Haem 10 Flashcards by Robert Grogan

Role of B12 and folate

Required for DNA synthesis

Absence leads to severe anaemia which can be fatal

Known as haematinics

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What is b12 needed for

DNA synthesis

2. Integrity of the nervous system (both CNS and PNS, independent of the effect on DNA synthesis)

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What is folic acid needed for

DNA Synthesis

Homocystine metabolism

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How is b12 and folate involved in DNA synthesis

dUMP–> dTMP

This methylation from deoxyuridinemonophosphate to deoxythymidine monophosphate requires donation of CH3 from folate intermediaries from the dietary folate.

B12 is needed to convert methyl-THF to THF from which these folate intermediaries are formed

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Areas affected by b12 and folate deficiency

ALL RAPIDLY DIVIDING CELLS ARE AFFECTED

Bone marrow
Epithelial surfaces of mouth and gut
Gonads
embryos

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Clinical features of b12 or folate deficiency

Anemia: weak, tired, short of breath
Jaundice
Glossitis and angular cheilosis
Weight loss, change of bowel habit
Sterility

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Type of anaemia associated with b12 or folate deficiency

Macrocytic and megaloblasic (BIG cells, not small like in iron deficiency)

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Causes of macrocytic anaemia

Vitamin B12/folate deficiency
Liver disease or alcohol
Hypothyroid
Drugs e.g. azathioprine (immune suppressive)
-Haematological disorders:
  -Myelodysplasia, 
  -aplastic anemia
  -Reticulocytosis e.g. chronic haemolytic anemia

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What does megaloblastic refer to

Describes a morphological change in the red cell precursors within the bone marrow

NOT size of blood cells

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Maturation of red cells

What happens to the nucleus and the cytoplasm in megaloblastic anaemia

Erythroblast
Normoblast: early/intermediate/late
Reticulocyte
Circulating red blood cell

Defined by asynchronous maturation of the nucleus and cytoplasm in the erythroid series.

We start of with a nucleus, which gets smaller and smaller through development, until it becomes pyknotic and is extruded.

Meanwhile, the cytoplasm is getting more and more pink because of increasing haemoglobin (red) and then the other proteins are not produced anymore .

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What changes is seen in normal red cell development on slides

Cytoplasm from blue (when there are lots of protein types) to pink (just Hb)

Nucleus condenses and then is ejected…..

Megaloblastic change is lack of synchronisation between cytoplasm and nucleus maturaton

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Indication of megaloblastic change in peripheral blood vs in blood marrow

Anisocytosis
Large red cells (oval macrocytes)
Hypersegmented neutrophils
Giant metamyelocytes

In marrow… mature red cells

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t/f thyroid disease can cause megaloblastic RBC

F!! Macrocytic red cells

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Tests with high MCV

b12/folate
LFT
TSH/T3/T4
Reticulocyte count

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Cause of hypersegmented neutrophil

folate deficiency or b12 deficiency (pernicious)

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Megaloblastic change cause

ONLY FOLATE AND B12 DEFICIENCY

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Where is dietary folate present but what is the catch

Fresh leafy vegetables

Destroyed by overcooking/canning/processing

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What causes decreased folate

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IGNORANCE
POVERTY
APATHY

and elderly and alcoholics

Increased demand

When can there be increased folate demand

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PHYSIOLOGICAL
-Pregnancy
-Adolescence
-Premature babies
PATHOLOGICAL
-Malignancy
-Erythoderma (red skin, big turnover of skin cells)
-Haemolytic anaemias

Lab diagnosis of folate

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FBC and film
Folate levels in the blood
(doesn’t necessarily mean anaemic yet, but want to then prevent anaemia so give folae)

Consequences of folate deficiency

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1,Megaloblastic, macrocytic anemia

Neural tube defects in developing fetus
Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism

Neural tube defects associated with folate deficiency

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Pregnant women with folate deficiency more likely to have kid with

spina bifida
acencephaly

Role of folate in homocysteine

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homocysteine is toxic, and converted to methionine with folate and b12

So note that the dietary methyl-THF is converted to THF using b12 as a cofactor to then allow THF to form the intermediates that can methylate dUMP–>dTMP.

