Exam 3

superficial fungi infections

Examples: athlete’s foot, ringworm, oral thrush

systemic fungal infections

Examples: candidiasis, aspergillosis, cryptococcosis

endemic mycoses

Cause: environmental fungi in specific geographic regions —> infection via inhaled spores

Common infections (Most —> Least Prevalent)

• Histoplasmosis - Histoplasma capsulatum)

  • bird or bad droppings (US river valleys)

• Coccidioidomycosis - Coccidioides

  • soil dust (southwest U.S)

• Blastomycosis - Blastomyces dermatitidis

  • moist soil, decaying organic matter (Great Lakes-Midwest-Southeast)

Transmission: inhalation of environmental spores

Treatment:

• itraconazole

• fluconazole

• amphotericin B

Major antifungal drug classes

1. Allylamines

• Example: terbinafine (dermatophytes)

2. Azoles

• Example: fluconazole, ketoconazole

3. Polyenes

• Example: amphotericin B (systemic), nystatin (topical/mucosal)

4. Echinocandins

• Example: caspofungin, micafungin

Allylamines

• inhibit squalene epoxidase —> block ergosterol synthesis —> disrupt

Example:

• terbinafine (dermatophytes)

Azoles

• inhibit ergosterol synthesis —> disrupt fungal membranes

Example:

• fluconazole

• itraconazole

• clotrimazole

• ketoconazole

Polyenes

• bind ergosterol —> membrane pores —> fungal cell death

Example:

• amphotericin B (systemic)

• nystatin (topical/mucosal)

Echinocandins

• inhibit B-1, 3-D-glucan —> block fungal cell wall synthesis

Example:

• caspofungin

• micafungin

• anidulafungin

Risk factors of fungal infections

• Immunocompromised state: HIV/AIDS, chemotherapy, transplant, long-term corticosteroids

• Chronic disease: diabetes, cancer, malnutrition

• Healthcare exposure: central lines, ICU stay, prolonged hospitalization

• Disruption of normal flora: broad spectrum antibiotic use

Dermatophyte (Superifical/Cutaneous) Infections

Causes: fungi that infect keratinized tissues (skin, hair, nails)

• usually occur in health individuals and remain superficial

Common Infections:

1. tinea pedis

2. tinea corporis

3. tinea capitis

4. tinea cruris

5. tinea unguium

Transmission: direct contact with infected person, animals, or contaminated surfaces (locker rooms, towels)

Treatment:

• topical antifungals (terbinafine, clotrimazole, miconazole)

• oral antifungals for severe or nail infections (terbinafine, itraconazole)

Tinea pedis

athlete’s foot

• itching, scaling between toes

Tinea corporis

ringworm

• circular rash on skin

Tinea capitis

scalp infection

• hair loss, scaling

Tinea cruris

“jock itch”

• groin infection

Tinea unguium

onychomycosis

• fungal infection of nails

Opportunistic Fungal Infections

Causes: fungi that normally cause little disease but lead to serious infections in immunocompromised patients

Common infections (Highest —> Lowest Prevalence):

• Candidiasis: (normal flora overgrowth) mucosal infections (oral thrush, vaginal), may become invasive

• Aspergillosis: (soil/dust/decaying plants) lung infection that may become invasive

• Cryptococcosis: (bird droppings) lung infection that may spread to CNS causing meningitis

• Pneumocystis pneumonia (PCP): airborne organism that may cause sever organism in HIV/AIDs

Transmission: environmental exposure to spores or overgrowth of normal flora when immunity is weak

Treatment:

• Nystatin —> mucocutaneous Candida (oral thrush)

• Fluconazole —> invasive Candida, Cryptococcus

• Echinocandins (caspofungin) —> invasive candidiasis

• Amphotericin B —> severe systemic infections

• TMP-SMX —> Pneumocystis pneumonia

Invasive/Systemic Fungal Infections

Cause: fungi that invade deep tissues or organs and spread through the bloodstream

Common Infections (Highest —> Lowest Prevalence):

• Invasive candidiasis: bloodstream infection affecting multiple organs

• Invasive aspergillosis: severe pulmonary infection with possible dissemination

• Disseminated cryptococcosis: CNS infection causing meningitis

• Disseminated histoplasmosis: widespread infection affecting multiple organs

Transmission: usually begins with inhalation of spores or bloodstream spread from another infection site

Treatment: aggressive antifungal therapy (amphotericin B, echinocandins, azoles)

Terbinafine

Pharmacologic Class: allylamine antifungal

MOA: inhibits squalene epoxidase —> blocks ergosterol synthesis in fungal cell membranes —> toxic squalene accumulation —> fungal cell death

Indications: dermatophyte infections (tinea pedis, tinea corporis, tinea cruris), onychomycosis (fungal nail infections), tinea capitis

ADR:

• GI effects: N/V/D, abdominal pain, headache

• Skin reactions: rash, pruritus

Contraindications: liver disease, hypersensitivity to terbinafine

Nursing Considerations:

• monitor LFTs, especially with oral therapy

• oral therapy often required for onychomycosis (several weeks to months)

• advise patients to to report taste disturbances or signs of liver injury (dark urine, jaundice, fatigue)

• Preparations: PO (oral) and topical (cream, gel, spray)

