Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Disease
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Susana P. Arellano, RN, MAN, MSN
AIDS / HIV
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HIV
Human Immunodeficiency
Syndrome
A specific type of virus (a
retrovirus)
HIV invades the helper T cells to
replicate itself.
No Cure
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AIDS
Acquired Immunodeficiency Syndrome
HIV is the virus that causes AIDS
Disease limits the bodys ability to
fight infection
A person with AIDS has a very weak
immune system
No Cure
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Stage 1 - Primary
Short, flu-like
illness - occurs one
to six weeks after
infection
no symptoms at all
Infected person
can infect other
people
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Stage 2 - Asymptomatic
Lasts for an average of ten years
This stage is free from symptoms
There may be swollen glands
The level of HIV in the blood drops
to very low levels
HIV antibodies are detectable in
the blood
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Stage 3 - Symptomatic
The symptoms are
mild
The immune
system deteriorates
emergence of
opportunistic
infections and
cancers
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Opportunistic Infections
associated with AIDS
Bacterial
Tuberculosis (TB)
Strep
pneumonia
Viral
Kaposi Sarcoma
Herpes
Influenza (flu)
Susana P. Arellano, RN, MAN,
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Opportunistic Infections
associated with AIDS
Parasitic
Pneumocystis
carinii
Fungal
Candida
Cryptococcus
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Modes of HIV/AIDS
Transmission
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Without sterilization
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Through Sex
Intercourse (penile penetration into
the vagina)
Oral
Anal
Digital Sex
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Mother-to-Baby
Before Birth
During Birth
Postpartum
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Anonymous Testing
No name is used
Unique
identifying
number
Results issued
only to test
recipient
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23659874515
Anonymous
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Confidential Testing
Persons name is recorded along
with HIV results
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Administration
Blood
Urine
Oral
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Urine Testing
Urine Western Blot
As sensitive as testing
blood
Safe way to screen for HIV
Can cause false positives in
certain people at high risk
for HIV
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Oral Testing
Orasure
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Counseling
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Pre-test Counseling
Transmission
Prevention
Risk Factors
Voluntary & Confidential
Reportability of Positive Test
Results
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Post-test Counseling
Clarifies test results
Need for additional testing
Promotion of safe behavior
Release of results
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Treatment Options
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Antiretroviral Drugs
Nucleoside Reverse
Transcriptase inhibitors
AZT (Zidovudine)
Non-Nucleoside
Transcriptase inhibitors
Viramune (Nevirapine)
Protease inhibitors
Norvir (Ritonavir)
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Opportunistic Infection
Treatment
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Abstinence
It is the only 100 % effective method
of not acquiring HIV/AIDS.
Refraining from sexual contact: oral,
anal, or vaginal.
Refraining from intravenous drug use
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Monogamous relationship
A mutually monogamous (only one sex
partner) relationship with a person who is
not infected with HIV
HIV testing before intercourse is necessary
to prove your partner is not infected
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Protected Sex
Use condoms (female or male)
every time you have sex (vaginal or
anal)
Always use latex or polyurethane
condom (not a natural skin condom)
Always use a latex barrier during
oral sex
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Sterile Needles
If a needle/syringe or cooker is
shared, it must be disinfected:
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Addison's Disease
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INTRODUCTION
Addison disease is adrenocortical insufficiency
due to the destruction or dysfunction of the
entire adrenal cortex. It affects both
glucocorticoid and mineralocorticoid function.
The onset of disease usually occurs when 90%
or more of both adrenal cortices are
dysfunctional or destroyed.
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Mortality and
morbidity.
Morbidity and mortality usually are due to failure
or delay in making the diagnosis or a failure to
institute adequate glucocorticoid and
mineralocorticoid replacement.
If not treated promptly, acute addisonian crisis
may result in death. This may be provoked either
de novo, such as by adrenal hemorrhage, or in the
setting of an acute event superimposed on chronic
or inadequately treated adrenocortical
insufficiency.
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Causes:
idiopathic autoimmune
adrenocortical insufficiency:
- The most common cause.
- It accounts for more than 80% of
reported cases.
- It is resulting from autoimmune atrophy,
fibrosis, and lymphocytic infiltration of the
adrenal cortex, usually with sparing of the
adrenal medulla.
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malignancies:
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Drug-related causes:
-Ketoconazole inhibits the adrenal
cytochrome P450 steroidogenic enzymes.
-Aminoglutethimide blocks the early
conversion of cholesterol to pregnenolone by
inhibiting the 20,22-desmolase enzyme.
-Busulphan, etomidate, and trilostane inhibit
or interfere with adrenal steroid biosynthesis.
abdominal irradiation.
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Clinical presentation:
The onset of symptoms most often is insidious and
nonspecific.
- Hyperpigmentation of the skin and mucous
membranes often precedes all other symptoms by
months to years.
