Hematology and Blood Physiology

Blood Structure and Function

• Blood is connective tissue containing formed elements suspended in plasma
• Formed elements are the solid components comprised of erythrocytes, leukocytes, and thrombocytes.
• Plasma is the liquid portion of blood.
• Blood plasma contains water, proteins, gases, nutrients, and salts.

How Blood is Formed

• Hematopoiesis is the formation of blood in myeloid tissue.
• All red blood cells (RBCs) are produced in red bone marrow.
• All blood cells develop from stem cells, also known as hematocytoblasts.
• Erythropoiesis is the making of red blood cells (erythrocytes).
• Erythropoiesis occurs in red bone marrow until adolescence.
• Red bone marrow in long bones is replaced by fat marrow with age, therefore RBCs are then made in short and flat bones.

Erythrocytes

• Erythrocytes (RBCs) contain hemoglobin, which is an iron-containing compound that gives blood its red color.
• Erythrocytes are the most numerous blood cells.
  • Men average 4.5-6.2 million/uL.
  • Women average 4.2-5.4 million/uL.
• Iron allows for the transportation of respiratory gases, such as carbon dioxide and oxygen.
• Erythrocytes carry oxygen from the lungs to the body cells.
• Erythrocytes carry carbon dioxide from body cells to the lungs.
• Mature erythrocytes appear as biconcave discs lacking a nucleus.
• Erythropoiesis is red bllod cell development.
• Iron is contained in hemoglobin. Hemoglobin transports oxygen to tissue and exchanges it for carbon dioxide.
• Erythrocytes live approximately 120 days, then rupture in a process known as hemolysis.
• Hemolysis releases hemoglobin and cell fragments known as hemosiderin and bile pigments.
  • Most go to bone marrow to make new cells.
  • The liver excretes bile pigments.

Leukocytes

• Leukocytes (WBCs) range from 3200-9800/uL.
• Leukocytes provide body protection and defense, and aid in tissue repair.
• Leukocytes remove debris from injured tissue.
• Leukocytes ingest and destroy bacteria and foreign particles in a process called phagocytosis.
• Leukocytes migrate from the bloodstream into tissues through a process called diapedesis, enabling them to reach sites of injury or infection.

Types of Leukocytes

• There are five types of leukocytes, categorized into two groups: granulocytes and agranulocytes. Granulocytes include neutrophils, eosinophils, and basophils. Neutrophils, the most abundant white blood cells formed in the bone marrow, defend against infections through phagocytosis, contributing to pus formation during infections.Eosinophils also originate from the bone marrow and are particularly active during allergic reactions and parasitic infections. These specialized leukocytes respond to these conditions by phagocytosis complexesectively helping to modulate inflammatory responses and contributing to the degradation of larger pathogens that cannot be easily ingested by other immune cells.. Basophils, the least common, mediate allergic reactions and inflammation by releasing heparin and histamine. Agranulocytes consist of two primary types of white blood cells: lymphocytes and monocytes. Lymphocytes play a crucial role in the adaptive immune system, which is responsible for recognizing and responding to specific pathogens. These cells are predominantly produced in primary lymphoid organs, specifically the bone marrow and the thymus gland, where T-cells mature. Upon encountering antigens, lymphocytes are activated and undergo further differentiation in peripheral lymphoid organs, such as lymph nodes and the spleen, where they can mount a targeted immune response. This is vital for long-term immunity and memory against previously encountered pathogens. Conversely, monocytes are larger white blood cells that circulate in the bloodstream and differentiate into macrophages upon entering tissues. Macrophages are essential for phagocytosis, where they engulf and digest cellular debris, pathogens, and dead cells, thereby playing a significant role in maintaining tissue health and initiating the body's healing processes.

Inflammation

• Inflammation occurs when tissue goes through chemical or physical trauma or pathogenic invasion.
• Symptoms of inflammation include redness, heat, swelling, and pain.
• Histamines are released from basophils and increase flow to injured areas. Increased blood plasma and fibrinogen move to the the area.
• The inflamed Area becomes walled off by clotting and fibrinogen.
• Pus forms which includes dead tissue, dead and living bacteria, dead leukocytes and plasma.
• If inflammation is below epidermis, it is an abscess. If inflammation is on the surface, it is an ulcer.
• Pyrogens from hypothalamus raise body temperature causing fever / pyrexia.
• Leukocytosis is WBC > 10,000.
• Leukopenia is a decrease in WBC.

Platelets

• Platelets (thrombocytes) range from 150,000-350,000/uL.
• Technically, platelets are not true cells, but are only the fragments of cells, which make them the smallest blood element.
• Platelets control bleeding or hemostasis.
• The complex hemostasis process is composed of interrelated reactions.
  • Platelets become sticky by releasing thromboplastin which initiates clot formation.
  • Fibrinogen forms fibrin strands that act as a net trapping blood cells.
  • A mass of cells and fibrin becomes jelly-like and impedes blood flow, leading to hemostasis.
• Failure at any step in hemostasis results in loss of hemostasis.

Plasma Constituents

• Plasma is the liquid portion of blood containing cells.
• It includes water, plasma proteins, nutrients, electrolytes, hormones, vitamins, enzymes, and metabolic waste products.
• Plasma is colorless with the cells removed.
  • It contains 92% water.
• The plasma elements include albumin, globulin, fibrinogen, clotting factors, gases, nutrients, salts, and hormones.
• Plasma is able to leak from capillaries to deliver products to cells and exchange waste.
• Blood serum is blood plasma when fibrinogen and clotting factors are removed.

Plasma Proteins

• The three plasma proteins are fibrinogen, albumin, and globulin.
• Fibrinogen is necessary for blood clotting and is synthesized in the liver.
• Albumin is the most abundant protein.
  • Albumin maintains blood's osmotic pressure and volume and is a product of the liver.
  • Albumin provides the "pulse pressure" needed to hold and pull water from the tissue fluid back into the blood vessel.
• Globulin is made in the liver and lymphatic system.
  • Gamma globulin helps to make antibodies.
  • Prothrombin is formed in the liver.
  • Prothrombin helps to coagulate blood.
  • Vitamin K is necessary for prothrombin synthesis.

Hemostasis Steps

• Stopping or controlling bleeding is hemostasis.
• It includes vasoconstriction, external pressure, and clot formation.

Blood Clotting Steps

• Injured tissue releases thromboplastin.
• Blood vessel becomes rough and platelets disintegrate and release thromboplastin.
• Thromboplastin converts prothrombin to thrombin.
• Thrombin changes fibrinogen to fibrin (web-like) forming a clot.
• Plasma forms a crust, or scab.
• Anticoagulation with Coumadin or heparin must be neutralized by anti-thromboplastin and antiprothrombin.
• Prothrombin is made in liver and depends on vitamin K.

Lymphatic System Structures

• Lymphatic system structures include lymph nodes, lymph vessels, lymph fluid, tonsils, thymus, and spleen.

Lymphatic System Role

• The lymphatic system is an intricate and vital network composed of lymphatic vessels, lymph nodes, and various lymphoid tissues. Its primary function is to collect and drain excess interstitial fluid, which accumulates in the spaces between body tissues due to metabolic activities and the exchange of nutrients and waste products. By removing this fluid, the lymphatic system plays a crucial role in preventing edema, or swelling, which can negatively impact tissue function and overall health.

  Once the interstitial fluid is collected, it transforms into lymph—a clear fluid rich in white blood cells, particularly lymphocytes, which play a crucial role in immune responses. Lymphocytes are further divided into B cells and T cells, each serving different functions in identifying and neutralizing pathogens. The lymph, carrying these vital immune cells, then travels through the lymphatic vessels, which are structured to ensure unidirectional flow towards the heart. Ultimately, the lymph is returned to the bloodstream at specific points, such as the subclavian veins, where it mixes with the blood, reintroducing immune components back into the circulatory system.

  This process is not limited to fluid balance; it significantly enhances the body's immune response. By collecting and transporting lymph that contains pathogens and cellular debris, the lymphatic system facilitates the swift mobilization of immune cells to sites of infection or injury. Additionally, lymph nodes, distributed throughout the lymphatic system, act as filtering stations where harmful substances can be trapped and destroyed by these immune cells. Overall, this continuous cycle is vital for sustaining homeostasis, removing waste products, and providing robust defense mechanisms against infections and diseases, thus ensuring the body's overall well-being.

• This system plays a critical role in the immune response; it works closely with the immune system to maintain and facilitate the mobilization of various immune cells that are essential for defending the body against disease-causing agents, which can include harmful bacteria, viruses, and even cancerous cells. Through the lymphatic pathways, immune cells can patrol the body and respond effectively to infections or other threats.

• The lymphatic system is composed of various types of immune cells, including monocytes, which are precursors to macrophages and play key roles in phagocytosis, and lymphocytes, which include T cells and B cells that are pivotal for adaptive immunity and the production of antibodies. These cells interact within lymph nodes where they can quickly respond to pathogens.

Immune System Types

• The immune system protects the body against disease-causing organisms.
• Innate immunity is present at birth.
  • It includes skin barriers, tears, saliva, stomach acid.
  • It gives protection without any form of specificity (non-specific).
• Acquired Immunity develops throughout the life time with each encounter with a foreign substance.
  • It is specific, the method to destroy each specific antigen is custom made.
  • The two types of acquired immunity are humoral/antibody and cellular immunity.

Acquired Immune Response

• The acquired immune response has three characteristics: recognition, specificity, and memory.
• Acquired immunity recognition is the ability to know what belongs to the body and what is foreign and potentially harmful.
• Acquired immunity specificity is the ability to "custom make" a defense unique to each antigen.
• Acquired immunity memory is the ability to recall how the antigen was destroyed during the first encounter and then repeat it over and over again with each subsequent encounter with the antigen.
• Monocytes become phagocytic macrophages to perform phagocytosis.
• B cells develop through humoral/antibody immunity to respond to a pathogen.
• T cells provide cellular immunity.

Iron-Deficiency Anemia

• Insufficient iron in the diet leads to a decrease in RBCs.
• Red blood cells take on a large, central pallor during microscopic examination.
• Iron-deficiency is the most common anemia in the US.
• It is common in adolescents and premenopausal women due to iron demands associated with blood loss during menses.
• Signs & Symptoms include extreme fatigue, cold hands and feet, and headaches.
• Iron-deficiency anemia treatment depends on severity and cause of the anemia .
  • Oral or parenteral (intramuscular or IV) iron supplements can be used.
  • Dietary modifications are commonly sufficient to restore lost iron reserves.
  • Red cell transfusions is possibly required in elderly patients.

Pernicious Anemia

• Inadequate levels of vitamin B12, needed for red cell development, causes pernicious anemia .
• Commonly from the result of insufficient amount of intrinsic factor, needed for vitamin B12 absorption.
• Leads to characteristic formation of large, abnormal RBCs (macrocytes).
• Signs & Symptoms include weakness, nausea, vomiting, inflammation of nerves (neuritis), muscular incoordination, lightheadedness, and impaired memory.
  • Neurological signs and symptoms progress.
• Pernicious anemia treatment includes vitamin B12 injections and dietary changes to include red meats and liver. Lifelong treatment may be required.

Sickle Cell Anemia

• Anemia is a hereditary condition where RBCs take on an abnormal crescent shape.
• Such abnormal shapes prevent blood cells from passing through blood vessels.
• Causes episodic attacks of intense pain (pain crises) in arms, legs, or abdomen due to impaired circulation.
  • Clinical manifestations occur in many body systems and organs.
  • Jaundice is visible in the white of the eye (sclera).
• Painful crises are possibly triggered by infections, stress, and extremes in temperature.
• Sickle cell anemia treatment involves analgesics, adequate hydration, regular blood transfusions, and possibly a bone marrow transplant in severe cases.

Leukemia

• Leukemia is a type of malignancy of the bone marrow causing proliferation of white blood cells (WBCs) that cannot function normally.
• Results in Crowding out of RBCs and platelets by malformed WBCs, leading to anemia and bruising and bleeding problems.
  • Can be acute and chronic forms.
• Signs and symptoms include splenomegaly, hepatomegaly, lymphadenopathy, fatigue, malaise, easy bruising, and exercise intolerance.
  • Night sweats and joint pain may occur.
  • Some forms are asymptomatic until late in the disease.
• Leukemia treatment depends on the type of leukemia and the stage of development.
  • A variety of chemotherapeutic agents and bone marrow transplants can be used for treatment.

Lymphedema

• Lymphedema is the abnormal accumulation of fluid within tissues.
• It is especially common in arms and legs.
• Lymphedema is possibly caused by injury to the tissue, as in burns, or blockage of the lymph channels.
• Lymphedema potentially leads to fibrosis and inflammation of the tissues.
• Signs and symptoms include generalized swelling of an arm or leg which may occur after surgery when a chain of lymph nodes has been removed.
• Insufficient drainage of tissue fluid, leading to edema may occur.
• The most common cause is radical mastectomy with removal of underarm lymph nodes.
• Other causes: injury (trauma), radiation therapy, surgery, skin infections, and tumors.
• Lymphedema treatment includes compression (usually with multilayered bandages) to limit swelling.
  • Manual lymph drainage, elevation of the body part, and range-of-motion exercises may also be prescribed.

