Clinical Lab Review

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Clinical Lab review

Urine Studies

I.                   Routine Urinalysis

i.        Screening test for many conditions, but an important test you use to pick up many types of conditions especially urinary infections.  Also very good for first line in early identification of renal disease and also just as important as an early sign of metabolic disorders such as diabetes

1.      Infections

2.      Renal disease- both infection, trauma, calculi, hereditary, glomerular function, tubular function, as a screening, not diagnostic for

3.      Metabolic problems – early indicator

II.                Colors

a.       Amber – think of bilirubin or bile

b.      Pink to red range – heme or myoglobin, any bleeding within renal system, hemoglobin – urea, outside renal system

c.       Remember the ambers and reds

III.             Odor

IV.             Appearance

a.       Turbid or cloudy

b.      Pathological or benign,

c.       Path is increase in WBCs, infections in renal

d.      Benign – amorphic sediment b/c urine was set out for over an hour pH changed and things precipitated out of the urine

e.       Ex.  Urgency, frequency and burning on urination with cloudy urine probably white cells and lots of bacteria

V.                Interfering factors

a.       Specimen greater than 1 hr old

a.       PH changes, urea to ammonia

b.      Bacteria love to grow in warm urine

c.       PH change and start to precipitate crystals and amorphous sediment

Microscopic Exam

Chem dipstick

I.                   Glucose

a.       Diabetes I or II

i.        Blood level threshold is 160 to 180 mg/dL

ii.      Any value greater than 1000 mg/dL – critical value in serum, not representative of what is in blood but what is getting dumped out of renal system

II.                Ketones positive – with glucose greater than 1000 mg d/L = ketoacidosis

a.       Cushing’s leads to hyperglycemia

b.      PCOS – can see hyperglycemia

c.       Acromegaly – can see positive glucose

d.      Metabolic Syndrome X

e.       Thyrotoxicosis – increased metabolic need

f.       Renal tubular disease – positive glucose

g.      Liver and pancreatic diseases especially if tail end of pancreas is affected can see positive glucose

a.       Liver disease can increase glucose as well

Interfering factors

III.             Bilirubin (typically when in urine it is conjugated)

a.       Do not normally see bilirubin in urine, any bilirubin urine is abnormal

b.      Anything positive, no matter how positive, you need to work it up with other labs

c.       Before you see other S/Sx will see a positive dipstick bilirubin, will see jaundice after you see bilirubin in urine, an early sign.  Bilirubin is either indicating intra-hepatic liver disease such as hepatitis (then do LV enzymes, then do Hep panel screens, then do AI, alcoholic etc.) or it is post-hepatic and/or biliary obstruction, no a pre-hepatic condition (hemolysis)

d.      Usually picking up conjugated bilirubin in the urine, bilirubin that has been processed by the liver. It is getting shunted into the bloodstream and Kidneys are trying to clear it out.

e.       Unconjugated bilirubin is typically hemolysis, before it gets processed in the liver

f.       Confirmatory test – Ictotest – get a positive bilirubin, this is the confirmatory test in the laboratory for urine bilirubin.  This test is specific meaning that the only thing it comes up positive for is the bilirubin. 

g.      Bilirubin is sensitive to light, so leaving that cup out will decrease the bili, it is will be broken down by light

IV.             Ketones

a.       Metabolism of fatty acids

b.      Leads to increased Ketones and possibly ketoacidosis, significant in diabetes b/c of the problems with diabetes and how it can go to ketoacidosis as its mechanisms for energy

c.       Starvation and fasting, can see a mild positive ketones, even after a 12 hour fast

d.      Carbohydrate sparing, will convert into a ketosis – can be large amount of ketones, indicator that the diet is doing what it is supposed to do (what the diet books say)

e.       Increased metabolic states

i.        Fever

ii.      Thyrotoxicosis

f.       Can’t interpret ketones outside of the clinical picture of the patient

V.                Specific gravity

a.       Below 1.005 on a morning specimen, need to investigate it, unless they are drinking a liter of water in the middle of the night, a low sp gravity on first morning catch is concerning

b.      Diabetes insipidus – what you think on low sp gravity on first morning catch

c.       Hydration affects sp gravity

d.      A certain molecule such as glucose and protein can also affect specific gravity

i.        DM – increased sp gravity (b/c of glucose being spilled) and increased urine volume

ii.      CHF can lead to increased specific gravity, edema, not urinating as much as they should, so give diuretics to clear some fluid

iii.    Excessive water loss

1.      Dehydration, V and diarrhea

VI.             pH (acid/base)

i.        Measures free hydrogen

ii.      Looking at renal calculi

iii.    Uric acid and cystine crystals are in acidic urine

iv.    Calcium oxalate – common, typically in an neutral to alkaline urine

v.      Ca phosphate – tends to be alkaline, anything phosphate tends to be alkaline

vi.    A very acidic urine, typically would not form calcium oxalate crystals

vii.  So knowing pH in person with renal calculi helps you to speculate type of stones

viii.                        PH as indicator of when you work with them via diet so as to prevent renal calculi

ix.    Can see pH change sin UTI, e coli is in acidic urine, protease and klebsiella they split urea so have more of an alkaline urine.

x.      Naturopaths typically like alkaline urine, but when treating UTIs, Fischbach says keep urine acidic

xi.    Hi protein diet leads to more acidic urine and vegetarian leads to more alkaline urine

xii.  Acidosis and alkalosis wither it is respiratory or metabolic

1.      But will follow blood gases or electrolytes to further understand the condition

VII.          Protein

i.        Strenuous exercise, fever,

ii.      0-trace is not abnormal

iii.    1+ and above – 30 mg/dL of protein is abnormal

iv.    Look at their clinical picture

1.      If asymptomatic and continue to get a positive protein, need to figure out what is going on if nothing else explains it

v.      In young adults a positive protein can be caused by orthostatic protein urea, benign.  Do a first morning specimen, and there should not be any protein, rule out the benign, if still there then do a 24 hour urine protein

1.      Tells you how much protein lost through the renal system

2.      If elevated looking at some type of renal problem

vi.    Bence Jone Proteins – multiple myeloma – but best way is to do a urine protein electrophoresis or to do a test for a Bence Jone Proteins

VIII.       Hgb – presence of RBCs – heme, intact RBCs, and myoglobin

i.        Blood in urine needs to be explained/worked up – it is abnormal – shouldn’t be there, needs to be investigated

ii.      True hemoglobin urea is pre-renal, i.e. hemolysis of some kind, heme getting through glomerular filtration system

iii.    Would have other signs an symptoms such as anemia on CBC so verify this with CBC

iv.    Look on Microscope and see no red blood cells in hemolysis, even if you see ghost or shadow cells than blood is coming from renal system, not pre-renal

v.      Hemoglobin urea – hemoglobin, pre-renal

1.      Hypotonic urine, cells will lyse and can get pre-heme

2.      Pre-renal

3.      Can get Hgb urea within the renal system if they lyse – can lyse if you leave cup sitting out

4.      Key is when you look on microscope see intact RBCs or ghost cells= will be hematuria, not pre-renal

vi.    Hematuria – from renal system, intact RBCs – glomerular nephritis, pyelonephritis

vii.  Trauma, neoplasms, inflammation (Secondary to infection)

viii.                        Strenuous exercise is a big cause of hematuria, aggressive basketball, marathon, etc – can have a bit of hematuria

IX.             Urobilinogen

i.        Increased urobilinogen – think hemolysis!

ii.      If increased without bilirubin, absolutely hemolysis

iii.    Can get in liver damage, because there are three ways to get rid of urobilinogen

1.      bowels

2.      stool

3.      urine

4.      circulates back into liver

a.       if it can’t then the urobilinogen will end up more being released out through the kidneys

iv.    Cholelithiasis

v.      Pancreatic cancer

vi.    Clay colored stools

vii.  Urine probably not best marker

X.                Nitrites

i.        Gram negative bacteria

1.      E coli

2.      will also see a positive leukocytes

3.      Send out for a culture and sensitivity

ii.      But if nitrite is negative, not a negative UTI, check with leukocyte esterase as there could be another organism or early on and hasn’t converted nitrate to nitrite?

XI.             Epithelial cells

i.        Squamous cell contamination

ii.      Renal tubular cells = damage in the kidneys, should not be there

XII.          Casts

a.       All cases t are associated with some type of renal dysfunction, even hyaline casts – dehydration, stasis, strenuous exercises

b.      WBCs casts are pyelonephritis

c.       RBC casts indicate glomerular nephritis

c.renal tubule epithelial cells very rare

d.      Hyaline cases and see

e.       Granular casts are common in kidney disease, not sure what causes it but it is significant if you see it.

f.       See a cast think of renal disease and specifically tubules

g.      Waxing are pathological end stage severe states !!!

h.      WBCs greater than 5 per high powered field, see also positive leukocytes, indication of inflammation or infection, positive nitrite, leukocytes, white cells greater than 5 with clinical picture or see a bit of blood = some type of UTI, just in pelvic region see cystitis, or if also have low back pain and fever  - might see lots of WBCs and casts then you’ve got pyelonephritis

XIII.       RBCs

a.       Hematuria

XIV.       Crystals

a.       benign ones don’t have significance unless history of renal calculi

b.      Uric acid crystals  can form renal calculi

c.       Ca oxalate can form renal calculi

d.      Will also have blood in urine, pelvic pain, and possibly history

e.       Cystine crystals is hereditary

f.       Leucine and lysine and tyrosine are all liver disease

g.      Consider pH when trying to ID crystals

h.      Uric acid crystals in acidic urine

XV.          Bacteria

a.       Shouldn’t be there, consider vaginal contamination, otherwise there should be none in a clean catch specimen

b.      Can come fro urethra, bladder, or kidneys

c.       Parasite in urine is in little kids = pinworm

d.      Yeast is vaginal contamination usually

24-hour urine test

Difficult for people to do

a.       Do for metabolic reasons, creatine or protein, there is diurnal variations in how much is released so random specimens are not the best way to test what is coming through the kidneys, need to do 24 hour, calculate what they are looking for with volume of urine

b.      On all 24 urine tests, they always do a check for creatinine clearance

c.       Also creatinine clearance – used if have renal disease, checking glomerular filtration, do creatinine clearance to tell you how well filtration is working

