Patho sheet.hematology#1 - Sarah waya

View previous topic View next topic Go down

Patho sheet.hematology#1 - Sarah waya

Post by Shadi Jarrar on 14/5/2011, 1:10 am

بسم الله الرحمن الرحيم

____________________________
4shared.com/file/kXSIkj_j/Sheetdocx_pathology_hematology.html
____________________________


Sheet #1 Hematology
I have used this star (*) whenever the doctor mentioned something out of the handout.
The recording starts from extravascular hemolysis ( P.2 in the handout)
Extravascular hemolysis : occurs in the mononuclear phagocytes of the spleen and other organs due to red blood cell membrane injury ,which occurs due to reduced deformability or oponization . In this case there is no hemoglobinemia or hemoglobinuria.
The first example of hemolytic anemias is :
Hereditary spherocytosis
Predominantly an autosomal dominant disorder in 75 % of cases.
Red blood cell cytoskeletal protein defect (spectrin) renders the erythrocytes spheroidal,less deformable and vulnerable to splenic sequestration and destruction.
**Any change in the shape of RBCs make them less deformable and they are therefore trapped and destroyed in the spleen.
In peripheral blood spherocytic cells appear small with no central pallor ,the bone marrow exhibits erthroid hyperplasia ,patients are present with anemia ,moderate splenomegaly and jaundice.
**Normal RBCs have central pallor ,the diameter of the central pallor is 1/3 the diameter of the RBC. In spherocytosis ,the central pallor disappears.While in iron deficiency anemia ,the central pallor increases.
Infection with parvovirus can induce aplastic crisis, half of adults develop pigmented gall stones (at an earlier age )from chronic hyperbilirubinemia.
The laboratory findings include increased osmotic fragility of RBCs.


**Page 3 in the handout (figure 12.1 in the book )
The photo on the left shows the membrane bilayer : many defects in spectrin causes sphercytosis ,most important of which are :defects in the ankyrin,band 3 and glycophorin.
Page 4 (figure 12.2 in the book ) : note the central pallor in normal RBCs, and note the spherocytes ,they appear smaller and with no central pallor.
Glucose -6-phosphate –dehydrogenase deficiency
G6PD is an enzyme in the hexose monophosphate shunt that produces reduced glutathione that protects the RBCs from oxidative injury.
In G6PD deficient cells oxidant stress induces hemoglobin denturation and precipitation as Heinz bodies which attached to the inner cell membrane reducing deformability causing both intra and extravascular hemolysis.
It is a sex linked disorder with several variants, only two variants , G6PDA- and G6PD Mediterranean lead to significant hemolysis.
**G6PD Mediterranean is also called fauvism (results from eating fresh green beans)
**Page 5 ( figure 12.7 in the book )
A case of G6PD deficiency , precipitated hemoglobin (Heinz bodies ) are revealed by supravital staining.
Sickle cell disease
A hereditary disorder resulting from substation of valine for glutamic acid at the sixth position of B-globin chain, transforming normal hemoglobin A (alpha 2 beta 2 ) into mutant hemoglobin S ( alpha 2 beta s 2)
** Glutamic acid is hydrophilic while valine is hydrophobic and charged. So when we have valine instead of glutamic acid ,polymerization of the beta chain results due to its hydrophobicity.
Deoxygenated hemoglobin S undergoes aggregation and polymerization into long stiff chains that deform (sickle) red blood cells.In the homozygous state ,irreversibly sickled cells can be readily identified in peripheral blood.
** In a smear we can only see the irreversibly sickled cells. The reversible ones can only be seen if we deoxygenate the smear.
Many factors influence sickling of RBCs:
1-the amount of Hbs and its interaction with other hemoglobin chain in the cell (the most important factor) HbF,HbA,HbC
**Hbs with HbF for example,the influence is much less because HbF reduces the polymerization,that’s why signs and symptoms appear after 6 months of birth(as u know babies are born with HbF ) .HbF has gamma chains (no beta chains) .
** Alpha chains with hemoglobin S reduce the signs and symptoms.
**Hemoglobin C with Hbs :some people have 2 substitutions (double heterozygous).The condition is worse,more polymerization.
2- *Dehydration increases the the Hb concentration and therefore increases the Hbs concentration and increases the polymerization.
*In alpha thalessemia ,Hb concentration is decreases due to alpha chains and therefore the sickling severity is decreased.
3- sluggish blood flow increases the rate of polymerization.
4-**repeated episodes of vasoocclusion (infarction)in the spleen >> progressive scarring and shrinkage (autosplenectomy) >>increases the susceptibility to infection by streptococcus pneumonia and haemophilus influenza (they both are encapsulated bacteria >meaning we need opsonization to get rid of them )
And for unknown reasons those patients are also susceptible to infection by salmonella and osteomyelitis.
*Page 8 (figure 12.3)
A peripheral blood smear for a patient with sickle cell disease. They are very deformed ,therefore they get trapped in the spleen.
Thalassemia syndrome
Defects that lead to reduced synthesis of alpha or beta chains.
Beta chains are encoded by a single gene on chromosome 11, while the alpha chains are encoded by two closely related linked genes on chromosome 16.
B-thalassemia syndromes are characterized by defiecient synthesis of B-globin.
In B (zero) thalassemia there is total absence of B-globin chains in the homozygous state.
In B+thalassemia ,there is reduced B-globin synthesis in the homozygous state.
Several different point mutations affecting transcription,processing or translation of B-globin mRNA can cause B-thalassemia. Mutations causing aberrant mRNA splicing are the most common.
Alpha thalassemia is characterized by reduced alpha-globin synthesis due to deletion of one or more of alpha-globin genes. (we have 2 genes)
The consequences of diminished synthesis of one globin chain derived from both low intracellular hemoglobin and relative excess of the other chain.

