Test Plan
Clinical Laboratory Diagnosis
Midterm II
Total questions – 70: Questions on white cells and leukemias – 14; Questions on hemostasis – 11;
Electrolytes/pH – 8; Carbohydrates/diabetes – 19; Cholesterol/cardiac – 12; Cumulative on past material
–6
There are three cases with several questions related to them. Some questions are mini-cases. 27
questions are basic “factoid/memory” questions. All others require at least a minimal level of
interpretation and sometimes 2-3 levels of synthesis.
There will be ONE OR MORE SLIDE(S) for identification of some object or clinical presentation.
The slide(s) might be used in conjunction with a case. The slide(s) will be from the notes or something
very close to the slides in the notes. I will not choose some radically dissimilar picture.
Numbers you must know
pH range - Google: 7.35-7.45
what counts as a leukemoid reaction - WBCs>50,000/mm or >5% band/immature
the platelet count cutoff for spontaneous bleeding <20,000= spontaneous bleeding (from gums, nose, vagina,
etc - mucosal linings)
the upper limit of plasma glucose 65-100mg/dl
the range of impaired fasting glucose 100-125 mg/dl
the serum threshold of glucose spilling into the urine typically 180 mg/dL
the upper limit of total cholesterol (above that number is abnormal or undesirable) <200mg/dl
the upper limit of LDL cholesterol <130mg/dl
the lower limit of HDL cholesterol <45mg/dl
Triglycerides <15mg/dl
What cardiac troponins levels should essentially be and the number of days it takes for them to wash out
(for troponins T and I); I am not asking you to memorize the washout periods for any other enzymes. I in
7 days, T in 14 days
Any other ranges or numbers will be provided to you if necessary.
Tests you must understand, interpret, and apply
see test plan I: CBC – various cell counts, indices, RDW, differential; Serum iron, serum ferritin, TIBC,
bone marrow exam (in context of a case); Serum folate, RBC folate, serum B 12, Schilling test
Platelet count (what it means in context) Counting of platelets per microliter of blood - just numbers,
not testing functionality (bleeding times is needed for that)
bleeding time (BT) - test for platelet fxn (adhesion & aggregation), detects qualitative defects. monitors
the time it takes for bleeding to stop - may be longer due to low platelets, low hct, 1o platelet disorders,
vWB dz, aspirin meds & non-steroidal anti-inflammatory drugs
Prothrombin Time (PT) evaluates the extrinsic (made in liver, therefore liver issues or vit k def may
prolong) & common pathways. Measures time for clot to form after adding tissue factor & Ca++
Activated Partial Thromboplastin Time (APTT) evaluates the intrinsic & common
pathways.Measures time to form clot after adding Ca++ & contact phase activator. Also assess effect of
heparin
Fibrinogen - produced by the liver, time needed to form a clot post addition of factor IIa is measured
Thrombin Time (TT) evaluates the conversion of fibrinogen->fibrin. Screens for
dysfibrinogenemia/abnormal fibrinogen - may be due to liver issues or congenital
Specific Factor Assay detects abnormalities in specific factors/proteins
D-dimer Assay specific for fibrinolysis/fibrin degradation products; different than FDP which is testing
for both fibrinolysis & fibrinogenolysis
Anti-platelet antibodies Google: assesses for presence of AB against your platelets, tests for blood
transfusion compatibility & presence of thrombocytopenia, autoimmune, etc
Routine electrolytes Sodium, Potassium, Chloride, & Bicarb
o Anion gap or Chloride shift (no mathematical calculations) mathematical approx of the diff
in unmeasured cations & unmeasured anions in serum. DDx of metabolic acidosis. Accounts for
all the other stuff in serum. in healthy people the unmeasured anions>cations .'. usually positive.
Gap indicates a loss of bicarb w/o ^ in chloride -- lactic or ketoacidosis.
C-peptide (see below) byproduct of insulin production - can help ddx Type 1 & Type 2
Fasting Blood Glucose (FBG) requires a 6-8 hour fast (typically done in mornings) detects disorders of
carbohydrate metabolism, mainly used to dx & monitor DM gold standard test for DM dx. Chief
criteria = fasting specimen >126 on 2 occasions or >126 w/ classic sx.
Glucose Tolerance Test (GTT) glucose loading test that measures beta-cells' ability to increase insulin
production. Can be used to detect DM, but not typically used for that - typically used for dx G-DM.
Blood test ~5x during.
