2016
ILA- ENDOCRINE SYSTEM
Q1/ What do you think the main problem in this patient?
A/ The patient has increasing tiredness, thirst, and passing large volume
of urine. He has noticed that he is losing weight and developed blurring
of vision.
Q2/ What do you think the main cause of his problem?
A/ The cause of his problem is hyperglycemia as a result of type 2
diabetes mellitus.
( or insulin resistance)
Q3/ How do you explain his clinical presentation?
A/
Polyuria is caused by osmotic diuresis secondary to hyperglycemia.
Thirst is a response to the hyperosmolar state and dehydration.
Fatigue and weakness (tiredness) may be caused by muscle wasting
from the catabolic state of insulin deficiency, hypovolemia, and
hypokalemia.
Blurred vision results from the effect of the hyperosmolar states on the
lens and vitreous humor. Glucose and its metabolites cause osmotic
swelling of the lens, altering its normal focal length,
anothor causes of Blurred vision are atherosclerosis and the effect of
neuropathy.
losing weight because of depletion of water and a catabolic state with
reduced glycogen, proteins, and triglycerides.
Skin boils are usually caused by bacteria, typically Staphylococcus
aureus or Streptococcus,
Staph is the most common cause of infections at insulin pump needle
sites.
also hyperglycemia (high blood glucose) tends to reduce blood flow to
the skin. It can also cause damage to blood vessels and nerves.
Decreased blood circulation can lead to changes in the skin‘s collagen.
This changes the skin‘s texture, appearance, and ability to hea
Q4/How Energy is produced from glucose metabolism in cells?
Draw a diagram referring to the key regulatory enzymes in such
pathways.
Typically, a breakdown of one molecule of glucose by aerobic
respiration (i.e. involving both glycolysis and Krebs cycle) is about 3335 ATP.
This is categorized as:
Anaerobic breakdown by glycolysis - yielding 8-10 ATP
Aerobic respiration by Krebs cycle - yielding 25 ATP
The rate limiting steps (the key enzymes are) in the glycolytic pathway
are: (i) the phosphorylation of glucose by hexokinase or glucokinase;
(ii) the phosphorylation of fructose-6-phosphate to form fructose-1,6bisphosphate by fructose-6-phosphate kinase; and (iii) the conversion of
phosphoenolpyruvate to pyruvate by pyruvate kinase ...
Q5/State the pathophysiology oh his problem.
A/ Diabetes Mellitus Type 2 Pathophysiology:Type 2 diabetes is caused by either inadequate production of the
hormone insulin or a lack of response to insulin by various cells of the
body.
Normal regulation of blood sugar :Glucose is an important source of energy in the body. It is mainly
obtained from carbohydrates in the diet which are broken down into
glucose for the various cells of the body to utilize. The liver is also able
to manufacture glucose from its glycogen stores.
In a healthy person, a rise in blood sugar after a meal triggers the
pancreatic beta cells to release the hormone insulin. Insulin, in turn,
stimulates cells to take up the glucose from the blood. When blood
glucose levels fall, during exercise for example, insulin levels also
decline.
As well as insulin stimulating the uptake of glucose from the blood by
body cells, it also induces the:
Stimulates the conversion of glucose to pyruvate (glycolysis) to release
free energy
Conversion of excess glucose to glycogen for storage in the liver
(glycogenesis)
Uptake and synthesis of amino acids, proteins, and fat
Pathology of type 2diabetes :In type 2 diabetes, the body either produces inadequate amounts of
insulin to meet the demands of the body or insulin resistance has
developed. Insulin resistance refers to when cells of the body such as the
muscle, liver and fat cells fail to respond to insulin, even when levels are
high. In fat cells, triglycerides are instead broken down to produce free
fatty acids for energy; muscle cells are deprived of an energy source and
liver cells fail to build up glycogen stores.
This also leads to an overall rise in the level of glucose in the blood.
Glycogen stores become markedly reduced and there is less glucose
available for release when it may be needed. Obesity and lack of
physical activity are thought to be major causes of insulin resistance.
Q6/ Look at the diagram and identify the parts pointed
A/
7-
Enumerate three other symptoms that the patient may has.
A/
123-
numbness & inn-continence of urine
delay injurey healing " effect on immunity and delays WBC
deep venous thrombosis " disturbance in blood flow
Q8/ List the risk factors that predispose this patient to this disease.