- It is caused by the stimulant effect of excess
adrenocorticotrophic hormone (ACTH) on the
melanocytes to produce melanin. on the sunexposed areas of the skin, extensor surfaces,
knuckles, elbows and knees in addition to mucous
membranes; dentogingival margins and buccal
areas.
- vitiligo: common in autoimmune Addison
disease as a result of melanocytes destruction.
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Physical examination:
Physical examination in long-standing cases
most often reveals increased pigmentation of
the skin and mucous membranes, with or
without areas of vitiligo.
Patients show evidence of dehydration,
hypotension, and orthostasis.
Female patients may show an absence of
axillary and pubic hair and decreased body
hair. This is due to loss of the adrenal
androgens, a major source of androgens in
women.
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Management: lab
studies
rapid ACTH stimulation test:
-Blood is drawn in 2 separate tubes for
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- hyponatremia, hyperkalemia, and a mild nonaniongap metabolic acidosis due to the loss of the sodiumretaining and potassium and hydrogen ion-secreting
action of aldosterone.
- elevated blood urea nitrogen (BUN) and creatinine due
to the hypovolemia, a decreased glomerular filtration
rate, and a decreased renal plasma flow.
- Hypoglycemia may be present in fasted patients, or it
may occur spontaneously. It is caused by the increased
peripheral utilization of glucose and increased insulin
sensitivity. It is more prominent in children and in
patients with secondary adrenocortical insufficiency.
- Urinary and sweat sodium also may be elevated.
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CBC:
- may reveal a normocytic normochromic anemia.
Thyroid-stimulating hormone:
- Increased thyroid-stimulating hormone (TSH), with or
without low thyroxine, with or without associated thyroid
autoantibodies, and with or without symptoms of
hypothyroidism, may occur in patients with Addison
disease and in patients with secondary adrenocortical
insufficiency due to isolated ACTH deficiency. These
findings may be slowly reversible with cortisol
replacement.
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Management: imaging:
Chest x-ray:
CT scan:
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Histological finding:
In cases due to idiopathic autoimmune
adrenocortical atrophy, the adrenal glands
usually are atrophic, with marked lymphocytic
infiltration and fibrosis of the adrenal capsule.
The adrenal medulla is spared.
In cases due to TB, the adrenal glands may be
enlarged and contain caseating granulomas.
Diffuse calcification may be evident, and the
adrenal medulla usually is involved.
In patients with AIDS, the adrenal glands may
show necrotizing inflammation, hemorrhage,
and infarction.
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Management:
outpatient
Patients on steroid replacement therapy need to
be closely monitored by their primary care
physician and by an endocrinologist for any signs
of inadequate replacement (e.g., morning
headaches, weakness, and dizziness) and any
signs of over-replacement (e.g., cushingoid
features). A periodic bone dual-energy x-ray
absorptiometry (DEXA) detecting early
osteoporosis in patients who are over-replaced
with maintenance steroids.
Patients should be instructed to double or triple
their steroid replacement doses in stressful
situations such as a common cold or tooth
extraction.
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Special concern:
surgery
Continuous IV infusion of 10mg per hour
hydrocortisone or an intermittent IV bolus
injection every 6-8 hours may be used.
After the procedure, the hydrocortisone may
be rapidly tapered within 24-36 hours to the
usual replacement doses, or as gradually as
the clinical situation dictates.
Mineralocorticoid replacement usually can be
withheld until the patient resumes daily
replacement steroids.
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Diabetes Mellitus
Overview and Treatments
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Diabetes Mellitus :
1) Type 1 diabetes
2) Type 2 diabetes
3) Gestational diabetes
Complications :
- Stroke
- Heart attack
- Kidney disease
- Eye Disease
Susana P. Arellano, RN, MAN,
Nerve
Damage
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Diabetes Mellitus
Type 1 Diabetes
Type 2 Diabetes
Gestational Diabetes
3-5% of pregnant women in the US
gestational diabetes
Susana P. Arellano,develop
RN, MAN,
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Testing :
Fasting Plasma Glucose Test
(FPG) - (cheap, fast)
*fasting B.G.L. 100-125
mg/dl signals pre-diabetes
*>126 mg/dl signals diabetes
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Diabetes - Insulin
Discovered in 1921 by Banting
and Best
Consist of A & B chains linked
by 2 disulfide bonds
(plus additional disulfide in A)
A = 21amino acids B = 30 amino acids
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Diabetes Insulin
(synthesis, storage, secretion)
Produced within the pancreas by cells islets of Langerhans
insulin mRNA is translated as a single chain precursor called preproinsulin
removal of signal peptide during insertion into the endoplasmic reticulum generates proinsulin
Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases which excise the C peptide, thereby generating the
Stored as granules
Zn
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Diabetes Insulin
(Biochemical Role)
-Tyrosine Kinase
receptors are the
locks
in which the insulin
key fits
- Involved in signal
transduction
(insulin hormone being 1st
messenger)
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Pancreatic Hormones
Insulin
Amylin
Glucagon
Somatostatin
Pancreatic Polypeptide
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A chain
B chain
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amino acids
uptake
glucose
uptake
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glycogen
synthesis
fat
synthesis
It inhibits production of
certain enzyme.
