Hematopoiesis

• Term used to describe the normal formation

of blood cells in the bone marrow.
Bone Marrow
• Produces all the hematopoietic cells in
adults.
• Present in all bone marrow cavities at birth
and early childhood
• By age 20 – 25 years, red marrow is present
in cranial bones, vertebrae, sternum, ribs,
clavicle, scapula, pelvis, proximal end of the
femur and humerus.
Processof RBC formation
Substances needed for
erythropoiesis:
• Iron
• Vitamin B12
• Copper and Cobalt
• Folic Acid
• Pyridoxine (vitamin B6)
 Aging or
abnormal
erythrocytes
Lysed by the liver
and spleen

•Iron is recycled by
transferrin
•Heme molecule is Urine:
converted to urobilinogen GIT: Bile
unconjugated
bilirubin

Conjugated with
Excreted
protein in the
liver
Blood are classified into different
groups and typed according to
antigens present on the red cell
membrane
 Rh type is determined by the presence
or absence of the Rhesus factor.
 Unlike the ABO antigens, the only ways
antibodies are developed against the Rh
factor are through placental
sensitization or transfusion
 85% of whites and 95% of African
Americans in the US are Rh+
 Incompatibility happens when the
mother is Rh- and the baby is Rh+
A group of condition characterized by
an increase in the hematocrit.

Problem: viscosity of the blood

increases.
Causes:
• Hypoxemia
High altitutes
Chronic pulmonary diseases
• Overproduction of erythropoietin
Renal diseases
Malignant tumors
Disturbance of renal blood flow
Characterized by normal erythrocyte
count and a reduced plasma volume.
Cause: dehydration
Myeloproliferative disorder in which
there is an increase production of all
the formed elements of blood.
Abnormally low number of circulating
RBCs or hemoglobin level, or both,
resulting in diminished oxygen-
carrying capacity.
Most common hematologic condition
Causative factors:
• Excessive loss of RBCs
• Excessive destruction
• Deficient RBC production
• Bone marrow failure
• Signs and symptoms caused by tissue
hypoxia.
Angina, night cramps, fatigue, weakness, and
dyspnea
• Brain hypoxia: headache, faintness, and
dim vision.
• Pallor of the skin, mucous membranes,
conjunctiva, and nailbeds.
• Tachycardia and palpitations
• Diffuse bone pain and sternal tenderness.
• Jaundice (in hemolytic anemia)
• Petechiae and purpura (in aplastic
anemia)
 Bleeding  iron and other components
of the erythrocytes are lost from the
body.
 May be acute or chronic
 RBC concentration returns to normal
within 3 – 4 weeks if the bleeding is
controlled and when sufficient iron
stores are available.
 Patients are commonly asymptomatic
until the hemoglobin level is less than 8
g/dL.
Characterized by the premature
destruction of RBCs
RBCs have shortened lifespan
Bone marrow is usually hyperactive
A. RED CELL MEMBRANE DEFECTS
1. Hereditary Spherocytosis
2. Acquired Immune Hemolytic
anemia
3. Hemolytic Blood Transfusion
Reactions
A group of inherited hemolytic anemias
that are mainly due to inherited
autosomal dominant conditions that
result in a molecular defect of the RBC
membrane.
 Characteristic:
• RBCs are spherical in shape and are
prematurely destroyed in the spleen.
 Manifestations:
• Jaundice
• Splenomegaly
• Signs of anemia
Resultfrom premature destruction of
the RBCs by autoantibodies in the
immune system that have specificity
against blood group antigens.
Antigen of the person may react with
plasma or cells of another, especially
during or after a blood transfusion.
When incompatible blood is
transfused, the antigen-antibody
reactions within the recipient of
transfusion cause systemic reactions.
 types causes symptoms
Febrile Recipient antibodies Rise in temperature
to donor leukocytes within two hours after
Bacterial transfusion.
Allergic contamination
Recipient responds to chills
Flushing, Hives, Itching,
donor proteins Dyspnea,Stridor,Hypotens
Severe immune ion
response to a foreign
substance
Acute hemolytic Administration of Fever, chills, nausea,
incompatible blood dyspnea, low back pain,
Preexisting antibodies hemoglobinurea, pain at
against transfused transfusion site,
RBCs tachychardia,
Improper hypotension
Delayed administration
Extravascular Chills, pallor, fatigue,
hemolytic hemolysis of RBCs anemia, dyspnea,
jaundice, unexpected
drop of hemoglobin
An autosomal recessive disease in
which the normal amino acid,
glutamic acid, is replaced by valine
Stimulus for sickling: low oxygen
tension
• Sickle cell hemoglobin acquires a crystal-
like formation
 Genetic defect

Replacement of glutamic acid by valine

Altered globin chain (HbS)

Low oxgyen
tension
RBCs become sickled
shape

Blood vessel Shortened red cell

occlusion survival (hemolytic
anemia)

•Microinfarction •Anemia
•Ischemic tissue •Jaundice
pain •Gallstones
•Ischemic organ
malfunction
•Autoinfarction of
Disorders that demonstrate large,
immature, poorly functional
erythrocytes.
Causes:
• Vitamin B12 deficiency (Pernicious
anemia)
• Folate (Folic Acid) deficiency
Cause: malabsorption of Vitamin
B12 due to:
• An autoimmune disease leading to
progressive loss of parietal cells in the
stomach, causing failure of secretion of
hydrochloric acid and intrinsic factor
(Pernicious Anemia)
Intrinsic factor:
A glycoprotein essential to bind Vitamin B12 and
protect it from degradation by intestinal enzymes.
• Increase in demand
Vitamin B12:
• Normal functioning of the brain
• Formation of blood
•Hereditary gastric mucosal
atrophy
•Autoimmune disorder
•Gastric or small bowel
surgery
STOMACH

Destruction/absence of
•Increased
parietal cells in the
requirement –
stomach
pregnancy
Inability to form •Intestinal parasites
intrinsic factor

Malabsorption of Demand > supply

vitamin B12

Faulty RBC
production
Anemia
NORMAL RBC MEGALOBLASTIC ANEMIA
Inhibited growth of all cells
• Anemia
• Leukopenia
• Thrombocytopenia
Demyelination of Peripheral nerves to
spinal cord
TRIAD SYMPTOMS:
• Weakness
• Sore tongue
• Paresthesia and other neurologic symptoms
 Folic Acid
• Necessary for normal RBC production
 Causes:
• Poor dietary intake
• Poor GI absorption
• Folate antagonists (anticancer drugs and
anticonvulsants)
• Inborn errors of metabolism
• Increased requirement
 Effect:
impaired DNA synthesis and
megaloblastic transformation of the
RBCs
Characterized by deficient
hemoglobin synthesis caused by lack
of iron.
Cells become macrocytic and
hypochromic because of low
concentrations of hemoglobin.
Most common type of anemia
Causes:
• Increase loss (hemorrhage and hookworm
infestations)
• Decreased dietary intake
Children
Elderly
Adolescents
Indigents
• Pernicious anemia
• Gastrectomy
• Malabsorption syndromes
Clinical manifestations
• Fatigue
• Tachycardia
• Irritability
• Pallor
• Sore tongue
• Cheilosis
• Koilonychia
• Pica
Occurs as a result of reduced bone
marrow function
Effect: Pancytopenia  drop in all
levels of all blood elements.
Causes:
• genetic failure of bone marrow development
• Injury to stem cells
Viral infections
Medications
Toxins
Pathology:
• Marrow is hypocellular or is replaced with
fat