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Physiology

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.

Heart sounds


Heart sounds are a result of beating heart and resultant blood flow . that could be detected by a stethoscope during auscultation . Auscultation is a part of physical examination that doctors have to practice them perfectly.
Before discussion the origin and nature of the heart sounds we have to distinguish between the heart sounds and hurt murmurs. Heart murmurs are pathological noises that results from abnormal blood flow in the heart or blood vessels.
Physiologically , blood flow has a laminar pattern , which means that blood flows in form of layers , where the central layer is the most rapid . Laminar blood flow could be turned into turbulent one .

Turbulent blood flow is a result of stenotic ( narrowed ) valves or blood vessels , insufficient valves , roughened vessels` wall or endocardium ,  and many diseases . The turbulent blood flow causes noisy murmurs inside or outside the heart.

Heart sounds ( especially first and second sounds ) are mainly a result of closure of the valves of the heart . While the third sound is a result of vibration of ventricular wall and the leaflets of the opened AV valves after rapid inflow of blood from the atria to ventricles . 

Third heart sound is physiologic in children but pathological in adults.

The four heart sound is a result of the atrial systole and vibration of the AV valves , due to blood rush during atrial systole . It is inaudible neither in adults nor in children . It is just detectable by the phonocardiogram .


Characteristic of heart sounds :

1. First heart sound  (S1 , lub ) : a soft and low pitch sound, caused by closure of AV valves.Usually has two components ( M1( mitral ) and T1 ( tricuspid ). Normally M1 preceads T1.

2. Second heart sound ( S2 , dub) : sharp and high pitch sound . caused by closure of semilunar valves. It also has two components A2 ( aortic) and P2 ( pulmonary) . A2 preceads P2.

3. Third heart sound (S3) : low pitched sound.

4. Fourth heart sound ( S4) very low pitched sound.

As we notice : the first three sounds are related to ventricular activity , while the fourth heart sound is related to atrial activity.
Closure of valves is not the direct cause for heart sounds , but sharp blocking of blood of backward returning of blood by the closing valve is the direct cause.
 

Graded Contractions and Muscle Metabolism

The muscle twitch is a single response to a single stimulus. Muscle twitches vary in length according to the type of muscle cells involved. .

 

Fast twitch muscles such as those which move the eyeball have twitches which reach maximum contraction in 3 to 5 ms (milliseconds).  [superior eye] and [lateral eye] These muscles were mentioned earlier as also having small numbers of cells in their motor units for precise control.

The cells in slow twitch muscles like the postural muscles (e.g. back muscles, soleus) have twitches which reach maximum tension in 40 ms or so.

 The muscles which exhibit most of our body movements have intermediate twitch lengths of 10 to 20 ms.

The latent period, the period of a few ms encompassing the chemical and physical events preceding actual contraction.

This is not the same as the absolute refractory period, the even briefer period when the sarcolemma is depolarized and cannot be stimulated. The relative refractory period occurs after this when the sarcolemma is briefly hyperpolarized and requires a greater than normal stimulus

Following the latent period is the contraction phase in which the shortening of the sarcomeres and cells occurs. Then comes the relaxation phase, a longer period because it is passive, the result of recoil due to the series elastic elements of the muscle.

We do not use the muscle twitch as part of our normal muscle responses. Instead we use graded contractions, contractions of whole muscles which can vary in terms of their strength and degree of contraction. In fact, even relaxed muscles are constantly being stimulated to produce muscle tone, the minimal graded contraction possible.

Muscles exhibit graded contractions in two ways:

1) Quantal Summation or Recruitment - this refers to increasing the number of cells contracting. This is done experimentally by increasing the voltage used to stimulate a muscle, thus reaching the thresholds of more and more cells. In the human body quantal summation is accomplished by the nervous system, stimulating increasing numbers of cells or motor units to increase the force of contraction.

2) Wave Summation ( frequency summation) and Tetanization- this results from stimulating a muscle cell before it has relaxed from a previous stimulus. This is possible because the contraction and relaxation phases are much longer than the refractory period. This causes the contractions to build on one another producing a wave pattern or, if the stimuli are high frequency, a sustained contraction called tetany or tetanus. (The term tetanus is also used for an illness caused by a bacterial toxin which causes contracture of the skeletal muscles.) This form of tetanus is perfectly normal and in fact is the way you maintain a sustained contraction.