In each case, insulin triggers
these effects by binding to the
insulin receptor.
protein
synthesis
enzyme
production
glycogen
breaking
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.
Its intracellular tyrosine
kinase domain is
activated by binding of
insulin, leading to a
cascade of signaling
events.
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Treatment
subcutaneous injection
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Types of insulin
Regular insulins
Insulin analogs
Pre-mixed insulin
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Regular insulins:
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Types of insulin
Regular insulins
Insulin analogs
Pre-mixed insulin
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Insulin Analogs:
Fatty Acid Acylated insulins
Insulin Lispro (Humalog) (1996)
Insulin Aspart (NovoLog) (2000)
Insulin Glargine (Lantus) (2002)
Insulin Detemir (Levemir) (Jun.,2005)
Insulin Glulisine (Apidra) (Jan., 2006)
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B- chain Position
chai
n
Position
Source/
Type
A21
B3
B28
B29
B30
Human
Asn
Asn
Pro
Lys
Thr
Aspart
Asn
Aspartic
acid
Lys
Thr
Lispro
Asn
Lys
Pro
Thr
Glulisin
e
Asn
Pro
Glu
Thr
Glargine
Gly
Pro
Lys
Thr
Lys
Myristic
acid
Detemir
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Lys
B31
And
B32
rapid-acting
Arg
long-acting
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drugs
Thiazolidinediones
Alpha-glycosidase inhibitors
Meglitinides
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Rel. Potency
b
i
n
d
t
o
p
r
o
t
e
i
n
1st generation
(1)Orinase
(tolbutamide)
(3)Tolinase (tolazamide)
(6)Diabinese (chlorpropamide)
2-(p-aminobenzenesulfonamido)-5-isopropyl
-thiadiazole (IPTD) was used in treatment of typhoid
fever in 1940s hypoglycemia
Currently > 12,000
generation
(75)Glucotrol
(glipizide)
(150)Glucotrol XL (ex. rel. glipizide)
(150)Micronase, Diabeta (glyburide)
(250)Glynase (micronized glyburide)
3rd generation
(350)Amaryl
(glimepiride)
Susana P. Arellano, RN, MAN,
*Hydroxylation of the aromatic ring appears to be the most favored metabolic pathway
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MSN
*Hydroxylated derivatives have much lower hypoglycemic activity
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Mechanism of Action
Sulfonylureas interact with receptors on
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Metformin
- Glucophage, Fortamet,
Riomet
N
N
H
+
N
R
HCl
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NH
&
NH
S
&
O
O
NH
H
+
HCl
Cl
1-[[ p-[ 2-( 5-chloro-o-anisamido) ethyl] phenyl] sulfonyl]-3-cyclohexylurea
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Pioglitazone
S
NH
- Actos, Avandia
O
5-{4-[2-(5-Ethyl-pyridin-2-yl)-ethoxy]-benzyl}-thiazolidine-2,4-dione
- binds to and activates the gamma isoform of the peroxisome proliferator-activated rec
- PPAR is a member of the steroid hormone nuclear receptor superfamily, and is found
cardiac and skeletal muscle, liver and placenta
PPAR -
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AGIs
- Precose (acarbose),
- Glyset (miglitol)
H
O
H
O
N
H
1-(2-Hydroxy-ethyl)-2-hydroxymethylpiperidine-3,4,5-triol
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Meglitinides
O
- Prandin (repaglinide)
OH
NH
2-Ethoxy-4-{[3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoic acid
- Starlix (nateglinide)
NH
O
O OH
2-[(4-Isopropyl-cyclohexanecarbonyl)-amino]-3-phenyl-propionic acid
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6 Classes :
Sulfonylureas stimulate cells
Biguanides improves insulins ability to move glucose
Sulfonylureas and biguanide combination
drugs BOTH
Thiazolidinediones cells more sensitive to insulin
Alpha-glycosidase inhibitors Block enzymes that help
digest starches
Meglitinides
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In Conclusion :
2 major types of diabetes
(3 with Gestational)
Type 1 => insulin dependant (5-10%)
Type 2 => may treat with oral medication
which may alter insulin production &/or
sensitivity ; disease often succumbs to
insulin dependence (>90%)
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Ulcerative Colitis
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Extent of involvement
UC is normally continuous from the rectum up the colon. The disease is
classified by the extent of involvement, depending on how far up the
colon the disease extends:
Distal colitis, potentially treatable with enemas:
Proctitis:
Involvement limited to the rectum.
Proctosigmoiditis:
Involvement of the rectosigmoid colon, the portion of the colon adjacent
to the rectum.
Left-sided colitis:
Involvement of the descending colon, which runs along the patient's left
side, up to the splenic flexure and the beginning of the transverse colon.
