MAKALAH PRINT!

1

METABOLISM AND NUTRITION MODULE

B SCENARIO

PROBLEM BASED LEARNING

PRESENTED BY:

GROUP 16th

FACULTY OF MEDICINE

AIRLANGGA UNIVERSITY

3rd SEMESTER – 2010


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B SCENARIO


Scenario Creator

Prof. Dr. Suhartati, dr., MS

Edhi Rianto, dr., MS


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16th Group Members

Leader :

Shaleh Muhammad D 010911171

Members:

Muhammad Achdiar R 010911152

Filipus Michael Yofrido 010911154

Togar Erkasan Sitorus 010911155

Christopher Njotokusgito 010911157

Karin Dhia Fahmita 010911158

Dini Nur Aini 010911163

Wirawan Indra P. 010911169

Rizal Constantino Susilo 010911170

Agnes Candra Pradhita 010911172

Tutor :

dr. Subagio


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CONTENTS

Cover ..................................................................................................................................1

Scenario Creator................................................................................................................2

Group Members ................................................................................................................3

Contents .............................................................................................................................4

Instructional Objectives ...................................................................................................5

Chapter I : 1st Tutorial .....................................................................................................6

1.1 Scenario..............................................................................................................61.2 Main Problem ....................................................................................................61.3 Keywords ..........................................................................................................61.4 Additional Information......................................................................................71.5 Early Hypothesis ...............................................................................................81.6 Early Mind Mapping .........................................................................................91.7 Learning Issue 1...............................................................................................10

Chapter II : 2nd Tutorial .................................................................................................11

2.1 Methods and Steps to Find the Information.....................................................11

2.2 The Answer of Learning Issue 1......................................................................11

2.3 Learning Issue II .............................................................................................41

Chapter III : 3rd Tutorial ................................................................................................42

3.1 The Answer of Learning Issue 1I.....................................................................42

3.2 Analysis ...........................................................................................................69

3.3 Final Hypothesis .............................................................................................76

3.4 Final Mind Mapping........................................................................................77

3.5 Group Opinion.................................................................................................79

3.6 Obstacles..........................................................................................................79

References ........................................................................................................................80

EBL & Critical Appraisal ..............................................................................................83

Appendix (Journal Appraisal) .......................................................................................91

Journal ............................................................................................................................97


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INSTRUCTIONAL OBJECTIVES

5

EIGHTH MODULE

HUMAN FUNCTION MODULE


After finishing this module, students of Airlangga university- School of

Medicine in third semester can explain the patophysiology of health problem

through understanding the intermediate metabolism.


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A woman, came to the outpatient polyclinic with complaints often

sleepy, sometimes feel tingling in both feet.

1.1 Scenario

1.3 Key Words

1.2. Main Problem

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CHAPTER I

FIRST TUTORIAL

Often feels sleepy

Often feels sleepy and numbness

1.3.1. Female

1.3.2. Numbness in both lower extremities

1.3.3. Outpatient treatment

1.3.4. Sleepy


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1.4 Additional Information

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1.4.1. Woman, age: 41 years old

1.4.2. Status: Married with 1 child

1.4.3. Occupation: Housewive

1.4.4. Address: Kupang Indah; Surabaya

1.4.5. She has been feeling numbness for 1 month

1.4.6. Almost every night wakes up to go to the toilet

1.4.7. Medical Record: No hypertension

Body weight has decreased 3 kg recently

1.4.8. Family Medical Record: Her father passed away due to complication

Her brother passed away in the age of 40

years old with smelly and can-not-heal

wound in his leg

1.4.9. Husband’s occupation: Private Company Officer

1.4.10. Physical Examination: Body weight: 89 kg

Height: 157 cm

Blood Pressure:120/80 mmHg

Pulse: 80 times per minute

RR: 20 times per minute

Body temperature: 37ºC

No anemic sign

No cyanotic sign

No icterus sign

Heart and Lung: Normal condition

Hepar and Spleen: cannot be sense

Abdomen Circle measurement 92 cm

No acytes sign

No extremity abnormality


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1.6 Early Mind Mapping

1.5 Early Hypothesis

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Diabetes Mellitus

Malnutrition deficiency

Anemia

Neuron disorders

Cardio-vascular disorders

Lipid metabolism disorders

Hypoxia


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FINANCIALCONDITION

1.7 Learning Issue 1

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1.7.1. What are the causes of drowsiness?


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Early hypothesis:DM

Malnutrition DeficiencyNeuron Disorders

Physical Examination:

Weight 89 kgHeight 157cm

BP 120/80 mmHgPP 80 tpmRR 20 tpm

Temperature 37 ºC

Anamnesis:TinglingSleepy

Weight Loss

Supporting Exam:Hepar & Spleen normalHeart & Lung normalNo anemic, cyanotic,

icterus

Female; 41 y.o

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1.7.2 How is the mechanism of numbness/tingling?

1.7.3 How is the patophysiology of Diabetes Mellitus?

1.7.4 What are the symptoms of Diabetes Mellitus?

1.7.5 What is normal stomach circumference of human?

1.7.6 What are the risk factors of Diabetes Mellitus?

1.7.7 What are the complications of Diabetes Mellitus?

1.7.8 What is blood gas analysis?

1.7.9 How is the normal blood glucose measurement?

1.7.10 How is the normal rate of TG?

1.7.11 How is the normal rate of Haemoglobin?

1.7.12 What is anion gap?

1.7.13 What are the symptoms of anemia?


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2.1 METHODS AND STEPS TO FIND THE INFORMATION

2.2 THE ANSWERS OF LEARNING ISSUES I

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CHAPTER II

SECOND TUTORIAL

To get the information we need, we use some sources, such as:

1. Text Books

We used text books from library, our relative’s books. We also

bought some books to get more information.

2. Internet

We got information from internet in the form of scientific journals

and articles. By typing the keywords in the search engine, we got

much information both in English and in Indonesian.

Sources in English are cited directly into this report but sources in

Indonesian are translated into English first.

2.2.1 What are the causes of drowsiness?

Having to work long hours or different shifts (nights, weekends)

Medications (tranquilizers, sleeping pills, antihistamines)

Medical conditions (such as hypothyroidism, hypercalcemia, and

hyponatremia /hypernatremia)

Not sleeping for long enough

Sleep disorders (such as sleep apnea syndrome and narcolepsy)


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2.2.2 How is the mechanism of numbness/tingling?

Any time you remain still for a long period, particularly if you're leaning

on your arm or sitting cross-legged, you are bound to develop a pins-and-needles

sensation in one or more limbs. This feeling results from temporary nerve

compression and diminished blood flow, and it passes as soon as you move

around a bit.

Many medical conditions, however, cause a persistent tingling sensation

— usually in the hands, arms, feet, or legs — that is unrelated to posture and

unrelieved by movement. While several of these conditions originate in the

peripheral nervous system (the network of nerves branching out from the spinal

cord to the extremities), others are based primarily in different parts of the body.

In general, persistent tingling is a troubling symptom that requires a thorough

medical workup.

2.2.3 What are the patophysiologies of Diabetes Melitus?

Diabetes is a chronic metabolic disorder in which the body cannot

metabolize carbohydrates, fats, and proteins because of a lack of, or ineffective

use of, the hormone insulin. Diabetes is classified into three primary types that are

different disease entities but share the symptoms and complications of

hyperglycemia (high blood glucose). Impaired glucose tolerance, formerly known

as "borderline diabetes" is a degree of hyperglycemia that may precede type 2

diabetes.

The pathophysiology of diabetes mellitus in all forms is related to the

insulin hormone. Insulin is secreted by cells in the pancreas and is responsible for

regulating the level of glucose in the bloodstream. It also aids the body in

breaking down the glucose to be used as energy. When someone suffers from

diabetes, however, the body does not break down the glucose in the blood as a

result of abnormal insulin metabolism. This results in elevated levels of glucose in


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the blood, which is known as hyperglycemia. When glucose levels remain high

over an extended period of time, severe complications including cardiovascular

disease, kidney damage, eye disorders, and nerve problems can occur. Diabetes

mellitus occurs in three different forms - type 1, type 2, and gestational.

I. Type 1 (previously called insulin dependent diabetes mellitus (IDDM) or juvenile onset diabetes)A. Causes

1. Genetic predisposition.

2. Environmental exposure: virus, toxin, stress.

3. Autoimmune reaction: beta-cells that produce insulin in the pancreas are

destroyed. When 80-90% of the beta-cells are destroyed, overt symptoms

occur.

B. Characteristics1. Usually occurs before 30 years of age, but can occur at any age. Peak

incidence occurs during puberty, around 10-12 years of age in girls and

12-14 years in boys.*

2. Abrupt onset of signs and symptoms of hyperglycemia: increased thirst

and hunger, frequent urination, weight loss, and fatigue.

3. Ketosis prone.

* Source: American Diabetes Association. Diabetes Facts. November, 2003.C. Treatment

1. Insulin by injection with syringes or pumps

2. Diet

3. Exercise

4. Education

5. Monitoring

II. Type 2 (previously called non-insulin-dependent diabetes mellitus, NIDDM, or adult onset diabetes)A. Causes


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1. Insulin resistance: unable to utilize insulin that the body makes because of

cell-receptor defect; glucose is unable to be absorbed into cells for fuel.

2. Decreased insulin secretion: pancreas does not secrete enough insulin in

response to glucose levels.

3. Excess production of glucose from the liver: result of defective insulin

secretor response; dawn phenomenon (see glossary) is an example.

B. Characteristics

1. Usually occurs after 30 years of age, but is now occurring in children and

adolescents.

2. Increased prevalence in some ethnic groups, e.g., African Americans,

Hispanic/Latino, Native Americans, Asian Americans, and Pacific

Islanders.

3. Strong genetic predisposition.

4. Frequently obese.

5. Not prone to ketoacidosis until late in course or with prolonged

hyperglycemia.

6. May or may not have symptoms of hyperglycemia.

7. May also have extreme tiredness, blurred vision, delayed healing,

numbness and tingling of hands and feet, recurring yeast infection.

8. Children between the ages of 10-19 that have one or more of the following

are at an increased risk:

• Family history

• Member of certain ethnic populations listed above in B.2.

• Overweight

• Sedentary lifestyle

• Pre-puberty.

• Signs of insulin resistance or conditions associated with insulin

resistance (acanthosis nigricans [dirty-neck syndrome],

hypertension [high blood pressure], dyslipidemia [lipoproteins

inbalance], polycystic ovarian syndrome [PCOS]).


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C. Treatment

1. Diet/weight management

2. Exercise/increase physical activity

3. Oral hypoglycemic/antihyperglycemic agents, insulin sensitizers, or

insulin

4. Education

5. Monitoring

6. Treatment of co morbid conditions (e.g., hypertension, lipid abnormalities)

III. Gestational Diabetes Mellitus (GDM)

A. Causes

1. Insulin resistance due to pregnancy

2. Genetic predisposition

B. Characteristics

1. Carbohydrate intolerance during pregnancy identified via 1-hour screen

using a 50-g oral glucose load (performed between 24th and 28th week of

gestation unless otherwise indicated). If the 1-hour screen for glucose is

>140 mg/dl (>7.8 mmol/l), a full diagnostic 100-g, 3-hour oral glucose

tolerance test (OGTT) is indicated.

C. Treatment

1. Diet: provide adequate calories without hyperglycemia or ketonemia

2. Exercise: program that does not cause fetal distress, contractions, or

hypertension (>140/90 mmHg).

3. Insulin: if unable to consistently maintain blood glucose <95 mg/dl fasting

(<5.3 mmol/ l) and <140 mg/dl (<7.8 mmol/l) 1 hour postprandial and

<120 mg/dl (<6.7 mmol/l) 2 hours postprandial.


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D. Monitoring

1. Blood glucose: required to determine effectiveness of treatment and

possible need for insulin. Glucose should be checked fasting and 1-2 hours

postprandial.

2. Ketones: test for ketones using first morning urine sample. Presence of

ketones may indicate starvation rather than hyperglycemic ketosis.

2.2.4 What are the symptoms of Diabetes Mellitus?

Excessive thirst and increased urination

Excessive thirst and increased urination are classic diabetes signs and symptoms. When you have diabetes, excess sugar (glucose) builds up in your blood. Your kidneys are forced to work overtime to filter and absorb the excess sugar. If your kidneys can't keep up, the excess sugar is excreted into your urine along with fluids drawn from your tissues. This triggers more frequent urination, which may leave you dehydrated. As you drink more fluids to quench your thirst, you'll urinate even more.

Fatigue

You may feel fatigued. Many factors can contribute to this. They include dehydration from increased urination and your body's inability to function properly, since it's less able to use sugar for energy needs.

Weight loss

Weight fluctuations also fall under the umbrella of possible diabetes signs and symptoms. When you lose sugar through frequent urination, you also lose calories. At the same time, diabetes may keep the sugar from your food from reaching your cells — leading to constant hunger. The combined effect is potentially rapid weight loss, especially if you have type 1 diabetes.

Blurred vision

Diabetes symptoms sometimes involve your vision. High levels of blood sugar pull fluid from your tissues, including the lenses of your eyes. This affects your ability to focus.

Left untreated, diabetes can cause new blood vessels to form in your retina — the back part of your eye — as well as damage established vessels. For most people, these early changes do not cause vision problems. However, if these changes progress undetected, they can lead to vision loss and blindness.


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Slow-healing sores or frequent infections

Doctors and people with diabetes have observed that infections seem more common if you have diabetes. Research in this area, however, has not proved whether this is entirely true, nor why. It may be that high levels of blood sugar impair your body's natural healing process and your ability to fight infections. For women, bladder and vaginal infections are especially common.

Tingling hands and feet

Excess sugar in your blood can lead to nerve damage. You may notice tingling and loss of sensation in your hands and feet, as well as burning pain in your arms, hands, legs and feet.

Red, swollen, tender gums

Diabetes may weaken your ability to fight germs, which increases the risk of infection in your gums and in the bones that hold your teeth in place. Your gums may pull away from your teeth, your teeth may become loose, or you may develop sores or pockets of pus in your gums — especially if you have a gum infection before diabetes develops.

2.2.5 What is normal stomach circumference of human?

To determine whether suffering abdominal obesity or not, the people of

Indonesia have the ideal waist size. Usually, women's waist size 90 inches biggest

meter and men's 80 inch meter. If more than that, they sign congested hormone

bad fats in the stomach. This will trigger the spread of various diseases metabolic

disorders.

If someone has abdominal circumference more than the normal number,

then it could be said he was experiencing abdominal obesity. What causes

obesity? It is said that there are two factors causing the genetic and lifestyle

factors. However, more cases of abdominal fat due to diet and an increasingly

unbalanced motion.

In fact, unhealthy lifestyle diseases (metabolic syndrome), stage 1 has

been ongoing since early 1990, particularly in urban areas. Since then the

Indonesian people begin to experience obesity. Especially since the fast-food

restaurants to grow and increasingly giving kemudahkan for people to eat all the

time. Meanwhile, the pattern of motion (sports) in the stomach the less. Whereas


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most high mobility of fat in the abdomen and the nature of fat is more dangerous

than the fat in the thighs or in other organs.

Also explained that the fat can not be removed through liposuction,

because the fat inside the abdomen, rather than under a layer of skin. The

hormone estrogen source of fat in the thighs, the center of power, and bearing, on

the contrary in the stomach, the hormone is more dangerous, and in abdominal fat,

there are a lot of the mobility of free fatty acids to the liver and

muscles. Furthermore, it will affect the fatty acid metabolism and pancreatic

work.

