The endocrine system along with the nervous system functions in the regulation of body activities.  The nervous system acts through electrical impulses and neurotransmitters to cause muscle contraction and glandular secretion and interpretation of impulses.  The endocrine system acts through chemical messengers called hormones that influence growth, development, and metabolic activities

Principal heart sounds

1. S1: closure of AV valves;typically auscultated as a single sound 

Clinical note: In certain circumstances, S1 may be accentuated. This occurs when the valve leaflets are “slammed” shut in early systole from a greater than normal distance because they have not had time to drift closer together. Three conditions that can result in an accentuated S1 are a shortened PR interval, mild mitral stenosis, and high cardiac-output states or tachycardia.

2. S2: closure of semilunar valves in early diastole , normally “split” during inspiration . S2: best appreciated in the 2nd or 3rd left intercostal space

Clinical note: Paradoxical or “reversed” splitting occurs when S2 splitting occurs with expiration and disappears on inspiration. Moreover, in paradoxical splitting, the pulmonic valve closes before the aortic valve, such that P2 precedes A2. The most common cause is left bundle branch block (LBBB). In LBBB, depolarization of the left ventricle is impaired, resulting in delayed left ventricular contraction and aortic valve closure.

3. S3: ventricular gallop, presence reflects volume-overloaded state 
 
 Clinical note: An S3 is usually caused by volume overload in congestive heart failure. It can also be associated with valvular disease, such as advanced mitral regurgitation, in which the “regurgitated” blood increases the rate of ventricular filling during early diastole.
 
4. S4: atrial gallop, S4: atrial contraction against a stiff ventricle, often heard after an acute myocardial infarction.

Clinical note: An S4 usually indicates decreased ventricular compliance (i.e., the ventricle does not relax as easily), which is commonly associated with ventricular hypertrophy or myocardial ischemia. An S4 is almost always present after an acute myocardial infarction. It is loudest at the apex with the patient in the left lateral decubitus position (lying on their left side).

A heart rate that is persistently greater than 100bpm is termed tachycardia. A heart rate that is persistantly lower than 60 pulse per min  is termed bradycardia. Let's examine some factors that could cause a change in heart rate:

• Increased heart rate can be caused by:
  • Increased output of the cardioacceleratory center. In other words, greater activity of sympathetic nerves running to the heart and a greater release of norepinephrine on the heart.
  • Decreased output of the cardioinhibitory center. In other words, less vagus nerve activity and a decrease in the release of acetylcholine on the heart.
  • Increased release of the hormone epinephrine by the adrenal glands.
  • Nicotine.
  • Caffeine.
  • Hyperthyroidism - i.e., an overactive thyroid gland. This would lead to an increased amount of the hormone thyroxine in the blood.
• Decreased heart rate can be caused by:
  • Decreased activity of the cardioacceleratory center.
  • Increased activity of the cardioinhibitory center.
  • Many others.

1 - Passive processes - require no expenditure of energy by a cell:

• Simple diffusion = net movement of a substance from an area of high concentration to an area of low concentration. The rate of diffusion is influenced by:
  • concentration gradient
  • cross-sectional area through which diffusion occurs
  • temperature
  • molecular weight of a substance
  • distance through which diffusion occurs
• Osmosis = diffusion of water across a semi permeable membrane (like a cell membrane) from an area of low solute concentration to an area of high solute concentration

• Facilitated diffusion = movement of a substance across a cell membrane from an area of high concentration to an area of low concentration. This process requires the use of 'carriers' (membrane proteins). In the example below, a ligand molecule (e.g., acetylcholine) binds to the membrane protein. This causes a conformational change or, in other words, an 'opening' in the protein through which a substance (e.g., sodium ions) can pass.

2 - Active processes - require the expenditure of energy by cells:

• Active transport = movement of a substance across a cell membrane from an area of low concentration to an area of high concentration using a carrier molecule
• Endo- & exocytosis - moving material into (endo-) or out of (exo-) cell in bulk form

• 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

   

Hemostasis - the  stopping of the blood. Triggered by a ruptured vessel wall it occurs in several steps:

1) vascular spasm - most vessels will constrict strongly when their walls are damaged. This accounts for individuals not bleeding to death even when limbs are crushed. It also can help to enhance blood clotting in less severe injuries.

2) platelet plug - platelets become sticky when they contact collagen, a protein in the basement membrane of the endothelium exposed when the vessel wall is ruptured. As they stick together they can form a plug which will stem the flow of blood in minor vessels.

3) Formation of the Blood Clot:

A) release of platelet factors - as platelets stick together and to the vascular wall some are ruptured releasing chemicals such as thromboxane, PF3, ADP and other substances. These become prothrombin activators. Thromboxane also makes the platelets even stickier, and increases the vascular constriction. These reactions are self perpetuating and become a cascade which represents a positive feedback mechanism.

B) prothrombin activators : prothrombin (already in the blood) is split into smaller products including thrombin, an active protease.

C) thrombin splits soluble fibrinogen, already present in the plasma, into monomers which then polymerize to produce insoluble fibrin threads. The fibrin threads weave the platelets and other cells together to form the actual clot. This occurs within four to six minutes when the injury is severe and up to 15 minutes when it is not. After 15 minutes the clot begins to retract as the fibrin threads contract, pulling the broken edges of the injury together and smoothing the surface of the clot causing the chemical processes to cease. Eventually the clot will dissolve due to enzymes such as plasmin also present in the blood.

The extrinsic pathway: when tissues are damaged the damaged cells release substances called tissue thromboplastin which also acts as a prothrombin activator. This enhances and speeds coagulation when tissue damage is involved.

Anti-thrombin III - this factor helps to prevent clotting when no trigger is present by removing any thrombin present. Its function is magnified many times when heparin is present. Therefore heparin is used clinically as a short-term anticoagulant.

Vitamin K - stimulates the production of clotting factors including prothrombin and fibrinogen in the liver. This vitamin is normally produced by bacteria in the colon. Coumarin (or coumadin) competes with Vitamin K in the liver and is used clinically for long-term suppression of clotting.

Several factors important to clotting are known to be absent in forms of hemophilia. These factors are produced by specific genes which are mutated in the deficient forms. The factors are  VIII, IX, and XI.

Calcium is necessary for blood clotting and its removal from the blood by complexing with citrate will prevent the blood from clotting during storage