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Extensive
inflammation
beyond the
enemas:
colitis,
extending
reach of
Pancolitis: Involvement of
the entire colon, extending
from the rectum to the
cecum, beyond which the
small intestine begins.
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Severity of disease
In addition to the extent of involvement, UC patients may also
be characterized by the severity of their disease.
Mild disease correlates with fewer than four stools daily, with or
without blood, no systemic signs of toxicity, and a normal
erythrocyte sedimentation rate (ESR). There may be mild
abdominal pain or cramping. Patients may believe they are
constipated when in fact they are experiencing tenesmus, which
is a constant feeling of the need to empty the bowel
accompanied by involuntary straining efforts, pain, and
cramping with little or no fecal output. Rectal pain is uncommon.
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Extraintestinal features
As UC is a systemic disease, patients may present
with symptoms and complications outside the colon.
These include the following:
Ophthalmic .
Iritis or uveit.
Episcleritis.
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Musculoskeletal:
oligoa rthritis (affecting one or two joints), or may affect many small joints
of the hands and feet
Cutaneous
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inflammation
of
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clubbing,
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Similar conditions
The following conditions may present in a similar manner and should be
excluded:
Crohn's disease
Infectious colitis,
Pseudom embranous
Ischemic colitis,
the elderly
Radiation colitis
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Ulcerative Colitis
Commonly
Seldom
Involves colon?
Involves rectum?
Usually
Seldom
Always
Usually
Peri-anal involvement
Commonl
Seldom
Not associated
Distribution of Disease
Patchy areas of
inflammation
Continuous area of
inflammation
Endoscopy
Continuous ulcer
Depth of inflammation
Shallow, mucosal
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Commonly
Seldom
Biopsy
Surgical cure ?
Smoking
Usually cured by
removal of colon, can
be followed by
po uchitis
Higher risk for smokers Lower risk for smokers
Autoimmune disease
Generally regarded as
an autoimmune
disease
No consensus
Cancer risk?
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Endoscopic
The best test for diagnosis of UC remains endoscopy. Full colonoscopy to the
cecum and entry into the terminal ileum is attempted only if diagnosis of UC is
unclear.
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Histologic
Biopsies of the mucosa are taken to definitively diagnose UC and
differentiate it from Crohn's diseas, Microbiological samples are
typically taken at the time of endoscopy.
The pathology in UC typically involves distortion of crypt architecture,
inflammation
of
crypts
(cryptitis),
frank
crypt
abscesses,
and
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Treatment
Standard treatment for UC depends on extent of involvement
and disease severity.
The goal is to induce remission initially with medications,
followed by the administration of maintenance medications to
prevent a relapse of the disease.
The concept of induction of remission and maintenance of
remission is very important.
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Drugs used
Aminosalicylates
are
the
mainstay
of
UC
pharmacotherapy
for
induction
and
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Mesalazine, also known as 5-aminosalicylic acid, mesalamine, or 5ASA. (Asacol, Pentasa, Mezavant, Lialda, and Salofalk).
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Corticosteroids
It is often required for the one-third of patients who fail
to respond to 5-ASAs, But it is not useful for
maintenance of remission and carry significnat
undesirable side effects, as osteoporosis, glucose
intolerance, and increased risk of infection.
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Immunosupressive drugs
It have a role in maintenance of remission in moderate to severe UC.
Their relatively slow onset of action precludes their use during flares of
the disease, and the use of these agents has been reported to
potentially increase the risk of lymphoma in patients with IBD. It
requires intense monitoring, and may cause irreversible nephrotoxicity,
all of which limit its use to severe cases only.
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Methotrexate.
Tacrolimus.
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Biological treatment
It refers to the use of medication that is tailored to specifically target an
immune or genetic mediator of disease. The, molecules that are
involved in the disease process have been identified, and can be
targeted for biological therapy; many of these molecules, which are
mainly cytokines, are directly involved in the immune system.
Biological therapy has found a niche in the management of cancer,
autoimmune diseases, and diseases of unknown cause that result in
symptoms due to immune related mechanisms .
(Infliximab ,Visilizumab)
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Infliximab
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This agent inhibits the binding of 47 integrin to its ligand, the mucosal
addressin cell adhesion molecule-1 (MAdCAM-1) which is highly
expressed on GI mucosa-associaetd endothelium and high endothelial
venules of mesenteric lymph nodes.
Binding of integrin antagnosit to 47 on lymphocytes disrupts
lymphocyte migration into inflamed GI mucosa, thus providing a
potential therapeutic option for patients with UC.
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Surgery
Failure of medical therapy leads to colectomy in (9% - 35%) of patients
with UC within 5 years. Colectomy is considered to be an important
adjunct treatment for refractory UC; however, colectomy with ileal
pouch anal anastomosis (the standard surgical therapy) has many
limitations and is associated with its own set of complications, including
high stool frequency, female infertility, and a cumulative incidence of
chronic pouchitis of 50% at 10 years.
