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molecular chemical biology

Proteins make half of our bodies by dry weight.

Outside this, they're part of our sustainable future.

Structural Biology, the study of the molecular structure of biological macromolecules, emerged in the early 20th century with the discovery of X-ray diffraction.

This technique, pioneered by Max von Laue and the Braggs, allowed scientists to visualize the atomic structure of crystals, including biological molecules like the one seen of myoglobin on the left.

LATEST UPDATE

November 2024

For now, I'll be sharing my studies this semester.

With an increased workload between both school and job, I've taken interest in the Feynman Technique: break down concepts simply. Here, I'm most interest in remembering concepts for Clinical Chemistry.

To get started: a refresher on ions and what they do

Ions are atoms that carry an electric charge. They can carry a positive charge—called an cation. The mnemonic I use is that cations, like cats with paws, are pawsitive. By remembering this, we already know the latter for anions: ions with a negative charge. You could also remember anion as 'A Negative Ion' as an acronym of this. When exposed to an electric field, cations travel toward the cathode and anions travel toward the anode.

Something crucial to remember: though cations are positive, for them to be attracted to the cathode means the cathode is negatively charged. This is easily confused between the two sometimes, so I best try to stick with the 'pawsitive cations' in the back of mind. Conversely, the anode is positively charged.

Ions are essential for bodily function

Namely, the major ions that sustain life-sustaining reactions are Sodium, Chlorine, Potassium, Calcium, Magnesium, and Zinc.

Again, these are all isolated atoms on their own—so elements—that hold an electric charge. Because of this characteristic, our cells have taken advantage of select ions and their respective charge to carry out chief processes that keep ourselves alive.

If you aren't already versed in the element symbols for these ions, here they are:

Sodium — Na
Chlorine — Cl
Potassium — K
Calcium — Ca
Magnesium — Mg
Zinc — Zn

Here's a rundown for what these ions are mostly associated with in the body:

Cell volume and osmotic pressure is managed via Na, Cl, and K.
Myocardial rhythm and general muscle contraction via K, Mg, and Ca.
Cofactors in enzyme activation via Mg, Ca, and Zn.
Blood coagulation via Ca and Mg.

Because ions carry two complimenting charges, their balance in tissue are important. So, for a healthy patient, you can imagine each body compartment for where these ions are found remains generally neutral: this is called Electroneutrality, and isn't too tough to remember in respecting the rule that the number of anions is equal to the number of cations (# anion = # cation).

The unit related to this rule is measured in terms of reactivity as mEq/L or mmol/L instead of milligrams (mg) commonly used for other substances in the lab. Reactivity is suuper small here knowing these are single atoms at play. One milliequivalent of any cation (respecting Electroneutrality) will combine with one milliequivalent of any anion. So again, if charge (also called valence) is 1 then, mEq/L = mmol/L.

Atomic Weight versus Equivalent Weight

These two terms are still a little confusing to me, but that's alright. For the sake of an example: Na, K, Cl and Bicarbonate have a charge of 1. Because these all have a change of 1 and knowing mEq/L = mmol/L when charge is 1, then we don't have to work out any math for this.

What about Calcium? It has a charge of 2. It's here we need to work out its Equivalent Weight from Calcium's Atomic Weight. To determine an ion's Equivalent Weight, we simply divide Atomic Weight by its charge—or valence should you choose to call it that, again.

Working out the math with Calcium in finding Equivalent Weight…

Calcium's Atomic Weight is 40 with a valence of 2.
So, divide Atomic Weight by valence:
40 / 2 = 20 Equivalent Weight

Not only this, but we need to know how to convert mg/dL to either mEq/L, or mmol/L, too:

mEq/L = (mg/dL • 10) / Equivalent Weight

and

mmol/L = (mg/dL • 10) / Atomic Weight

I'm not one to get excited when confronted with math, mind you. And with multiple pieces to now remember can be overwhelming. In this case, I stick to mnemonics again: to get mEq/L, put Equivalent Weight on the bottom of your fraction. From there, converting to mmol/L isn't too crazy for placing Atomic Weight on the bottom, too.

