Biochemistry in Nutrition

• Biochemistry is used to come up with nutrition diagnoses and is used in the Monitoring and Evaluation of patient response to nutritional intervention.
• It is important to check the reference ranges as different test kits can have different values.

Samples Types

• Blood, the most common type of sampling fluid
• Serum, the fluid from blood after blood cells are removed
• Plasma, fluid from blood centrifuged with anticoagulants
• Erythrocytes, red blood cells
• Leukocytes, white blood cells
• Other tissues, scrapings and biopsy samples
• Urine, random samples or timed collections
• Feces, random samples or timed collections
• Less common: saliva, nails, hair, sweat

Stages if Analysis

• Timing of samples, like menstrual cycle for hormone profiles, can impact results
• Storage timings of samples can lead to changes with results
• Preparation and the chosen method of analysis can effect results

Blood Considerations

• Blood is easily accessible, easy to analyze, and non-expensive
• Blood tends to reflect recent dietary intake, making it an acute, rather than long-term biomarker
• Homeostasis can cause nutrients in blood to be of normal level, even if evidence of functional impairments
• Blood iron levels may be stable due to release of iron from stores, indicating the importance of checking ferritin levels
• When interpreting blood results, it is important to consider factors such as fasting, hydration, inflammation, stress, and trauma

Mechanisms for Fluid and Electrolyte Movement

• Diffusion is the movement of molecules from high to low concentration
• Selective Permeability involves channels specific for a particular molecule that moves from high to low concentration via active or passive transport
• Facilitated diffusion is the spontaneous passive transport of molecules across a biological membrane via specific transmembrane integral proteins
• Active transport is the movement of ions/molecules across a cell membrane into a region of higher concentration with assistance from enzymes and requiring energy
• Osmosis is the spontaneous net movement of solvent molecules through a semi-permeable membrane into a region of higher solute concentration
• Hydrostatic pressure is exerted by pumping action
• Oncotic pressure is exerted by proteins, notably albumin, in a blood vessel's plasma, tending to pull water into the circulatory system, opposing hydrostatic pressure

Body Water Content

• Total body water in an average adult is 60% of the body weight
• This is divided into extracellular fluid, which is 20% of body weight; and intracellular fluid, which is 40% of body weight
• Extracellular fluid consists of Plasma, which is 5% of body weight; and Interstitial fluid, which is 15% of body weight

Electrolyte Distribution

• The cell membrane functionally divides intra and extracellular fluid
• The sodium pump helps maintain sodium in the extracellular space as its main osmotic skeleton
• Potassium is kept in the intracellular fluid as the main cation with the help of large negatively charged intracellular proteins
• Major ICF ions include K+ and PO42-
• Major ECF ions include Na+ and Cl-

Fluid Balance

• Fluids can be lost via urine, vomiting, aspirated NGT, drains, fistulas, ooze, faeces, and ileostomy.

Electrolyte Ranges

• Sodium levels should be between 135-145 mmol/L
• Potassium levels should be between 3.5-5.1 mmol/L
• Phosphate levels should be between 0.87-1.45 mmol/L
• Magnesium levels should be between 0.65-1.05 mmol/l
• Urea levels should be between 1.7-8.3 mmol/L
• Creatinine levels should be between 45-84 μmol/L
• Albumin levels should be between 33-45 g/L
• CRP levels should be less than 5 mg/L
• GFR levels should be greater than 50 ml/min
• HbA1C levels should be between 4.5-6.4%

Markers for Dehydration

• Reduced urine volume
• Changes in urine color, which can be affected by Vit B supplements or certain drugs like Rocephine
• Rapid changes in body weight
• Decline in blood pressure, especially diastolic
• Postural hypotension and dizziness
• Decreased skin turgor on the back of the hand

Biochemistry Markers of Dehydration

• In dehydration, plasma volume decreases, so plasma components become more concentrated
• Sodium and Chloride, Na+ and Cl-, increase
• Hemoglobin, Hb, and hematocrit, PCV, levels increase
• Potassium, K+, and Magnesium, Mg 2+, levels remain the same

Markers of Fluid Overload

• Rapid weight gain
• Oedema
• Shortness of breath
• Plasma electrolytes dilution, Na+ decrease, Urea decrease, and Heamoglobin decrease

