L6 Clinical Chemistry

🧠 Concepts Introduced

LIST
FROM "00 Archive/Objects/Concepts"
WHERE lecture = this.file.link

Common Blood Chemistry Tests

Learning outcome: To understand the commonly-used blood testing and their indication to human health

Learning Outcome

• Common Blood Chemistry Tests
• To understand the complete blood count and their indication to human health

provide important information on the function of kidneys, liver, heart, and other organs screening and diagnosis of various human diseases treatment monitoring

Lipids

organic, nonpolar compounds

mainly composed of atoms C, H & O with carbon-hydrogen (C-H) bonds (hydrocarbon chains)

i) rich source of energy & storage for excess calories

ii) integral part of cell membrane

iii) protection & heat insulation

iv) precursors for steroid hormones, prostaglandins, leukotrienes & lipoxins

Fatty Acids

esterified form in plasma (as building blocks for triglycerides)

free fatty acid (unesterified form) form non-covalent bond with albumin

relatively small amount

linear hydrocarbon chains with terminal carboxyl group (-COOH)

amphipathic molecule

categorization based on the length of hydrocarbon chain:

i) short-chain FA: < 6 carbons

ii) medium-chain FA: 8-12 carbons

iii) long-chain FA: 14-18 carbons

iv) very-long-chain FA: > 20 carbons

examples: palmitic acid (16C) & stearic acid (18C)

categorization based on the degree saturation in the hydrocarbon chain:

i) saturated FA

ii) unsaturated FA (one or more C=C double bonds)

• monounsaturated FA
• polyunsaturated FA

Triglyceride

• in human can be synthesized in liver & stored in adipose tissue

consists of 1 molecule of glycerol attached to 3 fatty acid molecules by

ester bonds

no polar hydrophilic group → hydrophobic

in plant & animal fat; can be synthesized in liver & adipose tissue

Cholesterol

unsaturated = have double bond

4 hydrocarbon rings (A, B, C & D) +

1 hydrocarbon side chain tail

unsaturated, amphipathic lipid

almost exclusively synthesized by animals

present in dietary fat; synthesized in liver

precursor of steroid hormones & bile acids; does not serve as a source of energy fuel

Lipoproteins

when there is higher percentage of protein, the lipoprotein has a higher density

Consists of a non-polar core of triglycerides & cholesteryl esters

Surrounded by a polar surface layer of phospholipids, cholesterol & apolipoproteins

Abnormal Concentration of Lipids

Dyslipidemias

diseases associated with abnormal lipid concentrations

due to

• genetic abnormalities
• environment / lifestyle imbalances
• secondary to other diseases

complication: arteriosclerosis, coronary heart disease, sudden cardiac death, stroke

Checking if concentration of lipids is abnormal

diagnosed by laboratory analyses measuring the concentrations of: a.k.a lipid panel, lipid profile, lipid test, cholesterol panel, coronary risk panel

i) Total cholesterol: overall cholesterol level ii) LDL: risk of cardiovascular disease iii) VLDL: abnormal lipid metabolism iv) HDL: "good cholesterol" v) Triglycerides: cardiovascular disease

serum / plasma specimens are collected after fasting for at least 12 hours serum / plasma specimens can be refrigerated at 4 °C for several days

1. Cholesterol measurement

enzymatic assay using spectophotometer

2. HDL measurement

two-step procedure i) add precipitation reagent to serum / plasma

• aggregates non-HDLs which are then sedimented via centrifugation ii) quantify HDL (supernatant) via enzymatic assays

3. LDL measurement

via Friedewald calculation total cholesterol, triglycerides and HDI are quantified

• VLDL is estimated as = triglyceride level / 5
• IDI = total cholesterol - HDL - VLDI

4. Triglyceride measurement

enzymatic assay

Lipid Disorders

Arteriosclerosis

deposition of lipids (esterified cholesterol) in artery walls

fatty streaks → thin streaks of lipoprotein-loaded macrophages

mature plaques (↑ number of smooth muscle cells, extracellular lipid, calcification & fibrous tissue)

partial / complete occlusion of blood flow → myocardial infarction, stroke

Familial Hypercholesterolemia

associated with genetic abnormalities in the LDLR, APOB, and PCSK9 genes -> predispose to elevated level of LDL

total cholesterol >190 mg/dL in adults; >160 mg/dL in children normal should be below 200

homozygotes (rare) extremely high level of total cholesterol -> first heart attack in childhood /teenage years heterozygotes -> heart disease in 20s - 50s

