Lecture 10: Systemic Effects of Inflammation PDF

Lecture 10 Systemic Effects of Inflammation Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students will be able to 1. Discuss the systemic effects of inflammation...

Lecture 10 Systemic Effects of Inflammation Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students will be able to 1. Discuss the systemic effects of inflammation 2  Signs of Acute Inflammation Local Signs. Systemic Signs.  Local Signs of Inflammation 1) Heat (calor). 2) Redness (rubor). 3) Edema (tumor). 4) Pain (dolor). 5) Functio Lasen (loss of function)  Systemic Effects of Inflammation Inflammation, even if localized, is associated with cytokine induced systemic reactions that are collectively called the acute-phase response Cytokines TNF-α, IL-1 and IL-6 are the most important mediators of acute phase reaction. Cytokines are produced by leukocytes in response to infectious agents or immunologic reactions, are released into the circulation  Systemic Effects of Inflammation Acute phase response consists of several clinical and pathologic changes: 1. Fever 2. Elevated Plasma Levels of Acute Phase Proteins. 3. Leukocytosis (most common). 4. Leukopenia (rare) 5. Other manifestations: 6. Anemia 7. Septic shock.  1. Fever is a Clinical Hallmark of Inflammation Characterized by an elevation of body temperature, usually by 1°C to 4°C One of the most prominent manifestations of the acute-phase response, especially when inflammation is associated with infection Coordinated by the hypothalamus & by cytokines (IL -1, TNF-α) released from macrophages and other cells. Cytokines (TNF & IL-1) stimulate production of prostaglandins in hypothalamus.  1. Fever is a Clinical Hallmark of Inflammation Fever produced in response to substances called pyrogens: Bacterial products (Exogenous pyrogens, e.g., Lipopolysaccharides:LPS) Cytokines, principally IL-1 and TNF (called endogenous pyrogens) Act by stimulating prostaglandin synthesis in the vascular and perivascular cells of the hypothalamus. Stimulate the production of neurotransmitters; function to reset the temperature set point at a higher level.  2. Elevated Levels of Acute Phase Proteins Plasma proteins, mainly synthesized by liver. Concentration of acute phase proteins increases several hundred-fold in inflammation. Acute phase proteins 1. C-Reactive protein( CRP). 2. Fibrinogen. 3. Serum amyloid A (SAA) Protein. Synthesis of these molecules in hepatocytes is stimulated by cytokinesIL-6 (for CRP and fibrinogen) and IL-1 or TNF (for SAA)  Acute phase proteins Fibrinogen binds to erythrocytes (RBCs), causes them to form stacks (rouleaux); sediment more rapidly at unit gravity than individual erythrocytes. (Erythrocyte sedimentation rate) ESR: Simple test for inflammation. ESR is elevated in most cases of chronic inflammation  Acute phase proteins Serial measurements of ESR and CRP are used to assess therapeutic responses in patients with inflammatory disorders such as rheumatoid arthritis. Elevated serum levels of CRP used as a marker for increased risk of myocardial infarction or stroke. It is believed that inflammation is involved in the development of atherosclerosis; CRP is a measure of inflammation.  3. Leukocytosis Leucocytosis: Elevation in total white blood cell count. Increased to 15,000- 20,000 cells/cumm (Normal total WBC count in adults: 4000-11,000 cells/cu mm) Leucocytosis: A common feature of inflammatory reactions, especially those induced by bacterial infection. The leucocytosis occurs because of accelerated release of cells (due to cytokines release) from bone marrow pool. Both mature and immature cells can be seen in peripheral blood  3. Leukocytosis Acute bacterial infections: Neutrophilia and neutrophilic leucocytosis Viral infections, such as infectious mononucleosis, mumps, and German measles, cause an absolute increase in the number of lymphocytes (lymphocytosis). Eosinophilia: In some allergies and helminth infestations, there is an increase in the absolute number of eosinophils: Example: Bronchial asthma, hay fever Leucopenia:Decreased number of circulating white cells Typhoid fever and infections caused by some viruses, rickettsiae, and certain protozoa  5. Other Manifestations Anemia: chronic inflammation is accompanied by anaemia of varying degree. Increased heart rate and blood pressure. Decreased sweating. Rigors. Chills. Anorexia. Somnolence and malaise; probably secondary to the actions of cytokines on brain cells.  6. Septic Shock. In severe bacterial infections (Sepsis). Bacterial products stimulate production of cytokines like IL-1 and TNF. Cause disseminated intravascular coagulation (DIC) and metabolic disturbances including acidosis, and hypotensive shock. This clinical triad is described as Septic Shock. Severe form is Systemic Inflammatory Response Syndrome  References 1. Robbins and Cotran Pathologic Basis of Disease; 10th ed. 2021 2. HarshMohan Textbook of Pathology. 7th edition. 16 Thank You 17