Question

15. immunoglobulins Clinical Models - Risk Factors, Chical Manifestations, Diagnostic Tests. Treatment and BASIC PATHOPHYSIOLOGY(chapter 1, 2, 3, 4, 5, 8, 9, 10, & 11) 1. acute and chronic gastritis 2 allergylanaphylaxis 3. HIV/AIDS 4. systemic lupus erythematosus (SLE) 5. Viral hepatitis (A, B, C) 6. tuberculosis (TB) 7. urinary tract infection (UTI) and pyelonephritis 8. meningitis 9. spinal cord injury (SCI) - spinal shock and neurogenic shock 10. multiple sclerosis (MS) 11. Parkinson's disease (PD) 12. acute and chronic pancreatitis 13. inflammatory bowel disease - Crohn's disease (CD) and ulcerative colitis (UC)

Answer 1

Acute and Chronic gastritis:which is caused by the bacterium Helicobacter pylori

acute:sudden inflammation,chronic :longterm inflammation,it can be last years or untreated.

The medical condtion is  inflammation or swelling in the protective lining of the stomach.

Risk factors:junk and spiecy foods,longterm use of medication for ingestion and acid reflux.

high salts and preservatives intake,smoking,consumption of alcohol,use of NSAIDS9ibuprofen and naproxen)/corticosteroids,

Clinical manifestations:loss of appetite,hiccups,Abdominal pain. recurrent upset stomach and nausea,Abdominal bloating

Diagnostic tests:urea breath test for check for H. pylori infections,medical history,fecal test  to check for both H. pylori and signs of bleeding, esophagogastroduodenoscopy, or endoscopy,  gastric tissue biopsy,blood tests

Treatment: combination of antacids and antibiotics

Antacids.this contain magnesium, calcium, sodium, or aluminum salts,help for neutralize stomach acids

Proton-pump inhibitors (PPIs):ex:lansoprazole and omeprazole

H2 blockers: antihistamines,used for reduce stomach acid production.

HIV/AIDS(Acquired Immune Deficiency Syndrome (AIDS) :

PATHOGENESIS:After entering a person's body,

–The Virus infects CD4 T cells and macrophages and starts to replicate in them.

–The virus induces the body system to produce antibodies specific to HIV

–The period between the actual infection and production of detectable HIV antibodies is called the window period(2-12 weeks)

–The virus is then uncoated and its genomic RNA is transcribed to pro viral DNA by enzyme reverse transcriptase. So formed pro viral DNA is integrated in T cell genome

•During this period the person is highly infectious but may not test positive on common HIV antibody tests

•Up to 30%-50% of people have a recognizable acute illness at the time of infection characterized by fever, lymphadenopathy, night sweats, skin rash, headache and cough

•Budding and syncytia formation:The infected CD4 + T cells possess budding viral particles due to multiplication, which further attack more number of CD4 + T cells resulting in syncytia formation.

Cytopathic effect:There is a quantitative depletion of CD4 + T cells due to direct cytolysis as well as qualitative defect in the form of inability of these T cells to respond to antigens.

Clinical manifestations:

•Major signs include,

–Weight loss (more than 10% of body weight).

–Chronic diarrhea of more than one month duration.

–Prolonged fever may be intermittent or continuous for more than one month

•Minor signs include,

–Persistent cough for more than one month duration

–Persistent generalized lymphadenopathy

–Pruritic dermatitis

–Recurrent oropharyngeal candidiasis

–Recurrent Herpes zoster infection

LABORATORY DIAGNOSIS OF HIV INFECTION

•Enzyme linked immunosorbent assay (ELISA) also called Antibody sandwich capture technique

•Western blot assay.

•Immunoflurosence test

•DNA recombinant technique

•Counting of CD4 + T cells

•Lymph node biopsy

•Rapid tests - particle agglutination, lateral flow membrane, through flow membrane, and comb or dipstick based assay systems.

