Glomerular filtration

Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.

The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .

Filtration occurs through the filtration unit , which includes :

1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .

2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .

3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .

Many forces drive the glomerular filtration , which are :

1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .

2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .

3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .

The net pressure is as follows :

Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .

Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.
 

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.

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

GENERAL SOMATIC AFFERENT (GSA) PATHWAYS FROM THE BODY

Pain and Temperature

Pain and temperature information from general somatic receptors is conducted over small-diameter (type A delta and type C) GSA fibers of the spinal nerves into the posterior horn of the spinal cord gray matter .

Fast and Slow Pain

Fast pain, often called sharp or pricking pain, is usually conducted to the CNS over type A delta fibers.

Slow pain, often called burning pain, is conducted to the CNS over smaller-diameter type C fibers.

Touch and Pressure

Touch can be subjectively described as discriminating or crude.

Discriminating (epicritic) touch implies an awareness of an object's shape, texture, three-dimensional qualities, and other fine points. Ability to recognize familiar objects simply by tactile manipulation.

The conscious awareness of body position and movement is called the kinesthetic sens

Crude (protopathic) touch,  lacks the fine discrimination described above and doesn't generally give enough information to the brain to enable it to recognize a familiar object by touch alone.

Subconscious Proprioception

Most of the subconscious proprioceptive input is shunted to the cerebellum.

Posterior Funiculus Injury

Certain clinical signs are associated with injury to the dorsal columns.

 As might be expected, these are generally caused by impairment to the kinesthetic sense and discriminating touch and pressure pathways.

 They include

 (1) the inability to recognize limb position,

 (2) as­tereognosis,

 (3) loss of two-point discrimination,

 (4) loss of vibratory sense, and

 (5) a positive Romberg sign.

Astereognosis is the inability to recognize familiar objects by touch alone. When asked to stand erect with feet together and eyes closed, a person with dorsal column damage may sway and fall. This is a posi­tive Romberg sign.

The large intestine (colon)

The large intestine receives the liquid residue after digestion and absorption are complete. This residue consists mostly of water as well as materials (e.g. cellulose) that were not digested. It nourishes a large population of bacteria (the contents of the small intestine are normally sterile). Most of these bacteria (of which one common species is E. coli) are harmless. And some are actually helpful, for example, by synthesizing vitamin K. Bacteria flourish to such an extent that as much as 50% of the dry weight of the feces may consist of bacterial cells. Reabsorption of water is the chief function of the large intestine. The large amounts of water secreted into the stomach and small intestine by the various digestive glands must be reclaimed to avoid dehydration.

1.Rhythmicity ( Chronotropism ) :  means the ability of heart to beat regularly ( due to repetitive and stable depolarization and repolarization )  . Rhythmicity of heart is a myogenic in origin , because cardiac muscles are automatically excited muscles and does not depend on the nervous stimulus to initiate excitation and then contraction . The role of nerves is limited to the regulation of the heart rate and not to initiate the beat.

There are many evidences that approve the myogenic and not neurogenic origin of the rhythmicity of cardiac muscle . For example :
-  transplanted heart continues to beat regularly without any nerve supply.
-  Embryologically the heart starts to beat before reaching any nerves to them.
-  Some drugs that paralyze the nerves ( such as cocaine ) do not stop the heart in given doses.

Spontaneous rhythmicity of the cardiac muscle due to the existence of excitatory - conductive system , which is composed of self- exciting non-contractile cardiac muscle cells . The SA node of the mentioned system excites in a rate , that is the most rapid among the other components of the system ( 110 beats /minute ) , which makes it the controller or ( the pacemaker ) of the cardiac rhythm of the entire heart.

Mechanism , responsible for self- excitation in the SA node and the excitatory conductive system  is due to the following properties of the cell membrane of theses cells :
1- Non-gated sodium channels
2- Decreased permeability to potassium
3- existence of slow and fast calcium channels.

These properties enable the cations ( sodium through the none-gated sodium voltage channels , calcium through calcium slow channels) to enter the cell and depolarize the cell membrane without need for external stimulus.

The resting membrane potential of non-contractile cardiac cell is -55 - -60 millivolts ( less than that of excitable nerve cells (-70) ) . 

The threshold is also less negative than that of nerve cells ( -40 millivolts ).

The decreased permeability to potassium from its side decrease the eflux  of potassium during the repolarization phase of the pacemaker potential . All of these factors give the pacemaker potential its characteristic shape

Repeating of the pacemaker potential between the action potentials of contractile muscle cells is the cause of spontaneous rhythmicity of cardiac muscle cells.

Factors , affecting the rhythmicity of the cardiac muscle :

I. Factors that increase the rate ( positive chronotropic factors) :
1. sympathetic stimulation : as its neurotransmitter norepinephrine increases the membrane permeability to sodium and calcium.
2. moderate warming : moderate warming increases temperature by 10 beats for each 1 Fahrenheit degree increase in body temperature, this due to decrease in permeability to potassium ions in pacemaker membrane by moderate increase in temperature.
3. Catecholaminic drugs have positive chronotropic effect.
4. Thyroid hormones : have positive chronotropic effect , due to the fact that these drugs increase the sensitivity of adrenergic receptors to adrenaline and noreadrenaline .
5. mild hypoxia.
6. mild alkalemia : mild alkalemia decreases the negativity of the resting potential.
7. hypocalcemia.
8. mild hypokalemia

II. Factors that decrease rhythmicity ( negative chronotropic):

1.Vagal stimulation : the basal level of vagal stimulation inhibits the sinus rhythm and decrease it from 110-75 beats/ minute. This effect due to increasing the permeability of the cardiac muscle cell to potassium , which causes rapid potassium eflux , which increases the negativity inside the cardiac cells (hyperpolarization ).
2. moderate cooling
3. severe warming : due to cardiac damage , as a result of intercellular protein denaturation. Excessive cooling on the other hand decrease metabolism and stops rhythmicity.
4. Cholenergic drugs ( such as methacholine , pilocarpine..etc) have negative chronotropic effect.
5. Digitalis : these drugs causes hyperpolarization . This effect is similar to that of vagal stimulation.
6. Hypercapnia ( excessive CO2 production )
7. Acidemia.
8. hyper- and hyponatremia .
9. hyperkalemia
10. hypercalcemia
11. Typhoid or diphteria toxins.