NEET MDS Lessons
Physiology
Excitability ( Bathmotropism ) : Excitability means the ability of cardiac muscle to respond to signals. Here we are talking about contractile muscle cells that are excited by the excitatory conductive system and generate an action potential.
Cardiac action potential is similar to action potential in nerve and skeletal muscle tissue , with one difference , which is the presence of plateau phase . Plateau phase is unique for cardiac muscle cells .
The resting membrane potential for cardiac muscle is about -80 mV.
When the cardiac muscle is stimulated an action potential is generated . The action potential in cardiac muscle is composed of four phases , which are :
1. Depolarization phase (Phase 0 ) :
A result of opening of sodium channels , which increase the permeability to sodium , which will lead to a rapid sodium influx into the cardiac muscle cell.
2. Repolarization : Repolarization in cardiac muscle is slow and triphasic :
a. Phase 1 (early partial repolarization ) : A small fast repolarization , results from potassium eflux and chloride influx.
b. Phase 2 ( Plateau ) : After the early partial depolarization , the membrane remains depolarized , exhibiting a plateau , which is a unique phase for the cardiac muscle cell. Plateau is due to opening of slow calcium-sodium channels , delay closure of sodium channels , and to decreased potassium eflux.
c. Phase 3 ( Rapid repolarization) : opening of potassium channels and rapid eflux of potassium.
d. Phase 4 ( Returning to resting level) in other words : The phase of complete repolarization. This due to the work of sodium-potassium pump.
Absolute refractory period:
Coincides wit phase 0,phase1 , and phase 2 . During this period , excitability of the heart is totally abolished . This prevents tetanization of the cardiac muscle and enables the heart to contract and relax to be filled by blood ..
Relative refractory period :
Coincides with the rapid repolarization and allows the excitability to be gradually recovered .
Excitation contraction relationship : Contraction of cardiac muscle starts after depolarization and continues about 1.5 time as long as the duration of the action potential and reaches its maximum at the end of the plateau. Relaxation of the muscle starts with the early partial repolarization.
Factors , affecting excitability of cardiac muscle:
I. Positive bathmotropic effect :
1. Sympathetic stimulation : It increase the heart , and thus reduces the duration of the action potentia; . This will shorten the duration of the absolute refractory period , and thus increase the excitability .
2. Drugs : Catecholamines and xanthines derivatives .
3. Mild hypoxia and mild ischemia
4. Mild hyperkalemia as it decreases the K+ efflux and opens excess Na+ channels .
5. Hypocalcemia
II. Negative bathmotropic effect :
1. Parasympathetic stimulation: The negative bathmotropic effect is limited to the atrial muscle excitability , because there is no parasympathetic innervation for the ventricles. Parasympathetic stimulation decreases the heart rate , and thus increases the duration of cardiac action potential and thus increases the duration of the absolute refractory period.
2. moderate to severe hypoxia
3. hyponatremia , hypercalcemia , and severe hyperkalemia.
Clinical Physiology : Extrasystole is a pathological situation , due to abnormal impulses , arising from ectopic focus .It is expressed as an abnormal systole that occur during the early diastole .
Extrasystole is due to a rising of excitability above the normal , which usually occurs after the end of the relative refractory period ( read about staircase phenomenon of Treppe)
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.
Concentration versus diluting urine
Kidney is a major route for eliminating fluid from the body to accomplish water balance. Urine excretion is the last step in urine formation. Everyday both kidneys excrete about 1.5 liters of urine.
Depending on the hydrated status of the body, kidney either excretes concentrated urine ( if the plasma is hypertonic like in dehydrated status ) or diluted urine ( if the plasma is hypotonic) .
This occurs thankful to what is known as countercurrent multiplying system, which functions thankfully to establishing large vertical osmotic gradient .
To understand this system, lets review the following facts:
1. Descending limb of loop of Henle is avidly permeable to water.
2. Ascending limb of loop of Henly is permeable to electrolytes , but impermeable to water. So fluid will not folow electrolytes by osmosis.and thus Ascending limb creates hypertonic interstitium that will attract water from descending limb.
Pumping of electrolytes
3. So: There is a countercurrent flow produced by the close proximity of the two limbs.
Juxtamedullary nephrons have long loop of Henle that dips deep in the medulla , so the counter-current system is more obvious and the medullary interstitium is always hypertonic . In addition, peritubular capillaries in the medulla are straigh ( vasa recta) in which flow is rapid and rapidly reabsorb water maintaining hypertonic medullary interstitium.