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of:
exsanguinating
hemorrhage,
frank
perforation
or
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Moderate
High dose
ASA-5
Remissio
n
High dose
maintenance
Prepared by:
Severe
Extensive
Colitis
NO
NO
Remissi Steroids Remissi
on
on
Remissio
n
ASA-5
CsA
AZA / 6-MP
Remissio
n
Failure
AZA/6-MP
maintenanceColectomy
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Alternative treatments
Smoking :
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Bacterial recolonization
Probiotics may have benefit. And promise for people with UC.
Fecalbacteriotherapy involves the infusion of human probiotics
through fecal enemas. It suggests that the cause of UC may be
a previous infection by a still unknown pathogen.
This initial infection resolves itself naturally, but somehow
causes an imbalance in the colonic bacterial flora, leading to a
cycle of inflammation which can be broken by "recolonizing" the
colon with bacteria from a healthy bowel. There have been
several reported cases of patients who have remained in
remission for up to 13 years.
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Intestinal parasites
IBD is less common in the developing world. Some have suggested
that this may be because intestinal parasites are more common in
underdeveloped countries. Some parasites are able to reduce the
immune response of the intestine, an adaptation that helps the parasite
colonize the intestine. The decrease in immune response could reduce
or eliminate the IBD.
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GLOMERULONEPHRITIS
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Glomerulonephritis
The acute nephritic syndrome is
characterized by hematuria and
RBC cast in the urine sediment
along whith other signs of acute
inflammatory renal injury, including
proteinuria, peripheral edema,
hypertension, or renal insufficiency
with or without oliguria.
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GENRALITIES
G
L
O
M
E
R
U
L
A
R
I
N
J
U
R
Y
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CLINICOPATHOLOGIC
PRIMARY MECHANISMS
CORRELATION
BETWEEN SITE AND
PRESENTATION
CLASIFICATION
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GENERALITIES
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GLOMERULI
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GLOMERULI
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PATHOGENETIC
MECHANISMS
Gomerulus: modified capillary
network that delivers an
ultrafiltrateof plasma to Bowman`s
space.
Approximately 1.6 milion glomeruli
are present in two mature kidneys
and collectively produce 120 to
180 L of ultrafiltrate daily.
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GLOMERULAR FILTRATION
Glomerular filtration rate is dependent
on glomerular blood flow, ultrafiltration
pressure, and surface area.
Regulated through:
Changes in afferent and efferent arteriolar
tone.
Mesangial cell contractility
(modulated by neurohumoral factors, local
myenteric reflexes, and endothelium derived
vasoactive substances)
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GLOMERULAR FILTRATION
In health, glomerular endothelium
is antithrombotic and antiadhesive
for leukocytes and platelets,
Prevent vascular thrombosis and
inflammation during the filtration
process.
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NOMENCLATURE
Glomerulonephritis: (GN) injury with
evidence of inflammation such as
leukocyte infiltration, antibody
deposition, and complement activation.
GN primary: pathology is confined to the
kidney.
GN secondary: when part of a multisystem
disorder.
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NOMENCLATURE
Acute: glomerular injury occurring
over days or weeks.
Subacute or rapidly progressive:
over weeks or a few months.
Chronic: over many months or
years.
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NOMENCLATURE
Diffuse: affect > 50% of glomeruli.
Focal: affect < 50% of glomeruli.
Global: affect > 50% of glomerular
tuft.
Segmental: < 50% of glomerular tuft
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NOMENCLATURE
Proliferative:
glomerular cell number
(intracapillary and extracapillary)
A crescent: is a half-moon shaped. Cells in
Bowman`s space.
Membranous : expansion of the GBM by
immune deposits.
Sclerosis: nonfibrilar extracellular
material
Fibrosis: Collagens type I and III
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GENRALITIES
G
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CLINICOPATHOLOGIC
PRIMARY MECHANISMS
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CLINICOPATHOLOGIC
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Diffuse proliferative GN
Clinical Presentation
Acute nephritic syndrome, acute renal failure over
Pathology Findings
Diffuse increase in cellularity of tufts. Infiltration
Etiologies
Immune complex GN, idiopathic, postinfectious,
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Crescentic GN
Clinical Presentation
Rapidly progresive GN, subacute renal failure,
Pathology Findings
Fibrinoid necrosis and crescents in Bowman`s
Etiologies
Inmune Complex GN, pauci-immune GN,
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Focal proliferative GN
Clinical Presentation
Mild to moderate glomerular inflammation.
Pathology Findings
Segmental areas of proliferation and necrosis
Etiologies
Early and milder forms of most diseas causing
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Mesangial proliferative GN
Clinical Presentation
Chronic glomerular inflammation: proteinuria,
Pathology Findings
Proliferation of mesangial cells and matrix
Etiologies
Early and milder forms of most diseas causing
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Membanoproliferative GN
Clinical Presentation
Combination of nephritic and nephrotic
Pathology Findings
Diffuse proliferation of mesangial cells and
Etiologies
Immune complex GN, In association with
thrombotic microangiophaties, in
association with deposition diseases.
