Acute Phase Proteins Flashcards
What are the 5 characteristics of inflammation?
DRCTF
1) Dolor (pain)
2) Rubor (redness)
3) Calor (heat)
4) Tumor (swelling)
5) Functio laesa (loss of function)
- atleast 3 needs to be available
Give examples of inflammation triggers.
1) Cancer
2) Pathogens
3) Tissue damage
4) Allergies
What are the components of blood?
How much percentage of the blood is protein?
1) Plasma (lots of proteins)
2) Buffy coat (WBC from adaptive and innate immune system)
3) Red cell pellets (RBC & platelets)
- ~40%
What are the proteins in the blood, and their percentages in resting blood?
1) Albumin (58%)
2) Immunoglobulin (38%) - IgA, IgM, and IgG
3) Fibrinogen (4%)
What changes to proteins happen upon inflammation?
1) Albumin - DOWN
2) CRP - UP
3) Serum amyloid A - UP
4) Acute phase reactants - UP
Give examples of positive acute phase reactants, and their functions.
1) CRP
- Binds to C-polysaccharides on pneumococcus (i.e. streptococcus pneumonia)
2) Serum amyloid A
- From mouse models
- role in innate immune system (macrophages, monocytes, and neutrophils)
- Chemotactic effect
3) C3
- activates membrane attack complex in complement pathway
4) Haptoglobin
- binds to free haem during intra-vascular haemolysis
4) Fibrinogen
- converted to fibrin via thrombin -> binds to GP2B/3A receptors on platelets -> activates bridges between platelets
- Targeting GP2B/3A receptors for treatment of unstable angina
Give examples of negative acute phase reactants, and their functions
1) Albumin
- Cell signalling
- Oncotic pressure
2) Transferrin
Where are most plasma proteins made?
How is acute phase reactant production stimulated?
- Liver (regenerates throughout life)
- IL1, IL6, TNF-a stimulate hepatocytes to produce APR
Family, Function, Normal range, and Severe infection range of CRP.
FAMILY - pentraxin
FUNCTION - CFOC
1) Binds to C-polysaccharides on pneumococcus
2) Binds to Fc receptors on monocytes and neutrophils -> stimulate cytokine production
3) Opsonin
4) Activates complements
NORMAL RANGE - <1 mg/L to 7 mg/L (less than 10)
SEVERE INFECTION - >320 mg/L
What are the 3 main complement pathways? and what are they triggered by?
1) Lectin pathway -> triggered by polysaccharides in bacterial cell wall
2) Classical pathway -> triggered by immunoglobulins
3) Alternative pathway -> turbo boost -> makes more C3
What are the 3 main complement pathways? and what are they triggered by?
1) Lectin pathway -> triggered by polysaccharides in bacterial cell wall
2) Classical pathway -> triggered by immunoglobulins
3) Alternative pathway -> turbo boost -> makes more C3
Activated, Activates, and Function of C3.
ACTIVATED by classical and alternative pathway
ACTIVATES membrane attack complex (C5b, 6, 7, 8, 9)
FUNCTION - AMCO
1) dilates Arterioles -> increases blood supply (RTC)
2) stimulates degranulation of Mast cells -> releases histamine
3) Chemotaxis of phagocytes
4) Opsonisation of microbes
Define CHEMOTAXIS.
Chemical in the environment influences the movement of a mobile species.
- IL8 influences neutrophils
- C3 indirectly influences phagocytes (by increasing its affinity to bind to pathogens)
Define OPSONISATION. Give examples.
Process by which opsonins bind to foreign pathogens for elimination by phagocytes.
- CRP tag foreign and damaged cells
- C1 and C3 tag bacteria
- IgM and other immunoglobulins
Give examples of inflammatory markers.
1) CRP 2 ESR (lags behind CRP)
Dangers of blood clot in acutely unwell patient, and how it is prevented?
- Blood clot -> pulmonary embolism -> death
- prophylactic clexane (or blood thinner if surgery)
What is ESR, 3 clinical characteristics, normal range, and when is it increased?
ESR - erythrocyte sedimentary rate, i.e. how fast RBC stick to each other
CLINICAL CHARACTERISTICS
- relatively sensitive, not specific (lags behind CRP)
- not diagnostic
- marker for chronic inflammation
NORMAL RANGE - 30 to 40 mm/h
INCREASES with
1) Age (increase serum amyloid A and anaemia)
2) Acute phase proteins and immunoglobulin
Conditions and typical CRP and ESR values:
- OA
- Abscess
- Pneumonia
- RA
- Psoriatic arthritis (PsA)
- SLE
- GCA
- Myeloma
- Axial spondyloarthritis (AxSp)
- Dermatomyositis
- Furuncles
- Polymyalgia rheumatica (PMR)
- OA -> degenerative -> no CRP, no ESR
- Abscess -> infection -> v high CRP, v high ESR
- Pneumonia -> inflammation of lung -> yes CRP, yes ESR
- RA -> if flare present -> yes CRP, yes ESR, otherwise no
- *Psoriatic arthritis (PsA) -> swollen joint and excess fluid -> no CRP, no ESR
- SLE -> autoimmune disease -> no CRP (unless additional infection present), yes ESR
- GCA -> chronic vasculitis -> CRP and ESR over 50
- Myeloma -> blood cancer (anaemia) -> no CRP, yes ESR
- Axial spondyloarthritis (AxSp) -> chronic autoinflammatory disease -> CRP >20, no ESR
- Dermatomyositis -> inflammation of muscle -> CRP unlikely, ESR slightly
- Furuncles -> soft tissue infection -> yes CRP, yes ESR
- Polymyalgia rheumatica (PMR) -> muscle inflammation -> yes CRP, yes PMR
What is SEPSIS 6?
TAKE 3
1) bloods
2) urine output
3) serial lactase
- suggest low BP -> poor tissue perfusion -> increase O2 demand, resus, NA pump (raises BP via vasoconstriction)
- NO adrenaline -> potent -> risk of tachyarrhythmia -> heart will not pump efficiently
GIVE 3
1) IV fluids
2) antibiotics
3) oxygen
