vit b12/folic acid Flashcards by Adam Haq

B12 is required for…..

DNA synthesis

2. Integrity of the nervous system

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Folic acid is required for…..

DNA Synthesis

Homocystine metabolism

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what is the link between B12 and folate with DNA synthesis

Both are needed for the production of deoxythymidine a crucial building block in DNA synthesis. deoxythymidine is made from deoxyuridine.

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Deoxythymidine (dTMP) is a major building block of DNA synthesis. How is it produced?

methylation of deoxyuridine (dUMP)
requiresrelease of methyl groups from methyl-tetrahydrofolate by the action of B12 as a cofactor

accompanied by the conversion of homocysteine to methionine.

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In what reaction is B12 a co-factor?

The conversion of homocysteine to methionine

Enzyme = methionine synthetase

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what cells are affected in b12/folate deficiency

ALL RAPIDLY DIVIDING CELLS ARE AFFECTED
Bone marrow
Epithelial surfaces of mouth and gut
Gonads
embryos

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clinical features if b12/folate deficiency

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

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what its glottis and angular Cheilosis

Glossitis - red, raw tongue that is quite painful

Angular Cheilosis - soreness in the corner of your mouth

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types of anaemia in b12/folate deficiency

macrocytic and megaloblastic

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define Macrocytic Anaemia

average red cell size is above the normal range

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Causes of Macrocytic Anaemia

Vitamin B12/folate deficiency - OVAL macrocytes
Liver Disease or Alcohol - ROUND macrocytes
Hypothyroidism
Drugs e.g. azathioprine
Haematological Disorders

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what Haematological disorders cause macrocytic anaemia

Myelodysplasia
aplastic anemia (characterised by a failure of blood cell production resulting in pancytopenia)
Reticulocytosis e.g. chronic haemolytic anemia

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what is Myelodysplasia

a group of disorders in which the production of any one or all types of blood cells by the bone marrow is disrupted. Look for hypogranular neutrophils and/or monocytosis

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define megoblastic anaemia

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

REMEMBER IT IS CONFINED TO CHANGES IN THE BONE MARROW

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describe Normal red cell maturation

Erythroblast (precursor)
Normoblast: early/intermediate/late
Reticulocyte (young no nucleus)
Circulating red blood cell

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As the cell gets more mature they….

get smaller and go from blue to pink
chromatin goes open to dense before nucleus emitted

The more DNA you have in the cytoplasm the more blue it is and the more haemoglobin you have, the pinker it is

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So to determine whether the cells in the lineage are normal you have to look at

The chromatin and how open it is

Colour of the cytoplasm and how blue it is

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what goes wrong In Megaloblastic anemia

there is ASYNCHRONOUS maturation of the nucleus and cytoplasm in the erythroid (red cell) series

So the nucleus doesn’t mature but the cytoplasm does

You get this immature open nuclear chromatin with normal mature haemoglobinisation of the cytoplasm

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Peripheral blood in megalobastic anemia

Anisocytosis
Large red cells
Hypersegmented neutrophils
Giant metamyelocytes

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Give 3 tests that you would do if someone had a macrocytosis

FBC
Folate level
B12 level

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Dietary folate sources

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Fresh leafy vegetables

Destroyed by overcooking/canning/processing

Folate : decreased intake causes

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IGNORANCE
POVERTY
APATHY

……..consider - elderly -alcoholics

causes of increased folate demand

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PHYSIOLOGICAL
Pregnancy
Adolescence
Premature babies

PATHOLOGICAL
Malignancy
Erythoderma (whole body rash)
Haemolytic anaemias (increased RBC production more folate required)

Laboratory diagnosis of folate deficiency

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FBC and film

Folate levels in the blood

Assessing cause of decreased folate

EASY – history (diet/alcohol/illness) | EXAMINATION – skin disease/ alcoholic liver disease

Consequences of folate deficiency

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

what neural tube defects occur in folate deficiency

Spina bifida | Anencephaly

folate and pregnancy

ALL PREGNANT WOMEN TAKE FOLIC ACID 0.4MG PRIOR TO CONCEPTION AND FOR FIRST 12 WEEKS

Very high homocysteine levels are associated with

atherosclerosis | premature vascular disease

Mildly elevated levels of homocysteine are associated with:

cardiovascular disease DEFINITELY arterial thrombosis PROBABLY venous thrombosis POSSIBLY

Consequences of B12 deficiency

Neurological problems Bilateral peripheral neuropathy Subacute comined degeneration of the cord (Posterior and pyramidal tracts of the spinal cord) Optic atrophy dementia

b12 deficiency symptoms

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

B12 deficiency - examination

Absent reflexes and upgoing plantar responses

B12 deficiency Cause

POOR ABSORPTION Reduced dietary intake: Stores are large and last for 3-4 years Animal produce Vegans are at risk Infections/infestations: Abnormal bacterial flora (stagnant loops) Tropical sprue Fish tapeworm

Normal B12 absorption location and storage

Occurs in small intestine – B12 is then stored – when stores are saturated excess B12 is excreted in the urine

methods of b12 absorption

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

B12 absorption needs

THREE THINGS ARE ESSENTIAL Intact Stomach Intrinsic factor Functioning small intestine

causes of Reduction in intrinsic factor

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

define Pernicious anemia who does it affect

Autoimmune condition associated with SEVERE LACK OF IF Peak age: 60 years Family history

effect of PA in men

Males have a decreased life expectancy | Ca stomach

Auto-antibodies in PA

Intrinsic factor antibodies: Occasionally found in other conditions Parietal cell antibodies: 90% adults with PA 16% normal females over age of 60 Increased in relative of patients with PA

what cause Diseases of small bowel (terminal ileum) impaired b12 absorption

a) Crohns b) Coeliac disease c) surgical resection

2 main causes of impaired b12 absorption

Diseases of small bowel (terminal ileum) | Reduction in intrinsic factor

infections associated with 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 to identify these causes 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)

des scribe the Shilling test

Give b12 injection to replenish stores administer 2 b12 capsules orally (radiolabelled) Part 1) B12 alone Part 2) B12 + IF complex Collect urine 24h after administration and measure proportions of each isotope

how does shilling test works out the cause of the malabsorption of B12

Both isotopes excreted: NORMAL B12-IF complex only: PA Neither excreted: Inflamatory disease of terminal ileum

if both isotopes low

Measure methylmalonyl acid Measure homocysteine Look for anti-intrinsic factor antibodies Treat as B12 deficiency until you get all of the results back

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

vit b12/folic acid Flashcards

(50 cards)