Blood physiology 3

- anaemias:-

-anaemia a functional in ability of the blood to supply the tissue with adequate oxygen for proper metabolic function , caused by reduction ( below normal ) in number of rbcs , quantity of hb & volume of pcv per 100 ml of blood .

-there are two main classifications of anaemia:-

(1):-the pathogenetic & aetiological classification .
(2):-morphological classification .

(1):-pathogenetic & aetiological classification:-
-the main pathogenic & aetiological factors responsible for causing anaemia are :-

(a):- impaired rbc’s production due to deficiency of various factors promoting erythropoiesis :-
eg :- iron deficiency anaemia:-
-iron deficiency is a state in which body iron stores are depleted . the causes of iron deficiency are related to poor dietary supplementation , diminished absorption increased requirements & excessive iron (blood) loss .
-the iron enzyme myeloperoxidase is essential to neutrophil phagocytosis & bacterial killing & both functions may be diminished with iron depletion, so cell – mediated immunity (a t- cell function) can be impaired , but antibody production (a b – cell function) is normal .

-distribution of body iron
form amount of iron average adult
male (gm) female (gm) % of total
haemoglobin 2.4 1.7 65
ferritin & haemosiderin 1.0 0.3 30
myoglobin 0.15 0.12 3.5
haeme enzymes
cytochromes 0.02 0.015 0.5
catalase
peroxidase
flavoprotein
transferrin bound iron 0.004 0.003 0.1

-an anaemia due to adeficiency of iron (iron deficiency anaemia) is associated with a deficiency of hb in the red cells ( hypochromic anaemia ) & cells that are smaller than normal (microcytic anaemia ) .
-other example is megaloblastic macrocytic anaemia:- due to deficiency of vitamin b12 or folic acid & cobalt . as described above , impaired dna synthesis can be caused by vit . b12 & folic acid deficiency . this anaemia is associated with a deficiency of red cells, but the cells that are present will be larger than normal & will contain an adequate amount of hb . in order to differentiate between these two types of anaemia , a red cell count ,a haemoglobin estimation & a haematocrit determination are made .

(b):-excessive loss of blood whether acute or chronic:-

-in acute blood loss , after rapid hemorrhage the body replaces the plasma within one to three days , but this leaves a low concentration of rbc’s . if a second hemorrhage dose not occur , the rbc’s concentration returns to normal within three to four weeks .

-in chronic blood loss , the person frequently cannot absorb enough iron from the intestine to form hb as rapidly as it is lost .
-therefore , rbc’s are then produced with too little hb inside them , giving rise to microcytic hypochromic anaemia .

-for examples of this anaemia are :

-acute post – haemorrhagic anaemia .
-chronic post – haemorrhagic anaemia .

(c):-excessive destruction of rbc’s as in :-

-haemolytic anaemia :-
-a haemolytic state exists when the in vivo survival of the red cell is shortened .
-the presence of anaemia in an individual patient is , however , dependent on the degree of hemolysis & the compensatory response of the erythroid elements of the bone marrow . -normal bone marrow is able to increase its output about six –to eight – fold , so that anaemia is not manifest until this capacity is exceeded , corresponding to a red cell lifespan of about 15 to 20 days or less.

-haemolytic anaemias may be classified as follows:-

(1):-intracorpuscular defects:-

-such as hereditary defects:-
as the following :-
-defects in the red cell membrane.
-enzyme defects.
-hemoglobinopathies.
-thalassemia syndromes.

(2):-extracorpuscular defects:-
-such as:-
-immune haemolytic anaemia.
-chemicals & toxins.
-physical agents.
-splenic sequestration ( hypersplenism ).
-infections.

-the examples of the red cell membrane defects are :-

-hereditary spherocytosis (hs)

-in which the rbc’s are very small in size & they
are spherical in shape rather than being
biconcave discs .
-in hs is a loss of surface area of the red cell resulting in adecreased surface – to –volume ratio , therefore these cells less deformable than normal .
-therefore , on passing through the splenic pulp they are easily ruptured by even slight compression .

-hereditary elliptocytosis ( ovalocytosis) (he)

-he is a disorder characterized by the presence of large numbers of elliptical red cells in the peripheral blood .

-hereditary stomatocytosis
-stomatocytes have a linear slit like unstained area in the center & gives the appearance of amouth – like orifice ( hence the name – stomatocyte ).

