Bone Marrow Structure,Function,Clinical and Significance_pdf

Bone marrow overview

2. Introduction to Bone Marrow
What is Bone Marrow?
Semi-solid tissue found within the spongy portions of bones,
responsible for blood cell production
Location
Found in the medullary cavities of bones
Primarily in: Pelvis, Sternum, Ribs, Vertebrae, Ends of long bones
Importance
Primary site of hematopoiesis (blood cell formation)
Produces: Red blood cells, White blood cells, Platelets
Contains hematopoietic stem cells that can di{erentiate into all blood cell
types

3. Anatomy of Bone Marrow
Physical Structure
Spongy tissue Highly vascular
Flexible connective tissue Contains sinusoids
Location Within Bones
Medullary cavities Trabecular bone spaces
Central cavity of long bones Flat bones (pelvis, sternum)
Cellular Components
Hematopoietic Cells
Blood-forming stem cells and
progenitors
Stromal Cells
Supportive framework for
hematopoiesis
Adipocytes
Fat cells, more prevalent in yellow
marrow
Vascular Sinusoids
Specialized blood vessels for cell
release
Microenvironment
Stem cell niche Cell signaling
Extracellular matrix Blood supply
Cellular Organization
Hematopoietic stem cells Progenitor cells
Precursor cells Mature blood cells

4. Types of Bone Marrow: Red vs. Yellow
Red Bone Marrow
Characteristics
Highly cellular Rich in blood supply
ContainshematopoietictissueLow fat content
Distribution
Flat bones Pelvis Sternum Ribs
Vertebrae Ends of long bones
Primary Functions
Hematopoiesis - blood cell production
Produces red blood cells, white blood cells, and platelets
Primary site of blood formation in adults
Converts to yellow marrow with age
Yellow Bone Marrow
Characteristics
High fat content Less vascular
Containsadipocytes
(fat
cells)

Some mesenchymal stem
cells
Distribution
Central cavities of long bones Sha|s of long bones
Increases with age Replaces red marrow over time
Primary Functions
Energy storage in the form of fat
Can convert back to red marrow in severe blood loss
Maintains bone structure and support
Source of mesenchymal stem cells

5. Composition of Bone Marrow

Cellular Components

Hematopoietic Cells
Stem cells and progenitor cells
that produce all blood lineages

Stromal Cells
Support cells including fibroblasts,
adipocytes, and endothelial cells

Mature Blood Cells
Erythrocytes, leukocytes, and
megakaryocytes at various stages

Extracellular Matrix

Structural Proteins
Collagen, fibronectin, and laminin
providing structural support

Glycosaminoglycans
Hyaluronic acid and proteoglycans
forming hydrated gel

Cytokines & Growth Factors
Signaling molecules regulating cell
growth and di{erentiation

Vascular Supply

Sinusoids
Specialized capillaries with
discontinuous endothelium

Arterial Supply
Nutrient artery entering through
bone cortex

Venous Drainage
Central veins collecting blood from
sinusoids
Component Interactions

Stem cell niche: Specialized microenvironment for
hematopoietic stem cells

Cell migration: Movement from marrow to bloodstream

Signaling pathways: Communication between cells and matrix

Protective barrier: Sinusoidal endothelium regulates cell
passage

6. Functions of Bone Marrow

Hematopoiesis
Production of all blood cells
Contains hematopoietic stem
cells
Maintains blood cell balance
Responds to body's needs

Fat Storage
Yellow marrow stores fat
Energy reserve for body
Can convert to red marrow when
needed
Provides structural support

Immune Support
Produces white blood cells
Generates lymphocytes
Creates immune response cells
Houses immune cell precursors
Clinical Significance

