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Physiology - NEETMDS- courses
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Physiology

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.

Maintenance of Homeostasis


The kidneys maintain the homeostasis of several important internal conditions by controlling the excretion of substances out of the body. 

Ions. The kidney can control the excretion of potassium, sodium, calcium, magnesium, phosphate, and chloride ions into urine. In cases where these ions reach a higher than normal concentration, the kidneys can increase their excretion out of the body to return them to a normal level. Conversely, the kidneys can conserve these ions when they are present in lower than normal levels by allowing the ions to be reabsorbed into the blood during filtration. (See more about ions.)
 
pH. The kidneys monitor and regulate the levels of hydrogen ions (H+) and bicarbonate ions in the blood to control blood pH. H+ ions are produced as a natural byproduct of the metabolism of dietary proteins and accumulate in the blood over time. The kidneys excrete excess H+ ions into urine for elimination from the body. The kidneys also conserve bicarbonate ions, which act as important pH buffers in the blood.
 
Osmolarity. The cells of the body need to grow in an isotonic environment in order to maintain their fluid and electrolyte balance. The kidneys maintain the body’s osmotic balance by controlling the amount of water that is filtered out of the blood and excreted into urine. When a person consumes a large amount of water, the kidneys reduce their reabsorption of water to allow the excess water to be excreted in urine. This results in the production of dilute, watery urine. In the case of the body being dehydrated, the kidneys reabsorb as much water as possible back into the blood to produce highly concentrated urine full of excreted ions and wastes. The changes in excretion of water are controlled by antidiuretic hormone (ADH). ADH is produced in the hypothalamus and released by the posterior pituitary gland to help the body retain water.
 
Blood Pressure. The kidneys monitor the body’s blood pressure to help maintain homeostasis. When blood pressure is elevated, the kidneys can help to reduce blood pressure by reducing the volume of blood in the body. The kidneys are able to reduce blood volume by reducing the reabsorption of water into the blood and producing watery, dilute urine. When blood pressure becomes too low, the kidneys can produce the enzyme renin to constrict blood vessels and produce concentrated urine, which allows more water to remain in the blood.

  • 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

     

Cells, cytoplasm, and organelles:

  • Cytoplasm consists of a gelatinous solution and contains microtubules (which serve as a cell's cytoskeleton) and organelles
  • Cells also contain a nucleus within which is found DNA (deoxyribonucleic acid) in the form of chromosomes plus nucleoli (within which ribosomes are formed)
  • Organelles include:
  1. Endoplasmic reticulum : 2 forms: smooth and rough; the surface of rough ER is coated with ribosomes; the surface of smooth ER is not , Functions include: mechanical support, synthesis (especially proteins by rough ER), and transport
  2. Golgi complex consists of a series of flattened sacs (or cisternae) functions include: synthesis (of substances likes phospholipids), packaging of materials for transport (in vesicles), and production of lysosomes
  3. Lysosome : membrane-enclosed spheres that contain powerful digestive enzymes , functions include destruction of damaged cells & digestion of phagocytosed materials
  4.  Mitochondria : have double-membrane: outer membrane & highly convoluted inner membrane
    1. inner membrane has folds or shelf-like structures called cristae that contain elementary particles; these particles contain enzymes important in ATP production
    2. primary function is production of adenosine triphosphate (ATP)
  5. Ribosome-:composed of rRNA (ribosomal RNA) & protein , primary function is to produce proteins
  6. Centrioles :paired cylindrical structures located near the nucleas , play an important role in cell division
  7. Flagella & cilia - hair-like projections from some human cells
    1. cilia are relatively short & numerous (e.g., those lining trachea)
    2. a flagellum is relatively long and there's typically just one (e.g., sperm)
    • Villi  Projections of cell membrane that serve to increase surface area of a cell (which is important, for example, for cells that line the intestine)

A small fraction of cardiac muscle fibers have myogenicity and autorhythmicity.

Myogenicity is the property of spontaneous impulse generation. The slow sodium channels are leaky and cause the polarity to spontaneously rise to threshold for action potential generation. The fastest of these cells, those in the SA node, set the pace for the heartbeat.

Autorhythmicity - the natural rhythm of spontaneous depolarization. Those with the fastest autorhythmicity act as the 1. heart's pacemaker.

Contractility - like skeletal muscle, most cardiac muscle cells respond to stimuli by contracting. The autorhythmic cells have very little contractility however. Contractility in the other cells can be varied by the effect of neurotransmitters.

Inotropic effects - factors which affect the force or energy of muscular contractions. Digoxin, epinephrine, norepinephrine, and dopamine have positive inotropic effects. Betal blockers and calcium channel blockers have negative inotropic effects 

Sequence of events in cardiac conduction: The electrical events in the cardiac cycle.

1) SA node depolarizes and the impulse spreads across the atrial myocardium and through the internodal fibers to the AV node. The atrial myocardium depolarizes resulting in atrial contraction, a physical event.

2) AV node picks up the impulse and transfers it to the AV Bundle (Bundle of His). This produces the major portion of the delay seen in the cardiac cycle. It takes approximately .03 sec from SA node depolarization to the impulse reaching the AV node, and .13 seconds for the impulse to get through the AV node and reach the Bundle of His. Also during this period the atria repolarize.

3) From the AV node the impulse travels through the bundle branches and through the Purkinje fibers to the ventricular myocardium, causing ventricular depolarization and ventricular contraction, a physical event.

4) Ventricular repolarization occurs.

Functions

Manufacture - blood proteins - albumen, clotting proteins , urea - nitrogenous waste from amino acid metabolism , bile - excretory for the bile pigments, emulsification of fats by bile salts

Storage - glycogen , iron - as hemosiderin and ferritin , fat soluble vitamins A, D, E, K

Detoxification -alcohol , drugs and medicines , environmental toxins

Protein metabolism -

  • transamination - removing the amine from one amino acid and using it to produce a different amino acid. The body can produce all but the essential amino acids; these must be included in the diet.
  • deamination - removal of the amine group in order to catabolize the remaining keto acid. The amine group enters the blood as urea which is excreted through the kidneys.

Glycemic Regulation - the management of blood glucose.

  • glycogenesis - the conversion of glucose into glycogen.
  • glycogenolysis - the breakdown of glycogen into glucose.

gluconeogenesis - the manufacture of glucose from non carbohydrate sources, mostly protein

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

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