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Physiology

Heart is a hollow muscular organ , that is located in the middle mediastinum  between the two bony structures of the sternum and the vertebral column ( a very important location for applying Cardiopulmonary Resuscitation - CPR- ) .
It has a shape of clenched fist , which weighs about 300 grams ( with mild variation between male and female ).
  Heart has an apex that is anteriorly , inferiorly , and leftward oriented , and a base , that is posteriorly , superiorly and rightward oriented   .
 In addition to its apex and base the heart has anterior , posterior and left surfaces.
 
 The wall of the heart is composed of three layers :
 
1. Endocardium : The innermost layer , which lines the heart chambers and is in direct contact with the blood . It is composed of endothelial cells that are similar to those , that line the blood vessels , and of connective tissue too. 
 Endocardium has a smooth surface that prevents blood clotting, as it ensures laminar blood flow .

 Clinical Physiology 
 Endocarditis is the inflammation of the endocardium , which is resistant to antibiotic treatment and difficult to cure.Endocarditis usually involves heart valves and chordae tendineae too.

 2. Myocardium  : The middle layer of the cardiac wall . It is the thickest among the three layers , and is composed of two types of cardiac muscles :
a. contractile muscle cells (form about 98-99% of the cardiac muscle ) .
 b- non-contractile muscle cells ( form about 1-2 % of the cardiac muscles and are the cells that form excitatory-conductive system of the heart).
 The cardiac muscle cells are similar to the skeletal muscles in that they are striated , but similar to the smooth muscles in being involuntary and connected to each others via gap junctions , that facilitate conduction of electrical potential from one cell to the others. Desmosomes adhere cardiac muscle cells to each others .

 3- Epicardium :  is the outermost and protective layer of the heart . It is composed of connective tissue , and form the inner layer of the pericardium ( visceral pericardium - see bellow).

 Pericardium: 
The heart is surrounded by a fluid-fill sac , which is known as pericardium . Pericardium is composed of two layers ( doubled layer membrane ) , between which a fluid-fill pericardial cavity exist .

 The outer layer is called fibrous pericardium , while the inner layer is called serous pericardium , which is subdivided into parietal pericardium and visceral pericardium . The visceral pericardium is the previously mentioned outermost layer of heart ( epicardium) .
Pericardial sac plays an important role in protection of heart from external hazards and infections , as it fixes the heart and limits its motion. It also prevents excessive dilation of the heart.

Clinical physiology: 

When there is excessive fluid in the pericardial cavity as a result of pericardial effusion , a cardiac tamponade will develop . cardiac tamponade means compression of the heart within the pericardial sac , which will prevent the relaxation of the heart ( heart will not be able to fully expand ) , and thus the circulating blood volume will be decreased (obstructive shock) . This is a life threatening situation which has to be urgently cured by  pericardiocentesis . 


Chambers of the heart : 

Heart has four chambers : two atria and two ventricles . The two right and left atria are separated from the two ventricles by the fibrous skeleton , which involves the right ( tricuspid ) and left ( bicuspid ) valves. Right and left atria are separated from each other by the interatrial  septum .
The two ventricles are separated by the interventricular septum.Interventricular septum is muscular in its lower thick part and fibrous in its upper thin part.
The two atria holds the blood returning from the veins and empty it only in a given right moment into the ventricles. Ventricles pump the blood into the arteries . 

Heart valves : 


There are four valves in the heart : Two atrioventricular valves and two semi-lunar valves:
1. Atrioventricular ( AV ) valves: These valves are found between the atria and ventricles , depending on the number of  the leaflets , the right atrioventricular valve is also called tricuspid valve (has three leaflets ) , while the left one is called bicuspid valve (has two leaflets ) . The shape of the bicuspid valve is similar to the mitre of bishop , so it is also called the mitral valve.
The leaflets of the valves are attached to fibrous threads (composed of collagen fibers ) , known as chordae tendineae , which from their side are attached to papillary muscles in the ventricles. These valves prevent backward flow of blood from ventricles during the systole. 

2. Semi-lunar valves : 

These valves are located on the base of the arteries ( aorta and pulmonary artery ) . They prevent the backward flow of blood from the arteries into ventricles.
The structure of the semilunar valves is quite different from that of the AV valves , as they have crescent-shaped cusps that do not have chorda tendinea , instead these cusps are like pockets which are filled of blood when it returns to the ventricles from the lumen of arteries during the diastole  , so they get closed and prevent the backward flow of blood.

