Week 4 Flashcards
1
Q
What is systemic lupus erythematosus?
A
An autoimmune disease that can affect any tissue or organ in the body, but most often affects the skin, kidneys, and joints
2
Q
What is the cause of systemic lupus erythematosus?
A
It is unknown, but it occurs as a result of genetics and the environment
3
Q
____ is an environmental risk factor for lupus
A
UV radiation/sunlight is an environmental risk factor for lupus
4
Q
____ are present in in the body in almost all cases of lupus
A
Antinuclear antibodies are present in the body in almost all cases of lupus
5
Q
Antigens and antibodies bind to another in the body in a case of lupus to create an antigen-antibody complex. After binding together, what do they do?
A
They get into the blood, drift away, and deposit/stick to the vessel wall in all organs and tissues
6
Q
What are the organs and tissues that antigen-antibody complexes stick to their vessel walls?
A
- Kidneys
- Skin
- Joint
- Heart
7
Q
Antigen-antibody complexes that deposit/stick to the vessel walls of organs and tissues lead to what?
A
The initiation of local inflammatory reactions
8
Q
What chain of events is caused by the initiation of local inflammatory reactions, as caused by the antigen-antibody complexes that deposit/stick to the vessel walls of organs and tissues?
A
The initiation of local inflammatory reactions causes damage to the activation of the complement system, which after a huge cascade of enzyme activation, leave cell membrane with channels that let food and molecules pass through with no problems, causing the cell to burst and die
9
Q
What is a type 3 hypersensitivity reaction?
A
When there is tissue damage that occurs as a result of immune complexes
10
Q
What are the other potential triggers that has been associated with lupus?
A
- Cigarette smoking
- Viruses
- Bacteria
- Use of certain medications, like procainamide, hydralazine, and isoniazid
- Sex hormones, particularly estrogen
11
Q
True or False
Lupus is more common in women
A
True, lupus is more common in women due to estrogen being a trigger. Hence why it is more common in women during reproductive years, than it is during non reproductive years
12
Q
What is a type 2 hypersensitivity reaction?
A
When antibodies target red and white blood cells, and molecules like phospholipids, which can mark them for phagocytosis and destruction, which leads to additional symptoms of lupus
13
Q
What is the classic presentation of lupus?
A
- Fever
- Joint pain
- Rash
In a woman of childbearing age
14
Q
Why is the diagnosis of lupus difficult?
A
It can affect a wide variety of people and has a wide variety of symptoms
15
Q
What are the general symptoms of lupus?
A
- Fever
- Weight loss
16
Q
What are the specific symptoms of lupus based on?
A
It is based on the organ/tissue being affected
17
Q
When is a diagnosis of lupus given to a person?
A
Only when 4 or more of the 11 diagnostic criteria is met
18
Q
What are the diagnostic criteria for lupus?
A
- Malar rash: a rash on the cheek that spares the nasal, labial folds. Also called a butterfly rash
- Discoid rash: plaque like, chronic rash found in sun exposed areas that can form a sort of patchy redness and scar
- General skin photosensitivity: other rashes from sun exposed areas that typically last a couple of days
- Ulcers in the mucous(inner) membranes of the mouth, and nose
- Serositis which is the inflammation of the outer membrane of a cell and can lead to: pleuritis which is inflammation of the lining around the lungs or chest cavity. Or pericarditis: inflammation of the lining of the heart
- Arthritis of 2 or more joints
- Renal disorders like: abnormal amounts of urine protein, diffuse proliferative glomerulonephritis(inflammation of the glomeruli)
- Neurological disorders like seizures and psychosis
- Hematologic disorders: Anemia if RBCs are affected, thrombocytopenia if platelets are affected, leukopenia if WBCs(immune cells) are affected
- Presence of antinuclear antibodies(very sensitive, but not specific, bcos it is seen in other diseases)
- Other autoantibodies like, anti-smith which targets ribonucleoproteins, anti-dsDNA which targets double stranded DNA and is often seen during periods of active disease, and anti-phospholipid which targets protein that are bound to phospholipids
19
Q
What other parts of the heart can lupus affect?
