Clin Path - Proteins

drraythe's version from 2015-12-05 22:39


Question Answer
where are almost all plasma proteins produced?The liver
what are the major proteins produced by the liver?Albumin, alpha-globulins, and beta-globulins (aka fibrinogen)
which plasma proteins are NOT produced in the liver? WHERE are they produced?gamma-globulins (immunoglobulins) are produced in the B-lymphocytes and plasma cells
beta-globulins akafibrinogen
gamma-globulins akaimmunoglobulins
what is the average value of plasma total protein? what are the MAJOR components of the total protein? in what amounts?PTP= 7.6 g/dL(5-8g/dl). The two main components are (1) Albumin (3.5g/dL) and (2) ALL of the globulins (4.1g/dL). [If SERUM total protein, then globulins are 3.8g/dL b/c the fibrinogen aka beta-globulins are consumed]
which protein is not in SERUM total protein?beta-globulin (which is fibrinogen) because to get serum you clot the blood sample, which uses up the fibrinogen
a change in total protein usually indicates a change in what?either albumin, or one or more of the globulin values
what are the major roles for albumin?(1) binding prot for many substances, esp important fxn regarding total serum [Ca++] (2) Major contributor to oncotic pressure\
major physiologic role of lipoproteins? examples?transporting lipids. (chylomicrons, VLDL, LDL, HDL)
major physiologic role of Antiprotease proteins?Inactivate inflammatory proteases (a1-antitrypsin, etc)
major physiologic role of Haptoglobin?Binds hemoglobin dimers in plasma
major physiologic role of Transferrin?Transports iron (Fe3+)
major physiologic role of Immunoglobulins?Bind antigens (opsonization)
major physiologic role of Fibrinogen?converts to fibrin for hemostasis
what is the half life of plasma albumin? any sp diffs? significance?Usually about 1 week (dogs). In horses can be 3 weeks. SIGNIFICANCE= if cease production of albumin, wont see for minimum of 1 week, and takes longer for hypoalbuminemia to develop when albumin production decreases in horses esp.

Importance of Proteins in Pathology

Question Answer
what is Protein dyscrasia? what is Dysproteinemia?dyscrasia= abnormal protein. Dysproteinemia= abnormal concentration OR abnormal protein
what does Nonselective dysproteinemia mean? examples?means all proteins affected(by abnormal conformation or concentration). examples are how dehydration/hemodilution make ALL proteins an abnormally high/low concentration
what does Selective dysproteinemia mean? examples? not all proteins affected(abnormal or abnormal concentration). Examples include chronic inflammation (dec albumin and inc globulins), or protein-losing nephropathy (albumin is smaller so most of it's lost, not all globulins will be lost)
how do albumin and globulins act in inflammation?alb dec and glob inc (Al hides from inflammation. and things will GLOB UP in inflammation)
what are acute-phase proteins?Changes in production occur soon after onset of inflammation (therefore, part of acute response)
explain the time frame for positive acute-phase proteins. Give examples of these in concentration a few hours to a few days after onset of inflammation. examples include haptoglobin, fibrinogen (if inflammation or damage, need clotting right away and need to clean up blood right away)
explain the time frame for negative acute-phase proteins. Give examples of these proteinsdec in concentration in weeks. examples include albumin, transferrin (Al runs away from inflammation, and does so by transferring schools)
what are delayed response proteins? examples? (what is the diff between the acute and the delayed response proteins?)Changes in concentrations occur 1-3 wk after onset of inflammation. Examples include Ig’s, complement proteins.(remember, immune response takes a while to form) The ACUTE proteins are usually inc in specific ones, and might not inc the TP. The delayed response proteins may cause inc in TP
methods for measuring TP--> what would you use to measure pTP of CBC? How about for Chemistry profile?(1)CBC (serum or plasma): Use a refractometer. (2) Chemistry(serum or heparinized plasma): Uses Biuret reaction. (you're probably Bi if you like chemistry)
How does a refractometer work? What must be known/considered when using this?works by measuring bending of light due to presence of proteins. so the prot conc is inversely proportional to the refractive index. It is important to know that the refractometer assumes that non-protein solids are the same levels(are not abnormal) and any change in the refractive index is due to a change in proteins alone
what are some non-protein solids which can screw with a refractometery reading? which WOULDNT interfere?and inc in glucose, urea, Na+, and Cl- would interfere with a reading. any amount of lipemia, or Excess EDTA in blood would also interfere. Her notes say "bilirubin, no inc, does not interfere"
what is the most common TP measurement for SERUM? How does it work?Biuret reaction. Copper binds to peptide bonds in proteins. (Bi guys wear lots of copper jewlery)
how would you measure albumin? how does it work/interferences?BCG dye-binding reaction. Dye binds preferentially to albumin, but might also dye to some globulins, and hemolysis interferes also (might bind to heme pigment or Hb) (can also use protein electrophoresis) (Al is a BigCockGobbler)
how do you measure globulins?you subtract the albumin value from the TP value. only as accurate as first two measurements. (can also use protein electrophoresis)
how can you measure fibrinogen concentration in plasma?Heat precipitant method! first get TP refractometery value. Then heat sample, and then measure again. Then [TPpreheat]-[TPpostheat]= apprx fibrinogen value. (ok for finding HYPERfibrinogenemia, not so much for HYPO".)

