Definition of Terms

1. Alpha 1-antitrypsin - an acute phase protein that increases in acute inflammatory reactions

2. Anti-Centromere Antibody - an antibody that targets the centromere, a component of the chromosomes found in all
nucleated cells

3. Angiotensin I converting enzyme - is the key part in regulating blood pressure in the renin angiotensin system, converts
Angiotensin I to Angiotensin II

4. Anti-Smooth Muscle Antibody - antibodies directed against actin, a protein found in smooth muscle and other tissue
especially the liver

5. Anti-Scleroderma Antibody - antinuclear antibody specific for the diagnosis of scleroderma

6. Anti-Sjogren Antibody - antinuclear antibodies which are extracted from human B lymphocytes
7. Antinuclear Antibody - antibodies that react against normal components of a cell nucleus
8. Acetylcholine Receptor Antibody - antibodies that bind to the acetylcholine receptors of the
post-synaptic neuromscular junction
9. Cervical Mucus Test - used to indicate the timing of ovulation & evaluation of infertility
10. Sims-Huhner Test - also known as postcoital test (PCT) is designed to assess the viability of the
sperm in the cervical mucus several hours after coitus
Acetylcholine

Receptor Antibody

- First neurotransmitter discovered

- Main neurotransmitter

at the neuromuscular junction.

NICOTINIC ACETYLCHOLINE RECEPTORS

IONOTROPIC

NICOTINE

METABOTROPIC

MUSCARINIC ACETYLCHOLINE RECEPTORS

MUSCARINE

Types of ACHR

- BINDING

- BLOCKING

- MODULATING

ASSAY OF BINDING-ACETYLCHOLINE RECEPTOR ANTIBODY:

- Measure the antibody that binds to I-a-bungarotoxin-labeled Acetylcholine receptors

- LABORATORY TESTING:

- RADIOIMMUNOASSAY (RIA)
 - ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)

- Antibody present in almost 90% of Myasthenia Gravis patients

MYASTHENIA GRAVIS

● Myasthenia gravis is an autoimmune disorder caused by autoantibodies against the nicotinic acetylcholine receptor on the
postsynaptic membrane at the neuromuscular junction

● Myasthenia gravis is caused by variable block of neuromuscular transmission related to an immune-mediated decrease in
the number of functioning nicotinic acetylcholine receptors

● In approximately 80% of cases, antibodies to the skeletal muscle nicotinic acetylcholine receptor are present and lead to
loss of receptor function

● Some patients seronegative for these antibodies have antibodies against the muscle-specific receptor tyrosine
kinase(MuSK) that is involved in the clustering of acetylcholine receptors during development and is also expressed in
mature neuromuscular junctions

● Sites of involvement in disorders of neuromuscular transmission. At left, normal transmission

● involves depolarization-induced influx of calcium (Ca) through voltage-gated channels. This stimulates release of

● acetylcholine (ACh) from synaptic vesicles at the active zone and into the synaptic cleft. ACh binds to ACh receptors

● and depolarizes the postsynaptic muscle membrane. At right, disorders of neuromuscular transmission result from

● blockage of Ca channels (Lambert-Eaton syndrome or aminoglycoside antibiotics), impairment of Ca-mediated ACh

● release (botulinum toxin), or antibody-induced internalization and degradation of ACh receptors (myasthenia gravis)

Clinical findings

● Patients present with a history of weakness and fatigability of muscles on sustained or repeated activity
 ● The external ocular muscles are affected initially in about 50% and eventually in 90% of cases

● Ptosis (weakness of levator palpabrae) that is often partial and may be unilateral, is a common presenting feature; it is
often fluctuating in nature

● The presence of an eyelid twitch response (Cogan’s lid twitch) is characteristic of myasthenia gravis

● There may also be a weakness of orbicularis oculi leading to difficulty in eye closure

● Dysphonia may result from laryngeal weakness

● Dysphagia is a common presentation due to the fatigue of muscles involved in chewing and swallowing

Edrophonium Test or Anticholinesterase Test

● high sensitivity for generalized MG- 60% to 95% of patients with ocular myasthenia and in 72% to 95% with generalized MG

● The edrophonium test is associated with a low, but serious risk of bradycardia and/or hypotension

● The dose is administered in two parts because some patients react to edrophonium with side effects

ICE PACK

● application of an ice pack to lids of the affected eyes

● does not require cardiac monitoring

● Response is explained on the basis of improvement in safety factor of the neuromuscular junction with local cooling
presumably caused by slowing the kinetics of AChRs.

● An ice pack is applied to the affected upper eyelid for 2-5 minutes. A positive test is the improvement of ptosis by > 2mm or
more. This transient improvement in ptosis is due to the cold decreasing the acetylcholinesterase break-down of
acetylcholine at the neuromuscular junction.

ACHR AB test

● The presence of anti-AChR antibodies is virtually diagnostic of MG, but a negative test does not exclude the disease.

● now considered a diagnostic ‘‘gold standard’’.