A
- Endocardium: which presents as libman-sacks endocarditis, where vegetations(made up of fibrin and immune cells) form on the mitral valve
- Myocardium
20
Q
What are the types of other autoantibodies that are specific to lupus?
A
- Anti-smith which targets ribonucleoproteins
- Anti-dsDNA which targets double stranded DNA and is often seen during periods of active disease
21
Q
What are the types of anti-phospholipids?
A
- Anticardiolipin: can cause a false positive for syphilis
- Lupus anticoagulant
- Anti beta2 glycoprotein 1
22
Q
What is anti-phospholipid syndrome?
A
Where anti-phospholipid antibodies cause a hyper-coagulable state, meaning that they are more prone to developing clots and complications like DVTs, hepatic vein thrombosis, and a stroke
23
Q
What do patients with anti-phospholipid syndrome end up needing?
A
Lifelong anticoagulant therapy
24
Q
What is lupus characterized by?
A
Periods of flare ups and remittance
25
What is the treatment of lupus often aimed at?
Preventing flare ups or limiting their severity
26
What are some ways that may help prevent lupus flare ups?
Avoid sunlight
27
What are some ways that may help limit the severity of lupus flare ups?
- The use of corticosteroids to help limit immune responses
| - The use of immunosuppressants when flare ups are really severe
28
What is HIV?
A type of virus that infects human immune cells. Over time, immune cells are lost, which weakens the immune system and allows patients to be infected by other viruses and develop several types of tumors
29
What is AIDS?
Acquired immuno-deficiency syndrome, which are the viruses and tumors that is acquired after the immune system weakness has been developed
30
What type of HIV is more commonly associated with AIDS in the US and worldwide?
HIV-1
31
What type of HIV is more commonly associated with AIDS in the western Africa and southern Asia?
HIV- 2
32
What type of HIV is the most uncommon?
HIV- 2
33
What type of cells does HIV target?
CD4+cells on them
34
What types of cells have CD4+cells on them?
- T helper cells
- Macrophages
- Dendritic cells
35
What is the role of CD4 on cells?
It helps immune cells communicate, and are particularly important for when they are launching attacks on pathogens
36
How does HIV cells attach to CD4?
Via a protein called gp120
37
What does HIV need to attach to before it can get inside a cell?
It has to attach to BOTH the CD4 molecule and the co-receptor
38
What is the most common co-receptor that HIV uses?
- CXCR4 co-receptor, which is found mainly at T-cells
| - CCR5 co-receptor, which is found on T-cells, macrophages, monocytes and dendritic cells
39
What are the things that can make the spread of HIV difficult?
- Homozygous mutation, which makes co-receptors resistant or immune to attachment
- Heterozygous mutation, which can result in a slower disease progression
40
What kind of cell is HIV?
A single stranded, positive sense, enveloped RNA retrovirus
41
What is the mechanism of the action of HIV?
It injects its single stranded RNA into the T-helper cell, and it needs to use the enzyme, reverse transcriptase, to transcribe a complementary double stranded piece of proviral(ready to be integrated into the host's DNA) DNA. The new strand enters the T-helper cell nucleus, and inserts itself into the cell's DNA and is ready to be transcribed into new viruses
42
During replication, DNA cells are prone to making errors. What does this lead to?
It leads to different strains of the virus being created in the body, and they target different cells, which is called viral tropism
43
What strain of HIV binds to the CCR5 co-receptor?
R5 strain
44
What type of symptoms do patients typically experience during the acute phase of HIV?
Flu- like symptoms
45
At which point does a patient enter into the chronic or clinically latent phase of HIV?
At 12 weeks
46
How long does the chronic or clinically latent phase of HIV last?
