MLS 2211 Exam 6

Explain the general principle of Ion-Selective Electrodes (ISE) for measuring electrolytes

The activity (concentration) of electrolyte on one side of an electrode membrane, as compared to a fixed concentration of that electrolyte on the other side of the membrane, causes an electrical potential to be built-up across the membrane.

The electrical potential is proportional to the electrolyte concentration of the test solution.

What is the selectivity of a pH ISE?

pH spec. due to H+ ions

What is the filler in a pH ISE

HCl

What is the selectivity for a sodium ISE

Na+

What is the filler for a sodium ISE

NaCl

What is the selectivity for a potassium ISE

Coated w/ Valinomycin

What is the filler for a potassium ISE

KCl

What is the selectivity for a chloride ISE

AgCl crystals

What is the filler for a chloride ISE

Theres no filler

What is the selectivity for a CO2 ISE

Sample reacts with weak acid

What is another name for a CO2 ISE

Severinghaus electrode

What is the filler for a severinghaus electrode

No filler

For coulometric chloridometers such as the Buchler-Cotlove chloridometer, what is a common source of error

Generator electrode gets dirty and pitted – irratic response and premature assay termination.

Other electrodes get dirty – must be cleaned often.

Cannot distinguish between Chloride and other Halogens or radicals that act like halogens (perchlorates, thiocyanates, cyanates, etc.)

What are the two most abundant electrolytes (2) in Blood Plasma:

Sodium and chloride 

What are the two most abundant electrolytes (2) in RBCs (intracellular):

Potassium and magnesium

What electrolytes that would be falsely elevated on hemolyzed specimen:

K+

Mg++

Phosphates (Inorganic Phosphorous)

Iron

What electrolytes that are impacted by incorrect anticoagulants and their corresponding values

EDTA or Oxalate/Fluoride plasma will have:

K+ = Stupid High (9.0 – 25.0 mmol/L)

Ca++ = Stupid Low (0.0 – 2.2 mg/dL)

Mg++ = Stupid Low (0.0 – 1.0 mg/dL)

What is the function of sodium in the body

Main electrolyte controlling osmotic pressure of blood and body fluid.

All parts of renal tubules can secrete Na into the glomerular filtrate, but is regulated by Aldosterone in the Distal Tubules. Aldosterone causes retention of Na, with a corresponding loss of K (by exchange).

What happens in hypernatremia and what can cause it 

Hypertension, strokes, renal failure, and heart failure due to over-exertion.

Conn’s Disease (excessive Aldosterone)High dietary intake, Cushing’s Syndrome, dehydration.

What happens in hyponatremia and what can cause it 

Hypotension, edema, muscle weakness, neurological failure (seizures, etc.)

Adrenal insufficiency (Addison’s)Low Dietary intake, diarrhea, vomiting,burns, ATN, hypothyroidism.

What is the refrence range for sodium 

136-146 mMol/L

What does potassium do in the body

Very critical to Cardiac Nodes and myocardial muscle.

Very critical to other Muscle function (both striated and smooth)

All parts of nephron tubules can secrete K+, but in Distal Tubule elimination is regulated by Aldosterone, in an exchange with Na+. Aldosterone causes excretion of K+.

What happens in hyperkalemia

Bradycardia, flat-line EKG. Heart fails to pump blood

Muscle weakness, poor muscle coordination.

What happens in hypokalemia

Super-excitability of nodes of heart and myocardium. Arrhythmias, finally ending with Ventricular Fibrillation.

Muscle cramping, spasms, seizures.

Potassium Shift: Shifts______ in Acidosis, shifts______ with Alkalosis. Each _____ pH increase, causes a K+ decrease of _______. The inverse is also true.

Shifts out in Acidosis, shifts in with Alkalosis. Each 0.1 pH increase causes a K+ decrease of 0.6. The inverse is also true.

If a pH of 7.4 shifts to 7.3 and the K was 5.0 before, what will the K be after the pH shifts? 

5.6 

If a pH of 7.4 shifts to 7.5, and the K was 5.0 what would the K be after the pH shift? 

4.4

What is the reference range for potassium

3.5-5.1 mMol/L

What is the function of chloride

Tends to follow what Na+ does.

We measure it as part of the Electrolyte panel, but not because it (itself) does anything. We measure it to see if another electrolyte is there in elevated amounts, or decreased amounts

No critical values for Chloride. If it is low, it means that some other electrolyte is high.

If it is high, it means that something else is low.

