Acute Phase Proteins

Question 1

What are the 5 characteristics of inflammation?

Answer 1

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

Question 2

Give examples of inflammation triggers.

Answer 2

1) Cancer
2) Pathogens
3) Tissue damage
4) Allergies

Question 3

What are the components of blood?

How much percentage of the blood is protein?

Answer 3

1) Plasma (lots of proteins)
2) Buffy coat (WBC from adaptive and innate immune system)
3) Red cell pellets (RBC & platelets)

• ~40%

Question 4

What are the proteins in the blood, and their percentages in resting blood?

Answer 4

1) Albumin (58%)
2) Immunoglobulin (38%) - IgA, IgM, and IgG
3) Fibrinogen (4%)

Question 5

What changes to proteins happen upon inflammation?

Answer 5

1) Albumin - DOWN
2) CRP - UP
3) Serum amyloid A - UP
4) Acute phase reactants - UP

Question 6

Give examples of positive acute phase reactants, and their functions.

Answer 6

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

Question 7

Give examples of negative acute phase reactants, and their functions

Answer 7

1) Albumin
- Cell signalling
- Oncotic pressure
2) Transferrin

Question 8

Where are most plasma proteins made?

How is acute phase reactant production stimulated?

Answer 8

• Liver (regenerates throughout life)

- IL1, IL6, TNF-a stimulate hepatocytes to produce APR

Question 9

Family, Function, Normal range, and Severe infection range of CRP.

Answer 9

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

Question 10

What are the 3 main complement pathways? and what are they triggered by?

Answer 10

1) Lectin pathway -> triggered by polysaccharides in bacterial cell wall
2) Classical pathway -> triggered by immunoglobulins
3) Alternative pathway -> turbo boost -> makes more C3

Question 10

What are the 3 main complement pathways? and what are they triggered by?

Answer 10

1) Lectin pathway -> triggered by polysaccharides in bacterial cell wall
2) Classical pathway -> triggered by immunoglobulins
3) Alternative pathway -> turbo boost -> makes more C3

Question 11

Activated, Activates, and Function of C3.

Answer 11

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

Question 12

Define CHEMOTAXIS.

Answer 12

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)

Question 13

Define OPSONISATION. Give examples.

Answer 13

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

Question 14

Give examples of inflammatory markers.

Answer 14

1) CRP 
2 ESR (lags behind CRP)

Question 15

Dangers of blood clot in acutely unwell patient, and how it is prevented?

Answer 15

• Blood clot -> pulmonary embolism -> death

- prophylactic clexane (or blood thinner if surgery)

Question 16

What is ESR, 3 clinical characteristics, normal range, and when is it increased?

Answer 16

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

Question 17

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)

Answer 17

• 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

Question 18

What is SEPSIS 6?

Answer 18

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