Treppe is not a way muscles exhibit graded contractions. It is a warmup phenomenon in which when muscle cells are initially stimulated when cold, they will exhibit gradually increasing responses until they have warmed up. The phenomenon is due to the increasing efficiency of the ion gates as they are repeatedly stimulated. Treppe can be differentiated from quantal summation because the strength of stimulus remains the same in treppe, but increases in quantal summation

Length-Tension Relationship: Another way in which the tension of a muscle can vary is due to the length-tension relationship. This relationship expresses the characteristic that within about 10% the resting length of the muscle, the tension the muscle exerts is maximum. At lengths above or below this optimum length the tension decreases.

Oxygen Uptake in the Lungs is Increased About 70X by Hemoglobin in the Red Cells

  • In the lungs oxygen must enter the blood
  • A small amount of oxygen dissolves directly in the serum, but 98.5% of the oxygen is carried by hemoglobin
  • All of the hemoglobin is found within the red blood cells (RBCs or erythrocytes)
  • The hemoglobin content of the blood is about 15 gm/deciliter (deciliter = 100 mL)
  • Red cell count is about 5 million per microliter

Each Hemoglobin Can Bind Four O2 Molecules (100% Saturation)

  • Hemoglobin is a protein molecule with 4 protein sub-units (2 alphas and 2 betas)
    • Each of the 4 sub-units contains a heme group which gives the protein a red color
    • Each heme has an iron atom in the center which can bind an oxygen molecule (O2)
    • The 4 hemes in a hemoglobin can carry a maximum of 4 oxygen molecules
  • When hemoglobin is saturated with oxygen it has a bright red color; as it loses oxygen it becomes bluish (cyanosis)

The Normal Blood Hematocrit is Just Below 50%

  • Blood consists of cells suspended in serum
  • More than 99% of the cells in the blood are red blood cells designed to carry oxygen
    • 25% of all the cells in the body are RBCs
  • The volume percentage of cells in the blood is called the hematocrit
  • Normal hematocrits are about 40% for women and 45% for men

At Sea Level the Partial Pressure of O2 is High Enough to Give Nearly 100% Saturation of Hemoglobin

  • As the partial pressure of oxygen in the alveoli increases the hemoglobin in the red cells passing through the lungs rises until the hemoglobin is 100% saturated with oxygen
    • At 100% saturation each hemoglobin carries 4 O2 molecules
    • This is equal to 1.33 mL O2 per gram of hemoglobin
  • A person with 15 gm Hb/deciliter can carry:
    • Max O2 carriage = 1.33 mL O2/gm X 15 gm/deciliter = 20 mL O2/deciliter
  • A plot of % saturation vs pO2 gives an S-shaped "hemoglobin dissociation curve"
  • At 100% saturation each hemoglobin binds 4 oxygen molecules

At High Altitudes Hemoglobin Saturation May be Well Below 100%

  • At the alveolar pO2 of 105 mm Hg at sea level the hemoglobin will be about 97% saturated, but the saturation will fall at high altitudes
  • At 12,000 feet altitude alveolar pO2 will be about 60 mm Hg and the hemoglobin will be 90% saturated
  • At 29,000 feet (Mt. Everest) alveolar pO2 is about 24 mm Hg and the hemoglobin will be only 42% saturated
  • At very high altitudes most climbers must breath pure oxygen from tanks
  • During acclimatization to high altitude the hematocrit can rise to about 60%- this increases the amount of oxygen that can be carried
  • Hematocrits above 60% are not useful because the blood viscosity will increase to the point where it impairs circulation

Water: comprises 60 - 90% of most living organisms (and cells) important because it serves as an excellent solvent & enters into many metabolic reactions

  • Intracellular (inside cells) = ~ 34 liters
  • Interstitial (outside cells) = ~ 13 liters
  • Blood plasma = ~3 liters

40% of blood is red blood cells (RBCs)

plasma is similar to interstitial fluid, but contains plasma proteins

serum = plasma with clotting proteins removed

intracellular fluid is very different from interstitial fluid (high K concentration instead of high Na concentration, for example)

  • Capillary walls (1 cell thick) separate blood from interstitial fluid
  • Cell membranes separate intracellular and interstitial fluids
  • Loss of about 30% of body water is fatal

 

Ions = atoms or molecules with unequal numbers of electrons and protons:

  • found in both intra- & extracellular fluid
  • examples of important ions include sodium, potassium, calcium, and chloride

Ions (Charged Atoms or Molecules) Can Conduct Electricity

  • Giving up electron leaves a + charge (cation)
  • Taking on electron produces a - charge (anion)
  • Ions conduct electricity
  • Without ions there can be no nerves or excitability
    • Na+ and K+ cations  
    • Ca2+ and Mg2+ cations  control metabolism and trigger muscle contraction and secretion of hormones and transmitters

Na+ & K+ are the Major Cations in Biological Fluids

  • High K+ in cells, high Na+ outside
  • Ion gradients maintained by Na pump (1/3 of basal metabolism)
  • Think of Na+ gradient as a Na+ battery- stored electrical energy
  • K+ gradient forms a K+ battery
  • Energy stored in Na+ and K+ batteries can be tapped when ions flow
  • Na+ and K+ produce action potential of excitable cells

Oxygen Transport in Blood: Hemoglobin

A.    Association & Dissociation of Oxygen + Hemoglobin

1.    oxyhemoglobin (HbO2) - oxygen molecule bound
2.    deoxyhemoglobin (HHb) - oxygen unbound
    
H-Hb     +    O2  <= === => HbO2 + H+

3.    binding gets more efficient as each O2 binds
4.    release gets easier as each O2 is released

5.    Several factors regulate AFFINITY of O2

a.    Partial Pressure of O2
b.    temperature
c.    blood pH (acidity)
d.    concentration of “diphosphoglycerate” (DPG)

B.    Effects of Partial Pressure of O2

1.  oxygen-hemoglobin dissociation curve

a.    104 mm (lungs) - 100% saturation (20 ml/100 ml)
b.    40 mm (tissues) - 75% saturation (15 ml/100 ml)
c.    right shift - Decreased Affinity, more O2 unloaded
d.     left shift- Increased Affinity, less O2 unloaded


C.    Effects of Temperature
    
1.    HIGHER Temperature    --> Decreased Affinity (right)
2.    LOWER Temperature        --> Increased Affinity (left)

D.    Effects of pH (Acidity) 

1.    HIGHER pH    --> Increased Affinity (left)
2.    LOWER pH    --> Decreased Affinity (right) "Bohr Effect"
a.    more Carbon Dioxide, lower pH (more H+), more O2 release

E.    Effects of Diphosphoglycerate (DPG)

1.    DPG - produced by anaerobic processes in RBCs
2.    HIGHER DPG    > Decreased Affinity (right)
3.    thyroxine, testosterone, epinephrine, NE - increase RBC metabolism and DPG production, cause RIGHT shift

F.    Oxygen Transport Problems

1.    hypoxia - below normal delivery of Oxygen

a.    anemic hypoxia - low RBC or hemoglobin
b.    stagnant hypoxia - impaired/blocked blood flow
c.    hypoxemic hypoxia - poor lung gas exchange

2.    carbon monoxide poisoning - CO has greater Affinity than Oxygen or Carbon Dioxide 
 

GENERAL VISCERAL AFFERENT (GVA) PATHWAYS

Pain and Pressure Sensation via the Spinal Cord

Visceral pain receptors are located in peritoneal surfaces, pleural membranes, the dura mater, walls of arteries, and the walls of the GI tube.

Nociceptors in the walls of the GI tube are particularly sensitive to stretch and overdistension.

General visceral nociceptors conduct signals into the spinal cord over the monopolar neurons of the posterior root ganglia. They terminate in laminae III and IV of the posterior horn as do the pain and temperature pathways of the GSA system , their peripheral processes reach the visceral receptors via the gray rami communicantes and ganglia of the sympathetic chain

Second-order neurons from the posterior horn cross in the anterior white commissure and ascend to the thalamus in the anterior and lateral spinothalamic tracts,

Projections from the VPL of the thalamus relay signals to the sensory cortex.

The localization of visceral pain is relatively poor, making it difficult to tell the exact source of the stimuli.

Blood Pressure, Blood Chemistry, and Alveolar Stretch Detection

The walls of the aorta and the carotid sinuses contain special baroreceptors (pressure receptors) which respond to changes in blood pressure. These mechanoreceptors are the peripheral endings of GVA fibers of the glossopharyngeal (IX) and vagus (X) nerves

The GVA fibers from the carotid sinus baroreceptors enter the solitary tract of the brainstem and terminate in the vasomotor center of the medulla (Fig-14). This is the CNS control center for cardiovascular activity.

Stretch receptors in the alveoli of the lungs conduct information concerning rhythmic alveolar inflation and deflation over GVA X fibers to the solitary tract and then to the respiratory center of the brainstem. This route is an important link in the Hering-Breuer reflex, which helps to regulate respiration.

Carotid body chemoreceptors, sensitive to changes in blood PO2 and, to a lesser extent, PCO2 and pH, conduct signals to both the vasomotor and respiratory centers over GVA IX nerve fibers

GVA X fibers conduct similar information from the aortic chemoreceptors to both centers

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