Anatomy

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Anatomy PhysiologyBio 2402 Lecture

• Instructor Daryl Beatty
• Day 2 Class 2
• Hemostasis, Bleeding Disorders

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Review

• Look back at first day

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Microscopic view - Whole Blood
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Microscopic view - Whole Blood

• Plasma
• Formed Elements
• Erythrocytes
• Leukocytes
• Thrombocytes
• Blood Proteins (in solution)
• Electrolytes (in solution)

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Erythrocytes - Morphology

• Bi-concave disk
• Benefits
• Flexible
• Maximum surface/volume ratio
• Size - uniform

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Erythrocytes - Components

• Water 65
• Hemoglobin 35
• No
• Nucleus
• Cell organelles

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Hemoglobin Structure
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Hemoglobin Structure

• 2 Types Globin Chains Alpha, Beta, 2 each
• Pigment - Heme

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Hemoglobin Chemistry

• O2 binds to heme (Iron) 97 carried this way
• CO2 binds to globin 20 bound, 80 free in
  plasma
• CO2 causes acidity in plasma, effects the pH
  balance of the blood (later chapter)
• Blood can carry both at one time different
  binding

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Sickle Cell Trait Disease

• Discovered 1904 man from Grenada
• Beta chain has 146 Amino acids position 6 is
  altered.
• Causes the Hb to become sticky, especially when
  Hypoxic
• Trait half Hb is normal
• Disease all Hb is sickle - fatal

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Sickle Cell Trait Disease
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Sickle Cell and Malaria

• Mutation arose thousands of years ago in Malarial
  Africa
• Millions die of malaria there
• Homozygous (Disease) is always fatal
• Trait conveys resistance to malaria -

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Thalassemia

• Another defect of Hb, where either the alpha or
  beta chain is missing or defective
• Hundreds of different types, many mutations can
  cause them
• All detrimental, some malarial protection

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Interesting sidelight

• Malaria (Plasmodium falciparum) has mutated to
  chloroquine resistance (change at 2 points in a
  protein) happened only twice in history
• Human Hb has mutated to malarial resistance (one
  point in a protein)
• Simple changes, random mutations can easily
  explain and adapt to
• What about more difficult and complex problems?

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Erythropoiesis

• Process (Page 652)
• Hemocytoblast stem cell directs ribosomes to
  make globin for Hb.
• Happens in red marrow
• Takes 3-5 days and becomes committed

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Erythropoiesis

• Dietary Requirements
• Adequate Protein
• Carbs Lipids
• Iron, B-12, Folic Acid

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Erythropoiesis Clinical Significance

• Normal Reticulocyte count 1-2
• High count Cancer, internal bleeding,
• Low count Radiation, chemotherapy, resulting in
  anemia.
• See picture

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Regulation of Erythropoiesis

• Page 653 Diagram

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Clinical Significance- Bilirubin

• Jaundice also called Bilirubinemia
• What is the cause?
• RBCs may breaking down at high rate
• Liver may not be processing bilirubin
• Cirrhosis
• Hepatitis
• Bile duct may be occluded (gall stones)
• Infants GI tract may not be prepared to
  eliminate it. (HDN Hemolytic Disease of the
  Newborn)

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Erythropoiesis Clinical Significance

• Anemia Not enough RBCs
• Discuss several types later -

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Blood Disorders

• Disorders of the Erythrocytes
• Polycythemia
• Anemia

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Anemias (Page 655)

• Several different types
• May be insufficient number of RBCs
• May be enough, but not functioning
• KEY Not enough Oxygen reaching the tissues,
  caused by insufficient carrying capability of the
  blood.

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Anemias Symptoms

• Lethargy
• Loss of stamina energy
• Winded rapid respiration
• Pallor
• Depressed metabolic rate

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Anemias Types (655)

• Hemorrhagic internal bleeding
• Hemolytic anemia erythrocytes rupture
  prematurely
• Aplastic anemia Red marrow not functioning,
  (drugs, radiation, virus,)
• - It also results in loss of immunity and
  clotting.
• - Treatment with cord blood or bone marrow
  transplant

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Polycythemia

• Excessive levels of RBCs
• Polycythemia Vera Type of Bone Marrow cancer
• Count may be 8-11 M vs. 4-5 M cells/ ul
• Hematocrit may reach 80
• Blood volume may double
• Treated remove blood and replace with saline

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Polycythemia

• Excessive levels of RBCs
• Secondary Polycythemia 6-8 M RBCs/ul commonly
  those living at high altitudes.

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Clotting Reaction (Hemostasis)

• AP 1 review remember 2 instances of positive
  feedback?
• Childbirth
• Blood Clotting

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Hemostasis

• Hemostasis Clotting sequence
• Must be limited to area of damage
• Three main steps

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Hemostasis Three steps(663)

• Vascular Spasm Step 1
• What is a muscle spasm?
• Structure of the vessel? Smooth muscle in wall
• Reaction to injury spasm
• Reduces diameter
• Cuts flow almost instantly

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Hemostasis Step 2

• Platelet Plug Formation Step 2 (665)
• Smooth vessel walls do not attract platelets
• (Blood vessels platelets both charged)
• Rough surfaces cause platelet adhesion
• Once attracted, they release serotonin (enhance
  the vascular spasm)
• Also, ADP, Thromboxane A (prostaglandin)
• Within one minute this occurs
• Platelet plug will stop very minor leaks
• If a severe cut, we move to step 3.

