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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.

Blood Pressure

Blood moves through the arteries, arterioles, and capillaries because of the force created by the contraction of the ventricles.

Blood pressure in the arteries.

The surge of blood that occurs at each contraction is transmitted through the elastic walls of the entire arterial system where it can be detected as the pulse. Even during the brief interval when the heart is relaxed — called diastole — there is still pressure in the arteries. When the heart contracts — called systole — the pressure increases.

Blood pressure is expressed as two numbers, e.g., 120/80.

Blood pressure in the capillaries

The pressure of arterial blood is largely dissipated when the blood enters the capillaries. Capillaries are tiny vessels with a diameter just about that of a red blood cell (7.5 µm). Although the diameter of a single capillary is quite small, the number of capillaries supplied by a single arteriole is so great that the total cross-sectional area available for the flow of blood is increased. Therefore, the pressure of the blood as it enters the capillaries decreases.

Blood pressure in the veins

When blood leaves the capillaries and enters the venules and veins, little pressure remains to force it along. Blood in the veins below the heart is helped back up to the heart by the muscle pump. This is simply the squeezing effect of contracting muscles on the veins running through them. One-way flow to the heart is achieved by valves within the veins

Exchanges Between Blood and Cells

With rare exceptions, our blood does not come into direct contact with the cells it nourishes. As blood enters the capillaries surrounding a tissue space, a large fraction of it is filtered into the tissue space. It is this interstitial or extracellular fluid (ECF) that brings to cells all of their requirements and takes away their products. The number and distribution of capillaries is such that probably no cell is ever farther away than 50 µm from a capillary.

When blood enters the arteriole end of a capillary, it is still under pressure produced by the contraction of the ventricle. As a result of this pressure, a substantial amount of water and some plasma proteins filter through the walls of the capillaries into the tissue space.

Thus fluid, called interstitial fluid, is simply blood plasma minus most of the proteins. (It has the same composition and is formed in the same way as the nephric filtrate in kidneys.)

Interstitial fluid bathes the cells in the tissue space and substances in it can enter the cells by diffusion or active transport. Substances, like carbon dioxide, can diffuse out of cells and into the interstitial fluid.

Near the venous end of a capillary, the blood pressure is greatly reduced .Here another force comes into play. Although the composition of interstitial fluid is similar to that of blood plasma, it contains a smaller concentration of proteins than plasma and thus a somewhat greater concentration of water. This difference sets up an osmotic pressure. Although the osmotic pressure is small, it is greater than the blood pressure at the venous end of the capillary. Consequently, the fluid reenters the capillary here.

Control of the Capillary Beds

An adult human has been estimated to have some 60,000 miles of capillaries with a total surface area of some 800–1000 m2. The total volume of this system is roughly 5 liters, the same as the total volume of blood. However, if the heart and major vessels are to be kept filled, all the capillaries cannot be filled at once. So a continual redirection of blood from organ to organ takes place in response to the changing needs of the body. During vigorous exercise, for example, capillary beds in the skeletal muscles open at the expense of those in the viscera. The reverse occurs after a heavy meal.

The walls of arterioles are encased in smooth muscle. Constriction of arterioles decreases blood flow into the capillary beds they supply while dilation has the opposite effect. In time of danger or other stress, for example, the arterioles supplying the skeletal muscles will be dilated while the bore of those supplying the digestive organs will decrease. These actions are carried out by

  • the autonomic nervous system.
  • local controls in the capillary beds

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

Blood is a liquid tissue. Suspended in the watery plasma are seven types of cells and cell fragments.

  • red blood cells (RBCs) or erythrocytes
  • platelets or thrombocytes
  • five kinds of white blood cells (WBCs) or leukocytes
    • Three kinds of granulocytes
      • neutrophils
      • eosinophils
      • basophils
    • Two kinds of leukocytes without granules in their cytoplasm
      • lymphocytes
      • monocytes

Remember the following principles before proceeding :
- Reabsorption occurs for most of substances that have been previously filterd .
- The direction of reabsorption is from the tubules to the peritubular capillaries
- All of transport mechanism are used here.
- Different morphology of the cells of different parts of the tubules contribute to reabsorption of different substances .
- There are two routes of reabsorption: Paracellular and transcellular : Paracellular reabsorption depends on the tightness of the tight junction which varies from regeon to region in the nephrons .Transcellular depends on presence of transporters ( carriers and channels for example).


1. Reabsorption of glucose , amino acids , and proteins :

Transport of glucose occurs in the proximal tubule . Cells of proximal tubules are similar to those of the intestinal mucosa as the apical membrane has brush border form to increase the surface area for reabsorption , the cells have plenty of mitochondria which inform us that high amount of energy is required for active transport , and the basolateral membrane of the cells contain sodium -potassium pumps , while the apical membrane contains a lot of carrier and channels .