Vital for survival 
Transplantable tissue 
Therapeutic target

7. Hematopoiesis: Overview
Definition
The process of blood cell formation, development, and maturation from
hematopoietic stem cells
Process of Blood Cell Formation
1
Hematopoietic Stem Cells (HSCs)
Multipotent stem cells capable of self-renewal and di{erentiation
2
Progenitor Cells
Committed to specific blood cell lineages but still proliferative
3
Precursor Cells
Immature cells undergoing maturation and specialization
4
Mature Blood Cells
Functional cells released into circulation
Importance
Constant replenishment of blood cells
Maintains blood cell balance
Responds to injury and infection
Essential for immune function

In adults, hematopoiesis primarily occurs in the bone marrow, while in fetuses it occurs in the yolk sac, liver, and spleen
before shi|ing to bone marrow

8. Hematopoietic Stem Cells

Characteristics
Multipotent - can di{erentiate into all blood cell types
Rare - comprise only 0.01-0.05% of bone marrow cells
CD34+ surface marker expression
Quiescent in G0 phase of cell cycle

Self-Renewal
Asymmetric division - produces one stem cell and one
di{erentiated cell
Maintains stem cell pool throughout lifetime
Regulated by transcription factors (e.g., HOXB4)
Influenced by bone marrow microenvironment

Di{erentiation Potential
Myeloid lineage - RBCs, platelets, granulocytes,
monocytes
Lymphoid lineage - T cells, B cells, NK cells
Hierarchical di{erentiation process
Responsive to cytokines and growth factors
Clinical Applications

Bone marrow transplantation 
Gene therapy 
Regenerative medicine

9. Red Blood Cell Production

Erythropoiesis Process
1
Hematopoietic Stem Cell
Multipotent stem cell in bone marrow
2
Proerythroblast
First committed RBC precursor
3
Erythroblast Series
Basophilic → Polychromatophilic → Orthochromatic
4
Reticulocyte
Immature RBC with residual RNA
5
Mature Erythrocyte
Biconcave disc without nucleus

Regulation
Erythropoietin (EPO) - primary regulator
Produced by kidneys in response to hypoxia
Stimulates stem cell di{erentiation
Production cycle: 7 days
Feedback mechanism maintains RBC count
Key Requirements
Iron - essential for hemoglobin synthesis
vitamin Vitamin B12 and Folate - DNA synthesis
protein Proteins - for cell structure
Energy - ATP for cell processes
Functions of Mature RBCs

Oxygen transport

CO removal

pH balance

10. White Blood Cell Production

Leukopoiesis
Process of white blood cell formation from
hematopoietic stem cells
Two main lineages: myeloid and lymphoid
Production time: 2-14 days depending on cell type
Increases during infection and inflammation

Types of White Blood Cells
Neutrophils
Most abundant WBCs; first
responders to infection
Eosinophils
Combat parasites and
allergic reactions

Basophils
Release histamine in
inflammatory responses

Monocytes
Become macrophages;
phagocytose pathogens

Lymphocytes
T cells, B cells, NK cells;
adaptive immunity

Regulation
Colony-stimulating factors (G-CSF, GM-CSF)
Interleukins (IL-3, IL-7)
Feedback mechanisms based on cell counts
Stress responses increase production
Key Functions

Immune defense 
Phagocytosis 
Immunological memory

11. Platelet Production

Thrombopoiesis Process
1
Hematopoietic Stem Cell
Multipotent stem cell in bone marrow
2
Megakaryoblast
Committed platelet precursor
3
Megakaryocyte
Large cell with multi-lobed nucleus
4
Proplatelet Formation
Cytoplasmic extensions develop
5
Platelet Release
2000-3000 platelets per megakaryocyte

Regulation
Thrombopoietin (TPO) - primary regulator
Produced by liver and kidneys
Stimulates megakaryocyte development
Production cycle: 5-10 days
Feedback mechanism maintains platelet count
Platelet Characteristics
Anucleate cell fragments
2-3 μm diameter; disc-shaped
Lifespan: 7-10 days
Contain granules with clotting factors
Functions in Hemostasis

Primary hemostasis

Clot formation

Wound repair

12. Bone Marrow and Immune System

Immune Cell Development
Primary lymphoid organ for B-cell development
Produces all white blood cell lineages
Provides specialized microenvironment (niches)
Maintains stem cell pool for immune response

