Autoimmune + vasculitides (sleroderma sjogren) Flashcards
(127 cards)
1
Q
The central disturbance in SLE is ……………………..
A
excessive autoantibody production due to loss of self-tolerance
2
Q
What antibodies are the most characteristic feature of SLE?
A
anti-nuclear antibodies - ANA
3
Q
Why there is complement consumption in SLE?
A
Autoantibodies bind to self antigens –> leads to formation of circulating immune complexes –> deposit in various organs + activates complement
4
Q
What hematologic abnormalities occur in SLE?
A
pancytopenia + anemia due to chronic inflammation
5
Q
Pancytopenia in SLE. What hypersensitivity?
A
autoantibodies against blood cell antigens = typer II hypersensitivity
6
Q
Anemia in SLE. Mechanisms?
A
- Anemia - due to chronic inflammation;
- Autoimmune hemolytic anemia - due to antibodies agains RBCs antigens –> spherocytosis, positive direct Coombs, extravascular hemolysis
7
Q
Thrombocytopenia in SLE. Mechanism?
A
Antiplatelet antibodies –> thrombocytopenia resembling ITP
8
Q
Leukopenia in SLE. Mechanims?
A
Antibody mediated destruction of neutrophils
9
Q
Where occurs effect that cause hematologic abnormalities in SLE?
A
chronic inflammatory effects on bone marrow + autoimmune hemolysis
10
Q
What causes lupus nephritis in SLE. What hypersensitivity?
A
Immune complex deposition in the mesangium, subendothelial and/or subepithelial spaces. type III hypersensitivity
11
Q
What is the most common pattern in lupus nephritis in SLE?
A
diffuse proliferative GN
12
Q
What are 4 test changes are in lupus nephritis?
A
incr. creatinine, proteinuria, hematuria or RBC’s on urinalysis
13
Q
What 3 antibodies in SLE?
A
ANA, anti-dsDNA, anti-Smith
14
Q
SLE ANA. Specificity and sensitivity?
A
Low spec, but high sensitivity
15
Q
SLE anti-dsDNA. Specificity and sensitivity?
A
high spec, low sensitivity (60proc)
16
Q
SLE anti-Smith. Specificity and sensitivity?
A
high spec, low sensitivity (20-30proc)
17
Q
Against what structures are anti-Smith antibodies?
A
antibodies against small nuclear ribonuclear ribonucleoproteins
18
Q
What changes are in mouth in SLE?
A
ulcers on hard palate
19
Q
SLE is assoc. with increased risk of what disorders? Why?
A
Arterial and venous thrombosis - due to antiphospholipid antibodies production
20
Q
what antibodiies cause drug-induced lupus?
A
antihistone antibody
21
Q
What medications cause drug-induced lupus?
A
procainamide, hydralazine, isoniazid, D-penicillamine
22
Q
What are the symptoms in drug-induced lupus?
A
Symptoms resemble SLE, but no renal or CNS involvement. ANA positiver by definition.
23
Q
What hypersensitivity is henoch schonlein purpura?
A
Type III - IgA complexes deposits triggers complement activation and inflammation of small vessels throughout the body.
24
Q
HSP follows what infection?
A
upper resp. tract infection
25
4 manifestations of HSP?
Palpable purpura/petechiae on the lower exctremities
Arthritis/arthralgias
abdominal pain/GI bleeding
Renal injury
26
where in the vessels occurs inflammation in HSP?
Within papillary dermis --> nonthrombocytic palpable purpura on dependent areas (buttocks, lower extremities)
27
immunocomplexes in HSP consists of .......(2)
IgA and C3
28
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
29
What is leukocytoclasis?
neutrophil breakdown?
30
How is called neutrophils breakdown?
Leukocytoclasis
31
Leukocytoclasis leads to the formation of .................
Perivascular nuclear debris
32
Treatment of HSP in children?
benign and self-limiting
33
What risk increases HSP in adults?
renal complications --> nephrotic syndrome + acute kidney injury
34
Patho DIC vs HSP?
DIC - intravascular fibrin deposition without vessel inflammation
HSP - vessel inflammation + fibrin thrombi MAY BE seen
35
Churg Strauss vs HSP manifestation?
Churg - renal, skin and joint involvement BUT INITIALLY PRESENTS WITH ASTHMA SYMPTOMS - which are not seen in HSP
36
What mechanism cause colicky abdominal pain in HSP?
local vasculitis
37
What joints are affected in HSP?
hips, knees, ankles
38
location of IgA complex depositions in kidney?
