Case Studies Three and Four NUR 7202 - Ashley's...

Running head: CASE STUDIES THREE AND FOUR NUR 7202 1

Case Studies Three and Four NUR 7202

Ashley Peczkowski

Wright State University

NUR 7202

CASE STUDIES THREE AND FOUR NUR 7202 2

Case Study Three

1. Which of the following processes can produce postoperative hypotension?

A. Hypovolemia secondary to blood or fluid loss

B. Sepsis

C. Adrenal insufficiency

D. Perioperative myocardial infarction

E. All of the above

Postoperative hypotension can be caused by many complications such as hypovolemia

secondary to blood or fluid loss, sepsis, adrenal insufficiency, and perioperative myocardial

infarction. Fluid or blood loss is a common cause of hypotension in abdominal surgeries. There

is much controversy over how much fluid should be given during abdominal surgery because of

the delicate fluid balance necessary to maintain tissue perfusion without developing edema. Fluid

loss during abdominal surgery is related to blood loss, gastric secretion loss, and insensible fluid

loss. Insensible fluid loss is not measureable however it can be estimated based on surgery. Each

of these parameters should be closely monitored and replaced as accurately as possible.

Normovolemia with aggressive fluid replacement has been shown to reduce postoperative

mortality, promote faster recovery, increase tissue oxygenation, and increase microcirculatory

perfusion. However, this balance is often difficult to achieve and therefore the patient will

frequently experience hypotension or fluid overload. Hypotension secondary to fluid loss without

adequate fluid resuscitation results in hypovolemia, hypoperfusion, and organ dysfunction; while

fluid overload leads to tissue edema, impaired oxygenation, and predisposition to anastomotic

breakdown. Replacement of loss fluid is further complicated by extravascular fluid shifts that

develop from increased endothelial permeability secondary to release of cytokines from


mechanical stress, endotoxin exposure, ischemia-reperfusion injury, and inflammation brought

on by surgical trauma. To ensure adequate fluid resuscitation, central venous oxygen saturation

and goal directed fluid therapy should be monitored. The central venous oxygenation saturation

is an early indicator of hypoxia because it monitors the delivery consumption relationship. Low

venous oxygenation saturation levels with adequate respiratory ventilation indicate a

hypovolemic state. In the goal directed fluid therapy an esophageal Doppler probe is used to

monitor blood measurements in the descending aorta. Through this a continuous measurement of

the aorta’s blood velocity and diameter is obtained and fluid adjustments are made based on

these readings (Futier et al., 2010).

Infection and abscess formation after abdominal surgery is not an uncommon

complication due to the bacteria naturally present in the bowel. Occasionally these infections can

lead to sepsis; a condition known to cause hypovolemia. Sepsis leads to immunosuppression,

lymphocyte apoptosis, and increased vascular permeability which in turn lead to multisystem

organ failure. Before the development of multisystem organ failure, sepsis results in

subcutaneous and body-cavity edema from increased vascular permeability which creates

decreased oxygenation and microvascular collapse. Increased permeability is the result of gaps

that develop in the endothelium from displacement of binding proteins. Bacteria presence in the

blood activates the inflammatory process and the release of vascular endothelial growth factors.

These growth factors cause VE-cadherin displacement to the interior of the endothelium cell.

VE-cadherin is a protein complex responsible for tightly binding endothelial cells together to

prevent gaps. When the growth factors displace the VE-cadherin then gaps, large enough for

leukocytes to enter are created and intravascular fluid develop. The increased permeability leads

to fluid shifts related to the intravascular fluid moving to extravascular space, increasing the


parenchymal and interstitial fluid. This excess fluid results in excessive pressure on the

microvascular system and incites collapse. Decreased intravascular fluid and vascular collapse

are the mechanisms behind the hypotension seen in sepsis (Lee & Slutsky, 2010).

Adrenal insufficiency should be considered in patients with postoperative hypotension

despite adequate fluid resuscitation. The hypothalamic-pituitary-adrenal (HPA) axis controls the

body’s response to stress caused by events, such as surgery, by increasing the body’s blood

pressure to maintain hemodynamics. This process is impaired in adrenal insufficiency, resulting

in uncontrolled hypotension. The main cause is decreased mineralocorticoids and can be

improved by administration of mineralocorticoids. This deficiency results in hypotension by

reducing vascular response to angiotensin II and norepinephrine and inhibiting production of

renin substrate, while increasing prostacyclin production. These are all common features in

shock hence why adrenal insufficiency crisis often presents itself as hypovolemic shock (Hohl &

Schwartz, 2010; Nieman, 2012).

