GEP (Foundation Module) Week 3 Flashcards

Question

What is Anaemia?

Answer 1

Anaemia is defined as low blood concentration of Hb (erythrocytes) ## Footnote Men: <130 g/L Non-pregnant women: <120 g/L Pregnant women: <110 g/L 1st trimester, <105 g/L 2nd & 3rd

Answer 2

HB: concentration of Hb (g/L or g/dL) HCT: percentage of blood volume as RBCs (%) MCV: average size of RBCs (fL) MCH: Average Hb content in each RBC (pg) MCHC: Average Hb concentration in RBCs (g/dL) RDW: Range of deviation of RBC size WBC: Number of white blood cells per unit of volume

Answer 3

**Non-specific symptoms:** Fatigue/lethargy Dyspnoea Palpitations Feeling faint Headache Pallor Tachycardia Insomnia Systolic flow murmur (severe cases) **Specific** Koilonychia (spoon shaped nails) : iron deficiency anaemia Jaundice: haemolytic anaemia Leg ulcers: sickle-cell anaemia, haemolytic anaemia Bone deformities: thalassemia major

Answer 4

Reticulocyte count Blood film Bone Marrow Aspirate & Trephine Haematinic levels: B12 & folate Iron studies: ferritin, serum Fe, TIBC ## Footnote Reticulocytes are immature blood cells Size : big, small, normal Shape : fragments, tear drop, spiculated, ovalocyte, spherocyte, eliptocyte Colour: pale, normal, polychromasia Inclusions: howell-jolly bodies, nuclear reminants, malarial parasites, basophilic stippling Iron transported from enterocytes then enter into plasma or stored as ferritin Once attached to transferrin it is transported and binds to transferrin receptors on RBC precursors A state of iron deficiency will see reduced ferritin stores and then increased transferrin Serum Fe Hugely variable during the day Ferritin Primary storage protein & providing reserve, Water soluble Transferrin Saturation Ratio of serum iron and total iron binding capacity – revealing %age of transferrin binding sites that have been occupied by iron Low = anaemia TIBC (Total Iron Binding Capacity) Measurement of the capacity of transferrin to bind iron High = anaemia as lots wants to bind

Answer 5

* Iron: Too little coming or too much going Malabsorbtion Bad diet Increased demand to normal Heavy bleeding (haemorrhage/menstruation) Parasites * Overall lack of iron

Answer 6

* 3 types: -Failure of production B12, Folate, Iron deficiency Epo deficiency in CKD Bone marrow failure: eg Aplastic Anaemia -Failure of appropriate utilisation Anaemia of chronic disease -Increased destruction Blood loss, haemolysis (AI, sickle, HS, TTP) Reticulocytosis

Answer 7

Autosomal recessive condition, affecting the gene that codes for beta-globin.

Answer 8

Due to a point mutation, glutamate (hydrophilic) becomes valine (hydrophobic). This creates a hydrophobic region outside of the beta-globin. So when a RBC is deoxygenated its protien conformation changes exposing a hydrophobic region which valine binds onto, creating the sickle cell shape.

Answer 9

**Pain:** can be acute: - vaso-occlusive crisis (incredibly painful); - splenic sequestration crisis; and - aplastic crisis. chronic neuropathic **Other features** -Haemolytic anaemia due to increased haemolysis. Sickel cell life is 30 days -Other features include dactylitis (painful swelling in the hands and feet) and priapism (= prolonged erection without appropriate stimulation). There is also increased risk of stroke.

Answer 10

**Bloods: ** ↓ haemoglobin (anaemia). ↑ reticulocyte count (bone marrow compensating for ↑ haemolysis). ↑ LDH (an enzyme in RBCs) and ↑ bilirubin (from the breakdown of haem). **Blood film: ** -Sickle cells. -Polychromasia (reticulocytes are larger and stain a bluish colour). -Target cells (= dark centre, surrounded by lighter ring). ## Footnote LDH: Lactate dehydrogenase is an enzyme released from RBCs. You can find it in other locations in the body too. Blood film = smearing a thin layer of blood on a microscope slide and then staining it so that you can see the cells. Polychromasia = many colours = reticulocytes are present (they stain a bluish colour, in contrast to the pink RBCs). Target cells = erythrocytes with a dark centre, surrounded by lighter ring (due to abnormal distribution of haemoglobin). Howell-Jolly bodies: These are nuclear remnants inside RBCs, which is not normal. On a blood film, the Howell-Jolly bodies are typically dark-purple-to-red in colour. Normally, these RBCs would be haemolysed by the spleen, but if the patient has a non-functioning spleen (e.g., due to damage caused by SCD), or their spleen has been removed, then the RBCs with Howell-Jolly bodies inside them will persist in the blood.