N-Telopeptide

a.       Screening for resorption of CA in kidneys, osteoporosis indicator, not diagnostic, need DEXA, good way to monitor treatment and screen people

HCG

a.        In office test, does not give specific amount, can be sensitive, so first morning specimen

b.      Male = positive HCG – used to be screening test for testicular cancer

c.       Hydeniform and choriocarcinomas

VMA and catecholamine fractions

Pheochromocytoma – very high BP, run this test.

Urine calcium

a.       Rarely run this, any type of osteoclastic activity or breakdown in bone, but serum tests are better to see for increase in Calcium, do alk phoso to also check for bone disorder

Urine oxalates – problems with kidney stones

Estrogen metabolites –  Looking at level of 2 and 16

Fractionated estrogens for infertility testing, amenorrhea,

Urine protein electrophoresis

a.       Suspect multiple myeloma or monoclonal gammopathy  of unspecified significance will see M spike

b.      Tests all different proteins, could use it in renal disease to distinguish glomerular vs tubular

MCV<80

MCV>80<100

MCV >100

CBC

Great screening test, not always diagnostic, good for identifying infections, inflammation, anemia, bleeding conditions

Use it as a screening test

WBC

1.      Leukocytosis – increased WBCs

a.       Could be infection, viral or bacterial

b.      Some viral could cause a very high WBC

c.       Flus can see a decrease in WBC without knowing what the flu is

d.      Low white counts, virus, high white counts bacteria, not as clear as this

e.       Measles has a high white count

f.       Have to look at the population of cells

g.      Leukemoid Reaction - looks as high as leukemia, but secondary to some type of infection

h.      Can be from septicemia

i.        Inflammation – any type of tissue trauma – ulcerative colitis is inflammatory no infectious

j.        Diverticulitis – inflammatory

k.      Polycythemia vera- myeloproliferative condition, very high WBC with hi Hgb, RBC and Hct

2.      Leukopenia – decreased in WBC

a.       Bone marrow dysfunction, aplastic anemia – secondary to drugs and chemo often (leukopenia)

b.      Pernicious anemia can cause a leukopenia – problem with DNA component, in long term PA, decreased productions secondary to DNA problem, so White count down, Red count down, platelets down – will end up with pancytopenia – like n aplastic anemia.  Hi MCV, hypersegmented neutrophil (*megaloblastic anemia)

RBC

1.      Hct – percentage of packed red cells in total volume

2.      Hgb – measure of heme concentration in the RBCs

a.       Many things can lead to decrease in RBCs

b.      Anemia in RBCs, Hct, Hgb – all low

c.       Increased RBCs or others = polycythemia vera – myelproliferative disorder, a dehydrated individual, high fevers, alcoholics, Hct can drop with hydration

To understand if all are decreased – what is causing the anemia – secondary to hemolysis?  Is there RBC loss – bleed, hypofunctioning bone marrow?  Or a nutritional deficiency that decreases the production of RBCs, Chronic disease affecting RBC production and EPO production

Most common cause of anemia worldwide is iron deficiency

First look at the MCV to differentiate

Classify the anemias based on their size

Most common anemia is iron deficiency anemia in women and children, secondary to nutritional deficiency or nutritional compounded by menstrual cycle of heavy menstrual bleeding.  Chronic disease can also fall in this category.

MCV <80 = Microcytic anemia

1.      Iron Def

2.      Chronic disease

3.      Hemaglobinopathies

a.       Most common will be thalassemia

b.      Hgb C

c.       Sickle Cell

4.      Problems with heme synthesis  - sideroblastic anemia – porphyrias

                Sideroblastic anemias

a.       Thalassemia – ferritin is normal typically

b.      Chronic disease – ferritin can be normal or elevated

MCV >80<100 – Normocytic

1.      Destruction – hemolytic anemias

a.       Hereditary

2.      Acquired from blood transfusion

3.      Hypofunction of the bone marrow

4.      Aplastic anemias, may see a pancytopenia

5.      Hemorrhage/blood loss

a.       Most common area of blood loss is GI track

b.      Female – look at menstrual

c.       Then consider GI

d.      Then renal

Secondary tests:  Reticulocytes (immature RBC and required to differentiate between bone marrow and non bone marrow associated condition

Second test is Coombs testing antibody/Ag reaction or atypical antibodies to differentiate type of hemolysis

MCV >100 Macrocytic

1.      Megaloblastic

a.       B12 and folate:  either acquired – meaning nutritional, or AI = Pernicious anemia – so then do Autoantibodies against Intrinsic Factor.  Schilling test comes into determine acquired vs. autoimmune – checking to see if you can absorb the B12 orally or not vs. giving an injection of B12.  AI is the loss of Intrinsic Factor.  Easier to order the antibody test instead of the schilling test (long and involved – urine and blood tests)

2.      Non-megaloblastic

a.       Liver, increased metabolic needs

Hgb and mean corpuscular hgb concentration – MCH goes with the MCV

Iron def anemia – decreased MCV, so MCH will usually also be low, and hypochromic

If MCH is elevated, more likely it is macrocytic

MCHC:  ?

