BLOOD

 I-BLOOD

Blood is a tissue which circulates in a closed system of blood vessels.

Composition of blood
A-The blood Cells:	45 % blood volume
RBC's	4.5-5.5 million / mL
Platelets	150,000 -250,000 / mL
WEC's	5,000 -10,000 mL
B-The plasma	55 % of blood volume (yellow in color due to presence of small amount of bilirubin and carotenoids).

THE BLOOD CELLS

I-Platelets: They contain proteins and relatively high concentration of phospholipids, especially cephalins. They contain the different blood clotting factors and high concentration of histamine and serotonin.

II-Leukocytes:

Similar to other cells but they are rich in nucleoproteins.

1-Lympbocytes: contain large amounts of g-globulins.

2-Basophils: rich in heparin and histamine.

3-Granulocytes and Monocytes: have a high content of phosphatases, glycolytic and proteolytic enzymes, the latter being related to the phagocytic action of these cells. III-Red Blood Cells: the mature erythrocyte does not possess a nucleus or cytoplasmic subcellular structures. Erythrocytes have a solid content 35 %, 32 % as hemoglobin and the remaining 3 % is in the form of proteins and lipids.

Composition of RBC's

 I-Organic constituents: This mainly in the form of Hb. Other organic constituents include; proteins, the blood group substances, glutathione, free amino acids, enzymes, glucose, products of glucose metabolism and lipids (mainly glycolipids, phospholipids and cholesterol). 2-Inorganic constituents: The erythrocytes contain high concentration of K⁺, Zn²⁺ (activator of carbonic anhydrase) and phosphate, less amount of Na⁺ and Mg²⁺, but no Ca²⁺.

 Metabolism of erythrocytes:

1-Glycolysis (conversion of glucose to lactic acid) is the only source of energy in red cells. Also, it provides NADH for reduction of methemoglobin.

The Rapoport Luebering Cycle:

It provides 2,3-bisphosphoglycerate which facilitates the delivery of oxygen to the tissues in circumstances of low oxygen tension, and it was found that the concentration of bisphosphoglycerate in erythrocytes is increased in cases of hypoxia e.g. high altitude.

2-Energy is, required for preservation of the integrity of erythrocyte morphology (biconcavity), composition and function including transport of many substances across the cell membrane e.g. sodium and potassium.

3-HMP provides NADPH for reduction of glutathione. Reduced glutathione is utilized for reduction of H₂O₂. This protects red cells from oxidative damage and prevents oxidation of hemoglobin to methemoglobin.

4-Carbonic anhydrase enzyme plays an important role in CO₂ transport.

5-Rhodanese (cyanide sulfur transferase) catalyzes the transformation of cyanide to thiocyanate. Other enzymes are present e.g. peptidases, catalase, phosphatases and choline esterase.

Abnormalities of Red Cell

1-Favism or Glucose 6-phosphate dehydrogenase deficiency

2-Pyruvate kinase deficiency causes hemolysis

3-Hereditary spherocytosis due to genetic mutation of the gene encoding spectrin and results in loss of the biconcave shape of red cells and become abnormally fragile.

4-Abnormalities of hemoglobin

e.g. methemoglobenemia sickle cell anemia and thalassemia.

The Plasma

Plasma contains 8 to 9 % solids, composed mainly of proteins. The constituents of plasma are distributed as follows:

Composition of Plasma	Value range (normal value)
I-Plasma Proteins	6.0 -8.0 g/dL
a-Albumin	3.5 -5.5 g/dL   [55%]
b-Globulin	2.S -3.5 g/dL   [45%]
a1-globulin	0.2 -0.4 g/dL
a2-globulin	0.5 -1.0 g/dL
b-globulin	0.5 -1.2 g/dL
g-globulin	0.5 -1.6 g/dL
c-Fibrinogen	0.2 -0.6 g/dL
II-Non-Protein Nitrogenous (NPN) Compounds: 15-60 mg/dL
a-Urea	10 -50 mg/dL
b-Free amino acid (N)	3 -6 mg/dL
c-Uric acid	3-7 mg/dL
d-Creatinine	0.8 -1.2 mg/dL
e-Creatine	0.2 -0.9 mg/dL
f-Ammonia	0.05 -0.1 mg/dL
III-Carbohydrates:
a-Glucose		70 105 mg/dL
b-Fructose		5 -10 mg/dL
c-Pentoses		2 -3 mg/dL
d-Mucopolysaccharides  (GAG)		80 -120 mg/dL
IV-Lipids:400 -700 mg/dL
a-Cholesterol		120-240  mg/dL (180)
b-Phospholipids		150 -250 mg/dL (200)
§  Lecithins		125 mg/dL
§  Cephalins		50   mg/dL
§  Sphingomyelin		25   mg/dL
c-Triacylglycerols		0-150   mg/dL  (100)
d-FFA (free fatty acid)		10 -30  mg/dL   (20)
VI-Bile Pigments up to 1.2 mg/dL
a-Direct bilirubin		up to 0.3 mg/dL
b-Indirect bilirubin		up to 0.9 mg/dL
VII-Inorganic constituents
Sodium		136 -145 meq/L
Chloride		96 -106 meq/L
Potassium		3.5-5 meq/L
Calcium		9-11 mg/dL
Phosphorus		3-5 mg/dL
Sulfur		0.5-1.5 mg/dL
Iron		50-150 mg/dL

