Tải bản đầy đủ - 0 (trang)
15 Basic Statistical Analysis: Student t-Test and Related Tests

# 15 Basic Statistical Analysis: Student t-Test and Related Tests

Tải bản đầy đủ - 0trang

64

CHAPTER 4:

Laboratory Statistics and Quality Control

In Gaussian distributions, the mean 6 1 SD contains 68.2% of all values, the

mean 6 2 SD contains 95.5% of all values, and the mean 6 3 SD contains 99.7% of

all values in the distribution.

The reference range when determined by measuring an analyte in at least 100

healthy people and the distribution of values in a normal Gaussian distribution is

calculated as mean 6 2 SD.

For calculating sensitivity, specificity, and predictive value of a test, the following

formulas can be used, where TP 5 true positive, FP 5 False positive, TN 5 True

negative, and FN 5 False negative: (a) Sensitivity (individuals with disease who

show positive test results) 5 (TP/(TP 1 FN)) 3 100; (b) Specificity (individuals

without disease who show negative test results) 5 (TN/(TN 1 FP)) 3 100; and

(c) Positive predictive value 5 (TP/(TP 1 FP)) 3 100.

In a clinical laboratory, three types of control materials are used: assayed control where

the value of the analyte is predetermined, un-assayed control where the target value is

not predetermined, and homemade control where the control material is not easily

commercially available (e.g. an esoteric test).

Quality control in the laboratory may be both internal and external. Internal quality

control is essential and results are plotted in a LeveyÀJennings chart; the most

common example of external quality control is analysis of CAP (College of

American Pathologists) proficiency samples.

“Waived tests” are not complex and laboratories can perform such tests as long as

they follow manufacturer’s protocol. Enrolling in an external proficiency-testing

program such as a CAP survey is not required for waived tests.

“Non-waived tests” are moderately complex or complex tests and laboratories

performing such tests are subjected to all CLIA regulations and must be inspected

by CLIA inspectors every two years or by inspectors from non-government

organizations such as CAP or Joint-Commission on Accreditation of Healthcare

Organization (JCAHO). In addition, for all non-waived tests laboratories must

participate in an external proficiency program, most commonly CAP proficiency

surveys, and must successfully pass proficiency testing in order to operate legally.

A laboratory must produce correct results for four of five external proficiency

specimens for each analyte, and must have at least an 80% score for three

consecutive challenges.

Since April 2003, clinical laboratories must perform method validation for each

new test, even if such test is already FDA approved.

A LeveyÀJennings chart is a graphical representation of all control values for an

assay during an extended period of laboratory operation. In this graphical

representation, values are plotted with respect to the calculated mean and

standard deviation. If all controls are within the mean and 6 2 SD, then all

control values were within acceptable limits and all runs during that period have

acceptable performance. A LeveyÀJennings chart must be constructed for each

control (low and high control, or low, medium, and high control) for each assay

the laboratory offers. The laboratory director or designee must review all

Key Points

LeveyÀJennings charts each month and sign them for compliance with an

accrediting agency.

Usually Westgard rules are used for interpreting LeveyÀJennings charts, and for

certain violations, a run must be rejected and the problem must be resolved prior

to resuming testing of patients’ samples. Various errors can occur in

LeveyÀJennings charts, including shift, trend, and other violations. Usually 12s is a

warning rule and occurs due to random error; other rules are rejection rules (see

Table 4.1).

A delta check is important to identify laboratory errors and can be based on any of

the criteria, including delta difference, delta percent change (delta difference/

current value), rate difference (delta difference/delta interval 3 100), or rate percent

change (delta percentage change/delta interval). Usually within and between runs

precision is expressed as CV. Then linearity of the assay is revalidated. Detection

limits should be determined by running a zero calibrator or blank specimen 20

times and then determining the mean and standard deviation. The detection limit

(also called the lower limit of detection) is considered as a mean 1 2 SD value, but

more sophisticated methods of calculating limit of detection have also been

described.

Comparison of a new method with an existing method is a very important step in

method validation. For this purpose, at least 100 patient specimens must be run

with the existing method in the laboratory at the same time as the new method.

Then values are plotted and a linear regression equation determines the line of

best fit as expressed by the equation y 5 mx 1 b, where “m” is the slope of the

line and “b” is the intercept. The computer calculates the equation of the

regression line using a least squares approach. The software also calculates “r,”

the correlation coefficient, by using a complicated formula. The ideal value of

m is 1, while the ideal value of b is zero. In reality, if slope is less than 1.0, it

indicates negative bias with the new method compared to the old method, and if

the slope is over 1.0, it indicates positive bias.

