Electrolytes, Trace Elements, and Vitamins.1 Flashcards

7-cholecalciferol is present in the skin, upon exposure to ultraviolet light, it is transformed into the inactive form of Vitamin D. This inactive form, must first go to the liver and be 25-hydroxylated, and become 25 hydroxy Vitamin D. This then goes to the kidneys to be 1-hydroxylated to becomev1,25-dihydroxy Vitamin D (The active form of Vitamin D which will have the actions on the gut, bone, and kidneys as described above.

Vitamin D: ↑ Ca reabsorption (↓ Ca excretion)
↑ PO4 reabsorption (↓ PO4 excretion)

Parathyroid Hormone:

↑ Ca reabsorption (↓ Ca excretion)
↓ PO4 reabsorption (↑ PO4 excretion)

• Calcitonin:

↓ Ca reabsorption (↑ Ca excretion)

Vitamin D: ↑ Ca absorption

Parathyroid Hormone:↑ Ca absorption

Calcitonin: -

Vitamin D: ↑ bone mineralization(Ca deposition into bone)

Parathyroid: Hormone:↑ bone resorption(harvesting Ca and PO4)

Calcitonin: Inhibited osteoclastic activity (Inhibited bone resorption)

Vitamin D stores Ca in the bones and PTH makes free Ca²⁺ out of the osteoid matrix

Excrete Ca in the kidneys or increase Phosphate

Reduction in renal Calcium excretion

Increases the body’s “set point” for Calcium

excess Activation of osteoclasts (bone resorption)

excess Increased absorption of Ca in the GI tract and decreased Ca excretion in the kidney

Hypercalcemia, alkalosis, peptic ulcer disease, and renal impairment

Elevated PTHrP levels or hypercalcemia

The correct answer is B) PTHrP. Remember this is a protein that functions a whole lot like PTH, but it’s not. It’s production is also unregulated by the body. This will lead to an unregulated increase in Calcium levels. PTHrP is commonly associated with squamous
cell carcinoma of the lung, melanoma, and breast cancer.

The correct answer is C) Vitamin D increases the reabsorption of Ca in the kidneys. All of these answers correctly describe actions of Vitamin D, but they’re NOT the primary reason why the physician is not worried about Vitamin D producing kidney stones. Think, the reason is because Vitamin D increases the reabsorption of Ca in the kidneys will cause less Ca to be in the tubular fluid, therefore the more likely reason for her would be either dehydration (which would increase the relative concentration of Ca in the kidneys), or a problem related to PTH.

Answer:
The correct answer is B) HCTZ. This is one of those medications to remember, because it’s a commonly used first line antihypertensive agent that we give to most patients presenting with high blood pressure. Remember, HCTZ, Lithium, Vitamin A, Vitamin D, and Milk Alkali syndrome are the ones to remember for exogenous causes of hypercalcemia. A quick mnemonic to remember the symptoms of hypercalcemia is stones (kidney stones), bones (bone pain), groans (constipation), psychiatric overtones (depression, anxiety, insomnia)

Age: prepubescent children

Abnormal Mineralization: Yes

Decreased bone mass: No

Bone deformation: Yes

Duration: Permanent

Primary pathology: Vitamin D deficiency

Age: Adults

Abnormal Mineralization: Yes

Decreased bone mass: No

Bone deformation: No

Duration: Temporary, until corrective action is taken.

Primary pathology: vitamin D deficiency

Age: Elderly

Abnormal Mineralization: No

Decreased bone mass: Yes

Bone deformation: No

Duration: Temporary, until corrective action is taken.

Primary pathology: Calcium deficiency, Sunlight deficiency Weight-bearing, activity deficiency

Osmolarity of volume based (osmoles/L) and osmolality is weight based (osmoles/kg)

Because most of human physiology is water-based and 1 L of water is roughly 1kg, these numbers are fairly similar when we’re talking about HUMAN PHYSIOLOGY. Outside of human physiology with other substances, they can vary drastically

Low levels (<3.5 mmol/L) because the kidneys are trying desperately to hold on to any Na that it comes in contact with, at the expense of K.

