Lecture Outline: Blood, Hemopoiesis, and Hemostasis
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    - Introduction to the Circulatory System and Blood
        
            - Official Organ Systems
                
                    - 11 official organ systems exist
- The circulatory system is an official organ system
- The cardiovascular system is NOT an official organ system
                        
                            - Cardiovascular refers to the heart (cardio) and vessels (vascular)
- It does not include blood
- It is not considered a complete organ system
- The circulatory system, however, includes the heart, vessels, AND blood
 
 
- Lecture Structure
                
                    - The circulatory system lecture is split into two slideshows
- The first slideshow focuses on Blood
- The next slideshow will cover the cardiovascular system, which comprises the rest of the circulatory system after blood
 
- Blood as a Connective Tissue
                
                    - Blood is histologically categorized as a connective tissue
- All connective tissues contain two major components:
                        
                            - A cellular component
- An extracellular matrix
 
- Blood adheres to these guidelines, having both components
 
 
- Components of Whole Blood
        
            - The Formed Elements (Cellular Component)
                
                    - Constitute slightly less than half of whole blood volume
- They include all blood cells and platelets
- There are six major kinds of formed elements:
                        
                            - Red Blood Cells (Erythrocytes)
                                
                                    -  Only one kind is found in each human
-  They vastly outnumber white blood cells and platelets
-  Approximately 5 million are present per cubic millimeter of blood
 
- White Blood Cells (Leukocytes)
                                
                                    -  There are five different kinds
-  They fall into two main categories
 
- Platelets
                                
                                    -  They are not truly complete cells, lacking a nucleus
-  They are cell fragments with a cellular origin
-  They are included in the formed elements due to their cellular origin and membrane
-  There are typically 150,000 to 400,000 platelets per cubic millimeter
-  They are very tiny, contributing little to the overall volume of blood
 
 
 
- The Extracellular Matrix (Plasma)
                
                    - It comprises everything else besides the formed elements
- It makes up a little over half of whole blood volume
- After centrifugation, it floats above the formed elements because it is less dense
- Its composition includes:
                        
                            - Mostly water (90%)
- Various solutes:
                                
                                    -  Salts (electrolytes)
-  Plasma proteins (dissolved proteins carried in the blood)
 
- Transported substances, whose levels can fluctuate:
                                
                                    -  Nutrients: such as glucose, fatty acids, amino acids, and vitamins
-  Waste products: including urea and uric acid, resulting from the breakdown of proteins
-  Respiratory gases: primarily oxygen and carbon dioxide
-  Hormones: picked up from glands and distributed throughout the body, affecting only cells with specific receptors
 
 
 
 
- Red Blood Cells (Erythrocytes)
        
            - Appearance and Structure
                
                    - In prepared slides, they appear as small brown or pink circles and are far more numerous than white blood cells
- A healthy red blood cell has a biconcave disc shape
                        
                            - It is caved in on both sides, resembling a donut without a complete hole
- This shape allows for the maximum possible hemoglobin content
 
- Mature red blood cells lack a nucleus
                        
                            - The nucleus is lost during their development
- This leads to a short lifespan, requiring millions to be replaced daily
- They are an exception among most body cells, as most cells have one nucleus, and some are multi-nucleated
 
- Red blood cells are packed with hemoglobin, containing millions of molecules per cell
                        
                            - Hemoglobin is a protein
- It is produced based on instructions stored in DNA, specifically hemoglobin genes
- The unique sequence of amino acids dictates the protein's specific shape
 
 
- Function
                
                    - The main job of red blood cells is to carry respiratory gases
                        
                            - They pick up oxygen at the lungs and deliver it to body cells through reversible binding
- They pick up carbon dioxide from body cells and deliver it to the lungs for exhalation, also through reversible binding
 
- Oxygen is essential for cellular respiration, serving as the final electron acceptor in the process
- A circulatory system is necessary in large organisms for efficient oxygen delivery to deep cells, as diffusion alone is insufficient
 
- Sickle Cell Disease (Abnormal Red Blood Cells)
                
                    - This disease is caused by a mutation in the DNA, specifically a single nucleotide error in the hemoglobin gene
- This genetic error results in a wrong amino acid sequence for hemoglobin
- The abnormal hemoglobin causes the red blood cells to adopt a sickle shape
- The consequences include:
                        
                            -  Hemoglobin performs poorly in carrying oxygen and carbon dioxide
-  Hemoglobin molecules clump together, leading to the symptoms of the disease
 
- This illustrates the critical importance of the information contained in DNA for determining protein shape and function
 
 
- White Blood Cells (Leukocytes)
        
            - General Characteristics
                
                    - They are less numerous than red blood cells
- They are crucial for immunity, protecting the body from harm
 
- Granulocytes (characterized by visible granules under a microscope)
                
