Inflammation - Mechanisms of Disease - Cytokines; Hypersensitivity Reactions; Lab Diagnosis; Intro to Immune Disease Flashcards
Are most inflammatory cytokines long- or short-lived mediators?
Can they often _______ other mediators.
Short-lived;
activate
What are the two preliminary molecules to be released during inflammation?
Histamine, serotonin
(vasoactive amines)
What cell is the main mediator of histamine/serotonin release?
Mast cells
What endothelial receptor does histamine bind?
What are the effects?
H1;
arteriolar dilation,
increased venule permeability,
some smooth muscle contraction
Serotonin (5-HT) functions mainly as a _______________.
It is a neurotransmitter in the _______ _______ (in contrast to its role in the brain).
Vasoconstrictor;
GI tract
Which arachidonic metabolites mediate vasodilation?
PGI2, PGE1, PGE2, and PGD2
Which arachidonic metabolites mediate vasoconstriction?
Thromboxane A2, leukotrienes C4, D4, and E4
Which arachidonic metabolites mediate vascular permeability?
Leukotrienes C4, D4, and E4
Which arachidonic metabolites mediate leukocyte chemotaxis and adhesion?
Leukotriene B4;
HETE
Arachidonic acid is derived from ________ acid.
Linoleic
What type of receptor do arachidonic acid metabolites bind?
GPCRs
What is the role of COX-1?
What is the role of COX-2?
Expressed in most tissues — homeostatic function;
inflammation
What two arachidonic acid metabolites act to balance one another out?
PGI2 — TXA2
(vasodilation, anti-platelet agreggation — vasoconstriction, pro-platelet aggregation)
PGD2 is produced by _____ cells and causes vaso________ and ________ vessel permeability.
It is a ___________ chemoattractant.
Mast,
-dilation,
increased;
neutrophil
PGE2 causes vaso________ and is _______algesic.
It can cause cytokine-induced ______.
-Dilation, hyper;
fever
5-HETE is a ___________ chemoattractant.
Neutrophil
What are the main products derived from prostaglandin H2?
Prostaglandins (PGI2, PGD2, PGE2);
TXA2
What are the main products derived from the action of 5-lipoxygenase?
5-HETE;
leukotrienes (B4, C4, D4, E4);
lipoxins (A4, B4)
What lipoxygenase products inhibit neutrophil adhesion and chemotaxis?
Lipoxin A4,
lipoxin B4
What cytokines promote neutrophil chemotaxis?
Leukotriene B4;
5-HETE;
IL-8;
C3a;
C5a
What effects do leukotrienes C4, D4, and E4 have?
Vasoconstriction;
bronchoconstriction;
venule permeability
What arachidonic acid metabolites are anti-inflammatory?
Lipoxins
What drug blocks lipoxygenase?
What drugs block leukotriene receptors?
Zileuton;
montelukast, zafirlukast
What cell types produce TNF and IL-1?
Macrophages;
dendritic cells
What effect(s) does TNF have on metabolism?
And appetite?
Increased lipid and protein mobilization;
suppressed
__________ chemokines maintain tissue architecture.
Homeostatic
C5a activates the __________ pathway of arachidonic acid metabolism.
Lipoxygenase
Which arachidonic acid metabolites counteract the inflammatory effects of leukotrienes?
Lipoxins
Which arachidonic acid metabolite counteracts the inflammatory effects of thromboxane A2?
PGI2
Anti-leukotriene medications (zileuton, montelukast, zafirlukast) are able to relieve the effects of asthma by reducing what leukotriene-mediated process?
Bronchospasm
Name the produced local inflammatory effect of TNF and IL-1 action on each of the following:
Endothelium
Leukocytes
Endothelium - increased permeability and leukocyte adhesion
Leukocytes - activation
Name the produced systemic protective effects of TNF, IL-1, and IL-6 action on each of the following:
Brain
Liver
Bone marrow
Brain - fever
Liver - increased acute phase proteins
Bone marrow - leukocyte production
What pathological effect does TNF have on the heart?
What pathological effect does TNF have on endothelial cells?
What pathological effect does IL-1 have on skeletal muscle and adipose?
Low cardiac output;
hypercoagulability and increased permeability;
insulin resistance
TNF blockers increase patient susceptibility to _____bacterial infections.
TNF blockers increase patient susceptibility to mycobacterial infections.
What is the main inhibitory factor of the complement cascade?
C1 inhibitor
(C1 INH)
Hereditary angioedema is an inherited deficiency of what?
C1 inhibitor
Delay accelerating factor prevents the formation of what complement structure?
CD59 prevents the formation of what complement structure?
C3 convertase (C4b/C2b);
the MAC
What disorder is here described:
a deficiency in delay accelerating factor and/or CD59 leads to increased complement-mediated hemolysis, particularly at night.