What happens in high chloride

It means that some other electrolyte is low

What happens in low chloride

It means that some other electrolyte is high 

What is the function of CO2 (Bicarb)

The Base (salt) component of the major blood buffer system (Carbonic Acid/Bicarb). At a pH of 7.40, the ratio of base to acid is 20 (20 to 1).

Low levels = Metabolic Acidosis

High levels = Metabolic Alkalosis

What happens in metabolic acidosis

Theres a low level of bicarb

Not eating

Barfing (anorexia + bulimia)

Gets consumed when buffering acids

Losing it in the urine (renal disease)

What happens in metabolic alkalosis 

Theres a high level of bicarb

Iatrogenically caused - Excessive intake (Tums, Rolaids)

But not always -

Compensating for chronic Respiratory Acidosis.

What is the function of calcium 

Ca++ has very pronounced effects on smooth muscle and skeletal muscle.

Low levels causes muscle spasms, charley-horses, cramps, etc.

High levels cause muscle weakness (flacid paralysis), but also cause calcification of soft tissues and the formation of Ca++Phosphate crystals (kidney stones and arthritis). High Calcium is being scrutinized as a MI (heart attack) risk factor.

What happens in the body with low calcium levels

Low levels causes muscle spasms, charley-horses, cramps, etc.

What happens in the body with high calcium

High levels cause muscle weakness (flacid paralysis), but also cause calcification of soft tissues and the formation of Ca++Phosphate crystals (kidney stones and arthritis). High Calcium is being scrutinized as a MI (heart attack) risk factor.

What happens to Ca in acidosis

In acidosis, the Ionized Ca++ increases (shifts off of proteins). No change in Total Calcium.

What determines potassium blood levels

Dietary Intake

Renal Excretion

All parts of nephron tubules can secrete K+, but in Distal Tubule elimination is regulated by Aldosterone, in an exchange with Na+. Aldosterone causes excretion of K+.

Shifts

Moves in and out of the Cellular compartments vs. pH changes.

What happens to calcium in alkalosis

In alkalosis, the Ionized Ca++ decreases (shifts back onto proteins). No change in Total Calcium.

What are the three forms of Ca in a total calcium 

Ionized (free) Ca++ (50%)

Non-ionized (unionized) Ca++ which is bound to protein. Mainly Albumin, but can bind to globulins as well. (49.5%)

Ca-Carbonates and Phosphates (less than 0.5%)

What determines calcium blood levels 

Dietary intake

Renal excretion

Renal disease favors Ca++ loss in urine.

Bone metabolism Bone breakdown elevates Ca++

What is the function of magnesium in the body

Metabolism of Magnesium is essentially the same as for Calcium, except that all cells (including RBCs) contain a lot of Magnesium.

Diet, renal function, and bone metabolism affect the blood levels. Chemically works the same way as Calcium does.

Dietary deficiency results in “Calcium-Resistant Ricketts.” Renal disease favors losing Mg++ in the urine.

What happens in the body with low magnesium

In alkalosis, the Ionized Mg++ decreases (shifts back onto proteins). No change in Total Magnesium.

What are the three forms of magnesium 

Ionized (free) Mg++ (50%)

Non-ionized (unionized) Mg++ which is bound to protein. Mainly Albumin, cut can bind to globulins as well. (49.5%)

Mg-Carbonates and Phosphates (less than 0.5%)

What happens in the body with high magnesium 

In acidosis, the Ionized Mg++ increases (shifts off of proteins). No change in Total Magnesium.

Magnesium Shift: Shifts _____ in acidosis, shifts ______ with alkalosis.

Shifts off of proteins in acidosis, shifts back onto proteins with alkalosis.

What do phosphates do in the body

An anion that normally shows an inverse relationship with Calcium.

Bone salts are the bodies’ stores of Phosphorous. It, along with Calcium are important bone metabolism markers.

A component of the Phosphate Buffer system of the blood.

Describe the "Chloride Shift" and identify the two anions participating in the shift.

A shift between Chloride and Bicarbonate.

Shift between Intracellular compartments and the Extracellular compartments

Explain what is meant by the Anion Gap

Normal Anion Gap means there is NOT a significant amount of abnormal, ugly, or perverse anions present (ketones, lactates, salicylates, formates, etc.)

If the Chloride Shift is not apparent, then you got wierdos and pervo anions!

explain the physiological significance of an abnormal anion gap.

If the gap is high (greater than 16) it means you are not seeing the expected Chloride Shift, and suggests that there is a significant amount of some other anion present (Dang weirdo, pervo, or unnatural anions like Salicylates, Drugs, Lactate, Oxalates, etc.).

Addison’s Disease is about the only time you expect to get Negative Gaps. Usually a Low or Negative Gap means an error in the assay (low Na+ or high Chlorides).

