Chemistry total 1.2-1.3 combined

what is endocrine?

secrete internally

-hormones released into bloodstream

what is exocrine tissue?

secrete externally

-digestive enzy,es released into small intestine

what do alpha cell secrete in the islets of langerhans?

glucagon

what do beta cells secrete in islets of langerhans?

insulin

what are the acinar glands?

exocrine tissue that has proteolytic enzymes, lipid-digesting enzymes, carbohydrate-splitting enzyme and bicarbonate neutralizes gastric HCL in the duodenum

what are the types of proteolytic enzymes that are found in acinar glands?

trypsin, chymotypsin, elastase

what are the types of lipid digesting enzymes in acinar glands?

lipase

what are the types of carbohydrate-splitting enzymes in acinar glands?

amylase

how does the pancreas regulate the body?

activity is under both nervous and endocrine control

-vagus nerve branches trigger secretion when food is smelled or seen

what do cell in the duodenum secrete?

• secretin= stimulates bicarb-rich, alkaline pancreatic fluid

• cholecystokinin (CCK)= triggers enzymes release from the acinar cells

what is pancreatitis?

inflammation of the pancreas —> autodigestion

what is the result of pancreatitis?

result of reflux bile or duodenal contents into the pancreatic duct which causes

-gallstones

-alcohol

-increase in trig

what are the laboratory findings of pancreatitis?

increase lipase and amylase and decreased calcium

why is there an increased lipase in pancreatitis?

more sensitive/specific than amylase

-almost all lipase comes from the pancreas

why is there decreased calcium (hypocalcemia) in pancreatitis?

pancreas leakis lipase —> destroys nearby fat —> calcium binds to fatty acids —> serum calcium level drops

how is the fecal fat analysis used for assessment of pancreatic function?

to evaluate suspected fat malabsorption

-exocrine pancreatic insufficiency or intestinal disorder

what are the sources fecal lipids are derived from?

• unabsorbed ingested lipids

• lipids excreted into the intestine

  • predominantly in bile from liver (cholesterol and phospholipids)

• cells shed into the intestine

• metabolism of intestinal bacteria

what is steatorrhea?

excess fat in stool

what is the qualitative screening for fecal fat analysis?

fat soluble stains (Sudan III) and steatorrhea indicated by increased number and size of stained fat droplets

-screening test

what is the quantitative test of fecal fat analysis?

72 hour stool collection

-gravimetric method: fatty acids are extracted and weighed

-definitive

what is the reference range for quantitative fecal fat analysis?

1-7 g fecal lipid per 24 hours

what are the limitations of quantitative fecal fat?

>90% of exocrine pancreatic function must be lost before a 72 hour fecal fat test becomes positive

How can fecal enzymes test pancreatic function?

fecal elastase-1

-chymotrypsin-like enzyme, stable in transit

-passes unmodified inot the feces

what is the reference range for fecal enzymes?

>200 ug/g is normal

100-200= moderate pancreatic insufficiency

<100 severe pancreatic insufficiency

what is the methodology of testing glucose in serum/plasma? glucose oxidase -peroxidase pathway

glucose + O₂ + 2H₂O —^{glucose oxidase} —> gluconic acid + 2H₂O₂

2H₂O₂ + reduced chromagen —^{horseradish peroxidase}—> oxidized chromagen + H₂O

what are interferences when testing for glucose in serum/plasma glucose oxidase -peroxidase pathway?

uric acid, ascorbic acid, bilirubin, glutathione

what is the methodology of testing serum/plasma in the glucose hexokinase pathway?

glucose + ATP —^{hexokinase /mg++} —> glucose 6 phosphate +ADP

G6P + NAD+ —^G6PasePD—> 7 phosphogluconate + NADH + H+

what are interferences to testing plasma in the glucose hexokinase pathway?

some drugs, hemolysis, high tri/lipemia, high bilirubin/ icterus

what is the methodology for testing urine in glucose?

dipstick glucose oxidase method or nonspecific copper reduction methods

what is the methodology for testing glucose in CSF?

glucose oxidase or hexokinase (same as serum)

what is the clinical significance of testing glucose?

inborn errors of carbohydrate metabolism, hypoglycemia, diabetes mellitus

what is hypoglycemia?

plasma glu lower than 50 mg.dL w/ associated symptoms of

• sweating

• shaking tachycardia

• anxiety

• hunger

• weakness

• dizziness

• inappropriate behavior

• blurred vision

• coma

• death

what is whipple’s triad?