2-hour Post Prandial (PP) simple glucose loading test - result generally evaluated in conjunction w/
FBG to screen/monitor for DM
1-hour PP (for G-DM only) simple glucose loading test @ 24-48wk gestation.If >140mg/dl, full GTT
Glycosylated Hb (and its various names) index of long-term plasma glucose control (covers 1-2 mths)
indicating compliance/efficacy of DM therapy. Glucose modifies the RBC, [modified protein] is directly
related to protein life span (RBCs = 3 mths)& average chemical concentration during this time
Total cholesterol fasting preferred but not required, as levels show no significant change after a meal
LDL major contributor to CAD, usually calculated not measured. Fasting recommended.
HDL higher levels correlated with decreased risk of atherosclerosis. Fasting recommended
protein electrophoresis Proteins have different amounts of charge & can be separated by charge.
Positive end on one side & negative on the other allows protein separation & identification
Triglycerides fasting (8-12hr) is essential, as levels sig rise directly following a meal.
Total Creatine Kinase (CK) released from skeletal & cardiac muscle, .'. you may be dying if elevated
levels - not specific to MI. Limited diagnostic value
CK isoenzymes Gold standard for early dx of AMI. CK is made of: CKBB, CKMB, & CKMM
CK-MB isoforms CKMB has 2 subforms CKMB1 & CKMB2. Should be equal, in a MI 2>1
LD isoenzymes dying. There are 5 kinds - care about 1 &2. 2>1 normally, in a MI 1>2.
Myoglobin muscle protein that optimizes uptake of O2, not tested for consistently but appears rapidly
after injury .'. sensitive early marker for MI
Cardiac troponins I and T and their washout times measured routinely now. I washed out in 7 days,
T in 14. highly specific for myocardial injury
DO NOT memorize detailed biochemistry such as how glucose attaches to hemoglobin or what
hemoglobin looks like.
Cumulative questions
For these you should review sensitivity and specificity. There will be one question using these in clinical
application, not just a definition.
For the anemias, focus on the lab testing and interpretation. For this test you need not re-memorize the clinical
symptoms and exam findings of the various anemias in detail, but it would be helpful if you scan these.
White cells and leukemias
You should know all terminology and phrases to describe white cell counts and differentials. What is the
meaning of immature forms in different circumstances? What do the cells primarily respond to; what can they
do, what do they become (if anything) and what can they make (if anything).
Leukopoiesis: process of WBC differentiation and proliferation. Leads to Leukocytosis vs leukopenia.
Band/stab cell = immature WBC (usually a max of 5, unless a 'shift to the left' has occurred - denotes
and overall increase in WBC production)
^ Neutrophils = usually bacterial (neutrophilia vs neutropenia). ^ lymphocytes = viral (inverted diff
means Lymph>neutrophils. Lymphocytosis vs lymphocytopenia). ^ Eosinophils = Parasites/allergies
(contains myeloperoxidase & major basic protein - damages parasite & adjacent tissues)(eosinophilia vs
eosinopenia).
o Basophils release histamine, heparin, & SRS-A (basophilia)
o Monocytes become macrophages & secretes inflammatory mediators (monocytosis vs
monocytopenia)
You should be familiar with the 4 main leukemias and their clinical findings, age groups, and lab findings. You
should know identifiers such as Auer rods, Philadelphia chromosome, smudge cell, etc.
Leukemia: progressive malignant dz of the bone marrow characterized by unregulated proliferation of
cells & replacement of bone marrow with malignant leukemia cells
o Myelocytic/myelogenous/nonlymphoctic = granulocytes dominate
o lymphocytic = lymphocytes dominate
Auer Rods = rod shaped inclusion bodies/cytoplasmic structures. Commonly found in immature cells.
Indicative of AML
Philadelphia chromosome = piece of chrom #8 switches with piece of #22. One is now extra long & one
extra short. Abnormal BCR-ABL gene
Smudge cells = damaged neoplastic cells due to weakened cell membrane
Clinical Findings
Age Groups
Lab findings
Fever, weakness, bleeding, infection,
Children: 2-10 proliferation of
Acute
Double peak - lymphoblasts, anemia
Lymphoblastic bone pain, lymphadenopathy, occasional
splenomegaly & hepatomegaly
middle age +
Leukemia
Fever, weakness, bleeding, infection,
Middle aged + proliferation of myeloblast &
Acute
bone pain, lymphadenopathy, occasional
immature myeloid series
Myelocytic
splenomegaly & hepatomegaly
cells, anemia, Auer Rods
Leukemia
Fatigue & weakness, occasional enlarged Adults, median "Blast crisis". Philadelphia
Chronic
lymph nodes, usually organ involvement
age ~50
chromosome. Leukmoid
Myelocytic
(ex splenomegaly), weight loss, anorexia,
rxn. Shift to the Left.