Another example would be to convert 200 mg/dL of Na+ to mEq/L. And knowing mEq/L requires us to place our Equivalent Weight on the bottom of the fraction get…

Na+ atomic weight = 23 (single + for 1 valence)
So it's (200 mg/dL • 10) / 23
= 87 mEq/L

Let's do another one: express 10 mg/dL of Ca++ in both mEq/L and mmol/L…

Ca++ atomic weight = 40 (++ for 2 valence)
So Equivalent Weight is 40 / 2 = 20
Where mEq/L is (10 mg/dL • 10) / 20
= 5 mEq/L

And to find mmol/L, do (10 mg/dL • 10) / 40
= 2.5 mmol/L

We'll jump back on this again later, but for now, let's move on.

Things to know about Water

By average, water makes up to 40% to 75% of human body weight. As we age, our water content decreases where women have less water percentage than men—this is attributed to higher fat content in women.

Not only this, but water is also incredibly powerful in acting as a universal solvent. It helps in transporting nutrients to cells, dictates a cell's volume from by the rate at which water enters and exists a cell, and is essential in removing waste from our body in the form of urine. Even sweat, made by most parts water, serves as a coolant for temperature regulation.

Water is found as intracellular fluid (ICF), and extracellular fluid (ECF):
Intra-, inside cells
Extra-, outside cells

Two-thirds (2/3) of our total body water is found inside cells, so most of our percentage (40-75%) as said earlier is located within cells. The remaining water content, a third (1/3) of this percent, forms the extracellular water around cells where this percentage can be further divided into what's called Intravascular Cellular Fluid (abbreviated ECF-plasma). ECF-plasma is interstitial fluid, fancy for fluid that surrounds tissue cells.

When examining ECF-plasma (or just plasma), most of this is water, too at 93%. The remaining 7% part of plasma's volume is derived from lipids and protein molecules. So mostly water, and shy of a tenth lipids and proteins.

The concentration of ions, wherever they are, need to be maintained. This is again respecting Electroneutrality as we already touched on. Two major ways of maintaining ion concentration are diffusion and active transport.

Active transport needs energy to move ions via ATP across cell membranes.

Diffusion requires no ATP; it's passive, depending on an ion's size and membrane makeup.

And what about Osmolality? It's a physical property of a solution based on the concentration of solute—or things dissolved in solution—measured in millimoles per kilogram of solvent. Because it's milimoles of solute per kilogram of solvent, it's a measure of solute relative to the mass of the solvent in a given solution (weight/weight).

Not only this, but Osmolality is also important because it's related to a solution's property that changes in a way unlike water, such as a decreased freezing point or vapor pressure. In a clinical setting, Osmolality is important as it's how our brain responds in inducing a feeling of thirst. Our hypothalamus responds to an increased blood osmolality through a want to drink fluids. When blood osmolality is increased, the hypothalamus goes into effect to induce this feeling through the secretion of a substance called Arginine Vasopressin Hormone (AVP) made by posterior pituitary gland. To keep it short n' sweet, thirst is a consequence of increased blood osmolality caused by our hypothalamus responding with AVP.

When thirsty, we drink fluids which in turn, increase water content of the ECF or fluid outside of cells. Because there is more water now in ECF, this dilutes sodium (Na+) levels and decreases plasma osmolality. This is how our bodies respond, balance, and correct for osmolality. Again, AVP is secreted by the posterior pituitary gland and more specifically, acts on the cells of the collecting ducts within kidneys to absorb water more.

Because sodium contributes most of plasma's osmotic force, up to 90%, controlling this through fluid intake with thirst is how osmotic pressure is regulated. Our hearts work most effectively with adequate blood pressure, so the regulation of both sodium and water is a big part in controlling blood volume.

To maintain balance for when blood pressure is decreased or low, Renin is created to stimulate the hormone Angiotensin to cause vasoconstriction. I think it of Angiotensin as it's tensing the walls of blood vessels to increase blood pressure. Renin is also good for stimulating the secretion of Aldosterone, increasing the retention of sodium. To remember, Renin causes vasoconstriction and sodium retention for increasing blood pressure, should it be low. The clinical lab measures osmolality through either serum or urine.

The series of Electrolytes: Na+

For starters, sodium (Na+) is the most abundant cation (positive ion) in the fluid around cells (ECF). 90% of the ions in this fluid are sodium ions and as described earlier, determines osmolality of plasma. And if it's the most abundant ECF cation, then it's not hard to know there's more sodium in ECF than ICF (inside cells).

