fall chem week 3

endocrine

hormones secreted internally into blood stream

exocrine tissue

digestive enzymes secreted externally into the small intestine

islets of langerhans

endocrine tissue, alpha cells secrete glucagen, beta secrete insulin, delta somatostatin, gamma secrete pancreatic polypeptide PP, epsilon secrete ghrelin

acinar glands

exocrine tissue, proteolytic enzymes (trypsin, chymotrypsin, elastase), lipid-digesting enzymes (lipase), carb splitting enzyme (amylase), bicarbonate neutralizes HCl in duodenum

pancreatic regulation

nervous and endocrine control, vagus nerve branches trigger secretion when food is smelled/seen, duodenum cells secrete secretin and cholecystokinin CCK

secretin

secreted by cells in th duodenum, stimulates bicarbonate-rich alkaline pancreatic fluid

cholecystokinin CCK

secreted by cells in th duodenum, triggers enzyme release from acinar cells

pancreatitis

inflam of pancreas, autodigestion, due to reflux of bile or duodenal contents in pancreatic duct caused by gallstones, alc, high trig over 1000

pancreatitis increases

lipase- more specific/sens than amylase, almost all in pancreas, little in stomach lingual glands, liver

amylase- also in salivary glands, clears faster than lipase

increase in lipase and amylase interpretation

magnitude of elevation does not correlate with severity of pancreatitis (that is determined by surrounding tissue damage)

pancreatitis decreases

calcium (hypocalcemia), pancreas leaks lipase> destroys nearby fat> calcium binds to fatty acids> serum calcium level drops

fecal fat analysis

evaluate suspected fat malabsorption- exocrine pancreatic insufficiency or intestinal disorder, steatorrhea (excess fat in stool)

fecal lipids are deprived from

unabsorbed ingested lipids, lipids excreted into intestine (mainly in bile from liver, cholesterol, phospholipids), cells shed into intestine, and metabolism of intestinal bacteria

cells shed into intestine and metabolism of intestinal bacteria

phospholipid membranes that fecal lipids are deprived from

fecal fat analysis qualitative screening

fat soluble stains (sudan III), steatorrhea increased number and size of stained fat droplets

fecal fat analysis quantitative screening

definitive, 72 hr stool collection, gravimetric method- fatty acids extracted and weighed, ref 1-7 g fecal lipid per 24 hrs

fecal fat analysis limitations

more than 90% of oxocrine pancreatic function must be lost before 72 hr fecal fat test becomes pos

fecal elastase-1

chymotrypsin like enzyme, stable in transit, passes unmodified into the feces, norm over 200, moderate insufficiency 100-200, sever less than 100

carb serum/plasma ref range

fasting 8-16 hrs, method-dependent 70-99, critical under 40 or over 500

carb urine ref range

less than 15 or neg

carb csf ref range

glycorrhachia, 50-80, 60-70% of plasma glucose

serum / plasma glucose oxidase - peroxidase

interferences (uric acid, ascorbic acid, bilirubin, glutathione)

serum / plasma glucose hexokinase

ref method, most specific, increased absorbance 340 nm, interferences (drugs, hemolysis, high trig/lipemia, high bilirubin/icterus), NADPH

urine methodology

dipstick glucose oxidase, non specific copper reduction methods (clinitest tablets)

csf methodology

same as serum, glucose oxidase, hexokinase

whole blood collection

glucose is 15% lower than serum/plasma

serum/plasma collection and handeling

separated within an hr bc glycolysis, grey top tubes (sodium fluoride prevents glycolysis) if delayed centrifuge

hypoglycemia

plasma glu under 50, sweating, shaking cachycardia, anxiety, hunger, weak, dizzy, coma, blurry, inapropriate behavoir, diagnose with whipples triad

whipples triad

signs and symptoms, low plasma glu during signs and symptoms, alleviation of symptoms with the ingestion of glu and increase in plasma glu

drug induced hypoglycemia

alc, insulin, sulfonylureas

fasting hypoglycemia

liver enzyme def, insulinomas (low plasma glu with elevated insulin), severe liver or renal disease, def ketogenesis, islet cell adenoma or carcinoma, non beta cell tumor

reactive hypoglycemia

2-4 hrs after eating, delayed and exaggerated increase plasma insulin, predictor of type 2 diabetes, fructose intolerance, galactosemia, adrenal def

diabetes mellitus hypoglycemia due to defects in

insuline production, function, or both, type 1, type 2, gestational, and other/2ndary

diabetes mellitus uncontrolled clinical features

polydipsia, polyphagia, polyuria, dehydration, 7th leasing cause of death

diabetes mellitus uncontrolled labs

hyperglycemia, glucosuria, electrolyte imbalance, decreased blood and urine pH, increase serum with urine osmolality or specific gravity

