Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Rheumatology > 1 - What is Rheumatology and Phenotype of Systemic Inflammation > Flashcards

1 - What is Rheumatology and Phenotype of Systemic Inflammation Flashcards

1
Q

What is Rheumatology a subspecialty of?

A

Internal Medicine

Pediatrics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the key areas of expertise of a Rheumatologist?

A

Musculoskeletal Medicine

Systemic Auto-immune and Auto-inflammatory Conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the overlap between musculoskeletal medicine and auto-immune/auto-inflammtory diseases?

A

Arthritis/Arthralgia

Myalgia/Myopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

The bright side of having a systemic inflammatory response

A

Defense against infection
Cancer surveillance
Hemostasis/Homeostasis after acute tissue damage/injury
Wound healing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

The dark side of having a systemic inflammatory response

A

Overly excessive inflammatory response
Chronic expression
Pleiotropic effects of inflammatory mediators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Septic Arthritis

A

Inflammation is NECESSARY to clear the infection
Prevent entrenchment or dissemination (bacteremia has high mortality rate)
Inflammation CAUSES most of the irreparable damage to the joint. UGH

This also happens in ARDS and post-inflammatory changes after encephalitis or CVA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Lymphotoxin

A

TNF-β

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Systemic Inflammatory Response - Immune Effectors

A

Macrophages
Neutrophils
T-Cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Systemic Inflammatory Response - Cytokines

A 
TNF-α
IL-6
IL-1
IFN
Lymphotoxin
Chemokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Cytokine Targets

A 
Bone Marrow
CNS
Liver
Muscle
Adipose
Blood Vessels
ReticuloEndothelial System
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Cytokines - Effect on Bone Marrow

A

Leukocytosis

Thrombocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Cytokines - Effect on CNS

A

Fever
Somnolence
Lethargy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cytokines - Effect on Liver

A 
Synthesis of Acute Phase Reactants
Complement
Hepcidin
Triglycerides
Reduced glycogenesis
Reduced albumin synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cytokines - Effect on Muscle

A

Reduced glucose uptake

Sarcopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Cytokines - Effect on Adipose

A

Lipolysis
Free Fatty Acid Release
Adipokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Cytokines - Effect on Blood Vessels

A

Endothelium primed for leukocyte transmigration
Plaque rupture
Atherogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Cytokines - Effect on ReticuloEndothelial System

A

Migration of dendritic cells to lymph nodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Acute Phase Reactants - Induced in response to

A

Cytokines and other extra-cellular signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Acute Phase Reactants - Importance in systemic inflammatory response

A

Varies depending on reactant

Pro-inflammatory vs. Anti-inflammatory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Acute Phase Reactants - Test characteristics

A

Circulate in much higher concentrations than cytokines, easily identified as markers for disease processes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Examples of Acute Phase Reactants

A 
Complement
CRP
Fibrinogen
Serum Amyloid A
Haptoglobin
Ferritin
Mannose binding lectin
Others

Macrophages produce TNF-α and IL-1
These induce IL-6
This induces the liver to produce the above.

22
Q

Lab Measures of Acute Phase Reactants

A

C-Reactive Protein (CRP)

Erythrocyte Sedimentation Rate (ESR)

23
Q

C-Reactive Protein

A

Pentamer of 23kDa subunits
Synthesized by hepatocytes under cytokine (primarily IL-6) stimulation
Fixes complement
Binds to macrophages to induce inflammatory cytokines
Binds to endothelial cells to expose tissue factor
May have putative anti-inflammatory effects

Primarily used to measure the inflammatory response in patients

24
Q

Erythrocyte Sedimentation Rate

A

The rate at which RBCs will migrate over an hour, the distance they will travel in an upright tube in that time.

