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ACP > Iron Deficiency Anaemia and Megaloblastic Anaemia > Flashcards

Iron Deficiency Anaemia and Megaloblastic Anaemia Flashcards

1
Q

Clinical manifestations of Iron Deficiency

A

Impaired growth and psychomotor development
Fatigue, irritable, low work productivity
Dysphagia, oesophageal web (plummer vinson syndrome)
Koilonychia, glossitis, angular stomatitis

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2
Q

Iron metabolism, source, function

A

Transferrin - carrier for Fe in circulation
Ferritin - intracellular store of Fe; reflects macrophage store
Serum Fe and transferrin saturation - reflect Fe delivery to erythroid precursors
Hepcidin - inhibits ferroportin which decreases release of Fe from macrophages, hepatoctyes and enterocytes

Source: meats
Function: Hb synthesis

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3
Q

Iron cycle, main site of Fe in body

A

Absorption –> transferrin in plasma –> released to erythroblast for Hb synthesis at BM –> release circulating Hb –> after 120 days, RBC dies and Fe released to macrophages which act as a temporary store –> mobilised and released back to plasma transferrin

1-1.5 mg daily absorption at duodenum and proximal jejunum
- normally just enough to make up for losses (1mg)

Most Fe in the body is at circulating Hb –> menorrhagia or haemorrhage can cause severe iron deficiency

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4
Q

Causes of Fe Deficiency

A

BLOOD LOSS!!

  • GI (ulcer, tumour, varices, NSAIDS etc.)
  • Uterine (menorrhagia)
  • Renal (haematuria, haemoglobinuria, chronic dialysis)
  • Pulmonary (haemosiderosis)
  • Transfer to foetus (pregnancy, multiparity)
  • Insufficient intake (no meats), malabsorption (Celiac, atrophic gastritis)
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5
Q

Iron toxicity: effects, causes

A

Highly reactive with O2
Can cause fatal toxicity (deposition in multiple organs)
- cardiomyopathy, liver cirrhosis, HCC, endocrine abnormalities (DM, hypothyroid), arthropathy, hypogonadism

Causes

  • chronic anaemia e.g. thalassemia major – requiring blood transfusions –> Fe overload
  • reduced excretion
  • haemochromatosis
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6
Q

Lab features of Fe deficiency: CBC, serum biochemistry, BM

A

CBC

  • MCV, MCH, MCHC, RBC, Hb, Hct all decrease
  • RDW increase (anisocytosis - variable RBC sizes)
  • Plt increase (most sensitive to increased haemopoiesis)
  • reticulocyte decrease (can’t produce)

Serum biochemistry
- Iron profile: Ferritin, %saturation, Fe low; TIBC high
(vs other differentials e.g. chronic disease, thalassemia, sideroblastic anaemia)
- Normally do Hb pattern studies at the same time when evaluating microcytic hypochromic anaemia

BM aspirate (unnecessary unless suspect BM problems)
- absent Fe, decrease sideroblasts, erythroid hyperplasia
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7
Q

Iron deficiency management

A
  1. Look for source of blood loss, rule out malignancy and test stool for occult blood
    - GI and GU workup
  2. Correct cause of blood loss
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8
Q

Iron deficiency treatment: precautions, best absorption, standard preparation, side effects, indication for parenteral therapy

A
  • No extended release capsules/enteric coated capsules as they are absorbed in lower part of GI tract
  • Impaired absorption with food
  • Take 2hrs before or 4hrs after ingestion of antacids

Best absorption as FERROUS SALT in mildly acidic medium –> take with tablet of Vitamin C

Tx: ORAL ferrous sulfate (65mg elemental Fe/tablet) – 150-200 mg/day

  • takes time to replenish stores so only useful when patient can tolerate anaemia
  • side effects: 10-20% nausea, constipation, epigastric distress ==> give smaller dose, take tablet with meals

Parenteral Fe therapy (IV) - rare

  • can’t tolerate oral form
  • Fe loss exceeds replacement
  • IBD
  • dialysis, anaemic cancer patients (functional Fe deficiency in chronic diseases = oral not useful; IV Fe can directly bind to transferrin)
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9
Q

Functional Fe deficiency: causes, mechanism, iron profile, treatment

A

Anaemia of chronic disease
- can be normochromic or hypochromic

Chronic inflammatory (infectious + non-infectious) vs Malignant cause

Mechanism: stimulation of hepcidin which inhibits ferroportin and release of Fe from macrophages/ hepatocytes/ enterocytes

Iron profile (decrease TIBC, transferrin receptor, serum Fe; increase/normal ferritin)

Treatment - parenteral Fe therapy

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10
Q

Vit B12 source, body stores, absorption

A

Acquired through diet (can’t synthesise ourselves)
- liver, meat, fish, dairy product

Body stores sufficient for 2-4 yrs

Absorption

  • released from protein binding in food –> complex with IF from gastric parietal cells
  • B12-IF complex adsorbed at terminal ileum
  • B12 released and attaches to transcobalamin (TCII) at epithelium –> enter either systemic circulation or portal blood
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11
Q

B12 protein binding

A

Haptocorrin (TCI)

  • synthesised by granulocytes and macrophages
  • functionally inert
  • 70-90% of total vitamin B12

Transcobalamin (TCII)

  • active portion of vitamin B12
  • 10-30% of total

==> TCII bound B12 testing is now available which gives a more accurate reflection of body B12 status than total B12

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12
Q

Functions of Vit B12 and related clinical effects

A

Methyl B12

  • cofactor for methionine synthase –> enzyme involved in methylation of homocysteine to methionine using methylTHF
  • methionine then used for methylation of DNA, MYELIN, amines etc

Deoxyadenosyl B12
- conversion of methylmalonyl CoA to succinyl CoA

Clinical significance ==> B12 deficiency can increase homocysteine and methymalonyl CoA

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13
Q

Folic acid absorption, body stores

A

Acquired through diet - liver, greens, yeast
Absorption: converted to methyl THF and absorbed in upper small intestine

Body stores only sufficient for 4 months –> higher risk of deficiency with acute changes in demand

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14
Q

Folic acid functions and related clinical effects

A

Required for DNA synthesis!