Kaposi's sarcoma

• A malignancy of connective tissue, especially the cells that line the lymph and blood vessels.
• Tumors or blotches called lesions appear in the affected areas.
• This sarcoma Invades internal organs possibly including the lungs, intestines, and liver, and can become life-threatening.
• Closely associated with HIV infection and considered an AIDS-defining condition.
• Kaposi sarcoma signs and symptoms are purple, red, or brown lesions appear on the skin or mucous membranes.
  • Lesions appear on lower extremities or spreading to: upper body, face, and mucous membranes of the mouth and throat.
  • Weight loss as a result of pain by eating is caused when lesions are in the mouth or throat .
  • Dyspnea occurs if found in the lungs.
• Kaposi sarcoma treatment depends on stage of infection and degree of metastasis.
  • Typically uses includes radiation therapy, chemotherapy, surgery, chemo and immunotherapy. -Palliative treatment and good oral hygiene (essential).

Systemic Lupus Erythematosus

• Also known as SLE.
• Is an Autoimmune disease, causes the development of autoantibodies that attack the skin, joints, and other organs.
• Effects range from mild to life-threatening symptoms.
• Presents a Pattern of “flares” (exacerbations) and remissions. More common in women than men.
• Signs and symptoms; fatigue, joint pain, anemia, abnormal blood clotting and edema.
  • Butterfly-shaped rash appears over the nose and cheeks. sensitivity to light and sun.

Thrombocytopenia

• Occurs due to a Deficiency in the circulating number of platelets,
• The most common cause is Hemorrhagic disorders where the platelet plays a vital role in the Hemostasis and coagulation.
• Signs and symptoms includes Bruising, Bleeding from Nose and Gums, prolonged Bleeding after injury or dental procedures.
• Petechiae forms on the Skin .

DIC

• Dis Seminated Intravascular Coagulation(DIC) by an Abnormal activation of proteins involved in blood coagulation.
• Infection, severe trauma, Inflammation, Cancer.
• Blood clots form in small Vessels, cutting off blood Supply to distal Tissues, Eventual exhaustion of cLotting Proteins, leading to profuse Bleeding.
• Signs and Symptoms includes Bruising, Bleeding from Mucusal Tissues (Thrombus formation that can affect Kidneys and the Liver.) and leads to organ failure. Also Petechia (High tension).

Pharmacology

• Important pharmacological categories; Anticoagulants, Antifibrinolytics, Antiretrovirals, Immunosuppressants, Thrombolytics.

Apheresis

• Using a procedure used to separate out a particular component of blood. By using channeling it through a device that collects the desired component and returns the remainder of the blood back to the patient.
• Types:
  • Plasmapheresis
  • Leukapheresis
• Plateletpheresis
• Stem cell harvest

Plasmapheresis

• This is a Specialized type of apheresis which involves removal of the plasma portion of blood from a patient.
• Used especially in autoimmune diseases to remove auto antibodies, the plasma component is responsible for autoimmune symptoms.
• Use in treatment of such autoimmune disease such as my asthenia Travis, multiple sclerosis, and muscular dystrophy.

Blood Transfusion

• A procedure use by, intravenous transfer of whole blood, blood cells, or plasma to an individual. It's a treatment for a wide variety of Anemia.
• Two important Types include : -Autologous one's Own Blood
  • Homologous with (Allogenic ) Use a component from a compatible blood donor.

Bone Marrow Transplant .

• Procedure use to replace damaged or destroyed bone marrow cells with healthy bone marrow stem cells.
• Stem cells use are developed during the blood cell cycle.
• It's use is commonly for the treatment of leukemia, multiple myeloma, serious forms of anemia, and other autoimmune diseases. It can decrease the chance of rejection with prior immunosuppressant treatment but increase in some cases the Chance of infections.
• Complications are possible ; Donors cells may attempt to reject the recipient cell or Graft failure.

Procedures (part 6)

• Bone marrow aspiration is a withdrawal of bone marrow for microscopic evaluation (usually from the pelvic bone or, rarely, the sternum).

Procedures (part 7)

• Sentinel node excision is the removal of the first lymph node (sentinel node) receiving drainage from a tumor site and the one most likely to contain cancer cells.
• *If cancer cells are not found in the sentinel node, the regional nodes are commonly not removed.

Explore key concepts in hematology, including hemostasis, inflammation, blood composition, and immune responses. Questions cover the roles of thromboplastin, fibrinogen, WBC counts, and the lymphatic system's support for circulation. Also learn about liver function in blood clotting and the impact of anticoagulants.