A/
1-FAMILY HISTORY: Type 2 diabetes has a hereditary factor.
2-RACE/ETHNICITY: Certain ethnic groups are more likely to develop type 2 diabetes
, including African-Americans, Hispanic
Americans, Native Americans, and Asian
Americans.
It‘s interesting to point out that as certain countries have become more Westernized and
their lifestyle choices—particularly their food choices—have become more ―American
,‖ the incidence of type 2 diabetes has gone up. For instance, China used to have
a low rate of type 2 diabetes. As the country has become more industrialized—more
people
working in offices and fewer people working in the fields—and as their diet has shifted,
the incidence of type 2 has increased.
Many Americans‘ lifestyles are conducive to developing type 2 diabetes—less physical
activity, consuming more calories. larger portions than necessary, and being overweight
(BMI greater than 25). It seems that certain non-white (not Caucasians) groups of people
are susceptible to type 2, but that risk is especially heightened if they live in America.
3-AGE: The older you are, the more at risk you are for developing type 2 diabetes. At age 4
5, your risk starts to rise, and after age 65, your risk increases exponentially.
4-GESTATIONAL DIABETES: If you developed diabetes while you were pregnant, that
increases your risk for developing type 2 diabetes later on.
5-POLYCYSTIC OVARY SYNDROME (PCOS): Polycystic ovary syndrome(PCOS)
also raises the risk for type 2 diabetes because it‘s related to insulin resistance.(female)
6-lifestyle choices do play a major role in the development of type 2 diabetes. not eating
well, not doing exercise and not being physically fit can also be considered risk factors
for type 2.
7-.Obesity or being overweight
8-high-blood pressure ,heart disease.
9-cholesterol level is low., triglyceride level is high
Q9/Name the biochemical investigations in confirming the diagnosis
and follow-up of a diabetic patient.
A/ Diabetes is confirmed by;1- Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL)
2- Randome plasma glucose ≥11.1 (200 mg/dL)
3- Two-hour plasma glucose ≥200 mg/dl (11.1 mmol/L) after 75 gm
glucose load.
4- HB A1c ≥ 6.5%
5- Urinary glucose = normally glucose doesn‘t appear in urine until the
plasma glucose rises above 10 mmol/L or more
Q10/Outline the treatment lines of this patient.
A/
In new cases of diabetes, adequate glycaemic control can be obtained by
diet and lifestyle advice alone in approximately 50%, 20–30% will need
oral anti-diabetic medication, and 20–30% will require insulin.
Regardless of aetiology, the choice of treatment is determined by the
adequacy of residual β-cell function. However, this cannot be
determined easily by measurement of plasma insulin concentration
because a level which is adequate in one patient may be inadequate in
another, depending upon sensitivity to insulin . Also the age and weight
of the patient at diagnosis, usually indicate the type of treatment
required. However, in each individual, the regimen adopted is
effectively a therapeutic trial and should be reviewed regularly.
The ideal management for diabetes would allow the person to lead a
completely normal life, to remain not only symptom-free but in good
health, to achieve a normal metabolic state and to escape the long-term
complications of diabetes.
The lines of management can be as simple as a healthy diet and
exercise or might require pharmaceutical interventions .
Diet and lifestyle The importance of lifestyle changes such as undertaking regular
physical activity, observing a healthy diet and reducing alcohol
consumption should not be underestimated in improving glycaemic
control, but many people, particularly the middle-aged and elderly, find
them difficult to sustain. Patients should also be encouraged to stop
smoking.
- Healthy eating
All people with diabetes need to pay special attention to their diet. They
should have access to a dietitian at diagnosis, at review and at times of
treatment change. Nutritional advice should be tailored to individuals
and take account of their age and lifestyle. Many people with type 2
diabetes require dietary advice for achieving weight loss, to include
caloric restriction and, in particular, reduced fat intake. Structured
education programmes are available for both common types of diabetes.
Drugs to reduce hyperglycaemiaBiguanides
Metformin is the only biguanide now available. It is now widely usedas
first-line therapy for type 2 diabetes, irrespective of body weight.
Classically considered an ‗insulin sensitiser‘ because it lowers insulin
levels, its main effects are on fasting glucose and are insulin
independent. Metformin reduces hepatic glucose production, may also
increase insulin-mediated glucose uptake, and has effects on gut glucose
uptake and utilisation. It is a potent blood glucose-lowering treatment
that is weight-neutral, does not cause hypoglycaemia and has
established benefits in microvascular disease.