Sodium Levels

• Normal range: 135-145 mmol/L
• Sodium is a major cation and osmotic agent in the ECF
• Around 22,400 mmol of sodium is filtered through the kidney daily, and 22,300 mmol are reabsorbed in the renal tubules
• The kidney responds via the renin-aldosterone system and other hormones to control sodium excretion and maintain a steady state in the ECF
• Hypotension and hyponatremia stimulate the kidney to release renin/angiotensin, which stimulates the adrenal cortex to secrete aldosterone
• This increases sodium reabsorption from renal tubules, decreasing sodium loss in urine and improving blood pressure
• Altered sodium levels can reveal electrolyte imbalances, where low values are seen in cases of cardio or pulmonary diseases

Hyponatremia

• Hyponatremia (Na+ levels < 135 mmol/L) may be caused by loss of sodium containing fluids like excessive sweating, vomiting, or diarrhea
• Other causes include low salt diets in heart patients, especially when combined with diuretic use, excessive water intake, or infusion of hypotonic solutions
• Signs include acute weight gain, peripheral oedema, distended neck veins, elevated BP
• Treatment includes NaCl and restricting fluid intake

Hypernatremia

• Hypernatremia (Na+ levels > 146 mmol/L ) may be present in cases of dehydration
• Other causes include loss of thirst mechanism, often seen in neurological damage and the elderly, or prolonged periods of rapid respirations
• An example of rapid respiration is hyperventilation secondary to COPD or panic attacks
• Signs include weight loss, decreased skin turgor, dry mucous membranes, dry tongue, orthostatic hypotension
• Treatment includes oral fluids or IV Dextrose 5%

Potassium Levels

• Normal range: 3.5-5.1 mmol/L
• Potassium is the main cation in the ICF, retained to balance the -ve protein charges in the cell
• Normally 60-80% of potassium is reabsorbed through renal proximal convoluted tubules
• Adrenal cortex cells are sensitive to potassium in the blood, so an increase in potassium will lead to aldosterone secretion
• The increase in aldosterone secretion increases secretion of potassium from renal tubules into urine

Hypokalemia

• Hypokalemia; K+ levels < 3.5 mmol/L, Signs: muscle weakness, irregular heart beat and respiration, polyuria
• May be caused by severe vomiting and diarrhoea
• Other causes include administration of IV solutions in the absence of potassium replacement
• Certain drugs can also cause hypokalemia, including glucocorticoids, non-potassium sparing diuretic use e.g furosemide, bumetanide
• A cause is also featured in refeeding syndrome when there is rapid cellular uptake of potassium and glucose and amino acids to synthesis glycogen and protein
• Treatment: Potassium supplements PO or IV, caution if low urine output!!

Hyperkalemia

• Hyperkalemia; K+ levels > 5 mmol/L, causes cardiac arrest, ventricular fibrillation, bradycardia, abdo cramping, nausea and vomiting
• May be caused by the use of potassium-sparing diuretics such as Spironolactone, Amiloride
• Other causes include conditions such as renal failure, due to the loss of the ability of effectively excrete potassium
• Using potassium-containing salt substitutes can also contribute, and it is seen in heart patients complying to dietary sodium restrictions
• In massive cell destruction e.g burns, crush trauma, potassium leaks out of cells and into interstitial fluid
• During catabolic state, protein breakdown during proteolysis and release amino acids, these escape through cell membrane and draw potassium with them
• Treatment: stop potassium intake, shift potassium form ECF to ICF with sodium bicarbonate, increase potassium excretion with diuretics, dialysis, avoid high K+ foods

Phosphate Levels

• Normal range: 0.87-1.45 mmol/L
• Phosphate is the primary anion in ICF
• It is deposited with calcium for bone and tooth structure and mostly bound in bones
• Phosphate is a major component of bones, provides mineral strength to the skeleton
• It is essential for function of many metabolic processes as combines with many coenzymes
• Most of the phosphate filtered by the kidney is reabsorbed

