Cystic Fibrosis
→ Thick mucus coagulates in ducts, produces obstruction, Too thick for cilia to move
 
→ Major Systems Affected: Respiratory System, G. I. Tract,Reproductive Tract

→ Inherited, autosomal recessive gene, most common fatal genetic disorder

→    Major characteristic, Altered electrolyte composition (Saliva & sweat Na+, K+, Cl-)

→    Family history of Cystic Fibrosis
→    Respiratory Infections & G.I.Tract malabsorption
→    Predisposes lung to Secondary infection (Staphylococcus, Pseudomonas)
→    Damages Respiratory Bronchioles and Alveolar ducts, Produces Fibrosis of Lungs, Large cystic dilations)

A small fraction of cardiac muscle fibers have myogenicity and autorhythmicity.

Myogenicity is the property of spontaneous impulse generation. The slow sodium channels are leaky and cause the polarity to spontaneously rise to threshold for action potential generation. The fastest of these cells, those in the SA node, set the pace for the heartbeat.

Autorhythmicity - the natural rhythm of spontaneous depolarization. Those with the fastest autorhythmicity act as the 1. heart's pacemaker.

Contractility - like skeletal muscle, most cardiac muscle cells respond to stimuli by contracting. The autorhythmic cells have very little contractility however. Contractility in the other cells can be varied by the effect of neurotransmitters.

Inotropic effects - factors which affect the force or energy of muscular contractions. Digoxin, epinephrine, norepinephrine, and dopamine have positive inotropic effects. Betal blockers and calcium channel blockers have negative inotropic effects 

Sequence of events in cardiac conduction: The electrical events in the cardiac cycle.

1) SA node depolarizes and the impulse spreads across the atrial myocardium and through the internodal fibers to the AV node. The atrial myocardium depolarizes resulting in atrial contraction, a physical event.

2) AV node picks up the impulse and transfers it to the AV Bundle (Bundle of His). This produces the major portion of the delay seen in the cardiac cycle. It takes approximately .03 sec from SA node depolarization to the impulse reaching the AV node, and .13 seconds for the impulse to get through the AV node and reach the Bundle of His. Also during this period the atria repolarize.

3) From the AV node the impulse travels through the bundle branches and through the Purkinje fibers to the ventricular myocardium, causing ventricular depolarization and ventricular contraction, a physical event.

4) Ventricular repolarization occurs.

Ingestion: Food taken in the mouth is

• ground into finer particles by the teeth,
• moistened and lubricated by saliva (secreted by three pairs of salivary glands)
• small amounts of starch are digested by the amylase present in saliva
• the resulting bolus of food is swallowed into the esophagus and
• carried by peristalsis to the stomach.

Ventilation simply means inhaling and exhaling of air from the atmospheric air into lungs and then exhaling it from the lung into the atmospheric air.
Air pressure gradient has to exist between two atmospheres to enable a gas to move from one atmosphere to an other.
 

During inspiration: the intrathoracic pressure has to be less than that of atmospheric pressure. This could be achieved by decreasing the intrathoracic pressure as follows:
 

Depending on Boyle`s law , the pressure of gas is inversely proportional to the volume of its container. So increasing the intrathoracic volume will decrease the intrathoracic pressure which will allow the atmospheric air to be inhaled (inspiration) . As decreasing the intrathoracic volume will increase the intrathoracic pressure and causes exhaling of air ( expiration)

So. Inspiration  could be actively achieved by the contraction of inspiratory muscles : diaphragm and intercostal muscles. While relaxation of the mentioned muscles will passively cause expiration.
 

Contraction of diaphragm will pull the diaphragm down the abdominal cavity ( will move inferiorly)  , and then increase the intrathoracic volume ( vertically)  . Contraction of external intercostal muscle will pull the ribs upward and forward which will additionally increase the intrathoracic volume ( transversely  , the net result will be increasing the intrathoracic volume and decreasing the intrathoracic pressure.
 

Relaxation of diaphragm will move it superiorly during expiration, the relaxation of external intercostal muscles will pull the ribs downward and backward , and the elastic lungs and chest wall will recoil. The net result is decreasing the intrathoracic volume and increasing intrathoracic pressure.
 

All of this occurs during quiet breathing. During forceful inspiration an accessory inspiratory muscle will be involved ( scaleni , sternocleidomastoid , and others) to increase negativity in the intrathoracic pressure more and more.
 

During forceful expiration the accessory expiratory muscles ( internal intercostal muscles and abdominal muscles ) will be involved to decrease the intrathoracic volume  more and more and then to increase  intrathoracic pressure more and more.

The pressure within the alveoli is called intralveolar  pressure . Between the two phases of respiration it is equal to the atmospheric pressure. It is decreased during inspiration ( about 1 cm H₂O ) and increased during expiration ( about +1 cm H₂O ) . This difference allow entering of 0.5 L of air into the lungs.

Intrapleural pressure is the pressure of thin fluid between the two pleural layers . It is a slight negative pressure. At the beginning of inspiration it is about -5 cm H2O and reachs -7.5 cm H₂O at the end or inspiration.

At the beginning of expiration the intrapleural pressure is -7.5 cm H₂O and reaches -5 cmH₂O at the end of expiration.
The difference between intralveolar pressure and intrapleural pressure is called transpulmonary pressure.

Factors , affecting ventilation :
 

Resistance : Gradual decreasing of the diameter of respiratory airway increase the resistance to air flow.
 

Compliance : means the ease , which the lungs expand.It depends on both the elastic forces of the lungs and the elastic forces , caused by the the surface tension of the fluid, lining the alveoli.
 

Surface tension: Molecules of water have tendency to attract each other on the surface of water adjacent to air. In alveoli the surface tension caused by the fluid in the inner surface of the alveoli  may cause collapse of alveoli . The surface tension is decreased by the surfactant .

Surfactant is a mixture of phospholipids , proteins and ion m produced by type II pneumocytes.

Immature newborns may suffer from respiratory distress syndrome , due to lack of surfactant which is produced during the last trimester of pregnancy.
 

The elastic fibers of the thoracic wall also participate in lung compliance.

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 .

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.

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.