🧬 HCR-240 Pathophysiology

Injury, infection, or irritant triggers the initial response. Can be caused by:

• Physical trauma (cut, burn, fracture)
• Chemical agents (toxins, acids)
• Biological agents (bacteria, viruses, fungi)
• Immune reactions (autoimmune, hypersensitivity)
• Ischemia (loss of blood supply)

Mast cells (found in connective tissue) are activated by injury and release histamine.

Effects of Histamine:

• Causes vasodilation → ↑ blood flow → redness and heat
• Increases vascular permeability → fluid and proteins leak into tissue → swelling
• Contributes to pain by sensitizing pain receptors

Chemotaxis = directed migration of leukocytes (WBCs) toward the injury site, guided by chemical signals.

How it works:

• Injured tissue releases chemical mediators (cytokines, complement)
• WBCs respond to the chemical gradient and travel toward the site
• Diapedesis: WBCs squeeze through capillary walls to reach tissue
• Neutrophils arrive first (first responders) → Monocytes/Macrophages follow

WBCs (especially neutrophils and macrophages) engulf and destroy pathogens, debris, and dead cells.

• Neutrophils: first responders; short-lived; destroy bacteria
• Macrophages: arrive later; long-lived; clean up debris; present antigens
• Pus = dead neutrophils + bacteria + tissue debris

Pyrogens = fever-inducing substances that act on the hypothalamus to raise body temperature.

Two Types:

• Exogenous pyrogens: from outside the body (bacteria, bacterial toxins)
• Endogenous pyrogens: made by our own immune cells (IL-1, IL-6, TNF-α)

Why Fever Helps:

• ↑ body temp makes environment less hospitable for pathogens
• Stimulates immune cell activity
• Promotes antibody production

Pathophysiology:

Defective CFTR (Cystic Fibrosis Transmembrane conductance Regulator) protein → faulty chloride channel → chloride stays inside cells → water follows → mucus becomes abnormally thick and sticky

Most Common In:

Caucasians, Ashkenazi Jews; most common fatal genetic disease in white populations in the US

Systems Affected:

• Lungs: Thick mucus → chronic bacterial infections (Pseudomonas, Staph aureus), bronchiectasis, respiratory failure
• Pancreas: Mucus blocks pancreatic ducts → malabsorption, steatorrhea (fatty stools), diabetes
• Reproductive: Males: vas deferens obstruction → infertility. Females: reduced fertility
• Sweat glands: High sodium/chloride in sweat → salty-tasting skin (diagnostic clue)

Diagnosis:

• Sweat chloride test — >60 mEq/L = positive (gold standard)
• Newborn screening, genetic testing

Nursing Interventions & Treatments:

• Chest physiotherapy (CPT) / airway clearance — percussion, vibration, postural drainage. Perform 1 hour before meals to prevent aspiration.
• Bronchodilators — open airways before CPT
• Mucolytics (DNase / dornase alfa) — break down DNA in mucus to thin it
• Acetylcysteine (Mucomyst) — mucolytic; educate patient about the unpleasant odor (normal and expected)
• Corticosteroid inhalers — decrease lung inflammation
• Pancreatic enzyme replacement — taken with every meal and snack to aid digestion
• High-calorie, high-protein diet — needed due to malabsorption
• CFTR modulators (e.g., ivacaftor, elexacaftor) — newer targeted therapy that corrects the defective CFTR protein

Pathophysiology:

Deficiency of Hexosaminidase-A (Hex-A) enzyme → GM2 ganglioside (a fatty substance) accumulates in neurons → progressive destruction of nerve cells in brain and spinal cord

Most Common In:

Ashkenazi Jews, French-Canadians, Cajun populations (carrier rates significantly higher)

Infantile Form (Classic — most severe):

• Baby appears normal at birth
• Symptoms begin ~3–6 months: exaggerated startle response, muscle weakness (floppy baby)
• Progressive loss of: vision, hearing, swallowing ability, motor function
• "Cherry-red spot" on macula (visible on fundoscopic exam)
• Seizures, paralysis, dementia follow
• Prognosis: Fatal by age 4–6 years

Late-Onset Form:

• Occurs in teens to adults (30s–40s)
• Usually NOT fatal
• Muscle weakness, poor coordination, psychiatric symptoms

Treatment:

No cure. Supportive care only: seizure management, nutrition, respiratory support, comfort measures.