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Hemostasis Step 3

• Coagulation Page 664
• Very complex about 30 substances
• Good illustration of irreducible complexity
• 13 clotting factors most from liver
• About 30 total chemicals

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Coagulation -Two triggers

• Intrinsic
• Extrinsic

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Coagulation Key step 1

• Either route leads to PTA (Prothrombin Activator)

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Coagulation Key step 2

• PTA catalyzes Prothrombin to Thrombin

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Coagulation Key step 3

• Thrombin converts Fibrinogen to Fibrin.
• Fibrin is insoluble (picture on next slide)

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Coagulated Clotted

• End product Clot formation
• RBCs connected by Fibrin
• Where are the platelets?

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Hemostasis Summary

• Coagulation Page 664
• Very complex about 30 substances
• 13 clotting factors most from liver
• About 30 total chemicals
• Illustration of irreducible complexity
• Contrast to adaptation of sickle cell to
  P.falciparum (Malaria).

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Hemostasis Clinical Application

• Drugs may interfere with clotting (can be good or
  bad)
• Aspirin Often recommended for those over 50,
  reduces stickiness of platelets.
• Coumadin Maintenance for those prone to
  clotting and in atrial fibrillation
• Plavix Newer maintenance drug
• Heparin Used in IV lines and blood collection
• Typically suspend these before surgery

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Hemostasis Clinical Application

• Larger cuts stimulate faster clotting
• Major arterial bleeding has too much pressure for
  clotting (aneurisms and trauma lethal)

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Bleeding Disorders (667-8)

• Thromboembolic Conditions
• (Defined as formation of undesired clots)
• Thrombus (Stationary clot) obstructing flow
• strokes, heart attacks, DVTs
• Atheroschlerosis plaque deposits
• Embolus portion of a thrombus which has broken
  free into the blood flow, (or any other material
  that can obstruct flow.)

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Bleeding Disorders (667-8)

• Thromboembolic Conditions
• DIC Disseminated intravascular coagulation
• Widespread clotting
• Severe Bleeding
• Why both?
• Causes are
• Septicemia
• Incompatible transfusions

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Bleeding Disorders (667-8)

• Thromboembolic Conditions
• Thrombocytopenia (668)
• Spontaneous bleeding widespread
• Caused by bone marrow suppression
• Sign - Platelet count of lt50,000/ul
• Platelet transfusions for temporary relief.

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Bleeding Disorders (667-8)

• Hemophilia
• Hemophilia A most common
• Genetic expressed mainly in males
• Hemophilia C less common, both sexes
• Symptoms joints debilitated, bleeding, bruising
• Genetic defect of clotting factor.
• Treatment Plasma transfusions, Synthetic
  factors now available.

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Bleeding Disorders (667-8)

• Role of impaired liver function (Cirrhosis
  Hepatitis)
• Synthesizes the pro-coagulants
• Also produces bile
• Bile is important in fat absorption
• Vitamin K from bacteria is fat soluble, and hence
  hard to absorb with poor fat digestion.
• Vitamin K is one of the critical clotting
  factors, and is absorbed from the Large Intestine
  -

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Steps in Healing 1. Clot retraction

• Platelets contain contractile proteins (Actin
  Myosin) and growth factors for vessel repair
• Begins rapidly within about 1 hour
• Review Primary Secondary Unions

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Steps in Healing 2. Fibrinolysis (Pg 666)

• Define Fibrinolysis - Breaking up the clot
• Plasminogen is in the clot (inactive form)
• Plasmin is a protein digesting enzyme
• TPA Tissue Plasminogen Activator released about
  2 days later from the cells of the endothelium of
  the vessel.

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Clinical Application

• TPA Tissue Plasminogen Activator
• Clinical Application TPA also used in ischemic
  strokes and some heart attacks
• Must be given in first 4 hours
• What happens if TPA given in hemorrhagic stroke?

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Undesired Clotting

• Why would plaque initiate clotting?

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Factors Limiting Clot Formation

• Homeostasis
• Removal of clotting factors quickly
  (concentration away from site)
• Inhibition of clotting factors must reach a
  critical concentration to trigger the sequence.

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Factors Limiting Clot Formation

• Platelet charge () repels vessel wall
• Natural Anticoagulants
• Antithrombin III prevents Thrombin activity
• Prostacyclin inhibits platelets from sticking
• Heparin- from endothelium and Basophils masts
• Vitamin E Inhibits platelets (but some
  studies have not shown it to reduce heart
  attacks, as aspirin will).

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Factors Limiting Clot Formation - Application

• Blood flow prevents coagulation
• DVT Deep vein Thrombosis from sitting
• Blood transfusion Storage
• Citrate or oxalate is used to bind Ca.
• Heparin is used in IV lines. -

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