Tired all the time

Question 1

What does the structure of the RBC provide

Answer 1

biconcave shape and no nucleus - pliable, high surface area/volume

Question 2

What is reticulin?

Answer 2

remnants of mRNA left once the nucleus of a maturing RBC has been extruded (removed by spleen in 1-2 days)

a useful measure of marrow response to anaemia or treatment

Question 3

What is hepcidin?

Answer 3

regulates iron absorption and release from macrophages - increased in inflammatory disease hence less iron available

Question 4

How is iron transported and stored?

Answer 4

transferrin: transport/regulation –> transferin receptors increased in iron deficiency
ferritin: insoluble form of storage –> better measure of iron stores

Question 5

Folic Acid:
Where is it absorbed?
How can deficiency come about?

Answer 5

Absorbed in the upper small bowel

Deficiency due to poor intake/absorption/increased need

Question 6

B12/Cobalamin:
Where is it absorbed?
How is it transported?
How does deficiency come about?

Answer 6

Absorbed in the terminal ileum
transported on transcobalamin II via portal circulation to liver
dietary deficiency in vegans or pernicious anaemia

Question 7

How is erythropoiesis switched on?

Answer 7

tissue hypoxia or anaemia
high altitude
epo producing tumors e.g. renal

Question 8

Structure of Hb and abnormalities

Answer 8

2 alpha chains (chromosome 16)
2 beta like chains (chromosome 11)
Hb (adult) is 2 alpha, 2 beta
Hb (foetal) is 2 alpha, 2 gamma

Thalassaemia: inherited defect in globin chain production
sickle cell disease: one amino acid change in beta chain

Question 9

neutrophils morphology and function

Answer 9

Morphology – large, copious cytoplasm lobed nucleus.

• chemokines released by activated tissues and immune cells attract neutrophils to sites of infection
• phagocytose microbes and digest in cytoplasmic vesicles

Question 10

lymphocytes features and functions

Answer 10

• Circulate in the blood and reside in lymph nodes
• Unique antgen specific surface receptor
• B cell receptors recognise soluble antigen
• T cells can only recognize antigen presented in MHC class I or class II molecules.
• MHC are host identifiers, class I on all cells at risk of infection or damage.
• Class II only on professional antigen presenting cells – macrophages, B lymphocytes and Dendritic cells

Question 11

Natural Killer cells features

Answer 11

• Large lymphocyte cells with granular cytoplasm.

• do not have antigen specific receptors
• recognise virus ingected cells
• part of the innate lymphoid cell group

Question 12

monocytes: function and features

Answer 12

• Morphology – large cells with a kidney shaped nucleus and copious cycoplasm

• blood monocytes can phagocytose, degrade and present antigen
• monocytes continually migrate to tissues and differentiate to become machrophages

Question 13

macrophage functions

Answer 13

• phagocytosis
• disposal of infected/damaged cells
• induce inflammation: secrete cytokines and chemokines and inflammatory mediators
• actively recruit other cells to site of infection
• present antigen from degraded pathogen to MHC class II t-helper cells

Question 14

dentritic cells features

Answer 14

• immature dendtritic cells migrate from the bone marrow through the blood stream to mature in the tissues
• degrade pathogens that they take up
• main role = present antigens to T-cell and send signals to immune mediators

Question 15

what inhibtits thrombin production?

Answer 15

Heparin and thrombomodulin produced in the endothelial cells

Question 16

What reduces platelet adhesion?

Answer 16

prostaglandin and Nitric Oxide produced in the endothelial cells

Question 17

coagulation cascade

Answer 17

Diagram

Question 18

Coagulation tests

Answer 18

• bleeding time
• prothrombin time (PT)
• Activated partial thromboplastin test (APTT)
• Fibrinogen (final substrate for making fibrin)
• Correction tests and factor assays

Question 19

Inherited blood disorders

Answer 19

• Haemophillia A+B: X linked defect in VIII or IX gene
• Von-Willebrand disease: autosomal dominant defect in platelet adhesion and binding of VIII
• Acquired coagulation disease - liver disease: bleeding due to abnormal clotting (all clotting factors made in liver)
• Acquired coagulation diseae - DIC: activation of coagulation cascade due to multiple reasons e.g. trauma, malignancy, sepsis etc.
• thrombocytopaenia: abnormal marrow function
• thrombophilia: Inherited defects in coag inhibitors