• signs and symptoms of hypoglycemia

• low plasma and experiencing symptoms

  • alleviation of symptoms when ingesting glucose and increase plasma glucose

what drugs can induce hypoglycemia?

alcohol, insulin, sulfonlurase

how can fasting cause hypoglycemia?

liver enzyme deficiencies, insulinomas, severe liver or renal disease

how is hypoglycemia reactive?

• happens 2-4 hours after eating

• delayed and exaggerated increase in plasma insulin

  • may be predictor of type 2 diabetes

what is diabetes mellitus?

hyperglycemia due to defects in insulin production, function, or both

what are the 4 categories of diabetes mellitus?

type 1, type 2, gestational, other/secondary

what are the clinical features of diabetes mellitus?

polydipsia, polyphagia, polyuria, dehydration

what are the lab results of uncontrolled diabetes mellitus?

• hyperglycemia

• glucosuria

• electrolyte imbalance

• decrease blood and urine pH

• increased serum + urine osmolatlity

• increased serum + urine specific gravity

what are complications of diabetes mellitus?

• primary cause of blindness

• glucosuria damages kidneys

• dyslipidemia causes increased risk of hypertension, arteriosclerosis, heart disease, stroke

• nervous system damage + poor circulation + hyperglycemia

what is diabetic retinopathy?

blindness

what causes end stage renal disease and diabetic nephropathy?

glucosuria that damages kidneys

what causes amputation of the lower limbs?

nervous system damage + poor circulation + hyperglycemia

what is urine microalbumin?

albumin in the urine

what is microalbumin used for?

to diagnose and monitor diabetic nephropathy

what is the reference range for microalbumin?

<30 mg/24 hrs

what is type 1 diabetes?

insulinopenia= absolute insulin deficiency

what is the onset of type 1 diabetes?

• abrupt

• sudden weight loss

• nausea

• blurred vision

• confusion

• dehydration

  • prone to diabetic ketoacidosis

what is DKA?

excess ketones decrease pH causing metabolic acidosis

• the breakdown of fat produces ketones, when then build up in the bloodstream

what are ketones?

produced by liver from catabolism of fatty acids

what are the 3 major ketones?

acetone (2%)

acetoacetic acid (20%)

beta-hydroxybuyric acid (78%)

how do you test urine ketones?

reagent strip for acetoacetic acid

-uses sodium nitroprusside

how do you test urine in serum?

spectrophotometry for beta hydroxybutyrate

what is type 2 diabetes?

strong genetic predisposition, gradual onset, insulin resistance

-manageable or even reversible with diet and exercise

what happens if your type 2 diabetes is uncontrolled?

cause hyperosmolar hyperglycemic state (HHS)

-glucose > 600

-typically no ketones

what is gestational diabetes?

glucose intolerance during pregnancy

-due to metabolic and hormonal changes

-usually returns to normal after pregnancy

what are the risks for gestational diabetes?

• birthweight > 9IBs

• baby’s high insulin secretion may cause hypoglycemia after birth

  • associated with risk of obesity and diabetes later in child’s life

what is secondary diabetes?

• genetic defects of beta cell function

• disease of pancreas

• endocrinopathies

• drug or chemical induced

  • genetic syndromes

what is the diagnostic criteria for diabetes?

A1C > 6.5%

what is glycosylated hemoglobin?

aka A1C

hemoglobin A with addition of glucose on one or both of the beta chains

-the result is a % of hemoglobin A1C that have glycated

-index of average blood glucose for the last 2-3 months

why is A1C the prefered test?

-lest variable than glucose

-does not require fasting or special pt prep

-good indicator of pt compliance or diabetes control

what is the reference range of A1C?

<5.7% is norma

5-7-6.4% is prediabetes

diabetes: <7% is well controlled

what is the methodology of glycoslated hemoglobin?

• HPLC

• enzymatic

• electrophoresis

  • immunoassay

what are the limitations of glycosylated hemoglobin?

• hemoglobinopathies

  • increased cell turnover

what is the alternative to A1C?

fructosamine

what is the diagnostic criteria of diabetes?

