Blood & The Immune System I

Medicine before the 17th century

If unhealthy, key to restore balance is: 1. lifestyle 2. medication. “opposites cure opposites”

Functions of the circulatory system

1. Transportation of all substance essential for cellular metabolism - respiratory (RBCs), nutritive (digestive), excretory (waste)

2. regulation - hormonal and temperature

3. protection - from injury (clotting), from pathogens (immune)

Hematopoiesis

Formation of blood cells

What is the major hematopoietic organ of the fetus

Liver

What is the major hematopoietic organ after birth

Bone mrrow

What play important roles in hematopoiesis

Cytokines

What are RBCs samples in centrifugation

Most abundant blood cells, biconcave disc shape, packed at the bottom

What are WBC, platelets in centrifugation

Thin, light interface - “buffy coat”

Where does plasma fluid sit in centrifugation

At the very top

Erythropoiesis

Involves uncommitted stem cells undergoing stages in the bone marrow, forming reticulocytes and then being released into circulation as mature red blood cells (RBCs)

Red Blood Cells (Erythrocytes)

Cytoskeleton creases unique concave shape, flexible, swelling in hypotonic medium and shrinking in hypertonic medium. Some illnesses, like Sickle Cell and Anemia, affect shape

Erythrocytes and Hemoglobin

Blood red colour is due to Hb binding to red blood cells, which consist of four globin proteins with heme groups binding iron molecules, releasing oxygen into tissue

Total arterial O2 carrying capacity in blood

200 mL O2/L blood

Oxygen Saturation

Depends on its location, with blood entering tissues having 200mL O2/L, leaving tissues with 155 mL/ O2/L, and systemic arteries having 97% oxygen saturation, leaving veins with 75% saturation

Physiological factors can affect O2 binding in skeletal muscles

Decreased pH decreases Hb affinity for O2, while increased temperature weakens the bond between O2 and Hb. Muscle fibers produce lactic acid, while higher temperatures increase O2 offlload

2,3-Diphosphoglyceric Acid (2,3-DPG)

A side reaction in the glycolytic pathway results in the production. When oxyhemoglobin levels decrease, 2,3-DPG production increases and an increase concentration of 2,3-DPG increases O2 unloading.

Mature red blood cells (RBCs)

Lack nuclei, mitochondria and ER, and cannot respire aerobically. They obtain energy through anaerobic glucose metabolism.

RBC Lifecycle

Develop in 7 days, age and become fragile with 120 lifespan. Bilirubin is produced when old RBCs are destroyed in the spleen, excreted into bile by liver enzymes, and can be aided by phototherapy.

Janudice

A condition characterized by high blood bilirubin concentrations due to RBC death, yellow cast on skin and eyes, and can be caused by healthy newborns experiencing rapid blood hemoglobin decrease at birth, preemies lacking liver enzymes or phototherapy with blue light

Thalassemia

Inherited defect in hemoglobin, primarily found in Mediterraneans. It results in decreased alpha and beta Hb chain synthesis, excessive RBC destruction, stillbirth, anemia, growth abnormalities, and iron overload

Sickle Cell Anemia

Inherited, recessive disease with a single amino acid substitute in the beta globin chain. It leads to chronic complications and a lifelong lifespan, with a high resistance to malaria due to the heterozygous environment

Plasma

A straw coloured liquid, contains 92% water, 1% dissolved solutes, trace elements and gases, along with 7% organic molecules

Proteins found in blood plasma

Albumin, produced in the liver, provide osmotic pressure and account for 90% of plasma proteins. Globulins, including alpha and beta globulins, transport lipids and vitamins, while gamma globulins are antibodies produced by lymphocytes for immunity. Fibrinogen, also produced in the liver, is crucial for clot formation

Agglutination (clumping of RBCs)

Occurs when A-type RBCs are mixed with anti-A type antibodies, while B-type RBCs are mized with anti-B-type antibodies, which is a process involved in blood typing

Rh Factor

A group of antigens found on red blood cells, with Rh positive being more common than Rh negative. Rh antibodies can cross placenta, potentially causing issues during birth if the mother has an Rh+ baby. At birth, the mother may become sensitized and produce antibodies against Rh antigen, leading to fetal hemolysis and hemolytic disease in the newborn

3 Steps in Blood Clotting

1. vasocontriction

2. formation of platelet plug

3. production of a web of fibrin proteins that penetrate and surround platelet plug

Clot formation

Fibrinogen is converted by thrombin to fibrin via extrinsic pathway in vivo or intrinsic pathway in vitro

Extrinsic pathway in blood clotting

Initiated by tissue factor in blood vessels and surrounding tissues, is activated by blood vessel injury, exposing it to factors VII and X, resulting in the production of thrombin

Clot dissolution

Plasminogen converted to plasmin which digests fibrin

Myocardial Infarction

Chewable aspirin is used initially in heart attack patients to prevent platelet clumping, followed by angioplasty or clot-dissolving drugs. TPAs are commonly used in US emergency departments and are applicable for stroke and blood clots

ST Elevated Myocardial Infarction (STEMI)

Most severe type of heart attack where the blood supply to the heart becomes blocked. Fibrinolytic drugs are the preferred treatment due to their ability to achieve reperfusion, cleaving fibrin and restoring blood flow to ischemic tissues