and Blood Body Defenses
Jim Pierce Bi 145a Lecture 10, 2007-08
Blood
Blood is a connective tissue
Cells Extracellular Matrix
Blood
Hematopoeisis in utero
Hematopoeisis in utero
Hematopoiesis
Bi 214 Hematopoiesis
Great model of: A Developmental System Cell Differentiation Cell Signaling Epigenesis
Hematopoietic Systems
Reticuloendothelial System
Comprised of
Endothelial Cells Monocyte Derivatives Hepatocytes
Located
Bone Marrow Liver Spleen Blood Vessels
Hematopoietic Systems
Reticuloendothelial System
Roles
Making
new hematopoietic cells Making new connective tissue cells (??) Cleaning up old circulating cells
Control
of iron metabolism
Bone Marrow
The "classic" location of Hematopoiesis
Thymus
Child Thymus
(in adult it's mostly fat)
Spleen
Spleen
Spleen
Liver
We'll talk more about the liver next term
Hematopoietic Systems
Mononuclear Phagocyte System
Comprised of
Monocyte
derived cells
Located in
Every
part of the body
Hematopoietic Systems
Mononuclear Phagocyte System examples:
Kupffer
cell in the liver Alveolar macrophages in the lung Professional antigen presenting cells like the dendrititc cell in the lymph node Peritoneal macrophages in the abdomen Osteoclasts on the bone Microglia in the nervous system Histiocytes in the connective tissues Giant cells at the site of a granulomatous infection Macrophages in a maturing scar
Hematopoietic System
We'll talk more about these monocyte derived cells in each organ system For further discussion of immune function check out Bi 114 - Immunology
Hematopoetic Cells
Red Blood Cells White Blood Cells Platelets
Megakaryocytes Pluripotent Stem Cells Multipotent Stem Cells
Bone Marrow Aspiration
Bone Marrow Biopsy
Peripheral Blood Smear
Lymphocyte
Monocyte
Neutrophils
Eosinophil
Basophil
Megakaryocyte
Erythrocytes
Erythrocytes
Erythrocyte population is in steady state equilibrium Erythrocytes are constantly produced
Erythrocytes
Interestingly, the bone marrow churns out huge numbers of committed progenitors who would become erythrocytes Most of these undergo apoptosis Erythropoietin is the "survival factor"
Hematopoiesis
Hematopoiesis, in general, is a wonderful model system for considering positive and negative factors controlling cell proliferation and differentiation
Cells and Cell Functions
Red Blood Cell
Transport
Oxygen Carbon Protons Large
Dioxide
Proteins by Cell Surface Receptors
Cells and Cell Functions
Red Blood Cell
Metabolism
Acid-Base
Metabolism Repair of Oxidative Stress Repair of Reductive Stress Catabolism of neurohormones
Cells and Cell Functions
White Blood Cells
Body Defense
Self
versus Non-self Self versus Damaged-self Innate versus "thinking"
Cells and Cell Functions
White Blood Cells
Body Repair
Wound
Healing Scar Maturation
Metabolism
Control
of blood ECM (regular, acute inflammatory, chronic inflammatory) Control of body Iron stores
Cells and Cell Functions
Platelets
Coagulation Anticoagulation Thrombolysis Inflammation Wound Healing
Extracellular Matrix
Plasma versus Serum
Clotting Factors, Fibrinogen
Serum Protein Electrophoresis
Albumin Globulins
Alpha-1,
Alpha-2, Beta-1, Beta-2 "Gamma"-globulins (immunoglobulins)
SPEP
Serum Protein Electrophoresis
SPEP band intensity
Gamma Globulins
Extracellular Matrix
Proteins and their bound water Small covalent compounds
Some bound to protein (lipophilic) Some with bound water
Lipoproteins Salts and their bound water
Sodium, Chlorine Bicarbonate
Extracellular Matrix
The source of the ECM is wide spread.
Proteins often come from the liver Salt is often regulated by the kidneys Acid / Base balance is regulated by the kidneys and the lungs Hormones are produced and consumed everywhere.
