Pathophysiology Exam 1

Pathology

Study of Disease

Pathologist

One who studies disease

Pathogens

Microorganisms or agents that cause disease

Pathologic

Caused by a disease process

Pathogenesis

Description of how a particular disease progresses

Pathogenesis: Acute Disease

Short-term disease with sudden onset

Pathogenesis: Chronic Disease

Long-term disease or slow healing process

Homeostasis

State of normalcy in the body

Disease

Change from normal where symptoms occur with a pathologic state present

Disorder

Abnormality of cellular or organ function

Syndrome

Group of symptoms caused by a specific disease

Etiology

The cause of a disease

Etiology: Idiopathic

Cause of disease is unknown

Etiology: Iatrogenic

Problem related to medical treatment (e.g., chemotherapy N/V)

ex: no thyroid → new problems

Etiology: Nosocomial

Disease acquired in a hospital setting

Top 2 Nosocomial Infections

Urinary Tract Infection (UTI) and Pneumonia (2nd most common but most deadly)

Predisposing Factors

Age, sex, environment, lifestyle, and hereditary factors that increase disease risk

Subjective Data

Patient-reported information (Chief Complaint, history of present illness (HPI), medical/social history)

Objective Data

Measurable healthcare findings (Physical Exam, Vitals, Labs, Diagnostic Tests)

Differential Diagnosis (DDx)

Systematic diagnostic method used to identify a disease when multiple alternatives exist. We use the DDx as guidelines to run tests to rule out or confirm the actual diagnosis.

Ex: pt complains of chest pain

DDx: Angina, MI, costochondritis, anxiety, PE, etc.

Nucleus Function

Cellular site of DNA synthesis and DNA transcription into RNA

Ribosome Function

Cellular organelles (free or attached to ER) that translate RNA into proteins

Mitochondria Function

Cellular site of aerobic metabolism producing ATP

Aerobic Respiration

Consumes Glucose and O2 in mitochondria to yield 32-36 ATP

Anaerobic Respiration

Consumes Glucose without O2 in cytoplasm, producing 2 ATP and Lactic Acid (produced in cytoplasm)

Anabolic Reactions

Energy-consuming chemical reactions ('building' or 'synthesis')

Catabolic Reactions

Energy-releasing chemical reactions ('breakdown' or 'digestion')

Potassium Gradient ([K+])

[K+]ECF < [K+]ICF; Potassium diffuses out of the cell

Sodium Gradient ([Na+])

[Na+]ECF > [Na+]ICF; Sodium diffuses into the cell

Calcium Gradient ([Ca2+])

[Ca2+]ECF > [Ca2+]ICF; Calcium is stored in ER and mitochondria with low cytosolic levels

Cell Stress Outcomes (not testable?)

Cellular adaptation, reversible cell injury, irreversible cell injury, apoptosis, or necrosis

Causes of Cell Injury

Hypoxic injury (lack of oxyxgen) → MCC, unintentional/intentional physical trauma (many types), free radicals/ROS, radiation, nutritional imbalances (kwashiokor, vitamin A toxicity), chemical injury, infections, immunologic injury, and temperature extremes

Saturated Fat Excess

Risk factor for Atherosclerosis (decreases blood flow, most common cause of death and heart disease)

Sugar Excess

Risk factor for Type II Diabetes Mellitus

Anemia Deficiencies

Deficiency in Iron, Vitamin B9 (Folate), or Vitamin B12

Scurvy Cause

Deficiency of Vitamin C (affects collagen)

Pellagra Cause & Symptoms

Deficiency of Vitamin B3 (Niacin); characterized by 3 D's: Dementia, Dermatitis, Diarrhea

Kwashiorkor Cause

Severe protein deficiency

Distended abdomen

Albumin → has to do with absorption; lots of fluid pools in abdomen

Marasmus Cause

Severe total calorie deficiency (proteins, sugars, and fats)

Free Radicals

Electrically uncharged atoms or atom groups with an unpaired, unstable electron

Reactive Oxygen Species (ROS)

Physiologic free radicals used in the electron transport chain and released during inflammation

Types of free radicals found in the mitochondria and neutrophils

Antioxidants > free radicals

Oxidative Stress

Occurs when Free Radicals > Antioxidant system capacity

Can cause a chain reaction of damage:

• lipid peroxidation → destruction of phospholipid bilayer

• alteration of proteins → misfolding

• alteration of DNA → mutations

Lipid Peroxidation

destruction of unsaturated fatty acids generates ROS → chain reaction → destruction of phospholipid bilayer (organelles and cell) → ‘leaky cell’

Cellular adaptation: Atrophy

Decrease in cell size

Cellular adaptation: Hypertrophy

Increase in cell size due to increased work demand or hormones (e.g., Cardiomegaly from HTN)

Cellular adaptation: Hyperplasia

Increase in cell number due to increased rate of cellular division (e.g., BPH, callus)

Cellular adaptation: Metaplasia

Reversible replacement of one mature cell type by another less mature cell type

Ex: Bronchial metaplasia

Ex: Barrett’s Esophagus

Barrett's Esophagus

Esophageal metaplasia where normal stratified squamous epithelium is replaced by simple columnar epithelium with goblet cells (usually found in lower GI)

Cellular adaptation: Dysplasia

Deranged cellular growth ('abnormal cell'); Not a true cellular adaptation but rather an atypical hyperplasia. Abnormal changes in the size, shape, and organization of mature cells.

Clinical: The amt of dysplasia determines the tumor grade

Ex: cervical dysplasia seen on a pap smear

Bronchial Metaplasia

Reversible replacement of bronchial ciliated columnar cells with stratified squamous epithelial cells due to smoking

Loss of cilia and mucus producing glands

Bronchial metaplasia can be reversed if the inducing stimulus (cigarette smoking) is removed

Hypoxic injury: Hypoxia

Lack of sufficient oxygen to cells; Most Common Cause (MCC) of cellular injury

Hypoxic injury: Ischemia (reduced blood supply)

Lack of blood flow into vessels that supply the cell with oxygen and nutrients

Ex: Atherosclerosis, thrombus, high altitude, anemia

Hypoxic injury: Anoxia

Total lack of oxygen supply (e.g., embolus causing MI, CVA, PE)

Effects of Hypoxic Cell Injury: 1. ATP depletion

• Anaerobic metabolism - until glycogen stores are depleted

• Na+/k+ ATPase & Ca2+ ATPase are affected

  • Increased intracellular Na+ & Ca2+

  • H2O follows Na+ → cell swelling

  • RER swelling → ribosomes detach → decrease in protein synthesis

Effects of Hypoxic Cell Injury: 2. Intracellular Calcium Effects

• Ca2+ activates intracellular catabolic enzymes

  • Decrease in ATP, membrane damage, DNA damage

  • Increase in mitochondrial permeability → increase in ROS (reactive oxygen species)

Effects of Hypoxic Cell Injury: 3. Oxygen-derived free radicals

Oxygen-derived free radicals = Reactive oxygen species (ROS)

• Destruction of cell membrane and nucleus

Effects of Hypoxic Cell Injury: 4. Defects in membrane permeability

• Leakage of intracellular enzymes, can be detected in the blood

• How do you diagnose an MI? Liver failure?

Cellular response to stress: Irreversible Injury (Cell death): Apoptosis

• Apoptosis

  • Programmed cell death ('cell suicide') characterized by cell shrinkage without inflammation

Cellular response to stress: Irreversible Injury (Cell death): Necrosis

Unprogrammed cell death characterized by cell swelling and inflammatory changes

Necrosis: Coagulative Necrosis

• MC in kidney, heart, skin

• Cause: hypoxia/ischemia/anoxia → infarction

• Tissue appears pale

Necrosis: Liquefactive

• Typically affects neurons/glial cells in the brain, GI

• Cells ‘digested’ by their own hydrolases - tissue becomes soft

• Walled off from healthy tissue, forming cysts

Necrosis: Caseous (cheese like)

• MC w/ infection of mycobacterium tuberculosis → lungs

• Combo of coagulative and liquefactive

• Cells disintegrate/denature but debris is walled off

Necrosis: Fat

• MC in breast, pancreas, liver

• Saponification (soap)

Gangrenous Necrosis: Dry Gangrene

Gangrene from coagulative necrosis; skin is dry, dark brown/black, and shrunken

Gangrenous Necrosis: Wet Gangrene

Gangrene from liquefactive necrosis of internal organs; swollen, cold, black, almost always infected → foul odor

Gangrenous Necrosis: Gas Gangrene

Wet gangrene caused by Clostridium infection, bacteria forma gas bubbles in tissue