Paroxysmal nocturnal hematuria
Why does the hemolysis of paroxysmal nocturnal hematuria occur at night?
Hypoxic stress
(increased while sleeping)
Which are the clotting factors dependent on vitamin K?
II, VII, IX, and X;
proteins C and S
True/False.
Calcium binds the γ-carboxylated aspartic acid residues on clotting factors II, VII, IX, and X.
False.
Calcium binds the γ-carboxylated glutamic acid residues on clotting factors II, VII, IX, and X.
Which clotting factors are specific to the intrinsic pathway?
Which clotting factors are specific to the extrinsic pathway?
Which clotting factors are specific to the common pathway?
XII, XI, IX, V;
VII, TF;
X, V, prothrombin, fibrinogen
Which clotting test assesses the functioning of the intrinsic pathway?
Which clotting test assesses the functioning of the extrinsic pathway?
PTT (XII, XI, IX –> X, V, II, fibrinogen);
PT (VII –> X, V, II, fibrinogen)
True/False.
Factor XII (Hageman factor) can be activated by collagen, basement membranes, and activated platelets.
True.
Factor XII (Hageman factor) can be activated by collagen, basement membranes, and activated platelets.
Describe the common pathway of the coagulation cascade.
X+ V –>
cleave prothrombin to thrombin –>
cleaves fibrinogen to fibrin
What protein activates plasminogen to plasmin?
What serum protein is released by the liver to bind (and reduce the activity of) activated plasmin?
Tissue plasminogen activator (TPA);
α2-antiplasmin
Clotting factor ____ activates kallikrein (thus activating the bradykinin cascade).
Clotting factor VIIa activates kallikrein (thus activating the bradykinin cascade).
True/False.
Different infectious agents can cause different types of inflammation (e.g. acute vs. reactive; purulent vs. granulomatous vs. necrosis vs. scarring; etc.).
True.
Different infectious agents can cause different types of inflammation (e.g. acute vs. reactive; purulent vs. granulomatous vs. necrosis; etc.).
Many purulent (suppurative) infections are caused by gram-________ cocci and gram-________ bacilli (rods).
Many purulent (suppurative) infections are caused by gram-positive cocci and gram-negative bacilli (rods).
True/False.
Purulent (suppurative) inflammation due to infectious causes typically rises due to chronic bacterial infections.
False.
Purulent (suppurative) inflammation due to infectious causes typically rises due to acute bacterial infections.
Staphylococcal and streptococcal infections are causes of ____________ inflammation (acute).
TB and syphilis infections are causes of ____________ inflammation (chronic).
Staphylococcal and streptococcal infections are causes of suppurative (purulent) inflammation.
TB and syphilis infections are causes of granulomatous (mononuclear) inflammation.
Mycobacterium tuberculosis stain with acid-fast due to the presence of _______ ______ in their cell walls (as opposed to LPS).
Mycobacterium tuberculosis stain with acid-fast due to the presence of mycolic acids in their cell walls (as opposed to LPS).
Most cytopathic/cytoproliferative inflammatory reactions are caused by _______ infections.
Most cytopathic/cytoproliferative inflammatory reactions are caused by viral infections (e.g. HHSV, HPV, CMV).
Which of the four hypersensitivity reactions are antibody-mediated?
I, II, III
(IV is mediated by T cells)
Which antibody class mediates type I hypersensitivity reactions?
IgE
Which antibody classes mediate type II hypersensitivity reactions?
IgG, IgM
Which antibody classes mediate type III hypersensitivity reactions?
IgG, IgM, IgA
What cell type mediates type IV hypersensitivity reactions?
T cells
Type I hypersensitivity reactions are basically just errant _____ _____ degranulations due to ____ receptor cross-linking.
This is the cause of anaphylactic reactions.
Type I hypersensitivity reactions are basically just errant mast cell degranulations due to IgE receptor cross-linking.
This is the cause of anaphylactic reactions.
Type __ hypersensitivity reactions are basically just errant mast cell degranulations due to IgE receptor cross-linking.
This is the cause of ___________ reactions.
Type I hypersensitivity reactions are basically just errant mast cell degranulations due to IgE receptor cross-linking.
This is the cause of anaphylactic reactions.
Type ___ hypersensitivity reactions are basically just errant antibody-self interactions (can be cytotoxic or altering to normal cell physiology).
Type II hypersensitivity reactions are basically just errant antibody-self interactions (can be cytotoxic or altering to normal cell physiology).
Type III hypersensitivity reactions are mediated by ________-_______ immune complexes.
Type III hypersensitivity reactions are mediated by antibody-antigen immune complexes.
Which two hypersensitivity reactions can be mediated via complement?
