Blood is a specialized connective tissue that plays a vital role in maintaining homeostasis and supporting life. It performs a variety of functions, categorized into transportation, regulation, and protection.
1. Transportation Functions
Blood serves as a transport medium for various substances throughout the body:
Oxygen Transport:
Blood carries oxygen from the lungs to tissues via hemoglobin in red blood cells (RBCs).
Carbon Dioxide Transport:
Blood transports carbon dioxide from tissues to the lungs for exhalation.
Nutrient Transport:
Absorbs nutrients from the digestive system and delivers them to cells.
Waste Removal:
Transports metabolic waste products (e.g., urea, creatinine) to kidneys for excretion.
Hormone Transport:
Carries hormones from endocrine glands to target organs.
Heat Distribution:
Helps in thermoregulation by distributing heat generated by metabolic processes.
2. Regulatory Functions
Blood helps regulate various physiological parameters to maintain homeostasis:
pH Balance:
Blood maintains an optimal pH (around 7.35–7.45) using buffer systems (e.g., bicarbonate buffer).
Temperature Regulation:
Blood absorbs and distributes heat to regulate body temperature.
Fluid and Electrolyte Balance:
Maintains proper fluid volume and electrolyte composition for cellular function.
3. Protective Functions
Blood protects the body against infection, blood loss, and other threats:
Immune Defense:
White blood cells (WBCs) fight infections and foreign invaders.
Antibodies and complement proteins neutralize pathogens.
Clot Formation:
Platelets and clotting factors (e.g., fibrinogen) prevent blood loss by forming clots.
Detoxification:
Blood transports toxins to the liver for detoxification and removal.
4. Other Specialized Functions
Transport of Plasma Proteins:
Proteins like albumin maintain osmotic pressure and fluid balance.
Globulins aid in immunity.
Fibrinogen plays a role in clotting.
Oxygen Reserve:
Hemoglobin serves as a reserve for oxygen during hypoxia or increased demand.
Summary of Blood Functions
Category
Function
Details
Transportation
Oxygen and CO₂ transport
From lungs to tissues and vice versa
Nutrient and waste transport
Nutrients to cells, wastes to excretory organs
Hormone delivery
Endocrine glands to target organs
Heat distribution
Thermoregulation
Regulation
pH balance
Buffer systems
Temperature regulation
Distribution of heat
Fluid balance
Maintains hydration and electrolytes
Protection
Immune defense
WBCs, antibodies, complement proteins
Clot formation
Platelets and clotting factors prevent blood loss
Detoxification
Toxins transported to liver
Physical characteristics, Components
Physical Characteristics and Components of Blood
Physical Characteristics of Blood
Color:
Oxygenated Blood: Bright red due to oxygen-rich hemoglobin.
Deoxygenated Blood: Dark red due to reduced oxygen content.
Volume:
Adult Male: 5–6 liters.
Adult Female: 4–5 liters.
Blood volume is approximately 7–8% of total body weight.
Viscosity:
Blood is about 4–5 times more viscous than water due to its cellular components and plasma proteins.
pH:
Slightly alkaline, with a pH range of 7.35–7.45.
Regulated by buffer systems like the bicarbonate buffer.
Temperature:
Blood temperature is slightly higher than body temperature, at ~38°C (100.4°F).
Specific Gravity:
Whole blood: 1.05–1.06.
Plasma: 1.025–1.029.
Osmotic Pressure:
Maintained by plasma proteins (mainly albumin) and electrolytes to regulate fluid balance.
Salinity:
Blood contains about 0.9% sodium chloride.
Components of Blood
Blood is a specialized connective tissue composed of plasma (liquid part) and formed elements (cellular components).
1. Plasma (55% of Blood Volume)
The liquid portion of blood that serves as a transport medium for cells and various substances.
Composition:
Water (~90%):
Acts as a solvent and medium for chemical reactions.
Transported from endocrine glands to target organs.
Waste Products:
Urea, creatinine, bilirubin.
2. Formed Elements (45% of Blood Volume)
The cellular components of blood, produced in the bone marrow.
Red Blood Cells (RBCs) or Erythrocytes:
Function: Transport oxygen and carbon dioxide.
Count:
Male: 4.7–6.1 million/µL.
Female: 4.2–5.4 million/µL.
Structure:
Biconcave discs with no nucleus, containing hemoglobin.
Lifespan: ~120 days.
White Blood Cells (WBCs) or Leukocytes:
Function: Immunity and defense against infections.
Count: 4,000–11,000/µL.
Types:
Granulocytes:
Neutrophils, Eosinophils, Basophils.
Agranulocytes:
Lymphocytes (B cells, T cells), Monocytes.
Lifespan: Few hours to days (depending on type).
Platelets or Thrombocytes:
Function: Blood clotting (hemostasis).
Count: 150,000–400,000/µL.
Structure: Small, disc-shaped cell fragments.
Lifespan: ~7–10 days.
Summary of Blood Components
Component
Percentage
Main Functions
Plasma
~55%
Transport of nutrients, gases, hormones, and waste.
RBCs
~45%
Oxygen and carbon dioxide transport.
WBCs
<1%
Immune defense and protection.
Platelets
<1%
Blood clotting and prevention of bleeding.
Formation of blood cells
Formation of Blood Cells (Hematopoiesis)
Hematopoiesis is the process by which blood cells are formed. It occurs primarily in the bone marrow, but during fetal development, other organs like the liver and spleen also contribute. The process ensures the continuous production of red blood cells (RBCs), white blood cells (WBCs), and platelets to meet the body’s needs.
Sites of Hematopoiesis
During Fetal Development:
Yolk Sac: First site of blood cell formation (early weeks of gestation).
Liver and Spleen: Main sites of hematopoiesis from the second trimester.
Bone Marrow: Becomes the primary site by the third trimester.
