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molecular basis of disease > nutritional anemia > Flashcards

nutritional anemia Flashcards

1
Q

Define anemia

A
  • anemia is a condition in which the number of red blood cells (and consequently their oxygen carrying capacity ) is insufficient to meet the body’s physiological needs
  • insufficient oxygen carrying capacity is due to reduced hemoglobin concentration as seen with insufficient RBC
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2
Q

What is hemoglobin?

A
  • iron containing oxygen transport metalloprotein within RBCs
  • reduction in hemoglobin = anemia (bc of reduction in oxygen carrying capacity)
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3
Q

What components does red blood cell require for maturation and normal erythropoietin?

A
  • vitamin B12 and folic acid (for DNA synthesis)

- iron (for hemoglobin synthesis)

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4
Q

What makes someone anemic?

A
  1. failure of production of RBC: hypo proliferation reticulocytopenic
  2. inneffictive erythropoiesis
  3. Decreased survival : blood loss, haemolysis, reticulocytosis
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5
Q

What are 3 categories of mean cell volume and how can we use that to investigate different deficiency?

A

MCV = average size of RBC

  1. microcytic : iron deficiency (thalassamia)
    - smaller cell, bc not enough Hb , less iron binding
  2. Normocytic : sickle cell (normal size but shape different)
  3. Macrocytic : B12 deficiency, folate deficiency.
    - not enough B12 and folate bc the cell too big and uses it up
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6
Q

Define nutritional anaemias?

A
  • iron deficiency
  • vitamin B12 deficiency
  • folate deficiency
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7
Q

Why is iron essential?

A
  • for O2 transport
  • most abundant trace element in body
  • daily requirement for iron for erythropoiesis varies depending on gender and physiological needs
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8
Q

How does daily iron requirement vary?

A

males and females:
- 7 months to 13 year old same requirements
- females 14-50 have higher iron requirements than males 14-50 y/o
51+ females and males
-lower requirements
-females: higher requirements during pregnancy

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9
Q

What is the distribution of iron in adults?

A 
=>muscle: 300mg
=>duodenum : 1-2 mg
=>bone marrow: 300 mg
=>reticuloendothelial macrophages : 600 mg
=>liver : 1000 mg 
=>plasma transferrin : 3mg 
=> circulating erythrocytes Hb: 1,800 mg

menstruation/other blood loss average : 1-2mg per day iron loss.

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10
Q

What are 2 stable forms of iron?

A
  • ferric (Fe3+)

- ferrous (Fe2+)

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11
Q

What are 2 main storage proteins and where are they found?

A
  • ferritin and haemosiderin

- found in cells of liver, spleen and bone marrow

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12
Q

Why is iron absorption really important?

A
  • iron absorption is the only way iron is regulated.

- iron can’t be excreted only lost during menstruation.

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13
Q

How is iron absorption regulated?

A
  • regulated by GI mucosal cells
  • hepcidin in duodenum and proximal jejunum binding to ferroportin receptors on enterocytes.(high levels of hepicidin = less absorption)
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14
Q

What does amount of iron absorbed depend on?

A
  • type ingested
  • heme , ferrous (red meat) > than non-red meat
  • heme iron makes up 10-20% of dietry iron
  • other foods, GI acidity , state of iron storage levels and bone marrow activity affect absorption.
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15
Q

What is the function of hepcidin?

A

-binds to ferroportin (iron export channel) causing it to be broken down by lysosomes decreasing iron export into blood plasma

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16
Q

What is hepcidin feedback regulated by?

A

-iron concentrations in plasma and liver and by erythropoietic demand for iron.

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17
Q

How is iron transported?

A
  • iron is transported from enterocytes and then either into plasma or stored as ferritin if excess.
  • in plasma: iron attaches to transferrin and then transported to bones marrow where it binds to transferrin receptors on RBC precursors

A state of iron deficiency will see reduced ferritin stores and increased transferrin

18
Q

What will a state of iron deficiency cause?

A

-reduced ferritin stores and then increased transferrin

19
Q

What is the main component you measure in labs iron studies?

A
  1. ferritin levels = iron storage
    - low ferritin levels indicate low iron levels
    - ferritin levels are also high when your unwell so it doesn’t always mean you have high levels of iron
  2. Transferrin saturation = ratio of serum iron and total iron binding capacity
  3. Transferrin = made by liver, production inversely to Fe stores, vital for iron transport.
  4. Total iron binding capacity: measurement of the capacity if transferrin to bind iron, indirect measurement of transferrin.
20
Q

What do results of an iron deficient patient look like?

A 
ferritin = low
TF saturation = low
Transferrin = high 
TIBC = high 
serum iron = low/normal
21
Q

What does iron lab study show?

