Autoimmune + vasculitides (sleroderma sjogren) Flashcards
The central disturbance in SLE is ……………………..
excessive autoantibody production due to loss of self-tolerance
What antibodies are the most characteristic feature of SLE?
anti-nuclear antibodies - ANA
Why there is complement consumption in SLE?
Autoantibodies bind to self antigens –> leads to formation of circulating immune complexes –> deposit in various organs + activates complement
What hematologic abnormalities occur in SLE?
pancytopenia + anemia due to chronic inflammation
Pancytopenia in SLE. What hypersensitivity?
autoantibodies against blood cell antigens = typer II hypersensitivity
Anemia in SLE. Mechanisms?
- Anemia - due to chronic inflammation;
- Autoimmune hemolytic anemia - due to antibodies agains RBCs antigens –> spherocytosis, positive direct Coombs, extravascular hemolysis
Thrombocytopenia in SLE. Mechanism?
Antiplatelet antibodies –> thrombocytopenia resembling ITP
Leukopenia in SLE. Mechanims?
Antibody mediated destruction of neutrophils
Where occurs effect that cause hematologic abnormalities in SLE?
chronic inflammatory effects on bone marrow + autoimmune hemolysis
What causes lupus nephritis in SLE. What hypersensitivity?
Immune complex deposition in the mesangium, subendothelial and/or subepithelial spaces. type III hypersensitivity
What is the most common pattern in lupus nephritis in SLE?
diffuse proliferative GN
What are 4 test changes are in lupus nephritis?
incr. creatinine, proteinuria, hematuria or RBC’s on urinalysis
What 3 antibodies in SLE?
ANA, anti-dsDNA, anti-Smith
SLE ANA. Specificity and sensitivity?
Low spec, but high sensitivity
SLE anti-dsDNA. Specificity and sensitivity?
high spec, low sensitivity (60proc)
SLE anti-Smith. Specificity and sensitivity?
high spec, low sensitivity (20-30proc)
Against what structures are anti-Smith antibodies?
antibodies against small nuclear ribonuclear ribonucleoproteins
What changes are in mouth in SLE?
ulcers on hard palate
SLE is assoc. with increased risk of what disorders? Why?
Arterial and venous thrombosis - due to antiphospholipid antibodies production
what antibodiies cause drug-induced lupus?
antihistone antibody
What medications cause drug-induced lupus?
procainamide, hydralazine, isoniazid, D-penicillamine
What are the symptoms in drug-induced lupus?
Symptoms resemble SLE, but no renal or CNS involvement. ANA positiver by definition.
What hypersensitivity is henoch schonlein purpura?
Type III - IgA complexes deposits triggers complement activation and inflammation of small vessels throughout the body.
HSP follows what infection?
upper resp. tract infection
4 manifestations of HSP?
Palpable purpura/petechiae on the lower exctremities
Arthritis/arthralgias
abdominal pain/GI bleeding
Renal injury
where in the vessels occurs inflammation in HSP?
Within papillary dermis –> nonthrombocytic palpable purpura on dependent areas (buttocks, lower extremities)
immunocomplexes in HSP consists of …….(2)
IgA and C3
What are pathophysiological changes in HSP in vessels?
Leukocytoclastic inflammation = small superficial vessels are damaged by perivascular neutrophils inflammation –> results in fibrin depositions in the wall (fibrinoid necrosis) + RBCs extravasation
What is leukocytoclasis?
neutrophil breakdown?
How is called neutrophils breakdown?
Leukocytoclasis
Leukocytoclasis leads to the formation of ……………..
Perivascular nuclear debris
Treatment of HSP in children?
benign and self-limiting
What risk increases HSP in adults?
renal complications –> nephrotic syndrome + acute kidney injury
Patho DIC vs HSP?
DIC - intravascular fibrin deposition without vessel inflammation
HSP - vessel inflammation + fibrin thrombi MAY BE seen
Churg Strauss vs HSP manifestation?
Churg - renal, skin and joint involvement BUT INITIALLY PRESENTS WITH ASTHMA SYMPTOMS - which are not seen in HSP
What mechanism cause colicky abdominal pain in HSP?
local vasculitis
What joints are affected in HSP?
hips, knees, ankles
location of IgA complex depositions in kidney?
Mesangium
What neurological manifestation ins SLE?
psychosis (cognitive dysfunction), seizures
2 sjogren complications in eyes and mouth?
corneal ulcerations (due to diminished lacrimal gland function); dental caries (due to diminished salivary gland function)
Dry eyes in sjogren are called …………….
keratoconjuctivitis sicca
dry mouth is called ……….
xerostomia
Why may occur arthralgias and cutaneous vasculitis in sjogren?
due to deposition of circulating complexes
Arthritis in SLE?
symmetric, migratory
In what areas are affected glands in sjogren?
salivary, lacrimal;
vaginal gland involvement is also common.