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.

Cardiac Control: The Cardiac Center in the medulla.

Outputs:

The cardioacceleratory center sends impulses through the sympathetic nervous system in the cardiac nerves. These fibers innervate the SA node and AV node and the ventricular myocardium. Effects on the SA and AV nodes are an increase in depolarization rate by reducing the resting membrane polarization. Effect on the myocardium is to increase contractility thus increasing force and therefore volume of contraction. Sympathetic stimulation increases both rate and volume of the heart.

The cardioinhibitory center sends impulses through the parasympathetic division, the vagus nerve, to the SA and AV nodes, but only sparingly to the atrial myocardium, and not at all to ventricular myocardium. Its effect is to slow the rate of depolarization by increasing the resting potential, i.e. hyperpolarization.

The parasympathetic division controls the heart at rest, keeping its rhythm slow and regular. This is referred to as normal vagal tone. Parasympathetic effects are inhibited and the sympathetic division exerts its effects during stress, i.e. exercise, emotions, "fight or flight" response, and temperature.

Inputs to the Cardiac Center:

Baroreceptors in the aortic and carotid sinuses. The baroreceptor reflex is responsible for the moment to moment maintenance of normal blood pressure.

Higher brain (hypothalamus): stimulates the center in response to exercise, emotions, "fight or flight", temperature.

Intrinsic Controls of the Heart:

Right Heart Reflex - Pressoreceptors (stretch receptors) in the right atrium respond to stretch due to increased venous return. The reflex acts through a short neural circuit to stimulate the sympathetic nervous system resulting in increased rate and force of contraction. This regulates output to input

The Frank-Starling Law - (Starling's Law of the Heart) - Like skeletal muscle the myocardium has a length tension curve which results in an optimum level of stretch producing the maximum force of contraction. A healthy heart normally operates at a stretch less than this optimum level and when exercise causes increased venous return and increased stretch of the myocardium, the result is increased force of contraction to automatically pump the increased volume out of the heart. I.e. the heart automatically compensates its output to its input.

An important relationship in cardiac output is this one:

Blood Flow =  D Pressure / Resistance to Blood Flow      

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) .
 

Micturition (urination) is a process, by which the final urine is eliminated out of the body .
After being drained into the ureters, urine is stored in urinary bladder until being eliminated.

Bladder is a hollow muscular organ, which has three layers:

- epithelium : Composed of superficial layer of flat cells and deep layer of cuboidal cells.

- muscular layer : contain smooth muscle fibers, that are arranged in longitudinal, spiral and circular pattern . Detrusor  muscle is the main muscle of bladder. The thickening of detrusor muscle forms internal urinary sphinctor which is not an actual urinary sphincter. The actual one is the external urinary sphincter, which is composed of striated muscle and is a part of urogenital diaphragm.

- adventitia: composed of connective tissue fibers.

So: There are two phases of bladder function that depend on characterestics of its muscular wall and innervation :

1. Bladder filling : Urine is poured into bladder through the orifices of ureters. Bladder has five peristaltic contraction per minute . These contraction facilitate moving of urine from the ureter to the bladder as prevent reflux of urine into the ureter.. The capacity of bladder is about  400  ml. But when the bladder start filling its wall extends and thus the pressure is not increased with the increased urine volume.

2. Bladder emptying : When bladder is full stretch receptors in bladder wall are excited , and send signals via the sensory branches of pelvic nerves to the sacral plexus. The first urge to void is felt at a bladder volume of about 150 ml. In sacral portion of spinal cord the sensory signals are integrated and then a motor signal is sent to the urinarry blader muscles through the efferent branches of pelvic nerve itself.

In adult people the neurons in sacral portion could be influenced by nerve signals coming from brain ( Micturition center in pons ) that are also influenced by signals coming from cerebral cortex.

So: The sensory signals ,transmitted to the sacral region will also stimulate ascending pathway and the signals be also transmitted to the micturition center in the brain stem and then to the cerebrum to cause conscious desire for urination.

If micturition is not convenient the brain sends signals to inhibit the parasympathetic motor neuron to the bladder via the sacral neurons. 

It also send inhibitory signal via the somatomotor pudendal nerve to keep external urinary sphincter contracting.

When micturition is convenient a brain signal via the sacral neurons stimulate the parasympathetic pelvic nerve to cause contraction of detruser muscle via M-cholinergic receptors and causes relaxation of external urinary sphincter and the micturition occurs.

