the pacemaker potential its characteristic shape

Repeating of the pacemaker potential between the action potentials of contractile muscle cells is the cause of spontaneous rhythmicity of cardiac muscle cells.

Factors , affecting the rhythmicity of the cardiac muscle :

I. Factors that increase the rate ( positive chronotropic factors) :
1. sympathetic stimulation : as its neurotransmitter norepinephrine increases the membrane permeability to sodium and calcium.
2. moderate warming : moderate warming increases temperature by 10 beats for each 1 Fahrenheit degree increase in body temperature, this due to decrease in permeability to potassium ions in pacemaker membrane by moderate increase in temperature.
3. Catecholaminic drugs have positive chronotropic effect.
4. Thyroid hormones : have positive chronotropic effect , due to the fact that these drugs increase the sensitivity of adrenergic receptors to adrenaline and noreadrenaline .
5. mild hypoxia.
6. mild alkalemia : mild alkalemia decreases the negativity of the resting potential.
7. hypocalcemia.
8. mild hypokalemia

II. Factors that decrease rhythmicity ( negative chronotropic):

1.Vagal stimulation : the basal level of vagal stimulation inhibits the sinus rhythm and decrease it from 110-75 beats/ minute. This effect due to increasing the permeability of the cardiac muscle cell to potassium , which causes rapid potassium eflux , which increases the negativity inside the cardiac cells (hyperpolarization ).
2. moderate cooling
3. severe warming : due to cardiac damage , as a result of intercellular protein denaturation. Excessive cooling on the other hand decrease metabolism and stops rhythmicity.
4. Cholenergic drugs ( such as methacholine , pilocarpine..etc) have negative chronotropic effect.
5. Digitalis : these drugs causes hyperpolarization . This effect is similar to that of vagal stimulation.
6. Hypercapnia ( excessive CO2 production )
7. Acidemia.
8. hyper- and hyponatremia .
9. hyperkalemia
10. hypercalcemia
11. Typhoid or diphteria toxins.

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⁺)

Glomerular filtration

Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.

The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .

Filtration occurs through the filtration unit , which includes :

1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .

2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .

3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .

Many forces drive the glomerular filtration , which are :

1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .

2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .

3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .

The net pressure is as follows :

Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .

Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.
 

GENERAL SOMATIC AFFERENT (GSA) PATHWAYS FROM THE BODY

Pain and Temperature

Pain and temperature information from general somatic receptors is conducted over small-diameter (type A delta and type C) GSA fibers of the spinal nerves into the posterior horn of the spinal cord gray matter .

Fast and Slow Pain

Fast pain, often called sharp or pricking pain, is usually conducted to the CNS over type A delta fibers.

Slow pain, often called burning pain, is conducted to the CNS over smaller-diameter type C fibers.

Touch and Pressure

Touch can be subjectively described as discriminating or crude.

Discriminating (epicritic) touch implies an awareness of an object's shape, texture, three-dimensional qualities, and other fine points. Ability to recognize familiar objects simply by tactile manipulation.

The conscious awareness of body position and movement is called the kinesthetic sens

Crude (protopathic) touch,  lacks the fine discrimination described above and doesn't generally give enough information to the brain to enable it to recognize a familiar object by touch alone.

Subconscious Proprioception

Most of the subconscious proprioceptive input is shunted to the cerebellum.

Posterior Funiculus Injury

Certain clinical signs are associated with injury to the dorsal columns.

 As might be expected, these are generally caused by impairment to the kinesthetic sense and discriminating touch and pressure pathways.

 They include

 (1) the inability to recognize limb position,

 (2) as­tereognosis,

 (3) loss of two-point discrimination,

 (4) loss of vibratory sense, and

 (5) a positive Romberg sign.

Astereognosis is the inability to recognize familiar objects by touch alone. When asked to stand erect with feet together and eyes closed, a person with dorsal column damage may sway and fall. This is a posi­tive Romberg sign.

Red blood cell cycle:

RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. RBCs require Vitamin B12, folic acid, and iron. The lifespan of RBC averages 120 days. Aged and damaged red cells are disposed of in the spleen and liver by macrophages. The globin is digested and the amino acids released into the blood for protein manufacture; the heme is toxic and cannot be reused, so it is made into bilirubin and removed from the blood by the liver to be excreted in the bile. The red bile pigment bilirubin oxidizes into the green pigment biliverdin and together they give bile and feces their characteristic color. Iron is picked up by a globulin protein (apotransferrin) to be transported as transferrin and then stored, mostly in the liver, as hemosiderin or ferritin. Ferritin is short term iron storage in constant equilibrium with plasma iron carried by transferrin. Hemosiderin is long term iron storage, forming dense granules visible in liver and other cells which are difficult for the body to mobilize.

Some iron is lost from the blood due to hemorrhage, menstruation, etc. and must be replaced from the diet. On average men need to replace about 1 mg of iron per day, women need 2 mg. Apotransferrin (transferrin without the iron) is present in GI lining cells and is also released in the bile. It picks up iron from the GI tract and stimulates receptors on the lining cells which absorb it by pinocytosis. Once through the mucosal cell iron is carried in blood as transferrin to the liver and marrow. Iron leaves the transferrin molecule to bind to ferritin in these tissues. Most excess iron will not be absorbed due to saturation of ferritin, reduction of apotransferrin, and an inhibitory process in the lining tissue.

Erythropoietin Mechanism:

Myeloid (blood producing) tissue is found in the red bone marrow located in the spongy bone. As a person ages much of this marrow becomes fatty and ceases production. But it retains stem cells and can be called on to regenerate and produce blood cells later in an emergency. RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. This hormone triggers more of the pleuripotential stem cells (hemocytoblasts) to follow the pathway to red blood cells and to divide more rapidly.

It takes from 3 to 5 days for development of a reticulocyte from a hemocytoblast. Reticulocytes, immature rbc, move into the circulation and develop over a 1 to 2 day period into mature erythrocytes. About 1 to 2 % of rbc in the circulation are reticulocytes, and the exact percentage is a measure of the rate of erythropoiesis.