Chapter 3 : Blood

Lecture 5

3.9 Plasma

-Blood plasma is a straw-colored, sticky fluid. -Composition:

water - about 90% dissolved solutes – 10%

Organic substances 9g% Anorganic substances

1g%

Non-protein nitrogenous Non-nitrogenous

Protein nitrogenous
organic substances
Chloride,

organic substances 8g%

1g%

25-35mg% Phosphates,

bicarbonates,

Glucose 0.1g%

Na,

Urea
 Lipids 0.6-0.8g%

Albumin 4.5g%
Uric acid

K,

Lactic acid

Globulin 3g%
Creatinine Creatine
Citric acid

Ca,

Fibrinogen 0.2- 0.4g% Amino acids Oxalic acid

Mg
Ethyl alcohol

Plasma proteins are the most numerous plasma solutes, accounting for about 8% by weight of
plasma volume. Except for hormones and gamma globulins, most plasma proteins are produced
by the liver.

3.10 Plasma proteins



3.10.1. Normal range :
7 - 8g % = euproteinemia

3.10.2. Variations :

↑: > 8g% = hyperproteinemia

a) Apparent : - physiological : heavy sweating


- pathological : diarrhea, increased diuresis, vomiting

b) Real : - Chronic infections : ↑γ globulin

- Tumors of plasma cells

↓ : < 6g % = hypoproteinemia

a)  Apparent, physiological : increased water ingestion 


b)  Real : - Insufficient intake of protein 


- Disorders of digestion and absorption of proteins
- Decreased protein synthesis due to chronic liver disease 

- Loss of body protein : trough urine (nephrosis), skin (extensive burns), chronic
suppurations, after hemorrhage. 


3.10.3. The role of plasma proteins :

1. Maintain constant plasma volume 


2. Ensure blood viscosity necessary to convert intermittent flow in laminar flow 


3. Nutritional role 


4. Role of transportation: metabolites, metals, ions, hormones, drugs 


5. Maintain acid-base balance (through buffers) 


6. Role in coagulation and fibrinolysis 


7. Protection role, through antibodies 


3.10.4. Electrophoresis :

=> Protein fractionation in continuous electric field

The electrophoretic mobility of a protein depends on its molecular weight (size and shape) as well
as its electrical charge.

Albumin : 56-60%

Globulins : α1-globulins : 3-5%

α2-globulins : 5-7%

β-globulins : 10-14%

γ-globulins : 16-18%

Other : fibrinogen, coagulation factors, etc

3.10.4.1 - Albumin
- The most abundant protein

- Synthesized in the liver at the rate of about 15 g per day

Functions :

- The major contributor to the colloid osmotic pressure of the blood; (↓albumin →
peripheral edema)

- It can carry in loose combination certain hormones (i.e., corticosteroids), bilirubin, fatty
acids, salts of bile, heavy metals (i.e., mercury and copper) and some drugs.

- It also plays a role as a buffer for plasma H+ ions and carries a small amount of CO2 as a
carbamino complex.

> Hypoalbuminemia = lowered plasma albumin


- Malnutrition, nephrotic syndrome, liver failure

> Albuminuria = albumin is excreted into urine


- Nephrotic syndrome, inflammatory conditions of urinary tract.

- Albumin/ globulin ratio → normal value ≈1-2

3.10.4.2- Globulins
1- α1-globulins

a) α 1 antitrypsin

= Antiprotease synthesized in the liver (hepatocytes and macrophages)


- Inhibits of serine proteases (trypsin, elastase)

-↑ : acute phase reaction => inhibition of elastase, which degrades connective tissue

b) thyroxine binding globulin (TBG)


c) transcortin (corticosteroid-binding globulin)

d )transcobalamin : carrier protein which binds cobalamin (vitamin B12)

2- α2-globulins

a) Haptoglobin (Hp)

- Binds free hemoglobin and delivers it to the reticuloendothelial cells (liver)


- Free Hb passes through glomerulus, enters tubules and tends to precipitate ―> kidney damage

- However, complex Hb-Hp is too large (155 kDa) to pass through glomerulus ―> prevention of
loss of free Hb and iron (Fe)

b) Ceruloplasmin

- Carries 90% of copper (Cu) in plasma (Cu – cofactor for a variety of enzymes), 1 molecule binds
6 → 8 atoms of Cu

- Scavenger for superoxide radical (oxygen reactive species)

2+ 3+ 3+
- Role in Fe metabolism -> oxidation of Fe to Fe ; transferrin can bind only Fe .

c) α2 - Macroglobulin

- Anti-protease = inhibits a large number of proteases

d) kininogen : precursors of bradykinin (vasodilator)

e) angiotensinogen : precursors of angiotensin I

3- β-globulins

a) Transferrin

3+
- Transports Fe in plasma as ferric ions (Fe ) ; tight binding but reversible ; < 0,1% of body
Fe <-> 80-120 μg%

- Protect the body against the toxic effects of free iron

- Normally, 1/3 saturated with iron

b) Lipoproteins

- Chylomicrons

- VLDL (very low density lipoprotein)

- LDL (low density lipoprotein)

4- γ-globulins

- Immunoglobulins = structurally related proteins that function as antibodies
- Major Immunoglobulins in plasma are :

IgG :
- Most abundant antibody

- Neutralizes toxins,

- Activates complement system,

- Capable of crossing feto-placental barrier

IgA :

- Located in secretion: saliva, tears, milk etc

- Defense against viral and bacterial infection

IgM :

- Usually first to be made in immune response

IgE :

- Secreted in skin, gastrointestinal tissue, respiratory tract


- Contribute to inflammation and allergic reactions, by triggering release of histamine

3.10.4.3 - Other types of plasma proteins :


a) Fibrinogen:

= Coagulation factor I = key factor in blood clotting

- Coagulation process : fibrinogen → fibrine (insoluble)

3.10.4.4 - Acute - phase proteins

= A class of proteins whose plasma concentrations increase in response to acute stress
(infection, trauma, disease) => acute-phase reaction

CRP

Fibrinogen

α 1 antitrypsin

C3 complement fraction

Ceruloplasmin

Haptoglobin

3.11 Erythrocytes (diameter 7-8 μm)

3.11.1. Structure :

Structure

- lack of : > Nucleus (anucleate cells)

> Most organelles 


> No mitochondria!

