The bulk of the pancreas is an exocrine gland secreting pancreatic fluid into the duodenum after a meal. However, scattered through the pancreas are several hundred thousand clusters of cells called islets of Langerhans. The islets are endocrine tissue containing four types of cells. In order of abundance, they are the:

• beta cells, which secrete insulin and amylin;
• alpha cells, which secrete glucagon;
• delta cells, which secrete somatostatin, and
• gamma cells, which secrete a polypeptide of unknown function.

Beta Cells

Beta cells secrete insulin in response to a rising level of blood sugar

Insulin affects many organs. It

• stimulates skeletal muscle fibers to
  • take up glucose and convert it into glycogen;
  • take up amino acids from the blood and convert them into protein.
• acts on liver cells
  • stimulating them to take up glucose from the blood and convert it into glycogen while
  • inhibiting production of the enzymes involved in breaking glycogen back down (glycogenolysis) and
  • inhibiting gluconeogenesis; that is, the conversion of fats and proteins into glucose.
• acts on fat (adipose) cells to stimulate the uptake of glucose and the synthesis of fat.
• acts on cells in the hypothalamus to reduce appetite.

Diabetes Mellitus

Diabetes mellitus is an endocrine disorder characterized by many signs and symptoms. Primary among these are:

• a failure of the kidney to retain glucose .
• a resulting increase in the volume of urine because of the osmotic effect of this glucose (it reduces the return of water to the blood).

There are three categories of diabetes mellitus:

• Insulin-Dependent Diabetes Mellitus (IDDM) (Type 1) and
• Non Insulin-Dependent Diabetes Mellitus (NIDDM)(Type 2)
• Inherited Forms of Diabetes Mellitus

Insulin-Dependent Diabetes Mellitus (IDDM)

IDDM ( Type 1 diabetes)

• is characterized by little or no circulating insulin;
• most commonly appears in childhood.
• It results from destruction of the beta cells of the islets.
• The destruction results from a cell-mediated autoimmune attack against the beta cells.
• What triggers this attack is still a mystery, although a prior viral infection may be the culprit.

Non Insulin-Dependent Diabetes Mellitus (NIDDM)

Many people develop diabetes mellitus without an accompanying drop in insulin levels In many cases, the problem appears to be a failure to express a sufficient number of glucose transporters in the plasma membrane (and T-system) of their skeletal muscles. Normally when insulin binds to its receptor on the cell surface, it initiates a chain of events that leads to the insertion in the plasma membrane of increased numbers of a transmembrane glucose transporter. This transporter forms a channel that permits the facilitated diffusion of glucose into the cell. Skeletal muscle is the major "sink" for removing excess glucose from the blood (and converting it into glycogen). In NIDDM, the patient's ability to remove glucose from the blood and convert it into glycogen is reduced. This is called insulin resistance. NIDDM (also called Type 2 diabetes mellitus) usually occurs in adults and, particularly often, in overweight people.

Alpha Cells

The alpha cells of the islets secrete glucagon, a polypeptide of 29 amino acids. Glucagon acts principally on the liver where it stimulates the conversion of glycogen into glucose (glycogenolysis) which is deposited in the blood.

Glucagon secretion is

• stimulated by low levels of glucose in the blood;
• inhibited by high levels, and
• inhibited by amylin.

The physiological significance of this is that glucagon functions to maintain a steady level of blood sugar level between meals.

Delta Cells

The delta cells secrete somatostatin. Somatostatin has a variety of functions. Taken together, they work to reduce the rate at which food is absorbed from the contents of the intestine. Somatostatin is also secreted by the hypothalamus and by the intestine.

Gamma Cells

The gamma cells of the islets secrete pancreatic polypeptide. No function has yet been found for this peptide of 36 amino acids.

Regulation of glomerular filtration :

1. Extrinsic regulation : 

- Neural regulation : sympathetic and parasympathetic nervous system which causes vasoconstriction or vasodilation respectively .
- Humoral regulation : Vasoactive substances may affect the GFR , vasoconstrictive substances like endothelin ,Angiotensin II , Norepinephrine , prostaglandine F2 may constrict the afferent arteriole and thus decrease GFR , while the vasodilative agents like dopamine , NO , ANP , Prostaglandines E2 may dilate the afferent arteriole and thus increase the filtration rate .

2. Intrinsic regulation : 

- Myogenic theory ( as in the intrinsic regulation of cardiac output) .
- Tubuloglomerular feedback: occurs by cells of the juxtaglomerular apparatus that is composed of specific cells of the distal tubules when it passes between afferent and efferent arterioles ( macula densa cells ) , these cells sense changes in flow inside the tubules and inform specific cells in the afferent arteriole (granular cells ) , the later secrete vasoactive substances that affect the diameter of the afferent arteriole.

