Lipids, ESR, CRP, Misc Labs

lipoprotein consists of

• Esterified cholesterol - Protective form of cholesterol

• Free cholesterol - Biologically active and cytotoxiy, High level increased risk of CAD

• Triglycerides

• Phospholipids

• Protein

5 major lipoproteins in blood

• Chylomicrons

• VLDL

  • No way to directly measure

  • Approx by dividing measured TG/5

  • High levels associated w. plaque deposits in artery walls

  • Exercise, weight loss, avoiding sugary foods, and alcohol help lower both VLDL and TG levels

• IDL

• LDL

• HDL

standard serum lipid panel/profile measures

total cholesterol

HDL

ratio (Total/HDL)

LDL

TGs

total cholesterol

• Can vary d/t multiple factors

  • Stress

  • Minor illness

  • Posture

• Mild seasonal variation

  • Peak in winter and trough summer

    • Hearty foods w/ more limited PA

• >1 measurement of total cholesterol should be obtained when txt considerations demand a precise determination

  • Redo in 3 months

HDL

(Good)

• Directly measured

• Higher HDL-C reduce CVD risk

• Captures excess cholesterol in circulation

• Obtained in fasting or nonfasting individuals

• Only small, clinically insig differences in these values b/w measurements in fasting or non-fasting

• Increase level of HDL-C

  • Exercise

  • Diet

  • Reduce EtOH

  • Smoking cessation

ratio (Total/HDL)

• Categorize pops into high and low-risk subgroups

LDL

(Bad)

• Directly measured

  • Assays avail to directly measure LDL cholesterol concentration and considered in pts w/ total TG >400mg/dL

  • Calculated by Friedewald equation

    • LDL cholesterol = Total cholesterol - (VLDL + HDL)

    • Progressively inaccurate as TG levels increase

    • Only applied to lipid values measured in fasting state

  • Indications

    • Measuring LDL periodically can be helpful in determining cardiac risk factors

    • Check effectiveness or compliance w/ txt of cholesterol lowering agents

    • If managing w/ lifestyle exchanges only can help determine if med will be needed

TGs

• Carried in chylomicron and VLDL particles

• TG levels influenced by recent food intake and measured in fasting state

  • 8-12 hrs

• Indications to measure

  • Establishing connection b/w elevated TGs and pancreatitis

    • Acute pancreatitis causes inadequate lipid metabolism

      • Elevated TGs

    • Hypertriglyceridemia-induced pancreatitis (HTGP)

      • >500 = concern

      • >1,000 = intervention

      • If TGs slightly elevated, check status of pancreas

        • Lipase

        • Amylase

  • Monitoring of hypertriglyceridemia

  • Screening family members for familial hypertriglyceridemia

apolipoproteins ApoA1 & ApoB (markers for CVD)

• ApoA1

• ApoB

• ApoB/ApoA1 ratio performs better than tradition al lipid profiles as risk determinant

• Lipoprotein a (Lp(a)) valuable in high risk

  • Genetics key

ApoA1

• Primary protein component of HDL

  • Nonpathogenic

ApoB

• Primary protein component of LDL

  • Atherogenic

  • Elevated levels confer risk even in settings of acceptable LDL levels

    • Component of VLDL and IDL

types of familial lipid disorders

• FCHL (Familial Combined Hyperlipidemia)

• Familial defective ApoB-100

• Familial dysbetalipoproteinemia (Type 3 Hyperlipoproteinemia)

• Familial hypertriglyceridemia

• Heterozygous familial hypercholesterolemia

FCHL (Familial Combined Hyperlipidemia)

• High total

• High LDL

  • >190mg/dL

• High TGs

• Low HDL

Familial Defective ApoB-100

• High total

  • 350-550mg/dL

Familial dysbetalipoproteinemia (type III Hyperlipoproteinemia)

• High total

• High TG

  • 300-1,000mg/dL

Familial hypertriglyceridemia

• Very high TGs

  • 200-500mg/dL

Heterozygous familial hypercholesterolemia

• High total

  • 350-550mg/dL

elevated LDL-C txt

• Behavioral therapy

  • Exercise

  • Diet

    • Lean protein

    • Mediterranean diet

  • Smoking cessation

  • Alcohol avoidance/limitation

  • Sleep

  • Manage stress

• Statins

  • Pleiotropic impact on CVD

• Txt for familial lipid disorders

  • High LDL

    • PCSK9inhibtors

      • Inclisiran (Leqvio)

  • High TGs

    • Niacin

    • Fish oil

    • Fibrates

    • Statins

APR (Acute Phase Reactants)

