Immunodeficiency Disease: Prepared By: 1 Susana P. Arellano, RN, MAN, MSN

Immunodeficiency Disease
Prepared by:
Susana P. Arellano, RN, MAN, MSN
Prepared by:
AIDS / HIV
Prepared by:
Is HIV and AIDS the same thing?
Prepared by:
HIV
Human Immunodeficiency Syndrome A specific type of virus (a retrovirus)
HIV invades the helper T cells to replicate itself. No Cure
Prepared by:
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 6
New HIV Infections in 2002 by Age Group
Prepared by:
Four Stages of HIV
Prepared by:
Stage 1 - Primary
Short, flu-like illness - occurs one to six weeks after infection
no symptoms at all Infected person can infect other people
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

Stage 3 - Symptomatic
The symptoms are mild
The immune system deteriorates emergence of opportunistic infections and cancers
Stage 4 - HIV AIDS

The immune system weakens
The illnesses become more severe leading to an AIDS diagnosis
Opportunistic Infections associated with AIDS

Bacterial
Tuberculosis (TB) Strep pneumonia
Viral
Kaposi Sarcoma Herpes Influenza (flu)
Opportunistic Infections associated with AIDS

Parasitic
Pneumocystis carinii
Fungal
Candida Cryptococcus
Modes of HIV/AIDS Transmission
Prepared by:
15
Through Bodily Fluids

Blood products Semen Vaginal fluids Breast Milk
Prepared by:
16
Through IV Drug Use

Sharing Needles
Without sterilization
Increases the chances of contracting HIV
Prepared by:
17
Through Sex
Intercourse (penile penetration into the vagina) Oral Anal Digital Sex
Prepared by:
18
Mother-to-Baby
Before Birth During Birth Postpartum
After the birth
Prepared by:
19
Testing Options for HIV
Prepared by:
20
Anonymous Testing
No name is used Unique identifying number Results issued only to test recipient
23659874515
Anonymous
Prepared by:
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:
22
Administration
Blood Urine Oral
Prepared by:
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:
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:
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!
Susana P. Arellano, RN, MAN, MSN 26
Prepared by:
Counseling
Prepared by:
27
Pre-test Counseling
Transmission Prevention Risk Factors Voluntary & Confidential Reportability of Positive Test Results
Prepared by:
28
Post-test Counseling
Clarifies test results Need for additional testing Promotion of safe behavior Release of results
Prepared by:
29
Treatment Options
Prepared by:
30
Antiretroviral Drugs
Nucleoside Reverse Transcriptase inhibitors
AZT (Zidovudine)
Non-Nucleoside Transcriptase inhibitors
Viramune (Nevirapine) Norvir (Ritonavir)

Protease inhibitors
Prepared by:
Opportunistic Infection
Treatment
Issued in an event where antiretroviral drugs are not available
Prepared by:
32
Four ways to protect yourself?

Abstinence Monogamous Relationship Protected Sex Sterile needles
Prepared by:
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:
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:
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:
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 oil-based condoms
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:
38
Needle Exchange Program

Non-profit Organization, which provides sterile needles in exchange for contaminated ones
Addison's Disease
Prepared by:
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:
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 longchain fatty acid metabolism.
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
Prepared by:
insufficiency.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:
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.
- 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.
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:
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:
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.
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 sun-exposed 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.
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.
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.
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:
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.Susana P. Arellano, RN, MAN, MSN Prepared by: 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:
55
- hyponatremia, hyperkalemia, and a mild non anion-gap metabolic acidosis due to the loss of the sodium-retaining 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.
Urea and electrolyte:
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. RN, MAN, MSN Prepared by: Susana P. Arellano, 57
Management: imaging:
- The chest x-ray often normal except in evidence of TB or fungal infection that initially cause Addison disease. - 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.
Chest x-ray:
CT scan:
Prepared by:
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:
59
Medical treatment: inpatient care

