Exam #1: Chronic Inflammation II Flashcards
What is granulomatous inflammation?
Type of chronic inflammation that is seen in a limited number of infections & some non-infectious causes (e.g. a foreign body)
What are the characteristics of granulomatous inflammation?
- Aggregates of activated macrophages with an “epitheliod” appearance
- Purpose is to contain an offending agent that is indigestible and difficult to get rid of
When does granulomatous inflammation occur?
- Forms in the setting of persistent T-cell responses to microbes & fungi
- T-cell derived cytokines are responsible for persistent macrophage activation
*Recall that strong T-cell activation leads to macrophage activation–>injures normal tissue
What is the prototype of granuloma formation?
TB
What are the components of a graunloma?
Granulomas are a focal area of inflammation
- Consists of microscopic aggregates of macrophages i.e. epitheloid cells
- Macrophages are surrounded by mononuclear cells i.e. lymphocytes & occasionally plasma cells
Describe the histological appearance of a granuloma.
- Ring of epithelioid macrophages
- Langhan’s “Giant cell”
- Peripheral rim of lymphocytes
What is the difference between granuloma & granulation tissue?
Granulation tissue= tissue repair i.e. histological appearance of “granulation tissue” characterized by fibroblasts, capillaries, and loose ECM
What is a Langhan’s cell? How does the presentation of these cells differ in infectious & foreign body induced granulomas?
Multinucleated giant cells
*These are seen in a peripheral arrangement in infectious granulomas; haphazard arrangement in foreign body
What is a foreign body granuloma?
Granuloma formed in response to inert foreign body–>forms when material is too large to be phagocytosed by a single macrophage
- Splinter suture material
- Breast implant
- Piece of glass
*In surgery, be sure to completely cut the silk thread used for sutures; if you don’t, can form granuloma at the incision
Describe the histological appearance of a granuloma formed in response to a foreign body.
Haphazard giant cells that do NOT form a ring like what is seen in an infectious granuloma
What can granuloma formation lead to in the lung?
Granulomatous inflammation with extensive tissue destruction i.e. caseous necrosis
What is lymphangitis?
Inflammation of the lymphatic channels
*Clinically, red streaks up the arm or leg are called “blood poisoning”–>this is actually an infected lymphatic vessel or “lymphangitis”
What is reactive lymphadenitis?
Inflammation of draining lymph nodes
What happens if an infection overwhelms lymph nodes?
The infection gains access to the blood, causing bacteremia
*Bacteremia is NOT sepsis, but bacteremia can lead to sepsis
What are the systemic effects of inflammation?
Acute phase response or SIRS (Systemic Inflammatory Response System)
Clinically, what are the effects of inflammation?
- Fever
- WBC
- Anorexia
- Altered sleep
- Increase in serum acute phase proteins
What cytokines lead to the systemic effects of inflammation?
IL-1 & TNF-a
How is a fever produced in the body?
Cytokines stimulate PG synthesis in hypothalamic thermoregulatory center
–>resets body thermometer
What happens to heart rate in the presence of fever?
Increase in HR by 10 bpm per every increase in fever by 1 degree C
What is the main exogenous pyogen that induces fever?
LPS
What is the effect of IL-1 & TNF in the acute phase response?
- Increased COX that convert AA into PG
Cyclooxygenases convert arachnadoinic acids into prostaglandins
What are the serum acute phase proteins?
Plasma proteins that are mostly synthesized in the liver (hepatocytes); concentrations increased 100-fold in the presence of inflammatory stimuli
Include:
- CRP (C-reactive proteins)
- Fibrinogen
- SSA (serum amyloid A protein)
What is the function of the serum acute phase proteins?
Proteins bind microbial cell walls & may act as opsonins & fix complement
What is leukocytosis?
Increase in total WBC count from the normal range 4,000- 10,000 to levels around 15,000- 20,000
What is a leukemoid reaction?
Extremely high white cell count
- 40,000- 100,000
What is a left shift?
- Increase in immature WBCs due to accelerated release from the bone marrow
I.e. band cells are being released from the bone marrow before maturing to full WBCs
What is neutrophilia?
An increase in the number of neutrophils seen in most bacterial infections
What is Lymphocytosis?
Increase the in absolute number of lymphs; seen in viral infection
What is eosinophilia?
Increase in absolute number of eosinophils; seen in asthma, hay fever, and parasitic infections
What is Leukopenia?
Decrease in absolute number of WBCs; seen in certain infections & in debilitated hosts/ overwhelming infection
- This can be an indication of a MORE SEVERE infection in the elderly or immunocompromised despite WBC numbers in the “normal” range
What are the autonomic manifestations of systemic inflammation?
- Increased pulse and blood pressure
- Decreased sweating secondary to redirection of blood flow from cutaneous to deep vascular beds
What are the behavioral manifestations of systemic infection?
- Shivering
- Chills
- Anorexia
- Somnolence
- Malaise
What happens in severe bacterial infections?
Large numbers of organisms & LPS lead to large quantities of cytokines, esp. TNF-a & IL-1
- Cardiovascular decompensatin
- DIC
- Liver injury–> hypoglycemia
- Overproduction of NO
- Heart failure
- Decreased blood pressure
What is the triad of septic shock?
- DIC
- Hypoglycemia
- CV failure
What is the difference between defective inflammation & excessive inflammation?
Defective= increased susceptibility to infections & delayed wound healing
Excessive= inflammation leading to tissue injury & contributing to athersclerosis, heart disease, neurodegenerative disease & cancer
What is the cancer associated with gastritis? What is the etiologic agent?
Gastric adenocarcinoma, MALT
- H. pylori
What is the cancer associated with Schistosomiasis? What is the etiologic agent?
Bladder, liver, & rectal carcinoma
- Schistosomes
*****Schistosomiasis is a disease caused by parasitic worms of the Schistosoma type. It may infect the urinary tract or intestines.
What is the cancer associated with Cholangitis? What is the etiologic agent?
Cholangiocarcinoma
- Colon carcinoma
*****Note that Cholangitis= inflammation of the common bile duct
What is the cancer associated with chronic cholecystitis? What is the etiologic agent?
Gallbladder cancer
- Bacteria
- Gallstones
What is the cancer associated with Hepatitis? What is the etiologic agent?
Hepatocellular carcinoma
- Hep B & Hep C
What is the cancer associated with PID? What is the etiologic agent?
Ovarian and cervical carcinoma
- Gonorrhea, chlamydia, or papillomavirus
What is the cancer associated with Osteomyelitis? What is the etiologic agent?
Skin carcinoma in draining sinuses
- Various bacterial infections
