Blood II Flashcards
RBC (erythrocytes)
5 x 10^6/μL
Diameter: 7.2 μm
Lifespan: 120 days
Platelets (Thrombocytes)
250,000-400,000/μL
Diameter: 2-3 μm
Lifespan: 7-8 days
WBC (Leukocytes)
8,000-10,000/μL
Diameter: 10-18 μm
Lifespan: hours - years
Hematopoiesis
All blood cells are derived from a common multi-potential, pluri-potential hematopoietic STEM cell
- Erythopoiesis (2 -3 x 10^6 RBCs produced per second)
- Thrombopoiesis
- Leukopoiesis
Hematopoietic Growth Factors
(HGFs)
influence the proliferation and differentiation of blood cell precursors
Cytokines
substances (proteins or peptides) released by one cell that affect the growth, development, and activity of another cell
Sites of Hematopoiesis
-3 months: Yolk Sac
-5 months: Liver and spleen
-Birth: Shifts to bone marrow
-Post Birth: Axial skeleton and Proximal epiphyses of long bones
(long bones stop as site by 30 y/o)
RBC Shape
“Bioconcave Disk” due to presence of “spectrin”
Spectrin: a fibrous protein forming a flexible network lined to cell membrane
- MAX surface area and MIN diffusion distance increase efficiency of O2 and CO2 diffusion
- Flexible in capillaries
Complete blood count (CBC)
RBC, WBC, platelet count, Hematocrit, Hb concentration
RBC size and Shape
Normocytic
Microcytic
Macrocytic
Sickle Cell (sickle shape)
Spherocyte (smaller and darker)
RBC count
Males: 5.1 –5.5 x 10^6/μL
Females: 4.5 -4.8 x 10^6/μL
~25 x 10^12 in 5L of blood
RBC Rate of production = RBC Rate of destruction
~2 x 10^6/second
RBC Enzyme Systems
Must make energy with no mitochondria
- Glycolytic Enzymes generates energy anaerobically
- Carbonic Anhydrase converts CO2 to bicarbonate which is easier to transport
RBC Components
Mostly water
33% Hemoglobin
Lipids, proteins, ions
Contain no organelles, nucleus, mitocondria
Hemoglobin - Oxygen complex
1 molecule of Hb binds to 4 O2
oxyhemoglobin = O2 + Hb (red in lungs)
deoxyhemoglobin = O2 released (dark blood in tissues)
Hemoglobin Structure
200-300 x 10^6 Hb molecules/RBC
MW = 64 kDa
Four subunits of chain with heme group
4 Heme - Iron (Fe) - O2 bonds
Hemoglobin Functions
- Transport O2 / CO2
- Increase O2 solubility in blood
- Acts as a buffer
Hemoglobin Values
Males: 16 g/100 ml blood
Females: 14 g/100 ml blood
O2 carrying capacity of blood: 20 ml O2/100 ml blood
Factors affecting ability of Hb to bind and release O2
- Temperature
- Ionic Composition
- pH
- pCO2 (partial pressure CO2)
- Intracellular enzyme concentration
Hematopoiesis Cell Lines
2 Cell lines
-Lymphoid stem cell (lymphocyte only)
-Myeloid stem cell (all others)
RBC Precursor Proliferation
(3-5 days)
1. Decrease in size (18 -> 7 μm)
2. Loss of nucleus and organelles
3. Accumulation of Hb
Erythropoiesis
- STEM Cell
- Myeloid cell line
- RBC Precursor Proliferation
- Reticulocyte
- Mature RBC
Reticulocyte
< 1 % of RBCS
Reflects the amount of effective erythropoiesis in bone marrow
24 hours
Factors determining # of RBCs
- O2 requirements
- O2 availability
RBC increases with decreased O2
Erythropoietin (EPO)
A glycoprotein hormone/cytokine produced mainly by the kidney
Stimulus for release is Hypoxia
-decreased RBC count
-decreased O2 availability
-increased tissue demand for O2
Regulation of Erythropoiesis
- Kidney senses hypoxia
- Kidney (renal cortex) releases EPO
- Increase EPO in plasma
- Stimulation of Bone Marrow
- Increased production of erythrocyte precursor
- Increased RBCs and oxygen in plasma