- 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.
In case of adrenal crisis:
Prepared by:
Clinical improvement, especially blood pressure response, should be evident within 46 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.
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 9alpha-fludrocortisone, usually in doses of 0.05-0.10 mg per day or every other day.
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 dualenergy x-ray absorptiometry (DEXA) detecting early osteoporosis in patients who are overreplaced 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.
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:
64
Diabetes Mellitus Overview

and Treatments
Prepared by:
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 :
Prepared by:
- Stroke - Heart attack - Kidney disease - Eye Disease - Nerve Damage
66
Diabetes Mellitus
Type 1 Diabetes
- cells that produce insulin are destroyed - results in insulin dependence - commonly detected before 30
Type 2 Diabetes
- 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 develop gestational diabetes
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 with very low levels of insulin secretion. Prepared by: Susana P. Arellano, RN, MAN, 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:
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 This light micrograph of a section
Stored as granules
Zn
Prepared by:
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 blue and white lines in the islets of Langerhans are blood vessels that carry P. Arellano, the rest Susana the insulin to RN, MAN,
MSN
70
Diabetes Insulin
(Biochemical Role) -Tyrosine Kinase receptors are the locks in which the insulin key fits - Involved in signal
(insulin hormone being 1st messenger)
transduction
Prepared by:
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:
72
Pancreatic Hormones and Insulin Receptor Agonists
Prepared by:
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.
Pancreatic Hormones Insulin Amylin Glucagon Somatostatin Pancreatic Polypeptide
Prepared by:
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 c i r c u l a t i n g 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 It inhibits production of certain enzyme.
glucose uptake glycogen synthesis amino acids uptake protein synthesis
fat synthesis
In each case, insulin triggers these effects by binding to the insulin receptor.
enzyme production
glycogen breaking
Prepared by:
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:
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:
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.
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.
Types of insulin
Regular insulins Insulin analogs Pre-mixed insulin
Short peptide mimics
Prepared by:
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:
83
Types of insulin
Regular insulins Insulin analogs Pre-mixed insulin
Short peptide mimics
Prepared by:
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:
85
Amino Acid Substitutons

Achai n Position
Source/ Type Human Aspart Lispro Glulisin e Glargine A21 Asn Asn Asn Asn Gly Lys B3 Asn
B- chain Position
B28 Pro Aspartic acid Lys Pro Pro
B29 Lys Lys Pro Glu Lys
B30 Thr Thr Thr Thr Thr
B31 And B32
rapid-acting
Arg
Detemir
Lys
Myristic acid
long-acting
Prepared by:
86
Prepared by:
87
Diabetes Oral Medications

6 Classes :
Sulfonylureas Biguanides
Sulfonylureas and biguanide combination
drugs Thiazolidinediones Alpha-glycosidase inhibitors Meglitinides

Sulfonylureas : stimulate cells to produce

more insulin
1st generation
bind to protein
(1)Orinase
may become dislodged delayed activity
(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
Rel. Potency
2nd generation
(75)Glucotrol
(glipizide) (150)Glucotrol XL (ex. rel. glipizide) (150)Micronase, Diabeta (glyburide) (250)Glynase (micronized glyburide)
3rd generation
(350)Amaryl
(glimepiride)
89
*Hydroxylation of the aromatic ring appears to be the most favored metabolic pathway Prepared by: Susana P. Arellano, RN, MAN, MSN *Hydroxylated derivatives have much lower hypoglycemic activity
Mechanism of Action
Sulfonylureas interact with receptors on
pancreatic b-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:
90
Biguanides : improves insulins ability to

move glucose into cells (esp. muscle)
R N
H
R R N N N R N R R R
Metformin
N H N H + N H
N N H
- Glucophage, Fortamet, Riomet
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 of overweight patients with diabetes (UKPDS 1998).
Prepared by:
91
Sulfonylurea & Biguanide Combo drugs/ Cocktails

Glucovance (Glyburide & Metformine HCl)
&
NH O S O NH O
H N N N H + N H H
&
O O NH
H N
HCl
Cl 1-[[ p-[ 2-( 5-chloro-o-anisamido) ethyl] phenyl] sulfonyl]-3-cyclohexylurea
Prepared by:
92
Thiazolidinediones (TZDs) : make

cells more sensitive to insulin (esp. fatty cells)
O
Pioglitazone
- Actos, Avandia
O S NH
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 receptor (PPAR
- PPAR is a member of the steroid hormone nuclear receptor superfamily, and is found in adipose t 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 -
lpha glycosidase inhibitors :

