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Monday, February 4, 2008

PLASMA PROTEIN

kinds of plasma protein

Effects of Protein Meals on the Urinary Excretion of Various Plasma Proteins in Healthy Subjects
Takuma Narita, Hiroji Kitazato, Jun Koshimura, Katsunori Suzuki, Masahiko Murata, Seiki Ito

Division of Geriatric Medicine, Akita University Hospital, Akita, Japan

Address of Author

Nephron 1999;81:398-405 (DOI: 10.1159/000045323)

Key Words

  • Acute protein loading
  • Urinary excretion, proteins
  • Size selectivity

goto top of pageAbstract

To examine whether hemodynamic changes in response to acute protein loadings with different protein sources cause increases in urinary excretion of plasma proteins in healthy subjects, urinary excretions of various plasma proteins with various molecular radii and isoelectric points, namely albumin (Alb), IgG, IgG4, ceruloplasmin (CRL), and alpha2-macroglobulin (A2), were measured in healthy subjects after ingestion of a beef meal or of a tuna fish meal. Significant increases in urinary excretions of the negatively charged IgG4 and CRL and of the neutrally charged IgG were found in parallel with enhanced creatinine clearances after each protein ingestion. These renal responses returned to basal levels 9 h after the test. This finding suggests that in healthy subjects, the increase in glomerular filtration rate after acute protein loading caused selective enhancement of urinary excretions of plasma proteins with a molecular radius of approximately 55 Å (the radius of IgG, IgG4, and CRL), irrespective of the charge barrier of the glomerulus. The increases in these three plasma proteins may be induced by leakage via the shunt pathway in the glomerulus, as proposed earlier (see text). In contrast, increases in urinary excretions of A2 and Alb were not found. The former finding may be explained by the possibility that A2 would not pass through this pathway, since the molecular radius of A2 (88 Å) is larger than that of IgG, although the latter finding may be partially explained by preferential renal tubular reabsorption of Alb.

1

The Blood

Chapter 11

The blood is the medium for

the transport of substances

around the body.

•The blood is composed of:

–Mostly water-plasma 54-58%

–Red blood cells (41-45%

–Everything else (WBC’s, plateletes,

proteins, etc) 1%

Packed cell

volume, or

hematocrit

Plasma = 55% of whole blood

“Buffy coat”

<1%

Platelets

White blood cells

Red blood cells =

45% of whole blood

Three types of cellular elements

in the blood are: erythrocytes,

leukocytes, and platelets.

• The plasma is the liquid part of the blood.

– About 99% of the cells are erythrocytes.

– The hematocrit is the percentage of total blood

occupied by erythrocytes. It averages 42% in

women and 45% in men.

– The plasma is 90% water.

• Let’s look at it first.

Plasma consists of water

and other substances.

• The plasma consists of water (90%)

which is a transport medium for all blood

borne substances, &

• Ions, gases, nutrients, hormones, and

plasma proteins (10%).

• The majority is plasma proteins (8%).

Plasma Proteins

• Plasma Proteins have numerous functions:

–Establish an osmotic gradient between the

blood and interstitial fluid. (osmotic pressure)

–Proteins buffer pH changes.

–Aid in the transport of many blood-borne

substances (hormones, etc.)

–Function in immunity as antibodies (some).

–Fibrinogen is a key factor in blood clotting.

2

The other main component of the

blood is red blood cells (RBCs) or

Erythrocytes = transport oxygen.

• They also transport carbon dioxide and hydrogen ions.

• The diameter of an erythrocyte is about 8 um.

• This cell lacks a nucleus, organelles, and ribosomes.

• It is mainly a package of hemoglobin molecules +

iron.

• Its flat, biconcave, disc shape is well-suited to carry

out its main function: carry Oxygen.

• The plasma membrane of the erythrocyte is flexible.

This allows it to slide through a capillary (which

averages 7 um).

Hemoglobin is a molecule

consisting of two parts.

• The globin is four, folded polypeptide chains.

• The heme (iron) part is non-protein. Each of its

four iron atoms is bound to one of the

polypeptides and can combine with one molecule

of oxygen gas.

• Hemoglobin can also combine with carbon

dioxide, hydrogen ions, carbon monoxide, and

nitric oxide.

• Hemoglobin can buffer pH by binding with

hydrogen ions.

Polypeptide chain

Polypeptide chain Polypeptide chain

Polypeptide chain

Heme groups

The bone marrow

produces erythrocytes.

• Erythrocytes lack a nucleus so cannot

reproduce.

• Erythropoiesis (erythrocyte production) is the

production of new red cells, replacing the wornout

cells in the circulation.