2.2.6 What are the risk factors of Diabetes Mellitus?

You have a higher risk for diabetes if you have any of the following:

Age greater than 45 years

Diabetes during a previous pregnancy

Excess body weight (especially around the waist)

Family history of diabetes

Given birth to a baby weighing more than 9 pounds

HDL cholesterol under 35 mg/dL

High blood levels of triglycerides, a type of fat molecule (250 mg/dL or

more)

High blood pressure (greater than or equal to 140/90 mmHg)

Impaired glucose tolerance

Low activity level (exercising less than 3 times a week)

Metabolic syndrome

Polycystic ovarian syndrome

A condition called acanthosis nigricans, which causes dark, thickened skin

around the neck or armpits

Persons from certain ethnic groups, including African Americans,

Hispanic Americans, Asian Americans, and Native Americans, have a higher risk

for diabetes.


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Everyone over 45 should have a blood sugar (glucose) test at least every 3

years. Regular testing of blood sugar levels should begin at a younger age, and be

performed more often if you are at higher risk for diabetes. (MedlinePlus, 2010)

2.2.7 What are the complications of Diabetes Mellitus?

Without proper management it can lead to various complications such as

cardiovascular disease, kidney failure, blindness and nerve damage. Short-term

complications:

Low blood sugar (hypoglycaemia)

A person who takes insulin is going to face the problem of their blood

sugar falling too low at some point (because they have overestimated the

insulin they need, have exercised more than anticipated or have not eaten

enough). Hypoglycaemia can be corrected rapidly by eating some sugar. If

it is not corrected it can lead to the person losing consciousness.

It is important that the person with diabetes recognises the signs of

hypoglycaemia.

Ketoacidosis

When the body breaks down fats, acidic waste products called ketones are

produced. The body cannot tolerate large amounts of ketones and will try

to get rid of them through the urine. However, the body cannot release all

the ketones and they build up in your blood, causing ketoacidosis.

Ketoacidosis is a severe condition caused by lack of insulin. It mainly

affects people with type 1 diabetes.

Lactic acidosis

Lactic acidosis is the build up of lactic acid in the body. Cells make lactic

acid when they use glucose for energy. If too much lactic acid stays in the

body, the balance tips and the person begins to feel ill. Lactic acidosis is

rare and mainly affects people with type 2 diabetes.

Bacterial/fungal infections


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People with diabetes are more prone to bacterial and fungal infections.

Bacterial infections include sties and boils. Fungal infections include

athlete’s foot, ringworm and vaginal infections.

Long-term complications:

Eye disease (retinopathy)

Eye disease, or retinopathy, is the leading cause of blindness and visual

impairment in adults in developed societies. About 2% of all people who

have had diabetes for 15 years become blind, while about 10% develop a

severe visual impairment.

IDF fact sheet on diabetes and eye disease

Kidney disease (nephropathy)

Diabetes is the leading cause of kidney disease (nephropathy). About one

third of all people with diabetes develop kidney disease and approximately

20% of people with type 1 diabetes develop kidney failure.

IDF fact sheet on diabetes and kidney disease

Nerve disease (neuropathy)

Diabetic nerve disease, or neuropathy affects at least half of all people

with diabetes. There are different types of nerve disease which can result

in a loss of sensation in the feet or in some cases the hands, pain in the foot

and problems with the functioning of different parts of the body including

the heart, the eye, the stomach, the bladder and the penis. A lack of

sensation in the feet can lead to people with diabetes injuring their feet

without realising it. These injuries can lead to ulcers and possibly

amputation.

Diseases of the circulatory system

Disease of the circulatory system, or cardiovascular disease, accounts for

75% of all deaths among people with diabetes of European origin. In the

USA, corony heart disease is present in between 8% and 20% of people

with diabetes over 45 years of age. Their risk of heart disease is 2-4 times


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higher than those who do not have diabetes. It is the main cause of

disability and death for people with type 2 diabetes in industrialized

countries.

IDF fact sheet on diabetes and cardiovascular disease

Amputation

Diabetes is the most common cause of amputation that is not the result of

an accident. People with diabetes are 15 to 40 times more likely to require

lower-limb amputation compared to the general population. (International

Diabetes Federation, 2010)

2.2.8 What is the blood gas analysis?

Blood Gases, Arterial (ABG)—Blood Norm.

Must be corrected for body temperature.

SI Units

pH

Adults 7.35–7.45 7.35–7.45

Panic values ≤7.2 and >7.6 ≤7.2 and >7.6

Children

Birth to 2 months 7.32–7.49 7.32–7.49

2 months to 2 years 7.34–7.46 7.34–7.46

>2 years 7.35–7.45 7.35–7.45

PaCO2 35–40 mm Hg 4.7–5.3 kPa

Panic values <20 mm Hg <2.7 kPa

>70 mm Hg >9.4 kPa

PaO2 80–100 mm Hg 10.7–13.3 kPa


HCO3- 22–31 mEq/L 22–31 mmol/L


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SI Units

Panic values <10 mEq/L <10 mmol/L

>40 mEq/L >40 mmol/L

O2 Saturation 96%–100% 0.96–1.00

Panic value <60% <0.60

Oxyhemoglobin Dissociation Curve No shift

Increased pH.

Alkali ingestion, Cushing's disease, diarrhea, fever, high altitude,

hyperventilation, hysteria, intestinal obstruction (pyloric, duodenal), metabolic

alkalosis, peptic ulcer therapy, renal disease, respiratory alkalosis, salicylate

intoxication, and vomiting (excessive). Drugs include sodium bicarbonate.

Increased PaCO2.

Acute intermittent porphyria, aminoglycoside toxicity, asthma (late stage), brain

death, coarctation of the aorta, congestive heart failure, electrolyte disturbance

(severe), emphysema, empyema, hyaline membrane disease, hyperemesis,

hypothyroidism (severe), hypoventilation (alveolar), metabolic alkalosis, near

drowning, pleural effusion, pleurisy, pneumonia, pneumothorax, poisoning,

pulmonary edema, pulmonary infection, renal disorders, respiratory acidosis,

respiratory failure, shock, tetralogy of Fallot, transposition of the great vessels,

and vomiting. Drugs include aldosterone, ethacrynic acid, metolazone,

prednisone, sodium bicarbonate, and thiazides.

Increased PaO2.

Hyperbaric oxygenation and hyperventilation.

Increased HCO3-.

Anoxia, metabolic alkalosis, and respiratory acidosis.

Increased O2 Saturation.


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High altitudes, hypocapnia, hypothermia, increased cardiac output, hyperbaric

oxygenation, increased oxygen affinity for hemoglobin, oxygen therapy, positive

end-expiratory pressure (PEEP) added to mechanical ventilation, respiratory

alkalosis.

Decreased pH.

Addison's disease, asthma, cardiac disease, diabetic ketoacidosis, diarrhea,

emphysema, dysrhythmias, hepatic disease, hypercapnia, hypoventilation,

malignant hyperthermia, metabolic acidosis, myocardial infarction, nephritis,

nephrosis, pneumonia, pulmonary edema, pulmonary embolism, pulmonary

infection, pulmonary malignancy, pulmonary obstructive disease, renal disease,

respiratory acidosis (also caused by large volumes of lactated Ringer's),

respiratory failure, sepsis, and shock.

Decreased PaCO2.

Dysrhythmias, asthma (early stage), diabetic ketoacidosis, diabetes mellitus,

fever, high altitude, hyperventilation, metabolic acidosis, respiratory alkalosis,

and salicylate intoxication. Drugs include acetazolamide, dimercaprol, methicillin

sodium, nitrofurantoin, nitrofurantoin sodium, tetracycline, and triamterene.

Decreased PaO2.

Acute respiratory distress syndrome, anoxia, anesthesia, aortic valve stenosis,

arteriovenous shunt, asthma, atelectasis, atrial septal defect, berylliosis, carbon

monoxide poisoning, cerebrovascular accident, coarctation of the aorta,

emphysema, flail chest, Hamman-Rich syndrome, head injury, hyaline membrane

disease, hypercapnia, hypoventilation, lung resection, lymphangitic

carcinomatosis, near drowning, phrenic nerve paralysis, pickwickian syndrome,

pain causing restricted diaphragmatic breathing, pleural effusion, pneumonia,

pneumothorax, poisoning, poliomyelitis (acute), pulmonary adenomatosis,

pulmonary embolism, pulmonary infection, pulmonary hemangioma, pulmonic

stenosis, respiratory failure, sarcoidosis, shock, smoke inhalation, status


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epilepticus, tetanus, transposition of the great vessels, tricuspid atresia, and

ventricular septal defect.

Decreased HCO3-.

Hypocapnia, metabolic acidosis, and respiratory alkalosis.

Decreased O2 Saturation.

Acute respiratory distress syndrome, anesthesia, anoxia, anorexia, aortic valve

stenosis, arteriovenous shunt, asthma, atelectasis, atrial septal defect, berylliosis,

carbon monoxide poisoning, cerebrovascular accident, coarctation of the aorta,

congenital heart defects, decreased cardiac output, decreased oxygen affinity for

hemoglobin, emphysema, fever, flail chest, Hamman-Rich syndrome, head injury,

hyaline membrane disease, hypercapnia, hypoventilation, hypoxia, lung resection,

lymphangitic carcinomatosis, near drowning, phrenic nerve paralysis, pickwickian

syndrome, pain causing restricted diaphragmatic breathing, pleural effusion,

pneumonia, pneumothorax, poisoning, poliomyelitis (acute), pulmonary

adenomatosis, pulmonary embolism, pulmonary infection, pulmonary

hemangioma, pulmonic stenosis, respiratory acidosis, respiratory failure,

sarcoidosis, shock, smoke inhalation, status epilepticus, tetanus, transposition of

the great vessels, tricuspid atresia, and ventricular septal defect.

Oxyhemoglobin Dissociation Curve.

See diagram.

Shift to Left.

2,3-DPG deficiency, high altitude, hypocapnia, hypothermia, and respiratory

alkalosis.

Shift to Right.

Cluster headaches, emphysema, fever, hypercapnia, increased production of 2,3-

DPG, and respiratory acidosis.


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Description.

The arterial blood gas test measures the dissolved oxygen and carbon dioxide in

the arterial blood and reveals the acid-base state and how well the oxygen is being

carried to the body. The pH is the measurement of free H+ ion concentration in

circulating blood. Intracellular metabolism results in the continuous production of

hydrogen ions, which are buffered as either an acid (HCO3-) or a base (H2CO3).

The body demands that pH remain constant. The kidneys and lungs regulate pH

by preserving the ratio of acid to base. Any alteration in the ratio between

bicarbonate and carbonic acid will cause a reciprocal change in release or uptake

of free H+, thereby altering pH value. Significant deviations in pH can be life

threatening. Both bicarbonate (HCO3-) and carbonic acid (H2CO3) are components

of the body's acid-base system that influence pH. The partial pressure of carbon

dioxide (pCO2, PaCO2) is the amount of carbon dioxide in the blood based on the

pressure it exerts in the bloodstream and represents the degree of alveolar

ventilation occurring. When pH decreases, more CO2 dissociates from carbonic

acid and is exhaled through the lungs, counteracting the pH reduction and

increasing the breathing rate. The partial pressure of oxygen (pO2, PaO2) is the

amount of oxygen dissolved in plasma and represents the status of alveolar gas

exchange with inspired air. Oxygen saturation (O2Sat) is the amount of oxygen

actually bound to hemoglobin (as a percentage of the maximum amount that could

be bound) and available for transport throughout the body. SaO2 applies to arterial

hemoglobin saturation:

The oxyhemoglobin dissociation curve represents the affinity of hemoglobin for

oxygen by demonstrating the normal levels of arterial oxygen saturation (O2Sat,

SaO2) of hemoglobin at varying partial pressures of oxygen. P-50 is the partial

pressure of oxygen at which the given hemoglobin sample is 50% saturated. The

Hem-O-Scan machine analyzes and plots the hemoglobin-oxygen dissociation on

a curve. When the curve is shifted to the left, more oxygen is delivered to the

tissues for a given partial pressure of oxygen; when the shift is to the right, less

oxygen is delivered to the tissues. Generally, decreased oxygen saturation to less


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than 90%–92% must be addressed by thorough assessment of the client and

clinical status.

Blood Gases, Venous—Blood Norm.


SI Units

pH 7.32–7.43 7.32–7.43

Panic value <7.2 or >7.6 <7.2 or >7.6

pCO2 35–45 mm Hg 4.6–6.0 kPa

pO2 20–49 mm Hg 2.6–6.5 kPa



>40 mEq/L >40 mEq/L

O2 Saturation 60%–80% 0.60–0.80

Increased pH.

See Blood gases, Arterial—Blood .

Increased pCO2.


Increased pO2.

Interpretation of oxygen levels is not appropriate on venous blood specimens.

Increased HCO3-.



Interpretation of oxygen saturation is not appropriate on venous blood specimens.


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Decreased pH.


Decreased pCO2.


Decreased pO2.

Interpretation of oxygen levels is not appropriate on venous blood specimens.

Decreased HCO3-.



Interpretation of oxygen saturation is not appropriate on venous blood specimens.

Description.

A method for assessing acid-base status and for cellular hypoxia without

performing an arterial puncture. Venous blood gases may be used in situations

where assessment of oxygenation is unnecessary. (See Blood gases, Arterial—

Blood for complete descriptions of the test components.)

Blood Gases, Capillary—Blood Norm.


SI Units

pH

Adults 7.35–7.45 7.35–7.45

Panic values <7.2 or >7.6 <7.2 or >7.6

Children (arterialized capillary sample)

Birth to 2 months 7.32–7.49 7.32–7.49

2 months to 2 years 7.34–7.46 7.34–7.46


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28

SI Units

>2 years 7.35–7.45 7.35–7.45

pCO2 26.4–41.2 mm Hg 3.5–5.4 kPa


>70 mm Hg >9.4 kPa

pO2 75–100 mm Hg 10.0–13.3 kPa




>40 mEq/L >40 mmol/L

O2 Saturation 96%–100% 0.96–1.00

Panic value <60% <0.60

Increased pH.


Increased pCO2.


Increased pO2.


Increased HCO3-.




Decreased pH.


Decreased pCO2.


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29


Decreased pO2.

Capillary pO2 interpretation is limited to assessment for hypoxia.

Decreased HCO3-.




Description.

A method for determining acid-base status from a heel stick for capillary blood.

Used mostly in infants to assess pH and pCO2. (See Blood gases, Arterial , for

complete description of the test components.) (Chernecky & Berger, 2008)

2.2.9 How is the normal blood glucose measurement?

Glucose—Blood Norm.

Dependent on time and content of last meal. In normal clients, glucose levels return to the fasting level (given in these norms) within 2 hours after the last meal.

SI Units

Whole Blood

Adults 60–89 mg/dL 3.3–4.9 mmol/L

>60 years 68–98 mg/dL 3.8–5.4 mmol/L

Children

Cord blood 38–82 mg/dL 2.1–4.6 mmol/L

Premature infant 17–51 mg/dL 0.9–2.8 mmol/L

Neonate 25–51 mg/dL 1.4–2.8 mmol/L

Newborn to 24 hours 34–51 mg/dL 1.9–2.8 mmol/L

Newborn >24 hours 42–68 mg/dL 2.3–3.8 mmol/L


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30

SI Units

Child 51–85 mg/dL 2.8–4.7 mmol/L

Serum

Adults 65–100 mg/dL 3.6–5.5 mmol/L

>60 years 80–115 mg/dL 4.4–6.4 mmol/L

Children

Cord blood 45–96 mg/dL 2.5–5.3 mmol/L

Premature infants 20–60 mg/dL 1.1–3.3 mmol/L

Neonates 30–60 mg/dL 1.7–3.3 mmol/L

Newborn to 24 hours 40–60 mg/dL 2.2–3.3 mmol/L

Newborn >24 hours 50–80 mg/dL 2.8–4.4 mmol/L

Child 60–100 mg/dL 3.3–5.5 mmol/L

NOTE: Whole-blood glucose values are about 15% less than serum glucose values because of greater dilution.