2- 10 years
47
As the HIV virus increases in the body during the chronic phase, what happens to the amount of T-cells?
It decreases
48
What types of infections become more common and severe in patients with HIV?
Tuberculosis
49
During the chronic phase of the HIV infection, some patients develop a X4 strain of HIV. What does it do?
The X4 strain of HIV targets the CXCR4 co-receptor, which is essentially only T-cells. The X4 strain of HIV lays low in the lymphoid tissues and steadily destroy T-cells.
50
What happens when a patient's T-cells have dropped to 200-500 Tcells/mm?
- Swollen lymph nodes (lymphadenopathy)
- Hairy leukoplakia(white patch on the tongue caused by epstein barr virus, that causes mono-nucleosis)
- Oral candidiasis (yeast infection in the mouth)
51
What happens when a patient's T-cells is below 200 Tcells/mm?
- Immunse system is severely compromised
- Disease has progressed from HIV to AIDS
- Persistent fever
- Fatigue
- Weight loss
- Diarrhea
- Significant increase in HIV content of the blood
52
What are the AIDS defining conditions that occur once a patient's T-cells is below 200 Tcells/mm?
- Recurrent bacterial pneumonia
- Pneumocystis pneumonia
- Fungal infections like candidiasis of the esophagus
- Tumors and malignancies like kaposi sarcoma(lesions of the skin and other soft tissue), and primary lymphoma of the brain
53
___ is the most common transmission of HIV in the US
*Male to male* is the most common transmission of HIV in the US
54
___ is the most common transmission of HIV in resource limited settings
*Male to female* is the most common transmission of HIV in resource limited settings
55
Where is HIV present in infected women?
In the vaginal and cervical fluids
56
What percent of contracted HIV is from sexual intercourse?
75%
57
What are the other common means of HIV transmission?
- Intravenous drug abuse
| - Mother to child transmission either through the placenta, delivery or via breast milk
58
What are the other less common modes of HIV transmission?
- Accidental needle stick
| - Blood products like a transfusion
59
What are the ways that HIV can be diagnosed?
- Antibody test for antibodies that body might have made against HIV
- Antibody/antigen test, used to detect antibodies against HIV and HIV itself
- RNA/DNA test. RNA test to look for viral RNA and DNA test to look for copies of the viral RNA in DNA
60
What is the 1st recommended test to do in the diagnosis of HIV?
Antibody/antigen test
61
What should be done after the 1st test for HIV has been found to be positive?
Perform a confirmatory 2nd test, via the antibody test or the RNA/DNA test
62
What are the characteristics of the treatment of HIV?
- Help patient live a longer and healthier life
| - Reduce the risk of transmission
63
What is the primary method of HIV treatment?
Anti-retroviral therapy
64
What is anti-retroviral therapy?
A combination of medications, which are considered a HIV regimen, and is used to slow HIV replication and helps the immune system recover and fight other infections effectively
65
What is rheumatoid arthritis?
A chronic inflammatory disorder that mostly affects the joints, but can also affect other organ systems like the skin and the lungs.
An autoimmune condition where the immune system attacks the joints.
66
What are the human leukocyte antigen that can predispose a person to rheumatoid arthritis?
HLA-DR1 and HLA- DR4
67
What are the environmental factors that in conjunction to the genetic factors will predispose a person to RA?
- Cigarette smoke
| - Pathogens like gut bacteria
68
Wha do environmental factors cause in a person?
It causes the modification of our own antigens, such as IgG antibodies, type 2 collagen and vimentin
69
Through what process does type 2 collagen and vimentin get modified?
Citrullination
70
What is citrullination?
When arginine, which is found in type 2 collagen and vimentin is converted to citrulline
71
Once antigen presenting cells have been carried to the lymph node, what is the chain of events that occur after?
- Antigens presenting cells activate CD4, T-helper cells
- T helper cells stimulate B-cells
- B cells proliferate and differentiate into plasma cells, which produce specific autoantibodies against self- antigens
72
In RA, T helper cells and antibodies enter the circulation and reach the joints. Once they enter the joints, what occurs?
