The Physiology of Blood: 121 and 123

1
The Physiology of Blood 1/21 and 1/23

• How much blood do we have?
• How do we describe blood and the RBCs found in
  it?
• How do we form blood and the hemoglobin that
  carries oxygen in the RBCs?
• How long do RBCs last in the circulation?
• What happens when RBCs undergo lysis?
• How do we form a hemostasis?
• How do we break up blood clots?
• What are the drugs associated with manipulating
  the clotting process?

2
For the Friday Quiz limited to CH 17 (ch15 is
review right?)Quiz at last 20 minutes on Friday
at end of lecture
Please include First and Last name ID
Number Email Watch eraser quality! Fill dots
completely! Get new scantron if needed Written
questions ON BACK Extra Credit ON BACK
3
WHAT ARE THE BASIC FUNCTIONS OF BLOOD?WHY DO WE
NEED IT? (DO WE NEED IT?)

• Partial List of Functions
• 1 Oxygen/Carbon dioxide-
• 2 Nutrients/Wastes-
• 3 Hormones-
• 4 Protection-
• 5 Transport of Heat-
• Critical Concept Without hemoglobin inside the
  erythrocyte, your blood cannot deliver enough
  oxygen to keep you alive!
• Oxygen has a LOW solubility in water by itself.
• What does blood look like Oxygenated vs.
  Deoxygenate

4
HOW MUCH BLOOD DO YOU HAVE? Your body is mostly
water and the blood represents about 8 of your
body weight! (This will be a T.Q.)

• If a person weighed 220 lbs, how many liters of
  blood are there?
• If the person lost half their blood how much
  would you need to add to replace the lost blood?
• Memorize 1,000 ml H201 liter1 kg 2.2 pounds
• Assume 1kg body wt. is about 1 liter of fluid
• How many kg is the person? (220
  lbs)(1kg/2.2lb)100kg
• How much blood does the person contain? (100
  kg)(0.08)8 kg
• 8kg of blood is about the same as 8 liters of
  blood!
• To replace the lost volume you would need 4
  liters (half of what they started with).
• Try doing similar calculation for persons with
  different body weights on your own or in
  Supplemental Instruction.
• Folks have to do this all the time in an
  emergency room after major traumatic accidents.

5
What does a erythrocyte RBC look like and what is
so special about the shape?

• How many erythrocytes do we have in our
  blood? About 5 million/microliter?5
  billion/ml?5 trillion/liter
• Typical Size is 2X7.5 micrometers/cell
• What happens to the RBC size in hypertonic or
  hypotonic environments? When would crenation or
  lysis occur?
• RBCs have donut-like shape to maximize their
  surface area and the rate of oxygen and carbon
  dioxide diffusion into/out of the cell.
• Shape? Take a balloon and squeeze two sides
  towards the center
• Are there any RBC Organelles? NO!
• RBCs are Anucleate they cant replace proteins
  if they become damaged. This limits their
  life-span to about 120 days and this is a huge
  problem!

6
What are the characteristics used to describe
blood and the erythrocytes that contain the
oxygen carrying hemoglobin?
7

• RBCs are produced in the red marrow of bone in
  response to hypoxia and EPO.
• RBCs live and deliver oxygen for about 120 days,
  but they get old, damaged and fragile.
• Fragile RBCs are destroyed by the spleen and
  liver.
• RBC parts are re-cycled to make new RBCs
• With the exception of heme which leaves the body
  in the urine or feces.

8
Hypoxia stimulates the formation of the endocrine
hormone erythropoietin (EPO) by the kidney (also
liver). EPO promotes erythropoiesis in the red
marrow and ?? O2 carrying capacity.

• How Does Erythropoiesis effect PCV and oxygen
  carrying capacity of the blood (why is hemoglobin
  required)?
• Hypoxia is-
  Anoxia is not-
• Anemia is-
  Polycythemia is not-
• What stimulates erythropoiesis?
• Why is EPO involved with Olympic Athletes, High
  altitude, Emphysema, Smoking, Cancer treatment!
• Why do RBCs provide negative feedback to continue
  EPO secretion?

9
Erythropoietin is typically administered as a
recombinant protein.

• Recombinant means they clones the gene that makes
  it into a bacterial or other cell line. They
  then harvest the human protein and use it as a
  drug in humans.
• PROCRIT is a very popular form of recombinant
  EPO.
• See this link and consider these questions
• http//www.procrit.com/
• 1) Who does Procrit work for?
• 2) How does the drug work?
• 3) Why might taking it give you the ability to
  survive continued dialysis or chemotherapy?
• 4) What happens to the continuance of your
  treatment (dialysis, chemo or AZT) if you
  hematocrit is too low?