Dehydration

Serum Ca and Mg are both slightly higher in children

Chloride

Our patient is in diabetic ketoacidosis, undergoing anaerobic glycolysis, and producing lactic acid

The correct answer is A) Ketoacidosis. She is likely a Type 1 diabetic, her anion gap is 159 - (111+30) = 18, which is mildly elevated so we must have caught it early. She has dehydration because she urinated so many times on the hike and the glucose is causing an osmotic diuresis. She has a low potassium level because her kidneys are attempting to retain all the sodium that they can to maintain her blood pressure, but that is in exchange for the potassium. Her potassium situation is actually more significant that this because of the potassium shift in acidosis. The extracellular hydrogen ions are exchanged for intracellular potassium because the cells want to help the body to handle the extra acid. Upon correction of the acidosis, her potassium may drop below 2 mg/dL. She has prerenal failure, which is consistent with dehydration. BUN/Cr ratio is ~27, which also is not too bad yet, so we’ve caught it before lots of bad things can happen.

The correct answer is D) Na - 164 mg/dL K - 3.1 mg/dL Cr - 1.1 mg/dL Remember, aldosterone is the hormone that retains sodium in exchange for potassium. If you have a lot of aldosterone in your blood, then you’re going to have a very high sodium and a low potassium. The Creatinine value is not significantly elevated because of this pathology.

The patient will have to have some sort of exposure, and will almost always have neurologic side effects

Answer: It’s going to be very hard to do that, as both heavy metals cause similar constellations of symptoms. The key to understanding the cause will be in the question stem, if they mention either Mercury or Lead, or I want you to think of Lead poisoning if they mention plasma aminolevulinic acid, whole blood zinc protoporphyrin, or free erythrocyte protoporphyrin.

Neurologic effects like behavioral changes, headaches, clumsiness

Serum Iron ↑ TIBC ↓ % Sat ↑ Transferrin ↓ Ferritin

Total Copper and Ceruloplasmin

mass spectrometry

The correct answer is B) Copper. This deficiency is only commonly seen in premature infants and adults with malabsorptive pathologies. The presentation would include anemia, hepatosplenomegaly, and osteoporosis. Knowledge of this will help you understand the pathologies presented to you on the Registry exam, so you can get the right answer.

Transferrin ↓ Ferritin ↑
In a state of Iron excess, like hereditary hemochromatosis, the body already has a lot of Iron, so it will likely downregulate the amount of transferrin because it doesn’t want to transport extra iron. The US Preventative Task Force has found insufficient evidence to
recommend for or against using Transferrin as a screening test for Hereditary Hemochromatosis. An increased Ferritin level could just indicate Iron overload. A specific test for Hereditary Hemochromatosis is demonstrating a genetic mutation in the HFE gene.

Arsenic causes a whole slew of symptoms, but primarily gastrointestinal symptoms at low doses. Also hematopoietic, neurologic, renal, and hepatic deficiencies. Remember that chronic exposure to this compound can predispose one to skin, liver, lung, bladder, and kidney cancers

Albumin, Transthyretin, Transferrin, CRP, or the Nitrogen Balance equation

Stored in the liver, important in vision, immune function, and growth; deficiency can lead to blindness

Synthesized in sequential steps in the skin, liver, and kidney, important in calcium homeostasis, associated with sun exposure; deficiency leads to osteomalacia

Prevents oxidative stress that cause aging and diseases like hemolytic anemia

Synthesized by intestinal bacteria and absorbed from leafy green vegetables; deficiency leads to prolonged bleeding

Answer: If a patient has fat malabsorption, then every one of these vitamins can be decreased. It usually takes a while for the symptoms to show up because we have a few months worth of supply stored in our fatty tissues.

