Which of the Following Continually Circulate From Blood to Interstitial Space to Lymph to Blood

Cardiovascular System (Blood)

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Content

Blood
Hematocrit
Elements of Blood
Formation of Blood Cells
Red Blood Cells ( Erythrocytes)
Hemoglobin
Erythropoiesis
Type of White Blood Cells (WBC)
Platelets (Thrombocytes)
Hemostasis
Clotting Cascade
Blood Groups and Blood Types
Anemia
Sickle-Cell Anemia (SCA)
Hemophilia
Leukemia

Cells of the Body are Serviced by 2 Fluids

• Blood composed of plasma and a variety of cells, transports nutrients and wastes
• Interstitial fluid (fluid between the cells) that bathes the cells of the body
• Nutrients and oxygen diffuse from the blood into the interstitial fluid & then into the cells
• Wastes move in the reverse direction

Blood

• Blood is a connective tissue.
• Blood is made of a liquid matrix called plasma and 3 types of formed elements (cells or cell fragments)
• There are no visible fibers in plasma, but there are proteins that can be converted to fibers under certain conditions (e.g. blood vessel damage).

Functions of Blood

• Transportation

The blood transports dissolved gases, nutrients, hormones, and metabolic wastes

• Blood picks up O2 from the lungs and drops off CO2.
• Blood picks up nutrients from the digestive tract.
• Blood picks up hormones from endocrine glands.
• Blood picks up wastes and carries it to the kidneys, lungs, and other organs of excretion

• Protection
• The blood restricts fluid losses through damaged vessels. Platelets in the blood and clotting proteins minimize blood loss when a blood vessel is damaged.
• The blood also defends against pathogens and toxins. White blood cells (leukocytes) in the blood help defend against infection
• Regulation
• Blood regulates the pH and electrolyte composition of the interstitial fluids. Buffers in the blood stabilize the pH of the fluid surrounding cells (extracellular fluid).
• The blood also regulates body temperature. Blood vessels in the skin are dilated (relaxed) or constricted so that heat from the body can be given off or conserved.

Physical Characteristics of Blood

• More viscous than water - flows more slowly than water
• Temperature of 100.4 degrees F, pH 7.4 (7.35-7.45)
• Blood volume: 5 to 6 liters in average male, 4 to 5 liters in average female
• Negative feedback systems (hormones) maintain constant blood volume and pressure

Components of Blood

•  ~ 55% plasma
  • 90% water
  • 7% plasma proteins (albumin, globulins, fibrinogen)
  • 3% other substances - electrolytes, nutrients, hormones, gases, waste products
•  ~ 45% cells
  • 99% RBCs
  • < 1% WBCs and platelets

Major Blood Proteins

• Blood proteins are made in the liver and confined to the bloodstream

1. Albumins (54% of blood proteins)

• These maintain the osmotic pressure of the blood. This pressure is important in driving fluid into capillaries from the interstitial space.
• Albumins also buffer the blood.
• Albumins contribute to the thickness (viscosity) of blood.
• Albumins can transport lipids and steroid hormones

2. Globulins (immunoglobulins) (38% of blood proteins)

• These proteins include antibodies (immunoglobulins) which attack foreign proteins and pathogens.
• There are also smaller globulins that bind, support, and protect certain water-insoluble or hydrophobic ions, hormones and other compounds that might otherwise be filtered out of the blood at the kidneys or have very low solubility in water.

3. Fibrinogens(7% of blood proteins)

• Are proteins important in clotting of blood following trauma to the blood vessels
• They are converted to another protein called fibrin during clotting.

There are also regulatory proteins such as enzymes involved in the chemical reactions that occur in the blood and hormones that are being transported throughout the body to their target cells.

