Blood Chemistry

blood chemistry
constituents of blood
the chemistry composition of blood is complex . it is an aqueous solution of ions and organic molecules which also have suspended particles . suspended particles in blood are red blood cells (erythrocytes ) , white blood cells ( leukocytes ) and platelets . blood without suspended particles is called blood plasma . blood serum is obtained when fibrinogen , a particular protein is removed from plasma . the major blood constituents are shown in table 17.1.

a.when blood is drawn and allowed to clot , a clear liquid ( serum ) licudes from the clotted . plasma on the other hand separates the cells only when blood is prevented from clotting
b. the blood clot is formed by a protein (fibrinogen ) which is present in the soluble form in the plasma and which is transformed to an insoluble network of fibrous material ( fibrin , the substance of the blood clot ) by the clotting mechanism
c. the change of fibrinogen into fibrin is caused by thrombin , which in fluid blood looks as prothrombin . the conversion of prothrombin depends on the action of thromboplastin and calcium .
anticoagulants
clot formation may be prevented by a number of substances as well by vitamin k deficiency . dicemerol , related to coumarin which comes from clover , inhibits prothrombin synthesis in the liver . it may be used clinically when there is danger of thrombosis by reducing clotting tendency .
heparin heparin
a sulphated polysaccharide which inhibits the formation of thrombin from prothrombin , is the most satisfactory



table 17.1 : blood constituents

compounds normal values possible pathology
haemoglobin 14-16 g/100 ml whole blood high in polycythaemia.
low in anaemias.
non–protein nitrogen 25-25 mgm/100 ml
whole blood high in nephritis and addison s disease
uric acid 3-5
mgm/100 ml
whole blood high in gout
total plasma proteins 6-5-8.2g/100 ml plasma low in nephrotic syndrome and malnutrition
cholesterol 150-300
mgm/100 ml
plasma or serum high in nephrotic
syndrome and hypothyroidism. low in pernicious anaemia and liver disease
glucose 80-110
mgm/100 ml
whole blood high in diabetes.
low in addison s disease
co2 combining power 53-80 ml. co2/100 ml plasma low in acidosis, uncontrolled-led diabetes and nephritis.
inorganic phosphates 3-4 mgm/100 ml plasma or serum high in renal rickets and nephritis. low in infantile rickets
chloride 570-620 mgm (as nacl)per 100 ml plasma or serum high in nephritis.
low in fever or pneumonia