B-Thalassemia
-Thalassemia major ,homozygotes for B thalassemia gene have severe transfusion dependant anemia,hemoglobin levels are 3-6 gm/dl. Excessive erthropoiesis results in bone deformities .Multiply transformed patients develop progressive iron overload and secoundary hemochromatosis.
**B zero B zero are transfusion dependant patients,they a need huge amount of blood that’s why they develop secoundary hemochromatosis ,iron accumulates in the liver,pancreas and some endocrine organs like pituitary and testis.
-Thalassemia minor,heterozygous are usually asymptomatic due to sufficient B-globin synthesis,blood film shows microcytic hypochromatic anemia,recognition is important for genetic counseling.
**these patients are not discovered unless they do a blood test , and usually have mild anemia.
If two patients with B-thalassemia minor got married ,the possibility is high that their child is born with B-thalassemia major.
-Thalassemia intermedia : clinical features are intermediate between major and minor,these patients are genetically heterozygotes.
*The following cases are different : B0 B0 ,B+B0, B+B+
B+ means there is some synthesis of the Beta chains
B0 means there is no synthesis at all.
**Page 10 : figure 12.6
So here we have reduced B-globin chain with relative excess of alpha globin chain. Excess of the alpha chain causes the deformity and precipitation of the RBC. (Abnormal erythroblast) This leads to ineffective erthropoiesis >> in which we have bone marrow hyperplasia ,but elements of the blood are obstructed in the bone marrow (as if we have hemolysis in the bone marrow)
*Those patients have hyperbiliribinemia, hypohaptoglobin* and increased hemoglobin in the circulation. The resulting anemia from the destruction of RBCs causes tissue anoxia which induces the release of erythropoietin from the kidney and leads to bone marrow expansion and skeletal deformities.(thickening of the jaw,skull,etc...)
Most patients with B-thalassemia have skeletal abnormalities.
*Dietary iron is absorbed in higher quantities from the GI and is deposited in the liver,heart and pancreas leading to secoundary hemochromatosis.
**’’Haptoglobin : a protein that binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system (mostly the spleen) ‘’ wikipedia
Alpha-thalassemia
Severity is related to the number of alpha chains genes deleted :
-Silent carrier state (single gene deleted)
-Alpha thalassemia trait (2 genes deleted)
-HbH disease (3 genes are deleted) excess tetramers of B-globins
-Hydrops fetalis (all 4 alpha genes are deleted):
Gamma chain tetramers ( Hb Barts) with extremely high oxygen affinity and inability to release oxygen to tissues ,this case is incompatible with life.

B12 dificiency anemia
Impaired vitamin B12 absoprption can results from :
-Achlorohydria
-gastrectomy
-pernicious anemia
-Resection of distal anemia
-Malabsorption syndrome
-increased requirement (pregnancy)
-inadequate diet
Pernicious anemia is an autoimmune disease to gastric parietal cells resulting in chronic atrophic gastritis and marked parietal cell loss,followed by defficient-IF (intrinsic factor) production:
**Gastric parietal cells are important for the production of HCl ,and the intrinsic factor that is essential for the absorption of vitamin B12.
-Type I antibodies block binding of B12 to IF
-Type II antibodies prevent IF or IF-B12 complex binding to ileal receptors.
-Antibodies against gastric proton pump bind to parietal cells and affect acid secretion.
There is a significant association between pernicious anemia with other autoimmune disorders.
**All autoimmune disorders are linked together and are called polyglandular syndromes.
Bone marrow changes include megaloblastic erythroid hyperplastic giant metamegalocytes and hypesegmented neutrophils.
** The first thing we notice in peripheral blood in cases of B12 deficiency is hypersegmented neutrophils. (neutrophils normally have 3 to 5 segments)
In 75% of cases ,lesions in the central nervous system are characterized by demyelination of the dorsal and lateral columns of the spinal cord.
Anemia of folate deficiency induces a megaloblastic anemia .Clinically and hematologically indistinguishable from that seen with vitamin B12 deficiency,except that gastric atrophy and neurologic changes do not occur.

** So neurologic changes occur only with Vitamin B12 deficiency .(It is thought that it has an association with the myelination of nerves).
While megaloblastic anemia occurs with both,vitamin B12 and folate deficiency.

Sorry for the delay & good luck in your finals.
Sarah Waia



























avatar
Shadi Jarrar
مشرف عام

عدد المساهمات : 997
النشاط : 12
تاريخ التسجيل : 2009-08-28
العمر : 27
الموقع : Amman-Jordan

http://jude.my-rpg.com

Back to top Go down

View previous topic View next topic Back to top

- Similar topics

 
Permissions in this forum:
You cannot reply to topics in this forum