Answer 11

Sickle solubility test: Mix the patient’s blood with sodium dithionite. If HbS is present, a precipitate forms → turbid solution. This will be positive in patients who have SCT and patients who have SCD. Electrophoresis: Blood sample is treated to release Hb. Sample is placed in gel and subjected to an electric charge. Sample moves through the medium, forming characteristic patterns. HPLC: High-performance liquid chromatography. Blood sample is treated to release Hb. Sample is injected into HPLC at high pressure. Different types of Hb move through at different speeds. This enables the HPLC to measure percentage of Hb variants. Therefore, the machine can produce a graph.

Answer 12

Conservative: ↑ fluid intake and trigger avoidance (e.g., strenuous exercise). Medical: Folate supplementation, immunisations, and antibiotic prophylaxis. Prevention of Vaso-Occlusive Crises (VOCs): Top-up blood transfusions and hydroxycarbamide (aka hydroxyurea, which increases HbF, thereby diluting HbS and reducing the risk of sickling). Management of Chronic Complications: Blood transfusions risk iron overload → chelation therapy. Monitor for organ damage: ECG, BP, retinal screening, and urinalysis to check for protein (kidney damage). ## Footnote Folate supplementation: Folate plays a role in erythropoiesis. Antibiotic prophylaxis: Taking abx regularly to prevent infections. Hydroxycarbamide = hydroxyurea = drug that increases HbF (this dilutes the concentration of HbS and reduces the risk of sickling). Chelation therapy = Kel-AY-shun therapy = drugs that bind a potentially harmful substance and allow it to be excreted safely. BP = Blood pressure. Organ damage: Sickle cell disease can damage many parts of the body, such as the heart, eyes, and kidneys – you need to monitor this. I won’t provide an in-depth explanation of why you do ECGs, BP measurements, retinal screening, or urinalysis. This will become more obvious as the year progresses and you learn more about the human body.

Answer 13

Pain relief within 30 mins and reassess every 30 mins. -O2. -IV fluids. -Antibiotics (if they have an infection). -Blood transfusion.

Answer 14

Thalassaemia is the disorder of globulin chain synthesis, it is inherited. There is either underproduction or absence of Beta or alpha globulin chain. -4 Alpha gene: 2 on each chr 16 -2 Beta gene: 1 on each chr 11 Alpha thalassaemia: is usually due to large deletion in alpha globin complex Beta thalassaemia: usually due to point mutation in he beta gene

Answer 15

One gene deleted * Clinical state is normal - silent carrier * Occasional low RBC indices Two genes deleted (microcytic anaemia) * Thalassaemia trait – mild anaemia and low RBC indices 3 α genes deleted * HbH disease: (ß4) tetramers form * Anaemia, low MCV, MCH * Haemolysis features: Body doesn’t like the weird beta only haemoglobin. Hepatosplenomegaly, leg ulcers, jaundice Deletion of all four α genes * Barts Hydrops Fetalis: Death in utero or at term * Hb Barts: γ4 self assembles – cannot transport O2 * No α chain production

Answer 16

β0: absent globin production β+: reduced production abnormality in 1 inherited gene: b-thal trait Microcytic anaemia, high HbA2 Abnormality in both genes: b-thal intermedia or b-thal major (BTM) Transfusion requirements and varying severity

Answer 17

Anaemia investigations PLUS -Hb electrophoresis.: HbA1 absent, HbA2 raised, increased (80-100%) -Radiography: Medullary expansion – marrow hypertrophy – hair on end appearance on X ray skull