Sodium as a single atom ion means it's significantly small compared to the cellular landscape. So small amounts of Na+ can diffuse into the cell membrane. However, our bodies and cells fight this equilibrium though tactics of active transport: ATP to push sodium back out from the cell via ATPase ion pumps. They're literally small, molecular ion pumps to siphon sodium back out from the cell.

There are 3 main strategies our cells deploy to regulate plasma Na+ concentration:

1) Water intake
via thirst

2) Water excretion via AVP
in responding to vol./osmolality

3) Blood volume status
affects Na+ excretion (Aldosterone/Angiotensin)

Sodium (Na+) levels can be low when measured, called Hyponatremia. This is clinically identifiable once sodium concentration becomes less than 135 mmol/L in serum. Hyponatremia can be tell-tale of renal failure, liver cirrhosis, heart failure or found with those an excessive need for water intake. In short, it means increased sodium loss.

On the other end, Hypernatremia suggests the opposite: high sodium levels. This is found once a sodium concentration passes 145 mmol/L in serum. Profuse sweating, prolonged diarrhea (oof), or those suffering from sudden mental impairment. With significant water loss, sodium levels increase.

The specimen types for sodium level determination is either serum, plasma, whole blood, urine and sweat. Should plasma be used, lithium heparin (Li Hep), ammonium heparin, or lithium oxalate (grey top tube) can be used. The best way to test for sodium is via Ion-Selective Electrodes (ISE) for analysis. With two electrodes, that being the anode and cathode, and a semipermeable membrane, the ISE method works with two different ion concentrations on either side of the membrane.

For ISE, one electrode is the reference electrode, sustaining a constant potential and the opposite electrode serves to measure the desired ion of choice. An ion's activity is measured and the difference in potential between the reference and measuring electrodes determines Na+ concentration.

Most ISE methods in clinical chemistry analysis use a glass ion-exchange membrane for measuring sodium. When measuring sodium via ISE, we find a healthy patient typically has a sodium level of 135 - 145 mmol/L. Critical, or panic values, occur at a level below 110 mmol/L or above 170 mmol/L. Severely low sodium values, because sodium is commonly found in the nervous system, can induce seizures or even coma. Anything greater than 170 mmol/L can cause muscle weakness.

Potassium (K+), major ICF cation

Potassium is mostly found in cells, where it is 20 times greater intracellularly than extracellularly. This is why hemolysis of RBCs can elevate K+ levels when testing as most of K+ is stored here.

K+ is responsible for regulating a number of things in the body, but mostly to deal with neuromuscular excitability, heart contraction, ICF volume—knowing it's 20 times here—and hydrogen ion (H+) concentration. Most people take in more K+ than is needed and for any surplus amount the kidneys rid in urine. If kidney's cannot excrete this into urine, K+ may elevate to toxic levels which suggests renal disease.

Our cells do a good job of adjusting to acute rises in K+ by absorbing this in ECF to trap inside themselves, as ICF. This usually happens from the increased intake that most of our diets include.

The distribution of K+ can also be affected from the inhibition of active transport mechanisms like ATPase ion pumps. This happens those with hypoxia, low Magnesium (Mg++) or digoxin overdose. A lack of active transport for K+ leads to decreased ECF levels.

Other ways K+ ECF levels can be low is through insulin, where insulin increases K+ cations to enter the muscle and liver (ICF). Catecholamines, most commonly attributed to epinephrine, can also increase the cellular entry of K+ (ECF to ICF).

As said how insulin can cause K+ to enter cells, exercising can do the opposite in freeing, releasing K+ from cells (ICF to ECF), increasing plasma K+ levels. Hyperosmolality surrounding cells causes them to give up water content and K+ to circulate as ECF, being processed by the kidneys eventually as urine. This depletes and decreases K+ levels.

Hypokalemia means low plasma K+ levels, levels less than 3.4 mmol/L. Cellular shifts like alkalosis, a time where body pH increases to become more alkaline, is mitigated through H+ cations fleeing RBCs to decrease ECF pH. With a lack of cations now in RBCs drives K+ cations to replace this in maintaining Electroneutrality. Because there is now K+ in cells leads to a decreased ECF level, called Hypokalemia. K+ that is higher than normal—more than 5.0 mmol/L—is termed Hyperkalemia.

