Brief Summary
Alright, folks! This LR (Live Revision) session is all about tackling key pathology concepts for NEET PG, FMGE, and INI-CET exams. We're diving deep into hematology and general pathology, covering everything from anemia types and diagnostic needles to leukemias, genetic disorders, and those tricky immunofluorescence patterns. Plus, there's a bunch of bonus slides with need-to-know info for that last-minute revision.
- Bone marrow needles and aspiration sites
- Anemia classification, indices, and differentials
- Thalassemias, sickle cell anemia, and related genetic counseling
- Leukemias, lymphomas, and diagnostic approaches
- Key genetic mutations and inheritance patterns
- Amyloidosis and immunofluorescence patterns
BMA Needles and Anemia Basics
Alright, let's kick things off with the must-know needles for bone marrow procedures. For bone marrow aspiration (BMA), you've got the Salah's needle with its side screw and the Klima needle with a longitudinal screw. Remember, Jamshidi's needle, that T-shaped one, is for bone marrow biopsy (BMB). The preferred site for these procedures is the posterior superior iliac spine (PSIS), but if that's not doable, go for the anterior superior iliac spine (ASIS). In kids, you can also use the anteromedial aspect of the tibia.
Next up, we're tackling anemia. Reticulocytes, those red blood cell precursors, are made of ribosomal RNA and need supra vital staining to be visible. New methylene blue is your go-to stain here. To calculate the corrected reticulocyte count (CRC), use the formula: (Retic count x Patient's Hemoglobin) / Normal Hemoglobin. Remember, this is especially important in severe anemia cases where hemoglobin is less than 7.
MCV, MCH, RDW and Thalassemias
Now, let's talk about red blood cell indices. MCV tells you the size (normal range 80-100 fL), MCH indicates the hemoglobin in a red blood cell, and MCHC shows the hemoglobin concentration. RDW, on the other hand, tells you about the variation in size. For microcytic anemias (MCV < 80), remember "Sheetal": sideroblastic, iron deficiency, thalassemia, anemia of chronic disease, and lead poisoning.
Here's a tricky one: thalassemia vs. iron deficiency anemia. In iron deficiency, RDW is usually increased because iron levels fluctuate with diet and supplements. But in thalassemia, RDW is often normal because it's a genetic disorder, so the RBC size stays consistent. To differentiate, use Mentzer's index (MCV/RBC). A value less than 13 suggests thalassemia. For confirmation, check HbA2 levels; if they're above 3.5%, it's likely thalassemia trait.
Thalassemia Traits and Screening
If two individuals with thalassemia trait get hitched, there's a 25% chance their kid will have thalassemia major. But if a thalassemia trait marries a normal person, there's no risk of thalassemia major in their kids. For thalassemia screening, remember the Nestro test, which checks red cell osmotic fragility. In thalassemia, RBCs are tough and don't break easily in saline, so you won't see the lines behind the test tube.
Iron Deficiency vs. Sideroblastic Anemia
Let's decode iron profiles. In iron deficiency anemia, serum iron, ferritin, and transferrin saturation are all low, while TIBC (total iron-binding capacity) is high. For sideroblastic anemia, it's the opposite: iron, transferrin saturation, and ferritin are high, while TIBC is low. Sideroblastic anemia happens when iron is available but can't bind with protoporphyrin to form hemoglobin. This can be due to ALA synthase or dehydratase deficiencies (requiring vitamin B6), isoniazid use, or lead poisoning.
Anemia of Chronic Disease and B12 Deficiency
In anemia of chronic disease, interleukin-6 increases, leading to hepcidin release. Hepcidin hijacks iron absorption and storage, so serum iron and transferrin saturation are low, but ferritin is high, and TIBC is low. Rheumatoid arthritis is a classic cause. Remember, anemia of chronic disease can be microcytic hypochromic or normocytic normochromic, with the latter being more common.
Moving on to B12 deficiency, look for hyperpigmentation of the knuckles. You'll also see Howell-Jolly bodies (single, made of DNA remnants) in red blood cells. These are also seen post-splenectomy. Other findings include Cabot rings (figure-of-eight appearance) and hypersegmented neutrophils (six or more lobes).
RBC Abnormalities and Supra Vital Stains
Time for some image recognition! Acanthocytes (spur cells) with spikes are seen in abetalipoproteinemia (MTTP gene mutation). Burr cells (echinocytes) with blurry membranes are seen in burns and uremia. Target cells (codocytes) are seen in thalassemias and hemoglobinopathies.
After splenectomy, you'll see Howell-Jolly bodies (single, DNA remnants). Pappenheimer bodies (multiple, iron-containing) are seen in sideroblastic anemia and stain with Prussian blue. Heinz bodies (denatured hemoglobin) are seen in G6PD deficiency and require crystal violet staining (a supra vital stain). Remember, supra vital stains like new methylene blue, brilliant crystal blue, and crystal violet don't use methanol fixation.
Parvovirus, Sickle Cell Anemia and Thalassemias
Parvovirus B19 attacks P antigen on red blood cell precursors, causing dog-ear inclusions and pure red cell aplasia or aplastic crisis. In sickle cell anemia, the beta 6 position (now updated to beta 7) has a glutamate to valine substitution. Look for crew cut appearance on skull X-ray. Initial treatment involves blood transfusion and hydroxyurea. Sickle cell trait is diagnosed with a sickling test using 2% sodium metabisulfite. Hemoglobin electrophoresis shows HbAS, while HPLC is the gold standard.
