Scheda di revisione: Understanding Lipid and Metabolic Functions

📋 Course Outline

1. Cholesterol & Functions
2. Triglycerides & Energy Storage
3. Hyperlipidemia & Types
4. Uric Acid & Purine Metabolism
5. Serum Protein & Components
6. Serum & Plasma Preparation
7. Urinalysis & Examination
8. Kidney Function Tests
9. Serum Electrolytes & Balance
10. Calcium & Blood Regulation

📖 1. Cholesterol & Functions

🔑 Key Concepts & Definitions

• Cholesterol: A waxy, fat-like substance found in blood and body tissues; essential for cell membrane integrity and precursor for hormones and acids.
• Serum Cholesterol: The amount of cholesterol present in blood serum, used to assess cardiovascular risk.
• Triglycerides (TG): Body’s storage form of fat, providing energy; circulating levels influence lipid profile.
• Hyperlipidemia: Elevated levels of lipids (cholesterol and/or triglycerides) in blood, increasing risk for atherosclerosis.
• LDL (Low-Density Lipoprotein): "Bad" cholesterol that deposits in arteries, promoting plaque formation.
• HDL (High-Density Lipoprotein): "Good" cholesterol that helps remove excess cholesterol from blood.

📝 Essential Points

• Sources of Cholesterol: 70% synthesized in the liver; 30% obtained from animal-based foods (meat, eggs, dairy).
• Functions:
  • Structural component of cell membranes.
  • Precursor for steroid hormones (e.g., cortisol, estrogen).
  • Formation of bile acids necessary for fat absorption.
• Cholesterol Levels & Risks:
  • Desirable: below 200 mg/dl.
  • Borderline: around 240 mg/dl (high risk).
  • Elevated levels are associated with coronary artery disease.
• Measurement Considerations:
  • Fasting not required for total cholesterol.
  • Long-term eating patterns influence levels more than single meals.
• Triglycerides:
  • Normal: less than 150 mg/dl.
  • Elevated TG linked to obesity, diabetes, fatty liver, and cardiovascular disease.
  • Fasting for 12 hours is necessary before testing.
• Hyperlipidemia Types:
  • Primary: Genetic causes affecting lipid metabolism.
  • Secondary: Due to diseases (diabetes, hypothyroidism), lifestyle, or drugs.
• Clinical Significance:
  • Monitoring lipid profile helps assess cardiovascular risk.
  • Management includes lifestyle changes and medication if necessary.

💡 Key Takeaway

Cholesterol is vital for cell structure and hormone synthesis, but maintaining balanced levels is crucial; elevated blood cholesterol and triglycerides significantly increase the risk of cardiovascular diseases, making regular monitoring essential for prevention and management.

📖 2. Triglycerides & Energy Storage

🔑 Key Concepts & Definitions

• Triglycerides (TGs): The main form of stored fat in the body, composed of three fatty acids attached to a glycerol backbone. They serve as a significant energy reserve.
• Adipose Tissue: Specialized connective tissue that stores triglycerides, acting as the body's primary fat reservoir.
• Energy Source: Triglycerides provide energy during fasting or physical activity, especially when carbohydrate stores are depleted.
• Postprandial Lipemia: The rise in blood triglyceride levels after a fatty meal, which can be measured to assess lipid metabolism.
• Hypertriglyceridemia: Elevated triglyceride levels in blood (>150 mg/dl), associated with increased risk of cardiovascular diseases and fatty liver.
• Fasting Requirement: Triglyceride levels are affected by recent meals; hence, fasting for 12 hours is necessary for accurate measurement.

📝 Essential Points

• Storage and Mobilization: Most triglycerides are stored in adipose tissue, mobilized during energy demand to supply fatty acids for muscle and other tissues.
• Blood Circulation: Circulating triglycerides originate mainly from dietary fats and are transported in lipoproteins like chylomicrons and VLDL.
• Relation to Disease: Elevated triglycerides are linked to atherosclerosis, heart disease, fatty liver, and metabolic syndrome.
• Measurement: Triglyceride testing requires fasting (12 hours) due to meal influence; levels should be less than 150 mg/dl.
• Lipid Metabolism: Triglycerides are synthesized in the liver and intestines; excess intake leads to increased blood levels, especially in obesity and diabetes.
• Hyperlipidemia Types: Hypertriglyceridemia can be primary (genetic) or secondary (due to conditions like diabetes, hypothyroidism, or alcohol use).

