Pathophysiology of the Endocrine System, MSN 570 Advance Patho,
MSN 570 HESI, HESI Exit Pathophysiology, Alterations of
Cardiovascular Function, Pathophysiology (HESI), MSN 570
Diabetes Mellitus
- Diabetes mellitus is a syndrome of impaired carbohydrate, fat, and protein metabolism
caused by either lack of insulin secretion or decreased sensitivity of the tissues to
insulin.
insulin
- causes rapid uptake, storage, and use of glucose by almost all tissues of the body
(with exception to the brain).
Insulin plays an important role in storing the excess energy.
In the case of excess carbohydrates, insulin causes them to be stored as
______________ mainly in the _________________ and _______________.
- In the case of excess carbohydrates, insulin causes them to be stored as glycogen
mainly in the liver and muscle.
Excess carbohydrates that cannot be stored as glycogen are converted under the
stimulus of insulin into _____________ and stored in ___________________.
- fats, adipose tissue
When insulin binds to the membrane receptor, it increases transportation of what into
the cells?
- glucose
Additionally, the cell membrane becomes more permeable to many of the amino acids,
potassium ions, and phosphate ions, causing increased transport of these substances
into the cell.
glucagon
- hormone secreted when the blood glucose concentration falls, most important of these
is to increase the blood glucose concentration, an effect that is exactly the opposite of
insulin.
Glucagon can elevate the blood glucose concentration by 25% in about 20 minutes and
therefore is called the hyperglycemic hormone.
what are the major effects of glucagon on glucose metabolism?
- Major effects of glucagon on glucose metabolism are
(1) glycogenolysis (breakdown of liver glycogen) and
,(2) increased gluconeogenesis (generation of glucose from non-carbohydrate
substrates).
glycogenolysis - breakdown of liver glycogen
gluconeogenesis - generation of glucose from non-carbohydrate substrates
A fasting blood glucose above this value often indicates diabetes mellitus or at least
marked insulin resistance.
- A fasting blood glucose (early morning) >110 mg/100 mL is the upper limit of normal.
islets of Langerhans
- cell clusters in the pancreas that form the endocrine part of that organ
what are the 3 major cells types of the islets of Langerhans and what do they secrete? -
alpha (25%) - secrete glucagon
beta (60%) - secrete insulin
delta (10%) - secrete somatostatin
somatostatin
- Somatostatin depresses the secretion of both insulin and glucagon,
decreases the motility of the stomach, duodenum, and gallbladder,
and decreases both secretion and absorption in the gastrointestinal
tract.
The principal role is to extend the period over which the food
nutrients are assimilated into the blood and decrease the utilization
of the absorbed nutrients by the tissues, thus preventing rapid
exhaustion of the food.
Type 1 Diabetes
- Deficiency of Insulin Production by Beta Cells of the Pancreas
Also called insulin
-dependent diabetes mellitus (IDDM) is caused by lack of insulin secretion
injury to the beta cells of the pancreas (viral infection / autoimmune disorders) impair
insulin production. The cause of T cell-mediated autoimmune destruction of beta cells in
the pancreas is unknown, although environmental triggers such as viruses, drugs, or
chemicals may initiate the autoimmune process in genetically susceptible hosts.
Production of antibodies to beta cell antigens with loss of beta cell function precedes the
onset of clinical diabetes
,The lack of insulin decreases the efficiency of peripheral glucose utilization and
augments glucose production, raising plasma glucose to 300-1200 mg/100 mL. The
increased plasma glucose has multiple effects.
3 principle sequelae of type 1 DM
- (1) increase blood glucose.
(2) increased utilization of fats for energy for formation of cholesterol by the liver.
(3) depletion of the body's proteins.
what are the consequences of increased plasma glucose levels?
- Loss of Glucose in the Urine
Dehydration
The increased osmotic pressure in the extracellular fluids causes osmotic transfer of
water out of the cells.
Additionally, the loss of glucose in the urine causes osmotic diuresis.
Thus polyuria (excessive urine excretion), and increased thirst are classic symptoms of
diabetes
Tissue Injury
blood vessels in multiple tissues throughout the body begin to function abnormally and
undergo structural changes that result in inadequate blood supply to the tissues.
This in turn leads to increased risk for heart attack, stroke, end-stage kidney disease,
retinopathy and blindness, and ischemia or gangrene of the limbs.
causes damage nerves.
Peripheral neuropathy (abnormal function of peripheral nerves) and autonomic nervous
system dysfunction
.
