Inflammation: Acute and Chronic Responses

Inflammation

• A vascularized tissue's response to cell damage
• Characteristics: Inflammatory mediators, fluid, and leukocytes move from blood to extravascular tissue
• Purpose: Minimize damage, remove damaged tissue, promote new tissue growth
• Causes: Trauma, surgery, infection, hypoxia, ischemia

Acute Inflammation

• Short duration and self-limited
• Neutrophils are the first cells to arrive

Chronic Inflammation

• Lasts for weeks, months, or years
• Characterized by mononuclear cells, lymphocytes, and fibroblasts

Vascular Phase of Acute Inflammation

• Hemodynamic changes in the small blood vessels at the site of injury
• Vasodilation: Increased capillary pressure, fluid outflow, swelling, pain, and functional impairment
• Vasoconstriction: Minimizes blood loss, maintains blood flow, and blood pressure
• Vascular Changes:
  • Immediate transient response: Minor injury
  • Immediate sustained response: More severe injury, lasts several days, damages vessels
  • Delayed hemodynamic response: Increased capillary permeability, 4 to 24 hours after injury (e.g., sunburn)

Cellular Phase

• White blood cell activation
• Two types of leukocytes in acute inflammation:
  • Granulocytes: Neutrophils, basophils, and eosinophils
  • Monocytes: Largest white blood cell type

Phagocytosis

• Five steps:
  • Chemotaxis: Cell migration towards chemical stimulus
  • Adherence and Opsonization: Attachment to and recognition of foreign material
  • Ingestion: Receptor activation, engulfment of targeted material
  • Digestion: Fusion with lysosomes, breakdown of engulfed material
  • Intracellular Killing: Removal of foreign material

Cardinal Signs of Inflammation

• Rubor (redness)
• Tumor (swelling)
• Calor (heat)
• Dolor (pain)
• Functio laesa (loss of function)

Systemic Signs of Inflammation

• Fever
• Malaise (feeling unwell)

Inflammatory Mediators

• Increase body's response to injury
• Chemotaxis: Direct migration of a cell in response to a chemical stimulus

Plasma-Derived Mediators

• Kinin system: Causes pain
• Clotting system: Forms clots to prevent infection spread and stop bleeding
• Complement system: Causes vasodilation

Chemical Mediators

• Histamine: Released in response to trauma and immune reactions
• Serotonin: Similar actions to histamine

Arachidonic Acid Metabolites

• Prostaglandins: Induce inflammation, similar effects to histamine
• Leukotrienes: Similar functions to histamine

Nitric Oxide

• Produced by various cells, plays a role in inflammation
• Relaxes smooth muscle in vessel walls
• Regulates leukocyte movement

Inflammatory Exudates

• Serous exudate: Watery fluid, low protein content, plasma entering the site
• Hemorrhagic exudate: Severe tissue injury, blood vessel damage
• Membranous exudate: Forms on mucus membrane surfaces
• Purulent exudate: Contains pus
• Fibrinous exudate: Contains large amounts of fibrin

Granulomatous Inflammation

• Associated with:
  • Foreign bodies (splinters, sutures)
  • Microorganisms causing tuberculosis, syphilis, and deep fungal infections

Body's Protective Response

• Involves:
  • Inflammatory reaction
  • Immune response
  • Tissue repair

Manifestations of Inflammation

• Increased plasma proteins
• Increased skeletal muscle breakdown
• White blood cell alterations
• Fever

Fever Patterns

• Intermittent: Normal temperature between fevers
• Remittent: Temperature remains above normal, fluctuates more than 1 degree in 24 hours
• Sustained: Temperature remains above normal, fluctuates less than 1 degree in 24 hours
• Neurogenic: Caused by brain and spinal cord trauma

Dangers of Fever

• 1-degree increase leads to a 15-beat-per-minute increase in heart rate

Body Organ and Tissue Structure

• Parenchymal tissue: Contains the functioning cells of an organ or body part
• Stromal tissue: Supports connective tissue, blood vessels, and nerve fibers

Two Types of Healing

• Regeneration- replacement of injured cells with cells of the same type
• Repair - replacement of lost cells with connective tissue

Types of Hypersensitivity

• Type I - Immediate, IgE-mediated, mast cells degranulate, histamine release, examples: allergic reations, anaphylaxis,
• Type II - Antibody dependent cytotoxic, antibodies (IgM,IgG) attack antigens, examples: Rh disease, drug reactions, involves neutrophils, macrophages and IgG,IgM
• Type III - Immune complex medicated, antigen is not attached to cells, inflammatory response produces the damage, examples: lupus, serum sickness, Arthur's reaction
• Type IV - Cell-mediated hypersensitivity, T cells attack antigen, examples: Tuberculin test, allergic contact dermatitis

Transplant Reaction Types

• Hyperacute reactions: Occur immediately after transplantation
• Acute rejection: Occurs within a few months after transplantation

HIV and AIDS

• HIV: The virus
• AIDS: Manifestations of the infection
• Diagnosis:
  • ELISA: Initial screening test
  • Western blot: Confirmation test

Opportunistic Infections

• Respiratory diseases: Tuberculosis, pneumonia
• GI diseases: Thrush, protozoal infections, diarrhea
• Nervous system: AIDS dementia, Toxoplasmosis (neurological dysfunction)
• Malignancies: Kaposi's sarcoma (affects blood vessel lining)
• Wasting syndrome: Involuntary weight loss, weakness, fever

Ions

• Negative: Anions
• Positive: Cations

Body Fluid Functions

• Transport gases, nutrients, and waste
• Metabolic processes
• Maintain body function

Body Fluid Distribution

• Intracellular compartment: Inside the cell, 2/3 of body water, high potassium concentration
• Extracellular compartment: Outside the cell, 1/3 of body water, high sodium concentration

Fluid Exchange at Capillaries

• Four forces control water movement between capillaries and interstitial spaces
• Starling's Law of Capillaries: The volume reabsorbed equals the volume filtered

Edema (Fluid Accumulation)

• Occurs when filtration exceeds reabsorption
• Concerns: Increased diffusion distance, impaired function, blood vessel compression
• Common sites: Stomach, lungs, heart

Water Gain and Loss

• 2500 ml intake, 2500 ml output

Physiological Mechanisms Regulating Body Water

• Thirst: Primary regulator of water intake
• ADH (Antidiuretic Hormone): Regulates water output

Ways to Lose Water

• Insensible loss: Sweat, respiration
• Measurable loss: Urine, vomit, diarrhea

Sodium Regulation

• Kidney: Main regulator, monitors arterial pressure, retains sodium when pressure is low, eliminates it when pressure is high

Thirst Triggers

• Osmoreceptors in the hypothalamus

Types of Thirst

• Hypodipsia: Inability to sense thirst
• Polydipsia: Excessive thirst

Disorders of ADH Expression

• Diabetes insipidus: Excessive water loss in urine
• SIADH (Syndrome of Inappropriate Antidiuretic Hormone): Impaired negative feedback system regulating ADH release

Types of Diabetes Insipidus

• Central or neurogenic: Defect in ADH synthesis or release
• Nephrogenic: Kidneys do not respond to ADH

Disorders of Sodium and Water Balance

• Changes can be proportional (isotonic) or disproportionate (hypertonic or hypotonic)

Isotonic Fluid Volume Deficit (Hypovolemia)

• Water and electrolytes lost in equal proportions
• Causes: High salt intake
• Manifestations: Increased thirst, dry mucous membranes

Isotonic Fluid Volume Excess (Hypervolemia)

• Disproportionate intake or retention of water and sodium

Sodium Needs

• 500 mg per day

Importance of Sodium

• Maintains serum osmolality
• Acid-base balance
• Electrical impulse transmission
• Cell integrity (sodium-potassium pump)

Hyponatremia

• Low sodium levels

Types of Hyponatremia

• Hypertonic hyponatremia: Osmotic water shift due to high blood glucose
• Hypovolemic hypotonic hyponatremia: Most common, ECF loss due to sweating, vomiting, diarrhea
• Normovolemic hypotonic hyponatremia: Associated with SIADH, post-operative, high ADH levels
• Hypervolemic hypotonic hyponatremia: Least common

Hypernatremia

• High sodium levels
• Causes: Excessive sodium intake or water loss
• Euvolemic: Water from ICF shifts to ECF
• Hypovolemic: Water loss exceeds sodium loss
• Hypervolemic: Addition of hypertonic solution containing sodium and water

Potassium Distribution and Regulation

• Key role in muscle contraction and nerve impulse transmission
• Regulation:
  • Renal excretion: Main regulator, influenced by aldosterone
  • Cellular uptake, shifting between ICF and ECF

Disorders of Potassium Balance

• Hypokalemia: Low potassium levels
• Hyperkalemia: High potassium levels

Acid-Base Balance

• Normal pH: 7.35-7.45
• Regulation:
  • Buffers
  • Respiratory system (lungs)
  • Renal system (kidneys)

Acid-Base Disorders

• Primary: Initiating event
• Compensatory: Attempting to correct pH change

Types of Acid-Base Disorders

• Metabolic: Involves bicarbonate (HCO3-)
• Respiratory: Involves carbon dioxide (CO2)

Metabolic Acidosis

• Primary deficit of bicarbonate, decreased pH

Causes of Metabolic Acidosis

• Decreased kidney function
• Increased bicarbonate loss

Manifestations of Metabolic Acidosis

• Increased respiration
• Hyperkalemia

Metabolic Alkalosis

• Increased pH due to increased bicarbonate ions

Causes of Metabolic Alkalosis

• Loss of acids (e.g., vomiting)
• Increased bicarbonate retention

Respiratory Acidosis

• Increased CO2, carbonic acid, and decreased pH

Causes of Respiratory Acidosis

• Acute: Always accompanied by low oxygen
• Acute respiratory failure: Severe drop in pH, minimal change in bicarbonate

Respiratory Alkalosis

• Decreased CO2, carbonic acid deficit, and increased pH

Causes of Respiratory Alkalosis

• Panic attacks, fever, excessive stress