💡 Key Takeaway

Triglycerides are vital energy storage molecules, with blood levels reflecting long-term dietary and metabolic health; elevated levels increase the risk of cardiovascular and liver diseases, making fasting lipid profiles essential for accurate assessment.

📖 3. Hyperlipidemia & Types

🔑 Key Concepts & Definitions

• Hyperlipidemia: Elevated levels of lipids (cholesterol and triglycerides) in the blood, increasing the risk of atherosclerosis and cardiovascular disease.
• Cholesterol: A waxy fat found in blood, essential for cell membrane integrity, hormone synthesis, and nutrient absorption; can be dietary (animal sources) or synthesized in the body.
• Triglycerides (TG): The main form of stored fat in the body, derived from dietary fats and synthesized in the liver; serve as energy reserves.
• Primary Hyperlipidemia: Genetic disorder causing abnormal lipid metabolism, leading to elevated cholesterol and triglycerides.
• Secondary Hyperlipidemia: Result of other conditions like diabetes, hypothyroidism, liver or kidney disorders, obesity, or lifestyle factors such as diet and alcohol intake.
• Fasting Requirement: Triglyceride measurement requires fasting (12 hours) due to meal influence; cholesterol measurement generally does not.

📝 Essential Points

• Cholesterol Levels:
  • Desirable: <200 mg/dL
  • Borderline: 200–239 mg/dL
  • High: ≥240 mg/dL (high risk for heart disease)
• Triglycerides:
  • Normal: <150 mg/dL
  • Elevated: >150 mg/dL, associated with obesity, diabetes, fatty liver, and cardiovascular risk.
• Hyperlipidemia Types:
  • Hypercholesterolemia: Elevated cholesterol, often linked to genetic factors or diet.
  • Hypertriglyceridemia: Elevated triglycerides, associated with metabolic syndrome, obesity, and diabetes.
• Risk Factors & Complications:
  • Elevated lipids contribute to atherosclerosis, leading to coronary artery disease, stroke, and peripheral vascular disease.
  • Lifestyle modifications and medications (statins, fibrates) are primary management strategies.
• Diagnosis & Monitoring:
  • Lipid profile includes total cholesterol, LDL, HDL, and triglycerides.
  • Fasting blood samples are preferred for triglycerides; non-fasting samples are acceptable for cholesterol.
• Genetic vs. Acquired:
  • Primary hyperlipidemia is inherited, often involving mutations affecting lipid metabolism enzymes or receptors.
  • Secondary hyperlipidemia results from other health conditions or lifestyle factors.

💡 Key Takeaway

Hyperlipidemia encompasses elevated blood lipids, primarily cholesterol and triglycerides, which significantly increase cardiovascular risk; effective management involves lifestyle changes and pharmacotherapy tailored to the type and severity of lipid abnormalities.

📖 4. Uric Acid & Purine Metabolism

🔑 Key Concepts & Definitions

• Uric Acid: A waste product formed from the breakdown of purines, primarily excreted via the kidneys. Elevated levels can lead to gout and kidney stones.
• Purines: Nitrogenous bases (adenine and guanine) found in DNA, RNA, and certain foods; they are metabolized into uric acid.
• Hyperuricemia: Abnormally high serum uric acid levels, often associated with gout, kidney stones, and metabolic disorders.
• Gout: An inflammatory arthritis caused by the deposition of monosodium urate crystals in joints due to hyperuricemia.
• Uric Acid Synthesis: Occurs mainly in the liver through purine catabolism; involves enzymatic steps converting purines into uric acid.
• Uric Acid Excretion: Primarily through the kidneys; a small amount is eliminated via the gastrointestinal tract.