A receiverÀoperator curve (ROC) is often used to make an optimal decision level

for a test. ROC plots the true positive rate of a test (sensitivity) either as a scale of

0À1 (1 is highest sensitivity) or as percent on the y-axis versus a false positive rate

(1-specificity).

Six sigma goal is achieved if the error rate is only 3.4 out of one million processes,

or error rate is only 0.00034%.

The likelihood of “n” test results falling within the reference range can be

calculated from the formula % results falling within normal range 5 0.95n 3 100.

Therefore % results falling outside the reference range in normal people is

(1 2 0.95n) 3 100.

The Student t-test is useful for determining if one set of values is different from

another set of values based on the difference between mean values and standard

deviations. This statistical test is also useful in clinical research to see if values of

65

66

CHAPTER 4:

Laboratory Statistics and Quality Control

an analyte in the normal state are significantly different from the values observed

in a disease state.

REFERENCES

[1] Jenny RW, Jackson KY. Proficiency test performance as a predictor of accuracy of routine

patient testing for theophylline. Clin Chem 1993;39:76À81.

[2] Theolen D, Lawson NS, Cohen T, Gilmore B. Proficiency test performance and experience

with College of American Pathologist’s programs. Arch Pathol Lab Med 1995;119:307À11.

[3] Boone DJ. Literature review of research related to the Clinical Laboratory Improvement

Amendments of 1988. Arch Pathol Lab Med 1992;116:681À93.

[4] Armbuster DA, Pry T. Limit of blank, limit of detection and limit of quantification. Clin

Biochem Rev 2008;29(Suppl. 1):S49À51.

[5] Dasgupta A, Tso G, Chow L. Comparison of mycophenolic acid concentrations determined

by a new PETINIA assay on the Dimension EXL analyzer and a HPLC-UV method. Clin

Biochem 2013;46:685À7.

CHAPTER 5

Water, Homeostasis, Electrolytes, and

AcidÀBase Balance

CONTENTS

5.1 DISTRIBUTION OF WATER AND ELECTROLYTES

IN THE HUMAN BODY

5.1 Distribution of

Water and Electrolytes

in the Human Body... 67

Water is a major constituent of the human body that represents approximately 60% of body weight in men and 55% of body weight in women.

Two-thirds of the water in the human body is associated with intracellular

fluid and one-third is found in extracellular fluid. Extracellular fluid is composed mostly of plasma (containing 92% water) and interstitial fluid. A

major extracellular electrolyte is sodium. The human body contains approximately 4,000 mmol of sodium out of which 70% is present in an exchangeable form; the rest is found in bone. The intracellular concentration of

sodium is 4À10 mmol/L. The normal sodium level in human serum is

135À145 mmol/L. Potassium is the major intracellular electrolyte with an

intracellular concentration of approximately 150 mmol/L. The normal potassium level in serum is usually considered to be 3.5À5.1 mmol/L. The balance

between intracellular and extracellular electrolytes is maintained by a

sodiumÀpotassium ATPase pump present in cell membranes.

5.2 Plasma and Urine

Osmolality .................. 68

Along with sodium and potassium, other major electrolytes of the human

body are chloride and bicarbonate. Electrolytes are classified either as positively charged ions known as cations (sodium, potassium, calcium, and magnesium, etc.) or negatively charged ions known as anions (chloride,

bicarbonate, phosphate, sulfate, etc.). Four major electrolytes of the human

body (sodium, potassium, chloride, and bicarbonate) play important roles

in human physiology, including:

5.8 Hypokalemia and

Hyperkalemia ............ 75

Maintaining water homeostasis of the body.

Maintaining proper pH of the body (7.35 to 7.45).

Maintaining optimal function of the heart.

Participating in various physiological reactions.

Co-factors for some enzymes.

