Megaloblastic Anemia Flashcards
Passive transport:
active transport :
equally through buccal, duodenal, and ileal mucosa → rapid but extremely inefficient, with <1% of an oral dose.
Through the ileum and is efficient for small (a few micro-grams) oral doses of cobalamin, and it is mediated by gastric intrinsic factor (IF).
البروتينات الناقلة للكوبالامين في البلازما
TC I : milk, gastric juice, bile, saliva, and other fluids.
TC II→→
liver cells are involved in the removal of TC I from plasma, (which it binds more effectively than IF) to the liver for excretion in bile.
TC II→→ gives up cobalamin to marrow, placenta, and other tissues
وقتي خلايا جدارية خراوبوود /
Dec of Intrinsic factor
Dec of HCL +pepsin
Dec of serum pepsinogen 1
Inc of gastrin
Gastric causes of cobalamin malabsorption can lead to
Mixed inflammatory cell infilterate
Intestinal metaplasia
Two types of IF IgG Ab may be found :
The “blocking,” or type I, → prevents the combination of IF and cobalamin,
the “binding,” or type II→ prevents attachment of IF to ileal mucosa
CONGENITAL INTRINSIC FACTOR DEFICIENCY
OR
FUNCTIONAL ABNORMALITY
Autosomal recessive.
The child usually has no demonstrable IF but has a normal gastric mucosa and normal secretion of acid.
Parietal cell Ab and IF Ab are absent
in the first to third year of life → megaloblastic anemia
a few have presented as late as the second decade.
FOOD COBALAMIN MALABSORPTION
Failure of release of cobalamin from binding proteins in food is → more common in the elderly. → low serum cobalamin levels, with or without raised serum levels of MMA (methyl-malonic acid)and homocystein.
……………….occurs in Intestinal Stagnant Loop Syndrome
colonization of the upper small intestine by fecal organisms.
خشتةي س8 مهم
Nearly all patients with acute and subacute………… show malabsorption of cobalamin → megaloblastic anemia or neuropathy due to cobalamin deficiency → → Absorption of cobalamin usually improves after antibiotic therapy and, in the early stages,………………
tropical sprue
folic acid therapy
With removal of ≥1.2 m of terminal ileum
colonic bacteria may contribute further to the onset of cobalamin deficiency
Fish 🐠 tape worm causing cobalamin deficiency
دايفيلو/ بوثريوم /لاتوم
Sever chronic pancreatitis ,causes cobalamin deficiency due to
Lack of trypsin
megaloblastic anemia or neuropathy with HIV infection is …………..despite cobalamin deficiency
Rare
Zollinger-Ellison Syndrome :
high acidity → inactivation of……………. as well as interference with IF binding of cobalamin
pancreatic trypsin
metformin lowers serum B12 by lowering ………….
TC I level
Infants with TC II deficiency usually present with megaloblastic anemia within a………….
few weeks of birth
Acquired Abnormality of Cobalamin Metabolism:
Due to Nitrous Oxide Inhalation.
Ex/patients undergoing prolonged N2O anesthesia (In ICU) → Megaloblastic anemia
Gluten induced enteropathy cause deficiency of
1/ vit B 12
2/vit B9
Not sever
Major /specially in association with dermatitis herpetiformis
Minor causes of vit B9 deficiency
Extensive jejunal resection, Crohn’s disease, partial gastrectomy,CHF (chronic heart failure), Whipple’s disease(A bacterial infection), scleroderma, amyloid, diabetic enteropathy, systemic bacterial infection, lymphoma, sulfasalazine (Salazopyrin)
Whipple’s disease
Not to be confused with Whipple’s triad or Whipple procedure.
Is a rare systemic infectious disease caused by the bacterium Tropheryma whipplei.