Key Immune Cells Produced
B Lymphocytes
Antibody production;
humoral immunity
T Lymphocytes
Cell-mediated immunity;
mature in thymus

Natural Killer Cells
Innate immunity; target
infected cells

Dendritic Cells
Antigen presentation; bridge
innate & adaptive

Neutrophils
First responders;
phagocytosis

Macrophages
Phagocytosis; cytokine
production

Immune Response Regulation
Increases production during infection
Cytokine signaling pathways
Memory cell production for long-term immunity
Maintains immune homeostasis
Clinical Significance

Vaccine response transp t
Transplant rejection 
Autoimmune disorders

13. Leukemia
Types of Leukemia

Acute
Lymphoblastic
(ALL)
Rapid progression; a{ects
lymphoid cells

Acute Myeloid
(AML)
Rapid progression; a{ects
myeloid cells

Chronic
Lymphocytic (CLL)
Slow progression; a{ects
lymphoid cells

Chronic Myeloid
(CML)
Slow progression; a{ects
myeloid cells
Causes & Symptoms
Causes: Genetic mutations, radiation exposure, chemical
exposure, certain viruses
Common symptoms: Fatigue, fever, frequent infections,
unexplained weight loss
Blood-related: Anemia, easy bruising, bleeding,
petechiae
Physical: Enlarged lymph nodes, spleen, liver; bone pain
Diagnosis
Blood tests: Complete blood count, peripheral blood
smear
Bone marrow aspiration & biopsy - definitive diagnosis
dna Genetic testing: Cytogenetics, FISH, PCR for
specific mutations
Imaging: CT, MRI, PET scans to detect organ involvement
Treatment Approaches

Chemotherapy
transp t
Stem cell transplant

Targeted therapy

Radiation therapy

Immunotherapy

Supportive care

14. Lymphoma
Types of Lymphoma

Hodgkin
Lymphoma
Characterized by Reed-
Sternberg cells
Classical HL
aost common subtype
(95%)

Non-Hodgkin
Lymphoma
Diverse group of blood
cancers
NHL Subtypes
B-cell, T-cell, NK-cell origins
Causes & Symptoms
Risk factors: Age, weakened immune system, infections
(EBV, HIV), autoimmune disorders
Common symptoms: Painless swollen lymph nodes,
fever, night sweats, weight loss
Systemic: Fatigue, loss of appetite, itching, chest pain,
di{iculty breathing
B symptoms: Fever, drenching night sweats, unexplained
weight loss (>10% in 6 months)
Diagnosis
Lymph node biopsy - definitive diagnosis
Blood tests: Complete blood count, LDH, blood
chemistry
Imaging: CT, PET, MRI scans to determine stage
dna Bone marrow biopsy to check for involvement
Treatment Approaches

Chemotherapy

Radiation therapy

Immunotherapy

Targeted therapy
transp t
Stem cell transplant

Watchful waiting

15. Multiple Myeloma

Overview & Causes
Cancer of plasma cells - a type of white blood cell that
produces antipodies
Risk factors: Age (>65), male gender, African ancestry,
family history, opesity
Precursor conditions: Monoclonal gammopathy of
undetermined significance (MGUS)
dna Genetic factors: Chromosomal apnormalities, gene
mutations

Symptoms & Diagnosis
CRAB features: HyperCalcemia, Renal insu{iciency,
Anemia, Bone lesions
Bone symptoms: Bone pain, fractures, spinal cord
compression
Systemic: Fatigue, weakness, recurrent infections,
weight loss
Diagnostic tests: Blood/urine protein electrophoresis,
pone marrow biopsy, skeletal survey
Imaging: X-rays, CT, MRI, PET scans to detect bone
involvement
Treatment Approaches

Chemotherapy 
Targeted therapy 
Immunotherapy
transp t
Stem cell transplant 
Radiation therapy 
Supportive care

