Fluid and Hemodynamics 2

Osmolality
- It’s a measure of solutes in a fluid. You can do an osmolality for urine, spinal
fluid, sweat, …
- Calculating Osmolality
o It’s two times the sodium; (2x Na+).
o The glucose is divided by 18; (Glucose/18)
o Blood Urea Nitrogen (BUN)
 Urea Cycle
 The urea cycle is located in the liver (part is in the cytosol
and part is in the mitochondria; urea came from
ammonia).
 The end product of the urea cycle is urea, but ammonia is
what is fed into the system.
 The normal amount of ammonia is about 12 and you divide it by 3
so you get about 4; (Ammonia/3)
- Quick Estimate
o In a normal person, sodium is responsible for plasma osmolality. You
double the serum sodium and add ten; this will be roughly what the
measured osmolality would be.
- Compartmentalization
o Sodium and glucose are limited to the ECF compartment.
o Urea if increased can equilibrate between the ECF and ICF across the
cell membrane.
o Because sodium and glucose are limited to the ECF compartment, then
changes in its concentration can result in the movement of water from
low to high (against the gradient and against diffusion); this is called
osmosis.
- Mental Status Abnormalities and Changes in Sodium Concentration
o If you have hyponatremia, water is going to go from ECF (the lower part
is in the ECF) to ICF (it gets expanded by the law of osmosis).
 If the brain were a single cell, we’d see cerebral edema.
 We will have mental status abnormalities.
 Signs and symptoms of hyponatremia would include
mental status abnormalities (by the law of osmosis). The
intracellular fluid compartment of all the cells in the brain
would be expanded.
o If you had hypernatremia, you would have water going from ICF to ECF.
 The ICF gets contracted.
 In the brain, the intracellular compartments of the cells get
contracted; this produces mental status abnormalities.
o Whether you get hypo- or hypernatremia, you’re going to get mental
status abnormalities.
- Glucose Affecting Osmosis
 o If you have diabetic ketoacidosis and you have 1000 mg % blood sugar.
Glucose now is the major factor in osmosis (both sodium and glucose are
limited to the ECF compartment).
o Sugars are only in sufficient quantity in the ECF
 Glycolysis doesn’t lead to glucose in the intracellular fluid
compartment; all sugars are phosphorylated to trap them.
 Glucose always goes in with phosphorous. Glucose immediately
becomes glucose-6-phosphate and is immediately metabolized.
 Fructose and galactose also get phosphorylated and metabolized
immediately; fructose into fructose-1-phosphate and galactose into
galactose-1-phosphate.
o Water moves in the direction of the hyperglycemia, from ICF to ECF.
ECF normally has 140 mEq of sodium in it. The addition of water from
ICF to ECF causes the serum sodium concentration goes down; it’s called
dilutional hyponatremia.
- The two things that control water movement in the ECF compartment are sodium
and glucose; in a normal situation, sodium is the major factor.

