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Clinical Pathology > Protein & Protein Disorders > Flashcards

Protein & Protein Disorders Flashcards

1
Q

What are the 2 types of plasma proteins? What are their 4 overall functions?

A

albumin and globulins

  1. exert colloid osmotic pressure
  2. participate in immune/inflammatory responses and clotting processes
  3. nutritive functions
  4. aid in the maintenance of acid-base balance
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2
Q

What 2 systems synthesize plasma proteins?

A
  1. liver
  2. immune system - cytokines, immunoglobulins
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3
Q

In what animals do age-related changes in plasma and serum protein concentrations occur? How does this change occur?

A

mammals and birds

  • plasma and serum protein concentrations are low at birth and increase after the absorption of colostrum
  • declines over 1-5 weeks as colostrum is metabolized
  • increases to adult levels within 6 months
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4
Q

How does the concentration of proteins compare in plasma and serum?

A

PLASMA —> anticoagulation frees clotting factors and fibrinogens, making proteins levels higher

SERUM —> coagulation means that clotting factors and fibrinogen are no longer free, making protein levels low

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5
Q

What 2 values are in the total protein?

A
  1. albumin
  2. globulins

(not separate —> one value)

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6
Q

How much of the serum protein concentration does albumin make up? Where is it synthesized?

A

35-50%

synthesized in the liver, regulated by IL-1 and other cytokines

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7
Q

What is the half-life of albumin in dogs, horses, and cattle?

A
  • DOG = 8 days
  • HORSE = 19 days
  • CATLLE = 2-3 weeks
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8
Q

What are the 2 major functions of albumin?

A
  1. transport proteins
  2. maintains oncotic pressure in about 75% of colloidal osmotic activity of plasma by affecting the concentration of other plasma constituents
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9
Q

How are globulins categorized? What are the 3 types?

A

based on electrophoretic motility from serum samples (no fibrinogen to alter results)

  • α-globulins
  • β-globulins
  • γ-globulins
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10
Q

Where are α-globulins produced? What is their primary function?

A

liver

transport proteins and inactivate proteases, making them anti-inflammatory proteins

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11
Q

Where are β-globulins produced? What are their primary functions? What are 3 examples of proteins in this category that are not present in serum protein fractions?

A
  • LIVER by transferrin (transport proteins, complement C3)
  • B-LYMPHOCYTES/PLASMA CELLS in response to antigenic stimulation (IgM, IgA)

fibrinogen, prothrombin, plasminogen

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12
Q

What is te most common type of γ-globulins? Where are they produced?

A

IgG antibodies produced by B-lymphocytes and plasma cells

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13
Q

What are the 3 major methods of measuring proteins?

A
  1. refractometry
  2. biuret method by colorimetric automated chemistry analyzers
  3. turbidometric method by precipitation or dye-binding methods
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14
Q

What is the most common method of measuring total solid concentrations in plasma, serum, and other fluids? What causes a difference in the protein concentration in plasma and serum?

A

refractometry

coagulation = serum lacks fibrinogen = less protein

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15
Q

What 4 things cause falsely elevated levels of proteins in refractometry readings? What also has a possibility?

A
  1. CHolesterol/lipemia
  2. Hemoglobin
  3. Urea
  4. GLucose
    (CHUGL)

sodium chloride

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16
Q

How does bilirubin affect refractometry?

A

alters color, but does not affect the reading

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17
Q

What 3 analytes are reported in protein measurements from chemistry analyzers? Which one is calculated?

A
  1. TP measured by spectrophotometry (more accurate than refractometry)
  2. albumin measured by spectrophotometry
  3. globulin calculation (TP - albumin)
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18
Q

How is globulin calculated? How are the different globulin fractions separated?

A

total protein - albumin = globulin

serum protein electrophoresis (SPE)

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19
Q

How does serum protein electrophoresis (SPE) separate globulin fractions? Why is this commonly done?