Sympathetic hypogastric nerve does not contribute that much to the micturition reflex. It plays role in prvrntion reflux of semen into urinary bladder during ejaculation by contracting bladder muscles.

The Kidneys

The kidneys are the primary functional organ of the renal system.

They are essential in homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and the regulation of blood pressure (by maintaining salt and water balance).

They serve the body as a natural filter of the blood and remove wastes that are excreted through the urine.

They are also responsible for the reabsorption of water, glucose, and amino acids, and will maintain the balance of these molecules in the body.

In addition, the kidneys produce hormones including calcitriol, erythropoietin, and the enzyme renin, which are involved in renal and hemotological physiological processes.

Anatomical Location

The kidneys are a pair of bean-shaped, brown organs about the size of your fist. They are covered by the renal capsule, which is a tough capsule of fibrous connective tissue.

Right kidney being slightly lower than the left, and left kidney being located slightly more medial than the right.

The right kidneys lie  just below the diaphragm and posterior to the liver, the left below the diaphragm and posterior to the spleen.

Resting on top of each kidney is an adrenal gland (adrenal meaning on top of renal), which are involved in some renal system processes despite being a primarily endocrine organ.

They are considered retroperitoneal, which means that they lie behind the peritoneum, the membrane lining of the abdominal cavity.

The renal artery branches off from the lower part of the aorta and provides the blood supply to the kidneys.

 Renal veins take blood away from the kidneys into the inferior vena cava.

The ureters are structures that come out of the kidneys, bringing urine downward into the bladder.

Internal Anatomy of the Kidneys

There are three major regions of the kidney:

1.         Renal cortex

2.         Renal medulla

3.         Renal pelvis

The renal cortex is a space between the medulla and the outer capsule.

The renal medulla contains the majority of the length of nephrons, the main functional component of the kidney that filters fluid from blood.

The renal pelvis connects the kidney with the circulatory and nervous systems from the rest of the body.

Renal Cortex

The kidneys are surrounded by a renal cortex

The cortex provides a space for arterioles and venules from the renal artery and vein, as well as the glomerular capillaries, to perfuse the nephrons of the kidney. Erythropotein, a hormone necessary for the synthesis of new red blood cells, is also produced in the renal cortex.

Renal Medulla

The medulla is the inner region of the parenchyma of the kidney. The medulla consists of multiple pyramidal tissue masses, called the renal pyramids, which are triangle structures that contain a dense network of nephrons.

At one end of each nephron, in the cortex of the kidney, is a cup-shaped structure called the Bowman's capsule. It surrounds a tuft of capillaries called the glomerulus that carries blood from the renal arteries into the nephron, where plasma is filtered through the capsule.

After entering the capsule, the filtered fluid flows along the proximal convoluted tubule to the loop of Henle and then to the distal convoluted tubule and the collecting ducts, which flow into the ureter. Each of the different components of the nephrons are selectively permeable to different molecules, and enable the complex regulation of water and ion concentrations in the body.

Renal Pelvis

The renal pelvis contains the hilium. The hilum is the concave part of the bean-shape where blood vessels and nerves enter and exit the kidney; it is also the point of exit for the ureters—the urine-bearing tubes that exit the kidney and empty into the urinary bladder. The renal pelvis connects the kidney to the rest of the body.

Supply of Blood and Nerves to the Kidneys

•  The renal arteries branch off of the abdominal aorta and supply the kidneys with blood. The arterial supply of the kidneys varies from person to person, and there may be one or more renal arteries to supply each kidney.

•  The renal veins are the veins that drain the kidneys and connect them to the inferior vena cava.

•  The kidney and the nervous system communicate via the renal plexus. The sympathetic nervous system will trigger vasoconstriction and reduce renal blood flow, while parasympathetic nervous stimulation will trigger vasodilation and increased blood flow.

•  Afferent arterioles branch into the glomerular capillaries, while efferent arterioles take blood away from the glomerular capillaries and into the interlobular capillaries that provide oxygen to the kidney.

•  renal vein

The veins that drain the kidney and connect the kidney to the inferior vena cava.

•  renal artery

These arise off the side of the abdominal aorta, immediately below the superior mesenteric artery, and supply the kidneys with blood.

Physiology - science that describes how organisms FUNCTION and survive in continually changing environments  

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