Hyper- and Hypo- Immune Disorders Flashcards
1
Q
What are the two branches of the immune system?
A
- Innate
2. Adaptive
2
Q
What is the innate immune system?
A
non-specific response that targets many common pathogens;
NOT PATHOGEN SPECIFIC, limited diversity
3
Q
Does the innate immune system need prior exposure?
A
NO
4
Q
How does one develop an innate immune system?
A
passed on from previous generation;
does NOT need previous exposure to pathogen
5
Q
What compromises the innate immune system?
A
- epithelial & mucous membranes
- complement factors
- neutrophils
- macrophages
- monocytes
6
Q
What is the adaptive immune system?
A
system that must be developed individually; develops memory & is specific towards antigens
delayed response
7
Q
Which is faster, the innate or adaptive immunity?
A
innate,
adaptive is delayed
8
Q
What types of cells are involved in adaptive immunity?
A
lymphocytes;
B lymphocytes
T lymphocytes
9
Q
What are the principle cells of the innate immune system?
A
myeloid cells
→ macrophages, neutrophils, dendritic cells
10
Q
What is the innate immune system mediated by?
A
cells and plasma proteins that are ALWAYS present
11
Q
Is the adaptive immune system weak or powerful?
A
powerful; usually “silent” until pathogen is found
12
Q
What creates the receptors of the adaptive immune system?
A
rearrangements of antigen-receptor genes that occur during the maturation of the lymphocytes
13
Q
What are the principle cells of the adaptive immune system?
KNOW!!
A
B lymphocytes
T lymphocytes
14
Q
The adaptive immune system is mediated by what TWO mechanisms?
A
- Humoral Immunity
→ mediated by antibodies produced by B cells - Cell-Mediated
→ T cells activated by protein antigens from antigen presenting cells (APCs)
15
Q
What type of cell mediates humoral immunity?
of the adaptive immune system
A
B cells.
antibodies
1. NEUTRALIZE MICROBES 2. opsonize microbes for phagocytosis 3. activate the complement system
16
Q
What type of cell mediates, cell-mediated adaptive immunity?
A
T cells. [2 types]
→ activated by protein antigens from antigen presenting cells (APCs)
require repeat antigen stimulation
17
Q
What are the 2 types of T cells?
A
CD4+ helper T cells [secrete cytokines to activate macrophages; helps B cells make antibodies; stimulates inflammation]
CD8+ helper T cells [kill infected & transformed cells]
18
Q
The three dysfunctions of the innate immune system are:
A
- inadequate response
- excessive response
- misdirected response
19
Q
What are 4 types of an inadequate innate immune system response?
A
- neutropenia
- abnormal phagocytosis
- deficient in the complement system
- hyposplenism
20
Q
What are 3 types of excessive innate immune response?
A
- neutrophilia
- monocytosis
- asthma
*over-reaction
21
Q
What is one example of a misdirected innate immune response?
A
angioedema
*body responds, but edema is sent to the wrong place
22
Q
What are 6 dysfunctions of the adaptive immune system?
A
- defects in antibody production
- defects in T lymphocytes
- combined immune system defects (SCIDs)
- allergic reactions
- anaphylaxis
- autoimmune disorders
23
Q
” -penia”
A
lack of, poverty, deficiency
24
Q
” -philia”
A
affinity, attraction, fondness
25
allergy
reactions against normally harmless environmental antigens
26
hypersensitivity
excessive immunologic reactions to microbes or environmental agents dominated by inflammation
27
atopy
propensity or genetic tendency to develop allergic reactions
[ie. lots of food and/or environmental allergies]
28
Antibody (Ab) is also known as...
an immunoglobulin (Ig)
29
What is an antibody?
large, Y-shaped, protein USED by the immune system TO IDENTIFY and NEUTRALIZE FOREIGN OBJECTS such as pathogenic bacteria and viruses
30
Where do T cells come from?
Thymus
31
Where do B cells come from?
Immature cells are released from the bone marrow; mature in the circulation
32
How are neutrophils formed?
by stems cells in the bone marrow
33
What % of WBCs are neutrophils?
40-70%
34
What are neutrophils?
phagocytes that are found in the blood stream;
FIRST RESPONDERS TO INFLAMMATION
[especially bacterial]
*predominant cells in pus
35
What is neutropenia?
neutrophil count <1500/mm3
36
What are 5 types of neutropenia?
1. neonatal sepsis
2. Kostmann syndrome (autosomal recessive)
3. acquired defects (chemo, antivirals)
4. autoimmune (Lupus, RA)
5. Infection [rate of production is inadequate for consumption]
37
What are the treatments for neutropenia?