Plasma Functions
Coagulation and Inflammation Transport
The ECM that does not rely just on diffusion Nutrients and Wastes Signals (Endocrine, Neuroendocrine, Immune) Cells
Metabolism
Blood Transport
One of the main roles of the blood is Gas Transport The first way we can describe "amount of gas" is by partial pressure pO2 = partial pressure of oxygen pCO2 = partial pressure of carbon dioxide
Gas Transport
The second way we can describe "amount of gas" is by concentration (Volume of gas per Liter of blood)
CO2 = Oxygen concentration (in mL/L) CCO2 = Carbon dioxide concentration (in mL/L)
It's a silly and confusing symbol to use capital C for this purpose
Gas Transport
Why Concentration (ml/L)? Tissue consumes mL of O2 / min
Heart pumps L of blood / min Blood carries mL of O2 / L blood
Thus, heart delivers mL O2 / min
Gas Transport
Why Concentration (ml/L)? Tissue produces mL of CO2 min
Heart / pumps L of blood / min Blood carries mL of CO2 / L blood
Thus, heart delivers mL CO2 / min
Oxygen Transport
Oxygen Transport (Gas Number One) Oxygen does not dissolve well
One liter of plasma holds 3 ml Oxygen One liter of blood has 55 % plasma Thus, one liter of blood carries only 1.65 ml Oxygen
Oxygen Transport
The Erythrocyte has specialized to carry Oxygen
Hemoglobin and Hemoglobin Allostery One g of Hemoglobin carries 1.34 ml Oxygen One dL of Blood has 14 g of Hemoglobin Thus, one liter of blood carries 187 ml Oxygen
Hemoglobin
Oxygen Transport
Hemoglobin
Tetrameric Tertiary Structure Two each of alpha and beta globulins Each globulin has a heme group with an iron
These irons are in the reduced state (Fe++) The oxygen is bound as a ligand to iron with no electron transfer (oxygenated not oxidized)
There is sigmoidal oxygen binding from allostery
Oxygen Transport
Hemoglobin Saturation
As pO2 increases, hemoglobin carries more O2 There is a maximal carried O2
Experimentally
found to be 1.34 mL per g Hgb
For a given concentration of hemoglobin, we can describe the amount of oxygen carried by the hemoglobin saturation. Sat Hgb % = actual carried O2 / maximal O2
Oxygen Transport
Oxygen Transport
Concentration of Oxygen
The total number of milliliters of oxygen carried per liter of blood.
CO2 = (mL dissolved O2) + (mL carried O2) CO2 = (.003 * pO2) + (1.34 *Hgb Sat%)
Oxygen Transport
Saturation of Hemoglobin
CO
2
= (.003 * pO2) + (1.34 *Hgb Sat%) % = CO2 / (1.34 *Hgb)
Saturation
Knowing saturation gives us an idea of:
Volume of gas (see above) Partial pressure of gas (allosteric binding)
That's why we like Saturation so much
Oxygen Transport
Measuring Saturation of Oxygen
Iron absorbs light Different ligands change iron's absorption Hemoglobin absorbs light
Different ligands change hemoglobin's absorption. Different hemoglobin saturations cause differing absorption.
Oxygen Transport
Co-oximitery
Beer's Law A=BC Lots of Beer's Law A=B1C1+B2C2+ ...
For each wavelength used...
we observe % absorbed
That tells us some linear combination of the concentrations of everything that absorbs that wavelength.
Oxygen Transport
Co-oximitery
The two most common iron states in blood:
Fe++ Fe++
- Heme, H2O Ligand Bonding - Heme, O2 Ligand Bonding
Other reasonably common iron states:
Fe++
- Heme, CO Ligand Bonding Fe+++ - Heme H2O Ligand Bonding
Oxygen Transport
Co-oximitery
One sample of blood, one concentration of Hgb Four amounts of each iron state Four wavelengths Four absorbances Four linear combinations of these four states One linear combination of four states = total Solvable for percent hemoglobin in each state.
Oxygen Transport
Co-oximitery
Results:
% %
Saturation O2
Unsaturated Hgb % Saturation CO % Methemoglobin
Pulse Oximetry
Pu...