Leukemia
headache, & nonspecific complaints
Fatigue & weakness, occasional enlarged MC adulthood Hypogammaglobulinemia
Chronic
lymph nodes (lymphadenopathy), usually leukemia,
(no AB). possible Leukmoid
Lymphocytic
organ involvement (ex splenomegaly), & median age
rxn. normo-normo anemia.
Leukemia
nonspecific complaints
~55
Smudge cells.
Hemostasis
You should know the physical findings associated with abnormalities and normal function.
Purpura(um) = bruise. Ex: petechia(um) = <2mm diameter. Ecchymosis= >2mm. Hematoma= 3D
What is primary and secondary hemostasis and what mediators are involved in each? What are the 4 steps of
primary hemostasis? What are the four factor groups in secondary hemostasis? What activates platelets,
extrinsic pathway, intrinsic pathway (do not memorize the pathways – just know what starts them off
specifically). What is tissue factor and vWF? What things would affect Vitamin K and therefore Vitamin K
dependent factors?
Hemostasis = controlled activation of coagulation factors & platelets leading to clot formation, w/
subsequent clot lysis.
Primary Hemostasis: platelets
o Adhesion to collagen @ site (triggered by damaged endothelial cells) (mediated in part by von
Willebrand factor & glycoprotein Ib)
o Release of platelet contents
o Aggregation of additional platelets (mediated by glycoprotein IIb/IIIa-integrin protein)
o Provision of phospholipid surfaces
Secondary Hemostasis: coagulation cascade (intrinsic + extrinsic + common pathway)
o Activators: tissue factor (also called thromboplastin or factor III, exposed when endothelium
disrupted) activates factor VII -> VIIa (extrinsic) & collagen activates XI-> XIa (intrinsic)
o Vitamin K-Dependent Factors VII, IX, X, & II (prothrombin): Made in liver (therefore things
like hepatitis & cirrhosis can interrupt), modified by y-carboxylase (inhibited by coumadin &
anticoagulants (ex: antithrombin III)) to allow Ca++ binding
o Cofactors: factors IXa requires VIIIa & Xa requires Va
o Fibrinogen: converts to fibrin to allow polymerization of fibrin monomers & clot
What are the three components in clot formation?
Blood clot needs: Vasoconstriction. Platelet activation/aggregation (1o hemostasis). Coagulation
cascade (2o hemostasis).
What substances are inhibitors of coagulation (do not memorize extensively about these, just know what they
are).
Negative feedback to prevent excessive clotting.
Tissue plasminogen activator (TPA) turns plasminogen into plasmin which breaks down clots/fibrin
Antithrombin III = natural anticoagulant -- inhibits Vit K dependent factors (IIa, Xa, IXa) in presence of
tissue or exogenous heparin
Protein C (Vit K dependent enzyme) & protein S work together to cleave & destroy VIIIa & Va
Know the platelet disorders; ITP, DIC, vWF disease. Know cascade disorders and specific factors for those,
such as hemophilia.
Platelet disorders: may be due to decreased # of platelets or abnormal platelets - usually acquired usually
in relation to something marrow related. Can present with spontaneous bleeding
Idiopathic/Immune Thrombocytopenia Purpura (ITP) - autoantibodies directed against platelets. Usually
drug induced (ex. Heparin). Only 1o Hemostasis affected.
Disseminated Intravascular Coagulation (DIC) - systemic activation of coagulation -> widespread
thrombosis. Uses up all the coagulation factors -> hemorrhage. Can be acute or chronic. PT, APTT, &
FSP are all increased. Platelet count & fibrinogen decreased (factors used up & clot clearing)
von Willebrand's Dz - def in vWB factor (cofactor for VIII activity & platelet adhesion/aggregation).
Affects intrinsic & platelet cascades .'. BT is not activating (increased), increased APTT, & platelet agg.
assay = decreased activity, vWB factor antigen = quantization decreased.
Acquired cascade disorders: often due to liver damage -> extrinsic pathway -> PT increased
Hemophilia A = def in factor VIII -> inc APTT & Hemophilia B = def in IX/Christmas factor -> inc
APTT. More commonly seen in males, X-linked. Intrinsic pathways.
Acquired hypercoagulable states - often pts w/ lupus & autoimmune dz, they make antiphospholipid
antibodies (binds to the things that trigger intrinsic pathways -> inappropriate clotting). Prolonged
APTT, prone to thrombosis
Congenital hypercoagulable states - def in AT III, protein C (MC), protein S. Allows normal clots but
inhibits breakdown - homozyg = infant fatality, heterozyg = 2nd/3rd decade presentation
Electrolytes
The major routine electrolytes and what happens to these in disease states, especially sodium and potassium.