Hereditary Spherocytosis and G6PD Deficiency
Hereditary spherocytosis (HS) is autosomal dominant (usually ankyrin mutation), causing spherical RBCs destroyed by the spleen. Treat with splenectomy and pre-splenectomy vaccination against encapsulated organisms. Diagnose with eosin-5-maleimide binding test. Autoimmune hemolytic anemia (AIHA) is the most common cause of spherocytes (positive Coombs test).
G6PD deficiency is X-linked recessive, triggered by infections, fava beans, or primaquine. Look for bite cells (degmacytes) and Heinz bodies. Diagnose by measuring G6PD levels.
WBC Identification and Acute Leukemias
Normal TLC (total leukocyte count) is 4,000-11,000. Remember "Never Let Monkeys Eat Bananas" for the order of WBCs: neutrophils (3-5 lobes), lymphocytes (round nucleus), monocytes (kidney-shaped nucleus), eosinophils (orange, spectacle-shaped nucleus, increased in allergies and parasitic infections), and basophils (blue-black granules, increased in CML and polycythemia vera).
Acute leukemias have >20% blasts. ALL (acute lymphoblastic leukemia) often shows hyperdiploidy, trisomy 4, or translocation (12;21), which have a good prognosis. Translocation (9;22) (BCR-ABL fusion) is associated with CML but has a poor prognosis in ALL.
AML Subtypes and CLL
AML M3 (acute promyelocytic leukemia) is associated with DIC and Auer rods. Translocation (15;17) (PML-RARα fusion) is treated with ATRA and arsenic trioxide. AML M2 has translocation (8;21), and AML M4 has inversion 16. These AML subtypes have a good prognosis. AML M7 (acute megakaryoblastic leukemia) is most common in Down syndrome patients under 3 years old.
CLL (chronic lymphocytic leukemia) is the "convent school girl" with uniform lymphocytes. Diagnose with lymphocyte count >5,000/mm3, flow cytometry (CD5+, CD23+), and bone marrow lymphocytes >30%. Deletion 13q is a common genetic abnormality. CLL can be associated with Evans syndrome (AIHA and ITP) or Richter transformation (transformation to DLBCL).
CML and Hodgkin Lymphoma
CML (chronic myelogenous leukemia) presents with splenomegaly and increased TLC with a shift to the left. Translocation (9;22) (BCR-ABL fusion, 210 kDa) is treated with imatinib. Fish is used to detect the translocation.
Classical Hodgkin lymphoma has Reed-Sternberg cells (CD15+, CD30+, PAX5+). Mixed cellularity is most common in India. Nodular sclerosis shows lacunar Reed-Sternberg cells. Lymphocyte-rich Hodgkin lymphoma has mononuclear Reed-Sternberg cells. Lymphocyte-depleted Hodgkin lymphoma has mummified Reed-Sternberg cells (worst prognosis). Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has popcorn cells (best prognosis).
Hairy Cell Leukemia and Multiple Myeloma
Hairy cell leukemia presents with massive splenomegaly. It's BRAF V600E positive and shows annexin A1 positivity. It's associated with MAC infections. Bone marrow biopsy shows fried egg appearance, and bone marrow aspirate results in a dry tap. Trap stain is positive.
Multiple myeloma presents with low back pain and osteolytic lesions. Look for Russell bodies (cytoplasmic) and Dutcher bodies (nuclear) in plasma cells. Serum protein electrophoresis (SPEP) shows an M spike (usually IgG). Immunofixation electrophoresis identifies the type of immunoglobulin.
Waldenstrom Macroglobulinemia and Blood Bank Basics
Waldenstrom macroglobulinemia shows an IgM M spike. It's also known as lymphoplasmacytic lymphoma (LPL). It presents with hyperviscosity symptoms. It's associated with MYD88 mutation.
Packed red blood cells are stored at 2-6°C. Platelets are stored at 20-24°C in a platelet agitator (5-day shelf life). Fresh frozen plasma is stored at <-18°C (1-year shelf life). Cryoprecipitate contains fibrinogen, factor XIII, factor VIII, and von Willebrand factor.
Vacutainer Colors and Amyloidosis
Gray vacutainers (potassium oxalate and sodium fluoride) are used for glucose testing. Lavender vacutainers (K2EDTA) are used for CBC and glycated hemoglobin (HbA1c). Remember the order: "Stop Light Red Yellow Green Light Go."
For amyloidosis, remember: AL (multiple myeloma), AA (chronic inflammation), Aβ2M (hemodialysis), Aβ (Alzheimer's), ATTR (senile systemic amyloidosis and familial amyloidotic polyneuropathy), and ACal (medullary thyroid carcinoma). Diagnose with Congo red stain (apple-green birefringence under polarized light). Abdominal fat aspiration is the preferred biopsy site.
Pedigree Analysis
For pedigree analysis, follow the 2G rule: gender and generation. Autosomal dominant affects all generations, while autosomal recessive skips generations. XLR affects mostly males, while Y-linked affects all males. X-linked dominant (XLD) passes from dad to all daughters.
Fragile X Syndrome and Immunofluorescence Patterns
Fragile X syndrome (CGG repeats in FMR1 gene) shows long face, large mandible, large ears, and macroorchidism. It's diagnosed with amplicon length analysis.
Immunofluorescence patterns: Homogeneous (entire nucleus), peripheral (periphery more intense), nucleolar (nucleolar staining), speckled (dots within nucleus), and centromeric (sharp dots representing chromosomes). Crest syndrome shows centromeric pattern.
Bonus Slides and Wrap Up
Don't forget to check out the bonus slides for a quick review of necrosis, special stains, giant cells, granulomas, tumor markers, and autoimmune disorders.