10
Excessive erythropoiesis (polycythemia) can be
fatal! Why cant welive permanently at an
altitude of above about 17,000 feet? What would
happen to your circulatory system if the PCV was
60? Why is this a potential problem for
athletes that abuse EPO? Why is EPO popular for
athletes in the Tour De France?
11
Erythropoiesis requires making new hemoglobin.
Iron is required for making functional
hemoglobin. Iron can only be added to the system
though intake in the diet. Often times people
(vegetarians) have problems related to iron
uptake from the gut and develop anemia.
Only 10-35 of Fe is absorbed (ferrous iron is
type found on hemes in meat) A meager 2-10 of
dietary Fe is absorbed (ferric iron type in
most plants)
12
RBCs last about 120 days. What happens to RBCs at
the end of their functional lifetimes?

• Volume produced/day
• Why does Red Cross gets a pint every 56 days?
• What are Old RBC/WBC Reserve Storage Sites When
  do they become clinically significant?
• Normal RBC Disposal
• Extra tiny 2-3 µM passages trap/test RBCs for
  viability in Spleen and Liver
• The good cells flex and pass through, while the
  old cells rupture (lysis)
• Macrophages and remnants create cellular waste
  Biliverdin/bilirubin/bile
• Potentially toxic to neonates/adults!

13
Red blood cell parts are recycled following lysis
in healthy bodies.Most RBC lysis occurs in the
spleen (Can you live after a splenectomy?)What
is the livers connection to hemoglobin,
bilinogen and jaundice? What happens to this
balance if you have malaria or sickle cell
anemia?
14
How are the types of anemia clinically
categorized?

• 1) Anemia from Inadequate Erythropoiesis
• -Inability to make Hb-
• -Inability to make RBC-
• -Nutritional causes-
• -Hormonal cause (kidney damage)-
• -Cancer treatment-
• 2) Hemorrhagic Anemia
• Blood Loss Acute or Chronic
• 3) Hemolytic Anemia
• A function of cellular fragility? Cell
  Hemolysis
• -Sickle Cell Anemia
• -Rh Factor and erythroblastosis fetalis

15
There are Three Sequential Steps that lead to
Hemostasis

• Injury to a blood vessel creates a chain
  reactions that lead to hemostatis.
• Does blood need to leave the body when you bleed?
  (Think Bruises!)
• 1) Vascular Spasm/Vasoconstriction Make Vessel
  Narrower
• Injury? Pain and synaptic endings on smooth
  muscle
• Also Epinephrine, Serotonin, Prostaglandins
• Ultimately?Smooth Muscle Cells Contract and
  Vessel lumen Narrows
• 2) Platelet Plug Formation Platelets adhere to
  the exposed collagen and to each other and begin
  massive degranulation!
• Degranulation/Exocytosis releases ADP, Serotonin,
  Thromboxane
• Positive feedback loop is initiated to make other
  platelets stickier to collagen and each other!
  Adherent platelets fill hole in vessel!
• 3) Coagulation or Clotting Blood Clot Formation
• Last but MOST EFFECTIVE HEMOSTATIC METHOD
• Non-sticky fibrinogen?sticky fibrin?TOUGH FIBRIN
  POLYMER
• Clotting Cascade describes the enzyme pathway
  leading to Polymer.

16
Prostacyclin and Nitric Oxide are produced by
healthy endothelial cells and prevent platelet
adhesion to vessel wall! No Clotting! Large
Clot Thrombus
17
Coagulation is initiated by chemical signals that
originate in the blood (intrinsic) or tissues
(extrinsic). The lack of a factor could be
fatal, and alternately inhibiting any step could
save your life!

• Preventative
• Drugs
• Aspirin
• Coumadin
• Warfarin
• Hirudin
• Problem Clots
• Heart Attack
• Stroke
• Pulmonary Emboli
• Bruise
• Hematoma

18
The inability to break up clots
(fibrinolysis/thrombolysis) is fatal! Why is
thrombolysis important if you experience a heart
attack? How does one balance hemostasis and
thrombolysis?
This lets blood flow to your heart return after a
temporary blockage by a clot. Hopefully blood
flow returns before the infarct is too large!
19
How do we manipulate blood clotting
clinically?Plasma has clotting factors intact
Serum has clotting factors removed

• Factors Preventing Blood Clotting
  collagen/tissue factor InvitroEDTA vs. calcium,
  Sodium citrate vs. calcium
• Invivo drugs and enzymes
• Coumadin vs. VitaminK
• Heparin vs. Thrombin
• Aspirin vs. Cyclooxygenase
• Genetics Hemophilia
• Factor VIII 1/5000 males, extremely rare in
  females AIDS risk in survivors of hemophilia
• Why are hematomas so common in persons taking
  anticoagulant medications? Why do they test
  clotting time so frequently?
• Factors Promoting Plasmin and Clot Lysis
• Tissue plasminogen activator and Streptokinase
• Anticoagulation therapy and potential for
  bruising in elderly?
• Effects of diet alcohol, garlic, grapes,
  cranberries?