Up to 60 ml of blood loss is normal in normal menstrual cycle, with well functioning bone marrow, should be able to compensate.

Could be a normal menstrual cycle with decreased nutritional intake, or abnormal menstrual cycle with heavy bleeding or with fibroids or adenomyosis – hemorrhaging and eating enough iron, but can’t compensate for normal loss

1.      RBC distribution width = RDW

a.       Can indicate big variation in shapes and sizes of cells

b.      From smallest cell to largest cell is the differentiation, can get normal small variations, but when you have say sickle cell anemia the RDW is wacky, very small cells and big cells and abnormally shaped cells

c.       Hi RDW – over 20 – iron def anemia is biggest cause

d.      Thalassemia trait, MCV might be hi normal, but body is just cranking out same size little cells, but lost, only with problem in abnormal production then you get a problem.

e.       Thalassemia trait – hi RBC with nm l Hgb and Hct – making small cells genetically, will produce the amt it needs, but with lots of small cells, so high normal RDW.  Bone marrow compensates

Anisocytosis – variation in size

Pokilocytosis – abnormal shape

See list in handout, know these

WBC differential

1.      White count – elevated or decreased, look at the differential to see what is being affected.

a.       Elevated WBC with neutrophilia – inflammation, infection, etc.

b.      Leukemias – in myelogenous series – neutrophils, basophils, eosinophils and monocytes

2.      Neutrophils

a.       Left Shift! (must know for NPLEX) more immature neutrophils, increased in banded neutrophils

b.      Acute infections such as appendicitis – normal response, should see this in an acute infection

c.       If there is a low neutrophil count and no reaction – not responding well, poor prognosis

d.      Right shift – hypersegmentation - think of B12 deficiency

e.       Neutropenia – acute infection poor prognosis, viral infections – absolute counts, depends on what you’re looking at (percentage or as absolute account).  Can have neutropenia in face of lymphocytosis

f.        

Increased lymphocytes- think of viral, EBV is very common, measles, CMV, etc.

Absolute increase in lymphocytes with atypical lymphocytes with fatigue, pharyngitis, adenopathy, and fever – Mono

3.      Monocytes

a.       See elevated in myeloproliferative disorders, remember the line of cells

b.      Elevated infection or trauma as they are recovering is a good thing – shows healthy immune response, it is second line of defense, scavengers, neutrophils are primary.  So open heart surgery and very high white count and watching and neutrophils drop and monocytes go up = good recovery

4.      Eosinophils – parasites and allergies

a.       Mildly elevated in allergies – asthma hay fever, eczema,

b.      In parasites in an infestation can be very high – up to 30% she has seen

c.       Myelogenous series, so can see it up, including some lymphomas – Hodgkin’s

5.      Basophils

a.       Hang out in the tissue, called mast cells, only if very elevated think acute basophilc leukemia or myeloproliferative disorder

Percent vs. Absolute – Absolute is the real count.  WBC differential using percentages can be misleading can see elevations in one cell line and the other is decreased, need to check against absolute values to determine true elevations.

Platelet count

a.       Count the number of platelets in blood, associated with clotting

b.      Causes problems if thrombocytopenia – secondary to a bone marrow hypofunction or drugs that are suppressing bone marrow

c.       Idiopathic thrombocytopenic purpura – typically in children who receivers or rebound easily- secondary to viral (Check this?)

d.      Adults – could be long term – will look at antibodies to see if that is the cause

e.       Severe disease, can see deceased platelets in that

f.       DIC – sucks up the platelets

Thrombocytosis – rule out malignancies

a.       Myelogenous leukemias

b.      Polycythemia vera

c.       Look at volume and size of platelets to help differentiate

Reticulocyte count

a.       Helps you understand bone marrow function

b.      Use it with a normocytic anemia – trying to determine if it is hypfunction, or destruction and loss

c.       Can also monitor bone marrow response when supplementing.  So if iron def anemia – 100-150 mg of iron per day, go back and check reticulocyte count and it should respond.