HSR II and HSR III
Which cell type mediates the first phase (immediate) of type I hypersensitivity (allergies)?
Which cell type mediates the second phase (after four hours) of type I hypersensitivity (allergies)?
Mast cells;
neutrophils, eosinophils, monocytes, basophils, CD4+ lymphocytes
What is the primary chemical mediator of type I hypersensitivity (allergies)?
Histamine
What are the three subtypes of type II hypersensitivity?
1. Antibody-mediated ___________
2. Antibody-mediated ___________ or ___________
3. _________-mediated
What are the three subtypes of type II hypersensitivity?
1. Antibody-mediated cytotoxicity
2. Antibody-mediated cellular dysfunction or anti-receptor
3. Complement-mediated
In type III hypersensitivity reactions, antigen-antibody complexes deposit where?
In tissues
Name a few tissues that are favorable deposit spot for type III hypersensitivity reaction antigen-antibody complexes.
Kidneys
______
______
______
Serosal membranes
Heart
Kidneys
Skin
Joints
Vessels
Serosal membranes
Heart
Name a few tissues that are favorable deposit spot for type III hypersensitivity reaction antigen-antibody complexes.
______
Skin
Joints
Vessels
______ ______
______
Kidneys
Skin
Joints
Vessels
Serosal membranes
Heart
Name the hypersensitivity reaction associated with each of the following disorders, respectively:
Hashimoto’s thyroiditis
Arthus reaction
Transfusion reaction
Anaphylaxis
II
III
II
I
Name the hypersensitivity reaction associated with each of the following disorders, respectively:
Grave’s hyperthyroidism
SLE
Chronic transplant rejection
Hay fever
II
III
IV
I
Name the hypersensitivity reaction associated with each of the following disorders, respectively:
Pemphigus vulgaris
Myasthenia gravis
Goodpasture’s syndrome
T1DM
II
II
II
IV
What are the two main types of type IV hypersensitivity reaction?
A. Delayed (cellular mediation by TH cells and macrophages)
B. Cytotoxic (cellular mediation by TC cells)
Which type of type IV hypersensitivity reaction is involved in the macrophage recruitment and granuloma formation seen in diseases such as sarcoidosis or TB?
Delayed type IV HSR
Which type of type IV hypersensitivity reaction involves very large, complex antigens?
Delayed type IV HSR
Name the type IV hypersensitivity reaction subtype associated with each of the following disorders, respectively:
Graft rejection
Tuberculosis granulomas
Fungal granulomas
Cytotoxic (TC cells)
Delayed (TH cells and macrophages)
Delayed (TH cells and macrophages)
Name the type IV hypersensitivity reaction subtype associated with each of the following disorders, respectively:
Sarcoidosis
Tumor cell surveillance
Viral infection response
Delayed (TH cells and macrophages)
Cytotoxic (TC cells)
Cytotoxic (TC cells)
The necrotizing ________ is the hallmark of a delayed type IV hypersensitivity reaction.
It is characterized by macrophage (e.g. histiocytes, giant cells) accumulation and potential caseation.
The necrotizing granuloma is the hallmark of a delayed type IV hypersensitivity reaction.
It is characterized by macrophage (e.g. histiocytes, giant cells) accumulation and potential caseation.
What are the three main categories of transplant rejection (host-vs.-graft)?
- Hyperacute
- Acute
- Chronic
Most cases of transplant rejection are mediated via type ____ hypersensitivity reactions.
Most cases of transplant rejection are mediated via type IV hypersensitivity reactions.
(Note: hyperacute rejection is a type II HSR.)
_________ transplant rejection is caused by preformed recipient _________ and can lead to fever and rapid failure of the organ shortly after the recipient blood flow is anastomosed to the donor organ.
Hyperacute transplant rejection is caused by preformed recipient antibodies and can lead to fever and rapid failure of the organ shortly after the recipient blood flow is anastomosed to the donor organ.
There are two overlapping subcategories of acute transplant rejection, _________ and _________ transplant rejection.
These processes are mediated by _______ cells.
There are two overlapping subcategories of acute transplant rejection, cellular and vascular transplant rejection.
These processes are mediated by TC cells.
True/False.
All of the following are potential characteristics of acute transplant rejection:
Endotheliitis
Vasculitis
Renal tubulitis
Irreversible damage
Thrombosis
False.
All of the following are potential characteristics of acute transplant rejection:
Endotheliitis
Vasculitis
Renal tubulitis
Reversible damage
Thrombosis
How long after transplantation will hyperacute transplant rejection first manifest?
How long after transplantation will acute transplant rejection first manifest?
How long after transplantation will chronic transplant rejection first manifest?
Nearly instantaneous;
weeks-to-months;
months-to-years
Hyperacute rejection is especially likely in recipient females that have a history of ___________.
