Concentration versus diluting urine 

Kidney is a major route for eliminating fluid from the body to accomplish water balance. Urine excretion is the last step in urine formation. Everyday both kidneys excrete about 1.5 liters of urine.
Depending on the hydrated status of the body, kidney either excretes concentrated urine ( if the plasma is hypertonic like in dehydrated status ) or diluted urine ( if the plasma is hypotonic) .
This occurs thankful to what is known as countercurrent multiplying system, which functions thankfully to establishing large vertical osmotic gradient .
To understand this system, lets review the following facts:
1. Descending limb of loop of Henle is avidly permeable to water.
2. Ascending limb of loop of Henly is permeable to electrolytes , but impermeable to water. So fluid will not folow electrolytes by osmosis.and thus Ascending limb creates hypertonic interstitium that will attract water from descending limb.
Pumping of electrolytes
3. So: There is a countercurrent flow produced by the close proximity of the two limbs.                   
                                                   
Juxtamedullary nephrons have long loop of Henle that dips deep in the medulla , so the counter-current system is more obvious and the medullary interstitium is always hypertonic . In addition, peritubular capillaries in the medulla are straigh ( vasa recta) in which flow is rapid and rapidly reabsorb water maintaining hypertonic medullary interstitium.

In distal tubules water is diluted. If plasma is hypertonic, this will lead to release of ADH by hypothalamus, which will cause reabsorption of water in collecting tubules and thus excrete concentrated urine.

If plasma is hypotonic ADH will be inhibited and the diluted urine in distal  tubules will be excreted as diluted urine.

Urea  contributes to concentrating and diluting of urine as follows:

Urea is totally filtered and then 50% of filtrated urea will be reabsorbed to the interstitium, this will increase the osmolarity of medullary interstitium ( becomes hypertonic ). Those 50% will be secreted in ascending limb of loop of Henle back to tubular fluid to maintain osmolarity of tubular fluid. 55% of urea in distal nephron will be reabsorbed in collecting ducts back to the interstitium ( under the effect of ADH too) . This urea cycle additionally maintain hypertonic interstitium.

Membrane Structure & Function

Cell Membranes

• Cell membranes are phospholipid bilayers (2 layers)
• Bilayer forms a barrier to passage of molecules in an out of cell
• Phospholipids = glycerol + 2 fatty acids + polar molecule (i.e., choline) + phosphate
• Cholesterol (another lipid) stabilizes cell membranes
• the hydrophobic tails of the phospholipids (fatty acids) are together in the center of the bilayer. This keeps them out of the water

Membranes Also Contain Proteins

• Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long
• Hydrophobic = doesn't like water = likes lipids
• Membrane proteins have many functions:
  • receptors for hormones
  • pumps for transporting materials across the membrane
  • ion channels
  • adhesion molecules for holding cells to extracellular matrix

cell recognition antigens

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.

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.

The Nervous System Has Peripheral and Central Units

• The central nervous system (CNS) is the brain and spinal column
• The peripheral nervous system (PNS) consists of nerves outside of the CNS
• There are 31 pairs of spinal nerves (mixed motor & sensory)
• There are 12 pairs of cranial nerves (some are pure sensory, but most are mixed)

The pattern of innervation plotted on the skin is called a dermatome

The Nervous System Has Peripheral and Central Units

• The central nervous system (CNS) is the brain and spinal column
• The peripheral nervous system (PNS) consists of nerves outside of the CNS
• There are 31 pairs of spinal nerves (mixed motor & sensory)
• There are 12 pairs of cranial nerves (some are pure sensory, but most are mixed)

The pattern of innervation plotted on the skin is called a dermatome

Blood Pressure

Blood moves through the arteries, arterioles, and capillaries because of the force created by the contraction of the ventricles.

Blood pressure in the arteries.

The surge of blood that occurs at each contraction is transmitted through the elastic walls of the entire arterial system where it can be detected as the pulse. Even during the brief interval when the heart is relaxed — called diastole — there is still pressure in the arteries. When the heart contracts — called systole — the pressure increases.

Blood pressure is expressed as two numbers, e.g., 120/80.

Blood pressure in the capillaries

The pressure of arterial blood is largely dissipated when the blood enters the capillaries. Capillaries are tiny vessels with a diameter just about that of a red blood cell (7.5 µm). Although the diameter of a single capillary is quite small, the number of capillaries supplied by a single arteriole is so great that the total cross-sectional area available for the flow of blood is increased. Therefore, the pressure of the blood as it enters the capillaries decreases.

Blood pressure in the veins

When blood leaves the capillaries and enters the venules and veins, little pressure remains to force it along. Blood in the veins below the heart is helped back up to the heart by the muscle pump. This is simply the squeezing effect of contracting muscles on the veins running through them. One-way flow to the heart is achieved by valves within the veins

Exchanges Between Blood and Cells

With rare exceptions, our blood does not come into direct contact with the cells it nourishes. As blood enters the capillaries surrounding a tissue space, a large fraction of it is filtered into the tissue space. It is this interstitial or extracellular fluid (ECF) that brings to cells all of their requirements and takes away their products. The number and distribution of capillaries is such that probably no cell is ever farther away than 50 µm from a capillary.

When blood enters the arteriole end of a capillary, it is still under pressure produced by the contraction of the ventricle. As a result of this pressure, a substantial amount of water and some plasma proteins filter through the walls of the capillaries into the tissue space.

Thus fluid, called interstitial fluid, is simply blood plasma minus most of the proteins. (It has the same composition and is formed in the same way as the nephric filtrate in kidneys.)

Interstitial fluid bathes the cells in the tissue space and substances in it can enter the cells by diffusion or active transport. Substances, like carbon dioxide, can diffuse out of cells and into the interstitial fluid.

Near the venous end of a capillary, the blood pressure is greatly reduced .Here another force comes into play. Although the composition of interstitial fluid is similar to that of blood plasma, it contains a smaller concentration of proteins than plasma and thus a somewhat greater concentration of water. This difference sets up an osmotic pressure. Although the osmotic pressure is small, it is greater than the blood pressure at the venous end of the capillary. Consequently, the fluid reenters the capillary here.

Control of the Capillary Beds

An adult human has been estimated to have some 60,000 miles of capillaries with a total surface area of some 800–1000 m². The total volume of this system is roughly 5 liters, the same as the total volume of blood. However, if the heart and major vessels are to be kept filled, all the capillaries cannot be filled at once. So a continual redirection of blood from organ to organ takes place in response to the changing needs of the body. During vigorous exercise, for example, capillary beds in the skeletal muscles open at the expense of those in the viscera. The reverse occurs after a heavy meal.

The walls of arterioles are encased in smooth muscle. Constriction of arterioles decreases blood flow into the capillary beds they supply while dilation has the opposite effect. In time of danger or other stress, for example, the arterioles supplying the skeletal muscles will be dilated while the bore of those supplying the digestive organs will decrease. These actions are carried out by

• the autonomic nervous system.
• local controls in the capillary beds