Chem lec: Amino acids and proteins (Globulins) PT:2

What does globulins consist of ? (4)

- a1
- B
- a2
- gamma

What do the A1 globulins consist of? (2)

- a1-antitrypsin
- a1-fetoprotein

This is an acute phase reactant a1 globulin

a1-antitrypsin

What causes increased a1-antitrypsin in the body? (3)

- inflammatory reactions
- pregnancy
- contraceptive use

When are decreased levels of a1-antitrypsin seen in the body?

in neonatal emphysema

This is a principal fetal protein globulin

a1-fetoprotein

What causes increased a1-fetoprotein in the body? (5)

- spina bifida
- anencephaly
- fetal distress
- hepatocellular carcinoma
- testicular and ovarian cancers

What are a2-globulins? (3)

Haptoglobin, ceruloplasmin, a2-macroglobulin

This is an acute phase reactant that binds hemoglobin.

haptoglobin

What causes increased haptoglobin in the body? (2)

- inflammatory disease
- rheumatic disease

What causes decreased haptoglobin in the body? (2)

- hemolytic anemia
- liver disease

This is an acute phase reactant. It is involved in redox activity and 90% of copper is found here.

ceruloplasmin

What causes increased levels of ceruloplasmin in the body? (4)

- inflammation
- severe infection
- tissue damage
- pregnancy

What causes decreased levels of ceruloplasmin in the body? (4)

- Wilson's disease
- malnutrition
- malabsorption
- severe liver disease

This globulin inhibits proteases

a2-macroglobulin

What causes increased levels of a2-macroglobulin? (3)

- nephrosis
- diabetes
- liver disease

What are the B-globulins? (6)

- transferrin
- hemopexin
- lipoprotein
- fibrinogen
- complement
- CRP

This globulin transports iron, prevents iron loss, is a negative acute phase reactant

transferrin

When is transferrin increased?

iron deficiency anemia (IDA)

What causes decreased transferrin levels? (3)

- liver disease
- nephrotic syndrome
- malnutrition

This B globulin is an acute phase reactant that binds free heme

hemopexin

What causes increased hemopexin levels? (3)

- inflammation
- diabetes mellitus
- melanoma

What causes decreased hemopexin levels?

hemolytic anemia

This glycoprotein transports lipids, mainly LDL

lipoprotein

What causes increased lipoprotein levels? (4)

- atherosclerosis
- heart disease
- diabetes mellitus
- hypothyroidism

This is a precrusor of the fibrin clot

fibrinogen

What causes increased fibrinogen levels? (3)

- acute phase of inflammatory processes
- pregnancy
- oral contraceptives

When is fibrinogen levels decreased?

during excessive coagulation

This is released during an immune response

complement

What causes increased complement levels? What causes decreased levels of complement? (2)

1. inflammation
2. malnutrition, hemolytic anemia

This is a B- globulin that is an acute phase reactant.

CRP

What causes increased CRP levels? (2)

- tissue necrosis
- cardiac disease

What are the types of Y-globulins? (5)

- IgG
- IgA
- IgM
- IgD
- IgE

What causes increased IgG levels? (3)

- liver disease
- infections
- parasitic disease

What causes decreased immunoglobulins levels (specifically IgG, IgA, IgM)? (2)

-immunodeficiency
- decreased protein synthesis (IgA)

What causes increased IgA levels? (3)

- liver disease
- infections
- autoimmune disease

What causes increased IgM levels?

- toxoplasmosis

What causes increased IgD levels?

infections

What antibody is found in secretions? What antibody is involved with early response? What antibody is associated with allergies?

1. IgA
2. IgM
3. IgE

What are other proteins of importance? (10)

- myoglobin
- troponin (CTn)
- B-type natriuretic peptide (BNP)
- N-terminal BNP (NT-BNP)
- fibronectin
- adioponectin
- B-trace protein
- cross-linked C-telopeptides (CTX)
- Cystain C
- amyloid

What proteins are cardiac markers? (3)

- myoglobin
- troponin (for MI)
- BNP (distinguishes MI and CHF)

What protein is used to predict short term risk of premature delivery?

fibronectin

What does total protein measure?

all proteins in plasma

What do total protein measurements reflect? (3)

- nutritional status
- kidney disease
- liver disease

What is the level of hypoproteinemia? What is hypoproteinemia due to?

1. <6.4g/dL
2. negative nitrogen balance

What causes hypoproteinemia? (4)

- excessive loss
- decreased intake
- decreased synthesis
- acceleration of catabolism of proteins

How are proteins excessively lost which results in hypoproteinemia? (3)

- renal disease
- blood loss
- burns

How does decreased intake cause hypoproteinemia? (2)

- malnutrition
- intestinal malabsorption

How does decreased synthesis of proteins cause hypoproteinemia? (2)

- liver disease
- inherited immunodeficiency

How does the acceleration of catabolism of proteins cause hypoproteinemia? (2)

- burns
- trauma

What protein level is considered hyperproteinemia?