Pathophysiology:

Mutation in the HTT gene — abnormal expansion of CAG trinucleotide repeats (>40 repeats) → toxic mutant huntingtin protein → progressive neurodegeneration (especially striatum, cerebral cortex)

Key Features:

• Late onset: typically 30s–40s (adult onset)
• Genetically inevitable — if you have the gene, you will develop HD
• Genetic testing possible — but ethical complexities around testing asymptomatic adults

Symptom Progression:

• Early: Mood changes, irritability, depression; subtle movement issues
• Middle: Chorea — involuntary, jerky, dance-like movements (pathognomonic); cognitive decline; difficulty with ADLs
• Late: Severe chorea, dysphagia, dementia, loss of independence; aspiration pneumonia is common cause of death

Treatment:

• No cure; no disease-modifying therapy available
• Tetrabenazine or deutetrabenazine — reduce chorea
• Antidepressants, antipsychotics for psychiatric symptoms
• Supportive: speech therapy, physical therapy, dysphagia precautions

Cause:

Trisomy 21 — 3 copies of chromosome 21. Caused by meiotic non-disjunction (failure of chromosomes to separate) in 95% of cases. Translocation in ~4%; Mosaic in ~1%

Risk Factor:

Advanced maternal age is the strongest risk factor. Risk at 35 = 1 in 350; at 45 = 1 in 30

Diagnosis:

• Prenatal: Chorionic villus sampling, amniocentesis, NIPT (non-invasive prenatal testing)
• Postnatal: Karyotyping — gold standard to confirm chromosomal pattern

Clinical Features:

• Flat facial profile, epicanthal folds, upslanting palpebral fissures
• Hypotonia (decreased muscle tone) — especially at birth
• Simian crease (single palmar crease)
• Short stature, small hands/feet
• Intellectual disability (variable severity)

Associated Complications:

• Congenital heart defects — present in ~40–50% (AV canal most common)
• Gastrointestinal atresias (duodenal atresia)
• Hypothyroidism
• ↑ Risk of acute leukemia (AML, ALL)
• Early-onset Alzheimer's disease (nearly universal by 40s–50s)
• Atlantoaxial instability (cervical spine instability) — screen before athletic activity

Mechanism:

Botulinum toxin is one of the most potent known toxins. It blocks the release of acetylcholine (ACh) at the neuromuscular junction → nerve impulse cannot be transmitted to muscle → flaccid paralysis (muscles are floppy, cannot contract)

Sources:

• Improperly canned or home-canned foods (anaerobic environment)
• Wound botulism (contaminated wounds)
• Infant botulism (honey in infants <1 year — spores colonize gut)

Symptoms (Descending Paralysis):

• Begins with cranial nerves: blurred/double vision, drooping eyelids, difficulty swallowing/speaking
• Progresses downward: weakness, then respiratory failure
• No fever; patient is alert

Treatment:

• Antitoxin (if given early)
• Mechanical ventilation for respiratory failure

Mechanism:

Tetanus toxin (tetanospasmin) blocks inhibitory neurotransmitters (GABA, glycine) at the spinal cord → muscles cannot relax → sustained, painful muscle spasms (spastic paralysis)

Source:

• Deep puncture wounds, contaminated soil, rusty objects
• Can also occur in burns, surgical wounds

Symptoms:

• Trismus (lockjaw) — masseter muscle spasm; cannot open mouth
• Risus sardonicus — spastic facial expression ("evil grin")
• Opisthotonos — severe arching of the back from spasm
• Generalized muscle spasms triggered by stimuli (light, noise, touch)
• Seizures, respiratory failure

Prevention:

• DTaP immunization series in childhood
• Tdap booster every 10 years in adults
• Tetanus prophylaxis for wounds

Normal Staph aureus:

Common skin colonizer. Causes skin infections, abscesses, food poisoning (enterotoxin), pneumonia, bacteremia, septic arthritis, osteomyelitis.