5.3 Hormones Involved

in Water and

Electrolyte Balance ... 69

5.4 ReninÀ

AngiotensinÀ

Aldosterone System.. 70

5.5 Diabetes

Insipidus..................... 71

5.6 The Syndrome of

Inappropriate

Antidiuretic Hormone

Secretion (SIADH) ..... 72

5.7 Hyponatremia, Sick

Cell Syndrome, and

Hypernatremia .......... 73

5.9 Introduction to

AcidÀBase Balance .. 77

5.10 Diagnostic

Approach to

AcidÀBase

Disturbance................ 78

5.10.1 Metabolic

Acidosis....................79

5.10.2 Metabolic

Alkalosis...................80

67

A. Dasgupta and A. Wahed: Clinical Chemistry, Immunology and Laboratory Quality Control

DOI: http://dx.doi.org/10.1016/B978-0-12-407821-5.00005-X

68

CHAPTER 5:

W a t e r , H om e o s t as i s , E le c t r o l y t e s , a n d A c i dÀB a s e B a l a n c e

5.10.3 Respiratory

Acidosis....................81

5.10.4 Respiratory

Alkalosis...................81

5.11 Short Cases:

AcidÀBase

Disturbances.............. 81

Key Points .................. 82

References ................. 84

It is important to drink plenty of water and take in adequate salt on a daily basis

to maintain proper health. Healthy adults (age 19À50) should consume 1.5 g

of sodium and 2.3 g of chloride each day or 3.8 g of salt each day to replace lost

salt. The tolerable upper limit of daily salt intake is 5.8 g (5800 mg), but many

Americans exceed this limit. The average daily sodium intake is 3.5À6 g

(3,500À6,000 mg) per day. Processed foods contain high amounts of sodium

because manufacturers add it for food preservation. For example, a can of

tomato juice may contain up to 1,000 mg of sodium. Adults should consume

4.7 g of potassium each day, but many Americans do not meet this recommended potassium requirement. Potassium-rich foods include bananas, mushrooms, spinach, almonds, and a variety of other fruits and vegetables. High

sodium intake may cause hypertension. The Dietary Approaches to Stopping

Hypertension (DASH) eating plan recommends not more than a daily intake of

1,600 mg (1.6 g) of sodium. In general, high sodium intake increases blood

pressure; replacing a high sodium diet with a diet low in sodium and high in

potassium can decrease blood pressure. Sodium and potassium are freely

absorbed from the gastrointestinal tract, and excess sodium is excreted by the

kidneys. Potassium filtered through glomerular filtration in the kidneys is

almost completely reabsorbed in the proximal tubule and is secreted in the distal tubules in exchange for sodium under the influence of aldosterone.

Interestingly, African Americans excrete less urinary potassium than Caucasians

even while consuming similar diets in the DASH trail. However, consuming a

diet low in sodium may reduce this difference [1].

5.2 PLASMA AND URINE OSMOLALITY

Plasma osmolality is a way to measure the electrolyte balance of the body.

Osmolality (measured by an osmometer in a clinical laboratory) is technically different than osmolarity, which can be calculated based on the measured sodium, urea, and glucose concentration of the plasma. Osmolality is

a measure of osmoles of solutes per kilogram of a solution where osmolarity

is a measure of osmoles per liter of solvent. Because one kilogram of plasma

is almost one liter in volume, osmolality and osmolarity of plasma can be

considered as the same for all practical purposes. Normal plasma osmolality

is 275À300 milliosmoles/kg (mOsm/kg) of water while urine osmolality is

50À1,200 mOsm/kg of water. Although plasma and urine osmolality can be

measured by using an osmometer, it is also calculated by the following formula (Equation 5.1):

Plasma osmolality 5 2 3 Sodium 1 Glucose

1 Urea ðall concentrations in mmol=LÞ

ð5:1Þ

5.3 Hormones Involved in Water and Electrolyte Balance

Although the sodium value is expressed as mmol/L, in clinical laboratories

concentrations of glucose and urea are expressed as mg/dL. Therefore the

formula can be modified as follows to calculate osmolality (Equation 5.2):

Plasma osmolality 5 2 3 ½Sodium in mmol=L

1 ½Glucose in mg=dL=18 1 ½BUN in mg=dL=2:8

ð5:2Þ

Here, BUN stands for blood urea nitrogen.

Although this formula is commonly used, a stricter approach to calculate

plasma osmolality takes into account other osmotically active substances in

plasma such as potassium, calcium, and proteins by adding 9 mOsm/kg to

yield Equation 5.3:

Plasma osmolality 5 1:86 ½Sodium in mmol=L

1 ½Glucose in mg=dL=18 1 ½BUN in mg=dL=2:8 1 9

ð5:3Þ

Plasma osmolality increases with dehydration and decreases with over hydration. Plasma osmolality regulates secretion of antidiuretic hormone (ADH).