After Birth:
Bone Marrow:
Active hematopoiesis occurs in red bone marrow, primarily in flat bones (sternum, pelvis, ribs) and the proximal ends of long bones (femur, humerus).
Yellow bone marrow (adipose tissue) in long bones is inactive but can revert to red marrow during high demand.
Process of Hematopoiesis
Hematopoiesis begins with hematopoietic stem cells (HSCs), which are multipotent cells capable of differentiating into all blood cell types.
Stages of Hematopoiesis:
Hematopoietic Stem Cells (HSCs):
Reside in the bone marrow and serve as the source of all blood cells.
Interleukins (ILs): Regulate differentiation and proliferation of specific WBCs.
Bone Marrow Microenvironment:
Stromal cells, extracellular matrix, and cytokines in the bone marrow provide a supportive environment for HSCs.
Negative Feedback Mechanisms:
Hematopoiesis is adjusted based on the body’s needs (e.g., hypoxia increases EPO production, infections stimulate leukopoiesis).
Lifespan of Blood Cells
Blood Cell Type
Lifespan
Site of Removal
RBCs
~120 days
Spleen and liver (reticuloendothelial system).
WBCs
Hours to years
Site of infection or spleen.
Platelets
~7–10 days
Spleen and liver.
Erythropoiesis,
Erythropoiesis
Erythropoiesis is the process of red blood cell (RBC) production. It occurs in the red bone marrow and is tightly regulated to maintain adequate oxygen delivery to tissues.
Site of Erythropoiesis
Fetal Development:
Early Stages: Yolk sac.
Mid Gestation: Liver and spleen.
Late Gestation: Red bone marrow.
After Birth:
In adults, erythropoiesis occurs in the red bone marrow of flat bones (e.g., sternum, pelvis, ribs) and the ends of long bones (e.g., femur, humerus).
Stages of Erythropoiesis
The process begins with hematopoietic stem cells (HSCs) and progresses through several stages:
Hematopoietic Stem Cell (HSC):
Multipotent stem cells in the bone marrow differentiate into myeloid progenitor cells.
Myeloid Progenitor Cell:
Gives rise to committed precursors of RBCs.
Proerythroblast:
First recognizable precursor in erythropoiesis.
Large nucleus with basophilic cytoplasm.
Basophilic Erythroblast:
Intensely basophilic cytoplasm due to high ribosome content for hemoglobin synthesis.
Polychromatic Erythroblast:
Cytoplasm changes color due to increasing hemoglobin content.
Orthochromatic Erythroblast (Normoblast):
Nucleus becomes smaller and eventually extruded.
Cytoplasm becomes pinkish due to hemoglobin.
Reticulocyte:
Immature RBC released into the bloodstream.
Lacks a nucleus but retains residual ribosomal RNA.
Matures into an erythrocyte within 1–2 days.
Erythrocyte (Mature RBC):
Biconcave, flexible cell without organelles.
Lifespan: ~120 days in circulation.
Regulation of Erythropoiesis
1. Erythropoietin (EPO):
Primary Hormone: Secreted by the kidneys (and partly by the liver).
Stimulus for Release:
Hypoxia (low oxygen levels) sensed by renal cells.
Examples: High altitude, anemia, hemorrhage.
Action:
Stimulates proliferation and differentiation of erythroid progenitors in the bone marrow.
2. Nutritional Requirements:
Iron: Essential for hemoglobin synthesis.
Vitamin B12: Required for DNA synthesis and cell division.
Folic Acid: Important for nucleotide synthesis.
Proteins and Amino Acids: For hemoglobin and structural components.
Nutritional deficiencies (e.g., iron, vitamin B12, or folate deficiency).
Bone marrow disorders (e.g., aplastic anemia, myelodysplasia).
Clinical Relevance
1. Anemia:
Iron-Deficiency Anemia:
Inadequate hemoglobin synthesis due to iron deficiency.
Megaloblastic Anemia:
Impaired DNA synthesis due to vitamin B12 or folic acid deficiency.
Aplastic Anemia:
Reduced erythropoiesis due to bone marrow failure.
2. Polycythemia:
Excess RBC production, increasing blood viscosity and workload on the heart.
3. Reticulocyte Count:
Used clinically to assess erythropoiesis.
Increased in conditions like hemorrhage or hemolysis.
Decreased in bone marrow suppression.
Summary of Erythropoiesis
Stage
Features
Key Events
Proerythroblast
Large nucleus, basophilic cytoplasm
Begins hemoglobin synthesis
Basophilic Erythroblast
Deeply basophilic cytoplasm
Active protein synthesis
Polychromatic Erythroblast
Mixed cytoplasmic staining due to hemoglobin
Hemoglobin accumulates
Orthochromatic Erythroblast
Nucleus shrinks and is extruded
Final stage in marrow
Reticulocyte
Residual RNA; no nucleus
Released into bloodstream, matures in 1–2 days
Erythrocyte
Mature RBC with biconcave shape
Transports oxygen and carbon dioxide
Functions of RBC
Functions of Red Blood Cells (RBCs)
Red blood cells (RBCs), also known as erythrocytes, are specialized cells in the blood primarily responsible for the transportation of gases and the maintenance of acid-base balance. Their biconcave shape and hemoglobin content make them uniquely suited for these roles.
Primary Functions of RBCs
1. Oxygen Transport:
RBCs transport oxygen from the lungs to tissues.
Hemoglobin, the oxygen-carrying protein in RBCs, binds to oxygen molecules in the lungs and releases them in peripheral tissues.
Mechanism:
Oxygen binds to the iron in the heme portion of hemoglobin.
Each hemoglobin molecule can carry four oxygen molecules.
2. Carbon Dioxide Transport:
RBCs carry carbon dioxide from tissues to the lungs for exhalation.
