Exam 1 NURS352

PathoPharm (352) - inflammation, infection, COVID, UTI, HIV, Cardiac pt 1/2

Inflammation response involves

1. vascular response
2. cellular
3. cell mediators

Innate immunity

physical, bio-chemcial barriers (normal microbiome, external barriers, secreted substances)

Inflammation

Adapative immunity

lymphocytes (T-, B-, macrophages, dendritic cells)

Inflammation

non specific response to any tissue injury

purpose: minimize injury/infection, remove damaged tissue, gen new tissue and encourage healing

Infection

invasion of host tissues by disease causing agent

multistep process: est presence, X of organisms in tissues, reaction of host tissues to organisms and toxins -→ mild to life-threatening

Immediate transient response to minor injury

Redness (erythema), pain, heat, mild

Immediate sustained response (several days)

Damaged vessels (moderate)

Delayed hemodynamic response

Increase capillary permeability 4-24 hours after injury -> radiation burns (severe)

Acute inflammation

healing occurs in 2-3 weeks, neutrophils are predominant cell type at site of inflammation

Subacute inflammation

persists longer than acute

Chronic inflammation

may last for years

mostly involved - lymphocytes and macrophages

may result from changes in immune system (ex: autoimmune disease)

Acute inflammation (vascular)

injury > inflammation > rapid vasoconstriction > rapid vasodilation > vascular permeability increases

Acute inflammation (cellular)

movement of phagocytic cells to site \[adhesion, margination\]

release of chemical mediators of mast cells, basophils and macrophages > transmigration of WBC > inflammation

increase capillary permeability > allow leukocytes move > move WBC toward inflammation \[chemotaxis\]

Complement cascade

C3 → Degranulation of mast cell; promotes phagocytosis; is a chemical attractant for WBC to inflammation; breaks down bacterial membrane

Clotting cascade

All modes of clotting lead to the activation of factor X and thrombin

Kinin cascade

Bradykinin → histamine-like effects: increased vascular permeability and induces pain

Localized clinical presentation

erythema, heat, swelling, pain, loss of function

Systematic clinical presentation

leukocytosis, fever

Serous exudate

watery, early inflammation, low protein

fibrinous exudate

thick, large amount of fibrinogen

Purulent exudate

pus, bacterial infection, degraded white cells, protein and tissue debris

Hemorrhagic exudate

contains blood → bleeding, severe leakage of red cells from capillaries

Leukocytosis

increase WBC, 11,000/mL

left shift: immature > mature

immature neutrophils are not able to do their job

Mast Cells Degranulation/Synthesis

related to allergies and inflammation

activated mast cells > synthesis of other chemicals of inflammation

* platelet-activating factor
* cyclooxygenase pathway - synthesis of prostaglandins and thromboxane
* lipoxygenase pathway - synthesis leukotrienes

Cytokines

small, signaling proteins, produced during all phases of immune response

made by t cells and macrophages

act on other immune cells in response to foreign bodies

can be proinflammatory or anti inflammatory

hypothalamus

regulate body temperature and emotions

Pharmacologic treatment of fever

antipyretic medication

Antipyretic medication

NSAID - aspirin, ibuprofen

Antipyretic only (not anti-inflammatory) - acetaminophen

NSAID’s

non-steroidal anti-inflammatory drugs

COX 1 “good”

* Found in many body tissues
* Response to reaction product
* Gastric protection
* Platelet aggregation
* Maintenance of renal function
* Effect of inhibition
* Gastric ulceration, gastritis, bleeding tendencies protection against MI
* Renal impairment (both, kidneys)

COX 2 “bad”

* Primarily produced at site of injury
* Response of reaction product
* Vasodilation
* Maintenance of renal function
* Inflammation, pain, fever
* Colorectal cancer promotion
* Effect of inhibition
* Vasoconstriction
* Renal impairment
* Reduced inflammation, analgesia, reduced fever
* Colorectal cancer protection

Chronic inflammation

self-perpetuating - weeks, months, years

chronic inflammation causes

* chronic low-level irritants
* certain bacteria
* RA
* Systemic lupus erythematosus
* obesity

chronic inflammation results

fibrosis (loss of function) and angiogenesis > tissue damage

inadequate responses

immune deficiency

inappropriate responses

hypersensitivity

factors that lead to infectious disease

* communicability
* infectivity
* virulence
* pathogenicity
* portal of entry
* toxigenicity

communicability

ability to spread

infectivity

ability to invade and multiply

virulence

capacity for severe disease

pathogenicity

ability to produce disease

portal of entry

route to invade host

toxigenicty

ability to produce toxins

characteristics of a bacteria

self-replicating, prokaryotes, have a cytoplasm - contains reproductive and metabolic machinery, have cytoplasmic membrane, cell wall

bacteria shape classification

round (cocci), rod-shaped, spiral

viruses

smallest intracellular pathogens, no organized cell structure, contains a protein coat around nucleic core, cannot replicate outside host cell

viral replication

copying of genetic material, new virions released from cell to infect other host cells, some virus remain latent in host cells until activated by stress, hormone changes, diseases

fungi infection

eukaryotic (contains nucleus), found in all enviro, few cause illness in healthy people, opportunistic, often temperature sensitive outside of body

factors that impact infection

HAI, MDRO, survival on environmental surfaces, direct and indirect transmission

infection pathology

enter host cells cause death or induce host responses

Bioflim in Common Infections

bacteria - stick and colonize environmental surfaces

Biofilm - structuered community of bacteria

* access to nutrients - elimination of wastes
* intracellular as much as 80% of infections

