Asthma = Reversible Bronchioconstruction 4%-5% of population
    Extrinsic / Atopic = Allergic, inherited (familia), chromosome 11
    IgE, Chemical Mediators of inflammation
    
a.    Intrinsic = Negative for Allergy, Normal IgE, Negative Allergic Tests

    Nucleotide Imbalance cAMP/cGMP: cAMP = Inhibits mediator release, cGMP = Facilitates mediator release
b.    Intolerance to Asprin (Triad Asthma)
c.    Nasal Polyps & Asthma

d.    Treatment cause, Symptoms in Acute Asthma
    1.    Bronchial dilators
    2.    steroids edema from Inflamation
    3.    Bronchiohygene to prevent Secondary Infection, (Remove Excess Mucus)
    4.    Education

Hypoxia

• Hypoxia is tissue oxygen deficiency
• Brain is the most sensitive tissue to hypoxia: complete lack of oxygen can cause unconsciousness in 15 sec and irreversible damage within 2 min.
• Oxygen delivery and use can be interrupted at several sites

• Causes:
  • Hypoxic: high altitude, pulmonary edema, hypoventilation, emphysema, collapsed lung
  • Anemic: iron deficiency, hemoglobin mutations, carbon monoxide poisoning
  • Ischemic: shock, heart failure, embolism
  • Histotoxic: cyanide poisoning (inhibits mitochondria)

• Carbon monoxide (CO) poisoning:
  • CO binds to the same heme Fe atoms that O₂ binds to
  • CO displaces oxygen from hemoglobin because it has a 200X greater affinity for hemoglobin.
  • Treatment for CO poisoning: move victim to fresh air. Breathing pure O₂ can give faster removal of CO

• Cyanide poisoning:
  • Cyanide inhibits the cytochrome oxidase enzyme of mitochondria
  • Two step treatment for cyanide poisoning:
    • 1) Give nitrites
      • Nitrites convert some hemoglobin to methemoglobin. Methemoglobin pulls cyanide away from mitochondria.
    • 2) Give thiosulfate.
      • Thiosulfate converts the cyanide to less poisonous thiocyanate.

Urine is a waste byproduct formed from excess water and metabolic waste molecules during the process of renal system filtration. The primary function of the renal system is to regulate blood volume and plasma osmolarity, and waste removal via urine is essentially a convenient way that the body performs many functions using one process. Urine formation occurs during three processes:

Filtration

Reabsorption

Secretion

Filtration

During filtration, blood enters the afferent arteriole and flows into the glomerulus where filterable blood components, such as water and nitrogenous waste, will move towards the inside of the glomerulus, and nonfilterable components, such as cells and serum albumins, will exit via the efferent arteriole. These filterable components accumulate in the glomerulus to form the glomerular filtrate.

Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys to undergo filtration; this is called the filtration fraction. The remaining 80% of the blood flows through the rest of the body to facilitate tissue perfusion and gas exchange.

Reabsorption

The next step is reabsorption, during which molecules and ions will be reabsorbed into the circulatory system. The fluid passes through the components of the nephron (the proximal/distal convoluted tubules, loop of Henle, the collecting duct) as water and ions are removed as the fluid osmolarity (ion concentration) changes. In the collecting duct, secretion will occur before the fluid leaves the ureter in the form of urine.

Secretion

During secretion some substances±such as hydrogen ions, creatinine, and drugs—will be removed from the blood through the peritubular capillary network into the collecting duct. The end product of all these processes is urine, which is essentially a collection of substances that has not been reabsorbed during glomerular filtration or tubular reabsorbtion.

Phases of cardiac cycle :

1. Early diastole ( also called the atrial diastole , or complete heart diastole) : During this phase :

- Atria are  relaxed
- Ventricles are relaxed
- Semilunar valves are closed
- Atrioventricular valves are open
During this phase the blood moves passively from the venous system into the ventricles ( about 80 % of blood fills the ventricles during this phase.

2. Atrial systole : During this phase :

- Atria are contracting
- Ventricles are relaxed
- AV valves are open
- Semilunar valves are closed
- Atrial pressure increases.the a wave of atrial pressure appears here.
- P wave of ECG starts here
- intraventricular pressure increases due to the rush of blood then decrease due to continuous relaxation of ventricles.

The remaining 20% of blood is moved to fill the ventricles during this phase , due to atrial contraction.

3. Isovolumetric contraction : During this phase :

- Atria are relaxed
- Ventricles are contracting
- AV valves are closed
- Semilunar valves are closed
- First heart sound
- QRS complex.
The ventricular fibers start to contract during this phase , and the intraventricular pressure increases. This result in closing the AV valves , but the pressure is not yet enough to open the semilunar valves , so the blood volume remain unchanged , and the muscle fibers length also remain unchanged , so we call this phase as isovolumetric contraction ( iso : the same , volu= volume , metric= length).

