Immunodeficiency

Disease

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

Prepared by:
Susana P. Arellano, RN, MAN, MSN

AIDS / HIV

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

Is HIV and AIDS the same

thing?

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

HIV
Human Immunodeficiency
Syndrome
A specific type of virus (a
retrovirus)
HIV invades the helper T cells to
replicate itself.
No Cure
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

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

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

New HIV Infections in 2002 by Age

Group

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

Four Stages of HIV

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

Stage 1 - Primary
Short, flu-like
illness - occurs one
to six weeks after
infection
no symptoms at all
Infected person
can infect other
people
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

10

Stage 3 - Symptomatic
The symptoms are
mild
The immune
system deteriorates
emergence of
opportunistic
infections and
cancers
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

11

Stage 4 - HIV AIDS

The immune
system weakens
The illnesses
become more
severe leading
to an AIDS
diagnosis
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

12

Opportunistic Infections
associated with AIDS
Bacterial
Tuberculosis (TB)
Strep
pneumonia

Viral
Kaposi Sarcoma
Herpes
Influenza (flu)
Susana P. Arellano, RN, MAN,

Prepared by:

MSN

13

Opportunistic Infections
associated with AIDS
Parasitic

Pneumocystis
carinii

Fungal
Candida
Cryptococcus

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

14

Modes of HIV/AIDS
Transmission

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

15

Through Bodily Fluids

Blood products
Semen
Vaginal fluids
Breast Milk

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

16

Through IV Drug Use

Sharing Needles

Without sterilization

Increases the chances of contracting

HIV

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

17

Through Sex
Intercourse (penile penetration into
the vagina)
Oral
Anal
Digital Sex

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

18

Mother-to-Baby

Before Birth
During Birth
Postpartum

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After the birth

Susana P. Arellano, RN, MAN,

MSN

19

Testing Options for HIV

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

20

Anonymous Testing
No name is used
Unique
identifying
number
Results issued
only to test
recipient
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

23659874515
Anonymous

21

Confidential Testing
Persons name is recorded along
with HIV results

Name and positive results are

reported to the State Department and
the Centers for Disease Control and
Prevention

Results issued only to test

recipient
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

22

Administration
Blood
Urine
Oral

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

23

Blood Detection Tests

Enzyme-Linked
Immunosorbent Assay/Enzyme
Immunoassay (ELISA/EIA)
Radio Immunoprecipitation
Assay/Indirect Fluorescent
Antibody Assay (RIP/IFA)
Polymerase Chain Reaction
(PCR)
Western Blot Confirmatory test

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

24

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

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

25

Oral Testing
Orasure

The only FDA

approved HIV antibody.
As accurate as blood
testing
Draws blood-derived
fluids from the gum
tissue.
NOT A SALIVA TEST!

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

26

Counseling

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

27

Pre-test Counseling
Transmission
Prevention
Risk Factors
Voluntary & Confidential
Reportability of Positive Test
Results

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

28

Post-test Counseling
Clarifies test results
Need for additional testing
Promotion of safe behavior
Release of results

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

29

Treatment Options

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

30

Antiretroviral Drugs
Nucleoside Reverse
Transcriptase inhibitors

AZT (Zidovudine)

Non-Nucleoside
Transcriptase inhibitors

Viramune (Nevirapine)

Protease inhibitors

Norvir (Ritonavir)

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

31

Opportunistic Infection
Treatment

Issued in an event where

antiretroviral drugs are not available

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

32

Four ways to protect

yourself?
Abstinence
Monogamous Relationship
Protected Sex
Sterile needles

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

33

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

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

34

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

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

35

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

36

When Using A Condom

Remember To:
Make sure the package is not expired
Make sure to check the package for
damages
Do not open the package with your
teeth for risk of tearing
Never use the condom more than
once
Use water-based rather than oilbased condoms
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

37

Sterile Needles
If a needle/syringe or cooker is
shared, it must be disinfected:

Fill the syringe with undiluted bleach

and wait at least 30 seconds.
thoroughly rinse with water
Do this between each persons use

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

38

Needle Exchange Program

Non-profit
Organization,
which provides
sterile needles in
exchange for
contaminated
ones
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

39

Addison's Disease

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

40

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

41

Race: is no association with race.

Sex: Idiopathic autoimmune Addison disease
tends to be more common in females and children.
Age: The most common age in adults is 30-50
years, but the disease could present earlier in
patients with: polyglandular autoimmune
syndromes, congenital adrenal hyperplasia (CAH),
or if onset is due to a disorder of long-chain fatty
acid metabolism.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

42

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

43

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

44

Idiopathic autoimmune Addison disease may occur

in isolation or in association with other autoimmune
phenomena such as:
- Schmidt syndrome: The association of Addison
disease and Hashimoto thyroiditis.
- polyglandular autoimmune syndrome type 1:
The association of Addison disease with
hypoparathyroidism and mucocutaneous candidiasis.
It may have an autosomal recessive mode of
inheritance. It has no human leukocyte antigen
(HLA) associations.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

45

- polyglandular autoimmune syndrome type2:

The association of Addison disease with type 1
diabetes mellitus and Hashimoto thyroiditis or Graves
disease. It may be associated with HLA-B8 and DR-3.

Chronic granulomatous diseases:

TB, sarcoidosis, histoplasmosis, blastomycosis, and
cryptococcosis could involve the adrenal glands.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

46

 malignancies:

Malignant infiltration of the adrenal cortices, as with Hodgkin and

non-Hodgkin lymphoma and leukemia, may cause Addison disease.
Metastatic malignant disease: Bilateral involvement of the adrenal
glands could occur in the setting of metastatic cancer of the lung,
breast, or colon or renal cell carcinoma.

Infiltrative metabolic disorders :

Amyloidosis and hemochromatosis could involve the adrenal
glands and lead to primary adrenocortical insufficiency.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

47

Acquired immunodeficiency syndrome:

as a result of invasion of cytomegalovirus,
Mycobacterium avium intracellulare, cryptococci,
or Kaposi sarcoma.