Finally perioperative myocardial infarction (MI) is a complication that can result in

postoperative hypotension. Many patients experience perioperative MI and often have delayed

diagnosis related to surgery effects. Sometimes the only presentation of a perioperative MI is

hypotension, tachycardia, and congestive heart failure. Because of the muscle skeletal injury the

creatinine kinase-MB isoenzyme is already elevated and not a reliable test for cardiac

musculoskeletal injury. Continuous heart monitoring will commonly only show a slight ST-

segment depression that is either prolonged, transient, or develops postoperatively. While ST-

segment elevation can occur, this occurs in less than two percent. ST-segment depressions are

more difficult to detect and are often not diagnosed until 24-48 hours after injury. Historically

troponin levels have been diagnostic for MI injury; however, in postoperative high risk cardiac


patients it is common to see lower, but statistically significant, increases in troponin levels

without evidence of cardiac ischemia. Close monitoring of all parameters are necessary to

quickly diagnosis a perioperative MI. Tachycardia is a common finding postoperatively because

of the increased oxygen demand placed on the body from surgery. This further increases the

myocardial oxygen demand leading to cardiac ischemia and MI. Further insult to the delivery of

oxygen to the heart can be caused by hypovolemia/ hypoxia from blood loss, fluid loss, and

hypercarbia. Ischemia to the myocardial cells results in cellular dysfunction, death, and

apoptosis. This causes ventricular dyssynchrony and reduced cardiac output causing further

hypotension (Landesberg, Beattie, Mosseri, Jaffe, & Alpert, 2009).

2. Which of the following is the most appropriate method to diagnose BMAH?

A. Cortrosyn stimulation test

B. CT scan of adrenal glands

C. CT scan of adrenal glands and Cortrosyn stimulation test

D. Random plasma cortisol level

The most appropriate method to diagnosis bilateral massive adrenal hemorrhage (BMAH)

is a cortrosyn stimulation test and a computed tomography (CT) scan of the adrenals. There are

several tests used to assess the HPA axis depending on the patient (ambulatory, hospitalized, or

critically ill). The best test for a critically ill patient is the cortrosyn stimulation test because it

does not rely on normal blood levels of blood sugar or albumin. The cortrosyn test is performed

by injecting either 1µg (low dose) or 250µg (high dose) of cosyntropin into the blood stream.

Cortisol levels are measured by blood collection at 30 minutes and then again at 60 minutes. The

level of cortisol measured indicates the amount of HPA axis stimulation response (Yong,

Coulthard, & Wrzosek, 2012). The low dose cortrosyn test is usually reserved for non-critically


ill patients due to the fact that in critically ill patients, low dose cortisol variation was shown to

increase the mortality rate and length of vasopressor therapy. The high cortrosyn test has a

sensitivity of 0.68 and a specificity of 0.65 with a baseline cortisol level less than ten µg/dL

having a high specificity of critical illness-related corticosteroid insufficiency. Low cortisol

levels less than 10µg/dL are indicative of adrenal insufficiency; whereas higher levels greater

than 34-44µg/dL indicate normal adrenal response. After the 250µg/dL cortrosyn injection, the

30 minute cortisol level should be increased by 7mcg/dL and increased by 11mcg/dL after 60

minutes, indicating a normal response. Less than this indicates adrenal insufficiency and further

testing is needed to determine primary or secondary adrenal insufficiency. High dose cortrosyn

reduced mortality by 70% compared to low dose (100% mortality) leading practitioners to

assume mortality in the ICU was related to this adrenal dysfunction. This is where steroid use in

septic shock trials originated. Based on this information, patients with less than 9µg/dL were

placed on hydrocortisone and fludrocortisone for seven days. These patients compared to the

placebo group showed a 53% decreased mortality rate compared to the 63% decrease in the

placebo group (hazard ratio, 0.67; 95% CI, 0.47-0.95; p=0.02) and were shown to have reduced

vasopressor withdrawal time. This test however also proves that a patient may have an

inadequate response when stimuli such as shock and hypoglycemia produce lower levels of

cortisol resulting in a test with higher specificity and a lower sensitivity (Moraes, Czepielewski,

Friedman, & Lucas de Borba, 2011).

Once the diagnosis of primary adrenal insufficiency has been established then a

computed tomography (CT) scanning of the adrenal glands can be performed to help with the

differential diagnosis. Enlarged or calcified adrenal glands may indicate infection, hemorrhage,

or metastatic cause (Ioachimescu & Hamrahian, 2010). Bilateral massive adrenal hemorrhage is


uncommon but carries a high mortality rate. Adrenal hemorrhage has characteristic findings on

CT of round or oval mass, periadrenal stranding, retroperitioneal hemorrhage, and crural

thickening. Attenuation will be high in acute bleeds and decreases over time with resolution at

one year. Chronic hematomas are called adrenal pseudocysts and have hypodense centers with or

without calcifications (Simon & Palese, 2009).