Hypertriglyceridemia

fasting serum triglyceride levels > 150 mg/dL

genetic factors and other risk factors (eg., hormonal abnormalities, type 2 diabetes mellitus or nephrosis)

imbalance between synthesis & clearance of triglyceride-rich lipoproteins

independent risk factor for cardiovascular diseases

Carbohydrates

Large macromolecules containing C, H & O atoms

Generic formula: C(H₂O),

Contain C=O and -OH functional groups

Identification of Carbohydrate

1. Based on the number of carbon:

• trioses (3C)
• tetroses (4C)
• pentoses (5C)
• hexoses (6C)

2. Based on the location of the C=O functional group

3. Based on the number of saccharide

• monosaccharide (l) (eg., glucose, fructose, galactose)
• disaccharide (2) (eg., lactose, maltose, sucrose)
• oligosaccharide (3-10) (eg.,oligofructose, maltotriose)
• polysaccharide (>10) (eg., amylose, glycogen)

Saccharide units > joined by glycosidic linkage

Glucose

Major energy supply, esp for brain

Primarily stored as glycogen in liver & muscle (storage)

Abnormal regulation of carbohydrate metabolism:

• hyperglycemia
• hypoglycemia

L2 Cell Biology#Carbohydrates

Hyperglycemia

Hyper (high) + glykys (sweet/sugar) + haima (blood)

High blood glucose level

i) Fasting hyperglycemia (> 130 mg/dL) ii) Postprandial/after-meal hyperglycemia (> 180 mg/dL)

Glucose homeostasis → balance between hepatic glucose production and peripheral glucose uptake & utilization (insulin & glucagon)

normal levels: • 70 to 99 mg/dL (3.9 to 5.5 mmol/L) • Two hours after a meal: Less than 140 mg/dL (7.8 mmol/L) • HbA1c (Average over 3 months): Below 5.7%

Imbalance hormones insulin & glucagon ↓ Impaired glucose homeostasis

Caused by:

• certain medications, eg. corticosteroids, beta-blockers
• pregnancy
• medical conditions that affect the pancreas or cause insulin resistance

Complications: • Diabetic Retinopathy: Damage to the tiny blood vessels in the retina of the eye causes swelling, leaking fluid, or abnormal new vessel growth. This can result in blurred vision, retinal hemorrhages, or permanent vision loss.

• Diabetic Nephropathy: Damage to the small filtering units (glomeruli) in the kidneys reduces their ability to filter waste. It often starts with protein leaking into the urine (albuminuria) and can progress to chronic kidney disease or end-stage renal disease.

• Diabetic Neuropathy: High blood sugar injures the tiny blood vessels and neurons that supply the nerves. It most commonly causes peripheral neuropathy (tingling, numbness, or pain in the feet and hands) and autonomic neuropathy (affecting digestion, heart rate, or blood pressure).

Hypoglycemia

Blood glucose level is lower than the standard range

Common among type 1 & 2 diabetic patients who are on insulin/ medication

Causes:

• Incorrect dosage of insulin / medication
• Correct dosage but???

Rare in individuals with normal glucose metabolism Confirm diagnosis if demonstrating: (i) hypoglycemic symptoms (ii) low plasma glucose concentration < 50 mg/dL (iii) symptoms are relieved by administering glucose / glucagon

Diabetes Mellitus

Metabolic disorder of carbohydrate metabolism characterized by

impaired ability to produce sufficient insulin; or

impaired response to insulin / impaired action of insulin (insulin resistance) ↓ Chronic Hyperglycemia

Type 1 diabetes mellitus pancreatic islet B-cells (insulin-producing) destruction autoimmune disorder (imune cells destroy beta cells in the pancreas) insulin is absent or extremely low

Type 2 diabetes mellitus more common insulin resistance / insulin deficiency multifactorial; mainly obesity & aging

