Plasma Proteins

Question 1

What protein is not synthesized by the liver?

Answer 1

Immunoglobulins (B cells and Plasma cells- transformed B cells)

Question 2

Function of Plasma Proteins

Answer 2

Albumin exerts colloidal osmotic pressure- keeps the protein in our blood vessels. Nutrition, help maintain acid base (albumin= anion), enzymes, Abs, coag factors, hormones, acute phase proteins, transport substances (CALCIUM!)

Question 3

What are the two main types?

Answer 3

Albumin- 55% of total protein (colloid osmotic pressure!)
Globulins- alpha, beta, and gamma. Include: Immunoglobulins, complement, transferrin (iron transporter), fibrinogen, CRP (c reactive protein), haptoglobin, SAA (serum amyloidase)

Question 4

Acute phase proteins

Answer 4

Proteins that increase or decrease conc. in plasma in response to inflammatory cytokines. Involved in mediating fever, dropping iron in the face of inflamm (so bugs can’t get the iron), etc.

• extremely sensitive and rises first for inflammation.
• moderate APP, marked APP. Fibrinogen is only moderate which means only increases 5-10 fold, takes a couple weeks to go back down. A couple days to increase. A Marked rises rapidly and goes down rapidly.

Horse vet- use SAA.
Which of the following proteins is not a positive APP?

Question 5

Negative APP

Answer 5

IN the face of inflamm. it is inhibited (albumin for example- synthesis is inhib.) in favor or producing globulins that are needed.

Question 6

Positive APP

Answer 6

Fibrinogen for example- ramped up in the face of inflamm.

Question 7

How do we measure APPs?

Answer 7

CBC, biochem- imp. to understand similarities. Measuring the same thing just in different ways.
Serum- blood has been allowed to clot. Measuring same proteins just minus fibrinogen and other proteins involved in the clotting process. SERUM WOULD BE LOWER (TOTAL PROTEIN)
Whereas plasma- fluid from whole blood- the blood tubes contain EDTA (an anticoagulant) (would be HIGHER because you are measuring all proteins)

Question 8

What is a refractometer measuring?

Answer 8

Total solids (sometimes called total protein- should annotate by writing ref next to TP). Reported as part of CBC.
False increase- glucose, urea, sodium, chloride, gross lipaemia. Haemolysis.

Question 9

Why measure fibrinogen? How?

Answer 9

Acute phase response. (heating gets rid of fibrinogen). Measure TP of normal plasma vs. heated plasma. The difference equals fibrinogen amount. Using refractometer.

Question 10

Serum TP

Answer 10

Huge advantage- can measure both TP and Albumin. But you can calculate globulins. Globulins= TP- Albumin. Need to know Globulin for diagnosis/ interpretation.

Question 11

Serum Protein Electrophoresis

Answer 11

Rarely used in practice but allows quantification and separation of globulins. Differentiated types of globulins- helps with diagnosis. Could it be neoplasia? Was it monoclonal? Is inflammation? Separates proteins based on level of anion. Albumin is attracted most strongly to the source because it is a strong anion. Because it is serum- no fibrinogen.

Question 12

What is serum missing?

Answer 12

Fibrinogen.

Question 13

Dysproteinaemia

Answer 13

alternations in protein levels

Question 14

Problem with refractometers

Answer 14

Is the protein level up or down. Can be useful to also use the PCBTB.

Question 15

What is a common cause hyperproteinaemia?

Answer 15

Dehydration- equal rise in globulin and albumin. Relative increase due to plasma water loss. Pre-renal azotaemia. sunken eyes, skin tenting, tacky mucous membranes.

Question 16

What is a common cause of hypoproteinaemia?

Answer 16

Haemorrhage (non selective loss)- so both globuns and albumins would be down

Question 17

Hyperfibrinogenaemia

Answer 17

Dehydrated but also inflamm- how can you differentiate. Is it true inflamm on top of dehydration? Elevated PP: F ratio to help differentiate. e.g. > 15 in cattle or >20 in horses

Question 18

Hyperglobulinaemia

Answer 18

Dehydration- relative increase due to plasma water loss.
Inflammation- abs. inc. due to production of positive acute phase proteins and immunoglobulins.
B-lymphocytes neoplasia- multiple myeloma. (need SPE to tell if neoplasia)

Question 19

Monoclonal

Answer 19

Width is the same or less than albumin. Associated with neoplasia.