anticoagulant , since it produced no change in the composition of the blood . however , oxalate and citrate have most widely used as they are cheaper . use of more of these salts may bring appreciable changes in the distribution of water between the cells and plasma .
potassium oxalate
it has been most commonly used since it is more soluble . it acts by precipitating calcium ions as calcium oxalate .
sodium citrate
citrate dose not precipitate calcium but converts it to non- ionized form . citrated plasma is not as satisfactory as serum for calcium estimation . ethylenediamine tetra acetic acid (edta) and its salts act by chelating calcium ions .
sodium fluoride
it also acts as an anticoagulant but large amounts are required . for blood glucose estimation a mixture of sodium fluoride and potassium oxalate is used as fluoride acts as a preservative by inhibiting glycolytic enzymes .
functions of blood
1. carrying the products of digestion from the small intestine to various organs and tissues
2. accepting oxygen in the lungs and releasing it in the tissues.
3. carrying co2 from the tissues for elimination by the lungs
4. removal of waste products from tissues for excretion by the kidneys.
5. maintenance of water balance and temperature control .
6. syntheses of antibodies for the protection against bacterial infection.
7. distribution of hormones , vitamins and enzymes to their sites of action .
oxygen transport
during respiration , gases co2 and o2 are interchanged between the body and the environment . this process can occur due to the haemoglobin present in red blood cell (rbc) . the function of the rbc is to carry the inhaled oxygen from lungs to tissues , where it is utilized for their growth , development and sustenance . haemoglobin is a globular protein . it consists of four polypeptide chains arranged in a tetrahedral configuration . haemoglobin contains a non – protein constituent called heme . heme is an iron porphyrin and is responsible for the red colour of blood . each of the polypeptide chains of haemoglobin is associated with one heme unit . haemoglobin combines with oxygen in the lungs ( where oxygen is present in higher concentration ).such a combination results in the formation of oxyhaemoglobin . myoglobin stores oxygen in the muscle tissues . in contrast to haemoglobin it consists of only a single polypeptides chain and is associated with one heme unit .
formation of co2 and its distribution in blood
co2 is formed in large amounts in the body as the end product of normal metabolism . in tissues about 200 ml of co2 is formed perminute at rest and 4 litres at maximal exercise . co2 enters the blood stream and from there reaches the lungs .the chief acid present in the blood is co2 .co2 dissolves in water to from h2co3 which on dissociation yields h+ and hco3- .
h2o + co2 h2co3 h+ + hco-3
the only alkali present as such in blood is bicarbonatehco3 . it dissociates in water as follows :
na hco3 + h2o h2co3 + naoh
plasma proteins
plasma proteins constitute almost 70 per cent of the plasma and are usually divided into 3 groups : albumin , globulins and fibrinogen . approximately 55 per cent of the plasma protein is albumin , 38.5 per cent globulins and 6.5 per cent is fibrinogen . albumin , like other plasma proteins , cannot pass through the walls of the blood vessels ( because they are colloids and colloids cannot pass through membranes ) . since albumin is principal plasma protein and the smallest plasma protein both in size and weight ( it consists of a single chain of 610 amino acids ) , it accounts for most of the colloid osmotic pressure of the blood . this colloid osmotic pressure is caused by the small amounts of plasma that pass through the capillary membranes and tend to accumulate as the venous end of the capillaries . if the plasma protein ( primarily albumin ) are present in decreased ( as during a low protein diet or in nephritis ) the osmotic pressure of the plasma decreases . this decreases osmotic pressure of the blood cause a greater net pressure outward at the arterial end of the capillary and a lower net inward venous pressure at the venous end of the capillary . when this occurs , water (fluid) accumulates in the tissues . such a condition is known as an oedema .
kwashiorkor
a severs protein deficiency disease , is characterized by edema of the abdomen and extremities . in children a swollen belly is characteristic . kwashiorkor is caused by a droping in plasma protein particularly albumin . under these conditions , water moves from the blood stream into the tissues causing swelling . oedema can also occur because of heart disease , whereby there is an increase in venous hydrostatic pressure . many terminal illnesses cause oedema . this becomes a serious problem and tapping and draining may be necessary . concentrated albumin infusions (25 g in 100 ml diluent) are helpful in the treatment of shock , to increase the blood volume , and to remove fluid from the tissues . the amount of albumin present in the blood is lowered in liver disease because albumin is formed in the liver . another function of albumin in the blood is to act as a carrier for fatty acids , trace elements and many drugs .
globulins
the globulins present in the plasma can be separated into different groups by a process known as electrophoresis whereby charged protein particles migrate at varying rates to electrodes of opposite charge , with albumin migrating the fastest . the distribution of the plasma proteins during electrophoresis. the globulins from complexes (loose combination ) with such substances as carbohydrates ( mucoprotein and glycoprotein ) , lipids ( lipoprotein ) and metal ions ( transferring for fe and ceruloplasmin for cu ) . these complexes can be transported to all parts of the body . the y- globulins (immunoglobulins ) include the antibodies with which the body fights infectious diseases . y – globulin has been found to contain as many as 20 different antibodies for immunity against such diseases as measles , infections hepatitis , poliomyelitis , mumps and influenza . some people lack the ability to make y – globulin . these people are quite susceptible to infections because they have no antibodies to counteract such diseases . the lack of y- globulin is called agmmaglobinemia and can be combated by the administration of y- globulin .
blood buffers
the normal ph range of the blood is 7.35 to 7.45 . when the ph falls below this range , the condition is called acidosis . alkalosis occurs when the ph rises above its normal value . acidosis is more common than alkalosis because many of the metabolic products produced during digestion are acidic .
maintenance of acid – base balance ( ph)
the mechanisms operating in the body to accomplish the maintenance of acid – base balance are :
1. buffer systems of the blood
2. respiratory mechanisms
3. renal mechanisms
a. excretion of excess acid or base
b. formation and excretion of ammonia
blood buffers
the blood maintains its ph between 7.35 and 7.45 because of buffers . these buffers are present both in the plasma and in the rbcs . those in the plasma are primarily sodium buffers those in blood cells are mainly potassium buffers . buffers are substances , usually a mixture of a weak acid and a salt of a weak acid that resist change in ph. the blood buffers consist of:
a. bicarbonate buffers
b. phosphate buffers
c. protein buffers (including hemoglobin and oxyhemoglobin).
bicarbonate buffers
the bicarbonate buffers system in the red blood cells consists of carbonic acid (h2co3) and potassium bicarbonate (khco3).
the bicarbonate buffer system in the blood plasma consists of carbonic acid and n2hco3. if a strong acid (such as hci) is added to a sample of blood, it will react with the salt part of the buffer and undergo the following reactions.
hci + khco3 h2co3 + kci (in blood cells)
hci + nahco3 h2co3 + naci (in blood plasma)
the carbonic acid (h2co3) produced is part of the original buffer.
note that the strong acid hci, has been replaced by a very salts and will not affect the ph of the system.
if a strong base like koh or naoh is added to a sample blood, the following reactions will occur with the bicarbonate buffer system:
koh + h2co3 khco3 + h2o( in blood cells)
naoh + h2co3 nahco3 + h2o (in blood plasma)
the salts khco3 and nahco3 are part of the original buffer system and the water produced is neutral, so the ph again is not affected. in both cases (reaction with a strong acid or a strong base) more of the buffer is produced plus a neutral compound. the bicarbonate buffers control the ph of blood and the phosphate buffers have an important role inside the cell and the urine.