1. stop causative agent
2. granulocyte stimulating factor (filgrastim)
3. bone marrow transplant
38
What does the spleen do?
primary creator of RBCs in fetal life (up to 5 months old)
1. removes old RBCs
2. blood reservoir (250mL)
3. recycles iron
4. metabolizes hemoglobin
5. stores 1/4 circulating lymphocytes
6. stores & clears platelets
7. synthesizes antibodies in the white pulp
8. removes antibody-coated bacteria
39
How is hemoglobin broken down?
globin is degraded into amino acids
heme is metabolized into bilirubin [which is removed by the liver]
40
How do the spleen & liver "work together"?
the spleen "eats" bacteria, blood flow goes to the liver where toxins are removed & "cleansed" from the blood
41
What is the size of the spleen?
healthy adult:
2.8in x 5.5in
between 1oz-8oz
42
Asplenia
absence of normal spleen function;
type of immuno-dysfunction
** sepsis risk is increased 350-fold d/t inability to clear bacteria from the blood [S.pneumoniae, E.coli, H.flu, malaria]
43
Hyposplenism
reduced spleen function
44
How can sickle cell affect the spleen?
sickle cell can cause auto-infarction, resulting in vaso-occlusive disease
45
What is leukocytosis?
WBC count is above normal range;
normal reaction as an inflammatory response but can be from
- tumors
- leukemias
- stress
- pregnancy
- convulsions
- medications [corticosteroids, lithium, beta agonists]
46
What are the 5 types of leukocytosis?
1. neutrophilia
2. eosinophilia
3. basophilia
4. monocytosis
5. lymphocytosis
47
What is eosinophilic esophagitis?
chronic immune system disease in which a type of WBC (eosinophil) builds up in the lining of the esophagus
→ reaction to foods, allergens or acid reflux
- inflame or injure esophageal tissue; can lead to difficulty swallowing or food to get stuck
*food aversion or non-specific s/s
48
Neutrophilia
>7000/mm3
49
4 causes of neutrophilia
1. pancreatitis
2. pyelonephritis
3. peritonitis
4. pneumonia
50
Leukostasis; count & blood
>100,000/mm3;
| thick blood flow and WBC clumping, can lead to TIAs & strokes
51
Myeloproliferative disorder or hematologic malignancy
>50,000/mm3
52
What is asthma?
exaggerated bronchoconstrictor response to stimuli
53
Cause of extrinsic asthma:
IgE production, allergens
54
Cause of intrinsic asthma:
triggers are unrelated to the immune system:
- ETT placement
- cold
- exercise
- stress
- inhaled irritants
55
When does extrinsic asthma typically develop?
childhood or early adulthood
56
When does intrinsic asthma typically develop?
later in adulthood
57
Having a personal and/or family history of asthma is most related to which kind of asthma?
extrinsic asthma
58
What type of asthma is considered a hypersensitivity reaction to an allergen?
extrinsic
59
Increased IgE levels are most often found in what kind of asthma?
extrinsic
60
Does intrinsic asthma include recognizable allergens? elevated IgE levels?
no recognizable allergens;
| normal IgE levels
61
When do s/s of intrinsic asthma appear?
after respiratory infection, emotional reactions, exercise, handling chemicals, taking aspirin, etc.
62
What is the hallmark sign of misdirected innate immunity?
angioedema
63
What are the two types of misdirected innate immunity?
1. hereditary
| 2. acquired
64
What two types of edema form in misdirected innate immunity?
SQ and submucosal
65
What structures are involved in misdirected innate immunity angioedema?
face, extremities, GI tract
66
What is the most important thing to remember about acquired misdirected innate immunity?
it will NOT respond to epinephrine
67
Deficiency in ___ is the most common form of hereditary angioedema.
C1 esterase inhibitor
[autosomal dominant deficiency/dysfunction]
C1INH deficiency is Type 1.
C1INH dysfunction is Type 2.
68
How does a lack of C1 esterase inhibitor lead to edema?
absence of C1 esterase inhibitor leads to the RELEASE of VASOACTIVE MEDIATORS that increase vascular PERMEABILITY...... producing edema via bradykinin
69
How long will edema d/t C1 esterase deficiency last?
24-72 hours
70
How do ACEi cause bradykinin induced angioedema?
ACEi block bradykinin catabolism leading to elevated levels of bradykinin.
71
How does a person develop acquired bradykinin mediated angioedema?
Patients with lymphoproliferative disorders can develop antibodies to the C1 inhibitor... giving rise to a syndrome that closely resembles hereditary angioedema.