A
  1. Serum Fe = variable during the day
  2. Ferritin = primary storage protein and provide reserve, water soluble
  3. transferrin saturation= ratio of serum iron and total iron binding capacity
  4. transferrin = made by liver, production inversely proportional to Fe stores. Vital for Fe transport.
  5. total iron binding capacity = measurement of capacity of transferrin to bind iron it is an indirect measurement of transferrin.
22
Q

what are causes of iron deficiency?

A
  1. not enough in:
    - poor diet
    - malabsorption
    - increased physiological needs
  2. losing too much
    - blood loss
    - menstruation
    - GI tract loss
    - paraistes
23
Q

How do you investigate iron deficiency?

A
  1. FBC : Hb, Mean Cell Volume(MCV) , Mean Cell Hb(MCHC), Reticulocyte count.
  2. iron studies : ferritin , transferrin saturation
  3. blood films
24
Q

What are the 2 terms used to describe appearance of blood cells?

A
  1. cell size:
    - microcytic or macrocytic
  2. cell colour :
    - hyperchromic or hypochromic
25
Q

Define reticulocytopenia.

A
  • reticulocytes are new, immature blood cells made in the bone marrow and sent into blood stream.
  • reticulocytopenia is a medical term for an abnormal decrease in reticulocytes.
26
Q

What are characteristics of moderate anemia?

A
  • microcytic and hypochromic
  • reticulocytopenic
  • ferritin 8
27
Q

What are symptoms and signs of iron deficiency aneamia?

A

symptoms:
-fatigue, lethragy, and dizziness
signs :
-pallor of mucous membranes
-bounding pulse
-systolic flow murmurs
-smooth tongue
-koilonychias

28
Q

What does B12 and folate deficiency lead to/lab findings?

A
  • macrocytic anaemia
  • low Hb
  • high MCV
  • normal MCHC
29
Q

What can Macrocytic aneamia be characterised into?

A
  1. megaloblastic: low retinculocyte count
    -vitamin B12/folic acid deficiency
    -drug related (inference with B12/FA metabolism)
  2. nonmegaloblastic
    - alcoholism ++
    - hypothyroidism
    -liver disease
    myelodysplastic syndromes
    -reticulocytosis (hemolysis)
30
Q

what components of blood is important for final maturation of RBC and for synthesis of DNA?

A
  1. vitamin B12 (cobalamin)
  2. folic acid

both needed for thymidine triphoshpate synthesis.

31
Q

What is the difference between megablastic vs non megablastic anemia?

A
  1. megablastic:
    - macrovalocytes and hypersegmented neutrophils
    - B12 and folic acid deficiency
  2. non-megablastic anemia:
    - myelodysplastic syndrome with several macrocytes.
32
Q

How is folate deficiency diagnosis made?

A
  • reticulocytes: 20
  • folate 0.9 (5-15)
  • B12 163 (180-350)
33
Q

What is folate needed for?

A

-folate necessary for DNA synthesis: adenosine, guanine and thymidine synthesis.

34
Q

What are causes of folate deficiency?

A
  1. increased demand
    - pregnancy
    - disseminated cancer
    - urinary loss
  2. decreased intake
    - poor diet
    - chronic alcohol intake
    - elderly
  3. decreased absorption
    - medication
    - coelic
    - jejunal resection
35
Q

What is vitamin B12 needed for?

A
  • essential co-factor for methylation in DNA and cell metabolism
  • intracellular conversion to 2 active coenzymes necessary for homeostasis of methylomonic acid (MMA) and homocysteine.
36
Q

What foods contain vitamin B12 and what are intake recommendations?

A 
food:
fish, meat, dairy 
uk intake: 1.5mcg/day
USA intake : 2.4 mvg
EU : 1mcg
body liver storage : 1-5 mg.
37
Q

what does vitamin B12 require to be absorbed if made in parietal cells?

A
  • requires the presence of intrinsic factor for absorption in terminal ileum
  • IF made in parietal cells in stomach
  • transcobalamin II and transcobalamin I transport vitB12 to tissues
38
Q

What is pernicious anaemia?

A
  • autoimmune disorder caused by Lack of intrinsic factors leading to lack of B12 absorption
  • gastric parietal cell antibodies
  • IF antibodies
39
Q

What are clinical consequences of anemia?

A
  1. brain = cognition, depression, psychosis
  2. neurology = myelopathy, sensory changes, ataxia, spasticity (SACDC)
  3. infertitily
  4. cardiac cardiomyopathy
  5. tongue: glossitis, taste impairment
  6. blood : pancytopenia
40
Q

What are treatments for deficiency?

A

treat the underlying cause

  1. iron - diet, oral, pareteral iron supplementatin, stopping the bleeding
  2. folic acid - oral supplements
  3. B12- oral vs intramuscular treatment,
41
Q

what is microcytic anemia characterised by?

A

Microcytic anemia is usually characterised by low mean cell volume (average size of RBC)

42
Q

What are some causes of B12 deficiency

A
  • impaired absorption
  • decreased intake
  • congenital causes
  • increased requirements
  • medication

molecular basis of disease (29 decks)

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