• Proteins whose serum concentrations increase or decrease by at least 25% during inflammatory states

• Accompany chronic as well as acute inflammatory states

• Associated w/ Infection, Trauma, Infarction, Inflammatory arthritides, Systemic autoimmune and inflammatory dz, Neoplasms

APR Key Points

• Abnormalities reflect presence and intensity of inflammatory process

• Change in levels may reflect activity of dz

  • Temporal arteritis

  • Polymyalgia rheumatic

• Measurements not specific to any dx

  • Use to R/o not R/i

• Cannot distinguish infection from other causes of acute and chronic inflammation

APR Indications

• RA

• SLE

• PMR (Polymyalgia rheumatica)

• TA

• Infection

• Malignancy

• CVD

APR measures

ESR

CRP

ESR

• Rate (mm/hr) at which erythrocytes settle out of anticoagulated blood when placed in vertical tube for 1 hr

• Normally settle relatively slowly

  • Rate increases w/ inflammation in body

    • Inflammation = more protein in blood

  • Protein in blood causes RBCs to clump, clumped cells heavier

  • Heavier RBCs fall faster than usual = increased sedimentation rate

common causes of elevated ESR

• Systemic and localized inflammatory dz

  • Temporal arteritis

  • Giant cell arteritis

• Infectious dz

• Malignant neoplasms

• Tissue injury/ischemia

• Trauma

common causes of decreased ESR

• Polycythemia vera

  • Increased viscosity

• Sickle cell anemia

  • Abnormal shape affects sedimentation rate

• Spherocytosis

  • Abnormal shape affects

• Hypofibrinogenemia

• Leukocytosis

  • Too many WBCs

• Low plasma proteins from liver or kidney dz

factors that influence ESR

• Age

  • Older > younger

• Female sex

  • Female > Male

• Anemia

• CKD

• Obesity

• Technical factors

normal ESR values

0-15 in men

0-20 in women

caution ESR values

>100 = active dz

CRP

• Elevation of CRP occurs in associated w/ acute and chronic inflammation d/t ID, Noninfectious inflammatory disorders, CVD, Other

• Produced by hepatocytes and endothelial tissues in response to inflammation

  • More specific than ESR

• High sensitivity version can detect inflammation in vascular system

  • Elevated hs-CRP = predictor of developing HF, DM

  • Predictor of cardiac death, stroke, MI, stent thrombosis

  • Not good test to r/I or r/o ACS

CRP lab values

low <1.0mg/L

avg 1-3 mg/L

high >3 mg/L

CRP important considerations

• Elevations of APR can occur together but may not happen uniformly

• Discordance between ESR and CRP happen

• If ESR and/or CRP elevated, procalcitonin may prove useful in ddx bacterial vs other inflammatory stimuli (viral or autoimmune)

drugs of abuse (DOA) screen

• Amphetamine

• Cocaine

• Marijuana (THC)

• Opioids

• Phencyclidine (PCP)

• Other

drug testing indications

• Seizure/status epilepticus

• CVD events

  • ACS

  • MI

  • Aortic dissection

• Psychiatric event

  • Acute psychosis

• Pt awaiting organ transplant may be ineligible if DOA screen (+)

• Ped pt w/ sxs of abuse

  • (+) DOA screen undergo further eval

  • Siblings might be screened

• Drug rehab, pain management, and some areas of psychiatry

• Pre-employment screening

  • Most common

• DOT requirement for commercial drivers, bus drivers, pilots

Typical periods during which testing (+) after substance use

• Amphetamines 1-3 days

• Cocaine 1-3 days

• Opioids 1-3 days

  • Methadone more variable d/t long 1/2 life

    • May detect for 3-10 days

• Marijuana Days-Months

  • Depends on chronicity of use

    • If chronic user, remain (+) months after discontinuation

• BZDs - vary sig by 1/2 life

  • Generally 1-7 days

  • Diazepam metabolites may be detected for weeks after discontinuation

• Phencyclidine (PCP) 1-7 days

• Ketamine 3-7 days

false (+) d/t other substances - Amphetamine

• Pseudoephedrine

• Ephedrine

• Phenylephrine

• Propranolol

• Atenolol

• Levodopa

• Carbidopa

false (+) d/t other substances - Opioid

• Poppy seed ingestions

  • Bagels

  • Pastries

false (+) d/t other substancesw - PCP results

• OTC cold med

  • Doxylamine

  • Dextromethorphan

  • Tramadol

false (+) d/t other substances - Cannabinoid/marijuana results

• Hemp-containing food products & rare med exposures

  • Marinol

    • Antiemetic w/ synthetic THC

false (-) DOA testing

• Improper specimen collection

• Transport issue

• Specific testing procedures not followed

• Pt may use variety of methods to subvert testing

  • Ingestion or addition of large amounts of water in order to dilute urine

  • Ingestion of masking agents intended to hide presence of DOA

  • Addition of adulterants intended to prevent detection of DOA

  • Substitution of drug-free urine sample obtained from another person/synthetic urine

