Anemia, B12, folic acid Flashcards
what is microcytic anaemia?
LOW MEAN CELL VOLUME ‘TAILS’ for microcytic anaemias: Thalassaemia Anaemia of chronic disease (ACD) Iron deficiency anaemia Lead poisoning Sideroblastic anaemia
Which would be the most appropriate treatment for a patient with pernicious anaemia?
Intramuscular injection of a B12 supplement **Pernicious anaemia results from INTRINSIC FACTOR deficiency which prevents absorption. Orally administed B12 supplement would therefore also NOT be absorbed. In the past B12 injections were usually given to treat the disease. However nasal sprays containing B12 are now more frequently used.
What would the presence of Howell-Jolly bodies in circulating red blood cells be a sign of? How do they look
damaged SPLEEN Tiny dots in the RBC DNA REmnants
define anemia?
what r the 3 clinical signs of anemia?
Hb concentration LOWER than the normal range
(normal range will vary with sex, ethnicity, age)
Pallor, tachycardia, systolic murmur
**anemia itself is not a disorder, but a manifestation of an underlying disease state!
what r normal Hb ranges?
.
how is anemia classified
Depending on their size -Microcytic -Normocytic -Macrocytic
why might anaemia develop?
-due to abnormalities in Production, function, removal of RBC…or excessive blood loss
Explain how the body adapts to anaemia.
increase SV>> to increase blood supply to tissues Increase BPG to promote oxygen dissociation
Symptoms of anemia
-fatigue -dypnenoa -palpitation and headache OLDER PATIENTS -angina -claudication -
Signs of anemia
-pallor -tachycardia -systolic murmour
Iron deficiency can cause can cause changes to epithelial cells. Why might this happen?
Iron is needed for the NORMAL FUNCTIONG and formation enzymes in the ETC (ex: cytocrome C & catalase)….
The patient is given an oral iron supplement and the antacid, Gaviscon®. What effect might the Gaviscon® have on absorption of the iron supplement?
Gaviscon and iron interact >>which will prevent the uptake of Iron in the gi tract
What is Anisocytosis?, poikilocytosis? Hypochromia?
Unequal sized RBC Abnormality shaped RBC’s Lack of Hb to cell colume >> make cell paler
what is aplastic anaemia?
deficiency of all types of blood cell caused by failure of bone marrow development.
what goes wrong in chronic kidney disease?
production of EPO is insufficient to stimulate normal levels of erythropoiesis and anaemia develops.
causes of megaloblastic anaemia, describe how the RBC will look like
MACROCYTIC MEGOBLASTIC ANEMIA deficiency in folate and B12 leads to megoblastic anaemia>> due to inability for red cell precursors to synthesise DNA and divide. ***Normally, NUCLEAR maturation runs along side CYTOPLASMIC maturation here, nuclear maturation and cell devision LAG cytoplasmic development, therefore, nucleus will be large w/ open chromatin, bc folate and B12 do NOT interfere w/ rna formation, Hb will still be formed making the RBC MEGA-(large).
when does iron deficiency develop, what may cause it?
if supply of iron is inadequate for the requirement of haemoglobin synthesis -poor diet (anorexia) -blood loss for bleeding (nose, lungs, renal tract, uterine,GT) -increased demand (ex: sports, pregnancy, lactation) -decreased absorption (coeliac disease) -anemia of chronic disease (functional lack of iron)
longstanding iron deficiency anomie can result in changes in….
(Symptoms)
-epithelial tissues -nail (khoilonychia) -mouth (angular shelties) -Esophageous (plummer-vinson syndrome)
what is anaemia of chronic disease? explain the pathogenesis
common cause of anaemia associated with chronic inflammatory condition mthl RA, TB, malignancy. Increased MACROPHAGES in these condition reduce the life span of RBC and singling through the EPO recepter is blunted. MOST common in hospitilised patients! the chronic release of IL-6 >>increased procession of the acute phase reactant HEPCIDIN, by the liver. it’ll bind to ferroportin resulting in it degradation, therefore decreasing absorption of IRON.
mutations in the genes that encode for the globin proteins can also lead to anaemia…. name 2
-thalesseimia -sickle cell
describe the RBC of mega plastic anaemia
large nuclei & open chromatin
Approx when does the switch from fetal to adult Hb occur?
3-6 months of age
Everything about iron deficiency Anemia is in ur notes lalls
ok
in iron deficiency anaemia, u can get webbing of the oesophagus, that can cause difficulty swallowing, what is the term for this?