Another important laboratory parameter is the osmolar gap, defined in

Equation 5.4:

Osmolar gap 5 Observed osmolality 2 Calculated osmolality

ð5:4Þ

If the measured osmolality is higher than the calculated osmolality then this is

referred to as the osmolar gap and can be due to the presence of abnormal

osmotically active substances such as overdose with ethanol, methanol, and

ethylene glycol, or if fractional water content of plasma is reduced, due to

hyperlipidemia or paraproteinemia. Although normal urine osmolality of random urine is relatively low, fluid restriction can raise urine osmolality to

850 mOsm/kg or higher (although within the normal range of urine osmolality). However, greater than normal urine osmolality may be seen when:

There is reduced renal perfusion (e.g. dehydration, shock, renal artery

stenosis).

Excessive water retention without renal hypoperfusion (e.g. SIADH).

Osmotically active substances in urine (e.g. glycosuria).

5.3 HORMONES INVOLVED IN WATER AND

ELECTROLYTE BALANCE

Antidiuretic hormone (ADH) and aldosterone play important roles in the

water and electrolyte balance of the human body. ADH along with oxytocin

69

70

CHAPTER 5:

W a t e r , H om e o s t as i s , E le c t r o l y t e s , a n d A c i dÀB a s e B a l a n c e

are produced in the supraoptic and paraventricular nuclei of the hypothalamus. These hormones are stored in the posterior pituitary and released in

response to appropriate stimuli. ADH secretion is regulated by plasma osmolality. If plasma osmolality increases, it stimulates secretion of ADH, which

acts at the collecting duct of the nephron where it causes reabsorption of

only water and produces concentrated urine. In this process water is conserved in the body, and as a result, plasma osmolality should be reduced. A

low serum osmolality, on the other hand, reduces secretion of ADH and

more water is excreted as urine (diluted urine) and plasma osmolality is corrected. However, ADH at high concentrations causes vasoconstriction, thus

raising blood pressure. Increased water retention due to ADH can result in

the following conditions:

Concentrated urine

Increased plasma volume

Reduced plasma osmolality.

Therefore, it is logical to assume that ADH secretion is stimulated by low

plasma volume and increased plasma osmolality. In humans, urine produced

during sleep is more concentrated than urine produced during waking hours.

Usually urine in the morning (first void) is most concentrated. This may be

partly due to less or no fluid intake during sleeping hours, but plasma ADH

concentration is also higher during the night than during the day. It has been

postulated that rapid eye movement (REM) sleep or dreaming sleep induces

5.4 RENINÀANGIOTENSINÀALDOSTERONE

SYSTEM

With low circulating blood volume, the juxtaglomerular apparatus of the kidney secretes renin, a peptide hormone, into the blood stream. Renin converts

angiotensinogen released by the liver into angiotensin I, which is then converted into angiotensin II in the lungs by angiotensin-converting enzyme

(ACE). Angiotensin II is a vasoconstrictor and also stimulates release of aldosterone from the adrenal cortex. This is defined as the “ReninÀAngiotensinÀ

Aldosterone” system. Aldosterone is a mineralocorticoid secreted from the

zona glomerulosa of the adrenal cortex. It acts on the distal tubules and

collecting ducts of the nephron and causes:

Retention of water

Retention of sodium

Loss of potassium and hydrogen ions.

Retention of water and sodium results in increased plasma volume and blood

pressure. An increase in plasma potassium is a strong stimulus for aldosterone

5.5 Diabetes Insipidus

synthesis and release. Atrial natriuretic peptide (ANP) and brain natriuretic

peptide (BNP) are secreted by the right atrium and ventricles, respectively. The

main stimulus for secretion of these peptides is volume overload.

5.5 DIABETES INSIPIDUS

Diabetes insipidus is an uncommon condition that occurs when the kidneys

are unable to concentrate urine properly. As a result, diluted urine is produced, affecting plasma osmolality. The cause of diabetes insipidus is lack of

secretion of ADH (cranial diabetes insipidus, also known as central diabetes

insipidus) or is due to the inability of ADH to work at the collecting duct of

the kidney (nephrogenic diabetes insipidus). Cranial diabetes insipidus is

due to hypothalamic damage or pituitary damage. The major causes of such

damage include the following conditions:

Stroke

Tumor

Infections affecting the central nervous system

Sarcoidosis

Surgery involving the hypothalamus or pituitary.

Diabetes insipidus due to viral infection is rarely reported, but one report illustrates diabetes insipidus due to type A (sub-type: H1N1, swine flu) influenza

virus infection in a 22-year-old man who produced up to 9 liters of urine per

day [2]. Neuroendocrine complication following meningitis in neonates may

also cause diabetes insipidus [3]. Pituitary abscess is a rare life-threatening

condition that may also cause central diabetes insipidus. Autoimmune diabetes insipidus is an inflammatory non-infectious form of diabetes insipidus

that is rare and is presented with antibodies to ADH secreting cells.

