Clin path

fasting glucose plasma level

anything above 126 mgm/dI on two different occasions indicates diabetes

random glucose level

above 200 mgm/di indicates diabetes

what are relevant antibodies for diabetes type 1

glutamic acid decarboxylase 65 (GAD 65), insulin antibodies (IAA), and islet cell antigen 512 (IC-512)

where are beta cells found

inside islet cells in the pancreas

what is the cause of type 1 diabetes

autoimmune destruction of beta cells(causing no insulin production)

glycemic control

this is a test for type-2 diabetes done every 3 months, it can help prevent microvascular complications. The standard test is AIC, using hemoglobin

what test can be used for people with diabetes and hemolytic anemia

glycosylated protein testing (fructosamine). This testing can be done every 3 weeks due to the short half life of fructosamine.

what may cause hypoglycemia

self-injection of insulin or sulfonylurea drugs. Alcohol use can also prevent the liver’s production of glucose.

how can you determine if hypoglycemia is self-induced or disease based

look at the c-peptide levels. If insulin is high but c-peptide is low this indicates exogenous insulin

what are the hormone deficiencies for hypoglycemia

catecholamines, glucagon, cortisol, and growth hormone

what is non-islet cell tumor hypoglycemia (NICTH)

mesenchymal tumors made of fibrous tissue that make insulin like products (insulin-like growth factor II, IGFII). The high levels of IGFII increase glucose utilization, this can also lead to suppression of endogenous glucose production

what are the tests for checking non-islet tumors

fasting hypoglycemia, low insulin levels, low proinsulin, and low c-peptide

what is the first pathway of diabetes complications

the formation of advanced glycation end products (AGEs) effects and non-enzymatic glycosylation of proteins. This will lead to accellerated atherogenesis

what is the second pathway of diabetes complications

activation of protein kinase-c effects, the production of pro-angiogenic molecule vascular endothelial growth factor (VEGF), implicated in the neurovascularization of diabetic retinopathy.

what is the third pathway of diabetic complications

intracellular hyperglycemia with disturbances in polyol pathways, leading to reduction in GSH; which leads to increased susceptibility to oxidative stress and accumulation of sorbitol

what are the morphologic changes in the pancreas for type-1 diabetes

reduction in size and number of islet cells, insulitis, beta cell degranulation, and eosinophils in newborns.

what are the morphologic changes in the pancreas for type-2 diabetes

amyloid replacement of islet cells. Newborns will have hyperplasia of islet cells to protect themselves from their diabetic mothers. Silent MI and gangrene is also seen.

what is an insulinoma

beta cell tumor, typically benign, small tumor size, has small round cells, and crystals with granules on EM. Clinical symptoms may include hypoglycemia, confusion (fainting) and low tolerance for exercise.

what is zollinger-ellision syndrome (gastrinoma)

there is an excess of gastrin produced, leading to excess acid. This can cause peptic ulcers in the stomach and increased motility in the small bowel, causing diarrhea.

what are alpha cell tumors

there is increased glucagon, mild diabetes, shin rash (itchy skin), and anemia.

what are the clinical signs of delta cell tumors

diabetes, steatorrhea (fatty stool) and cholelithiasis

what are the clinical symptoms of VI POMA/WDHA syndrome

watery diarrhea, hypokalemia, and achlorhydria. It is typically locally invasive but it can met

what is the clinical presentation for pancreatic carcinoid tumors

nausea, vomiting, thirst, weakness, increased glucose, increased potassium, and acidosis with an increased anion gap.

what are the tests used for the old standard in cardiovascular testing

cKMP serial determination of LD flipped ratio

what are the isoenzymes of creatine kinase

CKMB: found in the heart, CKBB: found in the brain, and CKMM: found in skeletal muscle.

what are the important times for CK testing

CK starts to rise 4-6 hours after event, peaks at 12 hours, and stays elevated up to 72 hours. You should do serial measurements every 3-4 hours.

