Hyper- & Hypo Immune Disorders Flashcards
Hyper- & Hypo- Immune Disorders
Inadequate innate immunity
- Neutropenia, abnormal phagocytosis, complement system deficiency, hypersplenism
Excessive innate immunity
- Neutrophilia, monocytosis, asthma
Misdirected innate immunity
- Angioedema
Inadequate adaptive immunity
- T lymphocytes deficiency (DiGeorge Syndrome), SCIDs
Excessive adaptive immunity
- Allergic reactions, anaphylaxis, drug allergies
Misdirected adaptive immunity
- Hypersensitivity to self-antigens, SLE, rheumatoid arthritis, hepatitis
Anesthesia & immunocompetence
- Graft vs. host disease
- Tumor lysis syndrome
Innate Immunity
NON-SPECIFIC response that targets common pathogens
No prior exposure required to elicit response
Passed on to each generation
Epithelial & mucus membranes, complement factors, neutrophils, macrophages, & monocytes
RAPID response
Mediated via cells & plasma proteins that are always present
Principle cells = myeloid cells (macrophages, neutrophils, dendritic cells)
NOT pathogen specific
Adaptive Immunity
Developed individually
Delayed response, develops memory & specific towards antigen, B & T lymphocytes
Powerful, normally silent but active & adapt to antigens
Specialized, unique specificity
Receptors created by rearrangement antigen-receptor genes that occur during lymphocyte maturation
Principle cells = T & B lymphocytes
Humoral Mediated Immunity
Mediated by antibodies produced by B cells
Antibodies neutralize microbes, opsonize them for phagocytosis, & activate the complement system
Cell Mediated Immunity
T cells activated by protein antigens from antigen presenting cells (APCs)
Requires repeat antigen stimulation to perform their functions
CD4+ helper T cells secrete cytokines to activate macrophages, helps B cells make antibodies, & stimulate inflammation
CD8+ helper T cells kill infected & transformed cells
Adaptive Immune Dysfunction
Defects in antibody production or T lymphocytes Combines immune system defects (SCIDs) Allergic reactions Anaphylaxis Autoimmune disorders
-penia
Lack of, poverty, deficiency
Neutropenia = lacking neutrophils
-philia
Affinity, attraction, fondness
Allergy
Reactions against normally harmless environmental signs
Autoimmune
Reactions against self-antigens
Hypersensitivity
Excessive immunologic reactions to microbes or environmental agents dominated by inflammation
Atopy
Propensity or genetic tendency to develop allergic reactions
Antibody (Ab)
Immunoglobulin (Ig) large Y-shaped protein used by the immune system to identify & neutralize foreign objects such as pathogenic bacteria & viruses
Neutrophils
Formed by stem cells in the bone marrow
Make up 40-70% all WBCs in humans
Phagocytes found in the bloodstream
FIRST RESPONDERS to inflammation - especially bacteria
Predominant cells in pus (create yellow/white-ish color)
Neutropenia
<1,500/mm^3
Types include neonatal sepsis, Kostmann syndrome, acquired defects, autoimmune, infection
Treatments include medication cessation, granulocyte colony-stimulating factor, & bone marrow transplants
ASEPSIS important
Spleen
Lymphatic system
Large lymph node - primary blood filter
Primary RBC creation site fetal up to 5mos
Function: 250mL blood reservoir, removes old RBCs, recycles iron, metabolizes hemoglobin, lymphocyte storage, clears platelets
Globin → amino acids
Heme → bilirubin (removed via liver)
Synthesizes antibodies
Asplenia
Absence normal spleen function
Type immuno-dysfunction
Increased sepsis risk 350x d/t spleen unable to clear bacteria from the blood
Hyposplenism
Reduced spleen function
Sickle Cell Anemia
Auto-infarction w/in spleen results in vaso-occlusive disease
Leukocytosis
WBC count above normal range
Normal reaction - inflammatory response
Other causes include tumor, leukemias, pregnancy, convulsions & medications
Left Upper Shift
↑ratio immature to mature neutrophils
Bone marrow trying to make more
Right Shift
↓ratio immature to mature neutrophils
Shows bone marrow suppression (radiation sickness)
Leukemia
Acute - immature WBCs present in the peripheral blood
Chronic - mature, non-functioning WBCs in peripheral blood
Eosinophilic Esophagitis
Chronic immune system disease where type WBC (eosinophil) build-up in esophagus lining