T-cells secrete cytokines like interferon-y and interferon-17, to recruit more inflammatory cells, like macrophages into the joint space. Macrophages also produce cytokines like, TNF alpha, interleukin-1 and interleukin-6, which together with the T-cell cytokines, stimulate synovial cells to proliferate
73
What does the increase in synovial and immune cells in the joint lead to?
It creates a pannus, which is a thick swollen synovial membrane with granulation tissue made up of fibroblasts , myofibroblasts, and inflammatory cells.
74
What does pannus lead to overtime?
It causes damage to the cartilage, and other soft tissues. It also erodes the bone.
75
What does activated synovial cells also do?
It secretes proteases, which breaks down the proteins in the articular cartilage, which leads to the underlying bones being exposed and directly rub against each other
76
What does inflammatory cytokines do to T-cells?
It increases the protein on the surface of T-cells, known as RANKL
77
What is the function of RANKL?
It allows T-cells to bind RANK, which is a protein on the surface of osteoclasts, to get them to start breaking down bone.
78
What is a name of an antibody that enters the joint space in the case of RA?
- Rheumatoid Factor(RF), an IgM antibody, that targets the constant FC domain of altered IgC
- Anti - CCP, which targets citrullinated proteins, which after they bind to their targets, they form immune complexes, which accumulate in the synovial fluid, and activate the complement system
79
What is the complement system?
A family of 9 small proteins that work in an enzymatic cascade to promote joint inflammation and injury
80
What does the chronic inflammation seen in RA cause?
It leads to angiogenesis, the formation of new blood vessels around the joint, which allows more inflammatory cells to arrive
81
Inflammatory cytokines travel out of the joint spaces and into the blood stream, where it travels to different organs and cause extra- articular problems. What are some of the places that these cytokines travel to?
- Interleukin 1 or 6 travel to the brain, where they act as pyrogens and cause a fever
- In the skeletal muscle, they promote protein breakdown
- In the skin and many visceral organs they lead to the formation of rheumatoid nodules
- Blood vessels get inflammed
82
What are rheumatoid nodules?
Round shaped collections of macrophages and lymphocytes, which a central area of necrosis
83
What happens to the liver in response to inflammatory cytokines?
The liver starts to produce high amounts of hepcidin, which is a protein that causes a decrease in serum iron levels, by inhibiting its absorption by the gut, and trapping it into macrophages or liver cells
84
What happens to the lungs in response to inflammatory cytokines?
Within the lung interstitium, fibroblast gets activated and proliferated, causing fibrotic or scar tissue, that makes it harder for the alveolar gas exchange.
The pleural cavity surrounding the lungs can get enflamed, and fill up with fluid, causing pleural effusion.
85
What is the usual presentation of RA?
- Usually 5 joints
| - Symmetrical
86
What are the small joint that are commonly affected by RA?
- Metacarpo-phalangeal (MCP) joints
- Proximal inter-phalangeal (PIP) joint
- Metatarsal phalangeal (MTP) joint
87
As RA worsens, it can start to affect large joints. What are the joints that is affected by this?
- Shoulders
- Elbows
- Knees
- Ankles
88
What happens to the joints affected by RA, during flare ups?
- Swollen
- Warm
- Red
- Painful
- Become stiff over time, especially in the morning.
89
People with RA may develop specific deformities. What are they?
- Ulnar deviation to the fingers
- Boutonniere "buttonhole" deformity
- Swan neck deformity
90
When does a boutonniere "buttonhole" deformity occur?
When the extensor tendon of the finger slips, and the head of the PIP pokes through, causing flexion of the PIP an extension of the DIP
91
What happens in the case of a swan neck deformity?
There is PIP hyperextension and flexion of the DIP
92
What is a baker(popliteal) cyst?