Tonicity
- Salines
o Normal saline is 0.9%.
o Hypotonic salines are ½ normal, ¼ normal, and 5% dextrose in water.
o Hypertonic sallies are 3% and 5%.
- Tonicity
o The tonicity of plasma is controlled by serum sodium.
- Types of tonicity
o Isotonic State
o Hypotonic State
o Hypertonic State
- When we do the serum sodium concentration in a laboratory, it is a reflection of
your total body sodium divided by your total body water.
o You can have hypernatremia and have a normal total body sodium by
losing total body water.
o Hyper- and hypornatremia is really a ratio of total body sodium to total
body water.
- Total body sodium is not measured; clinical exam determines your total body
sodium (edema). Serum sodium can be measured in plasma (serum).
- There are different kinds of fluid abnormalities; we can lose or gain a certain
tonicity of fluid.
o Isotonic loss of fluid (an example is diarrhea)
 It means you’re losing equal amounts of salt and water.
 The fluid would be lost from the ECF compartment.
 Your serum sodium concentration would be normal.
 Your ECF compartment would be contracted.
 You wouldn’t have an osmotic gradient for water movement into or
out of the ICF.
  Examples are hemorrhage and diarrhea.
o Isotonic gain of fluid
 We gain an equal amount of salt and water.
 An example is a person getting too much isotonic saline.
 Serum sodium would be normal b/c it has equal amount of salt and
water.
 The excess isotonic saline would be in the ECF compartment.
 There wouldn’t be any osmotic gradient for water movement.
o Hypotonic solutions
 The most common cause is hyponatremia. Hypoglycemia can’t
produce a hypotonic condition (b/c it is divided by 18).
 An example is if we lost more salt than water, then the serum
sodium would be decreased.
 A diuretic would cause the loss of a hypertonic urine and you end
up with hyponatremia and hyponatremia.
 ICF has water move into it.
o Gaining pure water
 An example is inappropriate ADH syndrome (SIADH).
 Small cell carcinoma of the lung causes secretion of aldosterone.
 ADH renders the distal collecting and collecting tubule permeable
to water (free water).
 You absorb water into the ECF compartment, diluting the serum
sodium, and the ECF would be expanded. The ICF would be
expanded as well b/c of osmosis.
 Small cell carcinoma would lead to mental status changes b/c of
the reabsorption of water.
 The treatment of choice for inappropriate ADH is to restrict
water (not salt; the total body sodium is normal). When ADH is
present, you’re going to be concentrating the urine.
 The lowest serum sodiums are in inappropriate ADH. Serum
sodium < 120; SIADH is always the answer.
 Oral sulfonureas (especially the first generation ones) produce
ADH 30% of the time.
 We would have a hypotonic gain of fluid and have a hypertonic
loss of salt producing hyponatremia.
 Edema
 You get water and salt (a little more water than salt). You
still end up with hyponatremia.
 Right heart failure, cirrhosis of the liver, …
 Your kidneys reabsorb a little more water than salt. You
end up with hyponatremia and pitting edema.
 The total body sodium (not the same as serum sodium;
takes into account total body water), when it’s increased,
always produces pitting edema.
o The total body sodium is in the ECF compartment;
the biggest compartment of that is the interstitial.
 Whenever you have an increase in total body
sodium, most of it is in the interstitial space; it
expands with a transudate and you end up with
pitting edema.
o Hypertonic state
 It means you have hypernatremia or hyperglycemia (any patient
who is in diabetic ketoacidosis is by definition in a hypertonic
condition; it’s more common than hypernatremia).
 When you have hypernatremia, the ICF compartment is
contracted. You can gain more salt than water.
 It can be seen in primary aldosteronism.
 When we lose pure water it’s called diabetes insipidus.
 We can lose a little more water than salt in the urine; this is
called osmotic diuresis.
 When you have glucose or mannitol in your urine, you’re
losing hypotonic salt solution in your urine.
 Baby Diarrhea
 Baby diarrhea is a hypotonic salt solution; adult is
isotonic.
o If a baby had no access to water, and a baby had a
rotavirus infection, their serum sodium would be
high.
o They lose more water than salt and have
hypernatremia.
o Treatment for the baby is pedialyte (a hypotonic salt
solution); it replaces what you lost.
 Pedialyte and Gatorade have to have glucose to reabsorb
sodium in the GI tract. Sodium has to be reabsorbed with
glucose or galactose (fructose doesn’t facilitate it).
 Scenario
o In the oral replacement of patients with cholera,
what has to be in that in order for sodium to be
reabsorbed?
o Glucose (b/c of the cotransport trump).
 Sweat is also a hypotonic salt solution. If you were sweating on
a hot day, you should have hypernatremia.