What are the isoenzymes of lactate dehydrogenase

LD1: is RBC and heart, LD2:non-specific, LD3: lung, LD4: non-specific, and LD5: liver. LD levels don’t rise until 24-36 hours after event. It will last for 3 days. You use the flipped ratio to see if LD1 is higher than LD2 (indication an event)

what are we looking for with myoglobin testing

myoglobin is present in heart and skeletal muscles. You cannot distinguish between heart and muscle myoglobin, but the test can let you know if its elevated and you should do further testing

what are the three subunits of troponin

TnI: inhibitory subunit, TnT: tropomyosin-binding, and TnC: calcium-binding subunit. TnI has a cardiospecific form never seen in other tissues and TnT should have a myocardial specificity approaching 100%.

what are the levels for TnI in acute MI

elevates 4-8 hours after cardiac event, peaks at 12-16 hours, and remains elevated for 5-9 days

What are the important troponin levels

less than 0.5mg/dl is healthy, 0.5-2 mg/dI is unstable angina, and MI values are above 2 mg/dI

what are other uses for troponin and CK-MB tests

to document infarction, to monitor extent of disease, to detect reinfarction, monitor drug performance, and detect AMI during surgery

what are markers for coronary risk

high LDL cholesterol serum

what is c-reactive protein and what are some important values

this is an inflammation marker that can inform the risk of heart failure. A normal value is 1 mgm/L, AMI risk is 1.51 mgm/L, and stroke risk of 1.38 mgm/L. This test is highly sensitive

BNP (beta type natriuretic peptide)

is a marker for early HF that is diagnostic and prognostic.

HCY

Homocysteine can indicate diminished levels of metabolic enzymes. In familial cases it can cause, osteoporosis, mental retardation, dislocation of the lens downward, psychiatric disturbances, and thromboembolic diseases.

How does HCY impact risk of heart failure

People with HCY levels in the upper 5% have a 3-4 fold increase in risk. The cardioprotective effect of lowering HCY in pt with acquired HCY is folic acid.

what are some tests used to check the immune system

CBC, T-cell count, B-cell count, immunoglobulins, complement, and phagocytosis

what can flow be used for

to check T and B cells, and with T-cells look at PHA stimulation

how do we test for phagocytosis

NBT (nitro-blue-tetrazolium). To test for NBT, superoxide produced by activated PMN’s which reduces NBT to formazan (dark blue granules). There are no granules in CGD.

B-cell IgA deficiency

pt will present with recurrent respiratory tract infections, malabsorption, diarrhea, and giardia infection. There is a risk of anaphylactic reaction if plasma given to a patient is IgA positive (the patient MUST be given IgA negative)

common variable immune deficiency

B-cells are defective in plasma cell maturation. There will be recurrent infections and low helper T-cells. This poses a high risk for B-cell lymphoma.

bruton’s agammaglobulinemia

X-linked, manifest at 6 mo. after baby does not have mothers IgG cells. Will have recurrent infections.

DiGeorge’s Syndrome

Caused by a defect in the 3rd and 4th pharyngeal pouches. The baby is born with no thymus, therefore no T-cells, no parathyroid hormone. They may have tetany, hypocalcemia, facial abnormalities, and heart issues.

SCID

(severe combined immunodeficiency)This is a combined T and B cell disease. 50% are X-linked and caused by genetic mutations. The common alpha chain shared by the receptors for cytokines IL-2, IL-4, IL-9. 50% is autosomal recessive due to a mutation in ADA (adenosine deaminase).

Wiskott-Aldrich Syndrome

due to a defect in the WASP protein. It is x-linked, will have repeated infections since birth, thrombocytopenia with small platelets, low CD4, eczema, low IgM, high IgA, and high IgE.

Complement

there are 9 different types, C5a is needed for chemotaxis, C3b is to enhance phagocytosis.

Give the steps of the complement pathway

1. Recognition and attachment: with IG and CC3b, the high affinity receptors recognize opsonized organisms and we will have chemotaxis of the WBC towards the infection via C5.

2. Engulfment: the infection will bind to the phagocyte receptor and the phagosome will enclose it.

3. Killing: the phagosome binds to a lysosome in the cell, filled with digestive enzymes, that will release granules to kill and destroy the infection

what are the deficiencies of complement and how to the present

C3: infection

C2 & C4: autoimmune diseases like RA and Lupus

Chediak-Higashi Syndrome

defects in the CHS1 gene, responsible for cellular organelle trafficking. There is a defect in lysosome and vesicle fusion. On peripheral smear, there will be giant lysosomes in leukocytes. With this syndrome there is a higher risk for lymphoma and leukemia.