Panic Levels

Adults <40 mg/dL or >700 mg/dL

<2.2 mmol/L or >38.6 mmol/L

Neonates <30 mg/dL or >300 mg/dL

<1.6 mmol/L >16.0 mmol/L

Increased.

Acromegaly, anesthesia, burns, carbon monoxide poisoning, cerebrovascular

accident, convulsions, Cushing's disease, Cushing's syndrome, cystic fibrosis,

diabetes mellitus, eclampsia, encephalitis, erectile dysfunction, gigantism,

hemochromatosis, hemorrhage, hyperosmolar hyperglycemic nonketotic coma

(HHNK), hyperthyroidism, hyperpituitarism, hyperadrenalism, hypertension,

hypervitaminosis A (chronic), infections, injury, malnutrition (chronic),

meningitis, myocardial infarction, obesity, pancreatic carcinoma, pancreatic

insufficiency, pancreatitis (chronic), pheochromocytoma, pituitary adenoma,

pregnancy, shock, subarachnoid hemorrhage, stress, trauma, and Wernicke's


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31

encephalopathy. Drugs include anabolic steroids, androgens, arginine, ascorbic

acid, asparaginase, aspirin, atenolol, baclofen, benzodiazepines, bisacodyl

(prolonged use), chlorpromazine, chlorthalidone, cimetidine, clonidine,

corticosteroids, corticotropin, dextran, dextrothyroxine, diazoxide, disopyramide

phosphate, epinephrine, epinephrine bitartrate, epinephrine borate, epinephrine

hydrochloride, estrogens, ethacrynic acid, furosemide, glucose infusions,

haloperidol, imipramine, isoproterenol hydrochloride, heparin calcium, heparin

sodium, hydralazine hydrochloride, hydrochlorothiazide, indomethacin, isoniazid,

levodopa, levothyroxine sodium/T4, lithium carbonate, magnesium hydroxide

(prolonged high doses), meperidine, mercaptopurine, methimazole, methyldopa,

methyldopate (hydrochloride), metronidazole, nalidixic acid, niacin, nicotine,

nicotinic acid, oral contraceptives, oxazepam, p-aminosalicyclic acid,

phenolphthalein, phenytoin, phenytoin sodium, progestins, promethazine

hydrochloride, propranolol (in diabetic clients), propylthiouracil, protease

inhibitors, reserpine, rifampin, risperidone, ritodrine hydrochloride, sildenafil,

terbutaline sulfate, tetracyclines, thiazides/thiazide diuretics, thyroglobulin,

thyroid medications, tolbutamide (SMA methodology), and triamterene.

Decreased.

Addison's disease, adrenal medulla unresponsiveness, alcoholism, carcinoma

(adrenal gland, stomach, fibrosarcoma), cirrhosis, cretinism, diabetes mellitus

(early), dumping syndrome, exercise, fever, Forbes' disease (type III glycogen

deposition disease), fructose intolerance, galactosemia, glucagon deficiency,

hepatic phosphorylase deficiency (type VI glycogen storage disease), hepatitis,

hyperinsulinemia, hypopituitarism, hypothermia, hypothyroidism, infant of

diabetic mother, insulin overdose (factitious hypoglycemia), insulinoma,

kwashiorkor, leucine sensitivity, malnutrition, maple syrup urine disease, muscle

phosphofructokinase deficiency (type VII glycogen storage disease), myxedema,

pancreatic islet cell tumor, pancreatitis, postoperatively (after gastrectomy or

gastroenterostomy), postprandial hypoglycemia, Reye's syndrome, Simmonds'

disease, vomiting, von Gierke's disease (type I glycogen storage disease),


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32

Waterhouse-Friderichsen syndrome, and Zetterstrom syndrome. Drugs include

acetaminophen, allopurinol, amphetamines, aspirin, atenolol, beta-adrenergic

blockers, caffeine, cerivastatin, chlorpropamide, clofibrate, edetate disodium,

ethyl alcohol (ethanol), gatifloxacin, guanethidine sulfate, isoniazid, insulin,

isocarboxazid, marijuana, nitrazepam, oral hypoglycemic agents, p-aminosalicylic

acid, pargyline hydrochloride, phenacetin, phenazopyridine, phenelzine sulfate,

phenformin, propranolol (in diabetics), tetracyclines, theophylline, and

tranylcypromine sulfate. Herbs or natural remedies include zhi mu (‘know-

mother,' Anemarrhena asphodeloides, an herb) and shi gao (‘stone-plaster,'

calcium sulfate, gypsum) taken in combination; xuan shen (‘black ginseng,'

Scrophularia ningpoensis, figwort) and cang zhu (‘green-shu/zhu herb,'

Atractylodes lancea, var. ovata) taken in combination; shan yao (‘mountain-

medicine,' Dioscorea batatas, potato yam) and huang qi (‘yellow-old 60,'

Astragalus reflexistipulus, or A. hoantchy, yellow vetch) taken in combination;

and karela (Momordica charantia, balsam apple) taken in combination with

chlorpropamide. Herbs or natural remedies include teas (decoctions, infusions)

containing chromium, karela, ginseng, guar gum, meshasringi (Gymnema

sylvestre, mesha shringi, Indian milkweed vine), methi (fenugreek leaves),

syzigium cumini (jamun), tundika (Coccinia indica).

Description.

Glucose is a monosaccharide found naturally occurring in fruits. It is also formed

from the digestion of carbohydrates and the conversion of glycogen by the liver

and is the body's main source of cellular energy. Glucose is essential for brain and

erythrocyte function. Excess glucose is stored as glycogen in the liver and muscle

cells. Hormones influencing glucose metabolism include insulin, glucagon,

thyroxine, somatostatin, cortisol, and epinephrine. Fasting glucose levels are used

to help diagnose diabetes mellitus and hypoglycemia. A randomly timed test for

glucose is usually performed for routine screening and nonspecific evaluation of

carbohydrate metabolism. The American Diabetes Association criteria for


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33

diagnosis of diabetes mellitus include a fasting plasma glucose level of >126

mg/dL (7 mmol/L).

Glucose, 2-Hour Postprandial—Serum Norm.

SI Units

Newborn to 50 years 65–140 mg/dL

3.6–7.7 mmol/L

50–60 years 65–150 mg/dL

3.6–8.3 mmol/L

>60 years 65–160 mg/dL

3.6–8.8 mmol/L

American Diabetes Association diagnosis of diabetes (after 75-g glucose load)

>200 mg/dL

>11 mmol/L

Usage.

Screening for diabetes mellitus and assessing control of hyperglycemia.

Increased.

Acromegaly, anoxia, anxiety, brain tumor, cirrhosis, convulsive disorders,

Cushing's disease, Cushing's syndromea, diabetes mellitus, dumping syndrome

(after gastrectomy), hepatic disease (chronic), hyperlipoproteinemia,

hyperthyroidism, infarction (myocardial, cerebral), lipoproteinemias, malnutrition,

malignancy, nephrotic syndrome, pancreatitis, pheochromocytoma, preeclampsia,

pregnancy, sepsis, and stress (physical, emotional). Drugs include those discussed

under Glucose—Blood.

Decreased.


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Addison's disease, adrenal insufficiency, anterior pituitary insufficiency,

congenital adrenal hyperplasia, hepatic insufficiency, hyperinsulinism,

hypoglycemia, hypopituitarism, hypothyroidism, insulinoma, islet cell adenoma,

malabsorption syndrome, myxedema, steatorrhea, and von Gierke's disease. Drugs

include those discussed under Glucose—Blood.

Description.

The 2-hour postprandial glucose test is the measurement of serum glucose level 2

hours from the beginning of a meal containing a specific amount of carbohydrate.

In normal clients, glucose should return to fasting levels within 2 hours after the

ingestion of the test meal. (Chernecky & Berger, 2008)

2.2.10 How is the normal rate of TG?

Triglycerides—Blood Norm.

Serum Values SI Units

Adult Females

20–29 years 10–100 mg/dL 0.11–1.13 mmol/L

30–39 years 10–110 mg/dL 0.11–1.24 mmol/L

40–49 years 10–122 mg/dL 0.11–1.38 mmol/L

50–59 years 10–134 mg/dL 0.11–1.51 mmol/L

>59 years 10–147 mg/dL 0.11–1.66 mmol/L

Adult Males

20–29 years 10–157 mg/dL 0.11–1.77 mmol/L

30–39 years 10–182 mg/dL 0.11–2.05 mmol/L

40–49 years 10–193 mg/dL 0.11–2.18 mmol/L

50–59 years 10–197 mg/dL 0.11–2.22 mmol/L


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Serum Values SI Units

>59 years 10–199 mg/dL 0.11–2.24 mmol/L

Children

Female: 1–19 years 10–121 mg/dL 0.11–1.36 mmol/L

Male: 1–19 years 10–103 mg/dL 0.11–1.16 mmol/L

NOTE: Plasma values are lower by about 3%.

Classification of Triglyceride Levels

Borderline high 200–400 mg/dL 2.3–4.5 mmol/L

High 400–1000 mg/dL 4.5–11.3 mmol/L

Very high >1000 mg/dL >11.3 mmol/L

Increased.

Alcoholism, aortic aneurysm, aortitis, arteriosclerosis, diabetes mellitus, diet

(recent high-carbohydrate, prolonged high-fat), familial hypertriglyceridemia, fat

embolism, glycogen storage diseases, gout, hepatic cholesterol ester storage

disease, hypercholesterolemia, hyperlipoproteinemia, hypothyroidism, metabolic

syndrome (>150 mg/dL), myocardial infarction (for up to 1 year), myxedema,

nephrotic syndrome, obesity, pancreatitis, pregnancy, renal insufficiency

(chronic), starvation (early), stress, Tangier disease, and von Gierke's disease.

Tobacco use. Drugs include cholestyramine, corticosteroids, estrogens, ethyl

alcohol (ethanol), miconazole (intravenous), oral contraceptives, and

spironolactone.

Decreased.

Abetalipoproteinemia, acanthocytosis, cirrhosis (portal), chronic obstructive

pulmonary disease, hyperalimentation, hyperthyroidism, malabsorption, and

malnutrition. Drugs include ascorbic acid, asparaginase, clofibrate,

dextrothyroxine, gemfibrozil, heparin, lovastatin, metformin, niacin, phenformin,


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pravastatin, and sulfonylureas. Herbal or natural remedies include Cordyceps

sinensis, garlic (aged extract taken over time), and soy.

Description.

Also known as “fat,” triglyceride is a compound consisting of fatty acid or

glycerol ester that constitutes a major part (up to 70%) of very-low-density

lipoproteins (VLDLs) and a small part (<10%) of low-density lipoproteins (LDLs)

in fasting serum samples. Dietary triglycerides are carried as part of chylomicrons

through the lymphatic system and bloodstream to adipose tissue, where they are

released for storage. Triglycerides are also synthesized in the liver from fatty

acids and from protein and glucose above the body's current needs and then stored

in adipose tissue. They may be later retrieved and formed into glucose through

gluconeogenesis when needed by the body. Triglyceride levels are taken into

consideration with total cholesterol, high-density lipoprotein cholesterol, and

chylomicron levels when categorizing a client's serum into lipoprotein phenotypes

that represent genetic lipoprotein abnormal-ities. Treatments differ for the

different phenotypes. (Chernecky & Berger, 2008)

2.2.11 How is the normal rate of Haemoglobin?

Hemoglobin (Hb, Hgb) Norm.

SI Units

Females 12–16 g/dL 7.45–9.90 mmol/L

Pregnant 10–15 g/dL 6.3–9.9 mmol/L

Males 13.6–18.0 g/dL 8.44–11.17 mmol/L

Children

Neonates 14–27 g/dL 8.69–16.76 mmol/L

3 months 10–17 g/dL 6.21–10.55 mmol/L

1–2 years 9–15 g/dL 5.58–9.31 mmol/L


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37

SI Units

6–10 years 11–16 g/dL 6.82–9.92 mmol/L

Panic Levels <5 g/dL <3.10 mmol/L

>20 g/dL >12.41 mmol/L

Increased.

Burns (severe), congestive heart failure, chronic obstructive pulmonary disease

(COPD), dehydration, diarrhea, erythrocytosis, hemorrhage, hemoconcentration,

high altitudes, intestinal obstruction (late), polycythemia vera, snorers, and

thrombotic thrombocytopenic purpura. Also conditions that increase red blood

cells (RBCs). Drugs include gentamicin, methyldopa, and pentoxifylline.

Decreased.

Andersen's disease, anemia (iron deficiency), carcinomatosis, cirrhosis, cystic

fibrosis, fat emboli, fatty liver, fluid retention, hemorrhage, hemolysis, hemolytic

reaction to chemicals or drugs or prosthetics, Hodgkin's disease, hydremia of

pregnancy, hyperthyroidism, hypervitaminosis A, hypothyroidism, idiopathic

steatorrhea, intravenous overload, leukemia, lymphoma, platelet apheresis,

pregnancy, renal cortical necrosis, sarcoidosis, severe hemorrhage, systemic lupus

erythematosus, tetralogy of Fallot, and transfusion of incompatible blood. Also,

conditions that decrease RBCs. Drugs include antibiotics, antineoplastic agents,

Apresoline (hydralazine HCl with hydrochlorothiazide), aspirin, hydantoin

derivatives, indomethacin, monoamine oxidase inhibitors, primaquine, rifampin,

sulfonamides, tridione, and zidovudine (AZT); vegetarian diet.

Description.

Hemoglobin is the oxygen-carrying pigment of the RBCs. It is composed

of amino acids that form a single protein called “globin” and a compound called

“heme.” Heme contains iron atoms and the red pigment porphyrin. Each


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erythrocyte contains approximately 300 million molecules of hemoglobin.

(Chernecky & Berger, 2008)

2.2.12 What is anion gap?

Definition & Clinical Use

The term anion gap (AG) represents the concentration of all the

unmeasured anions in the plasma. The negatively charged proteins account for

about 10% of plasma anions and make up the majority of the unmeasured anion

represented by the anion gap under normal circumstances. The acid anions (eg

lactate, acetoacetate, sulphate) produced during a metabolic acidosis are not

measured as part of the usual laboratory biochemical profile. The H+ produced

reacts with bicarbonate anions (buffering) and the CO2 produced is excreted via

the lungs (respiratory compensation). The net effect is a decrease in the

concentration of measured anions (ie HCO3) and an increase in the concentration

of unmeasured anions (the acid anions) so the anion gap increases.

AG is calculated from the following formula:

Anion gap = [Na+] - [Cl-] - [HCO3-]

Reference range is 8 to 16 mmol/l. An alternative formula which includes

K+ is sometimes used particularly by Nephrologists. In Renal Units, K+ can vary

over a wider range and have more effect on the measured Anion Gap.