Mechanisms of CO₂ Transport:
Bicarbonate Buffer System (70%):
RBCs contain the enzyme carbonic anhydrase, which converts CO₂ and water into carbonic acid.
Carbonic acid dissociates into bicarbonate ions and hydrogen ions.
Bicarbonate ions are transported in plasma.
Carbaminohemoglobin (20–25%):
CO₂ binds to the globin portion of hemoglobin.
Dissolved CO₂ (5–10%):
CO₂ dissolves directly in plasma.
3. Acid-Base Balance:
RBCs play a critical role in maintaining the pH of blood (normal range: 7.35–7.45).
Carbonic Anhydrase:
Facilitates the conversion of CO₂ into bicarbonate, a key buffer in the blood.
Helps neutralize pH changes caused by metabolic processes.
4. Hemoglobin as a Buffer:
Hemoglobin buffers hydrogen ions (H⁺) produced during metabolism, preventing drastic pH changes.
This helps stabilize the blood’s acid-base balance.
5. Nutrient Transport (Minor Role):
RBCs can bind and transport small amounts of nutrients like amino acids, though this is not their primary function.
6. Maintaining Blood Viscosity and Volume:
RBCs contribute to the viscosity of blood, aiding in the regulation of blood flow and pressure.
Their concentration directly influences hematocrit, the percentage of RBCs in blood, affecting overall blood volume.
Structural Adaptations for Function
Biconcave Shape:
Increases surface area for gas exchange.
Provides flexibility to navigate through narrow capillaries.
Lack of Nucleus:
Maximizes space for hemoglobin, enhancing oxygen-carrying capacity.
Rich in Hemoglobin:
Each RBC contains ~250 million hemoglobin molecules, crucial for oxygen and CO₂ transport.
Clinical Relevance
Anemia:
Reduced RBC count or hemoglobin impairs oxygen delivery, leading to fatigue, pallor, and shortness of breath.
Causes include iron deficiency, vitamin B12 deficiency, and chronic diseases.
Polycythemia:
Excessive RBC production increases blood viscosity, risking thrombosis and hypertension.
Carbon Monoxide Poisoning:
Hemoglobin binds to carbon monoxide (CO) more strongly than oxygen, reducing oxygen delivery.
Sickle Cell Anemia:
Abnormally shaped RBCs reduce oxygen transport and can block blood flow.
Hypoxia:
Insufficient oxygen in tissues due to low RBC count, lung disease, or high altitude.
Summary of RBC Functions
Function
Details
Oxygen Transport
Hemoglobin binds oxygen in the lungs and releases it in tissues.
Carbon Dioxide Transport
CO₂ is carried as bicarbonate, carbaminohemoglobin, or dissolved gas.
Acid-Base Balance
Maintains pH via bicarbonate buffer and hydrogen ion binding.
Blood Viscosity
RBCs contribute to blood thickness, influencing flow and pressure.
Hemoglobin Buffering
Buffers excess hydrogen ions to stabilize pH.
RBC life cycle
Life Cycle of Red Blood Cells (RBCs)
The life cycle of a red blood cell (RBC) spans approximately 120 days, during which it performs essential functions like oxygen and carbon dioxide transport. The cycle includes stages of production, circulation, and removal.
Stages of the RBC Life Cycle
1. Production (Erythropoiesis)
Site: Red bone marrow of flat bones (e.g., sternum, pelvis) and the ends of long bones (e.g., femur).
Stimulus: Low oxygen levels (hypoxia) stimulate the kidneys to produce erythropoietin (EPO), which promotes RBC production.
Steps:
Hematopoietic Stem Cell (HSC):
Differentiates into myeloid progenitor cells.
Proerythroblast:
First committed precursor for RBCs.
Basophilic Erythroblast:
Starts producing hemoglobin.
Polychromatic Erythroblast:
Cytoplasm changes color due to hemoglobin accumulation.
Orthochromatic Erythroblast (Normoblast):
Nucleus shrinks and is eventually extruded.
Reticulocyte:
Immature RBC released into the bloodstream.
Matures into an erythrocyte within 1–2 days.
Duration: Erythropoiesis takes about 5–7 days.
2. Circulation
Mature RBCs enter the bloodstream and perform their primary functions:
Oxygen Transport:
Hemoglobin binds oxygen in the lungs and releases it to tissues.
Carbon Dioxide Transport:
Hemoglobin and the bicarbonate buffer system transport CO₂ from tissues to the lungs.
pH Regulation:
Maintains acid-base balance by buffering hydrogen ions.
Characteristics:
RBCs are anucleate and lack organelles, maximizing space for hemoglobin but limiting repair ability.
3. Aging and Senescence
As RBCs age (~120 days), they undergo structural and functional changes:
Reduced Flexibility:
Makes it difficult for RBCs to pass through narrow capillaries.
Oxidative Damage:
Hemoglobin and membrane proteins degrade over time.
Signal for Removal:
Senescent RBCs expose specific markers (e.g., phosphatidylserine) recognized by macrophages.
4. Destruction and Removal
Site: The majority of old RBCs are removed by the reticuloendothelial system (RES), primarily in the spleen, liver, and bone marrow.
Process:
Phagocytosis:
Macrophages engulf and break down senescent RBCs.
Hemoglobin Breakdown:
Globin: Broken down into amino acids for reuse.
Heme:
Iron: Recycled and transported to the bone marrow via transferrin.
Porphyrin Ring: Converted to biliverdin, then bilirubin, which is excreted in bile.
Iron Recycling:
Iron is stored in the liver as ferritin or hemosiderin for future erythropoiesis.
Key Features of the RBC Life Cycle
Stage
Event
Duration
Production
Erythropoiesis in red bone marrow
~5–7 days
Circulation
Oxygen and CO₂ transport in the bloodstream
~120 days
Destruction
Removal by macrophages in spleen, liver, and bone marrow
Continuous after aging
Regulation of the RBC Life Cycle
Erythropoietin (EPO):
Produced by the kidneys in response to hypoxia.