Block enzymes that help digest starches slowing the rise in B.G.L.
AGIs
- Precose (acarbose),
- Glyset (miglitol)
O
H O H N
H 1-(2-Hydroxy-ethyl)-2-hydroxymethylpiperidine-3,4,5-triol
Prepared by:
94
Meglitinides : Stimulate more insulin

production ; dependant upon level of glucose present
Meglitinides
O
- Prandin (repaglinide)
N NH
O O
OH
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:
95
Diabetes Oral Medications

Summary
6 Classes :
Sulfonylureas Biguanides
stimulate cells 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.)

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:
97
Ulcerative Colitis
Prepared by:
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.
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:
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.
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:
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:
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:
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.
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.
Extensive colitis, inflammation extending beyond the reach of enemas:
Pancolitis: Involvement of the entire colon, extending from the rectum to the cecum, beyond which the small intestine begins.
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:
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:
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:
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:
112
Patients with ulcerative colitis can occasionally have aphthous ulcers involving the tongue, lips, palate and pharynx
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 inflammation of subcutaneous tissue involving the lower extremities Pyoderma gangrenosum, which is a painful ulcerating lesion involving the skin
Prepared by:
Deep venous thrombosis and pulmonary embolism

Autoimmune hemolytic anemia
clubbing,
Primary sclerosing cholangitis, or inflammation of the bile ducts
Prepared by:
115
Similar conditions The following conditions may present in a similar manner and should be excluded:

Crohn's disease Infectious colitis,
which is typically detected on stool cultures
Pseudom embranous
colitis, or Clostridium difficile-ssociated colitis, bacterial upsets often seen following administration of antibiotics
Ischemic colitis,
inadequate blood supply to the intestine, which typically affects the in patients with previous pelvic radiotherapy
elderly
Radiation colitis
Chemical colitis
resulting from introduction of harsh chemicals into the colon from an enema or other procedure.
Prepared by:
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:
117
Comparisons of various factors in Crohn's disease and ulcerative colitis

Crohn's Disease
Involves terminal ileum Commonly
Ulcerative Colitis
Seldom
Involves colon? Involves rectum? Peri-anal involvement

Bile duct involvement? Distribution of Disease
Usually Seldom Commonl

Not associated Patchy areas of inflammation
Always Usually Seldom

Higher rate of Primary sclerosing cholangitis Continuous area of inflammation
Endoscopy
Depth of inflammation
Prepared by:
Linear and serpiginous (snake-like) ulcers

May be transmural, deep Susana into tissues MSN P. Arellano, RN, MAN,
Continuous ulcer
Shallow, mucosal
118
Comparisons of various factors in Crohn's disease and UC (Cont.)

Fistulae, abnormal passageways between organs Biopsy Commonly Seldom
Can have granulomata
Crypt abscesses and cryptitis
Surgical cure ?
Smoking
Usually cured by removal of colon, can be followed by po uchitis Higher risk for smokers Lower risk for smokers
Often returns following removal of affected part
Autoimmune disease
Generally regarded as an autoimmune disease Lower than ulcerative colitis

No consensus
Cancer risk?
Prepared by:
Higher than Crohn's

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:
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:
121
Prepared by:
122
Prepared by:
123
Prepared by:
124
Prepared by:
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:
126
Colonic pseudopolyps of a patient with intractable ulcerative colitis. Colectomy specimen.
Prepared by:
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:
128
Prepared by:
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:
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:
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.
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:
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:
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 5-aminosalicyclic 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.
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:
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.
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.
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.
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:
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:
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.
The 4b7 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:
143
This agent inhibits the binding of 4b7 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 4b7 on lymphocytes disrupts lymphocyte migration into inflamed GI mucosa, thus providing a potential therapeutic option for patients with UC.
Prepared by:
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:
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.
Moderate
Severe Extensive Colitis NO Remissio n NO Remissio n CsA AZA / 6-MP
High dose 5-ASA Remission High dose maintenance

Prepared by:
Steroids
Remission
Remission
Failure
5-ASA
AZA/6-MP maintenance Colectomy

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:
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
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:
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:
151
GLOMERULONEPHRITIS
Prepared by:
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:
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:
154
SIGNS AND SYMPTOMS

Flank pain Hematuria Hipertension Generalized edema Proteinuria Elevated serum creatinine
Prepared by:
155
GENRALITIES
G L O M E R U LA R I N J U R Y
CLINICOPATHOLOGIC PRIMARY MECHANISMS CORRELATION BETWEEN SITE AND PRESENTATION CLASIFICATION

Prepared by:
GENERALITIES
Prepared by:
157
GLOMERULI
Prepared by:
158
GLOMERULI
Prepared by:
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.
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)
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:
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.

