BIO230 Chapter 10 Extended

1) The big picture: what hematology is really doing

When you run a CBC, you’re basically asking three life-or-death questions:

  1. Can this person deliver oxygen to tissues?
    → RBCs + hemoglobin + hematocrit + RBC indices

  2. Can this person fight infection / inflammation?
    → WBC total + differential (neutrophils, lymphocytes, etc.)

  3. Can this person stop bleeding appropriately?
    → platelets (and in the next chapter: coag tests)

Hematology is about connecting the numbers to the biology behind them.

2) Hematopoiesis: where blood cells come from (and why you care)

What it is

Hematopoiesis = the process of making blood cells in the bone marrow.

Why it matters

Your lab results can tell you whether:

  • the marrow is working hard (responding appropriately), or

  • the marrow is failing/suppressed, or

  • the marrow is producing abnormal malignant clones (leukemia).

How it works (conceptual)

Start with a hematopoietic stem cell (HSC). It can go down two major “career paths”:

  • Myeloid line → RBCs, platelets, neutrophils, eosinophils, basophils, monocytes

  • Lymphoid line → lymphocytes (B, T, NK)

Key teaching point:
If a patient has low RBCs + low WBCs + low platelets all together (pancytopenia), that screams:
➡ “This could be a bone marrow production problem,” because all lines are affected.

3) RBCs: how they’re built for oxygen delivery

What RBCs do

RBCs are basically hemoglobin delivery vehicles.

Why their shape matters

RBCs are biconcave discs, which is not just trivia:

  • More surface area → better gas exchange

  • Flexible → squeeze through tiny capillaries

  • No nucleus/mitochondria → more space for hemoglobin, and they don’t “use up” the oxygen they carry

RBC lifespan: why hemolysis vs production matters

RBCs live ~ 120 days. The body constantly balances:

  • Production (bone marrow)
    vs

  • Destruction/removal (spleen/liver macrophages)

So anemia can happen by 3 big mechanisms:

  1. Blood loss (out the body)

  2. Decreased production (marrow can’t keep up)

  3. Increased destruction = hemolysis (RBCs destroyed early)

This framework shows up everywhere.

4) Hemoglobin: the “why” behind oxygen binding

What hemoglobin is

Hemoglobin is a tetramer (4 globin chains) + 4 heme groups with iron (Fe²⁺).

How oxygen binding actually behaves (high-yield “why”)

Hemoglobin shows cooperativity:

  • When the first O₂ binds, it becomes easier for the next O₂ to bind.
    This is why the oxygen dissociation curve is sigmoidal (S-shaped).

Why iron state matters (methemoglobin)

Iron must be Fe²⁺ to bind oxygen.
If it becomes Fe³⁺, you get methemoglobin, which can’t bind oxygen well → functional hypoxia.

Why CO is dangerous (carboxyhemoglobin)

Carbon monoxide (CO) binds hemoglobin much more strongly than oxygen.
So even if the person is “breathing,” hemoglobin is occupied → tissues starve.

5) WBCs: what each one is “for” (and how to interpret changes)

A CBC with differential is not just “high or low WBC.”
It’s: Which team is activated?

Neutrophils — “bacterial first responders”

  • Main job: phagocytosis (eat bacteria)

  • If neutrophils are high: often bacterial infection, inflammation, stress response

  • Toxic changes (toxic granulation, etc.) happen when neutrophils are produced rapidly under severe inflammatory demand (your body is pumping them out fast).

How to think:
➡ High neutrophils = “frontline innate immunity is activated.”

Lymphocytes — “adaptive immunity intelligence”

  • B cells, T cells, NK cells

  • Viral infections often → lymphocytosis (classically)

How to think:
➡ High lymphocytes = “adaptive immune response is prominent.”

Monocytes — “cleanup crew / macrophage pipeline”

  • Become macrophages in tissues

  • Chronic inflammation can elevate monocytes

Eosinophils — “parasites & allergies”

  • Parasites, asthma/allergies, drug reactions

Basophils — “histamine & hypersensitivity”

  • Release histamine, involved in hypersensitivity pathways

6) Platelets: why they’re essential and how low vs high behaves

What platelets do

Platelets are for primary hemostasis:

  1. stick to damaged vessel wall (adhesion)

  2. activate (release granules, recruit others)

  3. clump together (aggregation) to form a platelet plug

Why low platelets cause mucosal bleeding

Platelet problems often → petechiae, easy bruising, gum bleeding, nosebleeds
(because small vessels need platelet plugs constantly).

7) The specimen: why EDTA matters

Hematology uses whole blood with EDTA because EDTA chelates calcium and prevents clotting while preserving cell morphology.

Why you care:
Bad sample handling can create fake disease:

  • clots → falsely low platelets/WBCs

  • too old → cell swelling or degeneration → weird indices or smear artifacts

8) The CBC measurements: what they mean + what the lab is actually measuring

Hemoglobin (Hb)

What it is: amount of hemoglobin in blood.
Why it matters: this is directly tied to oxygen-carrying capacity.

Hematocrit (Hct / Packed Cell Volume)

What it is: percent of blood volume made of RBCs.
How it’s measured conceptually: either centrifuged (“packed cells”) or calculated by analyzers.

RBC count

Number of RBCs per volume.

Key teaching point:

You can have a “normal-ish” RBC count but low Hb if the cells are tiny/pale (microcytic/hypochromic). That’s why indices are essential.

9) RBC indices: the “why” behind anemia classification (THIS is test gold)

These indices aren’t random numbers — they describe the RBCs in a way that points to cause.