This alternative formula is:

AG = [Na+] + [K+] - [Cl-] - [HCO3-]

The reference range is slightly higher with this alternative formula. The

[K+] is low relative to the other three ions and it typically does not change much

so omitting it from the equation doesn’t have much clinical significance.


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Major Clinical Uses of the Anion Gap

To signal the presence of a metabolic acidosis and confirm other findings

Help differentiate between causes of a metabolic acidosis: high anion gap

versus normal anion gap metabolic acidosis. In an inorganic metabolic

acidosis (eg due HCl infusion), the infused Cl- replaces HCO3 and the

anion gap remains normal. In an organic acidosis, the lost bicarbonate is

replaced by the acid anion which is not normally measured. This means

that the AG is increased.

To assist in assessing the biochemical severity of the acidosis and follow

the response to treatment

The Anion Gap can be Misleading

It is determined from a calculation involving 3 other measured ions, so the

error with an AG is much higher than that of a single electrolyte determination.

The commonest cause of a low anion gap is laboratory error in the electrolyte

determinations. The 95% error range for the AG is about +/- 5 mmol/l (ie a

10mmols/l range!)

If the AG is greater than 30 mmol/l, than it invariably means that a metabolic

acidosis is present.

If the AG is in the range 20 to 29 mmol/l, than about one third of these patients

will not have a metabolic acidosis.

Other clinical guides should also be used in deciding on the presence and

severity of a metabolic acidosis. Significant lactic acidosis may be associated with

an anion gap which remains in the reference range. Lactate levels of 5 to 10

mmols/litre are associated with a high mortality if associated with sepsis, but the

AG may be reported as within the reference range in as many as 50% of these

cases! (Dorwart & Chalmers 1975).

The anion gap is useful especially if very elevated or used to confirm other

findings. Causes of a high anion gap acidosis can be sorted out more specifically


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by using other investigations in addition to the history and examination of the

patient. Investigations which may be very useful are:

Lactate

Creatinine

Plasma glucose

Urine ketone test

Key Fact: Hypoalbuminaemia causes a low anion gap

Albumin is the major unmeasured anion and contributes almost the whole

of the value of the anion gap. Every one gram decrease in albumin will decrease

anion gap by 2.5 to 3 mmoles. A normally high anion gap acidosis in a patient

with hypoalbuminaemia may appear as a normal anion gap acidosis. This is

particularly relevant in Intensive Care patients where lower albumin levels are

common. A lactic acidosis in a hypoalbuminaemic ICU patient will commonly be

associated with a normal anion gap.

2.2.13 What are the symptoms of anemia?

The severities of the clinical features are dependent not only on the degree

of anemia, but on the rapidity of its development. Common symptoms are general

fatigue and lassitude, breathlessness on exertion, giddiness, dimness of vision,

headache, insomnia, pallor of the skin and, much more important for diagnosis, of

mucous membranes, palpitation, functional anorexia and dyspepsia, tingling and

‘pins and needles’ in the fingers and toes (paraesthesiae). Angina pectoris (due to

myocardial hypoxia), is often present in elderly patients. Physical signs include

tachycardia, functional systolic murmurs, evidence of cardiac dilatation and, in

severe cases oedema of the ankles and crepitations at the bases of the lungs. In

addition to these general features of anemia there may be signs of nutritional

deficiency, particularly angular stomatitis, koilonychias and glossitis. Atrophy of

the papillae and mucous membrane gives the tongue a smooth glazed appearance

(chronic atrophic glossitis). The atrophy begins at the edges and later affects the


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http://www.anaesthesiamcq.com/AcidBaseBook/ab8_1.php

2.3 LEARNING ISSUES II

41

whole tongue. As a result the tongue appears moist and exceptionally clean.

Koilonychia is the name given to certain changes in the nails; first there is

brittleness and dryness: later there is flattening and thinning and finally concavity

(spoon-shaped nails).

2.3.1 What is the connection between Diabetes Mellitus and drowsiness?

2.3.2 How is the pathogenesys of Neuropathy?

2.3.3 What is the connection between Diabetes Mellitus and polydipsi,

polyfagia, and polyuria?

2.3.4 What is the connection between Diabetes Mellitus and body

weight?

2.3.5 What are the causes of Diabetes Mellitus Type 2?

2.3.6 What is the connection between DM Type 2 with Carbohydrate

Metabolism?

2.3.7 What is the connection between DM Type 2 with Lipid

Metabolism?

2.3.8 What is the connection between DM Type 2 with Protein

Metabolism?

2.3.9 What is the normal rate of Insulin, Haematocrit, and Creatinin?

2.3.10 What is the solution of this problem?


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3.1 THE ANSWERS OF LEARNING ISSUES II

42

CHAPTER III

THIRD TUTORIAL

3.1.1 What is the connection between Diabetes Mellitus and drowsiness?

Two possible causes are often sleepy at this woman is atherosclerosis and

sleep apnea.

With time, the fatty streaks grow larger and coalesce, and the surrounding

fibrous and smooth muscle tissues proliferate to form larger and larger plaques.

Also, the macrophages release substances that cause inflammation and further

proliferation of smooth muscle and fibrous tissue on the inside surfaces of the

arterial wall. The lipid deposits plus the cellular proliferation can become so large

that the plaque bulges into the lumen of the artery and greatly reduces blood flow,

sometimes completely occluding the vessel. Even without occlusion, the

fibroblasts of the plaque eventually deposit extensive amounts of dense

connective tissue; sclerosis (fibrosis) becomes so great that the arteries become

stiff and unyielding. Still later, calcium salts often precipitate with the cholesterol


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43

and other lipids of the plaques, leading to bony-hard calcifications that can make

the arteries rigid tubes. Atherosclerotic arteries lose most of their dispensability,

and because of the degenerative areas in their walls, they are easily ruptured.

Also, where the plaques protrude into the flowing blood, their rough surfaces can

cause blood clots to develop, with resultant thrombusor embolus formation,

leading to a sudden blockage of all blood flow in the artery. With the obstructive

on the artery, it can also decrease blood flow to the brain; it is this which is the

reason why women are often sleepy.

Besides atherosclerosis, other thing that easily allows the woman drowsy

is sleep apnea. Most patients develop diabetes after age 40 years, and, although

much progress has been made in therapy, the majority of diabetic patients

continue to die from macrovascular complications (i.e., cardiovascular disease).

Recently it has become clear that sleep disturbances (e.g., chronic insomnia, sleep

apnea) have an impact on health and quality of life. Neuropathy may also

contribute to the significant reduction in quality of life for patients. These

problems are frequently overlooked on routine medical interviews; furthermore, in

some cases, short-term disturbances of sleep may evolve into chronic conditions.

The indiscriminate use of sleeping pills may further disrupt the sleep-wake cycle

and contribute to stress in patients with sleep disorders. In type 2 diabetes, sleep

disturbances are believed to be common and have been attributed to impaired

glucose metabolism and general physical distress. So because this woman's

quality of sleep less, and even when sleep is enough, then it cause of this woman

is easy sleepy during the day.

3.1.2 How is the pathogenesys of Neuropathy?

The most common form of neuropathy associated with diabetes mellitus is distal

symmetric sensorimotor polyneuropathy, often accompanied by autonomic

neuropathy. This disorder is characterized by striking atrophy and loss of

myelinated and unmyelinated fibers accompanied by Wallerian degeneration,


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44

segmental, and paranodal demyelination and blunted nerve fiber regeneration. All

values for nerve conduction velocity in sensory and motor nerves were slower,

and the sensory amplitude of the radial nerve and the motor amplitude of the

median nerve were lower. (Partanen et al., 1995) In both humans and laboratory

animals, this progressive nerve fiber damage and loss parallels the degree and/or

duration of hyperglycemia. Several metabolic mechanisms have been proposed to

explain the relationship between the extent and severity of hyperglycemia and the

development of diabetic neuropathy. One mechanism, activation of the polyol

pathway by glucose via AR, is a prominent metabolic feature of diabetic rat

peripheral nerve, where it promotes sorbitol and fructose accumulation, myo-

inositol depletion, and slowing of nerve conduction by alteration of neural Na(+)-

K(+)-ATPase activity or perturbation of normal physiological osmoregulatory

mechanisms. ARIs, which normalize nerve myo-inositol and nerve conduction

slowing, are currently the focus of clinical trials. Other specific metabolic

abnormalities that may play a role in the pathogenesis of diabetic neuropathy

include abnormal lipid or amino acid metabolism, superoxide radical formation,

protein glycation, or potential blunting of normal neurotrophic responses.

Metabolic dysfunction in diabetic nerve is accompanied by vascular insufficiency

and nerve hypoxia that may contribute to nerve fiber loss and damage. (Greene, et

al, 1992)

3.1.3 What is the connection between Diabetes Mellitus and polydipsi,

polyuria, and polyfagia??

Excessive thirst (polydipsia): A person with diabetes develops high blood

sugar levels, which overwhelms the kidney's ability to reabsorb the sugar as the

blood is filtered to make urine. Excessive urine is made as the kidney spills the

excess sugar. The body tries to counteract this by sending a signal to the brain to

dilute the blood, which translates into thirst. The body encourages more water


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45

consumption to dilute the high blood sugar back to normal levels and to

compensate for the water lost by excessive urination.

Excessive urination (polyuria): Another way the body tries to get rid of the

extra sugar in the blood is to excrete it in the urine. This can also lead to

dehydration because excreting the sugar carries a large amount of water out of the

body along with it.

Excessive eating (polyphagia): If the body is able, it will secrete more

insulin in order to try to deal with the excessive blood sugar levels. Moreover, the

body is resistant to the action of insulin in type 2 diabetes. One of the functions of

insulin is to stimulate hunger. Therefore, higher insulin levels lead to increased

hunger and eating. Despite increased caloric intake, the person may gain very

little weight and may even lose weight.

3.1.4 What is the connection between Diabetes Mellitus and body

weight?

Obesity can increase risk factor to type 2 diabetes mellitus.In type 2 DM, insulin resistance is often associated with abdominal obesity

(as opposed to hip and thigh obesity) and hypertriglyceridemia (Kasper, 2005).

Type 2 DM is characterized by three pathophysiologic abnormalities:

impaired insulin secretion, peripheral insulin resistance, and excessive hepatic

glucose production. Obesity, particularly visceral or central (as evidenced by the

hip-waist ratio), is very common in type 2 DM. Adipocytes secrete a number of

biologic products (leptin, TNF-α, free fatty acids, resistin, and adiponectin) that

modulate insulin secretion, insulin action, and body weight and may contribute to

the

insulin


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46

resistance. In the early stages of the disorder, glucose tolerance remains normal,

despite insulin resistance, because the pancreatic β cells compensate by increasing

insulin output. As insulin resistance and compensatory hyperinsulinemia progress,

the pancreatic islets in certain individuals are unable to sustain the

hyperinsulinemic state. IGT, characterized by elevations in postprandial glucose,

then develops. A further decline in insulin secretion and an increase in hepatic

glucose production lead to overt diabetes with fasting hyperglycemia. Ultimately,

β cell failure may ensue. Markers of inflammation such as IL-6 and C-reactive

protein are often elevated in type 2 diabetes (Kasper, 2005).

The decreased ability of insulin to act effectively on peripheral target

tissues (especially muscle and liver) is a prominent feature of type 2 DM and

results from a combination of genetic susceptibility and obesity (Kasper, 2005).

Another emerging theory proposes that elevated levels of free fatty acids, a

common feature of obesity, may contribute to the pathogenesis of type 2 DM.

Free fatty acids can impair glucose utilization in skeletal muscle, promote glucose

production by the liver, and impair β cell function (Kasper, 2005).

Diabetes mellitus can reduce body weight.

Body weight is dynamic due to fat accumulation (triacylglicerol) in

adipocytes cells. Fat is dynamic because the amount of fat follow the energy

situation in one's body. If someone is having excess energy, the food material will

be deflected into the path of formation triacylglicerol. However, if someone

experienced hunger, triacylglicerol stored will be split into 3 fatty acids and 1

glycerol. Fatty acids will be distributed and to enter into the lane on the

mitochondrial oxidation β cells that would produce, acetyl CoA. Acetyl-CoA will

enter the Krebs cycle which produces nucleoside phosphate compounds-energy

high (Murray, 2003).


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47

In solving triacylglycerol (lipolysis) is required enzyme hormone-sensitive

lipase enzyme which is sensitive to insulin levels. The enzyme is inhibited by

insulin. However, if insulin levels are decreased (as in diabetes), the inhibition of

lipolysis is greatly reduced. Thus, the rate of formation of fatty acids will increase.

Fatty acid that increases will shift the use of glucose as energy to the use of fatty

acids for energy. Swift fatty acids will result in the number of acetyl-CoA

resulting in β oxidation. Acetyl-CoA which many will be deflected towards the

formation of ketone compounds which, if too many will lead to many

complications associated blood acidosis (Murray, 2003).

Thus, low levels of insulin will lead to lower the barriers for hormone-

sensitive lipase, so that the process of lipolysis will go well. The number of

reserves will result in triacylglycerol lipolysis in adipocytes cells is reduced, so

that the weight will decrease.


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3.1.5 What are the causes of Diabetes Mellitus Type 2?

Diabetes Mellitus (DM) is one health problem impact on productivity and

can lower the Human Resources. This disease affects not only individually, but

the health system a country. Although no national survey, in line with changes

lifestyle, including eating patterns of Indonesian society is estimated patient. DM

is increasing, especially in adults and older age groups in all socio-economic

status. Currently, efforts to control disease DM has not occupied the main

priorities in health care, although the known negative impact thereof large enough

between, other chronic complications in chronic heart disease, hypertension,

brain, system nerve, liver, eyes and kidneys. DM is a degenerative disease, where

an interruption occurs metabolism of carbohydrates, fats and proteins and is

characterized by high blood sugar levels (hyperglycemia) and in urine.

Clinically, this disease is progressive travel and tend to involve too fat or

protein metabolism disorders. Increased blood glucose levels because of

utilization that are not going perfectly in turn often led to the clinical

abnormalities of blood lipid levels. To obtain a normal glucose levels in the blood

necessary drugs that can stimulate beta cells to increase insulin secretion (insulin

secretagogue) or when required by the substitution of insulin, in addition to

efficacious drugs that reduce insulin resistance (insulin sensitizers).

Inadequate phase 1, which is then followed by performance improvement

phase 2 insulin secretion, in the early stages will not cause disruption to the blood

glucose levels. Clinically, then at the stage of decompensation, can be detected

condition called impaired glucose tolerance which is also called as a prediabetic

state. At this stage of compensatory mechanisms have started no longer adequate,

the body that may be deficient in relative terms, an increase in postprandial blood

glucose levels. In impaired glucose tolerance (IGT) was found postprandial blood

glucose levels, or after being fed a solution of 75 g glucose load with Oral

Glucose Tolerance Test (oral glucose tolerance), ranged between 140-200 mg /

dl. Also known as prediabetes, when fasting blood glucose levels between 100-


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126 mg / dl, which is also known as Fasting Blood Glucose Disturbed (GDPT).

State of hyperglycemia that occurs, both at the stage of chronic diabetes,

or acute postprandial hyperglycemia that occurred were ulangkali every day since

the stage of IGT, has negative long-term tissue complications of chronic

diabetes.Tingginya blood glucose levels (glucotoxicity) which followed by

dyslipidemia (lipotoxicity) is responsible for tissue damage both directly through

oxidative stress, and widespread process of glycosylation.