(تروفيريما وپيلاي)
Hematologic diseases that may cause excess utilization or loss of B9
chronic hemolytic anemias,
sickle cell anemia
thalassemia major
myelofibrosis
Excess utilization or loss of B9
Physiologic
Malignancy
Inflammatory
1/Pregnancy and lactation, prematurity
2/carcinoma, lymphoma, leukemia, myeloma
3/tuberculosis, psoriasis, exfoliative dermatitis, malaria
Antifolate drugs :
Anticonvulsant drugs :
(phenytoin, primidone, barbiturates), sulfasalazine , Nitrofurantoin, tetracycline, antituberculosis
Excess urinary loss of vit B9 in:-
CHF, active liver disease , Hemodialysis, peritoneal dialysis
Homocystinuria causes ………….deficiency
B9
Some clinical features of megaloblastic anemia
Glossitis
Angular cheilitis
Unconjugated jaundice
Infections due to leukopenia particularly of the respiratory and urinary tracts.
raised urine urobilinogen /reduced haptoglobins and positive urine hemosiderin
raise serum LDH
reversible melanin skin …………….also may occur with a deficiency of either folate or cobalamin.
hyperpigmentation
Neurological manifestations of cobalamin deficiency
1/bilateral peripheral neuropathy .
2/degeneration(demyelination) of the cervical and thoracic posterior and lateral (pyramidal) tracts of the spinal cord .less frequently, of the cranial nerves and of the white matter of the brain.
3/Optic atrophy and cerebral symptoms including dementia, depression, psychotic symptoms, and cognitive impairment .
4/may also be anosmia and loss of taste.
5/The patient, more frequently male, typically presents with paresthesias, muscle weakness, or difficulty in walking but sometimes may present with dementia, psychotic disturbances, or visual impairment.
6/There is usually loss of proprioception and vibration sensation with positive Romberg and Lhermitte signs.
7/Gait may be ataxic with spasticity (hyperreflexia).
8/ Autonomic nervous dysfunction can result in postural hypotension, impotence, and incontinence.
After the marrow, the next most frequently affected tissues from( vit B9+12)deficiencies are:-
Epithelial cell surfaces of the mouth (with glossitis), stomach, and small intestine and the respiratory, urinary, and female genital tracts.
Hyperhomocysteinemia (HHcy), or increased circulating levels of Hcy, is generally recognized as an independent risk factor for
coronary, cerebral, and peripheral atherosclerosis
Some studies but not all about B9 aids
Prophylactic B9 at pregnancy reduce the subsequent incidence of acute (ALL) in childhood also protects against colon adenomas.
Hematological findings of megaloblastic anemia
neutrophils are hypersegmented (more than five nuclear lobes).
Oval macrocytes, anisocytosis and poikilocytosis.
The marrow is hypercellular
Giant and abnormally shaped metamyelocytes and enlarged hyperpolyploid megakaryocytes
Serum homocysteine is raised in both early cobalamin and folate deficiency but may be raised in other conditions, for example:-
CKD,
alcoholism, smoking,
pyridoxine deficiency B6,
hypothyroidism,
therapy with steroids, cyclosporine
In patients with cobalamin deficiency sufficient to cause anemia or neuropathy, the serum………. level is raised.
MMA methyl-malonic acid
Sensitive methods for measuring MMA and homocysteine in serum provide…………… of cobalamin deficiency,
Early diagnosis
even in the absence of hematologic abnormalities or subnormal levels of serum cobalamin
Serum folate rises in severe cobalamin deficiency
because of the block in conversion of MTHF(methyl -tetra -hydro -folate ) to THF(tetra- hydro -folate) inside cells.
Due to absorption of bacterially synthesized folate.
raised levels have been reported in the intestinal stagnant loop syndrome.
Red Cell Folate assay:-
.
is a valuable test of body folate stores.
It is less affected than the serum assay by recent diet and traces of hemolysis.
False-normal results may occur if a folate-deficient patient has received a recent blood transfusion or if a patient has a raised reticulocyte count.
A response of the anemia of cobalamin deficiency to folate therapy is
Neuropathy
Long-term folic acid therapy
Chronic dialysis
Hemolytic anemias.
Gluten-induced enteropathy that does not respond to a gluten-free diet
Folic acid deficiency may be associated with
diabetes mellitus
deafness
presence of many ringed sideroblasts in the marrow.
MEGALOBLASTIC ANEMIA NOT DUE TO
COBALAMIN OR FOLATE DEFICIENCY OR ALTERED METABOLISM
may occur with many Anti-metabolic drugs
(e.g., hydroxyurea,cytosine arabinoside, 6-mercaptopurine. Antiviral nucleoside analogues used in treatment of HIV infection).
Megaloblastic anemia → responsive to thiamin B1
May be associated with diabetes mellitus,deafness,presence of many ringed sideroblasts in the marrow.
Treatment
40-48
