Tumors & NPN's

What are characteristics of benign tumors?

1. Slow growing

2. Well-differentiated cells

3. Encapsulated

4. Little risk of spreading

What are characteristics of malignant tumors?

1. Disorganized mass of cells

2. Not encapsulated; invasive

3. Crab-like appearance on histology

What is the difference between protooncogenes and oncogenes?

Protooncogenes are normal genes that have a positive influence on cell proliferation and development. Oncogenes are proto-oncogenes that have become mutated and lead to cancer cell growth.

What kind of cancers are the most immunogenic? Which kind of cancers are the least immunogenic?

1. Most: virally-induced

2. Least: chemically-induced

What are five methods used in the detection of tumors?

1. Tumor morphology (direct histology)

2. Immunohistochemistry

3. Immunoassays

4. Enzymatic activity assays

5. Molecular methods

What are six ideal characteristics of tumor markers?

1. Produced by tumor or in response to tumor

2. Secreted into a biological fluid; inexpensively and easily quantified

3. Have a circulating half-life long enough to permit its concentration to rise with increasing tumor load

4. Reach clinically significant levels while disease is still treatable

5. Have high clinical sensitivity (present in people with malignancy)

6. Have high clinical specificity (not present in people without malignancy)

Two oncofetal tumor markers

1. Alpha fetoprotein (AFP)

2. Carcinoembryonic Antigen (CEA)

Enzymatic tumor markers

1. PSA

2. ALP

3. CK

4. LD

Glycoprotein tumor marker

CA 125

Hormone tumor markers

1. HCG

2. Aldosterone

Receptor tumor markers

1. Estrogen

2. Progesterone

Oncogenes and tumor-surpressing genes

1. HER2/neu

2. BRCA1

Where is AFP normally synthesized, and when does it decline? What cancers is it associated with?

1. Fetal liver and yolk sac

2. 1 year of age

3. Hepatocellular carcinoma, testicular, and ovarian cancer

What two benign conditions is AFP increased in?

1. Twin pregagnancy

2. CMV infection

CEA is associated with what cancer? Should you use this for screening?

1. Colorectal cancer

2. No

What two benign conditions can cause an increase in CEA?

1. Cirrhosis

2. COPD

What is PSA and what cancer is it associated with? How do you measure it?

1. Enzyme that regulates seminal fluid viscosity

2. Prostate cancer

3. Immunoassay

How do you differentiate between a benign and malignant prostate tumor?

Benign prostate tumors have a higher % free PSA level than malignant ones. In malignant tumors, more PSA is bound to proteins

ALP can be used to detect tumors in what three tissues?

1. Bone

2. Liver

3. Small intestine

Creatinine Kinase can be used to detect tumors in what five tissues?

1. Prostate

2. Lung

3. Breast

4. Colon

5. Ovarian

Lactate Dehydrogenase can be used to detect tumors in what four tissues?

1. Liver

2. Lymph nodes

3. Leukemias

4. Testicles

What is CA 125 used to detect?

Ovarian cancer

CA 125 can be increased in what four conditions?

1. Endometriosis

2. Gall bladder inflammation

3. Liver cirrhosis

4. Lung cancer

What are four examples of hormone markers used to detect tumors?

1. Beta-human chorionic gonadotropin (HCG)

2. Urinary VMA, HVA

3. Adrenocorticotropin hormone (ACTH)

4. Aldosterone

What are estrogen and progesterone receptors useful for in breast cancer?

Distinguishing whether to use hormonal therapy. ER+/PR+ cells respond to hormonal therapy whereas negative cells do not.

How do you treat cancers that are positive for the Her-2-neu gene?

anti-Her2-neu Ab

What is Her2-neu used to detect?

Breast and ovarian cancers

What is the BRCA1 gene used to detect?

Breast and ovarian cancer

What specimen tube should you collect blood in that’ll be tested for BRCA1 gene?

EDTA whole blood

What are four NPN’s?

1. Urea

2. Creatinine

3. Uric acid

4. Ammonia

What is the NPN with the highest concentration in the peripheral blood?

Urea

What produces urea and why?

The liver produces urea from ammonia to reduce ammonia levels since they are toxic

How is urea transported?

Inside RBC’s

How is urea filtered and removed?

Kidney’s filter urea and 50% is passively reabsorbed by the tubules

The plasma concentration of urea is influenced by what four things?

1. Diet

2. Rate of protein catabolism

3. Kidney function

4. Perfusion

What is azotemia and how is it different from uremia?

Azotemia is increased nitrogen concentration. Uremia is azotemia with renal failure

What are three types of azotemia?