In distal tubules water is diluted. If plasma is hypertonic, this will lead to release of ADH by hypothalamus, which will cause reabsorption of water in collecting tubules and thus excrete concentrated urine.
If plasma is hypotonic ADH will be inhibited and the diluted urine in distal tubules will be excreted as diluted urine.
Urea contributes to concentrating and diluting of urine as follows:
Urea is totally filtered and then 50% of filtrated urea will be reabsorbed to the interstitium, this will increase the osmolarity of medullary interstitium ( becomes hypertonic ). Those 50% will be secreted in ascending limb of loop of Henle back to tubular fluid to maintain osmolarity of tubular fluid. 55% of urea in distal nephron will be reabsorbed in collecting ducts back to the interstitium ( under the effect of ADH too) . This urea cycle additionally maintain hypertonic interstitium.
Carbohydrates:
- about 3% of the dry mass of a typical cell
- composed of carbon, hydrogen, & oxygen atoms (e.g., glucose is C6H12O6)
- an important source of energy for cells
- types include:
- monosaccharide (e.g., glucose) - most contain 5 or 6 carbon atoms
- disaccharides
- 2 monosaccharides linked together
- Examples include sucrose (a common plant disaccharide is composed of the monosaccharides glucose and fructose) & lactose (or milk sugar; a disaccharide composed of glucose and the monosaccharide galactose)
- polysaccharides
- several monosaccharides linked together
Examples include starch (a common plant polysaccharide made up of many glucose molecules) and glycogen (commonly stored in the liver)
Cardiac Output:
Minute Volume = Heart Rate X Stroke Volume
Heart rate, HR at rest = 65 to 85 bpm
Each heartbeat at rest takes about .8 sec. of which .4 sec. is quiescent period.
Stroke volume, SV at rest = 60 to 70 ml.
Heart can increase both rate and volume with exercise. Rate increase is limited due to necessity of minimum ventricular diastolic period for filling. Upper limit is usually put at about 220 bpm. Maximum heart rate calculations are usually below 200. Target heart rates for anaerobic threshold are about 85 to 95% of maximum.
Terms:
End Diastolic Volume, EDV - the maximum volume of the ventricles achieved at the end of ventricular diastole. This is the amount of blood the heart has available to pump. If this volume increases the cardiac output increases in a healthy heart.
End Systolic Volume, ESV - the minimum volume remaining in the ventricle after its systole. If this volume increases it means less blood has been pumped and the cardiac output is less.
EDV - ESV = SV
SV / EDV = Ejection Fraction The ejection fraction is normally around 50% at rest and will increase during strenuous exercise in a healthy heart. Well trained athletes may have ejection fractions approaching 70% in the most strenuous exercise.
Isovolumetric Contraction Phase - a brief period at the beginning of ventricular systole when all valves are closed and ventricular volume remains constant. Pressure has risen enough in the ventricle to close the AV valves but not enough to open the semilunar valves and cause ejection of blood.
Isovolumetric Relaxation Phase - a brief period at the beginning of ventricular diastole when all valves are closed and ventricular volume is constant. Pressure in the ventricle has lowered producing closure of the semilunar valves but not opening the AV valves to begin pulling blood into the ventricle.
Dicrotic Notch - the small increase in pressure of the aorta or other artery seen when recording a pulse wave. This occurs as blood is briefly pulled back toward the ventricle at the beginning of diastole thus closing the semilunar valves.
Preload - This is the pressure at the end of ventricular diastole, at the beginning of ventricular systole. It is proportional to the End Diastolic Volume (EDV), i.e. as the EDV increases so does the preload of the heart. Factors which increase the preload are: increased total blood volume, increased venous tone and venous return, increased atrial contraction, and the skeletal muscular pump.
Afterload - This is the impedence against which the left ventricle must eject blood, and it is roughly proportional to the End Systolic Volume (ESV). When the peripheral resistance increases so does the ESV and the afterload of the heart.
The importance of these parameters are as a measure of efficiency of the heart, which increases as the difference between preload and afterload increases
A rise in blood pressure stretches the atria of the heart. This triggers the release of atrial natriuretic peptide (ANP). ANP is a peptide of 28 amino acids. ANP lowers blood pressure by:
- relaxing arterioles
- inhibiting the secretion of renin and aldosterone
- inhibiting the reabsorption of sodium ions in the collecting ducts of the kidneys.