72
Angioedema can be caused via two different physiological mechanisms, these two pathways are...
1. release of mast cell mediators
| 2. bradykinin release (no allergy symptoms)
73
Angioedema caused by the release of mast cell mediators is associated with what other s/s?
urticaria, bronchospasm, flushing, hypotension
74
What is the treatment of mast cell mediated angioedema?
drugs usually used to treat allergy & anaphylaxis.
- epinephrine
- antihistamines
- glucocorticoids
75
What is the treatment of bradykinin mediated angioedema?
C1 inhibitor concentrate (is the preferred treatment).
- kallikrein inhibitor
- bradykinin receptor antagonist
FFP can be administered if the above are unavailable [it contains the deficient enzyme]
76
What is the treatment of ACEi mediated angioedema?
STOP offending drug & administer supportive care.
→ glucocorticoids have been noted to INCREASE the expression of ACE = accelerate bradykinin METABOLISM
[opposite of the ACEi]
77
What do kallikrein inhibitors do?
block the conversion of kininogen to bradykinin
78
What medication blocks the conversion of kininogen to bradykinin?
plasma kallikrein inhibitor
79
How does FFP treat bradykinin induced angioedema?
provides the deficient enzyme
80
What two medications are NOT effective in acute episodes of bradykinin-mediated angioedema?
catecholamines & antihistamines
81
When are catecholamines & antihistamines NOT effective?
in bradykinin mediated angioedema
82
What are the two types of immunodeficiency disorders?
| aka. inadequate adaptive immunity
1. Primary (congenital)
| 2. Secondary
83
What causes primary (congenital) immunodeficiencies?
gene mutations that are usually inherited
84
Gene mutation that causes a defect in T lymphocytes is known as ____ syndrome.
DiGeorge syndrome
85
What are secondary immunodeficiencies encountered in high income countries?
- chemotherapy
| - radiation
86
What are secondary immunodeficiencies encountered in low-income countries?
- malnutrition
| - acquired immunodeficiency syndrome (AIDS)
87
Gene mutations that cause dysfunction in T- B- or NK- cell functions, cause ____ syndromes.
severe combined immunodeficiency syndromes
88
What is the treatment of severe combined immunodeficiency syndromes?
(SCID)
bone marrow or stem cell transplant
gene therapy
enzyme replacement
89
What organ causes the immune deficiency in DiGeorge Syndrome?
How does this affect severity?
Thymus hypoplasia
→ degree of immunocompromise correlates with the amount of thymus tissue present
90
What organs can be affected in DiGeorge Syndrome?
thymus, thyroid, parathyroid
(hypoplasia)
Can also have cardiac defects & facial dysmorphisms
- truncus arteriosus
- TOF
- cleft palate
91
What gene deletion causes DiGeorge Syndrome?
22q11.2
92
What cell level is abnormal in DiGeorge Syndrome?
T cells are decreased;
B cells are normal
93
Complete absence of the thymus results in what sundrome?
severe combined immunodeficiency syndrome (SCID)
94
Severe combined immunodeficiency syndromes (SCID) affect what cells?
T cells
B cells
NK cells
95
SCID is linked to what chromosome?
X-linked.
boys are affected
girls are carriers
96
What is the abnormality in the most common form of severe combined immunodeficiency syndrome?
mutation in the gene that codes for interleukin receptors
lack of interleukin receptors → lack of interleukin signaling → lack of T, B, NK cell differentiation/maturation
97
What are four categories of excessive adaptive immunity?
- anaphylaxis
- bronchial asthma
- allergic rhinitis, sinusitis
- food allergies
98
What are the clinical & pathological manifestations of anaphylaxis?
[may be caused by drugs, bee sting, food]
- vascular dilation = fall in blood pressure (shock)
| - airway obstruction d/t laryngeal edema
99
What are the clinical & pathological manifestations of bronchial asthma?
airway obstruction d/t smooth muscle hyperactivity
inflammation & tissue injury caused by late-phase reaction
100
What are the clinical & pathological manifestations of allergic rhinitis, sinusitis?
increased mucous secretion
inflammation of upper airways & sinuses
101
What are the clinical & pathological manifestations of food allergies?
increased peristalsis d/t contraction of intestinal muscles = vomiting & diarrhea
102
What are hypersensitivity disorders?
persistent, misdirected, or inadequately regulated immune reactions against a variety of antigens
"overreaction of the immune system"
103
What does it mean when an individual is "sensitized"?
they have been exposed to and react against an antigen
104
What are 3 categories of hypersensitivity disorders?
