An aldehyde, ketone, or a compound that yields either aldehyde or ketone after hydrolysis
Carbohydrates
*Phil setting: based on response of body based on insulin levels
General formula of monosaccharide
CnH2nOn
Aldoses and ketoses are
monosaccharides
Classifications of carbohydrates based on conromation
D and L Monosaccharides/
Fischer Projection
Haworth Projection
basis of fischer projetion
position of OH group (D or L)
*alpha-below beta-above (Haworth)
In the Embden-Meyerhoff Pathway, Glyceraldehyde-3-Phosphate is converted to?
Dihydroxyacetonephosphate (DHAP) or continue to the
Kreb’s Cycle
Glycolysis converts glucose to
pyruvate
*If body does not need sugar, glucose is shunted to PPP and etc
hormones from pancreatic beta cells (I of L) in fed state
insulin
*promotes cellular uptake of glucose (allowing transport of sugars from blood; anabolic)
How is proinsulin converted to insulin?
removal of C peptide (proinsulin: a + b + c peptides)
What are the requirements for insulin release?
− Glucose
− Other amino acids that can ramp up release of insulin
(Leucine, Arginine, Histidine, Phenylalanine)
− Sulfonylureas (tolbutamides)
− ACTH, GH
o As ACTH increases, cortisol increases which leads to an increase in glycolysis
What causes release inhibition of insulin?
− Thiazide diuretics (hypertensive drug)
− Dilantin (antiseizure)
− Human placental lactogen (diabetes of pregnancy)
What causes decreased tissue response to insulin?
− Glucocorticoids (Obesity)
− Estrogens (Inactivity)
− Progestins (Low carbohydrate diet)
Insulin INCREASES these metabolic pathways
lipogenesis
protein synthesis
glycogenesis
Insulin DECREASES these metabolic pathways
lipolysis
ketone formation
gluconeogenesis
glycogenolysis
hormones involved in unfed/fasting state
glucagon (from pancreatic alpha cells; catabolic)
What happens to glycogen in the liver? muscle?
liver: glycogen is converted to glucose, and released into the blood
Muscle: glycogen converted to glucose-6-phosphate, and remains in the muscle for its own energy needs
Its action is similar to glucagon and it is immediately expended
“Fight or Flight” epinephrine from adrenal medulla
Hormones involved in gluconeogenesis
cortisol (hydrocortisone)- from adrenal cortex; inhibits glucose entry to muscle, connective and lymphoid tissue Adrenocorticotropic Hormone (ACTH)- from anterior pituitary gland and stimulates prod of cortisol
Cortisols stimulates release of
gluconeogenic amino acids from the muscles
*also promotes conversion of amino acids into glucose by liver
What does cortisol stimulate in adipose cells?
lipolysis by releasing glycerol for conversion to glucose by liver
T or F: glycolysis stops in the sample once it is drawn
false
*Serum/plasma must be separated from cells soon after collection to avoid a falsely decreased glucose result
→ Ideally, processing must be done within 1 hour
What are the conditions of glucose reabsorption and glycosuria in PCT?
(renal threshold)
→ Reabsorbs all glucose if <180 mg/dL
→ Glycosuria results if blood glucose >180mg/dL
* >600 mg/dL in the kidney: greater than blood glucose threshold because of countercurrent mechanism
Increase in plasma glucose levels due to hormone imbalance
hyperglycemia
glucose reference ranges
74-106 mg/dL
increased if >110-120 mg/dL
Why does blood sugar increase at night?
fasting blood sugar (body undergoes gluconeogenesis at night to supply energy for the body’s organs)
How is fasting blood sugar counteracted?
insulin production so glucose enters cells and cortisol becomes active (basal metabolic rate) to increase blood sugar
fasting blood sugar can have this effect on diabetics
somogyi effect
Why shouldnt diabetics* take extra insulin shots before sleeping?
*in a constant catabolic state
Blood sugar goes down over the course of the night leading to hypoglycemia and a surge in cortisol from 4am-6am leads to hyperglycemia rebound leading to diabetic coma
Immediate effects of hyperglycemia
increased extracellular osmotic pressure (increased glucose in plasma = water out of cells; dehydration)
acidosis (respiratory > metabolic)
[Hyperglycemia effects] Results if glucos remains uncontrolled
acidosis
If patient’s cells are not able to take in glucose, fats are converted to fatty acids = keto acids
[Hyperglycemia effects] hyperventilation of body to offset acidity
respiratory acidosis (not much change in pH)
[Hyperglycemia effects] excess acids go to kidneys
metabolic acidosis (noticeable change in pH)
physiological long term effects of hyperglycemia
→ Heart attacks/stroke → Diabetic retinopathy (blindness) → Kidney failure → Neurological defects → Susceptibility to infections
What chemical is formed as a long term effect of hyperglycemia (result of prolonged elevation of plasma glucose)?