📝 Essential Points

• Sources of Purines: Endogenous synthesis and dietary intake (meat, seafood, certain vegetables). High purine foods can elevate serum uric acid.
• Metabolism Pathway: Purines are broken down into hypoxanthine → xanthine → uric acid, catalyzed by xanthine oxidase.
• Regulation: Balance between uric acid production and renal excretion determines serum levels.
• Clinical Significance:
  • Hyperuricemia: Can result from increased production (e.g., high purine diet, cell turnover in leukemia) or decreased excretion (renal impairment).
  • Gout: Crystals form when uric acid exceeds solubility, depositing in joints causing pain and inflammation.
  • Other Conditions: Kidney stones, uric acid nephropathy, and certain metabolic syndromes.
• Diagnostic Testing:
  • Serum uric acid levels (reference: men 3.5–7.2 mg/dl; women 2.6–6 mg/dl).
  • Elevated levels suggest gout or risk for kidney stones.
  • Decreased levels may occur in liver disease or with certain medications like allopurinol.
• Factors Affecting Uric Acid:
  • Diet, renal function, genetic predisposition, alcohol intake, certain drugs, and metabolic conditions.

💡 Key Takeaway

Uric acid is a metabolic waste product derived from purine breakdown, and its serum level reflects a balance between production and excretion; disturbances in this balance can lead to gout, kidney stones, and other metabolic disorders. Proper regulation and understanding of purine metabolism are essential for diagnosing and managing related diseases.

📖 5. Serum Protein & Components

🔑 Key Concepts & Definitions

• Serum: The clear, yellowish fluid remaining after blood clotting, devoid of clotting factors like fibrinogen.
• Plasma: The liquid component of blood containing clotting factors, obtained by centrifuging anticoagulated blood.
• Total Protein: The sum of all proteins in serum or plasma, primarily including albumin, globulins, fibrinogen, and hormone-binding proteins.
• Albumin: The most abundant plasma protein, responsible for maintaining osmotic pressure and transporting substances.
• Globulins: A diverse group of proteins involved in transport and immune functions, separated into alpha, beta, and gamma globulins.
• Fibrinogen: A clotting protein that converts into fibrin during coagulation, essential for blood clot formation.

📝 Essential Points

• Serum vs. Plasma: Serum is obtained after blood clotting and removal of clotting factors; plasma is obtained with anticoagulants and contains clotting factors.
• Protein Functions: Proteins maintain osmotic balance, transport hormones and lipids, and participate in immune responses.
• Measurement: Total protein is measured via spectrophotometry; albumin and globulins are often evaluated separately.
• Clinical Significance:
  • Hyperproteinemia: Elevated serum proteins, often due to inflammation, infections, or multiple myeloma.
  • Hypoproteinemia: Reduced serum proteins, associated with malnutrition, liver/kidney disease, or malabsorption.
• Albumin/Globulin Ratio: Useful in diagnosing liver disease, immune disorders, and protein-losing conditions.
• Sample Handling:
  • Serum should be separated promptly, stored at 2–8°C, and protected from freeze-thaw cycles.
  • Hemolyzed, icteric, or lipemic samples can interfere with tests.

💡 Key Takeaway

Serum protein analysis provides vital insights into nutritional status, liver and kidney function, and immune health, with precise sample handling being crucial for accurate results. Elevated or decreased protein levels can indicate a range of systemic conditions requiring further investigation.

📖 6. Serum & Plasma Preparation

🔑 Key Concepts & Definitions

• Serum: The clear, yellowish fluid obtained after blood clotting and removal of clotting factors like fibrinogen; used for various biochemical tests.
• Plasma: The liquid component of blood containing clotting factors, obtained by centrifuging blood treated with anticoagulants.
• Centrifugation: A process that separates blood components by spinning at high speed, allowing the separation of serum or plasma from blood cells.
• Anticoagulants: Substances like EDTA, citrate, or heparin used to prevent blood clotting during plasma collection.
• Hemolysis, Icteric, Lipemic Samples: Samples with red cell rupture, jaundice, or excess lipids, respectively; can interfere with test accuracy.
• Aliquot: A measured sub-volume of a sample used for storage or analysis to prevent repeated freeze-thaw cycles.

📝 Essential Points

• Serum Preparation:

  • Collect blood in a clot-activating tube.
  • Allow blood to clot at room temperature (~15–30 min).
  • Centrifuge at 1,000–2,000 x g for 10 min.
  • Transfer serum immediately into a clean tube; store at 2–8°C if not analyzed immediately.
  • Avoid freeze-thaw cycles; aliquot samples for long-term storage at –20°C or lower.
  • Hemolyzed, icteric, or lipemic samples can invalidate tests.