Allgrove syndrome: congenital adrenocortical

unresponsiveness to ACTH typically presents in
childhood with failure to thrive, features of
adrenocortical insufficiency and hypoglycemia.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

48

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

49

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

50

Dizziness with orthostasis due to

hypotension occasionally may lead to syncope.
This is due to the combined effects of volume
depletion, loss of the mineralocorticoid effect of
aldosterone, and loss of the permissive effect of
cortisol in enhancing the vasopressor effect of
the catecholamines.
Myalgias and flaccid muscle paralysis may
occur due to hyperkalemia.
progressive weakness, fatigue, poor
appetite, and weight loss.
gastrointestinal symptoms may include
nausea, vomiting, and occasional diarrhea.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

51

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

52

Management: lab
studies
rapid ACTH stimulation test:
-Blood is drawn in 2 separate tubes for

baseline cortisol and aldosterone values.

-Synthetic ACTH (1-24 amino acid sequence)
in a dose of 250 mcg (0.25 mg) is given IM or
IV.
-Thirty or 60 minutes after the ACTH injection,
2 more blood samples are drawn; one for
cortisol and one for aldosterone.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

53

Interpreting rapid ACTH stimulation test:

-Two criteria are necessary for diagnosis: (1) an
increase in the baseline cortisol value of 7 mcg/dL
or more and (2) the value must rise to 20 mcg/dL
or more in 30 or 60 minutes, establishing normal
adrenal glucocorticoid function.
In patients with Addison disease, both cortisol and
aldosterone show minimal or no change in response
to ACTH.
-When the results of the rapid ACTH do not meet
the 2 criteria mentioned above, further testing
might be required to distinguish Addison disease
from secondary adrenocortical insufficiency.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

54

In acute adrenal crisis, where treatment

should not be delayed in order to do the tests,
a blood sample for a random plasma cortisol
level should be drawn prior to starting
hydrocortisone replacement.
A random plasma cortisol value of 25 mcg/dL
or greater effectively excludes adrenal
insufficiency of any kind.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

55

Urea and electrolyte:

- 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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

56

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

57

Management: imaging:
Chest x-ray:

- The chest x-ray often normal except in evidence

of TB or fungal infection that initially cause
Addison disease.

CT scan:

- Abdominal CT scan may be normal but may

show bilateral enlargement of the adrenal glands
in patients with Addison disease because of TB,
fungal infections, adrenal hemorrhage, or
infiltrating diseases involving the adrenal glands.
- In idiopathic autoimmune Addison disease, the
adrenal glands usually are atrophic.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

58

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

59

Medical treatment: inpatient

care
In case of adrenal crisis:

- IV access should be established urgently.

- an infusion of isotonic sodium chloride solution
should be begun to restore volume deficit and
correct hypotension. Some patients may require
glucose supplementation.
- The precipitating cause should be sought and
corrected where possible.
-Administer 100 mg of hydrocortisone in 100 cc of
isotonic sodium chloride solution by continuous IV
infusion at a rate of 10-12 cc/h. Infusion may be
initiated with 100 mg of hydrocortisone as an IV
bolus.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

60

Clinical improvement, especially blood pressure

response, should be evident within 4-6 hours of
hydrocortisone infusion.
After 2-3 days, the stress hydrocortisone dose
should be reduced to 100-150 mg, infused over a
24-hour period, irrespective of the patient's clinical
status. This is to avoid stress gastrointestinal
bleeding.
As the patient improves and as the clinical
situation allows, the hydrocortisone infusion can
be gradually tapered over the next 4-5 days to
daily replacement doses of approximately 3 mg/h
(72-75 mg over 24 h) and eventually to daily oral
replacement doses, when oral intake is possible.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

61

As long as the patient is receiving 100 mg or more

of hydrocortisone in 24 hours, no mineralocorticoid
replacement is necessary. The mineralocorticoid
activity of hydrocortisone in this dosage is
sufficient.
Thereafter, as the hydrocortisone dose is weaned
further, mineralocorticoid replacement should be
instituted in doses equivalent to the daily adrenal
gland aldosterone output of 0.05-0.20 mg every 24
hours. The usual mineralocorticoid used for this
purpose is 9-alpha-fludrocortisone, usually in doses
of 0.05-0.10 mg per day or every other day.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

62

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

63

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

64

Diabetes Mellitus
Overview and Treatments

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

65

Diabetes Mellitus :

a group of diseases characterized by high levels of blood glucose resulting

from defects in insulin production, insulin action, or both

20.8 million in US ( 7% of population)

estimated 14.6 million diagnosed (only 2/3)
Consists of 3 types:

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
Prepared by:
MSN

66

Diabetes Mellitus
Type 1 Diabetes

Type 2 Diabetes

- cells that produce insulin are

destroyed
- results in insulin dependence
- commonly detected before 30

- blood glucose levels rise due to

1) Lack of insulin
production
2) Insufficient insulin
action (resistant cells)
- commonly detected after 40
- effects > 90%
- eventually leads to -cell failure
(resulting in insulin dependence)

Gestational Diabetes
3-5% of pregnant women in the US
gestational diabetes
Susana P. Arellano,develop
RN, MAN,
Prepared by:

MSN

67

Testing :
Fasting Plasma Glucose Test
(FPG) - (cheap, fast)
*fasting B.G.L. 100-125
mg/dl signals pre-diabetes
*>126 mg/dl signals diabetes

Oral Glucose Tolerance Test

(OGTT)
*tested for 2 hrs after
glucoserich drink
*140-199 mg/dl signals prediabetes
*>200 mg/dl signals diabetes

A.K.A.: Glycated Hemoglobin tests

A1C

80 to 90 mg per 100 ml, is the normal fasting

blood glucose concentration in humans and most
mammals which is associated
very low
Susana with
P. Arellano,
RN, MAN,
levels
of
insulin
secretion.
Prepared by:
MSN

68

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

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

69

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

mature form of insulin

Stored as granules

Zn

Prepared by:

This light micrograph of a section

of the human pancreas shows one
of the islets of Langerhans,
center, a group of modified
glandular cells. These cells
secrete insulin, a hormone that
helps the body metabolize
sugars, fats, and starches. The
Susana
P. lines
Arellano,
RN, MAN,
blue
and white
in the islets
of Langerhans are MSN
blood vessels

70

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)

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

71

In the case of type 1 diabetes, insulin levels

are grossly deficient. Thus type 1 diabetes is
invariably treated with insulin
Type 2 diabetes is frequently associated with
obesity. Serum insulin levels are normal or
elevated, so this is a disease of insulin
resistance. A number of treatment options
may be employed.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

