Question

Part II – Joyce Snyder

After the high school group finishes their tour, Dr. Williams sees two patients.

Joyce Snyder is a biochemist working for a bio-warfare lab at a university. She is working on a project using sarin as a model substance. Suddenly, while working, the lab alarms go off and Joyce accidentally knocks a vial of sarin over and a bit of the liquid splashes onto her arm between her gloves and lab coat.

She suddenly starts to feel dizzy, her heart starts pounding harder than ever, and she has shortness of breath. She feels incredibly sluggish and tries to get to the exit. As she approaches the lab door, her muscles cramp and she falls down and hits her head, knocking her unconscious. Her colleagues from across the hall happen to see her fall and call for help. Joyce is given oxygen and taken to the nearby hospital.

Joyce is admitted to the hospital and Dr. Williams examines her. Joyce is unconscious but seems to be experiencing some paralysis, so Dr. Williams orders blood work. The results are listed in Table 1 below, the top line represents her initial readings; the following three rows are for subsequent time points. You must work with your team members to interpret all clinical values.

Dr. Williams looks over the results and knows from Joyce ’s colleague that she is a bioweapons biochemist. Dr. Williams figures out that Joyce has been working on synthesizing a new sarin-like biochemical weapon and suspects she has a type of poisoning that is like that of sarin.

Questions [Critical Thinking]

2. What symptoms is Joyce experiencing?

3. What is the role of AChE in the NMJ?

4. Examine Table 1 below. Fill-in the normal range of values for each of the variables in the last (blank) row.

Table 1. Lab values for Joyce Snyder. (Serum)

Time Point

BP

Temp.

(°F)

Hemat.

(%)

Glucose

(mg/dL)

Na+

(mEq/L)

K+

(mEq/L)

AChE

Activity

(% of normal)

Thyroxine

(pmol/L)

Serum

Triiodothyronine (FT3)

(pg/dL)

Antibodies for Ach Receptors

1

105/65

99.4 °F

37.5%

88 mg/dL

139 mEq/L

3.8 mEq/L

44%

9.1 pmol/L

112 pg/dL

none

2

108/70

100.1 °F

38.0%

100 mg/dL

135 mEq/L

5.0 mEq/L

42%

8.5 pmol/L

100 pg/dL

none

3

130/92

98.0 °F

36.2%

95 mg/dL

132 mEq/L

5.2 mEq/L

50%

10.0 pmol/L

150 pg/dL

none

4

115/85

99.2 °F

36.9%

80 mg/dL

144 mEq/L

3.5 mEq/L

88%

12.0 pmol/L

82 pg/dL

none

Normal Values

Questions [Critical Thinking and Communication and Quantitative]

5. Which of Joyce ’s levels are abnormal and at what time point?

6. What is the mechanism of action of sarin or a sarin-like chemical?

7. How would exposure to a sarin-like poison affect the amounts of Na+ going into the muscle cell? Explain why.

8. How would exposure to a sarin or sarin-like chemical affect Ca2+ levels inside the sarcoplasmic reticulum? Why?

9. How do these altered Ca2+ levels affect the position of the actin and myosin filaments? Why/how?

10. What needs to happen to Joyce’s post-synaptic membrane to remedy her paralysis? Physiologically what do we need more of, and where?

Answer 1

Sarin: Sarin is a neurotoxin , O - isopropyl methyl phosphnoflouridate, used as a chemical weapon.

2. Joyce Synder is experiencing the symptoms of Sarin toxicity. Sarin is a neurotoxin, that act as Cholinestrase inbihibitors at receptor sites, in Red blood cells and in plasma. Choliesrases are catalysts that stimulates the hydrolysis of neurotransmitters, that are cholinergic in nature. As a result there will be accumulation of Acetylcholine in the tissues and all over the body. It can affect Neuromuscular-junctions and nervous system. Sarin poisoning causes the symptoms such as chest tightness, blurring of vision, bowel and bladder evacuation, running nose, excessive tears, convulsions and paralysis.

3 . Role of NMJ and AChE

NMJ : Neuromuscular junction is the synapse of the axon terminal of a motor neuron with muscle. In Simple terms NMJ is the junction between a neuron( nerve cell ) and a muscle . Role of NMJ is to facilitate the conversion or transmission of action potential from presynaptic motor neuron to post synaptic muscle fiber.

ACh E : Acetylcholine Esterase is the enzyme that stimulate or catalyses the lysis or breakdown of Cholinergic neurotransmitters, especially Acetylcholine . It mainly found in NMJ and in chlolnergic synapses . AChE  inhibits the function of Acetylcholine by breaking down it.

4. Normal levels :

BP: 120/ 80 mm of Hg

Temperature:98.6

Heamatocrit: 37 to 48%

Glucose: 70 to 90 mg / dl

Sodium : 135 to 145 m/ eq/ l

Potassium : 3.6 to 5 mmol/L

AchE activity : more than 35 % indicates severe poisoning

Thyroxine : 0.7 - 1.9 ng/ dl ( 9 - 23 pmmol/ L)

Triiodo thyronine :   80 - 180ng/ dL ( 260- 480 pg / dL)

Antibodies for Ach receptors : normally none.

5.

Blood pressure: low  BP at first and second time , high at 3rd and 4th time.

Temp:

second time high, third time low

Heamatocrit: normal at all all times. ( Females : 37 to 48 %)

Glucose level : second and third time slightly high

Sodium : normal

Potassium: third time slightly high

AchE activity level : more than 35 % indicates severe poisoning.

First , second, third and fourth time indicates abnormal values and indicates poisoning.

Thyroxine : second time slightly low

Tri iodo thyronine: Too low at first, second, third and fourth time.

Antibodies for Ach receptors: normal ( usually none found).

6. Mechanism of Action of Sarin

Sarin is a neurotoxin . It is a potent inhibitor of Acetylcholine Esterase( enzyme that helps in the lysis of Acetylcholine. ). As a result Acetylcholine accumulates in the NMJ and chemical synapses. This adversely affects the muscle and nerves of the body and its normal functions.

7. As a result of Sarin's action, ACh E gets inhibited and Acetylcholine accumulates in the NMJ and chemical synapses. This accumulation stimulates cholinergic receptors to open continually for the sodium ions to get in to the muscle fibers. This results in the continuation of depolarization of the muscle cell membrane.

8. Sarcoplasmic reticulum is found in the sarcoplasm, the interfibrillar cytoplasm of striated muscles. As a result of Sarin action Acetylcholine accumulates in the NMJ and chemical synapses and it results in the continous stimulation of electrical signal in the sarcoplasmic reticulum. Troponine gets binded by the Calcium ions as a result of opening of Calcium channels by the stimulation of continous Acetylcholine activity .

( sorry . Time limit, couldn't finish . Thank you)