When the body is in a state of acidosis, or low pH, H+ ions move from plasma move into RBCs to be buffered through hemoglobin. Because H+ ions rush into RBCs, this displaces and drives K+ ions out of blood cells to increase pH and balance this. Because there is now a surplus of K+ ions in plasma (ECF), this is now a state of Hyperkalemia.

When collecting specimens avoid hemolysis at all costs, as said earlier, hemolysis increases K+ knowing it's 20 times the value inside cells than out floating around them. Ruptured cells increase K+ values. Between serum and plasma, serum generally has higher K+ levels as platelets release potassium ions for clotting. The more platelets there are, the higher K+ is in serum. If this is known to be a problem with the patient or a redraw of blood is needed, then it's an obvious answer to use plasma EDTA as it prevents clotting.

Other factors maybe not thought about at the site of draw is leaving the tourniquet on for over a minute, increasing hemoconcentration and K+ levels, or repeatedly clenching their first knowing muscles can release K+ ions.

Serum, plasma, and urine work for measuring K+ levels. If plasma is used, heparin is the best anticoagulant here. For urine specimens a 24-hour timed urine is used for this, too. Like determining Na+ cation levels, K+ also uses ISE with the only difference being the membrane. For Na+ it's glass, but for K+ it's valinomycin—an antibiotic. This valinomycin membrane binds K+ ions that causes an impedance change that can determine K+ concentration.

K+ levels in a patient are from 3.4 to 5.0 mmol/L. When values fall below 2.5 or exceed 6.5 mmol/L is when irregular heartbeat occurs. Again, K+ works with heart contractions.

Chloride (Cl-), major ECF anion

Cl- serves as a major ion outside the cells. It maintains osmolality, helps to regulate blood volume, and maintains electroneutrality in a couple of ways.

The proximal tubules of the kidneys serve to absorb both Na+ and Cl- ions. The amount of Na+ reabsorbed is limited by the amount of Cl- available to respect electroneutrality. Think of it as the proximal tubules want to make salt (NaCl) to keep balance—not that they do, but it helps me to remember at least.

A Chloride Shift is also a thing: CO2 produced by tissues finds itself in plasma and RBCs. As for CO2 inside RBCs, this CO2 becomes H2CO3 (carbonic acid) and when combined with water, separates into H+ and HCO3- (bicarbonate). And recalling that hemoglobin inside RBCs act to buffer H+ ions, hold this back while the HCO3- finds its way back into ECF plasma. Cl- diffusing into RBCs serves to maintain electroneutrality by replacing HCO3-, bicarbonate. To summarize: tissues make CO2 which moves into RBCs—once inside RBCs, Cl- acts to neutralize this by accompanying this, driving HCO3- out.

Cl- is found in the diet and mostly absorbed via the GI tract. When measuring for Cl- levels, there is always a range to keep in mind with an associated term for high and low. For high plasma Cl- levels, called Hyperchloremia, is usually when there is a loss of HCO3- through the GI tract or kidney excretion. Renal tubular acidosis (RTA) can also cause this as well as metabolic acidosis (the lungs work to resolve this).

When the body is in a state of Acidosis, or low pH balance, HCO3- (bicarbonate) is consumed to buffer the H+ cations that are lowering the pH. This raises pH to flee Acidosis, however, because HCO3- flees RBCs to take on the H+ ions in the acidic ECF, Cl- ions replace the otherwise consumed HCO3- to maintain electroneutrality. Notice the reoccurring theme: like bases replace their counterparts in the tissues, whether ICF or ECF, another hallmark of electroneutrality.

As for low levels of Cl-, called hypochloremia, is usually found with those who have experienced prolonged vomiting, are in diabetic ketoacidosis (which includes vomiting, losing Cl- ions in this), or metabolic alkalosis in increasing HCO3- (bicarbonate) and decreasing Cl- inversely.

Serum, plasma, urine and sweat are candidates for determine Cl- levels. Think of this as a chemistry test, lithium heparin is best here for plasma as it is usually for chem tests. However, the best method is a 24-hour timed urine collection for determining Cl- levels in patients. A good way to remember this is to not pee in the pool please, where pools have chlorine. So, the best way to measure Cl- levels is how? Urine; a 24-hour timed urine.

