Review - Weeblyjumed16.weebly.com/uploads/8/8/5/1/88514776/physio-sh14.pdf · 1 - Hematocrit Exercise: ... 5 = Plasma volume / 1 ... Ex: A- If there was an increment in Na+ concentration

Review:

In the previous lecture, we have seen how to measure total body fluids volume by using

tritiated water (water that has hydrogen atoms with one proton and two neutrons) or

by using Antipyrine.

Also, we saw how we measure extra-cellular fluids (ECF) by using radioactive Na (in this

case we measure Na space and from this we can measure the ECF), also, we can use

radioactive Iodine Thalamate (125I-iothalamate) or by using Thiosulfate or by using Inulin

(in this case we measure Inulin space).

We said that we can’t measure intra-cellular fluid (ICF) because we have substances

that can only be distributed inside cells. But we can calculate ICF (ICF = Total - ECF).

Review is over.

Measuring intra-vascular fluid:

We may measure plasma volume only or total blood volume.

If we centrifuged a blood sample, blood cells will be deposited down, and what remains

up is the plasma (Figure 1).

So, Plasma = Blood – Cells

Figure 1: Centrifuged blood. Plasma is 55 % of the blood

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Note: If you coagulate all the blood sample at first (this will consume all the coagulation

proteins -including fibrinogen- on the blood), and then centrifuged the sample, we will

get cells and serum instead of plasma.

The volume percentage (%) occupied by blood cells is called the Hematocrit (also known

as packed cell volume -PCV-), we get this percentage by calculating Blood cells volume × 100%

Total blood volume (This is calculated using a sample –not whole body blood volume)

or by calculating Blood cells height × 100%

Total blood height

(Normally, the Hematocrit is around 43-45%).

Note: Anemia test and some other test are done by measuring the Hematocrit.

Plasma is composed of: - Water (>90%) - Small molecules (2%)

- Proteins: 60-80 gram of proteins per 1 liter of plasma, most of these proteins is

albumin (40-50 g/L = 54%), also there is globulin (α1, α2, β, γ) (20-30 g/L = 38%), and

fibrinogen which is involved in coagulation process (7%).

Note: γ globulins are the anti bodies.

Note: We will not be asked on all these details, we shall know them just in brief.

Now, the thing that is important to us is methods used to measure the plasma volume.

There is two methods:

1- 125I-Albumin (iodine-labeled albumin): Most of the proteins are found in plasma (mostly albumin), and very low amount is found in the interstitial fluid, so we can use radio iodine serum albumin (radioactive I-albumin) to measure the plasma volume. By injection of that albumin we are getting distribution and that albumin will not

leave vessels and by measuring the activity we can get the concentration of this albumin and then we can measure plasma volume.

2- Evans Blue (a dye which is not leaving vessels): We can use substances that bind to proteins, once these substancesbind we can assay them and measure plasma

volume.

Albumin proteins are the most determiners for the colloid-osmotic pressure (oncotic pressure).

To measure total blood volume, we have two methods:

1- We can use red blood cells labeled by radioactive chromium (51Cr). By

introducing these labeled cells we can measure total blood volume using the

indicator-dilution principle.

Also these RBC are labeled with biotin that can give fluorescence with other

product and by the fluorescence methods we can measure the total blood

volume.

2- We can calculate total blood volume, but firstly we must know plasma volume

and the Hematocrit then we can use this equation to calculate the total blood

volume.

Total blood volume = Plasma volume 1 - Hematocrit

Exercise: If the hematocrit is 0.40 (40%) and total blood volume is 5 liters, calculate:

a- Plasma volume. b- Blood cells volume.

Solution:

a- Total blood volume = Plasma volume

1 - Hematocrit

5 = Plasma volume / 1 - 0.40 Plasma volume = 3 liters.

b- We can calculate it in two ways:

- Hematocrit = Cells volume / Total volume.

- Total volume = Plasma volume + Cells volume.

By using the first method: Cells volume = Total volume × Hematocrit = 5 × 0.40 = 2 liters.

Regulation of fluids volume:

The amount of fluid in our bodies is very well regulated, this regulation involves

Regulation of osmolality and regulation of volume of ECF.

Note: There are many mechanisms for these regulations and these mechanisms are

overlapped and confusing. Actually, different body systems use these mechanisms.

