Plasma Proteins Functions and Production

Plasma Proteins
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
RDGMC

Last class questions??
 Average number of RBC in males 5,20,000+/-
300,000
 In women, 4,700,000 +/- 300,000
 Why male and female difference???
 Persons living at high altitudes have greater
number of RBC’s
 Why ???

Learning objectives
 List the major plasma proteins of the blood
 Describe the functions of plasma proteins
 Define plasmapheresis and its potential uses

Introduction
 Major types of plasma proteins present in the
plasma are
1. Albumin – Provides colloidal osmotic pressure
in plasma which prevents plasma loss from
capillaries
2. Globulin – responsible for body’s natural and
acquired immunity
3. Fibrinogen- forms blood clots that help repair
leaks in the circulatory system

Formation of plasma proteins
 All the albumin and fibrinogen of plasma
proteins and 50-80% of globulins, are formed in
the liver.
 The remaining globulins are formed almost
entirely in the lymphoid tissues.
 They are mainly gamma globulins that
constitute the antibodies used in immune
system.

 The rate at which plasma proteins formed by
the liver can be extremely high, as much as
30g/day.
 Certain disease conditions cause rapid loss of
plasma proteins:
 severe burns that denude large surface areas
of skin can cause loss of several liters of
plasma through denuded area each day.

 The rapid production of plasma proteins by
liver is valuable in preventing death in disease
states.
 A person with severe renal disease loses as
much as 20g of plasma protein in urine each
day for months.
 It is continuously replaced mainly by the liver
production of the required proteins.

 In cirrhosis of liver, large amounts of fibrous
tissue develop among the liver parenchymal
cells
 Causes decrease in their ability to synthesize
plasma proteins.
 Decrease in the plasma colloidal osmotic
pressure
 Generalized edema

Plasma proteins
 Normal plasma protein concentration is 6-8
gm/dl of blood.
Electrophoresis

Fluid filtration across capillaries
 Fluid shift hypothesis
 Starling’s hypothesis
 The hydrostatic pressure in the capillaries tends
to force the fluid and its dissolved substances
through the capillary pores into the interstitial
spaces (out driving force)
 Conversely, C.O.P, tends to cause the fluid
movement by the osmosis from interstitial fluid
into the blood (In driving force)

 Four primary forces determine weather the fluid
moves out of the blood or into the blood.
 These forces are called “Starling forces” in
honor of the Physiologist Ernst Starling who first
demonstrated their importance
1. Capillary pressure (pc) – force fluid outward
through capillary membrane
2. Interstitial fluid pressure (Pif) – force the fluid
inward through capillary membrane

 Four primary forces determine weather the fluid
moves out of the blood or into the blood.
 These forces are called “Starling forces” in
honor of the Physiologist Ernst Starling who first
demonstrated their importance
3. Capillary plasma colloidal osmotic pressure –
osmosis of the fluid inwards
4. Interstitial fluid colloidal osmotic pressure –
Osmosis of the fluid outwards

 If the sum of these forces – Net filtration
pressure (NFP) is positive, there will be a net
fluid filtration across the capillaries
 If the sum of the starling forces is negative, there
will be a net fluid absorption, from interstitial
fluid into the capillaries.
 NFP is slightly positive under normal conditions
 Results net filtration of fluid into the interstitial
space

Capillary hydrostatic pressure
 To estimate capillary hydrostatic pressure
1. Direct micropipette cannulation of the
capillaries, which has given an average mean
capillary pressure about 25 mmHg in some
tissues such as skeletal muscles and gut
2. Indirect functional measurement of capillary
pressure- which has given a capillary pressure
averaging about 17 mmHg in these tissues

Interstitial fluid hydrostatic pressure
 In loose subcutaneous tissues – negative interstitial
fluid hydrostatic pressure
 Kidneys – Positive (greater than atmospheric
pressure)
1. Direct micropipette cannulation of the tissues with
micropipette
2. Measurement of the pressure from implanted
perforated capsules
3. Measurement of the pressure from a cottonwick
inserted into the tissue

Plasma Colloidal osmotic pressure
 Molecules or ions that can not pass through the pores of
a semi permeable membrane exert osmotic pressure
 Proteins are the only dissolved constituents in the
plasma and interstitial fluids that do not readily pass
through capillary pores
 It is the proteins of the plasma and interstitial fluids that
are responsible for osmotic pressures on the two sides of
the capillary membrane
 The osmotic pressure exerted by plasma proteins is
called colloidal osmotic pressure or oncotic pressure

 The term “colloid” osmotic pressure is derived from
the fact that a protein solution resembles a colloidal
solution despite the fact that it is actually a true
molecular solution
 The C.O.P of normal human plasma averages about
28 mmHg
 19 mmHg of this is caused by molecular effects of
dissolved protein
 9 mmHg by Donnan effect- extra osmotic pressure
caused by sodium, potassium and other cations held
in the plasma by the proteins.