A random plasma cortisol level is a useful test only in critically ill patient with an

albumin level greater than 2.5g/dL. Cortisol is mostly bound to cortisol-binding globulin and

albumin so only a small amount of free cortisol is active. During critically ill times a random

cortisol level less than 15µg/dL is indicative of adrenal insufficiency. If the patient has an

albumin level less than 2.5g/dL then the patient will have subnormal serum total cortisol

concentrations. There are currently no studies with normal free cortisol ranges under different

levels of stress (Ioachimescu & Hamrahian, 2010).

3. Which of the following can occur in patients with primary adrenal insufficiency?

A. Electrolyte abnormalities

B. Hypotension

C. Mental status changes

D. Abdominal pain

E. All of the above

Common findings in adrenal insufficiency include electrolyte abnormalities, hypotension,

mental status changes, abdominal pain, and many other findings. Signs and symptoms associated

with adrenal insufficiency are related to the glucocorticoid and mineralocorticoid deficiency and

can develop slowly over time or acutely in times of stress. Adrenal insufficiency affects almost

every aspect of the body, presenting with a wide variety of symptoms depending on the patient.


Musculoskeletal manifestations include muscle weakness, fatigue, and joint or muscle pain;

gastrointestinal symptoms include weight loss, anorexia, nausea, vomiting, abdominal pain,

constipation or diarrhea; integumentary symptoms are vitiligo, hyperpigmentation or

hypopigmentation, bluish/ black oral mucosa, and decreased body hair; cardiovascular symptoms

include orthostatic hypotension, dehydration, anemia, and arrhythmias; neurological

manifestation are headache, lethargy, depression, confusion, mood swings, and tremors; finally

other symptoms include decreased sweat tolerance, fever, and salt craving (Crawford & Harris,

2011). Many symptoms resonate from the inability of the body to control electrolytes.

Normocytic anemia is common because cortisol is needed to mature blood progenitor cells. This

also affects the body’s response to immune and inflammatory changes because lymphocytosis

and eosinophilia are usually present. Hypoglycemia is common because decreased

glucocorticoid secretion inhibits the body’s ability to regulate blood glucose levels and decreased

cortisol release depletes glycogen stores. Other electrolytes are altered by reduced

mineralocorticoid production. Mineralocorticoid deficiency reduces aldosterone secretion which

affects the renin-angiotensin-aldosterone system which in turn causes increased sodium and

water excretion causing hyponatremia and dehydration. Severe dehydration can lead to vascular

collapse and kidney damage creating increased serum creatinine levels. Potassium retention

related to kidney damage is also common which can lead to hyperkalemia, arrhythmias,

hypercalcemia, and reabsorption of hydrogen ions causing acidosis and decreased urea nitrogen

excretion. Finally adrenal androgen deficiency causes low serum levels of

dehydroepiandrosterone (DHEA) sulfate in patients less than 40 year of age and can cause loss

of body hair, dry skin, and loss of libido. Life threatening abnormal laboratory finding can


develop quickly in times of high stress of the body such as during surgery, trauma, or infection

when higher levels of cortisol and aldosterone are needed (Arlt, 2009).

Orthostatic hypotension or atrial hypotension is often present and exacerbated by acute

stress. Due to the mineralocorticoid deficiency, sodium and therefore water is excreted

abnormally without the correction response from the renin-angiotensin aldosterone system. This

leads to dehydration and hypotension. In acute crisis, this dehydration leads to shock requiring a

central line and a large volume of crystalloid fluids. Vague to severe abdominal pain is also

report in adrenal insufficiency. The exact cause of abdominal pain is multifaceted or without

cause. Dehydration and hypotension leads to decreased vascular supply to the gastrointestinal

system which can lead to necrosis and pain. Also seen in adrenal insufficiency is reduced gastric

secretion and reduce absorption of nutritional elements (Arlt, 2009; Crawford & Harris, 2011).

Lastly mental status changes such as confusion, depression, and coma can be seen in primary

adrenal insufficiency. This is caused mainly by the acidosis from increase absorption of

hydrogen ions in the renal tubules. Acidosis reduced the amount of calcium that is bound to

albumin which causes elevated serum calcium levels. Calcium is an essential electrolyte for

neurological function and neuromuscular function. Hypercalcemia alters the neuro-electrical

transmission, preventing important neurological transmission from transmitting. This is the

primary cause of the altered mental status (Skugor & Milas, 2010).

4. Which of the following is not a risk factor for developing BMAH?

A. Postoperative state

B. Coagulopathy

C. Thromboembolic disease

D. Diabetes


E. Sepsis

Diabetes is the only answer that is not a risk factor for development of bilateral massive

adrenal hemorrhage (BMAH). Adrenal hemorrhage is a complication that can occur after acute

stress, neonatal stress, blunt trauma, sepsis, underlying tumor, coagulopathic state, or idiopathic

disease. The number one cause (80%) of all BMAH is blunt force trauma and account for 0.8%

to two percent of all traumas (Zhu, Van der Schaaf, Van der Valk, Bartenlink, & Nix, 2010).

Historically BMAH has been diagnosed only post mortem and had a high mortality rate due to

poor treatment. This missed diagnosis has become increasing discovered with the development

and improvement of imaging. The exact pathology of BMAH is not well understood and is

thought to be multifactorial. Trauma being the most common cause is related to disruption of the

vascular system from a blunt trauma. This can also include extracorporeal shock-wave lithotripsy

and electroconvulsive therapy. Spontaneous BMAH can occur from a variety of conditions and

predisposing factors such as adrenal neoplasia and sepsis. Sepsis causing BMAH is called

Waterhouse-Frederichson’s syndrome and is commonly associated with meningococcal

septicaemia. Other conditions and risk factors include: myoleiosarcoma, phaochromocytoma,

antiphospholopid syndrome, heparin induced thrombocytopenia, anticoagulation or non-steroidal

anti-inflammatory use, thrombocytosis, thromocytopaenia, adrenal aneurysms, steroid use,

known adrenal insufficiency, ACTH administration, pancreatitis, stress, post-surgery, burns,

pregnancy, pre-eclampsia, hypertension, and hypovolemia. Possible pathophysiology

explanation for spontaneous BMAH is that, the adrenals are very sensitive to changes in vascular

supply and are unable to tolerate vascular strain. Increased strain plus the addition of endothelial

damage from risk factors causes increased pressure resulting in vascular breakage and therefore

hemorrhage (Bharucha, Broderick, Easom, Roberts, & Moore, 2012).


A postoperative state is a risk factor because patients postoperatively experience the use

of anticoagulation, had intraoperative procedures performed, experience hypovolemia, may have

pre-existing adrenal insufficiency, or they may be taking or placed on chronic steroid use after.

Coagulopathy caused by the use of anticoagulation therapy, such as warfarin, or physiological

conditions such as thrombocytopenia, predisposes the adrenals to massive bleeding under any

minor increase in strain to the adrenals. Thromboembolism reduces to outflow of blood from the

adrenals while creating increased backflow pressure leading to rupture and hemorrhage. This

vascular supply sensitivity is due to the physiology of the adrenals which have three arteries

feeding the adrenals but only one vein to drain into. Finally sepsis can lead to BMAH by

multiple causes. The high level of stress on the body causing continuous release of ACTH has

been shown to lead to BMAH; although the exact cause is unknown. Sepsis also causes

coagulopathies, inflammatory state, and hypovolemia, all of which are known risk factors

(Bharucha, Broderick, Easom, Roberts, & Moore, 2012).

5. Which of the following statements regarding the long-term management of patients

with BMAH is correct?

A. Glucocorticoid therapy is needed only during acute illnesses

B. Patients should be discharged on maintenance doses of glucocorticoids

and mineralocorticoids

C. Patients do not need mineralocorticoid therapy

D. Adrenal function is likely to recover over 4 to 6 months with no further need

for glucocorticoids


Patients with BMAH need to be discharged home on maintenance doses of oral

glucocorticoids and mineralocorticoids. Based on the cause of the hemorrhage, most patients do

not need exploratory surgery and can be managed non-operatively, unless in the presence of

ongoing bleeding. Typically adrenal hematomas decrease in size over time with resolution or

calcification at one year. Atrophy of the adrenals is commonly seen after hematoma resolution

indicating little to no function remaining. Non-operative therapy includes supportive care,

assessment of adrenal function, and long term oral steroid replacement. Most patients will need

to be on oral therapies for life; however, some studies have shown that some long term follow up

patients developed some recovered adrenal function (Zhu et al., 2010). Glucocorticoid therapy is

administered immediately after diagnosis with 15-25mg of hydrocortisone orally. The body

naturally produces about five to ten mg/m2 of cortisol daily, so to meet this amount 15-25mg of

oral hydrocortisone is needed. Hydrocortisone has a variable peak concentration and has shown

to produce a supraphysiological range followed by a rapid decline five to seven hours after

ingestion. Because of this it is recommended to administer hydrocortisone one of two ways:

15mg orally in the morning followed by five mg six hours later or ten mg orally in the morning

followed by five mg four hours and then again at eight hours. Neither the two dose regimen or

three dose regimen has shown to be more effective than the other, so patient preference is

encouraged. This drug is a CYP3A4 hepatic inducer so co-administered drugs need to be

thoroughly evaluated to prevent under or over treatment. Initial levels of T4 and TSH are

encouraged before staring glucocorticoid therapy because hyperthyroidism causes increased

hydrocortisone metabolism whereas hypothyroidism can precipitate an adrenal crisis. The last

dose of hydrocortisone should not be taken in the late evening as this has been shown to cause

sleep disturbances and fatigue. This effect is caused by the normal circadian rhythm of cortisol


production in the body where levels rise between two and four am, peak one hour after waking,

and drop to low levels in the evening. Other glucocorticoid therapy options include cortisone

acetate, prednisolone, and dexamethasone. Cortisone acetate has a more variable

pharmacokinetics with 25mg of cortisone acetate being equivalent to 15mg of hydrocortisone.

Prednisolone and dexamethasone are long acting glucocorticoid steroids and are used as a last

resort. Side effects of these long acting glucocorticoid steroids are higher cortisol levels at night

causing sleep disturbances and fatigue, decreased insulin sensitivity, and osteoporosis.

Prednisolone is indicated for insulin dependent diabetes to prevent rapid changes in glucose

control that can be seen in short acting hydrocortisone. Glucocorticoid level adjustment is based

solely on clinical judgment based on signs of over replacement (weight gain, central obesity,

stretch marks, osteoporosis, impaired glucose tolerance, and hypertension) and under

replacement (weight loss, fatigue, nausea, myalgia, and lack of energy) (Arlt, 2009). According

to the Ohio Board of Nursing (OBN) nurse practitioners may prescribe glucocorticoids (Ohio

Board of Nursing, 2013).

Next the patient should be started on mineralocorticoid therapy. Fludrocortisone is the

drug of choice for mineralocorticoid therapy because fludrocortisone binds to the

mineralocorticoid receptor and produces exclusive mineralocorticoid action. A staring dose of

100µg of oral fludrocortisone daily in the morning is recommended with the dosing range

varying from 50-250µg every 24 hours based on parameters. Replacement therapy and dose

range is guided by blood pressure, edema, serum sodium and potassium levels, and renin levels.

Signs of over replacement include hypertension, edema, and altered renin activity. Signs of under

replacement mainly include postural hypotension. Fludrocortisone dose many need to be

increased in patient with high salt diet or live in a warmer, humid climate whereas, pregnant


individuals many need lower doses in the third trimester (Arlt, 2009). According to the OBN a

nurse practitioner may only prescribe mineralocorticoids if it has been physician initiated or

consulted (Ohio Board of Nursing, 2013).


Case Study Four

A 43 year old male presents to the emergency room with complaints of weakness,

tingling, and numbness in his arms and legs. The patient states he started developing muscle

weakness and numbness about 5 hours ago in his feet that has gradually gotten worse and

progressively moved up his legs and arms. He states he first noticed it about five hours ago when

he tripped while walking up his stairs at home. His assessment reveals 3/5 strength in his

bilateral lower extremities, 4/5 strength in his bilateral upper extremities, quadriparesis that is

more distal than proximal, and hyporeflexia. He was recently seen by his primary care physician

two weeks ago for a viral illness, skin rash, and arthralgias but is has otherwise been healthy. He

does not smoke, drink, or take illegal drugs.

A lumbar puncture is performed in the emergency department that showed

abluminocytologic dissociation, white blood count of 35/µl, and increased protein level. The

patient was admitted to the critical care unit for observation. A nerve conduction study was

performed that indicated Guillain-Barre syndrome and treatment therapy was started.

1. What is the differential diagnosis for this patient? Place in order of most likely to

least likely.

2. Create a table of CFS findings in Guillain-Barre syndrome compared to normal

findings.

3. What is the most likely cause of the patients Guillain-Barre?

4. What is the most appropriate treatment?


1. What is the differential diagnosis for this patient?

Some of the differential diagnosis for this patient in order of most likely to least likely is:

Guillain-Barre syndrome (GBS), hypokalemia, myasthenia gravis (MG), and acute myopathy.

There are a wide variety of differential diagnosis available for GBS including infection related

(lyme disease, diphtheria), inflammatory related (neurosarcoid), paraneoplastic, malignant,

vasculitic, metabolic (beri-beri), and of course autoimmune/ post-infectious such as GBS;

however, the previously mentioned are the most common and will be discussed. Guillain-Barre

syndrome is the most likely cause of this patient’s neuropathy because of the CSF findings and

ascending nature of the weakness. The GBS was discovered in 1916 and is to date the most

common cause of acute paralysis. About 20% of all patients with GBS remain disabled while the

mortality rate remains up to five percent despite treatment. The ration of men to women is about

1.78 with a 95% confidence interval (1.36 to 2.33) (Yuki & Hartung, 2012). The exact cause of

GBS is unknown but over 60% of patients who develop GBS have recently had an upper

respiratory infection or gastrointestinal infection. Other risk factors are recent immunization

(more commonly the influenza vaccination), recent surgery, pregnancy, or trauma. Guillain-

Barre syndrome occur in about one to two per 100,000 a year and is characterized during the

early stages by vague symptoms such as weakness, neck pain, back pain, or paresthesia. Atypical

symptoms are also seen in these patients such as unusual disturbances of weakness in the upper

extremities or respiratory muscles only, making diagnosis difficulty. The typical presentation of

a patient with GBS presents with symmetrical quadriplegia, possible respiratory, facial, or bulbar

muscle weakness, pyramidal weakness distribution, hyporeflexia followed by areflexia,

progression of weakness in two or more limbs from normal to nadir in less than four weeks, and

pain. A variant of GBS called Miller-Fisher syndrome (MFS) also includes ataxia,


opthalmoplegia, and areflexia but can also include widespread cranial nerve involvement

(Pritchard, 2010). There are several different sub-types of GBS with acute inflammatory

demyelinating polyradiculoneuropathy (AIDP) being the most common. Other sub-types include

acute motor axonal neuropathy (AMAN) which affects motor fibers only and acute motor and

sensory axonal neuropathy (AMSAN) which affects motor and sensory fibers. In North America

about 95% of all GBS are AIDP sub-type with the remaining five percent the AMAN and

AMSAN sub-types. Worldwide AMAN and AMSAN account for 30-47% of all cases. While

any infection can cause GBS Campylobacter jejuni, Cytomegalovirus, Epstein-Barr virus, and

Mycoplasma are associated with a higher incident of GBS development within six weeks of

infection. Campylobacter jejuni is typically the bacterial causative agent when clusters of GBS

are seen post outbreak of bacterial enteritis (Hughes & Cornblath, 2005)

In AIDP GBS the pathology of the disease involves multifocal mononuclear cell

infiltration in the peripheral nervous system. This inflammation in the peripheral system is what

defines the classical symptoms seen in GBS. This is caused by CD4 T-cell de-regulation in

which the DC4 T-cells mediate a response against one of the myelin proteins: P2, P0, or PMP22

(Pritchard, 2010). The CD4 T-cell crosses the blood-nerve barrier and cross react with antigens

in the endoneurium, releasing cytokines which attract the macrophages. Macrophages, targeted

by antigens, enter intact myelin sheaths and denude the axons. These antigens are located on the

Schwann cells or myelin sheath causing entering macrophages to attack the Schwann cell

basement membrane through matrix metalloproteinases, toxic nitric oxide radicals, and other

mediators. The other possible cause is that the antigen binds to the Schwann cell and fixation of

the complement causing damage to the cell and vesicular dissolution of the myelin prior to


macrophage attacks. This cause is evident in the early course of the disease (Hughes &

Cornblath, 2005).

In AMAN sub-type the pathology of the disease is different. Macrophages attack the

nodes of Ranvier by targeting Fc-receptor-mediated binding against ganglioside antigens. T-cells

and IL-2 receptor concentrations are increased in the acute phase with oligoclonal expansion of

Vβ and Vδ gene usage caused by T-cell dis-regulation. The exact antigenic target of the dis-

regulated T-cell is unknown but contraindicating reports highlight P0 and PMP22. Simultaneous

loss of regulatory mechanisms seen in patient with immunosuppression and is associated with

cytomegalovirus infections. The macrophages move in between the axon and the Schwann cell

axolemma which leaves the myelin sheath intact. In more severe cases the axons in the ventral

root are damaged which in turn causes the degeneration of the whole axon. More commonly the

damage blocks conduction without severing the axon giving to the classic presentation of

AMAN in which patients becomes nadir quicker but also recovers faster than in AIDP. The last

sub-type AMSAN is similar to AMAN except for in AMSAN the dorsal and ventral root is

affected (Hughes & Cornblath, 2005; Yuki & Hartung, 2012).

Hypokalemia is the most commonly missed differential diagnosis for GBS (Hughes &

Cornblath, 2005). Hypokalemia periodic paralysis (HypoPP) presents as recurrent generalized

flaccid weakness brought on by carbohydrate-induce hypokalemia or cold exposure. Progressive

weakness seen in HypoPP is caused by structural myopathy with vacuoles and T-tubular

aggregates. Hypokalemia induces weakness by depolarizing myofiber membranes through

extracellular potassium concentration reduction which diminishes currents with hyperpolarizing

effects. This hyperpolarization outward, decreases with depolarization that progresses until other

outward potassium currents stabilize the membrane at a less negative value. Stabilization at a


less negative value causes bimodal distribution of membrane potential leading to weakness.

HypoPP is caused by mutations in two voltage-gated cation channels in the skeletal muscle.

Mutation-induced leak of cations through aberrant pores that remain open during the resting

potential lead to permanent inward sodium current in which the Na/K-ATPase pump cannot

compensate. Mycoplasmic sodium levels exceeding normal values are myotoxic leading to

edema and vacuoles or T-tubular aggregates; again leading to muscle weakness. Hypokalemia is

differentiated from GBS by the generalized allover progressive weakness seen as compared to

GBS where weakness presents starting in two limbs and is ascending in nature.

Myasthenia gravis (MG) is the next differential diagnosis to consider in this patient.