These abnormalities can result in impaired cardiovascular reflexes, impaired bladder
control, and decreased sensation in the extremities.
Hypertension secondary to renal injury and atherosclerosis secondary to abnormal lipid
metabolism often develop and amplify the tissue damage caused by the elevated
glucose.
Excess fat utilization in the liver occurring over a long time causes the amounts of
cholesterol in the circulating blood and increased deposition of cholesterol in the arterial
walls.
Increased Utilization of Fats and Metabolic Acidosis
, Shift from carbohydrate to fat metabolism increases the release of keto acids
(acetoacetic acid / B-hydroxybutyric acid) into the plasma more rapidly than they can be
taken up and oxidized by the tissue cells.
As a result, the patient develops metabolic acidosis from the excess keto acids.
80-90% of beta cell function must be lost before hyperglycemia occurs.
diabetic ketoacidosis
- High glucose levels exceed the threshold for renal tubular absorption, which creates a
significant osmotic diuresis with marked hypovolemia.
Characteristically with type 1 diabetes and precipitated by infection or acute illness
(stress-related events).
The insulin-dependent diabetic is unable to secrete insulin to counterbalance the serum
elevations of glucose, free fatty acids, and ketone bodies.
Unless exogenous insulin is provided, the glycemic event may progress to severe
ketoacidosis, dehydration, and acute metabolic decompensation.
Develops over 24 hours
DKA symptoms
- Develops over 24 hours
Symptoms include hyperglycemia, volume depletion (average 5L), tachycardia, anion
gap metabolic acidosis (due to increased production ketoacids), hyperosmolarity, N/V,
abdominal pain, and lethargy
Low pH stimulates Kussmaul respiration
(rapid/deep breathing)
Fruity 'acetone breath'. Acetone is an acid
produced when excess free fatty acids are
converted in the liver to ketones. Acetone is
excreted via the lungs.
Type 2 Diabetes - Resistance to the Metabolic Effects of Insulin
In contrast to type 1, is associated with increased plasma insulin concentration
(hyperinsulinemia). This occurs as a compensatory response by the pancreatic beta
cells for diminished sensitivity of target tissues to the metabolic effects of insulin, a
condition referred to as insulin resistance.
The decrease in insulin sensitivity impairs carbohydrate utilization and storage raising
blood glucose and stimulating a compensatory increase in insulin secretion.
MSN 570 HESI, HESI Exit Pathophysiology, Alterations of
Cardiovascular Function, Pathophysiology (HESI), MSN 570
Diabetes Mellitus
- Diabetes mellitus is a syndrome of impaired carbohydrate, fat, and protein metabolism
caused by either lack of insulin secretion or decreased sensitivity of the tissues to
insulin.
insulin
- causes rapid uptake, storage, and use of glucose by almost all tissues of the body
(with exception to the brain).
Insulin plays an important role in storing the excess energy.
In the case of excess carbohydrates, insulin causes them to be stored as
______________ mainly in the _________________ and _______________.
- In the case of excess carbohydrates, insulin causes them to be stored as glycogen
mainly in the liver and muscle.
Excess carbohydrates that cannot be stored as glycogen are converted under the
stimulus of insulin into _____________ and stored in ___________________.
- fats, adipose tissue
When insulin binds to the membrane receptor, it increases transportation of what into
the cells?
- glucose
Additionally, the cell membrane becomes more permeable to many of the amino acids,
potassium ions, and phosphate ions, causing increased transport of these substances
into the cell.
glucagon
- hormone secreted when the blood glucose concentration falls, most important of these
is to increase the blood glucose concentration, an effect that is exactly the opposite of
insulin.
Glucagon can elevate the blood glucose concentration by 25% in about 20 minutes and
therefore is called the hyperglycemic hormone.
what are the major effects of glucagon on glucose metabolism?
- Major effects of glucagon on glucose metabolism are
(1) glycogenolysis (breakdown of liver glycogen) and
,(2) increased gluconeogenesis (generation of glucose from non-carbohydrate
substrates).
glycogenolysis - breakdown of liver glycogen
gluconeogenesis - generation of glucose from non-carbohydrate substrates
A fasting blood glucose above this value often indicates diabetes mellitus or at least
marked insulin resistance.
- A fasting blood glucose (early morning) >110 mg/100 mL is the upper limit of normal.
islets of Langerhans
- cell clusters in the pancreas that form the endocrine part of that organ
what are the 3 major cells types of the islets of Langerhans and what do they secrete? -
alpha (25%) - secrete glucagon
beta (60%) - secrete insulin
delta (10%) - secrete somatostatin
somatostatin
- Somatostatin depresses the secretion of both insulin and glucagon,
decreases the motility of the stomach, duodenum, and gallbladder,
and decreases both secretion and absorption in the gastrointestinal
tract.