Fluconazole

Pharmacologic Class: azole antifungal

MOA: inhibits synthesis of ergosterol in fungal cell membranes

Indications: candidiasis, invasive candidiasis, cryptococcosis, coccidioidomycosis

ADR: N/V/D, headache, SJS/TENS, QT prolongation, hepatotoxicity, nephrotoxicity, thrombocytopenia, leukopenia, anaphylaxis, strongly inhibits CYP 450 = DDI

Contraindications: liver disease, low K+, pregnancy

Nursing Considerations:

• assess for rash or severe skin reactions (SJS)

• monitor EKG in patients at risk for QT prolongation

• review drug interactions

• monitor electrolytes, especially potassium

• assess for signs of hepatotoxicity (jaundice, dark urine, abdominal pain)

• IV or PO

Nystatin

Pharmacologic Class: polyene

MOA: binds to ergosterol in fungal cell membranes and causes leakage of cellular contents

Indications: oral, vaginal, cutaneous, and GI candidiasis

ADR: generally mild, including skin irritation or mild GI upset

Nursing Considerations:

• Oral:

  • administer after meals to reduce GI upset

  • swish liquid in mouth for several seconds then swallow

  • avoid eating/drinking for 30 minutes after use

• Topical

  • creams, powders, and ointments

  • clean and dry affected area before applying

  • apply a thin layer to the affected area 2-3X a day

  • monitor for skin irritation

Amphotericin B

Pharmacologic Class: polyene

MOA: binds to ergosterol in fungal cell membranes, creating pores that lead to cell death

Indications: invasive (systemic) candidiasis, aspergillosis, cryptococcosis, histoplasmosis, coccidiomycosis, blastomycosis

ADR: fever, chills, nausea, vomiting, rigors, hypotension = infusion rxns

• nephrotoxicity: kidney injury, hypokalemia, hypomagnesemia

• cardiotoxicity: arrhythmias, electrolyte disturbances

• hepatotoxicity: elevated liver enzymes (rare)

• hematologic toxicity: anemia, thrombocytopenia, leukopenia

• neurotoxicity: headache, dizziness, seizures (rare)

• hypersensitivity: anaphylaxis, rash

Contraindications: nephrotoxicity, hypokalemia

Nursing Considerations:

• monitor renal function (BUN, creatinine) —> high risk of nephrotoxicity

• monitor electrolytes, especially K+ and Mg++

• assess for infusion rxns

• premedication may be required (acetaminophen, antihistamines, corticosteroids_ to reduce infusion rxns

• PO or IV - monitor IV site —> risk of phlebitis

• adequate hydration to reduce kidney toxicity

Caspofungin

Pharmacologic Class: echinocandin

MOA: inhibits B-1, 3-D-glucan synthesis in the fungal cell wall —> disrupting fungal cell wall synthesis —> fungal cell death

Indications: invasive candidiasis, candidemia, esophageal candidiasis, salvage therapy for invasive aspergillosis

ADR: infusion rxns: fever/chills, hypotension, flushing, rash, hepatoxicity, N/V/D, phlebitis at infusion site (rare)

Contraindications: caution in hepatic impairment

Nursing Considerations:

• monitor LFTs

• observe for infusion related rxns

• administer IV slowly to reduce histamine-mediated rxns

Intestinal Protozoal Infections

Transmission: fecal-oral (contaminated water or food)

Diagnosis: stool O&P, antigen testing, or PCR

GI illness: diarrhea, abdominal cramps, nausea, dehydration

Major infections:

• amebiasis

• giardiasis

• crytopsporidiosis

Amebiasis

• bloody diarrhea, invasive disease

• may cause liver abscess

• Treatment —> metronidazole/tinidazole —> then luminal agent\

• caused by Entamoeba histolytica

Giardiasis

• malabsorption, bloating, foul-smelling greasy stools

• often associated with contaminated water or camping exposure

• Treatment —> metronidazole, tinidazole, or nitazoxanide

• caused by giardia lamblia

Cryptosporidiosis

• profuse watery diarrhea

• severe disease in immunocompromised patients (HIV)

• Treatment —> nitazoxanide + hydration

Trichomoniasis

Cause: protozoan parasite

Transmission: sexual contact

Symptoms:

• vaginal discharge (frothy, yellow-green)

• vaginal irritation or dysuria

• many infections asymptomatic

Diagnosis: microscopy or NAAT testing

Treatment: metronidazole or tinidazole

Important: treat sexual partners to prevent reinfection

Malaria (plasmodium infection)

Cause: plasmodium parasites transmitted by female anopheles mosquito

• species: P. falciparum (most severe), P. vivax, P. ovale, P. malariae, P. knowlesi

Pathophysiology: parasites infect liver —> then red blood cells —> RBC rupture —> cyclic fever, chills, anemia, splenomegaly

Symptoms: fever, chills, sweats, headache, fatigue

• sever disease (P. falciparum) —> cerebral malaria, anemia, organ failure

Diagnosis: blood smear (gold standard)

• rapid diagnostic tests or PCR

Treatment:

• P. falciparum —> artemisinin-based combination therapy (ACT_

• chloroquine-sensitive species —> chloroquine

Prevention: mosquito control and traveler prophylaxis

Chloroquine

Therapeutic Class: antimalarial drug

Pharmacologic Class: heme complexing drug

MOA: prevents the parasite from converting toxic heme (a byproduct of hemoglobin digestion in RBCs) into a harmless form —> toxic heme accumulates —> parasite dies

