Download 2005b(12)98b(6)Briefly discuss the physiological roles of plasma

Blood
2005b(12): Briefly discuss the physiological roles of plasma proteins
General: Plasma proteins serve numerous roles
- 1° plasma protein = albumin (45g/l)
- Others are present in less quantity
o Globulins (25g/l) → α1, α2, β, γ
o Fibrinogen (3g/l)
o Others
- Roles in
o Proteolytic (complement, kinins, coagulation, fibrinolysis)
o Role in acid-base (buffering)
o Oncotic pressure
o Transport (hormones, energy substrates, drugs)
o Enzyme systems (α1 antitrypsin)
o Immunological
o Metabolic (store of amino acids / energy source)
- Proteins are produced 1° by liver, although some production occurs within
other cells (eg macrophages, bone, plasma cells)
o ↓protein metabolism /↑protein metabolism with starvation
- smaller proteins are exchangeable with the extravascular protein pool
o important in sequestration of immune related proteins
o oncoproteins
Capillary fluid dynamics
Capillaries have semi-permeable membranes
- Impermeable to large proteins (1° albumin)
Bulk flow of fluid and solutes from the capillary into the interstitium is dependent
on the interaction of 4 Starling forces
- Pc: hydrostatic pressure within the capillary
- πp: plasma oncotic pressure
- Pi: Interstitial hydrostatic pressure
- πi: interstitial fluid oncotic pressure, such that
NFP = k[(Pc – Pi) – σ(πc - πi)]
Where k = diffusion coefficient (SA x hydraulic permeability), σ = reflection
coefficient (leakiness of capillary) 0-1.
- net production of 4L/day of interstitial fluid → absorbed by lymphatics
back into systemic circulation
- ↓πp
o >4L/day interstitial fluid production → exceed the absorption
capabilities of lymphatic system → results in interstitial oedema
Albumin
1. Acid-Base → 2nd to Hb (<imidazole moieties, ↓conc): 15% total
2. Oncotic pressure → 80% total
3. Transport
a. bilirubin, Ca2+, hormones (cortisol, T3, T4)
b. CO2 (carbamino compounds → less than Hb), Cu, FFA
By Amanda Diaz
Blood
c. Drugs:
i. Neutral / Acidic drugs (barbiturates) → bound to albumin
ii. Has BZ (II) and warfarin (I) binding sites
iii. Competition of drugs for binding sites
4. Metabolism → storage forms of amino acids transported to periphery for
catabolism
Globulins
- α1
o anti-trypsin (protease inhibitor) → inhibits trypsin, chymotrypsin,
plasmin, other proteases
o Lipoproteins → chylomicrons, VLDL, LDL, HDL
 Not true drug binding → VDW force interaction
 Partition lipophilic drugs (eg fentanyl)
o Acid-glycoprotein → acute phase reactant (APR), unknown
physiological role, binds basic drugs (LAs, morphine)
 Low concentration / low capacity system
- α2
o Macroglobulin → protease inhibitor (see anti-trypsin)
o Prothrombin
o Haptoglobin → scavenges free Hb
o Caeruloplasm → Cu binding, APR, free radical scavenger
- β
o Transferrin → apotransferrin + 2Fe3+
o Haemopexin → scavenges free Hb
- γ
o Immunoglobulins derived from B cells
 IgG 76%, IgA 16%, IgM 7%, IgE 1%
- Fibrinogen
o Final step in coagulation cascade → soluble finbrinogen →
insoluble fibrin in the presence of Thrombin, factor XIIIa and Ca2+
- Others
o Cytokines → IL / IFN / chemokines / TNF
o Complement factors → Innate immunity (non-specific)
 Complement system: 25 heat labile serum proteins
• Produced by hepatic parenchymal cells /
macrophages
• Important in control of inflammation, opsonisation
o CRP, fibrinectin
 2° produced in liver
 Role in opsonisation and regulation of inflammatory
mediators
o Coagulation factors
 Biological amplification system
 Present in the blood in inactive co-factors
• Activated in cascade by activation of enzyme systems
in response to vessels wall damage
By Amanda Diaz