What is the formula for anion gap

Na - (Bicarb + Chloride)

What is a normal anion gap?

7-16

What test are in an electrolyte panel

pH, Total CO2, Na, K, and Cl

What would you expect an electrolyte panel to look like for a patient with Addisons disease

Low sodium

high potassium 

normal chloride

normal bicarb

low glucose 

normal BUN

normal creatinine 

normal calcium 

Abnormal anion gap

What would you expect an electrolyte panel to look like for a patient with Cushing’s disease

High sodium

low potassium

normal chloride

normal bicarb

high glucose
normal BUN
normal creatinine
normal calcium
normal anion gap

What would you expect an electrolyte panel to look like for a patient with early renal failure

low sodium

high potassium

normal chloride

normal bicarb

normal glucose

high BUN

high Creatinine

low calcium

normal anion gap

What would you expect an electrolyte panel to look like for a patient with late renal failure

Low sodium 

High potassium 

low chloride

low bicarb 

normal glucose 

High BUN

high creatinine

normal Ca

abnormal anion gap

What would you expect an electrolyte panel to look like for a patient with type II DM with ketosis

low sodium 

high potassium 

low chloride

low bicarb

high glucose 

normal BUN

high creatinine 

normal calcium 

abnormal anion gap 

What would you expect an electrolyte panel to look like for a patient with type I DM with ketosis

low sodium
high potassium
low chloride
low bicarb
high glucose
normal BUN
high creatinine
normal calcium
abnormal anion gap

What would you expect an electrolyte panel to look like for a patient with metabolic acidosis (salicylate overdose) 

Normal sodium

high potassium

low chloride

low bicarb

normal glucose

normal BUN

normal creatinine

normal calcium

What would you expect an electrolyte panel to look like for a patient with lactic acidosis

Low sodium

high potassium

low chloride

low bicarb

low glucose

high BUN

high creatinine

low ca

abnormal anion gap 

What would you expect an electrolyte panel to look like for a patient with Anorexia Nervosa - Bulimia

low sodium

high potassium

low chloride

low bicarb

low glucose

Low BUN

high creatinine

normal ca

normal anion gap 

Explain the clinical rationale of performing CSF Chloride and CSF Lactate assays, and how these tests distinguish between bacterial and viral meningitis.

Bacteria ferment glucose into Lactic Acid, thus CSF Lactate will be elevated.

Viruses don’t cause CSF Lactate to increase.

Normal CSF Lactate rules-out Bacterial Meningitis, and is consistent with Viral Meningitis.

Bacteria ferment glucose into Lactic Acid, thus CSF Lactate will be elevated.

As Lactic Acid increases, CSF Chloride must decrease (anion gap thing in CSF).

Note: Normal CSF Chloride is118 –132 mmol/L.

Viruses don’t affect CSF Chloride levels.

Explain the relationship of sweat chloride with Cystic Fibrosis

Cystic Fibrosis also involves defective distal tubules of the sweat glands. This causes decreased electrolyte reabsorption.

Affects Chloride, Na+, and K+, and results in high levels of these electrolytes.

explain how a sweat specimen is collected using Pilocarpine Iontophoresis.

PCN must be iontophoresed into the sweat gland by an electrical current.

Clean appropriate area of skin.

Apply PCN, place positive electrode over it. Negative electrode is placed on skin nearby.

What is the clinical significance of a high iron level

Hemolytic Anemia (Fe from Hemoglobin)

Megaloblastic Anemia (Fe – cells dying)

Heme Synthesis blockages (heavy metals)

Severe Hepatitis (Iron stores released)

Iron Intoxication (biggie for children)

If Serum Iron is high, there is probably a hemolytic condition (free Fe++ from hemoglobin), or Ferritin and Hemosiderin spilling from the liver into the blood, or an increased intake of Iron

What is the clinical significance of a low iron level

Dietary Iron Deficiency (least common)

Chronic blood loss (most common)

Pregnancy (increased demand for Fe)

Malabsorption

If Serum Iron is low, there is an Iron deficiency from something

What is the clinical significance of a high TIBC level

Pregnancy (compensation)

Iron Deficiency (compensation)

Chronic hemorrhage (compensation)

Hepatic disease (not compensation – due to release of Hemosiderin and Ferratin).

Big-time Iron Poisoning. (not compensation, you’re measuring free Iron, Dude!).