Answer: If a patient is taking long-term antibiotics, these can decrease the number of good intestinal bacteria which synthesize about half of your body’s Vitamin K which will cause you to be deficient

Coagulation, in German, it’s spelled Koagulation

Function is to promote blood coagulation: for the coaguation factors 7,9, and 2

Trick 7, 92, blood coagulates for you

Effect: Coenzyme in decarboxylation of
carbohydrates and branched-chain
amino acid pathways

Deficiency: Alcoholism, Causes beriberi

Effect: Various oxidation-reduction reactions

Deficiency: Nutritional deficiencies,
alcoholism, chronic malabsorption

Effect: Numerous functions

Deficiency: Uremia, malabsorption,
malignancies, or alcoholism
Causes hyperhomocysteinemia

Effect: Formation of reducing substances
NADH and NADPH

Deficiency: Alcoholism, Causes Pellagra

Effect: Coenzymes in various one-carbon
transfer reactions

Deficiency: Adolescence, lactation, or
alcoholism Causes megaloblastic anemia
without neurologic effects

Effect: Coenzyme necessary for hematopoiesis

Deficiency: Pernicious anemia, strict vegan
diet, tapeworm, or malabsorption Causes megaloblastic anemia with neurologic effects

Effect: Stabilization of collagen, cross-linking of tyrosine to
catecholamines

Deficiency: Deficiency seen in low fruit and vegetable intake, known as Scurvy Excess Vitamin C is rare because it is excreted in the urine

Either low intake (malnutrition) or alcoholism

Magnesium

Vitamin B12. Diphyllobothrium latum is a voracious tapeworm with an appetite for Vitamin B12. This will cause an infected individual to become deficient rather quickly. Symptoms of Vitamin B12 deficiency are neuropathies (i.e. loss of sense of balance, and sense of touch), and megaloblastic anemia. The physician would likely order a vitamin B12 level, CBC, and Folate level. The symptomatic difference between Folate and Vitamin B12 deficiencies is that Folate only produces megaloblastic anemia without neurologic effects.

all of the above. Sorry I didn’t add that option on purpose, because I wanted you to think about the probabilities of each of these vitamins individually. B1 and B2 are the most likely vitamins to be deficient in this scenario of chronic alcoholism. Vitamin C is also dependent upon diet, and unless she has no access to any citrus or vegetables, it would be quite rare for people who are not stuck on a boat at sea to come down with Scurvy (Vitamin C deficiency). Vitamin B12 is a horse of a different color. Yes, it is water soluble, but we have stores in the liver that can last us for years at a time. So, one has to be deficient in B12 for many years before symptoms begin to arise

The correct answer is A) Vitamin A. Vitamin A primarily enhances vision, but is also is important in immune function, and growth. It has been found to decrease peroxidation of lipids, which will enhance a youthful appearance. Caution should be taken because too much of a good thing isn’t always good. Hypervitaminosis A can occur and cause, ironically, blurry vision, sun sensitivity, dry rough skin, hair loss, and confusion. Not exactly the intended effects of the supplement. This is one of the many reasons why patients should always discuss their supplement usage with their physicians

Vitamin A

Vitamin D

Vitamin E

Vitamin K

Memorize ADEK, or KADE, or DEAK or something similar

offers a place for storage for vitamins A, B12, D, E, K, and the minerals Iron, and Copper

Thiamine

• AKA Carotenoid,

1. Vitamin D is produced in the skin by sunlight
2. Exposed to 25-hydroxylase in the liver
3. Exposed to 1-hydroxylase in the kidney
4. Active product is 1,25-dihydroxy Vitamin D

• Increases total body Calcium, necessary for bone health
• Associated with rickets in children
• Vitamin D deficiency commonly seen in individuals who live at higher latitudes and rarely venture outside
• Hypervitaminosis D is only present with mega doses of Vitamin D supplements

1. Absorption is in the small intestine
2. Deficiencies can occur in malabsorption, bile duct obstruction, pancreatitis, or liver failure
3. Newborns usually need a shot of vitamin K to promote clotting in the first few days
4. Measured using HPLC with electrochemical or fluorometric detection