NEGATIVE FEEDBACK LOOP
Erythropoietin (EPO) acts on…
committed erythrocyte precursors
EPO stimulates proliferation and accelerates maturation of committed stem cell into mature RBC
Hormonal Effects on EPO
Testosterone increases release of EPO and sensitivity of RBC precursors to EPO
Estrogen has opposite effects
Males have more RBCs than females
Destruction of RBCs
Macrophages perform phagocytosis of old RBCs (120 days) and components are recycled
RBC component recycling
Global: Amino acid pool
Iron: Binds to Transferrin and is moved to storage in liver, spleen, and gut
Hb: broken into Heme -> Bilirubin
Bilirubin
Heme waste or yellow plasma pigment that passes through liver and intestinal tract to be excreted in feces
Backup of > 1mg/dL causes Jaundice
Infant Jaundice
excess of RBCs are lysed and Bilirubin is released
Jaundice Causes
Liver damage and bile duct obstruction block pathways of Bilirubin leading to a buildup in body
RBC Dynamics
Production > Destruction = Polycythemia
Production < Destruction = Anemia
Measured by # of RBC, Hb, Ht
Ht and abnormal RBC dynamics
We can not rely on Ht measurement as increased/decreased Ht can be due to dehydration/fluid retention and not polycythemia/anemia
Polycythemia
(more RBCs)
> 18 g% Hb
> 6 x 106 RBCs/μL
increases blood viscosity and can slow flow into blood clots
Relative Polycythemia
due to decreased plasma volume
Absolute Polycythemia
Physiological: secondary effect due to higher O2 needs or lower O2 availability
Pathological: primary effect due to tumors producing EPO, unregulated RBC production
Polycythemia vera
PATHOLOGICAL
-7 -8 x 10^6RBCs/μL
-Ht~70%
due to stem cell dysfunction
Anemia
A decrease in the oxygen-carrying capacity of blood
- Decreased RBC Count
Males: < 4 x 10^6/μL
Females: < 3.2 x 10^6/μL - Decreased Hb content
Males: < 11 g%
Females: < 9 g%
Classification of Anemias
Microcytic (Shrunk)
Normocytic
Macrocytic (Enlarged)
Normochromic ~33% Hb
Hypochromic <33% Hb (Pale)
Hyperchromic >33% Hb (Too dark)
Aplastic (Hypoplastic Anemia)
Diminished Production: Abnormality at site of production (bone marrow)
Normocytic, Normochromic
May be caused by exposure to chemicals, drugs, or radiation
Stimulation Failure Anemia
Diminished Production: Inadequate stimulus
Normocytic, Normochromic
Renal disease causes less EPO production
Iron Deficiency Anemia (Most common)
Diminished Production: Inadequate raw materials
Microcytic, Hypochromic
Increased requirement of Fe or inadequate supply of Fe
Anemia Causes
- Diminished RBC production
- Ineffective RBC maturation
- Increased RBC destruction or reduced RBC survival (RBC survival disorders)
Iron (Fe)
Total in Body: 4g
Hb: 65% Stored: 30% Myoglobin: 5% Enzymes: 1%
Daily Intake in diet: ~15 -20 mg
Daily absorb in gut:
Males: ~1 mg Fe/day
Females:~2 mg Fe/day
Erythropoiesis and Iron
Normal erythropoiesis requires 25 mg Fe/day
Normal RBC destruction releases 25 mg Fe/day
1. 1 mg is lost
2. 24 mg are recycled
So males and females require intake of dietary iron to make up for losses (more for females)
Maturation Failure Anemia
Ineffective Maturation: Deficiencies of Vitamin B12 and Folic Acid
(both required for DNA synthesis)
Macrocytic, Normochromic
Intrinsic Factor Deficiency
Can lead to Maturation Failure Anemia / Pernicious Anemia
Intrinsic Factor is a glycoprotein needed to transport Vitamin B12
Hemolytic Anemias
RBC survival disorders: may be accompanied by jaundice