Myasthenia gravis is an autoimmune disorder whose origin of formation is unknown. In many

patients with MG the thymus gland is found to be hyperplasia or neoplasia indicating the residual

thymus tissue many be implicated in the development of anti-skeletal muscle acetylcholine

receptors (AChR). Acquired MG presents as fatigable weakness involving specific muscle

groups that fluctuates from day to day or hour to hour. Weakness progresses with activity and

gets better with rest. The most common presentation is ocular weakness, which presents as ptosis

or diplopia. Other characteristics include dysarthria, dysphagia, dyspnea, facial weakness, or

limb fatigue or axial weakness. The incidence of MG has increased to 20 per 100,000 and affect

women three times more than men during adulthood less 40 years of age; equal prevalence

during puberty and after 40 years of age; and higher in men after 50 years of age. Neuromuscular

transmission starts with the nerve action potential entering the nerve terminal. This initiates the

release of acetylcholine causing calcium to enter the depolarized nerve terminal through voltage-

gated Ca2+ channels to exocytosis the vesicles around the acetylcholine. The acetylcholine then

diffuses across the synaptic cleft and binds with the AChRs in the postsynaptic membrane which


depolarizes the endplate potential and is terminated by acetylcholinesterase. In MG the AChRs

lose their function, lowering the endplate potential amplitude below the threshold for muscle

fiber action potential causing neuromuscular transmission failure. This AChR loss of function is

caused by antibodies (IgG1 or IgG3) binding to extracellular domain of the AChR molecule

resulting in the destruction of the muscle endplate. Acquired MG is differentiated from GBS by

the selective muscle group weakness that varies by day or hour, improves with rest, and worsens

with activity; whereas, GBS affects bilateral extremities in an ascending manner, progressively

worsens, and does not improve with rest (Meriggioli & Sanders, 2009).

Acute myopathy is more commonly seen in intensive care patients (ICU) but can be

present in non ICU patients. Acute myopathy is characterized by profound muscle weakness or

paralysis that follows an inflammatory/immune event such as mechanical ventilation, multiple

organ failure, or sepsis. Respiratory and limb fatigue are both common in myopathy and can take

weeks to months and even years to regain. Patients present with a wide variety of symptoms

related to muscle weakness including: acute respiratory failure with normal chest x-ray,

tachypneic, dyspnea, diaphoresis, tachycardia, inadequate cough, hypoxia, staccato speech, use

of accessory muscles, and symmetrical limb weakness without facial weakness. Although acute

myopathy is similar to GBS, it is less likely to be the diagnosis in this patient because he has not

suffered an ICU admission, was not mechanically intubated, or has not suffered a severe

systemic infection. Acute myopathy is difficult to differentia from GBS based on clinical

symptoms because of the similarities. Sensory nerve conduction studies and needle

electromyography in the upper and lower limbs is the best test to differentiate acute myopathy

from GBS (Latronico & Rasulo, 2010).


2. Create a table of CFS findings in Guillain-Barre syndrome compared to normal

findings.

Table 1

Cerebral Spinal Fluid (CFS) Findings

CSF findings: Normal and in GBS

Normal GBS

Pressure 70-180mm H2O 70-180mm H2O

Appearance Clear, Colorless Clear to Cloudy

Total Protein 20-45mg/dl Greater than 45mg/dl

Glucose 50-80mg/dl or greater than 2/3

of blood sugar levels

50-80mg/dl or greater than 2/3

of blood sugar levels

Lymphocytes 0-5/µl Normal to 10/µl but not

greater than 50/µl

Hemoglobin None none

Adapted from: (1) Griggs, R., Jozefowicz, R., & Aminoff, M. (2007). Approach to the patient

with neurologic disease. In L. Goldman & D. Ausiello (Eds.), Cecil Medicine (23rd ed.). (chpt

418). Philadelphia Pa: Sanders Elsevier. (2) Moses, S. (2013). Cerebrospinal fluid examination.

Family Practice Notebook: Neurology Book. Retrieved from:

http://www.fpnotebook.com/neuro/lab/CrbrspnlFldExmntn.htm. (3) Pritchard, J. (2010).

Guillain-Barre syndrome. Clinical Medicine, 10(4). 399-401. Retrieved from:

http://dx.doi.org/10.7861/clinmedicine.10-4-399.


3. What is the most likely cause of the patients Guillain-Barre?

The most likely cause of this patient GBS is a post viral autoimmune reaction. This

patient was recently seen by his primary care physician for an upper respiratory infection, skin

rash, and arthralgia. The exact cause is unknown and the timing of occurrence of GBS post

infection varies but peaks between two to four weeks and should not exceed eight weeks.

