haemoglobin a path i es

7/27/2019 Haemoglobin a Path i Es

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Haemoglobin apathies

Haemoglobin is the iron-containing oxygen-transport methlloprotein in the red blood cell of all

vertebrates and the tissue of some vertebrates. Haemoglobin in blood is what transports oxygen

from the lungs to the rest of the body where it releases the oxygen for cell use, and collects carbon

dioxide to bring it back to the lungs.

Haemoglobin has oxygen binding capacity which increases the total blood oxygen capacity.

Haemoglobin is involved in the transport ofother gases: it carries some of the bodys respiratory

carbon dioxide as carbaminoheamoglobi, in which CO2 is bound to the globin protein. The

molecule also carries the important regulatory molecule nitric oxide bound to globin protein thiol

group, releasing it at the same times as oxygen. Haemoglobin also found outside the red blood cells

and their progenitor lines. Other cells that contain haemoglobin include macrophages, alveolar cells

and mesangial cells in the kidney. In these tissues, haemoglobin has a non-oxygen-carrying

function as an antioxidant and a regulatory of iron metabolism.

Genetically haemoglobin consists of protein (the globin chain), and these proteins, in turn, are

composed of sequences of amino acids. In all proteins, it is the variation in the type amino acids in

the protein sequence of amino acids, which determines the proteins chemical properties and

functions. The sequence of amino acids may affect crucial functions such as the proteins affinity

oxygen. Mutations in the genes for the haemoglobin protein in a species result in haemoglobin

variants. Many of these mutant forms of haemoglobin cause no disease. Some of these mutant

forms of haemoglobin, cause a group of hereditary disease termed the

HEAMOGLOBINOPATHIES. These disease known as SICKLE-CELL AND THALASSEMIA

involves underproduction of

In Case Synthesis haemoglobin is synthesized in a complex series of steps. Haemoglobin (HB) is

tetramer of 4 globin chains each with own haem group. Each heam contains fe2+. The heam part is

synthesized in series steps in the mitochondria and cytosol of immature red blood cells, while the

globin protein parts are synthesized by ribosomes in the cytosol. Heam prosthetic group flat

molecule located in a pocket in the globin chains. This pocket has many non-polar amino acids.

Normal adult blood contains 3 types of Hb: Hb A= a2B2, Hb F =a2y2 and Hb a2= a2s2. Genes for

globin chains occur in 2 clusters: chromosomes 16 and 11. Globin genes arranged in order they are

expressed. A-globin gene is duplicated (a1 and a2). Both genes on each chromosome are active.

B-globin expressed at low level in early foetal life. Increased production after birth; switch toadult Hb (a2b2). Largely replaces y chain 3-6 months after birth. A-globin - expressed in foetal life;

production maintained.

HAEMOGLOBINOPATHIES

Haemoglobin abnormalities result from: synthesis of an abnormal Hb caused by amino acid

substitution in a or b-globin.inherited, e.g. sickle cell anaemia (Hb SS)

Reduced rate synthesis of normal a-or b-globin chains heterogeneous group of genetic disorders e.g

a and b-thalassemias. Genetic defect of haemoglobin


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Sickle cell disease (SCD)

Sickle cell diseases is a group of haemoglobin disorder in which the sickle B-globin gene is

inherited. In case of sickle cell anaemia, homozygous (HbSS) is the most common. Hb S (Hb a2B2

S) is soluble and forms crystals when exposed to low O2 tension. Deoxygenating sickle

haemoglobin polymerizes into long fibres each consists of seven intertwined double strands with

cross-linking. The red cells sickle and may block different area of the microcirculation or large

vessels cause infarcts of various organs. One in four West African, maintained at this level because

of the protection against malaria that is afforded by the carrier state.

Clinical Features

Homozygous disease is the most common form of sickle cell anaemia. Its clinical features are of

severe haemolytic anaemia punctuated by crises. Symptoms of anaemia are often mild in relation to

severity of the anaemia. Hb S gives up oxygen to the tissue and can be relatively compared to Hb

A.

Clinical expression of Hb SS is very variable, some patient tend to have normal life free of crisis

other develop severe crises in early childhood or as young adult and my die as result of crises

such as vaso-occlusive, visceral, aplastic or haemolysis.

Clinical features - Crises

Painful vaso-occlusive crises is most frequenct and are precipitated by such factors as infection,

acidosis, dehydration, deoxygenating. Infracts can occur in variety of organ s including the bones,

lungs, spleen, brain , spinal cord.

Visceral sequestration crises these are cause by sickling within organs and pooling blood. Present

with enlarge spleen seen in infants, falling haemoglobin and abnormal pain. Attach tend to be

recurrent and usually splenectomy my needed.

Aplastic crises these occur as result of infection with parvovirus or from folate deficiency and

characterised by sudden fall of haemoglobin and reticulocytes

Haemolytic crises increase rate of haemolysis with fall haemoglobin and rise in reticulocytes and

usually accompany with painful crisis. Other clinical features are ulcers of the low legs are common

as result of vascular stasis and local ischemia. Spleen enlargement in infancy and earlier but later

reduces in size due to infarcts (autosplenectomy). Pulmonary hypertensions are common and

increase risk of death. A proliferative Retinopathy and priapism. Chronic liver damage may accurs

through gallstone to microinfarcs. Pigment (bilirubin) gallstones are frequent. Kidneys vulnerable

to infarcts of the medulla failure to conc urine aggravates dehydration and crisis Nocturnal

enuresis (bedwetting) is common. Osteomyelitis (usually from Salmonella).

Laboratory findings

Blood film will show Sickle and target cells seen; Features of splenic atrophy (e.g. Howell-Jolly

bodies).Hb low in cf symptoms of anaemia (6-9 g/dL). Screening tests for sickling are positive


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when blood is deoxygenated (e.g. dithionate, Na2HPO4). Hb electrophoresis: no Hb A is

detected.Hb F variable; usually 5-15%. Larger amounts normally associated with milder disorder.

TREATMENT

Prophylactic avoid factors known to precipitate crises specially dehydration, anoxia, infections,and cooling of the skin surface. Good nutrition, hygiene; folic acid (5mg weekly). Crises treat by

rest, warmth, rehydration by oral fluids and or intravenous normal saline and antibiotics. Suitable

drugs are paracetamol, opiates (e.g diamorphine and anti-inflammatories. Exchange transfusion

my be needed if there is neurological damage, VS crisis, repeated painful crises.

Hb S < 30% in severe cases >= 2 year after stroke. Hydroxyurea (15-20mg/kg) can increase HB F

improves clinical course >=3 painful crises each year. Immunisation e.g pneumococcal,

haemophilus, Meningococcal vaccines and regular oral penicillin (equivalent if allergic) for

example hepatitis B vaccination as transfusions may be required.

Blood transfusion sometimes given if there is severe anaemia with systems. The aim is to suppress

Hb S production over months and years and treat iron overload. Particular care is need in pregnancy

and anaesthesia. In pregnancy transfusions needed to increase Hb S level during, pre-delivery andminor operations. In the case of the anaesthesia recovery techniques much be used to avid

hypoxemia or acidosis. Stem cell transplantationcan cure dieases. Reseach into other drugs and

gene therapy to enhance the Hb F synthesis and to increase solubility of Hb S is taking place


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haemoglobin a path i es

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