Question 20

Symptoms of anaemia

Answer 20

shortness of breath
muscle pain on exersion
dizziness
angina

Question 21

clinical signs of anaemia

Answer 21

• palor in skin and conjuctiva
• tachycardia
• rapid breathing
• peripheral oedema if severe
• Peripheral oedema if severe anaemia

Question 22

name classification of anaemia according to MCV

Answer 22

microcytic, normocytic and macrocytic

Question 23

describe the classification of anaemia according to MCV

Answer 23

• normocytic: blood loss, anaemia of chronic disease, renal impairment
• macrocytic: megaloblastic anaemia - B12/folate deficiency, myelodysplasia
• microcytic: iron deficiency, thalassaemia

Question 24

describe the Buffer system in the red cell

Answer 24

diagram

Question 25

Composition of circulating white blood cells

Answer 25

* Neutrophils 60-70% * Lymphocytes 20-30% * Eosinophils 2-4% * Basophils <1% * Monocytes 3 – 8% * Mast cell precursors * Not macrophages

Question 26

What are the main constituents of coagulation?

Answer 26

* Vessel wall lined by endothelium * Platelets- derived from megakaryocytes in marrow * Coagulation factors in un-activated state * Inhibitors of coagulation * Fibrinolytic system and inhibitors

Question 27

What are endothelial cells?

Answer 27

• Line blood vessels and form a barrier • Produce: - thrombomodulin and heparin sulphate to inhibit thrombin production - Enzymes to degrade platelet granule- derived molecules - Prostacyclin and nitric oxide (NO) to reduce platelet adhesion

Question 28

What are the coagulation inhibitors?

Answer 28

* Protein C activated by thrombomodulin-thrombin complex * With co-factor- Factor S- Va and VIIIa are degraded * Antithrombin inhibit Xa and IIa • Heparin cofactor II inhibits Ila * Heparin stimulates antithrombin and heparin cofactor II

Question 29

What is B12 anaemia?

Answer 29

• macrocytic anaemia - Often bilirubin and LDH raised • Can also cause peripheral neuropathy- demyelination and posterior column damage • B12 result can be falsely low in pregnancy/oral contraceptive/on metformin • Pernicious anaemia- gastric atrophy and auto antibodies to parietal cells and intrinsic factor preventing absorption • Strict vegan or terminal ileal disease also possible

Question 30

B12 deficiency treatment

Answer 30

* Hydroxocobalamin 1mg IM | * Cyanocobalamin available orally

Question 31

Describe anaemia of chronic disease

Answer 31

* normocytic anaemia associated with chronic inflammatory disease * Plentiful iron stores but poor transfer to RBC due to hepcidin and cytokines

Question 32

Describe thalassaemia

Answer 32

* Inbalance of globin chain production * Beta thalassaemia- as Hb F (2 alpha, 2 gamma chains) declines after birth * Progressive iron overload

Question 33

what is the difference between race and ethnicity?

Answer 33

Race: Biological division of the species into groups based on the frequency of hereditary traits Ethnicity: Social division of people into groups based on their identification with shared origin

Question 34

Explain cultural competency and cultural humility

Answer 34

Cultural competency: - Mastery of a finite body of knowledge and information - Endpoints defined by exams - Commitment to competency Cultural humility: Humility - To assess anew the cultural dimensions of each patient - To engage in self-reflection - To check the power imbalances in clinical relationship No endpoint Commitment to social justice

Question 35

What are the anaemia drugs?

Answer 35

``` Ferrous Sulfate Iron Dextran Hydroxocobalamin Folic Acid Darbepoeitin Alfa Hydroxycarbamide ```

Question 36

Indications, MOA, dose and side effects of Ferrous Sulfate

Answer 36

Iron deficiency anaemia replaces iron stores. Ferrous ion absorbed in small intestine, bound to transferrin in the plasma and used for haemoglobin synthesis 200mg orally once (prophylaxis) or 2-3 times (treatment) Abdominal cramping, diarrhoea or constipation, nausea.

Question 37

Indications for Iron Dextran

Answer 37

Parenteral iron is reserved for use when oral therapy is unsuccessful due to intolerance or noncompliance, continuing blood loss or malabsorption.

Question 38

Indications for folic acid

Answer 38

Folic acid must not be used alone in undiagnosed megaloblastic anaemia due to the risk of vitamin B12 deficiency leading to peripheral neuropathy. Given with hydroxocobalamin

Question 39

Indications of Hydroxycarbamide

Answer 39

used for reduction of elevated platelet counts in ‘at risk’ | patients with essential thrombocythaemia.