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Deposition diseases
Clinical Presentation
Combination of nephritic and nephrotic
Pathology Findings
Mesangial expansion and thinckening of
Etiologies
Amyloid, Cryoglobulinemia, Light chain
deposition disease.
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GENRALITIES
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CLINICOPATHOLOGIC
PRIMARY MECHANISMS
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Primary Mechanisms of
Glomerular Injury
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Inmunologic
Defects
Inmmunoglobulin
Cell-mediated injury
Cytokine (or other soluble factor)
Persistent complement activation
Glomerular Disease
Immune complex-mediated GN
Pauci-immune GN
Primary focal segmental glomerulosclerosis
Membranoproliferative GN type II
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Metabolic
Defects
Hyperglicemia
Fabri`s disease
Glomerular Disease
Diabetic nephropathy
Focal segmental glomerulosclerosis
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Hemodynamic
Defects
Systemic hypertension
Intraglomerular hypertension
Glomerular Disease
Hypertensive nephrosclerosis
Secondary focal segmental
glomerulosclerosis
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Toxic
Defects
E. Colli derived verotoxin
Therapeutic drugs (NSAIDs)
Drugs (heroin)
Glomerular Disease
Thrombotic microangiopathy
Minimal change disease
Focal segmental glomerulosclerosis
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Deposition
Defects
Amyloid fibrils
Glomerular Disease
Amyloid nephrophathy
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Infectious
Defects
HIV
Subacute bacterial endocarditis
Glomerular Disease
HIV nephropathy
Immune complex glomerulonephritis
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Inherited
Defects
Defect in gene for 5 chain of type IV
collagen
Abnormally thin basement membrane
Glomerular Disease
Alport`s syndrome
Thin basement membrane disease
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GENRALITIES
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CLINICOPATHOLOGIC
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Endothelial cell
Physiologic Role
Maintains glomerular perfusion
Prevents leukocyte adhesion
Prevents platelet aggregation and clotting
Response to Injury
Vasoconstriction
Leukocyte infiltration
Intravascular microthrombi
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Mesangial Cell
Physiologic Role
Controls glomerular filtration surface area
Response to Injury
Proliferation / increased matrix
glomerulosclerosis
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Basement membrane
Physiologic Role
Prevents filtration of plasma proteins
Response to Injury
Proteinuria
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Response to Injury
Proteinuria
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Response to Injury
Crescent formation
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GENRALITIES
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CLINICOPATHOLOGIC
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CORRELATION
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CLASIFICATION
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CLASSIFICATION
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INMUNOLOGIC
Antibody-mediated injury
Other mechanisms of antibodymediated injury
Antineutrophil Cytoplasmic Antibodies (ANCA)
Antiendothelial Cell Antibodies
C3 Nephritic Factor
Cell-mediated injury
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NONIMMUNOLOGIC
Metabolic
Diabetic nephropathy
Other Metabolic Disease
Hemodynamic
Systemic Hypertension
Glomerular Hypertension
Toxic glomerulopathies
Deposition Disease
Infectious Causes
Inherited
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Immunologic
Depostion of antibodies and
autoantibodies, in the glomerular
tuft, indicating dysregulation of
humoral immunity.
Cellular immune mechanism also
contribute to the pathogenesis of
antibody-mediated GN by
modulating antibody production.
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Antibody-mediated injury
Mechanisms:
1) Reactivity of circulating autoantibodies with
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Generation of nephritogenic
antibodies: mechanisms:
1) A foreign Ag, wose structure
resembles that ofn a host
glomerular Ag may stimulate the
production of auto AB that crossreact withe intrinsic glomerular AG.
(molecular mimickry).
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Deposition of nephritogenic
antibodies within the glomerulus
Anti-GBM antibody disease: patients have a
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Cell-mediated injury
T cell may be particularly
important as initiators of injury in
pauci-immune GN.
T cell are potent stimuli for further
leukocite recruitment, cytotoxicity,
and fibrogenesis
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NONIMMUNOLOGIC
Metabolic
Diabetic nephropathy
Other Metabolic Disease
Hemodynamic
Systemic Hypertension
Glomerular Hypertension
Toxic glomerulopathies
Deposition Disease
Infectious Causes
Inherited
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Metabolic
Diabetic nephropathy: The typical
glomerular lesion is
glomerulosclerosisdue to thickening of
the GBM and expansion of the
mesangium with extracellular matrix.
Other metabolic diseases: rare inhereited
lisosomas enzymedefects induce focal
segmental glomerulosclerosis, probably
by allowing acumulation of toxic
metabolites in renal cells.
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Hemodynamic
Systemic Hipertension: Chronic
sustained hypertension typically leades
to arteriolar vasoconstriction and
sclerosis.
Glomerular Hypertension: These
changes in glomerular hemodynamics
and pressure appear to precede the
development of systemic hypertension
and are independent risk factors.
