Blood Analytes Flashcards
Major source of energy in the body
Glucose
Chemical structure of glucose
mono, di and polysaccharides
Glucose Metabolism?
- Glycolysis, Glycogenesis, etc.
- Enzymes
Regulates glucose by increasing cellular uptake and promoting glycogenesis
Insulin
Regulates glucose by stimulating glycogenolysis and gluconeogenesis
Glucagon
Regulates glucose by elevating glucose levels
Epinephrine
Function to elevate glucose levels
GH, ACTH, Cortisol, and Thyroid hormones
Person has this when fasting blood sugars are greater than or equal to 120 mg/dL
Hyperglycemia
Causes of Hyperglycemia
Diabetes mellitus (type 1, 2, and gestational)
Liver Failure
Symptoms of Hyperglycemia
- Glucosuria
- nausea/vomiting
- malaise
- diarrhea
Person has this when fasting blood sugars are less than or equal to 50 mg/dL
Hypoglycemia
Causes of Hypoglycemia
- hormone deficiency
- drug reaction
- insulin excess
- genetic disorder
Symptoms of Hypoglycemia
- nausea
- trembling/sweating
- rapid pulse
- lightheadedness
- watch CNS symptoms
Diabetes mellitus type 1 (insulin dependent)
Caused by autoimmune destruction of pancreatic beta cells, juvenile onset
- hyperglycemia
- ketosis
Diabetes mellitus Type 2 (non-insulin dependent
Caused by insulin resistance and insulin deficiency
- obesity
Lab tests for blood glucose
Direct measurement
Urine
Glucose tolerance test (GTT)
- evaluates insulin response challenge
Glycosalated Hgb (Hgb A1c)
nitrogen-containing metabolite of protein catabolism
Urea
Blood urea nitrogen is synthesized in ____ (CO2 + NH3) and excreted in kidney
Liver
Urea (BUN) is dependent on
exogenous nitrogen intake and endogenous protein catabolism
Disorder of elevated urea
Azotemia
Causes of prerenal azotemia
- decreased renal blood flow; CHF,
shock, dehydration - increased protein breakdown
- high protein diet
- GI hemorrhage
- Obstruction
Azotemia brought on by renal failure
Renal azotemia
toxic condition; high serum urea accompanied w/renal failure
Uremia
Causes of Decreased BUN
- Liver failure
-Overhydration (SIADH)
-Negative nitrogen balance (protein depletion)
-Pregnancy
-Nephrotic syndrome
Creatinine levels in the blood
Relative to muscle mass and body weight
Low variance
Primarily measured for Glomerular Filtration Rate (GFR), # of functioning nephrons
Associated with BUN
BUN/Creatinine ratio
12-20 mg urea/mg creatinine.
Helps determine cause of azotemia
Both BUN & Creatinine elevated indicate post renal obstruction or prerenal azotemia superimposed on kidney disease
High BUN/Creatinine ratio
Indicates prerenal cause for azotemia
Low BUN/Creatinine ratio
Indicate acute tubular necrosis, low protein intake, starvation or liver disease
eGFR
Indicates renal function
eGFR (mL/min/1.73m3) = 1.86 x
(Pcr)^-1.154 x(age)^-0.203 x (0.742 if female)
x (1.210 if AA)
> 60mL/min/1.73m^3
Total Protein Lab study
Measures numerous classes of proteins;
- Albumin
- Alpha-1 (AAT, A1-Fetoprotein)
- Alpha-2 (Haptoglobin, Ceruloplasmin)
- Beta (CRP, Transferrin, Complement)
- Gamma (Immunoglobulins)
Main protein in our bladder?