72

Pancreatic Hormones and

Insulin Receptor Agonists

Prepared by:

Susana P. Arellano, RN, MAN, MSN

73

The bulk of the pancreas is an exocrine gland

secreting pancreatic fluid into the duodenum
after a meal.
Inside the pancreas are millions of clusters of
cells called islets of Langerhans. The islets are
endocrine tissue containing four types of cells.
In order of abundance, they are:
beta cells, which secrete insulin and amylin;
alpha cells, which secrete glucagon;
delta cells, which secrete somatostatin
gamma cells, which secrete a polypeptide.
Prepared by:

Susana P. Arellano, RN, MAN, MSN

74

Pancreatic Hormones

Insulin
Amylin
Glucagon
Somatostatin
Pancreatic Polypeptide

Prepared by:

Susana P. Arellano, RN, MAN, MSN

75

A chain

Insulin is a small protein consisting of an A

chain of 21 amino acids linked by two disulfide
(SS) bridges to a B chain of 30 amino acids.

Beta cells have channels in their

plasma membrane that serve as
glucose detectors. Beta cells secrete
insulin in response to a rising level of
circulating
glucose.
Prepared by:
Susana P. Arellano, RN, MAN, MSN

B chain
76

Insulin affects many organs:

It stimulates skeletal muscle

fibers.

It stimulates liver cells.

It acts on fat cells

amino acids
uptake

glucose
uptake

Prepared by:

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

Susana P. Arellano, RN, MAN, MSN

glycogen
breaking

77

The insulin receptor (IR) is

a transmembrane
glycoprotein, composed of
2 and 2 domains.

.
Its intracellular tyrosine
kinase domain is
activated by binding of
insulin, leading to a
cascade of signaling
events.

Prepared by:

Susana P. Arellano, RN, MAN, MSN

78

Who need insulin medicine

Type I (insulin dependent) diabetes patients whose
body produces no insulin.
Type 2 diabetes patients that do not always produce
enough insulin.

Treatment
subcutaneous injection

Prepared by:

Susana P. Arellano, RN, MAN, MSN

79

Insulin drug evolution

Stage 1 Insulin was extracted from the glands of
cows and pigs. (1920s)

Stage 2 Convert pig insulin into human insulin by

removing the one amino acid that distinguishes them
and replacing it with the human version.
Prepared by:

Susana P. Arellano, RN, MAN, MSN

80

 Stage 3 Insert the human

insulin gene into E. coli and
culture the recombinant
E.coli to produce insulin
(trade name = Humulin).
Yeast is also used to
produce insulin (trade name
=
Novolin) (1987).

Recombinant DNA technology has also made it possible to

manufacture slightly-modified forms of human insulin that
work faster (Humalog and NovoLog) or slower
(Lantus) than regular human insulin.
Prepared by:

Susana P. Arellano, RN, MAN, MSN

81

Types of insulin

Regular insulins

Insulin analogs

Pre-mixed insulin

Short peptide mimics

Prepared by:

Susana P. Arellano, RN, MAN, MSN

82

Regular insulins:

Human insulin: Humulin (from E.coli),

Novalin (from yeast)
NPH - neutral protamine Hagedorn (NPH),
protamine mixed.
Lente insulin / Ultralente insullinzinc added

Prepared by:

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83

Types of insulin

Regular insulins

Insulin analogs

Pre-mixed insulin

Short peptide mimics

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Susana P. Arellano, RN, MAN, MSN

84

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)

Prepared by:

Susana P. Arellano, RN, MAN, MSN

85

Amino Acid Substitutons

A-

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

Prepared by:

Lys

Susana P. Arellano, RN, MAN, MSN

B31
And
B32

rapid-acting

Arg

long-acting

86

Prepared by:

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87

Diabetes Oral Medications

6 Classes :
Sulfonylureas
Biguanides
Sulfonylureas and biguanide combination

drugs
Thiazolidinediones
Alpha-glycosidase inhibitors
Meglitinides
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

88

Sulfonylureas : stimulate cells to produce

more insulin

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

may become dislodged delayed

activity
nd

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
Prepared by:
MSN
*Hydroxylated derivatives have much lower hypoglycemic activity

89

Mechanism of Action
Sulfonylureas interact with receptors on

pancreatic -cells to block ATP-sensitive

potassium channels
This, in turn, leads to opening of calcium
channels
Which leads to the production of insulin

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

90

Biguanides : improves insulins ability to

move glucose into cells (esp. muscle)
H

Metformin
- Glucophage, Fortamet,
Riomet

N
N

H
+

N
R

HCl

- mechanism improves insulin sensitivity by increasing

peripheral glucose uptake and utilization.
- Zhou et al (2001) showed that metformin stimulates the
hepatic enzyme AMP-activated protein kinase
- Metformin was first described in the scientific literature in 1957
(Unger et al).
- It was first marketed in France in 1979 but did not receive FDA
approval for Type 2 diabetes until 1994.
Metformin is a widely used monotherapy, and also used in
combination with the sulfonylureas in treatment of type 2
diabetes
*only anti-diabetic drug that has been proven to reduce the complications of diabetes, as evidenced in a large study
Susana P. Arellano, RN, MAN,
of overweight patients with diabetes (UKPDS 1998).

Prepared by:

MSN

91

Sulfonylurea & Biguanide

Combo drugs/ Cocktails
Glucovance (Glyburide & Metformine HCl)

NH

&

NH
S

&

O
O

NH

H
+

HCl

Cl
1-[[ p-[ 2-( 5-chloro-o-anisamido) ethyl] phenyl] sulfonyl]-3-cyclohexylurea

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

92

Thiazolidinediones (TZDs) : make

cells more sensitive to insulin (esp. fatty cells)
O

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

- upon activation of this nuclear receptor by a ligand such as a TZD,

PPARligand complex binds to a specific region of DNA and thereby
regulates the transcription of many genes involved in glucose and fatty
acid metabolism.
- Marketed in USA in August of 1999

PPAR -
Prepared by:

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MSN

93

lpha glycosidase inhibitors :

Block enzymes that help digest starches slowing
the rise in B.G.L.