SPECIAL SOMATIC AFFERENT (SSA) PATHWAYS

Hearing

The organ of Corti with its sound-sensitive hair cells and basilar membrane are important parts of the sound transducing system for hearing. Mechanical vibrations of the basilar membrane generate membrane potentials in the hair cells which produce impulse patterns in the cochlear portion of the vestibulocochlear nerve (VIII)

Special somatic nerve fibers of cranial nerve VIII relay impulses from the sound receptors (hair cells) in the cochlear nuclei of the brainstem

These are bipolar neurons with cell bodies located in the spiral ganglia of the cochlea.

Vestibular System

The vestibulocochlear nerve serves two quite different functions.

The cochlear portion, conducts sound information to the brain,

The vestibular portion conducts proprioceptive information.

It is the central neural pathways

Special somatic afferent fibers from the hair cells of the macula utriculi and macula sacculi conduct information into the vestibular nuclei on the ipsilateral side of the pons and medulla.

These are bipolar neurons with cell bodies located in the vestibular ganglion.

 Some of the fibers project directly into the ipsilateral cerebellum to terminate in the uvula, flocculus, and nodulus, but most enter the vestibular nuclei and synapse there.

Vision

The visual system receptors are the rods and cones of the retina.

Special somatic afferent fibers of the optic nerve (II) conduct visual signals into the brain

Fibers from the lateral (temporal) retina of either eye terminate in the lateral geniculate body on the same side of the brain as that eye.

SSA II fibers from the medial (nasal) retina of each eye cross over in the optic chiasm to terminate in the contralateral lateral geniculate body.

Area 17 is the primary visual area, which receives initial visual signals.

Neurons from this area project into the adjacent occipital cortex (areas 18 and 19) which is known as the secondary visual area. It is here that the visual signal is fully evaluated.

The visual reflex pathway involving the pupillary light reflex - in which the pupils constrict when a light is shined into the eyes and dilate when the light is removed.

Some SSA II fibers leave the optic tract before reaching the lateral geniculates, terminating in the superior colliculi instead.

From here, short neurons project to the Edinger­Westphal nucleus (an accessory nucleus of III) in the midbrain, which serves as the origin of the preganglionic parasympathetic fibers of the oculomotor nerve (GVE III).

The GVE III fibers in turn project to the ciliary ganglia, from which arise the postganglionic fibers to the sphincter muscles of the iris, which constrict the pupils.

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) .

Vital Capacity: The vital capacity (VC) is the maximum volume which can be ventilated in a single breath. VC= IRV+TV+ERV. VC varies with gender, age, and body build. Measuring VC gives a device for diagnosis of respiratory disorder, and a benchmark for judging the effectiveness of treatment. (4600 ml)

Vital Capacity is reduced in restrictive disorders, but not in disorders which are purely obstructive.

The FEV₁ is the % of the vital capacity which is expelled in the first second. It should be at least 75%. The FEV₁ is reduced in obstructive disorders.

Both VC and the FEV₁ are reduced in disorders which are both restrictive and obstructive

Oxygen is present at nearly 21% of ambient air. Multiplying .21 times 760 mmHg (standard pressure at sea level) yields a pO₂ of about 160. Carbon dioxide is .04% of air and its partial pressure, pCO₂, is .3.

With alveolar air having a pO₂ of 104 and a pCO₂ of 40. So oxygen diffuses into the alveoli from inspired air and carbon dioxide diffuses from the alveoli into air which will be expired. This causes the levels of oxygen and carbon dioxide to be intermediate in expired air when compared to inspired air and alveolar air. Some oxygen has been lost to the alveolus, lowering its level to 120, carbon dioxide has been gained from the alveolus raising its level to 27.

Likewise a concentration gradient causes oxygen to diffuse into the blood from the alveoli and carbon dioxide to leave the blood. This produces the levels seen in oxygenated blood in the body. When this blood reaches the systemic tissues the reverse process occurs restoring levels seen in deoxygenated blood.

The Stomach :

The wall of the stomach is lined with millions of gastric glands, which together secrete 400–800 ml of gastric juice at each meal. Three kinds of cells are found in the gastric glands

• parietal cells
• chief cells
• mucus-secreting cells

Parietal cells : secrete

Hydrochloric acid : Parietal cells contain a H⁺ ATPase. This transmembrane protein secretes H⁺ ions (protons) by active transport, using the energy of ATP.

Intrinsic factor: Intrinsic factor is a protein that binds ingested vitamin B₁₂ and enables it to be absorbed by the intestine. A deficiency of intrinsic factor  as a result of an autoimmune attack against parietal cells  causes pernicious anemia.

Chief Cells : The chief cells synthesize and secrete pepsinogen, the precursor to the proteolytic enzyme pepsin.

Secretion by the gastric glands is stimulated by the hormone gastrin. Gastrin is released by endocrine cells in the stomach in response to the arrival of food.