Sodium: lactic or ketoacidosis = rel. up. hypernatremia: dehydration (diarrhea, vomiting, polyuria, etc)
or sodium excess (cushings, hyperaldosteronism, etc). Hyponatremia: depletion (excessive diuretics,
Addison's, etc) or dilutional (H2O retention, CHF, etc)
Potassium: lactic or ketoacidosis = rel. up. Hyperkalemia: absolute (renal failure, adrenocortical insuff,
etc) or shift (dehydration or diabetic ketoacidosis). Hypokalemia: decreased intake, redistribution
(alkalosis or insulin therapy) or loss (vomiting diarrhea, hyperaldosteronism)
Chloride: lactic or ketoacidosis = rel. down. Hyperchloremia: (dehydration, hyperparathyroidism, etc).
Hypochloremia: prolonged vomiting, respiratory acidosis, metabolic alkalosis, etc
Bicarb: lactic or ketoacidosis = rel. down
Carbohydrates and diabetes
The four glucose metabolic pathways. Insulin and counter regulatory hormones including which of these is the
chief one.
Glycolysis, Glycogenesis (+I), Glycogenolysis (+G), Gluconeogenesis (-I)(+G)
Insulin = decreases blood glucose. Glucagon, IGFs, GH, Cortisol, catacholamines, ACTH = increase
blood glucose.
C-peptide – determine what type of DM based on whether the levels are up or down as well as a predictor for
type 2 when a patient has impaired glucose tolerance.
C-peptide is a byproduct in the production of insulin. Type 1 cannot produce insulin .'. have decreased
C-peptide levels, while Type 2 = higher than normal levels.
Types of DM, DKA, NKHC, Gestational DM, Secondary DM (don’t memorize the list, but know what
secondary DM means, and specifically remember cortisol and its drug derivatives can cause it). Know the
symptoms and mechanisms of each of these and the laboratory results expected for the various problems.
DM - group of disorders caused by insulin def and/or resistance @ tissues (hinders glucose's ability to
enter cells & .'. increases blood glucose levels.
o Type 1 = usually juvenile, def due to autoimmune destruction of beta cells -- cannot make
insulin. Symptoms appear abruptly: polyuria, polydipsia, rapid weight loss, ketoacidosis. The
'polys': polyphagia (overeating), polyuria (inc urination), & polydipsia (inc thirst)
o Type 2: MC type of diabetes, usually adults. decreased insulin production of increased peripheral
resistance (not absolute) -- causes the levels of insulin to be unpredictable in any given person.
Symptoms: obesity (commonly associated w/ NIDDM), generally no ketoacidosis, often first real
sx is blurred vision. on average takes 2 yrs to dx.
Diabetic Ketoacidosis (DKA)- carbohydrate pathways severely compromised/overwhelmed. Inhibition
of glycolysis, stimulation of glycogenolysis & gluconeogenesis. Only Type 1. Triggered by infection or
physiologic stress that accelerates the break down of fat into FA -> ketones -> pH falls & pt= acidosis
o Polyuria, polydipsia, headache, nausea, vomiting, dyspnea, Kusmaul resp. Altered mental state
o Glucose: 300-500mg/dl, dec HCO3 & pH, Na+ down, K up, total CO2 down, ketone +
NonKetotic Hyperosmolar Coma (NKHC)- when insulin is present but inadequate for demand, glucose
goes up w/o developing ketoacidosis.
o Glucose levels initially hit 300-400 -> high urinary glucose -> polyuria -> H2O loss -> impaired
thrist perception -> dehydration -> glucose gradually increases to 1000-1500mg/dl
G-DM - onset during pregnancy & usually resolves after delivery. Insulin resistant. May be
asymptomatic -- most screened @ 24-48wks.
2o DM - Due to anouther condition (ex: glucocorticosteroids, Cushing's, hyperthyroid, anti-insulin
antibodies, cerebrovascular accident, pancreatic destruction (may be drug induced), etc)
Cholesterol and cardiac
Do not memorize all the biochemistry of the various molecules, but understand the 5 types and how these are
identified. Specifically know Type IV is hypertriglyceridemia with normal cholesterol. Know the “hamburger
and fries” type. Why are trigs important and to who(m)? What is the interpretation of the various cardiac tests?
How are isoenzymes and isoforms applied?
Type I, Type II - responds well to diet, “hamburger and fries”, Type III, Type IV - hypertriglyceridemia
with normal cholesterol, Type V
Triglycerides correlate with low HDL and increased risk for pancreatitis. independent risk factor in
women. Usually due to diet, but also alcohol abuse, DM, & renal failure.
Cardiac tests, Isoenzymes, & isoforms - see above.