ESR

a.       Use it as gross indicator of inflammation, screening test or to follow treatment, not diagnostic

b.      Women tend to have increased fibrinogen with increased estrogen, so tend to run a bit higher than men

c.       Pregnancy can elevate ESR

d.      Anemia can interfere with it

e.       A bit of a flawed test

f.       Really want to test for inflammation – order CRP (unless they have liver disease since it comes form the liver)

Immune typing of the lymphocytes

In relationship to CD4 and CD8 ration in context of HIV indicating AIDS infections

Blood Banking

*** Rh typing and hemolytic disease of the newborn, that is the key

a.       Rh-negative mother, Rh pos father, need to give Rogan, or mother may have produced antibodies, next child if positive you will have problems can lead to hemolytic type of anemia and won’t survive

Coombs testing – important

a.       Used to detect antibody antigen complexes and antibodies

b.      Direct is for transfusion reaction – looking for actual antibodies

c.       Indirect is checking for when women give birth and complexes coat RBCs- looking at actual RBCs and what is coating them

d.      Helpful for hemolytic anemias

Coagulation studies

a.       Bleeding Time – more indicative of platelet function

b.      Fibrinogen

c.       Fibrinogen to fibrin – very end of coagulation stages

d.      If fibrinogen is decreased – looking at both the PT and PTT and Thrombin time

e.       PT and PTT

f.       If someone coming in with bleeding gums, bruising, etc. – look at these two

g.      Hemophilia diagnosis  Von Will brands (VWF)

h.      All affected by liver diseases, all made in the liver, can all be elevated in liver diseases

Blood Gases

a.       Acid Base – looking at respiratory or ventilation function

b.      Depends on what you’re looking at

c.       Then look at pH – are they an acidosis or alkalosis?

d.      Then clinical picture, certain things will cause respiratory acidosis and alkalosis and other will cause metabolic acidosis or alkalosis

e.       Be able to differentiate –  pH and partial pressure of the CO2, O2 content or total CO2 to determine if it is metabolic or respiratory

O2 saturation – pulse oximeter – looking at O2 saturation in context of heme itself, doesn’t give total O2 content

a.       Direct O2 is pulse oximeter or calculate off blood gas

b.      Anything below 95 would make you worry – O2 saturation are in percentages – should be 95 and above

c.       In blood gas, the saturation of O2is a calculation using O2 content.

d.      V, D (vomiting and diarrhea) can also throw off blood gases

Serum tests

Electrolytes – most critical to look at sodium (extracellular) and potassium (intracellular).  Can look in relation to adrenals, Na starts to drop, hypofunction, K increase such as in Addison’s, - start to see a decrease in ratio

1.      K – hyperkalemia – associated renal failure and in Addison’s disease (primary hypoadrenal/cortical problem)

2.      Hypokalemia- cardiovascular

3.      Na – abundant opposite to potassium – hyponatremia – associated with Addison’s – hypocortico-adrenisms – elevated potassium and decreased Na, also CHF, edema, fluid loss,

4.      Hypernatremia think of dehydration, not very common

his

Anion Gap – measurement between the positive and negatives – 8-16, if low, think of low protein intake, poor diet, elevated then cations elevated – think o renal disease, potassium starts to go up.

Calcium – the carrier protein is albumin,

a.       If liver disease and albumin is decreased your calcium goes down, but not starting to see dysfunction because ionized calcium is normal

b.      Most active form in ionized, will not change

c.       If you see increased Calcium, look at hyperparathyroidism or bone disease – anything that causes a breakdown of bone

d.      Acute pancreatitis – decrease in Calcium

e.       Frank decreased Calcium symptom is muscle rigidity - tetany

Phosphorous – elevated think renal function and secondly depending on the calcium status, look at the parathyroid. 

Blood chem.

Liver and pancreatic enzymes,

a.       Amylase associated with pancreatitis or any inflammation in the area, acute onset, goes up and comes down quickly

b.      Lipase is a better indicator since it goes up and stays up later

AST, ALT GGT

a.       ALT and GGT more specific in liver disease

b.      AST and Alk phos can find in other parts of the body

c.       Alk phos may need to fractionate it to see if is been, liver, small intestine

d.      But as a general rule if these enzymes go up 10 fold to 100 fold

e.       GGT is the one we like to use for alcohol consumption – if abusing but don't have frank liver disease, GGT may go up.  Many drugs such as phenytoin/dilantin may also cause it to go up.  Pathways in the

f.       Alk Phos – good indicator of biliary destruction

g.      ALT can be elevate in biliary obstruction

h.      AST to ALT ratio – associated with acute extrahepatobiliary obstruction, to see where it is coming from

Cardiac Enzymes

a.       CK with MB band (creatine kinase enzyme) different bands (muscle, brain,)  MB for MI event, will go up.  A couple hours after the chest pain, esp if MB band starts to increase (btw skeletal muscle vs. heart)

b.      LD isoenzymes– monitor myocardial infarction, looking for LD1 to LD 2 flip, can monitor them several days out from actual chest pain incident

c.       Myoglobin – good test, protein from muscle metabolism, good test for early onset MI, the come in you take it, in normal limits,  repeat again in an a hour, if it never increases over a 3 hr period it decreases likelihood of MI.  Better used as a negative indicator.  Als doing CK intervals with troponins at same time