-the example for hereditary enzyme deficiencies is:-
glucose -6- phosphate dehydrogenase ( g6pd) deficiency:-

-g6pd deficiency is transmitted by a mutant gene , located on the x – chromosome .
-g-6- pd catalyzes the first step in the pentose phosphate pathway (aerobic pathway ).
-oxidative catabolism of glucose is accompanied by reduction of nadp to nadph ,which is required to reduce glutathione (gsh) .
- reduced glutathione is important source of reducing potential , that protects hb from oxidative denaturation .
- g6pd activity is highest in young erythrocytes & decreases as aging of the cell occurs .
- gsh deficiency results in oxidative destruction of certain erythrocyte components , including sulfhydryl group of globin chains & the cell membrane.
- more than 50 chemical agents may induce hemolysis in g6pd deficient erythrocytes .

-the drug – induced hemolytic results when g6pd deficient erythrocytes fail to produce sufficient nadph & subsequently fail to maintain adequate levels of gsh .
-drugs which may lead to haemolytic anaemia in g6pd deficiency :-
(a):-antimalarias – primaquin , chloroquin pamaquin , pentaquin .
(b):-analgesic – acetylsalicylic acid , & paracetamol .
(c):-anti – bacterial – sulphonamides , nitrofurones , penicillin , streptomycin , chloramphenicol .
(d):-miscellaneous – vitamin k methylene blue , naphthalene .
-certain g-6-pd- deficient individuals also exhibit asensitivity to the fava bean (favism) these individuals develope severe hemolysis after ingesting the fava bean or even after inhaling the plant’s pollen .

-hemoglobinopathy syndromes :-
-as in sickle cell anemia :-

-the amino acid sequences in the polypeptide chains of hb are determined by globin genes.
-so there are 2 major types of inherited disorders of hemoglobin in humans :
-the hemoglbinopathies ( siclcle cell anemia ). in which abnormal poly peptide chains are produced , & the thalassemias , in which the chains are normal in structure but produced in decreased amounts because globin genes have been deletingd or rendered nonfunctional .
-mutant genes that cause the production of abnormal hb are widespread & many abnormal hb have been described in humans .
-they are usually identified by letter – such as hbc ,e , i , j , s , etc .
-in most instances , the abnormal hb differ from normal hba in the structure of the polypeptide chains
-in sickle cell anemia :- the rbc’s contain an abnormal type of hb called hbs , in which the ? chains are normal but the b chains are abnormal , because among the 146 a . a . residues in each b polypeptide chain , one glutamic acid residue has been replaced by avaline residue .
-hbs is very insoluble at low o2tensions ,so when this hb is exposed to low concentration of o2 , it precipitates into long crystals inside the red blood cell
-these crystals elongate the cell & give it the appearance of being a sickle rather than abiconcave disc . the precipitated hb also damages the cell membrane. so that the cells become highly fragile .

-thalassemia:-
-is another hereditary type of anaemia in which the rbcs are unable to synthesize adequate amounts of either the alpha or beta poly – peptide chains required to form the hb.

-there are two major types of thalassemia:-

-alpha thalassemia :- which is caused by a defect in the rate of synthesis of ? chains .
-in ? thalassaemia hb a, a2 & f are equally depressed & there is microcytic, hypochromic anaemia . in the absence of ? chains ,b or y chains are produced more & form hb ( b4 ) or hb bart’s (y4).

-beta thalassemia :- caused by a defect in the rate of synthesis of beta chains .
-in ? thalassaemia is reduced b chain production there fore hba produced is less & the anaemia produced is microcytic , hypochromic anaemia .
-total hb is maintained by increase in gamma & delta chains so, hba2 &hbf increase.

(2):-morphological classification:-

-based on morphology of rbcs , which depend on the rbc indices .
- the rbc indices are the mean cell volume (mcv) mean cell hemoglobin (mch), & mean cell hemoglobin concentration (mchc) .
-the mcv :- is used as an estimation of the average size of the rbc, & may be either calculated by dividing the hematocrit by the number of rbcs , or directly measured using most automated cell counters .if the mcv is in the reference range then the rbcs referred to as being normocytic rbcs . when the mcv is less than normal , the rbcs are referred to as being microcytic , when greater than normal , macrocytic.