protein imbalances

Question Answer
When would you see hyperfibrinogenemia?minor increases in hemonconc(dehydration). Much larger increases in inflammation
when would you see hypofibrinogenemia?see during inc fibrinogen consumption--> DIC (also dec in production, but uncommon, causes would be hepatic insufficiency and Afibrinogenemia(congenital or inherited) )
Serum Protein Electrphoresis(SPE) determines what? how does it work?It determines PROTEIN FRACTIONS (how much of what protein). Works by Separate proteins into bands (groups) based on electrical charge and size of molecules. (place sample on one side of gel, run electricity through gel, proteins migrate and settle together in diff spots)
what does a normal electrophoresis of pTP look like?(reading L to R, sample places far R) one big first spike (albumin, the smaller protein, and lots of it, so at far end and tall spike/darkest band) and then 4-5 smaller spikes/bands that are the globulin fractions
Regions of the electrophoresis in order (L to R) are Albumin-->alpha1-->alpha2-->beta1-->beta2-->gamma. What is in each of these regions?albumin. a1=(stuff that has a1 in front of it). a2= Haptoglobulins. B1+B2 Has IgM and IgA. Gamma= DELAYED response proteins, ie, IgG's!
what are the three types/ways to get hyperproteinemia?(1)Hemoconcentration/Dehydration (2)Inflammation (3)B-lymphocyte neoplasm
Inflammatory causes of hyperproteinemia are in two categories--> what are they, and examples of each?(1) infectious (virus, bact,fungi, protozoa (2) noninfectious (necrosis, neoplasia, immune-mediated)
hyperproteinemia--> B-lymphocyte neoplasms. Two types of cells that can cause these, and the names of them?(1) Plasma cell (myeloma, plasmacytoma) (2) lymphocyte (lymphoma)
most common hyperproteinemia is? explain how it workshemoconcentration/dehydration. a loss of plasma water relatively concentrates proteins (NOTE: might still be WRI, if the RI is a wide range, or if they were hypo and then the dehydration bumped them into normal range)
Inflammation causes inc protein synth. The cytokines release in inflammation stimulate (1)_________ and (2)_________ to make more proteins. explain what (1) and (2) make, and in which situations(1)hepatocytes and (2)lymphocytes. (1) Hepatocytes respond for postitive/engative acute-phase proteins and take hours-->2 days for response. only cause a mild inc in TP. (2) lymphocytes are involved in the delayed response. which takes at least 1 week. there is a mild to marked inc in TP and there is "polyclonal gammopathy" aka many B-lymphocyte clones (INC PRODUCTION OF IGs)
if using electrophoresis, what does a "delayed response" pattern look like, and why?happens after 1-3 weeks. There is an inc in TP with a inc in globulins(delayed response proteins). There is also a dec in albumin(neg. acute-phase protein). So, the albumin spike/bar which is usually the highest/darkest will go down, and then the globulin range will go WAY up/get way darker (look at pic)
what is Polyclonal gammopathy? what does an electrophoresis look like from this?when there is many B-lymphocyte clones. Globulins go way up. The gamma globulin band goes up(more compact, restricted migration) and there is an inc in the alpha-2 region(pos acute phase --> haptoglobin)
Neoplastic B-lymphocytes (myeloma, plasmacytoma, lymphoma, lymphoid leukemia) produce what? how does the electrophoresis look?Produce lots of Ig's. so the albumin goes down and a narrow region of the globulin fractions goes way up.
polyclonal gammopathy vs monoclonal gammopathy. What does which indicate? what does the electrophoresis look like?polyclonal=many clones of diff B-lymphocytes--> indicates inflammation (mult portions of globulin regions are inc). Monoclonal= prolif of ONE type of B-lympho, indicates B-lympho neoplasm (usually a single concentrated spike in the globulin region)
what is happening in Pseudohyperproteinemia? how can you check if its a pseudo?inc of pTPdue to interferences. In refractometery, happens with inc glucose, inc urea, lipidemia, excess EDTA in blood. refractometer reading should be within 0.3 g/dL of biuret reading. if greater than this, elevated levels are prolly due to non-protein substance.
what are the two ways you can get a hypoprotenemia?(1) inc protein loss from vessels (2) dec protein production by liver