Mesangium
39
What neurological manifestation ins SLE?
psychosis (cognitive dysfunction), seizures
40
2 sjogren complications in eyes and mouth?
```
corneal ulcerations (due to diminished lacrimal gland function);
dental caries (due to diminished salivary gland function)
```
41
Dry eyes in sjogren are called ................
keratoconjuctivitis sicca
42
dry mouth is called ..........
xerostomia
43
Why may occur arthralgias and cutaneous vasculitis in sjogren?
due to deposition of circulating complexes
44
Arthritis in SLE?
symmetric, migratory
45
In what areas are affected glands in sjogren?
salivary, lacrimal;
| vaginal gland involvement is also common.
46
How in 2 ways can manifest sjogren?
independently or as another autoimmune syndrome (eg RA)
47
What are 2 specific antibodies in sjogren? What 2 are nonspecific?
specific - anti-Ro/SSA and anti La/SSB.
| Often seen RF and ANA
48
biopsy of sjogren in salivary glands?
periductal lymphocytic infiltrates + germinal centers (proliferatin lymphocytes)
49
How looks glandular tissue in sjogren biopsy?
atrophic and fibrotic
50
what muscle weakness is in polymyositis?
symetrical proximal (upper and lower extremities). Painless or diffuse myalgias
51
how differs dermatomyositis and polymyositis?
Similar, but dermatomyositis assoc with significant skin findings (heliotrope rash and Gottron papules)
Polymositis - no skin findings
52
2 ways how can manifest polymyositis and dermatomyositis'?
independently or as a paraneoplastic manifestation of an underlying malignancy (esp. adenocarcinoma)
53
What muscle enzymes can be elevated in poly/dermatomyositis?
creatine kinase and aldolase
54
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
55
how to differentiate poly and dermatomyositis?
biopsy
56
Polymyositis patho?
endomysial inflammation without prominent vascular involvement in a scattered or pathchy distribution
57
dermatomyositis patho?
perivascular inflammaition in a segment pattern without vasculopathy
58
what is endomysial inflammation?
direct invasion of individual muscle fibers
59
What is perifascicular inflammation?
inflammation localized around blood vessels and the septa between muscle fascicles
60
What triggers polymyositis?
inflammatory myopathy triggered by unknown, possibly viral, antigens
61
What is the immune response in polymyositis? Against what?
cell mediated against myocytes
62
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
63
what happens to muscle fibers in polymyositis'?
regeneration and fibrosis of muscle fibers
64
What types of cells infiltrate endomysium in polymyositis'??
macrophages and CD8 lymphocytes
65
what happens to joints and muscle in systemic sclerosis?
joint - arthralgias and contractures;
| muscle weakness is not seen
66
What biopsy changes seen in myastenia gravis and eaton lambert?
none, speciment is normal
67
how often occurs muscle weakness in myasthenia gravis and eaton-lambert?
myastenia - episodic;
| eaton lambert - fatigable weakness
68
How manifest polymyalgia rheumatica?
shoulder and pelvic gridle muscles pain + systemic symptoms. Muscle weakness is not seen
69
what is heliotrope rash?
erythematous or violaceous edematous eruption on the periorbital area/upper eyelids and cheeks
70
What is gottron papules?
raised erythematous plaques/red or violaceous, flat-tropped papules over joints and bony prominences, esp. on the hands.
71
What portion is affected in perifascicular inflammation?
contiguous portion of the fascicle and surrounding vessels (ie occurring along the periphery of the fascicles)
72
For what disease need to evaluate patients with poly/dermatomyositis?
malignancy (esp. adenocarcinoma in ovary, lung, pancreas)
73
what is innitial treatment of dermatomyositis?
systemic glucocorticoids (prednisone)
74
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).
75
What skin layer is affected in systemic sclerosis?
dermal layer
76
Why there is dermal layer expansion in systemic sclerosis?
due to diffuse deposition of collagen
77
What happens to adipose tissue and dermal appendages in systemic sclerosis?
atrophy
78
There is atrophy of what 2 structures in systemic sclerosis in dermal layer?
atrophy of intradermal adipose tissue and dermal appendages
79
What is considered ad dermal appendages?
hair follicles, glands
80
What system is seriously affected in systemic sclerosis apart from skin?
lungs --> interstitial lung disease and pulmonary hypertension
81
interstitial lung disease manifests in ............ systemic sclerosis
diffuse cutaneous SS
82
pulmonary hypertension manifests in ............ systemic sclerosis
limited cutaneous SS. often assoc with CREST syndrome
83
Atrophy of skin structures in systemic sclerosis leads to ............
thinning of the epidermis
84
What is renal injury in systemic sclerosis?