Troponin T and I test

Lipids

a.       Total – cut off is 200

b.      LDL – cut off is 100

c.       HDL for man greater than 40, for a woman greater than 50

d.      Best indicator is total cholesterol to HDL ratio, sometimes can have elevated cholesterol, but a high HDL, so look at total to HDL ration – so hi HDL – indicated decreased CVD risk

e.       Can look at LDL and HDL ration, LDL up and HDL down – then poor indicator, as HDL increases and LDL down, ration improves and decreased risk of CVD

f.       Triglycerides – more attention with metabolic syndrome risk and can be athrogenic depending on size of triglycerides.  If elevated, affects HDL esp with metabolic syndrome X or insulin resistance

g.      Lipoprotein a – risk factor for CVD, even in absence of abnormal cholesterol, hereditary

h.      Homocysteine – amino acid, metabolism of Vitamin B12 and folate- look at it as independent risk factor for CVD

i.        HsCRP – another independent risk factor, produced by liver, but has is measure din smaller increments to be more reflective of inflammation associated with CVD (new research shows CRP is elevated in periodontal disease, after extraction CRP decreases)

Glucose

Diabetes

a.       Fasting blood sugar alone can be flawed esp with insulin resistance type syndrome

b.      List of when to order this

a.       Family hx

b.      Obese

c.       Unexplained

Hypoglycemia -  more recognized postprandially can be a precursor or indication of diabetes further on down the line

a.       Increased glucose, increased metabolic need, pregnancy, hyperthyroidism, trauma, stress, surgery

b.      Many of these tests can be affected by anxiety, mental stress.

c.       Key with glucose, know the different types

d.      Fasting, random, timed postprandial, vs. true glucose tolerance test – all to understand glycemic control in an individual

e.       Fasting blood sugar levels have dropped – normal used to go up to about 109 or 110 on our labs it goes up to 100.

Classifying

a.       Fasting blood sugar Normal btw 60 and 100 – fasting – normal glycemic control

b.      Random blood sugar– there is no reference range, no normal for this as it depends on when the meal occurred, usually highest within hour right after the meal

c.       Impaired glucose tolerance – people who have insulin resistance PCOS, Cushing’s etc.  The numbers = FBS: greater than 100 –126 mg/dL in impaired glucose tolerance range, not frankly diabetic but picture of dysglycemia.  For a Random BS:  anything greater than 140 mg/dL. 

d.      Diabetes:  doesn’t matter what type of diabetes, it is greater than 126 or random greater than 200 mg/dL

e.       2 Hour post prandial – in an individual who could have dysglycemic problem could have a fasting blood sugar in normal range, but could be in upper range – of normal. 

Look at fasting blood sugar first.

So for 3-5 hr GTT 

Need at least 2 values to diagnose DM

	FBS (60-110)	Random – no nml value	2HPP	3-5Gtt
Impaired Glucose Tolerance	>100-126 mg/dL	>140	>140	>140
Diabetes Mellitus	>126	>200	>200	>200 x2

2 hr post-prandial and GTT to screen for gestational diabetes, >150 for pregnant female

Glycosolated Hgb – not meant to be diagnostic nml range up to 6 % if over then some type of problem exists.  Monitor their hemoglobin, anything below 7.8 is good glycemic control

End products of metabolism

a.       BUN and Creatinine think renal disease

b.      Creatine more sensitive for renal disease as it can be pre-renal and post renal.  Pre renal can be metabolism or breakdown (increased metabolic needs) and impairment of KD function

c.       Primary Addison’s – hypoadrenal, BUN goes up secondary to metabolic or a breakdown – get muscle wasting and heart size shrinks. IF you have a secondary hypoadrenocoritcal type problem = Addison’s disease – of the pituitary – BUN is not affected. 

d.      Creatinine, byproduct of muscle breakdown, more reflective of renal function than BUN.  Could be nml BUN and creatinine could creep up, Creatinine is more specific to kidney disease.  Look at the ratio to monitor renal failure. In early stages, could be just increased creatinine. 

Uric acid – gout – but when having a gout episode it is lower since the uric acid has moved into joints, so need to re-check afterwards to see if it goes up, and can do 24 hr.  Also for renal disease and leukemia

Bilirubin

a.       Total increase is associated with intrahepatic, prehepatic and extrahepatic conditions

b.      Direct – conjugated – related to liver, 

c.       Indirect – unconjugated – related to bili prior to liver after heme breakdown

d.      Hemolytic disease, check AST, ALT – typically not up unless associated with hepatomegaly. LDH may be elevated?

