The Sliding Filament mechanism of muscle contraction.

When a muscle contracts the light I bands disappear and the dark A bands move closer together. This is due to the sliding of the actin and myosin myofilaments against one another. The Z-lines pull together and the sarcomere shortens

The thick myosin bands are not single myosin proteins but are made of multiple myosin molecules. Each myosin molecule is composed of two parts: the globular "head" and the elongated "tail". They are arranged to form the thick bands.

It is the myosin heads which form crossbridges that attach to binding sites on the actin molecules and then swivel to bring the Z-lines together

Likewise the thin bands are not single actin molecules. Actin is composed of globular proteins (G actin units) arranged to form a double coil (double alpha helix) which produces the thin filament. Each thin myofilament is wrapped by a tropomyosin protein, which in turn is connected to the troponin complex. 

The tropomyosin-troponin combination blocks the active sites on the actin molecules preventing crossbridge formation. The troponin complex consists of three components: TnT, the part which attaches to tropomyosin, TnI, an inhibitory portion which attaches to actin, and TnC which binds calcium ions. When excess calcium ions are released they bind to the TnC causing the troponin-tropomyosin complex to move, releasing the blockage on the active sites. As soon as this happens the myosin heads bind to these active sites.

Respiratory system plays important role in maintaining homeostasis . Other than its major function , which is supplying the cells with needed oxygen to produce energy and getting rid of carbon dioxide , it has other functions :

1 Vocalization , or sound production.
2 Participation in acid base balance .
3 Participation in fluid balance by insensible water elimination (vapors ).
4 Facilitating venous return .
5 Participation in blood pressure regulation : Lungs produce Angiotensin converting enzyme ( ACE ) .
6 Immune function : Lungs produce mucous that trap foreign particles , and have ciliae that move foreign particles away from the lung. They also produce alpha 1 antitrepsin that protect the lungs themselves from the effect of elastase and other proteolytic  enzymes

1. PATHOPHYSIOLOGY OF THE CONDUCTION SYSTEM


2. Cardiac arrhythmias = deviation from normal rate, rhythm

    

   1. Heart block (types) = conduction system damage
      1. Complete Heart Block = 3rd degree block
         1. idioventricular beat (35-45/min)
         2. Atria at normal sinus rhythm
         3. Periods of asystole (dizziness, fainting)
         4. Causes = myocardial infarction of ventricular septum, surgical correction of interseptal defects, drugs
      2. Incomplete Heart Block = 2nd degree block
         1. Not all atrial beats reach ventricle
         2. Ventricular beat every 2nd, 3rd, etc. atrial beat, (2:1 block, 3:1 block)
      3. Incomplete Heart Block = 1st degree block
         1. All atrial beats reach ventricle
         2. PR interval abnormally long = slower conduction
      4. Bundle branch blocks (right or left)
         1. Impulses travel down one side and cross over
         2. Ventricular rate normal, QRS prolonged or abnormal
   2. Fibrillation
      1. Asynchronous contractions = twitching movements
      2. Loss of synchrony = little to No output
      3. Atrial Fibrillation
         1. Irregular ventricular beat & depressed pumping efficiency
         2. Atrial beat = 125 - 150/min, pulse feeble = 60 - 70/min
         3. Treatment = Digitalis - reduces rate of ventricular contraction, reduces pulse deficit
      4. Ventricular Fibrillation
         1. Almost no blood pumped to systemic system
         2. ECG = extremely bizarre
         3. Several minutes = fatal
         4. Treatment = defibrillation, cardiac massage can maintain some cardiac output

• 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

   

Urine is a waste byproduct formed from excess water and metabolic waste molecules during the process of renal system filtration. The primary function of the renal system is to regulate blood volume and plasma osmolarity, and waste removal via urine is essentially a convenient way that the body performs many functions using one process. Urine formation occurs during three processes:

Filtration

Reabsorption

Secretion

Filtration

During filtration, blood enters the afferent arteriole and flows into the glomerulus where filterable blood components, such as water and nitrogenous waste, will move towards the inside of the glomerulus, and nonfilterable components, such as cells and serum albumins, will exit via the efferent arteriole. These filterable components accumulate in the glomerulus to form the glomerular filtrate.

Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys to undergo filtration; this is called the filtration fraction. The remaining 80% of the blood flows through the rest of the body to facilitate tissue perfusion and gas exchange.

Reabsorption

The next step is reabsorption, during which molecules and ions will be reabsorbed into the circulatory system. The fluid passes through the components of the nephron (the proximal/distal convoluted tubules, loop of Henle, the collecting duct) as water and ions are removed as the fluid osmolarity (ion concentration) changes. In the collecting duct, secretion will occur before the fluid leaves the ureter in the form of urine.

Secretion

During secretion some substances±such as hydrogen ions, creatinine, and drugs—will be removed from the blood through the peritubular capillary network into the collecting duct. The end product of all these processes is urine, which is essentially a collection of substances that has not been reabsorbed during glomerular filtration or tubular reabsorbtion.

Clinical Physiology 

Heart Failure : Heart failure is inability of the heart to pump the enough amount of blood needed to sustain the needs of organism .
It is usually called congestive heart failure ( CHF) .

To understand the pathophysiology  of the heart failure ,  lets compare it with the physiology of the cardiac output :
Cardiac output =Heart rate X stroke volume

Stroke volume is determined by three determinants : Preload ( venous return ) , contractility , and afterload    (peripheral resistance ) . Any disorder of these factors will reduce the ability of the heart to pump blood .

Preload : Any factor that decrease the venous return , either by decreasing the intravenous pressure or increasing the intraatrial pressure will lead to heart failure .

Contractility : Reducing the power of contraction such as in  myocarditis , cardiomyopathy , preicardial tamponade ..etc , will lead to heart failure .

Afterload : Any factor that may increase the peripheral resistance such as hypertension , valvular diseases of the heart may cause heart failure.

Pathophysiology : When the heart needs to contract more to meet the increased demand , compensatory mechanisms start to develope to enhance the power of contractility  . One of these mechanism is increasing heart rate , which will worsen the situation because this will increase the demands of the myocardial cells themselves . The other one is hypertrophy of the cardiac muscle which may compensate the failure temporarily but then the hypertrophy will be an additional load as the fibers became stiff  .

The stroke volume will be reduced , the intraventricular pressure will increase and consequently the intraatrial pressure and then the venous pressure . This will lead to decrease reabsorption of water from the interstitium ( see microcirculation) and then leads to developing of edema ( Pulmonary edema if the failure is left , and systemic edema if the failure is right) .