ADR: N/D

• CNS and cardiac toxicity at high doses

• ocular toxicity (retinal damage, vision changes with prolonged use)

Contraindications: allergy, CKD, liver/blood diseases, alcohol use disorder, G6PD deficiency (increased risk of hemolysis)

Nursing Considerations:

• monitor EKG for arrhythmias

• check liver and kidney function

• monitor for vision changes

• monitor for hemolysis in G6PD deficiency

• avoid antacids and be cautious with drug interactions

Toxoplasmosis

Cause: toxoplasma gondii (intracellular protozoan parasite)

Transmission: ingestion of oocysts from contaminated food/water or cat feces; undercooked meat; congenital transmission during pregnancy and disease in immunocompromised persons

Pathophysiology:

• parasite invades host cells and forms intracellular cysts

• spreads via blood to brain, muscle, and retina

• inflammation and tissue necrosis —> encephalitis & ocular disease

• birth defects

Signs/Symptoms:

• often asymptomatic or mild flu-like illness

• immunocompromised: encephalitis, seizures, confusion

• congenital infection: neurologic damage and vision loss

Diagnosis:

• serology

• PCR in severe or congenital infection

Treatment: pyrimethamine + sulfadiazine + folinic acid

Prevention:

• avoid undercooked meat

• avoid cat litter exposure during pregnancy

Pyrimethamine

Pharmacologic Class: folic acid antagonist

MOA: inhibits protozoal folic acid synthesis —> blocks DNA synthesis —> inhibits parasite replication

Indications: toxoplasmosis (most common) & malaria (in combination regiments)

ADR: nausea, rash, elevated liver enzymes

• bone marrow suppression (anemia, leukopenia, thrombocytopenia)

Contraindications: folate deficiency/megaloblastic anemia, pregnancy (teratogenic risk)

Nursing Considerations:

• monitor CBC for bone marrow suppression

• give leucovorin to reduce folate toxicity

• monitor liver function (LFTs)

Helminths

Definition: parasitic worms transmitted through contaminated soil, food, or water —> infect intestines or tissues

Groups:

• Roundworms (nematodes): cylindrical worms in the intestine or migrating through tissues

  • Example: ascaris, hookworms, strongyloides

• Tapeworms (cestodes): flat segmented intestinal worms that absorb nutrients

• Flukes (trematodes): flat leaf-shaped worms infecting blood vessels or organs

Helminth infections

Pathophysiology:

• larvae enter via contaminated soil, food, and water

• mature worms colonize intestines or migrate through tissues (lungs, liver, blood)

• nutrient theft, blood loss, and immune inflammation —> tissue damage anemia

  • major global burden in low-resource regions with poor sanitation

Common symptoms:

• abdominal pain, bloating, diarrhea, weight loss

• cough or allergic symptoms during larval lung migration

Physical findings:

• anemia, malnutrition, hepatoslenomegaly, eosinophila

Diagnosis: stool O&P, serology, CT/MRI for tissue infections

Treatment:

• albendazole/mebendazole —> most intestinal roundworms

• ivermectin —> strongyloides

• praziquantel —> tapeworms & flukes

• supportive care —> treat anemia and malnutrition

Mebendazole

Therapeutic Class: anti-helminthic

Pharmacologic Class: microtubule inhibitor

MOA: blocks glucose uptake and energy production in the parasite —> parasite is starved of energy and dies

ADR: abdominal pain, distention, diarrhea

• Rare: seizures, agranulocytosis

Contraindications: hypersensitivity, serious hepatic impairment

Nursing Considerations:

• instruct patient to chew tablet for maximum effect

• monitor for side effect

Ectoparasites

Defintion:

• organisms that live on the external surface of their hosts, feeding on blood or skin

• they can cause irritation, itching, and sometimes infections

Common Infections:

• Scabies: caused by sarcoptes scabiei mite, leading to intense itching and skin rashes

• Lice: small, blood-feeding insects including head lice, body lice, and pubic lice, causing itching and irritation

Ectoparasitic Infections

Pathophysiology: parasites live on pr burrow into skin —> feed on blood/skin debris —> immune hypersensitivity rxn —> intense itching and skin inflammation

Symptoms:

• sever itching

• rash, sores, or blisters

Physical Findings:

• erythematous, excoriated skin

• mites, burrows, or lice eggs (nits) on hair shafts or skin folds

Diagnostic Tests: skin scraping for mites (scabies)

• visual identification of lice or nits

Treatment:

• Scabies: permethrin cream or oral ivermectin

• Lice: permethrin or pyrethrin pediculicides

Ivermectin

Therapeutic Class: anti parasitic

MOA: binds parasite glutamate-gated chloride channels —> paralysis and death of parasites

Indications: scabies (oral option when topical therapy fails); head lice

ADR: dizziness, headache, N/D, rash or itching

• Rare: hypotension, neurologic effects

Contraindications: pregnancy, caution in severe liver disease

Nursing Considerations:

• single oral dose - 200 mcg/kg, may repeat in 1-2 weeks

• monitor for neurologic symptoms and skin rxns

Permethrin

Pharmacologic Class: pyrethroid pediculicide

MOA: disrupts parasite sodium channels —> paralysis and death of mites and lice

Indications: scabies and head lice

ADR: mild burning or stinging, itching or skin irritation, rash (rare)