  • conversion of methyl THF to THF (with B12 help) –> THF then used to generate DNA bases
  • B12 part of “folate trap” into cells

Clinical significance:

  • methotrexate is a chemo drug which inhibits DHF reductase to prevent regeneration of THF for DNA synthesis
  • B12 deficiency can cause false elevation of serum folate because less transfer of methyl THF from plasma ==> always assess both at the same time!
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15
Q

Megaloblastic anaemia: characteristic abnormality, causes

A

Characteristic abnormality: Nuclear cytoplasmic maturation asynchrony
- maturation of nucleus slower than cytoplasm due to defective DNA synthesis

Causes:

  • Vit B12 or Folate deficiency
  • Abnormalities of B12 or folate metabolism e.g. TCII deficiency, NO inactivates B12
  • other defects of DNA synthesis (rare) e.g. enzyme deficiencies
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16
Q

Causes of Vit B12 deficiency

A

Gastric: Gastrectomy, atrophic gastritis, pernicious anaemia (decrease IF)

Pancreas: Pancreatic insufficiency

Small bowel: Bacterial overgrowth in intestines (blind loops), Terminal ileum resection or Crohn’s disease, malabsorption syndrome/celiac, fish tapeworm infestation

Diet: strict vegans

Drugs: PPI, N20 anaesthesia inhibits methionine synthase, metformin

17
Q

Vit B12 deficiency: schilling test

A

No longer performed due to radiation but was previously used to identify cause of malabsorption

Flushing dose of B12 given IM and then oral radioactive B12 –> radioactive B12 will be absorbed and excreted in normal subjects since stores replenished already
==> repeat test with IF/ gluten-free diet/ antibiotics/ pancreatic enzymes and observe changes

18
Q

Pernicious anaemia: pathogenesis, effects, associations, diagnosis

A

Autoimmune gastritis causing achlorhydria and impaired IF secretion

A/w other AI problems e.g. hypothyroidism, addison’s disease, hypoPTH, vitiligo
A/w increased risk of gastric CA

Diagnosis:
- anti-IF Ab (specific but not sensitive) and anti-parietal cell Ab (non-specific)

19
Q

Causes of Folate deficiency

A

Nutritional (especially in old age)

Malabsorption: celiac disease, gastrectomy, Crohn’s disease

  • *Excess utilisation
  • physiological: pregnancy and lactation
  • pathological: HA, myelofibrosis, malignancy, inflammation e.g. TB, RA, Crohn’s

Excess urinary loss e.g. CHF, acute liver disease

Drugs e.g. anticonvulsants

20
Q

Effect of B12 and Folate deficiency on CNS

A

B12 - subacute degeneration of cord

Folate - neural tube defect in foetus

21
Q

Megaloblastic anaemia: clinical presentations, diagnosis (CBC, peripheral smear, BM, biochemistry, confirmation assays)

A

Mild jaundice (rapid cell turnover of precursors in BM with ineffective erythropoiesis causes bilirubin release)
Glossitis
Angular stomatitis
Neurological symptoms (peripheral neuropathy and subacute combined degeneration of cord - irreversible!)
Subfertility

Diagnosis:
- CBC – macrocytic anaemia, reticulocyte low, WBC/Plt may be low in some cases (pancytopenia)

  • Peripheral smear – oval macrocytes, Howell Jolly bodies, hypersegmented neutrophils, poikilocytosis (variable shapes e.g. tear drop cells present)
  • BM (not mandatory) – hypercellularity (ineffective erythropoiesis), megaloblastic erythropoiesis, giant myelocytes and band cells
  • Biochemistry – high bilirubin and LDH (increased red cells and precursor turnover)
  • confirmation assays: low active B12, serum folate (paired tests)
22
Q

Megaloblastic anaemia: treatment - route of administration, prophylaxis, caution in treatment

A

B12 deficiency

  • IM hydroxocobalamin (or oral)
  • prophylactic for ileal resection and gastrectomy
  • caution: don’t give large doses of folic acid as it will aggravate neuropathy by increasing DNA synthesis and use of B12!!
  • caution: monitor K levels as hypoK may occur after B12 replacement and resumption of erythropoiesis

Folate deficiency

  • Oral folic acid
  • prophylactic for pregnancy, severe HA, dialysis
23
Q

Non-megaloblastic causes of macrocytic anaemia

A 
Alcohol
Liver disease
Hypothyroidism
MDS
Reticulocytosis
24
Q

Approach to patient with macrocytosis

A

Is it genuine macrocytosis? (falsely high results: any reticulocytosis? any red cell agglutination?)

Any apparent non-megaloblastic anaemia causes?

Hx: diet, drugs, predisposition to malabsorption, other autoimmune diseases, neurological symptoms, features of megaloblastic anaemia, other causes of macrocytosis

Tests:

  • serum active B12 + folate, anti-IF antibody
  • blood film
  • BM not required unless BM pathology suspected; OGD if pernicious anaemia suspected

Tx: replacement, avoid transfusions as far as possible

ACP (27 decks)

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