This is due to extra humoral antibodies developed against any of the thousands of fetal antigens found on fetal ______.
Hyperacute rejection is especially likely in recipient females that have a history of childbirth.
This is due to extra humoral antibodies developed against any of the thousands of fetal antigens found on fetal RBCs.
Which transplant rejection category is basically an immune-mediated atherosclerosis?
This process is mediated via what cell type?
Chronic transplant rejection;
TC lymphocytes
Chronic transplant rejection category is basically an immune-mediated ___________ characterized by interstitial fibrosis and vessel stenosis in the allograft that is unresponsive to treatment.
This process generally occurs over ______ or ______ (timeframe) post-transplantation.
Chronic transplant rejection category is basically an immune-mediated atherosclerosis characterized by interstitial fibrosis and vessel stenosis in the allograft that is unresponsive to treatment.
This process generally occurs over months or years (timeframe) post-transplantation.
Which transplant rejections are treatable?
(Hyperacute, acute, chronic)
Hyperacute, acute
_____-vs.-_____ disease is most commonly seen in bone marrow / stem cell transplants and results from donor lymphocytes attacking the recipient.
This condition is treated with ____________.
Graft-vs.-host disease is most commonly seen in bone marrow / stem cell transplants and results from donor lymphocytes attacking the recipient.
This condition is treated with corticosteroids (high-dose).
Preservation injury is a ________ (type of necrosis) organ necrosis most commonly caused by lengthy transport of the organ from the donor to the recipient.
Preservation injury is a coagulative organ necrosis most commonly caused by lengthy transport of the organ from the donor to the recipient (ischemic conditions).
What post-transplant disorder results in leukocyte hyperplasia and potential B cell malignancy?
Note: it is associated with the following factors:
Allograft antigen stimulation
EBV infection
Carcinogens
Immunosupressants
Post-transplant lymphoproliferative disorder
D. Delayed type
B. Complement-mediated cytotoxic reaction
E. CD-8 T Lymphocytes
A. Granulomatous lymphadenitis
D. Immune complex deposition with inflammatory tissue damage
F. T-lymphocyte cell-mediated cytotoxicity
What does an elevated sedimentation rate (ESR) indicate?
Inflammation
Chronic/active inflammatory conditions result in elevated sedimentation rate (ESR) because of increased __________.
Chronic/active inflammatory conditions result in elevated sedimentation rate (ESR) because of increased fibrinogen.
(leads to increased clumping –> faster sed. rate)
True/False.
An elevated sedimentation rate is a non-specific marker of inflammation.
True.
An elevated sedimentation rate is a non-specific marker of inflammation.
What rule of thumb allows for calculation of a patient’s expected sedimentation rate?
Women: < 20 mm/hr
Men: < 15 mm/hr
Rule of thumb:
Men: age / 2 mm/hr
Women: age / 2 + 5 mm/hr
True/False.
ESR is extremely variable from person to person.
True.
An increase in what plasma factors lead to an elevated sedimentation rate?
An decrease in what plasma factors lead to an elevated sedimentation rate?
Fibrinogen, immunoglobulins;
albumin
What changes in RBCs lead to an elevated sedimentation rate?
Anemia, macrocytosis
A patient presents with an ESR over 100 mm/hr. What conditions must be in your differential?
Neoplastic disease;
infection;
temporal arteritis
What purpose does serum protein electrophoresis allow in laboratory diagnosis?
Comparison of relative protein levels
(can be useful in diagnosing nephrotic syndrome, monoclonal gammopathies, agammaglobulinemias, cirrhosis, protein-loss, etc.)
What is the order of substances shown in a serum protein electrophoresis?
Albumin — α1 — α2 — β — γ
What are the main components of the α1 and α2 sections in a serum protein electrophoresis?
α1-antitrypsin;
α2-macroglobulin, haptoglobulin
What are the main components of the β section in a serum protein electrophoresis?
Complement;
transferrin
What are the main components of the γ section in a serum protein electrophoresis?
Immunoglobulins (IgM, IgG, IgA)
What condition does this serum protein electrophoresis show?
Hypogammaglobulinemia
What condition does this serum protein electrophoresis show?
Monoclonal gammopathy
(e.g. multiple myeloma; Waldenstom’s syndrome)
What condition does this serum protein electrophoresis show?
Hepatic cirrhosis
What condition does this serum protein electrophoresis show?
Nephrotic syndrome
What is a leukocyte left shift?
A leukocytosis characterized by immature WBCs
_________ infections usually result in neutrophilia.
_________ infections and _________ usually result in eosinophilia.
_________ infections usually result in lymphocytosis.
Bacterial infections usually result in neutrophilia.