Albumin
Causes of Hyperproteinemia
Dehydration
Excess immunoglobulins - Multiple Myeloma, Waldenstrom’s macroglobulinemia
Causes of Hypoproteinemia
Kidney disease
Blood loss
Malnutrition
Liver disease
Causes of Hypoalbuminemia
Inflammation - negative APP (acute phase protein)
Hepatic
Urinary loss
GI loss
Poor diet
Compounds that are soluble in organic solvents and insoluble in water
- fats
- steroids
lipids
Synthesized in the liver and intestine
Constituent of cell membranes
Precursor for hormones
Transported by LDL and HDL
Cholesterol
Partially synthesized in liver
Transported by chylomicrons and VLDL
Provides energy to cells
Insulates organs
Triglycerides
Transport vehicles for lipids
- Chylomicrons
- VLDL; degrades to LDL in circulation
- LDL; “bad” - cholesterol into cells
- HDL; “good” - remove excess cholesterol from cells
Lipoproteins
Remove excess cholesterol from cells
High Density Lipoproteins
Transport cholesterol into cells
Low Density Lipoproteins
Hyperlipidemia may be caused by __________ via diet, diabetes, ETOH, hormone defect in pancreas, hypothyroidism
Increased Triglycerides
Hyperlipidemia may be caused by ________ via genetic defects in liver, lack of specific receptor on cells, diet
Increased Cholesterol
Causes of Hypolipoproteinemia
Genetic defect - low LDL/HDL
Absent LDL (w/low cholesterol)
- failure to thrive
- steatorrhea
- CNS degeneration
- malabsorption of fats and vitamins
Decreased LDL
- increased life expectancy
- decreased risk of CAD/AMI
Reduced HDL
- increased risk of atherosclerosis/CAD
Absent HDL (Tangier’s disease)
- increased accumulation of cholesterol in tonsils, adenoids and spleen
Included in Lipid Panel
Cholesterol
Triglycerides
HDL
LDL
Produced by catabolism of heme (RBC’s)
Bilirubin
_______ bilirubin is bound to glucuronide
Conjugated (direct)
Free bilirubin that has not been attached to a glucuronide molecule
Unconjugated (indirect) bilirubin
a yellow color in the skin, the mucous membranes, or the eyes
Due to -
Newborn (HDN)
Inherited
Hepatic dysfunction
Jaundice
Affects about 30% of breast-fed babies. Due to B-glucuronidase in breast milk
(deconjugates bilirubin)
Breast-milk jaundice
Inadequate milk supply
Breast-feeding jaundice
Thought to be caused by a deficiency in the enzyme glucuronosyltransferase. Inherited bilirubin disorder causing jaundice
Gilbert’s syndrome
Absence or deficiency of uridine diphosphate (UDP) glucuronyl transferase. Inherited bilirubin disorder causing jaundice.
Crigler-Najjar syndromes
Types of Liver disorders
Prehepatic
Hepatic
Posthepatic
-urinalysis can affect
Function of Creatine Kinase (CK)
Production of ATP needed for muscle contraction
____ is needed as a cofactor for creatine kinase (CK)
Mg2+
Inhibitors of Creatine Kinase (CK)
Mn2+, Ca2+, Zn2+, Cu+
(Mg2+ in excess)
Occurs as a dimer with two subunits (isoenzymes)
Creatine Kinase structure
Brain type creatine kinase
CK-1(BB)
hybrid type, cardiac tissue creatine kinase
CK-2(MB)
muscle type (cardiac and skeletal) creatine kinase
CK-3 (MM)
Percentage of serum CK fraction that is MM from skeletal muscle
98-100%
Skeletal muscle CK distribution
CK-3 and CK-2
Brain CK distribution
CK-1
Heart CK distribution
CK-3 and CK-2
Smooth muscle CK distribution
CK-1
Devoid of CK
Liver and RBC’s
May be indicated as increased CK-2. Can detect reinfarction soon after initial episode. Testing being replaced by troponins
Myocardial infarction
can separate CK-MB into isoforms 1 & 2
- Clinical sensitivity @ 6hrs 90-95%
- Diagnostic specificity 89-100%
high voltage electrophoresis
Muscle disease indicated by increased CK-3
Muscular dystrophy (Duchenne type)
CNS disease indicated by increased CK-1 (70x)
Reye’s Syndrome
Indicated by increased CK-3 (5x)
Hypothyroid
CK is unstable above ____ degrees C. Best stored refrigerated or frozen. Not affected by slight hemolysis.
37
Protein that regulates muscle contraction
Troponins
How many subunits are there for Troponins?
3 - T,I,C
94-97% of troponins are located in ______.
Myofibrils
T and I subunits of troponins are useful in the diagnosis of _____.