AGIs
- Precose (acarbose),

- Glyset (miglitol)
H

O
H

O
N

H
1-(2-Hydroxy-ethyl)-2-hydroxymethylpiperidine-3,4,5-triol

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

94

Meglitinides : Stimulate more insulin

production ; dependant upon level of glucose present

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

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

95

Diabetes Oral Medications

Summary

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
Prepared by:

stimulate cells (dependant upon glucose conc.)

Susana P. Arellano, RN, MAN,
MSN

96

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%)

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

97

Ulcerative Colitis

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

98

Ulcerative colitis (UC) is a relapsing, remitting inflammatory

disease of the colonic mucosa and submucosa.
The prevalence of UC in the United States is 150-200/100,000 of
population. A genetic contribution to the disease is indicated by
the increased incidence of UC (of 30 to 100 times that of the
general poupulation) among first-degree relative of patients with
UC.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

99

The characteristic pathology is one of chronic

inflammation characterized by large numbers
of lymphocytes and histiocytes in the
diseased mucosa and submucosa with an
acute inflammatory infiltrate composed of
neutrophils variably present

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

100

UC: is a form of (IBD). It is a form of colitis, of that includes characteristic

ulcers, or open sores, in the colon.
The main symptom of active disease is usually diarrhea mixed with blood, of
gradual onset.
UC is, however, a systemic disease that affects many parts of the body outside
the intestine. Because of the name, IBD is often confused with irritable bowel
syndrome ("IBS"), a troublesome, but much less serious condition.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

101

UC is an intermittent disease, with periods of exacerbated

symptoms, and periods that are relatively symptom-free.
Although the symptoms of UC can sometimes diminish on their
own, the disease usually requires treatment to go into
remission.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

102

Although UC has no known cause, there is a

presumed genetic component to susceptibility.
The disease may be triggered in a susceptible person
by
environmental
factors.
Although
dietary
modification may reduce the discomfort of a person
with the disease, UC is not thought to be caused by
dietary factors.
Although UC is treated as though it were an
autoimmune disease, there is no consensus that it is
such
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

103

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

104

UC is a systemic disease that affects many parts of the body.

Sometimes the extra-intestinal manifestations of the disease are
the initial signs, such as painful, arthritic knees in a teenager. It
is, however, unlikely that the disease will be correctly diagnosed
until the onset of the intestinal manifestations.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

105

The clinical presentation of UC depends on the extent of the

disease process. Patients usually present with diarrhea mixed
with blood and mucus, of gradual onset.
They also may have signs of weight loss, and blood on rectal
examination.
The disease is usually accompanied with different degrees of
abdominal pain, from mild discomfort to severely painful cramps.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

106

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

107

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

108

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

109

Moderate disease correlates with more than four stools daily,

but with minimal signs of toxicity. Patients may display anemia
(not requiring transfusions), moderate abdominal pain, and low
grade fever, 38 to 39 C
Severe disease, correlates with more than six bloody stools a
day, and evidence of toxicity as demonstrated by fever,
tachycardia, anemia or an elevated ESR.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

110

Fulminant disease correlates with more than ten

bowel movements daily, continuous bleeding, toxicity,
abdominal tenderness and distension, blood
transfusion requirement and colonic dilation. Patients
in this category may have severe inflammation
extending beyond just the mucosal layer, causing
impaired colonic motility and leading to toxic
megacolon. If the serous membrane is involved,
colonic perforation may ensue. Unless treated,
fulminant disease will soon lead to death.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

111

Extraintestinal features
As UC is a systemic disease, patients may present
with symptoms and complications outside the colon.
These include the following:

aphthous ulcers of the mouth .

Ophthalmic .

Iritis or uveit.

Episcleritis.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

112

Patients with ulcerative colitis can occasionally have

aphthous ulcers involving the tongue, lips, palate and
pharynx
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Susana P. Arellano, RN, MAN,

MSN

113

 Musculoskeletal:

Seronegative arthritis, which can be a large-joint

oligoa rthritis (affecting one or two joints), or may affect many small joints
of the hands and feet

Ankylosing spondylitis, arthritis of the spine

Sacroiliitis, arthritis of the lower spine

Cutaneous

Erythemanodosum, which is a panniculitis, or

subcutaneous tissue involving the lower extremities

Pyoderma gangrenosum, which is a painful ulcerating lesion involving

the skin

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

inflammation

of

114

Deep venous thrombosis and pulmonary embolism

Autoimmune hemolytic anemia

clubbing,

Primary sclerosing cholangitis, or inflammation of

the bile ducts

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

115

Similar conditions
The following conditions may present in a similar manner and should be
excluded:

Crohn's disease

Infectious colitis,

Pseudom embranous

Ischemic colitis,

which is typically detected on stool cultures

colitis, or Clostridium difficile-ssociated colitis, bacterial upsets

often seen following administration of antibiotics
inadequate blood supply to the intestine, which typically affects

the elderly

Radiation colitis

in patients with previous pelvic radiotherapy

resulting from introduction of harsh chemicals into the colon from

an enema or other procedure.
Chemical colitis

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

116

Comparison to Crohn's Disease

The most common disease that mimics the symptoms of UC is Crohn's
disease, as both are IBD that can affect the colon with similar
symptoms.
It is important to differentiate these diseases, since the course of the
diseases and treatments may be different.
In some cases, however, it may not be possible to tell the difference, in
which case the disease is classified as indeterminate colitis.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

117

Comparisons of various factors in Crohn's disease and ulcerative

colitis
Crohn's Disease

Ulcerative Colitis

Involves terminal ileum

Commonly

Seldom

Involves colon?
Involves rectum?

Usually
Seldom

Always
Usually

Peri-anal involvement

Commonl

Seldom

Bile duct involvement?

Not associated

Higher rate of Primary

sclerosing cholangitis

Distribution of Disease

Patchy areas of
inflammation

Continuous area of
inflammation

Endoscopy

Linear and serpiginous

(snake-like) ulcers

Continuous ulcer

Depth of inflammation

May be transmural, deep

Susana P.
Arellano,
RN, MAN, MSN
into
tissues

Shallow, mucosal

Prepared by:

118

Comparisons of various factors in Crohn's disease and UC (Cont.)

Fistulae, abnormal
passageways between
organs

Commonly

Seldom

Biopsy

Can have granulomata

Crypt abscesses and

cryptitis

Surgical cure ?

Often returns following

removal of affected
part

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?

Lower than ulcerative

colitis

Higher than Crohn's

Prepared by:

Susana P. Arellano, RN, MAN, MSN

119

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.