MANAGEMENT

I. Reverse transcriptase inhibitors

1) Nucleoside reverse transcriptase inhibitors (NRTIs)

2) Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

II. Protease inhibitors (PIs)

Nucleoside reverse transcriptase inhibitors (NRTIs)

These are the derivatives of purine and pyrimidine based nucleosides and nucleotides.

These are phosphorylated intracellularly and then inhibit the viral reverse transcriptase enzyme by acting as a false substrate.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Abacavir

Didanosine

Non-nucleoside reverse transcriptase inhibitors (NNRTIs):

Delavirdine

Efavirenz

Protease inhibitors (PIs):
Amprenavir

Atazanavir

The current recommendation for treating HIV

•Minimum of 3 antiretroviral agents

•A typical regimen consists of 2 Nucleoside analogues with either a Protease Inhibitor (PI) or an NNRTI

systemic lupus erythematosus (SLE)

Definition: systemic lupus erythematosus (SLE) is a multisystem connective tissue disorder characterized by the presence of numerous auto antibodies, circulating immune complexes and widespread immunologically determined tissue damage.

SLE is caused by the interactions between susceptibility genes and environmental factors, resulting in abnormal immune responses.Hyper reactivity of T and B-lymphocytes is indicated by increased surface expression of molecules such as HLA-D and CD40L.

Clinical manifestations of SLE:

Systemic: fatigue, malaise, fever, anorexia, and weight loss.

Musculoskeletal: arthralgia, polyarthritis, myopathy, and ischemic necrosis of bone.

Cuteneous: photosensitivity, malar rash, oral ulcers, alopecia, discoid rashes, vasculitis

Hematologic: anemia, leucopoenia, lymphopenia, thrombocytopenia, splenomegaly, and lymphodenopathy

Neurologic: headache, mood disorders, seizures, stroke, TIA and cognitive disorders. Cardiopulmonary: myocarditis, endocarditis, pericarditis,coronary artey disease, pulmonary hyper tension and hemorrhages.

Thrombosis: venous, arterial.

Ocular: sicca syndrome, vasculitis, conjunctivitis, episcleritis.

Renal: protinuria> 500 mg/d, nephritic syndrome.

Treatment of SLE:

NSAIDS like salicylates doses towards their upper limit is beneficial.

Methotrexate: 10-25 mg once a week with folic acid. It should be decreased when CrCl <25 ml/min.}Glucocorticoids oral:

prednisone, prednisolone 0.5-1 mg/kg body weight per day for severe SLE. 0.07-0.3 mg /kg body weight for mild SLE.

Methyl prednisolone IV: for severe disease 1 g iv every 3 days.

Cyclophosphamide: IV 7-25 mg/kg every month for 6 months. ORAL 1.5-3 mg/kg per day.

Mycophenolate mofetil: 2-3 g/day

Azathioprine: 2-3 mg/kg per day PO decrease frequency of dose if Crcl is <50 ml/min.

parkinson's disease

•A chronic CNS disorder characterized by slowness and poverty of purposeful movements, muscular rigidity and tremor

–Tremor at rest

–Rigidity

–Hyperkinesias

–Bradykinesia

–Postural Instability

–Difficulty in stopping, starting and turning while walking

Epidemiology

•Incidence increases with age

•Approximately affects 1% world wide

•Age of onset for men and women and incidence is equal

•Prevalence increases with age

•Cause of Parkinson’s is not known

Stages of Parkinson’s

•Based on the severity of the disease

–Stage I – Unilateral involvement

–Stage II – Bilateral or midline; no impairment of balance

–stage III – Bilateral involvement

–Stage IV – Fully developed, severely disabled

–Stage V – Confined bed or chair unless aided

•Diagnosis is based on the presence of tremor, rigidity and bradykinesia, either together or alone.

•Many factors influence therapeutic decision-making, including the degree of confidence in the diagnosis, functional and social disability, age and the psychological and neurological condition of the patient.