Insulin resistance from prominent role since the change or conversion into

DMT2 TGT phase. It is said that at the start of dominant factor of insulin

resistance as a cause of hyperglycemia as well as a variety of tissue damage. This

is evident from the fact that in the early stages DMT2, although the serum insulin

levels are high enough, but hyperglycemia can still occur. Tissue damage occurs,

particularly microvascular, increased dramatically at this stage of diabetes,

whereas macrovascular disorders have emerged since prediabetes. Increasing

levels of insulin resistance can be seen also from increased levels of fasting and

postprandial blood glucose. Accordingly, at the higher levels of hepatic insulin

resistance, the lower the ability of inhibition to the process of glycogenolysis and

gluconeogenesis, causing the higher the level of hepatic glucose production.

We have to know that, Secreation of phase (Acute insulin secretion

responce = AIR) is the secretion of insulin that occurs immediately after

stimulation of beta cells, arise quickly and ended too quickly. Secretion of phase 1

(AIR) usually have a relatively high peak, because it is necessary to anticipate the

blood glucose levels typically rise sharply, immediately after eating. Performance

of a rapid and adequate water is essential for normal glucose regulation because

pasa turn contribute significantly in controlling postprandial blood glucose

levels. Thus, the presence of normal water needed to sustain the process of

physiological glucose metabolism. WATER normal lasting, beneficial in

preventing the occurrence of acute hyperglycemia after a meal or postprandial


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blood glucose spikes (postprandial spike) with all consequences thereof including

compensed inemia.

Furthermore, after the secretion phase 1 ended, appear secretion phase 2

(sustained phase, latent phase), where insulin secretion increased again slowly and

survive in a relatively longer time. After the end of phase 1, the task of blood

glucose regulation subsequently taken over by the secretion phase 2. Insulin

secretion phase 2, which lasted relatively long, how high the peak (quantitative)

will be determined by how much the blood glucose level at the end of phase 1, in

addition to insulin resistance factor. So, a kind of adjustment mechanism of

secretion of phase 2 to phase 1 previous performance. If the phase 1 secretion is

inadequate, there was a mechanism of compensation in the form of increased

secretion of insulin in Phase 2.Increased insulin production is essentially aimed at

meeting the needs of the body for blood glucose levels (postprandial) remained

within normal limits. In the prospective course of the disease, insulin secretion

phase 2 will be heavily influenced by phase 1.In the figure below (Fig. 2)

demonstrated the dynamics of insulin secretion in normal circumstances,

Disturbed Glucose Tolerance (IGT = Impaired Glucose Tolerance), and Type 2

Diabetes Mellitus.

Usually, with a normal phase 1 performance, accompanied also by the

action of insulin which is also normal in the network (without insulin resistance),

the secretion of phase 2 will also be normal. Thus no additional need (extra)

synthesis and secretion of insulin in Phase 2 above normal in order to maintain the

state of normoglycaemia.This is a physiological condition which is ideal for

without raising blood glucose levels that may impact glucotoxicity, also without

hyperinsulinemia with various negative impacts.


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So, it can be concluded trip DMT2 disease, initially determined by the

performance of Phase 1 which then gives a negative impact on the performance of

phase 2, and a direct result of elevated levels of blood glucose

(hyperglycemia). Hyperglycemia occurs not only due to impaired insulin secretion

(insulin deficiency), but at the same time also by the low response of body tissues

to insulin (insulin resistance).Disruption or environmental influences such as

lifestyle or obesity will accelerate progression of the disease. Impaired glucose

metabolism will continue in fat and protein metabolism disorders and the damage

to various body tissues. The series of disorders that are motivated by insulin

resistance, other than intolerance to glucose and its various consequences, often

leading to a collection of symptoms called metabolic syndrome.


16th Group

Insu

lin

Sec

reti

on

Intravenous glucose stimulation

First-Phase

SecondPhase

IGT

Normal

Type 2DM

Basal

52

3.1.6 What is the connection between Diabetes Mellitus Type 2 and

Carbohydrate Metabolism?

With type 2 diabetes, the impairment of glucose metabolism arises as a

result of a decreased sensitivity to insulin by the body’s cells. This means that the

cells do not respond to insulin to take up glucose from the bloodstream and utilize

it. This is known as insulin resistance. This causes glucose in human blood cannot

be converted into glycogen by hepar’s cells (glycogenesys doesn’t work). And

also other kind of cells do not use blood glucose due to its insensitivity caused by

the malfunction of beta cells of islets of Langerhans.

Compensatory mechanism:

The insulin levels in the blood are elevated, above the norm

(hyperinsulinemia) as the pancreas secretes higher amounts of glucose in an

attempt to overcome this resistance (compensatory mechanism). This

mechanism causes hyperinsulinemia until bile is overworked and

malfunctioned as well, leading to inappropriate amount of insulin in human

body.

Overlap point with lipogenesys:

Upon consuming foods, particularly carbohydrates, the digestive system along

with the liver, break down the food into simple sugars like glucose. Glucose

then enters the blood stream where it is transported to cells throughout the

body. Excess glucose is converted to glycogen and stored in the liver and

muscles. Any remaining glucose may be converted for fat storage. This blood

glucose regulating mechanism is primarily controlled by the hormone, insulin,

which is secreted by the pancreas (beta cells in the islets of Langerhan’s).

Insulin triggers cells to take up glucose from the blood so that individual

cells can burn this glucose for energy. Alternatively, excess glucose is converted

into glycogen and stored in the liver due to the action of insulin. In insulin

resistance, seen in impaired glucose tolerance (or pre-diabetes), the body’s cells

and liver do not respond to insulin. Excess glucose builds up in the blood stream


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and the pancreas attempts to secrete more insulin. This excess insulin secretion

may not always trigger the desired effect resulting higher than normal blood

glucose levels. Over time, insulin resistance and pre-diabetes will lead to type 2

diabetes, also known as adult-onset diabetes or non-insulin dependent diabetes.

3.1.7 What is the connection between Diabetes Mellitys Type 2 with

lipid metabolism?

After a normal meal there is an ample supply of carbohydrate, and the fuel

for most tissues is glucose. In the starving state, glucose must be spared for use by

the central nervous system (which is largely dependent on glucose) and the

erythrocytes (which are wholly reliant on glucose). Other tissues can utilize

alternative fuels such as fatty acids and ketone bodies. As glycogen reserves

become depleted, so amino acids arising from protein turnover and glycerol

arising from lipolysis are used for gluconeogenesis. These events are largely

controlled by the hormones insulin and glucagon. In diabetes mellitus there is

either impaired synthesis and secretion of insulin (type 1 diabetes mellitus) or

impaired sensitivity of tissues to insulin action (type 2 diabetes mellitus), leading

to severe metabolic derangement.

The nutritional state of the organism is the main factor regulating the rate

of lipogenesis. Thus, the rate is high in the well-fed animal whose diet contains a

high proportion of carbohydrate. It is depressed under conditions of restricted

caloric intake, on a fat diet, or when there is a deficiency of insulin, as in diabetes

mellitus. These latter conditions are associated with increased concentrations of

plasma free fatty acids, and an inverse relationship has been demonstrated

between hepatic lipogenesis and the concentration of serum-free fatty acids.

Insulin stimulates lipogenesis by several other mechanisms as well as by

increasing acetyl-CoA carboxylase activity. It increases the transport of glucose

into the cell (eg, in adipose tissue), increasing the availability of both pyruvate for

fatty acid synthesis and glycerol 3-phosphate for esterification of the newly

formed fatty acids, and also converts the inactive form of pyruvate dehydrogenase


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to the active form in adipose tissue but not in liver. Insulin also—by its ability to

depress the level of intracellular cAMP—inhibits lipolysis in adipose tissue and

thereby reduces the concentration of plasma free fatty acids and therefore long-

chain acyl- CoA, an inhibitor of lipogenesis.

Free fatty acids from the circulation are the main source during starvation,

the feeding of high-fat diets, or in diabetes mellitus, when hepatic lipogenesis is

inhibited. In adipose tissue, insulin stimulates glucose uptake, its conversion to

fatty acids, and their esterification; and inhibits intracellular lipolysis and the

release of free fatty acids. Insulin inhibits the release of free fatty acids from

adipose tissue, which is followed by a fall in circulating plasma free fatty acids. It

enhances lipogenesis and the synthesis of acylglycerol and increases the oxidation

of glucose to CO2 via the pentose phosphate pathway.

In poorly controlled type 1 diabetes mellitus, patients may become

hyperglycemic, partly as a result of lack of insulin to stimulate uptake and

utilization of glucose and partly because of increased gluconeogenesis from amino

acids in the liver. At the same time, the lack of insulin results in increased

lipolysis in adipose tissue, and the resultant free fatty acids are substrates for

ketogenesis in the liver.

Increased fatty acid oxidation is a characteristic of starvation and of

diabetes mellitus, leading to ketone body production by the liver (ketosis). Ketone

bodies are acidic and when produced in excess over long periods, as in diabetes,

cause ketoacidosis, which is ultimately fatal. Ketosis is mild in starvation but

severe in diabetes mellitus and ruminant ketosis.

Lipid is mobilized from adipose tissue as free fatty acids (FFA) attached to

serum albumin. Abnormalities of lipoprotein metabolism cause various hypo- or

hyperlipoproteinemias. The most common of these is diabetes mellitus, where

insulin deficiency causes excessive mobilization of FFA and underutilization of

chylomicrons and VLDL, leading to hypertriacylglycerolemia. Most other

pathologic conditions affecting lipid transport are due primarily to inherited

defects, some of which cause hypercholesterolemia, and premature

atherosclerosis. (Murray, 2003)


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3.1.8 What is the connection between Diabetes Mellitus Type 2 with

protein metabolism?

During the few hours after a meal when excess quantities of nutrients are

available in the circulating blood, not only carbohydrates and fats but proteins as

well are stored in the tissues; insulin is required for this to occur. The manner in

which insulin causes protein storage is not as well understood as the mechanisms

for both glucose and fat storage. Some of the facts follow.

1. Insulin stimulates transport of many of the amino acids into the cells .

Among the amino acids most strongly transported are valine, leucine,

isoleucine, tyrosine, and phenylalanine. Thus, insulin shares with

growth hormone the capability of increasing the uptake of amino acids

into cells. However, the amino acids affected are not necessarily the

same ones.

2. Insulin increases the translation of messenger RNA, thus forming new

proteins. In some unexplained way, insulin “turns on” the ribosomal

machinery. In the absence of insulin, the ribosomes simply stop

working, almost as if insulin operates an “on-off” mechanism.

3. Over a longer period of time, insulin also increases the rate of

transcription of selected DNA genetic sequences in the cell nuclei, thus

forming increased quantities of RNA and still more protein synthesis—

especially promoting a vast array of enzymes for storage of

carbohydrates, fats, and proteins.

4. Insulin inhibits the catabolism of proteins, thus decreasing the rate of

amino acid release from the cells, especially from the muscle cells.

Presumably this results from the ability of insulin to diminish he normal

degradation of proteins by the cellular lysosomes.

5. In the liver, insulin depresses the rate of gluconeogenesis. It does this

by decreasing the activity of the enzymes that promote


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gluconeogenesis. Because the substrates most used for synthesis of

glucose by gluconeogenesis are the plasma amino acids, this

suppression of gluconeogenesis conserves the amino acids in the

protein stores of the body.

In summary, insulin promotes protein formation and prevents the

degradation of proteins.

Insulin Lack Causes Protein Depletion and Increased Plasma Amino Acids.

Virtually all protein storage comes to a halt when insulin is not available.

The catabolism of proteins increases, protein synthesis stops, and large quantities

of amino acids are dumped into the plasma. The plasma amino acid concentration

rises considerably, and most of the excess amino acids are used either directly for

energy or as substrates for gluconeogenesis. This degradation of the amino acids

also leads to enhanced urea excretion in the urine. The resulting protein wasting is

one of the most serious of all the effects of severe diabetes mellitus. It can lead to

extreme weakness as well as many deranged functions of the organs. (Guyton and

Hall, 2006)

3.1.9 What is the normal rate of Insulin, Haematocrit, and Creatinin?

Insulin and Insulin Antibodies—Blood Norm.

Free insulin: fasting ≤25 IU/mL (<172.5 pmol/L, SI units). (Norms and

standardization of the test method vary widely by laboratory.)

Insulin Level via Radioimmunoassay:

SI Units

Adult, fasting level <17 μIU/mL or 1.00 mg/L <117 pmol/L

Newborn 3–20 μIU/mL 21–139 pmol/L

Infant <13 μIU/mL ≤89 pmol/L

Prepubertal child <13 μIU/mL ≤89 pmol/L


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SI Units

Panic levels >30 μIU/mL >207 pmol/L

Last trimester, amniotic fluid 11.3 μIU/mL 78 pmol/L

Insulin Antibodies.

Undetectable to less than 4% when using either bovine or porcine insulin as a

reagent. Insulin antibodies have been shown to occur more frequently with aging

and more in females than in males.

Increased Insulin.

Acromegaly, Beckwith-Wiedemann syndrome, beta-cell adenoma, Cushing's

syndrome, dystrophia myotonica, familial fructose and galactose intolerance,

hyperinsulinism, hypoglycemia, insulin-resistance syndromes, insulinoma, liver

disease, non–insulin-dependent diabetes mellitus, metabolic syndrome,

nesidioblastosis, obesity, overdose of insulin, pancreatic islet cell lesion, and

pheochromocytoma. Drugs include albuterol, calcium gluconate in the newborn,

estrogen, fructose, glucagon, glucose, insulin, levodopa, medroxyprogesterone,

oral contraceptives, prednisolone, quinine, quinidine, spironolactone, sucrose,

terbutaline, tolazamide, and tolbutamide.

Decreased Insulin.

Diabetes mellitus, hyperglycemia, hypopituitarism, and pancreatectomy-induced

diabetes. Drugs include beta-adrenergic blockers, asparaginase, calcitonin,

cimetidine, diazoxide, ethacrynic acid, ethyl alcohol (ethanol), ether, furosemide,

metformin, nifedipine, phenformin, phenobarbital, phenytoin, and thiazide

diuretics.

Positive Insulin Antibodies.

Factitious hypoglycemia, autoimmune insulin syndrome (AIS).


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Negative Insulin Antibodies.

Normal finding. Also negative in insulinoma.

Description.

Insulin is a hormone that regulates carbohydrate metabolism. It is produced in the

pancreas by the beta cells of the islets of Langerhans, and its rate of secretion is

determined primarily by the level of blood glucose. The radioimmunoassay test

measures endogenous insulin by using a series of tubes containing a fixed amount

of antibody label and an aliquot of standard, control, or unknown. The client's

unlabeled antigen in the blood competes with labeled antigen for antibody-binding

sites. The percentage of antigen bound to antibody is related to the total antigen

present and is reflected by the distribution of a radioactive label. Low

immunoreactive insulin levels have been associated with a higher risk of

developing degenerative diseases such as atherosclerosis, hypertension, and

dyslipidemia. Insulin antibodies, also referred to as anti–insulin-Ab, may be

present in diabetic clients treated for several weeks or more with conventional

insulin. These antibodies may also be present in persons who have never received

insulin but have autoimmune insulin syndrome (AIS), a rare condition

characterized by hyperinsulinemia and hypoglycemia. For diabetic clients, this

test may be used with C-peptide to determine whether hypoglycemia is caused by

insulin abuse. Insulin antibodies are transferred through the placenta and are

present in 30%–50% of children at the time of diagnosis before beginning insulin

therapy.

Hematocrit (Hct)—Blood Norm.