glycosylated hemoglobin (HbA1c)
*more accurate parameter in gauging level of hyper/hypoglycemic state as it takes into acct average plasma glucose levels for past 30 days
chronic hyperglycemia
diabetes
four categories of diabetes accdg to WHO and ADA
→ Type 1 Diabetes • Most severe and potentially lethal → Type 2 Diabetes • Affects the obese and those that are old and with poor diet → Other (Secondary Diabetes) → Gestational Diabetes Mellitus (GDM) •Transient •Unknown mechanism
Physiologic abnormalities in diabetes
Hyperglycemia
Ketosis (from fat metabolism to ketonemia then ketonuria)
Hyperlipidemia
Decrease blood pH (metabolic acidosis)
Urine abnormalities (glycosuria, polyuria, loss of electrolytes-washed out with urine)
most dangerous and potentially lethal type of diabetes
type 1 diabetes/ Insulin dependent diabetes mellitus (5-10% of cases)
Pathology of type 1 diabetes
disease triggered by viral illness or environmental factors that destroys beta cells in pancreas which leads to absolute insulin deficiency (autoantibodies are present)
Clinical symptoms of type 1 diabetes
• Classical triad → Polyphagia – Increased food uptake → Polydipsia – Increased thirst → Polyuria – Increase urine production • Other symptoms: → Mental confusion → Rapid weight loss or weight gain → Hyperventilation → Diabetic ketoacidosis
Laboratory findings for type 1 diabetes
- Hyperglycemia: plasma levels >110-120 mg/dL
- Glycosuria: urine glucose >180 mg/dL
- Decreased insulin
- Increased glucagon leading to Chronic Gluconeogenesis and Increase Lipolysis (fat breakdown to produce ketones; main sourceS of type 1 DM)
- Ketoacidosis
- Decreased blood pH (acidosis)
- ↓ Sodium, ↑Potassium, ↓ CO2
Other names for type 2 diabetes (most common)
• Non-Insulin Dependent Diabetes Mellitus (NIDDM)
• Hyperosmolar Nonketotic Diabetes Mellitus
*relative deficiency of insulin and disorder in insulin resistance
T or F: Type 1 DM patients take oral hypoglycemic meds
false, type 2
Difference between lab findings of type 2 DM vs type 1 DM
• Insulin is present
• Glucagon is not elevated
• No gluconeogenesis, lipolysis and no ketoacidosis
• Excess glucose is converted to triglycerides (which yields higher plasma triglycerides)
• Normal or increased Na+ or K+
• Increased BUN and Creatinine
→ Due to dehydration
→ BUN:Creatinine ratio ≥ 20:1 indicates dehydration while 10:1 indicates renal tubular disorder
→ Leads to decreased renal function
• Hyperosmolar plasma from hyperglycemia
T or F: type 2 DM develops gradually throughout years
true
Type of diabetes where plasma glucose is unable to enter cells
type 2 DM
*Contributory factors:
→ Obesity
→ Lack of exercise
→ Diet
→ Genetics
→ Drugs (diuretics, psychoactive drugs like Dilantin and Tegretol)
→ Increases in hormones that inhibit/antagonize insulin (GH and cortisol)
A genetic defect of beta cell and insulin function (genetic syndromes) and a pancreatic disease in alcoholics
secondary diabetes
*endocrinopathies and autoimmune diseases; drug or chemically induced
type of diabetes associated with glucose intolerance assoc. with pregnancy’s hormonal and metabolic changes
Gestational Diabetes
T or F: Although GD usually resolves after pregnancy, mother and infants are at increased risk for respiratory complications and hypoglycemia after birth
false, mothers= increased risk for diabets; infants only (macrosomic babies: >=4kg)
Criteria for diagnosing diabetes
• Symptoms of Diabetes + Random Blood Glucose of >200mg/dL
(RBS: used in encephalopathic patients in ER; FBS: confined patient)
• 2-hour postprandial glucose >200mg/dL using oral glucose
tolerance test (OGTT) (low sensitivity)
• HbA1c >6.5%
*urine glucose testing = inaccurate (not used)
definition of hypoglycemia
• Plasma glucose level falls <60 mg/dL
When is glucagon released to inhibit insulin?
when plasma glucose <70 mg/dL
*other hormones to inhibit insulin: Epinephrine, cortisol, and growth hormone
Why do hypoglycemic patients go into shock?
→ Body increases mean arterial pressure causing cerebral
edema
→ Death is caused by cerebral herniation
General treatment of hypoglycemia
small, frequent meals (5-6x/day) that are low in carbohydrates, and high in proteins
Symptoms of hypoglycemia
patient looks sleepy
- Increased hunger
- Sweating
- Nausea
- Vomiting
- Dizziness
- Shaking
- Blurring of speech and sight
- Mental confusion (Encephalopathic)
laboratory finding of hypoglycemia which is secondary to profound hepatopancreatobiliary disease
Whipple’s triad
→ Symptoms of hypoglycemia
→ Low plasma glucose at time of symptoms
→ Alleviation of symptoms with glucose ingestion
causes of HYPOGLYCEMIA (reactive process)
- Insulin overdose
- Ethanol ingestion (cytochrome p450 oxidase metabolizes ethanol; too much= enzyme depletion= increasing serum levels of ethanol)
- Fasting
- Insulin-producing tumors (ie Insulinomia)
- Hepatic dysfunction
- Sepsis
This clinical test is still used for gestational diabetes diagnosis
Glucose tolerance test
normal diet: 3 days prior; no food after regular evening meal prior test; fasting blood, urine specimen
When is serum taken for glucose tolerance test?
2 hours after drinking 100g glucose load within 5 minutes
*water ONLY during test
Other conditions, tests associated with Diabetes Mellitus
White cell antigens (HLA types DR3, DR4, DQB1, *0302 checked to see if constant hypoglycemic state is genetic)
Lipid studies (increased triglycerides from hyperlipoproteinemia type IV)
Microalbuminuria
Microangiopathies (retinal, renal, neural probs)
(all involve alteration in genetic process)
What are the diabetic resistant genes?
DR2, DQB1 *0602
Why does microangiopathy happen?
In the blood vessels, the intima and media layers have bloodcapillary
barriers called capillary endothelial barriers. When the glucose is high, these barriers become leaky and the sugar enters, destroying nerve endings and ultimately weakening the blood vessels.
(see management of DM and review qs)
(see management of DM and review qs)