4. Ejection phase : Blood is ejected from the ventricles into the aorta and pulmonary artery .

During this phase :

- Ventricles are contracting
- Atria are relaxed
- AV valves are closed
- Semilunar valves are open
- First heart sound
- Intraventricular pressure is increased , due to continuous contraction
- increased aortic pressure .
- T wave starts.

5. Isovolumetric relaxation:  This phase due to backflow of blood in aorta and pulmonary system after the ventricular contraction is up and the ventricles relax . This backflow closes the semilunar valves .

During this phase :

- Ventricles are relaxed
- Atrial are relaxed
- Semilunar valves are closed .
- AV valves are closed.
- Ventricular pressure fails rapidly
- Atrial pressure increases due to to continuous venous return. the v wave appears here. 
- Aortic pressure : initial sharp decrease due to sudden closure of the semilunar valve ( diacrotic notch) , followed by secondary rise in pressure , due to elastic recoil of the aorta ( diacrotic wave)  .
- T wave ends in this phase

Transport of Carbon Dioxide

A.    Dissolved in Blood Plasma (7-10%)

B.    Bound to Hemoglobin (20-30%)

1.    carbaminohemoglobin - Carb Dioxide binds to an amino acid on the polypeptide chains

2.    Haldane Effect - the less oxygenated blood is, the more Carb Diox it can carry

a.    tissues - as Oxygen is unloaded, affinity for Carb Dioxide increases
b.    lungs - as Oxygen is loaded, affinity for Carb Dioxide decreases, allowing it to be released

C.    Bicarbonate Ion Form in Plasma (60-70%)

1.    Carbon Dioxide combines with water to form Bicarbonate

CO₂ + H₂O <==> H₂CO₃ <==> H⁺ + HCO₃-

2.    carbonic anhydrase - enzyme in RBCs that catalyzes this reaction in both directions

a.    tissues - catalyzes formation of Bicarbonate
b.    lungs - catalyzes formation of Carb Dioxide

3.    Bohr Effect - formation of Bicarbonate (through Carbonic Acid) leads to LOWER pH (H+ increase), and more unloading of Oxygen to tissues

a.    since hemoglobin "buffers" to H⁺, the actual pH of blood does not change much

4.    Chloride Shift - chloride ions move in opposite direction of the entering/leaving Bicarbonate, to prevent osmotic problems with RBCs

D.    Carbon Dioxide Effects on Blood pH

1.    carbonic acid-bicarbonate buffer system
    
low pH       → HCO₃- binds to H⁺
high pH     →   H₂CO₃ releases H⁺
    
2.     low shallow breaths    → HIGH Carb Dioxide    → LOW pH (higher H⁺)
3.     rapid deep breaths     → LOW Carb Dioxide   → HIGH pH (lower H⁺)

Contractility : Means ability of cardiac muscle to convert electrical energy of action potential into mechanical energy ( work).
The excitation- contraction coupling of cardiac muscle is similar to that of skeletal muscle , except the lack of motor nerve stimulation. 

Cardiac muscle is a self-excited muscle , but the principles of contraction are the same . There are many rules that control the contractility of the cardiac muscles, which are:

1. All or none rule: due to the syncytial nature of the cardiac muscle.There are atrial syncytium and ventricular syncytium . This rule makes the heart an efficient pump.

2. Staircase phenomenon : means gradual increase in muscle contraction following rapidly repeated stimulation..

3. Starling`s law of the heart: The greater the initial length of cardiac muscle fiber , the greater the force of contraction. The initial length is determined by the degree of diastolic filling .The pericardium prevents overstretching of heart , and allows optimal increase in diastolic volume.

Thankful to this law , the heart is able to pump any amount of blood that it receives. But overstretching of cardiac muscle fibers may cause heart failure.

Factors affecting  contractility ( inotropism)

I. Positive inotropic factors:

1. sympathetic stimulation: by increasing the permeability of sarcolemma to calcium.
2. moderate increase in temperature . This due to increase metabolism to increase ATP , decrease viscosity of myocardial structures, and increasing calcium influx.
3. Catecholamines , thyroid hormone, and glucagon hormones.
4. mild alkalosis
5. digitalis
6. Xanthines ( caffeine and theophylline )

II. Negative inotropic factors:

1. Parasympathetic stimulation : ( limited to atrial contraction)
2. Acidosis
3. Severe alkalosis
4. excessive warming and cooling .
5. Drugs ;like : Quinidine , Procainamide , and barbiturates .
6. Diphtheria and typhoid toxins.