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Toxic
Verotoxin, derived from E Coli
during bouts of infective diarrhea,
is directly toxic to renal
endothelium and induces the
hemolytic-uremic sindrome .
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Deposition diseases
Are a group of diverse conditions in
which abnormal proteins are
deposited in glomeruli where they
provoke an inflammatory reaction
and / or glomerulosclerosis.
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Infectious causes
Different mechanisms:
1) By direct infection of renal cells
2) By elaborating nephrotoxins such
as E coli
3) By inciting intraglomerular dposition
of immune complexes
4) Chronic stimulus for amiloid fibril
formation.
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Inherited
Alport`s syndrome: The GMB is
irregular with longitudinal layering,
thickening, and patients develop
hematuria, progresive
glomerulosclerosis, and renal
failure.
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CLINICAL PRESENTATIONS
1)Acute nephritic syndrome
2) Asymptomatic abnormalities of
the urinary sediment
3) Chronic glomerulonephritis
4) nephrotic syndrome
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ACUTE NEPHRITIC
SYNDROME
ANS is the clinical correlate of acute
glomerular immflamation. Characterized
by sudden onset (over days to weeks)of
acute renal failure and oliguria
(<400ml/day).
Renal blood flow and glomerular filtration
rate fall as a result of obstruction of the
glomerular capillary lumen by infiltrating
inflammatory cells and proliferating
resident glomerular cells.
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PP
CLINICAL FEATURES
Glomerular injury
Inflammatory
glomerular capillary
Perfusion glomerular
capillary
FG
reabsorption
Tubular Na and
volume
H2O
Extracelular
Volume
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RED BLOOD
CELL CASTS
PROTEINURIA
HEMATURIA
AZOEMIA
OLIGURIA
HYPERTENSION
EDEMA
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3 Broad diagnostic
categories
1) Granular deposits of inmunoglobulin
(immune complex GN)
2) Linear deposition of immunoglobulin
along the GBM (anti-GBM disease)
3) paucity or absence of
immunoglobulin (pauci-immune GN)
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Immune-complex GN
Most cases being initiated either by
insitu formation of immune complexes
or less commonly by glomerular
trapping of circulating immune complex.
Typically have hypocomplementenemia
(low C3) and negative anti-GMB, and
ANCA serology.
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Pauci-immune GN
Most patients have circulating ANCA,
implicating dysregulation of humoral
immunity.
Serum complement leves are typically
normal, and anti-GBM titers are usually
negative in ANCA-associated renal disease.
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G. ADAPTATION TO
NEPHRON LOSS
Nephron loss is followed by
compensatory hyperfiltration in the
remaining functional glomeruli. Over
years however, the hyperfiltering
remnant nephrons develop focal and
segmental glomerulosclerosis, and
global sclerosis, that manifests
clinically as proteinuria, hypertension
and progressive renal insufficiency.
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Hypersensitivity
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Introduction
What is hypersensitivity?
It is excessive immune response
which leads to undesirable
consequences, i.e. tissue or organ
damage/ dysfunction.
Type: type, , , hypersensitivity
Ab mediated: type, ,
T-cell mediated: type
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Type hypersensitivity
IgE mediated, immediate
hypersensitivity/ allergy
Major features:
React and disappear quickly on reexposure to Ag
Dysfunction rather than severe
tissue and cell damage occurs
Obvious individual difference and
genetic correlation
Susana P. Arellano, RN, MAN,
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MSN
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Mast cells
Express high affinity IgE Fc receptor
FcR, granules contain mediators.
Distribution: connective tissues,
mucosa, skin
Anaphylaxis is triggered by
clustering of IgE receptors (FcR)
on mast cells and basophils through
cross-linking
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IgE-binding Fc recepors
FcR: high affinity receptor of IgE
on mast cell/ basophil, activate
mast cell/ basophil
FcR:low affinity
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Mechanism of
typehypersensitivity
Allergenhostspecific B-cellIgEFc
fragment of IgE binding FcRon mast
cells/ basophils
Allergen once again enter the host
binding IgE cross-linking of IgE
cross-linking of FcR mast cell
activation degranulation mediators
release anaphylaxis symptoms
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MSN
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Typical diseases of
anaphylaxis
Systemic anaphylaxis(anaphylactic
shock): fatal, venom from bee,
wasp; drugs such as penicillin,
antitoxins, etc.
Localized anaphylaxis(atopy): the
tend-ency to manifest localized
anaphylaxis is inherited and called
atopy. typical diseases: asthma,
hayfever, eczema,
food
allergy,
etc.
Susana P. Arellano, RN, MAN,
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Atopy
Allergic rhinitis: Hay fever, airborn
allergens, symptoms include shedding
tears, sneezing, coughing, etc.
Asthma: airborn/blood-born allergens.
Occur in lower respiratory tract
Cardinal clinic and physiological
features: variable airflow obstruction,
bronchial hyper-responsiveness.
