MLTS 2410 - Exam 2: Ch. 14, 8, & 9

What does calcium combine with and where?

phospate in bone and teeth

In plasma, what are three forms calcium exist as?

1. ionized (free)

2. protein bound

3. complexed

Ionized (Free) Calcium

active form (50% of total calcium)

Protein Bound Calcium

bound primarily to albumin (40% of calcium)

Complexed Calcium

bound w/ anions (10% of total calcium)

What calcium form is mostly performed in laboratory testing?

bound portion of calcium (BMP, CMP, renal, Ca²⁺)

What is the calcium reference interval?

8.6-10.0 mg/dL

Hypercalcemia

• muscle weakness, disorientation

• found in: hyperparathyroidism, malignancies, multiple myeloma, nephrolithiasis, renal failure

Hypocalcemia

• tetany: neurological muscle spasm

• found in hypoparathyroidism, decreased serum albumin, decreased vitamin D

If tetany is present, what mineral should be suspected first? Then?

decreased Ca²⁺, then decreased Mg²⁺ or decreased K⁺

Which anticoagulants bind or chelate calcium?

• sodium citrate (blue)

• EDTA (purple)

• sodium oxalate (gray)

How does hyperparathyroidism affect PTH, Ca²⁺, and PO⁴?

• PTH: increased

• Ca²⁺: increased

• PO⁴: decreased

How does hypoparathyroidism affect PTH, Ca²⁺, and PO⁴?

• PTH: decreased

• Ca²⁺: decreased

• PO⁴: increased

Why is ionized calcium (free calcium) the best indication of calcium status?

• b/c biologically active

• accurately determines calcium levels and useful for calcium therapy

• tightly regulated by PTH and vitamin D

• measured in blood using ion-selective electrodes

What does alkalosis and acidosis do to ionized calcium (free calcium)?

• alkalosis increased protein binding → decreased Ca

• acidosis decreases protein binding → increased Ca

What is the ionized calcium (free calcium) reference interval?

4.64-5.28 mg/dL

What should be done to preserve the integrity of an ionized calcium sample?

• collect in serum separator tube

• sensitive to both pH and temp.

• do not open tube or split the specimen

• do not expose to air at any time during collection or transport

• centrifuge within one hr.

What three hormones control calcium?

1. PTH: increases

2. vitamin D: increases

3. calcitonin: decreases

Parathyroid Hormone (PTH)

• synthesis by parathyroid glands stimulated by low calcium

• suppressed by high calcium concentrations

• PTH decreases, calcium increases

What can increase calcium?

• bone resorption by osteoclasts

• renal tubular reabsorption of calcium

• stimulation of 1,25 (OH)2D, which increases intestinal absorption of calcium and phosphate

Intraoperative PTH Monitoring

• management of primary hyperparathyroidism

• rapid (POCT) assaying of PTH during surgery—use to determine if abnormal PTH producing tissue has been removed

• baseline plasma PTH and then at 5 and 10 min. intervals after removal of the parathyroid tissue

What is decline percentage of PTH from 0-5 min. post excision?

>50%

Calcitonin

• produced by the parafollicular cells in the thyroid

• decreases calcium levels b/c of its effect on both bone and renal calcium

What is the effect of calcitonin in the bone?

inhibits bone resorption of calcium

What is the effect of calcitonin in the kidneys?

decreases the renal absorption of calcium, phosphorus, sodium, potassium, magnesium

What disease can elevate calcitonin?

medullary thyroid carcinoma

What diseases is calcitonin used as valuable treatment?

osteoporosis and Paget’s disease

Procalcitonin (PCT)

• normally made in thyroid and converted to calcitonin

• effective for treatment of sepsis

• useful marker to rule out sepsis but not diagnose sepsis

What is the reference interval for procalcitonin (PCT)?

< 0.1 ug/L

What do patients with a PCT > 2.0 ug/L have a high risk for?

progression to sepsis or septic shock

When does PCT levels increase and peak?

• increase 3-6 hrs. after onset of infection

• peak at 12-24 hrs.

Vitamin D

• produced in the skin by absorption of UV light or obtained by dietary intake

• fat soluble vitamin

What are two forms of vitamin D?

