# Systemic Inflammation > Systemic inflammation in MBBS Physiology: acute phase proteins, CRP and ESR kinetics, hepcidin anaemia and the shift from SIRS to Sepsis-3 definitions. - Canonical URL: https://prepelephant.com/topics/mbbs/physiology/inflammation-systemic-physiology - Exam / course: MBBS · Subject: Physiology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Systemic Inflammation", PrepElephant, https://prepelephant.com/topics/mbbs/physiology/inflammation-systemic-physiology ## 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.