diabetes mellitus diabetic retinopathy

primary cause of blindness

diabetes mellitus- glucosuria damages kidneys

primary cause of end stage renal disease, diabetic nephropathy

diabetes mellitus- dyslipidemia increases risk of

hypertension, artheriosclerosis, heart disease, stroke

diabetes mellitus- amputation of lower limbs due to

nervous system damage with poor circulation and hyperglycemia

urine microalbumin

albumin in urine, diagnose/monitor diabetic nephropathy, norm under 30, microalbuminuria 30-300/24hrs or /creatinine on 2-3 collections, proteinuria/macroalbuminuria over 300/24hrs

type 1 diabetes

insulinopenia (absolute insulin def), sudden weight loss, nausea, blurry, confusion, dehydration, prone to DKA, abrupt, under 20 yrs old, 80-90% autoab

DKA process

w/o insuline glu is unable to be processed, liver produces more glu to feed body, accumulates in bloodstream, body breaks down fat for energy producing ketones, build up in bloodstream, ketones and glu in urine, loss of water worsening

DKA

excess ketones decrease blood pH causing metabolic acidosis, osmotic diuresis causes dehydration from loss of water and electrolytes

ketones

produced by liver from catabolism of fatty acids, acetone 2%, acetoacetic acid 20%, beta-hydroxybutyric 78%

urine ketones

reagent strip for acetoacetic acid, sodium nitroprusside

ketones in serum/plasma

spectrophotometry for beta-hydroxybutyrate

type 2

90-95% of diabetics, strong genetic predisposition, gradual onset, insulin resistance, obese, if uncontrolled hyperosmolar hyperglycemic state HHS, glu over 600, no ketones, manage with diet and exercise

risk factors for type 2 diabetes

over 45 years, overweight, fam hx of diabetes, impaired fasting glu IFG, impaired glu tolerance IGT, hypertension, low HDL cholesterol

gestational

glucose intolerance during preg, due to metabolic and hormonal changes, returns to normal after preg, 30-60% probability of developing diabetes later in life

increased maternal glucose causes

birthweight over 9 lbs, babys high insulin secretion may cause severe hypoglycemia after birth, associated with risk of obesity and diabetes later in child’s life

low risk for gestation diabetes

under 25, weight normal before preg

2ndary or other diabetes

genetic defects of beta cell function, diseases of pancreas, endocrinopathies, drug/chem induced, genetic syndromes, hgb A1C over 6.5%

glycosylated / glycated hgb or hgb A1C

hgb A with addition of glu on one or both beta chains, less variable than glu, % of hgb A1C glycated, average blood glu for last 2-3 months, done biannually

glycosylated / glycated hgb or hgb A1C interpretation

1% increase= 30 mg change in glu does not require fasting or special pt prep, indicator of improvement, norm under 5.7%, prediabetes 5.7-6.4%, diabetes under 7% well controlled

glycosylated / glycated hgb or hgb A1C methodology

HPLC, enzymatic, electrophoresis, immunoassay, limitations- hemoglobinopathies and increased rbc turnover, alternative- fructosamine

diagnostic criteria

hgb A1C over 6.5%, fasting plasma glucose over 126, 2 hr post load glucose over 200, random plasma glu over 200 with hyperglycemia symptoms

glucose tolerance testing nonpreg pt

2 hr GTT, not routinely performed, collect fasted glu specimen, pt drinks 75g glu in 5 min, collect specimen 2 hrs later, greater than 200= diabetes mellitus, confirm

glu tolerance testing preg pt

older than 25 or high risk screened at 24-28 weeks, 2 part screening and diagnostic method

glu tolerance testing preg pt screen

no fasting, 50g drink, blood draw at 1 hr, over 130= step 2

glu tolerance testing preg pt diagnostic (step 2)

fasting overnight 8-16 hrs, 100g drink, blood draw glu high in 2 categories = GDM, 105 fasting,190 1hr, 165 2hr, 145 3hr)

affects of glu tolerance testing

gastrointestinal surgery and malabsorption, carb intake (150g for 3 days before), inactivity, obesity, stress, nausea, caffine, cigs, time of day, amount of glu ingested

fasting plasma glucose diagnosis

normal under 100, prediabetes or imapired fasting 100-125, diabetes millitus over 126

2hr postload glucose diagnosis

normal under 140, prediabetes or impaired glu tolerance 140-199, provisional diabetes mellitus over 200 must confirm

What is the major non-glucose-reducing substance present in serum?

ascorbic acid

What is the mechanism of insulin activity?

It stimulates glycogenesis and glycolysis in the liver