PNB 2265 Chapter Notes - Chapter 17: Hematopoietic Stem Cell, Membrane Transport Protein, Blood Proteins
16 May 2018
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CH 17 - BLOOD (TEXTBOOK)
FUNCTIONS
● Transport gases, nutrients, hormones, etc
● Buffering of pH, temp, osmolarity
● Defense against bacteria, viruses, dead body tissues
● Clotting of blood + wounds
○ Men: 5-6L
○ Women: 4-5L
○ Liquid connective tissues, part of extracellular fluid
○ Centrifuge is used to separate blood components
MADE OF
Blood consists of plasma and formed elements
● PLASMA
○ Liquid part of blood, 90% water
○ Good temp buffer
○ Colloid solution
: solution w/ small solutes that do not settle out of the solution
■ Na+, K+,Cl-,Ca2+
■ HCO3- is also present to buffer the pH
● Plasma Proteins
1. Albumins: most abundant, produced by liver, large do doesn’t leave bloodstream, regulator of
osmolarity + are carrier molecules - prevent swelling and shrinkage of cells
2. Globulins: circular proteins, 2nd most abundant, produced by liver and cells of Immune System,
acts as carrier proteins for immunoglobulins - defends body against foreign pathogens
3. Clotting factors: soluble proteins for blood clotting
4. Water soluble hormones: ligands for receptors in the body
5. Fibrinogens: prevent fluid loss during injury
● FORMED ELEMENTS
○ Erythrocytes are major formed element (RBC) → distinctive biconcave shape
■ Shape allows RBC to move through arteries, capillaries, veins
■ Capillaries only one cell thick so shape allows cells to bend/fold/stack to prevent
blockages
■ Shear stress created by flexing causes release of signaling mols like ATP
■ Also increases membrane surface area for gas exchange + diffusion
■ HOWEVER: RBC do not have nuclei a
nucleate
and are non-mitotic & have very
little DNA, unable to synthesize proteins for repair
● RBC ejects organelles as they mature and become biconcave
● Prone to apoptosis - cell death
● Avg lifespan of RBC is 3 months, then are replenished in erythropoiesis
process
■ Stem cells for RBCs are: hematopoietic stem cells
ERYTHROCYTES
○ Hematopoietic stem cells located in red bone marrow
(in long bones)
■ Can become RBC or WBC
● RBC - erythropoiesis
● WBC - leukopoiesis
● Depends on hormones + cytokines binding to specific receptors on stem
cell membranes
ERYTHROPOIESIS
○ Erythropoiesis takes about 2 weeks
○ 100 billion generated each day to replenish those that are lost
○ Regulated by hormones and environmental factors
■ Can increase or decreases RBC production
○ Hypoxia: stress condition caused by low oxygen in tissues
, a major biological sign that
regulates erythropoiesis
■ Causes kidney + liver to release glycoprotein hormone erythropoietin (EPO)
which drives erythrocyte maturation
■ EPO also triggered by testosterone + other hormones
○ REQ: Vitamin B, Folate, Iron
■ Iron is essential component of hemoglobin (Hb) protein
1. A hematopoietic stem cell differentiates into a myeloid stem cell.
2. This myeloid stem cell commits to a red blood cell fate by transforming into a
proerythroblast.
3. The proerythroblast executes a gene transcription program that begins its conversion
into a mature red blood cell.
4. The proerythroblast becomes a basophilic erythroblast. These precursor cells contain
many ribosomes, and begin producing proteins required by mature red blood cells (e.g.
hemoglobin).
5. From this point on, the various intermediates are characterized by the amount of
hemoglobin they contain, the degree of organelle degradation, and the size of the
nucleus (which gets continuously smaller). This change is visible in the conversion of
polychromatic erythroblasts, which have purple staining ribosomes, to
orthochromatic erythroblasts, which are pink. The pink staining demonstrates that
the cell is saturated with hemoglobin.
6. Orthochromatic erythroblasts become reticulocytes, characterized by their biconcave
shape, which eventually mature into erythrocytes.
Using stem cells to treat bloodborne diseases eliminates worries about
myoablation: when blood cell
production in bone marrow is greatly impaired
since hematopoietic cells regenerate quickly
● Autograft: bone marrow from own body
● Allograft: bone marrow from close relative
DEATH + RECYCLING OF ERYTHROCYTES
● When RBC reaches end of lifespan, they are engulfed by macrophages & hemoglobin degraded
into its components
○Proteins → amino acids
○Heme group (red) → biliverdin (green) → bilirubin (yellow)
■ Like a bruise changes color
○ → released by macrophages into plasma → transported by albumin to liver → turns into
bile → intestine gut bacteria convert into stercobilin (makes poop brown) + remainder
goes through urine (makes pee yellow)
○ Iron: very reactive so must be bound to carrier protein (globulin called transferrin) that
prevents it from reacting
■ Recycled back into bone marrow (site of erythropoiesis)
■ Excess iron stored in tissues with proteins ferritin & hemosiderin until needed
for erythropoiesis
● Hemolysis; premature rupturing of erythrocytes
○ Occurs due to immune rxn, infection, medication
○ Can be life threatening bc iron can damage tissues or RBC destruction can outpace
production
HEMOGLOBIN
● Globular tetrameric protein → 4 protein subunits (chains)
● In center of each of the 4 chains is heme group which has a Fe2+ (iron) to bind to single O2
atom = 1 HEMOGLOBIN → BINDS TO 4 O2
● In adults: Alpha globin → alpha chain && Beta globin → beta chain
Document Summary
Defense against bacteria, viruses, dead body tissues. Liquid connective tissues, part of extracellular fluid. Centrifuge is used to separate blood components. Colloid solution : solution w/ small solutes that do not settle out of the solution. Hco3- is also present to buffer the ph osmolarity + are carrier molecules - prevent swelling and shrinkage of cells acts as carrier proteins for immunoglobulins - defends body against foreign pathogens. Erythrocytes are major formed element (rbc) distinctive biconcave shape. Shape allows rbc to move through arteries, capillaries, veins. Capillaries only one cell thick so shape allows cells to bend/fold/stack to prevent blockages. Shear stress created by flexing causes release of signaling mols like atp. Also increases membrane surface area for gas exchange + diffusion. However: rbc do not have nuclei a nucleate and are non-mitotic & have very little dna, unable to synthesize proteins for repair. Rbc ejects organelles as they mature and become biconcave.