1. reactions against self-antigens
2. reactions against environmental antigens
3. excessive reactions against microbes
105
What occurs to cause autoimmunity?
an individual's self-tolerance breaks down
[normally an individual is tolerant to their own antigens]
106
What is an environmental allergy?
abnormal reaction against common and normally harmless environmental substance antigens
107
What happens in a hypersensitivity disorder involving excessive reactions against microbes?
the microbe is unusually persistent. the immune response itself becomes the cause of tissue injury
- example: tuberculosis
108
How many major types of hypersensitivity reactions are there?
4
109
What is Type 1 hypersensitivity reaction?
"allergy"
immediate, IgE mediated, mast cells
→ caused by IgE antibodies that recognize environmental antigens & sensitize mast cells leading to the release of mediators
ie. anaphylaxis
110
What is Type 2 hypersensitivity reaction?
antibody mediated
IgG / IgM
ie. myasthenia gravis, Graves disease
111
What is Type 3 hypersensitivity reaction?
immune complex mediated
ie. SLE (Lupus), glomerulonephritis
112
What is Type 4 hypersensitivity reaction?
T-lymphocyte mediated
(CD4+ / CD8+ T cells)
ie. rheumatoid arthritis, multiple sclerosis, contact dermatitis, T1DM
113
What is most important about the course of Type 1 hypersensitivity reactions?
early (w/n minutes) vascular & smooth muscle response
followed by
slow (hours) late-phase inflammatory response
→ do not let a patient go home right away
114
What are localized hypersensitivity clinical features?
skin
| GI tract
115
What are systemic hypersensitivity clinical features?
itching, urticaria, skin erythema
profound resp difficulty/bronchoconstriction, mucous production, laryngeal edema
vomiting, abdominal cramps, diarrhea
systemic vasodilation
116
What are clinical s/s a CRNA might see if a patient has an anaphylactic reaction?
unexplained...
| ↑ airway pressure, wheezing, increased & shark-fin ETCO2, ↓ BP, flushing, rash, ↑ mucous production, ↑ HR
117
Anaphylaxis is ___ mediated.
Immune mediated - IgE (60%)
118
What are life-threatening s/s of anaphylaxis?
CV collapse (tachycardia, hypovolemia)
Interstitial edema, urticaria
bronchospasm, laryngeal edema
119
After production of antigen-specific IgE antibodies, what causes anaphylaxis?
subsequent exposure to antigen results in marked mast cell and basophil degranulation
120
What is the difference between "anaphylactoid" reaction vs anaphylaxis?
"anaphylactoid" is NOT immune mediated, does NOT involve IgE
→ less common
→ not as profound
→ direct release of histamine from mast cells or basophils... no IgE involvement
121
___ is a vasoactive amine.
Histamine
122
Where is histamine stored?
mast cells
123
When is histamine released?
upon mast cell degranulation
124
What does histamine cause?
rapid vasodilation, increased vascular permeability, smooth muscle contraction
125
____ and ____ are lipid mediators of the immune system.
Prostaglandins & leukotrienes
126
What is the most abundant immune mediator generated by the cyclooxygenase pathway in mast cells?
Prostaglandin D2 (PGD2)
127
What mediator causes intense bronchospasm?
prostaglandin D2
128
What are the most potent vasoactive & spasmogenic mediators?
the leukotrienes
129
What mediators recruit, activate leukocytes & amplify the response?
cytokines;
| → tumor necrosis factor & chemokines
130
What are 4 major risk factors to anaphylaxis during anesthesia?
1. asthma
2. atopy
3. multiple past exposures to latex
4. hereditary conditions (angioedema)
131
What lab can be drawn to confirm anaphylactic reaction?
plasma tryptase concentration
132
What is tryptase?
stored in mast cells & released during immune-mediated reactions
→ indicator of mast cell activation
133
When do plasma histamine levels return to baseline after an allergic reaction?
30-60 minutes
134
Why isn't histamine level used to confirm anaphylactic reaction?
non-specific. histamine can be released from many causes
135
What is the management of perioperative anaphylaxis?
1. remove agent if possible
2. reverse hypotension & hypoxemia
3. replace intravascular fluid
4. inhibit further degranulation by stabilizing the membrane of mast cells [steroids / benadryl
5. inhibit release of vasoactive mediators
6. treat inflammation
7. relieve bronchospasm
136
What medications are given during management of perioperative anaphylaxis?