MRSA — Methicillin-Resistant Staphylococcus aureus:

• Resistant to beta-lactam antibiotics (penicillin, methicillin, most cephalosporins)
• Treatment: Vancomycin (IV) is the drug of choice
• Contact precautions: gown + gloves when entering patient's room
• HA-MRSA (hospital-acquired) vs. CA-MRSA (community-acquired)

VRSA — Vancomycin-Resistant Staphylococcus aureus:

• Also resistant to vancomycin — very limited treatment options
• Extremely concerning — last-line antibiotics required

Definition:

Inflammation of the meninges (3 protective membranes surrounding the brain and spinal cord: dura mater, arachnoid mater, pia mater)

Most Common Pathogens:

• Streptococcus pneumoniae (most common in adults)
• Neisseria meningitidis (common in teens/young adults; can cause epidemic outbreaks)
• Haemophilus influenzae (less common since Hib vaccine)
• Listeria monocytogenes (neonates, elderly, immunocompromised)

Classic Triad:

• Fever + Severe headache + Nuchal rigidity (neck stiffness)
• Plus: photophobia, phonophobia, altered mental status
• Petechial rash — seen with N. meningitidis (meningococcal), indicates septicemia (very serious)

Assessment Signs for Meningitis:

• Kernig's Sign — Patient supine, hip flexed to 90°; pain/resistance when you try to extend the knee. Positive = meningitis irritation.
• Brudzinski's Sign — Patient supine; passively flex the neck forward → knees involuntarily flex. Positive = meningeal irritation.

Diagnosis — Gold Standard: Lumbar Puncture (LP / Spinal Tap)

• CSF findings in bacterial meningitis: ↑ Protein, ↓ Glucose, ↑ WBC (neutrophils), Positive Gram stain/culture
• CT scan before LP if any papilledema or focal neurological signs (to rule out ↑ ICP)

Treatment:

• Immediate antibiotics (do NOT delay for CT/LP if clinically suspicious)
• Corticosteroids (dexamethasone) to reduce inflammation
• Isolation precautions: droplet precautions for N. meningitidis

Disease: Infectious Mononucleosis ("Mono" / "Kissing Disease")

Pathophysiology:

EBV infects B lymphocytes → immune response activates T lymphocytes → "atypical lymphocytes" on blood smear → lymphadenopathy, splenomegaly

Classic Triad:

• Fever + Severe sore throat (pharyngitis) + Lymphadenopathy (swollen lymph nodes, especially posterior cervical)

Additional Findings:

• Splenomegaly (enlarged spleen) — present in ~50%
• Fatigue (can be profound and prolonged — weeks to months)
• Hepatomegaly, elevated liver enzymes
• Rash if amoxicillin/ampicillin given (almost always causes diffuse maculopapular rash)

Serious Complication:

• Splenic rupture — rare but life-threatening
• Nursing: Avoid contact sports and strenuous activity for 4–6 weeks until spleen normalizes

Diagnosis:

• Monospot test (heterophile antibody test)
• CBC: lymphocytosis with atypical lymphocytes

Treatment:

• Supportive: rest, hydration, analgesics
• Avoid amoxicillin/ampicillin (causes rash)
• Corticosteroids for severe airway obstruction

Expectorants

Help loosen and expel mucus from the respiratory tract by increasing respiratory tract secretions

• Guaifenesin (Mucinex) — most common OTC expectorant
• Encourage: 8–10 glasses of water daily (hydration thins secretions)
• Used in: bronchitis, URTI, productive cough

Mucolytics

Break down chemical bonds in mucus to make it less viscous (thinner/easier to clear)

• Acetylcysteine (Mucomyst / NAC) — also used for acetaminophen overdose antidote
• Has very unpleasant sulfur odor — educate patient this is expected
• Dornase alfa (Pulmozyme) — used in CF; breaks down DNA in mucus