The main side-effects are diarrhoea, abdominal cramps, bloating and
nausea.
Sulphonylureas
Sulphonylureas are ‗insulin secretagogues‘, i.e. they promote pancreatic
β-cell insulin secretion. act by closing the pancreatic β-cell ATPsensitive potassium (KATP) channel, decreasing K+ efflux, which
ultimately triggers insulin secretion. Sulphonylureas are an effective
therapy for lowering blood glucose and are often used as an add-on to
metformin, if glycaemia is inadequately controlled on metformin alone .
The main adverse effects of sulphonylureas are weight gain and
hypoglycaemia
α-glucosidase inhibitors
They delay carbohydrate absorption in the gut by inhibiting
disaccharidases. Acarbose and miglitol are available and are taken with
each meal. Both lower post-prandial blood glucose and modestly
improve overall glycaemic control. They can be combined with a
sulphonylurea.
The main side-effects are flatulence, abdominal bloating and diarrhea.
Thiazolidinediones
TZDs have been prescribed widely since the late 1990s, but recently a
number of adverse effects have become apparent and their use has
declined. One popular TZD, rosiglitazone, was reported to increase the
risk of myocardial infarction and was withdrawn in 2010. The other
TZD in common use, pioglitazone, does not appear to increase the risk
of myocardial infarction but it does exacerbate cardiac failure by
causing fluid retention, and recent data show that it increases the risk of
bone fracture, and possibly bladder cancer. These observations have
reduced the use of pioglitazone dramatically.
Pioglitazone can be very effective at lowering blood glucose in some
patients and appears more effective in insulin-resistant patients. In
addition, it has a beneficial effect in reducing fatty liver and NASH.
Pioglitazone is usually added to metformin with or without
sulphonylurea therapy It may be given with insulin therapy, when it can
be very effective, but the combination of insulin and TZDs markedly
increases fluid retention and risk of cardiac failure, so should be used
with caution.
Incretin-based therapies: DPP-4 inhibitors and GLP-1 analogues
The incretin effect is the augmentation of insulin secretion seen when a
glucose stimulus is given orally rather than intravenously, and reflects
the release of incretin peptides from the gut.
The incretin hormones are primarily glucagon-like peptide 1 (GLP-1)
and gastric inhibitory polypeptide (GIP). These are rapidly broken down
by the peptidase DPP-4 (dipeptidyl peptidase 4). The incretin effect is
diminished in type2 diabetes, and this has stimulated the development of
two incretin-based therapeutic approaches. The ‗gliptins‘, or DPP-4
inhibitors, prevent breakdown and therefore enhance concentrations of
endogenous GLP-1 and GIP. The first DPP-4 inhibitor to market was
sitagliptin; others now available include vildagliptin, saxagliptin and
linagliptin. These drugs are very well tolerated and are weight-neutral.
Management of hyperglycaemia in type 2 diabetes.
‫‪Done by:‬‬‫‪ -1‬يوسف عباش حسي ‪D4‬‬
‫‪ -2‬علي سيف علي ‪C2‬‬
‫‪ -3‬هيٌت هازى سالن ‪D2‬‬
‫‪ -4‬علي سعد حوداى ‪C2‬‬
‫‪ -5‬فاطوت خالد دمحم ‪C4‬‬
‫‪ -6‬علي جاسن دمحم ‪C2‬‬
‫‪ -7‬هٌار ثائر حوداى ‪D2‬‬
‫‪ -8‬ريام عسام خلف ‪B1‬‬
‫‪ -9‬هدى كٌعاى صالح ‪D4‬‬
‫‪ -11‬هاريت سعد خاشع ‪D1‬‬
‫‪-11‬فرح عاهر كاظن ‪D1‬‬
‫‪ -12‬ضحي دمحم قاسن ‪C3‬‬
‫‪ -13‬غادة باسن حويد ‪C3‬‬
‫‪ -14‬هيثن سلواى دمحم ‪D3‬‬
‫‪ -15‬هصطفي صادق جعفر‬
‫‪ -16‬هرين ههٌدًاظن حكوت ‪D2‬‬
‫‪ً -17‬ور دمحم شاكر ‪D3‬‬
‫‪ -18‬يسر احوددمحم دمحم حسيي ‪D4‬‬
‫‪ -19‬فرح رائد سالن ‪C4‬‬