● These antibodies are found in nearly 80%–85% of patients with generalised myasthenia gravis and 50%–60% cases of ocular
myasthenia gravis

● mild disease can be associated with a high titre and a severe disease may be associated with a low titre

● decrease in titre means favourable response to the treatment

Anti-MuSK antibodies

● It is well known that about 10%–20% of patients do not have anti-AChR antibodies in their sera

● This region in the neuromuscular junction is a protein called muscle specific protein kinase or MuSK

● MuSK antibodies are rarely present in AChR antibody–positive patients or in patients with MG limited to ocular muscles.

● This group found antibodies to MuSK in some of the patients with seronegative myasthenia gravis but not in sera from
normal persons.
Electrodiagnostic Testing or Electrophysiological tests

● Electrophysiological tests include repetitive nerve stimulation test and single fibre electromyography

● Anti-AChE medication is stopped 6–24 h before testing

● Electric shocks are delivered. It is best to test weak muscles or proximal muscle groups

● in myasthenic patients, there is a rapid reduction of >10–15% in the amplitude of the evoked responses.

● This test is virtually always positive in generalised myasthenia gravis but may be negative in nearly 50% cases of ocular
myasthenia gravis

● Overall, sensitivity is about 75%.

● Single fibre electromyography is the most sensitive test (>95%) in myasthenia gravis

● The limitations of the electrophysiological tests include their false positivity in any condition with a reduced safety factor at
the neuromuscular junction *example

LEMS

- a presynaptic disorder of the neuromuscular junction that can cause weakness similar to that of MG

- muscles of the lower limbs are most commonly affected

- caused by autoantibodies directed against calcium channels at the motor nerve terminals

- Mostly associated with small-cell carcinoma of the lung

 - Tests:

- Radioimmunoassay (RIA)

- Electrophysiological studies, are done to measure muscle response and muscle strength

- Chest CT

- Other Associated Disorders

- Thymoma

- Hyperplasia

- Hashimoto’s thyroiditis

- Graves’ disease

- Rheumatoid arthritis

- Lupus erythematosus

- Skin disorders

- Family history of autoimmune disorder

MG

Symptoms- Ptosis, Diplopia

Autonomic changes- weakness worsens upon activity; absent

Location of Defect- postsynaptic

Autoantibody- achr

Association- thymoma

Tensilon Test- improves

LEMS

Proximal muscles of the lower limb

Weakness improves upon activity

Present

PREsynaptic

Antibody against calcium channels

Small Cell Lung Carcinoma

No improvement

The Sims‐Huhner or postcoital test (PCT) infertility test is used to evaluate how sperm interacts with the cervical mucus. This test is
one of the important steps in the investigation of the infertile couple.
The quality of preovulatory cervical mucus is described in terms of volume, stretchability, cellularity and drying pattern (ferning), and
measures the ability of the sperm to penetrate mucus & maintain motility.

Normal finding : cervical mucus adequate for sperm penetration,

survival & transmission ; 6 – 20 active motile sperm / HPO

Alpha-1-Antitrypsin (AAT) is known to be a normally occurring glycoprotein. As an acute-phase protein, it increases in acute
inflammatory reactions. AAT inhibits the action of some proteolytic enzymes, specifically trypsin and plasmin. The activity of these
proteases during digestion of microorganisms and other debris or in opposition to an irritant, is completely inhibited by this acute-
phase protein. When individuals whose AAT activity is defective, they frequently develop liver or lung conditions.

Deficiency of alpha-1-antitrypsin is usually associated with emphysema.

DEFINITION OF TERMS:

1. EMPHYSEMA – Destruction & enlargement of the air spaces of the alveoli/ lung tissue.

2. ELASTASE – A protease released by activated inflammatory cells. Destroys Elastin

3. ELASTIN – A highly elastic protein responsible for the recoil strength of the lung’s tissues. Keeps airways open.

PATHOPHYSIOLOGY:

4. 1. Alveolar macrophage phagocytose pathogens

5. 2. Cytokine release

6. 3. Inflammatory cells arrive, releasing protease to kill pathogens.

7. 4. Decreased AAT can’t stop elastase (protease).

8. 5. Elastase destroys elastin.

9. DIAGNOSIS:

10. AAT is a major faction of alpha-1 globulin. Abnormal levels are often detected by the lack of alpha 1- globulin band on
serum protein immunoelectrophoresis. Methods used to confirm electrophoresis results include radial immunodiffusion
and automated immunonephelometric assays. Alpha 1- antitrypsin being an acute phase reactant can also be increased in
cases of inflammation, therefore an increase in ESR can also be expected.Other tests which can support are arterial blood
gases analysis in cases of emphysema and enzymatic assays in cases of liver involvement and damage.

Anticentromere antibody (ACA)is an antibody which reacts with centromeric chromatin of metaphase and interphase cells. It is one
of Antinuclear Antibodies which is an autoantibody that targets the body’s own tissues. This is known to be highly selective for
CREST syndrome and found infrequently in the serum of patients with Systemic Lupus Erythematosus (SLE), systemic sclerosis and
Mixed Connective Tissue Disease (MCTD).

