Exam 1- red blood cells Flashcards by Michael Staunton

Where is EPO secreted from and in response to what?

Cortical interstitial cells of kidney; hypoxaemia

How well did you know this?

Not at all

Perfectly

What is the role of 2,3 BPG?

Promotes release of oxygen from Hb at low oxygen concentration

How well did you know this?

Not at all

Perfectly

What is the role of glutathione? In what condition is there a lack of reduced glutathione?

Protects against toxic effects of reactive oxygen species. Glucose 6 phosphate dehydrogenase deficieny

How well did you know this?

Not at all

Perfectly

Means of co2 transport in blood

As bicarbonate ion (60%)
Bound to Hb (30%)
Dissolved in solution (10%)

How well did you know this?

Not at all

Perfectly

Structure of adult Hb

4 protein subunits, each with a single haem group capable of binding one oxygen molecule

How well did you know this?

Not at all

Perfectly

Structure of

a) adult Hb
b) foetal Hb
c) haem group

a) alpha 2, beta 2
b) alpha 2, gamma 2
c) porphyrin ring with central Fe atom

How well did you know this?

Not at all

Perfectly

How does foetal haemoglobin differ from adult in function? ()

Higher affinity for oxygen

Lower affinity for 2,3 BPG

How well did you know this?

Not at all

Perfectly

Causes of microcytic (low MCV) anaemia (2)

Iron deficiency

Thalassaemia

How well did you know this?

Not at all

Perfectly

Diagnostic test for iron deficiency

Low serum ferritin (“storage” iron)

How well did you know this?

Not at all

Perfectly

Causes of iron deficiency (3)

Inadequate intake
Inadequate absorption
Increased loss through haemorrhage

How well did you know this?

Not at all

Perfectly

Name the transporter responsible for:

a) iron transport in the duodenum
b) iron export from enterocytes

a) DMT-1

b) ferroportin

How well did you know this?

Not at all

Perfectly

What is reticulocytosis indicative of?

Increased red cell production

How well did you know this?

Not at all

Perfectly

What is hereditary haemochromatosis caused by?

Autosomal recessive HFE mutations- causes excessive intestinal absorption of iron

How well did you know this?

Not at all

Perfectly

Clinical manifestations of hereditary haemochromatosis (5)

Fatigue
Joint pain
Liver cirrhosis
Diabetes
Cardiomyopathy

How well did you know this?

Not at all

Perfectly

Treatment of hereditary haemochromatosis

Venesection 450-500ml

How well did you know this?

Not at all

Perfectly

What is the underlying pathophysiology of megaloblastic macrocytic anaemia?

Defects in DNA synthesis and nuclear maturation due to b12/folate deficiency- these are essential co-factors in these processes

How well did you know this?

Not at all

Perfectly

What is pernicious anaemia?

Deficiency of intrinsic factor due to autoantibodies against IF or gastric parietal cells; results in megaloblastic anaemia as a result of vitamin B12 deficiency

How well did you know this?

Not at all

Perfectly

Where is the intrinsic factor-b12 complex absorbed?

Terminal ileum

How well did you know this?

Not at all

Perfectly

How is pernicous anaemia treated?

B12 injections

How well did you know this?

Not at all

Perfectly

Causes of folate deficiency

a) drugs
b) increased requirement
c) decreased absorption

a) anticonvulsants, trimethoprim
b) haemolysis, pregnancy, malignancy
c) crohns, coeliac disease, diet

How well did you know this?

Not at all

Perfectly

Symptoms/signs of B12/folate deficiency (3)

Anaemia symptoms
Glossitis
Diarrhoea

How well did you know this?

Not at all

Perfectly

Neurological problems caused by b12 deficiency (2)

Subacute combined degeneration of the spinal cord

Peripheral neuropathy

What are the two main groups of haemoglobinopathies?

Thalassaemias- decreased production

Structural variants e.g. sickle cell haemoglobin

How many alpha-genes need to be deleted for symptoms? What is this disease called?