Stimulates RBC production in the bone marrow.
Nutritional Factors:
Iron: Required for hemoglobin synthesis.
Vitamin B12 and Folic Acid: Necessary for DNA synthesis in developing RBCs.
Proteins: Needed for globin synthesis.
Homeostasis:
Negative feedback loop ensures a constant RBC count.
Hypoxia triggers increased erythropoiesis; normal oxygen levels suppress EPO release.
Clinical Relevance
Anemia:
Insufficient RBC production or excessive destruction.
Causes: Iron deficiency, vitamin B12 deficiency, chronic diseases, or bone marrow disorders.
Can result from high altitude or disorders like polycythemia vera.
Jaundice:
Excessive breakdown of RBCs leads to elevated bilirubin, causing yellowing of the skin and eyes.
Hemolysis:
Premature destruction of RBCs due to conditions like sickle cell disease or autoimmune disorders.
Erythropoietin Therapy:
Used to treat anemia in chronic kidney disease or chemotherapy patients.
WBC- types, functions
White Blood Cells (WBCs) – Types and Functions
White Blood Cells (WBCs), also called leukocytes, are a critical component of the immune system, protecting the body against infections, foreign invaders, and abnormal cells. They are produced in the bone marrow and circulate in the blood and lymphatic system.
Types of WBCs
WBCs are classified into granulocytes and agranulocytes based on the presence of granules in their cytoplasm.
Granulocytes
Neutrophils (50-70%)
Function:
First responders to bacterial and fungal infections.
Engulf and destroy pathogens through phagocytosis.
Release enzymes like lysozyme to kill microorganisms.
Lifespan: 6-8 hours in the bloodstream; a few days in tissues.
Eosinophils (2-4%)
Function:
Combat parasitic infections (e.g., helminths).
Regulate allergic reactions by moderating histamine release.
Involved in chronic inflammatory conditions like asthma.
Lifespan: 8-12 days.
Basophils (<1%)
Function:
Release histamine and other chemicals during allergic and inflammatory responses.
Play a role in hypersensitivity reactions.
Contribute to the defense against ectoparasites.
Lifespan: A few hours to a few days.
Agranulocytes
Lymphocytes (20-40%)
Function:
B-lymphocytes: Produce antibodies for humoral immunity.
T-lymphocytes: Directly attack infected or cancerous cells (cell-mediated immunity).
Natural Killer (NK) Cells: Destroy virus-infected cells and tumor cells.
Lifespan: Weeks to years, depending on the type.
Monocytes (2-8%)
Function:
Differentiate into macrophages or dendritic cells in tissues.
Perform phagocytosis to engulf pathogens and dead cells.
Present antigens to activate T-cells (antigen-presenting cells).
Lifespan: Circulate for 1-3 days, then migrate to tissues and live for weeks to months.
Functions of WBCs
Immune Defense: Protect the body against bacteria, viruses, fungi, and parasites.
Phagocytosis: Engulf and digest pathogens and debris (mainly neutrophils and monocytes).
Allergic Reactions: Regulate histamine release (basophils and eosinophils).
Antibody Production: B-lymphocytes produce specific antibodies.
Cytotoxic Activity: T-lymphocytes and NK cells kill infected or abnormal cells.
Regulation of Inflammation: Release of cytokines and chemokines to mediate immune responses.
Healing and Repair: Remove dead cells and aid in tissue repair.
Platelets-Function and production of platelets
Platelets: Function and Production
Platelets, also known as thrombocytes, are small, disc-shaped, anucleate cell fragments found in the blood. They are essential for maintaining hemostasis by aiding in blood clot formation and preventing excessive bleeding.
Production of Platelets
The process of platelet production is called thrombopoiesis and occurs in the bone marrow.
Origin: Platelets are derived from large bone marrow cells called megakaryocytes.
Thrombopoietin:
A hormone produced mainly in the liver and kidneys regulates platelet production.
Stimulates the differentiation and maturation of megakaryocytes.
Formation:
Megakaryocytes extend cytoplasmic projections called proplatelets into blood vessels in the bone marrow.
These proplatelets fragment into thousands of platelets, which are released into the bloodstream.
Lifespan:
Platelets have a lifespan of approximately 7–10 days.
Old or damaged platelets are removed by macrophages in the spleen and liver.
Functions of Platelets
Hemostasis (Prevention of Bleeding):
Platelets adhere to damaged blood vessel walls at the site of injury.
They form a temporary platelet plug by clumping together (platelet aggregation).
Release clotting factors that activate the coagulation cascade, leading to the formation of a stable blood clot.
Release of Granules:
Platelets contain granules (α-granules and dense granules) that release substances to promote clot formation and vascular repair:
ADP and thromboxane A2: Promote platelet aggregation.
Serotonin: Enhances vasoconstriction.
Platelet-derived growth factor (PDGF): Stimulates tissue repair and regeneration.
Vasoconstriction:
Platelets release substances like serotonin that cause constriction of blood vessels, reducing blood loss.
Wound Healing:
Platelets secrete growth factors such as vascular endothelial growth factor (VEGF) and PDGF, which aid in tissue repair and angiogenesis (formation of new blood vessels).
Immune Response:
Platelets play a role in modulating the immune response by interacting with white blood cells and releasing pro-inflammatory mediators.
Platelet Count
Normal range: 150,000–450,000 per microliter of blood.
Thrombocytopenia (low platelet count): Leads to increased bleeding risk.
Thrombocytosis (high platelet count): Can cause clotting disorders like thrombosis.
Clotting mechanism of blood,
Clotting Mechanism of Blood
The clotting mechanism, also known as hemostasis, is a complex physiological process that stops bleeding when a blood vessel is injured. It involves a series of cellular and molecular events that lead to the formation of a blood clot.