25
What increases the ESR?
``` Older Age Female Sex Temperature of sample Smoking Increase in plasma proteins(immunoglobulins, fibrinogen, etc) Microcytic anemia or variable RBC size Increase in plasma viscosity ```
26
What decreases the ESR?
Polycythemia Extreme leukocytosis Sickle cell anemia
27
You see an elevated or depressed ESR. What do you ask?
Is this because of a response to cytokines? | Is this because of another factor unrelated to inflammation?
28
Proposed benefits of fever during infection
Inhibition of bacterial growth Facilitates killing by macrophages and PMNs Sequesters iron Other
29
How do exogenous pyrogens and microbes cause a fever?
They stimulate leukocytes to produce endogenous pyrogens Mostly monocytes/macrophages and neutrophils IL-1 TNF-α Lymphotoxin (TNF-β) Interferons IL-6
30
Fever during Infection - Mechanism
Endogenous pyrogens circulate Endogenous pyrogens signal the CNS (multiple redundant mechanisms) Prostaglandins (PGE2) are synthesized This elevates the thermostatic set point of the hypothalamus (No PGE receptor = no fever) Fever is dampened by poorly-understood endogenous anti-pyrogens
31
Fever during Chronic Inflammatory Diseases - Mechanism
Same process as during infection, except instead of endogenous pyrogens triggering it, we have exogenous pyrogens: Synovitis Activated leukocytes Etc
32
Anemia of Inflammation
Anemia of Chronic Disease (previous name) Associated with chronic infections, inflammatory diseases, neoplastic disorders Affects Iron, Erythropoietin, RBC survival NOT resolved by exogenous Fe or Erythropoietin.
33
Anemia of Inflammation - Levels
Circulating iron is normal (Lecturer said normal, slide said decreased) Iron binding capacity is decreased Whole body iron stores are normal or increased Blunted response to endogenous and exogenous erythropoietin RBC life span is reduced NOT resolved by exogenous Fe or Erythropoietin
34
Anemia of Inflammation - Mechanism
IL-6 levels are high This raises hepcidin levels This destroys ferroportin This causes less iron to be absorbed, and for iron to get trapped in hepatocytes and macrophages. Treat with an IL-6 inhibitor!
35
Hepcidin
Small peptide/hormone (25aa) Synthesized in liver Expressed primarily in liver (less in kidney, heart, muscle, brain) Negative regulator of iron homeostasis Mutations in hepcidin lead to severe juvenile hemochromatosis
36
Hepcidin knockout leads to
Multi-organ iron overload
37
Hepcidin overexpression leads to
Severe Fe deficiency anemia
38
How does Hepcidin regulate iron?
In the duodenum, where iron is absorbed, hepcidin destroys ferroportin channels in the setting of iron excess. This prevents the basal translocation of further iron into the bloodstream, when we already have too much. This means iron is trapped in the hepatocytes, rather than allowed into the bloodstream. Iron can also be trapped in macrophages due to this process.
39
What are the regulators of Hepcidin?
``` Serum Iron (low serum iron suppresses hepcidin, high serum iron induces hepcidin) Inflammation (IL-6 via NF-κB) - THIS IS THE PRIMARY REGULATOR ```
40
Cachexia - Definition
Loss of lean (non-fat) mass in the setting of systemic inflammation Distinct from frank wasting (not associated with malnutrition, the fat is unaffected or even INCREASED) Related to, but distinct from aging-associated sarcopenia
41
Cachexia - Mechanism
Multifactorial: Cytokine-driven (TNF-α, IL-6, IL-1) Degradation mediated through NF-κB Reduced physical activity Effects of altered hormone signaling/insulin not well studied
42
Energy Metabolism - Normal
Glucose & Free Fatty Acids are essential sources of energy during infection, acute injury, healing
43
Energy Metabolism - Acute Inflammation
Cytokines facilitate release of glucose & free fatty acids into circulation These target liver, adipose & skeletal muscle
44
Energy Metabolism - Chronic exposure to the cytokines of acute inflammation leads to:
``` Diabetes Insulin resistance Atherogenic lipid profile Atherogenesis (particularly in the setting of energy excess and other CV risk factors) ```
45
TNF-α and Glucose Metabolism
Adipose - Acts through p55 receptor: Lipolysis Free Fatty Acid Release Liver Increased hepatic gluconeogenesis Increased triglyceride production (synergized under IL-1, IL-6) Increased VLDL production, enriched with triglyceride, decreased clearance Skeletal Muscle - Acts through the p55 receptor in combination with the free fatty acids released from the adipose tissue: Altered insulin-signaled glucose uptake
46
TNF-α and reduced insulin-stimulated glucose uptake in skeletal muscle - Mechanism
Inhibition of auto-phosphorylation of the insulin receptor
47
Pro-Inflammatory HDL
Apo A-1 (a component of HDL) promotes reverse cholesterol process Inflammation results in accumulation of oxidants in HDL This inactivates Apo A-1 This also facilitates the formation of oxidized LDL
48
Chronic Inflammation - Steps of Atherogenesis/Thrombosis
Chronic inflammation is linked to all stages of atherogenesis/thrombosis ``` Endothelial dysfunction (earliest stage) Atheroma formation (potentiated by other CVD risk factors) Plaque instability and rupture (results in MI) ```
49
Atherogenesis/Thrombosis - Effects (direct or indirect) of cytokines on the vasculature
``` Up-regulate vascular adhesion molecules Activate and recruit macrophages Upregulate other pro-inflammatory cytokines Remodel vascular matrix (MMPs, TIMPs) Regulate the apoptosis of vascular SMCs Induce pro-coagulant state (PAI-1) Modulate glucose metabolism Modulate fat/lipid metabolism Antagonize anti-inflammatory pathways ```
50
Vulnerable Plaque
"Thin capped fibroatheroma" Rupture is prone to a plaque weak at the "shoulders" Shoulders with few SMC, PG, collagen More macrophages and infiltrating t-cells
51
Cardio - Long term exposure to inflammtory cytokines leads to
Higher rates of cardiovascular events

Rheumatology (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions