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MEH > Lecture 7 > Flashcards

Lecture 7 Flashcards

1
Q

What is anaemia?

A

A Hb concentration lower than the normal range
-not a diagnosis, but manifestation of an underlying disease state
(Normal range varies with age,sex,ethnicity, location)

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2
Q

What are the signs and symptoms of anaemia?

A

Symptoms

  • breathlessness
  • palpitations
  • headaches
  • claudication (cramping pain in legs during exercise)
  • lethargy/weakness
  • angina
  • confusion

Signs

  • pallor (pale)
  • tachycardia
  • tachypnoea (fast breathing rate)
  • hypotension
  • systolic flow mumur
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3
Q

What are specific signs for severe anaemia?

A
  • nails look spoon shaped (Koilonychia-due to iron deficiency)
  • swollen, shiny tongue (Glossitis- vit B12 deficiency)
  • haemopoiesis in bone not expected e.g. facial bones-thalassaemia, rare in recent times due to early diagnosis
  • inflammation of corners of the mouth (Angular stomatitis- iron deficiency)

Don’t see these due to screening now.

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4
Q

How may anaemia develop?

A

In bone marrow:

  • reduced/dysfunctional erythropoiesis
  • abnormal haem synthesis
  • abnormal globin chain synthesis

Peripheral RBC’s:

  • abnormal structure
  • mechanical damage to membrane
  • abnormal metabolic pathway
  • excessive bleeding (e.g. bowel cancer)
  • increased activity of removal by RES
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5
Q

What is the negative feedback loop involving erythropoietin (EPO)?

A
  • low oxygen in blood
  • pericytes in kidney sense hypoxia, and produce EPO
  • EPO binds to receptors on erythroblasts (have nucleus, come before reticulocyte) in bone marrow stimulating RBC production
  • increased number of RBC’s > high blood oxygen
  • negative feedback to pericytes in kidney
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6
Q

How might defects in Hb synthesis develop?

A
  • mutations in globin chain proteins (alpha/beta thalassaemia, sickle cell)
  • sideroblastic anaemia (defects in haem synthesis)
  • insufficient iron (leads to iron deficiency anaemia)
  • anaemia of chronic disease (sufficient iron in body but not available for erythropoiesis)
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7
Q

How do abnormal structure/mechanical damage to blood cells lead to haemolytic anaemia ?

A

-damaged/abnormal RBC’s get removed quickly

Inherited
-mutations in genes coding for proteins involved in interactions b/w plasma membrane and cytoskeleton
-cause cells to become less flexible/more easily damaged
-break up in circulation/removed more quickly by RES
E.g. hereditary spherocytosis

Acquired damage

  • osmotic damage
  • heat damage
  • microangiopathic haemolytic anaemias result from mechanical damage (stress as cells pass through defective heart valve,cells snagging on fibrin strands in small vessels where clotting cascade has occured)
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8
Q

What are some metabolic abnormalities causing anaemia?

A

G6PDH deficiency

  • limits amount of NADPH
  • NADPH required for conversion of oxidised glutathione back to reduced glutathione
  • therefore oxidative defence mechanism not working
  • lipid peroxidation to cell membrane, protein damage causing aggregates of cross linked Hb
  • formation of heinz bodies
  • causing haemolysis (removed by spleen)

Pyruvate kinase deficiency

  • final enzyme in glycolysis
  • can’t undergo glycolysis and make energy properly
  • RBC’s rely on glycolysis due to lack of mitochondria
  • causes RBC’s to become rapidly deficient in ATP, so they undergo haemolysis
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9
Q

How can excessive bleeding cause anaemia?

A

Acute blood loss

  • injury
  • surgery
  • childbirth
  • ruptured blood vessel

Chronic bleeding (small amount of bleeding continuing over a long time)

  • heavy menstrual bleeding
  • GI tract bleeding (blood lost in stool)
  • repeated nosebleeds
  • haemorroids
  • kidney/bladder tumours (blood lost in urine)
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10
Q

Why does splenomegaly arise?

A

Due to haemolytic anaemias, as the spleen is doing extra work.

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11
Q

What is myelofibrosis?

A

Reactive bone marrow fibrosis from proliferation of mutated haematopoietic stem cells, so no space for bone marrow/growth of RBC’s
-mutated progenitor cells can colonise liver/spleen leading to extramedullary haemopoiesis (showing enlarged liver and spleen)

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12
Q

What is thalassaemia?

A
  • inhertied disorder resulting in absent/decreased beta globin chain development
  • microcytic hypohromic red cells
  • splenomegaly
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13
Q

What would you see an increase in if the patient is anaemic?

A

Reticulocytes
(If bone marrow is working)
(MCV is larger as reticulocytes are bigger than RBC’s)

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14
Q

What are the 2 key factors that help you work out the cause of anaemia?

A
  • RBC size (microcytic-small, macrocytic-big, normocytic-normal)
  • increase in reticulocyte count (yes= Bone marrow working)
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15
Q

If the bone marrow is functioning, what is the next sign to look for after presence of reticulocytes?

A

Evidence of haemolysis (high bilirubin/LDH)

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16
Q

What are the causes of macrocytic anaemia?

A

Megaloblastic anaemias

  • DNA synthesis gone wrong in RBC’s, nucleus can’t mature at same rate as cytoplasm
  • cell division is delayed, so cell gets larger while maturation occurs
  • formation of megaloblasts
    e. g.vit B12/folate deficiency, drugs interfering with DNA synthesis/erythroid leukaemias where DNA synthesis is retarded

Macronormoblastic

  • cells just larger (no difference in maturation of nucleus/cytoplasm)
  • erythroblasts are larger than normal so give rise to larger RBC’s
    e. g.liver disease, alcohol toxicity

Stress erythrpoiesis (macrocytic cells)

  • high reticulocyte count- reticulocytes are larger than RBC’s
  • high level of erythropoietin leads to accelerated erythropoiesis
    e. g. blood loss/haemolytic anaemia recovery
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17
Q

What is folate?

A
  • synthesised by bacteria and plants
  • present often in animal/veg food (often green leafy) or liver in pate
  • absorbed mainly by duodenum/jejunum
  • converted to tetrahydrofolate by intestinal cells
  • taken up by liver acting as a store (3-4 months of store)
  • provides carbons for other reactions

-important in reactions that involve DNA/RNA synthesis, as it is used in base formation

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18
Q

Causes of folate deficiency?

A
  • poor diet
  • increased requirement (more stress on bone marrow) e.g. pregnancy, haemolytic anaemia due to increased erythropoiesis, severe skin disease-losing folic acid via shed skin
  • diseases of duodenum/jejunum (Coeliac/Crohn’s)
  • drugs that inhibit dihydrofolate reductase (Methotrexate)
  • alcoholism (damage to intestinal cells)
  • urinary loss of folate in liver disease & heart failure
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19
Q

What are some symptoms of folate deficiency?

A
  • diarrhoea
  • those related to anaemia
  • sense of taste loss
  • numbness/tingling in feet/hands
  • depression
  • muscle weakness
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20
Q

Why is folate so important in pregnancy?

A
  • folate used for formation of neural tube

- can lead to spina bifida

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21
Q

What is the function of vit B12?

A
  • water soluable
  • essential co factor for DNA synthesis/erythropoiesis/normal functioning of CNS
  • produced by bacteria (in animals-commensal bacteria)
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22
Q

How is vit B12 absorbed?

A
  • B12 released from food proteins by proteolysis in stomach
  • binds to haptocorrin in stomach stopping it from being digested
  • enters small intestine
  • digested by pancreatic proteases, splitting B12 from haptocorrin
  • B12 binds to intrinsic factor in small intestine (intrinsic factor produced by gastric parietal cells)
  • B12/intrinsic factor complex binds to cubam receptor initiating receptor mediated endocytosis into enterocytes
  • B12 released into intestinal cell via lysosomal release
  • B12 exits via basolateral membrane (orientated away from lumen) via MDR1
  • B12 binds to transcobalamin in blood and transported around blood
  • stored in liver (3-6 years storage)
23
Q

Causes of B12 deficiency:

A
  • dietary deficiency
  • lack of intrinsic factor (pernicious anaemia)
  • diseases of ileum (this is where B12 intrinsic factor complex is absorbed)
  • lack of transcobalamin
  • chemical inactivation of B12 (nitrous oxide gas)
  • drugs can chelate intrinsic factors
  • parasitic infections (tapeworm in fish can trap B12)
24
Q

What is pernicious anaemia?

A

-lack of intrinsic factor
-exhaustion of B12 reverse
-autoimmune disease: cells damage cells in stomach so they can’t produce intrinsic factor
E.g.blocking/binding Ab

25
Q

Symptoms of B12 deficiency:

A
  • glossitis + mouth ulcers
  • those related to anaemia
  • paraesthesia
  • diarrhoea
  • disturbed vision
  • irritability
26
Q

What is subacute combined desegregation of the chord caused by and symptoms?

A

-deficiency in B12/folate
Folate: in pregnancy- neural tube defects
B12: associated with focal demyelination (often reversible but can result in SCDC- irreversible)
-degeneration of posterior/lateral columns of spinal chord

Symptoms

  • gradual onset weakness
  • numbness/tingling in arms/trunk which worsens
  • changes to mental state
27
Q

How is B12/folate linked?

A
  • combination of uracil instead of thymine
  • both required for creation of thymine
  • absence of thymine means uracil incorporated instead

Causes megaloblastic anaemia as B12/folate are necessary for nuclear maturation/division- open chromatin

28
Q

What are megaloblastic features in blood film?

A
  • tear drops
  • hypersegmented neutrophils
  • macrocytic red cells
  • ovalocytes
  • anisopoikilocytosis (variance in size and shape)
29
Q

What is the treatment of B12/folate deficiency?

A

-oral folic acid
-oral B12
-intramuscular hydroxycobalamine for pernicious anaemia NOT ORAL
(beware of hypokalaemia at beginning of treating pernicious anaemia due to increased requirement of K+ as erythropoiesis increases back to normal)

30
Q

Difference between signs and symptoms?

A

Symptoms: what the patient feels
Signs: what you can see

31
Q

Is anaemia alone a diagnosis?

A

No, it shows a manifestation of an underlying disease, so it is important to establish the cause of anaemia.

32
Q

What are pericytes?

A

Cells that wrap around endothelial cells that line capillaries.

33
Q

How may anaemia develop from low erythropoiesis?

A
  • kidney stops making erythropoietin
  • bone marrow being unable to respond to EPO
  • if marrow is infiltrated by cancer cells/fibrous tissue, number of normal haemopoietic cells is reduced
  • anaemia of chronic disease: iron not available to make RBC’s
  • myelodysplastic syndromes (abnormal clones of marrow stem cells limit capacity to make blood cells)
34
Q

How do autoimmune haemolytic anaemias work?

A

Autoantibodies bind to red cell membrane proteins causing them to be recognised by macrophages in spleen and destroyed.

35
Q

What is intravascular/extravascular anaemia?

A

Intra: damage occurs within the blood vessels
Extra: within RES system

36
Q

What are reticulocytes?

A
  • immature RBC’s
  • larger than RBC’s so increase in reticulocyte number, increase MCV
  • no nucleus & eliminate remaining mitochondria
  • 1 day to mature to RBC
37
Q

How would you evaluate anaemia?

A 
1) increased reticulocyte count?
NO= problem in bone marrow
2)RBC size? Micro:TAILS/macro:vit B12, folate deficiency, liver disease,alcohol/normo:bone marrow failure
YES= bone marrow functioning normally
2)evidence of haemolysis?
YES= autoimmune, enzyme/membrane defects
NO=blood loss, splenic sequestration
38
Q

Why can anaemia arise from chronic kidney disease?

A

Kidney stops producing erythropoietin

39
Q

How can anaemia develop from parovirus/chemotherapy?

A

Marrow is unable to respond to EPO

40
Q

How does myelofibrosis/cancer cause anaemia?

A

Marrow is infiltrated by cancer cells or fibrous tissue, so number of normal haemopoietic cells is reduced

41
Q

What are myelodysplastic syndromes/

A

Blood cancer

-cause abnormal clones of marrow stem cells which limit capacity to make red and white blood cells

42
Q

What does presence of schistocytes indicate?

A

Form of pathology is present

43
Q

What is haemolysis?

A

Rupture/destruction of RBC’s

44
Q

Why does chronic NSAID usage lead to anaemia?

A

(Aspirin, Ibuprofen, Naproxen)
Induce GI injury/bleeding via:
-direct cytotoxic effects on epithelium

45
Q

What are reticulocytes?

A

Immature RBC’s- just been released from marrow to blood

  • no nucleus & they eliminate mitochondria
  • 1 day to mature to erythrocytes
46
Q

What is dihydrofolate reductase?

A

Enzyme which converts folate to tetrahydrofolate

47
Q

What are some good sources of b12?

A 
Meat
Fish
Milk
Cheese
Eggs
Marmite
48
Q

What is pernicious anaemia?

A
  • decreased/absent intrinsic factor
  • exhaustion of B12 reserves
  • autoimmune disease
49
Q

Types of antibody involved in pernicious anaemia?

A
  • blocking antibody (blocks binding of B12 to IF)

- binding antibody (prevents receptor mediated endocytosis)

50
Q

What are gastric parietal cells?

A

Epithelial cells that secrete HCl and intrinsic factor

-in stomach

51
Q

What does thymine deficiency cause and what is it caused by?

A

Caused by folate/B12 deficiency
Causes
-uracil combined into DNA instead of thymine
-DNA repair enzymes detect errors and repair
-results in asynchronous maturation b/w nucleus and cytoplasm

52
Q

What can develop as B12/folate deficiency progresses?

A

Pancytopenia

-low platelets and neutrophils as well

53
Q

What is hydroxycobalamine/cyanocobalamine?

A

A form of vitamin B12 (cyanocobalamine is man made)

54
Q

What can blood transfusion in patients with severe anaemia caused by vitamin 12 deficiency cause?

A

High output cardiac failure (so if required transfuse a smaller volume with care)

MEH (22 decks)

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