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:
164
NOMENCLATURE
Diffuse: affect > 50% of glomeruli.
Focal: affect < 50% of glomeruli. Global: affect > 50% of glomerular tuft. Segmental: < 50% of glomerular tuft
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 Susana P. Arellano, RN, MAN, MSN Prepared by: 166
GENRALITIES

Prepared by:
CLINICOPATHOLOGIC
Prepared by:
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
Prepared by:
Immune Susana P. Arellano, RN, idiopathic, postinfectious, complex GN, MAN, MSN 169
Crescentic GN
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:
Focal proliferative GN
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:
171
Mesangial proliferative GN
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:
172
Membanoproliferative GN
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:
Deposition diseases
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:
174
GENRALITIES

Prepared by:
Primary Mechanisms of Glomerular Injury
Prepared by:
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
Metabolic
Defects
Hyperglicemia Fabri`s disease
Glomerular Disease
Diabetic nephropathy Focal segmental glomerulosclerosis
Prepared by:
178
Hemodynamic
Defects
Systemic hypertension Intraglomerular hypertension
Glomerular Disease
Hypertensive nephrosclerosis Secondary focal segmental glomerulosclerosis
Prepared by:
179
Toxic
Defects
E. Colli derived verotoxin Therapeutic drugs (NSAIDs)
Drugs (heroin)
Glomerular Disease
Thrombotic microangiopathy
Minimal change disease

Focal segmental glomerulosclerosis
Prepared by:
180
Deposition
Defects
Amyloid fibrils
Glomerular Disease
Amyloid nephrophathy
Prepared by:
181
Infectious
Defects
HIV Subacute bacterial endocarditis
Glomerular Disease
HIV nephropathy Immune complex glomerulonephritis
Prepared by:
182
Inherited
Defects
Defect in gene for a 5 chain of type IV
collagen Abnormally thin basement membrane
Glomerular Disease
Alport`s syndrome Thin basement membrane disease
Prepared by:
183
GENRALITIES

Prepared by:
Correlation between Site of G. I. And Clinicopathologic Presentation.
Prepared by:
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
Mesangial Cell
Physiologic Role
Controls glomerular filtration surface area
Response to Injury
Proliferation / increased matrix

Mesangioproliferative GN / glomerulosclerosis
Prepared by:
187
Basement membrane
Physiologic Role
Prevents filtration of plasma proteins
Response to Injury
Proteinuria

Membranous nephropathy
Prepared by:
188
Visceral epithelial cell

Physiologic Role
Prevent infiltration of plasma proteins
Response to Injury
Proteinuria