>8.3 g/dL

What causes hyperproteinemia? (2)

- dehydration
- excessive production of gamma blobulines

How does dehydration cause hyperproteinemia? (5)

- vomiting
- diarrhea
- diabetic acidosis
- hypoaldosteronism
- excess later loss leads to increased proteins

How does excessive production of gamma globulins cause hyperproteinemia? (2)

- multiple myeloma
- waldenstrom's macroglobulinemia

Given the following diseases, state the levels (increased, decreased, normal) of total protein, albumin, and globulin you would see.
- hepatic damage, burns, trauma, infections

- TP: N, D
- Albumin: Decreased
- Globulin: Increased

Given the following diseases, state the levels (increased, decreased, normal) of total protein, albumin, and globulin you would see.
- malabsorption, inadequate diet, nephrotic syndrome

- TP: Decreased
- Albumin: Decreased
- globulin: Normal

Given the following diseases, state the levels (increased, decreased, normal) of total protein, albumin, and globulin you would see.
- immunodeficiency syndromes

- TP: decreased
- albumin: normal
- globulin: decreased

Given the following diseases/disorders, state the levels (increased, decreased, normal) of total protein, albumin, and globulin you would see.
- dehydration

- TP: increased
- albumin: increased
- globulin: increased

Given the following diseases, state the levels (increased, decreased, normal) of total protein, albumin, and globulin you would see.
- multiple myeloma, monoclonal and polyclonal gammopathies

- TP: increased
- albumin: normal
- globulin: increased

What is the specimen collection for total protein? (2)

- serum
- avoid hemolysis and lipemia

What is the reference range for total protein?

- 6.4-8.3 g/dL

What do total protein measurements include? (hint: think percentages) (3)

- albumin (60%)
- globulins (40%)
- albumin to globulin ration (A/G)

What is the normal A/G ratio?

1-2

What are the serum protein measurements? (3)

- TP measured
- ALB measured
- TP-ALB= calculated globulin

What causes increased total protein concentrations? (4)

- inflammation
- multiple myeloma
- dehydration
- excessive infusion

What causes decreased total protein concentrations? (6)

- malnutrition
- malabsorption
- severe liver disease
- accelerate loss (nephrotic syndrome)
- increased plasma volume (CHF)
- hypogammaglobulinemia

What are the main albumin detection methods? (2)

- BCG (bromcresol green)
- BCP (bromcresol purple)

How is globulin concentration detected?

by subtracting albumin from total protein (Total protein- albumin= globulin)

How is the A/G ratio determined?

by dividing albumin concentration by calculated globulin

What are urinary proteins?

plasma proteins originating from kidney and urinary tract from sources like vagina and prostate

When do plasma proteins appear in urine?

passed through renal glomerulus and have not been reabsorbed by renal tubules

What are the sources of urinary protein? (5)

- blood
- kidney
- urinary tract
- vagina
- prostate

When proteins appear in urine they have not been _________ by the renal tubules.

reabsorbed

How is urinary protein screened? How is it quantitated?

1. urine dipstick
2. 12 or 24 hour urine

What type of urine is used for urinary protein?

- random but times more significant

What are the physiological causes of urinary protein (transient proteinuria)? (6)

- exercise
- emotional stress
- exposure to heat or cold
- fever
- pregnancy
- orthostatic/posstural

What are the pathologic causes of urinary protein? (9)

- glomerular nephritis
- pyelonephritis
- malignant hypertension
- increased permeability of glomerulus (toxins, infections, etc.)
- disturbance of reabsorption
- systemic disorders
- drugs
- chemicals
- myeloma-type disease (bence-jones)

This test detects small levels of blood protein (albumin) in urine

microalbumin test

What is a microabllumin test used to detect?

signs of kidney damage in people who are at risk of developing kidney disease

What are the difference between healthy kidneys versus kidney damage? (2)

- healthy kidneys hang on to albumin
- kidney damage causes protein leakage and exits body through urine

What is one of the first proteins to leak when the kidneys become damaged?

albumin

Microalbumin tests are recommended for who? (3)

- increased risk of kidney disease
- diabetes patients
- people with high blood pressure

Protein: useful in monitoring patients with diabetes mellitus. Elevated levels of microalbumin are detected with the progression of nephropathy in diabetic patients.

albumin

Protein: levels in urine elevate as nephropathy progresses. Increased microalbumin levels can detected proteins.

immunoglobulin

Protein: not usually present in urine. Presence indicates multiple myeloma, MGUS (monoclonal gammopathy of undetermined significance) or Waldenstrom Macroglobulinemia.

immunoglobin light chains (Bence-Jones protein)

Protein: only trace amounts are normally present in urine. Elevated levels indicate damage to renal tubules.

Beta-2-microglobulin

What happens to B2M levels when the glomeruli in the kidneys are damaged?

B2M unable to filtered out so blood levels rise, not urine levels

What is the reference range for CSF proteins?

15-45 mg/dL

What causes increased total CSF proteins? (4)

- bacteria, viral, fungal meningitis
- traumatic tap
- multiple sclerosis
- neoplasm

What protein is secreted uniquely by fetus toward term or when preterm labor is potentially imminent?

fetal fibronectin (fFN)

Where is fetal fibronectin detected?

in maternal cervical fluid

What is the fetal fibronectin test used to determine?

likelihood of premature delivery

What happens when there is a positive fetal fibronectin test? (2)

- warrants close monitoring
- risk of respiratory distress syndrome forming in infant due to immature pulmonary system

What does RDS result in?

risk of CO2 levels and respiratory acidosis in infant