Gestational diabetes mellitus glucose intolerance exact cause remains unknown metabolic & hormonal changes during pregnancy affect the ẞ-cell function & insulin sensitivity of other body cells

hormones produced during pregnancy sometimes affect to pancreas to produce less effective insulin

Recommendation: all nondiabetic pregnant women should be screened at 24-28 weeks of gestation

Perform 2-hr Oral Glucose Tolerance Test (OGTT) by using 75 g glucose load

• require overnight fasting of at least 8 hr
• measure fasting blood glucose level
• consume a special sweet drinks
• measure blood glucose level after 2 hours

Laboratory diagnosis

1. fasting blood glucose level

serum / plasma sample

enzymatic glucose assay (glucose oxidase, hexokinase, glucose dehydrogenase)

measurable intensity of coloured products proportional to glucose concentration

2. glycated hemoglobin (HbA1c) testing

hemoglobin + glucose → glycation rate of in vivo glycation is proportional to plasma glucose concentration ↑ blood glucose level→ ↑ HbA conc. HbA1c = average plasma glucose concentrations over the past 2- 3 months

average plasma glucose concentration during the last 30 days accounts for 50% of the HbA1 concentration HbA1 concentration = % of the total Hb

4.0-5.6 = normal 5.7-6.4 = prediabetes ->6.5 = diabetes mellitus

Prediabetes

Higher than normal blood glucose level

But insufficiently high to be considered as diabetes

Increased risk of developing type 2 diabetes mellitus, heart disease & stroke

It is reversible

Glucometer

Point-of-care measurement of blood glucose concentration

Rapid & easy home-based blood glucose monitoring

only a small amount of blood sample (from fingertip)

Particularly individuals with type 1, 2 & gestational diabetes mellitus

Complete Blood Count

To evaluate overall health

To screen, diagnose & monitor certain health disorders, eg., anemia, infection & leukemia

Measurement and/or counting of:

• red blood cells (RBCs)
• white blood cells (with and without differential) (WBCs)
• hemoglobin (Hb)
• hematocrit
• platelets
• mean corpuscular volume (MCV)

1. Red Blood Cells (erythrocytes)

measure the number of red blood cells, which carry oxygen from the lungs to the rest of our body

normal count (male): 4.35-5.65 million cells/ul

normal count (female): 3.92-5.13 million cells/ul

increased level may indicate: i) polycythemia ii) respiratory distress iii) high altitude

decreased level may be a sign of: i) iron anemia ii) vitamin B12, vitamin B6 and/or folic acid anemia iii) hemorrhage iv) liver & renal dysfunction

2. White blood cells

measure the total number of white blood cells (without differential)

measure the number of each of the 5 basic white blood cell types (differential)

→ neutrophils, eosinophils, basophils, lymphocytes & monocytes

→ expressed as percentage or absolute value

elevated white blood cells count may indicate inflammation or infection

low cells count may indicate autoimmune

diseases, bone marrow disorders or cancers

normal: 3.4-9.6 billion cells/liter

3. Haemoglobin

protein that carries oxygen in the red blood cells

normal (male): 132-166 g/L normal (female): 116-150 g/L

increased level

• dehydration, emphysema, asthma, polycythemia

decreased level

• iron deficiency anemia, internal bleeding, digestive inflammation

4.. Haematocrit (packed cell volume)

percentage of the total volume

occupied by packed red blood cells when a given volume of whole blood is centrifuged

normal (male): 38.3%-48.6% normal (female): 35.5%-44.9%

abnormal value indicates the similar clinical conditions as hemoglobin

5. Platelets

responsible for blood coagulation and vascular integrity

reference (male): 135-317 billion/L reference (female): 157-371 billion/L

increased level

• atheroslecrosis, rheumatoid /inflammatory arthritis, cancers

decreased level

• idiopathic thrombocytopenia, blood loss

6. Mean Corpuscular Volume (MCV)

• the volume in cubic microns occupied by an average single RBC
• T value (macrocytic RBCs): vitamin B 12 /folic acid anemia. dehvdration
• 1 value (microcytic RBCs): iron anemia, microscopic internal bleeding

other RBCs-related markers: i) MCH (mean corpuscular hemoglobin) ii) MCHC (mean corpuscular hemoglobin concentration)