Benign Hematology

Question 1

What is hereditary hemochromatosis

Answer 1

Clinical iron overload from genetic disorders leading to increased absorption of iron from the gut( 2-4 mg/ day vs normal 1 mg/day)

Question 2

Most common genetic cause of hereditary hemochromatosis?

Answer 2

HFE C282Y most common AR

Biallelic mutations are not sufficient to produce clinical iron overload- incomplete penetrance

Question 3

What are the different genetic causes of hemochromatosis?

Answer 3

Type 1 HFE- most common, adult onset AR
Type 2A HJV Hemojuvelin- juvenile HC AR
Type 2B HAMP Hepcidin- juvenile HC AR
Type 3 TfR2 Transferor receptor- AR
Type 4- SLC40A1 Ferroportin- autosomal dominant

Question 4

Major organ effects of lead poisoning?

Answer 4

Neurological- cognitive decline, frank encephalopathy at high levels
Hearing loss( high frequency)
Renal- tubular dysfunction, chronic interstitial nephritis

Interferes with vitamin D activation so can cause poor bone and tooth grown
Constipation and GI upset

Anemia is rare and when purely due to lead deficiency leads to a normocytic hemolytic anemia.

Question 5

Factors that make kids more susceptible to lead poisoning?

Answer 5

Absorb much more lead from gut
More likely to have iron deficiency which increases absorption of lead
Calcium deficiency can increase absorption of iron
More lead crosses BBB in kids

Question 6

Diagnostic tests for B12 deficiency?

Answer 6

Decreased B12

Elevated MMA and homocysteine ( MMA more specific for B12 deficiency)

Question 7

Non hematological features of B12 deficiency?

Answer 7

Subacute combined degeneration- degeneration of the posterior columns of the SC leading to weakness, parathesias, ataxia, loss of proprioception and eventual paraplegia

Glossitis

Neuro cognitive issues

Question 8

What is the etiology of the following RBC inclusions?

Howell jolly bodies
Heinz bodies
Pappenheimer bodies
Basophilloc stippling

Answer 8

1-nuclear remnants
2- supravital stain denatured hemoglobin
3- iron inclusions from impaired utilization of iron
4- ribosomal RNA remnants from impaired translation

Question 9

Differential diagnosis of polycythemia?

Answer 9

Cardiac and pulmonary conditions including smoking, OSA

JAK 2 MPD- polycythemia Vera

EPO secreting tumor( RCC)
doping with epo or testosterone

High affinity hemoglobin states- hemoglobinopathies causing high affinity to hemoglobin, or methhemoglobinemia

Primary polycythemia- mutation of the EPO receptor or the VHL gene ( chuvash polycythemia)

Question 10

Define megaloblastic anemia and describe findings

Answer 10

This is due to impaired DNA synthesis
The nucleus of red cells requires DNA synthesis for division
The cytoplasm is more dependent on RNA and protein which is more intact

Most common causes are B12 or folate deficiency

The findings are large red cell precursors
Nuclear- cytoplasmic asynchrony in the red cells
Hyper segmented neutrophils
Macrocytosis

Question 11

Describe B12 absorption

Answer 11

Haptocorrin (R factor) secreted by the salivary glands
Complexes with cobalamin in the stomach
Basic pH releases this
Intrinsic factors released by the parietal cells complexes with cobalamin and is absorbed in the ileum

B12 requires for function off methionine synthase