SI Units

Females

Adult 37%–47% 0.37–0.47

Pregnant 30%–46% 0.30–0.46

Adult Males 40%–54% 0.40–0.54


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SI Units

Children

Neonates 40%–68% 0.40–0.68

3 months 29%–54% 0.29–0.54

1–2 years 35%–44% 0.35–0.44

6–10 years 31%–45% 0.31–0.45

Panic Levels <15% or >60% <0.15 or >0.60

Panic Level Symptoms and Treatment—Increased

NOTE: Treatment choice(s) depend(s) on client's history and condition and episode history.

Cause Symptoms Possible Treatments

Hemoconcentration Decreased pulse pressure and volume, decreased skin turgor, decreased venous filling, dry mucous membranes, low central venous pressure, orthostatic hypotension, tachycardia, thirst and weakness

Administer IV fluids.monitor hematocrit.Stop or reduce dose of diuretics if they are contributors to condition.

True polycythemia overtransfusion

Extremity pain and redness, facial flushing, irritability, anasarca decreasing QRS voltage with severe fluid overload

Administer IV fluids.Monitor hematocrit.Observe for signs of thrombosis.Perform bloodletting by venipuncture (phlebotomy).

Panic Level Symptoms and Treatment—Decreased


Hemodilution Rales, anxiety, edema, hypertension, jugular venous distention, restlessness, and shortness of breath

Administer diuretics.Restrict sodium.Restrict fluids.Monitor hematocrit and intake and output.Administer oxygen.

Blood loss Hypotension, bleeding, hypoxia Identify and treat cause of


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bleeding.Give isotonic fluids.Perform blood transfusion.Administer omeprazole (if blood loss is caused by bleeding esophageal varices).Protect airways; administer oxygen as needed.

Increased.

Addison's disease, blood doping (autologous transfusion to improve athletic

performance), burns (severe), dehydration (severe), diabetes mellitus, diarrhea,

eclampsia, erythrocytosis, hemorrhage, hemoconcentration, pancreatitis (acute),

polycythemia, shock, and tetralogy of Fallot. Any condition that increases red

blood cells (RBCs).

Decreased.

Anemia, bone marrow hyperplasia, burns (severe), cardiac decompensation,

cirrhosis, congestive heart failure, cystic fibrosis, fatty liver, fluid overload,

hemolytic reactions to chemicals or drugs or prosthetics, hemorrhage, hydremia of

pregnancy, hyperthyroidism, hypothyroidism, idiopathic steatorrhea, intestinal

obstruction (late), leukemia, overhydration, pancreatitis (hemorrhagic),

pneumonia, and pregnancy. Also, conditions that decrease RBCs. Drugs include

acetaminophen, acetohexamide, aminosalicylic acid, amphotericin, antimony

potassium tartrate, antineoplastic agents, antibiotics, atabrine hydrochloride,

chloramphenicol, chloroquine hydrochloride or phosphate, doxapram

hydrochloride, ethosuximide, ethotoin, furazolidone, haloperidol, hydralazine

hydrochloride, indomethacin, isocarboxazid, isoniazid, mefenamic acid,

mephenytoin, mercurial diuretics, metaxalone, methaqualone, methsuximide,

methyldopa, methyldopate hydrochloride, nitrates, nitrofurantoin, novobiocin

sodium, oleandomycin, oxyphenbutazone, paramethadione, pargyline

hydrochloride, penicillins, phenacemide, phenelzine sulfate, phenobarbital,


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phensuximide, phenylbutazone, phenytoin sodium, phytonadione, primidone,

radioactive agents, rifampin, spectinomycin hydrochloride, sulfonamides,

tetracyclines, thiazide diuretics, thiocyanates, thiosemicarbazones, tolazamide,

tolbutamide, tranylcypromine sulfate, trimethadione, tripelennamine

hydrochloride, troleandomycin, valproic acid, vegetarian diet, vitamin A, and

zidovudine (AZT).

Description.

Hematocrit is the percentage of red blood cells in a volume of whole blood.

Creatinine—Serum Norm.

SI Units

Jaffe, Manual Method 0.6–1.6 mg/dL 52–142 μmol/day

Jaffe, Kinetic or Enzymatic Method

Adults

Females 0.5–1.1 mg/dL 44–97 μmol/L

Males 0.6–1.2 mg/dL 53–105 μmol/L

Elderly May be lower May be lower

Children

Cord blood 0.6–1.2 mg/dL 53–105 μmol/L

Newborn 0.8–1.4 mg/dL 71–124 μmol/L

Infant 0.7–1.7 mg/dL 62–150 μmol/L

1 year, female ≤0.5 mg/dL ≤44 μmol/L

1 year, male ≤0.6 mg/dL ≤53 μmol/L

2–3 years, female ≤0.6 mg/dL ≤53 μmol/L

2–3 years, male ≤0.7 mg/dL ≤62 μmol/L





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SI Units








Increased.

Values are 20–40% higher in the late afternoon than in the morning. Acromegaly,

allergic purpura, amyloidosis, analgesic abuse, azotemia (prerenal, postrenal),

congenital hypoplastic kidneys, congestive heart failure, diabetes mellitus, diet

(high meat content), gigantism, glomerulonephritis (chronic), Goodpasture's

syndrome, gout, hemoglobinuria, high dietary intake, hypovolemic shock,

hypothyroidism, infants (first 2 weeks of life), intestinal obstruction, Kimmelstiel-

Wilson syndrome, micro albuminemia, metal poisoning, multiple myeloma,

muscle destruction, nephritis, nephropathy (hypercalcemic, hypokalemic),

nephrosclerosis, pancreatitis (necrotizing), polyarteritis nodosa, polycystic

disease, preeclampsia, pyelonephritis, renal artery stenosis or thrombosis, renal

cortical necrosis, renal failure, renal vein thrombosis, renal tuberculosis,

rheumatoid arthritis (active), scleroderma, sickle cell anemia, subacute bacterial

endocarditis, systemic lupus erythematosus, testosterone therapy, toxic shock

syndrome, uremia, urinary obstruction, and vomiting. Drugs include

acetohexamide, acyclovir, ammonia (inhaled), amphotericin B, androgens,

arginine, bleomycin-induced pulmonary toxicity, Bromsulphalein, captopril,

cephalosporins (Cefoxitin, cephalexin), cimetidine, cinchophen, clofibrate,

corticosteroids, diacetic acid, diuretics, disopyramide phosphate, dopamine,

fenofibrate, fosinopril, fructose, gentamicin sulfate, glucose, hydralazine

hydrochloride, hydroxyurea, Lipomul, lithium carbonate, losartan, mannitol,


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meclofenamate sodium, methicillin sodium, metoprolol tartrate, minoxidil,

mithramycin, nitrofurantoin, nitrogen oxide (inhaled), propranolol, protein,

pyruvate, sulfobromophthalein, sulfonamides, streptokinase, testosterone,

testosterone cypionate, testosterone enanthate, testosterone propionate,

triamterene, and viomycin. Herbal or natural remedies include products

containing aristolochic acids (Akebia spp., Aristolochia spp., Asarum spp.,

birthwort, Bragantia spp., Clematis spp., Cocculus spp., Diploclisia spp.,

Dutchman's pipe, Fang chi, Fang ji, Guang Kan-Mokutsu, Menispernum spp.,

Mokutsu, Mu tong, Sinomenium spp., and Stephania spp.).

Decreased.

Diabetic ketoacidosis (artifactual decrease) and muscular dystrophy. Drugs

include cefoxitin sodium, cimetidine, chlorpromazine, chlorprothixene, marijuana,

thiazide diuretics, and vancomycin. Herbal or natural remedies include Cordyceps

sinensis.

Description.

Creatinine is produced continuously as a nonprotein end product of anaerobic

energy-producing creatine phosphate metabolism in skeletal muscle. Because it is

continually and easily excreted by the renal system, increased levels indicate a

slowing of the glomerular filtration rate. Creatinine is thus a very specific

indicator of renal function, revealing the balance between creatinine formation

and excretion. A diurnal variation in creatinine may be related to meals, with

troughs occurring around 0700 (7 AM) and peaks occurring around 1900 (7 PM).

Lipid Profile—Blood Norm.

See individual test listings for age-specific norms, including norms for children.

SI Units

Lipids, total 400–800 mg/dL 4.0–8.0 g/L


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SI Units

Triglycerides 10–190 mg/dL 0.2–4.8 mmol/L

HDL cholesterol

Females 35–85 mg/dL 0.9–2.2 mmol/L

Males 30–65 mg/dL 0.8–1.7 mmol/L

LDL cholesterol 80–190 mg/dL 2.0–4.9 mmol/L

VLDL cholesterol (calculated) ≤30 mg/dL <0.78 mmol/L

Total-to-HDL cholesterol ratio Median = 5

Condition Triglycerides Total Cholesterol HDL LDL

Alcoholism Increase Increase Increase Increase

Aortic aneurysm Increase Increase Increase Increase

Aortitis Increase Increase Increase Increase

Arteriosclerosis Increase Increase Decrease Increase

Diabetes mellitus Increase Increase Increase Increase

Glycogen storage Increase — — Increase

Hyperalimentation Decrease Decrease Decrease Decrease

Hypercholesterolemia Increase Increase — Increase

Hyperlipoproteinemia Increase Increase Increase Increase

Hypothyroid Increase — Decrease —

Malabsorption Decrease Decrease Decrease Decrease

Myxedema Increase Increase Increase Increase

Nephrotic syndrome Increase Increase Increase Increase

Pancreatitis Increase Increase Increase Increase

Description.

Lipid profile is a battery of laboratory studies to help determine the risk factors in

coronary artery disease. Blood lipids comprise cholesterol, triglycerides, and

phospholipids. Fasting lipid profiles are recommended every 5 years in clients


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older than age 19. See individual test sections for further descriptions of the

components of the lipid profile, as well as levels for which lifestyle changes and

therapeutic drug regimens are recommended. (Chernecky & Berger, 2008)

Total Cholesterol—Coronary Heart Disease Risk

Desirable Borderline High Risk High Risk

Norm mg/dL

SI Units mmol/L

mg/dL SI Units mmol/L


Adult <200 <5.18 200–239

5.18–6.19 ≥240 ≥6.22

Child <170 <4.40 170–199

4.40–5.15 ≥200 ≥25.18

HDL Cholesterol—Coronary Heart Disease Risk

Very Low Risk Low Risk Moderate Risk High Risk





Adults >60 >1.554 45–59 1.16–1.53

35–45 0.91–1.16

<35 <0.91

Total to HDL Ratio

Coronary Heart Disease Risk

Average Risk 2 × Average Risk

3 × Average Risk

Male 5.0 9.6 23.4

Female 4.4 7.1 11.0

LDL Cholesterol—Coronary Heart Disease Risk

Low Risk Moderate Risk High Risk

Optima Near Optimal Borderline High High Very High

mg/dL SI Units mg/dL SI Units mg/dL SI Units mg/dL SI Units mg/dL SI Units

<100 <2.59 100– 2.59– 130– 3.37– 160– 4.14– >190 >4.92


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129 3.34 159 4.12 189 4.89

3.1.10 What is the solution of this problem?

The aim of treatment of diabetes mellitus is consistently normalize blood

glucose levels with minimum variation. Recent studies suggest that maintaining

blood glucose levels as normal and as often as possible to reduce morbidity and

mortality. This objective is achieved through a variety of ways, each of which is

adjusted individually.

Insulin: Type 1 diabetes requires insulin therapy. There are various types

of insulin with the origin and purity of different. Insulin also vary in

aspects of work, the peak time of work, and length of work. Although the

injection of subcutaneous insulin is usually given 3-4 times a day after the

basal blood glucose levels measured, but treatment for people with type 1

diabetes in the future will most likely be directed toward a more frequent

injections. Available subcutaneous insulin pump that can be programmed

for release a certain amount of insulin within a certain time interval per

day. If the planned changes to the regular schedule, then the pump can be

programmed to increase or reduce the amount of insulin secreted. Insulin

pump has the advantage that is not needed injection, an important

consideration for all people with diabetes, especially children. Lack of

programming failure pump is likely causing hypoglycemia or

hyperglycemia, as well as damage to the pump which caused the death. In

addition, there is danger of infection given the interruption of blood flow


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67

and decreased immune system that occurs in most patients with diabetes.

The pump is also very expensive.

People with type 2 diabetes, although considered not insulin dependent,

can also benefit from insulin therapy. In people with type 2 diabetes, may

occur insulin deficiency or insulin release produced less effective because

a slight change. People with type 2 diabetes can be treated with oral

hypoglycemic drugs. These medications can be used effectively only if the

individual shows insulin secretion. These drugs appear to work by

stimulating pancreatic beta cells to increase insulin release and increased

sensitivity to insulin receptor cells. These drugs also appear to reduce

gluconeogenesis by the liver. Oral hypoglycemic medications vary in

aspects of work, time fatherly reached peak employment, and length of

work. Drugs are contraindicated for individuals with kidney disease.

Education and adherence to the diet: Another important component in the

treatment of diabetes type 1 and 2. Diabetes diet plan is calculated on an

individual basis depending on the needs of growing, weight loss plan

(typically for patients with type 2 diabetes), and activity level.

Distribution is usually 50-60% of calories from complex carbohydrates,

20% from protein, and 30% from fat. Diet also includes fiber, vitamins,

and mineral. Most patients with type 2 diabetes recovering near-normal

blood glucose levels with dietary intervention only because of the role of

obesity factor.

Sports programs, especially for people with type 2 diabetes. It is the third

therapeutic interventions for diabetes mellitus. Exercise, combined with

the liberation of the diet, will promote weight loss can improve insulin

sensitivity distinction. For both types of diabetes, exercise is proven to

increase the use of glucose by the cells so that blood glucose levels down.

Exercise also can increase the sensitivity of cells to insulin.

People with type 1 diabetes must be careful when exercising, due to a

decline in blood glucose that triggers hypoglycemia. This right is

especially true if insulin is not adapted to the exercise program.


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68

Prevention: for diabetic ketoacidosis, the most important aspect of

treatment is prevention, this form of monitoring of blood glucose levels

carefully and diet, especially on the sata-time stress or illness. If present,

then the diabetic ketoacidosis treated with insulin and measures for

balancing fluid and electrolytes.

Fluid: nonkelotik hiperglikemik hyperosmolar coma treated by giving

fluids in bulk and slow correction of potassium deficit. This incident can

be prevented by good diet control.

Pharmacological interventions that can be considered to be given to

patients with diabetes are antihypertensive medications. Anti-hypertensive

medications have been proven to reduce hypertension in patients with

diabetes and kidney disease awitan slow.

Replacement of the island of Langerhans cells: recent advances in the

techniques of replacement cells of Langerhans islands enables more than

3000 people worldwide were treated with the island of Langerhans cell

transplantation. Treatment in this manner gives hope for diabetes cure in

the future.

Insertion of genes for insulin: is currently also being carried out

preliminary experiments designed to allow insertion of the insulin gene to

type 1 diabetes. In future, this procedure is to provide hope for healing

diabetes, compared with drug therapy.


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3.2 ANALYSIS

69

A woman came with problems of her drowsiness and her tingling. In order

to get the diagnosis and the possible patophysiology of her problems, series of

anamnestic question, physical examination, and laboratory test should be done

Anamnesis

Age : 41 years

Marital status : Married, have 1 child

Address : Kupang Indah Surabaya

Job : Housewife

She has tingling since 1 month ago, all the time and progressive.

She often fell sleepy.

