Pathology of Fever Flashcards
____ is defined as an elevation in body temperature and is the clinical hallmark of inflammation due to a number of causes.
Fever (Pyrexia)
What are the major causes of fever?
Infection Cancer Autoimmune disease Strenuous exercise Environmental temperatures myocardial infarcts or strokes
How can a fever due to infection be classified?
Local infection (abscess) Systemic Infection (sepsis causing pneumonia or endocarditis)
Which neoplasms are most likely to cause fever?
Acute Leukemias (myelogenous and lymphoblastic)
Hodgkins and Non-Hodgkins Lymphoma)
Renal Cell Carcinomas and Hepatocellular carcinomas
Primary Brain Tumors in Hypothalamus (temp. reg)
How can the systemic inflammatory diseases causing fever be further classified
Autoimmune (Systemic Lupus, Rheumatoid Arthritis, Vasculitutudes)
Granulomatous (Sarcoidosis, Crohn’s, Giant Cell Arteritis)
Which drugs have the ability to cause fever?
Antihistamines
Antipsychotics (thorazine, haldol)
Tricyclic Antidepressants (TCA’s)
Monoamine Oxidase Inhibitors
Cocaine, PCP, Amphetamines, LSD
What other conditions may cause fever?
- Malignant Hyperthermia (anesthesia)
- Neuroleptic Malignant Syndrome
- Hyperthyroidism and Pheochromocytoma
- Environmental
- AMI, Stroke, PE/Infarct, CHF, Transfusion Reaction, Transplant Rejection, Sickle Cell, Seizure, Pancreatitis, Dehydration and Gout
Which three body systems are responsible for the most infections?
Respiratory, Urinary, skin and soft Tissue.
Concentrate on theses systems with a fever of unknown origin (FUO)
Which area of the brain regulates our temperature?
Hypothalamus
What is a pyrogen?
Any substance that causes a fever.
How does the release of pyrogens cause fever?
Release of exogenous pyrogens by bacteria, viruses or fungi directly affects the hypothalamic thermoregulatory center.
They also stimulate endogenous pyrogenic mediators of inflammation called cytokines.
What are the dominant cytokines that cause fever?
IL-1, IL-2, IL-6, and TNF
What are innate immune receptors?
Microbes that penetrate an epithelial barrier to enter a tissue site are encountered by tissue sentinel immune cell: Macrophages, monocytes, Mast Cells, and dendritic cells, which all have receptors that recognize structural molecules derived from theses microbes, like OPS.
What are the names for innate immune receptors on our immune cells?
Toll-like receptors
How do Toll-like receptors work?
Stimulation of toll-like receptors on macrophages, monocytes, etc, by the microbe, leads to the synthesis and secretion of cytokines initiating an inflammatory response leading to the further recruitment of blood infection fighters, like neutrophils.
TLR’s recognize constituents of the microbial cell walls or viral-specific nucleic acids.
Which of the cytokines affect the hypothalamus.
IL-1, IL-2 and TNF stimulate prostaglandin synthesis from the hypothalamus.
Aspirin blocks fever by inhibiting IL-1 stimulated PGE-2 synthesis in the hypothalamus.
What is septic or endotoxic shock?
Gram-negative endotoxic shock resulting from the spread of bacteria from a severe localized infection into the blood stream.
Can also occur with gram-positive and fungal infections.
What are the most common organisms in that cause septic shock?
Caused by endotoxin producing gram-negative bacteria such as E. coli, Proteus, Serratia, Pseudomonas, K. pneumoniae, and the anaerobe Bacteroides.
What are endotoxins?
Bacterial cell wall lipopolysaccharides (LPS) in gram-negative bacteria that forms a complex with LPS binding protein in the serum. Binds toll-like receptors on WBC’s and tissue cells causing release of inflammatory mediators.
Is there an association with Cancer and Fever?
Cancer patients often present with a fever of unknown origin (FUO). Fever may correlate with tumor growth. Tumor cells may themselves release pyrogens or the inflammatory cells in the tumor stroma can produce IL-1.
What is hypothalamic fever? Is it common?
elevated temperature caused by abnormal hypothalamic function.
What are some causes of hypothalamic fever?
Local head trauma, hemorrhage or tumor in the hypothalamus.
What is malignant hyperthermia?
Autosomal dominant inherited abnormality of skeletal muscle sarcoplasmic reticulum that causes a rapid increase in intercellular calcium levels. (rare)
What causes malignant hyperthermia?
Usually a response to Halothane or other inhalation anesthetics or to Succinylcholine.
What are the clinical presentations of hyperthermia?
Increased temperature and muscle metabolism, rigidity, rhadomyolysis and cardiovascular instability.
What is neuroleptic malignant syndrome?
Disorder seen in the setting of a neuroleptic agent: Anti-Psychotics Phenothiazines (Thorazine) Haloperidol (Haldol) Metoclopramide (Reglan
What is the cause and clinical features of Neuroleptic malignant syndrome?
Inhibition of dopamine receptors in the hypothalamus which results in increased heat generation and dissipation leading to muscle rigidity, autonomic dysregulation and hyperthermia.
____ is when mediators of inflammation act on the bone marrow, stimulating a rapid release of leukocytes.
Leukocytosis