Otherwise, a flexible sigmoidoscopy is sufficient to support the diagnosis. The

physician may elect to limit the extent of the exam if severe colitis is encountered
to minimize the risk of perforation of the colon. Endoscopic findings in UC include
the following:
Loss of the vascular appearance of the colon, Erythema (or redness of the mucosa)
and friability of the mucosa Superficial ulceration, which may be confluent, and
Pseudopolyps.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

120

UC is usually continuous from the rectum,

with the rectum almost universally being
involved. There is rarely peri-anal disease,
but cases have been reported. The degree of
involvement endoscopically ranges from
proctitis or inflammation of the rectum, to left
sided colitis, to pancolitis, which is
inflammation involving the ascending colon

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

121

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

122

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

123

Prepared by:

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124

Prepared by:

Susana P. Arellano, RN, MAN,

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125

Endoscopic image of ulcerative colitis affecting the

left side of the colon. The image shows confluent
superficial ulceration and loss of mucosal
architecture. Crohn's disease may be similar in
appearance, a fact that can make diagnosing UC a
challenge.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

126

Colonic pseudopolyps of a patient with

intractable ulcerative colitis. Colectomy
specimen.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

127

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

hemorrhage or inflammatory cells in the lamina propria. In cases where

the clinical picture is unclear, the histomorphologic analysis often plays
a pivotal role in determining the management.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

128

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

129

Course and complications

Progression or remission

Patients with UC usually have an intermittent course, with periods of disease

inactivity alternating with "flares" of disease. Patients with proctitis or left-sided
colitis usually have a more benign course: only 15% progress proximally with
their disease, and up to 20% can have sustained remission in the absence of
any therapy. Patients with more extensive disease are less likely to sustain
remission, but the rate of remission is independent of the severity of disease

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

130

UC and colorectal cancer

There is a significantly increased risk of colorectal cancer in patients with UC
after 10 years if involvement is beyond the splenicflexure. Those with only
proctitis or rectosigmoiditis usually have no increased risk.
It is recommended that patients have screening colonoscopies with random
biopsies to look for dysplasia after eight years of disease

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

131

Primary sclerosing cholangitis (PSC)

UC has a significant association with (PSC), a progressive
inflammatory disorder of small and large bile ducts. As many as
5% of patients with UC may progress to develop (PSC).
Mortality
The effect of UC on mortality is unclear, but it is thought that the
disease primarily affects quality of life, and not lifespan.
Prepared by:

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132

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.

Prepared by:

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MSN

133

The medications used to induce and maintain a remission somewhat

overlap, but the treatments are different. Physicians first direct
treatment to inducing a remission which involves relief of symptoms
and mucosal healing of the lining of the colon and then longer term
treatment to maintan the remission.
Current treatments have been effective for many patients with UC but
have numerous limitations for patients with modeate to severe disease.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

134

Drugs used
Aminosalicylates

are

the

mainstay

of

UC

pharmacotherapy

for

induction

and

maintenance of remission for patietns with mild to moderate disease.

Sulfasalazine has been a major agent in the therapy of mild to moderate

UC for over 50 years. In 1977 Mastan S.Kalsi et al determined that 5aminosalicyclic acid (5-ASA and mesalazine) was the therapeutically
active compound in sulfasalazine. Since then many 5-ASA compounds
have been developed with the aim of maintaining efficacy but reducing
the common side effects associated with the sulfapyridine moiety in
sulfasalazine.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

135

 Mesalazine, also known as 5-aminosalicylic acid, mesalamine, or 5ASA. (Asacol, Pentasa, Mezavant, Lialda, and Salofalk).

Sulfasalazine, also known as Azulfidine.

Balsalazide - Disodium , also known as Colazal.
Olsalazine, also known as Dipentum.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

136

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

137

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

138

 Mercaptopurine, also known as 6-Mercaptopurine, 6-MP and

Purinethol.

Azathioprine, also known as Imuran, Azasan or Azamun, which

metabolises to 6-MP.

Methotrexate.
Tacrolimus.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

139

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)

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

140

Infliximab

is known as a "chimeric monoclonal antibody" (the

term "chimeric" refers to the use of both mouse (murine) and

human components of the drug.
The drug blocks the action of TNF (tumour necrosis factor
alpha) by binding to it and preventing it from signaling the
receptors for TNF on the surface of cells. TNF is one of the
key cytokines that triggers and sustains the inflammation
respone.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

141

Visilizumab is a humanized monoclonal antibody. It is

being investigated for use as an immunosuppressive
drug in patients with UC

and Crohn's disease.

Visilizumab binds to the CD3 receptor on certain

activated T cells without effecting resting T cells. It is
currently under clinical studies.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

142

The 47 integrin is a heterodimeric cell surface glycoprotein

present on the surface of subsets of circulating memory CD4+
and CD8+T cells and most B cells.
It has received particular attention in the context of mucosal
immune responses because of its intimate involvement in
lymphocyte recruitment to normal gastrointestinal (GI) mucosa
and associated lymphoid tissue.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

143

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

144

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

145

Unlike Crohn's disease, UC can generally be cured by surgical

removal of the large intestine. This procedure is necessary in the
event

of:

exsanguinating

hemorrhage,

frank

perforation

or

documented or strongly suspected carcinoma. Surgery is also

indicated for patients with severe colitis or toxic megacolon.
Patients with symptoms that are disabling and do not respond to
drugs may wish to consider whether surgery would improve the
quality of life.
In rare cases the extra-intestinal manifestations of the disease may
require removal of the colon.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

146

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

Susana P. Arellano, RN, MAN, MSN

147

Alternative treatments
Smoking :

Unlike Crohn's disease, UC has a lesser prevalence in smokers than

non-smokers .
Dietary modification :

Dietary modification may reduce the symptoms of the disease.

Lactose intolerance is noted in many ulcerative colitis patients. Those
with suspicious symptoms should get a lactose breath hydrogen test.

