EXPLORATION OF ENDOCRINE SYSTEM

EXPLORATION OF ENDOCRINE PANCREAS HORMONAL EXPLORATION IN PREGNANCY EVALUATION OF BODY MASS INDEX What do we do in this lab?

EXPLORATION OF ENDOCRINE PANCREAS The pancreas has both endocrine and exocrine functions. The endocrine tissue is grouped together in the islets of Langerhans and consists of four different cell types each with its own function. Alpha cells produce glucagon. Beta cells produce proinsulin. Proinsulin is the inactive form of insulin that is converted to insulin in the circulation. Delta cells produce somatostatin. F or PP cells produce pancreatic polypeptide.

Endocrine pancreas -insulin -glucagon

Target tissues: - muscle - liver - fat tissue

Efficient disposition of the nutrient input from meals. Flow of endogenous

glucose free fatty acids amino acids other substrate molecules

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in order to ensure that energy needs are met in the basal state during exercise

The plasma insulin response to stepwise infusion of glucose in humans. No insulin is secreted below a plasma glucose level of 50 mg/dl. Half maximum secretion occurs at 125 to 150 mg/dl.

Insulin

anabolic hormone uptake and storage after meal of

glucose amino acids fats

Acutely: reduces blood sugar. Consequently: fall in plasma insulin increases blood glucose.

Insulin on glycose metabolism

LIVER: - inhibits glycogenolysis (its breakdown) - stimulates glycogen synthesis - inhibits gluconeogenesis (synthesis of glucose from noncarbohydrate sources) - increases glucose utilisation (glycolysis) - overall effect is to increase hepatic glycogen stores. MUSCLE: - increase facilitated transport of glucose via GLUT4 transporter - stimulate glycogen synthesis and glycolysis. ADIPOSE TISSUE: - increases glucose uptake by GLUT4 - Facilitates formation of glycerol, which esterified with fatty acids forms triglycerides.

Insulin on fat metabolism

Insulin on protein metabolism

stimulates uptake of amino acids into muscle and increases protein synthesis decreases protein catabolism inhibits oxidation of amino acids in the liver.

increases synthesis of fatty acid and triglyceride in adipose tissue and in liver inhibits lipolysis, partly via inactivation of lipases inhibits the lipolytic actions of adrenaline, growth hormone and glucagon

Glucagon

main physiological stimuli to glucagon secretion is the concentration of amino acids in the plasma ingestion of a high protein meal is followed by an increase in secretion Glucagon secretion is
stimulated by low levels inhibited by high levels of: Plasma glucose Plasma fatty acids

Glucagon

increases blood glucose stimulates glycogen breakdown stimulates gluconeogenesis causes breakdown of fat and protein inhibits glycogen synthesis and glucose oxidation. Its metabolic actions on target tissues are the opposite of those of insulin. It increases the rate and force of contraction of the heart.

Glucagon metabolism Insulin metabolism

Exploration of endocrine pancreas is connected with the diagnosis and treatment of diabetes mellitus. This is a complex disease characterized - primarily by relative or absolute insufficiency of insulin secretion and - concomitant insensitivity or resistance to the metabolic action of insulin on target tissues.

Two-phase release of insulin in response to constant glucose infusion

Pathophysiology of Diabetes Mellitus

Laboratory tests used in order to explore the pancreas endocrine function are :

Fasting blood glucose Oral Glucose Tolerance Test (OGTT) HBA1c level (also called glycosylated haemoglobin level) Urine glucose level Urinary ketone bodies Insulin blood level measured by RIA ( n. value :10-20 uU/ml ; 21U = 40ug insulin) Glucagon secretion measured by RIA (n. value: 50-85 pg/ml fasting level) Islet Cell Antibody tests Fructosamine level

Fasting blood glucose

Normal value :
70 -110 mg/dl (venous blood)

Variations :
>110 mg/dl hyperglycaemia 50-60 mg/dl - hypoglycaemia

Oral Glucose Tolerance Test (OGTT)

During the oral glucose tolerance test your blood glucose is tested two hours after drinking 75 grams of glucose (1 g glucose/kg body weight) solved in 200300 ml water Normal values : fasting value < 110 mg/dl 2 hours < 140 mg/dl

Diabetes mellitus
-fasting

glucose -2 hours Impaired glucose tolerance (IGT)

-fasting

> 110 mg/dl > 200 mg/dl

glucose -2 hours Impaired fasting glycaemia ( IFG)

-fasting

> 110 mg/dl 140 - 200 mg/dl

glucose -2 hours

> 110 mg/dl < 140 mg/dl

Glycosylated hemoglobin or hemoglobin A1c

This test is a measurement of how high blood sugar levels have been in the last 120 days. Excess blood glucose is attached to the hemoglobin found in red blood cells. The percentage of hemoglobin that has had excess blood sugar attached to it can be measured in the blood. The test involves having a small amount of blood drawn.
HbA1c (%) Normal value Good control Medium control Poor control 4-6 6-8 8-10 >10 Blood glucose level ( mg/dl) 110 160 200 >200

Urine glucose concentrations

- Normal value: undetectable amounts of glucose in the urine. (Benedict method) - Variations: Diabetic patients secrete glucose in small to large amounts into the urine (glycosuria).
The level of glycosuria depends on the severity of the disease and the intake of carbohydrates. The renal threshold for glucose (the arterial blood level at which glycosuria appears) is reached when the glucose concentration in plasma is above 180 mg/dl).

Urinary ketone bodies

- Normal value: normal individuals do not lose ketone bodies in the urine (Legal - Imbert method) - Variations: the identification urinary ketone bodies and their level is important in the diagnosis of the severity of the diabetes.

Diabetes mellitus - recurrent or persistent hyperglycemia - diagnosed by demonstrating any of the following:

Fasting plasma glucose level:

7.0 mmol /L (126 mg/dL)

Glucose tolerance test: two hours after a 75 g oral glucose intake, plasma glucose level
11.1 mmol /L (200 mg/dL)

Symptoms of hyperglycemia and casual plasma glucose level

11.1 mmol/L (200 mg/dL)

Glycated hemoglobin (hemoglobin A1C) 6.5% (recommended by the American Diabetes Association in 2010).

HORMONAL EXPLORATION IN PREGNANCY

Pregnancy tests

All pregnancy tests work by detecting a certain hormone in the urine or blood that is only there when a woman is pregnant. This hormone is called human chorionic gonadotropin (hCG or pregnancy hormone). HCG is being produced by the placenta and enters the blood stream as soon as implantation happens, about one week after fertilization and ovulation, when the embryo implants and the placenta develops. Quantitative tests ( blood tests): - hCG < 5 mIU/ml: Negative i.e. not pregnant - hCG : 5-25 mIU/ml: "Equivocal". Repeat test in a couple of days - hCG > 25 mIU/ml: Positive i.e. pregnant

hCG Information

hCG is measured in milli-international units per milliliter (mIU/ml) There is a wide range of normal hCG levels and values Values are different in blood serum or urine. Urine hCG levels are usually lower than serum (blood) hCG levels. Blood hCG testing is much more sensitive than a urine HPT (becomes positive earlier, 2-3 days after implantation or 8-9 days after fertilization) Urine tests measure the urine HCG qualitatively, which means that the HPT results are either "positive" or "negative." Around the time of the first missed period (14+ days after ovulation), over 95% of HPTs are usually positive.
About 85% of normal pregnancies will have the hCG level double every 48 - 72 hours. As you get further along into pregnancy and the hCG level gets higher, the time it takes to double can increase to about every 96 hours

hCG Information

1. Higher than normal levels of human chorionic gonadotropin (hCG) may indicate: a normal pregnancy multiple pregnancy, such as twins or triplets a tumor of the placenta with death of the fetus ovarian cancer and other types of cancer in some cases blood or protein in the urine, which can interfere with the result use of medications to prevent seizures, drugs to treat Parkinsons syndrome, or phenothiazine drugs, such as chlorpromazine, by the mother

2. Lower-than-normal human chorionic gonadotropin (hCG) levels may indicate: ectopic pregnancy miscarriage or abortion.

Home Pregnancy Tests ( HPT) - qualitative tests

Home Pregnancy Tests (HPT)

SPECIMEN COLLECTION AND PREPARATION : For optimal detection of early pregnancy, a "first morning" urine specimen is preferred, (highest concentration of hCG). Randomly collected urine specimens may also be used. Collect the urine specimen in a clean container. If testing is not immediate, the specimen should be refrigerated for up to twenty-four hours. Bring the urine specimen to room temperature prior to testing.

atc anti-hCG + hCG Positive test: (on the stick) (urine) = coloured reaction

READING TEST RESULTS:

1. Negative: One (1) colored band appears in the control region (C). No apparent band is detectable in the test region (B). 2. Positive: In addition to the control band, a clearly distinguishable band also appears in the test region (B), indicating the presence of hCG in the sample. 3. Inconclusive: The test is inconclusive in the absence of distinct color bands in both the control (C) and test window (B). In this case, it is recommended that the test be repeated, or a fresh specimen be obtained and tested 48 hours later.

EVALUATION OF NUTRITIONAL STATUS - overweight and obesity

Body weight ( kg):

IBW - Estimated ideal body weight in (kg) Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet. Females: IBW = 45.5 kg + 2.3 kg for each inch (2.5 cm) over 5 feet (152 cm). Lorentzs formula for ideal body weight: Weight=Height (cm) 100 (Height-150)/4

ABW - Estimated adjusted body weight (kg) If the actual body weight is greater than 30% of the calculated IBW, calculate the adjusted body weight (ABW) ABW = IBW + 0.4 (actual weight - IBW)

Body Mass Index (BMI) - is a statistical measure which compares a person's weight and height - it does not actually measure the percentage of body fat, - it is used to estimate a healthy body weight based on a person's height - it is the most widely used diagnostic tool to identify weight problems within a population,
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BMI Categories: Underweight BMI18.5 Normal weight BMI: 18.5-24.9 Overweight BMI: 25-29.9 Obesity BMI 30

Body Mass Index (BMI)

Body Mass Index (BMI)

Obesity and insulin resistance

In the obese:

adipose tissue releases

non-esterified fatty acids Glycerol Hormones proinflammatory cytokines causing insulin resistance.

In response to changes in insulin sensitivity

insulin release increases or decreases to maintain normal glucose tolerance.

impaired glucose tolerance = individuals who are at high risk of developing type 2 diabetes failure to control blood glucose levels = diabetes mellitus
insulin resistance + dysfunction of pancreatic islet -cells

What do we do in this lab? Fasting glucose plasma level (if youve fasted for the last 8-12 hours) Random plasma glucose levels (if youve not) Oral glucose tolerance test (youll ingest 75 g glucose in 200 ml water, measurement in 2 hours) Pregnancy test BMI calculation, ideal body weight