                    - Neutrophils
                        
                            - They are the most numerous white blood cell, making up 40-70% of all WBCs
- Their occurrence is typically 3,000-7,000 per cubic millimeter
- Their function is as phagocytes, meaning they perform "cell eating"
                                
                                    -  They engulf and remove harmful substances from the body
 
 
- Eosinophils
                        
                            - They are less numerous, comprising about 2% of WBCs
- Their functions include killing various kinds of parasitic worms and playing roles in allergy attacks
 
- Basophils
                        
                            - They are the rarest type of white blood cell
- They stain well with basic (alkaline) dyes
- Their function is in the inflammatory response
                                
                                    -  They release histamine, a chemical signal that causes vasodilation (widening of blood vessels), increasing blood flow to an inflamed area
-  They also release heparin, an anticoagulant that prevents blood clots from forming
 
 
 
- Agranulocytes (do not have visible granules)
                
                    - Monocytes
                        
                            - They are the largest of all white blood cells
- Their function is as phagocytes, acting as a "cleanup team"
                                
                                    -  They leave the bloodstream
-  They engulf debris and potentially harmful things outside the bloodstream
 
 
- Lymphocytes
                        
                            - There are several different categories of lymphocytes, such as B lymphocytes and T lymphocytes
- B lymphocytes are responsible for producing antibodies, which are vital for immunity
- T lymphocytes mature in the thymus, which is where their "T" designation comes from
- All blood cells, including lymphocytes, originate in the bone marrow
 
 
 
- Platelets
        
            - Description
                
                    - They are cell fragments, not complete cells
- They originate from huge cells that break into many smaller pieces
- Though very tiny, they are numerous, ranging from 150,000 to 400,000 per cubic millimeter
 
- Function: Hemostasis (the stoppage of bleeding)
                
                    - They are important in the formation of blood clots
 
 
- Hemopoiesis (Blood Cell Formation)
        
            - Stem Cells: These are cells capable of developing into several different kinds of cells
                
                    - This contrasts with non-stem cells, such as skin cells, which typically only produce copies of themselves
 
- Hemocytoblasts (also known as Hemopoietic Stem Cells)
                
                    - These are the stem cells responsible for producing all the formed elements of the blood
- They are located in the red marrow of bones
- When activated by specific signals:
                        
                            - One stem cell will replace itself
- The other will differentiate and develop into one of several formed elements
 
 
- Developmental Pathways from Hemocytoblasts
                
                    - Myeloid stem cells: These can develop into basophils, eosinophils, neutrophils, monocytes, platelets, or erythrocytes
- Lymphoid stem cells: These can develop into the major kinds of lymphocytes
 
- Erythropoiesis (The Specific Production of Red Blood Cells)
                
                    - This process is regulated by the oxygen level in the blood, maintaining homeostasis
- The stimulus for erythropoiesis is a decreased oxygen level in the blood, which can be caused by factors like a reduced red blood cell count due to bleeding, insufficient hemoglobin production, or low oxygen availability
- The kidneys are responsible for sensing low oxygen levels
- In response, the kidneys release the hormone Erythropoietin (EPO) into the bloodstream
- The target tissue for EPO are the cells in the red marrow (hemocytoblasts)
- The effect of EPO binding to these cells is the activation of stem cells to specifically produce more red blood cells
- The result is an increase in red blood cells, which enhances the blood's oxygen-carrying capacity, thereby returning the oxygen level in the blood to normal through negative feedback
 
 
- Hemostasis (Stoppage of Bleeding)
        
            - Definition: Hemostasis is the body's natural, built-in ability to stop bleeding after an injury occurs
- It occurs in sequential steps:
                
                    - Step 1: Vascular Spasm
                        
                            - The stimulus is a tear in a blood vessel, which exposes connective tissue to the blood that is normally only in contact with epithelial cells
- The response is a contraction of the smooth muscle lining the blood vessel
- The result is vasoconstriction, or narrowing of the vessel
                                
                                    -  This makes it harder for blood to flow through the injured area
-  It immediately reduces blood loss
 
 
- Step 2: Platelet Plug Formation
                        
                            - The process involves chemical signals released at the injury site, which instruct platelets to stick together
- The mechanism is the interaction of proteins located on the surface of these platelets
- The result is the formation of a platelet plug
                                
                                    -  This provides a quick, initial seal for the hole
-  However, it is not very strong and serves only as a temporary solution
 
 
- Step 3: Coagulation (Blood Clotting)
                        
                            - This step involves numerous plasma proteins
- A key protein is fibrinogen, which is normally a dissolved protein in the plasma
- An enzyme called thrombin, which is itself a protein, plays a crucial role
                                
                                    -  Thrombin is produced in response to the injury
-  It catalyzes the rapid conversion of fibrinogen into fibrin
 
- Fibrin is different from fibrinogen because it is insoluble and precipitates out of the plasma
- The result is that fibrin molecules form a strong mesh
                                
                                    -  This mesh traps red blood cells, which then die and harden, along with platelets
-  This collective structure forms what is called a clot, which is significantly stronger and provides a long-term solution compared to the platelet plug
-  The clot continues to harden over time, improving its effectiveness
 
 
 
- Clot Dissolution: Eventually, once the epithelial cells of the vessel heal and replace themselves, the body chemically dissolves the clot.
 