A cyst formed by the synovial sac of the knee bulging posteriorly
93
What are the extra- articular symptoms of RA?
- Fever
- Low appetite
- Malaise
- Weakness
94
What are some organ specific manifestations of RA?
- Rheumatoid nodules, which are most commonly found around pressure points on the skin
-
95
Where are rheumatoid nodules found, even though it is rare?
Lungs, heart, and sclera
96
In patients with RA, there is an increased risk of atherosclerosis, which also increases the risk of what?
Heart attacks and stroke
97
A syndrome that is unique to RA, is felty syndrome. What is this?
A triad of rheumatoid arthritis, splenomegaly, and granulocytopenia, which can lead to life threatening infections
98
What does the diagnosis of RA usually involve?
- Blood test to look for the presence of rheumatoid factor and anti- citrullinated peptide (Anti-CCP) antibody
- Imaging like x-ray used to see decreased bone density, soft tissue swelling, narrowing of the joint space, and bony erosions
99
What does the long term management of RA involve?
- Disease modifying anti-rheumatic medications (DMARDs) such as methotrexate, hydroxychloroquine, and sulfasalazine which suppresses inflammation
- Biologic response modifiers like abatacept(suppress T-cells) and rituxinab(suppress Bcells)
100
What is the function of biologic response modifiers: adalumumab, etanercept and influximab in the treatment of RA?
Block chemokines, like tumor necrosis factor
101
What is the function of biologic response modifiers: anakinra in the treatment of RA?
Blocks interleukin 1
102
What is the function of biologic response modifiers: tocilizumab in the treatment of RA?
Blocks interleukin 6
103
What are the management methods of acute flares of RA?
Anti-inflammatories like NSAIDs and glucocorticoids which are used for a short term period
104
What is an autoimmune pathology?
Disorders of the autoimmune system, in which it attacks healthy cells by mistake
105
What is patient population that is affected by lupus?
* African-American, Latino, and Asian women
* Women:men- 9-10:1
* Age: 15-45
106
Even though there is no cure, what are the methods of self management for the avoidance of lupus?
* Avoid exposure to sunlight
* Avoid smoking
* Stress management
* Prolonged rest at night (i.e. 12 hours)
* Regular exercise
107
What are the common signs and symptoms of lupus?
```
• Joint inflammation
• Kidney disease
• Skin rashes with butterfly shape over the nose and cheeks
• Fatigue
• Muscle pain
• Unexplained fever
• Loss of hair
• Raynaud’s phenomenon
• Seizures
• Sensitivity to the sun
• Swelling – edema in legs
or around eyes
• It may affect the heart, lungs, blood, and brain in more severe cases
```
108
What are the ways lupus can be diagnosed medically?
* Blood tests
| * Tissue biopsy
109
What are the medical management methods for lupus?
* Corticosteroid creams
* NSAIDs for joint pain and fever
* Antimalarial medications to help with joint pain and rashes
* Corticosteroid pills or intravenously.
110
What are the PT management methods for lupus?
• Not a medical emergency
• Medical consultation
• Manage patient’s energy
levels, so always ask how they feel
111
What is dermatomyositis?
An autoimmune disease that causes inflammation of the skin, resulting in typical kinds of rash
112
What are the typical skin presentation of dermatomyositis?
* Pink cheeks
* Purple hue over the eyelids
* Red skin rashes along the elbows, knuckles and knees
113
What are the typical muscle presentation of dermatomyositis?
* Inflammation
* Weakness
* Achy
* Tiredness, fever and chills
114
What is the main feature of the symptoms of dermatomyositis?
They get worse over time, and the patient gets weaker, which may interfere with ADLs
115
What is the prognosis of dermatomyositis?