Parasitic infections and allergies usually result in eosinophilia.
Viral infections usually result in lymphocytosis.
True/False.
Elevated CRP is a marker of inflammation while elevated fibrinogen is a marker of a lack of inflammation.
False.
Both elevated CRP and elevated fibrinogen are markers of inflammation.
Immunodeficiency disorders may be classified as ___-cell (antibody) or ___-cell (cellular) or combined ___ and ___ cell deficiencies.
The defects may be primary (congenital) or secondary (acquired).
Immunodeficiency disorders may be classified as B-cell (antibody) or T-cell (cellular) or combined B and T cell deficiencies.
The defects may be primary (congenital) or secondary (acquired).
What disorder is described below?
‘A block in differentiation of pre-B cells into B cells due to mutation of tyrosine kinase called Bruton’s tyrosine kinase (btk) gene on the x-chromosome.’
Bruton’s X-linked agammaglobulinemia
What cell type is deficient in X-linked agammaglobulinema (Bruton’s disease)?
B cells
True/False.
Patients with X-linked agammaglobulinema are at increased risk of most pyogenic viral infections.
False.
Patients with X-linked agammaglobulinema are at increased risk of most pyogenic bacterial infections.
Which immunoglobulin classes are decreased in X-linked agammaglobulinemia (Bruton’s disease)?
All classes
(IgG, IgA, IgM, IgE, IgD)
The patient described below is most likely to be what gender?
A 9 month year old ______ presents with recurrent pneumonia due to S. aureus infection. Further examination reveals decreased serum levels of all immunoglobulin classes, absent peripheral B cells, and rudimentary tonsils.
Male
(Bruton’s X-linked agammaglobulinemia)
Why can patients with Bruton’s X-linked agammaglobulinema handle most viral, fungal and parasitic infections?
Intact T cell activity
What is the most common primary immunodeficiency syndrome?
What is the most common presentation?
Selective IgA deficiency;
most patients are asymptomatic
Selective IgA deficiencies lead to an increased risk of what infection types?
Sinopulmonary and gastrointestinal
What disease type is similar to Bruton’s X-linked agammaglobulinema but presents equally in both men and women?
Common variable immunodeficiency
Which primary immunodeficiency type is characterized by hypotonia, T cell absence, and underdeveloped lymph node paracortex and absent thymus?
Afflicted patients are at an increased risk of what infection types?
DiGeorge syndrome;
viral, fungal and protozoal infections
What constellation of immunodeficiency disorders is characterized by decreased levels of T cells, B cells, and all immunoglobulin types?
SCID
Name the disorder described below:
- X-linked immunodeficiency characterized by 1) recurrent infections, 2) hemorrhage 2° to thrombocytopenia and eczema.
- Presents in babies in the first few months of life with petechia and infections – otitis media.
Wiscott-Aldrich Syndrome
The three characteristic components of Wiscott-Aldrich syndrome are:
(1) Recurrent ___________
(2) _____cyto_____
(3) _________
The three characteristic components of Wiscott-Aldrich syndrome are:
(1) Recurrent infections
(2) Thrombocytopenia
(3) Eczema
In particular, congential defects in T-cell function cause increased susceptibility to _________ infections.
In particular, congential defects in T-cell function cause increased susceptibility to Candida infections.
(E.g. chronic mucocutaneous candidiasis)
Hyper-IgM syndrome is mainly caused by defective _____ on ___ cells.
Hyper-IgM syndrome is mainly caused by defective CD40L on TH cells.
(CD40L is necessary for Ig class-switching)
True/False.
Bruton’s X-linked agammaglobulinemia leads to increased risk of Giardiasis.
True.
The risk of graft-vs.-host disease (GVHD) is __________ in patients with SCID due to _________ T cells.
The risk of graft-vs.-host disease (GVHD) is increased in patients with SCID due to maternal T cells.
True/False.
Selective IgG deficiencies are the most common primary immunodeficiency. Afflicted patients may present with anaphylaxis if given blood transfusions (due to IgG in transfusion).
False.
Selective IgA deficiencies are the most common primary immunodeficiency. Afflicted patients may present with anaphylaxis if given blood transfusions (due to IgA in transfusion).
Selective IgA deficiencies often present with combined Ig__ deficiency.
Selective IgA deficiencies often present with combined IgG deficiency.
True/False.
The following immunodeficiencies all predispose patients to rheumatoid conditions:
Bruton’s X-linked agammaglobulinema
IgA deficiency
Common variable immunodeficiency
True.
What is the metabolic basis of gout?
Hyperuricemia
____% of cases of acute gout affect the hallux.
50% of cases of acute gout affect the hallux.
Many cases of acute gout are preciptated by some form of _______.