Plummer Vinson syndrome
Another name for Vitamin B12 is_____
cobalamin
what is effected if you have folate deficiency? (2)
it’ll have a huge effect on the DNA synthesis. and can result in neural tube defects in the developing fetus!
what is meant by the suffix “cytic”
size
where is folate found? which foods are rich in them? which type of ppl may be deficient in them?
found in bacteria and plants, and is present in a variety of LEAFY green vegtables. Alchoholics, since their damaged intestinal cells cannot absorb well Increased demand during lactation and pregnancy.
once absorbed, folate is converted into______
Tetrahydrofolate (FH4) by intestinal cells
what is the function of Tetrahydrofolate (FH4), aka (folic Acid)?
It is important in forming something called the ‘carbon pool’ so basically, in metabolism it acts as a one-carbon carrier, it accepts carbons from many stuff like ( glycine, serene, histidine) and then it oxidizes and reduces them, wa ywaza3 il carbon for other metabolic reactions (3a6ona 3eedeeya!) for example: Thymidine synthesis (base pair of DNA)
Describe how G6PDH deficiency can cause a defect in red cell metabolism!
describe the lab findings!
G6PDH is the rate limiting enzyme in PENTOSE PHOSPHATE PATHWAY!
**where it’s the only source of NADPH in RBC’s
Nadph is needed to convert glutathione nack to its reduced form, where it can help w/ preventing oxidative stress!
no G6PDH> no NADPH> No glutathione> oxidative stress!> HEMOLYTIC ANEMIA> lipid peroxidation> protein damage> aggregates of cross-linked Hb>heinz bodies
Stress makes me eat bites of fava beans w/ heinz ketchup
Lab: blood smear of RBC with heinz bodies and bite cells!
where do u get your V b12 from? which ppl r at risk? where & how is Vb12 absorbed from the diet? what is it required for? (2)
Meat products ONLY! vegans! should take (2mg a week)
iLEUM
- forms complex with Haptocorrins
- pancreatic lipases degrade this complex and releases B12
- B12 binds w/ INTRINSIC FACTOR in parietal cells of stomach (indigestible complex)
(important bc it allows b12 to get into ileum cells)
-once in, it binds to TRANSCOBALAMIN II and released into the blood.
What causes pernicious anaemia?
‘VEGANS r precious to animals ;P’ a deficiency in intrinsic factor from lack of Vb12!
why is it when those who go vegans, they experience a deficient in vB12 after 3-6 yrs!
bc the liver takes up half the Vb12 in our body and stores it! so we’ve got plenty
describe how folate and Vb12 work together
Vb12 is responsible for transferring a methyl group from FH4 (folate) to homocystine to form Methionine! but in Vb12 deficient Folate will is trapped in its methyl-FH4 form and ma ygdr yiwaza3 3eedeeya (carbons) essential form the formation of DNA. “functional folate deficiency”
Describe what “functional folate deficiency” is?
if Vb12 deficient Folate will is trapped in its methyl-FH4 form and ma ygdr yiwaza3 3eedeeya (carbons) essential form the formation of DNA. “functional folate deficiency” REMiNDER: folate is important in forming ‘carbon pool’ if u forgot it lalls, look it up previous cards.
what is Anemia of chronic disease?
anemia associated with chronic inflammatory conditions, ex: RA, TB, malignancy.
increased activity of macrophages in these conditions, reduce lifespan of RBC and signalling through EPO aint workin.
chronic release of Cytokines>IL-6> increase production of hepcidin by liver>
1) ferroportin destroyed> less Fe absorbed!
i hate chronic inflammation and HEP :)
in which type of anemia would u find abnormal Hb synthesis?
Iron deficiency anemia!
________resluts froma decreased or absent A or B globin chain!
a or b thalassemia
The relative excess of the other globin chain (eg insoluble aggregates of alpha chains) contributes to the defective nature of the red cell – most of the maturing erythroblasts are destroyed within the bone marrow and there is excessive destruction of mature red cells in the spleen
what r the 2 metabolic functions of Vb12?
1) transfers methyl group from L-methylmalonyl-Coa>>>>>Succinyl-Coa
2) transfer of methyl group from FH4 (folate)
what is the function of pyruvate kinase? which anemia is classified if there is a deficiency?
how come its this enxymes that RBC r so sensitive if its defiecient
HEMOLYTIC ANEMIA
FINAL STEP OF GLYCOLYSIS! >> conversion of Phophoenypyruvate into PYRUVATE
(by this it paying it pack)
giving back the ATP it stole earlier!
