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Yr 2 Gastrointestinal > Wk 2 - Haematology: Anaemia > Flashcards

Wk 2 - Haematology: Anaemia Flashcards

1
Q

What is blood composed of?

A
  • Cellular
    • Red blood cells (erythrocytes)
    • White blood cells (leucocytes)
    • Platelets (thrombocytes)
  • Plasma
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2
Q

Define ‘haematopoiesis’.

A
  • Haematopoiesis is the process whereby blood cells are made
  • The yolk sac and later the liver and spleen are important in fetal life
  • After birth – haematopoiesis is normally restricted to the bone marrow
  • In adults bone marrow is normally confined to the central skeleton
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3
Q

In adults, haematopoiesis is restricted to ____ in the ____ of the skeleton.

A

In adults, haematopoiesis is restricted to bone marrow in the central part of the skeleton.

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4
Q

What are the two types of cells (found in bone marrow) that have a role in haematopoiesis?

A
  1. Common primitive stem cells in the bone marrow have the capacity to self-replicate, proliferate & differentiate into increasingly specialised progenitor cells
  2. Stromal cells of the marrow (fibroblasts, endothelial cells, macrophages and fat cells) provide support for the stem cells and keep them viable
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5
Q

Red cells contain ______ which allows them to carry oxygen and carbon dioxide.

A

Red cells contain haemoglobin which allows them to carry oxygen and carbon dioxide.

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6
Q

______ binds between beta chains to reduce affinity for O2 allows O2 release to the tissues.

A

2,3-DPG binds between beta chains to reduce affinity for O2 allows O2 release to the tissues.

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7
Q

What controls the production of RBCs?

A

Erythropoietin

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8
Q

Where is erythropoietin produced?

A

In the kidneys

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9
Q

What stimulates erythropoietin secretion?

A

Secretion is stimulated by reduced O2 supply to the kidney receptors

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10
Q

All cells in the body have nuclei except for…

A

mature reb blood cells (in bone marrow, unmatured ones have nuclei)

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11
Q

List the main factors needed for red blood cell production.

A
  • Iron
  • Vitamin B12
  • Folate
  • Erythropoietin
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12
Q

Deficiency in iron, B12 or folate would lead to…

A

Anaemia (too little RBCs)

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13
Q

List some of the symptoms of anaemia.

A
  • Shortness of breath
  • Lethargy
  • Headache
  • Angina

More marked if severe, if it is of rapid onset, and in older or frail people

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14
Q

What are the possible causes of anaemia?

A
  1. Bleeding
  2. Dietary deficiency
  3. Malabsorption in the gut
  4. Systemic illness
  5. Haemolysis (red cell breakdown)
  6. Bone marrow failure eg in cancer leukaemia or eg aplastic anaemia
  7. Inherited red cell disorders eg haemoglobinopathies
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15
Q

How is anaemia classified?

A

Simplest is according to red cell size

  1. Microcytic – small cells – eg. Iron deficiency, thalassaemia
  2. Normocytic – normal-sized red cells – eg. anaemia of chronic disease (associated with systemic illness)
  3. Macrocytic – big red cells – eg. B12 or folate deficiency
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16
Q

List some causes of microcytic anaemia.

A
  • Iron deficiency
  • Thalassaemia
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17
Q

List some causes of normocytic anaemia.

A

Anaemia of chronic disease

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18
Q

In the body, iron is contained in…

A
  1. Haemoglobin
  2. Reticuloendothelial system (macrophages) – as ferritin & haemosiderin
  3. Muscle – myoglobin
  4. Plasma – bound to transferrin
  5. Cellular enzymes – catalases, cytochromes
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19
Q

The body’s reticuloendothelial system for iron storage is regulated by…

A

Iron-responsive element-binding protein (IRE-BP) mechanism – body regulates uptake & storage of iron by RES.

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20
Q

The average western diet contains ___ mg of iron per day but only about ___ mg is absorbed in the small intestine.

A

The average western diet contains 10-15 mg of iron per day but only about 1 mg is absorbed in the small intestine.

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21
Q

What vitamin enhances iron uptake?

A

Vitamin C

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22
Q

How might iron deficiency occur?

A
  • Blood loss
    • 500ml of normal blood contains 200-250mg iron
    • Uterine, gastrointestinal, rarely other blood loss
  • Malabsorption of nutrients (ie iron) from the gut
  • Poor dietary intake & increased demand
    • Especially in children, menstruating women, pregnancy, poor people, strict vegetarians
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23
Q

List the clinical features of iron deficiency anaemia.

A
  • General features of anaemia (common)
  • Special features of iron deficiency (uncommon)
    • Nail deformity
    • Sore tongue (glossitis) & corners of the mouth (angular cheilosis)
    • Pica (abnormal appetite) – a compulsive eating disorder in which people eat nonfood items – VERY RARE
  • Features of the underlying cause
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24
Q

How does iron deficiency look on laboratory tests?

A
  • Low haemoglobin
  • Red cells appear pale (hypochromic), small (microcytic)
  • Low ferritin (low iron stores) – in infection, this could be in the normal range so might mask anaemia
  • Transferrin receptors (sTR assay) increased
  • Blood film appearances
    • Hypochromic, microcytic cells
    • Pencil shaped cells – look like a long oval
    • Target cells – dark area in middle then large area of palor
    • Increased variation in red cell shape
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25
Q

Other than iron deficiency, what else causes microcytic anaemia?

A

Haemoglobinopathies e.g.

  • Thalassaemia (disease state)
  • Thalassaemia trait (carrier state) – sometimes not always causes anaemia but will always have smaller than normal RBCs
  • Some variant haemoglobins and their carrier states
    • Sickle cell disease Hb S disease (some
    • cases)
    • Hb C disease
    • Hb E disease
26
Q

What is thalassaemia?

A

Thalassaemia is the name for a group of inherited conditions that affect a substance in the blood called haemoglobin. People with thalassaemia produce either no or too little haemoglobin, which is used by red blood cells to carry oxygen around the body. This can make them very anaemic (tired, short of breath and pale).

27
Q

What two groups are thalassaemia divided to?

A
  • Reduced α (α-thalassaemia) globin chains
  • Reduced β (β-thalassaemia) globin chains
28
Q

Clinically, thalassaemia is divided to…

A
  1. hydrops fetalis – usually die as fetus
  2. thalassaemia major - transfusion dependent
  3. thalassaemia intermedia - moderate anaemia, splenomegaly, iron overload
  4. thalassaemia minor - usually symptomless carrier state
29
Q

In thalassaemia major, patients are usually…

A

transfusion dependent

30
Q

What blood tests are used to detect whether a patient has a haemoglobinopathy?

A
  • Blood count and look at the blood film
  • Haemoglobin electrophoresis
    • Detects abnormal haemoglobins
  • Specialised studies
    • DNA analysis to detect specific genetic mutations
31
Q

List some causes of macrocytic anaemia.

A

B12 or folate deficiency

32
Q

Folate is an essential coenzyme required for the synthesis of _____, which is essential for the manufacture of DNA.

A

Folate is an essential coenzyme required for the synthesis of thymidine monophosphate (TMP), which is essential for the manufacture of DNA.

33
Q

B12 is an essential coenzyme for the reaction which converts the plasma form of _____ to the cellular form of _____, which is used as a co-enzyme in DNA manufacturing.

A

B12 is an essential coenzyme for the reaction which converts the plasma form of folate (methyl-THF) to the cellular form of folate (THF), which is used as a co-enzyme in DNA manufacturing.

34
Q

Both folate and vitamin B12 are essential co-enzymes in the…

A

manufacturing of DNA (folate directly co-enzyme while B12 works indirectly by converting folate)

35
Q

Normal body stores of vitamin B12 last…

A

2-4 years

36
Q

Briefly describe the physiological pathways of B12 uptake.

A
  • Dietary B12 combines with intrinsic factor secreted from gastric parietal cells
  • IF-B12 complex attaches to ileal receptors & B12 is absorbed
    • Passive absorption (0.1% of oral B12) also occurs through the buccal, gastric & duodenal mucosae
  • Absorbed B12 attaches to transcobalamin (TC) II
  • TCII carries B12 in plasma to the liver, bone marrow, brain & other tissues
  • Most B12 in plasma attaches to a second B12 binding protein, TC I, which is inactive (TC I is manufactured by granulocytes – WBCs)
37
Q

List the clinical features of vitamin B12 deficiency.

A
  1. Gradual onset anaemia – bc body has good stores of B12
  2. Mild jaundice due to ineffective red cell production (erythropoiesis) – bc RBCs are fragile –> broken down more rapidly
  3. Glossitis & angular cheilosis
  4. Sterility or reduced fertility (either sex – if very severe)
  5. Neuropathy (if very severe) - vary from:
    • Subacute combined degeneration of the cord (very rarely seen bc no more B12 deficiency that severe)
    • Peripheral neuropathy
    • Pins & needles, difficulty in gait, visual & psychiatric problems
  6. B12 & folate deficiency are associated with increased homocysteine levels which is associated with arterial and venous blood clots (thrombosis)
  7. Deficiency in pregnancy is associated with an increase in neural tube defects in the fetus
38
Q

What is pernicious anaemia?

A

Autoimmune form of vitamin B12 deficiency

  • Autoimmune gastritis
  • Reduced secretion of IF
  • Often associated with other autoimmune diseases such as hypothyroidism
  • Antibodies to IF and gastric parietal cells occur in serum & gastric secretions
  • Associated with early greying of hair, blue eyes, blood group A, family history of PA, 2-3 x risk of gastric cancer
  • Peak incidence 60 years
39
Q

B12 & folate deficiency are associated with increased ____ levels which is associated with _____.

A

B12 & folate deficiency are associated with increased homocysteine levels which is associated with arterial and venous blood clots (thrombosis).

40
Q

What would you find on laboratory testing of a patient with vitamin B 12 deficiency?

A
  • Macrocytic (big) & oval red cells
  • Hypersegmented neutrophils (>5 nuclear lobes – ie too many lobes)
  • Moderate reduction in white cells & platelets (severe cases)
  • Bone marrow is hypercellular and looks megaloblastic
  • Bilirubin is raised (mild jaundice)
  • B12 is low
  • Special tests to determine underlying cause
41
Q

List the causes of vitamin B12 deficiency.

A
  • Not enough in – poor/inadequate diet
    • Vegans
    • Infants born to B12-deficient mothers & breastfed may get failure to thrive from B12 deficiency
  • Gastric malabsorption
    • Pernicious anaemia (PA)
    • Total/subtotal gastrectomy
    • Congenital IF deficiency (rare)
  • Intestinal malabsorption
    • Bacterial colonisation of the small intestine
    • Stagnant bowel loop syndromes
    • Congenital & acquired defects of the ileum
      • Ileal resection
      • Crohn’s disease (inflammatory bowel disease)
      • Congenital B12 malabsorption (rare)
42
Q

List some of the causes of folate (folic acid) deficiency.

A
  • Poor diet in green leafy vegetables (most common)
    • Institutions, poverty, famine, alcoholism
  • Malabsorption
    • Gluten enteropathy – coeliac disease
  • Increased utilisation
    • Increased cell turnover & DNA synthesis can exhaust folate supply
    • Causes include pregnancy, red cell breakdown (haemolysis), severe chronic inflammatory & malignant disease, anticonvulsant drugs
    • Dialysis removes folate
43
Q

Folate deficiency clinical presentation is the same as B12 deficiency except that patients with folate deficiency do NOT present with…

A

Neuropathy

44
Q

Folic acid supplementation in early pregnancy reduces _____.

A

Folic acid supplementation in early pregnancy reduces neural tube defects.

45
Q

List some causes of macrocytosis (i.e. red blood cells that are larger than normal) that are NOT usually associated with anaemia.

A
  • Alcohol (most common)
  • Liver disease
  • Thyroid disease
  • Physiological
    • Pregnancy
    • Neonatal
46
Q

List some causes of macrocytosis (i.e. red blood cells that are larger than normal) that are usually associated with anaemia.

A
  • Causes of increased reticulocytes
    • Acute haemorrhage
    • Active haemolysis
  • Cytotoxic drugs
  • Aplastic anaemia
  • Some haematological malignancies
    • Myeloma
    • Myelodysplasia
47
Q

What are reticulocytes?

A

Reticulocytes are red blood cells that are still developing. They are also known as immature red blood cells. Reticulocytes are made in the bone marrow and sent into the bloodstream. They are generally larger than RBCs.

48
Q

List some causes of normocytic anaemia.

A
  • Anaemia of chronic disease
    • Infection
    • Collagen disease
    • Malignancy
    • Renal disease
  • Acute blood loss
  • Mixed deficiency
    • iron + B12/folate
  • Splenomegaly
49
Q

_____ is the most common cause of normocytic anaemia.

A

Anaemia of chronic disease is the most common cause of normocytic anaemia.

50
Q

Why does anaemia of chronic disease occur?

A
  • Mild decrease in red cell life-span – usually at a level which can be compensated (becomes more difficult as reserve falls with age or other factors)
  • Disturbance of erythropoiesis due to reduced sensitivity to physiological stimuli & reduced iron utilisation
  • Interaction of cytokines – IL-1, IL-6, TNF, TGF-β - with marrow stromal cells & erythroid progenitors
  • Erythropoietin – often inappropriately low
  • Inhibitory cytokine levels are high
  • Low serum iron (within 24 hours of onset of illness) with adequate stores but reduction in iron in marrow red cell precursors - enough iron in the body stores but not enough released in circulation
  • Impaired flow of iron from cells to plasma
    • Substances produced which compete with transferrin for iron
51
Q

Describe the breakdown of RBCs.

A
  • RBCs broken down by macrophages to globin and haem
  • Haem is further broken down into biliverdin (+ iron*)
  • Biliverdin is metabolised to bilirubin
  • Bilirubin conjugated to glucuronide in liver & excreted
    • Faeces – stercobilinogen
    • Urine – urobilinogen (after reabsorption)
  • Iron is recycled – bound to transferrin
  • Some iron is taken up by macrophages – stored as ferritin (mostly) or haemosiderin
52
Q

Describe what happens to iron in RBC metabolism.

A
  1. Iron is recycled – bound to transferrin
  2. Some iron is taken up by macrophages – stored as ferritin (mostly) or haemosiderin
53
Q

Define haemolytic anaemia.

A

Hemolytic anaemia is a form of anaemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular).

  • Caused by shortened red cell lifespan
  • Normal rbc lifespan = 120 days
  • Anaemia if rbc lifespan < 15days
54
Q

Broadly, what are the causes of haemolytic anaemia?

A
  1. Fault in red cell – usually inherited
  2. Fault in environment – usually acquired
55
Q

List some examples of hereditary haemolytic anaemia.

A
  1. Membrane
    • Hereditary spherocytosis
    • Hereditary elliptocytosis
  2. Metabolism
    • G6PD deficiency
  3. Haemoglobin
    • Hb defects (HbS, sickle cell disease)
56
Q

List some examples of acquired haemolytic anaemia.

A
  • Immune (mediated by antibodies)
    • Autoimmune
    • Alloimmune
      • Haemolytic transfusion reactions
      • Haemolytic disease of the newborn
  • Non-Immune (not mediated by antibodies)
    • Red cell fragmentation syndromes
      • Cardiac valves
      • DIC (disseminated intravascular coagulation) – MAHA (microangiopathic haemolytic anaemia)
    • Infections
      • Malaria
    • Chemicals & poisons
57
Q

What is the clinical presentation of individuals with haemolytic anaemia?

A
  • Anaemia
  • Jaundice
  • Increased incidence of pigment gallstones
  • May have mild splenomegaly in some types
58
Q

What is pancytopenia?

A

Pancytopenia occurs when a person has a decrease in all three blood cell types: red blood cells, white blood cells and platelets.

59
Q

List three causes of pancytopenia.

A
  1. Bone marrow infiltration
    • eg leukaemia and lymphoma
  2. Bone marrow failure
    • Drugs
      • regularly cause - chemotherapy
      • sometimes cause - chloramphenicol, sulphonamides
    • Chemicals – benzene & other organic solvents, insecticides etc
    • Ionising radiation
    • Idiopathic aplastic anaemia
    • Viral hepatitis and HIV (in end-stage disease)
  3. Peripheral consumption/destruction
    • Septicaemia
    • Hypersplenism
    • Autoimmune destruction
60
Q

List causes of bone marrow failure (leading to pancytopenia).

A
  • Bone marrow failure Drugs
    • regularly cause - chemotherapy
    • sometimes cause - chloramphenicol, sulphonamides
  • Chemicals – benzene & other organic solvents, insecticides etc
  • Ionising radiation
  • Idiopathic aplastic anaemia
  • Viral hepatitis and HIV (in end-stage disease)

Yr 2 Gastrointestinal (37 decks)

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