Pathophysiology of Anaemia 2 Flashcards
Normal RBC production:
- Drive is from __________/___
- Recipe is from ____
- Ingredients are ___, ___, _____, _______
Normal RBC production:
- Drive is from erythropoietin/EPO
- Recipe is from genes
- Ingredients are B12, iron, folate, minerals
Haemoglobinopathies:
These are inherited conditions.
Can be due to:
- relative lack of normal _____ ____ e.g. _________
- abnormal _____ ____ e.g. _____ ___ ______
Haemoglobinopathies:
These are inherited conditions.
Can be due to:
- relative lack of normal globin chains e.g. thalassaemias
- abnormal globin chains e.g. sickle cell disease
Good pics for normal haemoglobin genetics.
In folder.
Thalassaemias =
relative ___ of _____ ___.
- _ genes for alpha globin on chromosome __. This means we have _ genes total for alpha globin chains (2 from mum 2 from dad)
- The beta globin gene is on chromosome __ along with others (g_____, d___). This means we have _ beta globin genes in total.
Thalassaemias =
relative lack of globin genes.
- 2 genes for alpha globin on chromosome 16. This means we have 4 genes total for alpha globin chains (2 from mum 2 from dad)
- The beta globin gene is on chromosome 11 along with others (gamma, delta). This means we have 2 beta globin genes in total.
Alpha gene mutations causing thalassaemia.
–> ______ thalassaemia:
2 alpha genes from one parent but only 1 from the other.
–> homozygous alpha(+) thalassaemia:
_ _____ ____ ___ _____.
–> _____ thalassaemia:
Two alpha genes from one parent but none from the other.
–> HbH disease
_ alpha gene from one parent and then _ from the other. Excess ___ _____ form a tetramer called HbH.
–> ____ _____ thalassaemia
No alpha genes - incompatible with life.
EASIER to understand with Pic in folder.
Alpha gene mutations causing thalassaemia.
–> alpha(+) thalassaemia:
2 alpha genes from one parent but only 1 from the other.
–> homozygous alpha(+) thalassaemia:
1 alpha from each parent.
–> alpha(0) thalassaemia:
Two alpha genes from one parent but none from the other.
–> HbH disease
1 alpha gene from one parent and then 0 from the other. Excess beta chains form a tetramer called HbH.
–> alpha major thalassaemia
No alpha genes - incompatible with life.
EASIER to understand with Pic in folder.
Clinical significance of alpha thalassaemia:
- missing 1 gene:
mild _________ - missing 2 genes:
_________, [[increased or decreased]] RBCs, mild _______ - missing 3 genes:
significant ______, bizarre shaped + small ___, ___ disease - missing 4 genes:
incompatible with life, need alpha chains for _____ haemoglobin.
Clinical significance of alpha thalassaemia:
- missing 1 gene:
mild microcytosis - missing 2 genes:
microcytosis, increased RBCs (probs cos trying to make more RBCs), mild anaemia (RBCs not in shortage but rather the heme) - missing 3 genes:
significant anaemia, bizarre shaped + small RBCs, HbH disease - missing 4 genes:
incompatible with life, need alpha chains for foetal haemoglobin.
Beta thalassaemia major:
- missing both beta globin genes
- autosomal ______
- unable to make ____ haemoglobin (___)
- dyserythropoiesis
- _______ dependant from early life (age 1)
- multiple _______, ineffective ________ and increased ___ ___ absorption all leads to iron overload, which has major impact on mortality
Beta thalassaemia major:
- missing both beta globin genes
- autosomal recessive
- unable to make adult haemoglobin (HbA) (remember it is 2 alpha + 2 beta)
- dyserythropoiesis
- transfusion dependant from early life (age 1)
- multiple transfusions, ineffective erythropoeisis and increased gut iron absorption all leads to iron overload, which has major impact on mortality
Sickle cell disease:
- haemoglobin variant / abnormal haemoglobin
- mutation of chromosome __
- single amino acid substitution on the ___ _____ gene at position _
- ________ becomes ______ and forms HbS
- ________ becomes ______ and forms HbC
Sickle cell disease:
- haemoglobin variant / abnormal haemoglobin
- mutation of chromosome 11
- single amino acid substitution on the beta globin gene at position 6
- glutamine becomes valine and forms HbS
- glutamine becomes lysine and forms HbC
Autosomal recessive remember so need both parents to have mutation.
Sickle cell patho:
- HbA = 2alpha+2beta
- HbA2 = 2alpha+_____
- HbF = 2alpha+2gamma
–> ___ = 2alpha + ________
HbS will continuously polymerise, rate of polymerisation depends on __ ________.