location - dental plaque, catheter infections

Goal with infections

* deliver to infected site
* allow sufficient time for drugs to work
* local factors cannot interfere drug activity
* host defenses activated
* adjunctive therapies - surgical drains

antibacterial drugs

narrow spectrum antibiotics

broad spectrum antibiotics

anti-mycobacterial drugs

antifungal drugs

target fungi/mold

antiviral drugs

antivirals, anti-retroviral

actions by antibiotics

inhibit cell wall synthesis, protein synthesis, nucleic pathway

interrupts metabolic pathways

disrupt cell membrane permeability

Inhibit enzyme important in microorganism function

bactericidal effects

drug actually kills bacteria

bacteriostatic effects

drug inhibits bacterial reproduction so host defenses can kill

culture (antimicrobial drug concepts)

identification of the bacteria

sensitivity

what type of antibiotic can kill the bacteria

intermediate

patient given a low dose of antibiotics but no change, therefore provider will prescribe a higher dose

antibiotic resistance

genetic mutation in patient themselves, modification of target molecule, increase active efflux of antibiotic

antibiotic resistance causes…

lack of compliance with therapeutic regimen, overuse: destruction of normal microbiome

factors that impact antimicrobial resistance

id offending organism is paramount (rapid tests for some organisms, culture using specific media)

id takes days, weeks → give broad spectrum drugs → more specific drug ASAP

principles of antimicrobial selection and admin

* Match “drug with bug”
* ID pathogen: culture, gram stain
* culture and sensitivity
* ID specialist - suggest appropriate therapy, prevent overuse/inappropriate use of antimicrobial
* consider drug spectrum
* consider combination therapy (broad + narrow)
* site of infection
* maintain adequate blood levels (antibiotics can be administered on an empty stomach)

antibiotic combinations

* different mechanisms may be synergistic
* mixed infections with more than one bacterial species (ex: TB)
* some antibiotic resistance is discouraged by combinations

Antimicrobial complications

* normal gut flora are killed → diarrhea → pave way for colonization with pathogenic bacteria (C. diff)
* Suprainfection
* Allergy/Cross over allergy

supra-infection

infection with a second (antibiotic resistant) organism that occurs during antibiotic therapy

pseudomembranous colitis

bowel colonized with C. diff → severe diarrhea → sometimes fatal

Allergy

most common with penicillins

COVID treatment

* supportive care (ex: oxygenation - nasal cannula → invasive mechanical ventilation)
* Medications: antivirals, antibodies, anti-inflam agents

UTI treatments

* antibiotic therapy based on culture and sensitivity

Complicated UTIs

doxycycline, ciprofloxcin, levoFLOXacin, azithromycin, cefTRIAXone, cephalosporin

Uncomplicated UTIs

sulfamethoxazole-trimethoprim

Allerigies to sulfamethoxazole trimethoprim/resistance to E. coli

nitrofurantonin macrocrystals

UTIs during pregnancy

nitrofurantonin macrocrytstals, amoxicillin, cephalexin

continous antimicrobial prophylaxis for chronic UTIs

sulfamethozazole-trimethoprim x nitrofurantonin macrocrystals

Relief of dysuria

phenazopyridine for 1-2 days, treat the symptoms of UTI, orange urine

Pathophysiology of HIV

HIV - ribonucleic acid virus

* retroviruses because replicate “backward” manner going from RNA to DNA
* CD4+T cell - target cell for HIV
* type of lymphocyte
* binds to cell through fusion

HIV proteins bind to cell

HIV replication process

HIV Medication

2 major coronary arteries

left and right coronary arteries

Coronary arteries arise from

coronary sinus

When are coronary arteries are perfused?

when aortic valve closes (diastole)

Diastole

relaxing

Systole

contraction

CAD

vascular disorder that narrows or occludes coronary arteries \> MI and angina

What is the most common cause of CAD?

atherosclerosis

What happens if blood flow is inadequate (when O2 demand increase)?

ischemia produces angina

MI

myocardial cell/tissue death due to long-term O2 (

Plaque formation

do not occlude the whole coronary artery \> narrowing/restrict blood flow

Unstable angina

unstable and rupture \> clot formation \> completely occlude the artery \> death of cardiac cells downstream that are supplied by that artery (large lipid center, inflammation and thin cap)

Unstable angina symptoms

pain at rest (\> 20 mins), new onset, more severe, prolonged or freq than previous angina symptoms, does not respond to NTG or rest

Collateral circulation

gradual occlusion of large coronary vessels, smaller collateral vessels ^ size to provide alternative channels for blood flow, collateral channels develop the same time the atherosclerotic changes are occurring [beltway exit closure analogy]

Stable angina

60% blockage, symptoms starting, body requirement of blood still met, fixed coronary obstructions, increase O2 demand \> decrease O2 \> pain, provoked by stressor --\> relieved with rest/NTG, sometimes asymptomatic (smaller lipid center and thicker fibrous cap)

Usual distribution of pain (stable angina)

left side, left arm, neck/chest pain

Less common sites of pain distribution (stable angina)

right side, jaw, epigastrium, back

Variant Angina

coronary artery spasms (not due to atherosclerosis), during rest/minimal exertion, nocturnal, dysrhythmias can occur, person usually aware, high risk sudden death

Angina management

nitrates, beta blockers, calcium channel blockers (lower O2 demand, increase perfusion)