A

separates proteins into multiple bands of the same size, charge, and shape of the protein and uses a densitometer to translate them into a tracing

distinguishes between hyperglobulinemia caused by innate/acquire immune response from that caused by neoplastic lymphoid proliferation

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20
Q

How do albumin and globulin levels compare in electrograms?

A

albumin is the smallest protein with the highest net negative charge, making it first on the x-axis because it migrates the fastest and furthest

globulins are larger, so they do not migrate as far - γ-globulin has the weakest negative charge and migrates the shortest distance, so it is the furthest to the right

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21
Q

What is the most common cause of hyperproteinemia? What are 2 causes of artifactual increase?

A

increased total protein concentration, most commonly caused by increased globulin production

  1. hemolysis
  2. lipemia
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22
Q

What causes relative hyperproteinemia?

A

dehydration - less water makes proteins seem more concentrated

23
Q

When can hyperproteinemia be considered due to dehydration?

A

when albumin is increased, regardless of globulin levels

24
Q

What are 4 common causes of hypoproteinemia?

A
  1. burns
  2. GI disease (protein-losing nephropathy)
  3. exudative dermatopathies (loss through inflammatory processes)
  4. whole blood loss
25
Q

What causes relative hypoproteinemia? How can it be identified?

A

dilution of plasma proteins by excess fluids —> excess fluid therapy

look at PCV

26
Q

What is hyperalbuminemia almost always associated with? What are 2 causes of artifactual increase?

A

dehydration

  1. hemolysis
  2. lipemia
27
Q

When is it common to find mild increases in albumin in dogs?

A

those undergoing glucocorticoid therapy, likely due to an increased synthesis or lifespan

28
Q

What are 6 causes of decreased production of albumin?

A
  1. maldigestion - EPI
  2. malabsorption - small intestinal disease
  3. malnutrition - dietary deficiency in amino acids, chronic parasitism
  4. catabolic states - pregnancy, lactation, malignant neoplasia
  5. advanced hepatic disease
  6. hyperglobulinemia - cytokines decreased albumin synthesis, compensation to maintain colloid osmotic pressure
29
Q

How much hepatic functional mass must be lost to affect its protein metabolism? What animals do not show this?

A

> 80% loss of mass will lead to a decreased synthesis of all plasma proteins, except immunoglobulins

horses with liver disease will not have hypoalbuminemia

30
Q

What are 4 common causes of increased loss or catabolism of albumin?

A
  1. renal disease with chronic proteinuria - protein-losing nephropathies, glomerular damage
  2. severe exudative skin disease
  3. ascites
  4. hypoadrenocorticism
31
Q

What are 3 causes of increased loss or catabolism of albumin and globulins?

A
  1. acute and chronic hemorrhage
  2. protein-losing enteropathies
  3. severe loss of plasma by burns or severe exudative inflammatory disorders
32
Q

What are 3 characteristics of nephrotic syndrome?

A
  1. hypoalbuminemia —> severe drop is colloid pressure causes ascites, hydrothorax, hydropericardium, pulmonary edema
  2. azotemia
  3. hypercholesterolemia
33
Q

What is a common iatrogenic cause of hypoalbuminemia?

A

fluid therapy —> dilutional

34
Q

How does calcium typically travel through the blood?

A

bound to albumin —> total serum/plasma calcium concentration will be decreased in animals with hypoalbuminemia

35
Q

What is the most common cause of hyperglobulinemia? What causes an increase in the concentration of globulin fractions?

A

hemoconcentration due to dehydration

infection, inflammation, or neoplasia releases cytokines, like IL-1, IL-6, IFN-γ, and TNF-α increases the production of globulins by hepatocytes and immunoglobulins by lymphocytes (acute phase of the innate immune system)

36
Q

When is protein electrophoresis indicated?

A

increased serum golbulins

37
Q

What does an increase in acute phase proteins lead to?

A

hyperglobulinemia and hyperproteinemia depending on the magnitude of disease

38
Q

What kind of globulins are acute phase proteins? What are 2 functions?

