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Physiology

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.

The endocrine system along with the nervous system functions in the regulation of body activities.  The nervous system acts through electrical impulses and neurotransmitters to cause muscle contraction and glandular secretion and interpretation of impulses.  The endocrine system acts through chemical messengers called hormones that influence growth, development, and metabolic activities

Glomerular filtration

Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.

The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .

Filtration occurs through the filtration unit , which includes :

1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .

2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .

3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .


Many forces drive the glomerular filtration , which are :

1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .

2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .

3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .

The net pressure is as follows :

Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .

Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.
 

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

1 - Passive processes - require no expenditure of energy by a cell:

  • Simple diffusion = net movement of a substance from an area of high concentration to an area of low concentration. The rate of diffusion is influenced by:
    • concentration gradient
    • cross-sectional area through which diffusion occurs
    • temperature
    • molecular weight of a substance
    • distance through which diffusion occurs
  • Osmosis = diffusion of water across a semi permeable membrane (like a cell membrane) from an area of low solute concentration to an area of high solute concentration
  • Facilitated diffusion = movement of a substance across a cell membrane from an area of high concentration to an area of low concentration. This process requires the use of 'carriers' (membrane proteins). In the example below, a ligand molecule (e.g., acetylcholine) binds to the membrane protein. This causes a conformational change or, in other words, an 'opening' in the protein through which a substance (e.g., sodium ions) can pass.

2 - Active processes - require the expenditure of energy by cells:

  • Active transport = movement of a substance across a cell membrane from an area of low concentration to an area of high concentration using a carrier molecule
  • Endo- & exocytosis - moving material into (endo-) or out of (exo-) cell in bulk form

Blood Groups

Blood groups are created by molecules present on the surface of red blood cells (and often on other cells as well).

The ABO Blood Groups

The ABO blood groups are the most important in assuring safe blood transfusions.

Blood Group

Antigens on RBCs

Antibodies in Serum

Genotypes

A

A

Anti-B

AA or AO

B

B

Anti-A

BB or BO

AB

A and B

Neither

AB

O

Neither

Anti-A and anti-B

OO

When red blood cells carrying one or both antigens are exposed to the corresponding antibodies, they agglutinate; that is, clump together. People usually have antibodies against those red cell antigens that they lack.

The critical principle to be followed is that transfused blood must not contain red cells that the recipient's antibodies can clump. Although theoretically it is possible to transfuse group O blood into any recipient, the antibodies in the donated plasma can damage the recipient's red cells. Thus all transfusions should be done with exactly-matched blood.

The Rh System

Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells. They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane. They are named for the rhesus monkey in which they were first discovered.

There are a number of Rh antigens. Red cells that are "Rh positive" express the one designated D. About 15% of the population have no RhD antigens and thus are "Rh negative".

The major importance of the Rh system for human health is to avoid the danger of RhD incompatibility between mother and fetus.

During birth, there is often a leakage of the baby's red blood cells into the mother's circulation. If the baby is Rh positive (having inherited the trait from its father) and the mother Rh-negative, these red cells will cause her to develop antibodies against the RhD antigen. The antibodies, usually of the IgG class, do not cause any problems for that child, but can cross the placenta and attack the red cells of a subsequent Rh+ fetus. This destroys the red cells producing anemia and jaundice. The disease, called erythroblastosis fetalis or hemolytic disease of the newborn, may be so severe as to kill the fetus or even the newborn infant. It is an example of an antibody-mediated cytotoxicity disorder.

Although certain other red cell antigens (in addition to Rh) sometimes cause problems for a fetus, an ABO incompatibility does not. Rh incompatibility so dangerous when ABO incompatibility is not

It turns out that most anti-A or anti-B antibodies are of the IgM class and these do not cross the placenta. In fact, an Rh/type O mother carrying an Rh+/type A, B, or AB fetus is resistant to sensitization to the Rh antigen. Presumably her anti-A and anti-B antibodies destroy any fetal cells that enter her blood before they can elicit anti-Rh antibodies in her.

This phenomenon has led to an extremely effective preventive measure to avoid Rh sensitization. Shortly after each birth of an Rh+ baby, the mother is given an injection of anti-Rh antibodies. The preparation is called Rh immune globulin (RhIG) or Rhogam. These passively acquired antibodies destroy any fetal cells that got into her circulation before they can elicit an active immune response in her.

Rh immune globulin came into common use in the United States in 1968, and within a decade the incidence of Rh hemolytic disease became very low.

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.

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