abnormalities of erythropoiesis
DESCRIPTION
Abnormalities of Erythropoiesis. Anemia 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 - PowerPoint PPT PresentationTRANSCRIPT
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)