Pharmacological Management

Early Parkinson’s disease

•It might be appropriate not to treat mild disease if symptoms are not causing disability or handicap.

•While levodopa is the most efficacious treatment, a dopamine agonist may sometimes be given alone in young patients (less than 50 years of age).

•Anticholinergic agents can also be the initial treatment in young patients with tremor-dominant disease.

levodopa+benserazide :50mg/12.5mg orally, 3 times daily, after meals, increase to 100mg/25mg 3 times daily over 1 to 2 weeks, depending on response.

levodopa+carbidopa :•50mg/12.5mg orally, 3 times daily, after meals, increase to 100mg/25mg 3 times daily over 1 to 2 weeks, depending on response.

•An increase in the total daily dose and the frequency of dosing is eventually necessary in most patients.

•In some patients, higher doses are necessary to control symptoms adequately.

•Dietary factors such as a high protein meal can impair the response to an individual dose.

Additional therapy

•The dopamine agonists, bromocriptine, cabergoline and pergolide, are not as effective as levodopa and are usually used in conjunction with levodopa.

•They may help reduce motor fluctuations and have the advantage of enabling the dose of levodopa to be lowered with a consequent lessening of the drug-induced dyskinesias.

•They should be used cautiously in the elderly because of possible acute psychotic reactions

Bromocriptine 2.5mg orally or

cabergoline 0.5mg orally, daily, up to 5mg once daily. Increase in increments of 0.5 to 1mg weekly up to optimal dose or

pergolide 0.05mg orally, twice daily, up to 1.5mg 3 times daily or

Entacapone 200mg orally initially, with each dose of levodopa. (Usual effective daily dose is 800 to 1400mg)

tremor.

•In young patients, an anticholinergic agent may be added to produce better control of tremor.

•benztropine 1 to 2mg orally, daily, up to 2mg twice daily    OR   

•benzhexol 2mg orally, 2 or 3 times daily, up to 5mg 3 times daily    OR

•biperiden 1mg orally, 2 times daily, up to 2mg, 3 to 4 times daily

Advanced Parkinson’s disease

Drug	Usual dosage	Adverse effects
Dopaminergic
levodopa+benserazide	100/25 to 250mg/62.5mg 3 times daily	·        nausea and vomiting (initially), involuntary movements, psychosis, postural hypotension, constipation
levodopa+carbidopa	100/25 to 250mg/50mg 3 times daily
Dopamine agonists
bromocriptine	5 to 15mg 2 times daily	·        neuropsychiatric, postural hypotension, erythromelalgia, fibrosis (pleuro, pulmonary, retroperitoneal)
cabergoline	0.5 to 5mg daily
pergolide	0.05 to 1.5mg 3 times daily

Drug	Usual dosage	Adverse effects
Dopaminergic
levodopa+benserazide	100/25 to 250mg/62.5mg 3 times daily	·        nausea and vomiting (initially), involuntary movements, psychosis, postural hypotension, constipation
levodopa+carbidopa	100/25 to 250mg/50mg 3 times daily
Dopamine agonists
bromocriptine	5 to 15mg 2 times daily	·        neuropsychiatric, postural hypotension, erythromelalgia, fibrosis (pleuro, pulmonary, retroperitoneal)
cabergoline	0.5 to 5mg daily
pergolide	0.05 to 1.5mg 3 times daily

Viral Hepatitis

¨Inflammation of liver due to,Virus infections – Hep A, B, C, D

Medications – methyldopa, INH

Immunologic abnormalities – autoimmune hepatitis

Acute or chronic. Chronic if hepatitis is for 6M or longer

Sign & Symptoms

Anorexia,Nausea,Diarrhea,Fever,Fatigue,Jaundice,Malaise,Abdominal discomfort,Dark urine

Pharmacotherapy

¨No specific treatment available

¨Supportive treatment

¨Liver transplantation is an option in hepatic failure