Contraindications: hypersensitivity

Nursing Considerations:

• apply topically to affected area

• Scabies: apply to entire body (neck down), wash off after 8-14 hrs

• Lice: apply to scalp/hair, repeat in 7-10 days if needed

• treat close contacts and wash bedding/clothing in hot water

Mycobacteria

• genus of slow growing bacteria

• acid-fast, meaning they retain a specific stain after being washed with acid-alcohol

• have a thick, waxy cell wall, which makes them resistant to many common antibiotics

Mycobacterial infections

Includes:

• tuberculosis (TB)

• leprosy

• mycobacterium avium complex (MAC)

Due to slow growth,

• long term treatment and a combination antibiotics are often required

Characterized by:

• chronic inflammation and granuloma formation

TB Transmission and Infection Process

1. Transmission: spreads via inhalation of airborne droplets containing M. tuberculosis bacilli

2. Infection Process: bacilli enter the lungs, where they are engulfed by macrophages and replicate, causing inflammation

3. Immune Response: immune system sends WBCs to site of infection, where they form tubercles to isolate and contain the TB bacteria

4. Tissue Response: scar tissue forms around the tubercles (granulomas), helping to make the bacteria inactive and preventing its spread

Latent TB

• inhaled mycobacteria activate macrophages, forming lung lesions

• scar tissue forms around the tubercle, making the bacteria dormant

• the bacteria remain inactive, and the person is asymptomatic and not contagious

Active TB

• dormant mycobacterium tuberculosis in granulomas reactivates when immune defenses weaken

  • granuloma breakdown —> bacteria released into lung tissue

• also possible —> no latent phase, especially in high-risk or immunocompromised patients

• progressive tissue destruction —> cavitary lesions —> spread in lungs

• patient becomes symptomatic and contagious

Symptoms: fever, night sweats, cough, weight loss

Transmission: airborne (coughing/sneezing)

• dissemination —> bloodstream/lymphatics —> extrapulmonary TB (bone, kidney, CNS)

Susceptibility to Tuberculosis

Immunocompromised:

• HIV/AIDS (20-40x risk)

• immunosuppressive therapy (chemotherapy, biologics, steroids)

• transplant recipients

Chronic conditions:

• diabetes mellitus

• CKD

• poor nutritional status

Exposure/Environment:

• close living conditions (shelters, correctional facilities, long-term care)

• unhoused populations

• healthcare workers

Geographic Risk:

• immigrants or recent travelers from TB-endemic regions

Symptoms of TB

• persistent cough (lasting more than 3 weeks)

• chest pain or discomfort

• fatigue or weakness

• loss of appetite

Signs of TB

• hemoptysis

• fever

• night sweats

• weight loss

• SOB (severe cases)

Diagnostic Testing for TB

1. Tuberculin Skin Test (TST)/ Mantoux (PPD):

• measures T-cel response to M. tuberculosis

• positive —> infection (latent or active)

• cannot distinguish between active vs latent; BCG false positives

2. Interferon-Gamma Release Assays (IGRAs):

• blood tests (QuantiFERON, T-SPOT) —> T-cell IFN-y response

• positive —> infection (latent or active)

• cannot distinguish; not affected by BCG

3. Chest x-ray (CXR):

• asses lung involvement (cavities, infiltrates)

• supports active TB suspicion

• not diagnostic; cannot distinguish active vs latent

4. Sputum testing (AFB smear, culture, NAAT)

• AFB smear — suggests active TB (x3 samples required)

• culture: gold standard —> confirms active TB

• NAAT: rapid detection

BCG vaccine

• vaccine developed from Mycobacterium bovis

• used primarily in countries with high TB prevalence

• provides protection against sever forms of TB (meningitis and disseminated TB) but is less effective against pulmonary TB

• can cause a false positive result on TB tests, particularly TST

Treatment for Latent TB

Goal: prevent progression —> active TB

Indications:

• positive TST/IGRA + no active TB

• high risk: HIV, immunocompromised, close contacts

• also treat many otherwise health patients with LTBI

Before Treatment: rule out active TB (symtoms, CXR, sputum)

Regimen Options:

• Isoniazid x 9 months

• Isoniazid + Rifapentine weekly x 12 weeks

• Rifampin x 4 months

Treatment for Active TB

Goal: eliminate active infection —> prevent transmission and resistance

Indications: confirmed or suspected active Tb infection

Before Treatment:

• obtain sputum (AFB smear, culture, NAAT)

• initiate airborne precautions

Regimen

• intensive phase (2 months): Isoniazid + Rifampin + Pyrazinamide + Ethambutol

• continuation phase (4 months): Isoniazid + Rifampin

Alternative

• Isoniazid + Pyrazinamide + Rifapentine + Moxifloxacin

• Duration: 4 months (non-severe TB)

Monitoring

• LFTs —> hepatoxicity

• Vision —> ethambutol (optic neuritis)

• Adherence —> prevent resistance

• airborne precautions till non-infectious

Isoniazid (INH)

Pharmacologic Class: mycolic acid inhibitor

MOA: inhibits the synthesis of mycolic acid, a vital component of the mycobacterial cell wall