Minimal change disease
Prepared by:
189
Parietal ephithelial cell

Physiologic Role
Maintains Bowman`s space
Response to Injury
Crescent formation

Crescentic GN
Prepared by:
190
GENRALITIES

Prepared by:
CLASSIFICATION
Prepared by:
192
INMUNOLOGIC
Antibody-mediated injury
Other mechanisms of antibodymediated injury
Antineutrophil Cytoplasmic Antibodies (ANCA) Antiendothelial Cell Antibodies
C3 Nephritic Factor
Cell-mediated injury
NONIMMUNOLOGIC
Metabolic
Diabetic nephropathy Other Metabolic Disease
Hemodynamic
Systemic Hypertension Glomerular Hypertension
Toxic glomerulopathies
Deposition Disease
Infectious Causes
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.
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:
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 cross-react withe intrinsic glomerular AG. (molecular mimickry).
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.
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:
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:
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:
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:
202
NONIMMUNOLOGIC
Metabolic
Diabetic nephropathy Other Metabolic Disease
Hemodynamic
Systemic Hypertension Glomerular Hypertension
Toxic glomerulopathies
Deposition Disease
Infectious Causes
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 Prepared by: 204 renal cells. Susana P. Arellano, RN, MAN, MSN
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.
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:
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:
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.
Inherited
Alport`s syndrome: The GMB is irregular with longitudinal layering, thickening, and patients develop hematuria, progresive glomerulosclerosis, and renal failure.
Prepared by:
209
CLINICAL PRESENTATIONS
1)Acute nephritic syndrome 2) Asymptomatic abnormalities of the urinary sediment 3) Chronic glomerulonephritis 4) nephrotic syndrome
Prepared by:
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 Prepared by: Susana P. Arellano, RN, MAN, MSN 211 cells.
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:
212
PP
Glomerular injury
Inflammatory glomerular capillary
CLINICAL FEATURES
RED BLOOD CELL CASTS PROTEINURIA HEMATURIA
Perfusion glomerular capillary FG reabsorption

Tubular H2O volume Extracelular Volume
Prepared by:
AZOEMIA
Na and
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:
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)
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:
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.
Prepared by:
Differential diagnosis: Good passteur`s syndrome

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 Prepared by: 218 nodosa. Susana P. Arellano, RN, MAN, MSN
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.
Hypersensitivity
Prepared by:
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
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
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
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:
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
IgE-binding Fc recepors
FcR: high affinity receptor of IgE on mast cell/ basophil, activate mast cell/ basophil FcR:low affinity
Prepared by:
226
Mediators released by mast cells

Primary mediators (preformed): heparin, histamine, neutral protease, eosinophil & neutrophil chemotactic factors, provoke early phase(immediate) reaction Secondary mediators(newly synthesized) : leukotrienes(LTB4, LTC4 and LTD4), PGD2, PAF, CKs(IL-4, GM-CSF), induce late phase reaction
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
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 neutrophils infiltration.
Prepared by:
The mechanism ofArellano, RN, MAN, MSN typehypersensitivity Susana P.
230
Typical diseases of anaphylaxis

Systemic anaphylaxis(anaphylactic shock): fatal, venom from bee, wasp; drugs such as penicillin, antitoxins, etc. Localized anaphylaxis(atopy): the tendency to manifest localized anaphylaxis is inherited and called atopy. typical diseases: asthma, hayfever, eczema, food allergy, etc.
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.
Food allergies: diarrhea, vomiting, wheal and flare reaction Atopic dermatitis: eczema, urticaria. itch, desquamation, pachyderma
Prepared by:
233
Prepared by:
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 anaphylactic shock
Atopic allergies and their treatment

Mediated by IgG and/or IgM Mechanism: Ag present on the surface of cells immunity activationAbtissue damage/ dysfunction Tissue damage caused by: Opsonic adherence: phagocytosis Complement: membrane damage ADCC: cell destruction
Mechanism of tissue damage of type hypersensitivity Prepared by: Susana P. Arellano, RN, MAN, 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:
239
Heamolytic diseases of newborn

Rh incompatibility: Rh blood groups Rh- mother has the first Rh+ baby mother sensitized by babys erythrocytes anti-Rh IgG Mother has the second Rh+ baby IgG enter the fetus through placenta destruction of fetal RBC
Prepared by:
Hemolytic disease of the newborn due to rhesus incompatibility

241
Drug-induced hemolytic anemia

Drug adsorb RBC proteinsAnti-RBC IgG/IgMcomplement, opsonization, ADCC RBC lysis, anemia
Prepared by:
242
Graves disease and myasthenia gravis

Special class of type hypersensitivity, Autoimmune diseases, tissue/organ dysfunction Graves disease: anti-TSH receptor Myasthenia gravis: anti-acetylcholine receptors
Prepared by:
243
Prepared by:
Graves disease Arellano, RN, MAN, MSN Myasthenia gravis Susana P. 244
Participate by IgG/IgM, induced by deposition of immune complex (IC) Formation of IC: Excess of antigen over a protracted period Deposition frequently observed: bloodvessel walls, synovial membrane of joints, glomerular basement of kidney
Mechanism of type hypersensitivity