> Only uses Glycolysis – based

ADP generation

 > No ribosomes

> No protein synthesis

- Life cycle – 120 days

- Shape : > biconcave disk

> the shape is maintained by a network of proteins (e.g.spectrins, ankyrins)

- Dimensions : > Diameter 7-8 μm


> Thickness : 2.5μm – maximal thickness point ; 1μm - center areas

- Advantages of shape and thickness : > biconcave shape : -flexibility

-increased surface area for

gas diffusion

> enables rapid diffusion of gases between


cell exterior and interior (cell thinness).

3.11.2. Roles of RBCs :

Transports :

• O2(from lungs to tissues)

• CO2(tissues to lungs)

- By means of Hemoglobin

Involved in maintainance of acido - base equillibrium

- Presence of carbonic anhydrase

carbonic anhydrase (CA)


60% in erythrocytes : CO2+H2O ————————————-→ H2CO3

(very fast)

+ -
H2CO3→H +HCO3

3.11.3 Normal number of RBCs and variations :

a) Normal range
Male : 5-5.5 mil/mm3 Female : 4-4.5 mil/mm3

b) Physiological variations :
• Gender : - Male : increased number

(testosterone: -> ↑the synthesis of proteins and erythropoietin =>

↑ erythropoiesis)

• Age : - Newborns → apparent polycythemia ( ↑no.of RBCs ) due to dehydration

- After few weeks → anemia (↓no.of RBCs), due to the persistence of fetal haemoglobin

(FHb), with higher affinity for O2 than adult Hb (AHb)


- 5-6 month of age, FHb ↓, AHb ↑ => normal range

• People living at a high altitude : - low-oxygen environment → ↑ erythropoiesis → ↑number of

erythrocytes

• Physical effort → splenic contraction => erythrocytes release

• Peripheral vasodilation → water and microelements will pass into tissues → blood 

concentration

• After administration of large amount of liquids => apparent ↓

c) Pathological variations :

↑ > 6mil/mm3 = polycythemia

3
> Primary polycythemia: > 10 mil/ mm

> Secondary polycythemia due to respiratory/cardiac diseases

↓ < 4mil/mm3 = anemia

> Regenerative anemia (red bone marrow is functional) :

- After hemorrhage

> A/ Hypo regenerative anemia (absent/reduced red bone marrow function) :

- Decreased level of factors implicated in erythropoiesis :

- Fe

- Proteins

- Vitamins

- Microelements

- Poisoning with organic solvents

- After ionizing radiation exposure

3.11.4. Hemoglobin (Hb) :

3.11.4.1 Normal value of Hb.

Male : 15 - 16g % Female : 14 - 15g %

3.11.4.2 Structure :
a) Physiological hemoglobin

- Each molecule : a protein formed of four subunits

- Each subunit : a molecular group = heme (red pigment)

a polypeptide chain = globin

- Each of the four heme groups contains one atom of iron (Fe 2+)

- Each Fe 2+ binds reversibly one molecule of oxygen => a single hemoglobin molecule can bind
four oxygen molecules

Hb + O2 ↔ HbO2 (oxihemoglobină)

- The polypeptide chains are different: α, β, δ, γ, ε, ζ (zeta)

- In adults :

HbA : α2β2 (major); α2δ2 ( minor - 2% )

- Fetal hemoglobin :

HbF : α2γ2- higher affinity for O2 than HbA

Starting the age of 5-6 months → the synthesis of γ chain decreases; → starts the synthesis of β
chains

After the first year of life, HbF = 1% of total Hb

b) Pathological hemoglobin

- HbD, HbE, HbS

-  the “heme” is normal

-  the chain structure is modified



Ex : HbS : glutamic acid, from β chain is replaced by valine at position 6 => Sickle-cell disease

3.11.4.3. Combinations of Hb

a) Oxyhemoglobin (HbO2)

- In the lungs

- New three dimensional shape- ruby red -instable structure

b) Reduced hemoglobin (HbH)

- In the tissues

- O2 detaches from iron => reduced hemoglobin or deoxyhemoglobin - dark red

c) Carbaminohemoglobin (HbCO2)

- In the tissues

- It binds to globin’s amino acids group (not the heme group)

d) Carboxyhemoglobin (HbCO)

- Carbon monoxide = colorless, odorless gas (incomplete combustion of hydrocarbons- gasoline)


- One of the more common causes of sickness and death due to poisoning, both intentional and
accidental

- Very high affinity for the oxygen-binding sites in Hb —210 times higher affinity than the affinity of
oxygen

- Decreases the unloading of oxygen from hemoglobin in the tissues

- Very stable structure

- Unbinding of CO can be obtained using administration of high pressure (hyperbaric) pure
oxygen (100%)

e) Methemoglobin (MetHb)

- Oxidative chemical substances

3+ 2+
- Iron in the heme group is in the Fe (ferric) state, not the Fe (ferrous) => cannot bind
oxygen, unlike oxyhemoglobin

- Bluish chocolate-brown

- Unbinding the compound can be done by administering substances with strong reduction
potential (methylene blue, vitamin C)