What is the clinical significance of a low TIBC level

Chronic Infections (decreased production of Transferrin)

Chronic Inflammation (decreased production of Transferrin)

Renal Disease (lose proteins in urine)

Nephrotic Syndrome (lose proteins in urine)

Hepatic Cirrhosis (not making Transferrin)

Mild Hepatic Disease (not making Transferrin)

What is UIBC

The results you get on the second assay is called the Total Iron-Binding Capacity (TIBC - how much Iron Transferrin can bind). Tells the total number of Iron seats on the bus! (Serum Iron + the UIBC)

The difference between the first and second serum Iron assays is called the Unbound Iron-Binding Capacity (UIBC).

Tells how many empty Iron seats were on the bus!

How do TIBC and iron relate to each other

Low Iron = High TIBC

High Iron = Low TIBC

What would you expect the iron and TIBC to be in Hemolytic anemia due to transfusion reaction

High iron and high TIBC

What would you expect the iron and TIBC to be in hemochromatosis (iron poisoning)

High iron and low TIBC

What would you expect the iron and TIBC to be in IDA or chronic blood loss

Low iron and high TIBC

What would you expect the iron and TIBC to be in anemia of chronic infections or inflammation

Low iron and low TIBC

What would you expect the iron and TIBC to be in hepatic necrosis

High iron and high TIBC

Explain the relationship of serum copper, ceruloplasmin, and Wilson's Disease

Wilson’s Disease is the most common cause of Copper Overload. In this disease, the liver cannot make Ceruloplasmin. Lacking Ceruloplasmin, copper gets deposited in the tissues.

Wilson’s Disease = Hemochromatosis with Copper “halo” in Iris of eyes, accompanied by low Ceruloplasmin levels.

What methods are used to assay sodium, potassium and lithium 

Ion-Selective Electrode

What methods are used to assay chloride 

Coulometric (Buchler-Cotlove)

Mercuric Thiocyanate

Ion-Selective Electrode

What methods are used to assay total CO1

pCO2 Severinghaus Electrode

PEPC Enzymatic method

What methods are used to assay calcium

Atomic Absorption
OCPC (o-Cresolphthalein Complexone)
Ion-Selective Electrode

What methods are used to assay inorganic phosphate

Molybdenum Blue (Fiske-Subbarow)

What methods are used to assay magnesium

Titan Yellow Dye or Methylthymol Blue Dye

Calmagite Dye

What methods are used to assay Iron and TIBC 

Ferrozine

Bathophenanthroline

The liver is pretty dang cool for many reasons. One in particular is when circulating iron levels become too high, leading to the risk of iron deposition in tissues, the liver compensates by decreasing the production of__________ to reduce iron transport in the bloodstream.

Transferrin

In a type I Diabetes Mellitus patient, what type of pattern would we expect to see on a BMP?

Low Na+, Cl-, and Bicarb, high K+

I am also a highly clinically significant electrolyte that is routinely ordered for nearly every patient. In MLS 2211/2213, my reference range is 3.5 mMol/L to 5.1 mMol/L. Which electrolyte am I?

Potassium

Magnesium can be measured using which method?

Buchler-Cotlove

Fiske-Subbarow

Ferrozine

Methylthymol Blue Dye

Methylthymol Blue Dye

Inorganic Phosphorus can be measured using which method?

OCPC

Fiske-Subbarow

Buchler-Cotlove

Methylthymol Blue Dye

Fiske-Subbarow

Iron can be measured using which method?

Ferrozine

Buchler-Cotlove

Methylthymol Blue Dye

Mercuric Thiocyanate

Ferrozine

Are we all totally on board to never ever draw, or knowingly run, a BMP on a EDTA (purple top) or Oxalate (grey top)?

Yes, I promise

In the CSF of a patient with bacterial meningitis, we would expect to see an increased CSF protein, decreased CSF glucose, and an increased CSF lactic acid. But what about CSF chloride??

We would expect to see a decrease in CSF Chloride

What condition is associated with excessive Aldosterone and hypernatremia?

Conn’s Disease

I am an ISE method who’s filler substance is KCl. Which ISE method am I?

Potassium

Which of the following ions shift into the cell in alkalosis to replace H+ ions moving from the cell into the plasma? Fun fact, magnesium does this too!

Potassium

A symptom of hemochromatosis is what?

bronzing of the skin

Chloride can be measured using which method?

Ferrozine

Mercuric Thiocyanate

Methylthymol Blue Dye

Buchler-Cotlove

Mercuric Thiocyanate

What is a common error for ISE membranes that causes irreproducible results.. aka test results that are inconsistent and cannot be reliably duplicated under the same conditions.

protein build-up

What should we be looking for results wise if a patient BMP is run on a purple or grey top?

Stupid High K+, Stupid Low Ca