Hypophosphatemia

• Hypophosphatemia features as muscle weakness, cardiac and respiratory failure, impaired consciousness, and death
• Causes include alcohol withdrawal or malnutrition, extreme dietary deficiency of phosphate
• Another cause is in refeeding syndrome due to phosphorylation of glucose and adenosine triphosphate in ATPs synthesis causing increased uptake of cells leading to low serum phosphate
• Excessive use of phosphate-binding antacids
• During recovery of diabetic ketoacidosis secondary to rapid glucose administration where there is an uptake of glucose with phosphate

Hyperphosphatemia

• Hyperphosphatemia is caused by renal failure or hypoparathyroidism
• In hypoparathyroidism, a decrease in calcitonin production induces osteoclastic reabsorption of Ca2+ into the serum, causing phosphate to follow
• Extreme burns or muscle necrosis secondary to trauma

Magnesium levels

• Normal range: 0.65-1.05 mmol/L
• Magnesium is mainly found in bone and ICF
• Essential component of many enzyme reactions

Hypomagnesemia

• Hypomagnesemia signs include neuromuscular irritability such as tremors, tetany, and in severe cases convulsions
• Causes include excess fluid loss e.g chronic diarrhoea or malabsorption syndromes, like Crohn's disease and celiac disease
• Concentrations of magnesium at the distal part of the small bowel is higher compared to the upper small bowel, so bowel resection at the distal part of small bowel can lead to low magnesium
• Another cause is polyuria, in poorly controlled diabetes mellitus
• A cause is a feature in refeeding syndrome when cellular uptake of magnesium increases for ATP synthesis
• Magnesium is bound to albumin, so low albumin can lead to low magnesium

Hypermagnesemia

• Hypermagnesemia signs include: mild hypotension and bradycardia.
• Causes include renal failure
• other causes include excessive or inappropriate use of antacids containing Magnesium or laxatives containing Magnesium
• Often occurs in conjunction to hypocalcaemia

Random Glucose Test

• Used as a basic level for glucose when fasting, ideally under 6mmol/L in Malta
• Done by pricking a finger and testing a drop of blood, where readings depend on when you last ate and what
• Abnormal results indicate the need for a repeat test on a separate day
• If two results return abnormal, an OGTT is used for further evaluation

Oral Glucose Tolerance Test (OGTT)

• Is a multiphase test used to determine the metabolic response to glucose
• Often used to diagnose diabetes
• The patient is instructed to fast for 8-14 hours
• The first blood draw occurs in the fasting state
• A 100-gram glucose pre-load is drank, and blood glucose is checked in 30-60 minutes and two more times every hour

Abnormal OGTT Results

• Fasting: greater than 5.2 mmol/L
• 1 hour: greater than 10 mmol/L
• 2 hour: greater than 8.6 mmol/L
• 3 hour: greater than 7.8 mmol/L

A1C- Glycosylated Hemoglobin

• Non-diabetic A1C: 4-6%
• A1C goal for diabetes: < 7%
• A1C in diabetes: 6.5 or higher
• As glucose molecules bind to hemoglobin, they become glycated, and the average life span of RBC is 8-12 weeks
• Checking HbA1c will indicate the average amount of glucose in the blood over 3 months
• This can be used to assess the efficacy of a patient's diabetic management, as it provides a "bigger picture" than just the current serum level
• Results should also be interpreted with random blood glucose, as A1C results could be good even if patient has a lot of hyper and hypo glycemia

Urea

• Normal range: 1.7-8.3 mmol/L
• Urea is a waste product of protein metabolism
• The liver breaks down amino acids, producing molecules of free ammonia that are then combined to form urea
• Urea is transported to the kidneys to be excreted
• Blood urea is used to measure kidney and liver function and hydration level
• Low urea levels may be related to severe hepatic failure due to processing of precursor molecules in the liver
• As well as overhydration and starvation
• Elevated urea levels may indicate impaired excretion function of the kidneys, high protein diet, gastrointestinal bleeding, and dehydration

Creatinine

• Normal range: 45-84 μmol/L
• Used to measure creatinine levels in blood, it is a waste product of muscle metabolism
• Levels are high in muscular weight lifters and in renal failure, and low in malnourished patients
• Useful in determining renal filtering function