Many cases of acute gout are preciptated by some form of stress (e.g. dietary overindulgencence, excessive alcohol intake, physical / emotional fatigue, etc.).
Chronic gouty arthritis occurs in __ - __% of gout patients.
Chronic gouty arthritis occurs in 10 - 15% of gout patients.
True/False.
The soft tissue tophi seen in chronic gout are painless and nontender.
True.
90% of chronic gout patients develop some form of ______ impairment.
Patients are also prone to develop arteriosclerosis and diabetes mellitus.
90% of chronic gout patients develop some form of renal impairment.
Patients are also prone to develop arteriosclerosis and diabetes mellitus.
Gouty joint fluid contains long needle sodium urate crystals that show strong __________ __________ under polarizing microscopy.
Gouty joint fluid contains long needle sodium urate crystals that show strong negative birefringence under polarizing microscopy.
Why does gout preferentially affect peripheral joints?
Decreased temperature
(lower urate solubility)
Net urate clearance is only ___% of the filtered load (due to reabsorption).
Net urate clearance is only 10% of the filtered load (due to reabsorption).
Name a few risk factors for gout.
Males;
older age;
high SES;
obesity;
high alcohol intake
A patient with no history of trauma or osteopenia presents with a tender and swollen right hallux.
Name a few joint pathologies that might be in your differential.
Gout;
septic arthritis;
pseudogout
Gout is caused by ____________ crystals that are _________ (birefringence-status).
Pseudogout is caused by ____________ crystals that are _________ (birefringence-status).
Gout is caused by monosodium urate crystals that are negatively birefringent.
Pseudogout is caused by calcium pyrophosphate crystals that are positively birefringent.
Each different clinical type of amyloidosis differs in the composition of the deposited _________. In any given patient the _________ molecule deposited in each organ is the same.
Each different clinical type of amyloidosis differs in the composition of the deposited protein. In any given patient, the amyloid molecule deposited in each organ is the same.
All amyloids stain red with the _______ _____ stain. But when these section are viewed with polarized light they exhibit a _______ birefrigency. This feature of amyloid can be used to identify it in tissue sections.
All amyloids stain red with the Congo red stain. But when these section are viewed with polarized light they exhibit a green birefrigency. This feature of amyloid can be used to identify it in tissue sections.
Each form of amyloidosis is characterized by deposits made of three main components:
- Fibrillary protein (95%)
- Amyloid P component (5%)
- Glycosoamynoglycan
Which part differs between amyloid disorders?
The fibrillary protein
You suspect a patient has amyloidosis. How do you confirm the diagnosis?
Skin or rectal biospy
True/False.
In all forms of systemic amyloidosis, the disease is ultimately fatal.
True.
True/False.
Isolated amyloidopathies only affect single organs and are not necessarily fatal.
True.
True/False.
The following chronic inflammatory diseases have all been shown to cause a decrease in patient risk of amyloidosis.
Tuberculosis.
Lung abcesses.
Osteomyelitis.
Reumatoid arthritis.
Systemic Lupus erythematous.
Drug addiction.
Hodgkin’s disease.
Renal Cell carcinoma.
False.
The following chronic inflammatory diseases have all been shown to cause a increase in patient risk of amyloidosis.
Tuberculosis.
Lung abcesses.
Osteomyelitis.
Reumatoid arthritis.
Systemic Lupus erythematous.
Drug addiction.
Hodgkin’s disease.
Renal Cell carcinoma.
What chemical stains amyloid in tissue?
Iodine
Progressive systemic sclerosis (scleroderma) is a systemic disease characterized by the presence of excessive _________ throughout the body.
Progressive systemic sclerosis (scleroderma) is a systemic disease characterized by the presence of excessive fibrosis throughout the body.
Systemic sclerosis is associated with CREST syndrome.
For what does CREST stand?
C __________
R __________ phenomenon
E __________ dysmotility
S Sclerodactyly
T Telangiectasia
C Calcinosis
R Raynaud’s phenomenon
E Esophageal dysmotility
S Sclerodactyly
T Telangiectasia
Systemic sclerosis is associated with CREST syndrome.
For what does CREST stand?
C Calcinosis
R Raynaud’s phenomenon
E Esophageal dysmotility
S __________
T __________
C Calcinosis
R Raynaud’s phenomenon
E Esophageal dysmotility
S Sclerodactyly
T Telangiectasia
Scleroderma patients are ANA-_______ (positive/negative).
Scleroderma patients are ANA-positive (95% of cases).
True/False.
Scleroderma likely arises from a combination of immunological and ischemic causes.
True.
Scleroderma likely arises from a combination of immunological and ischemic causes.
Scleroderma patients typically show what laboratory results?
