Abnormalities of ErythropoiesisAnemia is a condition of insufficient RBC’s or

hemoglobin (quality or quantity)It is most often the result of low iron intake, hemolysis,

autoimmune disease, blood loss, or lack of production in the bone marrow

Polycythemia is a condition of excess number of RBCs

It occurs in response to hypoxia (natural “blood doping” is training at high altitude), shots of EPO (illegal “doping”), smoking (COPD), or dehydration

AnemiasIron deficiency anemia is the most common

anemia in the U.S., and affects primarily menstruating women• In the United States, 20% of all women of

childbearing age have iron deficiency anemia, compared with only 2% of adult men

Hemorrhagic anemia is the result of precipitous blood loss, and results in an equal decrease in Hct, Hgb content, and RBC count

AnemiasSickle-cell disease (SCD), also called sickle-cell

anemia, is an autosomal recessive disorder. A genetic defect in the primary DNA sequence leads to production of a faulty Hgb β chain, and RBCs that take on a rigid, sickle-shape • Sickling decreases the cells' flexibility and results in a

variety of complications; life expectancy is shortened

RBC Life CycleRBCs live only about 120 days. To maintain

normal numbers, new mature cells must enter the circulation at the astonishing rate of at least 2 million/second, a pace that balances the equally high rate of RBC destruction• Ruptured RBCs are removed from circulation and

destroyed by fixed phagocytic macrophages in the spleen and liver—the breakdown products are recycled and used in numerous metabolic processes, including the formation of new RBCs

Red blood celldeath andphagocytosis

Key:in blood

in bile

Macrophage inspleen, liver, orred bone marrow

1

Globin

Red blood celldeath andphagocytosis

Key:in blood

in bile

Macrophage inspleen, liver, orred bone marrow

Heme2

1

Aminoacids

Reused forprotein synthesisGlobin

Red blood celldeath andphagocytosis

Key:in blood

in bile

Macrophage inspleen, liver, orred bone marrow

Heme

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Key:in blood

in bile

Macrophage inspleen, liver, orred bone marrow

Heme

4

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Liver

Key:in blood

in bile

Macrophage inspleen, liver, orred bone marrow

FerritinHeme

54

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

Key:in blood

in bile

Macrophage inspleen, liver, orred bone marrow

FerritinHeme

654

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:in blood

in bile

Macrophage inspleen, liver, orred bone marrow

FerritinHeme Fe3+

7

654

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Circulation for about120 days

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:in blood

in bile

Erythropoiesis inred bone marrow

Macrophage inspleen, liver, orred bone marrow

FerritinHeme Fe3+

8

7

654

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Circulation for about120 days

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:in blood

in bile

Erythropoiesis inred bone marrow

Macrophage inspleen, liver, orred bone marrow

FerritinHeme

Biliverdin Bilirubin

Fe3+

9

8

7

654

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Circulation for about120 days

Bilirubin

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:in blood

in bile

Erythropoiesis inred bone marrow

Macrophage inspleen, liver, orred bone marrow

FerritinHeme

Biliverdin Bilirubin

Fe3+

10

9

8

7

654

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Stercobilin

Bilirubin

Urobilinogen

Feces

Smallintestine

Circulation for about120 days

Bacteria

Bilirubin

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:in blood

in bile

Erythropoiesis inred bone marrow

Macrophage inspleen, liver, orred bone marrow

FerritinHeme

Biliverdin Bilirubin

Fe3+

12

1110

9

8

7

654

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Urine

Stercobilin

Bilirubin

Urobilinogen

Feces

Smallintestine

Circulation for about120 days

Bacteria

Bilirubin

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:in blood

in bile

Erythropoiesis inred bone marrow

Kidney

Macrophage inspleen, liver, orred bone marrow

Ferritin

Urobilin

Heme

Biliverdin Bilirubin

Fe3+

13 12

1110

9

8

7

654

3

2

1

Aminoacids

Reused forprotein synthesisGlobin

Urine

Stercobilin

Bilirubin

Urobilinogen

Feces

Largeintestine

Smallintestine

Circulation for about120 days

Bacteria

Bilirubin

Red blood celldeath andphagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:in blood

in bile

Erythropoiesis inred bone marrow

Kidney

Macrophage inspleen, liver, orred bone marrow

Ferritin

Urobilin

Heme

Biliverdin Bilirubin

Fe3+

14

13 12

1110

9

8

7

654

3

2

1

RBC Life Cycle

LeukocytesUnlike RBCs, white blood cells (WBCs) or

leukocytes have nuclei and a full complement of

other organelles - but they do not contain the

protein Hgb

LeukocytesLeukocytes are divided into two groups

depending on whether they contain

conspicuous chemical-filled cytoplasmic

granules (when stained)• Granulocytes include the neutrophils, eosinophils,

and basophils

• Agranulocytes are the monocytes and

lymphocytes

Leukocytes The most numerous WBC in normal blood (60-70% of

circulating white cells) is the neutrophil, or polymorphonucleocyte (PMN)– PMNs are granulocytes with a pinkish cytoplasm, and

they are one of the two major phagocytes in the body• their principal role is to fight bacterial infections

