Lecture 6 - Hematology/Liver/GI Lab Values

what is complete blood count (CBC) used for

evaluate symptoms (non-specific - fever, fatigue, bruising)

diagnose condition (anemia, infection, leukemia)

determine stage of disease (leukemia)

what does a CBC count provide

info on number of platelets, RBCs, WBCs

what does a Differential CBC provide

more detailed information on the number of different types of WBCs

what does a RBC indices provide

informaiton on RBC morphology(size, shape, colour) → classify type of anemia

• hemoglobin (Hgb)

• hematocrit (Hct)

what is mean corpuscular volume (MCV)

average size of RBCs

what is mean corpuscular hemoglobin (MCH)

average weight/amount of hemoglobin in a RBC

what is mean corpuscular hemoglobin concentration (MCHC)

average concentration of hemoglobin per volime of RBC

what is red blood cell distribution width (RDW)

measure of cell size distribution

how are levels of mean corpuscular hemoglobin concentration (MCHC) classified

hyperchromic (high concentration)

normochromic

hypochromic (low concentration)

how is mean corpuscular volume (MCV) classified 

macrocytic (large)

normocytic

microcytic (small)

what condition is associated with microcytic MCV

Iron deficiency anemia

what condition is associated with macrocytic MCV

vitamin B deficiency

what condition is associated with hypochromic MCHC

iron deficiency anemia

thalassemia 

what condition is associated with hyperchromic MCHC

hemolytic anemia

what are additional lab tests for anemia 

ferritin 

vitamin B12

folic acid

reticulocyte count

erythrocyte sedimentation rate (ESR)

C-reactive protein (CRP)

what does ferritin measure 

how much iron is stored in the body 

(iron deficiency produces microcytic anemia)

what does a vitamin B12 deficiency result in

macrocytic normochromic anemia

what does a lab test for folic acid indicate

involved in maturation of RBCs

can accompany vitamin B12 deficiency 

what is reticulocyte count measure

immature red blood cells

reflects erythropoietic activity of bone marrow → useful for anemia diagnosis and monitoring to medication therapy

what does erythrocyte sedimentation rate measure

presence/level of inflammation in the body 

usually a slow process 

what does C-reactive protein measure 

inflammation in the body, preferred over erythrocyte sedimentation rate

can indicate viral/bacterial infection, vasculitis, severe arthritis

what are the 3 types of granulocytes

neutrophils, eosinophils, basophils

what are the 2 types of agranulocytes

lymphocytes, monocytes

what is neutrophilia

increased neutrophils

can indicate bacterial infection, trauma, MI

can be caused by medications - corticosteroids, lithium, epinephrine

what is neutropenia 

decreased neutrophils 

can indicate vitamin B12/folate deficiency 

can be caused by medications - ganciclovir, clozapine, ticlopidine, cytotoxic meds

what is eosinophilia

increased eosinophils

can indicate allergic/acute reactions, parasitic infections

can be caused by medications - antibiotics (penicillins), ACEI, anticonvulsants (carbamezepine)

what is monocytosis 

increased monocytes 

can indicate recovery from bacterial infection, tuberculosis, endocarditis, leukemia

what is lymphocytosis

increased lymphocytes

can indicate infectious mononucleosis, viral infections, tuberculosis, syphilis, lymphoma

what is lymphopenia

decreased lymphocytes

can indicate HIV, radiation exposure, lymphoma (Hodgkins)

can be caused by medications (corticosteroids)

what does the liver produce

clotting factors, bile, albumin

what does the liver regulate and store 

carbohydrates, fats, proteins

what does the liver metabolize and eliminate

medications, bilirubin

what can liver laboratory values be used to assess

determine what is happening with the liver

detect the presence of disease

differentiate different types of liver disease

measure extent of liver damage

evaluate response to treatments

monitor side effects of certain medications

how is liver function assessed 

measure ability to synthesize 

measured by albumin, clotting factors 

how is liver injury assessed 

measure aminotransferases → ALT, AST

how is cholestasis assessed

measure abnormal bile flow

measured by alkaline phosphatase, gamma-glutamyl transpeptidase (GGT)