AMI
Troponins are more specific than CK-MB and are ______ in the serum of healthy and non-cardiac patients
Absent
Levels become elevated 2-3 hrs after AMI
Can remain increased up to for 7-10 days after AMI
Clinical sensitivity of 50 - 75% up to 4-6 hours after onset of chest pain
High clinical sensitivity (>90%) up to 4-7 days after AMI
Troponins T and I
Function of Lactate Dehydrogenase (LD/LDH)
H+ ion transfer enzyme w/ NAD as acceptor
Catalyzes the reversible reaction of pyruvate to lactate (based on pH)
L->P (pH 8.8-9.8)
P->L (pH 7.4-7.8)
Fractions of LD. Present in all cells cytoplasm. Tissue levels are 500x higher than serum
5 major + LD-X and LD-6
Isoenzyme of LD in mitochondria, 20-40% activity
LD-1 (HHHH)
Isoenzyme of LD - major form in serum. 35-46%
LD-2 (HHHM)
Isoenzyme of LD - 17-33%
LD-3 (HHMM)
Isoenzyme of LD - 9-18%
LD-4 (HMMM)
Isoenzyme of LD - major fraction in skeletal muscle (6-17%)
- Force conversion of pyruvate to lactate, regeneration of NAD
- Anaerobic glycolysis (cytoplasm)
LD-5 (MMMM)
Cardiac tissue and RBC’s have the highest concentration of which lactate dehydrogenase isoenzyme
LD-1
During AMI - LD rise within 12-24 hrs, peak within 48-72, may be elevated for 10 days
“______________”- 80% seen
Hemolysis (2 and 1 would flip flop to indicate MI)
Flipped pattern
Elevated LD 1 and 2 indicates
Megaloblastic anemia
10x total LD indicates
Liver; toxic hepatitis - lower in viral hepatitis
10x total LD indicates
normal - 2x total LD indicates
Cirrhosis/Obstructive jaundice
Germ cell tumors
elevated LD-1 indicates
elevated total LD indicates
Malignant Diseases
Elevated LD 2, 3 and 4 indicate
PLT destruction (ITP) (3 highest)
- Lymphatic system;
- Mono
- Lymphomas and leukemias
Elevated LD 5 indicates
- Liver disease
- Passive congestion (CHF)
- Skeletal injuries or disorders
Increase in all levels but normal pattern
- Hypoxia
- Hyperthermia
- Congestive heart failure
- Renal Disease
High LD activities will be seen in the _________ in 90% of bacterial infections
10% of viral infections
Specimen - free of hemolysis, separate from cells immediately
Cerebrospinal fluid
Functions of Alkaline Phosphatase
nonspecific enzyme
- catalyzes the hydrolysis of many phosphomonoesters at an alkaline pH
- movement of substances across cell membranes
- lipid transport in GI
- calcifying process in bone
Forms of Alkaline Phosphatase
Located at or in cell membranes
Major isoenzymes derived from liver, bone, intestine, placenta, spleen, and kidney (*most common elevation causes)
Placental (2nd and 3rd trimester)
Primary areas where you’ll see elevated phosphate
Liver and Bone
Present in most tissue
Liver - hepatocytes and biliary tract cells
Bone - osteoblasts (children and geriatrics)
Intestine - blood groups B or O who are secretors
Placenta; increased 1 - 1 ½ upper limit
- 16 - 20 weeks
Kidney
Distribution of Alkaline Phosphatase
alkaline phosphatase abnormality of bone disease- osteoblast involvement (highest) 10-25x UL
Paget’s disease
alkaline phosphatase abnormality of bone disease- moderate (2-4x UL)
Osteomalacia
alkaline phosphatase abnormality of bone disease- normal to slight increase
Osteoporosis
alkaline phosphatase abnormality of bone disease - high
Bone cancer
alkaline phosphatase abnormality of liver disease ( >3x UL)
Extrahepatic obstruction
alkaline phosphatase abnormality of liver disease (< 3x UL)
Intrahepatic obstruction
alkaline phosphatase abnormality of liver disease (<3x to normal)
Viral hepatitis
______ causes of increased synthesis of alkaline phosphatase -
pregnancy, healing fractures, infections
Transient
alkaline phosphatase abnormality causing slight to moderate increase in levels.