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
Immune complex-mediated (type ) hypersensitivity


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

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
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
Immune pathogenesis
CD8+CTL: primed CTLAg:MHC perforin/ Fas-FasLtarget cell death
Prepared by:
252
Prepared by:
253

Insulin-dependent diabetes mellitus (IDDM): insulin-producing cells Multiple sclerosis(MS): central nervous system, myelin Ag Contact dermatitis: foreign low molecular weight materials, hapten-carrier, topical Infectious diseases: tuberculosis Others: hashimotos thyroiditis, IBD
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:
256
Prepared by:
257
Summary
Therapy for typehypersensitivity: Allergen avoidance Hyposensitivity Drug treatment: antihistamines, adrenaline
Prepared by:
258
Anaphylaxis
IgE Mediated Hypersensitivity
Prepared by:
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 Susana P. Arellano, RN, MAN, MSN stings Prepared by:
260
History
1st recorded 2640BC in hieroglyphics
bee sting of a pharoah
Richet & Portier
South Seas Man-o-war coined term anaphylaxis
Prepared by:
261
IgE
Binds irreversible to FcRI receptors on mast cells, basophils, and eosinophils Is usually for parasitic infections E heavy chain
Prepared by:
262
Prepared by:
263
Prepared by:
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 Susana P. Arellano, RN, MAN, MSN Prepared by: 265
Prepared by:
266
Prepared by:
267
IgE FcRI Receptor
Prepared by:
268
Symptoms
Peripheral vasodilation
vascular permeablility (edema)
Bronchospasm Cardiac arrhythmias Smooth muscle contractions
Prepared by:
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
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:
271
Sensitization & Response
Prepared by:
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
Prepared by:
Inflammatory mediators are released upon degranulation

Prepared by:
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:
276
Prepared by:
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:
Tissue Effects of Histamine

Cardiovascular

Decreased blood pressure Increased heart rate Edema (separation of endothelial cells & increased permeability) broncho constriction Smooth muscle contraction and diarrhea
Respiratory
Gastrointestinal
Prepared by:
Skin
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

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 MAN, MSN Prepared by: Susana P. Arellano, RN,
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:
282

Immunodeficiency Disease: Prepared By: 1 Susana P. Arellano, RN, MAN, MSN

Încărcat de

Informații document

Descriere originală:

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

Immunodeficiency Disease: Prepared By: 1 Susana P. Arellano, RN, MAN, MSN

Încărcat de

Drepturi de autor:

Formate disponibile

Immunodeficiency Disease

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Is HIV and AIDS the same thing?

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

New HIV Infections in 2002 by Age Group

Susana P. Arellano, RN, MAN, MSN

Four Stages of HIV

Susana P. Arellano, RN, MAN, MSN

HIV antibodies are detectable in the blood

Stage 4 - HIV AIDS

Opportunistic Infections associated with AIDS

Prepared by: Susana P. Arellano, RN, MAN, MSN 13

Opportunistic Infections associated with AIDS

Prepared by: Susana P. Arellano, RN, MAN, MSN 14

Modes of HIV/AIDS Transmission

Susana P. Arellano, RN, MAN, MSN

Through Bodily Fluids

Susana P. Arellano, RN, MAN, MSN

Through IV Drug Use

Increases the chances of contracting HIV

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Before Birth During Birth Postpartum

After the birth

Susana P. Arellano, RN, MAN, MSN

Testing Options for HIV

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Results issued only to test recipient

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Blood Detection Tests

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Non-Nucleoside Transcriptase inhibitors

Viramune (Nevirapine) Norvir (Ritonavir)

Issued in an event where antiretroviral drugs are not available

Susana P. Arellano, RN, MAN, MSN

Four ways to protect yourself?

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

When Using A Condom Remember To:

Susana P. Arellano, RN, MAN, MSN

Needle Exchange Program

Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

Race: is no association with race.

Mortality and morbidity.

insufficiency.Susana P. Arellano, RN, MAN, MSN

Susana P. Arellano, RN, MAN, MSN

- polyglandular autoimmune syndrome type2:

Chronic granulomatous diseases:

Infiltrative metabolic disorders :

Acquired immunodeficiency syndrome: as a result of invasion of