How in 2 ways can manifest sjogren?
independently or as another autoimmune syndrome (eg RA)
What are 2 specific antibodies in sjogren? What 2 are nonspecific?
specific - anti-Ro/SSA and anti La/SSB.
Often seen RF and ANA
biopsy of sjogren in salivary glands?
periductal lymphocytic infiltrates + germinal centers (proliferatin lymphocytes)
How looks glandular tissue in sjogren biopsy?
atrophic and fibrotic
what muscle weakness is in polymyositis?
symetrical proximal (upper and lower extremities). Painless or diffuse myalgias
how differs dermatomyositis and polymyositis?
Similar, but dermatomyositis assoc with significant skin findings (heliotrope rash and Gottron papules)
Polymositis - no skin findings
2 ways how can manifest polymyositis and dermatomyositis’?
independently or as a paraneoplastic manifestation of an underlying malignancy (esp. adenocarcinoma)
What muscle enzymes can be elevated in poly/dermatomyositis?
creatine kinase and aldolase
What antibodies in poly/dermatomyositis?
anti-Jo-1 (anti-histidyl-tRNA synthetase) - less sensitive and more specific. ANA - in most cases, so it is sensitive but less specific
how to differentiate poly and dermatomyositis?
biopsy
Polymyositis patho?
endomysial inflammation without prominent vascular involvement in a scattered or pathchy distribution
dermatomyositis patho?
perivascular inflammaition in a segment pattern without vasculopathy
what is endomysial inflammation?
direct invasion of individual muscle fibers
What is perifascicular inflammation?
inflammation localized around blood vessels and the septa between muscle fascicles
What triggers polymyositis?
inflammatory myopathy triggered by unknown, possibly viral, antigens
What is the immune response in polymyositis? Against what?
cell mediated against myocytes
what immunology alterations probably lead to polymyositis?
increased expression of MHC I antigens on sarcolema leads to autoantigens to CD8 cytotoxic cells that subsequently initiate myocyte destruction
what happens to muscle fibers in polymyositis’?
regeneration and fibrosis of muscle fibers
What types of cells infiltrate endomysium in polymyositis’??
macrophages and CD8 lymphocytes
what happens to joints and muscle in systemic sclerosis?
joint - arthralgias and contractures;
muscle weakness is not seen
What biopsy changes seen in myastenia gravis and eaton lambert?
none, speciment is normal
how often occurs muscle weakness in myasthenia gravis and eaton-lambert?
myastenia - episodic;
eaton lambert - fatigable weakness
How manifest polymyalgia rheumatica?
shoulder and pelvic gridle muscles pain + systemic symptoms. Muscle weakness is not seen
what is heliotrope rash?
erythematous or violaceous edematous eruption on the periorbital area/upper eyelids and cheeks
What is gottron papules?
raised erythematous plaques/red or violaceous, flat-tropped papules over joints and bony prominences, esp. on the hands.
What portion is affected in perifascicular inflammation?
contiguous portion of the fascicle and surrounding vessels (ie occurring along the periphery of the fascicles)
For what disease need to evaluate patients with poly/dermatomyositis?
malignancy (esp. adenocarcinoma in ovary, lung, pancreas)
what is innitial treatment of dermatomyositis?
systemic glucocorticoids (prednisone)
Hypothyroid myopathy commonly presents with proximal muscle weakness. How differs from derma/polymyositis?
Prominent muscle pain and often have other hypothyroid features (eg, weight gain, cold intolerance).
What skin layer is affected in systemic sclerosis?
dermal layer
Why there is dermal layer expansion in systemic sclerosis?
due to diffuse deposition of collagen
What happens to adipose tissue and dermal appendages in systemic sclerosis?
atrophy
There is atrophy of what 2 structures in systemic sclerosis in dermal layer?
atrophy of intradermal adipose tissue and dermal appendages
What is considered ad dermal appendages?
hair follicles, glands
What system is seriously affected in systemic sclerosis apart from skin?
lungs –> interstitial lung disease and pulmonary hypertension
interstitial lung disease manifests in ………… systemic sclerosis
diffuse cutaneous SS
pulmonary hypertension manifests in ………… systemic sclerosis
limited cutaneous SS. often assoc with CREST syndrome
Atrophy of skin structures in systemic sclerosis leads to …………
thinning of the epidermis
What is renal injury in systemic sclerosis?
SS is assoc with scleroderma renal crisis
Why occurs scleroderma renal crisis?
due to vascular injury, not glomerulonephritis
Sclerodermal renal crisis manifest as …………….
hypertensive emergency with end-organ damage.
