Physiology - science that describes how organisms FUNCTION and survive in continually changing environments  

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.

Abnormalities of Salt, Water or pH

• Examples:
  • Hyperkalemia: caused by kidney disease & medical malpractice
    • High K+ in blood- can stop the heart in contraction (systole)
  • Dehydration: walking in desert- can lose 1-2 liters/hour through sweat
    • Blood becomes too viscous to circulate well -> loss of temperature regulation -> hyperthermia, death
  • Acidosis: many causes including diabetes mellitus and respiratory problems; can cause coma, death

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.

Functions of the nervous system:

1) Integration of body processes

2) Control of voluntary effectors (skeletal muscles), and mediation of voluntary reflexes.

3) Control of involuntary effectors (  smooth muscle, cardiac muscle, glands) and mediation of autonomic reflexes (heart rate, blood pressure, glandular secretion, etc.)

4) Response to stimuli

5) Responsible for conscious thought and perception, emotions, personality, the mind.

Neurophysiology

Transmission of an action potential. This occurs in two ways:

1) across the synapse - synaptic transmission. This is a chemical process, the result of a chemical neurotransmitter.

2) along the axon - membrane transmission. This is the propagation of the action potential itself along the membrane of the axon.

Synaptic transmission - What you learned about the neuromuscular junction is mostly applicable here as well. The major differences in our current discussion are:

1) Transmission across the synapse does not necessarily result in an action potential. Instead, small local potentials are produced which must add together in summation to produce an action potential.

2) Although ACh is a common neurotransmitter, there are many others and the exact effect at the synapse depends on the neurotransmitter involved.

3) Neurotransmitters can be excitatory or inhibitory. The result might be to turn off the next neuron rather than to produce an action potential

The basic steps of synaptic transmission are the same as described at the neuromuscular junction

1) Impulse arrives at the axon terminus causing opening of Ca²⁺ channels and allows Ca²⁺  to enter the axon. The calcium ions are in the extracellular fluid, pumped there much like sodium is pumped. Calcium is just an intermediate in both neuromuscular and synaptic transmission.

2) Ca²⁺  causes vesicles containing neurotransmitter to release the chemical into the synapse by exocytosis across the pre-synaptic membrane.

3) The neurotransmitter binds to the post-synaptic receptors. These receptors are linked to chemically gated ion channels and these channels may open or close as a result of binding to the receptors to cause a graded potential which can be either depolarization, or hyperpolarization depending on the transmitter. Depolarization results from opening of Na⁺ gates and is called an EPSP. Hyperpolarization could result from opening of K⁺ gates and is called IPSP. 

4) Graded potentials spread and overlap and can summate to produce a threshold depolarization and an action potential when they stimulate voltage gated ion channels in the neuron's trigger region.

5) The neurotransmitter is broken down or removed from the synapse in order for the receptors to receive the next stimulus. As we learned there are enzymes for some neurotransmitters such as the Ach-E which breaks down acetylcholine. Monoamine oxidase (MAO) is an enzyme which breaks down the catecholamines (epinephrine, nor-epinephrine, dopamine) and nor-epinephrine (which is an important autonomic neurotransmitter) is removed by the axon as well in a process known as reuptake. Other transmitters may just diffuse away.

Graded Potentials - these are small, local depolarizations or hyperpolarizations which can spread and summate to produce a threshold depolarization. Small because they are less than that needed for threshold in the case of the depolarizing variety. Local means they only spread a few mm on the membrane and decline in intensity with increased distance from the point of the stimulus. The depolarizations are called EPSPs, excitatory post-synaptic potentials, because they tend to lead to an action potential which excites or turns the post-synaptic neuron on. Hyperpolarizations are called IPSPs, inhibitory post-synaptic potentials, because they tend to inhibit an action potential and thus turn the neuron off.

Summation - the EPSPs and IPSPs will add together to produce a net depolarization (or hyperpolarization).

Temporal summation- this is analogous to the frequency (wave, tetany) summation discussed for muscle. Many EPSPs occurring in a short period of time (e.g. with high frequency) can summate to produce threshold depolarization. This occurs when high intensity stimulus results in a high frequency of EPSPs.

Spatial summation - this is analogous to quantal summation in a muscle. It means that there are many stimuli occurring simultaneously. Their depolarizations spread and overlap and can build on one another to sum and produce threshold depolarization.

Inhibition - When the brain causes an IPSP in advance of a reflex pathway being stimulated, it reduces the likelihood of the reflex occurring by increasing the depolarization required. The pathway can still work, but only with more than the usual number or degree of stimulation. We inhibit reflexes when allowing ourselves to be given an injection or blood test for instance.

Facilitation - When the brain causes an EPSP in advance of a reflex pathway being stimulated, it makes the reflex more likely to occur, requiring less additional stimulation. When we anticipate a stimulus we often facilitate the reflex.

Learned Reflexes - Many athletic and other routine activities involve learned reflexes. These are reflex pathways facilitated by the brain. We learn the pathways by performing them over and over again and they become facilitated. This is how we can perfect our athletic performance, but only if we learn and practice them correctly. It is difficult to "unlearn" improper techniques once they are established reflexes. Like "riding a bike" they may stay with you for your entire life!

Post-tetanic potentiation - This occurs when we perform a rote task or other repetitive action. At first we may be clumsy at it, but after continuous use (post-tetanic) we become more efficient at it (potentiation). These actions may eventually become learned reflexes

The Action Potential

The trigger region of a neuron is the region where the voltage gated channels begin. When summation results in threshold depolarization in the trigger region of a neuron, an action potential is produced. There are both sodium and potassium channels. Each sodium channel has an activation gate and an inactivation gate, while potassium channels have only one gate. 

A) At the resting state the sodium activation gates are closed, sodium inactivation gates are open, and potassium gates are closed. Resting membrane potential is at around -70 mv inside the cell. 

B) Depolarizing phase: The action potential begins with the activation gates of the sodium channels opening, allowing Na+ ions to enter the cell and causing a sudden depolarization which leads to the spike of the action potential. Excess Na+ ions enter the cell causing reversal of potential becoming briefly more positive on the inside of the cell membrane.

C) Repolarizing phase: The sodium inactivation gates close and potassium gates open. This causes Na+ ions to stop entering the cell and  K+ ions  to leave the cell, causing repolarization. Until the membrane is repolarized it cannot be stimulated, called the absolute refractory period.

D) Excess potassium leaves the cell causing a brief hyperpolarization. Sodium activation gates close and potassium gates begin closing. The sodium-potassium pump begins to re-establish the resting membrane potential. During hyperpolarization the membrane can be stimulated but only with a greater than normal depolarization, the relative refractory period.

Action potentials are self-propagated, and once started the action potential progresses along the axon membrane. It is all-or-none, that is there are not different degrees of action potentials. You either have one or you don't.