1. Antioxidant activity, iron absorption, biosynthesis of carnitine, and conversion of dopamine to norepinephrine
2. Symptoms are bleeding, petechiae, Waterhouse-Friedrichsen Syndrome (bloody adrenal glands with necrosis)
3. Hypervitaminosis C may cause ALT, LD, and uric acid to be elevated, and may form kidney stones
4. Assessment by HPLC or GC/MS

• Dry beriberi - primarily neurologic symptoms
• Wet beriberi - cardiovascular symptoms resulting from a thiamine-deficient pump
• Wernike-Korsakoff syndrome - long-term alcoholism, horizontal nystagmus, cerebral ataxia, and mental impairment
• Must supplement Thiamine to avoid refeeding syndrome and death when feeding starved individuals

Measured by HPLC

1. Allows for DNA synthesis and cell division to take place
2. Pernicious Anemia - Megaloblastic anemia due to impaired DNA synthesis and B12 deficiency
3. Indirect measurement by Methylmalonic Acid (MMA), plasma homocysteine, deoxyuridine suppression, or the vitamin B12 absorption test
4. Direct measurement by competitive binding protein assay using Co57 labeled cobalamin, immunometric methods, or chemiluminescent immunoassays
5. Requires Intrinsic factor for absorption in the ileum

1. Process one-carbon units
2. Major manifestation of deficiency is megaloblastic anemia, but without neurologic abnormalities (as opposed to Vitamin B12 deficiency)
3. Evaluate by chemiluminescence or enzymatic methods
4. Given to pregnant women to avoid neural tube defects in the fetus

Serum Albumin < 3.0 g/dL suggests possible malnutrition (Normal 3.5-5.0 g/dL)

Blood Urea Nitrogen <6.0 mg/dL suggests inadequate protein intake

HPLC for specific identification of vitamins

1.Small intestine

2.Kidneys/Liver

3.Skeleton

primary job is to increase circulating Ca ++

• Primary purpose is to increase the ionized Ca++ concentration in the blood
• A primary regulator of plasma Ca++ concentration
• Increases bone resorption (destruction, harvesting Calcium)
• Increases kidney reabsorption of Ca
• Removes PO₄ ^2- from the blood
• Increases intestinal absorption of Ca

- primary job is to increase total body Ca ++

- primary job is to decrease circulating Ca++

Calciton”IN” and Vitamin D put calcium INto the bones for storage, ParathyRoID Hormone gets RID of the Calcium in the bones

1.PTH Deficiency

2.PTH Resistance

3.Vitamin D Deficiency

4.Deficiencies in Bone Mineralization

5.Renal

6.Metastatic

1.Tumors release PTH-related Peptide

2.Osteolytic metastases

Total calcium: Increased

PTH: Increased

Total calcium: Increased

PTH: Decreased

Total calcium: Decreased

PTH: Decreased

- small ionizable constituents in the body

potassium, phosphate, calcium, magnesium

sodium, chloride, bicarbonate

the normal gap between measured cations and measured anions, the difference represents the unmeasured anions

the ones that we will worry about are iron, copper, and zinc

Intracellular fluid has a substantially higher level of potassium, proteins, organic phosphates and acids.

Notes type of pressure:

Oncotic pressure

Osmotic pressure

Hydrostatic pressure

Natriuretic effects released from the cardiac ventricles

Aldosterone System (RAAS):is a critical regulator of blood volume, electrolyte balance, and systemic vascular resistance

released from the kidney in response to low O2 saturation in renal blood

released as angiotensinogen from liver, becomes ATI, then is converted to ATII in lungs, potent vasoconstrictor

- secreted by adrenal glands, increase Na+ reabsorption in exchange for K+ and decrease H2O excretion

(2*Na) + (BUN/2.8) + (Glucose/18) =

Note: Normal Range: 275-295 mOsm/L

5-10 mOsm/kg

note: Anything above 5-10 indicates that there are osmotically active substances which differ from the ones we include in the calculation (e.g. Na, BUN, Glucose)

Expect very low plasma osmolality (e.g. <275 mOsm/kg)

Expect very high urine osmolality (>100 mOsm/kg)