Casts are not seen because it is not GN
Diffuse scleroderma is assoc with antibodies?
anti DNA topoisomerase I (Scl-70)
Antibodies in CREST?
anti-centromere
CREST acronym’?
Calcinosis, raynaud, esophageal dismotility, sclerodactyly, teleangiectasias
(CREST) Esophageal dysmotility is the result of …………….
It manifest as ………
Fibrosis of the distal esophagus with associated esophageal hypomotility. It manifests with symptoms of gastroesophageal reflux (heartburn and regurgitation).
What is sclerodactyly?
thickening of the skin in the hands and feet
What is initial presentation of sclerodactyly?
it begins as non-pitting edema of the hands and fingers
What is later manifestation of sclerodactyly?
Skin becomes thickened, tight and shinny. Thinning of the skin (atrophy) follows.
What is teleangiactasiias?
dilated blood vessels on the skin of face, hands, upper trunk, mucosa
Pathogenesis of systemic sclerosis ultimately results in …………….. (2)
excess fibrosis and vasculopathy
What 3 types of cells are involved in systemic sclerosis?
Vascular endothelial cells, T lymphocytes and fibroblasts
Vascular endothelial cells function in systemic sclerosis?
produce excessive endothelin 1 –> vasoconstriction and activation of fibroblasts + increase expression of adhesion molecules (facilitates binding of lymphocytes)
T lymphocytes function in systemic sclerosis?
migrate into the tissues and increase expression of numerous cytokines that activate tissue fibroblasts
Dermal fibroblasts function in systemic sclerosis?
Produce increasing quantities of collage in ground substance –> leads to thickening and stiffening of the tissues.
Early symptoms of sclerosis?
finger swelling and mild pruritus
With progression of the systemic sclerosis, patients may experience ……………… (4)
Dermal sclerosis (sclerodactyly), dermal ulcers, nail atrophy, and digital calcinosis
Antibodies against presynaptic Ca channels –> results in ………… (2)
decreased scetylchiline release and muscle weakness
Lambert Eaton is strongly assoc with …………. Why?
Small cell lung cancer.
Likely due to the immune recognition of voltage gated Ca channels that are present on the malignant cells.
What symtoms occur in lambert eaton due to autonomic dysfunction?
Autonomic symptoms such dry mouth or impotence
Why there is postexercise facilitation of muscle weakness in lambert eaton?
Muscle strength and deep tendon reflexes improve with exercise or repetitive movements (due to accumulation of calcium within the axon terminal
If cranial nerve and resp. muscle manifestaion occur in lambert eaton, then when?
If occur, then in later stage of the diseases.
In contrast - MG facial, periocular and bulbar weakness occur before extremity weaknes.
MG is caused by ………..
impaired functioning of nicotinic cholinergic receptors at the neuromuscular junction due to interference by IgG autoantibodies.
What class of antibodies occur in MG pathophysoilogy?
IgG and/or IgM autoantibodies
How to confirm diagnosis of MG?
adminiter anticholinesterase agents –> increased amount of ACh at the NMJ
Why ice packs can improve symptoms caused by weakness of superficial muscles (eg. ptosis)?
Acetylcholinesterase activity decreases at lower temperatures
What type of hypersensitivity is MG?
type II - IgG and/or IgM autoantibodies that bind cell surface antigens and/or extracellular matrix production.
What organ pathology is related to MG?
Thymus: thymoma or thymic hyperplasia
Thymus is derived from …………… as are ……………
third pharyngeal pouch, as are inferior parathyroid glands.
What 2 structures are derived from 3rd pharyngeal pouch?
thymus and inferior parathyroid glands
1st pharyngeal pouch gives rise to …………….
epithelium of middle ear and auditory tube
2nd pharyngeal pouch gives rise to …………….
epithelium of palatine tonsil crypts
epithelium of middle ear and auditory tube are derived from ……… pouch
1st pharyngeal pouch
epithelium of palatine tonsil crypts derived from ……… pouch
2nd pharyngeal pouch
The superior parathyroid glands and ultimobranchial body are derived from ……………. pouch
4th pharyngeal pouch
4th pharyngeal pouch gives rise to ……………
The superior parathyroid glands and ultimobranchial body
Tympanic membrane is derived from ……….
pharyngeal membrane (1st? wtf ten buvo zymejimas)
Epithelium of external canal is derived from …………
pharyngeal groove (1st? wtf ten buvo zymejimas)
Pharyngeal groove gives rise to ……………
epithelium of external ear canal
Pharyngeal membrane gives rise to …………
tympanic membrane
The floor of the foregut gives rise to ……………
Thyroid diverticulum
The thyroid diverticulum migrates caudally to the ………….
neck
The thyroid diverticulum migrates caudally to the neck, but remains attached ……………………
To the floor of the mouth by the thyroglossal duct