- oxygen
- epinephrine
- fluid bolus
- phenylephrine
- hydrocortisone
- diphenhydramine
- ranitidine (zantac)
- B2 agonist
137
Dose of oxygen to administer during anaphylaxis
ventilate with 100%
138
Dose of epinephrine to administer during anaphylaxis?
1-10mcg/kg IV bolus for ↓BP/bronchospasm
Q1-2min
may start infusion @ 0.05-1mcg/kg/min
139
Dose of fluid bolus to administer during anaphylaxis?
20mL/kg balanced salt solution; repeat as necessary
140
Dose of phenylephrine to administer during anaphylaxis?
0.1mcg/kg/min IV
titrate to effect if inadequate response to epinephrine
141
Dose of hydrocortisone to administer during anaphylaxis?
2-3mg/kg IV
Adults: 250mg IV
Child: 50-100mg IV
142
Dose of diphenhydramine to administer during anaphylaxis?
1-2mg/kg IV
143
Dose of ranitidine to administer during anaphylaxis?
1.5mg/kg IV
** don't forget H2 blocker to protect GI system from histamine!!!!
144
Why administer antihistamines during anaphylaxis?
to protect from H1/H2 receptors
→ helps decrease pruritus & bronchospasm
145
What medication is a histamine 1 antagonist?
diphenhydramine; competes with histamine for membrane receptor sites
146
What medication is a histamine 2 antagonist?
ranitidine
147
How does epinephrine work?
increases intracellular cAMP → restores/stabilizes membrane permeability → decreases the release of vasoactive mediators
148
What 3 medications can be given if the patient is unresponsive to epinephrine?
1. vasopressin
2. glucagon
3. norepinephrine
149
How do corticosteroids benefit during anaphylaxis?
may enhance B-agonist effects of other drugs or inhibition of the release of arachidonic acid responsible for production of leukotrienes and prostaglandins
→ no known effect on degranulation of mast cells or antigen-antibody interactions
** takes several hours for effect
150
Intolerance of a medication:
inability to tolerate the adverse effects of a medication
ie. muscle pains & statins
151
Idiosyncratic reaction to medication:
drug reactions not related to the known pharmacological properties of the drug
ie. antiepileptic drugs & dyskinesias
152
Toxic reaction to medication:
dose dependent, having too much drug in a person's system at one time
153
Most drug reactions manifest within how many minutes?
5-10
154
Reaction to ____ is typically delayed >30 minutes
latex
155
What are 5 common drugs associated with perioperative anaphylaxis?
1. muscle relaxants
2. antibiotics
3. latex
4. chlorhexidine
5. dyes
156
What are the 2 muscle relaxants most commonly associated with reactions?
- rocuronium
| - succinylcholine
157
Cross sensitivity occurs between benzylisoquinoliniums & ____.
(atracurium, Cisatracurium, mivacurium)
aminosteroids
over the counter cosmetics (contain ammonium ions & people can produce IgE antibodies to quarternary & tertiary ammonium ions)
morphine & neostigmine (contain ammonium ions)
158
Histamine from atracurium administration is immune mediated or nonimmune mediated?
nonimmune mediated
159
Antibiotic most commonly associated with reactions?
penicillin
IgE antibodies can wane over time... rxn as child may disappear as an adult
160
What are the two allergenic components found in penicillin?
beta-lactam ring (also found in cephalosporins, carbapenems, monobactams)
R-group side chain (also found in cephalosporins)
161
Cross sensitivity rate between penicillin & cephalosporins:
~2%
162
What antibiotic is the second most common for reactions?
sulfonamide;
| can cause STEVENS-JOHNSON syndrome
163
What is stevens-johnson syndrome?
severe cutaneous hypersensitivity reaction; macules spread & coalesce leading to epidermal blistering, necrosis, sloughing
164
What drugs can cause stevens-johnson syndrome?
sulfonamides, antiseizure drugs, antibiotics
165
What is the pathology of vancomycin reactions?
direct histamine release r/t rate of infusion.
NOT IgE mediated (has been report, but RARE)
166
What makes latex an allergen?
several Hevea proteins cause an IgE mediated response
Latex is produced from the rubber tree Hevea brasiliensis
167
What distinguishes a latex- induced reaction from other drug reactions?
delayed onset, typically longer than 30 minutes.
d/t absorption across skin/mucous membranes
168
What 4 patient characteristics increase the risk of having/developing a latex allergy?
1. spina bifida
2. multiple previous surgeries
3. Hx fruit allergy
4. healthcare workers
169
What food allergies are associated with a latex allergy?
avocado
kiwi
banana
170
What piece of equipment/container must be considered when a patient has a latex allergy?