* Prognosis is good
* Early detection and treatment improves outcomes
* It can rarely be recurrent
* Medical management using medications
* Treatment may take up to 2 years
* If it reoccurs, medication must be resumes
116
True or False
In the case of dermatomyositis, there can be skin manifestations in the absence of muscle
weakness and subtle skin
manifestations make it hard to diagnose
True, In the case of dermatomyositis, there can be skin manifestations in the absence of muscle weakness and subtle skin manifestations make it hard to diagnose
117
What is the main difference in the rash presentation between dermatomyositis and lupus?
In dermatomyositis, the nose and mouth are covered in rashes, while in lupus, they are not(butterfly rashes)
118
What is scleroderma?
A chronic connective tissue disease, generally classified as one of the rheumatic autoimmune diseases
119
What is the cause of scleroderma?
Unknown, but it is known that it involves an overproduction of collagen
120
What is the prognosis of scleroderma?
No cure
121
What is the incidence of scleroderma?
* Localized form is more common in children
* Systemic form is more common in adults (1/3 of cases)
* Women more predominant (4:1)
* Possibly genetic
* Age: 25-55
122
What are the medical management methods for scleroderma?
Medications. Greatly variable, due to the variability seen from patient to patient
123
What are the clinical manifestations of scleroderma?
* Hardening of the Skin (most visible manifestation)
* Affects different body parts
* Prompt and proper referral may minimize symptoms, and reduce the chance irreversible damage
124
What are the major classifications of scleroderma?
- Localized scleroderma
| - Systemic scleroderma
125
What is limited scleroderma?
A subset of systemic scleroderma, which is slower and more benign, and is found in about 50% of cases. It is also called CREST syndrome
126
What does the letters of CREST syndrome stand for?
```
Calcinosis
Raynaud Phenomenon
Esophageal dysfunction
Sclerodactyly
Telangiectasia
```
127
What are the medical diagnosis methods of scleroderma?
* Blood tests
| * Other specialized tests
128
Patient with limited scleroderma, and occasional those with diffuse scleroderma can develop ___
Patient with limited scleroderma, and occasional those with diffuse scleroderma can develop *pulmonary HTN, a condition in which the lung's blood vessels are narrow and lead to impaired blood flow to the lungs, and resulting in SOB*
129
What should be done if suspected that a patient might have scleroderma?
Refer out, but it is not a medical emergency
130
What is psoriatic disorder?
An autoimmune disease that is commonly associated with crohn's disease, and speeds up the life cycle of skin cells, by causing them to build up rapidly on the surface of the skin
131
What is the cause of psoriatic disorder?
Idiopathic, and is thought to be related to an immune system problem with T cells and other white cells/ neutrophils
132
What are the comorbidities that psoriatic disorder can be associated with?
* Autoimmune thyroid disease
* Diabetes
* Metabolic Syndrome
* Psoriatic Arthritis: present in 1/3 of the patient population and may manifest 10 years after diagnosis of the skin disease
133
What are the common signs and symptoms of psoriatic disorder?
* Red patches of skin covered with thick, silvery scales
* Small scaling spots (commonly seen in children)
* Dry, cracked skin that may bleed
* Itching, burning or soreness
* Thickened, pitted or ridged nails
* Swollen and stiff joints
134
What are the other clinical manifestations of psoriatic disorder?
Discomfort and pain
• Routine tasks difficult
• Concern about the appearance of patient’s skin
• Joint problems like pain, swelling, and the inability to perform daily tasks
135
What are the predisposing factors to psoriatic disorder?
• Infections, such as strep throat or skin infections
• Injury to the skin, such as a cut or scrape, a bug bite, or a
severe sunburn
• Stress
• Smoking
• Heavy alcohol consumption
• Vitamin D deficiency
• Certain medications — including lithium, which is prescribed for bipolar disorder, high blood pressure medications such as beta blockers, antimalarial drugs, and iodides
136
What are the medical management methods for psoriatic disorder?
* Diet
* Exercise
* Weight control
* Avoid smoking
* Medications such as TNF alpha inhibitors
* Monitor and treat signs of depression such as difficulty sleeping, anxiety and fatigue