The process can be divided into three key stages:
Vascular Spasm (Vasoconstriction)
Platelet Plug Formation
Coagulation (Clot Formation)
Steps of the Clotting Mechanism
1. Vascular Spasm (Vasoconstriction)
What happens:
Immediately after a blood vessel is injured, the smooth muscles in the vessel wall contract.
This reduces blood flow to the damaged area, minimizing blood loss.
Key mediators: Endothelin, serotonin, and thromboxane A2.
2. Platelet Plug Formation
Platelets adhere to the exposed collagen fibers of the damaged blood vessel.
Steps involved:
Adhesion: Platelets bind to von Willebrand factor (vWF) on the exposed collagen.
Activation: Platelets release chemicals like ADP, serotonin, and thromboxane A2, which activate more platelets.
Aggregation: Platelets clump together, forming a temporary platelet plug.
This plug is unstable and requires reinforcement through the coagulation cascade.
3. Coagulation (Clot Formation)
The coagulation cascade involves a series of enzymatic reactions that culminate in the formation of fibrin, which stabilizes the platelet plug.
Pathways:
Intrinsic Pathway: Activated by damage to the vessel’s endothelium.
Extrinsic Pathway: Activated by trauma to the tissue outside the vessel.
Both pathways converge into the common pathway.
Coagulation Cascade
A. Intrinsic Pathway:
Trigger: Contact with negatively charged surfaces (e.g., collagen).
Factors involved: XII → XI → IX → VIII → X.
B. Extrinsic Pathway:
Trigger: Release of tissue factor (TF) from damaged tissues.
Factors involved: VII → TF-VII complex activates X.
C. Common Pathway:
Factor X gets activated (Xa), initiating the conversion of prothrombin (Factor II) into thrombin (Factor IIa).
Thrombin converts fibrinogen (soluble) into fibrin (insoluble), forming the meshwork that stabilizes the clot.
Fibrinolysis (Clot Breakdown)
After the vessel is healed, the clot is dissolved to restore normal blood flow.
Plasminogen is converted into plasmin, which digests fibrin and dissolves the clot.
Key Factors in Blood Clotting
Platelets: Initiate and stabilize the clot.
Clotting Factors:
There are 13 clotting factors (e.g., Factor I = Fibrinogen, Factor II = Prothrombin).
Most are proteins synthesized in the liver (Vitamin K-dependent factors: II, VII, IX, X).
Calcium (Ca²⁺): Essential for many steps in the cascade.
Vitamin K: Required for the synthesis of certain clotting factors.
Simplified Overview
Injury → Vasoconstriction.
Platelet Plug → Platelets adhere, activate, and aggregate.
Coagulation Cascade → Formation of fibrin mesh to stabilize the clot.
Clot Retraction → Platelets contract, making the clot more compact.
Clot Dissolution (Fibrinolysis) → Plasmin dissolves the clot after healing.
clotting time,& bleeding time
Clotting Time and Bleeding Time
Both clotting time and bleeding time are important diagnostic tests used to assess hemostatic function.
1. Clotting Time
Definition:
The time taken for blood to form a clot after being drawn.
It evaluates the intrinsic and common pathways of the coagulation cascade.
Normal Range:
4–10 minutes (depending on the method used).
Clinical Significance:
Prolonged clotting time can indicate:
Hemophilia (deficiency of clotting factors like VIII or IX).
Liver diseases (impaired synthesis of clotting factors).
Vitamin K deficiency.
Anticoagulant therapy (e.g., heparin, warfarin).
Methods of Measurement:
Capillary Tube Method:
A capillary tube is filled with blood and broken at intervals to check for clot formation.
Lee-White Method:
Blood is collected in a test tube and observed for clotting.
2. Bleeding Time
Definition:
The time taken for bleeding to stop after a small, standardized incision or puncture.
It assesses platelet function and vascular integrity.
A blood pressure cuff is inflated on the upper arm, and a small incision is made on the forearm.
The time taken for bleeding to stop is recorded.
Duke Method:
A puncture is made on the earlobe or fingertip, and the time for bleeding to stop is noted.
Comparison of Clotting Time and Bleeding Time
Parameter
Clotting Time
Bleeding Time
Purpose
Assesses coagulation cascade.
Assesses platelet function.
Normal Range
4–10 minutes
2–7 minutes (Ivy method)
Significance
Intrinsic/common pathway defects
Platelet or vascular issues
Test Methods
Capillary tube, Lee-White
Ivy, Duke
Key Notes:
Clotting Time focuses on the chemical process of blood clot formation.
Bleeding Time evaluates the mechanical process of stopping bleeding, primarily involving platelets.
PTT
Partial Thromboplastin Time (PTT)
Partial Thromboplastin Time (PTT) is a laboratory test used to evaluate the clotting ability of blood. It measures the time it takes for blood to form a clot after certain reagents are added. The test assesses the intrinsic and common pathways of the coagulation cascade.
Purpose of PTT Test
To evaluate unexplained bleeding or clotting.
To monitor anticoagulant therapy (e.g., heparin therapy).
To detect clotting disorders such as:
Hemophilia A (Factor VIII deficiency).
Hemophilia B (Factor IX deficiency).
Von Willebrand disease (secondary).
To assess liver function, as most clotting factors are synthesized in the liver.
Normal Range
25–35 seconds (can vary slightly depending on the laboratory).
Prolonged PTT
A prolonged PTT means it takes longer for blood to clot and may indicate:
Clotting Factor Deficiency:
Deficiency of factors VIII, IX, XI, or XII.
Liver Disease:
Impaired synthesis of clotting factors.
Vitamin K Deficiency:
Necessary for factors II, VII, IX, and X synthesis.
