MD 2 · PBL Group B-1 Research
From marrow
to microcyte.
Iron-deficiency anemia — from the marrow to the blood film.
Under the supervision of
Dr. Waqas Hameed
Academic year
2026 – 2027
The case
Heavy bleeding. Less oxygen.
- Heavy, prolonged menstrual bleeding — months
- Diet low in iron-rich foods
Symptoms
FatigueDizzinessShortness of breathPalpitations
Signs
Pallor
Tachycardia
Hemoglobin8.9g/dL↓
MCV68fL↓
RDW18%↑
Reticulocytes0.7%
Blood filmMicrocytic · hypochromic
anisocytosis
anisocytosis
Iron studies↓ ferritin · ↓ iron
↑ TIBC · ↓ saturation
↑ TIBC · ↓ saturation
Why are her red cells small, pale and unequal?
Group B-1 case data
Six objectives
Choose an objective.
1–6 open an objective · H returns here from any slide
01
Student learning objective 1
Structure of
red bone marrow
Where every red cell begins.
SLO 1 · Hematopoiesis
A tissue built to make blood.
- Highly vascular connective tissue
- Stem cells → all blood cells
Regulated by
SCF
Cytokines
Erythropoietin
● Red marrow
Adults: axial skeleton
● Yellow marrow
Mostly adipose
Group B-1 research · Guyton & Hall, Ch. 33
SLO 1 · Microanatomy
Cords between
sinusoids.
Architecture
Marrow cords between vascular sinusoids
Sinusoids
Vascular channels between cords
Marrow cord
Reticular cells · reticulin (type III collagen)
Erythroblastic island
Erythroblasts around a central macrophage
Megakaryocyte
Beside the sinusoid → platelets into blood
Into the blood
Mature cells cross the sinusoid wall
Drag to rotate · illustrative 3D model
Group B-1 research · Li et al. 2020 · Machlus & Italiano 2013
01
SLO 1 · Key points
Red bone marrow
- 1Vascular tissue that makes all blood cells
- 2Cords separated by sinusoids
- 3Erythroblastic islands around macrophages
- 4Megakaryocytes release platelets into sinusoids
Our patientMarrow is stimulated — but short of iron
02
Student learning objective 2
Histology of
liver & spleen
Two organs that filter and recycle.
SLO 2 · Liver
The hepatic lobule.
Central vein
Centre of the hexagon
Hepatocytes
Plates / cords
Sinusoids
Blood → central vein
Portal triad
Portal vein · hepatic artery · bile duct
Kupffer cells
Macrophages — clear debris
Bile canaliculi
Bile → bile ducts
Drag to rotate · illustrative 3D model
Group B-1 research · NCBI Bookshelf: Anatomy, Liver · StatPearls: Physiology, Liver
SLO 2 · Spleen
Two pulps. One filter.
Capsule & trabeculae
Structural support
White pulp
Lymphocytes · immune responses
Red pulp
Cords + sinusoids · removes old RBCs
Group B-1 research · OpenStax Biology · StatPearls: Anatomy, Spleen
02
SLO 2 · Key points
Liver & spleen
- 1Hexagonal lobules around a central vein
- 2Portal triads sit at the corners
- 3Kupffer cells line the sinusoids
- 4Spleen: white pulp immunity · red pulp filter
Our patientThese organs recycle iron from her old red cells
03
Student learning objective 3
Liver & spleen in recycling
iron & red cells
Old cells retired. Iron reused.
SLO 3 · Removal of old red cells
120 days. Then the squeeze.
Aged cells stiffen → rupture in the red pulp → phagocytosed.
≈120days
Life span
≈8µm
Red cell
≈3µm
Red pulp spaces
Group B-1 research · Guyton & Hall, Ch. 33
SLO 3 · Iron recycling
Inside the red-pulp macrophage.
Erythrophagocytosis
Old red cells engulfed
Hemoglobin split
Globin → amino acids · heme
Heme oxygenase-1
Heme → free iron + bilirubin
Ferroportin
The only known iron exporter
Transferrin
Iron → bone marrow
Group B-1 research · StatPearls: Anemia
SLO 3 · The critical regulator
Hepcidin holds the key.
Hepcidin · from the liver
- Binds ferroportin
- Ferroportin degraded
- Iron trapped · plasma iron ↓
Iron deficiency Our patient
- Hepcidin ↓
- Ferroportin stays active
- More iron released
Inflammation
- IL-6 → hepcidin ↑
- Iron trapped in macrophages
- Anemia of inflammation
Group B-1 research · StatPearls: Physiology, Hepcidin · schematic, not to scale
SLO 3 · Role of the liver
Recycle the iron. Clear the pigment.
Group B-1 research · Guyton & Hall, Ch. 33
SLO 3 · Our patient
Recycling can’t outrun bleeding.
Our patientContinuous loss outpaces recycling → hemoglobin ↓
Guyton & Hall, Ch. 33 · Group B-1 research
03
SLO 3 · Key points
Recycling iron & red cells
- 1Old cells (≈120 days) removed in the red pulp
- 2Macrophage HO-1 frees iron from heme
- 3Ferroportin exports · transferrin carries
- 4Hepcidin controls the gate
Our patientRecycling can’t replace iron lost in bleeding
04
Student learning objective 4
Synthesis & breakdown —
anemia & polycythemia
Making, retiring — and the balance.
SLO 4 · Synthesis of red cells
Building a red cell takes iron.
Stem cell → erythroid lineage → erythrocyte
Iron-deficient → smaller, paler cells
Group B-1 research · stage names: Guyton & Hall, Ch. 33 · illustrative
SLO 4 · Our patient
The kidney calls. The marrow can’t answer.