• hemoglobin A1c >6.5%

• or fastin plasma glucose >126 mg/dL

• or 2 hour post load glucose >200 mg/dL

what is the glucose tolerance testing fo rnon pregnant patient?

• 2 hour GTT

• no longer routinely performed

• pt drinks 75g of glucose

• specimen collected 2 hours later

  • 2hr > 200 indicates diabetes but must be confirmed

what is GTT for pregnant patient?

• >25 yrs or high risk should be screened at 24-28 weeks

• most common in US is two part screening and diagnostic method

• screen is 50g drink and fasting is not required and if >130 have to do a diagnostic test

• diagnostic test is fasting and 100g drink and draw before, 1, 2, 3 hr

why is is bad when microalbuminuria is 30-300albumin/creatinine in 2-3 collections and not as bad when it is 30-300mg/24 or >300mg/24?

it is the same amount of protein released but over a shorter time so it is more damaging to the kidneys

what are the 4 types of cardio vascular disease (CVD)?

1. coronary artery disease/ heart disease

2. cerebrobascular disease

3. peripheral arterial disease

4. aortic atherosclerotic disease

what is coronary artery disease (CAD)/ heart disease (CHD)?

atherosclerosis narrowing the arteries feeding the heart

what is cerebrovascular disease?

interrupted blood flow (ischemia) to the brain, temporary or lasting

what is peripheral arterial disease (PAD)?

atherosclerosis narrowing arteries of the limbs, usually the legs

what is aortic atherosclerotic disease?

plaque buildup weakening/narrowing the aorta, risking aneurysm or dissection

what is coronary heart disease?

angina pectoris = chest pain

what is a myocardial infarction (MI)?

heart muscle death (necrosis) from loss of blood flow (ischemia)

what is heart failure?

heart can’t pump (or fill) well enough to meet the body’s needs

what is atherosclerosis?

chronic inflammatory disease of medium and large arteries

-endothelial dysfunction —> lipid retnetion —> plaque formation

what do plaque do to the blood vessel?

gradually narrow the artery, reduce blood flow, rupture or erode —> triggering thrombus formation

what damages the endotherlium?

• hypertension

• hyperlipidemia

• hyperhomosyteinemia

• tobacco smoke

  • hyperglycemia

what is the lumen?

the space blood flows through

what is the tunica intima?

endothelium plus subendothelium space

what is the internal elastic lamina?

divides intima from media

what is tunica media?

smooth muscle and elastic tissue

what is the first step in atherosclerosis?

damaged endothelium is more permeable to lipoproteins

-lipoproteins accumulate in intima space and are glycated and oxidzed

what is the second step in atherosclerosis?

oxidative stress from modified LDL induces local inflammatory cytokines

what are the third and fourth step to atherosclerosis?

cytokines raise adhesion molecule expression

-monocytes attach and migrate into the intima space

-become macrophages with abundant scavenger receptors

-scavenger receptors recognize oxidized LDL

what is the fifth step in atherosclerosis?

macrophages take up oxidized LDL and form foam cells

-no shut off and become overloaded

what is the sixth step in atherosclerosis?

smooth muscle cells moe from the media into intima, multiply, secrete collagen and elastin

-fibrous tissue build up strengthening the plaque

what is the 8th step of atherosclerosis?

• fibrosis continues

• calcification can occur

• smooth muscle cells die

• fibrous cap left with few living cells

• cap surrounds a lipid rich core

  • cap can rupture

what are the outcomes to atherosclerosis?

plaque narrows the lumen —> decreased blood flow —> ischemia

when do symptoms appear?

75% obstruction

what are stable plaque outcomes?

exertional symptoms that resolve with rest

(stable angina)

what can happen if a plaque cap ruptures?

exproses lipid-rich, thrombogenic core to blood stream —> trigger thrombosis —> sudden occlusion —> acute coronary syndrome, stroke, or limb ischemia

what is acute coronary syndrome (ACS)?

umbrella term for unstable ischemic heart disease

-angina: ischemia without cell death

-acute MI: ischemia with cell death

what is an initial evaluation of ACS?

physical examination, ECG, chest x-ray and cardiac biomarkers

what are the two types ECG splits MI into?

• ST-elevation MI (STEMI)= full thickness damage

  • non-st-elevation MI= inner-layer damage

what rules out MI?

cardiac bio markers

what is a myocardial injury?

no ischemic symptoms required, elevated cardiac marker present