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Therapy of
typehypersensitivity
Allergen avoidance: best if
possible, but often impractical. Skin
test
Hyposensitivity: repeated injection
of increasing doses of allergen.
Allergic rhinitis
Drug: antihistamines; epinephrine
(also called adrenaline), etc.
Immediate injection of adrenaline
could rescue
shock
Susanaanaphylactic
P. Arellano, RN, MAN,
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Type hypersensitivity
Mediated by IgG and/or IgM
Mechanism:
Ag present on the surface of cells
im-munity activationAbtissue
damage/ dysfunction
Tissue damage caused by:
Opsonic adherence: phagocytosis
Complement: membrane damage
ADCC: cell destruction
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Heamolytic diseases of
newborn
Rh incompatibility: Rh blood groups
Rh- mother has the first Rh+
baby mother sensitized by babys
erythrocy-tes anti-Rh IgG
Mother has the second Rh+ baby
IgG enter the fetus through
placenta destruction of fetal RBC
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Drug-induced hemolytic
anemia
Drug adsorb RBC proteinsAntiRBC IgG/IgMcomplement,
opsonization, ADCC RBC lysis,
anemia
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Type hypersensitivity
Participate by IgG/IgM, induced by
de-position of immune complex (IC)
Formation of IC: Excess of antigen
over a protracted period
Deposition frequently observed:
blood-vessel walls, synovial
membrane of joints, glomerular
basement of kidney
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Type associated
diseases
Localized type reaction: the Arthus
reaction, erythematous and
edematous, intense neutrophil
infiltration
Generalized type reaction:
Serum sickness: injection of foreign
protein (horse serum)
SLE: systemic lupus erythematosus,
DNA/ anti-DNA/ complement
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Type associated
diseases
Rheumatoid arthritis: rheumatoid
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Type hypersensitivity
Delayed-type(DTH), T-cell mediated, 2472 hr after Ag contact, Ab not involve
Results from excessive CMI, secondary
response, chronic granuloma
Mechanism:
CD4+Th1: TmAg:MHCeffector TcellMCP-1, IFN-, TNF, IL-2M
attraction and activationtissue damage
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Immune pathogenesis
CD8+CTL: primed CTLAg:MHC
perforin/ Fas-FasLtarget cell
death
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Type associated
diseases
Insulin-dependent diabetes mellitus
(IDDM): insulin-producing cells
Multiple sclerosis(MS): central nervous
system, myelin Ag
Contact dermatitis: foreign low
molecular weight materials, haptencarrier, topical
Infectious diseases: tuberculosis
Others: hashimotos
thyroiditis, IBD
Susana P. Arellano, RN, MAN,
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MSN
254
Summary
Hypersensitivity is excessive
immune response which leads to
undesirable consequences, i.e.
tissue or organ damage/
dysfunction.
Type: type, , , hypersensitivity
Ab mediated: type, ,
T-cell mediated: type
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Summary
Therapy for typehypersensitivity:
Allergen avoidance
Hyposensitivity
Drug treatment: antihistamines,
adrenaline
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Anaphylaxis
IgE Mediated Hypersensitivity
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What is anaphylaxis?
An acute systemic allergic reaction
The result of a re-exposure to an antigen
that elicits an IgE mediated response
Usually caused by a common
environmental protein that is not
intrinsically harmful
Often caused by medications, foods, and
insect stings
It is a Type I hypersensitivity
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History
1st recorded 2640BC in
hieroglyphics
South Seas
Man-o-war
coined term anaphylaxis
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IgE
Binds irreversible to FcRI
receptors on mast cells, basophils,
and eosinophils
Is usually for parasitic infections
E heavy chain
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Mast Cell
Has high affinity for IgE molecules (105 IgE/cell)
Originates in the bone marrow, reside in
connective tissues
Increases host response to parasitic infections
Contain immunological mediators in granules
ie. Histamine, ECF-A, HMW-NCF
2 populations that vary in granule content and
activity
Connective tissue
Mucosal
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Symptoms
Peripheral vasodilation
Bronchospasm
Cardiac arrhythmias
Smooth muscle contractions
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Sensitization
Antigen is presented by antigen
presenting cells
TH2 cells induce B cell activation
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What is happening?
Initial exposure sensitizes mast cells.
Antigen specific IgE molecules attach to
high affinity Fc receptors on the mast
cell surface.
Cross linking of IgE molecules on surface
causes intracellular signaling pathway
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Mediators Involved
Include histamine, proteases,
chemotactic factors, leukotrienes,
prostaglandin D, and cytokines
Primary: released before degranulation
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Histamine
Synthesized and stored in granules
The primary mediator in the granules
3 receptors
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Respiratory
broncho constriction
Gastrointestinal
Skin
Urticaria
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Treatments
Antihistamines
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Ant bites
Red Imported Fire Ant
Venom (antigen)
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Thank You!!!!
We have been made holy
through the sacrifice of the
body of Jesus Christ once for
all.
Hebrews 10:10
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