- Blood Typing (ABO Blood Group)
        
            - Importance: The ABO blood group is famous because incorrect blood transfusions can lead to death, unlike many other blood groups that typically do not cause problems
- Key Components:
                
                    - Antigens: These are foreign materials, such as molecules or parts of molecules, that the body is capable of recognizing
- Antibodies: These are proteins produced by the body specifically to recognize and target various kinds of antigens, similar to how vaccines work by stimulating antibody production against inactive antigens
 
- Red Blood Cell Antigens (located on the plasma membrane of red blood cells)
                
                    - A antigens
- B antigens
- These antigens are produced based on a person's genetic makeup, specifically the genes they possess for A and B antigens
 
- Plasma Antibodies (found in the plasma)
                
                    - These antibodies recognize and attack foreign antigens
- Crucially, a person does NOT produce antibodies against their OWN antigens, to prevent self-destruction
 
- ABO Blood Types and Characteristics
                
                    - Type AB Blood
                        
                            -  Antigens: Possesses both A and B antigens on red blood cells
-  Antibodies in Plasma: Has neither anti-A nor anti-B antibodies
-  Universal Recipient (of red blood cells): Can receive red blood cells from Type A, B, AB, or O individuals, because the AB person has no antibodies to attack them
-  Plasma Donation: Can donate plasma to anyone, as its plasma contains no antibodies that would interfere with recipient's antigens
-  Whole Blood Reception: Can only receive whole blood from another Type AB person, due to potential antibodies in other blood types' plasma
 
- Type B Blood
                        
                            -  Antigens: Possesses only B antigens on red blood cells
-  Antibodies in Plasma: Has anti-A antibodies
-  Can receive (Red Blood Cells): From Type B or Type O (as they do not have A antigens)
-  Cannot receive (Red Blood Cells): From Type A or Type AB (as they possess A antigens)
-  Can receive (Plasma): From Type AB (which has no antibodies) or Type B (which only has anti-A antibodies, not affecting B's own B antigens)
-  Cannot receive (Plasma): From Type A (which has anti-B antibodies that would attack B's own B antigens) or Type O (which has both anti-A and anti-B antibodies, attacking B's own B antigens)
-  Can donate (Whole Blood): Only to another Type B person
 
- Type A Blood
                        
                            -  Antigens: Possesses only A antigens on red blood cells
-  Antibodies in Plasma: Has anti-B antibodies
-  Can receive (Red Blood Cells): From Type A or Type O (as they do not have B antigens)
-  Cannot receive (Red Blood Cells): From Type B or Type AB (as they possess B antigens)
-  Can receive (Plasma): From Type AB (which has no antibodies) or Type A (which only has anti-B antibodies, not affecting A's own A antigens)
-  Cannot receive (Plasma): From Type B (which has anti-A antibodies that would attack A's own A antigens) or Type O (which has both anti-A and anti-B antibodies, attacking A's own A antigens)
-  Can donate (Whole Blood): Only to another Type A person
 
- Type O Blood
                        
                            -  Antigens: Possesses neither A nor B antigens on red blood cells
-  Antibodies in Plasma: Has both anti-A and anti-B antibodies
-  Universal Donor (of red blood cells): Can donate red blood cells to Type A, B, AB, or O, because Type O red blood cells lack antigens for antibodies to attack
-  Plasma Donation: Can only donate plasma to another Type O person, as its plasma contains both anti-A and anti-B antibodies, which would be dangerous for other blood types
-  Whole Blood Reception: Can only receive whole blood from another Type O person
 
 
- Blood Typing Test (Agglutination)
                
                    - The method involves taking a drop of a person's blood and adding specific antibodies to observe the reaction
- Agglutination, or clumping together, occurs when antibodies react with their corresponding antigens
- The test results are interpreted as follows:
                        
                            -  Type AB: Blood shows agglutination with both anti-A and anti-B antibodies
-  Type B: Blood shows no agglutination with anti-A antibodies, but strong agglutination with anti-B antibodies
-  Type A: Blood shows strong agglutination with anti-A antibodies, but no agglutination with anti-B antibodies
-  Type O: Blood shows no agglutination with either anti-A or anti-B antibodies