Secondary Hyperparathyroidism
The _____ type of amylase breaks 1,4 alpha linkages of sugars (random). This requires calcium and chloride.
Alpha
Amylase is readily _____ by the kidneys and has a pH optimum at 6.9 - 7.0
Filtered
Hydrolase; breakdown of polysaccharides, different rates
Functions of Amylase
- synthesized by acinar cells
- involved in major digestion of starches
Pancreatic (p-type) amylase
- In the mouth
- neutralized by stomach pH
Salivary (s-type) amylase
Distribution of amylase
Small conc. in other tissues (ovaries, testes, tears, colostrum, lungs, adipose tissue)
Salivary glands (greatest conc.)
Pancreas
Hyperamylasemia is seen in ______ in which serum levels rise w/in 5 - 8 hours of symptom onset
- 4-6x UL normal
- max conc. @ 12 - 72 hours
- RTN by day 3 - 4
Acute Pancreatitis
Hyperamylasemia seen in this - up to 4x UL.
Cholesystitis
Causes of Hyperamylasemia (levels not mentioned)
Obstruction
Salivary gland inflammation
Hyperamylasemia seen in this - 50x UL
Carcinomas; lung and ovary
Testing for hyperamylasemia can also detect
- pseudocyst
- ascites
- pleural effusion
- trauma
- alcoholism
Functions of Lipase
Hydrolyzes ester linkage of triglycerides to glycerol and fatty acids (carbons 1 & 3)
Bile salt and colipase assist in emulsification
Emulsification - fat to small sizes
Lipase sources
Pancreas
Tongue
Lipase increased levels seen in _______. Serum levels rise in 4-8hrs (2-50xUL), peak @ ~24hrs, decreases 8-14 days
Other causes;
- obstructions
More specific for pancreatitis than amylase levels.
Pancreatitis
Transaminases
Catalyze the reversible transfer of an amine from an alpha-amino acid to an alpha-keto acid
Participate in amino acid catabolism and biosynthesis
Alanine aminotransferase (ALT)
Catalyzes the reversible transfer of an amine group
Alanine + Oxoglutarate Pyruvate + glutamate
Widely distributed in tissues
Predominate source, liver & kidney
ALT is _________ and indicates Liver cell damage (Hepatocellular disorders, ie. Hepatitis)
Liver Specific
Aspartate + Oxoglutarate <-> oxaloacetate + glutamate
Tissue sources - widely distributed
- Heart and liver
- Skeletal muscle
- Kidney
Located in cytoplasm and mitochondria
Aspartate (AST)
Significance of AST
Could be use to determine if pt was having AMI. Rise 6-8 hrs, peak at 18-48, normal 4-5 days (ALT usually normal)
- avg. increase 4-5x, 10-15x = fatal infarct
Muscular dystrophy - ~8x UL
Liver Diseases
Gamma glutamyltransferase (GGT)
Transfer of gamma-glutamyl group from one peptide to another amino acid
Acts on glutamate residue
All cells (membrane) except muscle
Function of Gamma glutamyltransferase (GGT)
Transport of amino acids through cell membrane
Serum levels originates in the liver
Kidney shows highest activity
Can be liver function test
Significance of Gamma glutamyltransferase (GGT)
Elevated in all forms of Liver disease
- Hepatitis - moderate
- Liver cancer - high
- Cirrhosis - variable
Pancreatitis - 5-15x UL
Prostate malignancy
Anticonvulsant drugs
Intrahepatic or posthepatic biliary obstruction (highest) 5-30x normal
More sensitive of an indicator than ALP, ALT, AST for obstructive jaundice, cholecystitis & cholangitis (occurs earlier and persists longer)
GGT and Biliary Obstruction
Liver function tests (LFTs)
ALT
AST
GGT
Albumin/Total Protein
Bilirubin
ALP
PT
Cardiac Panel
Troponin T and/or I
CK-MB
Total CK
Myoglobin
LD (1/2)?
AST?
Pancreatic panel
Amylase
Lipase
Calcium
Triglycerides
Glucose