But at the same time as converting methyl-THF to THF , you convert homocysteine to methionine.

What is homocysteine levels assocaite with

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Very high homocysteine levels are associated with
-atherosclerosis
-premature vascular disease
(thrombosis)

Increased risk of what with mildly elevatted homocysteine levels Why is food fortified with folate in the US

Mildly elevated levels of homocysteine are associated with: cardiovascular disease DEFINITELY arterial thrombosis PROBABLY venous thrombosis POSSIBLY 1998 food and drug administration in the USA Grains fortified with folic acid (100micrograms/day)

Classic presentation of b12 deficiency Consequences of b12 deficiency

TINGINLING FINGERS! ROMBERG'S SIGN=PROPRIOCEPTION (fall over when eyes closed!) Neurological problems - Bilateral peripheral neuropathy - Subacute comined degeneration of the cord (Posterior and pyramidal tracts of the spinal cord) - Optic atrophy - dementia

History of b12 deficiency

``` Paraesthesiae Muscle weakness Difficult walking Visual impairment Psychiatric disturbance ```

b12 deficiency on examination

Absent reflexes and upgoing plantar responses showing peripheral and central nerve problems respectively

b12 deficiency cause

Poor absoprion Reduced dietary intake (stores large and last 3-4 years, in animal produce so only vegans at risk) Infections/infestations (Abnormal bacterial flora (stagnant loops), Tropical sprue, Fish tapeworm)

Normal b12 absorptin

Method 1: In duodenum (slow and inefficient) Method 2: B12 must combine with intrinsic factor Intrinsic factor is made in the stomach (parietal cells) B12-IF binds to ileal receptors

What is required for b12 absorption

Intact Stomach Intrinsic factor Functioning small intestine

3 causes of reduction in instrinsic factor

a) post gastrectomy b) gastric atrophy c) antibodies to intrinsic factor or parietal cells

What is pernicious anaemia

Autoimmune condition associated with very low IF... very gradual onset Peak age: 60 family history

How do you solve pernicious anaemia

Injectins of b12 (oral won't be absorbed as no IF!)

Males and pernicious anaemia

Males have a decreased life expectancy | - stomach cancer

How can you check antibodies in pernicious anaemia

Intrinsic factor antibodies (Occasionally found in other conditions) (not great): Parietal cell antibodies -90% adults with PA -16% normal females over age of 60 Increased in relative of patients with PA

Cuase of decreased b12 absorption (NOT pernicious anaemia)

2. Diseases of small bowel (terminal ileum) a) Crohns b) Coeliac disease c) surgical resection

Infections predisposing you to b12 deficiency

H pylori, giardia fish tapeworm bacterial overgrowth

Drugs associated with low b12

Metformin Proton pump inhibitors e.g. omeprazole Oral contraceptive pill

Tests for b12

What is the cause of B12 deficiency? Antibodies to parietal cells and intrinsic factor Anitbodies for coeliac disease Breath test for bacterial overgrowth Stool for H Pylori Test for Giardia OLDEN DAYS - Shilling test (part I and part II)

Outline the shilling test

Normally, b12 should come out in urine (radioactive label) If it doesn't, then it may coming out in the stool 1. Give radioactive drink in b12... if comes out in urine then they must have absorbed b12 (so no pernicious) If no b12 in urine.... they might not be absorbing b12 properly (pernicious anaemia OR small bowel disease) or haven't corrected b12 deficiency before test.. i.e. it will go straight to the stores 2. Give i.v IF and another radioactive b12..... if it comes out in the urine now, it means that there is pernicious anaemia. If still none in the urine, it must mean there is some small bowel disease.

Treatment for b12 deficiency

``` Injections of B12…. 1000ug (i.m) 3x/week for 2 weeks Thereafter every 3 months IF NEUROLOGICAL INVOLVMENT B12 injections alternate days until no further improvement – up to 3 weeks Thereafter every 2 months ```

SBA: A 49 y old man with grey hair and blue eyes presents with anaemia. His blood count is as follows: Hb 90g/l WBC 4 x 109/l platelets 160 x 109/l MCV 110fl tests?

Answer;

Haem 10 Flashcards

(43 cards)