1. D2 (ergocalciferol)

2. D3 (cholecalciferol)

D2 (Ergocalciferol)

dietary form found in fish, plants, and fungus

D3 (Cholecalciferol)

most produced by photosynthesis or in skin from sunlight exposure or dietary animal products

What active form does D2 and D3 metabolize into?

1,25-(OH)2D

1,25-(OH)2D

• increases calcium and phosphorus by increasing intestinal calcium and phosphorus absorption and renal absorption

• increases mineralization during bone formation

Vitamin D, 25 Hydroxy

• preferred test to diagnose vitamin D insufficiency and monitor response to therapy

• testing recommended only for patients at risk for vitamin D insufficiency

Magnisium

• 64% found in bones and 35% in cells

• needed for over 300 biochemical reactions; essential dietary mineral

What can cause magnesium to increase?

• renal failure

• after magnesium sulfate ingestion

• Epsom salt usage

What can cause a decrease in magnesium?

• cardiac disorders

• malabsorption

• seizures

Magnesium Sulfate therapy

used in women w/ pre-term labor to inhibit uterine contractions and delay delivery for at least 48 hrs.

Phosphorus

• controlled by parathyroid; enhances absorption of calcium

• 85% present in bone

• only inorganic phosphorus is measured by laboratories

• higher levels seen in children

When should phosphorus be measured?

when patient is fasting—decreases after a meal

What mineral is phosphorus the inverse or reciprocal relationship with?

• calcium

• calcium increased = phosphorus decreased

• calcium decreased = phosphorus increased

What can cause an increase in phosphorus?

• hyperparathyroidism

• renal failure

What can cause a decrease in phosphorus?

• hyperparathyroidism

• vitamin D deficiency

What are some metabolic bone disorders?

• osteoporosis

• osteopenia

• osteomalacia

• rickets

• Paget’s disease

Osteoporosis

• condition in which the bones become weak and brittle

• new bone creation does not keep up w/ bone removal

• associated w/ aging

• represents significant expense in healthcare

• patients experience fractures throughout the skeletal system

Osteopenia

• early sign

• reduced bone mass of lesser severity than osteoporosis

Osteomalacia

• decreased vitamin D = decreased calcium and phosphorus

• refers to a marked softening of the bones

Rickets

• softening and weakening in bones in children usually due to vitamin D deficiency

• characterized by imperfect calcification, softening, and distortion of the bones typically resulting in bow legs

Paget’s Disease

• disease that disrupts the replacement of old bone tissue w/ new bone tissue

• occurs most in pelvis, skull, spine, legs

• often progresses to osteoarthritis

• most frequently present before age of 40

Lipids

• found in all tissues; main source of energy and energy storage

• converted to hormones or hormone precursors—structural and functional components of cell membranes

• insulation for nerve conduction and heat retention

What are lipids soluble and insoluble in?

• soluble: in organic solvents

• insoluble: in water (b/c hydrophobic)

What are the major lipids?

• cholesterol

• triglycerides

• phospholipids

• glycolipids

Cholesterol

• found in animals and humans, where it is the primary sterol derivative

• serves as an essential component for vitamin D and steroid hormones (s-ex and adrenal hormones)

What is the reference range for cholesterol?

desirable < 200 mg/dL

Exogenous Cholesterol

• found in animal products

• absorbed in the diet, bile, intestinal secretions, cells

Endogenous Cholesterol

• produced by the liver

• made from simpler molecules, particularly acetate

What can cause an increase in cholesterol?

• atherosclerosis

• coronary artery disease

• myocardial infarction

Fatty Acids

• simplest forms of lipids

• classified according to the degree of saturation

What are the three degrees of saturation for fatty acids?

1. saturated fatty acids

2. monounsaturated fatty acids

3. polyunsaturated fatty acids

Saturated Fatty Acids

contain an alkyl chain w/h a double bond b/w C atoms

Monounsaturated Fatty Acids

contain one double bond

Polyunsaturated Fatty Acids

have more than one double bond

What are two forms of polyunsaturated fatty acids?

1. cis

2. trans

Cis Polyunsaturated Fatty Acids

• hydrogen bonds on the same side

• what most polyunsaturated fatty acids

Trans Polyunsaturated Fatty Acids

hydrogen bonds on the opposite side (harden fats)

Triglycerides

• most common glycerol esters in plasma, composed of glycerol and three fatty acids

• what mainly makes up the fat in food

What are triglycerides like in plants?