The principal role is to extend the period over which the food
nutrients are assimilated into the blood and decrease the utilization
of the absorbed nutrients by the tissues, thus preventing rapid
exhaustion of the food.
Type 1 Diabetes
- Deficiency of Insulin Production by Beta Cells of the Pancreas
Also called insulin
-dependent diabetes mellitus (IDDM) is caused by lack of insulin secretion
injury to the beta cells of the pancreas (viral infection / autoimmune disorders) impair
insulin production. The cause of T cell-mediated autoimmune destruction of beta cells in
the pancreas is unknown, although environmental triggers such as viruses, drugs, or
chemicals may initiate the autoimmune process in genetically susceptible hosts.
Production of antibodies to beta cell antigens with loss of beta cell function precedes the
onset of clinical diabetes
,The lack of insulin decreases the efficiency of peripheral glucose utilization and
augments glucose production, raising plasma glucose to 300-1200 mg/100 mL. The
increased plasma glucose has multiple effects.
3 principle sequelae of type 1 DM
- (1) increase blood glucose.
(2) increased utilization of fats for energy for formation of cholesterol by the liver.
(3) depletion of the body's proteins.
what are the consequences of increased plasma glucose levels?
- Loss of Glucose in the Urine
Dehydration
The increased osmotic pressure in the extracellular fluids causes osmotic transfer of
water out of the cells.
Additionally, the loss of glucose in the urine causes osmotic diuresis.
Thus polyuria (excessive urine excretion), and increased thirst are classic symptoms of
diabetes
Tissue Injury
blood vessels in multiple tissues throughout the body begin to function abnormally and
undergo structural changes that result in inadequate blood supply to the tissues.
This in turn leads to increased risk for heart attack, stroke, end-stage kidney disease,
retinopathy and blindness, and ischemia or gangrene of the limbs.
causes damage nerves.
Peripheral neuropathy (abnormal function of peripheral nerves) and autonomic nervous
system dysfunction
.
These abnormalities can result in impaired cardiovascular reflexes, impaired bladder
control, and decreased sensation in the extremities.
Hypertension secondary to renal injury and atherosclerosis secondary to abnormal lipid
metabolism often develop and amplify the tissue damage caused by the elevated
glucose.
Excess fat utilization in the liver occurring over a long time causes the amounts of
cholesterol in the circulating blood and increased deposition of cholesterol in the arterial
walls.
Increased Utilization of Fats and Metabolic Acidosis
, Shift from carbohydrate to fat metabolism increases the release of keto acids
(acetoacetic acid / B-hydroxybutyric acid) into the plasma more rapidly than they can be
taken up and oxidized by the tissue cells.
As a result, the patient develops metabolic acidosis from the excess keto acids.
80-90% of beta cell function must be lost before hyperglycemia occurs.
diabetic ketoacidosis
- High glucose levels exceed the threshold for renal tubular absorption, which creates a
significant osmotic diuresis with marked hypovolemia.
Characteristically with type 1 diabetes and precipitated by infection or acute illness
(stress-related events).
The insulin-dependent diabetic is unable to secrete insulin to counterbalance the serum
elevations of glucose, free fatty acids, and ketone bodies.
Unless exogenous insulin is provided, the glycemic event may progress to severe
ketoacidosis, dehydration, and acute metabolic decompensation.
Develops over 24 hours
DKA symptoms
- Develops over 24 hours
Symptoms include hyperglycemia, volume depletion (average 5L), tachycardia, anion
gap metabolic acidosis (due to increased production ketoacids), hyperosmolarity, N/V,
abdominal pain, and lethargy
Low pH stimulates Kussmaul respiration
(rapid/deep breathing)
Fruity 'acetone breath'. Acetone is an acid
produced when excess free fatty acids are
converted in the liver to ketones. Acetone is
excreted via the lungs.
Type 2 Diabetes - Resistance to the Metabolic Effects of Insulin
In contrast to type 1, is associated with increased plasma insulin concentration
(hyperinsulinemia). This occurs as a compensatory response by the pancreatic beta
cells for diminished sensitivity of target tissues to the metabolic effects of insulin, a
condition referred to as insulin resistance.
The decrease in insulin sensitivity impairs carbohydrate utilization and storage raising
blood glucose and stimulating a compensatory increase in insulin secretion.