• The average life span of a RBC is 120 days.

• The number of RBC’s normally remains

constant.

• Cell production equals cell death.

Erythropoiesis is controlled

by erythropoietin.

• If oxygen delivery to the tissues is decreased, the

kidneys detect this and increase the output of

erythropoietin and erythropoiesis increases.

• This increases the number of RBC’s and the

oxygen-carrying capacity to the tissues.

• Once the oxygen delivery to the tissues and

kidneys is sufficient, the kidneys decrease their

output of erythropoietin.

• Erythropoietin can be produced in the lab.

Kidney

Reduced oxygencarrying

capacity

Increased oxygencarrying

capacity

Relieves

Erythrocytes

Developing

erythrocytes

in red bone

marrow

Erythropoietin

3

Anemia is a lower than normal oxygen

carrying capacity of the blood .

There are many kinds of anemia:

• Nutritional anemia (low iron in diet).

• Pernicious anemia (vitamin B-12 deficiency)

• Aplastic anemia (failure of the bone marrow to

make adequate numbers of RBC’s).

• Renal anemia (kidney disease).

• Hemorrhagic anemia ( loss of blood).

• Hemolytic anemia (rupture RBC’s).

• Sickle cell disease

Polycythemia is an excess

in circulating erythrocytes.

• It produces an elevated hematocrit.

• Primary polycythemia is caused by an

tumorlike condition in the bone marrow.

• Secondary polycythemia is an erythropoietininduced

adaptive mechanism to improve the

oxygen-carrying capacity in the blood.

• Other conditions can elevate the hematocrit,

such as dehydration.

Normal

(hematocrit

= 45%)

Anemia

(hematocrit

= 30%)

Polycythemia

(hematocrit

= 70%)

Dehydration

(hematocrit

= 70%)

= Plasma = Erythrocytes

One of the other main

constituents of the blood

is Leukocytes (WBC’s)

These form one of the body’s major means

of defense against foreign invasion.

Leukocytes (also called white

blood cells WBCs) are the mobile

units of the body’s immune system.

• Defend against the invasion of pathogens (bacteria

& viruses, they form anitbodies).

• They identify cancer cells.

• They remove the body’s litter (waste) by

phagocytosis.

• They can leave the circulation and go to the sites of

invasion and tissue damage. (parasites & allergies)

• There are five kinds of leukocytes.

The five kinds of leukocytes

fall into two main categories.

1. neutrophils

2. eosinophils

3. basophils

4. monocytes

5. lymphocytes.

4

The last component of the

blood to be discussed

here is the platelets.

Platelets allow blood to clot which prevent

uncontrolled bleeding.

This is called: hemostasis

Platelets (thrombocytes)

function in hemostasis.

• Platelets are cell fragments derived from

undifferentiated blood cells from the bone

marrow.

• They remain functional for about 10 days.

• The hormone thrombopoietin increases

the number of platelets. Their overall

production is not well understood.

Hemostasis prevents blood loss

from damaged blood vessels.

• The first two steps to stop escaping blood

from a vessel are:

–vascular spasm - This reduces blood flow

through a damaged vessel.

–platelet plugging - An aggregation of

platelets forms a plug.

• The platelet plug seals a break in a vessel.

The third step to block escaping

blood is clot formation.

• This reinforces the platelet plug and converts

the blood to a gel in the area of the vessel

damage.

• The ultimate step in clot formation is the

conversion of fibrinogen (large and soluble

plasma protein) into fibrin (thread-like

protein).

• Fibrin threads trap RBCs, forming a clot.

• This process involves the clotting cascade.

The clotting cascade is a series of

steps involving twelve clotting factors.

• The clotting factors serve as proteolytic

enzymes in a series of reactions, the

clotting sequence.

• One factor in the sequence is activated

which, in term, activates another factor

and so on.

• This sequence is called the clotting

cascade.

Platelet

factor 3

(PF3)

Platelet

aggregation

Secretes

Other factors in Enhances

clotting cascade

Prothrombin Thrombin

Activation

Stimulates

conversion

Fibrinogen

Fibrin

(loose

meshwork)

Factor XIII

Activates

Fibrin

(stabilized

meshwork)

5

Figure 11.14

Page 407

Vessel damage

Exposed collagen

Platelet

aggregation

Activation of

factor XII

(Hageman

factor)

Activation

of thrombin

Activation of

next thrombin

Formation of

fibrin meshwork

of clot

Seal

damaged vessel

PF3

Clotting

cascade

One of the most important

functions of the blood is to

carry oxygen to the tissues.

The other part of oxygen delivery is the

Respiratory System, our next topic of

discussion.