Job’s Syndrome

also known as hyper IgE syndrome, presents as recurrent staph infections, very high IgE, eosinophilia, and defects in the Th1/Th2 balance

what does SF do

acts as a lubricant for joints

what are important values for inflammation in SF

leukocyte count 3000-75000/MI, mostly neutrophils (>50%)

what is reiter syndrome

this is an infection of the joints, with reiter cells, clinical manifestations are can’t walk, pee, or climb a tree

what are the 3 separations needed for SF testing

1- must be sterile for cultures and smears

2- put in sodium heparin for microscopic examination

3- put in plain tube, no anticoag, for chemical analysis

what does SF turbidity look like

there will be rice bodies (which are fragments of degenerating proliferative synovial cells and indicate damaged synovium and microinfarctions

what does viscous fluid need to be treated with before cell count

hyaluronidase

what is included in a microscopic examination of SF fluid and what can findings indicate

normal cell count is 150-200/MI, counts over 10,000 may be related to: gout, pseudogout, RA, SLE, and crystal induced arthritis. Counts less than 10,000 can indicate osteoarthritis or osteochondritis.

what are ragocytes

they are neutrophils containing fat droplets with blue-black granules, and are a sign of RA and pose as a poor prognosis.

what are the expected levels of macrophages/monocytes in SF

65% in normal. In abnormal you can see reiter cells (macrophages with degenerating neutrophils)

how should you test for SF crystals

do the first exam fresh, than refrigerate for 24 hours at 4 C and check again. An increase in the number of crystals indicates positive fluid.

what is the rope test and its implications

you place a stick in SF and swirl it around then pull up the stick and analyze the SF behavior. Normal SF will be viscous like honey and pull up, abnormal SF will be runny like water.

what is the first lab you will do to test for amenorrhea?

run HCG to R/O pregnancy, greater than 5 ml indicates pregnancy. Also check prolactin, TSH, and free T4.

what should you run if lab tests come back normal when testing for amenorrhea

look at endogenous estrogen status via progestin withdrawal test (give one injection or orally over 5-7 days). After 7 days you will see if there is bleeding withdrawl

what does it mean if after progestin withdrawal test that bleeding is absent

you need to perform imaging of the ovaries and asses for LH and FSH. High LH and FSH indicate primary ovarian failure. Low FSH and LH indicate secondary ovarian failure (i.e. weight loss, stress, ED, and Sheehan syndrome.

what can show as a risk for premature membrane rupture

if fetal fibronectin is secreted in the vagina. Though there may be false positives after intercourse. Intact membranes and increased fetal fibronectin may indicate risk of premature labor within 7 days.

what transport requirements are needed for seminal analysis

delivered within 1 hour of collection and kept warm during transport. Before collection it is also important that the bladder is empty.

when does HCG reach its peak in pregnancy

it reaches its peak at 10 weeks

what does it mean if HCG continues to rise after 10 weeks

it may be a trophoblastic tumor

what can alpha-fetal-protein (AFP) tell us

this can help us detect neural tube defects, if AFP is high, this indicates a neural tube defect. AFP may be lower in mothers that are obese, women with insulin dependent diabetes will have a lower MSAFP, twin gestations may have higher MSAFP. If the MSAFP is abnormal, you should check the amniotic fluid AFP.

what are the lab results that can indicate down syndrome

decreased MSAFP, decreased unconjugated estriol, increased HCG, and increased inhibin A

what should you see macroscopically in seminal fluid

there should be liquefaction within the first 20 minutes at room temp, failure to liquify indicates poor prostate secretion

what is the normal pH of seminal fluid

7.2-7.8, if it is greater than 8, it is a sign of acute infection, if it is less than 7 it is a sign of urine contamination, or an ejaculatory duct obstruction.

what do you need to do for the microscopic analysis of seminal fluid

take count in at least 4 different fields in 2 specimen aliquots, and record the mean of 8 different readings recorded

what are the grades of sperm motility

Grade 4: is the best and sperm move rapidly and in a straight line, with little yaw

Grade 3: sperm is slower moving

Grade 2: even slower moving and substantial yaw

Grade 1: no forward progression

Zero progression: no motility at all

If motility is less than 50%, a viability stain is done and Eosin with nigrosin is used as a counter stain

how do sperm look in brightfield

dead sperm will be red and live sperm will be unstained

what is done to post-vasectomy samples

the sample is spun and the pellet is examined for intact or damaged sperm fragments, the test should be done again 4-6 months post-op.