The effects on the kidney reduce the reabsorption of water by them thus increasing the flow of urine and the amount of sodium excreted in it (These actions give ANP its name: natrium = sodium; uresis = urinate). The net effect of these actions is to reduce blood pressure by reducing the volume of blood volume in the system.
The Heartbeat
During rest, the heart beats about 70 times a minute in the adult male, while pumping about 5 liters of blood.
The stimulus that maintains this rhythm is self-contained. Embedded in the wall of the right atrium is a mass of specialized heart tissue called the sino-atrial (S-A) node. The S-A node is also called the pacemaker because it establishes the basic frequency at which the heart beats.
The interior of the fibers of heart muscle, like all cells, is negatively charged with respect to the exterior. In the cells of the pacemaker, this charge breaks down spontaneously about 70 times each minute. This, in turn, initiates a similar discharge of the nearby muscle fibers of the atrium. A tiny wave of current sweeps over the atria, causing them to contract.
When this current reaches the region of insulating connective tissue between the atria and the ventricles, it is picked up by the A-V node (atrio-ventricular node). This leads to a system of branching fibers that carries the current to all parts of the ventricles.
The contraction of the heart in response to this electrical activity creates systole.
A period of recovery follows called diastole.
- The heart muscle and S-A node become recharged.
- The heart muscle relaxes.
- The atria refill.
The Electrocardiogram
The electrical activity of the heart can be detected by electrodes placed at the surface of the body. Analysis of an electrocardiogram (ECG or EKG) aids in determining, for example, the extent of damage following a heart attack. This is because death of a portion of the heart muscle blocks electrical transmission through that area and alters the appearance of the ECG
Control of the Heart
Although the A-V node sets the basic rhythm of the heart, the rate and strength of its beating can be modified by two auxiliary control centers located in the medulla oblongata of the brain.
- One sends nerve impulses down accelerator nerves.
- The other sends nerve impulses down a pair of vagus nerves
Accelerator Nerves
The accelerator nerves are part of the sympathetic branch of the autonomic nervous system, and like all post-ganglionic sympathetic neurons release noradrenaline at their endings on the heart.
They increase the rate and strength of the heartbeat and thus increase the flow of blood. Their activation usually arises from some stress such as fear or violent exertion. The heartbeat may increase to 180 beats per minute. The strength of contraction increases as well so the amount of blood pumped may increase to as much as 25-30 liters/minute.
Vigorous exercise accelerates heartbeat in two ways;
- As cellular respiration increases, so does the carbon dioxide level in the blood. This stimulates receptors in the carotid arteries and aorta, and these transmit impulses to the medulla for relay by the accelerator nerves to the heart.
- As muscular activity increases, the muscle pump drives more blood back to the right atrium. The atrium becomes distended with blood, thus stimulating stretch receptors in its wall. These, too, send impulses to the medulla for relay to the heart.
Distention of the wall of the right atrium also triggers the release of atrial natriuretic peptide (ANP) which initiates a set of responses leading to a lowering of blood pressure
The Vagus Nerves
The vagus nerves are part of the parasympathetic branch of the autonomic nervous system. They, too, run from the medulla oblongata to the heart. Their activity slows the heartbeat.
Pressure receptors in the aorta and carotid arteries send impulses to the medulla which relays these by way of the vagus nerves to the heart. Heartbeat and blood pressure diminish.
Neurons :
Types of neurons based on structure:
a multipolar neuron because it has many poles or processes, the dendrites and the axon. Multipolar neurons are found as motor neurons and interneurons. There are also bipolar neurons with two processes, a dendrite and an axon, and unipolar neurons, which have only one process, classified as an axon.. Unipolar neurons are found as most of the body's sensory neurons. Their dendrites are the exposed branches connected to receptors, the axon carries the action potential in to the central nervous system.
Types of neurons based on function:
- motor neurons - these carry a message to a muscle, gland, or other effector. They are said to be efferent, i.e. they carry the message away from the central nervous system.
- sensory neurons - these carry a message in to the CNS. They are afferent, i.e. going toward the brain or spinal cord.
- interneuron (ie. association neuron, connecting neuron) - these neurons connect one neuron with another. For example in many reflexes interneurons connect the sensory neurons with the motor neurons.