What are the Components of blood plasma?

(centrifuge)

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• 90% Water w/ solutes: Na+,K+, Cl-, Ca2+, Fe2+, CO2, O2, glucose, hormones, etc.
• Plasma proteins: 8% by weight
• Albumin-60% of plasma proteins

• Most abundant plasma protein
• same stuff as in egg whites
• synthesized in the liver
• carrier protein for lipophilic hormones & other substances
• Provides osmotic pressure for blood:
• Draws water into the blood

• Erythrocytes (RBCs)
• Leukocytes (WBCs)
• Plateletes

• Red Blood Cells
• Annucleate biconcave disc
• Essentially bags of hemoglobin (Hb)

What is Hemoglobin and it's functions? (Hb)

Globin protein = Heme Group

• Globin protein: 4 poly peptide chains
• 2 alpha chains + 2 beta chains
• Amino acids of globin carry CO₂
• Heme groups: contain Fe²⁺ which binds with O₂ at the lungs

• Oxyhemoglobin: Fe²⁺ picks up O₂ at lungs
• Deoxyhemoglobin: Fe²⁺ releases O₂
• Carbamino-hemoglobin: globin picks up CO₂ at tissues

Definition of

Hematopoiesis and Erythropoiesis

• Hematopoiesis: Blood Cell Formation
• Erythropoiesis: Red Blood Cell Formation

1. Hemocytoblast becomes committed to erythropoieses
2. Phase 1: Ribosome synthesis (Erythroblast)
3. Phase 2: Hemoglobin accumulation (Normoblast)
4. Phase 3: ejection of nucleus and release into blood stream (Reticulocyte)
5. Becomes Erythrocyte in the blood stream.

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Reticulocyte Count

Should be 1-2% of RBCs

Low count indicates that marrow isn't producing enough RBCs

• Kidneys produce hormone, erythropoietin (EPO) when O₂ in blood is low
• EPO stimulates erythropoiesis in bone marrow.

** EPOgen is genetically engineered EPO. Helps people with anemia due to kidney failure and can be abused by athletes.

• When RBCs age they are removed from circulation and destroyed by macrophages that are primarily in the spleen but also in bone marrow and liver.
• Hemoglobin is released from the phagocytized RBCs.

• Fe is released to the blood and transported to liver by transferrin(protein) and stored as ferritin(protein)
• Heme without Fe is converted to bilirubin (in macrophages) then released to the blood and transported by albumin to the liver.
• Globin(protein) is broken into amino acids which are reused in the cells to form other proteins

• Bilirubin is then secreted into bile and leaves body via the intestine.
• Metabolites of bilirubin turn feces brown, and urine and blood plasma yellow.
• High levels of bilirubin (or problems removing it) result in jaundice: yellow skin, sclera, mucous membranes.

• Anemia: Too few RBCs; low O₂ carrying capacity of the blood. 
• Low O₂ -> Low ATP -> cold, fatigue, pale
• Polycythemia: Too many RBCs
• Normally seen in athletes and people who live in high altitudes.
• Polycythemia vera is a bone marrow cancer which increases viscosity of blood and inhibits circulation. Characterized by dizziness and very high RBC count. (8-11 mill)

• Iron deficiency anemia-most common
• Pernicious Anemia:
• Lack of Vitamin B₁₂-needed for DNA synthesis to form RBCs.
• Usually an absorption issue- lack of intrinisic factor.
• intrinsic factor is produced by gastric mucosa which can be partially destroyed by immune system.

Iron deficiency anemia-most common

AKA microcytic anemia

• caused by blood loss or not enough Fe in diet
• RBCs are small and pale- microcytic anemia

• Lack of Vitamin B₁₂-needed for DNA synthesis to form RBCs.
• Usually an absorption issue- lack of intrinisic factor.
• intrinsic factor is produced by gastric mucosa which can be partially destroyed by immune system.
• Fewr RBCs which are large- macrocytic anemia

• The 6th amino acid (out 146) on the beta chain of Hb is abnormal.
• This causes the cell to take on a sickle shape in low O₂ conditions. 
• Sickle cells cause capillaries to clog which leads to organ disfunction and pain.
• RBCs are removed from circulation more readily which leads to anemia & jaundice

• Having 2 genes= Sickle cell disease
• Having 1 gene= Sickle Cell trait.
• Sickle Cell Trait protects against Malaria. 
• This is why Sickle Cell Disease is more common in countries where Malaria is a problem.

• Have a nucleus and organelles unlike RBCs
• Less than 1% of blood volume
• Use blood for transport
• Increase greatly in times of infection.
• Move through tissue by amoeboid motion and are attracted by molecules released by injured cells (positive chemotaxis)

• Granulocytes: have granules
• Agranulocytes: Don't have visible granules.

• Neutrophils
• Eosinophils
• Basophils

• Lymphocytes
• Monocytes

Never Let Monkeys Eat Bananas

Most abundant--------------------------------Least abundant

1. Neutrophils 
2. Lymphocytes
3. Monocytes
4. Eosinophils
5. Basophils

• Granulocyte
• Most abundant- 50-70% of WBCs
• Lilac colored cytoplasm
• Some granules are like lysosomes and others have defensive molecules (defensins) to fight bacteria
• Major phagocytes- take in bacteria and granules destroy it
• 3-6 lobed nucleus- In medicine neutrophils are called polymorphonuclear-PMNs or polys

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• Agranulocyte
• 25% of WBCs
• Large spherical nucleus that takes up most of the cytoplasm
• 2 types:
• B Lymphocytes: transform into plasma cells and produce anitbodies
• T lymphocytes: Destroy cancerous and virus infected cells

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• Agranulocyte
• 3-8% of WBCs 
• Largest of WBCs
• Leave the blood stream and transform into macrophages especially during chronic infections
• Phagocytize bacteria and can remove dead tissue debris
• Activate T & B cell lymphocytes in immune response

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• Granulocytes
• 2-4% of WBCs 
• Take eosin: red acidic stain
• granules are lysosome like
• bi-lobed nucleus
• Destroys parasitic worms by degranulating
• also increased in allergies and asthma

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• Interluekins (ILs)
• Colony Stimulating factors (CSFs)
• G-CSF stimulates production of neutrophils
• Neupogen (commercial G-CSF) is given to cancer chemotherapy patients when their neutrophil count falls.

• Magakarocyte gets close to a capillary (sinusoid) & fragments of the cell enter the blood stream as platelets

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• ADP-
• Thromboxane A2
• Serotonin

1. Vascular spasm: smooth muscle in blood vessels contract (vasoconstriction) to keep blood away from the tear.
2. Platelet plug formation: Tear in vessel allows collagen fibers to be expressed. Platelets become sticky by releasing granule contents and respond to positive feedback system.
3. Coagulation (Clotting): Complex process

• Complex process with 30 clotting factors that leads to a meshwork of fibrin that hold the torn vessel together until it's repaired
• Damage activates a protein factor that activates another factor until prothrombin activator is formed.
• Prothrombin--->Thrombin--->Fibrinogen
  --->Fibrin: crosslinked to create fibrin meshwork
  --->Clot: Strengthens and replaces platelet plug.
               Holds vessel together until tissue repair
               occurs 

1. Nearby blood vessel cells produce tPA (tissue Plasminogen Activator)
2. tPA activates Plasminogen within clot
3. Plasminogen produces Plasmin (proteolytic enzyme)
4. Plasmin breaks down fibrin-->Clot dissolves

** Genetically engineered tPA is a clot buster for heart attack and stroke victims. 

Condition in which one clotting factor is missing.

Even very small wounds can be life threatening