She often wakes up at night for micturing.

She losses 3 kg of her weight.

Diabetes : unknown

Hypertension : disputed

Family history :

Her father dead from complication

Her eldest sister dead in 40th years old with a wound in her leg which

cannot be healed and nasty smell


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70

She hasn’t received any treatments before.

She often feels thirsty and drinks much.

She often feel hungry too.

She rarely, practically never, does any sports

Physical Examination

General condition : good

Blood pressure : 120/80 mmHg

Pulse pressure : 80 times/minute

Respiratory Rate : 20 times/minute

Temperature : 37o Celsius

Weight : 89 kg

Height : 157 cm

Waist Circumference : 93 cm

No bad smell in her breath

Inspection :

Cyanosis, Anemia, Icterus = Negative (-)

Ascites = negative (-)

Palpation:

Hepar and Lien cannot be felt

Percussion :

Thorax :

Heart and Lungs = Normal

Laboratory Result

Fasting Glucose : 199 mg/dL

2-h PP Glucose : 317 mg/dL

Triachilglicerol 278 mg/dL

Hemoglobin : 12 g/dL

Creatinin Level : 0,7 mg/dL


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71

HDL : 38 mg/dL ; LDL : 94 mg/dL; Total Cholesterol : 171 mg/dl

From the data above, we think of the most possible disease called Diabetes

Mellitus. Diabetes mellitus is a group of metabolic diseases characterized by high

blood sugar (glucose) levels that result from defects in insulin secretion, or action,

or both. Diabetes mellitus, commonly referred to as diabetes was first identified as

a disease associated with "sweet urine," and excessive muscle loss in the ancient

world. Elevated levels of blood glucose (hyperglycemia) lead to spillage of

glucose into the urine, hence the term sweet urine. Normally, blood glucose levels

are tightly controlled by insulin, a hormone produced by the pancreas. Insulin

lowers the blood glucose level. When the blood glucose elevates (for example,

after eating food), insulin is released from the pancreas to normalize the glucose

level. In patients with diabetes, the absence or insufficient production of insulin

causes hyperglycemia. This high blood sugar produces the classical symptoms of

polyuria (frequent urination), polydipsia (increased thirst) and polyphagia

(increased hunger). Besides, there is a losing in the body weight. In this patient,

we found some conditions fit these symptomps.

First, the patient has an increase frequency in urination, especially at night

(polyuria,specifically nocturia). Because of losing many water from the body by

polyuria, the brain will compensate it by making a thirst signal that insist person

to drink more and more (polydipsia), and this patient also often feel thirsty. She

drinks much in order to fulfill her thirst. She often feels hungry too. This is what

we called polyphagia, a condition which someone never gets satisfied with their

intake. This polyphagia may occurs because diabetic patient can’t make much

energy from the glucose so it will force the diabetic patient to eat more in order to

make some energies. She also starts losing her body weight, because of the more

lipolysis and muscle (protein) degradation.

Over time, diabetes can lead to blindness, kidney failure, and nerve

damage. These types of damage are the result of damage to small vessels, referred

to as micro vascular disease. Diabetes is also an important factor in accelerating


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http://www.medicinenet.com/script/main/art.asp?articlekey=39262



http://en.wikipedia.org/wiki/Polyphagia

http://en.wikipedia.org/wiki/Polydipsia

http://en.wikipedia.org/wiki/Polyuria





72

the hardening and narrowing of the arteries (atherosclerosis), leading to strokes,

coronary heart disease, and other large blood vessel diseases. This is referred to as

macro vascular disease. This kind of damage may occur in the patient above. She

has tingling since 1 month ago. This tingling may come from the damage of the

small vessels which supply nerves which inervates the specific location. The

damage may occur because high blood glucose will make the glucose enters

endothelial cells easier because it doesn’t need any insulin. This damage will

make the nerve supplied by the damaged vessels starving and then damaged as

well. It is well known as neuropathy.

Somehow, patient also complains about her being sleepy easily recently.

This drowsiness may be a result from the fatigued cells and the bad quality of

sleep. Diabetic patient has 2 requirements becoming often sleepy. Because the

glucose can’t enter the cells well, the body will feel weaker because it lacks of

energy. Also, atherosclerosis made by the high glucose in diabetic patient will

make the cells receive oxygen less or we called it (hypoxia). Besides, in diabetic

patient, nocturia and sleep apnea often occur and make the patient has a bad

quality of sleep at night. It will be manifested in her drowsiness at day.

Insufficient production of insulin (either absolutely or relative to the

body's needs), production of defective insulin (which is uncommon), or the

inability of cells to use insulin properly and efficiently leads to hyperglycemia and

diabetes. This latter condition affects mostly the cells of muscle and fat tissues,

and results in a condition known as "insulin resistance." This is the primary

problem in type 2 diabetes. The absolute lack of insulin, usually secondary to a

destructive process affecting the insulin producing beta cells in the pancreas, is

the main disorder in type 1 diabetes. In type 2 diabetes, there also is a steady

decline of beta cells that adds to the process of elevated blood sugars. Essentially,

if someone is resistant to insulin, the body can, to some degree, increase

production of insulin and overcome the level of resistance. After time, if

production decreases and insulin cannot be released as vigorously, hyperglycemia

develops.


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73

The Insulin Resistance can be occurred in this patient in some ways.

According to Asia standard, her BMI (36,18 kg/m2) put into the condition of

obesity class II. In addition her waist circumference (93 cm) exceed female’s

waist circumference standard. It is called Central Obesity, and it is very dangerous

to our health. This obesity can increase the possibility to the damage of insulin

receptor in body cells someway. When it happens for a long time, sensitivity of

the body cells toward insulin will be more decrease and finally it is called Insulin

Resistance.

Glucose is a simple sugar found in food. Glucose is an essential nutrient

that provides energy for the proper functioning of the body cells. Carbohydrates

are broken down in the small intestine and the glucose in digested food is then

absorbed by the intestinal cells into the bloodstream, and is carried by the

bloodstream to all the cells in the body where it is utilized. However, glucose

cannot enter the cells alone and needs insulin to aid in its transport into the cells.

Without insulin, the cells become starved of glucose energy despite the presence

of abundant glucose in the bloodstream. In certain types of diabetes, the cells'

inability to utilize glucose gives rise to the ironic situation of "starvation in the

midst of plenty". The abundant, unutilized glucose is wastefully excreted in the

urine.

Insulin is a hormone that is produced by specialized cells (beta cells) of

the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind

the stomach.) In addition to helping glucose enter the cells, insulin is also

important in tightly regulating the level of glucose in the blood. After a meal, the

blood glucose level rises. In response to the increased glucose level, the pancreas

normally releases more insulin into the bloodstream to help glucose enter the cells

and lower blood glucose levels after a meal. When the blood glucose levels are

lowered, the insulin release from the pancreas is turned down. It is important to

note that even in the fasting state there is a low steady release of insulin than

fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In

normal individuals, such a regulatory system helps to keep blood glucose levels in

a tightly controlled range. As outlined above, in patients with diabetes, the insulin


16th Group



74

is either absent, relatively insufficient for the body's needs, or not used properly

by the body. All of these factors cause elevated levels of blood glucose

(hyperglycemia).

The fasting blood glucose (sugar) test is the preferred way to diagnose

diabetes.

Normal fasting plasma glucose levels are less than 100 milligrams per

deciliter (mg/dl).

Fasting plasma glucose levels of more than 126 mg/dl on two or more tests

on different days indicate diabetes.

A random blood glucose test can also be used to diagnose diabetes. A

blood glucose level of 200 mg/dl or higher indicates diabetes.

When fasting blood glucose stays above 100mg/dl, but in the range of

100-126mg/dl, this is known as impaired fasting glucose (IFG). While patients

with IFG do not have the diagnosis of diabetes, this condition carries with it its

own risks and concerns, and is addressed elsewhere.

We try to compare the patient’s blood glucose level with the standard

itself.

Her fasting plasma glucose are 199 mg/dL and the normal fasting plasma

glucose are less then 100 mg/dL.

Her 2-h PP plasma glucose are 317 mg/dL and it exceeds the normal 2-h

PP plasma glucose which is less than 200 mg/dL.

Those conditions above tell us that this patient truly suffers from

hyperglycemia, which is one of the characteristics of Diabetes Mellitus.

In the first, we think that she is suffered from type 2 Diabetes Mellitus,

because from the anamneses we know that she is 41 years old. In that time, before

we learn more about DM, we think that type 2 DM develop with increasing age

and type 1 DM develop in younger age. After that we get a data that explain about

the onset.


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75

“ Although type 1 DM most commonly develops before the age of 30, an

autoimmune beta cell destructive process can develop at any age. It is estimated

that between 5 and 10% of individuals who develop DM after age 30 have type

1A DM. Likewise, type 2 DM more typically develops with increasing age, but it

also occurs in children, particularly in obese adolescents.” (Kasper,2005)

So we should analyze more from other data.

We got a data about the risk factors for type 2 Diabetes Mellitus from Harrison's

Principles Of Internal Medicine, 16th Edition,2005 by Kasper.

In this patient, we find some risk factors for type 2 Diabetes Mellitus in

this patient. The first factor is she is obese (the BMI is about 36,1). Second, she is

habitual physical inactivity. Third, triglyceride level is > 250 mg/dL (278

mg/dL). There is one more risk factor that maybe she have but we aren’t sure

about that. That is she have family history of diabetes. From anamneses we know

that her father dead from complication and her eldest brother dead in 40 th years

old with a wound in her leg which cannot be healed and nasty smell. We think

that her father and her brother had suffered from diabetes, because uncontrolled

diabetes can make complication problem and diabetic patient often have wound

that hard to be healed (ulcer).


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3.3 FINAL HYPOTHESIS

76

Miss X , 41 years old, has the symptoms of Diabetes Mellitus Type 2 with

hyperglycemia, dysllipidemia due to the decreasing of sensitivity of insulin

receptor in cells caused by her obesity


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3.4 FINAL MIND MAPPING

77


16th Group

Decompensation of β cell of pancreas

Laboratory results:Fasting Glucose: 199 mg/dL

2-h PP Glucose: 317 mg/dL

Triachilglicerol 278 mg/dL

Hemoglobin: 12 g/dL

Creatinin Level: 0,7 mg/dL

HDL: 38 mg/dL ; LDL: 94 mg/dL; Total Cholesterol: 171 mg/dl

Palpation, percussion, & auscultation :

Ascites (-)Hepar & Lien normal

Obese

Compensated by pancreas to produce more insulin

Anamnesis:Tingling all time since a

month agoWake up at night for micturing

Often feel sleepy

3 kgs weight losses

Family sick: father dead from complication and eldest sister dead in 40 years old with a wound in her leg which can’t be healed and nasty smell

Often feels thirsty and drinks much

Often feel hungry too

Hasn’t received any treatments before

rarely, practically never, does any sports

vital sign examination:Pulse : 80/min

RR : 20/min

Temp: 37 oC

Blood pressure : 120/80 mmHg

Weight: 89 kgs

Height: 157 cms

Waist circumference: 93 cms

Inspections:Cyanosis, Anemia,

Icterus (-)

Ascites (-)

Extremity deformities (-)

High level of blood glucose

Type 2 Diabetes Mellitus

A Female, 41 years old

Examination

High lipotoxic from adipocyte

Sensitivity of insulin receptor is decreased

Other complications:Polyuria, polydipsia, polyphagia, tingling, sleepy, and other progressive complication like atherosclerosis, stroke, etc.

78

CASE MAPPING


16th Group

High level of blood glucose

Obese

Others factor

Polyphagya

Low level of insulin

Complication of diabetes melitus

High lypotoxic

Large amount of adipocytes

Glucose can not enter into cells with GLUT-4

Blood glucose increase

Decompensation of beta cell of pancreas

Compensated by pancreas to increase the insulin

production

Sensivity of insulin receptor decrease

progressively

Type 2 diabetes mellitus

Sensivity of insulin receptor decreased polydypsea polyuria

Chardiovascular disease

Renal disease

Neuropaty

Other complication

3.6 OBSTACLES

3.5 GROUP OPINION

79

Knowing that this woman has type 2 diabetic diseases which cells unable

to use insulin although insulin is produce, oral glucose-lowering agents can be

given to this woman. oral glucose-lowering agents are subdivided into agents that

increase insulin secretion, reduce glucose production, or increase insulin

sensitivity so it can decrease the level of blood glucose. We also suggest that this

woman should seriously change her habit. She should start to exercise, which

make glucose can be absorbed by the cells like skeleton muscle, etc without

insulin, so it can help the insulin’s receptor activity to fulfill the cell needs for

glucose. And the most important, this woman should have diet. She must be

decrease carbohydrate intake, she should has a struggle to restrain her apatite,

because if she is not change her diet, her glucose level will always be high that

have many risk for her health.

1. We are lack to ask more completely about patient examination so it’s

hard for us in making decision of analysis and final mind-map.


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80

2. Difficult for gathering the members of our group because of our

bustle.

3. Since all of us are involved in medical science held by the students of

Airlangga University Medical Faculty, we do not have enough time

to gather and discuss

References

U.S. National Library of Medicine, 2010. Drowsiness. Department of Health and

Human Services. Available at:

http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm (Accessed

on November 6th 2010)

National Institute of Neurological Disorders and Stroke, 2010, Peripheral

Neuropathy Fact Sheet, National Institute of Neurological Disorders and

Stroke. Available at:

http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheral

neuropathy.htm (Accessed on November 11th 2010)

Pathophysiology Of Diabetes Mellitus, unknown year. Pathophysiology Of

Diabetes Mellitus. [Online] (unknown updated date). Available at:

http://www.pathophysiologyofdiabetesmellitus.com/index.html (Accessed

November 7th 2010)

Unknown author, 2009. Phatophysiology of Diabetes. [internet] Diabetes

Manegement in School Setting. Available at:

http://www.dhss.mo.gov/diabetes/DMOverview.pdf (Accessed on

November 7th 2010)

Mayo Clinic, 2010. Diabetes symptoms: When diabetes symptoms are a concern.

[online] (Updated 12 Oct 2010). Available at:

http://www.mayoclinic.com/health/diabetes-symptoms/DA00125

(Accessed 7 November 2010)


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http://www.dhss.mo.gov/diabetes/DMOverview.pdf

http://www.pathophysiologyofdiabetesmellitus.com/index.html

http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm


http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm

81

Mayo Clinic, 2010. Diabetes symptoms: When diabetes symptoms are a concern.

[online] (Updated 12 Oct 2010). Available at:

http://www.mayoclinic.com/health/diabetes-symptoms/DA00125/NSECTI

ONGROUP=2 (Accessed 7 November 2010)

Hani L. .2010. Lingkar Perut Membesar dan Kegemukan. Available at

http://www.indonesiapower.co.id/index.php?

option=com_content&view=article&id=1145:lingkar-perut-membesar-

dan-kegemukan (Accesed on November 17th 2010)

MedlinePlus. 2010. Type 2 Diabetes – risk factors. A service of the U.S. National

Library of Medicine

National Institutes of Health (Online). Available at:

http://www.nlm.nih.gov/medlineplus/ency/article/002072.htm (Accessed

on Nopember 10th 2010)

International Diabetes Federation. 2010. Complications of diabetes. International

Diabetes Federation (Online). Available at:

http://www.idf.org/complications-diabetes, (Accessed on November 10th

2010)

Chernecky & Berger, 2008, Laboratory Tests and Diagnostic Procedures, 5th

Edition, Missouri: Saunders Elvesier

Brandis, Kerry. 2007. Acid-base Physiology. Availablet at

http://www.anaesthesiamcq.com/AcidBaseBook/ab3_2.php (Accessed on

November 8th 2010)

Davidson, S, et al., 1973. Human Nutritions and Dietetics. Edinburgh: English

Language Book Society.

