Systemic Inflammation
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Direct answer
Within hours of tissue injury or infection, interleukin-6 (with IL-1 and TNF-alpha) reaches the liver and switches on the acute-phase programme: C-reactive protein begins rising by 6-10 hours and peaks near 48 hours; serum amyloid A, fibrinogen, hepcidin and haptoglobin climb while albumin and transferrin fall. CRP binds phosphocholine on microbes and damaged cells, opsonising them for complement and phagocytes; fibrinogen promotes red-cell rouleaux, accelerating the ESR; hepcidin degrades ferroportin and locks iron inside macrophages and enterocytes — the mechanism of anaemia of chronic disease. The systemic response also resets the hypothalamus (fever), the marrow (neutrophilia with a left shift) and muscle (negative nitrogen balance; TNF-driven cachexia). The older SIRS criteria — two of temperature above 38 or below 36 degrees, heart rate above 90, respiratory rate above 20, white count above 12,000 or below 4,000 — have ceded staging ground to Sepsis-3's SOFA-based definitions, with qSOFA (respiratory rate 22 or more, altered mentation, systolic pressure 100 or less) as the bedside trigger.
What you must remember
- Positive acute-phase proteins: CRP (onset 6-10 h, peak ~48 h, plasma half-life near 19 h), serum amyloid A, fibrinogen (baseline 2-4 g/L), hepcidin, haptoglobin, alpha-1 antitrypsin; negative: albumin, transferrin.
- CRP versus ESR kinetics: CRP rises and falls within days, tracking the inflammatory flare; ESR moves slowly with fibrinogen and immunoglobulins over weeks — CRP for the acute question, ESR for the chronic (TB, rheumatologic follow-up in Indian practice).
- Hepcidin-iron story: hepcidin internalises ferroportin, trapping iron in macrophages and blocking gut absorption — low serum iron despite full stores, iron refractory until the inflammation settles.
- Marrow response: G-CSF-driven neutrophilia with band cells (left shift) beyond about 10%; toxic granulation on the film; extreme cases push into a leukaemoid reaction.
- Postoperative CRP course: expected peak on day 2-3 with halving by day 4-5; a second rise or failure to fall is a standard screen for surgical site infection and anastomotic leak.
- Definitions timeline: SIRS (1992) to Sepsis-3 (2016): sepsis equals infection plus an acute rise of two or more SOFA points; septic shock is vasopressor-dependence plus lactate above 2 mmol/L despite adequate fluids.
- Procalcitonin: rises with bacterial infection and guides antibiotic duration in ICU protocols; availability across Indian laboratories remains uneven, so CRP keeps the frontline role.
Reading a postoperative fever panel
A patient on surgical day 6 has fever to 38.6 degrees, heart rate 102, and a WBC of 14,800 with 12% bands. Day-2 CRP was 96 mg/L (expected peak) but today it reads 180 — the trajectory, not the number, convicts. Expected physiology says CRP should have halved by now; a second climb points at an anastomotic leak or deep collection, and the CT follows. The same logic reads chronic inflammation: a tuberculosis patient with ESR 80 and Hb 9.5 g/dL, microcytic-ish but with high serum ferritin — hepcidin has locked iron away, so iron therapy alone will not fix the anaemia; treating the infection will. Two panels, one principle: the acute-phase reaction is a kinetics exam, and serial values outperform any single measurement.
Where students slip
The anaemia of chronic disease is explained as "iron deficiency because infection consumes iron"; the correct chain is hepcidin-ferroportin sequestration — high ferritin, low serum iron, low total iron-binding capacity — and naming it in that order is what scores. ESR and CRP are used interchangeably: ESR lags by days to weeks and climbs with fibrinogen and rouleaux, CRP is a fast liver product with a 19-hour half-life — choosing the right test for the right time-course is the exam discriminator. Finally, SIRS is recited as current sepsis definition; it was abandoned by Sepsis-3 in 2016 in favour of SOFA-based criteria, but Indian examiners often ask for both, with dates — answer SIRS, then its replacement, then why (poor specificity of SIRS).
Frequently asked questions
Which cytokine chiefly drives the hepatic acute-phase response?
Interleukin-6, acting with IL-1 and TNF-alpha on hepatocytes to up-regulate CRP, serum amyloid A, fibrinogen and hepcidin.
How fast does CRP rise and fall?
It begins rising within 6-10 hours, peaks around 48 hours, and with a half-life near 19 hours falls quickly once the stimulus is removed — making serial values diagnostically useful.
Why does chronic inflammation cause anaemia with high ferritin?
Hepcidin degrades ferroportin, sequestering iron in macrophages and blocking absorption; stored iron (ferritin) rises while transport iron falls, and the anaemia resolves only when inflammation subsides.
What are the qSOFA criteria?
Respiratory rate of 22 per minute or more, altered mentation, and systolic blood pressure of 100 mmHg or less; two or more should prompt urgent assessment for sepsis.
How do SIRS criteria differ from the Sepsis-3 definition?
SIRS needs two of four physiological criteria (temperature, heart rate, respiratory rate, white count), while Sepsis-3 defines sepsis as infection plus an acute increase of two or more SOFA points.