phosphate buffers
the phosphate buffers consist of mixytures of k2hpo4 and kh2po4 (also nahpo4 and nah2po4) which function similarly the bicarbonate buffers in neutralizing excess acid and base.
hci + k2hpo4 kh2po4 + kci
koh + kh2po4 k2hpo4 + h2o more buffer
haemoglobin buffers
the haemoglobin buffers account for more than half of the buffering action in the blood. these are haemoglobin buffers and oxyhaemo-globin buffers.
hhb
khb haemoglobin buffer
hhbo2
khbo2 oxyhaemoglobin buffer
these buffers, as well as other proteins that act as buffers in the blood stream, pick up excess acid or base to help keep the ph of the blood at 7.35 to 7.45.
respiratory mechanism
the process of respiration, i.e. the intake of oxygen and removal of co2 requires the transport of these substances by blood. since co2 reacts to form hco-3 and oxygen forms oxyhaemoglobin which is more acidic than haemoglobin, the respiratory process is involved in the delicate acid-base balance of the body. maintenance of a constant ph of 7.35 to 7.45 is required for health. the respiratory centre in the ph of the blood and immediately causes an increase in the rate and depth of breathing until excess co2 (and hence excess h+) is removed. changes brought about by respiration are rapid.
renal mechanisms
this is by far the most effective mechanism, but it is slow, requiring hours to show result. the kidneys excrete more hco3- and hpo4-, when the blood ph is too high and more h+ (which it gains in exchange for na+) and h2po4 when ph is too low. also the kidney can increase its production of nh3 (ammonia) which will trap h+ to form nh4, thus lowering the acidity of the blood. since the cell membrane is not permeable to the charged nh4, it is trapped and excreted in the urine as ammonium salts. ammonia is produced in the epithelial cells largely by the deamidation of glutamine taken up from the arterial blood.
glutamine + h2o glutamic acid + nh3
urine is slightly acidic because of the phosphates and sulphates, formed principally from catabolism of the food, and extracted mainly as acid ions, h2po4- and hso4-. also organic acids formed in metabolism are extracted by the kidney if they do not undergo further metabolism.
measurement of acid-base balance
the definite way of assessing the state of acid-base balance of the body is to determine the ph of the blood. but clinically this is not always possible. as an alternative method, determination of the co2 content of the plasma is considered suitable for clinical purpose. acidosis and alkalosis – acid base imbalance – disturbance in h+ homeostasis . changes in the co2 level in blood and corresponding change in hco3- and ph
may be caused by respiratory acidoses , respiratory alkalosis, metabolic acidoses and metabolic alkalosis . if the ph is abnormally high or low , the alkalosis or acidosis is said to be uncompensated . disturbances in the acid – base balance are known as acidosis and alkalosis and these occur mostly due to abnormalities in respiratory system or due to disturbances in metabolism . accordingly acidosis and alkalosis are classified as :
1. a. respiratory acidosis
b. respiratory alkalosis
2. a. metabolic acidosis
b. metabolic alkalosis
respiratory acidosis
it is caused by depression of the respiratory centres by drugs , e.g. barbiturate poisoning , narcotics ingestion , in pulmonary disorders ( pneumonia ) due to mechanical obstruction of air passage and during breathing of air with high co2 content . there will be a decrease in blood hco3- content and increased levels of co2 ( h2co3) . the condition is compensated by the action of the kidneys .
respiratory alkalosis
it is relatively uncommon . it is caused by hypoventilation as in high fever , hysteria , high altitudes and salicylate poisoning or due to dry hot weather . it can also occur during anaesthetic procedures with manual control of breathing causing expulsion of co2 and in certain diseases of central nervous system affecting the respiratory system .
metabolic acidosis
in this condition , there is a deficit of plasma bicarbonate , without much change in the carbonic acid content . metabolic acidosis can occur in the following conditions :
a. uncontrolled diabetes m complicated with ketosis
b. vomiting with loss of fluid not containing acid
c. poisoning by an acid salt
d. starvation , high fever
e. violent exercise
f. lactic acidosis due to hemorrhage
g. ingestion of acidifying salts like acetyl salicylic acid , phosphoric acid . hcl , nh4cl
h. renal insufficiency : retention of acids normally produced , e.g. terminal stages of nephritis , destructive renal lesions , such as polycystic kidneys , pyelonephritis , renal tb. the co2 /bicarbonate buffer system in blood reflects changes in all buffer systems during disturbances . when ph falls , the ratio hco3- / co3 + h2co3 also decreases . excess of co2 is blown off through lungs that bring back the original ratio and ph. thus , acidosis is compensated by a respiratory response .




metabolic alkalosis
in metabolic alkalosis , the bicarbonate content of the plasma is increased without undue changes in the carbonic acid content.metabolic alkalosis occurs in the following conditions:
a. ingestion of large doses of alkalies in the treatment of pepticulcers .
b. excessive vomiting with loss of large amount of gastric juice as in cases of intestinal obstruction .
c. removal of large amounts of gastric secretion as in gastric suction. there is also loss of chloride . compensation is attempted by a depression of respiration so that more co2 is retained .