Chemical Pathology 2: Plasma Proteins And Enzymes Flashcards
Proteins
Physical properties:
- Molecular size
- Solubility
- Electrical charge
Functions:
- Nutritional store
- Carrier of drugs, hormones, oxygen etc.
- Enzymes
- pH buffer
- Antioxidants
Laboratory techniques to detect protein
- Chemical methods
- Dye binding methods for total protein - Immunoassay for specific proteins
- Protein electrophoresis
- Genetic testing
Acute phase proteins
- Group of proteins
- concentrations significantly alter in response to acute tissue injury
Major acute phase proteins:
- Fibrinogen, Haptoglobins, Ceruloplasmin
- α1-antitrypsin, transferrin, C-reactive protein (CRP), C3 complement, α1-antichymotrypsin, α1-acid glycoprotein
↓ in injury:
- Albumin (↓ up to 20%)
- Transport proteins (Transferrin, Prealbumin) (∵ ↑ capillary permeability)
↑ in injury:
- CRP
- C3
- Haptoglobin
- Ceruloplasmin
- α1 Antitrypsin
Total proteins
Total proteins = Albumin + Globulin (mostly immunoglobulin, others e.g. acute phase protein)
Normal A/G ratio >1
Reflect
- Nutrition status
- Immune status
- Liver synthetic function
- Kidney function
Albumin
- Most abundant plasma protein
- t1/2: 21 days
- Synthesised by liver —> controlled by Protein intake
- -ve charge, no CHO side chains
—> normally not seen in urine
Function:
- Control COP (Colloidal Osmotic Pressure)
- Negative acute phase reactant (i.e. ↓ during acute phase / inflammation)
- Carriers of free fatty acids, metals, drugs, hormones etc.
Low (Hypoalbuminemia —> low COP —> edematous):
- Severe liver disease (↓ production)
- Nephrotic syndrome (↑ loss)
- Infection
- GI loss
- Malnutrition
- Analbuminaemia (rare: very low amount of circulating serum albumin)
High:
1. Dehydration (contraction of extracellular space)
Immunoglobulins
Measured directly (Ig pattern) / Calculated from (Total protein - albumin)
↑:
- ALL infective processes
- Plasma cell malignancy
Albumin and Total Protein usually go in same direction
Multiple myeloma: IgG ↑, Albumin ↓ —> Total protein ↑ —> reversed A/G pattern with significant ↑ in globulins
Cirrhosis: Ig ↑, Albumin ↓
—> Abnormal Albumin / Protein ratio
—> may need protein electrophoresis to differentiate monoclonal / polyclonal increase
—> usually no sharp band except broad spectrum for IgG
—> sharp / strong band —> monoclonal proliferation
Elevated:
- IgG —> Autoimmune hepatitis / cirrhosis
- IgM —> Primary biliary cirrhosis
- IgA —> increased in ***ALL types of cirrhosis —> not specific for diagnostic purpose
- Total / specific IgE —> Allergic conditions
Case 1: History of Hypertension Low back pain Haemoglobin 6.6g/L ESR 121 mm/hr Albumin:Globulin: 38:41 g/L
- Low Hb
- High ESR
Electrophoresis:
- Albumin decreased
- Ig increased
Possible diagnosis:
- Cirrhosis
Haptoglobin
- Synthesised by liver
- 4 peptide chains
- Acute phase reactant
Function:
- Bind haemoglobin: Iron reservation (avoid renal excretion)
Low:
- Haemolysis (2x normal): depleted (Mainly used for investigation of haemolysis)
- Hepatic disease
Transferrin
- Synthesised by liver (+ Choroid plexus of brain)
- Negatively regulated by availability of Fe
- Negative APR
- binds Fe and other cations e.g. Cu, Zn, Ca
- Part of Fe profile
—> ***Reciprocal relationship with serum Fe
—> Low serum Fe —> High Transferrin - Carbohydrate-deficient transferrin:
—> present in CSF rhinorrhea
—> marker for Alcoholism
—> Carbohydrate-deficient glycoprotein syndrome
Ceruloplasmin
- Binds Cu (>95% in blood)
- Cu-bound Ceruloplasmin: longer t1/2: 5.5 days
- Non-Cu-bound Ceruloplasmin: shorter t1/2: 5 hours
- Regulating Fe’s ionic states (Fe2+)
- APR
- Mainly used for investigation of Wilson’s disease
Wilson’s disease
- Most common inherited hepatic disease
- Autosomal recessive
- Malfunction of ATP7B gene (ATPase, Cu transporting, beta-polypeptide gene)
—> DNA (e.g. 2304DupC, 2299delC) —> frameshift, truncation
—> Amino acid (e.g. G943D)
- Low Ceruloplasmin / Cannot incorporate Cu to ceruloplasmin —> Majority apoceruloplasmin
—> High nonceruloplasmin-bound serum Cu
—> Cu accumulation
—> damage to organs e.g. Liver
- Presentation: —> Kayser–Fleischer rings —> Hepatic and/or Neurological symptoms —> may have Haemolysis —> High urinary copper
- Treatment: Chelation therapy
Microalbuminuria
Small amount of albumin in urine (20-300 mg/L) not readily detectable by Dipstix
—> Predictor of future development of clinical renal disease in patients with HT / DM
α1 Antitrypsin
- Proteinase inhibitor
- APR (also stimulated by estrogen)
- Protection of elastin from damage of leukocyte elastase / other enzyme
- Low level resulting in cirrhosis, emphysema
- Genetic deficiency (>75% gene variants with different enzyme activity)
Enzymes
- Proteins with catalytic properties
- Factors affecting blood enzyme level:
Rate of entering circulation - Rate of removal / inactivation
Rate of entering:
- Altered enzyme production
- induced GGT in alcoholics - Leakage of enzyme from cells
- ischaemia, anoxia, toxin, physical trauma, viral damage to cell membrane etc.
- intracellular enzyme level»_space;> extracellular compartment
- size of molecules / location of enzyme affect time / sequencing / extent of rise in enzyme level
- Clearance of enzyme mainly by reticuloendothelial system
Utilities of enzymes
ALT
- liver, skeletal muscle
- Hepatic parenchymal disease
AST
- liver, skeletal muscle, heart, RBC
- Hepatic parenchymal disease, Muscle disease
ALP
- liver, bone intestinal mucosa, placenta
- Bone disease, Hepatobiliary disease
Amylase
- salivary glands, pancreas
- Pancreatic disease
Cholinesterase
- liver
- Organophosphate poisoning, Scoline apnea, Liver disease
CPK
- skeletal muscle, heart, brain
- Muscle disease, AMI
GGT
- liver, kidney
- Hepatobiliary disease
LDH
- heart, liver, skeletal muscle, RBC, platelets
- Haemolysis, AMI, Malignancy
Lipase
- pancreas
- Pancreatic disease
AST, ALT
- Part of standard LFT
- ALT: cytoplasmic, more liver specific
- AST: cytoplasmic, mitochondrial, old cardiac enzyme
- ALT, AST reflect liver damage
—> Raise in all kinds of liver damage (viral, toxic, alcoholic), tumour / ductal obstruction
—> maybe normal in cirrhosis (burn-out effect) - AST:ALT ratio (if >1) —> indicate severity, etiology (alcoholic)