 Albumin (4.5 grams/Deciliter) – contributes 21.8
mmHg of C.O.P
 Globulin (2.5 grams/Deciliter) – contributes 6.0
mmHg of C.O.P
 Fibrinogen (0.3 grams/Deciliter) – contributes 0.2
mmHg of C.O.P
 Total (7.3 grams/Deciliter) – contributes 28.0
mmHg of C.O.P

 About 80% of total C.O.P of the plasma results
from the albumin fraction
 20% from globulins
 Almost none from fibrinogen
 Albumin is important

Interstitial fluid Colloidal osmotic
pressure
 The size of capillary pores are smaller than the
molecular size of plasma proteins
 Not true for all capillary pores
 Small amounts of plasma proteins do leak
through pores and transcytosis in small vesicles

Filtration at the arterial end
Forces tending to move the fluid outward
1. Capillary hydrostatic pressure = 30 mmHg
2. Negative interstitial free fluid pressure = 3 mmHg
3. Interstitial fluid colloidal osmotic pressure =8 mmHg
4. Total out driving force is 41 mmHg
Forces tending to move the fluid inward
1. Plasma colloidal osmotic pressure = 28 mmHg
Net outward force = 41-28 =13 mmHg

Filtration at the arterial end
 This 13 mmHg filtration pressure causes an
average about, 1/200 of the plasma in the flowing
blood to filter out of the capillary at the arterial
end of the capillaries into the interstitial space
each time the blood pass through the capillaries

Filtration at the venous end
Forces tending to move the fluid outward
1. Capillary hydrostatic pressure = 10 mmHg
2. Negative interstitial free fluid pressure = 3 mmHg
3. Interstitial fluid colloidal osmotic pressure =8 mmHg
4. Total out driving force is 21 mmHg
Forces tending to move the fluid inward
1. Plasma colloidal osmotic pressure = 28 mmHg
Net inward force = 28-21 =7 mmHg

Filtration at the venous end
 In driving force is more than outdriving force
 The difference 7 mmHg is the net reabsorption
pressure
 Causes about 9/10th of the fluid that has filtered
out at the arterial end of the capillaries to be
reabsorbed at the venous end
 The remaining 1/10th of the fluid flows into the
lymphatic vessels and returns to the circulating
blood (Formation of Lymph).

Plasma proteins as carrier proteins
 Some plasma proteins acts as carriers for water
insoluble substances (lipophilic)
 Albumin acts as a carrier for steroid hormones, fatty
acids and thyroid hormones
 Other specific carrier proteins in the blood also
important in transporting lipophilic hormones to the
target cells
 Sex hormone binding globulin (SHBG) that binds
estradiol and testosterone
 Corticosteroid binding globulin (CBG)
 Thyroxine binding globulin (TBG)

Plasma proteins- source of amino acids
 When tissues are depleted of proteins
 Plasma proteins can act as a source of rapid
replacement
 Plasma proteins acts as a labile protein storage
medium
 Readily available source of amino acids
whenever a particular tissue require them

Reversible equilibrium between tissue
proteins and plasma proteins
 Constant state of equilibrium between plasma proteins,
amino acids of plasma and tissue proteins
 Radio active tracer studies demonstrated that about 400
grams of body protein is synthesized and degraded each
day as a part of continuous state of flux of amino acids
 Reversible exchange of amino acids among different
proteins of body
 Even during starvation or severe debilitating disease, the
ratio of total tissue proteins to total plasma proteins in
the body remains relatively constant (3:1)

Reversible equilibrium between tissue
proteins and plasma proteins
 Because of this reversible equilibrium between
plasma proteins and other proteins of the body
 One of the most effective therapies for severe,
acute whole body protein deficiency is
intravenous transfusion of plasma protein
 With in few days, or sometimes within few hours,
the amino acids of administered protein are
distributed throughout the cells of the body to
form new proteins as needed

Plasmapheresis
 Plasma can be removed from the blood without removing
RBC
 Blood is drawn from the patient and plasma separated
from it
 The RBC’s are returned to the body of the patient such
that there is no loss of these cells
 Yet some plasma was removed
 The process is used on patients who have excess of
plasma proteins in their blood, making it viscous
 Also can be used on those who have certain antibodies
present in their blood

Whipple’s experiment
 George Hoyt Whipple, an American Physician and
Biomedical researcher (Nobel Prize winner)
 Dog was bled and the cells were separated from
plasma
 Cells were re injected being suspended in Ringer-
Locke’s solution (protein free fluid)
 Plasma pheresis
 Continued several weeks until protein concentration
decreased to less than 4gm%
 Exhaustion of plasma protein reserves

Whipple’s experiment
 When plasma protein levels lowered to 4-5 gm%,
after a duration about half an hour, reserve labile
proteins are mobilized in circulation and
physiological level of plasma proteins is achieved in
a period of 2-7 days, if balanced diet with adequate
protein is supplemented during this period.
 If the protein levels decreased less than 4 gm%, the
protein store of the body gets exhausted
 The decrease in the protein store less than 2 gm%,
leads to shock and death of animal

Plasma Proteins Functions and Production

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