Total protein – albumin, alpha , beta, etc.

a.       Total protein and albumin, subtract to get globulin and A/G ratio

b.      Total protein decreased along with albumin – think of liver disease

c.       Increased protein with nml albumin – looking at globulins – so second line of testing serum protein electrophoresis to see what is going on with the individual.  Albumin heaviest and most abundant next to alphas, betas, and gammas.  Will see elevated total protein with nml albumin – think of multiple myeloma

d.      Decreased total protein and decreased albumin - think liver disease

e.       If albumin is low because of liver disease, will see calcium start to go down since it is a carrier protein.

f.       Elevated albumin –dehydration

g.      Globulins – look specifically to see where spike is IgG, IgA, etc

h.      Multiple myeloma – Bence Jones proteins

i.        Waldenstroms – check this

j.        Look at M spike, monoclonal spike

Iron studies

a.       Def states and utilization problems

Thalassemia and iron def – but ferritin is nml to elevated

Inflammatory – chronic can look microcytic – but check ferritin and can be nml to increased since body is not utilizing it

Vitamins

1.      B12

2.      Methylmalonic acid – elevated in B12 def

3.      Folic Acid

4.      Vit D 25 hydroxy is best indicator

i.        Every MS (look at Vit D status in MS patients)

Hormones

a.       Adrenal hormones

a.       Cortisol – can also test DHEA bound or Sulfite the bound form

b.      Unbound form in salivary testing

c.       Cortisol levels – if low cortisol levels – thinking adrenal hypofunction, need to determine is it primary situation or secondary situation?  Adrenal gland itself or hyp/pit axis?

               

d.      Can test ACTH in pituitary in secondary hypoadrenalism looks a bit elevated like Addison’s – it will be low

e.       If primary problem ACTH is elevated, cortisol is low

f.       When elevated – hi cortisol – Cushing’s – just testing ACTH doesn’t always tell you where it s coming forms since tumors can put out ACTH – such as one of the lung cancers (small cell)

g.      Do dexamethasone suppression test – for Cushing’s – testing cortisol afterwards

h.      Nml it would decrease your serum cortisols it would suppress ACTH

i.        In Cushing’s would still have elevated cortisol

j.        24 hr cortisol – good because of diurnal variations

b.      DHEA – free and unbound to differentiate PCOS ovarian cause vs. adrenal cause and Cushing’s which it would be elevated

a.       Hypof(x) state of adrenal glands would see a decrease in DHEA, and these are higher when younger and decreases as you age.

b.      Postmenopausal women, testosterone levels, fatigue in elderly

c.       Testosterone – total and free – total can be within nml limits but unbound elevated in PCOS

d.      Pituitary hormones

e.       FSH, LH

a.       LH   to understand amenorrhea, FSH greater than 30

b.      LH/FSH ration in PCOS

c.       Infertility will check FSH or LH right before ovulation

d.      Or to see if ovarian failure – stops menstruating under 40 yo

f.       Prolactin

a.       Amenorrhea, unexplained galactorrhea

b.      Seeing if there is a prolactin secreting tumor

g.      Fasting insulin with 3 hr GTT

a.       Insulin 6-26 in fasting – fasting insulin with fasting glucose in PCOS, can see ration of glucose to insulin. IF  insulin going up with nml glucose ration starts to drop, below 4.5 in a women with oligomenorrhea or amenorrhea, starting to think of PCOS.  Glucose to insulin ration should be greater than 4.5. IF insulin over 26, that drops that ratio below 4.5 = indicator of PCOS.  Better than FSH to LH ration

b.      Run with GTT – as there are nml ranges for 1/2 hr 1hr 2 hr and 3 hr. so for metabolic syndrome X their insulin go through the roof

h.      PTH

a.       For Ca metabolism

b.      Order if see elevated Ca in the face of a nml alk phosphatase

c.       Might look at PTH to see if that is what is going on

i.        Thyroid testing

a.       TSH is screening test

b.      Sensitive but not t very specific

c.       Free T4 at same time as TSH

d.      TSH – primary vs. secondary hypo or hyperthyroidism

e.       Pituitary vs. hashimotos or graves dz or post pregnancy or sub acute thyroiditis

f.       Hashimotos, Graves, sub acute thy, euthyroid sick syndrome and TSH, free t3, free T4, FTI – in each of these categories to understand the differences.

g.      FTI – free thyroid index was developed when we didn’t have the ability to measure the unbound form of thyroxine, so it was a calculation using total t4 to T3 resin uptake – indirect way of looking at binding capacity.  FTI – quasi indicator of active form of T4.  But now have free T4, so use this instead.  Many flaws with FTI esp with pregnancy and liver disease esp when binding globulins are affected by estrogen. Know its use

h.      FTI up -= hyper

i.        FTI down – hypothyroid

j.        Primary hypo – TSH up, free T4 drop

k.      Thyrotoxicosis – really elevated T3, very specific picture, T3 thyrotoxicosis is emergency situation – in initial phase or transitional phase of Hashimotos or graves

l.        T3 is key and extremely elevated

m.    Hypothyroidism such as has – Hi TSH, low T4 and low T3 eventually

n.      Graves – AI, secondary testing of anti..

o.      Suppressed TSH, Up free T4 and free T3

p.      Outside of AI disease

i.        Thyroiditis, secondary to pregnancy

ii.      Transient hyperthyroidism

q.      TSH elevated – in mildly elevated – still runs auto antibodies, can see a 3.5 TSH and runs autoantibodies, most come back with auto-immune esp if have strong family hx

r.        Reverse T3 – use it for Wilson’s Syndrome not disease correct handout

i.        Used to think more euthyroid sick syndrome, low nml TSH and lo nml T3 and T4, reverse T3 will see it elevated as it is moving into non-active form of hormone, which is a survival mechanism of body – she thinks – anorexia, starvation, acute illness, yoyo dieting.

