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Haem extra cards > vit b12/folic acid > Flashcards

vit b12/folic acid Flashcards

1
Q

B12 is required for…..

A
  1. DNA synthesis

2. Integrity of the nervous system

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2
Q

Folic acid is required for…..

A

DNA Synthesis

Homocystine metabolism

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3
Q

what is the link between B12 and folate with DNA synthesis

A

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

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4
Q

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

A

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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5
Q

In what reaction is B12 a co-factor?

A

The conversion of homocysteine to methionine

Enzyme = methionine synthetase

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6
Q

what cells are affected in b12/folate deficiency

A 
ALL RAPIDLY DIVIDING CELLS ARE AFFECTED
Bone marrow
Epithelial surfaces of mouth and gut
Gonads
embryos
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7
Q

clinical features if b12/folate deficiency

A 
Anemia: weak, tired, short of breath
Jaundice
Glossitis 
angular Cheilosis 
Weight loss, change of bowel habit
Sterility
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8
Q

what its glottis and angular Cheilosis

A

Glossitis - red, raw tongue that is quite painful

Angular Cheilosis - soreness in the corner of your mouth

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9
Q

types of anaemia in b12/folate deficiency

A

macrocytic and megaloblastic

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10
Q

define Macrocytic Anaemia

A

average red cell size is above the normal range

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11
Q

Causes of Macrocytic Anaemia

A

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

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12
Q

what Haematological disorders cause macrocytic anaemia

A

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

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13
Q

what is Myelodysplasia

A

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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14
Q

define megoblastic anaemia

A

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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15
Q

describe Normal red cell maturation

A

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

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16
Q

As the cell gets more mature they….

A

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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17
Q

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

A

The chromatin and how open it is

Colour of the cytoplasm and how blue it is

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18
Q

what goes wrong In Megaloblastic anemia

A

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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19
Q

Peripheral blood in megalobastic anemia

A

Anisocytosis
Large red cells
Hypersegmented neutrophils
Giant metamyelocytes

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20
Q

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

A

FBC
Folate level
B12 level

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21
Q

Dietary folate sources

A

Fresh leafy vegetables

Destroyed by overcooking/canning/processing

22
Q

Folate : decreased intake causes

A

IGNORANCE
POVERTY
APATHY

……..consider - elderly -alcoholics

23
Q

causes of increased folate demand

A

PHYSIOLOGICAL
Pregnancy
Adolescence
Premature babies

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

24
Q

Laboratory diagnosis of folate deficiency

A

FBC and film

Folate levels in the blood

25
Q

Assessing cause of decreased folate

A

EASY – history (diet/alcohol/illness)

EXAMINATION – skin disease/ alcoholic liver disease

26
Q

Consequences of folate deficiency

A

Megaloblastic, macrocytic anemia

Neural tube defects in developing fetus

Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism

27
Q

what neural tube defects occur in folate deficiency

A

Spina bifida

Anencephaly

28
Q

folate and pregnancy

A

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

29
Q

Very high homocysteine levels are associated with

A

atherosclerosis

premature vascular disease

30
Q

Mildly elevated levels of homocysteine are associated with:

A

cardiovascular disease DEFINITELY
arterial thrombosis PROBABLY
venous thrombosis POSSIBLY

31
Q

Consequences of B12 deficiency

A

Neurological problems

Bilateral peripheral neuropathy

Subacute comined degeneration of the cord
(Posterior and pyramidal tracts of the spinal cord)

Optic atrophy
dementia

32
Q

b12 deficiency symptoms

A 
Paraesthesiae
Muscle weakness
Difficult walking
Visual impairment
Psychiatric disturbance
33
Q

B12 deficiency - examination

A

Absent reflexes and upgoing plantar responses

34
Q

B12 deficiency Cause

A

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

35
Q

Normal B12 absorption location and storage

A

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

36
Q

methods of b12 absorption

A

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

37
Q

B12 absorption needs

A

THREE THINGS ARE ESSENTIAL

Intact Stomach
Intrinsic factor
Functioning small intestine

38
Q

causes of Reduction in intrinsic factor

A

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

39
Q

define Pernicious anemia who does it affect

A

Autoimmune condition associated with SEVERE LACK OF IF

Peak age: 60 years
Family history

40
Q

effect of PA in men

A

Males have a decreased life expectancy

Ca stomach

41
Q

Auto-antibodies in PA

A

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

42
Q

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

A

a) Crohns
b) Coeliac disease
c) surgical resection

43
Q

2 main causes of impaired b12 absorption

A

Diseases of small bowel (terminal ileum)

Reduction in intrinsic factor

44
Q

infections associated with b12 deficiency

A

H Pylori
Giardia
Fish tapeworm
Bacterial overgrowth

45
Q

Drugs associated with low B12

A

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

46
Q

tests to identify these causes of b12 deficiency

A

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)

47
Q

des scribe the Shilling test

A

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

48
Q

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

A

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

49
Q

if both isotopes low

A

Measure methylmalonyl acid
Measure homocysteine
Look for anti-intrinsic factor antibodies

Treat as B12 deficiency until you get all of the results back

50
Q

Treatment for b12 deficiency

A

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

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