Derm/Otolary/Rheum: OA + RA and Anti-Inflammatory Steroids + NSAIDs

Cortisol is a natural __________ hormone.

stress

Cortisol helps regulate __________ + __________ responses in the immune system.

inflammation, stress

Both OA + RA involve __________, but __________ normally helps dampen it.

inflammation, cortisol

Osteoarthritis is a chronic progressive joint disease involving loss of __________.

cartilage

OA is commonly called “__________” arthritis.

wear and tear

Loss of articular cartilage in OA is __________. Articular cartilage normally helps __________ joints.

irreversible, cushion

OA can cause __________ + __________, leading to pain + loss of __________.

synovial inflammation, bone thickening, joint function

Major OA risk factors include age >______, ______, ______, ______, and pro-inflammatory cytokines like ______ beta.

50 y/o, obesity, trauma, genetics, IL-1

Trauma during the ___ — ___ can accelerate cartilage breakdown later in life.

30s, 40s

Severe OA may require __________ or __________ to improve pain + mobility.

knee arthroplasty, joint replacement

RA is an __________ disease where the immune system attacks __________ tissues in joints.

autoimmune, synovial

RA usually begins in __________ joints of the hands + feet.

small and symmetric

Unlike OA, RA causes systemic symptoms such as __________ + __________.

fever, fatigue

In RA, activated B cells + T cells release cytokines such as __________, which drives __________.

TNR-alpha, chronic inflammation

__________ is overgrown synovial tissue that destroys cartilage + bone and is a hallmark of __________.

Pannus, RA

__________ + __________ are __________ used to diagnose RA, with __________ being more specific.

Rheumatoid Factor, ACPA, antibodies, ACPA

OA is primarily a __________ disease, while RA is a __________ disease.

localized and degenerative, systemic and autoimmune

HPA stands for __________ axis and is the body’s main __________.

Hypothalamic-Pituitary-Adrenal, stress regulator

Cytokines such as ______ + ______ can trigger the HPA axis.

IFN-alpha, IL-1

In the HPA axis: hypothalamus releases __________ → pituitary releases __________ → __________ produces cortisol.

CRH, ACTH, adrenal cortex

Cortisol __________ immune cells such as __________ + __________ while also increasing __________ and breaking down __________.

suppresses, lymphocytes, macrophages, blood sugar, protein

Cortisol is the body’s natural __________ hormone.

anti-inflammatory

The adrenal cortex has 3 layers: zona glomerulosa (produces __________), zona fasciculata (produces __________), and zona reticularis (produces __________).

aldosterone, cortisol, DHEA

Corticosteroids like prednisone mimic __________ and are used for powerful __________ effects.

cortisol, anti-inflammatory

Low-dose corticosteroids are mainly __________, while high-dose corticosteroids are __________.

anti-inflammatory, immunosuppressive

High doses of corticosteroids can __________ natural __________, so physicians aim for the __________ effective dose for the __________ duration.

shut down, cortisol production, lowest, shortest

Glucocorticoids reduce inflammation by __________, decreasing __________ + __________.

blocking phospholipase A2, prostaglandins, leukotrienes

Glucocorticoids enter the nucleus, bind to __________, increase __________ genes, and suppress __________ genes.

DNA, anti-inflammatory, pro-inflammatory

Glucocorticoids suppress immune responses by reducing __________, __________, and __________.

neutrophil migration, T-cell activation, B-cell antibody production

High cortisol can cause __________, __________ wasting, __________, and increased risk of __________.

hyperglycemia, muscle, fat breakdown, osteoporosis

Corticosteroid receptors are found throughout the body, including the __________, explaining __________ + __________ disturbances.

brain, mood, sleep

__________ is a MR that regulates __________ + __________ balance, helping control __________.

Aldosterone, sodium, potassium, BP

Aldosterone causes kidneys to reabsorb __________, and __________ follows it.

sodium, water

Excess aldosterone causes sodium + water __________, __________ levels, and __________.

retention, low potassium, hypertension

High cortisol can also activate __________ receptors, leading to __________ + __________ imbalances.

MR, edema, electrolyte

__________ has balanced __________ + ________-retaining effects, while __________ is especially strong at sodium retention.

Hydrocortisone, anti-inflammatory, sodium, fludrocortisone

Major corticosteroid side effects include ____glycemia, ____tension, __________, __________, __________ changes, __________, and __________.

hyper, hyper, infections, peptic ulcers, mood, cataracts, bone loss

Long-term corticosteroid use increases __________ risk because these drugs __________ the immune system.

infection, suppress

Corticosteroids are effective in arthritis because they boost the body’s natural __________ system.

anti-inflammatory

The HPA axis affects the __________, __________, __________, immune system, and nearly everything in between.

brain, bones, metabolism

OA is the most __________ type of arthritis and usually affects only ___ joints at a time.

common/frequent, 1-2

OA involves loss of articular cartilage, which normally cushions joints and __________.

reduces friction

Specific joint changes in OA include thickening of the __________ bone and synovial thickening/hyperplasia.

subchondral

In OA, chondrocytes release __________ that degrade the cartilage matrix.

proteinases

RA commonly begins during the ______ decade of life and is more common in __________.