Build-up reaction to foods, allergens, or acid reflux → inflame or injure the esophageal tissue
Damaged tissue → difficulty swallowing or cause food to get stuck
Neutrophilia
Granulocytes ↑2-3x
Neutrophilia >7,000/mm^3
- Pancreatitis, pyelonephritis, peritonitis, pneumonia
Leukostasis >100,000/mm^3
- Thick blood flow & WBC clumping → TIAs & strokes
Myeloproliferative disorder or hematologic malignancy >50,000/mm^3
Asthma
Exaggerated bronchoconstriction response to stimuli
EXTRINSIC Asthma
IgE production
Allergens
INTRINSIC Asthma
Triggers are unrelated to the immune system
Examples: ETT placement, cold, exercise, stress, inhaled irritants
Angioedema
Hereditary or acquired
Subcutaneous & submucosal edema formation
Often involves face, extremities, & GI tract
Bradykinin-Mediated Angioedema
Autosomal dominant deficiency/dysfunction C1 esterase inhibitor
ACEi drug-induced angioedema d/t ↑bradykinin
Acquired - lymphoproliferative disorders acquire C1 esterase inhibitor deficiency 2° antibody production
CATECHOLAMINE & ANTIHISTAMINES ARE NOT EFFECTIVE IN ACUTE EPISODES
Acute Angioedema Treatment
Androgens - prophylactic therapy
Antifibrinolytic therapy inhibiting plasmin activation
C1 inhibitor concentrate
Synthetic bradykinin receptor antagonist
Recombinant plasma kallikrein inhibitor - blocks kininogen → bradykinin conversion
FFP replaces the deficient enzyme
DiGeorge Syndrome
Thymic, thyroid, & parathyroid hypoplasia
Cause: 22q11.2 gene deletion
↓T cells (B cells are normal)
Cardiac malformations & facial dysmorphisms
- Truncus arteriosus & TOF
- Cleft palate
Immunocompromise degree correlates w/ amount thymus tissue present
Complete absence = severe combined immunodeficiency syndrome
Treatment: T-cell infusion or thymus transplant
Hypoparathyroidism - Ca2+ supplementation
Strict asepsis d/t infection risk
Severe Combined Immunodeficiency
Genetic mutations that affect T, B, & NK cell function/maturation
X-linked form 1/58,000 births
Appear healthy at birth but highly susceptible to severe infections
All newborns screened SCIDs
Gene mutations that encode for interleukin receptors
Treatment: bone marrow or stem-cell transplant, gene therapy, or enzyme replacement
Allergic Reactions
Immune-mediated
“Overreactions”
4 types:
Type I - IgE (anaphylaxis)
Type II - IgG/IgM (myasthenia gravis, Grave’s disease)
Type III - immune complex (SLE)
Type IV - T lymphocytes (rheumatoid arthritis, multiple sclerosis)
Type I
IgE
Histamine release & other mediators from mast cells
Vascular dilation, edema, smooth muscle contraction, mucus production, tissue injury, inflammation
Immediate hypersensitivity
Anaphylaxis, allergies, bronchial asthma
Type II
IgG/IgM production binds to antigen on target cell or tissue → phagocytosis or lysis target cell via activated complement
Leukocytes recruitment
Possibly delayed
Autoimmune hemolytic anemia
Type III
Immune complex formation (antigen-antibody complexes) → complement activation
Recruit leukocytes
Inflammation, necrotizing vasculitis (fibrinoid necrosis)
Delayed
SLE, glomerulonephritis, serum sickness
Type IV
Activated T lymphocytes
Release cytokines, inflammation, & macrophage activation
T cell-mediated cytotoxicity
Perivascular
Delayed
Chronic dermatitis, multiple sclerosis, type 1 diabetes, tuberculosis
Anaphylaxis
Life-threatening
Cardiovascular collapse (tachycardia, hypovolemia)
Interstitial edema, urticaria (cutaneous rash)
Bronchospasm, laryngeal edema
Immune mediated IgE 60%
Non-immune mediated “anaphylactoid” IgG or IgM
Less common
Direct histamine release from mast or basophils
Histamine
Vasoactive amine
Stored in mast cells
Release upon mast cell degranulation
Causes → vasodilation, ↑vascular permeability, & smooth muscle contraction
Prostaglandins
Lipid mediator Prostaglandin D2 (PGD2) most abundant mediator generated by cyclooxygenase pathway in mast cells → intense bronchospasm
Leukotrienes
Lipid mediator
Most potent vasoactive & spasmogenic agents known
Cytokines
Tumor necrosis factor & chemokines
Recruit, activate, & amplify leukocytes
Perioperative Anaphylaxis Management