Prepared by:

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148

Patients with abdominal cramping or diarrhea may find relief or a

reduction in symptoms by avoiding fresh fruits and vegetables,
caffeine, carbonated drinks and sorbitol-containing foods.
Many dietary approaches have purported to treat UC, including
the ElaineGottschall's specific carbohydrate diet and the "antifungal diet" (Holland/Kaufmann).
The use of elemental and semi-elemental formula has been
successful in pediatric patients
Prepared by:

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149

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

150

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

151

GLOMERULONEPHRITIS

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

152

All glomerular injury results in

impairment of glomerular filtration
or the inappropiate appearance of
plasma proteins and blood cells in
the urine.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

153

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

154

SIGNS AND SYMPTOMS

Flank pain
Hematuria
Hipertension
Generalized edema
Proteinuria
Elevated serum creatinine

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

155

GENRALITIES
G
L
O
M
E
R
U
L
A
R
I
N
J
U
R
Y
Prepared by:

CLINICOPATHOLOGIC

PRIMARY MECHANISMS

CORRELATION
BETWEEN SITE AND
PRESENTATION

CLASIFICATION

Susana P. Arellano, RN, MAN,

MSN

156

GENERALITIES

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

157

GLOMERULI

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

158

GLOMERULI

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

159

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

160

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)
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

161

GLOMERULAR FILTRATION
In health, glomerular endothelium
is antithrombotic and antiadhesive
for leukocytes and platelets,
Prevent vascular thrombosis and
inflammation during the filtration
process.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

162

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

163

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

164

NOMENCLATURE
Diffuse: affect > 50% of glomeruli.
Focal: affect < 50% of glomeruli.
Global: affect > 50% of glomerular
tuft.
Segmental: < 50% of glomerular tuft
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

165

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

166

GENRALITIES
G
L
O
M
E
R
U
L
A
R
I
N
J
U
R
Y
Prepared by:

CLINICOPATHOLOGIC

PRIMARY MECHANISMS

CORRELATION
BETWEEN SITE AND
PRESENTATION

CLASIFICATION

Susana P. Arellano, RN, MAN,

MSN

167

CLINICOPATHOLOGIC

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

168

Diffuse proliferative GN
Clinical Presentation
Acute nephritic syndrome, acute renal failure over

days to weeks, hipertension, edema,oliguria,

active urine sediment, subnephrotic proteinuria.

Pathology Findings
Diffuse increase in cellularity of tufts. Infiltration

by neutrophis ans monocytes, and proliferation of

glomerular endothelial and mesangial cells.

Etiologies
Immune complex GN, idiopathic, postinfectious,

SLE, cryoglobulinemia, Henoch Schnlein purpura.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

169

Crescentic GN
Clinical Presentation
Rapidly progresive GN, subacute renal failure,

active urine sediment, subnephrotic proteinuria.

Pathology Findings
Fibrinoid necrosis and crescents in Bowman`s

space (parietal epithelial cells), infiltrating

macrophages, and fibrin)

Etiologies
Inmune Complex GN, pauci-immune GN,

Wagener`s granulomatosis, microscopic

polyarteritis nodosa.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

170

Focal proliferative GN
Clinical Presentation
Mild to moderate glomerular inflammation.

Active urine sediment, and mild to moderate

decline in GF.

Pathology Findings
Segmental areas of proliferation and necrosis

in less than 50% of glomeruli, occasionally

with crescent formation

Etiologies
Early and milder forms of most diseas causing

diffuse proliferative and crescentic GN.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

171

Mesangial proliferative GN
Clinical Presentation
Chronic glomerular inflammation: proteinuria,

hematuria, hypertension, variable effect on GF.

Pathology Findings
Proliferation of mesangial cells and matrix

Etiologies
Early and milder forms of most diseas causing

diffuse proliferative and crescentic GN. IgA

nephropathy.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

172

Membanoproliferative GN
Clinical Presentation
Combination of nephritic and nephrotic

features, acute or subacute decline in GF.

Pathology Findings
Diffuse proliferation of mesangial cells and

infiltration of glomeruli by macrophages

Etiologies
Immune complex GN, In association with

thrombotic microangiophaties, in
association with deposition diseases.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

173

Deposition diseases
Clinical Presentation
Combination of nephritic and nephrotic

features. Renal failure over months to

years.proteinuria, hematuria and hypertension.

Pathology Findings
Mesangial expansion and thinckening of

glomerular capillari wall

Etiologies
Amyloid, Cryoglobulinemia, Light chain

deposition disease.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

174

GENRALITIES
G
L
O
M
E
R
U
L
A
R
I
N
J
U
R
Y
Prepared by:

CLINICOPATHOLOGIC

PRIMARY MECHANISMS

CORRELATION
BETWEEN SITE AND
PRESENTATION

CLASIFICATION

Susana P. Arellano, RN, MAN,

MSN

175

Primary Mechanisms of
Glomerular Injury

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

176

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

177

Metabolic
Defects
Hyperglicemia
Fabri`s disease

Glomerular Disease
Diabetic nephropathy
Focal segmental glomerulosclerosis

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

178

Hemodynamic
Defects
Systemic hypertension
Intraglomerular hypertension

Glomerular Disease
Hypertensive nephrosclerosis
Secondary focal segmental

glomerulosclerosis

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

179

Toxic
Defects
E. Colli derived verotoxin
Therapeutic drugs (NSAIDs)
Drugs (heroin)

Glomerular Disease
Thrombotic microangiopathy
Minimal change disease
Focal segmental glomerulosclerosis

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

180

Deposition
Defects
Amyloid fibrils

Glomerular Disease
Amyloid nephrophathy

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

181

Infectious
Defects
HIV
Subacute bacterial endocarditis

Glomerular Disease
HIV nephropathy
Immune complex glomerulonephritis

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

182

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

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

183

GENRALITIES
G
L
O
M
E
R
U
L
A
R
I
N
J
U
R
Y
Prepared by:

CLINICOPATHOLOGIC

PRIMARY MECHANISMS

CORRELATION
BETWEEN SITE AND
PRESENTATION

CLASIFICATION

Susana P. Arellano, RN, MAN,

MSN

184

Correlation between Site

of G. I. And
Clinicopathologic
Presentation.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

185

Endothelial cell
Physiologic Role
Maintains glomerular perfusion
Prevents leukocyte adhesion
Prevents platelet aggregation and clotting

Response to Injury
Vasoconstriction
Leukocyte infiltration
Intravascular microthrombi

Representative Glomerular Disease

Acute renal failure
Focal or diffuse proliferativa GN
Thrombotic microangiopathies
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