3rd, women

RA development involves both __________ and __________ contributions.

genetic, enviromental

RA classically starts in __________ joints but later can affect the __________, __________, __________, and __________.

small, shoulders, elbows, hips, knees

RA involves both adaptive immunity ( _______ cells) and innate immunity (mainly __________ in the synovium).

T and B, macrophages

Dendritic cells present __________ to __________ in RA pathogenesis.

antigens, T cells

Additional immune cells involved in RA inflammation include __________, __________, and __________ cells.

macrophages, neutrophils, mast

Important cytokines involved in RA include ______, ______, and ______.

TNR-alpha, IL-1, IL-6

Citrullination is the __________ of __________ into citrulline, creating abnormal antigens that can trigger __________.

deamination, arginine, autoimmunity

An important genetic marker associated with RA is HLA-__________.

DR4

Sjögren syndrome causes ________ + ________ due to destruction of the ________ and ________.

dry eyes, dry mouth, lacrimal, salivary glands

RA can have extra-articular manifestations such as Sjögren syndrome and __________ syndrome.

Felty

Rheumatoid Factor (RF) is an antibody directed against the __________ portion of __________.

Fc, IgG

RF is usually an __________ pentamer antibody.

IgM

RF is NOT exclusive to RA and may also be seen in hepatitis C, endocarditis, and other __________ diseases.

autoimmune

RF + IgG form __________ that stimulate __________-driven inflammation.

immune complexes, macrophage

Higher RF levels are associated with more __________ RA disease.

severe

Important RA labs include _____, _____, ESR, _____, ANA, and _____.

RF, ACPA, CRP, CBC

High cortisol levels decrease __________ + __________ through __________ feedback.

CRH, ACTH, negative

Too much cortisol can suppress the __________ and decrease natural __________.

HPA axis, cortisol production

The 2 main physiologic corticosteroids are __________ and __________.

cortisol, aldosterone

Aldosterone secretion is primarily regulated by __________ and serum __________ levels.

Ang II, potassium

Glucocorticoids bind to __________ glucocorticoids receptors.

intracellular

The glucocorticoid receptor acts as a __________.

nuclear transcription factor

Glucocorticoid binding causes __________ change, nuclear __________, binding to __________, and altered __________.

conformational, translocation, GREs, gene transcription

Major metabolic effects of glucocorticoids include increased __________, __________, and __________.

gluconeogenesis, protein breakdown, lipolysis

Inflammation activates phospholipase A2, producing __________ that is converted by the __________ enzyme into __________.

arachidonic acid, COX, prostaglandins

__________ is the key regulator of prostaglandin synthesis.

Phospholipase A2

__________ (lipocortin-1) __________ phospholipase A2, __________ prostaglandin production.

Annexin-1, inhibits, reducing

Aldosterone mainly acts on the __________.

renal collecting duct

Aldosterone binds the __________ receptor, also called the __________ receptor.

mineralocorticoid, MR

Aldosterone causes ______ Na⁺, ______ K⁺, and ______ H⁺ levels.

increase, decrease, decrease

Sodium retention leads to __________ and __________ blood pressure.

water retention, increased

Hypertension + hypokalemia + metabolic alkalosis + bilateral adrenal hyperplasia suggest __________ secretion.

excess aldosterone

Excess aldosterone production occurs in the zona __________ of the adrenal cortex.

glomerulosa

Hyperaldosteronism often presents with __________ plasma __________ levels.

suppressed, renin

High serum potassium directly stimulates the zona __________ to increase __________ synthesis.

glomerulosa, aldosterone

Anti-inflammatory potency mainly reflects ______ receptor binding, while sodium-retaining potency reflects ______ receptor binding.

GR, MR

TNF-alpha biologics produce one of the greatest reductions in __________ in __________.

joint inflammation, RA

Additional prednisone side effects include cataracts, glaucoma, __________, insomnia, seizures, __________, and __________.

headache, nausea, edema/swelling

Long-term __________ steroid use suppresses the HPA axis through negative feedback.

exogenous

Abrupt discontinuation of corticosteroids can cause __________.

adrenal insufficiency

Long-term corticosteroids must be __________ to allow __________ of natural cortisol production.

slowly tapered, recovery