what are non-specific markers for liver lab values

bilirubin, lactate dehydrogenase (LDH)

what is albumin liver function test 

major plasma protein that contributes to osmotic pressure, transport of hormones/medications

concentration decreases in chronic liver diseases (e.g. cirrhosis)

hypoalbuminemia → decreases osmotic pressure → peripheral edema, ascites 

what is clotting factors liver function test

vitamin K dependent factors: I, II, V, VII, IX, X (synthesized/stored in liver)

low factors = clotting abnormality → excessive bleeding, easy bruising

monitor by INR measurement

main causes of liver injury 

medications, alcohol, hepatitis, non-alcoholic fatty liver disease (NAFLD)

what are aminotransferases

used to assess liver injury

involved in metabolic processes, highest concentrations found in liver

(also found in cardiac/skeletal muscles, brain, kidney, lung, pancreas, blood cells)

what is alanine aminotransferase (ALT)

type of aminotransferase to assess liver injury

more specific for liver disease

what is aspatate aminotransferase (AST)

type of aminotransferase to assess liver injury 

less specific for liver

what to look for when assessing liver injury

magnitude of increase of aminotransferases

• mild = 5x ULN

• moderate = 5-10x ULN

• severe = >10x ULN

rate in change of enzyme levels (over days/months/years)

what is cholestasis

reduction of stoppage of bile flow

can be from impaired secretion from hepatocytes/obstruction of bile flow through intra-extra-hepatic bile ducts

what are symptoms of cholestasis

jaundice, pruritis, xanthomas (lipid deposition in skin), malabsorption of fat-soluble vitamine (ADEK), anorexia

what are the lab tests to identify cholestasis 

elevated alkaline phosphatase (ALP) (remember not specific to liver)

elevated gamma-glutamyl transpeptidase (GGT) (not very specific to liver)

concurrent rise in both indicates underlying hepatobiliary disease

what is another cause of elevated alkaline phosphatase (ALP)

skeletal disease, extrahepatic biliary obstruction

what is another cause of elevated gamma glutamyl transpeptidase (GGT)

alcohol abuse

what are the 2 non-specific markers of liver laboratory values

bilirubin

lactate dehydrogenase (LDH)

what do bilirubin levels indicate

bilirubin = product of hemoglobin metabolism in liver (RBC breakdown)

elevated associated with jaundice

measured as total and conjugated only (conjugated with glucuronide in liver to increase solubility)

some medications cause hemolytic anemia related to elevated bilirubin: antimalarials, benzos, sulfonamides, cytotoxic medications

what do lactate dehydrogenase levels indicate 

LDH = enzyme present in every tissue 

elevated = indicate cell damage (non-specific)

what is the Child Pugh Score in liver disease

predict mortality in cirrhosis patients

3 categories: A = good hepatic function, B = moderately impaired, C = advanced hepatic dysfunction

scoring based on: ascites, bilirubin concentration, albumin concentration, prothrombin time, encephalopathy

medications that may require surveillance of liver functions

HIV medications

statins

isotretinoin

tuberculosis medications (e.g. isoniazid)

rheumatoid arthritis medications (e.g. methotrexate)

how might doses need to be changed in patients with liver dysfunction 

reduce dose of drugs that undergo first pass metabolism in the liver

increase dose of prodrugs 

liver lab values in patients with lipid abnormalities

start statins

baseline monitoring to assess liver function → ALT

monitor after 3 months and compare to baseline

what are the 2 main lab tests used to assess the gastrointestinal system

amylase

lipase

both secreted by pancreas and salivary glands

what does an elevation of amylase and lipase indicate 

problem with exocrine function in pancreas (pancreatitis)

problem with gallbladder/bile duct blockage

inflammation or blockage of salivary gland

CKD (enzymes not cleared)

2 other common miscellaneous lab tests

serum creatinine → used to assess GFT

• waste product of creatine breakdown

blood urea nitrogen (BUN) → used to assess kidney function

• urea = end product of protein metabolism (concentration depends on protein intake, nitrogen metabolism)