NON PROTEIN NITROGENOUS COMPOUNDS

The total NPN compound in plasma is 15 to 60 mg /dL which include the following main fractions:

1-Urea: 10 -50 mg/dL

Urea is the chief end product of protein metabolism. It is formed in liver, transported into blood, and excreted by kidneys in urine.

Causes of increased urea level

-Temporarily after a high protein meal.

-Renal failure (impaired excretion).

-Increased protein catabolism e.g. after glucocorticoids.

Causes of decreased urea level

-Severe protein restriction.

-Increased protein synthesis e.g. during pregnancy growth and after administration or growth hormone, insulin, and testosterone (anabolic hormones).

-Severe liver disease (decreased formation)

II-Free amino acid (N): 3 -6 mg /dL

Causes of increased amino acid levels

 -After a protein meal.

 -Increased protein catabolism.

 -Liver damage (decreased deamination).

Causes of decreased amino acid levels

As during stimulation of protein synthesis e.g. after anabolic hormones.

III-Uric acid: 3 -6 mg/dL (female), 4 -7 mg/dL (male)

It is formed by catabolism or purines in liver and excreted

 by kidneys in urine.

 Causes of increased uric acid levels

-Gout (metabolic or renal).

-After nucleoprotein rich diet.

Causes of decreased uric acid levels

-Severe liver damage (due to decreased production).

-Enzyme deficiency causing hypouricemia e.g. xanthine oxidase, adenosine deaminase and purine nucleoside

Phosphorylase.

IV-Creatine (0.2-0.9 mg/dL) and Creatinine (0.6-1.2 mg/dL).

Creatinine is the metabolic end product of creatine metabolism. Creatinine level increases in cases or renal diseases (due to decreased excretion in urine).

V-Ammonia 0.05 -0.1 mg/dL

Its level in blood increases in case or liver diseases. Ammonia is formed by deamination of amino acids and by intestinal putrefaction; ammonia is removed by the liver mainly as urea and to lesser extent as glutamine.

PLASMA ENZYMES

Estimation of the activity of plasma enzyme is important in diagnosis of many diseases, for example:

I-Transaminases:

They originate mainly in liver heart and muscles. Alanine transaminase (ALT or GPT) and aspartate transaminase (AST or GOT) activity increase in the following acute hepatitis (higher ALT than AST), chronic hepatitis (higher AST than ALT) and myocardial infarction: high AST levels start few hours after the onset of infarction, reaches maximum within 48 hours and returns back to normal within 5 day.

2-Lactate Dehydrogenase (LDH):

It orginates mainly in liver, heart and muscles. H and M subunits are synthesized by distinct genes and are differentially expressed in different tissues. Estimation of LDH isozymes in plasma is of clinical importance. Isozymes 1 and 2 are mainly of cardiac origin and they are increased in cases of myocardial infarction and isozyme 5 is increased in case of liver diseases (hepatic origin) or muscle diseases (muscular origin).

3-Creatine Kinase

It is a dimer and is formed of two subunits termed M or B. It has three isozymes as folIows: CK1 (or CK-BB) present in brain tissues and its plasma level increases in case of brain infarction. CK2 (or CK-MB) present mainly in cardiac muscles and its plasma level increases in myocardial infarction CK3 (or CK-MM) present mainly in skeletal muscles and its plasma level increases in muscle diseases.

4-Amylase

It is derived mainly from the pancreas and salivary glands. An increase in plasma or serum amylase occurs in cases of acute pancreatitis, obstruction of pancreatic duct and in parotitis (inflammation of parotid gland).

5-Lipase

It originates from the pancrease and increases in case of pancreatitis and pancreatic duct obstruction.

6-Alkaline phosphatases

It originates mainly from bones (osteoblasts and to less extent osteoclasts). An increase in plasma occurs in the following:-

 a-Bone disorders: as osteomalicia, rickets, and paget's disease of bone (osteoblastic proliferation).

 b-Bile ducts

Obstruction and in certain cases of hepatic disease (obstructive and hepatocellular jaundice). This is mainly due to impaired excretion in bile.

c-Hyperparathyroidism

 7-Acid phosphatase

It originates mainly in liver and spleen; high amounts are formed by prostate, its level increases significantly in cases of prostatic carcinoma.

8-Choline esterase

It originates from liver, decreased level occurs in impaired liver functions.

Best Wishes: Dr.Ehab Aboueladab, Tel:01007834123 Email:ehab10f@gmail.com,ehababoueladab@yahoo.com