• Plasma Preparation:

  • Collect blood in tubes with anticoagulants (e.g., EDTA, citrate, heparin).
  • Centrifuge at 1,000–2,000 x g for 10–15 min.
  • Transfer plasma into a clean tube; store at 2–8°C if not analyzed immediately.
  • Avoid freeze-thaw cycles; store at –20°C or lower.
  • Hemolysis or lipemia can interfere with test results.

• Handling Tips:

  • Proper collection and immediate processing are critical.
  • Maintain samples at appropriate temperatures.
  • Use sterile, clean tubes to prevent contamination.
  • Document sample collection details for accurate interpretation.

💡 Key Takeaway

Proper preparation and handling of serum and plasma samples—through correct collection, centrifugation, and storage—are essential for accurate biochemical analysis, preventing sample degradation and interference that could compromise test results.

📖 7. Urinalysis & Examination

🔑 Key Concepts & Definitions

• Urinalysis: A diagnostic test analyzing urine's physical, chemical, and microscopic properties to detect abnormalities or disease states.
• Specimen Types:
  • First Morning Urine: Most concentrated, ideal for detecting trace substances.
  • Random, 2-hour Postprandial, 24-hour Collection: Used for specific diagnostic purposes.
• Physical Examination Parameters:
  • Color, Clarity, Odor, Volume: Visual assessment indicating hydration status, infection, or other conditions.
• Chemical Examination Parameters:
  • pH: Measures acidity or alkalinity.
  • Specific Gravity: Indicates urine concentration.
  • Proteins, Glucose, Ketones, Blood, Leukocytes, Nitrites: Chemical markers for various diseases.
• Microscopic Examination:
  • Cells, Casts, Crystals, Microorganisms: Detects infections, kidney damage, or metabolic disorders.
• Urinary Components:
  • Casts: Cylindrical particles indicating kidney conditions.
  • Crystals: May suggest stones or metabolic issues.
  • Bacteria, Yeasts: Sign of infection.

📝 Essential Points

• Sample Collection:
  • Use first morning urine for best results due to concentration.
  • Refrigerate samples if analysis is delayed beyond 1 hour; avoid older than 24 hours.
• Test Components:
  • Physical: Color, clarity, volume, odor.
  • Chemical: pH, specific gravity, proteins, glucose, ketones, blood, nitrites, leukocytes.
  • Microscopic: Cells, crystals, casts, bacteria.
• Interpretation:
  • Cloudy urine suggests infection or presence of crystals.
  • Proteinuria indicates kidney damage.
  • Glucosuria may point to diabetes mellitus.
  • Hematuria suggests bleeding or trauma.
• Procedure Highlights:
  • Macroscopic: Visual inspection.
  • Chemical: Dipstick testing.
  • Microscopic: Centrifugation, sediment examination under microscope.
• Clinical Significance:
  • Abnormal findings can indicate urinary tract infections, renal disease, metabolic disorders, or systemic illnesses.

💡 Key Takeaway

Urinalysis is a vital, non-invasive diagnostic tool that provides comprehensive insights into renal function, metabolic status, and systemic health through physical, chemical, and microscopic examination of urine samples.

📖 8. Kidney Function Tests

🔑 Key Concepts & Definitions

• Urea: A nitrogenous waste product formed in the liver from ammonia during protein metabolism; excreted primarily by the kidneys. Elevated levels indicate impaired renal function or increased protein breakdown.
• Creatinine: A waste product from muscle creatine metabolism; filtered and excreted by the kidneys. Its blood level reflects glomerular filtration rate (GFR) and kidney function.
• Uremia: The clinical condition resulting from high blood urea levels due to kidney failure, leading to symptoms like nausea, fatigue, and neurological disturbances.
• Glomerular Filtration Rate (GFR): The rate at which the kidneys filter blood, used to assess renal function; estimated from serum creatinine levels.
• Normal Ranges: Urea (15–45 mg/dl), Creatinine (0.4–1.4 mg/dl). Deviations suggest renal impairment or other metabolic disturbances.

📝 Essential Points

• Purpose: To evaluate kidney function by measuring waste products (urea and creatinine) in blood.
• Sample Collection: Serum or plasma; serum preferred for urea and creatinine testing.
• Interpretation: Elevated urea and creatinine indicate decreased renal clearance, suggestive of kidney disease or failure.
• Urea vs. Creatinine: Urea levels can be affected by diet, hydration, and liver function; creatinine is more specific for renal function.
• Clinical Significance: Used to diagnose and monitor chronic kidney disease, acute renal failure, and to assess the severity of renal impairment.
• Limitations: Factors like dehydration, high protein intake, or liver disease can influence results; thus, interpretation should consider clinical context.