- ANA-positive
- Elevated ESR
- Anemia
A 63-year-old man complains of chronic back pain has multiple lytic lesions in his vertebral bodies, with anemia, rouleaux formation, a monoclonal gammapathy with free IgG light chains in his urine and a bone marrow aspiration revealing sheets of plasma cells. Two years previously, he was told he had a “plasmacytoma”. Urinalysis reveals 4+ proteinuria A renal biopsy reveals focal and segmental glomerular and interstitial vascular deposits of amorphous eosinophilic material that is Congo-red positive and PAS negative.
What is the most likely diagnosis of this patient’s renal presentation?
Amyloid nephropathy secondary to multiple myeloma
Fracture healing follows the following steps:
- Fracture
- _________ formation
- Organized _________
- Fibrous _________
- Ossification
- Remodeling
Fracture healing follows the following steps:
- Fracture
- Hematoma formation
- Organized hematoma
- Fibrous callus
- Ossification
- Remodeling
Fracture healing follows the following steps:
- Fracture
- Hematoma formation
- Organized hematoma
- Fibrous callus
- __________
- __________
Fracture healing follows the following steps:
- Fracture
- Hematoma formation
- Organized hematoma
- Fibrous callus
- Ossification
- Remodeling
________ ________ (or ________ ________) is a non-infectious infarction of bone and bone marrow that can arise from a number of antecedent conditions.
Avascular necrosis (or aseptic necrosis) is a non-infectious infarction of bone and bone marrow that can arise from a number of antecedent conditions.
Many cases of avascular (aseptic) necrosis result due to changes in the __________ of the bone.
The list of related conditions other than post-traumatic includes idiopathic, _______-induced, and _______-induced necrosis.
Many cases of avascular (aseptic) necrosis result due to changes in the microcirculation of the bone.
The list of related conditions other than post-traumatic includes idiopathic, alcohol-induced, and corticosteroid-induced necrosis.
What is the most common cause of osteomyelitis?
Staphylococcus aureus
__________ is a general term meaning reduced bone mass.
Osteopenia is a general term meaning reduced bone mass (can encompass the terms osteoporosis or osteomalacia or both).
In osteomalacia, the bones are _____.
In osteoporosis, the bones are _____.
In osteomalacia, the bones are soft.
In osteoporosis, the bones are brittle.
What are two pathological conditions seen in the bone as a result of hyperparathyroidism?
Renal osteodystrophy (results from chronic renal disease);
osteitis fibrosa cystica
What disease is characterized by structurally weakened bones that have an abundance of cement lines (sometimes referred to as a mosaic pattern)?
Paget’s disease
A patient presents with increased hat size, gait changes, and deafness.
What diagnosis is at the top of your differential?
Paget’s disease
True/False.
Eczema mainly involves the dermis.
False.
Eczema mainly involves the epidermis.
What three forms of dermatitis mainly affect the epidermis?
Eczema;
erythema multiforme;
psoriasis
What disorder is described by the following?
“Characterized by widened intercellular space or with vesicles formation, scale crust, eosinophil infiltrate, and presented as papules, plaques or vesicles.”
Eczema
Erythema multiforme is an acute _________ eruption of _________ necrolytic dermatitis.
Erythema multiforme is an acute targetoid eruption of epidermal necrolytic dermatitis.
Erythema multiforme is usually secondary to what?
Infection;
drug use;
malignancy
Identify the disorder:
“Chronic scaly/pustular dermatitis with idiopathic neutrophil aggregates in the scaly upper epidermis and elongation of the rete ridges of the epidermis.”
Psoriasis
Name two forms of dermatitis that mainly affect the dermis.
Urticaria (hives);
scleroderma
Erythema __________ (a self-limited form of ________itis) exhibits ill-defined reddish, tender nodules on legs, often associated with infection, drug use, sarcoidosis, inflammatory bowel disease, and malignancy.
Erythema nodosum (a self-limited form of panniculitis) exhibits ill-defined reddish, tender nodules on legs, often associated with infection, drug use, sarcoidosis, inflammatory bowel disease, and malignancy.
___________ describes a pathological process of losing intercellular connections of the keratinocytes and therefore presenting as bulla clinically.
Acantholysis describes a pathological process of losing intercellular connections of the keratinocytes and therefore presenting as bulla clinically.
Pemphigus vulgaris involves antibodies against:
Bullous pemphgoid involves antibodies against:
Desmogleins (desmosomes);
BP1, BP2 (hemidesmosomes)
Dermatitis ____________: an autoimmune dermatitis with granular deposit of Ig__ against gliadin and reticulin at the tips of dermal papillae.
Associated with ___________ insensitivity.
Dermatitis herpetiformis: an autoimmune dermatitis with granular deposit of IgA against gliadin and reticulin at the tips of dermal papillae.
Associated with gluten insensitivity.
