Bone marrow pathology
How the marrow fails or turns clonal: stem-cell loss in aplastic anaemia, overproduction in myeloproliferative neoplasms, ineffective production in myelodysplasia, plasma cell myeloma and its CRAB effects, and infiltration and fibrosis.
By the end, you can
- Describe normal marrow cellularity, how it changes with age, and what an aspirate and a trephine each show.
- Explain why aplastic anaemia causes pancytopenia with a fatty, hypocellular marrow.
- Contrast the effective overproduction of the myeloproliferative neoplasms (JAK2, CALR, MPL, BCR::ABL1) with the ineffective haematopoiesis of the myelodysplastic neoplasms.
- Relate plasma cell myeloma and its precursor MGUS to the M protein, Bence Jones protein and the mechanisms of hypercalcaemia, renal injury, anaemia and bone lesions.
- Explain how marrow infiltration and fibrosis cause a leukoerythroblastic blood film, and what staging and risk scores measure in marrow neoplasms.
- Recognise the classic trephine and blood film appearances, classifications and tests of marrow disorders, and explain how immunosuppression, venesection, JAK inhibitors, hypomethylating agents, myeloma drugs and transplantation act on each.
What it is
Bone marrow pathology covers failure of blood production and the clonal disorders of marrow cells. The marrow may lose its stem cells (aplastic anaemia), be taken over by a stem-cell clone that overproduces mature cells (myeloproliferative neoplasms) or produces them ineffectively (myelodysplastic neoplasms), harbour a clone of antibody-secreting cells (plasma cell myeloma), or be replaced by metastatic tumour or fibrosis.
5 types to tell apart
- Aplastic anaemia
- Loss of stem cells, usually by immune attack: a fatty marrow and pancytopenia.
- Myeloproliferative neoplasms
- A clone with growth signalling switched on: too many mature cells, thrombosis and later fibrosis.
- Myelodysplastic neoplasms
- A clone that cannot mature properly: a busy marrow but low counts, with a risk of acute myeloid leukaemia.
- Plasma cell myeloma
- A plasma cell clone secreting one immunoglobulin, preceded by MGUS; causes bone, kidney and blood effects.
- Infiltration and fibrosis
- Replacement by carcinoma, lymphoma, granulomas or collagen: a leukoerythroblastic film.
US spelling: anaemia → anemia, tumour → tumor.
Normal function
Red marrow: cellularity, niches and sampling
Adult blood is made in red marrow, the between the of the pelvis, vertebrae, sternum, ribs and skull. Stem cells rest in niches beside bone and vessels, where stromal cells and growth factors control them. Their progeny mature in place: , and giant that shed platelets.
Marrow cellularity is the share of the space filled by blood-forming cells rather than . It is close to 100 per cent at birth and falls with age, by a rough rule to about 100 minus the age in years. In children red marrow fills most bones; in adults it retreats to the axial skeleton, but fatty marrow can turn red again when demand rises.
Mature cells leave through the , which normally holds immature cells back, so blood contains almost no nucleated red cells or myelocytes. Marrow is sampled two ways: an aspirate smear shows the detail of individual cells, and a trephine core shows cellularity, architecture, infiltrates and fibrosis.
Underlying change · Step 1 of 5
Aplastic anaemia: the stem cells are lost
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 2 of 5
Myeloproliferative neoplasms: growth signals switched on
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Myelodysplastic neoplasms: a busy marrow, empty blood
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
Plasma cell myeloma: one antibody, many effects
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Infiltration, fibrosis and the leukoerythroblastic picture
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .