Water, H2O
- Liquid at typical conditions of temperature and pressure
- Polar molecule
- Hydrogen bonding
- ‘universal solvent’ - many other chemicals/molecules like to bind to
and dissolve in water. This creates a solution.
– water = solvent
– other dissolved substance = solute
Diffusion
- A passive process, where chemicals move from high
concentration to low concentration - No energy is needed!
- This is simply following the 2nd law of thermodynamics
- Often we define the 2 spaces under consideration by using a theoretical separating line/plane or there is an actual barrier between the 2 spaces
- The rate of diffusion is proportional to the concentration differences
- Think of it as pressure
- Diffusion of water
- Often it is stipulated that it takes place across
a semi-permeable membrane so that only the
water moves and not any dissolved solute - Water essentially follows the solute
[water is the solvent, the chemicals dissolved in the
water are the solutes]
Fluid exchange at the capillary beds
- Fluid exchange at the capillary beds is a result of
osmotic and blood (hydrostatic) pressure forces - The high concentration of
proteins in blood (e.g. albumin)
creates a high osmotic force that
draws in water and helps to
retain water and volume to our
blood - High blood protein
concentration ~6mg/100mL - This is called oncotic pressure or
colloid osmotic pressure or
osmotic pressure
– around 25 mmHg
About 85% water is recovered – rest is recovered by lymphatic system
Lymphatic fluid collection
-Lymph retrieves excess interstitial fluid (ECF)and brings it back to blood
-The lymphatic
system is a one
way street. It
dumps fluid back
into the
bloodstream (at
the subclavian
veins near the
shoulders).
Lymphatic fluid collection diagram
Capillary types vary for diffusion and
transport purposes
Blood and pH
- pH is a measure of hydrogen ion (proton, H+
) concentration
– Scale of 1-14 (negative log transformed numbers)
– Low = acidic, High = basic/alkaline, 7= neutral - Acceptable blood pH range is rather narrow
– pH = 7.32-7.46 - Metabolism in cells and tissues generates many waste products that are acidic
(give off H+)
– e.g. lactate, pyruvate - Blood pH is largely regulated by bicarbonate (HCO3) = buffer
- When the pH level drops too low (high H+
levels):
– acidemia and acidosis - When the pH level rises too high (low H+
levels):
– alkalemia and alkalosis
Blood gases – CO2
- 200mL/minute are created from tissue metabolism
– Tissue = 46mmHg CO2
– Blood = 46-40mmHg CO2 - varies: higher in venous vs. arterial
- found in/outside cells as HCO3 and CO2 gas
– CO2 gas is about 7%, a little higher % and our blood would bubble!
– Incoming air = 0.3 mmHg CO2 - Flows by diffusion ‘downhill’ from tissues cells, to
blood, to the air in lungs
Blood gases – O2
- O2 is needed to accept electrons stripped away during
the process of aerobic respiration and oxidation that
our energy-harvesting metabolism is based upon - Ultimately, it acts as a e-waste acceptor
- The O2 concentration (pressure) is essentially the
reverse of CO2 - There are some other differences
– O2 is not as soluble as CO2 in water or plasma
– O2 is not directly contributing to pH - Each breath brings in about 20mL of O2 @160mmHg
– (air is essentially 79% N2 and 21% O2) - O2 partial pressure in alveoli ≈ 100 mmHg
- At tissue cells ≈ 20-40 mmHg
- But O2 solubility in plasma 1-2 mmHg
- Question: How is this O2
diffusion problem solved? HEMOGLOBIN
Hemoglobin!
- An assembly of proteins and prosthetic groups called heme
- 2 a-globin proteins, 2 b globin proteins
- ab dimers assemble into a tetramer
- Each globin protein is associated with a heme group
- Each heme group can bind a single O2
molecule - 270 million Hb/RBC (makes up 95% of mass of RBC that is not
water, almost crystalline or solid protein!) - Thus, each RBC can carry over 1 x 109
O2 molecules! - Allows blood to saturate with O2
(@ incoming level of 100 mmHg) - Effectively act as a sink or reservoir for O2
in blood - Globin proteins come in several forms from several genes, that is there is a gene family:
– a, b, g, d, e - Ancestral or earliest form was probably like myoglobin: a similar O2
-carrying protein in muscles and other tissues - Hemoglobin discovered in 1850, Otto Funke
- Hoppe-Seyler separates into protein and heme and gives it the name hematin, 1864-65
- MacMunn states that Hb is related to myoglobin (myohematin) but
Hoppe-Seyler disagreed - Many biochemical/genetic firsts were accomplished through the study of hemoglobin (X-ray structure, a.a. sequencing, balanced polymorphism)
Heme and Iron
- Heme is a type of porphyrin
- Porphyrins are multi-aromatic ring
structures: tetrapyrrole - Excellent shape for coordinating metal
atoms, e.g. Fe, Cu, Co, Ni - Excellent at absorbing electrons and
energy - Same porphyrins are found as electron
shuttles in mitochondria and chloroplasts - Light absorbing properties also produce
color. Many pigment molecules are built
out of these - It is has been suggested that life would
not be possible without such molecules - Iron atom, Fe, can exist in 2 redox states
– losing electrons is oxidation (LEO)
– gaining electrons is reduction (GER) - Fe3+ or ferric form = oxidized (methemoglobin
form) - Fe2+ or ferrous form = reduced
- The reduced form binds O2
, and oxidizes Hb - Release of O2 reverses this and we go back to the
reduced state - These changes are responsible for the color
changes of blood (red with O2
to dark red or
‘blue’ without O2) - Iron deficiencies create anemias, but excesses
can also cause problems
“Blue blood” or “Blue blooded”
– Apparently this terms derives from a
usage or application by the Castilian
aristocracy of Spain
– They were light skinned and wanted to
distinguish themselves from
competing claims of nobility by those
that were dark skinned
– You could only see the blue blood in
pale, white skin – a supposed sign of
true nobility and revealing ‘pure
blood’ or ‘noble race’
Bloody Queen Mary
– Mary Tudor or Mary I
– Queen of England 1553-1558
– Father is Henry VIII and is first
women to lead England on the throne
– A Catholic notorious for
condemning nearly 300
Protestants to death in an attempt
to reverse the Reformation
Hemoglobin and O2
binding
- Binding of O2
generates increased affinity for additional binding - This is known as cooperativity and is an emergent property
- Driven by allostery: a binding event that produces a change in shape and this improves the ability for O2
-Fe2+ interaction
(so called T-R state transition) - Results in a sigmoidal binding or oxygenation curve (aka
association/dissociation curve)
– Means that even at low oxygen pressures, Hb is good at binding O2 and is saturated even at low pressures
– The hemoglobin polypeptides also ensure that heme/Fe binding to O2 is not too tight and is reversible (remember that we have to go
back down the curve too)
Btw, carbon monoxide (CO) binds heme in an irreversible manner (250X tighter than O2) and makes blood bright, cherry red. O2 can no longer bind: Hb has been ‘poisoned’!!!
Metabolic modification to Hb oxygenation
rate is based on allostery
Why Blood?
Blood Clotting
- Complex process to prevent blood loss or
hemorrhaging - Aka, hemostasis, coagulation, thrombosis
– A clot may also be called a thrombus - Positive feedback loops drive the process
- Overall, it relies on tissue factors, platelets, many
proteins, enzymes, and cofactors - Lack of these can produce deficiencies in blood
clotting, known as hemophilia (lack of platelets
known as thrombocytopenia) - Key clot formers:
– Platelets
– Fibrinogen
– Thrombin
– Coagulation factors (e.g. Factor VIII) - vitamin K plays a role in producing thrombin and several coagulation factors
and it is what warfarin (a common blood thinner) inhibits
– Calcium (Ca++ ) - citrate binds this to limit its participation in clotting
- Key clot inhibitors
– Antithrombin/heparin - Key clot dissolvers (fibrinolysis):
– Tissue plasminogen activator (tPA)
– Plasminogen
Queen Victoria of England
(1837-1901)
– Likely carrier of X-linked mutation
in Factor IX of clotting pathway
– Passed on to several offspring: son
(Leopold) who had hemophilia and
two daughters (Alice and Beatrice)
who were carriers
– Marriage into Russian nobility
leads to another royal lineage
affected (Alexei Nikolaevich, heir
to Russian throne until Bolshevik
revolution of 1917)