Anticoagulant Therapy:
Use of heparin or other anticoagulants.
Presence of Inhibitors:
Lupus anticoagulant or specific clotting factor inhibitors.
PTT vs. aPTT (Activated Partial Thromboplastin Time)
PTT: Original test; slower due to less activation.
aPTT: Modified version with added activators to speed up the clotting process (used more commonly in clinical practice).
Clinical Application
Heparin Monitoring:
PTT is used to monitor the effectiveness of unfractionated heparin therapy.
Target range: 1.5–2.5 times the normal PTT.
Diagnosis of Clotting Disorders:
Prolonged PTT helps identify deficiencies in factors like VIII, IX, or XI.
Pre-Surgical Screening:
Helps rule out bleeding disorders.
Hemostasis –role of vasoconstriction
Hemostasis and the Role of Vasoconstriction
Hemostasis is the physiological process that prevents and stops bleeding (hemorrhage) after vascular injury. It involves a well-coordinated interaction between blood vessels, platelets, and coagulation factors. Hemostasis has three main stages:
Vascular Spasm (Vasoconstriction)
Platelet Plug Formation
Coagulation (Clot Formation)
Role of Vasoconstriction in Hemostasis
Definition:
Vasoconstriction is the narrowing of blood vessels due to the contraction of smooth muscle cells in the vessel walls.
Purpose:
To reduce blood flow to the damaged area.
To minimize blood loss until other hemostatic mechanisms, like platelet plug formation and coagulation, can take effect.
How Vasoconstriction Occurs in Hemostasis
Trigger:
When a blood vessel is injured, the endothelium (inner lining of the vessel) gets damaged.
This leads to the release of vasoconstrictive substances.
Key Mediators:
Endothelin: Released by endothelial cells; a potent vasoconstrictor.
Serotonin: Released by activated platelets to sustain vasoconstriction.
Thromboxane A2: Produced by platelets to amplify vasoconstriction.
Nervous Reflexes:
Local pain receptors are stimulated.
Reflex signals from the nervous system contribute to immediate vasoconstriction.
Duration:
Vasoconstriction is a temporary response lasting minutes to hours, providing time for the subsequent stages of hemostasis to occur.
Significance of Vasoconstriction
Immediate Response:
It is the first step in hemostasis, occurring almost immediately after vascular injury.
Rapid action buys time for platelet aggregation and coagulation.
Reduction of Blood Loss:
By narrowing the blood vessel, it reduces the volume of blood flowing through the area of injury, minimizing hemorrhage.
Enhances Platelet Adhesion:
Slower blood flow and turbulence caused by vasoconstriction facilitate the contact of platelets with the exposed collagen of the damaged vessel wall.
Triggers Platelet Activation:
Vasoconstriction helps create the conditions necessary for platelets to adhere and aggregate at the site of injury.
Clinical Relevance
Excessive Vasoconstriction: Can lead to tissue ischemia (e.g., in conditions like Raynaud’s disease).
Inadequate Vasoconstriction: Contributes to excessive bleeding in disorders like vascular disorders or coagulopathies.
Summary
Vasoconstriction is a critical temporary defense mechanism in hemostasis, reducing blood flow and creating favorable conditions for platelet plug formation and clot stabilization. It ensures that the body minimizes blood loss immediately after vascular injury.
platelet plug formation in hemostasis,
Platelet Plug Formation in Hemostasis
Platelet plug formation is the second stage of hemostasis, following vasoconstriction. It plays a vital role in temporarily stopping blood loss by forming a “primary plug” at the site of a vascular injury. This plug provides a foundation for the more stable clot formed in the coagulation phase.
Phases of Platelet Plug Formation
The process of platelet plug formation involves three key steps:
1. Platelet Adhesion:
Trigger: Exposure of subendothelial collagen and von Willebrand factor (vWF) at the site of vascular injury.
Mechanism:
Platelets adhere to collagen using glycoprotein receptors (e.g., GP Ib on platelets binds to vWF).
vWF acts as a bridge between collagen and platelets, anchoring them to the damaged site.
Outcome: Platelets stick to the damaged endothelium, initiating plug formation.
2. Platelet Activation:
Trigger: Platelets undergo shape change and degranulation after adhesion.
Mechanism:
Platelets release substances stored in their granules, including:
ADP: Stimulates further platelet activation and recruitment.
Thromboxane A2: Promotes vasoconstriction and platelet aggregation.
Serotonin: Enhances vasoconstriction.
Calcium ions: Critical for coagulation factor activation.
Outcome: Platelets become activated, change shape (from discoid to spiky), and increase their surface area for better aggregation.
3. Platelet Aggregation:
Trigger: Activated platelets release ADP and thromboxane A2, which recruit additional platelets.
Mechanism:
Platelets bind to one another using fibrinogen bridges.
Glycoprotein IIb/IIIa (GP IIb/IIIa) receptors on platelets interact with fibrinogen, forming cross-links between platelets.
Outcome: A temporary platelet plug is formed to reduce blood flow.
Stabilization of the Platelet Plug
The platelet plug is initially loose and unstable.
It is stabilized by fibrin, formed during the coagulation phase (third step of hemostasis).
Fibrin mesh reinforces the platelet plug, creating a more durable clot.
Role of Platelets in Plug Formation
Surface Receptors:
GP Ib binds to von Willebrand factor.
GP IIb/IIIa binds to fibrinogen and forms platelet-platelet bridges.
Degranulation:
Releases ADP, thromboxane A2, serotonin, and calcium, promoting aggregation and clot formation.
Shape Change:
Increases surface area and enhances adhesion and aggregation.
Key Mediators
Von Willebrand Factor (vWF): Essential for platelet adhesion to collagen.
Thromboxane A2: Promotes vasoconstriction and platelet aggregation.
ADP: Amplifies platelet activation.