Evidence shows that molecular mimicry might be responsible for the body’s immune response

against the axonal sheath. Many viral and bacterial bodies are composed of lipooliosaccharide’s

which closely resemble gangliosides which are ceramide attached to one or more sugars and

contain sialic acid linked to an oligosaccharide core. Gangliosides are important components in

the peripheral nerve make up. There are four gangliosides identified in the peripheral nerve:

GM1, GD1a, GT1a, and GQ1b. Studies show that some bacterial components obtained in

patients with GBS has GM1 or GD1a like lipooligosaccaride and those with Miller-Fisher

syndrome had GQ1b like lipooligosaccharides (Hughes & Cornblath, 2005). This mimicry is

what’s thought to induce the autoimmune reaction to the body previously discussed. Antibodies

to GM1 and GD1a are common in AMAN and AMSAN but not in AIDP. The difference in

AMAN preferential motor-axon injury is explained from the fact that motor and sensory nerves

have GM1 and GD1a complexes in the same quantities but there expression in different types of

tissues varies. Patients with Miller-Fisher syndrome have IgG antibodies to GQ1b and cross react

with GT1a. Those patients with pharyngeal, cervical, or respiratory muscle weakness are more

likely to have IgG antibodies to GT1a and cross react with GQ1b but less likely to have GD1a

antibodies. As the CD4 T-cells interact with the infectious membrane, it identifies the GM1,

GD1a, or GQ1b like lipooligosaccaride and produces antibodies. After the antibodies are

released macrophages are activated to kill the infectious agent. Some times after the infectious


agent has been fully removed dis-regulated DC4 T-cells identify the GM1, GD1a, or Gq1b

gangliosides as the previously recognized lipooligosaccaride and start reproducing antibodies.

This attracts macrophages to the Schwann and axonal sheath, where toxic components are

released as previously discussed (Hughes & Cornblath, 2005; Pritchard, 2010; Yuki & Hartung,

2012).

4. What is the most appropriate treatment?

Treatment for GBS first starts with admission to the hospital for careful observation of

declining respiratory function and medical complications. Of the patients admitted with GBs

about five percent of them will die from complications such as sepsis, pulmonary embolism, and

unexplained cardiac arrest, which are thought to be due to dysautonomia. Admission to a critical

care unit with cardiac and pulse ox monitoring is preferred because even patients without

respiratory distress may need mechanical ventilation if they have one major or two minor

criteria. Major criteria include hypercarbia, hypoxemia, and vital capacity less than 15ml per

kilogram of ideal body weight. Minor criteria include weak cough, dysphagia, or atelectasis.

Cardiac monitoring is an important aspect of GBS treatment because GBS patients have a 20%

chance of developing autonomic dysfunction such as an arrhythmia, extreme hypertension,

hypotension, and severe bradycardia requiring pacemaker placement. Some patients with GBS

are non-ambulatory and require DVT prophylaxis such as compression stocking and heparin to

prevent pulmonary embolism (Yuki & Hartung, 2012). An acute care nurse practitioner can

prescribe heparin for DVT prophylaxis according the OBN (Ohio Board of Nursing, 2013).

Other concerns include urinary retention, constipation, and pain management therapy. Pain

management in patient with GBS is most effective with opioids during the acute phase in

combination with either gabapentin or carbamazepine (Hughes & Cornblath, 2005). Medications


for pain management (ultram, hydrocodone-acetaminophen, oxycodone-acetaminophen,

morphine, hydromorphone, and fentanyl are commonly prescribed), neuropathic pain

medications, laxatives, and flowmax for urinary retention are all medications a nurse practitioner

may prescribe according to the OBN (Ohio Board of Nursing, 2013).

The first treatment found to improve GBS and decrease recovery time was plasma

exchange. The most effective time to start treatment is in the first two weeks after onset and

appeared to be more effective in patients who were unable to walk. Plasma exchange works by

removing all antibodies in the blood not specific to GBS antibodies. Plasma exchange takes,

depending on the patients’ severity, two to five exchanges over two weeks (Pritchard, 2010).

Since the development of immune globulins, immune globulins have now become the treatment

of choice in non-severe cases. Immune globulins have the same initiation criteria with treatment

being started within the first two weeks of onset being the most effective. The same principle is

applied to both plasma exchange and immune globulins. In plasma exchange antibodies are

removed before extensive damage has developed and in immune globulin antibodies are

neutralized and autoantibody-mediated complement activation is inhibited preventing further

nerve damage and promoting faster improvement. Immune globulins are more convenient and

more accessible than plasma exchange. Immune globulins are given as two grams per kilogram

of body weight over five days. Not every patient responds the same and some patients have been

shown to develop a smaller rise in IgG, leading to a poorer prognosis. These patients have been

shown to benefit from a second dose of immune globulins (Hughes & Cornblath, 2005; Yuki &

Hartung, 2012). According to the OBN acute care nurse practitioners can prescribe immune

globulins when it has been physician initiated or physician consulted (Ohio Board of Nursing,

2013). Lastly corticosteroids have not been shown to significantly improve GBS process or


symptoms and in some studies have been shown to generate less improvement (95% confidence

interval, 0.16 more to 0.88 less improvement). Based on this Cochrane review of studies it is not

recommended to treat patients with GBS with corticosteroids (Hughes, Swan, & Van Doorn,

2010).


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