what is agglutination

when motile sperm stick together in an orientation that is repeatable. There is head to head, tail to tail, side to side, and mixed. All of these indicate sperm antibodies and an immunologic cause for infertility.

what is the most obvious characteristic of abnormal sperm

variability of the acrosomal cap. Caps that are more than 1/3rd of the head surface is abnormal.

what does clumping mean in sperm

infection or debris and has a non-specific orientation.

what antibodies should you look for in sperm immunologic tests

IgA and IgG, IgA is most clinically significant. It is best read under phase contrast. Sperm antibodies in men can indicate post-vasectomy, infections, obstruction, cyrptorchidism, torsion, or testicular biopsy. Sperm antibodies in women will show severe mucosal inflammation of the genital tract

where does neutral alpha-glucosidase originate from

it comes solely from the epididymis and detects obstruction

what is renin and where does it come from

renin is a proteolytic enzyme made in the JG cells of the macula densa of the kidney. It comes from the larger protein big renin. Renin will be converted to its active form in the JG cells. It is regulated by cAMP.

what can renin trigger

hyponatremia, hyperkalemia, decrease in catecholamines, angiotensin II, arial naturetic hormone, and hydrostatic pressure.

what does renin do

it acts on angiotensinogen-alpha-2-globulin (made in the liver) and converts to to angiotensin I

how does angiotensin I become angiotensin II

the ACE enzyme (found in lung and vasculature epithelium) will convert I to II

what is angiotensin II responsible for

aldosterone stimulation, which can lead to increased BP (angiotensin II is split into angiotensin III, which modulate aldosterone secretion

where does aldosterone synthesis happen

zona glomerulosa of the adrenal gland

what are causes of hypertension and high renin

renal parenchymal disease, renin excreting tumors, malignant hypertension (diastolic BP higher than 110- can be treated with ACE inhibitors)

what can you do to see if surgery would be beneficial for renal vasculopathy

take the renin value from the impacted vein and divide it by the value of the normal vein, if the ratio is 1.5:1, surgery will improve the outcome

what is the cause for hypertension and low renin

licorice herb, which stimulates aldosterone production

what are causes for normal renin and hypertension

primary hyperaldosteronism, which can best tested using PAC (plasma aldosterone concentration)/PRA(plasma renin activity). PAC/PRA over 30 is suggestive and over 50 is diagnostic. Another test is the saline suppression test, if levels of aldosterone are greater than 5 ng/dI at the end of 4 hours it is diagnostic.

Wilson’s disease

autosomal recessive disease, with mutation in ATP7B enzyme (responsible for excreting copper into bile and out of body) leading to copper build up in liver and blood (then going to other organs like brain, eyes, and kidneys). Clinical symptoms may be CNS manifestations like tremors, Kayser-Fleischer rings, cirrhosis, and hemolytic anemia. To diagnose you need to do a liver biopsy and found the amount of copper per dry weight of the liver. Other screening can include KF rings, low ceruloplasmin, and increased 24 hours urine copper levels.

hereditary hemochromatosis

clinical symptoms can include pedal edema, diabetes, bronze skin, splenomegaly, and ascites. Screening tests include serum FE and TIBC (morning fasting specimens are recommended). Hepcidin negatively regulates interstitial Fe absorption (hepcidin will be low in these pt)

what does hepcidin regulate

macrophage Fe metabolism

antitrypsin deficiency and liver disease

in patients with the Z allele, AAT has a zyline substituted for glutamate, leading to spontaneous polymerization. The lack of the enzyme causes failure of neutrophil elastase inactivation, causing a breakdown of aveolar tissue (leading to emphysema). On liver biopsy there will be PAS + granules in the hepatocytes.

describe the process to get conjugated bilirubin, starting from heme

heme gets broken down to biliverdin via heme oxygenase. Then biliverdin gets converted to unconjugated bilirubin via biliverdin reductase. Unconjugated bilirubin will bind to albumin, making it water soluble. The water-soluble form is delivered to the liver. It will be conjugated in the liver (the enzymes involved in conjugation are UDP, UGT, and UGT1A1)

where is conjugated bilirubin excreted

the small intestine via the biliary tract to the ampulla of vater

what are 2 common disorders if you cannot secrete bilirubin

Rotor’s and Dubin-Johnson syndrome

what labs should you look at for hepatocyte integrity

LDH, AST, and ALT