Miss K.M.

22 year old female from Pietermaritzburg

Unwell 2/52

• Vomiting “everything she ate”

• Cough production of white sputum

• Increasing shortness of breath

• Fever

• Rigors

• Loose stools, occasional blood stained

Sistemic enquiry

Weight loss ± 4kg

Palpitations

Headaches

Generalised weakness

Medical history - nil of note

Surgical history - nil of note

No medication

Family history - nil

Social vegetarian for 13 years

not sexually active

No know allergies

No significant travel history

CLINICAL EXAMINATION

BP = 68/41 Pulse = 100/min, regular reduced volumeTemp = 37ºCPaleJaundicedDehydratedRespiratory system: moderate respiratory distress

Air entry equal bilaterallyLeft basal crepitation

CVS System: JVP elevatedapex: 5i.c.s.3/6 ESMno peripheral oedema

Abdomen: not distendedsoft2cm hepatomegalyno splenomegaly

CNS: CCS 15/15

Orientated but tirespupils n.a.d.no focal signs? Terminaly neck stiffness

CONCLUSION

Young vegetarian woman, pale jaundiced, dehydrated, dyspnoeicand with symptoms of heart failure.

HB = 2,4 Retic = 3,4%

HCT = 6,5

MCV = 121,1

WCC = 1,7

PLAT = 12

AST = 48 PTTpt = 14,5

LDH = 2320 INR = 1,25TbiL = 80DbiL = 14

ALP = 44GGT = 10ALT = 9

TP = 72ALB = 37UIE 131 / 3,3 / 94 /5,1 / 40

Urine dipstick: + urobilinogen

COBALAMIN

Complex organometallic compound in which a cobalt atom is situated within a corrin ringCannot be synthesized in the human body and must be supplied in the dietThe only dietary source is animal products: meat and dairy foodsMinimum daily requirement is 2,5mg

A normal individual will become deficient in cobalamin (if absorption were to cease abruptly) in about 3 – 6 years

FOLIC ACID Pteroylmonoglutamic acidSynthesized by many different plants and bacteriaPrimary dietary source: fruits and vegetables

Some form are labile and may be destroyed by cookingMinimum daily requirement is 50 mg, but this may be increased severalfold during periods of enhances metabolic demand such as pregnancy

Normal individuals have about 5 to 20mg folic acid in various body stores, half in the liver

A deficiency of folate will occur within minutes if dietary intake or intestinal absorption is curtailed

BIOCHEMICAL CONSIDERATIONS

FolatePrime function of this vitamin is to transfer 1-carbon moieties to various organic compounds

purines dTMP (deoxythymidylate monophostate) methionine

In human there are 2 metabolically active forms of cobalamin

Ø MethylcobalaminØ Adenosylcobalamin

METHYLCOBALAMINEssential cofactor in the conversion of homocysteine tomethionine (refer to figure 108-2)

Folate trap: in the absence of methylcobalamin tissue folatedeficieny develops megalbolistic hematopoiesis.

NB. Tissue folate stores in Cbl deficiency are substantially reduced despite normal or supranormal serum folate levels.

Also large doses of folate can produce a partial hematologic remission in patients with cobalamin deficiency.

v Decreased methionine production (due to impairment n the conversion of homocysteine to methionine) in cobalamin deficiency results in nervous system damanage and is partially responsible for the neurologic complications of this deficiency.

COBALAMIN

CLASSIFICATION OF THE MEGALOBLASTIC ANEMIAS

COBALAMIN DEFICIENCYI. INADEQUATE INTAKE: VEGETARIANS RARE

II. MALABSORPTIONA) Inadequate production of I.F.

i) Pernicious anemia ii) Gastrectomy iii) Congenital absence of functional abnormality of I.F

B) DISORDERS OF TERMINAL ILEUMi) Tropical Sprueii) Nontropical sprueiii) Regional enteritisiv) Intestinal resectionv) Neoplasms and granulomatous disorders (rare)

vi) Selective cobalamin malabsorptions(rare)C) COMPETITION FOR COBALAMIN

i) Fish tapewormii) Bacteria: “blind loop” syndrome

D) DRUGS: COMPETITION FOR COBALAMIN

III. OTHERA) Nitrous oxideB) Transcobalamin II deficiency (rare)

DIAGNOSIS

Clinical features involve:

1. The blood: anemia weaknessvertigopalpitations

anginasymptoms of congestive heart failure

2. The gut: sore tongue (smooth and beefy red)Anorexia with weight lossdiarrhee

3. The CNS: peripheral nerves numbness, paresthesiasweakness, ataxia

spinal cord reflexes diminished or increased

cerebrum Romberg and Babinski may be positive

position and vibration senses are diminished

disturbance of mentation: mild irritable dementia or frank psychosis

LABORATORY

FBC Significant macrocytosis MCV >100Low reticulocyte countleukocyte countplatelet count decreased

Blood smear:

Ø Anisocytosis and poikilocytosisMacroovalocytes (large, oval fully hemoglobinized erythrocytesNeutrophils show hypersegmentation of the nucleus (a single cell with a nucleus of 6 lobes or more!)

Bone marrow- hypercellular- decreased myeloid/erythroid ratio- abundant stainable iron

Ø Increased unconjugated bilirubinØ Increased LDH in plasmaØ Serum levels of cobalamin and/ or folateØ RBC folate level = index of folate stressØ Schilling test: - to establish the pathogenesis of

cobalamin deficiencyØ Serum methylmalonic acid level

Serum homocysteine level measure tissue vitamin stores

Ø Both are elevated in cobalamin deficiency Only homocysteine is elevated in folate deficiency

TREATMENT

Intramuscular cyanocobalamin life long.