LeukocytesChemicals released by microbes and inflamed

tissues attract phagocytes, a phenomenon called chemotaxis• This graphic shows a PMN phagocytizing a microbe

for internal digestion and destruction

Leukocytes• Eosinophils are characterized by their large red

granules – They are much less numerous than neutrophils (2-4%

of circulating WBCs), but their numbers increase slightly with parasitic infection• they have also been associated with the development of allergies

LeukocytesWhile monocytes are not granulocytes, they

come from the same immediate precursor cell as

the 3 granulocytes (the myeloid stem cell)• Along with neutrophils, monocytes are the other

major group of phagocytic cells. Even though they

constitute only 3-8% of the circulating WBCs, they are much more numerous in

the peripheral, tissues where they

act as “fixed” phagocytes

LeukocytesLymphocytes are the last of the 5 types of

WBCs, and in many ways they are quite different• Lymphocytes don’t have granules or phagocytize;

their cytoplasm is sparse compared to their very

large nucleus, and they develop from a different precursor stem cell

• Also, rather than acting as non-specific defenders, lymphocytes

develop as responders to very

specific foreign antigens

LeukocytesBasophils are the third type of granulocyte; they

contain large, dark blue, histamine containing granules • Normally, they are the lowest number of circulating

WBCs (only 0-1%), but they have an important role to play in the inflammatory responses

Leukocytes• Approximately 20-30% of circulating white cells

are lymphocytes: an increase above this

number is called a lymphocytosis and often

represents an acute viral infection

• Most lymphocytes continually move among

lymphoid tissues, lymph, and blood, spending

only a few hours at a time in blood

– Lymphocytes are the cornerstone

of the specific immune response

WBC IndicesFor diagnostic purposes, physicians measure

the total number of circulating WBCs• A leukocytosis is any WBC count > 10,000/mm3,

and usually indicate an infectious process or a cancer

• A leukopenia is any WBC count < 5,000/mm3, and usually indicates a severe disease (AIDS, bone marrow failure, severe malnutrition, or chemotherapy)

WBC IndicesTo enhance the diagnostic value of a WBC

count, the percentages of each of the 5 types

of WBCs is determined by using a machine to

do a statistical analysis of the blood sample.

This is called the WBC differential

WBC IndicesShifts in the normal percentages of circulating

WBCs will often point towards a bacterial infection (elevated percentage of neutrophils) or a viral infection (elevated percentage of lymphocytes• In this peripheral blood smear

a patient with lymphocytic leukemia has a WBC >150,000 and 90% of the WBCs arecancerous lymphocytes!

Lymphocytic leukemia.

Plasma is the fluid component of the blood and contains everything in blood except the formed elements, which, for collection purposes, have been centrifuged out• Plasma contains mostly water, with electrolytes,

hormones, proteins, dissolved gasses, and glucose and other nutrients

Plasma

Plasma Proteins The major protein in plasma is albumin; it also has many clotting

proteins, antibodies, and enzymes• Albumin is a relatively simple, water soluble protein

with a low molecular weight – it forms small heart-shaped globules just over 8 nm in size

Albumin is synthesized in the liver and contributes significantly to the blood viscosity and the body’s ability to maintain blood pressure

It also plays an important role as a carrier molecule

Plasma ProteinsAnother important group of plasma proteins are

the globulins, of which there are several types: α (alpha), β (beta), and δ (gamma). Globulins control blood osmotic pressure and act as carrier molecules• α-globulins carry bilirubin and steroids • β- globulins carry copper and iron • δ-globulins are immunoglobulins (antibodies) made

by activated B lymphocytes called plasma cells

HemostasisHemostasis is a sequence of responses that

stops bleeding• When blood vessels are damaged or ruptured, the

hemostatic response must be quick, localized to the region of damage, and carefully controlled in order to be effective

• Three mechanisms reduce blood loss1. Vascular spasm 2. Formation of a platelet plug 3. Blood clotting (coagulation)