_______ _______ (common wart): Discrete benign squamous papilloma (benign growth of the keratinocytes) caused by ______ infection.
Verruca vulgaris (common wart): Discrete benign squamous papilloma (benign growth of the keratinocytes) caused by HPV infection.
What is the most common bacterial infection presentation among children?
Impetigo: reddish macules / pustules on face and hands + shallow erosion / honey-colored crusts in later stage
Impetigo is characterized by reddish macules / pustules on the _______ and _______ + shallow erosion / honey-colored ______ in later stage
Impetigo is characterized by reddish macules / pustules on the face and hands + shallow erosion / honey-colored crusts in later stage
What are the two main infectious agents that cause impetigo?
Staphylococcus aureus;
Group A streptococcus (Streptococcus pyogenes)
What is here defined:
“superficial fungal infection confined to stratum corneum of the epidermis, hair/hair follicles, or nail — caused by dermatophytes”
Tinea (dermatophytosis)
Auto-reactive lymphocytes that are not removed in the process of clonal ________ will then be inactivated in the process of clonal ________.
Auto-reactive lymphocytes that are not removed in the process of clonal deletion will then be inactivated in the process of clonal anergy.
Which serum autoantibodies are highly diagnostic for SLE?
Anti-Smith
+
anti-dsDNA
____ out of the following 11 are necessary for clinical diangosis of SLE.
A. Malar rash – “Butterfly rash”
B. Discoid rash – Erythematous, Keratotic, scaling, follicular plugging and/or atrophic dermatitis.
C. Photosensitivity
D. Oral/Nasophayngeal ulcers, usually painless
E. Arthritis – non-erosive arthritis involving at least 2 joints
F. Serositis – pleuritic, pericarditis – effusions, friction ribs
G. Renal – significant proteinuria and/or cellular casts
H. Neuropsychiatric - seizures, psychosis
I. Hematologic – Hemolytic anemia, leukopenia, lymphopenia or thrombocytopenia
J. Immunologic disorder – Anti-DS-DNA, Anti-Sm antibodies, antiphospholipid antibodies, anti-cardiolipin antibodies, false positive serologic test for syphilis (VDRL)
K. ANA
4 out of the following 11 are necessary for clinical diangosis of SLE.
A. Malar rash – “Butterfly rash”
B. Discoid rash – Erythematous, Keratotic, scaling, follicular plugging and/or atrophic dermatitis.
C. Photosensitivity
D. Oral/Nasophayngeal ulcers, usually painless
E. Arthritis – non-erosive arthritis involving at least 2 joints
F. Serositis – pleuritic, pericarditis – effusions, friction ribs
G. Renal – significant proteinuria and/or cellular casts
H. Neuropsychiatric - seizures, psychosis
I. Hematologic – Hemolytic anemia, leukopenia, lymphopenia or thrombocytopenia
J. Immunologic disorder – Anti-DS-DNA, Anti-Sm antibodies, antiphospholipid antibodies, anti-cardiolipin antibodies, false positive serologic test for syphilis (VDRL)
K. ANA
Both SLE and rheumatoid arthritis are associated with R_________’s phenomenon.
Both SLE and rheumatoid arthritis are associated with Raynaud’s phenomenon.
Both SLE and rheumatoid arthritis are type _____ hypersensitivity reactions.
Both SLE and rheumatoid arthritis are type III hypersensitivity reactions.
What is the main causal mechanism of the damage caused by autoantibodies in SLE and rheumatoid arthritis?
Antibody complexes activate complement in tissues
Rheumatoid factor found in synovium forms immune complexes with Ig___ antibodies that fix _________, leading to a type III hypersensitivity reaction causing joint tissue damage.
Rheumatoid factor found in synovium forms immune complexes with IgG antibodies that fix complement, leading to a type III hypersensitivity reaction causing joint tissue damage.
Name the main cell type(s) or immune substrates involved in each of the following:
Hyperacute transplant rejection
Acute transplant rejection
Chronic transplant rejection
Immunoglobulins
CD8+ T cells
CD4+ T cells, macrophages
What are the three cytopathic ‘M’s of human herpes simplex virus infection seen in infected cells?
Multi__________
M__________
Nuclear M__________
Multinucleation
Molding
Nuclear Margination
(NOTE: above changes result in ground glass nuclei)
Describe the pathologic nuclei seen in CMV infection.
“Owl’s eye” nuclear inclusions with characteristic halo
Human herpes simplex virus
Multinucleation
Molding
Nuclear Margination
(ground glass nuclei)
Infection with what organism is apparent in these cells?
“Owl’s eye” nuclear inclusions with characteristic halo
Cytomegalovirus
(“Owl’s eye” nuclear inclusions with characteristic halo)