Remove triggering agent Reverse/treat hypotension & hypoxemia Replace intravascular fluid Inhibit further degranulation Inhibit release vasoactive mediators Treat inflammation Relieve bronchospasm
Antihistamines
Histamine 1 antagonist
Diphenhydramine competes w/ histamine
Histamine 2 antagonist
Ranitidine
↓pruritis & bronchospasm
Not as effective to treat anaphylaxis once vasoactive mediators have been released
Epinephrine
1-10mcg/kg IV bolus
Repeat every 1-2minutes as needed
↑intracellular cAMP, restores membrane permeability, & ↓release vasoactive mediators
β agonists relax bronchial smooth muscle
UNRESPONSIVE TO EPI → VASOPRESSIN, GLUCAGON, OR NOREPINEPHRINE
β2 Agonists
Albuterol delivered via MDI or nebulizer useful to treat bronchospasm
Corticosteroids
Several hours to take effect
Potentially enhance β agonist effects
Inhibit arachidonic acid release (leukotriene & prostaglandin production)
Intolerance
Inability to tolerate medication adverse effects
Example: muscle pain & statins
Idiosyncratic Reactions
Drug reactions not r/t known pharmacological drug properties
Example: antiepileptic drugs & dyskinesias
Toxicity
Dose-dependent
Too much drug present in patient system at one time
Perioperative Anaphylaxis Causes
MUSCLE RELAXANTS
Rocuronium & Succinylcholine
Atracurium histamine release = non-immune mediated
Perioperative Anaphylaxis Causes
ANTIBIOTICS
PCN & cross-sensitivity w/ cephalosporins (β-lactam ring)
Sulfonamide - second most common (Stevens-Johnson syndrome)
Vancomycin - non IgE mediated (direct histamine release r/t drug infusion rate)
Perioperative Anaphylaxis Causes
LATEX
Delayed onset >30min after exposure
Spina bifida, multiple previous operations, fruit allergy, & healthcare workers
Perioperative Anaphylaxis Causes
PROPOFOL
Contains lecithin (derived from egg yolk) & soybean oil as emulsifying agents Preservatives = EDTA or sodium metabisulfite/benzoate 2-isoproyl group
Perioperative Anaphylaxis Causes
ASA & NSAIDs
Rhinorrhea, bronchospasm, & angioedema
High risk patients = asthma, hyperplastic sinusitis, & nasal polyps
NON IgE mediated
Cyclooxygenase-1 inhibition promotes leukotriene synthesis → release mediators from basophils & mast cells
Perioperative Anaphylaxis Causes
RADIOCONTRAST MEDIA
0.1-3%
More common w/ ionic, high-osmolar contrast agents
↑iodine ↑risk adverse reaction
Non-immune mediated pretreat w/ corticosteroid & histamine antagonists
Perioperative Anaphylaxis Causes
OTHER
Midazolam, Etomidate, Ketamine, Heparin, Insulin
Opioids - Morphine, Codeine, & Meperidine directly release histamine
Local anesthetics <1%
Ester > Amide
Halothane induced hepatitis
Dyes - ICG or methylene blue
Chlorhexidine
Synthetic volume expanders - contain dextrans, gelatins, albumin, starch → both immune & non-immune reactions
Blood products
Rejection
Histocompatibility determines if tissue graft will be accepted (compatible) by the receiving individual
Major histocompatibility complex (MHC) are polymorphic genes that differ among individuals
- Function to recognize T cells
Graft donor expresses MHC molecules differ from those in the recipient host
- Graft recognized as foreign by recipient T cells
- Recipient CD4+ & CD8+ T cells specific for graft antigens are activated, migrate back into transplants, & cause its rejection
Graft Rejection Treatment
IMMUNOSUPPRESSION needed to prolong graft survival
- Corticosteroids, anti T-cell antibodies, T-cell function inhibition drugs
Immunosuppression → risk opportunistic fungal & viral infections
- Reactivation latex viruses (cytomegalovirus) ↑cancer risk in immunocompromised patients
Graft vs. Host Disease
Syndrome commonly associated w/ bone marrow & stem cell transplants
Donor WBCs remain w/ the donated tissue (graft) recognize the recipient (host) as foreign
NOT the same as transplant rejection
Donor immune system rejects the recipient body
Treatment: T-cell suppression
- Steroids & calcineurin inhibitors (cyclosporin & tacrolimus)
- Suppresses pro-inflammatory cytokine synthesis
Tumor Lysis Syndrome
Rare but potentially lethal
Massive lysis tumor cells results in intracellular substances release into the bloodstream
- Potassium, phosphate, uric acid
Causes: steroids & after chemoembolization or radiofrequency ablation treatments