Robert et al., 2003, Harper’s Illustrated Biochemistry, twenty six edition.USA:

Lange Medical

Lopes et al, 2005. Restless Legs Syndrome and Quality of Sleep in Type 2

Diabetes

Greene et al., 1992, Complications: neuropathy, pathogenetic considerations,

Diabetes Care December 1992 Vol. 15 no. 12. Avalable at:


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http://www.idf.org/complications-diabetes


http://www.indonesiapower.co.id/index.php?option=com_content&view=article&id=1145:lingkar-perut-membesar-dan-kegemukan



http://www.mayoclinic.com/health/diabetes-symptoms/DA00125/NSECTIONGROUP=2


82

http://care.diabetesjournals.org/content/15/12/1902 (Accessed on

November 11th 2010)

eMedicineHealth, 2010, Diabetes Symptoms. Available at

http://www.emedicinehealth.com/diabetes/page3_em.htm (Accessed

November 17th 2010)

Kasper, Dennis L. et al. eds. 2005. Harrison’s Principles of Internal Medicine 16th

ed. New York: McGraw-Hill Companies

Murray, Robert K. et al. 2003. Harper’s Illustrated Biochemistry 26th ed. New

York: Lange Medical Books

Manaf, A. MEKANISME SEKRESI DAN ASPEK METABOLISME. Available

at http://www.google.co.id/url?

sa=t&source=web&cd=2&ved=0CBkQFjAB&url=http%3A%2F

%2Frepository.unand.ac.id

%2F96%2F1%2FINSULIN__MEKANISME_SEKRESI_DAN_ASPEK_

METABOLISME.doc&ei=cPDjTOrFKYi3cIm6ra0M&usg=AFQjCNGSQ

oXZMYjqnExky-cWrgX8Al_FyQ (Accesed at November 17th 2010)

Direktur Gizi Masyarakat. Direktorat Jenderal Bina Kesehatan Masyarakat.

Departemen Kesehatan RI. 2003. PERAN DIIT DALAM

PENANGGULANGAN DIABETES. Available at

http://www.gizi.net/makalah/Makalah%20Pekan%20DM.PDF (Accesed

on November 17th 2010)

Efendic, et al, 1980, Insulin release, insulin sensitivity, and glucose intolerance,

Proceedings of the National Academy of Sciences. (Online), Vol. 77,

No.12. Available at: http://www.pnas.org/content/77/12/7425.full.pdf

(Accessed at November 11th 2010)

Murray, Robert K.2003.Harper’s Illustrated Biochemistry, Twenty-Sixth Edition.

Lange Medical Books/McGraw-Hill Medical Publishing Division.

Guyton, Hall. 2006. Textbook of Medical Physiology 11th Ed. Missisipi : Elsevier

Inc. p.966 - 967


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http://www.pnas.org/content/77/12/7425.full.pdf

http://www.gizi.net/makalah/Makalah%20Pekan%20DM.PDF

http://www.google.co.id/url?sa=t&source=web&cd=2&ved=0CBkQFjAB&url=http%3A%2F%2Frepository.unand.ac.id%2F96%2F1%2FINSULIN__MEKANISME_SEKRESI_DAN_ASPEK_METABOLISME.doc&ei=cPDjTOrFKYi3cIm6ra0M&usg=AFQjCNGSQoXZMYjqnExky-cWrgX8Al_FyQ



http://www.emedicinehealth.com/diabetes/page3_em.htm

http://care.diabetesjournals.org/content/15/12/1902

83

Corwin, Elizabeth (2001). Pathophysiology. Jakarta, EGC Penerbit Buku

Kedokteran


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84

EBL and Critical Apraissal

For AnsweringQuestion

Searching Method

Information Type

Validity Importance ApplicabilityFoundation Result Foundation Result Foundation Result

LEARNING ISSUES 1 http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm (Accessed on November 6th 2010)

1Internet

BrowsingDigital Article Yes

Content of information

YesIs it

applicable?Yes

http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm (Accessed on November 11th 2010)

2Internet



YesIs it

applicable?Yes

http://www.pathophysiologyofdiabetesmellitus.com/index.html (Accessed November 7th 2010)

3Internet

BrowsingDigital Idea No


YesIs it

applicable?Yes

http://www.dhss.mo.g

3Internet



YesIs it

applicable?Yes


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CRITICAL APPRAISAL












85

ov/diabetes/DMOverview.pdf (Accessed on November 7th 2010)http://www.mayoclinic.com/health/diabetes-symptoms/DA00125 (Accessed November 7th 2010)

4Internet



YesIs it

applicable?Yes

http://www.mayoclinic.com/health/diabetes-symptoms/DA00125/NSECTIONGROUP=2 (Accessed November 7th

2010)

4Internet



YesIs it

applicable?Yes

http://www.indonesiapower.co.id/index.php?option=com_content&view=article&id=1145:lin

5 Internet Browsing

Digital Idea No Content of information

Yes Is it applicable?

Yes


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86

gkar-perut-membesar-dan-kegemukan (Accesed on November 17th 2010)http://www.nlm.nih.gov/medlineplus/ency/article/002072.htm (Accessed on Nopember 10th 2010)

6Internet



YesIs it

applicable?Yes

http://www.idf.org/complications-diabetes, (Accessed on November 10th 2010)

7Internet



YesIs it

applicable?Yes

Laboratory Tests and Diagnostic Procedures, 5th Edition

8,9,10,11 eBook Digital Textbook YesContent of information

YesIs it

applicable?Yes

http://www.anaesthesiamcq.com/AcidBaseBook/

12 Internet Browsing

Digital Idea No Content of information


Yes


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87

ab3_2.php (Accessed on November 8th 2010)

Human Nutritions and Dietetics

13Borrowed from the library

Textbook Article YesContent of information

YesIs it

applicable?Yes

LEARNING ISSUES 2

Harper’s Illustrated Biochemistry, twenty six edition

1,4,7Personal Inventory

Textbook Textbook YesContent of information

YesIs it

applicable?Yes

Restless Legs Syndrome and Quality of Sleep in Type 2 Diabetes

1Borrowing from the library

Textbook Article YesContent of information

YesIs it

applicable?Yes

http://care.diabetesjournals.org/content/15/12/1902 (Accessed on November 11th

2 Internet Browsing

Digital (PDF)

Journal Yes Content of information


Yes


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88

2010)Partanen, et al.

1995. Natural

History of

Peripheral

Neuropathy in

Patients with

Non-Insulin-

Dependent

Diabetes

Mellitus. The

NEW

ENGLAND

JOURNAL of

MEDICINE.

(Online), Vol.

333 No. 2.

Available at:

http://www.nej

m.org/doi/pdf/1

0.1056/NEJM19

9507133330203

2 Internet Browsing

Digital (PDF)

Journal Yes Content of information


Yes


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http://www.nejm.org/doi/pdf/10.1056/NEJM199507133330203



89

(Accessed on

November 20th

2010)

http://www.emedicinehealth.com/diabetes/page3_em.htm (Accessed November 17th 2010)

3Internet



YesIs it

applicable?Yes

Harrison’s Principles of Internal Medicine 16th ed.

4Using

TextbookText Textbook Yes


YesIs it

applicable?Yes

http://www.google.co.id/url?sa=t&source=web&cd=2&ved=0CBkQFjAB&url=http%3A%2F%2Frepository.unand.ac.id%2F96%2F1%2FINSULIN__MEKANISME_SEKRESI_DAN_

5 Internet Browsing

Digital (Word)

Article Yes Content of information


Yes


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90

ASPEK_METABOLISME.doc&ei=cPDjTOrFKYi3cIm6ra0M&usg=AFQjCNGSQoXZMYjqnExky-cWrgX8Al_FyQ (Accesed at November 17th 2010)http://www.gizi.net/makalah/Makalah%20Pekan%20DM.PDF (Accesed on November 17th 2010)

5Internet

BrowsingDigital (PDF)

Article YesContent of information

YesIs it

applicable?Yes

http://www.pnas.org/content/77/12/7425.full.pdf (Accessed at November 11th

2010)

6Internet

BrowsingDigital (PDF)

Article YesContent of information

YesIs it

applicable?Yes

Harper’s Illustrated Biochemistry, Twenty-Sixth

7 Personal inventory

Textbook Text Yes Content of information


Yes


16th Group









91

Edition.Textbook of Medical Physiology 11th

Ed. Missisipi : Elsevier Inc. p.966 - 967

8Personal inventory

Textbook Text YesContent of information

YesIs it

applicable?Yes

Laboratory Tests and Diagnostic Procedures, 5th

Edition

9 eBook Digital Article YesContent of information

YesIs it

applicable?Yes

Pathophysiology 10Borrowing from the library

Text Report YesContent of information

YesIs it

applicable?Yes


16th Group

SCIENTIFIC PAPER APPRAISAL

Group : 16th group

Title : Natural History of Peripheral Neuropathy in Patients with Non-

Insulin-Dependent Diabetes Mellitus

1. PAPER COMPLETION :

Item Existence (with page)

Title Yes (page 89)

Abstract and or Summary Yes (page 89)

Introduction, Background Yes (page 89)

Method Yes (page 89)

Result Yes (page 89)

Discussion Yes (page 93)

Acknowledgement No

Reference Yes (page 93-94)

Conclusion : the format is not complete

PBL Group 1st Medical Faculty of Airlangga University Medical Ethic and Law Module 2009

2. RESEARCH VALIDITY

Objective: To determine the long-term risk of diabetic polyneuropathy and the factors affecting that risk.

Method: Cross-sectional Study

Item Items found (with page)

Design Cross-sectional study (Page 89)

Hierarchy of Evidence 5

Sample We recruited 133 patients with newly diagnosed NIDDM who were 45 to 64 years old at the time of Table 1Characteristics of the Patients with NIDDM and the Control Subjects at Base Line.diagnosis and 144 randomly selected nondiabetic control subjects in the same age group (Table 1Table 1Characteristics of the Patients with NIDDM and the Control Subjects at Base Line.).2 Both groups were evaluated between May 1, 1979, and December 31, 1981.4 The control subjects were recruited from among 180,000 inhabitants of the county of Kuopio in eastern Finland. At base line, 132 patients with NIDDM and 142 control subjects underwent clinical evaluation and measurement of nerve conduction velocity. Of these, 114 patients with NIDDM (86 percent) and 128 control subjects (90 percent) were evaluated after 5 years of follow-up, and 86 (65 percent) and 121 (85 percent), respectively, after 10 years. (Page 89)

Sample Size We recruited 133 patients with newly diagnosed NIDDM who were 45 to 64 years old at the


time of Table 1Characteristics of the Patients with NIDDM and the Control Subjects at Base Line.diagnosis and 144 randomly selected nondiabetic control subjects in the same age group (Table 1Table 1Characteristics of the Patients with NIDDM and the Control Subjects at Base Line.).2 Both groups were evaluated between May 1, 1979, and December 31, 1981.4 The control subjects were recruited from among 180,000 inhabitants of the county of Kuopio in eastern Finland. At base line, 132 patients with NIDDM and 142 control subjects underwent clinical evaluation and measurement of nerve conduction velocity. Of these, 114 patients with NIDDM (86 percent) and 128 control subjects (90 percent) were evaluated after 5 years of follow-up, and 86 (65 percent) and 121 (85 percent), respectively, after 10 years. (Page 89)

Eligibility Criteria We recruited 133 patients with newly diagnosed NIDDM who were 45 to 64 years old at the time of Table 1Characteristics of the Patients with NIDDM and the Control Subjects at Base Line.diagnosis and 144 randomly selected nondiabetic control subjects in the same age group (Table 1Table 1Characteristics of the Patients with NIDDM and the Control Subjects at Base Line.).2 Both groups were evaluated between May 1, 1979, and December 31, 1981.4 The control subjects were recruited from


among 180,000 inhabitants of the county of Kuopio in eastern Finland. At base line, 132 patients with NIDDM and 142 control subjects underwent clinical evaluation and measurement of nerve conduction velocity. Of these, 114 patients with NIDDM (86 percent) and 128 control subjects (90 percent) were evaluated after 5 years of follow-up, and 86 (65 percent) and 121 (85 percent), respectively, after 10 years. (Page 89)

Exclusion Criteria -

Sampling Frame Total Sampling

Collecting Data Method The diagnosis of diabetes4 was confirmed by an oral glucose-tolerance test, in which subjects were given 75 g of glucose after a 12-hour overnight fast5; the test was performed in both the diabetic patients and the control subjects. Information about cigarette smoking and the use of alcohol was obtained by questionnaire. (Page 89)

Measurement and or assessment Glucose tolerance was assessed by measuring blood or plasma glucose concentrations (in blood at base line and in plasma at 5 and 10 years) and serum insulin and C-peptide concentrations before and one and two hours after the oral administration of 75 g of glucose. Glucose was measured by the glucose oxidase method (at base line and at the 10-year examination) or the glucose dehydrogenase method (at 5 years).7 Serum insulin was measured by a double-antibody radioimmunoassay (at base line: Novo Industries, Copenhagen, Denmark; at 5 and 10 years:


Phasedeph, Pharmacia, Uppsala, Sweden). Serum C peptide was measured by radioimmunoassay (at 5 years: Novo-Nordisk, Copenhagen; at 10 years: 125-I, Incstar, Stillwater, Minn.).7

At all examinations, serum lipid concentrations were determined in samples obtained after the subjects had fasted for 12 hours. Lipoproteins were analyzed enzymatically after ultracentrifugation and precipitation.6,8 Glycosylated hemoglobin was measured at the 5-year and 10-year examinations by liquid cation-exchange chromatography (normal range, 4.0 to 6.0 percent). In the base-line study, albumin was measured by immunodiffusion in 24-hour urine samples (Behringswerke, Mahrburg Lahn, Germany). (Page 89-90)

Instrument The differences in mean values between the groups were analyzed by Student's t-test (two-tailed), the Mann-Whitney U test, or analysis of covariance with control for confounding variables. The categorical variables were analyzed by the chi-square test, McNemar's test, or Fisher's exact test. Time-related changes within a group were analyzed by paired t-tests or the Wilcoxon matched-pairs signed-rank test. Differences in the areas under the serum insulin curve (at base line, 5 years, and 10 years, with insulin-treated patients omitted) between the patients with and without neuropathy were analyzed by repeated-measures analysis of variance (for time of investigation, group, and fasting


glucose value at base line and at 5 and 10 years). Serum insulin concentrations were analyzed after logarithmic transformation. The area under the serum insulin curve was calculated by the trapezoidal rule. The Spearman correlation coefficient was calculated for the relation between nerve function and the metabolic variables (glycemic control and serum insulin values). All the data were analyzed with SPSS software (SPSS, Chicago). (Page 91)

Randomization -

Intervention -

Analysis Method Statistical Method (Page 91)

Coherence between design and objective: coherent

Coherence between measurement and instrument used: coherent

Conclusion: valid (ONLY BASED FROM TWO CONCLUSIONS ABOVE)

3. IMPORTANCE

CI : There is no CI.

P : 0.083

If this research were done repeatedly (100x), 8.3 researches will show the same

result as the previous result (by chance).

Conclusion : Because there is no CI, the importance can’t be

measured


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