Question 20

Polyclonal

Answer 20

Last peak is all the different types of IgG. Width is larger than albumin. Wide based immunoglobulin peak on electrophoresis. Associated with chronic inflammatory disease.

Question 21

Massive laceration on a horse- what is happening with protein? Time?

Answer 21

Low protein due to haemorrhage. What if less than 4 hours ago? Protein would show normal. Haemorrhage and loss of protein would depend on when it occurs. 4-12 hours to manifest. TP will appear normal for 4-12 hours.

Question 22

Hypoalbuminaemia causes

Answer 22

1. Increased albumin loss
2. Stop producing albumin
3. Haemodilution (uncommon)- overzealous fluid therapy. Or rare disease- brain produces too much ADH- so much fluid accumulation.

Question 23

Hypoalbuminaemia specific causes from increased loss of albumin

Answer 23

Increased loss:
Haemorrage (shows up after fluid redistribution), GI loss (protein losing enteropathy- pretty severe disease to see a drop in albumin), Renal loss, skin loss (protein losing dermatopathy- burns), protein rich effusion (pyothorax)

Question 24

Hypoalbuminaemia- stop production

Answer 24

Decreased functional hepatic mass (more than 70-80% loss of function), inflamm (negative acute phase protein, mild can take a few days to manifest), maldigestion/ malabsorption (intestinal mucosa disease, exocrine pancreatic insufficiency), malnutrition/ cachexia

Question 25

Hypoalbuminaemia- at what point does colloid osmotic pressure decrease?

Answer 25

When plasma albumin < 15 g/L… colloid osmotic pressure decreases. Can lead to ascites and oedema in tissue. Hydrothorax, hydropericardium, bottle jaw. I.e. parasite in the sheep’s body causing blood loss.

Question 26

Hypoglobulinaemia causes?

Answer 26

Decreased production, increased loss, failure of passive transfer (inadequate colostrum intake), SCID (severe combined immunodeficiency)- rare but seen (Arabian horses)- die at 5 months due to viral or protozoal infections- dont’ have immune response. no lymphoid tissue

Question 27

Hypofibrinogenaemia

Answer 27

Decreased synthesis (reduced functional hepatic mass 70-80%), increased consumption (DIC)

Question 28

Case 1) Main Coon Cat. 1 yo. Three week history of progressive lethargy, anorexia, and weight loss. CBC, biochem, urinalysis. Initial PCBTP from CBC- mild anaemia, super high protein by refractometer, serum biochemistry TP= 100 (dropped because we removed fibrinogen). Albumin was 20. Globulin would be 80 after calculation. Characteriste dysproteinaemia?

Answer 28

Hyperproteinaemia. Hyperglobuminaemia and hypoalbuminaemia (reflects acute phase response- negative acute phase protein).
What are we thinking?
Is the animal dehydrated?
No. PCB is low. No clin signs of dehydration.
Inflammation?
Neoplasia?
Run a SPE. Polyclonal- wide peak in immunoglobulins compared to albumins. Multiple immunoglobulins are being produced in this cat = INFLAMMATION.
MARKED hyperglobulinaemia. High protein, low cell count in body.
Feline Infectious Peritonitis. (FIP)- likely fatal. Other infectious processes could also cause this.

Question 29

Case 2) golden retriever 11 yo. 2 weeks decreased appetite and lethargy. Slightly icteric mucous membranes.
CBC- neutrophilia, bands, left shift. mild monotcytosis.

Answer 29

Inflammation. Infectious, neoplastic, toxin, immune mediated. etc. etc. Monocytosis- chronic.
Low albumin? Low globulin?
Hypoalbumin and normal globulin. Pure hypoalbuminaemia.
Low urea, high ALP (cholestasis- hepatocytes producing this because they are injured by bilestasis), high ALT, high GGT (cholestasis- hepatocytes producing this because they are injured by bilestasis), high bilirubin (ability to process bilirubin has been hampered)… LIVER!

SPE shows polyclonal because wide fraction. But fractions overlap. “beta gamma bridging”- occurs in many inflammatory conditions.