CASE REPORT

A 48-year-old woman with diffuse large cell lymphoma and

severe hepatic involvement presented with herpes zoster

infection on the right eye and was treated with acyclovir

orally. When she was undergoing chemotherapy, on the ninth

day she developed a fever, weakness, hypotension, pancytopenia, renal failure, and a highly elevated C-reactive protein.

A diagnosis of Gram-negative sepsis was made and she was

treated with intravenous antibiotic along with acyclovir, catecholamine, and hydrocortisone. Three days later she developed hypotonic polyuria (12 liters of urine per day) and a

diagnosis of diabetes insipidus was made based on low urine

osmolality of 153 mmol/kg and undetectable vasopressin

(ADH) levels. However, a brain MRI showed no pituitary

abnormality, but encephalitis was present as evidenced by

hyperintensities in the area of the left lateral ventricle of the

cerebrum. Analysis of cerebrospinal fluid showed herpes zoster infection. The authors concluded that central diabetes

insipidus was due to herpes encephalitis in this patient. The

patient responded to desmopressin (synthetic analog of vasopressin, also known as ADH) therapy [4].

71

72

CHAPTER 5:

W a t e r , H om e o s t as i s , E le c t r o l y t e s , a n d A c i dÀB a s e B a l a n c e

Nephrogenic diabetes insipidus is due to the inability of the kidney to concentrate urine in the presence of ADH. The major causes of nephrogenic diabetes include:

Chronic renal failure

Polycystic kidney disease

Hypercalcemia, hypokalemia

Drugs such as amphotericin B, demeclocycline, lithium.

In both types of diabetic insipidus, patients usually present with diluted

urine with low osmolality, but plasma osmolality should be higher than

normal. These patients also experience excessive thirst and drink lots of

fluid to compensate for the high urine output. Even if a patient is not

allowed to drink fluid, urine still remains diluted with a possibility of

dehydration. In contrast, in a normal healthy individual fluid deprivation

results in concentrated urine. This observation is the basis of the water

deprivation test to establish the presence of diabetes insipidus in a

patient. In order to differentiate cranial diabetes insipidus from nephrogenic diabetes insipidus, intranasal vasopressin is administered. If urine

osmolality increases then the diagnosis is cranial diabetes insipidus, but if

urine is still dilute with no change in urine osmolality, then the diagnosis

is nephrogenic diabetes insipidus. The congenital form of nephrogenic

diabetes is a rare disease and most commonly inherited in an X-linked

manner with mutations of the arginine vasopressin receptor type 2

(AVPR2) [5].

5.6 THE SYNDROME OF INAPPROPRIATE

ANTIDIURETIC HORMONE SECRETION (SIADH)

The syndrome of inappropriate antidiuretic hormone secretion (SIADH, also

known as SchwartzÀBartter syndrome) is due to excessive and inappropriate

release of antidiuretic hormone (ADH). Usually reduction of plasma osmolality causes reduction of ADH secretion, but in SIADH reduced plasma

osmolality does not inhibit ADH release from the pituitary gland, causing

water overload. The main clinical features of SIADH include:

Hyponatremia (plasma sodium ,131 mmol/L)

Decreased plasma osmolality (,275 mOsm/kg)

Urine osmolality .100 mOsm/kg) and high urinary sodium

( .20 mmol/L)

No edema.

Various causes of SIADH are listed in Table 5.1.

5.7 Hyponatremia, Sick Cell Syndrome, and Hypernatremia

Table 5.1 Causes of SIADH*

Type of

Disease

Pulmonary

diseases

Neurological

Malignancies

Pneumonia, pneumothorax, acute respiratory failure, bronchial asthma,

atelectasis, tuberculosis.

Meningitis, encephalitis, stroke, brain tumor infection.

Lung cancer especially small cell carcinoma, head and neck cancer,

pancreatic cancer.

Two genetic variants, one affecting renal vasopressin receptor and

another affecting osmolality sensing in hypothalamus have been

reported.

Use of desmopressin or oxytocin can cause SIADH.

Hereditary

Hormone

therapy

Drugs

Cyclophosphamide, carbamazepine, valproic acid, amitriptyline, SSRI,

monoamine oxidase inhibitors and certain chemotherapeutic agents

may also cause SIADH.