1. Pre-renal

2. Renal

3. Post-renal

What causes decreased urea?

1. Malnutrition

2. Severe liver damage

How do you differentiate between different azotemias?

BUN/Creatinine ratio

What is the normal BUN:Cr ratio?

10:1 to 20:1

What are the five causes of pre-renal azotemia?

1. Decreased renal perfusion (shock)

2. High protein diet

3. Dehydration

4. Increased protein catabolism (stress, fever)

5. GI bleed → reabsorption of blood

How is the BUN:Cr ratio affected in pre-renal azotemia?

Elevated BUN with normal Creatinine

What is the cause of post-renal azotemia?

Renal obstruction due to tumors, stones, or inflammation

How is the BUN:Cr ratio affected in post-renal azotemia?

Elevated BUN and Creatinine

What is the cause of renal azotemia?

1. Acute and chronic renal failure

2. Glomerular nephritis

What is the reference method for urease detection? What kind of test is it? What is the sample requirement?

1. Indirect Urease

2. Enzymatic fluorescent immunoassay

3. Serum or plasma in Li Heparin or Gold top SST

What tube should you not use for Urease detection and why?

Gray top, since fluoride inhibits urease

What is creatinine?

A waste product generated by normal breakdown of muscle tissue

What is creatinine proportional to, and how does this affect the interpretation of the amount of creatinine?

1. Muscle mass

2. Creatinine levels vary according to muscle mass, age ranges, and gender

What is creatinine useful for?

1. Determining sufficiency of kidney function

2. Determining severity of kidney disease

3. Monitoring progression of kidney disease/treatment

4. Calculating eGFR

What assay is used to measure creatinine?

Alkaline Picrate Jaffe assay

What color is formed when picric reacts with creatinine? Is the rate of color formation directly or inversely proportional to creatinine concentration?

1. Red

2. Directly proportional

What are four substances that cause false increases in the Alkaline Picric Jaffe assay?

1. Proteins

2. Glucose

3. Ketones

4. Hemolysis

What are two causes of false decreases in the Alkaline Picric Jaffe assay?

1. Bilirubin

2. Lipemia

How do enzymatic creatinine assays compare to calorimetric assays?

Enzymatic creatinine assays are less susceptible to interferences than calorimetric assays

What is uric acid a degradation product of? What organ is responsible for excreting it?

1. Prines (A, G)

2. Kidney, bacterial enzymes in GI tract

Why are humans unable to metabolize uric acid?

Silencing of urate oxidase (Uox gene) that codes for uricase

What are the benefits of uric acid in low concentrations?

1. Anti-oxidant

2. Maintains blood pressure

In what three conditions is there an increase in uric acid?

1. Gout

2. Chemotherapy

3. Renal disease

What concentration of uric acid in the plasma results in urate crystal precipitations?

> 6.8 mg/dL

How do you measure uric acid?

Enzymatic uricase reaction coupled with H2O2 attached to chromogen

How is ammonia formed and where does it go?

Ammonia is formed in the GI tract during protein degradation and sent to the liver for urea cycle

Ammonia is toxic to what?

CNS

What is the assay method for ammonia?

GLDH

What are the specimen requirements for ammonia?

1. Collect on ice

2. No hemolysis

3. Deliver within 15 mins

4. Green top Li heparin (no gel)

What are four symptoms of CKD?

1. Anorexia

2. Nausea

3. Vomiting

4. CNS abnormalities

Are NPN’s a sensitive indicator of renal function?

No; 50-75% of kidney must be damaged before you see a change in NPN concentration

What are two downsides of GFR?

1. Time consuming

2. Invasive

What two samples does Creatinine Clearance use?

1. 24 hour timed urine specimen

2. Blood sample

What is the CC equation?

CC = (urine creatinine x volume)/(plasma creatinine)

What are two potential errors with CC?

1. Mistimed urine samples

2. Hydration status of patient

What are three benefits of eGFR?

1. Does not require urine creatinine

2. Can be programmed into LIS

3. Automatic reporting

What is a downside of eGFR?

Factored race into the equation

What is Cystatin C, what is considered a normal level, and how do you measure it?

1. Protein made by all cells that’s not affected by muscle mass, diet, or gender

2. Normally very low levels in urine

3. Immunoassay

How is microalbumin useful in assessing kidney disease?

Low concentration of albumin present in urine that’s not detected with traditional protein dipstick. It allows for earlier treatment for renal disease

What is the sample for microalbumin?

early am spot urine or first void

What is the screening test and confirmation test for microalbumin?

1. Screening: UA MA dipstick

2. Confirmation: Immunoassay