Sickle cell patho:
- HbA = 2alpha+2beta
- HbA2 = 2alpha+2delta
- HbF = 2alpha+2gamma
–> HbS = 2alpha + 2betasickle
HbS will continuously polymerise, rate of polymerisation depends on Hb concentration.
Consequences of sickle cell disease:
- reduced RBC survival (due to _______)
- ______ _______ causes tissue hypoxia/infarction
Consequences of sickle cell disease:
- reduced RBC survival (due to haemolysis)
- vessel occlusion causes tissue hypoxia/infarction
Diseases/conditions from sickle cells:
- brain: ____ / moyamoya
- lungs: _________ _________
- bones: osteonecrosis (___ _ _____ _____ _ ___), ______ (sausage fingers)
- spleen: ________
- kidney: ________
- urogenital: priapism (______ _______)
- eyes: _______ ________
- _______: foetal loss
Pics of sickle cell consequences in folder.
Diseases/conditions from sickle cells:
- brain: stroke / moyamoya
- lungs: pulmonary hypertension
- bones: osteonecrosis (lack of blood supply to bone), dactilytis (sausage fingers)
- spleen: hyposplenic
- kidney: infarction
- urogenital: priapism (painful erection)
- eyes: vascular retinopathy
- placenta: foetal loss
Pics of sickle cell consequences in folder.
Sickle cell treatment:
- prevent crisis:
h______, p_____ v_______, a_______, f____ - Prompt management of crisis
o____, f____, a_______, t_______ of ___ - Bone marrow transplant
Sickle cell treatment:
- prevent crisis:
hydration, prophylactic vaccination, antibiotics, folate - Prompt management of crisis
oxygen, fluids, antibiotics, transfusion of RBCs - Bone marrow transplant
Haemolytic anaemia:
- anaemia related to ______ ___ ______
- __ blood loss
- __ haematinic deficiency
Haemolytic anaemia:
- anaemia related to reduced RBCs lifespan
- no blood loss
- no haematinic deficiency
Congenital Haemolytic Anaemia types:
- Abnormal RBC _______
e. g. h______ s_________ (AD, RBCs spherocytic + polychromatic, j_____, s________, treatment is s_________*) - Haemoglobin-opathies
e. g. _________, _____ ___ _____ - Abnormalities of RBC ______
(discussed on other card)
- after s________, patient will require ‘hyposplenic prophylaxis’ (preventive stuff for those without a spleen) for e________ organisms, such as pneumococcus and meningococcus.
Also require long term _____ _
- after s________, patient will require ‘hyposplenic prophylaxis’ (preventive stuff for those without a spleen) for e________ organisms, such as pneumococcus and meningococcus.
Congenital Haemolytic Anaemia types:
- Abnormal RBC membrane
e. g. hereditary spherocytosis (AD, RBCs spherocytic + polychromatic, jaundice, splenomegaly, treatment is splenectomy*) - Haemoglobin-opathies
e. g. thalassaemia, sickle cell disease - Abnormalities of RBC enzymes
- after splenectomy, patient will require ‘hyposplenic prophylaxis’ (preventive stuff for those without a spleen) for encapsulated organisms, such as pneumococcus and meningococcus.
Also require long term penicillin V.
- after splenectomy, patient will require ‘hyposplenic prophylaxis’ (preventive stuff for those without a spleen) for encapsulated organisms, such as pneumococcus and meningococcus.
Abnormalities of RBC enzymes:
- -> p______ k_____ deficiency anaemia:
- this enzyme part of glycolysis (glucose –> pyruvate)
- if deficient then ___ depletion results
- RBCs die
- causes chronic e_________ h______ a______
- Autosomal ________
- -> g_____ _ p______ d_________ deficiency
- causes acute i_________ h______ a______
- the acute i_________ h______ is from increased o________ s_____
- drugs (a_________, s________) and fava beans can suddenly trigger the haemolysis
- ________ recessive
Abnormalities of RBC enzymes:
- -> pyruvate kinase deficiency anaemia:
- this enzyme part of glycolysis (glucose –> pyruvate)
- if deficient then ATP depletion results
- RBCs die
- causes chronic extravascular haemolytic anaemia
- Autosomal recessive
- -> glucose 6 phosphate dehydrogenase deficiency
- causes acute intravascular haemolytic anaemia
- the acute intravascular haemolysis is from increased oxidative stress
- drugs (antimalarials, sulphonamides) and fava beans can suddenly trigger the haemolysis
- X-linked recessive