186

Mesangial Cell
Physiologic Role
Controls glomerular filtration surface area

Response to Injury
Proliferation / increased matrix

Representative Glomerular Disease

Mesangioproliferative GN /

glomerulosclerosis

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

187

Basement membrane
Physiologic Role
Prevents filtration of plasma proteins

Response to Injury
Proteinuria

Representative Glomerular Disease

Membranous nephropathy

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

188

Visceral epithelial cell

Physiologic Role
Prevent infiltration of plasma proteins

Response to Injury
Proteinuria

Representative Glomerular Disease

Minimal change disease

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

189

Parietal ephithelial cell

Physiologic Role
Maintains Bowman`s space

Response to Injury
Crescent formation

Representative Glomerular Disease

Crescentic GN

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

190

GENRALITIES
G
L
O
M
E
R
U
L
A
R
I
N
J
U
R
Y
Prepared by:

CLINICOPATHOLOGIC

PRIMARY MECHANISMS

CORRELATION
BETWEEN SITE AND
PRESENTATION

CLASIFICATION

Susana P. Arellano, RN, MAN,

MSN

191

CLASSIFICATION

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

192

INMUNOLOGIC
Antibody-mediated injury
Other mechanisms of antibodymediated injury
Antineutrophil Cytoplasmic Antibodies (ANCA)
Antiendothelial Cell Antibodies
C3 Nephritic Factor

Cell-mediated injury
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

193

NONIMMUNOLOGIC
Metabolic
Diabetic nephropathy
Other Metabolic Disease

Hemodynamic
Systemic Hypertension
Glomerular Hypertension

Toxic glomerulopathies
Deposition Disease
Infectious Causes
Inherited
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

194

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

195

Antibody-mediated injury
Mechanisms:
1) Reactivity of circulating autoantibodies with

intrinsic autoantigens that are components

of normal glomerular parenchyma
2) In situs formation of immune complexes
through interaction of circulating antibodies
and extrinsic antigens that have been
planted within the glomerulus.
3) Intraglomerular trapping of immune
complexes that have formed in the systemic
circulation.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

196

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).
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

197

2) The foreign AG may trigger aberrant

expression of major histocompatibility
complex class II molecules on
glomerular cells which present
previously invisible autoantigens to T
lymphocytes are thereby generate an
autoimmuneresponse.
3) The forign Ag can trigger polyclonal
activation of B lymphocytes dome of
which generate nephritogenic AB.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

198

Deposition of nephritogenic
antibodies within the glomerulus
Anti-GBM antibody disease: patients have a

circulating AB directed at type IV collagen

(preferentially expressed in glomerular and
pulmonary alveolar basement membranes)
Cryoglobulinemia, due to chronic hepatitis C
infection, is an example of GN initiated by
trapping of immune complexes.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

199

Recruitment of inflammatory cells:

Leukocytes express Fc receptors that can

directly engage the FC portion of Ig.

Resident glomerular macrophages,
endothelial cells, and mesangial cells also
express FC receptors, engagement of
wich can trigger release of an array of
inflammatory mediators that promotes
directed locomotion of leukocytes
(chemotaxis)
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

200

Other mechanisms of ABmediated injury

Antineutrophil Cytoplasmic
Antibodies (ANCA): stimulate human
neutrophils to generate reactive O2
species and injure endothelium.
Antiendothelial Cell Antibodies: have
been reported in several
inflammatory vasculities and GN
C3 nephritic factor:
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

201

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

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

202

NONIMMUNOLOGIC
Metabolic
Diabetic nephropathy
Other Metabolic Disease

Hemodynamic
Systemic Hypertension
Glomerular Hypertension

Toxic glomerulopathies
Deposition Disease
Infectious Causes
Inherited
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

203

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

204

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

205

Toxic
Verotoxin, derived from E Coli
during bouts of infective diarrhea,
is directly toxic to renal
endothelium and induces the
hemolytic-uremic sindrome .

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

206

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.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

207

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

208

Inherited
Alport`s syndrome: The GMB is
irregular with longitudinal layering,
thickening, and patients develop
hematuria, progresive
glomerulosclerosis, and renal
failure.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

209

CLINICAL PRESENTATIONS
1)Acute nephritic syndrome
2) Asymptomatic abnormalities of
the urinary sediment
3) Chronic glomerulonephritis
4) nephrotic syndrome

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

210

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

211

Extracellular fluid volume

expansion, edema and
hypertensiondevelope because of
impaired GFR and enhanced
tubular reabsorption of salt and
water.
As a result of injury to the
glomerular capillary wall,
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

212

PP

CLINICAL FEATURES

Glomerular injury
Inflammatory
glomerular capillary
Perfusion glomerular
capillary
FG
reabsorption
Tubular Na and
volume
H2O
Extracelular
Volume
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

RED BLOOD
CELL CASTS
PROTEINURIA
HEMATURIA

AZOEMIA

OLIGURIA
HYPERTENSION
EDEMA
213

Urianalisis typically reveal red

blood cell casts, dydmorphic red
blood cells, leukocytes, and
subnephrotic proteinuria of < 3.5
g per 24 h (nephritic urinary
sediment) Hematuria is often
macroscopic.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

214

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)
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

215

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.

Differential diagnosis: Idiopatic proliferative

GN, cresentic GN, MPGN, postinfectious GN,
Lupus nephritis.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

216

Anti- GBM disease

The glomerulus is the direct target of
immune attack.
Glomerular inflammation being initiated
by an autoantibody directed at a 28KDa autoantigen on the type Ivcollagen.
95% have circulating anti GBM
autoantibodies.

Differential diagnosis: Good passteur`s

syndrome

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

217

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.

Differential diagnosis: Wagener`s

granulomatosis, microscopic polyarteritis
nodosa.

