Homeostasis

NUR 320: Week 2 Study Notes

Goal for the Day

  • Review any questions

  • Lecture

  • Ticket to test

  • In-class post quiz

Homeostasis

Learning Objectives

  • By the end of this class, students will be able to:

    • Describe the structure and function of the cell.

    • Identify the mechanisms by which cells regulate.

    • Describe cell function and their relation to tissue.

    • Compare the four basic tissue types.

    • Analyze the role that cell communication plays in the disease process.

    • Describe the life cycle of various blood cells.

    • Explain hemostasis.

    • Explain the disease processes of hematologic disorders.

Cellular and Tissue Homeostasis

  • Cell Theory:

    • The cell is the basic functional unit of life.

    • All living things are composed of cells.

    • Humans are multicellular organisms.

    • Cells with similar structures and functions work together.

    • Groups of cells form tissues.

    • Tissues combine to form organs and organ systems.

    • Cells are the building blocks of all bodily structures and functions.

  • Homeostasis:

    • Homeostasis is maintained when cells function normally.

Cell Structure and Function

Eukaryotic Cells

  • Plasma Membrane:

    • Selectively permeable.

  • Cytoplasm:

    • Internal environment of the cell, composed of water, organic substances, and organelles.

  • Cytosol:

    • Composed of proteins, lipids, carbohydrates, and electrolytes.

  • Nucleus:

    • Contains chromosomes (humans have 46 chromosomes, 23 from each parent).

  • DNA:

    • Composed of nucleotides.

    • DNA Replication:

      • Occurs during mitosis.

    • Gene Expression:

      • DNA is transcribed into mRNA, which is translated into proteins for cell functions.

Nucleolus

  • Produces ribosomal RNA.

  • Participates in tRNA transcription.

  • An enlarged nucleolus is associated with tumor aggressiveness.

  • Dysregulated nucleolar function is linked to:

    • Cancer

    • Cardiovascular disease

    • Neurodegenerative disorders

    • Premature aging

Material Control in Cells

  • Endocytosis:

    • Phagocytosis: Engulfing large particles.

    • Pinocytosis: Cellular drinking of small molecules.

    • Receptor-mediated endocytosis: Selective uptake.

  • Role in Immune Response:

    • Engulfing foreign materials.

  • Insulin and Glucose Uptake:

    • Insulin binds to receptors for glucose entry; mechanism failure in type 1 diabetes leads to high blood glucose.

Passive and Active Transport

  • Simple Diffusion:

    • Driven by concentration differences.

    • Example: Oxygen diffusion in the lungs.

  • Facilitated Diffusion:

    • Requires transporter proteins.

  • Active Transport:

    • Requires cellular energy (ATP).

    • Example: Sodium/potassium pump:

      • Maintains low intracellular sodium and high potassium, using ATP for conformational changes, controls cell volume, enables electrical excitability in nerves and muscles, assists in glucose and amino acid transport.

Mitochondria

  • Responsible for energy transformation, converting dietary substances into ATP.

  • Inherited maternally.

  • High ATP demand is found in skeletal and cardiac muscle (many mitochondria present).

Apoptosis

  • Programmed Cell Death:

    • Vital for tissue remodeling and repair.

    • Controlled cell death, causes no damage.

  • Necrosis:

    • Uncontrolled cell death, causes inflammation.

Cell Communication

  • Types of Cell Communication:

    • Cardiac muscle cells use electrical coupling.

    • Epithelial cells regulate ion and nutrient flow.

  • Tight Junctions:

    • Separate different tissue spaces, prevent leakage of fluid, allow nutrient transport to the bloodstream, provide mechanical strength, prevent cell separation.

  • Gap Junctions:

    • Important in heart and smooth muscle. Loss of gap junctions results in dysregulation. In cardiac cells, it allows direct electrical communication between cardiomyocytes, ensuring efficient pumping of blood by the heart, is a target for antiarrhythmic drug development.

Chemical Signaling Systems

  • Autocrine Signaling:

    • Cells influence their own response.

  • Paracrine Signaling:

    • Neighbor influences another cell.

  • Endocrine Signaling:

    • Signals travel through the bloodstream to target cells.

  • Gap Junctions:

    • Allow signal sharing among directly connected cells.

Receptors, Signal, Transduction, and Altered Membrane Potentials

  • Insulin produced by pancreatic beta cells is released into the bloodstream and binds to specific receptors on target cells.

  • The insulin receptor is a receptor of tyrosine kinase. Binding induces receptor shape and change.

Paracrine Signaling

  • Target cells of endocrine signaling may be distant.

  • Paracrine signaling relies on close proximity, seen in the nervous system.

  • Nerve impulses influence target tissue, through ion movement across the plasma membrane, neuro-transmitter release, and receptor binding.

Cell Metabolism

  • Causes muscle fatigue and confusion due to glucose metabolism issues.

  • Glucose metabolism is crucial for energy production in cells.

  • ATP is the primary energy currency of the cell.

  • Carbohydrates are the dominant energy source in the human diet.

Cell Metabolism and Drugs

  • Drugs affect ATP production.

  • Important to consider medication effects on metabolism.

Tissue

Tissue Basics

  • Cells form the basis of tissues.

  • Tissues perform specific functions in organs and organ systems.

  • Four categories of tissue types:

    • Epithelial

    • Connective

    • Muscular

    • Nervous

Epithelial Tissue

  • Protects underlying tissue from mechanical damage and injury.

  • Responsible for secretion, transport, or absorption of materials.

  • Gland formation:

    • Exocrine Glands: Have ducts.

    • Endocrine Glands: Do not have ducts.

  • Detect sensations.

  • Simple: Single layer of cells.

  • Stratified: Multiple layers of cells.

Connective Tissue

  • Provides structural support, storage, immunologic defense, and medium for exchange.

  • Contain fibers for tensile strength and flexibility:

    • Collagen Fibers: Provide tensile strength and structural framework.

    • Elastic Fibers: Allow deformation and durable flexibility.

Muscle Tissue

  • Responsible for movement of air, blood, and food.

  • Requires synchronized muscle contraction:

    • Skeletal Muscle: Voluntary, controlled by the somatic nervous system.

    • Cardiac Muscle: Involuntary, inherent contractile ability.

    • Smooth Muscle: Involuntary.

Nervous Tissue

  • Conducts impulses, integrating electrochemical information.

  • Rapid receipt and conductance of impulses.

  • Transmits information to target tissue.

  • Diabetic Neuropathy:

    • Caused by excess glucose, oxidative stress, and mitochondrial damage, leading to numbness, tingling, burning, and loss of sensation.

Injury and Adaptation

Homeostasis and Injury Response

  • Cells maintain homeostasis by responding to stressors, employing adaptive changes for survival.

Types of Injury

  • Reversible Injury:

    • Complete or partial restoration of cellular structure and function.

  • Irreversible Injury:

    • Results in cell death.

Tissue Injury Effects

  • Cellular homeostasis is disturbed when cells are injured.

  • Injuries and diseases begin at the cellular level, which can alter tissue and organ function.

  • Common Mechanisms of Injury:

    • ATP depletion

    • Plasma membrane synthesis

    • Impaired protein synthesis

    • DNA damage

    • Mitochondrial damage

Causes of Tissue Injury

  • Oxygen Deficiency (Hypoxia):

    • Common cause of cellular injury, results from ischemia, anemia, or hypoxemia.

  • Physical Agents of Injury:

    • Thermal injury, mechanical trauma, radiation, electrical injury.

  • Chemical Agents:

    • Drugs, toxins, corrosive substances.

  • Biological Agents:

    • Bacteria, viruses, fungi.

  • Nutritional Imbalances:

    • Excess or deficiency of nutrients.

Adaptive Response to Injury

  • Cells attempt to repair or respond to injury:

    • Hyperplasia: Increase in cell number.

    • Hypertrophy: Increase in cell size.

    • Atrophy: Decrease in cell size.

    • Metaplasia: Conversion of one cell type to another.

    • Dysplasia: Change in nuclear shape or histological appearance.

Hemostasis

Week 2 Overview

  • Hemostasis:

    • Tight regulation maintains the integrity of the circulatory system.

    • Prevents excessive blood loss.

    • Enables tissue repair.

    • Involves interplay between endothelial cells, platelets, and the coagulation cascade, essential for survival.

Blood Cell Overview

  • Blood is a connective tissue composed of cells and plasma.

  • Essential for maintaining homeostasis.

  • Primary functions include:

    • Oxygen transport

    • Immune defense

    • Clot formation

    • Tissue repair.

  • Three Main Types of Blood Cells:

    • Red Blood Cells (RBC): Oxygen and gas transport (lifespan - 120 days).

    • White Blood Cells (WBC): Immune defense.

    • Platelets: Clot formation produced by stem cells in the bone marrow.

Normal Range for RBC

  • Children: 4.1-5.5 million/mcL

  • Adult Female: 4.2-5.4 million/mcL

  • Adult Male: 4.7-6.1 million/mcL

Normal Range for WBC

  • 4,000-11,000/L

  • Leukopenia: WBC < 4,000/L, associated with viral infections and immunocompromise.

  • Leukocytosis: WBC > 11,000/L, associated with bacterial infections, inflammatory responses, stress, and hematological cancers.

  • Granulocytes:

    • Neutrophils, basophils, eosinophils.

  • Agranulocytes:

    • Lymphocytes, monocytes.

Normal Range for Platelets

  • 150,000-450,000 per microliter (mcL)

  • Lifespan: 89 days.

  • Primary responsibility is clotting and hemostasis with functions including adhesion, activation, and aggregation.

Complete Blood Count (CBC) Overview

  • RBC Count:

    • Number of RBC per unit volume of blood affected by polycythemia vera and anemia.

    • Normal Range: 14-18 g/dL (males), 12-16 g/dL (females), used to diagnose anemia and assess response to blood transfusion.

  • Hemoglobin (Hb):

    • Main component of RBC.

  • Hematocrit (Hct):

    • % of RBC in blood.

    • Normal Range: 40-50% (males), 37-47% (females).

  • Bleeding Time (BT):

    • Normal Range: 2-7 minutes, measures platelet function.

    • Normal Range: 1.0 (without anticoagulation therapy), Therapeutic range: 2.0-3.5 (with anticoagulation therapy).

  • *International Normalized Ratio (INR)

  • Prothrombin Time (PT):

    • Normal Range: 11-15 seconds.

  • Partial Thromboplastin Time (PTT):

    • Normal Range: 25-40 seconds.

Coagulation Factors Overview

  • Clotting factors are essential proteins in the coagulation cascade, necessary for maintaining hemostasis after vascular injury.

  • Primary site of production: liver.

  • After injury, clotting factors interact to form and stabilize a blood clot; deficiency can lead to bleeding disorders.

  • Coagulation tests include: Bleeding time, PT, INR, PTT.

Hemostasis Process

  • Hemostasis is the process that stops bleeding following vascular injury through a cascade of coordinated events within the blood vessel.

  • Four basic stages of hemostasis:

    1. Vasoconstriction: Immediate narrowing of the blood vessel to reduce blood flow.

    2. Platelet Plug Formation: Platelets adhere, activate, and aggregate at the injury site.

    3. Coagulation Cascade Activation: Enzymatic reactions generate fibrin.

    4. Final Fibrin Clot Formation: Fibrin stabilizes the platelet plug into a firm clot. Early clot formation seals the injury, preventing further bleeding and initiating tissue regeneration.

  • As healing progresses, the clot remodels and dissolves, restoring normal tissue.

Primary and Secondary Hemostasis

  1. Primary Hemostasis:

    • Includes vasoconstriction, platelet adhesion, platelet activation, and platelet aggregation resulting in the formation of a temporary platelet plug.

  2. Secondary Hemostasis:

    • Activates the coagulation cascade, involving the intrinsic pathway, extrinsic pathway, and common pathway, producing fibrin which reinforces the platelet plug and forms a stable, insoluble clot.

Systems Contribution to Hemostasis

  • Hematopoietic System (Bone Marrow):

    • Produces platelets, RBC, and WBC.

  • Hepatic System (Liver):

    • Hepatocytes synthesize clotting factors, anticoagulant proteins, and proteins involved in coagulation pathways.

    • Liver disease can reduce clotting factor production and disrupt hemostatic balance.

  • Vascular System (Endothelium):

    • Produces clotting factors III and VIII, working with factor IV (calcium) from plasma.

    • Vitamin K dependence: Several clotting factors require Vitamin K, supporting calcium binding within the coagulation cascade.

Imbalance in Hemostasis

  • Can be altered by therapeutic medications and disease processes, placing clients at risk for:

    • Bleeding and Thrombosis:

    • Hypercoagulation: Excessive clot formation, leading to an increased risk of thrombotic events (thrombosis).

    • Hypocoagulation: Inadequate clot formation, leading to increased risk for bleeding and hemorrhage, which can be altered by medical treatment (iatrogenic coagulopathy).

Hypercoagulation

  • Increases risk for thrombotic events, where thrombosis refers to blood clots obstructing blood flow in arterial or venous structures.

  • Virchow's Triad:

    • Involves hypercoagulability, stasis, and trauma.

  • Hypercoagulability increases clotting tendencies associated with:

    • Cancer

    • Pregnancy

    • Infections

    • Inflammation

    • Trauma

    • Hormone replacement therapy

    • Heparin-induced thrombocytopenia.

  • Stasis (slowed blood flow): Occurs during periods of immobility, varicose veins, pregnancy, or cardiac dysfunction.

  • Vascular Injury (Trauma):

    • Damage to endothelial lining due to surgery, injury, or inflammation can injure the vascular endothelium.

  • Venous Thromboembolic Events (VTE):

    • Provoked: Occur due to known risk factors.

    • Unprovoked: No identifiable cause for the event.

  • Common thrombotic events include:

    • Deep Vein Thrombosis (DVT)

    • Pulmonary Embolism (PE)

    • Thrombotic stroke

    • Acute Myocardial Infarction (AMI).

Hypocoagulation

  • Impaired coagulation leading to bleeding risk and hemorrhagic diathesis.

  • Potential outcomes include severe blood loss, hemodynamic instability, and vital organ damage.

  • Causes:

    • Heritable bleeding disorders, such as von Willebrand disease (vWD) and hemophilia.

    • Acquired bleeding disorders like disseminated intravascular coagulation (DIC), liver dysfunction, and platelet disorders.

Iatrogenic Coagulopathy

  • Refers to the impact of medications used to block platelet function, mitigating clot formation.

  • Patients face risks of bleeding or hemorrhagic events.

  • Antidotes and Rescue Procedures include:

    • Vitamin K

    • Fresh frozen plasma

    • Platelet transfusion

    • Packed red blood cell transfusion

    • Plasmapheresis.

Hemostasis Throughout the Lifespan

  • Maturation of the endothelium begins in the embryonic phase.

  • Fetal hemostasis emerges mid-gestation.

  • VTE is uncommon in children; the highest risk is in individuals >75 years old. Risk for VTE increases with age.

Thrombocytopenia

  • Defined as a platelet count < 150,000 mcL.

  • Leading to increased bleeding risk:

    • Petechiae: Small red or purple spots.

    • Purpura: Larger areas of bleeding under the skin.

  • Causes include:

    • Decreased platelet production.

    • Increased platelet destruction.

    • Platelet redistribution.

  • Types of Thrombocytopenia:

    • Primary: Autoimmune disorder due to production of autoantibodies against platelets.

    • Drug-induced: May occur due to medications.

    • Heparin-induced: Can occur when exposed to heparin.

Neutropenia

  • Defined as a neutrophil count < 1500/L:

    • Mild: 1000-1499 L

    • Moderate: 500-999 L

    • Severe: <500 L

  • Causes:

    • Increased neutrophil destruction.

    • Ineffective granulopoiesis.

    • Decreased production and shift to tissue.

  • Intrinsic Defects: Genetic mutation impairing neutrophil production.

  • Extrinsic Factors: Include medications, infections, and autoimmune diseases.

  • Types:

    • Primary: Hereditary.

    • Secondary: Due to medications, infections, cancer, nutrition, bone marrow disorders, hypersplenism.

  • Symptoms:

    • Fatigue, night sweats, rashes.

  • Physical Findings:

    • Fever, gingivitis, skin infections, respiratory symptoms.

Granulocyte-Colony Stimulating Factor (G-CSF)

  • Promotes the production of neutrophils and stimulates the functional actions of mature neutrophils.

  • Commonly used for:

    • Neutropenia post-chemotherapy.

    • Acute myeloid leukemia.

    • Aplastic anemia.

Hemophilia

  • Types include hemophilia, disseminated intravascular coagulation (DIC), and von Willebrand Disease.

  • They are inherited bleeding disorders.

  • Symptoms vary based on severity.

  • Treatment includes:

    • Factor replacement therapy.

    • Desmopressin.

    • Recombinant factor infusion.

  • DIC:

    • A hypercoagulable state with widespread clotting and bleeding, can be a complication of other diseases like sepsis, cancer, and trauma.

    • Activation of the clotting cascade by tissue factor leads to microthrombi formation and consumption of clotting factors.

  • Von Willebrand Disease (vWD):

    • Most common inherited bleeding disorder characterized by deficiency or dysfunction of von Willebrand factor.

    • Common symptoms include: nosebleeds, easy bruising, prolonged bleeding, and heavy menstrual bleeding.

Anemia

  • Defined as low RBC or hemoglobin levels, leading to reduced oxygen carrying capacity of blood.

  • Primary Causes include:

    • Decreased RBC production (e.g., iron deficiency anemia).

    • Increased RBC destruction (e.g., hemolytic anemia).

    • Blood loss (e.g., trauma, DIC).

  • Untreated Anemia leads to fatigue, weakness, cognitive impairment, and cardiovascular complications.

  • Symptoms:

    • Cold hands, dizziness, fatigue, pallor, tachycardia, hypotension, shortness of breath (SOB), pica (craving for non-food substances), fingernail deformity, smooth tongue, cracked skin at mouth corners.

  • At-risk Groups:

    • Females of reproductive age are at the highest risk.

  • Causes of Iron Deficiency Anemia:

    • Dietary insufficiency, blood loss, malabsorption, chronic medical conditions.

  • Iron Absorption:

    • Occurs in the small intestines.

  • Lab Indicators:

    • Low serum ferritin (<30 ng/mL).

  • Treatment Options:

    • Oral iron therapy.

    • Intravenous (IV) iron therapy.

Erythropoiesis-Stimulating Agents (ESAs)

  • Used to treat anemia caused by bone marrow failure.

  • Mechanism of action resembles endogenous erythropoietin (EPO).

  • Administered subcutaneous (subQ) or IV (only for dialysis with end-stage renal disease - ESRD).

Pernicious Anemia

  • An autoimmune disorder affecting intrinsic factor production.

  • Leads to vitamin B12 deficiency and megaloblastic anemia.

  • Can stem from malabsorption disorders or certain medications.

  • Requires lifelong vitamin B12 supplementation.

  • Symptoms: Pallor, dry skin, jaundice, tachycardia, weight loss, peripheral neuropathy, cognitive impairment, and neurological symptoms.

Folate Deficiency Anemia

  • Causes include inadequate dietary consumption, excessive alcohol, illicit drug use, or medication interference.

  • Symptoms:

    • Swollen, beefy red tongue, discomfort or pain when swallowing, oral ulcers, depression, and memory concerns.

  • Treatment: Oral folic acid supplementation.