O2-carrying capacity
Hb × 1.34 mL O2 per g
0.7%
Reticulocytes
No appropriate rise
Group B-1 research · Guyton & Hall, Ch. 33 · StatPearls: Oxygen Transport
SLO 4 · Breakdown of red cells
Born in the marrow. Retired in the spleen.
≈120 days
Membrane loses pliability
Rupture & phagocytosis
Red pulp · Kupffer cells · marrow
Iron returns
Transferrin → marrow or ferritin
Pigment leaves
Porphyrin → bilirubin → bile
Group B-1 research · Guyton & Hall, Ch. 33
SLO 4 · Anemia
Anemia: one result, many causes.
Too few red cells — or too little hemoglobin.
Blood loss
Acute hemorrhage
Plasma replaced → cells diluted
Our patient
Blood loss
Chronic hemorrhage
Iron lost → microcytic, hypochromic
Marrow failure
Aplastic anemia
Stem cell damage
Maturation failure
Megaloblastic anemia
↓ B12 / folate → large, fragile cells
Hemolytic
Hereditary spherocytosis
Spheres rupture in the spleen
Hemolytic
Sickle cell anemia
HbS → sickling, vessel blockage
Hemolytic
Erythroblastosis fetalis
Rh− mother vs Rh+ fetus
Iron transport
Severe hypochromic
Transferrin deficiency
Group B-1 research · Guyton & Hall, Ch. 33
SLO 4 · Effects on the circulation
Too thin. Too thick.
Normal
- Viscosity ≈ 3× water
Anemia — too thin
- Viscosity ↓ · cardiac output ↑ (3–4×)
- Exertion → hypoxia, heart failure
Polycythemia vera — too thick
- Viscosity ↑ (up to 10×) → sluggish flow
- Cardiac output ≈ normal
Guyton & Hall, Ch. 33 (severe anemia & polycythemia vera values) · flow animation illustrative
SLO 4 · Polycythemia
Polycythemia: secondary or vera.
Secondary
Response to hypoxia
Altitude · heart failure
6–7million/mm³
Vera (erythremia)
Stem cell defect
Excessive, continuous production
7–8million/mm³
60–70%Hematocrit
Up to 2×Blood volume
≈⅓Hypertension
RuddyCyanotic tint
Group B-1 research · Guyton & Hall, Ch. 33
04
SLO 4 · Key points
Make, break, balance
- 1Erythropoiesis needs iron for hemoglobin
- 2Breakdown: iron reused · porphyrin → bilirubin
- 3Anemia: viscosity ↓ · cardiac output ↑
- 4Polycythemia: viscosity ↑ · sluggish flow
Our patientErythropoietin ↑ — reticulocytes only 0.7%
05
Student learning objective 5
Hb, Hct, MCV, MCH,
MCHC, RDW & RBC count
Seven numbers. One picture.
SLO 5 · The core three
Count. Space. Oxygen capacity.
Group B-1 research · illustrative
SLO 5 · Red cell indices
Size. Content. Concentration.
Drag to rotate · illustrative rendering
Group B-1 case values · intervals: StatPearls CBC; MCHC: Sarma, Clinical Methods
SLO 5 · Red cell distribution width
MCV is the average. RDW is the spread.
Group B-1 research · illustrative blood film
SLO 5 · Applying it to the case
Her blood count, decoded.
ResultMicrocytic, hypochromic anemia · ↑ RDW
Group B-1 case data · intervals: StatPearls CBC; MCHC: Sarma, Clinical Methods
SLO 5 · Pattern recognition
Size plus spread points to a cause.
Our patient
- Small + unequal cells
- Typical of iron deficiency
RDW alone can’t diagnose
- Read with the full CBC
- Confirm with iron studies
Group B-1 research
05
SLO 5 · Key points
Reading the indices
- 1Hb / Hct → is there anemia?
- 2MCV → what size?
- 3MCH / MCHC → how much hemoglobin?
- 4RDW → how varied in size?
Our patientMicrocytic, hypochromic · ↑ RDW
06
Student learning objective 6
Biochemical changes in
iron-deficiency anemia
From a missing atom to a microcyte.
SLO 6 · Iron metabolism
Absorb. Export. Carry. Store.
Duodenum · Fe3+ → Fe2+ · enters via DMT1
Stored as ferritin — or exported by ferroportin
Transferrin → bone marrow · stores
Hepcidin ↑ → less iron out · iron deficiency → hepcidin ↓
Our patient: loss > absorption → stores depleted
Absorb → export → carry → store · hepcidin sets the flow
Group B-1 research · StatPearls: Iron Absorption; Hepcidin · schematic
SLO 6 · Heme synthesis
The final step
needs iron.
Protoporphyrin IX + Fe²⁺ · drag to rotate
Group B-1 research · StatPearls: Heme Synthesis
SLO 6 · Case correlation
The iron studies confirm it.
MeaningIron stores depleted → less iron for red cells
Group B-1 research · StatPearls: Anemia; Iron-Binding Capacity · transferrin model illustrative
06
SLO 6 · Key points
The biochemistry
- 1DMT1 absorbs · ferroportin exports
- 2Transferrin carries · ferritin stores
- 3Ferrochelatase inserts Fe²⁺ → heme
- 4↓ Iron → ↓ heme → ↓ Hb → microcytes
Our patient↓ ferritin · ↓ iron · ↑ TIBC · ↓ saturation
Putting it together
One patient. One chain of events.
DiagnosisIron-deficiency anemia secondary to chronic menstrual blood loss
Group B-1 research
References
Sources.
PBL Group B-1
Thank you.
Questions are welcome.
Under the supervision of
Dr. Waqas Hameed
Program
MD 2 · 2026 – 2027