drug testing regulation & overnight

• Oversight/regulatory agencies

  • SAMHSA

  • Department of Health & Human Services

• Specific requirements for sample to be valid

  • Specific gravity

  • pH

  • Temp

  • Cr concentration

• Specific collection protocols and chain of custody

alcohol testing

• Testing triggered by suspicion of consumption while driving or at work

• Healthcare works obligation to report possible intoxicated coworkers

  • Pt safety come first

pancreatitis lab dx tests

amylase

lipase

acute pancreatitis biochem critieria dx

 Amylase or lipase elevation >3x ULN

amylase testing

• Sensitivity (67-83%)

• Specificity (85-98%)

• Rise within 6-12 hrs

• Normalize within 3-5 days

• Normal 23-85 U/L

• Levels indicate pancreatic damage >450 U/L

lipase testing

• Sensitivity/specificity of lipase >95%

• Increase within 4-8 hrs

• Normalize over 8-14 days

• Normal 0-160 U/L

• Levels indicate pancreatic damage >400 U/L

Causes of hyperamylasemia other than acute pancreatitis

• Abnormal and thoracic malignancies

• Biliary dz

• Dissecting thoracic aneurysm

• GI viscus perforation

• Head trauma w/ intracranial bleeding

• Intestinal obstruction

• Liver dz

• Macroamylasemia

• Mesenteric infarction

• MI

• Pancreatic pseudocyst

• Pancreatic dz not otherwise specified

• PE

• Renal insufficiency

• Ruptured ectopic pregnancy

• Salivary gland dz

• Biliary dz

• DKA

• HIV infection

• Intestinal obstruction

• Pancreatic carcinoma

• Renal failure

Gram stain - microbio tests

• Preparing smear of specimen and then using appropriate staining technique to detect relevant microorganisms

• Rapid and detects most types of bacterial pathogens if present in sufficient numbers

• Provides preliminary characterization

  • Gram +/-

    • Blue or pink

  • Morphology

    • Cocci

    • Coccobacilli

    • Bacilli

  • Arrange of cells

    • Individual

    • Pairs

    • Chains

    • Clusters

• Info on host response

  • +/- neutrophils

culture - microbio tests

• Gold standard for dx many types of infection

• Provides detection (1-3 days) of wide array of organism

  • Avail for definite identification and antimicrobial susceptibility testing

• Route cultures only detect typical bacteria

  • Atypical

    • Mycoplasma

    • Legionella

    • Chlamydia

  • Not identified w/ gram stain or routine cultures

  • May require specific antigen testing

abx sensitivity - microbio test

• Measurement of minimum inhibitory concentration (MIC)

  • Lowest organism of antimicrobial agent that inhibits growth of organisms

  • Interpreted as

    • Sensitive

    • Intermediate

    • Resistant

special microbio tests

antigen detection

nucleic acid amplifications

viral load assays

dx of HSV encephalitis

rapid assays for TB

dx of chlamydial genital infections

serology

antigen detection

• Potential to provide rapid detection of infectious agents

• Most common type of at home COVID19 tests

nucelic acid amplification test (NAAT)

• Potential for very high sensitivity and specificity

  • Numerous viruses, bacteria, and mycobacteria

viral load assays

monitoring HIV and HCV infections

serology of microbio

• Antibody not detected very early in course of infection

• May represent past infection and not acute condition

• IgM 1st ab that appear & persist for 6-12 months

• IgG takes longer to appear but overall predominant ab in body

• Can be used to dx infections that may be difficult to identify at various stages

  • Syphilis

cancer - tumor biomarkers

• Anything present in or produced by cancer cells or other cells of body in response to cancer

• Traditionally proteins or substances made by both normal and cancer cells but at higher amounts by cancer cells

• Found in - Blood, Urine, Stool, Tumors, Other tissues or bodily fluids

• Uses - Estimate prognosis, Detect cancer that remains after txt (Residual dz) or returned after txt, Assess response to txt, Monitor whether cancer become resistant to txt

• Examples - PSA, CEA (Recurrence of colorectal cancer after surgery)

circulating tumor markers

calcitonin - assess txt response, screen for recurrence, estimate prognosis in medullary thyroid cancer