ACA is sensitive and is specific for patients with CREST syndrome. CREST syndrome is a variant of systemic sclerosis. Out of the two
types of systemic sclerosis,CREST syndrome is under the category of limited cutaneous systemic sclerosis due to its five limited
symptoms.

The "E" stands for esophageal dysmotility, which causes difficulty in swallowing.

The "S" represents sclerodactyly which is tightening of the skin causing the fingers to bend.
Lastly, the letter "T" is for telangiectasia which is characterized by tiny red areas due to dilated vessels on the skin of the fingers,
face, or inside of the mouth.

Other tests that can support the diagnosis of CREST syndrome include the detection of antinuclear antibodies (ANA), and evaluation
of calcium and phosphate levels to exclude metabolic involvement. Indirect immunofluorescence (IF) using rapidly dividing HEp2
cells is used for detection of detected antinuclear antibodies. It is confirmed using Fluorescence enzyme linked immunoassay using
CENP-B antigen, IgG antibodies are detected or systemic sclerosis antibody immunoblotting. IF positive, titer is at 1:80-1:640.

SCLERODERMA

Scleroderma is an autoimmune disorder that may involve changes in the skin, blood vessels, muscles, and internal organs. There are
two main types: localized scleroderma and systemic scleroderma.

In patients with scleroderma, the immune system triggers other cells to produce too much collagen (a protein). This extra collagen is
deposited in the skin and organs, which causes hardening and thickening

protease (also called a peptidase or proteinase) is an enzyme that catalyzes (increases the rate of) proteolysis, the
breakdown of proteins into smaller polypeptides or single amino acids. They do this by cleaving the peptide bonds within
proteins by hydrolysis, a reaction where water breaks bonds

Proteases can be classified into seven broad groups:[1]

 Serine proteases - using a serine alcohol

 Cysteine proteases - using a cysteine thiol
 Threonine proteases - using a threonine secondary alcohol
 Aspartic proteases - using an aspartate carboxylic acid
 Glutamic proteases - using a glutamate carboxylic acid
 Metalloproteases - using a metal, usually zinc
 Asparagine peptide lyases - using an asparagine to perform an elimination reaction (not requiring water)
 Alpha-1 antitrypsin deficiency


 Alpha-1 antitrypsin (AAT) deficiency is a condition in which the body does not make enough of AAT, a protein that
protects the lungs and liver from damage. The condition can lead to COPD and liver disease (cirrhosis).
 Causes
 AAT is a type of protein called a protease inhibitor. AAT is made in the liver and it works to protect the lungs and liver.
 AAT deficiency means there is not enough of this protein in the body. It is caused by a genetic defect. The condition is most
common among Europeans and North Americans of European descent.
 Adults with severe AAT deficiency will develop emphysema, often before 40 years of age. Smoking can increase the risk of
emphysema.

Acute on chronic respiratory acidosis Respiratory acidosis and metabolic alkalosis

Volume depletion

Diuretics

Vomiting
Reexacerbation of COPD
Severe hypokalemia

Steroids

Posthypercapnic alkalosis
Respiratory acidosis and metabolic acidosis Resp. acidosis, met. acidosis, and met. alkalosis

Severe hypoxemia

Acute pulmonary edema

Renal failure

Sepsis Renal failure and vomiting

Severe hypoxemia and volume depletion
Shock Sepsis and hypokalemia

Diabetes mellitus

Acute alcoholism

Exogenous poisoning

Respiratory acidosis

Mechanisms of compensation consist of an increased renal reabsorption of bicarbonate and increased excretion of H

COPD’s pathology includes loss of tissue elasticity, emphysematous bullae, small airway obstruction, and destruction of
lung parenchyma. Persons with COPD are typically separated into one of two catagories: “pink puffers” (normal PaCO 2,
PaO2 > 60 mmHg) or “blue bloaters” (PaCO2 > 45 mmHg, PaO2 < 60 mmHg). Pink puffers have severe emphysema, and
characteristically are thin and free of signs of right heart failure. Blue bloaters, on the other hand, have frequent episodes
of right heart failure, and produce copious sputum resulting in coughing and respiratory infections. Blue bloaters presents
more of a chronic bronchitis picture although they too may exhibit emphysematous changes.

Pink puffers (normal PaCO2, PaO2 > 60 mmHg) have emphysematous lung tissue destruction. Diffusing capacity is
decreased by destroyed pulmonary capillaries. ABG’s are near normal due to compensatory hyperventilation. The only
subtle changes typically are a PaO2 slightly depressed (often in the mid 70’s, resulting in mild pulmonary
vasoconstriction), and a low-normal PaCO2.

Blue bloaters (PaCO2 > 45 mmHg, PaO2 < 60 mmHg) suffer from pulmonary hypoxic vasoconstriction from the marked
hypoxia and respiratory acidosis. This in turn leads to right ventricular hypertrophy and cor pulmonale. The right heart
failure then leads to systemic venous congestion, peripheral edema, hepatic congestion, and ascites. Secondary
erythrocytosis may occur, spurred by the hypoxia. Changes on ABG’s are much more pronounced.