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Macrocytic Anaemia. Elliot Catchpole PCMD. Recap. Mean Cell Volume = The size of each RBC. MACROCYTIC >96. Normocytic 76-96. Microcytic <76. Haemolysis. Non- Megaloblastic. -IRON deficiency Thalassaemias Sideroblastic. -Alcohol -Liver Disease - MYLODYSPLASIA. -G6PD Deficiency

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macrocytic anaemia

Macrocytic Anaemia

Elliot Catchpole

PCMD

recap
Recap
  • Mean Cell Volume = The size of each RBC

MACROCYTIC

>96

Normocytic

76-96

Microcytic

<76

Haemolysis

Non-Megaloblastic

  • -IRON deficiency
  • Thalassaemias
  • Sideroblastic

-Alcohol

-Liver Disease

-MYLODYSPLASIA

-G6PD Deficiency

-Hereditary spherocytosis

-Paroxysmal Nocturnal Haemoglobinurea

-Autoimmune Haemolysis

-Sickle Cell

Megaloblastic

B12andFolate

Chronic Disease

macrocytic anaemia1
Macrocytic Anaemia
  • So what do we mean by ‘megaloblastic’?
b12 and folate
B12 and Folate

ACTIVE Folate

Folate

Purines/pyrimadines = DNA synthesis

B12

Methione

INACTIVE (reduced)

Folate

Homocysteine

megaloblastic anaemia
‘Megaloblastic’ anaemia

Includes B12 and folate – will show megaloblasts (large and immature cells) due to poor DNA synthesis. These cells are large because B12/folate deficiency result in impaired DNA synthesis, so cells are stuck in the G2 phase of mitosis and carry on growing, so become large and fragile. Cytoplasm/cell contents will be disproportionate to the DNA. This is different from reticulocytes.ALSO will show hypersegmentedneutrophils – these have more than 4 nuclei (4 is normal) due to slowed DNA synthesis.They can be seen on a peripheral smear.

In contrast, alcohol and liver disease do not fall under this category.

Pregnancy and hypothroidism can also cause a mild non-megaloblastic macrocytosis.

common findings in b12 folate
Common findings in B12/Folate

LDH

Indirect Bilirubin

B12/Folate

MCV = Raised

  • ?Jaundice?Very mild, not as extreme as true haemolysis

Reticulocyte

b12 vs folate
B12 vs. Folate

Stores deplete very very slowlyDietary – VeganismPERNICIOUS ANAEMIA

Stores deplete quickly in monthsDietary – leaFy green vegetables Cell turnover – e.g. In SCD or psoriasis

CAUSES

Coeliac/malabsorption

NEUROLOGICAL SYMPTOMS- Most common = peripheral neuropathy

NO NEUROLOGICAL SYMPTOMS

SYMPTOMS

ANAEMIA

B12  HomocysteineMethylmalonic AcidAnti parietal/IF antibodies

Folate  HomocysteineMethylmalonic Acid

INVESTIGATIONS

B12

B12

TREATMENT

If Low

Folate

Give

Give

+

SUBACUTE COMBINED DEGENERATION OF THE CORD

To prevent...

COMPLICATIONS

Increased CVS risk(high homocysteine)

pernicious anaemia
Pernicious Anaemia
  • Parietal cells in Stomach produceIntrinsic Factor (IF)
  • IF is needed to absorb B12
  • B12 absorbed in terminal ileum
  • Autoimmune Ig attacks:Anti-parietal cell = parietal cellsAnti-IF = Intrinsic Factor
  • Look for these autoantibodies in those with suspected pernicious anaemia - E.g. Bariatric surgery (gastric bypass),ileum resection, gastritis
  • If autoantibodies negative, and PA still suspected,perform Schilling’s test
  • Treat with IM B12 (hydroxycobalamine)

Stomach

Duo.

Jej.

ILEUM

subacute combined degeneration of the spinal cord
Subacute Combined Degeneration of the spinal cord

Dorsal

  • Emergency – as irreversible!
  • Loss of:Dorsal column = SensorylossCorticospinal = MotorUMN signs(extensor plantars)LMN signs (absent knee reflexes)

Corticospinal

Treat with B12

slide11
CASE
  • A 78 year-old gentleman comes in with numbness and tingling in his hands and feet. He is a chronic alcoholic with no signs of liver disease on examination and no past medical hx.What do you do first?
questions
Questions
  • A 42 year old women has been increasingly tired over the past 6 months. She has felt faint upon exertion with palpitations. She is pale.
  • Results of testing show:Hb = 9.2MCV = 102fLSmear/film = hypersegmented polymorphs.
  • Which is the single most likely cause of her symptoms?1) Alcholism2) Liver disease3) Myxoedema4) Pernicious anaemia5) Pregnancy
questions1
Questions
  • A 45 year-old women presents to her GP with a 4-week history of increasing fatigue. She has noticed that the whites of her eyes are yellowing. She has had flitting joint pain over the last 6 months, which she has put down to ‘growing old’. She is otherwise well with no past medical Hx. On examination, she is mildly jaundiced with an erythematous rash over her cheeks and nose. She has slight splenomegaly but no lymphadenopathy or hepatomegaly. Her blood results are:Hb – 8.9MCV – 105fLBilirubin – 75 (3-17)What is the most likely diagnosis?1) Pernicious Anaemia2) Cold autoimmune haemolytic anaemia3) Warm autoimmune haemolytic anaemia 4) Anaemia of chronic disease5) Sickle Cell disease
questions2
Questions
  • An African-British man is taking a skydiving course. He is on his first time up in the plane at altitude, about to jump, when he develops severe chest, back, and thigh pain. When the plane returns to the ground for an emergency landing, he feels well. FBC is completely normal, as is his peripheral blood smear. He has no past medical Hx, only occasional dark urine.1) What is the most likely diagnosis?2) What is the most accurate diagnostic test?
questions3
Questions
  • A 54 year-old women presents to her GP with a 2 month Hx of worsening fatigue. She reports no other symptoms. On examination, she is mildly jaundiced, pale, and has a history of rheumatoid arthritis. Blood tests reveal:Hb = 7.9MCV = 118Bilirubin = 45 (3 -17)
  • What is the most likely diagnosis?1) Autoimmune haemolytic anaemia2) Pernicious Anaemia3) Iron Deficiency4) Anaemia of chronic disease5) Dietary B12 deficiency
slide16

The Patient is given appropriate therapy (which is????). She returns a month later. Although she noticed improvement, she still doesn't feel back to normal. She is starting to feel tired again and slightly breathless on exertion. Bloods show?Hb = 7.5MCV = 70

  • What is the most likely cause of her persistent anaemia?1) Inadequate B12 replacement2) Coexisting folate deficiency3) Iron deficiency4) Thalassaemia5) Haemolysis
questions4
Questions
  • A 52 year-old man has been feeling fatigued over the past year. He complains of foul oily stools and has intermittant abdominal pain. He admits to losing 5kg. His initial blood results are:Hb = 10.6 g/dL(13.5 – 18.0 g/dL)Vit. B12 = 0.35mmol/L (0.13 – 0.68mmol/L)Folate = 1.4 ug/L (~2.1 ug/L)Ferritin = 110ug/L (12 – 200 ug/L)Which is the single most appropriate further investigation to confirm the diagnosis?1) Anti-endomysial antibodies2) Anti-gastric parietal cell antibodies3) Liver function tests4) Peripheral blood film5) Thyroid function tests