Ca125 - monitoring response to therapy in women w/ known epithelial ovarian cancer

Beta-2-microglobulin (blood, urine, CSF) - MM, CLL, lymphomas

tissue tumor markers (found in actual tumors)

• Alpha-fetoprotein (AFP)

• Estrogen receptor &  progesterone receptor

• Epidermal growth factor receptor (EGFR) gene mutation analysis

• PD-L1

AFP

• Assess stage, estimate prognosis, and follow response to txt of germ cell tumors

  • Often located in ovaries, testes, abdomen, brain, lower back, and chest

• Screening for pops at very high risk for hepatocellular cancer

Estrogen receptor &  progesterone receptor

Determine whether txt w/ hormone therapy and some targeted therapies is appropriate in BC

Epidermal growth factor receptor (EGFR) gene mutation analysis

• Help determine txt

• Estimate prognosis in non-small cell lung cancer

PD-L1

• Many cancer types have PD-L1 and that tricks immune system into thinking cancer cells are normal cells

  • Testing can determine whether txt w/ a type of targeted therapy called "immune checkpoint inhibitor" is appropriate

genetic screening for cance risk & txt

• NCI report

  • >50 genetic variations identified predicting increased risk for cancer

    • BRCA1 and BRCA2 gene tests

      • Hereditary breast and ovarian

    • HER-2 gene tests

      • Predictive factor in BC, aid sin therapy

    • Lynch syndrome

      • Multiple protein mutations identified increase risk for colorectal cancer

      • Tumors in families and occur at young age

stool analysis tests

pathogens

ova/parasites

fat

H. pylori

blood

leukocytes

colon cancer

stool muscle fiber

• Normal

  • No undigested meat fibers

• Request pt to eat red meat 24-72 hrs before test

• Meat fibers present in malabsorption syndromes d/t

  • Biliary obstruction

  • Gastrocolic fistula

  • CF

urobilinogen

• 48 hr specimen collected

• Normal

  • 50-300mg/24 hrs

• Increased urobilinogen w/ hemolytic anemias

• Decreased w/

  • Severe liver dz

  • Oral abx

  • Complete biliary obstruction

    • Feces = clay-colored

trypsin/chymotrypsin

• Likely replaced by immunoassay

  • Unreliable in adults

    • Intestinal flora inactivates trypsin

• 3  random specimens collected

  • Each specimen tested within 2 hrs

• Barium and laxatives affect test results

• Normal

  • 20-950 U/g trypsin

  • 74-1,200mg/kg stool

• Decreased trypsin in pancreatic deficiency or CF

pathogens (stool culture)

• Useful w/ bloody diarrhea (dysentery, enterocolitis)

  • Watery diarrhea often caused by enterotoxins

• Most common pathogens causing diarrhea in US

  • Shigella

  • Salmonella

  • Campylobacter

• C. diff

  • Cause of abx associated colitis

  • Confirmed by detecting toxins in stool

• Cryptosporidiosis

  • In immunocompromised pts

  • Detected by ova and parasite exam

• At least 3 cultures collected on separate days are recommended if bacterium is suspected

• If (+), personal contacts should be tested as well to limit spread of infection

• Specimen must not be contaminated by urine, soap, tissue or diaper material, or be retrieved from the toilet

ova/parasites

• Stool or saliva

• Giardia, EIA, ova, and parasite testing

• >1 sample needed

  • 3 recommended

fat in stool

• Gold standard to dx steatorrhea

  • Fat malabsorption syndrome

• Seen in conditions

  • Celiac dz

  • Crohn's dz

  • Sprue

  • CF

  • Pancreatic dz

  • S/p intestinal resection

• Microscopy w/ 2-part staining procedure to identify

  • Neutral fats

  • Fatty acids

• Increase neutral fats (False +)

  • Ingestion of mineral or castor oil

  • Low-cal mayonnaise

  • Salad dressing

  • High fiber diet

blood in stool testing

• Passage of >2.0 mL in stool in 24 hrs sig

• Dark red to tarry black stool indicates 50-75cc loss of blood from upper GI

  • Diet and drugs can discolor stool

    • Chemical testing needed to confirm

• Chemical detection of occult blood

  • Most performed stool test

  • Small amounts of GI bleeding may not be seen on stool inspection

  • Many false (+) and false (-) results

  • Care in test collection increases accuracy

  • (+) Testing

    • Carcinoma

    • Gastritis

    • UC

    • Peptic ulcer

    • Hernia of diaphragm