The tight junction between the tubular cells of the proximal tubules are not that (tight) which allow paracellular transport.
Reabsorption of glucose starts by active transport of  Na by the pumps on the basolateral membrane . This will create Na gradient which will cause Na to pass the apical membrane down its concentration gradient . Glucose also passes the membrane up its concentration gradient using sodium -glucose symporter as a secondary active transport.


The concentration of glucose will be increased in the cell and this will enable the glucose to pass down concentration gradient to the interstitium by glucose uniporter . Glucose will then pass to the peritubular capillaries by simple bulk flow.

Remember: Glucose reabsorption occurs via transcellular route .
          Glucose transport has transport maximum . In normal situation there is no glucose in the urine , but in uncontrolled diabetes mellitus patients glucose level exceeds its transport maximum (390 mg/dl) and thus will appear in urine .
                   
                   
                   
2. Reabsorption of Amino acids : Use secondary active transport mechanism like glucose.

3. Reabsorption of proteins : 

Plasma proteins are not filtered in Bowman capsule but some proteins and peptides in blood may pass the filtration membrane and then reabsorbed . Some peptides are reabsorbed paracellulary , while the others bind to the apical membrane and then enter the cells by endocytosis , where they will degraded by peptidase enzymes to amino acids .

4. Reabsorption of sodium , water , and chloride:

65 % of sodium is reabsorbed in the proximal tubules , while 25% are reabsorbed in the thick ascending limb of loob of Henle , 9% in the distal and collecting tubules and collecting ducts .
90% of sodium reabsorption occurs independently from its plasma level (unregulated) , This is true for sodium reabsorbed in proximal tubule and loop of Henle , while the 9% that is reabsorbed in distal ,collecting tubules and collecting ducts is regulated by Aldosterone. 


In proximal tubules : 65% of sodium is reabsorbed . The initial step occurs by creating sodium gradient  by sodium-potassium pump on the basolateral membrane . then the sodium will pass from the lumen into the cells down concentration gradient by sodium -glucose symporter , sodium -phosphate symporter and by sodium- hydrogen antiporter and others                    
                   
After reabsorption of sodium , an electrical gradient will be created , then chloride is reabsorbed following the sodium  . Thus the major cation and anion leave the lumen to the the interstitium and thus the water follows by osmosis . 65% of water is reabsorbed in the proximal tubule.

Discending limb of loop of Henle is impermeable to electrolytes but avidly permeable to water . 10 % of water is reabsorbed in the discending thin limb of loob of Henle .

The thick ascending limb of loop of Henly is permeable to electrolytes , due to the presence of Na2ClK syporter . 25% of sodium is reabsorbed here .

In the distal and collecting tubules and the collecting ducts 9% of sodium is reabsorbed .this occurs under aldosterone control depending on sodium plasma level. 1% of sodium is excreted .

Water is not reabsorbed from distal tubule but 5-25% of water is reabsorbed in collecting tubules .

Production of Hormones

The kidneys produce and interact with several hormones that are involved in the control of systems outside of the urinary system.

Calcitriol. Calcitriol is the active form of vitamin D in the human body. It is produced by the kidneys from precursor molecules produced by UV radiation striking the skin. Calcitriol works together with parathyroid hormone (PTH) to raise the level of calcium ions in the bloodstream. When the level of calcium ions in the blood drops below a threshold level, the parathyroid glands release PTH, which in turn stimulates the kidneys to release calcitriol. Calcitriol promotes the small intestine to absorb calcium from food and deposit it into the bloodstream. It also stimulates the osteoclasts of the skeletal system to break down bone matrix to release calcium ions into the blood.
 
Erythropoietin. Erythropoietin, also known as EPO, is a hormone that is produced by the kidneys to stimulate the production of red blood cells. The kidneys monitor the condition of the blood that passes through their capillaries, including the oxygen-carrying capacity of the blood. When the blood becomes hypoxic, meaning that it is carrying deficient levels of oxygen, cells lining the capillaries begin producing EPO and release it into the bloodstream. EPO travels through the blood to the red bone marrow, where it stimulates hematopoietic cells to increase their rate of red blood cell production. Red blood cells contain hemoglobin, which greatly increases the blood’s oxygen-carrying capacity and effectively ends the hypoxic conditions.
 
Renin. Renin is not a hormone itself, but an enzyme that the kidneys produce to start the renin-angiotensin system (RAS). The RAS increases blood volume and blood pressure in response to low blood pressure, blood loss, or dehydration. Renin is released into the blood where it catalyzes angiotensinogen from the liver into angiotensin I. Angiotensin I is further catalyzed by another enzyme into Angiotensin II.

Angiotensin II stimulates several processes, including stimulating the adrenal cortex to produce the hormone aldosterone. Aldosterone then changes the function of the kidneys to increase the reabsorption of water and sodium ions into the blood, increasing blood volume and raising blood pressure. Negative feedback from increased blood pressure finally turns off the RAS to maintain healthy blood pressure levels.

  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

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