**stopper of a drug vial**
171
What are the three ingredients in propofol that may trigger an allergic reaction?
1. lecithin - egg
2. sulfite (preservative)
3. soybean oil - soy
peanut allergy?
172
Is a reaction to the sulfite or 2-isopropyl-group in propofol immune mediated or nonimmune mediated?
thought to be immune (IgE) mediated
173
Patients with ___, ___, or ___ should not receive ASA or NSAIDs.
asthma, hyperplastic sinusitis, nasal polyps
174
If ASA/NSAIDs is given to a patient with asthma, hyperplastic sinusitis, or nasal polyps, what three s/s can occur?
and why?
1. rhinorrhea
2. bronchospasm
3. angioedema
```
NOT IgE mediated
inhibiting COX1 (medication blocks the production of cyclooxygenase but pushes arachidonic acid to be formed into leukotrienes instead) =↑ synthesis of leukotrienes = basophil & mast cell degranulation
```
175
What type of contrast agents have higher rates of reactions?
ionic, high-osmolar agents
→ the higher the iodine, the greater the risk of a reaction
176
Nonimmune mediated reactions to contrast can be pre-medicated with what three medications?
1. hydrocortisone 1-2mg/kg IV
2. diphenhydramine 50mg IV
3. ranitidine 50mg IV
177
Nonimmediate reactions to contrast are mediated by what cells?
t cells
178
What type of local anesthetics are more likely to produce allergic reactions?
ester-type LA
179
What medications produce possible but rare allergic reactions?
```
midazolam
ketamine
etomidate
opioids
heparin
insulin
```
180
What 3 medications cause direct histamine release?
morphine
codeine
meperidine
181
What reaction is caused by Halothane?
halothane hepatitis
d/t halide metabolites
182
What is found in cosmetics that might produce prior sensitization particular medications?
Dye
CRNAs will give ...
- methylene blue
- indocyanine green (ICG)
183
Allergy to CHG may be ___ and under or over reported?
delayed;
under-reported
184
Synthetic volume expanders can cause what type of reactions?
both immune and nonimmune mediated
185
What are 4 synthetic volume expanders that can cause allergic reactions?
1. dextrans
2. gelatins
3. albumin
4. starch
186
Anaphylaxis to blood products occurs how often?
1: 20,000 - 50,000 transfusions
187
Type II hypersensitivity reactions occur when:
IgG and IgM antibodies inappropriate mark self-components as foreign; targeting them for phagocytosis or complement-mediated destruction
→ may have genetic predisposition
188
What are four autoimmune disorders?
Systemic Lupus erythematosus (SLE)
Scleroderma
Rheumatoid arthritis
Autoimmune hepatitis
189
What are three anesthetic considerations of autoimmune disorders?
1. specific vulnerable organs
2. consequences of therapy/treatment
3. acceleration of other/related disease processes
190
"marked" or "flagged" elements are destroyed by what?
spleen
→ this is why a splenectomy can be helpful in antibody-mediated diseases marked by low blood counts
191
Antibodies that are deposited in extracellular tissues can recruit and activate:
neutrophils & macrophages
= acute inflammation
→ antibodies can also activate or inhibit receptors on cell surfaces
192
What is the target antigen in autoimmune hemolytic anemia?
red cell membrane proteins
193
What is the target antigen in myasthenia gravis?
acetylcholine receptor
194
What is the target antigen in Graves disease (hyperthyroidism)?
TSH receptor
195
What is the target receptor in pernicious anemia?
intrinsic factor of gastric parietal cells
196
What is the mechanism of autoimmune hemolytic anemia?
opsonization and phagocytosis of red blood cells
197
What is the mechanism of myasthenia gravis?
antibody inhibits acetylcholine binding, down-modulates receptors
198
What is the mechanism of Graves disease (hyperthyroidism)?
antibody-mediated stimulation of TSH receptors
199
What is the mechanism of pernicious anemia?
neutralization of intrinsic factor, decreased absorption of vitamin B12
200
What are the clinicopathologic manifestations of autoimmune hemolytic anemia?
hemolysis, anemia
201
What are the clinicopathologic manifestations of myasthenia gravis?
muscle weakness, paralysis
202
What are the clinicopathologic manifestations of Graves disease (hyperthyroidism)?
hyperthyroidism
203
What are the clinicopathologic manifestations of pernicious anemia?
abnormal erythropoiesis, anemia
204
What is the pathology of Type III hypersensitivity? (immune complex-mediated)
complexes formed in the circulation deposit in blood vessels & induce inflammation.