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

218

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

219

Hypersensitivity

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

220

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

221

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,
Prepared by:

MSN

222

Component and cells

Allergen: An antigen that causes
allergy.
Hapten can turn into allergen by
carrier effect (hapten +carrier
immunogen)
Common allergen: inhalant allergen
(grass pollen, animal dander, feces
from mites in house dust, etc.), some
kinds of food and drugs
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

223

Reaginic antibody (IgE)

The main anaphylactic Ab in
human
IgE can bind FcRon mast cells
and basophils by its CH4 domain,
cause anaphylaxis

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

224

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

225

IgE-binding Fc recepors
FcR: high affinity receptor of IgE
on mast cell/ basophil, activate
mast cell/ basophil
FcR:low affinity

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

226

Mediators released by mast

cells
Primary mediators (preformed):
heparin, histamine, neutral protease,
eo-sinophil & neutrophil chemotactic
factors, provoke early
phase(immediate) reaction
Secondary mediators(newly
synthesi-zed) : leukotrienes(LTB4, LTC4
and LTD4), PGD2, PAF, CKs(IL-4, GMCSF), induce late phase reaction
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

227

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

228

Early phase response: short-lived,

resolve within 1 hr. Increase of
vasopermeability, smooth muscle
contraction, gland hypersecretion
and vasodilation
Late phase response:
inflammation, peak at around 5 hrs,
last for several days. Eosinophils,
mast cells, basophils, T-cells and
neutrophilsSusana
infiltration.
P. Arellano, RN, MAN,
Prepared by:

MSN

229

Susana P. Arellano, RN, MAN,

The
mechanism
of typehypersensitivity
Prepared by:
MSN

230

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,
Prepared by:

MSN

231

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.
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

232

Food allergies: diarrhea, vomiting,

wheal and flare reaction
Atopic dermatitis: eczema,
urticaria. itch, desquamation,
pachyderma

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

233

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

234

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,

Prepared by:

MSN

235

Atopic allergies and their treatment

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

236

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

237

Mechanism of tissue damage of type

Susana P. Arellano, RN, MAN,
hypersensitivity
Prepared by:
MSN

238

Type associated diseases

Transfusion reaction: mismatched
blood transfusion cause
complement-mediated hemolysis.
ABO blood group:
isohemagglutinins(IgM)
Prevention: cross-matching between
donor and recipient blood
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

239

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

240

Hemolytic disease of the newborn due to

Susana
P. Arellano, RN, MAN,
rhesus
incompatibility

Prepared by:

MSN

241

Drug-induced hemolytic
anemia
Drug adsorb RBC proteinsAntiRBC IgG/IgMcomplement,
opsonization, ADCC RBC lysis,
anemia

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

242

Graves disease and myasthenia

gravis
Special class of type
hypersensitivity, Autoimmune
diseases, tissue/organ dysfunction
Graves disease: anti-TSH receptor
Myasthenia gravis: antiacetylcholine receptors

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

243

Susana P. Arellano, RN, MAN,

Graves
disease
Myasthenia gravis
Prepared by:
MSN
244

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

245

Mechanism of type hypersensitivity

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

246

Tissue damage caused by:

Complement activation
and attraction of neutrophils: release tissue
damaging mediators
Stimulation of M:
release proinflammatory
cytokines
Aggregation of platelets: cause microthrombi
and vasoactive amine
release

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

247

Immune complex-mediated (type ) hypersensitivity

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

248

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

249

Type associated
diseases
Rheumatoid arthritis: rheumatoid

factor (RF): anti-IgG autoantibodies,

usually IgM. IgM-IgG complex deposit
in joints
Immune complex glomerulonephritis:
Ag-Ab-C3 deposit glomerular
basement membrane
Others: drug reactions, infectious
diseases
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

250

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

251

Immune pathogenesis
CD8+CTL: primed CTLAg:MHC
perforin/ Fas-FasLtarget cell
death

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

252

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

253

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,
Prepared by:

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

255

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

256

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

257

Summary
Therapy for typehypersensitivity:
Allergen avoidance
Hyposensitivity
Drug treatment: antihistamines,
adrenaline

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

258

Anaphylaxis
IgE Mediated Hypersensitivity

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

259

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
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

260

History
1st recorded 2640BC in
hieroglyphics

bee sting of a pharoah

Richet & Portier

South Seas
Man-o-war
coined term anaphylaxis

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

261

IgE
Binds irreversible to FcRI
receptors on mast cells, basophils,
and eosinophils
Is usually for parasitic infections
E heavy chain

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

262

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

263

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

264

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

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

265

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

266

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

267

IgE FcRI Receptor

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

268

Symptoms
Peripheral vasodilation

vascular permeablility (edema)

Bronchospasm
Cardiac arrhythmias
Smooth muscle contractions

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

269

Sensitization
Antigen is presented by antigen
presenting cells
TH2 cells induce B cell activation

CD40 ligand and cytokines

B cells undergo isotype switching

and produce antibody
Serum antibody is bound by the mast
cells
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

270

The allergic response

Secondary presentation of antigen
produces an immediate response
controlled by mast cells
Granule contents are released
Cell mediated response proceeds

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

271

Sensitization & Response

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

272

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

Inflammatory mediators are released upon

degranulation

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

273

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

274

Mediators Involved
Include histamine, proteases,
chemotactic factors, leukotrienes,
prostaglandin D, and cytokines
Primary: released before degranulation

Interleukin 4 used by T cells induces B cell

maturation
IL-3 and IL-5 released by T and mast cells
are chemo attractants for eosinophils

Secondary: come from granules

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

275

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

276

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

277

Histamine
Synthesized and stored in granules
The primary mediator in the granules
3 receptors

H1: Smooth muscle & endothelium

Increased IP3 & DAG

H2: Gastric mucosa, cardiac muscle, mast

cells
Increased cAMP

H3: Pre-synaptic brain

Decreases histamine release

Prepared by:

Susana P. Arellano, RN, MAN,

MSN

278

Tissue Effects of Histamine

Cardiovascular

Decreased blood pressure

Increased heart rate
Edema (separation of endothelial cells & increased
permeability)

Respiratory

broncho constriction

Gastrointestinal

Smooth muscle contraction and diarrhea

Skin
Urticaria
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

279

Treatments
Antihistamines

Block H1 and H2 receptors

Epinephrine for bronchospasms

stimulates the reformation of tight

junctions between endothelial cells

IV fluids to support blood pressure

Desensitization
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

280

Ant bites
Red Imported Fire Ant
Venom (antigen)

Composed largely of low MW alkaloids, also

different proteins
Each component is able to induce
anaphylaxis

Able to inject 100ng venom/bite

Venom induces venom specific IgE
antibody production
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

281

Thank You!!!!
We have been made holy
through the sacrifice of the
body of Jesus Christ once for
all.
Hebrews 10:10
Prepared by:

Susana P. Arellano, RN, MAN,

MSN

282