(ADP>ATP)
- bc the RBC has no mitochondria, so it relies on glycolysis only to get its ATP !*
- ATPase stops working> potassium lost> water follows> RBC shrinks> death> hemolytic anemia.*
Explain the significance of the reticulocyte count?
The reticulocyte count from a blood sample therefore provides a good diagnostic estimate of the amount erythropoiesis occurring in a patient’s bone marrow.
Explain the common causes of a haemolytic anaemia and the basic investigations to request.
Describe the role and complications associated with haematinic replacement treatment.
Describe the clinical and haematological features of the anaemia of chronic disease and explain how this is distinguished from iron deficiency.
In anemia of chrinic disease, ferritin is raised! Bc it also serves as an acute phase protien, and remember 9ayr infkammation in this type of anemia
while iron deficiency is not raised
Explain the common haematological abnormalities that can occur in patients with non-haematological systemic diseases.
Crohn’s disease is a cause of _________deficiency
Vb12, bc it effects the terminal ileum , where the b12 is absorbed there.
what transports Vb12 to the blood?
Transcobalmin 11
Folate deficiency can occur due to,
hint: alaa think of the things that could go wrong in location and …. then think of the causes
◦ Dietary deficiency
◦ Increased use: pregnancy, increased erythropoiesis eg haemolytic anaemia, severe skin disease – psoriasis, exfoliative dermatitis
duodenum and jejunum problems: proximal small bowel disease eg: coeliac disease, Crohn’s disease
: drugs which inhibit dihydrofolate reductase enzyme (eg Methotrexate)
Others: alcoholism (multifactorial); urinary loss of folate in liver disease and heart failure;
other drugs eg: anticonvulsants
what type of anemia is this?
Macrocytic Megoblastic Anemia
Hypersegmented neutrophills!
As deficiency progresses a pancytopenia can develop
Name the anemia
Macrocytic megoblastic anemia!
Vitamin B12 or folate? deficiency is also associated with neurological disease
what will happens as a consequence?
pick one
Vb12
baba adnan
focal demyelination affecting the spinal cord, peripheral nerves and optic nerves. Depression and dementia can also develop.
Describe the blood cell findings in Thalessemia
Low levels of intracellular haemoglobin accounts for hypochromic, microcytic red cells
TARGET CELLS
what is Hydrops fetalis
Deletion of all four α-globin genes
○ In the foetus, excess of γ-globin chains form tetramers (Hb Bart) that are unable to deliver the oxygen to tissues!!
Usually intrauterine death
Name the RBC shape
shperocyte
Red cell enzyme defects can lead to anaemia
give 2 examples of those enzymes
1) G6PDH deficiency
2) pyruvate kinase deficiency
what r 3 classes that fall under myeloproliferative neoplasms? describe the pathogensis
Myeloproliferative neoplasms are a group of diseases of the bone marrow in which excess cells are produced
They arise from genetic mutations in the precursors of the myeloid lineage in the bone marrow and many have a common molecular pathogenesis caused by mutation of the gene coding for the tyrosine kinase Janus Kinase 2 (JAK2).
All of these disorders involve dysregulation at the multipotent haematopoietic stem cell
Essential Thrombocythaemia is characterised by the overproduction of platelets by megakaryocytes,
Polycythaemia Vera is characterised by overproduction of RBC
myelofibrosis is characterised by replacement of the hematopoietic tissue by connective tissue leading to impairment of the generation of all blood cells (pancytopenia).
Name this abnormal rbc shape
Acanthocytes
what is Polycythaemia?
Polycythaemia is a disease state in which the volume percent of erythrocytes in the blood (the haematocrit) exceeds 55% .
This situation can arise from either:
an increase in the # erythrocytes (termed absolute polycythaemia)
a decrease in the plasma volume (termed relative polycythaemia).
Elliptocytes
Target cells
what is this shape called? where is it commonly seen?
Shistocyte>> DIC
theres been a Mechanical damage to red cells
what does the colour of the RBC depend on (which value)
MCHC
mean carpscular Hb concentration
most appropriate treatment for a patient with pernicious anaemia? and best way to take it?
Pernicious anaemia results from intrinsic factor deficiency which prevents absorption.
Orally administed B12 supplement would therefore also not be absorbed.
However nasal sprays containing B12!