Hematocrit

• Hematocrit is the percentage of blood volume occupied by red blood cells (RBCs)
  • female normal range 38 - 46% (average of 42%)
  • male normal range 40 - 54% (average of 46%)
• Anemia - not enough RBCs
  Polycythemia - too many RBCs (over 50%) - dehydration, tissue hypoxia, high altitude, blood doping in athletes

Formed Elements of Blood

• Formed elements means cells or cell fragments
• There are 3 formed elements in blood:
  1. Red BloodCells ( also called erythrocytes )
  2. White Blood Cells ( also called leukocytes )
     • Granular Leukocytes – neutrophils, eosinophils, basophils
     • Agranular Leukocytes – lymphocytes (T cells, B cells, and natural killer cells),monocytes
  3. Platelets (also called thrombocytes) These are special cell fragments involved in clotting

One Drop of Blood:

• Normal RBC count ~ 5 million/drop
  • Males ~5.4 million/drop
  • Females ~4.8 million/drop
• WBC count - 5-10,000 white blood cells
• Platelet count 150,000-400,000

Formation of Blood Cells

• Most blood cell types need to be continually replaced, depending on type they may die within hours, days or weeks
• The process of blood cells formation is hematopoiesis or hemopoiesis, in adults it only occurs in red marrow of flat bones like sternum, ribs, skull & pelvis and ends of long bones

Click here for an animation that describes the process of hematopoiesis (hemopoiesis)

Red Blood Cells ( Erythrocytes)

• Are cells with a biconcave shape
• The biconcave shape provides for increased surface area/volume ratio and flexible shape for narrow passagesContain oxygen-carrying protein hemoglobin that gives blood its red color,
• 1/3 of cell's weight is hemoglobin
• Has the shape of a biconcave disk
• Mature RBCs contain no nucleus and no mitochondria or other organelles
• RBCs have an average lifespan of about 120 days.
• Old RBCs are destroyed in the liver and spleen.
• The process of blood cells formation is hematopoiesis or hemopoiesis
• In adults hematopoiesis occurs only in red marrow of flat bones like sternum, ribs, skull, pelvis and ends of long bones
• New RBCs enter circulation at 2-3 million/second

Hemoglobin

• Is a globin protein consisting of 4 polypeptide (protein) chains
• Has one heme pigment attached to each polypeptide chain
• Each heme contains an iron ion (Fe+2) that can combine reversibly with one oxygen molecule
• Each hemoglobin molecule can carry 4 oxygen molecules
• Hemoglobin also acts as a buffer and balances pH of blood
• Hemoglobin transports 23% of total CO₂ waste  from tissue cells to lungs for release (the CO₂ combines with amino acids in globin portion of hemoglobin)

Normal Hemoglobin Levels :

• Infants have 14 to 20 g/100mL of blood
• Adult females have 12 to 16 g/100mL of blood
• Adult males have 13.5 to 18g/100mL of blood

Recycling of Red Blood Cells

• RBCs live only 120 days as they wear out from bending to fit through capillaries
• No repair is possible due to lack of organelles
• Worn out cells removed by fixed macrophages in  spleen & liver.
• Cells are broken down and components are recycled:
  • Globin portion broken down into amino acids and used to create new proteins
  • Heme portion split into iron (Fe+3) which is used in bone marrow for hemoglobin synthesis
    
  • Biliverdin converted to bilirubin (yellow), bilirubin secreted by liver into bile

Click here for an animation on how the components of a red blood cell are recycled. The animation is followed by practice questions.

Erythropoiesis:

• Erythropoiesis is the production of RBCs
• Proerythroblast starts to produce hemoglobin as it differentiates; eventually the nucleus is ejected and a reticulocyte is formed.
• Reticulocytes escape from bone marrow into the blood and within 1-2 days they eject the remaining organelles to become mature RBCs.
• Factors needed for erythropoiesis are
  • Hormone called erythropoietin from kidneys
  • Vitamin B12
  • Iron

Feedback Control of Erythorpoiesis

• When tissue hypoxia (cells not getting enough O₂ ), RBC production falls below normal
• The kidneys respond by releasing erythropoietin, which catalyzes the development of proerythroblasts into reticulocytes.

White Blood Cells (WBC)

• Less numerous than RBCs
• 5,000 to 10,000 WBCs per drop of blood
• 1 WBC for every 700 RBC
• Only 2% of total WBC population is in circulating blood at any given time, the rest is in lymphatic fluid, skin, lungs, lymph nodes & spleen
• 5 major types of WBCs:
  1. Neutrophils
  2. Basophils
  3. Eosinophils
  4. Monocytes
  5. Lymphocytes

Neutrophils

• Fastest response of all WBCs to bacteria and parasites
• Direct actions against bacteria
• Release lysozymes which destroy/digest bacteria
• Release defensive proteins that act like antibiotics
• Release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria

Basophils

• Involved in inflammatory and allergy reactions
• Leave capillaries & enter connective tissue as mast cells
• Release heparin, histamine, and serotonin
• Heighten the inflammatory response and account for hypersensitivity (allergic) reaction
• Heparin is a potent anti-coagulant that does not allow clotting within vessels

Eosinophils

• leave capillaries to enter tissue fluid
• Eelease histaminase which slows down inflammation caused by basophils
• Attack  parasitic worms
• Phagocytize antibody-antigen complexes

Monocytes

• Take longer to get to site of infection, but arrive in larger numbers
• Become wandering macrophages, once they leave the capillaries
• Destroy microbes and clean up dead tissue following an infection

Lymphocytes

There are 3 major types of lymphocytes:

• B cells destroy bacteria and their toxins, turn into plasma cells that produces antibodies
• T cells attack viruses, fungi, transplanted organs, cancer cells
• Natural killer cells attack many different microbes & some tumor cells destroy foreign invaders by direct attack

Differential WBC Count

• Detection of changes in numbers of circulating WBCs (percentages of each type)
• Indicates infection, poisoning, leukemia, chemotherapy, parasites or allergic reaction
  Normal WBC counts
  - Neutrophils 60-70% (up if bacterial infection)
  - Lymphocyte 20-25% (up if viral infection)
  - Monocytes   3 -- 8 % (up if fungal/viral infection)
  - Eosinophil   2 -- 4 % (up if parasite or allergy reaction)
  - Basophil   <1% (up if allergy reaction or hypothyroid)

Platelets (Thrombocytes)

• Are disc-shaped cell fragments with no nucleus
• Normal platelet count is 150,000-400,000/drop of blood
• Form in bone marrow by myeloid stem cells
• Eventually become megakaryocytes whose cell fragments form platelets
• Have a short life span (5 to 9 days in bloodstream)
• Aged ones are removed by fixed macrophages in liver and spleen

Hemostasis

• Hemostasis is the stoppage of bleeding in a quick & localized fashion when blood vessels are damaged
• It prevents hemorrhage (loss of a large amount of blood)

Process

1. Vascular spasm

• Damage to blood vessel stimulates pain receptors
• Reflex vasoconstriction of small blood vessels and arterioles occurs
• Can reduce blood loss for several hours until other mechanisms can take over

2. Platelet plug formation, 3 steps –

1.  Platelet adhesion

• Platelets stick to exposed collagen underlying damaged endothelial cells in vessel wall

2. Platelet Release Reaction

• Platelets activated by adhesion
• Extend projections to make contact with each other
• Release ADP, and vasoconstrictors called thromboxane A2 and serotonin (further decrease blood flow)
• Causes stickiness activating other platelets

3. Platelet Aggregation - activated platelets stick together and activate new platelets to form a mass called a platelet plug, plug reinforced by fibrin threads formed during clotting process

Blood clotting

• (coagulation = formation of fibrin threads)
• if blood drawn from the body, it thickens into a gel, separates into liquid (serum) and a clot of insoluble fibers (fibrin) in which the cells are trapped
• Substances required for clotting are Ca+2, enzymes synthesized by liver cells - clotting factors and substances released by platelets or damaged tissues
• Clotting is a cascade of reactions in which each clotting factor activates the next in a fixed sequence resulting in the formation of fibrin threads.

Overview of Clotting Cascade

• Key enzyme - prothrombinase is formed by either the intrinsic or extrinsic pathway
•  - Extrinsic Pathway, damaged tissues leak tissue factor thromboplastin into bloodstream activates Factor VII
  Prothrombinase forms in seconds
• - Intrinsic Pathway, - damage to endothelium of blood vessel activates Factor X11,  platelets come in contact with damaged endothelium (collagen) and platelets release phospholipids – Platelet Factor III (PF3), requires several minutes for prothrombinase to form

Common pathway -

• prothrombinase and Ca+2 catalyze the conversion of prothrombin to thrombin,
• Thrombin in the presence of Ca+2 converts soluble fibrinogen to insoluble fibrin threads
• activates fibrin stabilizing factor XIII - positive feedback cycle!

Clot retraction follows minutes after cascade - clot plugs ruptured area of blood vessel, platelets pull on fibrin threads causing clot retraction and expelling serum, edges of damaged vessel are pulled together, endothelial cells repair the blood vessel

Clot Dissolution

• Clot prevention in vessels - heparin from basophil acts as anticoagulants
• Fibrinolytic system dissolves small, inappropriate clots & clots at a site of a completed repair
• Fibrinolysis inactive plasminogen becomes plasmin which dissolves fibrin threads
• Clot formation remains localized - blood disperses clotting factors

Intravascular Clotting

• Thrombosis -  clot (thrombus) forming in an unbroken blood vessel, forms on rough inner lining of BV
  if blood flows too slowly (stasis) allowing clotting factors to build up locally & cause coagulation
  may dissolve spontaneously or dislodge & travel
• Embolus – free floating clot in the blood may cause  strokes, myocardial infarctions, low dose aspirin blocks synthesis of thromboxane A2 & reduces inappropriate clot formation

Blood Groups and Blood Types

RBC surfaces are marked by genetically determined glycoproteins & glycolipids
-agglutinogens or isoantigens
-distinguishes at least 24 different blood groups ie ABO, Rh, etc

ABO blood groups - based on 2 glycolipid isoantigens called A and B found on the surface of RBCs

If RBCs
- display only antigen A -- blood type A
- display only antigen B -- blood type B
- display both antigens A & B -- blood type AB
- display neither antigen -- blood type O

Plasma contains isoantibodies or agglutinins to the A or B antigens not found in your blood

anti-A antibody reacts with antigen A
anti-B antibody reacts with antigen B

Click here for an animation on blood types and the role of antibodies when donating or receiving blood.

The animation is followed by practice questions.

RH blood groups

• antigen was discovered in blood of Rhesus monkey
  
• People with Rh isoantigens on RBC surface are Rh+.
• Normal plasma contains no anti-Rh antibodies
  
• Antibodies develop only in Rh- blood type & only with exposure to the antigen
  
• Transfusion reaction upon 2nd exposure to the antigen results in hemolysis of the RBCs

HDN
Rh negative mom and Rh+ fetus will have mixing of blood at birth
Mom's body creates Rh antibodies unless she receives a RhoGam shot soon after first delivery, miscarriage or abortion. In 2nd child, hemolytic disease of the newborn may develop causing hemolysis of the fetal RBCs

Universal Donors and Recipients

• 
  People with type AB blood called "universal recipients" since have no antibodies in plasma
  only true if cross match the blood for other antigens
• 
  People with type O blood cell called "universal donors" since have no antigens on their cells
  theoretically can be given to anyone

Anemia = Not Enough RBCs
Symptoms:
-oxygen-carrying capacity of blood is reduced
-fatigue, cold intolerance & paleness
Types of anemia:
-iron-deficiency =lack of absorption or loss of iron
-pernicious = lack of intrinsic factor for B12 absorption
-hemorrhagic = loss of RBCs due to bleeding (ulcer)
-hemolytic = defects in cell membranes cause rupture
-thalassemia = hereditary deficiency of hemoglobin
-aplastic = destruction of bone marrow (radiation/toxins)

Sickle-Cell Anemia (SCA)
-Genetic defect in hemoglobin molecule (Hb-S) that changes 2 amino acids at low very O₂ levels, RBC is deformed by changes in hemoglobin molecule within the RBC sickle-shaped cells rupture easily = causing anemia & clots
-Found among populations in malaria belt: Mediterranean Europe, sub-Saharan Africa & Asia
-Person with only one sickle cell gene increased resistance to malaria because RBC membranes leak K+ & lowered levels of K+ kill the parasite infecting the red blood cells

Hemophilia
-Inherited deficiency of clotting factors
bleeding spontaneously or after minor trauma, subcutaneous & intramuscular hemorrhaging, nosebleeds, blood in urine, articular bleeding & pain
-Hemophilia A lacks factor VIII (males only)most common
-Hemophilia B lacks factor IX (males only)
-Hemophilia C (males & females) less severe because alternate clotting activator exists
Treatment is transfusions of fresh plasma or concentrates of the missing clotting factor

Leukemia
-Acute leukemia
uncontrolled production of immature leukocytes
crowding out of normal red bone marrow cells by production of immature WBC
prevents production of RBC & platelets
-Chronic leukemia
accumulation of mature WBC in bloodstream because they do not die
classified by type of WBC that is predominant---monocytic, lymphocytic.

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Source: https://www.austincc.edu/apreview/PhysText/Blood.htm

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