Congenital or Acquired (toxins, drugs, antibodies)
- Abnormal RBC membrane structure
- Abnormal enzyme systems
- Abnormal Hb structure (Sickle Cell)
Hemorrhage
Blood loss either externally or internally
Hematoma is accumulation of blood in the tissues
Hemostasis
Arrest of bleeding following vascular injury
1. Vascular injury
2. Vasoconstriction
3. Platelet Plug formation
4. Blood clot formation
Primary Hemostasis
Vascular Response
Platelet Response
Secondary Hemostasis
Blood clot formation
Vascular Response (vasoconstriction)
-Smooth muscle cells in vessel wall respond to injury by contracting
-Opposed endothelial cells stick together
Platelet Structure
~ 2-4 μm diameter
-No nucleus
-Many granules containing factors for constriction, clotting, aggregation
-Many filaments, microtubules, mitochondria, sER
Platelet Production
- Pluripotent stem cell
- Committed stem cell (Myeloid) stimulated by Thrombopoeitin (from liver)
- Megakaryocyte
- Megakaryocyte nucleus division into platelets
- Finger like projections release platelets into blood stream
Platelet Plug formation
- Collagen exposure
- Platelets adhere to vessel via von Willebrand Factor
- Platelets release platelet factors
- Platelets aggregate
- Platelet plug formation
Platelet factors
ADP
Thromboxane A2
Serotonin
PF3
Platelet Functions
- Release vasoconstricting agents/ cytokines
- Form Platelet Plug(White Thrombus)
- Release Clotting Factors
- Participate in Clot Retraction
- Maintain Endothelial Integrity
Petechia
small red/purple spots caused by bleeding into the skin due to lack of platelets
Abnormal primary Hemostatic Response
- Failure of blood vessel constricting
- Platelet deficiencies
(Numerical or Functional)
Aspirin inhibits synthesis and release of TXA2
Clot formation
A function of plasma NOT RBCS
-Injury to vessel wall causes activation of plasma proteins and clotting factors
-Clotting factors act as enzymes or co-factors in the presence of Ca++ or phospholipid agents
Intrinsic Pathway
3-6 mins
1. Damage to blood vessel
2. Interacting plasma factors
(Ca++ and PF3)
3. Prothrombinase cleaves Prothrombin into Thrombin
4. Thrombin cleaves Fibrinogen into Fibrin
5. Factor XIII cross links to form clot
Extrinsic Pathway
15- 20 secs
1. Damage to tissue outside vessel
2. Interacting plasma factors
(Ca++ and Phospholipids)
3. Prothrombinase cleaves Prothrombin into Thrombin
4. Thrombin cleaves Fibrinogen into Fibrin
5. Factor XIII cross links to form clot
Extrinsic Pathway and Intrinsic Pathway
-Extrinsic Pathway is closed after platelet plug formation
-Small amounts of THROMBIN generated in Extrinsic trigger strong positive feedback on Intrinsic generate larger quantities of THROMBIN
Clotting Factor Deficiencies
Congenital: single factor hereditary deficiencies (Factor VIII, Hemophilia)
Acquired: multi-factor deficiencies (liver disease, Vitamin K deficiency)
Vitamin K is a cofactor in the synthesis of Prothrombin, VII, IX, X
Clot Retraction
requires a contractile protein, thrombosthenin, released by platelets
Makes stable solid clot
Clot lysis
- Intrinsic/Extrinsic proactivators trigger plasminogen activator
- Plasminogen Activator cleaves plasminogen into plasmin
- Plasmin cleaves fibrin into small fragments to destroy the clot
Clotting Regulation
Inhibitors of platelet adhesion
Anticoagulants (Coumarin, Heparin)
Thrombolytic Drugs
promote clot lysis
Tissue plasminogen activator
Streptokinase