ADR: fever, rash, neurotoxicity, hepatoxicity (monitor LFTs), peripheral neuropathy (preventable with vitamin B6)

Contraindications: chronic hepatic disease, seizure disorder

Nursing Considerations:

• monitor LFTs regularly especially in high-risk patients (alcohol use disorder, older adults)

• administer vitamin B6 25-50 mg daily to prevent peripheral neuropathy

• avoid alcohol

Rifampin

Pharmacologic Class: rifamycin antibiotic

MOA: inhibits bacterial RNA synthesis by binding to bacterial RNA polymerase, preventing transcription

ADR: hepatoxicity, GI upset, red-orange discoloration of urine, sweat, and tears, flu like symptoms, DDI

Contraindications:

• use with HIV medications

• history of liver disease

Nursing Considerations:

• monitor LFTs and signs of liver toxicity

• educate patients about harmless red-orange discoloration

• asses for drug interactions

Pyrazinamide

Pharmacologic Class: nicotinamide derivative

MOA: disrupts the cell membrane potential and inhibits bacterial repair mechanisms, contributing to the eradication of TB bacteria

ADR: hepatoxicity, hyperuricemia (may precipitate gout), gastrointestinal discomfort, arthralgia

Contraindications: sever liver disease, acute gout

Nursing Considerations:

• monitor LFTs and assess for signs of gout

• hydrate patients to help prevent uric acid buildup

Ethambutol

Pharmacologic Class: ethylhydrazine derivative

MOA: inhibits arabinosyl transferase, an enzyme involved in cell wall synthesis in mycobacteria

ADR: optic neuritis (can lead to visual disturbances), hyperuricema, joint pain, GI upset

Contraindications: optic neuritis, patients with severe renal impairment

Nursing Considerations:

• monitor visual acuity, especially in long-term therapy

• assess renal function

• educate patients to report visual changes such as seeing red or green colors

Leprosy (mycobacterium leprae)

• chronic infection of skin, peripheral nerves, and eyes

Risk factors: immunocompromised, prolonged close contact

Transmission: respiratory droplets with prolonged exposure —> low infectivity

Pathophysiology:

• prefers cooler areas (skin, peripheral nerves) —> nerve damage —> loss of sensation —> repeated trauma/infection —> deformity

Signs/Symptoms:

• Skin lesions —> hypopigmented, numb

• Peripheral neuropathy —> numbness, muscle weakness

• Deformities —> claw hand, foot drop

• Tissue loss —> (digits/hands/feet) —> secondary to trauma

• Eye involvement —> dryness, vision risk

• Systemic (advanced) —> fever, fatigue, weight loss

Diagnosis: skin/nerve biopsy, slit-skin smear, PCR

Treatment: Rifampin + Dapsone + Clofazimine (6-12 months)

Dapsone (DDS)

MOA: inhibits folic acid synthesis —> decreasing mycobacterial growth

ADR:

• Common:

  • N/V

  • hemolysis (dose relayed)

  • methemoglobinemia —> cyanosis

  • photosensitivity, joint pain

• Serious:

  • blood dyscrasia (agranulocytosis)

  • hepatotoxicity

  • sever skin rxns (SJS/TEN)

  • vision changes, GI bleeding

  • discoloration of skin/fluids

Contraindications: blood disorders, severe liver disease

Nursing Considerations:

• monitor CBC, LFTs, renal function

• asses for hemolysis and methemoglobinemia

mycobacterium avium complex (MAC) infections

• group of mycobacterium that cause infections primarily in immunocompromised individuals, especially with those with HIV/AIDS, cancer, organ transplants, immunosuppressive therapies

1. pulmonary infections —> chronic cough, sputum, weight loss

2. disseminated infections —> fever, night sweats, diarrhea

3. lymphadenitis —> swollen lymph nodes, typically in children

Symptoms: fever, night sweats, weight loss, abdominal pain, diarrhea, cough, and fatigue

Treatment: combination therapy with macrolides (clarithromycin, azithromycin), rifampin, and ethambutol (18 months or longer)

WBC response in infection

• pathogen invasion —> bone marrow + immune activation —> neutrophils = first responders

Patterns:

• leukocytosis (>11K) —> active response

• leukopenia (<4K) —> immune exhaustion (poor prognosis)

Shift to Left

• bone marrow releases immature neutrophils (bands) early

• bandemia (>10%) —> high demand exceeds supply

Interpretation:

• increased neutrophils + bandemia —> acute bacterial infection/early sepsis

• decreased lymphocytes —> stress response

Clinical Meaning

• not just “infection present”

• reflects host response: strong vs overwhelmed

Sepsis

Definition: a life-threatening organ dysfunction caused by a dysregulated host response to infection

Key Points:

• infection leads to abnormal metabolism and metabolic acidosis

• if not recognized early and treated aggressively, can cause end-organ damage

Pathogenesis of Sepsis

• infection triggers the cascade of immune and inflammatory responses

• leads to metabolic acidosis,, poor perfusion, and organ dysfunction

Risk Factors of Sepsis

1. immunocompromised patients

2. chronic illnesses

3. trauma

4. recent surgery

5. malnutrition

6. people who inject drugs

7. indwelling devices

Early immune activation

• macrophages recognize patterns —> release cytokines

Key mediators: TNF-alpha, IL-1, IL-6

Effects:

• fever (hypothalamus)

• increased vascular permeability

• leukocyte recruitment

This stage is adaptive—until it becomes excessive

SIRS (systemic inflammatory response syndrome)

• cytokine amplification —> systemic inflammation

Effects:

• vasodilation (decreased SVR —> systemic vascular response)

• capillary leak (decreased circulating volume)

• activation of coagulation

Clinical Signs: tachycardia, tachypnea, fever

Key Concept: this is no longer localized infection

• tachypnea —> first sign of sepsis

Endothelial Dysfunction

• Endothelium becomes

  • pro-inflammatory

  • pro-thrombotic

  • permeable

• loss of barrier function —> fluid shifts to interstitial space

Result:

• decreased effective circulating volume

• tissue edema

Nursing implication:

• hypotension and third spacing

Microcirculatory failure

• capillary blood flow becomes uneven (shunting)

• microthrombi impair perfusion

• oxygen delivery becomes inconsistent

Key concept:

• patient may have “normal BP” but poor tissue perfusion

Clinical Signs:

• increased lactate, altered mental status, decreased urine

Cellular Dysfunction and Lactate

• cells unable to use oxygen effectively

• shift to anaerobic metabolism

• lactate production increases

Important nuance:

• lactate = marker of metabolic stress, not just hypoxia

Nursing role:

• trend lactate to assess response to treatment

Immune Paradox

Early:

• excessive inflammation —> tissue damage

Later:

• immune suppression (lymphocyte apoptosis)

Paradox:

• immune system is overactive and ineffective

• causes damage byt still fails to clear infection

Result:

• inability to clear the infection

• risk of secondary infections

Clinical implication:

• patient may initially improve then worsen

Organ Dysfunction

• perfusion failure + inflammation —> organ injury

Brain —> encephalopathy (confusion)

Kidneys —> decreased perfusion + inflammation —> AKI

Lungs —> capillary leak —> ARDS

Heart —> myocardial depression

ARDS (acute respiratory distress syndrome)

• alveolar-capillary membrane damage

  • increased capillary permeability (capillary leak)

  • protein-rich fluid moves from capillaries —> alveoli

  • surfactant dysfunction —> alveolar collapse

  • decreased gas exchange —> hypoxemia

Clinical: increased respiratory rate, decreased O2 sat, refractory hypoxia

Nursing: monitor oxygen needs + work of breathing

Sepsis-associated AKI

• not just hypoperfusion

• Also

  • inflammation

  • microvascular injury

• Signs:

  • oliguria (<0.5 mL/kG/hr)

  • rising creatinine

• Nursing:

  • early recognition via I&O

Cardiovascular dysfunction

1. vasodilation —> decreased SVR —> hypotension

2. capillary leak —> decreased preload

3. cytokines —> decreased contractility

Early:

• warm, flushed

Late:

• cool, clamy

Nursing:

• monitor perfusion, not just BP

Disseminated Intravascular Coagulation (DIC)

• inflammation activates clotting cascade

  • microthrombi form —> worsen perfusion

  • platelets consumed —> bleeding risk

Labs:

• decreased platelets, increased PT/INR

Nursing: monitor for bleeding + organ dysfunction

Septic Shock

• persistent hypotension despite fluids

• lactate > 2

Indicates: severe circulatory + metabolic failure

Sepsis Diagnostics

1. Lactate —> decreased perfusion/metabolic stress

2. WBC —> immune response

3. Procalcitonin —> bacterial infection likely

4. Cultures (blood, urine) —> identify organism (before antibiotics), do NOT delay antibiotics excessively

1-Hour Bundle

• lactate —> assess perfusion

• antibiotics —> remove infectious trigger

• fluids —> restore intravascular volume

• vasopressors —> restore vascular tone

Fluid Resuscitation

• capillary leak —> decreased intravascular volume

IV fluids: increase perload —> increase cardiac output

Evaluate:

• urine output

• mental status

• lactate trends

Vasopressors

• norepinephrine

  • vasoconstriction —> increased SVR

• used when fluids in sufficient

Goal:

• MAP >65 to maintain organ perfusion

Inflammation

Definition:

• the body’s protective response to injury, infection, or harmful stimuli

• purpose is to eliminate the cause of injury and initiate the healing process

Clinical Implications:

• essential for healing and tissue repair

• can lead to tissue damage if excessive or prolonged

• intensity of the response generally reflects the severity of injury

Major Goals:

• wall off the area of injury

• prevent spread of the injurious agent

• deliver immune cells and mediators to the affected site

Local inflammation

Causes:

• tissue injury —> trauma, surgery

• infection —> localized (bacteria, viruses, fungi)

• foreign bodies —> splinters, debris

• allergic rxns —> localized (contact)

• chemical/thermal injury —> burns, toxins

Signs: redness, heat, swelling, pain, decreased function

Systemic inflammation

Causes:

• widespread infection —> sepsis

• autoimmune disease —> body-wide activation

• chronic conditions —> obesity, metabolic disease

• malignancy —> tumor-driven inflammation

• severe injury —> trauma, burns, circulating triggers —> toxins, cytokins

Signs:

• fever, lethargy, malaise

• lymphadenopathy —> immune activation

• anorexia, sleepiness —> cytokines

• anemia —> chronic inflammation

• weight loss —> increased metabolism and decreased intake

Mediators and the Inflammatory Response

Injury:

• cell membrane phospholipids are activated —> converted to arachidonic acid

Arachidonic Acid Pathway:

• two key enzyme pathways generate inflammatory mediators:

  • COX pathway —> prostaglandins

  • LOX pathway —> leukotrienes

Importance:

• these mediators drive the inflammatory response

  • initiate vascular changes

  • recruit immune cells

  • promote fluid shifts

Flow:

• injury —> arachidonic acid —> mediators —> inflammatory phases

Key Inflammatory Mediators

Cytokines (IL-1, IL-6, TNF-alpha)

• cell signaling proteins —> coordinate and amplify the inflammatory response

Histamine

• released by mast cells —> vasodilation + increased vascular permeability —> redness, swelling

Bradykinin

• peptide mediator —> vasodilation and increased permeability —> pain

Prostaglandins (via COX pathway)

• promote vasodilation, pain, and fever

Leukotrienes

• promote inflammation —> especially bronchoconstriction in asthma/allergic responses

Platelet-Activating Factor (PAF)

• platelet aggregation and vasodilation and increased permeability

Phases of Inflammation

Vascular phase

• immediate response

• vasodilation and increased vascular permeability

• blood flow increases, fluid shift into tissue

Cellular phase

• immune cells respond

• neutrophils (first), then macrophages

• phagocytosis of pathogens and debris

Exudative phase

• fluid and cells accumulate

• protein-rich fluid (exudate) + WBCs in tissue

• edema, possible pus formation

Reparative (Healing) phase

• tissue recovery

• resolution, regeneration, or scar formation

Acute inflammation

Onset: rapid (minutes-hours)

Duration: short (hours-days)

Key Mediators: neutrophils, histamine, prostaglandins

Response: vasodilation and increased vascular permeability —> redness, heat, swelling, pain

End Effect: resolves injury —> promotes healing and tissue repair

Examples: trauma, infection, burns

Chronic inflammation

Onset: slow

Duration: long (months-years)

Key Mediators: macrophages, lymphocytes, cytokines, growth factors

Response: persistent inflammation —> ongoing tissue injury + fibrosis

End Effect: tissue damage, fibrosis, and loss of function

Examples: rheumatoid arthritis, inflammatory bowel disease, obesity

Laboratory markers of inflammation

C-reactive protein (CRP):

• key marker of inflammation —> increasing value = ongoing inflammation

• normal: <1 mg/L

Erythrocyte Sedimentation Rate (ESR):

• rate of RBC settling —> inflammation (less specific than CRP)

• normal: M<15 ; F<20 mm/hr

Leukocytosis:

• increased WBCs from bone marrow —> infection/inflammation

• normal WBC: 4-11 K/uL

Thrombocytosis:

• increased platelets from bone marrow —> inflammation

• normal platelets: 150-400 K/uL

White Blood Cells

Granulocytes (innate):

• Neutrophils

  • first responders —> bacterial infection —> bands = early/acute response

• Eosinophils

  • allergic + parasitic responses —> asthma, allergies

• Basophils

  • circulating granulocytes —> release histamine —> inflammatory/allergic responses

• Mast cells

  • tissue-resident (similar to basophils) —> release histamine

Agranulocytes (adaptive):

• Lymphocytes

  • (B cells, T cells, NK cells) —> adaptive immunity —> viral infection

• Monocytes —> Macrophages

  • arrive later (24-48 hrs) —> phagocytosis of pathogens + debris

NSAIDS - nonsteroidal anti-inflammatory drugs

Effect: decreased pain, decreased inflammation, decreased fever

MOA: inhibit COX —> decrease prostaglandins (key mediators of pain, fever, inflammation)

COX Pathways:

• Cox-1 (constitutive/protective): maintains GI mucosal protection + renal blood flow + platelet aggregation

• Cox-2 (inducible): produced at sites of injury —> drives inflammation, pain, fever

Clinical Indications:

1. pain (decreased prostaglandins —> decreased nociceptor sensitization)

2. inflammation (decreased prostaglandins —> decreased inflammatory response)

3. fever (decreased prostaglandins in hypothalamus —> decreased set point)

4. dysmenorrhea (decreased prostaglandins —> decreased uterine contractions)

5. aspirin: cardiovascular protection (decreased thromboxane —> decreased platelet aggregation)

NSAID Adverse Effects

GI irritation/bleeding (common)

• nausea, dyspepsia, ulcer/bleed; COX-1 inhibition —> decreased protective prostaglandins

Renal toxicity

• decreased renal blood flow —> AKI, fluid retention, increased BP (decreased prostaglandins)

Cardiovascular risk (less common; increased in COX-2)

• increased MI, stroke

Hepatic dysfunction (less common)

• increased liver enzymes with prolonged use

Hypersensitivity (less common; increased in asthma)

• rash, bronchospasm (increased leukotrienes)

Aspirin

Pharm Class: nonselective COX inhibitor

MOA: irreversibly inhibits COX-1 and COX-2 —> decreases prostaglandins (pain, fever, inflammation) and decreased thromboxane A —> decreased platelet aggregation

Indications: pain, fever, inflammation, antiplatelet (MI, stroke prevention)