A

most are α-globulins, but some are β-globulins

  1. plays a role in the immune system to protect against oxidative stress with anti-infective properties
  2. produced in response to physical stress and corticoisteroid administration
39
Q

What 3 cytokines stimulate acute phase protein synthesis? When does hepatic synthesis begin?

A
  1. IL-1 β
  2. IL-6
  3. TNF

24 hours after acute tissue injury

40
Q

What is the difference between major and moderate acute phase proteins?

A

MAJOR - increase in concentration by 100-1000x after stimulation and reach peak in 24-48 hours, falling rapidly on recovery

MODERATE - increase by 5-10x, reach a peak at 2-3 days and decrease more slowly

41
Q

What are the major and moderate acute phase proteins produced by cats, dogs, horses, cows, and pigs?

A

CATS: serum amyloid A, α1-acid glycoprotein - AGP, haptoglobin

DOGS: C-reactive protein, SAA - SAA, AGP, Hp, fibrinogen

HORSES: SAA - Hp, CRP, Fb

COWS: Hp, SAA - Fb, AGP, CRP

PIGS: pig major acute phase protein, CRP - AGP, Hp, SAA, CRP

42
Q

Where is fibrinogen produced? What kind of acute phase protein is it? What causes an increase?

A

liver

moderate —> late responder to acute and chronic inflammation, tissue damage, and neoplasia

43
Q

In what species is fibrinogen an important inflammatory indicator?

A

cattle —> more sensitive than total WBC count

  • can be useful in horses and dogs
44
Q

What are the 2 most common causes of hypofibrinogenemia?

A
  1. liver failure causes decreased production
  2. DIC increases consumption
45
Q

What kind of acute phase protein is serum amyloid A? When does it reach peak levels? Normal levels?

A

major acute phase protein, considered a rapid reactive APP

2 days after injury and returns to normal within 5-7 days

46
Q

How are serum amyloid levels used for diagnosis in horses and cattle/dogs?

A

HORSE - inflammation, monitoring therapy and post-operative recovery, prognosis

CATTLE/DOGS - severity of inflammation

47
Q

What is C-reactive protein? How do levels fluctuate?

A

major acute phase protein in the dog produced by the liver

concentrations in healthy dogs are low, marked increase occurs rapidly in response to acute inflammation, then decrease rapidly with resolution of inflammation

48
Q

How does the type of inflammation affect serum globulin levels?

A
  • in acute phase reactions, an initial increased concentrations of α and β-globulins are observed
  • as inflammation becomes chronic, albumin may decrease, α and β-globulins increase, and a broad-based peak of γ-globulin is seen (polyclonal gammopathy)
49
Q

What is polyclonal gammopathy characterized by? What 3 conditions is it most commonly seen in? Specifically in cats?

A

increased globulin fraction with a broad-based electrophoretic peak composed of a heterogeneous mixture of immunoglobulins

  1. chronic inflammatory diseases
  2. immune-mediated diseases
  3. liver disease

profound polyclonal peak occurs in cats with feline infectious peritonitis

50
Q

What characterizes monoclonal gammopathies? What is the most common cause?

A

increased globulin fraction with a narrow-based electrophoretic peak that is not wider than the albumin peak

single clone of neoplastic lymphoid cells produce immunoglobulins with identical structure - lymphoid neoplasia (lymphoma, plasma cell myeloma)

51
Q

How can the albumin peak be altered in monoclonal gammopathies?

A

peak may be decreased due to hyperviscosity syndrome in order to reduce colloid osmotic pressure

52
Q

What are 3 causes of hypoglobulinemia?

A
  1. decreased production - SCIDS (Arabians, Appaloosas), acquired immunodeficiency diseases
  2. abnormal loss - hemorrhage, protein-losing enteropathy
  3. failure of passive transfer in neonates
53
Q

What is characteristic of failure of passive globulin transfer at birth? What can cause this in neonates?

A

very low γ-globulin levels at birth

hypoglobulinemia reflecting inadequate absorption of colostral antibodies

Clinical Pathology (33 decks)

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