The Poop tests

Do not refrigerate stool cultures, kills bacteria

Get it to lab 2 hrs after fresh collection, or get it in Cary Bleir – 24 hrs

Stool electrolytes – run these in cases of diarrhea –– tells you that you are losing Na and K, an acute diarrhea that can kill you – such as shigella or typhus

Wet mount – read it, Trich dies if it gets cold

KOH scrapings – tinea, ptyrisias, candida

Autoimmune

a.       ANA a screening test, very sensitive but not specific, suspecting CT disease

b.      See handout

c.       Pos ANA >1:40

d.      Interpret pattern, and based on that some are specific to certain conditions

a.       Lupus – double stranded DNA or anti SM

b.      Scleroderma

c.       Sjogrens

d.      Mixed CT disease very high Anti-RNP

e.       Can do ANA reflective, depending on pos ANA and the pattern they will automatically run the specific antibodies

f.       AntiTPO most sensitive for hashimotos and graves disease

g.      Pos antiTPO – TSH suppressed hi T4T3, tachycardia, sweating, etc.

Rf – if you have symmetrical jt pain, jt inflammation of smaller jts esp in hands an in ankles, although Rf is not specific, sensitive but not specific, 70-80% of pts will be positive, will have others be false negative

Looking at CT tissue diseases, look at criteria for RA, Scleroderma, Lupus,

For RA need 4 out of 6 or 8 conditions– review from phys clin – Heberdens

CRP – best indicator of acute inflammation, declines rapidly

HLA – ankylosing spondylitis

Hepatitis

IgG – chronic

IgM- acute

  Best way to understand HCV Pos – then test PCR for viral load and get liver staging and monitor liver by looking at ALT

Hep B more complex as far as presentation b/c of underlying or superinfection Rule of thumb – if jaundice and concerned regarding Hep B run Hep B surface Antigen – virus still there, then look at core and

Surface doesn’t start to go up until about 2 weeks.

Once the antigen has dropped off, Hep B surface antigen and only see surface ab and or core together = convalescent phase, seroconverted and virus is gone. 

Hep B vaccine is surface – IgG

Hep B acute phase – IgM

Causes the fulminant hepatitis – kills people

HIV

ELISA vs. Western blot

ELISA is screening

Western blot is confirmatory

ELISA pos – automatically reflects into  a Western Blot

Western Blot pos = confirmed post HIV

Then looking at viral loads and CD4/CD8

CMV

Problematic in newborns since they don’t have the immune system to deal with it

Looks like mono but never has pharyngitis, primary affects the liver and spleen

Can be sexually transmitted

Have fatigue picture

CMV in acute can cause leukomoid reaction – hi WBC, lymphocytes and atypical lymphs

ASOT – looking for sequelae of group A hemolytic strep – esp with jt pain and renal problems  - rheumatic fever, glomerular nephritis, endocarditis

EBV

Only do if heterophile test is negative, and if need to go to CMV

Check with CFS and looking at a reactivation of the IgG antibodies – IgG antibodies would start tot spike back up.  IgM only in acute phase with mono

Syphilis

RPR, VLDL – screening

Confirm with see notes

There is screening and confirmatory

Classic test for spyhillis diagnosis is darkfield microscopy

H Pylori

Urea breath test

Biopsy from tissue

Serology test

Stool test now test for H pylori and/or treat for H pylori need to do urea breath test or stool test. 

Indicated in people with ulcers and gastritis

pulm function test

Acidosis – high CO2	Alkalosis – Low CO2
PH <7.4	PH > 7.4
Either Resp or Metabolic	Either Resp or metabolic
Measure arterial CO2 levels If pCO2>40 vs. pCO2being <40 mmHg IF pCO2 > 40 problem is probably in lungs because your lungs are not dumping it, not doing their job. Hypoventilation state with pCO2>40 – lung pathology, resp acidosis	Alkalosis pCO2< 40 vs. pCO2 > 40 If low CO2 – hypoventilation want more CO2 pCO2<40, lungs are not doing their job – should be brining up the CO2, in respiratory alkalosis, lungs not compensating
Metabolic acidosis with compensation, pCO2 < 40, lungs working, hyperventilating, blowing off their CO2 – so where is metabolic acidosis coming from	Resp – hyperventilation – pathological not compensatory, should be conserving CO2 Or early response to acid ingestion
Anion gap – Diarrhea – you are not reabsorbing your buffer so moving into acidic picture leads to metabolic acidosis Vomitting	Metabolic alkalosis pCO2 >40 – lungs are working but still in alkalosis – so V, diuretic use, antacid use, hyperaldosteronism Vomitting – losing HCl -  lungs will be hypoventilating, conserving CO2 = compensatory hypoventilation
Anion Gap