💡 Key Takeaway

Serum urea and creatinine are vital, cost-effective markers for assessing kidney function, with creatinine providing a more specific indication of glomerular filtration efficiency. Elevated levels point to renal impairment, guiding diagnosis and management.

📖 9. Serum Electrolytes & Balance

🔑 Key Concepts & Definitions

• Electrolytes: Minerals in blood and body fluids that carry an electrical charge, essential for fluid balance, nerve transmission, muscle contraction, and heart rhythm regulation.
• Sodium (Na⁺): The primary extracellular cation; regulates fluid volume, blood pressure, and nerve function.
• Potassium (K⁺): The main intracellular cation; crucial for muscle function, nerve signals, and maintaining cellular osmolarity.
• Calcium (Ca²⁺): Involved in bone health, blood clotting, muscle contraction, nerve transmission, and heart rhythm.
• Chloride (Cl⁻): An anion that helps maintain acid-base balance, osmotic pressure, and fluid regulation.
• Electrolyte Imbalance: Conditions like hyponatremia, hypernatremia, hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, and hypochloremia, which can disrupt physiological functions.

📝 Essential Points

• Fluid and Electrolyte Homeostasis: Maintained by kidneys, hormones (aldosterone, ADH, ANP), and cellular mechanisms.
• Sodium: Normal serum range 135-145 mmol/L. Imbalances cause symptoms like confusion, seizures, or dehydration.
  • Hyponatremia: Excess water, dehydration, or hormonal issues.
  • Hypernatremia: Dehydration or excessive sodium intake.
• Potassium: Normal serum range 3.5-5.1 mmol/L. Critical for cardiac and neuromuscular function.
  • Hypokalemia: Diuretics, vomiting, diarrhea.
  • Hyperkalemia: Kidney failure, acidosis, certain medications.
• Calcium: Normal serum range 8.5-10.5 mg/dl. Regulated by parathyroid hormone and vitamin D.
  • Hypercalcemia: Hyperparathyroidism, malignancies, vitamin D overdose.
  • Hypocalcemia: Hypoparathyroidism, vitamin D deficiency, renal failure.
• Chloride: Normal serum range 96-106 mmol/L. Often measured with sodium and bicarbonate to assess acid-base status.
  • Imbalances linked to acid-base disorders like metabolic acidosis or alkalosis.
• Measurement Techniques: Spectrophotometry, precipitation methods, and ion-selective electrodes.
• Clinical Significance: Electrolyte disturbances can cause neurological, muscular, cardiac, and metabolic issues requiring prompt diagnosis and correction.

💡 Key Takeaway

Electrolyte balance is vital for physiological stability; disturbances can lead to life-threatening conditions, making their assessment and management crucial in clinical practice.

📖 10. Calcium & Blood Regulation

🔑 Key Concepts & Definitions

• Calcium (Ca²⁺): An essential mineral involved in bone health, blood clotting, nerve transmission, and muscle contraction. Approximately 99% is stored in bones, with the remaining 1% in blood and tissues.
• Ionized Calcium: The free, active form of calcium in blood not attached to proteins; crucial for physiological functions.
• Total Calcium: The sum of bound (to proteins) and free (ionized) calcium in blood, reflecting overall calcium status.
• Hypercalcemia: Elevated blood calcium levels, often caused by hyperparathyroidism, certain cancers, or excessive vitamin D intake.
• Hypocalcemia: Reduced blood calcium levels, which may result from hypoparathyroidism, liver disease, malnutrition, or vitamin D deficiency.
• Parathyroid Hormone (PTH): Hormone secreted by the parathyroid glands that regulates calcium levels by increasing blood calcium through bone resorption, kidney reabsorption, and activation of vitamin D.