1- Regulation of osmolality: ( osmoreceptors sense the change in osmolality )

Osmolality depends mainly on Na+ concentration in our bodies, so we need to regulate

Na+ concentration to regulate osmolality.

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Ex: A- If there was an increment in Na+ concentration in the body, the body fluids will

become hypertonic. There are receptors in the body that sense these changes in fluids,

if it sensed an increment, the hypothalamus will respond by making the body feel

thirsty. By drinking water, the osmolality will decrease and return normal (Regulation of

intake) (this is the simplest way).

B- Also increment in osmolality will stimulate ADH (Antidiuretic hormone)by cells in

the pituitary gland, which in its role, will act over the kidney to get more reabsorption

of water and as a result the osmolality will decrease and the urine flow will decrease

also (Regulation of output) ( increasing water retention )

So, the purpose of these two mechanisms is decreasing of osmolality.

2- Regulation of ECF volume:

Ex: A- If there was a decrement in volume, this will result in decrement of blood flow

toward kidneys, this will activate Juxtaglomerular cells, and this will result in releasing

Renin.

Renin converts Angiotensinogen to Angiotensin I. Angiotensin I usually converted to

Angiotensin II (the active form) by lung tissue. Then Angiotensin II will stimulate the

release of Aldosterone. Aldosterone will result in an increment of Na+ reabsorption

which will increase osmolality, this increment in osmolality acts on the hypothalamus

centers to increase ADH, as ADH increases the volume will increase as a result of water

reabsorption (This method is called renin-angiotensin mechanism).

ADH is a hormone made by the hypothalamus in the brain and stored in the posterior

pituitary gland.

Note: Aldosterone is secreted from Suprarenal gland (Adrenal gland).

Note: Aldosterone is also called mineralocorticoid.

*ADH is also called vasopressin.

- Also we have another hormone which is released from the right

atrium and is called Atrial natriuretic peptide.

This hormone can reduce blood pressure and reduce salt it can also

decrease the angiotensin so it’s working against other systems.

You should know :

1- The increase in osmolarity will activate ADH release

2- The decrease in the volume results in a decrease of the blood flow

towards the kidney this will activate renin-angiotensis aldosteron

system.

Disorders of Volumes:

Increment in volume is called Hypervolemia.

Decrement in volume is called Hypovolemia.

Hypovolemia results by high loss of water (by sweating, urination, vomiting, diarrhea…).

Medical applications:

- Osmotic diuresis ادرار البول التناضحي) ): in this disease there are high glucose

concentration in urine, this will cause more attraction of water, and as a result

patient will have high urination Hypovolemia.

- Diabetes insipidus (مرض السكري الكاذب): in this disease there will be a decrement in

ADH, this will cause more loss of water Hypovolemia.

Hypervolemia results by high intake of water, or by disturbances of the mechanisms

examined earlier.

Ex: If there is high increment of ADH (abnormal case), this will result in more

reabsorption of water which will cause hypervolemia.

Note: In hypovolemia the osmolality increases and in hypervolemia the osmolality

decreases. So, we get a change in composition of fluids also (not only in volume).

Disorders of Osmolality:

Increment in osmolality is called Hypernatremia.

Decrement in osmolality is called Hyponatremia.

Hyponatremia results by:

- Excessive loss of Na+.

- Administration of hypotonic fluids.

- Loss of hypertonic fluids.

- Increment in ADH (reabsorption of water).

- Decrement in Aldosterone.

Hypernatremia results by:

- Excessive intake of Na+.

- Administration of hypertonic fluids.

- Loss of hypotonic fluids.

- Decrement in ADH (Loosing more water).

- Increment in Aldosterone.

So, these disorders may happen by disturbances of regulatory mechanisms not only by

intake or loss of hypertonic fluids or hypotonic fluids or so on.

Note: Always there is a relation between volume and osmolality.

Giving a person normal saline – hypervolemia and isonatremia

(no change in osmolality)

A person with injury in blood

vessels – the quality of his fluids

is hypovolemia and isonatremia

and then after 3 hours we are

getting an increase in ADH which

increases the reabsorption of

water so hyponatremia occurs.

Figure 2: Dehydration and over hydration.