• have large amounts of linoleum residues

• polyunsaturated fats (liquid at 4℃)

• form oils at room temp. (e.g. corn oil)

What are triglycerides like in animals?

• predominantly saturated fats

• form solids at room temp.

What are the five categories of lipoproteins?

1. chylomicrons

2. very-low-density lipoproteins (VLDL)

3. intermediate density lipoproteins

4. low-density lipoproteins (LDL)

5. high-density lipoproteins (HDL)

Chylomicrons

• majority found in triglycerides

• contain Apo-B-48

• transports exogenous triglycerides

• reflects light giving serum turbid/cloudy appearance (lipemia)

• will float to top of specimen and form creamy layer w/ overnight storage at 4℃

How are chylomicrons tested in the laboratory?

• requires fasting specimen sample

• appearance of plasma can be observed after a 12 hr. fast

What are the different clarities of plasma?

• clear: < 200 mg/dL

• hazy or turbid: > 300 mg/dL

• opaque and milky: > 600 mg/dL (due to chylomicrons; lipemia)

Very-Low-Density Lipoproteins (VLDL)

• contains apo B-100

• transports endogenous triglycerides

• reflects light giving a turbid / cloudy appearance (lipemia)

Low-Density Lipoproteins (LDL)

• contains apo B-100

• transports cholesterol to heart (BAD)

• responsible for atherosclerosis, increased lipids create “foam” cells which indicate thickening of the arteries

What can increase levels of LDL?

• atherosclerosis

• coronary artery disease

High-Density-Lipoproteins (HDL)

• smallest and most dense

• contain apo A-I

• transports cholesterol out of the heart

What does increased levels of HDL indicate?

decreased risk of heart disease

What does decreased levels of HDL indicate?

increased risk of heart disease

What is the desirable range for HDL-C

• ≥ 60 mg/dL

• gray area: 35-59 mg/dL

What range of HDL is a high risk for coronary artery disease?

< 35 mg/dL

Total Cholesterol

• most often ordered screening test for hyperlipidemia, followed by a lipid profile

• lipid profile: cholesterol + triglycerides + HDL + LDL

Hypercholesterolemia

• can be caused by familial hypercholesterolemia (FH)

• autosomal dominant trait that leads to an increase in LDL

• most patients w/ homozygous FH may have a heart attack and death by age 30

Hypertriglyceridemia

• associated w/ acute pancreatitis

• secondary to many disease conditions

Lipoprotein (a) (Lp(a))

• risk factor for atherosclerosis

• inhibits thrombolysis

• increased risk of chronic heart disease

Friedewald Formula

• calculates LDL-C if the total cholesterol, HDL-C and triglycerides have been determined

• LDL = CHOL - HDL - (TG/5)

When is the LDL calculation not valid?

if patient’s triglyceride level is over 400 mg/dL

What is the desirable range for LDL?

100-130 mg/dL

What LDL ranges are a high risk for coronary artery disease?

• 130-159 mg/dL is borderline high risk

• high risk: > 160 mg/dL

• very high risk: >190 mg/dL

Metabolic Syndrome

group of interrelated metabolic risk factors that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD)

What are the most commonly recognized metabolic risk factors?

• waist circumference: > 40 inches (men); > 35 inches (women)

• atherogenic dyslipidemia (low HDL, high LDL, elevated triglycerides (≥ 150 mg/dL)

• elevated blood pressure

• elevated blood glucose

National Cholesterol Education Program

• recommended that all adults (20 and older) have fasting lipoprotein (lipid) profile performed every 5 years

• recommendation: good diet, frequent exercise, no smoking, controlled blood pressure

Describe the structure of a protein.

• AA are the building blocks—what cellular growth, repair and maintenance depend on

• N-terminal (NH2) and C-terminal (-COOH) are bonded to the alpha carbon forming an AA

Amino Acids

• differ from one another by the chemical composition of their R (radical group)

• amino group of one AA can be linked with/ carboxyl group of another AA to form peptide bond

How many amino acids are required to build protein?

20

Polypeptide

chain of AA linked by peptide bonds

Isoelectric Point (pI)

• is the pH at which the AA or protein is neutral

• point at which the # of positively charged groups equal the # of negatively charged groups in a protein