Increased protein loss from vascular space cause be due to what 4 things?(1) blood loss (anemia) (2) Protein-losing nephropathy (proteinuria...caused by stuff like amyloidosis, GNitis) (3) Protein-losing enteropathy (diarrhea) (4) Protein-losing dermatopathy (burn victims)
Decreased protein synthesis cause be caused by what 3 main things? (some other not emphasized stuff too...)(1) Hepatic insufficiency (chronic acquired, or a congenital shunt--> >80%loss of fxn hepatocytes) (2) Malabsorption or maldigestion (diarrhea, weight loss) (3) Cachectic states (chronic wasting due to neoplasia or chronic dz). (also written in smaller txt is Lymphoid hypoplasia or aplasia, Failure of passive transfer, hemodilution)
can Hypoproteinemia be caused by common anorexia?no.
Protein-losing nephropathy can happen in what kinda conditions? what proteins WONT you lose?happen in stuff like amyloidosis or GNitis. You will lose albumin and smaller globulins, but super big globulins, like a2-macroglobulin, will stay in plasma
Protein-losing dermatopathy (burn patient) causes hypoproteinemia how?Plasma proteins oozing out of blood vessels--> nonselective
hypoproteinemia--> Extravasation of plasma proteins (2ndspace or 3rdspace). what is going on here? what are these "spaces"? what usually causes this?vasculitis/exudation will inc permeability of BVs-->Plasma (protein-rich fluid) oozes out of blood vessels into 2nd (extracellular space) and 3rd (body cavities) spaces. leads to non-selective hypoprotenemia.
in order for Hepatic insufficiency to show a hypoprotenemia, how much damage does the liver have to have? what proteins are not effected by this?80% damage or more must be sustained for the liver to start to not be able to produce enough proteins. Albumin and globulins will both go down, EXCEPT NOT GAMMAGLOBULINS, because those are immunoglobulins and are produced by plasma/B-cells. Thus, this is a SELECTIVE hypoproteinemia
hypoprotenemia--> Malabsorption is a prob with what organ? maldigestion is a prob with what organ? What is happening?absor--> intestine. diges--> exocrine pancreas. Not getting enough amino acids to make necessary proteins. might be selective or non-selective depending on situation
hypoprotenemia-->Cachectic States happen in what conditions? what is going on in this case?malignancies, chronic diseases are when this happens. The dz processes release chemicals that cause inappatance/anorexia. Lack of nutrients leads to a dec in protein production. there is ALSO a higher rate of protein degradation. leads to nonselective hypoprotenemia
Hypoalbuminemia's 2 basic mechanisms are?(1) dec albumin production by liver (2) inc albumin loss from vessels
can hypoalbuminemia be caused by common anorexia?no
Decreased albumin synthesis can be caused by what 4 main things?(1) inflammation (note: might have a HYPERproteinemia, but dec albumin!!!) (2) hepatic insufficiency (remember, 80% damage needed) (3) Malabsorption or maldigestion (4) Cachectic states
Increased albumin loss can be due to what 3 main things?(1) blood loss (2) protein-losing nephropathy (3) Protein-losing enteropathy ((also protein-losing dermatopathy and hemodilution)
*dont forget: what is albumins half life in blood? sp diffs?usually 1 week! in horses, 3 weeks.
Hyperglobulinemia has three types/causes. what are they?(just like hyperprotenemia) (1) hemoconc (2) inflammation (3) B-lymphocyte neoplasia
how do you differentiate between inflammatory and neoplastic Hyperglobulinemia?Serum Protein Electrphoresis (SPE). inflammatory= most of the globulin area will be raised--->polyclonal gammopathy. neoplastic= usually a single lare spike--> monoclonal gammopathy
Hypoglobulinemia usually has what two mechanisms?(like hypoprotenemia) (1) inc loss from vessels (2) dec production by liver (EXCEPT for immunoglobulins, which are made by plasma/B-cells
what does a dec. IgG usually indicate?failure of passive transfer
what is important to note about hyper/hypoglobulinemia?globulins have fairly broad reference ranges, so, there might be an abnormal change but the values could still be WRI
what can cause hyperalbuminema?usually HEMOCONCENTRATION!! then she had a bunch of random shit on the slide, like "Increased albumin synthesis"-->Hepatocellularcarcinoma producing albumin in a case study, or Hyperalbuminemiadue to steroid treatments Slight to mild increases. possible Falsely increased due to BCG-dye binding