Arterial Blood Volume

- Effective Arterial Blood Volume (EABV) is the same thing as stroke volume
and cardiac output.
- Baroreceptors
o The low pressure ones are on the venous side.
o The high pressure ones are on the arterial side (like carotids and arch of
the aorta). The high pressure ones are usually innervated by the ninth
and tenth nerve.
- Physiology of a Decrease in Arterial Blood Volume
 o When you have a decrease in arterial blood volume (aka a decrease in
stroke volume or cardiac output) you underfill the arch vessels and the
carotid.
o Instead of having a ninth and tenth nerve response, you have a
sympathetic nervous tissue response; catecholamines are released.
 The catecholamines constrict the venous system; it increases blood
returning to the right side of the heart.
 It will also increase the force of contraction and increase the stroke
volume a little.
 The systolic pressure will increase a little and the rate will also
increase. The arterioles on the systemic side will stimulate the beta
receptors in the smooth muscle.
 Your diastolic pressure is really due to the amount of blood in your
arteriole system while your heart is filling up in diastole.
 The amount of blood in the arteriole system when your
heart is filling up in diastole is controlled by the peripheral
resistance arterioles (this maintains the diastolic blood
pressure).
 When the arterioles constrict, there’s little blood going to
tissues; the bad news is the tissues won’t get a lot of blood,
but the good news is you keep your diastolic pressure up
(this is good b/c your coronary arteries fill up in diastole).
 This is all done by catecholamines.
 Catecholamines also stimulates the renin-angiotensin aldosterone
system.
o Renin-Angiotensin II
 Renin is released and angiotensin II is going to be present;
angiotensin II is a vasoconstrictor of the arterioles (thereby
increasing total peripheral resistance).
 Angiotensin II stimulates 18-hydroxylase, converts
corticosterone into aldosterone. Aldosterone will reabsorb salt
and water (get cardiac output up).
 If the stroke volume is decreased, then the renal blood flow to the
kidneys is also decreased. This is also a stimulus for the renin-
angiotensin aldosterone system.
 The receptors for juxtaglomerular apparatus are in the
afferent arteriole. ADH will be released; it just
contributes pure water (no salt).
- Normal saline can keep your blood pressure up; normal saline is plasma w/o
the protein. Normal saline stays in the ECF.
- Peritubular capillary pressures.
o Most sodium is reabsorbed in the proximal tubule (60-80%) into the
peritubular capillaries. In order for them to reabsorb, the starling forces
in the peritubular capillaries have to be amenable to it (have an increased
oncotic pressure).
  If renal blood flow is decreased (when your stroke volume and
cardiac output is decreased), the hydrostatic pressure in the
peritubular capillary is also decreased (and the oncotic pressure is
increased).
 The increase in oncotic pressure during a decrease in renal
blood flow is what’s responsible for reabsorbing anything into
the blood stream from the kidney.
 In any patient with a decrease in cardiac output, this will happen
automatically.
o When we have a decrease in ECF or a decrease in cardiac output, the
kidney normally reabsorbs a hypotonic solution.
 The tonicity of the fluid that you reabsorb out of the proximal
tubule is isotonic.
 Aldosterone (from the renin-angiotensin system) reabsorbs a
roughly isotonic solution from the distal tubule, but not as much
as the proximal tubule.
 ADH contributes pure water; this is what causes the overall
fluid being reabsorbed to be hypotonic.
- If the stroke volume and arterial blood volume were increased, then the reverse
would happen.
o The baroreceptors are going to be stretched; they’re innervated by the 9th
and 10th nerve.
o We don’t get a sympathetic nervous system response, but a
parasympathetic response.
o We have no aldosterone or ADH activation.
o The peritubular hydrostatic pressure now is higher than oncotic pressure;
even if salt was reabsorbed, you wouldn’t be able to reabsorb it into your
blood stream.
 You would lose a hypotonic fluid in your urine when you have
an increase in arterial blood volume.
- Atrial Natriuretic Peptide is a hormone made in the left and right atrium
released if you have dilatation in either atrium.
o It will cut off ADH and also cause a dumping of salt (acts like a
diuretic).
o ANP is only released in volume overloaded states.
- Scenario
o Patient is given 3% hypertonic saline.
o You’re adding a hypertonic salt solution, the osmolality increases.
o If you have an increase in osmolality, it would increase the ADH; an
increase in osmolality of plama or serum causes the release of ADH.
- Determining the total body sodium in a patient clinically
o If it’s high, they would have indentations in the skin
o If it’s low, their tongue would be dry.
o When you pinch someone’s skin and it goes down (testing turgor) you test
if the total body sodium is normal.
 o If you have dependent pitting edema, total body sodium is increased.
o If you had inappropriate ADH and you’re gaining pure water, the total
body sodium is normal, but the sodium serum concentration is low. Water
would have to be restricted.
- If you have right heart failure and dependent pitting edema your serum
sodium is going to be low (b/c you absorb a hypotonic solution; a little more
water than salt).
- Treatment for Edemas
o A non-pharmacologic treatment of any edema states (heart failure and
cirrhosis for example) is salt restriction and water restriction.
o Treatment for inappropriate ADH is restrict water.
o Treatment for any pitting edema state is restrict salt and water.
o Pharmacologic treatment of pitting edema is diuretics.

Shock
- Causes of hypovolemic shock
o Diarrhea (cholera)
o Blood loss
o Sweating
o Diabetes Insipidus does not cause hypovolemic shock (you lose pure water
and your total sodium is normal). Most of the pure water would be lost
from the ICF compartment.
o The salt is what’s important in hypovolemic shock.
- Scenario
o A woman when lying down had normal blood pressure and pulse. When
she sat up, her blood pressure went down but the pulse went up. What
does it mean?
o It means they’re volume depleted. This is called the tilt test.
o The patient’s blood pressure and pulse was normal because no effect of
gravity. When you sit the patient up, you decrease (by gravity) the venous
return to the right side of the heart. If you’re hypovolemic, it will show up
by a decrease in blood pressure and an increase in pulse. All these things
occur when your cardiac output is decreased; it’s due to catecholamines.
o Treatment would be normal saline.