See figure 2, assuming that the water is hypotonic. If we have excessive loss of water

like in (a), this will result in increasing of osmolality in ECF and water will move from

inside cells toward ECF. As a result, cells will shrink (This is called Dehydration).

If we have excessive intake of water like in (b), this will result in decreasing of osmolality

in ECF and water will move from ECF and enters cells. As a result, cells will swell (This is

called Overhydration).

Figure 3: Effects of isotonic,

hypertonic and hypotonic

solutions.

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See figure 3.

- If we give normal saline (isotonic solution) to a normal body as in (A), this will

result in increasing of ECF volume, without any change in ICF volume or

osmolarities.

- If we give hypertonic solution to a normal body as in (B), this will result in

increasing of ECF volume and osmolarity, this will cause fluid to move from ICF

to ECF, as a result, ICF volume decreases and its osmolarity increases.

- If we give hypotonic solution to a normal body as in (C), this will result in

increasing of ECF volume and decreasing of its osmolarity, this will cause fluid to

move from ECF to ICF, as a result, ICF volume increases and its osmolarity

decreases.

Remember this paragraph about hydrostatic pressure and filtration :

In the arteriole capillary we have high hydrostatic pressure and high colloid-osmotic

pressure but the hydrostatic pressure is higher so we are getting filtration of the

fluids (move from the intravascular fluid to the interstitial fluid) , then in the

venous capillary the hydrostatic pressure becomes lower than the colloid-

osmotic pressure so we get osmosis in this case (fluids move from the interstitial

fluid to the intravascular fluid ).

- Now we can have that reabsorbtion or filtration process affected and causes

accumulation of these fluids at the interstitial fluid. we are calling this type of

disorder (edema )

- In patients with liver diseases, forming less amount of albumin in plasma which

results in less reabsorption of fluids from the interstitial fluids (edema )

- In the nephrotic syndrome we have high loss of proteins from the plasma through

kidney, there will be hypoproteinema in the plasma (less amount of protein),

there will be less reabsorption of fluids and accumulation of fluids in the

interstitial fluid (edema).

- The causes of edema: increasing of hydrostatic pressure in capillaries (get more

filtration and less reabsorption), decreasing oncotic pressure, increase the

capillary permeability (protein passing from the vascular bath to the interstitial

fluid and getting more filtration) and also the low lymphatic drainage.

- Drainage of lymph: vessels called lymphatic vessels draining the big particles that

have been filtered in the interstitial fluid and getting these particles into the

general circulation through the thoracic duct which is a lymphatic structure (or

lymphatic vessels) connecting the lymph vessels from the interstitial fluid, and re-

introducing these particles again towards the general circulation.

ه

ب

What happen to the hydrostatic pressure by increasing the volume? Any time you have increased the volume, you have increased the hydrostatic pressure. But what happen at the level of the interstitial fluid? We have 2 types of events that happen The hydrostatic pressure in our interstitial fluid is below zero (negative range)

A. a small increase in the volume will result in a high increase in hydrostatic pressure ( this will cause preventing more fluids to move from vessels towards the interstitial fluid low compliance The interstitial fluid has low compliance (small volume with high pressure to prevent more filtration and more accumulation of fluids in the interstitial fluid)

B. High increase in volume will result in a low increase in hydrostatic pressure high compliance (causes edema). Compliance: مطاوعة

The interstitial fluid has low compliance normally and once it has high compliance, in this case we have edema.

*veins are having high compliance (veins don’t have thick wall like arteries so they have high compliance

لما يزيد حجم الدم بتتوسع ف بقل الضغط الشرايين, يعني عندها مطاوعة عالية النه الجدار مش سميك زي االوردة) تقبل زيادة قليلة لحجم الدم ف بكون الضغط عالي جدارها سميك عندها مطاوعة قليلة ف بت الشرايينعلى عكس

But normally at the level of the interstitial fluid we have low compliance to prevent the appearance of

edema because we have a small amount of fluids and a high pressure preventing more fluids to move to the interstitial fluid.

we will take this later on in more details

So we have 2 safety factors that trying to prevent edema :

1- Low compliance 2- Increased lymph flow: at any time you have more filtration of fluids, lymph vessels are trying to take

as much as possible of these fluids from the interstitial fluid so by increasing the lymphatic flow we are reducing the appearance of edema.