Megaloblastic Anemia

Question 1

Passive transport:

active transport :

Answer 1

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).

Question 2

البروتينات الناقلة للكوبالامين في البلازما
TC I : milk, gastric juice, bile, saliva, and other fluids.

TC II→→

Answer 2

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

Question 3

وقتي خلايا جدارية خراوبوود /

Answer 3

Dec of Intrinsic factor
Dec of HCL +pepsin
Dec of serum pepsinogen 1
Inc of gastrin

Question 4

Gastric causes of cobalamin malabsorption can lead to

Answer 4

Mixed inflammatory cell infilterate
Intestinal metaplasia

Question 5

Two types of IF IgG Ab may be found :

Answer 5

The “blocking,” or type I, → prevents the combination of IF and cobalamin,

the “binding,” or type II→ prevents attachment of IF to ileal mucosa

Question 6

CONGENITAL INTRINSIC FACTOR DEFICIENCY
OR
FUNCTIONAL ABNORMALITY

Answer 6

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.

Question 7

FOOD COBALAMIN MALABSORPTION

Answer 7

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.

Question 8

……………….occurs in Intestinal Stagnant Loop Syndrome

Answer 8

colonization of the upper small intestine by fecal organisms.

Question 9

خشتةي س8 مهم

Question 10

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,………………

Answer 10

tropical sprue

folic acid therapy

Question 11

With removal of ≥1.2 m of terminal ileum

Answer 11

colonic bacteria may contribute further to the onset of cobalamin deficiency

Question 12

Fish 🐠 tape worm causing cobalamin deficiency

Answer 12

دايفيلو/ بوثريوم /لاتوم

Question 13

Sever chronic pancreatitis ,causes cobalamin deficiency due to

Answer 13

Lack of trypsin

Question 14

megaloblastic anemia or neuropathy with HIV infection is …………..despite cobalamin deficiency

Answer 14

Rare

Question 15

Zollinger-Ellison Syndrome :

high acidity → inactivation of……………. as well as interference with IF binding of cobalamin

Answer 15

pancreatic trypsin

Question 16

metformin lowers serum B12 by lowering ………….

Answer 16

TC I level

Question 17

Infants with TC II deficiency usually present with megaloblastic anemia within a………….

Answer 17

few weeks of birth

Question 18

Acquired Abnormality of Cobalamin Metabolism:

Answer 18

Due to Nitrous Oxide Inhalation.

Ex/patients undergoing prolonged N2O anesthesia (In ICU) → Megaloblastic anemia

Question 19

Gluten induced enteropathy cause deficiency of
1/ vit B 12
2/vit B9

Answer 19

Not sever
Major /specially in association with dermatitis herpetiformis

Question 20

Minor causes of vit B9 deficiency

Answer 20

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)

Question 21

Whipple’s disease
Not to be confused with Whipple’s triad or Whipple procedure.

Answer 21

Is a rare systemic infectious disease caused by the bacterium Tropheryma whipplei.
(تروفيريما وپيلاي)

Question 22

Hematologic diseases that may cause excess utilization or loss of B9

Answer 22

chronic hemolytic anemias,
sickle cell anemia
thalassemia major
myelofibrosis

Question 23

Excess utilization or loss of B9

Physiologic
Malignancy
Inflammatory

Answer 23

1/Pregnancy and lactation, prematurity
2/carcinoma, lymphoma, leukemia, myeloma
3/tuberculosis, psoriasis, exfoliative dermatitis, malaria

Question 24

Antifolate drugs :

Answer 24

Anticonvulsant drugs :
(phenytoin, primidone, barbiturates), sulfasalazine , Nitrofurantoin, tetracycline, antituberculosis

Question 25

Excess urinary loss of vit B9 in:-

Answer 25

CHF, active liver disease , Hemodialysis, peritoneal dialysis

Question 26

Homocystinuria causes ………….deficiency

Answer 26

B9

Question 27

Some clinical features of megaloblastic anemia

Answer 27

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

Question 28

reversible melanin skin …………….also may occur with a deficiency of either folate or cobalamin.

Answer 28

hyperpigmentation

Question 29

Neurological manifestations of cobalamin deficiency

Answer 29

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.

Question 30

After the marrow, the next most frequently affected tissues from( vit B9+12)deficiencies are:-

Answer 30

Epithelial cell surfaces of the mouth (with glossitis), stomach, and small intestine and the respiratory, urinary, and female genital tracts.

Question 31

Hyperhomocysteinemia (HHcy), or increased circulating levels of Hcy, is generally recognized as an independent risk factor for

Answer 31

coronary, cerebral, and peripheral atherosclerosis

Question 32

Some studies but not all about B9 aids

Answer 32

Prophylactic B9 at pregnancy **reduce** the subsequent incidence of acute **(ALL)** in childhood also **protects** against **colon adenomas**.

Question 33

Hematological findings of megaloblastic anemia

Answer 33

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

Question 34

Serum homocysteine is raised in both **early** cobalamin and folate deficiency but may be raised in other conditions, for example:-

Answer 34

CKD, alcoholism, smoking, pyridoxine deficiency B6, hypothyroidism, therapy with steroids, cyclosporine

Question 35

In patients with cobalamin deficiency sufficient to cause anemia or neuropathy, the serum………. level is raised.

Answer 35

MMA methyl-malonic acid

Question 36

Sensitive methods for measuring MMA and homocysteine in serum provide…………… of cobalamin deficiency,

Answer 36

**Early diagnosis** even in the absence of hematologic abnormalities or subnormal levels of serum cobalamin

Question 37

Serum folate rises in severe cobalamin deficiency

Answer 37

because of the block in conversion of MTHF(methyl -tetra -hydro -folate ) to THF(tetra- hydro -folate) inside cells.

Question 38

Due to absorption of bacterially synthesized folate.

Answer 38

raised levels have been reported in the intestinal stagnant loop syndrome.

Question 39

Red Cell Folate assay:- .

Answer 39

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.

Question 40

A response of the anemia of cobalamin deficiency to folate therapy is

Answer 40

Neuropathy

Question 41

Long-term folic acid therapy

Answer 41

Chronic dialysis Hemolytic anemias. Gluten-induced enteropathy that does not respond to a gluten-free diet

Question 42

Folic acid deficiency may be associated with

Answer 42

diabetes mellitus deafness presence of many ringed sideroblasts in the marrow.

Question 43

MEGALOBLASTIC ANEMIA NOT DUE TO COBALAMIN OR FOLATE DEFICIENCY OR ALTERED METABOLISM

Answer 43

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.

Question 44

Treatment

Answer 44

40-48