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) .
 

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 .

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.

Excitability ( Bathmotropism ) : Excitability means the ability of cardiac muscle to respond to signals. Here we are talking about contractile muscle cells that are excited by the excitatory conductive system and generate an action potential.

Cardiac action potential is similar to action potential in nerve and skeletal muscle tissue , with one difference , which is the presence of plateau phase . Plateau phase is unique for cardiac muscle cells .
The  resting membrane potential for cardiac muscle is about -80 mV.
When the cardiac muscle is stimulated an action potential is generated . The action potential in cardiac muscle is composed of four phases , which are :

1. Depolarization phase (Phase 0 ) :

A result of opening of sodium channels , which increase the permeability to sodium , which will lead to a rapid sodium influx into the cardiac muscle cell.

2. Repolarization : Repolarization in cardiac muscle is slow and triphasic :

a. Phase 1 (early partial repolarization ) : A small fast repolarization , results from potassium eflux and chloride influx.
b. Phase 2 ( Plateau ) : After the early partial depolarization , the membrane remains  depolarized , exhibiting a plateau , which is a unique phase for the cardiac muscle cell. Plateau is due to opening of slow calcium-sodium channels , delay closure of sodium channels , and to decreased potassium eflux.
c. Phase 3  ( Rapid repolarization) :  opening of potassium channels and rapid eflux of potassium.
d. Phase 4 ( Returning to resting level) in other words : The phase of complete repolarization. This due to the work of sodium-potassium pump.

Absolute refractory period:

Coincides wit phase 0,phase1 , and phase 2 . During this period , excitability of the heart is totally abolished . This prevents tetanization of the cardiac muscle and enables the heart to contract and  relax to be filled by blood ..

Relative refractory period : 

Coincides with the rapid repolarization and allows the excitability to be gradually recovered .
Excitation contraction relationship : Contraction of cardiac muscle starts after depolarization and continues about 1.5 time as long as the duration of the action potential and reaches its maximum at the end of the plateau. Relaxation of the muscle starts with the early partial repolarization.

Factors , affecting excitability of cardiac muscle:

I. Positive bathmotropic effect :

1. Sympathetic stimulation : It increase the heart , and thus reduces the duration of the action potentia; . This will shorten the duration of the absolute refractory period , and thus increase the excitability .
2.  Drugs : Catecholamines and  xanthines derivatives .
3. Mild hypoxia and mild ischemia
4. Mild hyperkalemia as it decreases the K+ efflux and opens excess Na+ channels .
5. Hypocalcemia

II. Negative bathmotropic effect :

1. Parasympathetic stimulation: The negative bathmotropic effect is limited to the atrial muscle excitability , because there is no parasympathetic innervation for the ventricles. Parasympathetic stimulation decreases the heart rate , and thus increases the duration of cardiac action potential and thus increases the duration of the absolute refractory period.
2. moderate to severe hypoxia
3. hyponatremia , hypercalcemia , and severe hyperkalemia.

Clinical Physiology : Extrasystole is a pathological situation , due to abnormal impulses , arising from ectopic focus .It is expressed as an abnormal systole that occur during the early diastole .
Extrasystole  is due to a rising of excitability above the normal , which usually occurs after the end of the relative refractory period ( read about staircase phenomenon of Treppe)

Lung volumes and capacities: 
I. Lung`s volumes
1. Tidal volume (TV) : is the volume of air m which is inspired and expired during one quiet breathing . It equals to 500 ml.
 

2. Inspiratory reserve volume (IRV) : The volume of air that could be inspired over and beyond the tidal volume. It equals to 3000 ml of air.
 

3. Expiratory reserve volume (ERV) : A volume of air that could be forcefully expired after the end of quiet tidal volume. It is about 1100 ml of air.
 

4. Residual volume (RV) : the extra volume of air that may remain in the lung after the forceful expiration . It is about 1200 ml of air.
 

5. Minute volume : the volume of air that is inspired or expired within one minute. It is equal to multiplying of respiratory rate by tidal volume = 12X500= 6000 ml.
It is in female  lesser than that in male.
II. Lung`s capacities :
1. Inspiratory capacity: TV + IRV
2. Vital capacity : TV+IRV+ERV
3. Total lung capacity : TV+IRV+ERV+RV

Respiration occurs in three steps :
1- Mechanical ventilation : inhaling and exhaling of air between lungs and atmosphere.
2- Gas exchange : between pulmonary alveoli and pulmonary capillaries.
3- Transport of gases from the lung to the peripheral tissues , and from the peripheral tissues back to blood .
These steps are well regulated by neural and chemical regulation.

Respiratory tract is subdivided into upper and lower respiratory tract. The upper respiratory tract involves , nose , oropharynx and nasopharynx , while the lower respiratory tract involves larynx , trachea , bronchi ,and lungs .

Nose fulfills three important functions which are :

1. warming of inhaled air .

b. filtration of air .

c. humidification of air .

Pharynx is a muscular tube , which forms a passageway for air and food .During swallowing the epiglottis closes the larynx and the bolus of food falls in the esophagus .

Larynx is a respiratory organ that connects pharynx with trachea . It is composed of many cartilages and muscles and

vocal cords . Its role in respiration is limited to being a conductive passageway for air .

Trachea is a tube composed of C shaped cartilage rings from anterior side, and of muscle (trachealis muscle ) from its posterior side.The rings prevent trachea from collapsing during the inspiration. 

From  the trachea the bronchi are branched into right and left bronchus ( primary bronchi) , which enter the lung .Then they repeatedly branch into secondary and tertiary bronchi and then into terminal and respiratory broncholes.There are about 23 branching levels from the right and left bronchi to the respiratory bronchioles  , the first upper  17 branching are considered as a part of the conductive zones , while the lower 6 are considered to be respiratory zone. 

The cartilaginous component decreases gradually from the trachea to the bronchioles  . Bronchioles are totally composed of smooth muscles ( no cartilage) . With each branching the diameter of bronchi get smaller , the smallest diameter of respiratory passageways is that of respiratory bronchiole. 

Lungs are evolved by pleura . Pleura is composed of two layers : visceral and parietal .
Between the two layers of pleura , there is a pleural cavity , filled with a fluid that decrease the friction between the visceral and parietal pleura.
 

Respiratory muscles : There are two group of respiratory muscles:

1. Inspiratory muscles : diaphragm and external intercostal muscle ( contract during quiet breathing ) , and accessory inspiratory muscles : scaleni , sternocleidomastoid , internal pectoral muscle , and others( contract during forceful inspiration).
 

2. Expiratory muscles : internal intercostal muscles , and abdominal muscles ( contract during forceful expiration)