Manifest in acute vasculitis → can lead to fibrinoid necrosis of vessel wall & neutrophilic infiltration
205
What are three common locations of acute inflammation / sites of antigen-antibody complex deposition in type III hypersensitivity?
1. kidneys (glomerulonephritis)
2. synovium of joints (arthritis)
3. blood vessels in any tissue (vasculitis)
206
What is the prototypic human immune complex disease?
systemic lupus erythematosus (SLE)
207
Type IV hypersensitivity reaction is ___ mediated.
T cell
208
What are the 2 types of t cell reactions that cause tissue injury and disease?
1. cytokine-mediated inflammation (aka: delayed type hypersensitivity); cytokines produced by CD4+ t cells
2. cytotoxicity, mediated by CD8+ t cells
209
What are the typical manifestations of type IV hypersensitivity reaction?
[typical manifestations of this = chronic inflammation]
- rheumatoid arthritis (synovial inflammation and destruction of articular cartilage)
- multiple sclerosis (demyelination of CNS)
- T1DM (antigens of pancreatic islet beta cells)
- Inflammatory bowel disease
- psoriasis (cutaneous plaques)
210
What are the 2 categories of autoimmune disorders?
1. organ-specific
| 2. systemic
211
Systemic autoimmune disease involves what two particles?
and targets what 2 types of tissue?
1. immune complexes
2. autoantibodies
target: connective tissues & blood vessels of involved organs
212
What are the 5 systemic autoimmune diseases?
1. SLE
2. RA
3. scleroderma/systemic sclerosis
4. Sjogren syndrome
5. Inflammatory myopathies
213
Organ-specific autoimmune diseases are divided into what 3 categories?
1. Diseases mediated by antibodies
2. Diseases mediated by T cells
3. Diseases postulated to be autoimmune
214
What are 6 autoimmune diseases mediated by antibodies?
1. autoimmune hemolytic anemia
2. autoimmune thrombocytopenia
3. autoimmune atrophic gastritis of pernicious anemia
4. myasthenia gravis
5. graves disease
6. goodpasture syndrome
215
What are 2 autoimmune diseases mediated by T cells?
1. T1DM
| 2. multiple sclerosis
216
What are 3 diseases postulated to be autoimmune?
1. inflammatory bowel disease (Crohn dz, ulcerative colitis)
2. primary biliary cholangitis
3. autoimmune (chronic active) hepatitis
217
What is the pathology of SLE?
antibody & antigen complexes are deposited in kidneys and other organs;
antibodies coat blood cells leading to phagocytosis (Type II hypersensitivity)
218
What is the etiology hypothesis of SLE?
exposure to insult → apoptosis → improper clearance of fragments → failure of B and T cell tolerance activates lymphocytes specific for self antigens
*can affect any organ
219
Findings of SLE? (8)
Blood vessels: diffuse necrotizing vasculitis
Kidney: proliferative glomerulonephritis, nephritis
Skin: butterfly/macular rasha long nose/cheeks
CV: pericardial effusions, pericarditis, valvular endocarditis, CHF, HTN
Serosal cavities: effusions & fibrosis, avascular necrosis
CNS: depression, anxiety, psychosis, seizures, stroke
Blood: thrombocytopenia, anemia, anti-phospholipid syndrome (hypercoagulability)
Airway: cricoarytenoid arthritis, RLN palsy
**ask the patient!**
220
What are 3 other types of lupus?
1. Drug-induced Lupus Erythematosus
2. Cutaneous Lupus Erythematosus
3. Neonatal Lupus
221
What are 3 drugs that can trigger drug-induced lupus erythematosus?
1. hydralazine
2. procainamide
3. isoniazid
- s/s will disappear 6 months after drug is stopped
222
How does cutaneous lupus erythematosus present? What makes it worse?
- rashes & discoid lesions on face, arms, neck, shoulders, trunk
→ pigment change and hair loss
affected by sunlight & fluorescent
223
What causes neonatal lupus?
fetus in the womb of a mother who has lupus; exposure to mom's antibodies
224
How does neonatal lupus present?
infant born with skin rash, liver problems, low blood counts
→ may present with congenital heart block (HR 60s-70s) = will need a pacemaker placed!!
- disappear after some months
225
Drug categories for the treatment of lupus:
- tylenol
- NSAIDs
- immunosupressants
- corticosteroid: prednisone (Cushing syndrome)
- antimalarial: hydroxychloroquine, chloroquine
- anticoagulants: aspirin, heparin, warfarin
- monoclonal antibodies: Belimumab
- repository corticotropin injections: Acthar
226
What immunosuppressants are used in the treatment of lupus?
cyclophosphamide
methotrexate
azathioprine
mycophenolate mofetil
227
Anesthesia implications of lupus:
PRE-OP TESTING/EVALUATION
- PFTs
- ECHO
- EKG
- renal function
- labs
What drugs is the patient taking?