1.Sodium

2.Potassium “valinomycin”,

3.Chloride

• <135 mEq/L

note: Can cause hypovolemia, altered mental status, orthostatic hypotension,

• > 150 mEq/Lnote: generally caused by dehydration, burns, or after hypertonic saline

< 3.5 mEq/L, can be caused by K+ shift in treated acidosis, polyuria, diarrhea, blood dilution, mild dehydration, laboratory error, or sample collection error. This can cause low a K sample

> 6.1 mEq/L, can be caused by hypoaldosteronism, extreme dehydration, hemolysis, tourniquet during collection, laboratory error, or sample collection error

Critical Values - <3 mEq/L and >8 mEq/L

>108 mEq/L - Intake of Cl- exceeds the output and primarily caused by dehydration and other causes of Na+ retention. REMEMBER the chloride shifts out of cells in alkalosis

< 97 mEq/L - Output of Cl- exceeds intake caused by the same list as hyponatremia with an important exception, metabolic alkalosis. This is due to GI loss of Cl- but not Na+. REMEMBER the chloride shifts into cells in acidosis

Ceruloplasmin levels are very low , but there is a lot of copper deposition in the tissues. This relationship is similar to Iron and Transferrin

The deficiency is in a Copper transporter in the liver which removes the Copper from circulation into the bile, so these patients can’t get rid of their Copper!

Treatment is intravenous British Anti-Lewisite (BAL), D-penicillamine, or both because they will chelate the copper

Serum Copper and Serum Ceruloplasmin

Anion Gap = Na - [Cl + HCO 3 ] Reference range = 7-16 mEq/L

Common causes of metabolic acidosis with an elevated anion gap

• Methanol
• Uremia
• DKA
• Paracetamol
• Isoniazid
• Lactic Acidosis
• Ethanol
• Salicylates

for sweat chloride testing for Cystic Fibrosis in neonates we now used a PCR to find the gene.

Test: Serum Na

Sample: Serum or Plasma

Method: Ion-Selective Electrode

Result: 121 mg/dL
Reference Range
(136-146 mg/dL)

Disease/Physiology: Lipemia

Test: Serum Calcium

Sample: Serum or Plasma

Method: Ion-Selective Electrode

Result: 11.3 mg/dL
Reference Range
(8.4-10.2 mg/dL)

Disease/Physiology: Primary, Hyperparathyroidism

Test: Thiamine

Sample: Whole Blood

Method: Rapid HPLC

Result: 1.5 μg/dL
Reference Range
(2.5-7.5 ?g/dL)

Disease/Physiology: Chronic Alcoholism

Test: Serum Potassium and Calcium

Sample: Serum or Plasma

Method: Ion-Selective Electrode

Result: K+ 8.4 mg/dL
Ca++ 5.2 mg/dL
(3.5-5.0 mg/dL and
8.4-10.2 mg/dL)

Disease/Physiology: Sample Collected In Potassium EDTA

Test: PT/INR A prothrombin time (PT) test measures how long it takes for a clot to form in a blood sample. An INR (international normalized ratio) is a type of calculation based on PT test results

Sample: Citrated Plasma (Blue Top)

Method: PT/INR

Result: 32 sec
Reference Range
(11-13.1 sec)

Disease/Physiology: Vitamin K Dependent Coagulation Factor Deficiency

Test: Calcium

Sample: Serum or Plasma

Method: Ion-Selective Electrode

Result: 7.8 mg/dL
Reference Range
(8.4-10.2 mg/dL)

Disease/Physiology: Osteopenia Secondary To Vitamin D Deficiency

1. Serum Iron - specifically 3+ Iron bound to transferrin, NOT free floating 2+ Iron
2. Total Iron Binding Capacity - theoretical amount of iron that could be bound to all of the transferrin binding sites available
3. Percent Saturation - it measures the ratio of transferrin to bound iron
4. Transferrin - the transport protein for Iron, increased in anemia, decreased in hemochromatosis
5. Ferritin - the storage form of Iron