*SIADH: Syndrome of Inappropriate Antidiuretic Hormone Secretion.

5.7 HYPONATREMIA, SICK CELL SYNDROME, AND

HYPERNATREMIA

Hyponatremia can be either absolute hyponatremia or dilutional hyponatremia, although in a clinical setting, dilutional hyponatremia is encountered

more commonly than absolute hyponatremia. In absolute hyponatremia,

total sodium content of the body is low. The patient is hypovolemic, which

results in activation of the renin–angiotensin system, causing secondary

hyperaldosteronism and also increased levels of ADH. In dilutional hyponatremia total body sodium is not low, rather, total body sodium may be

increased. The patient is volume overloaded with resultant dilution of

sodium levels. Examples of such conditions include congestive heart failure,

renal failure, nephrotic syndrome, and cirrhosis of the liver. Although hyponatremia is defined as any sodium value less than reference range (135 mEq/

L), usually clinical features such as confusion, restlessness leading to drowsiness, myoclonic jerks, convulsions, and coma are observed at much lower

sodium levels. Hyponatremia is common among hospitalized patients, and

affects up to 30% of all patients [6]. However, a sodium level below

120 mEq/L is associated with poor prognosis and even a fatal outcome [7].

Major types of hyponatremia include:

Absolute hyponatremia (patient is hypovolemic) related to loss of

sodium through the gastrointestinal tract or loss through the kidneys

73

74

CHAPTER 5:

W a t e r , H om e o s t as i s , E le c t r o l y t e s , a n d A c i dÀB a s e B a l a n c e

due to kidney diseases (pyelonephritis, polycystic disease, interstitial

disease) or through the kidneys due to glycosuria or therapy with

diuretics or less retention of sodium by the kidney due to

Dilutional hyponatremia (patient hypervolemic). This condition is

related to SIADH or conditions like congestive heart failure, renal failure,

nephrotic syndrome, and cirrhosis of the liver.

Pseudohyponatremia as seen in patients with hyperlipidemia and

hypergammaglobulinemia (also known as factitious hyponatremia).

Sick cell syndrome is defined as hyponatremia seen in individuals with acute

or chronic illness where cell membranes leak, allowing solutes normally inside

the cell to escape into extracellular fluid. Therefore, leaking of osmotically

active solutes causes water to move from intracellular fluid to extracellular

fluid, causing dilution of plasma sodium and consequently hyponatremia.

Sick cell hyponatremia also produces a positive osmolar gap. Sick patients

also produce high levels of ADH, which causes water retention, causing

hyponatremia.

CASE REPORT

A 36-year-old man was hospitalized with 3 days history of

malaise, drowsiness, and jaundice. He had a history of agoraphobia and alcohol abuse. On admission there was no meningismus, focal neurological signs, or liver failure. However,

later the patient became unconscious and developed hypotension and grand mal seizure and was transferred to the

ICU. His serum sodium level was 101 mEq/L and potassium

was 3.6 mmol/L, but all liver function tests were abnormally

high. His serum osmolality was 259 mOsm/kg, but calculated

osmolality was 214 mOsm/kg with an osmolar gap of

135 mOsm/kg. His serum albumin was 2.8 mg/dL. The

patient deteriorated despite aggressive therapy and later

died. The patient suffered from critical illness with multiorgan failure. Standard causes of hyponatremia were ruled

out, and he showed a markedly positive osmolar gap with

severe hyponatremia due to sick cell syndrome [8].

Hypernatremia is due to elevated serum sodium levels (above 150 mEq/L).

Symptoms of hypernatremia are usually neurological due to intraneuronal

loss of water to extracellular fluid. Patients exhibit features of lethargy, drowsiness, and eventually become comatose. Hypernatremia may be hypovolumic

or hypervolumic. The most common cause of hypovolemic hypernatremia is

dehydration, which may be due to decreased water intake or excessive water

loss through the skin (heavy sweating), kidney, or gastrointestinal tract (diarrhea). Patients usually present with concentrated urine (osmolality over

800 mOsm/kg) and low urinary sodium (,20 mmol/L). Hypervolemic

hypernatremia may be observed in hospitalized patients receiving sodium

bicarbonate or hypertonic saline. Hyperaldosteronism, Cushing’s syndrome,

and Conn’s disease may also cause hypervolemic hypernatremia.

### Tài liệu bạn tìm kiếm đã sẵn sàng tải về

15 Basic Statistical Analysis: Student t-Test and Related Tests

Tải bản đầy đủ ngay(0 tr)

×