5 Cardinal Signs of Inflammation

Calor (heat), Rubor (redness), Tumor (swelling), Dolor (pain), Functio Laesa (loss of function)

Pain Definition

Unpleasant sensory & emotional experience associated with actual or potential tissue damage

Referred Pain

Pain felt in an area distant or removed from its original point of origin

Hypothalamus Temperature Control

Regulates heat production (shivering, BMR), heat conservation (vasoconstriction), and heat loss (vasodilation, sweating)

Fever Functions

1. Stimulate the immune system

2. Create an inhospitable environment for invading pathogens

Benefits of Fever

1. Kills many microorganisms

2. Decreases serum levels of iron, zinc, and copper - needed for bacterial replication

3. Promotes lysosomal breakdown and autodestruction of cells

4. Increases lymphocytic transformation and phagocyte motility

5. Augments antiviral interferon production and phagocytosis

Sepsis

Massive systemic inflammatory response to an infection

• Lungs (pneumonia is the MCC)

• Urinary tract (UTI is a very common cause of sepsis in elderly)

• Other locations: skin, abdominal organs

• 1/3 of the time, no identifiable source

Septic Shock

Sepsis accompanied by severe, refractory hypotension

Toxic Shock Syndrome (TSS)

Life-threatening bacterial infection causing high fever, hypotension, V/D, headache, myaglia, AMS, and sunburn-like rash

Predisposing factors: Age

Alzheimer’s, CVD

Predisposing factors: Sex

Hypothyroidism F>M

BPH, PCOS

Predisposing factors: Environment

Pollution, radiation

Predisposing factors: Lifestyle

ETOH, tobacco, drugs, unprotected sex, multiple sex partners, stress, lack of exercise, poor diet

To make a diagnosis: Medical history, physical exam, diagnostic labs and tests

• Medical history

  • Chief complaint

    • “what brought you in today”

  • HPI

    • many questions about the CC

• Physical exam

  • Inspection

  • Auscultation

  • Palpation

  • Percussion

• Diagnostic Labs & Tests

Medical History: SOAP

Subjective, Objective, Assessment (Diagnosis), Plan

Mitochondira contains many . . .

Free radicals (O-), isolated from the rest of the cell

Ions are always moving from . . .

High to low concentrations trying to reach their electrochemical equilibrium

ATP is required to move . . .

an electrolyte against its concentration gradient (active transport)

What would happen to intracellular concentrations if there were no ATP available?

Cell stressors: Trauma

Injured tissue can disrupt blood flow

Cell stressors slide: Pathologic

• Ionizing radiation (UV rays, X rays)

• Metabolism of certain chemicals (CCl4)

• Increased mitochondrial membrane permeability due to hypoxic cell injury

Cellular adaptation

The cell’s response to protect itself from injury

Toxic shock syndrome causes

• Staph aureus

• Group A beta hemolytic strep

• Tampons, contraceptive sponges/diaphragm

• Wounds, post surgical

Toxic shock syndrome testing

CBC, Blood culture

Slide: Sepsis and systemic inflammatory response syndrome

Slide: Sepsis: SIRS Criteria

Sepsis Summary Slide: Fever

IL-1, IL-6, TNF

Sepsis Summary Slide: Vasolidation

• Hypotension

• Impaired O2 delivery leads to tissue hypoxia

Sepsis Summary Slide: Treatment

• Antibiotics, IV fluids, ventilation

• Vasopressin (ADH) → causes vasoconstriction

Sepsis: Causes

• MCC: Bacterial infections (staph, strep, e. coli)

  • Very common in indwelling central line catheters

• Other causes: Fungal, viral, parasites

• Bacterial exotoxins that act as superantigens

Sepsis: Signs and Symptoms

• Signs and symptoms

  • Fever, tachycardia (increase in HR), tachypnea (increase in RR)

  • Pallor, altered mental status (AMS)

  • Bacteremia, leukocytosis

  • If hypotensive → septic shock

Fever: Pathogenesis

• Exogenous pyrogens (endotoxins from pathogens) stimulate phagocytes to release endogenous pyrogens (IL-1, IL-6, TNF-a)

• IL-1, 1L-6, & TNF-a stimulate the hypothalamus to make more PGE2 → raises the set point for the body temperature

• Body temp is now lower than the set point

  • Heat generation and heat conservation occur

Slide: Inflammatory Modulators

Gangrenous necrosis

Clinical term, death of tissue resulting from hypoxic injury