Factors , affecting glomerular filtration rate :

 Factors that may influence the different pressure forces , or the filtration coefficient will affect the glomerular filtration rate . 
 
1. Dehydration : Causes decrease hydrostatic pressure , and thus decreases GFR
2- Liver diseases that may decrease the plasma proteins and decrease the oncotic pressure , and thus increases glomerular filtration rate .
3- Sympathetic stimulation : will decrease the diameter of afferent arteriole and thus decreases glomerular filtration rate.
4- Renal diseases : Nephrotic syndrome for example decreases the number of working nephrons and thus decreases the filtration coefficient and thus decreases the glomerular filtration rate.
Glomerulonephritis will causes thickening of the glomerular basement membrane and thus decreases the glomerular filtration rate by decreasing the filtration coefficient too.

Structure and function of skeletal muscle.

Skeletal muscles have a belly which contains the cells and which attaches by means of tendons or aponeuroses to a bone or other tissue. An aponeurosis is a broad, flat, tendinous attachment, usually along the edge of a muscle. A muscle attaches to an origin and an insertion. The origin is the more fixed attachment, the insertion is the more movable attachment. A muscle acts to shorten, pulling the insertion toward the origin. A muscle can only pull, it cannot push.

Muscles usually come in pairs of antagonistic muscles. The muscle performing the prime movement is the agonist, the opposite acting muscle is the antagonist. When the movement reverses, the names reverse. For example, in flexing the elbow the biceps brachii is the agonist, the triceps brachii is the antagonist. When the movement changes to extension of the elbow, the triceps becomes the agonist and the biceps the antagonist. An antagonist is never totally relaxed. Its function is to provide control and damping of movement by maintaining tone against the agonist. This is called eccentric movement.

Muscles can also act as synergists, working together to perform a movement. This movement can be different from that performed when the muscles work independently. For example, the sternocleidomastoid muscles each rotate the head in a different direction. But as synergists they flex the neck.

Fixators act to keep a part from moving. For example fixators act as postural muscles to keep the spine erect and the leg and vertebral column extended when standing. Fixators such as the rhomboids and levator scapulae keep the scapula from moving during actions such as lifting with the arms.

 Pain, Temperature, and Crude Touch and Pressure

General somatic nociceptors, thermoreceptors, and mechanoreceptors sensitive to crude touch and pressure from the face conduct signals to the brainstem over GSA fibers of cranial nerves V, VII, IX, and X.

The afferent fibers involved are processes of monopolar neurons with cell bodies in the semilunar, geniculate, petrosal, and nodose ganglia, respectively.

The central processes of these neurons enter the spinal tract of V, where they descend through the brainstem for a short distance before terminating in the spinal nucleus of V.

Second-order neurons then cross over the opposite side of the brainstem at various levels to enter the ventral trigeminothalamic tract, where they ascend to the VPM of the thalamus.

Finally, third-order neurons project to the "face" area of the cerebral cortex in areas 3, 1, and 2 .

Discriminating Touch and Pressure

Signals are conducted from general somatic mechanoreceptors over GSA fibers of the trigeminal nerve into the principal sensory nucleus of V, located in the middle pons.

Second-order neurons then conduct the signals to the opposite side of the brainstem, where they ascend in the medial lemniscus to the VPM of the thalamus.

 Thalamic neurons then project to the "face" region of areas 3, I, and 2 of the cerebral cortex.

 Kinesthesia and Subconscious Proprioception

Proprioceptive input from the face is primarily conducted over GSA fibers of the trigeminal nerve.

The peripheral endings of these neurons are the general somatic mechanoreceptors sensitive to both conscious (kinesthetic) and subconscious proprioceptive input.

Their central processes extend from the mesencephalic nucleus to the principal sensory nucleus of V in the pons

The subconscious component is conducted to the cerebellum, while the conscious component travels to the cerebral cortex.

Certain second-order neurons from the principal sensory nucleus relay proprioceptive information concerning subconscious evaluation and integration into the ipsilateral cerebellum.

Other second-order neurons project to the opposite side of the pons and ascend to the VPM of the thalamus as the dorsal trigeminothalamic tract.

Thalamic projections terminate in the face area of the cerebral cortex.

Clinical Physiology 

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) .

DNA (Deoxyribonucleic acid) - controls cell function via transcription and translation (in other words, by controlling protein synthesis in a cell)

Transcription - DNA is used to produce mRNA

Translation - mRNA then moves from the nucleus into the cytoplasm & is used to produce a protein . requires mRNA, tRNA (transfer RNA), amino acids, & a ribosome

tRNA molecule

• sequence of amino acids in a protein is determined by sequence of codons (mRNA). Codons are 'read' by anticodons of tRNAs & tRNAs then 'deliver' their amino acid.
• Amino acids are linked together by peptide bonds (see diagram to the right)
• As mRNA slides through ribosome, codons are exposed in sequence & appropriate amino acids are delivered by tRNAs. The protein (or polypeptide) thus grows in length as more amino acids are delivered.
• The polypeptide chain then 'folds' in various ways to form a complex three-dimensional protein molecule that will serve either as a structural protein or an enzyme.

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 .