SS is assoc with scleroderma renal crisis
85
Why occurs scleroderma renal crisis?
due to vascular injury, not glomerulonephritis
86
Sclerodermal renal crisis manifest as ................
hypertensive emergency with end-organ damage.
| Casts are not seen because it is not GN
87
Diffuse scleroderma is assoc with antibodies?
anti DNA topoisomerase I (Scl-70)
88
Antibodies in CREST?
anti-centromere
89
CREST acronym'?
Calcinosis, raynaud, esophageal dismotility, sclerodactyly, teleangiectasias
90
(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).
91
What is sclerodactyly?
thickening of the skin in the hands and feet
92
What is initial presentation of sclerodactyly?
it begins as non-pitting edema of the hands and fingers
93
What is later manifestation of sclerodactyly?
Skin becomes thickened, tight and shinny. Thinning of the skin (atrophy) follows.
94
What is teleangiactasiias?
dilated blood vessels on the skin of face, hands, upper trunk, mucosa
95
Pathogenesis of systemic sclerosis ultimately results in ................. (2)
excess fibrosis and vasculopathy
96
What 3 types of cells are involved in systemic sclerosis?
Vascular endothelial cells, T lymphocytes and fibroblasts
97
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)
98
T lymphocytes function in systemic sclerosis?
migrate into the tissues and increase expression of numerous cytokines that activate tissue fibroblasts
99
Dermal fibroblasts function in systemic sclerosis?
Produce increasing quantities of collage in ground substance --> leads to thickening and stiffening of the tissues.
100
Early symptoms of sclerosis?
finger swelling and mild pruritus
101
With progression of the systemic sclerosis, patients may experience .................. (4)
Dermal sclerosis (sclerodactyly), dermal ulcers, nail atrophy, and digital calcinosis
102
Antibodies against presynaptic Ca channels --> results in ............ (2)
decreased scetylchiline release and muscle weakness
103
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.
104
What symtoms occur in lambert eaton due to autonomic dysfunction?
Autonomic symptoms such dry mouth or impotence
105
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
106
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.
107
MG is caused by ...........
impaired functioning of nicotinic cholinergic receptors at the neuromuscular junction due to interference by IgG autoantibodies.
108
What class of antibodies occur in MG pathophysoilogy?
IgG and/or IgM autoantibodies
109
How to confirm diagnosis of MG?
adminiter anticholinesterase agents --> increased amount of ACh at the NMJ
110
Why ice packs can improve symptoms caused by weakness of superficial muscles (eg. ptosis)?
Acetylcholinesterase activity decreases at lower temperatures
111
What type of hypersensitivity is MG?
type II - IgG and/or IgM autoantibodies that bind cell surface antigens and/or extracellular matrix production.
112
What organ pathology is related to MG?
Thymus: thymoma or thymic hyperplasia
113
Thymus is derived from ............... as are ...............
third pharyngeal pouch, as are inferior parathyroid glands.
114
What 2 structures are derived from 3rd pharyngeal pouch?
thymus and inferior parathyroid glands
115
1st pharyngeal pouch gives rise to ................
epithelium of middle ear and auditory tube
116
2nd pharyngeal pouch gives rise to ................
epithelium of palatine tonsil crypts
117
epithelium of middle ear and auditory tube are derived from ......... pouch
1st pharyngeal pouch
118
epithelium of palatine tonsil crypts derived from ......... pouch
2nd pharyngeal pouch
119
The superior parathyroid glands and ultimobranchial body are derived from ................ pouch
4th pharyngeal pouch
120
4th pharyngeal pouch gives rise to ...............
The superior parathyroid glands and ultimobranchial body
121
Tympanic membrane is derived from ..........
pharyngeal membrane (1st? wtf ten buvo zymejimas)
122
Epithelium of external canal is derived from ............
pharyngeal groove (1st? wtf ten buvo zymejimas)
123
Pharyngeal groove gives rise to ...............
epithelium of external ear canal
124
Pharyngeal membrane gives rise to ............
tympanic membrane
125
The floor of the foregut gives rise to ...............
Thyroid diverticulum
126
The thyroid diverticulum migrates caudally to the .............
neck
127
The thyroid diverticulum migrates caudally to the neck, but remains attached ........................
To the floor of the mouth by the thyroglossal duct