Fibrinogen: Acts as a bridge between platelets for aggregation.
Clinical Relevance
Platelet Dysfunction:
Disorders like Glanzmann thrombasthenia (defective GP IIb/IIIa) or Bernard-Soulier syndrome (defective GP Ib) impair plug formation.
Antiplatelet Therapy:
Drugs like aspirin (inhibits thromboxane A2) and clopidogrel (blocks ADP receptors) prevent platelet plug formation to reduce the risk of thrombosis.
coagulation factors,
Coagulation Factors
Coagulation factors are proteins in the blood plasma that work in a cascade to form a blood clot, an essential process in hemostasis. These factors are mostly synthesized in the liver, with some requiring Vitamin K for their production.
List of Coagulation Factors
Each factor is designated by a Roman numeral (I to XIII). Some factors are also known by specific names.
Factor Number
Name
Key Function
I
Fibrinogen
Converted to fibrin, forms the clot meshwork.
II
Prothrombin
Converted to thrombin, activates fibrinogen.
III
Tissue Factor (Thromboplastin)
Initiates the extrinsic pathway.
IV
Calcium (Ca²⁺)
Essential for all coagulation pathways.
V
Labile Factor
Cofactor for converting prothrombin to thrombin.
VII
Stable Factor
Activates Factor X in the extrinsic pathway.
VIII
Anti-Hemophilic Factor A
Cofactor for Factor IX in the intrinsic pathway.
IX
Anti-Hemophilic Factor B
Activates Factor X (intrinsic pathway).
X
Stuart-Prower Factor
Common pathway activator for prothrombin.
XI
Plasma Thromboplastin Antecedent
Activates Factor IX in the intrinsic pathway.
XII
Hageman Factor
Initiates the intrinsic pathway.
XIII
Fibrin-Stabilizing Factor
Cross-links fibrin, stabilizing the clot.
Coagulation Pathways
The coagulation cascade involves three interconnected pathways:
Intrinsic Pathway:
Activated by damage to the blood vessel endothelium.
Factors involved: XII → XI → IX → VIII → X.
Extrinsic Pathway:
Triggered by tissue factor (Factor III) released from damaged tissues.
Factors involved: III → VII → X.
Common Pathway:
Convergence of intrinsic and extrinsic pathways.
Factors involved: X → V → II (prothrombin) → I (fibrinogen) → fibrin clot.
Vitamin K-Dependent Coagulation Factors
Factors: II, VII, IX, X (along with proteins C and S, which regulate coagulation).
Vitamin K is required for the synthesis and activation of these factors in the liver.
Key Supporting Elements
Calcium (Factor IV): Essential cofactor for several steps.
Phospholipids: Provided by platelet membranes, required for activation complexes.
Deficiencies and Disorders
Factor Deficiencies:
Hemophilia A: Deficiency of Factor VIII.
Hemophilia B: Deficiency of Factor IX.
Hemophilia C: Deficiency of Factor XI.
Liver Disease: Affects synthesis of clotting factors.
Vitamin K Deficiency: Impairs synthesis of Vitamin K-dependent factors.
Clinical Importance
Coagulation Tests:
PT (Prothrombin Time): Assesses the extrinsic and common pathways (Factors II, V, VII, X).
aPTT (Activated Partial Thromboplastin Time): Assesses the intrinsic and common pathways (Factors VIII, IX, XI, XII).
Anticoagulants:
Warfarin: Inhibits Vitamin K-dependent factors.
Heparin: Enhances activity of antithrombin, which inhibits thrombin and Factor Xa.
intrinsic and extrinsic pathways of coagulation
Intrinsic and Extrinsic Pathways of Coagulation
The coagulation cascade is a series of enzymatic reactions that lead to the formation of a stable fibrin clot. It involves two initial pathways — intrinsic and extrinsic — that converge into a common pathway.
Intrinsic Pathway
Trigger: Activated by damage to the endothelium (inner lining of the blood vessel) or contact of blood with a negatively charged surface (e.g., collagen, glass).
Steps of the Intrinsic Pathway:
Factor XII (Hageman Factor) is activated (XII → XIIa).
XIIa activates Factor XI (XI → XIa).
XIa activates Factor IX (IX → IXa) in the presence of calcium (Ca²⁺).
IXa forms a complex with Factor VIIIa and calcium, which activates Factor X (X → Xa).
Key Factors Involved:
Factor XII (Hageman Factor)
Factor XI (Plasma Thromboplastin Antecedent)
Factor IX (Christmas Factor)
Factor VIII (Anti-Hemophilic Factor A)
Clinical Importance:
Assessed by the aPTT (Activated Partial Thromboplastin Time) test.
Disorders such as Hemophilia A (Factor VIII deficiency) and Hemophilia B (Factor IX deficiency) affect this pathway.
Extrinsic Pathway
Trigger: Activated by trauma to tissue outside the blood vessel, resulting in the release of Tissue Factor (Factor III).
Steps of the Extrinsic Pathway:
Tissue damage exposes Factor III (Tissue Factor).
Tissue Factor (III) binds with Factor VII, forming a complex (TF-VIIa) in the presence of calcium (Ca²⁺).
The TF-VIIa complex activates Factor X (X → Xa).
Key Factors Involved:
Factor III (Tissue Factor)
Factor VII (Stable Factor)
Clinical Importance:
Assessed by the PT (Prothrombin Time) test.
Prolonged PT indicates issues with the extrinsic pathway, often related to Vitamin K deficiency or liver disease.
Common Pathway
Both intrinsic and extrinsic pathways converge into the common pathway.
Steps of the Common Pathway:
Factor Xa converts prothrombin (Factor II) into thrombin (Factor IIa) in the presence of Factor Va, calcium, and phospholipids.
Thrombin:
Converts fibrinogen (Factor I) into fibrin.