Three out of four

Haemoglobin H disease (alpha thalassaemia), due to presence of HbH (tetramers of beta-globin)

What are the features of Haemoglobin H disease?

Microcytic anaemia Splenomegaly Jaundice (due to haemolysis)

How is HbH disease managed?

Transfusion (regularity depending on severity) | Folic acid supplementation

What is the severest form of alpha thalassaemia?

Barts hydrops fetalis

Diagnosis of alpha thalassaemia (3)

FBC and blood film High performance liquid chromatography PCR genotyping

What is beta-thalassaemia caused by and why does it only affect Haemoglobin A(adult)

autosomal recessive point mutations which either inactivate or reduce function of beta-globin because adult haemoglobin is the only one which has beta globin

Classification of beta thalassaemia (3)

Trait (asymptomatic) Intermedia (requires occassional tranfusion) Major (lifelong dependenceon transfusion)

What are the features of beta thalassaemia a) blood film b) HPLC

a) anisopoikilocytosis, microcytic anaemia, target cells | b) mostly HbF; elevated levels of HbA2 (alpha2 delta2)

Clinial features of beta thal. major (3)

Aged 6-24 months Failure to thrive Extramedullary haemopoiesis- hepatosplenomegaly,bone deformity e.g. skull

How is beta-thalassaemia treated? What is the major side effect of this and how is this managed?

Regular transfusion. Iron overload iron-chelating agents e.g. desferrioxamine

What causes sickle cell anaemia?

Autosomal recessive point mutations in beta globin gene, creating Hb which polymerises at low [o2] causing red cell membrane distortion

What are the consequences of red cells which sickle? (2)

``` Tissue infarction (sickle cell crises) Chronic haemolysis ```

What are the features of a sickle crisis? (5)

``` Bone pain Pleuritic chest pain CVA/seizures Splenic infarcts Priapism ```

Precipitants of a sickle crisis (4)

Hypoxia Cold Infection Dehydration

Management of a sickle crisis

Opiates, fluids, oxygen

Long term treatment of sickle cell anaemia (4)

Prophylactic penicillin Folic acid Vaccination against encapsulated organisms Hydroxycarbamide (induces HbF production)

What are the two main types of haemolysis?

Intravascular and extravascular

Test results/signs which indicate haemolysis a) serum biochemistry b) blood film c) full blood count d) clinical signs

a) high LDH, high bilirubin (unconjugated) b) reticulocytosis, spherocytes (extravascular) schistocytes (intravascular) c) anaemia d) hepatosplenomegaly

Automal dominant condition with defects in red cell cytoskeleton

Hereditary spherocytosis

In haemolytic patients infection with what virus causes an aplastic crisis?

Parvovirus

Why can chronic haemolysis cause megaloblastic anaemia?

Folate deficiency

Diagnostic test for hereditary spherocytosis?

Osmotic fragility test

What causes G6PD deficiency?

X-linked recessive mutations in G6PD making them vulnerable to oxidative stress,

Blood film results in G6PD deficiency (2)

Heinz bodies of denatured haemoglobin | "Bite cells" resulting from removal of denatured haemoglobin

Precipitants of G6PD crisis; how is crisis prevented?

Broad beans, antimalarials, infection | Avoid precipitants

Diagnostic test for autoimmune haemolytic anaemia

Direct antiglobulin test (Coombs test)

Causes of non-megaloblastic macrocytic anaemia (4)

Alcohol Liver disease Hypothyroidism Marrow failure

What causes acute haemolytic transfusion reactions? Why is the response so dramatic?

IgM antibodies against ABO group antigens; IgM is able to activate complement cascade and the membrane attack complex

What is often the consequence of an acute haemolytic reaction?

DIC and renal failure

Cause of a) delayed haemolytic transfusion reactions b) febrile non-haemolytic reactions

a) irregularr antibodies | b) contaminating white cells/cytokines and vasoactive susbstances produced by these WBCs during storage

Other than transfusion reactions what are the risks?

Circulatory overload (particularly old/heart failure) Bacterial/viral infection Acute lung injury (TRALI)