Cholesterol

• Total cholesterol levels: 2.0-5.16 mmol/L
• To work out the total cholesterol is calculated by a formula that considers the high density lipoproteins, HDL, low density lipoproteins, LDL, and triglycerides
• Total cholesterol of 5.17-6.18mmol/L= borderline high
• Total cholesterol greater than 6.2mmol/L= high
• Elevated cholesterol levels seen in pregnancy, smoking and CVD
• Low cholesterol levels can be seen in malnutrition and chronic anaemia

Low Density Lipoprotein (LDL)

• LDL levels: <3 mmol/L
• LDL is considered to be the bad cholesterol
• Obesity, sedentary lifestyle, and smoking are all implicated in high LDL levels

High Density Lipoprotein (HDL)

• Normal ranges greater than 1.55 mmol/L
• High levels are seen in people doing high exercise, mild alcohol intake, oestrogen, and insulin treatment
• Low levels of HDL is associated with low exercise, obesity, stress, and smoking
• Every 1mg/dL decrease in HDL increases the risk of CHD by 2-3%

C-Reactive Protein (CRP)

• Normal levels: 0-5ml/L
• C-reactive protein is produced by the liver in response to inflammation
• Non-specific clinical marker for inflammation
• CRP concentrations change rapidly, and can be used to determine the presence, levels, and monitor progress of inflammation
• High-sensitivity C-reactive protein, hs-CRP, is used to predict the risk of cardiovascular disease

Albumin

• Normal range 33-45 g/L
• Major serum protein
• Synthesized in the liver and maintains serum osmolarity
• Serum carrier of small molecules
• Serum albumin has a long half-life of 14–20 days and is not very sensitive to short-term changes in protein status
• Low albumin levels, contrary to popular belief, correlate poorly with nutritional status
• Abnormal albumin loss is seen in burns patients, or nephrotic syndrome if losing albumin through wounds or urine
• Abnormal albumin levels are also be effected by fluid status
• Congestive heart disease and fluid overload dilute serum, so lower albumin level and dehydration causes concentrated serum, so increase albumin level
• An albumin level of <33 g/L indicates the body's impaired ability to cope with major illness, surgical intervention or sepsis, and can be a useful part of a nutritional assessment
• It can take approximately 2 weeks to recover a fall in albumin levels
• The first aim in someone with low albumin is to get enough calorie intake not to increase protein intake or give albumin IV

Red Blood Cell

• Normal range: 3.6-5.4mg/dL
• RBCs transport oxygen to body tissues
• High levels may indicate dehydration; this is because the blood becomes less diluted with dehydration, so the number of RBCs will be more concentrated
• Low levels indicate a lack of oxygen, malnutrition, or blood loss
• Low RBCs levels from haemorrhage results in hypovolemia
• Common causes of hemorrhage include trauma, post-operative complications, and adverse effects from certain medications that reduce the viscosity of the blood, such as heparin and warfarin
• Use of IV fluid replacement commonly leads to low RBC levels because the blood becomes hypervolemic
• Small alterations are usually not concerning, risks exists when IV fluids are used excessively, especially in cardiac and renal patients
• Furthermore, hypervolemia from overhydration can also cause crucial electrolyte values to become deficient in comparison, such as sodium and potassium

Hemoglobin (Hgb)

• Normal range: F: 12-16 g/dL; M 13.8-17.2 g/dL
• Hemoglobin is the oxygen-carrying pigment found in RBCs
• Each hemoglobin contains a heme group that binds with iron molecules
• Hemoglobin levels are evaluated in dehydration and in high oxygen demands e.g COPD
• A low hemoglobin level can be caused from Anemia due to poor nutritional status, an acute disease state, or a chronic pathology which renders baseline the hemoglobin levels low
• Hemoglobin levels are often used to determine if a patient needs a blood transfusion; the cut-off point varies, but most mandate transfusion for values under 7-8 gm/dL

White blood cells

• Normal range: 5.0-10 mcL
• White blood cells are also called leukocytes
• High WBC shows signs of infection
• Leukopenia, a low WBC count, can result from chemotherapy, antibiotics, or bone marrow dysfunction
• Severe infections can result in leukemoid reaction, in which the WBC count becomes incredibly high
• Absolute lymphopenia is defined as WBC count less than 1,500 mm³; it's most common in immunocompromised viral infections such as AIDS