Physiology
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Muscle fatigue

- It is the reduction in muscle ability to generate force.

- It usually follows high intensity or prolonged low/ moderate intensity exercise.
It also occurs easily when there is an interruption of the muscle blood flow.

- It can be explained by:

■ Depletion of energy stores in the muscle (glycogen, ATP, creatine phosphate).

■ Depletion of acetylcholine at the neurons supplying the muscle.

■ Accumulation of metabolites
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TYPES OF CONTRACTION:

1/ Isometric ("same measure" or length):

Contraction without an appreciable decrease in the length of the whole muscle.
In isometric contraction there is Increasing tone.
Isometric = No change in length + Increased tension


2/ Isotonic ("same tension").
Contraction against a constant load with a decrease in muscle length, (e.g. when lifting a light object).

Isotonic= No change in tension + Decreased length

Note: because work is the product of force times distance, isotonic contractions do work, whereas isometric contractions do not.
The oxygen debt mechanism :
Is extra amount of oxygen consumed after exercise.

1/ It takes oxygen from myoglobin.
2/ It metabolizes glucose anaerobically to lactic acid to synthesize ATP.
3/ It uses phosphorylcreatine to synthesize.

⭕️ After exercise extra amount of oxygen (oxygen debt) is provided by hyperventilation.


Oxygen debt it is used to:

1/ Repay oxygen taken from myoglobin

2/ Catabolize lactic acid to carbon dioxide and water

3/ Replenish phosphorylcreatine.

N.B: Oxygen debt does not occur in the cardiac muscle
Physiology
Photo
Post = noradrenaline except:
Sweet glads
arterioles of skeletal muscles
Pilo_erector muscles
Hydrolysed by :
1/Monoamine oxidase MAO
2/Catechol_O_methyl_transferase COMT

Metabolites of catecholamines → vanillylmandelic acid VMA (urine )+ Metaepinephrine + Metanephrine

High excretion of VMA indicates hyper production of catecholamines due to
pheochromocytoma (tumor in adrenal medulla)
Other neurotransmitter:

Substance P: released by some GIT postganglionic parasympathetic neurons.

Nitric oxide (NO); released by some GlT postganglionic parasympathetice.

Dopamine: Released by some interneurons in sympathetic ganglial.

GnRH: Released by some preganglionic neurons.



Co-transmitters:

VIP (vasoactive intestinal peptide) : May be released with acetylcholine.

ATP, Neuropeptide Y: May be released with noradrenaline.
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Acetylcholine receptors:

1- Nicotinic receptors (N1 & N2)

- Described as nicotinic because they can be stimulated by small amount enicotine (the chemical substance found in tobacco).

- They act as ion channels (their stimulation results in Na+ influx & K+ efflux)

- They are found at the following sites: Motor end plate (N1),
sympathetic ganglial (N2), parasympathetic ganglia (N2), Adrenal medulla (N2) &
the brain (N2),

2- Muscarinic receptors :(M1-M5)

Described as muscarinic because they can be stimulated by small amount muscarine (a toxin that is derived from a poisonous mushroom).

There are many subtypes of muscarinic receptors (M1-M5).

* Their stimulation:
results in either activation of phospholipace C to increase inositol triphosphate (IP3) & intracellular calcium (M1, M3 & M5), or inhibition of adenylate cyclase decreased cAMP (M2 & M4).

- They are found in the organs (not ganglia).

These include:
_All organs supplied by postganglionic parasympathetic neurons.

_The organs supplied by cholinergic postganglionic sympathetic neurons(sweat glands, arterioles of skeletal muscles & piloerector muscles).

_The brain (has both nicotinic & muscarinic receptors).

-Their stimulation causes parasympathetic effects.
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Noradrenaline receptors:

1/ Alpha receptors (a)

Have many subtypes (a1& a2).
Alpha 1 receptors (a1 Rs):

a1 Rs are found in smooth muscle of many organs (e..g., blood vessels.
urethral sphincter & dilator pupillae muscle).

They induce induce smooth muscle contraction resulting in many effects
(e.g., vasoconstriction, reduced urine flow and dilation of the eye pupil).a1 Rs act through activation of phospholipase C (PLC), which increases intracellular inositol triphosphate (IP3), calcium & diacylglycerol (DAG).

Alpha 2 receptors (a2 Rs ):

_a2 Rs are found in the presynaptic membranes of sympathetic neurons.

_The released norepinephrine acts on them to inhibit its own release (Negative Feedback). This results in reduction of the sympathetic effects.

_Sites of a2 Rs include the pancreas and GIT sphincters. Their stimulation results in reduced insulin secretion and contraction of GIT sphincters.

- Other sites of a2 Rs include the GIT wall (causing relaxation) and the CNS (causing analgesia & sedation).

_a2 Rs act through inhibition of adenylate cyclase to decrease cAMP.

Beta receptors (B):

Beta 1 receptors (B1 Rs):

- B1 Rs are dominant in the heart, renin secreting cells & adipose tissue:

_Their stimulation in the heart increases the heart rate (+ve chronotropeffect), contractility (+ve inotropic effect) & conduction velocity +ve dromotropic effect). Other effects include renin secretion & lipolysis.

Beta 2 receptors (ẞ2 Rs):

B2 Rs cause relaxation of smooth muscle. They are dominant in many organs (e.g., lung bronchioles, GIT wall, urinary bladder wall & uterus). Their stimulation results in bronchodilation reduced GIT motility, relaxation of the urinary bladder wall & relaxation of the uterus.

Beta 3 receptors (B3 Rs):

B3 Rs are also dominant in the adipose tissue. They cause lipolysis.
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N.B:
Certain organs are not supplied by the parasympathetic (although they supplied by the sympathetic); and therefore, they are do not have muscarinic receptors. These include ventricles of the heart, radial muscle of the iris & some blood vessels (of the skin, abdominal viscera and the kidney).
⭕️ Epinephrine acts better on beta-receptors whereas, norepinephrine acts better on alpha-recpeptors.
Autonomic Blockers:
1/ competitive blockers
2/ Depolymerizing blockers
Blockers of Acetylcholine:

1/Competitive nicotinic blockers:
_Curare.
_Hexamethonium.

2/Depolarizing nicotinic blocker:
Large amount of nicotine

3/Competitive muscarinic blockers:
_Atropine.
_Scopolamine.

4/Depolarizing muscarinic blocker:
_large amount muscarine
Blockers of Noradrenaline:

1/ Alpha-blockers:
phentolamine, prazosin→ alpha 1
yohimbine → Alpha 2

Effect vasodilation (to treat hypertension) and relaxation of sphincters (to facilitate micturition in prostatic hypertrophy patients).

2/ Beta-blockers:

_B1 & B2 Rs (e.g., propranolol)
_ẞ1 Rs (e.g., atenolol)
_ẞ2 Rs (e.g., butoxamine)

Effect: decreased heart rate & decreased contractility (to treat
diseases like hypertension & myocardial infarction).
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The Frank Starling Law :

states" within certain limits, the energy of contraction is directly proportional to the initial length of the muscle fibres"
Ejection fraction:
Indicates contractility
= SV/EDV
Normally= 70%
Low in MI
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شوية حباسات في ال ANS و ال Excitable tissues و الكارديو
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