Pathology of Fever

Question 1

____ is defined as an elevation in body temperature and is the clinical hallmark of inflammation due to a number of causes.

Answer 1

Fever (Pyrexia)

Question 2

What are the major causes of fever?

Answer 2

Infection
Cancer
Autoimmune disease
Strenuous exercise
Environmental temperatures
myocardial infarcts or strokes

Question 3

How can a fever due to infection be classified?

Answer 3

Local infection (abscess)
Systemic Infection (sepsis causing pneumonia or endocarditis)

Question 4

Which neoplasms are most likely to cause fever?

Answer 4

Acute Leukemias (myelogenous and lymphoblastic)
Hodgkins and Non-Hodgkins Lymphoma)
Renal Cell Carcinomas and Hepatocellular carcinomas
Primary Brain Tumors in Hypothalamus (temp. reg)

Question 5

How can the systemic inflammatory diseases causing fever be further classified

Answer 5

Autoimmune (Systemic Lupus, Rheumatoid Arthritis, Vasculitutudes)
Granulomatous (Sarcoidosis, Crohn’s, Giant Cell Arteritis)

Question 6

Which drugs have the ability to cause fever?

Answer 6

Antihistamines
Antipsychotics (thorazine, haldol)
Tricyclic Antidepressants (TCA’s)
Monoamine Oxidase Inhibitors

Cocaine, PCP, Amphetamines, LSD

Question 7

What other conditions may cause fever?

Answer 7

1. Malignant Hyperthermia (anesthesia)
2. Neuroleptic Malignant Syndrome
3. Hyperthyroidism and Pheochromocytoma
4. Environmental
5. AMI, Stroke, PE/Infarct, CHF, Transfusion Reaction, Transplant Rejection, Sickle Cell, Seizure, Pancreatitis, Dehydration and Gout

Question 8

Which three body systems are responsible for the most infections?

Answer 8

Respiratory, Urinary, skin and soft Tissue.

Concentrate on theses systems with a fever of unknown origin (FUO)

Question 9

Which area of the brain regulates our temperature?

Answer 9

Hypothalamus

Question 10

What is a pyrogen?

Answer 10

Any substance that causes a fever.

Question 11

How does the release of pyrogens cause fever?

Answer 11

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.

Question 12

What are the dominant cytokines that cause fever?

Answer 12

IL-1, IL-2, IL-6, and TNF

Question 13

What are innate immune receptors?

Answer 13

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.

Question 14

What are the names for innate immune receptors on our immune cells?

Answer 14

Toll-like receptors

Question 15

How do Toll-like receptors work?

Answer 15

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.

Question 16

Which of the cytokines affect the hypothalamus.

Answer 16

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.

Question 17

What is septic or endotoxic shock?

Answer 17

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.

Question 18

What are the most common organisms in that cause septic shock?

Answer 18

Caused by endotoxin producing gram-negative bacteria such as E. coli, Proteus, Serratia, Pseudomonas, K. pneumoniae, and the anaerobe Bacteroides.

Question 19

What are endotoxins?

Answer 19

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.

Question 20

Is there an association with Cancer and Fever?

Answer 20

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.

Question 21

What is hypothalamic fever? Is it common?

Answer 21

elevated temperature caused by abnormal hypothalamic function.

Question 22

What are some causes of hypothalamic fever?

Answer 22

Local head trauma, hemorrhage or tumor in the hypothalamus.

Question 23

What is malignant hyperthermia?

Answer 23

Autosomal dominant inherited abnormality of skeletal muscle sarcoplasmic reticulum that causes a rapid increase in intercellular calcium levels. (rare)

Question 24

What causes malignant hyperthermia?

Answer 24

Usually a response to Halothane or other inhalation anesthetics or to Succinylcholine.

Question 25

What are the clinical presentations of hyperthermia?

Answer 25

Increased temperature and muscle metabolism, rigidity, rhadomyolysis and cardiovascular instability.

Question 26

What is neuroleptic malignant syndrome?

Answer 26

Disorder seen in the setting of a neuroleptic agent:
Anti-Psychotics
Phenothiazines (Thorazine)
Haloperidol (Haldol)
Metoclopramide (Reglan

Question 27

What is the cause and clinical features of Neuroleptic malignant syndrome?

Answer 27

Inhibition of dopamine receptors in the hypothalamus which results in increased heat generation and dissipation leading to muscle rigidity, autonomic dysregulation and hyperthermia.

Question 28

____ is when mediators of inflammation act on the bone marrow, stimulating a rapid release of leukocytes.

Answer 28

Leukocytosis