- corticosteroids
- immunosuppressants
- anticoagulants
AIRWAY INVOLVEMENT
228
What type of airway involvement can lupus have?
CRICOARYTENOID ARTHRITIS = hoarseness
laryngeal function (pre- & post-op)
?smaller tube needed
?airway may be "stiff"
?airway may be red/irritated
229
What is scleroderma?
"Hard Skin"
injury to vascular endothelium results in leakage of proteins into interstitial space
inflammation → fibrosis of skin, small blood vessels, and viscera
**COLLAGEN production is not slowed down and gets deposited throughout the body
230
Etiology of scleroderma:
Unknown:
collagen vascular disease & autoimmune characteristics
onset is 20-40 years old; women; accelerated in pregnancy
231
What is CREST syndrome?
*know*
presents in scleroderma:
Calcinoses: Ca deposits
Raynaud's phenomenon: [evaluate ulnar perfusion before radial a-line placement!]
Esophageal hypomotility
Sclerodactyly: thickened, tight skin [affects mouth opening]
Telangiectasia: dilated capillaries
232
Skin & musculoskeletal manifestations of scleroderma:
thick skin, diffuse edema (can involve airway), contractures, skeletal muscle myopathy, arthritis & limited joint mobility, avascular necrosis
233
Nervous system manifestations of scleroderma:
PNS & CNS neuropathies d/t nerve compression by thickened connective tissue
```
trigeminal neuralgia (pain to forehead, mid, & lower face)
dry eyes
```
234
Cardiovascular manifestations of scleroderma: (7)
- sclerosis of coronary arteries & conduction system
- cardiac tissue replaced with fibrous tissue
- systemic & pulm HTN
- pericarditis
- pericardial effusion
- intermittent peripheral vasospasm
- RAYNAUD'S PHENOMENON
235
Respiratory manifestations of scleroderma:
- diffuse interstitial pulmonary fibrosis (up to 80% of patients)
- arterial hypoxemia secondary to decreased diffusion capacity
- decreased pulmonary compliance
236
Renal manifestations of scleroderma:
- renal artery stenosis d/t arteriolar intimal proliferation → decreased renal blood flow → HTN
237
GI manifestations of scleroderma:
- dry oral mucosa
- progressive fibrosis of GI tract
- dysphagia
- hypomotility
- ↓ lower esophageal sphincter tone
- malabsorption; vitamin K deficiency (GI tract cannot absorb nutrients)
238
Anesthetic implications of scleroderma: (9)
- difficult intubation d/t limited mouth opening
- difficult IV access d/t dermal thickening
- pulmonary HTN
- ↓ pulm compliance & ↓ O2 diffusion
- systemic HTN
- aspiration risk d/t hypotonia of LES
- SENSITVE TO RESPIRATORY DEPRESSANTS
- protect eyes from corneal abrasion
- renal dysfunction with altered drug elimination
*regional anesthesia may be challenging d/t contractures and ↓ joint mobility
239
Sjogren Syndrome
chronic inflammation & destruction of lacrimal & salivary glands
→ dense infiltrates of CD4+ t cells
- dry eyes & mouth; may also involve other exocrine glands lining the respiratory & GI tracts, vagina
240
Clinical features of Sjogren syndrome:
- dryness of the eyes
- risk for corneal abrasions
- dry mouth (xerostomia0
- nasal dryness causing risk of bleeding/perforation with instrumentation
**patient's need eye drops every couple of hours
241
Rheumatoid Arthritis:
chronic, systemic inflammatory autoimmune disease; exaggerated immune response [interleukins, B cells, cytokines, collagenase, leukocyte infiltration]
particularly affects joints; genetic & environmental risk factors
Raynaud phenomenon common
→ inflammation, swelling, destruction of cartilage
242
Anesthetic implications of rheumatoid arthritis:
**atlantoaxial INSTABILITY**
SUBLUXATION of the joint.
→ can impair blood flow through vertebral arteries
243
Pathophysiology of RA:
inflammatory cytokines convert the synovium into a thick ABNORMAL LAYER OF GRANULATION TISSUE "pannus"
→→ Macrophages stimulate the release of platelet-rich growth factor and other enzymes that result in proliferation of cartilage fibrosis & joint destruction