16. Aplastic Anemia and Bone Marrow Failure Syndromes
Overview
Bone marrow failure occurs when marrow doesn't
produce enough blood cells
Aplastic anemia: Pancytopenia with hypocellular
marrow
Inherited syndromes: Fanconi anemia, Dyskeratosis
congenita
Myelodysplastic syndromes: Ine{ective hematopoiesis
Causes & Diagnosis
Acquired causes: Autoimmune attack, toxins, radiation,
viruses, medications
dna Genetic causes: Inherited DNA repair defects,
telomere disorders
Symptoms: Fatigue, infections, bleeding, pallor,
petechiae
Diagnosis: Blood counts, bone marrow biopsy, genetic
testing
Laboratory findings: Pancytopenia, hypocellular
marrow, abnormal cell morphology
Treatment Approaches
transp t
Stem cell transplant

Immunosuppressive therapy

Growth factors

Blood transfusions

Supportive care

Gene therapy

17. Diagnostic Procedures: Bone Marrow Aspiration
Technique
Procedure to remove liquid bone marrow for
examination
1
Patient Positioning
Prone or lateral decubitus position
2
Local Anesthesia
Skin and periosteum numbed
3
Needle Insertion
Special needle into posterior iliac crest
4
Sample Collection
Syringe used to withdraw liquid marrow
Indications
Unexplained cytopenias - anemia, thrombocytopenia,
leukopenia
Suspected hematologic malignancies - leukemia,
lymphoma, myeloma
Staging of known cancers to assess bone marrow
involvement
fever Fever of unknown origin with suspected
hematologic cause
Storage diseases and other infiltrative disorders
Sample Analysis
Morphology - cell appearance and maturity
Cellularity - ratio of hematopoietic to fat cells
Di{erential count - percentages of cell types
Iron stores assessment
Interpretation

Hypercellular marrow 
Hypocellular marrow 
Abnormal cells

Dysplastic changes 
Increased blasts 
Iron deficiency/overload

18. Diagnostic Procedures: Bone Marrow Biopsy
Technique
Procedure to remove a small core of bone marrow
tissue for histological examination
1
Site Selection
Posterior iliac crest most common
2
Local Anesthesia
Skin, subcutaneous tissue, periosteum
3
Biopsy Needle Insertion
Jamshidi or similar needle with stylet
4
Core Extraction
1-2 cm cylindrical tissue sample obtained
Indications
Assessment of marrow architecture and cellularity
Staging of hematologic malignancies - lymphoma,
myeloma
Evaluation of fibrosis and other stromal abnormalities
Diagnosis of metastatic cancer to bone marrow
Follow-up of treatment response in hematologic
disorders
Sample Analysis
Histology - tissue architecture and cell distribution
Cellularity assessment - percentage of hematopoietic
tissue
Fibrosis evaluation - reticulin and collagen staining
Immunohistochemistry for cell typing and markers
Interpretation

Normal architecture 
Disorganized structure 
Abnormal infiltrates

Fibrosis patterns 
Cellularity changes 
Megakaryocyte morphology

19. Bone Marrow Transplantation: Overview

Types of Transplantation
Medical procedure to replace damaged or diseased
bone marrow with healthy stem cells
Autologous
Patient's own stem cells
collected before treatment
Allogeneic
Stem cells from a compatible
donor
Syngeneic
Stem cells from identical
twin
Haploidentical
Partially matched family
donor

Indications
Malignant disorders: Leukemias, Lymphomas, Multiple
myeloma
Bone marrow failure: Aplastic anemia, Myelodysplastic
syndromes
dna Genetic disorders: Sickle cell disease,
Thalassemia, Immunodeficiencies
Metabolic disorders: Hurler syndrome,
Adrenoleukodystrophy

Success Factors
HLA matching between donor and recipient
Donor selection and compatibility testing
Patient's overall health and disease status
Conditioning regimen e{ectiveness
Basic Principles