ADRs: GI irritation/bleeding, tinnitus (toxicity), renal effects, bleeding risk, Reye’s syndrome (children)

Nursing Considerations:

• take w/ food

• monitor for GI bleeding/bruising

• avoid in children/adolescents (<18) w/ viral illness

• caution w/ anticoagulants

• monitor for toxicity (tinnitus)

  • check combination products

  • treat toxicity with sodium bicarbonate

Ibuprofen

Pharm Class: nonselective COX inhibitor

MOA: inhibits COX-1 and COX-2 —> decreased prostaglandins —> decreased pain, fever, inflammation

Indications: pain (mild-moderate), fever, inflammation (musculoskeletal, arthritis)

ADRs: GI irritation/bleeding, renal toxicity (AKI, fluid retention), increased BP , CV risk (less common), hypersensitivity

Nursing Considerations:

• take with food

• monitor GI symptoms, renal function, BP

• avoid in high-risk GI/CV patients

• caution w/ anticoagulants/steroids

• avoid in late pregnancy

Celecoxib

Pharm Class: COX-2 selective inhibitor

MOA: selectively inhibits COX-2 —> decrease prostaglandins —> pain, inflammation (spares COX-1 —> less GI effect)

Indications: osteoarthritis, rheumatoid arthritis, acute pain

ADRs: increased cardiovascular risk (MI, stroke), HTN, renal toxicity, edema, sulfa allergy rxns

Nursing Considerations:

• monitor BP, renal function

• increased CV risk (avoid in high-risk patients)

• assess for edema

• caution with sulfa allergy

Corticosteroids (Steroidal anti-inflammatory drugs)

Effect: decreased inflammation and decreased immune response

MOA:

• inhibit phospholipase A —> decrease arachidonic acid —> decreased prostaglandins and leukotrienes

• alter gene expression —> decrease pro-inflammatory cytokines (IL-1, TNF-alpha)

• broad suppression of inflammation

Clinical indications for corticosteroids

Inflammatory conditions

• decreased cytokines + eicosanoids —> decrease inflammation

Autoimmune disorders

• decreased cytokines —> decrease immune activation —> decrease tissue damage

Allergic rxns/asthma

• decrease leukotrienes + cytokines —> decreased bronchoconstriction and inflammation

Acute conditions

• decreased inflammatory mediators —.> deecrease severe inflammation and airway swelling

Post-surgical inflammation

• decreased cytokines and eicosanoids —> decreased pain and edema

Corticosteroid adverse effects

Immunosuppression/infection risk (common)

• increased infection risk, poor wound healing (decreased cytokines —> decreased immune response)

Hyperglycemia (common)

• increased blood glucose, steroid induced diabetes (increased gluconeogenesis and decreased insulin sensitvity)

Fluid retention/HTN (common)

• edema, increased blood pressure (mineralocorticoid effects —> Na+/water retention)

Osteoporosis (long-term)

• decreased bone density, fractures (decreased osteoblasts and increased bone resorption)

Adrenal suppression (long-term)

• decreased endogenous cortisol, adrenal crisis risk if abrupt stop (HPA axis suppression)

Mood/psychiatric effects (variable)

• insomnia, mood swings, psychosis (CNS effects)

Prednisone

Pharm Class: glucocorticoid

MOA: binds nuclear receptors —> decreased cytokines and decreased phospholipase A —> decreased arachidonic acid —> decreased prostaglandins + leukotrienes

Indications: autoimmune, allergic/asthma, inflammatory conditions, acute rxns, transplant rejection

ADRs: immunosuppression/infection, hyperglycemia, fluid retention/HTN, osteoporosis, adrenal suppression, mood changes

Nursing Considerations:

• take w/ food

• monitor glucose, BP, weight/edem

• monitor due to infection risk (avoid live vaccines)

• taper doses — do not stop abruptly

• long term —> monitor bone health

Fever in inflammation

Systemic response: inhibits pathogen replication

Pyrogens (IL-1, TNF-alpha)—> hypothalamus —> increased temperature

Clinical

• fever (>100.4)

• tachycardia (>90 bpm) —> tachypnea (> 20)

• Labs: increased WBC (>12K) —> CRP, ESR

High fever

• risk of seizures/brain injury

• goal < 102

Antipyretics —> decreased prostaglandins (acetaminophen, ibuprofen, aspirin)

Antipyretics

Effect: decrease fever

MOA: inhibit COX in CNS —> decreased prostaglandin E —> reset hypothalmic temperature set point

Key concept:

• fever is driven by cytokines (IL-1, TNF-alpha) —> increase PGE in hypothalamus —> antipyretics block this pathway

Nursing Considerations:

• monitor temperature response

• assess liver function (acetaminophen)

• avoid overdose; caution in liver disease/alcohol use

• avoid aspirin in children/adolescents

Acetaminophen

Pharm Class: non opioid analgesic

MOA: inhibits COX in CNS —> decrease prostaglandin (PGE) —> decrease fever and pain

Indications: fever, mild-moderate pain (headache, musculoskeletal, post-op)

ADRs: hepatotoxicity (dose-dependent, acute overdose), rare rash

Nursing Considerations:

• monitor daily dose (max 3-4 g/day)

• assess liver function; avoid alcohol

• check for combination products; antidote = N-acetylcysteine