Repeating this again: like Na+, K+ and now Cl-, ISE is the most commonly used method for Cl- testing in the clinical laboratory.

For healthy patients, Cl- levels fall within 98 - 108 mmol/L. Those who have Cystic Fibrosis, a sweat chloride (hence the name) test can be done. Cystic Fibrosis is a mutation of the CFTR gene which cause exocrine glands, or glands which secrete substances not into the bloodstream, but instead into or on parts of the body—so Cystic Fibrosis commonly affects the pancreas, lungs, and sweat glands. Thinking about NaCl salt again, the concentration of Cl- and Na+ is significantly high in the sweat of those affected by this disease, usually before clinically identifiable symptoms begin to develop.

For collecting sweat from those with Cystic Fibrosis, a technique called Iontophoresis is done. Pilocarpine is applied to an area of skin which induces sweating; this drug is useful for timely collecting regarding a sweat chloride test. A dry paper disc with an already known weight is then applied which allows to find the amount of sweat once reweighed after. A Cl- selective electrode can then be applied to the skin where it is directly measured.

Because Cl- is higher for those who have Cystic Fibrosis, we can anticipate Cl- levels to be a minimum of 60 mmol/L or greater.

HCO3-, the second most abundant ECF anion

Bicarbonate or HCO3- follows right behind Cl- as an ECF anion and remains as the major buffering system in blood. As said, Cl- and HCO3- can swap places inside an RBC should the body need to compensate for acidic pH. Earlier it was said CO2 finds itself inside the RBC and then becomes HCO3-, but how? An enzyme catalyzes this reaction with the following:

Carbonic Anhydrase (CA) turns CO2 and water into H+ and HCO3-

CO2 + water + CA forms H2CO3-,
H2CO3 with CA forms H+ + HCO3-
and vise-versa.

CO2 can be toxic to tissues if suspended for too long, trapped inside the cell. Carbonic Anhydrase (CA) serves to mitigate this effect by taking this CO2 and transforming it into HCO3- which can buffer excess elevated acidic pH with H+ cations, and when it's no longer needed as a buffer, CA can do a reversable reaction in converting HCO3- with H+ back into CO2 where the lungs do the job of eliminating this potentially toxic gas, away from the tissues.

HCO3- or bicarbonate makes about 95% of the total CO2 in the body, so it's safe to assume a total CO2 measurement is indicative of the amount of HCO3- present. Because HCO3- makes such a large percentage, both HCO3- or CO2 can be used interchangeably to mean the same thing for total CO2. When total CO2 is measured, it is also reported with the other electrolytes instead of only reporting HCO3-. So though most of total CO2 is HCO3-, it also includes dissolved CO2 gas as well as carbonic acid—the same substance Carbonic Anhydrase acts on to create HCO3-. Carbonic acid if you recall, is H2CO3.

Most of the HCO3- that finds itself in the kidneys is mostly absorbed by the proximal tubules (85%) and the remaining percentage via the distal tubules (15%). I think of proximal in its meaning: closer, where 85% is closer to 100% than distal, meaning further away at 15%. Proximal tubules absorb more HCO3- than distal tubules.

During metabolic alkalosis, where the lungs have difficulty in regulating alkaline pH (higher pH on average), the kidneys increase the excretion of HCO3- to compensate, decreasing the body's pH. Thinking once more in the other direction, metabolic acidosis, HCO3- is consumed to balance the low pH to allow H+ that is otherwise floating around in the ECF to fall back into RBCs where it is again buffered by hemoglobin.

Serum or plasma work for determining HCO3- (or nicknamed CO2) levels. To round it up again: Na+, K+, Cl-, and now HCO3- all use the ISE method for patient testing. Second to this, an enzyme may also be used—called a coupled enzymatic procedure—to convert all CO2 to HCO3- where it is then pieced with PEP (scary name, I'm leaving the acronym as is) with carboxylase to form Oxaloacetate and H2PO4-. This Oxaloacetate with NADH and H+ is then converted to Malate and NAD+ where the absorbance of the solution is measured to determine HCO3-, or CO2, concentration. HCO3- falls between 22 - 28 mmol/L for a healthy patient.