MCV = size of RBC (microcytic vs macrocytic)

  • Low MCV (microcytic) → often hemoglobin synthesis problem
    (iron deficiency, thalassemia)

  • High MCV (macrocytic) → often DNA synthesis problem
    (B₁₂/folate deficiency)

WHY size changes:

  • If you can’t make hemoglobin properly, RBCs divide more times → smaller cells.

  • If you can’t make DNA properly, cell division slows → larger cells.

MCH = amount of Hb per cell

Often parallels MCV.

MCHC = concentration of Hb inside RBCs (chromia)

  • Low MCHC = hypochromia (paler cells), classic in iron deficiency.

RDW = variability in RBC size (anisocytosis)

This is your “mixed population” detector.

HOW RDW helps you clinically:

  • Early iron deficiency: RDW often rises before MCV drops dramatically
    (because you start producing smaller cells while older normal cells are still circulating).

  • Thalassemia trait: often very low MCV but RDW may be normal-ish (cells are uniformly small).

That’s a powerful “why” difference.

10) Automated hematology analyzers: how machines count cells (and why smears still matter)

How automated counts work (conceptual)

Analyzers use combinations of:

  • Electrical impedance: cells pass through an aperture → change in resistance → size/count

  • Optical scatter (lasers): scatter patterns → cell size + granularity/complexity

  • Sometimes flow-based methods for differential patterns

Why you still do a manual smear

Automation is great until:

  • abnormal cells appear (blasts, severe anemia shapes, platelet clumping)

  • the machine flags something suspicious

So manual review answers questions like:

  • Are platelets clumped (falsely low platelet count)?

  • Are there abnormal RBC shapes suggesting hemolysis?

  • Are there blasts suggesting leukemia?

11) Reticulocytes: the marrow’s “report card”

What retics are

Reticulocytes are immature RBCs recently released from marrow.

Why retics are crucial

They tell you if anemia is due to:

  • underproduction (low retic response)
    or

  • loss/destruction (high retic response because marrow is compensating)

How to reason it out:

  • Anemia + high retic = body is trying to fix it → think blood loss or hemolysis

  • Anemia + low retic = marrow isn’t responding → think iron deficiency not yet treated, marrow suppression, nutrient deficiency, chronic disease, etc.

12) ESR: what it really indicates (and why it’s nonspecific)

What ESR measures

How fast RBCs settle in a tube over time.

WHY inflammation increases ESR

Inflammation increases plasma proteins (like fibrinogen) that make RBCs stack (“rouleaux”) and settle faster.

Why it’s nonspecific

ESR does not tell you the cause — only that inflammation is likely present (infection, autoimmune disease, malignancy, etc.).

13) Peripheral blood smear: how to “read” it like a scientist

A smear answers:

  • RBC morphology: size, color, shape, inclusions

  • WBC differential and abnormalities

  • Platelet number and appearance

RBC morphology (high-yield categories)

  • Anisocytosis = varying sizes (often correlates with ↑ RDW)

  • Poikilocytosis = varying shapes (often suggests pathology)

  • Hypochromia = pale RBCs (often low MCHC)

Platelet estimation

On smear you can estimate platelets per oil field — helpful when machine counts are questionable.

Differential count (why absolute counts matter)

Relative % can mislead.
Example: 60% neutrophils could be normal or not depending on total WBC.
That’s why labs report absolute neutrophil/lymphocyte counts too.

14) Anemias: how to classify them logically (not memorization)

Step 1: Confirm anemia

Low Hb and/or Hct.

Step 2: Use MCV to classify

  • Microcytic

  • Normocytic

  • Macrocytic

Step 3: Use reticulocytes to decide “production vs loss”

  • Low retic = production issue

  • High retic = loss/destruction issue

Step 4: Use RDW + smear to narrow cause

  • RDW high = mixed populations/variable size

  • smear tells you shape clues

That’s the “how” pathway.

15) Nonmalignant WBC disorders: the “pattern” approach

  • Leukocytosis/leukopenia = overall high/low WBC

  • Then ask: which line is responsible?

    • Neutrophilia → bacterial/inflammation

    • Lymphocytosis → viral/immune patterns

    • Eosinophilia → parasites/allergy

    • Monocytosis → chronic inflammation

And then: are there toxic changes? abnormal forms?

16) Leukemias: teaching the WHY behind “acute vs chronic” and “myeloid vs lymphoid”

Acute vs chronic (the why)

  • Acute leukemia: marrow is flooded with immature blasts → rapid onset, severe symptoms

  • Chronic leukemia: more mature-appearing cells, slower progression

Myeloid vs lymphoid (the how)

  • Myeloid line includes granulocytes, monocytes, RBC/platelet precursors

  • Lymphoid line includes lymphocytes

So:

  • AML = acute + myeloid blasts

  • ALL = acute + lymphoid blasts

  • CML = chronic myeloid proliferation (classically associated with Philadelphia chromosome in many curricula)

  • CLL = chronic lymphocytic proliferation

Lab thinking tip:
If you see very high WBC and lots of immature-looking cells flagged, you’re thinking acute leukemia until proven otherwise → smear review becomes urgent.

17) Lymphoid & plasma cell neoplasms (why plasma cells matter)

Plasma cells make antibodies. When they become neoplastic (like multiple myeloma), you can get:

  • abnormal amounts of a single immunoglobulin type (monoclonal production)

  • clinical effects from protein burden and marrow disruption