📝 Essential Points

• Regulation of Calcium: Maintained by PTH, vitamin D, and calcitonin. PTH increases blood calcium by stimulating bone resorption, increasing renal reabsorption, and promoting active vitamin D synthesis.
• Blood Calcium Range: Normal total calcium levels are 8.5–10.5 mg/dL. Ionized calcium constitutes about half of this and is the physiologically active form.
• Physiological Roles:
  • Bone strength and structure
  • Blood clotting mechanism
  • Nerve impulse transmission
  • Muscle contraction and relaxation
  • Heart rhythm regulation
• Clinical Significance:
  • Hypercalcemia: May indicate hyperparathyroidism, malignancies, vitamin D overdose, or certain granulomatous diseases.
  • Hypocalcemia: Can cause neuromuscular irritability, tetany, or cardiac issues; linked to hypoparathyroidism, malnutrition, or vitamin D deficiency.
• Testing and Interpretation:
  • Serum calcium measured via spectrophotometry.
  • Do not use EDTA, citrate, or oxalate plasma samples.
  • Total calcium reflects both bound and free calcium; ionized calcium provides active calcium status.
• Related Conditions:
  • Hyperparathyroidism: Excess PTH causes hypercalcemia.
  • Hypoparathyroidism: PTH deficiency causes hypocalcemia.
  • Cancer: Certain tumors can elevate calcium levels.
  • Vitamin D Disorders: Affect calcium absorption and regulation.

💡 Key Takeaway

Calcium regulation is vital for multiple physiological processes, primarily controlled by parathyroid hormone and vitamin D; abnormal levels can indicate serious health conditions requiring precise diagnosis and management.

📊 Synthesis Tables

Aspect	Cholesterol & Lipids	Uric Acid & Purine Metabolism
Main Function/Role	Structural component, hormone precursor, bile acids	Waste product from purine breakdown, gout risk
Primary Sources	Synthesized in liver (~70%), dietary intake	Derived from purine metabolism in liver and diet
Transport in Blood	Lipoproteins (LDL, HDL)	Circulates freely or bound to proteins
Key Lipid Types	Cholesterol, triglycerides	N/A
Measurement Units	mg/dl	mg/dl
Fasting Requirement	Not required for total cholesterol; fasting for triglycerides	Fasting recommended for accurate uric acid levels
Disease Associations	Hyperlipidemia, atherosclerosis, CAD	Gout, kidney stones, hyperuricemia

Aspect	Hyperlipidemia & Types	Serum & Plasma Preparation
Main Abnormality	Elevated lipids (cholesterol, triglycerides)	Sample collection, anticoagulants, processing
Types	Primary (genetic), Secondary (lifestyle/disease)	Serum (clotting, no anticoagulant), Plasma (with anticoagulant)
Fasting Needed	Triglycerides: yes; cholesterol: optional	Fasting recommended for lipid profile
Clinical Significance	Cardiovascular risk, atherosclerosis	Accurate assessment of biochemical parameters
Sample Handling	Avoid hemolysis, proper storage	Centrifuge promptly, avoid hemolysis

⚠️ Common Pitfalls & Confusions

1. Believing fasting is required for total cholesterol testing
2. Confusing LDL ("bad") and HDL ("good") functions and implications
3. Misinterpreting hyperlipidemia as solely dietary, ignoring genetic factors
4. Failing to differentiate primary vs. secondary hyperlipidemia
5. Assuming uric acid levels are unaffected by diet or medications
6. Overlooking the need for fasting before triglyceride measurement
7. Confusing serum and plasma components and preparation procedures
8. Misunderstanding the role of lipoproteins in lipid transport
9. Ignoring the influence of recent meals on lipid profile results
10. Confusing hyperuricemia with gout without clinical correlation
11. Overlooking the importance of sample handling in biochemical tests

✅ Exam Checklist

• Describe the functions and sources of cholesterol in the body
• Explain the significance of HDL and LDL in cardiovascular health
• State the normal and abnormal ranges for serum cholesterol and triglycerides
• Discuss the types and causes of hyperlipidemia (primary and secondary)
• Outline the fasting requirements for lipid profile testing
• Define uric acid, its metabolic pathway, and associated disorders like gout
• List the main sources of purines and their metabolism into uric acid
• Describe the process of serum and plasma sample collection and preparation
• Identify the components of urinalysis and their clinical relevance
• List the kidney function tests and what they evaluate
• Explain the role and normal ranges of serum electrolytes (Na+, K+, Cl-, HCO3-)
• Describe calcium regulation and its importance in blood and bone health