Anion gap and respecting electroneutrality

An anion gap, abbreviated as AG, measures the difference between unmeasured anions and cations as a very easy to-do equation. The AG gap is created by the concentration difference between commonly measured cations, like Na+ and K+ and anions, like Cl- and HCO3-.

AG can indicate an increase in one or more unmeasured anions in serum, including organic acids like ketoacids or lactic acids, and serves as an important tool also in finding out the degree of metabolic acidosis. Sometimes it's also called an indirect measure of quality control for an analyzer when measuring electrolytes. By the chance an analyzer reports several patients with a decreased AG, then it's safe to assume there is something wrong with the machine as part of systematic error.

(Cation1+Cation2) - (Anion1+Anion2)

For example:
(Na + K) - (Cl + HCO3)

Healthy is 12-20 mmol/L

An elevated AG would suggest uremia or renal failure, the likely result of retaining PO4- and SO4-. Ketoacidosis knowing the anion is higher than cation (acidic ECF) is also a culprit. Others include methanol, ethanol, ethylene glycol, or salicylate poisoning. Lactic acidosis, hypernatremia or even systematic or random errors found with analyzers are possible, too.

An elevated AG is a lot more common than a decreased AG, keep in mind. Hypoalbuminemia, a decrease in measured anions could cause this or hypercalcemia, an increase in unmeasured cations.

Na+ is 142, K+ is 4, Cl- is 103, and HCO3- is 28

What's AG?

(142 Na + 4 K) - (103 Cl + 28 HCO3)
(142 + 4) - (103 + 28)
(146) - (131)
= 15 mmol/L (healthy)

Remember, if it's more than 20 mmol/L, there is more anions, so ECF is acidic, otherwise, less than 12 mmol/L means there is an excess of cations, an alkaline ECF.

Mineral Metabolism

Minerals, like electrolytes, are needed for bodily functions. To name several functions carried out by minerals would include enzyme activity, allowing blood to coagulate, skeletal formation and hemoglobin production.

These atoms play crucial aspects in our everyday living, and yet though they're sometimes free-floating, carry out tasks that even tell large molecules like proteins, what to do. The small stuff does push around the big, so we should minerals (and lytes), our ode.

The most abundant mineral, Calcium (Ca++)

99% of calcium remains in our bones, and until it is needed, only 1% finds its way into blood and other ECF. Of that 1%, 45-50% Ca++ floats around as free cations, 40-50% paired with proteins, and the least of it at 5-10% is pieced with anions.

Ca++ is associated with neuromuscular activity, heart contraction, blood hemostasis, structural support like our teeth and bones, and is fundamental to cell membrane activity.

The major form of Ca++ is protein-bound, which is attached to proteins that are not in an active form. Something to know is because Ca++ is suspended with non-active proteins, an increase in total protein will also give an increase in total calcium. However, protein levels won't affect the free-floating calcium as it's not part of this total knowing it's not associated with proteins.

Free Ca++ or just floating cations of this make 45-50% of total calcium levels, the other half that is not otherwise bound to proteins. Free Ca++ cations is considered an active form as it can cross cell membranes as single ions. Remembering that these ions can diffuse into ICF means they carry out tasks in the cell, so in that way, you can imagine them as active operators inside the cell: the active form of Ca++. Because active Ca++ is so important in ICF, alterations in this affect cells, eventually leading to clinical symptoms.

Because active, free Ca++ are ions, they can be easily pressured when pH changes. A decreased pH, a state of acidosis, increases Ca++ levels. This has to deal with the H+ ions outcompeting with Ca++ on the negatively charged proteins—usually albumin in this case. Because H+ can wick Ca++ off from proteins, they are then free to float around in ECF. So acidosis increases Ca++ levels.

When pH is increased for a more alkaline ECF, free or ionized Ca++ decrease. Once pH increases, H+ cations are off on their way to compensate for the ECF pH being high to supply acidic H+ in decreasing ECF pH back to normal. As this happens, Ca++ can take place of H+ that was once suspended on these negatively charged proteins and thus, Ca++ ECF concentration decreases.

The remaining tiny bit of Ca++—the original 5%—dances with anions like citrate and phosphate which we'll get into here soon. This Ca++ is said to be complexed, being paired with select anions. Think of Ca++ and its ++ partnering with something negative like magnets: opposites attract here, too.