Myeloablation

Stem cell infusion

Engra|ment

Gra|-versus-tumor e{ect

Gra|-versus-host disease

Immune reconstitution

20. Bone Marrow Transplantation: Process
1Donor Matching
HLA typing of patient and potential donors
Matching at HLA-A, B, C, DRB1 loci
Sibling donors preferred (25% match chance)
Unrelated donor registries for matches
2Conditioning
Myeloablative or reduced-intensity regimens
High-dose chemotherapy and/or radiation
Eradicates malignant cells and suppresses immunity
Typically 5-10 days before transplantation
3Transplantation
Stem cell collection from donor via apheresis or marrow
harvest
Infusion similar to blood transfusion
Patient monitored for reactions during infusion
Specialized transplant unit for recovery
4Recovery
Engra|ment typically occurs in 2-4 weeks
Close monitoring for infections and GVHD
Immunosuppressive medications for allogeneic
transplants
Full recovery may take 6-12 months or longer
Key Outcomes

Disease remission 
Blood count recovery 
Immune reconstitution 
Quality of life

21. Bone Marrow Donation

Donation Process
1
Registration
Join donor registry with tissue typing
2
Matching
HLA compatibility testing with patient
3
Medical Evaluation
Comprehensive health assessment
4
Donation
Outpatient procedure under anesthesia

Eligibility
Age: Typically 18-60 years old
Health: Good overall health, no active infections
Weight: Minimum weight requirements (usually >50kg)
Exclusions: Certain cancers, heart disease, autoimmune
disorders

Donation Types
Marrow Harvest
Surgical extraction from
pelvic bones under
anesthesia
PBSC Collection
Non-surgical, peripheral
blood stem cell apheresis
Recovery time: 1-2 days for PBSC, 1-2 weeks for marrow
Side e{ects: Temporary pain, fatigue, low back
discomfort
Impact on Donors

Psychological reward

Life-saving potential

Minimal long-term e{ects

Complete marrow regeneration

Post-donation follow-up care

Option to meet recipient

22. Recent Advances in Bone Marrow Research

New Technologies
dna Single-cell sequencing for detailed hematopoietic
analysis
3D bone marrow models for better disease
understanding
Microfluidic devices for stem cell manipulation
Advanced imaging techniques for real-time monitoring

New Treatments
CAR-T cell therapy for refractory blood cancers
Gene editing (CRISdR) for genetic blood disorders
Targeted therapies with reduced side e{ects
Haploidentical transplants expanding donor options
Future Directions

Ex vivo marrow expansion 
Bioengineered marrow 
Personalized therapies

AI-driven diagnostics 
Stem cell reprogramming 
Targeted drug delivery

23. Support Resources for Patients
Organizations
Bone Marrow & Cancer
Foundation - Patient support
services
NMDP/Be The Match - Donor
registry and patient support
Leukemia & Lymphoma Society
- Disease-specific resources
AAMDSIF - Bone marrow failure
information
Financial Assistance
Treatment grants for
uninsured/underinsured patients
Housing assistance during
treatment away from home
Transportation programs for
medical appointments
Medication assistance programs
for costly drugs
Emotional Support
Support groups for patients and
caregivers
One-on-one counseling with
mental health professionals
Peer mentoring programs with
survivors
Family support services and
resources
Additional Resources

Educational materials

Return-to-work programs

Online communities

Patient conferences

Helplines

Survivorship guides

24. Summary and Conclusion
Structure & Function
Spongy tissue in bone cavities
Red marrow: hematopoietic
tissue
Yellow marrow: fat storage
Primary site of blood cell
production
Hematopoiesis
Begins with hematopoietic stem
cells
Produces all blood cell lineages
Critical for immune system
function
Maintains blood cell homeostasis
Clinical Significance
Site of various malignancies
Bone marrow failure syndromes
transp tTransplantable
for life-
threatening
conditions
Advancing research and therapies

Bone marrow is a vital organ essential for life, responsible for blood cell production, immune function, and
serving as a key focus for medical research and treatment of numerous diseases