Activates Factor XIII, which cross-links fibrin strands to stabilize the clot.
Key Factors in Common Pathway:
Factor X (Stuart-Prower Factor)
Factor V (Labile Factor)
Factor II (Prothrombin)
Factor I (Fibrinogen)
Factor XIII (Fibrin-Stabilizing Factor)
Comparison of Intrinsic and Extrinsic Pathways
Feature
Intrinsic Pathway
Extrinsic Pathway
Trigger
Endothelial damage
Tissue damage
Primary Factor
Factor XII (Hageman Factor)
Tissue Factor (Factor III)
Speed
Slower
Faster
Test
aPTT (Activated Partial Thromboplastin Time)
PT (Prothrombin Time)
Key Disorders
Hemophilia A and B, von Willebrand Disease
Vitamin K deficiency, liver disease
Summary of Pathways
Intrinsic Pathway:
Activated by internal damage.
Involves Factors XII, XI, IX, VIII.
Slower process.
Extrinsic Pathway:
Activated by external trauma.
Involves Factors III, VII.
Faster process.
Common Pathway:
Convergence of both pathways.
Involves Factors X, V, II, I, XIII.
Leads to the formation of a stable fibrin clot.
Blood groups and types
Blood Groups and Types
Blood grouping is a classification of blood based on the presence or absence of antigens on the surface of red blood cells (RBCs). The two main systems used for classification are the ABO system and the Rh (Rhesus) system.
ABO Blood Group System
The ABO system is determined by the presence of antigens (A and B) on the surface of RBCs and corresponding antibodies in the plasma.
Blood Types:
Type A:
Antigens on RBCs: A
Antibodies in Plasma: Anti-B
Type B:
Antigens on RBCs: B
Antibodies in Plasma: Anti-A
Type AB:
Antigens on RBCs: A and B
Antibodies in Plasma: None
Universal Recipient: Can receive blood from all types (A, B, AB, O).
Type O:
Antigens on RBCs: None
Antibodies in Plasma: Anti-A and Anti-B
Universal Donor: Can donate blood to all types.
Rh (Rhesus) System
Based on the presence (Rh-positive) or absence (Rh-negative) of the Rh (D) antigen on RBCs.
Rh-positive: D antigen is present.
Rh-negative: D antigen is absent.
Clinical Relevance:
Incompatibility in Rh factor, such as Rh-negative mother and Rh-positive fetus, can lead to hemolytic disease of the newborn (HDN).
Common Blood Types in ABO and Rh Systems
There are eight major blood types combining the ABO and Rh systems:
A-positive (A⁺)
A-negative (A⁻)
B-positive (B⁺)
B-negative (B⁻)
AB-positive (AB⁺)
AB-negative (AB⁻)
O-positive (O⁺)
O-negative (O⁻)
Blood Type Compatibility
For Blood Transfusion:
Donor blood type must be compatible with the recipient’s blood type to prevent hemolytic reactions.
Recipient Blood Type
Can Receive From
A⁺
A⁺, A⁻, O⁺, O⁻
A⁻
A⁻, O⁻
B⁺
B⁺, B⁻, O⁺, O⁻
B⁻
B⁻, O⁻
AB⁺
A⁺, A⁻, B⁺, B⁻, AB⁺, AB⁻, O⁺, O⁻
AB⁻
A⁻, B⁻, AB⁻, O⁻
O⁺
O⁺, O⁻
O⁻
O⁻
For Plasma Transfusion:
Plasma compatibility is the reverse of RBC compatibility because of the antibodies present in plasma.
Inheritance of Blood Types
Blood type is inherited from parents.
ABO System:
Controlled by a single gene with three alleles (IA, IB, i).
IA and IB are codominant, while i is recessive.
Rh System:
Controlled by a separate gene.
Rh-positive is dominant over Rh-negative.
Clinical Importance
Blood Transfusion:
Requires compatibility testing to prevent adverse reactions.
Pregnancy:
Rh incompatibility can lead to HDN.
Rh immunoglobulin (RhoGAM) is administered to Rh-negative mothers.
Organ Transplant:
Blood group matching is essential for successful transplantation.
Forensics:
Blood group typing is used in paternity testing and crime investigations.
Functions of reticulo-endothelial system, Immunity
Functions of the Reticulo-Endothelial System (RES)
The Reticulo-Endothelial System (RES), also known as the mononuclear phagocyte system, is a network of specialized cells responsible for phagocytosis and immune regulation. These cells include monocytes, macrophages, and dendritic cells, found in the blood and tissues like the spleen, liver, lymph nodes, and bone marrow.
Key Functions of the RES:
Phagocytosis:
Engulfs and digests foreign particles, microorganisms, and dead cells.
Macrophages in tissues (e.g., Kupffer cells in the liver, alveolar macrophages in the lungs) perform phagocytosis.
Recycling of Erythrocytes:
Removes old and damaged red blood cells (RBCs).
In the spleen and liver, macrophages break down hemoglobin, recycle iron, and excrete bilirubin.
Antigen Presentation:
Macrophages and dendritic cells act as antigen-presenting cells (APCs).
They process antigens and present them to T-lymphocytes, initiating the adaptive immune response.
Storage of Iron:
Stores iron in the form of ferritin or hemosiderin released during RBC breakdown.
Prevents free iron from promoting bacterial growth.
Inflammation Regulation:
Releases cytokines and chemokines to attract immune cells and mediate inflammation.
Forms the first line of defense by rapidly responding to pathogens.
Immunity
Immunity refers to the body’s defense system against pathogens, toxins, and abnormal cells. It is divided into two main types: innate immunity and adaptive immunity.
Types of Immunity:
Innate Immunity (Non-Specific):
Present at birth and provides immediate defense.
Components:
Physical Barriers: Skin, mucous membranes.
Chemical Barriers: Stomach acid, enzymes in saliva.