The regulation of Ca++ is through a secreted hormone. Parathyroid Hormone (PTH) serves to increase Ca++ levels via a process called bone resorption (fancy for breakdown) to release Ca++ from bone, where most of it is hosted. Not only this, but PTH causes our GI tract to absorb more Ca++ so both bone and our diet can help benefit introducing more Ca++ in places that are needed. PTH stimulates the production of Vitamin D, which really what gives this hormone magic as itself alone cannot increase the absorption of Ca++ in our GI tract, it simply signals Vitamin D to be made, allowing our gut to readily absorb more Ca++.

Other places Ca++ can be increased when needed is renal reabsorption. PTH helps our renal—or kidney system—to pick out bits of Ca++ more attentively rather than leaving it to be excreted out of our bodies as urine. Because of PTH, this makes kidneys work extra to retain and reabsorb Ca++ than letting it flow into the production of urine as waste. Remember the importance of Vitamin D for increasing the reabsorption of Ca++ in our food once in our GI tract.

Calcitonin, like melatonin, puts the body in absorbing or freeing Ca++ to rest. It's secreted by our thyroid unlike PTH from the parathyroid gland. Calcitonin inhibits bone resorption (again, breakdown) and inhibits our kidneys to pool Ca++ back into ECF and instead blocks it off to find its way into urine, causing an increased renal Ca++ excretion.

As with ranges, Hypercalcemia is associated with disorientation, fatigue, muscle weakness, renal impairment, kidney stones, polyuria—or increased urination, nausea and vomiting, and acid-base disorders. Possible causes for Hypercalcemia could be due to hyperparathyroidism—thinking PTH—can cause an increase in the release and resorption of Ca++. Malignancy with bones can increase bone breakdown which elevates Ca++, or excess Vitamin D as what PTH affects the production of. Secondary to renal failure can also be a factor for increased Ca++.

Low Ca++ levels can cause muscle spasms, seizures, an upset GI, tetanus which could be grouped in muscle spasms, brittle hair, skin drying, and hypotension. Like hyperparathyroidism, this same organ can also cause problems for underperforming through hypoparathyroidism. This is important to know as Ca++ is decreased, yet PO4-- (phosphate) is then increased. Thinking back to our hyper-associated conditions, Vitamin D deficiency, impaired bone resorption, decreased serum albumin, and chronic renal failure are part of this but reversed.

Atomic Absorption Spectrophotometry (AAS) is the reference method for determining Total Calcium levels but its not widely used. Instead, colorimetric (color sensing) methods are used on analyzers and are more common for finding Total Calcium via the CPC colorimetric method. An acid is added to help detach Ca++ from negatively charged proteins and once Ca++ is free with CPC, forms a complex called Ca-CPC complex. Ca-CPC is a red colored complex at an alkaline pH, too.

Additionally, 8-hydroxyquinoline is added to this method to prevent Mg++ interference. Arsenazo dye is usually used more often than CPC if available. Serum or lithium heparin plasma are best suited for collecting and determining Total Calcium levels. If you don't already know, Ca++ helps with clotting and if used in an anticoagulant that binds this cation, won't be able to be readily measured. A healthy patient has a Total Calcium of 8.6-10.0 mg/dL.

Rather than finding Total Calcium, finding the free, ionized Ca++ is also crucial. Serum is best here for specimen collection and accurate reporting and kept away from air (anaerobically) and to remain at room temperature until collected—which should be within an hour of collection. 4.5-5.3 mg/dL is the range of ionized Ca++ for a healthy patient, as it makes 45-50% of the Total Calcium percentage, so around half.

Major ICF anion: Phosphate

Notes from 11/20

Liver is the main organ for lipid and protein synthesis.

Monday 1 section, Tues 2nd section, prelab, present info to identify knowledge gaps, self-assess after each unit like a quiz.

pH = 7.35 - 7.45 … 35 - 45 mm Hg
Insulin "IN" drives substances, like K+, glucose, etc. into the cell.
Measuring Potentiometric => potential charge between electrodes
Measuring Charge (or titration) => Coulometric
Measuring Current => Amperometry for measuring pCO2 in arterial blood

pO2 = 80-100 mm Hg => 80100 => BOIOO for remembering pO2 range (remember it, Bethany!)

Blood tonometry: measures partial pressure of pCO2 and pO2

THANKS MARY!!

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