Pathoma 1: Growth and Immune stuff Flashcards
What are the permanent tissues that only undergo hypertrophy?
Skeletal muscle, Cardiac muscle, and Nerves
Osteoblastic bone metastasis
prostate cancer, small cell lung ca, hodgkin lymphoma
What symptoms for CO poisoning?
Cherry red appearance, confusion.
How to treat CO poisoning?
100% O2
How to treat methemoglobinemia
methylene blue
What are the irreversible signs of ischemic injury?
Membrane damage (plasma, mitochondria, lysosome)
When do you see calcium saponification?
Fat necrosis: trauma to fat and fatty acids are released. Can get dystrophic calcification.
What is the outcome of malignant hypertension?
Fibrinoid necrosis
What are the causes of fibrinoid necrosis
malignant hypertension and vasculitis
Draw the Apoptosis pathways. What are the different pathways and how are they activated? What do they all converge on?
Intrinsic: Release of Cytochrome C from the mitochondria is sensed and prevented by Bcl-2. –> Caspases
Extrinsic: FasL on T cells binds FAS R (CD95). Or TNF binds TNF R on target.
CD8 Tcell pathway: Perforins/Granzyme
What are the avenues of free radial injury?
Cytochrome C oxidase (during oxphos) Ionizing radiation Inflammation, Metals Acetaminophen (decreased glutathione) Carbon Tetrachloride (metabolized by P450, causes decreased apolipoproteins, then fat accumulation--> fatty change in liver)
What are the two types of systemic amyloid protein deposition?
Primary: AL from iG light change and is associated with plasma cell dyscrasias (MGUS, MM, Waldenstroms)
Secondary: AA from SAA, which is an acute phase reactant. Associated with chronic inflammatory state or familial mediteranean fever (episodes of fever, serosal inflammation)
When do you suspect and how can you diagnose systemic amyloid deposition?
Nephrotic syndrome, Restrictive cardiomyopathy, HSM, tongue enlargement
What are some manifestation of amyloid deposition in tissues?
Senile cardiac amyloidosis, NIDDM, Alzheimer’s (AB amyloid on chromosome 21), Dialysis associated (B2 microblogin in joints), Medullary carcinoma of thyroid (C-Cells- tumor cells in amyloid background)
Draw the aracondonic acid pathway? What are the two enzymes that control the first branch?
COX: makes prostaglandins which vasodilate, increase permeability in post cap venule. PGE2 produces Fever and Pain.
5-Lipooxygenase: makes Leukotrienes. LTB4 attracts PMNs. LTC4, D4, E4 produce vasoconstriction, bronchospasm, and increase vascular permeability
What attracts PMNs?
C5a, LTB4, Bacterial products, IL8
How are Mast cells activated?
1) C3a/C5a
2) Cross-linking of IgE by antigen
3) Tissue trauma
What are the immediate and delayed activities of mast cells
1) Histamine degranulation
2) Produces aracodonic acid derivatives, particularly leukotrienes
What complements trigger mast cells?
C3a and C5a
What complement recruits neutrophils?
C5a
What complement serves as an opsonin for phagocytosis?
C3b
Where is Hageman factor produced and how is it activated?
By the liver and by the endothelium
What does Hageman factor do?
It activates coagulation/fibrin, complement, and the kinin system
How does fever work?
Macrophages release IL-1 and TNF which promotes hypothalamus to increase COX activity and increase PGE2 levels.
What are Weible Palade bodies and what do they produce?
Produce P selectin and VWF
How are E selectins promoted?
TNF and IL-1
Chediak Higashi Syndrome
Defect.
Clinical Syndrome.
Lysosomal trafficking regulator gene –> microtubule problem.
Albinism, increased pyogenic infections, peripheral neuropathy, giant granules in leukocytes, defective primary hemostasis.
Leukocyte adhesion deficiency
Inheritance.
Defect.
Clinical syndrome.
AR.
Decreased integrins (CD18 subunit)
Delayed umbilical cord separation, increased ciruclating PMNS, recurrent bacterial infections that lack purulence.
Chronic Granulomatous Disease
Defect
Clinical syndrome
What test do you use?
NADPH Ox defect.
Catalase + bacteria infections. Staph a., Pseudomonas, Nocardia, Aspergilus
NBT test
MPO Deficiency
Candida infections
NBT is normal
What are the two ways B cells are activated?
1) Antigen binding to surface IgM or IgD
1) B cell presentation to MHC II and then 2) CD40L to CD40R
Formation of granulomas. What cytokines are involved?
MO secrete IL-12 to activate TH1 cells.
TH1 cells secrete INF to activate histiocytes.
Digeorge syndrome.
chromosome abnormality.
Clinical syndrome.
22q11
Thymus aplasia, no T cells, lack of parathyroids causes hypocalcemia, cardiac outlet? problems
Severe Combined Immune Deficiency
Etiologies
Bugs
Tx
Adenosine deaminase deficiency, cytokine receptor defects, MHC class II deficiency.
Fungal, viral, bacterial, no live vaccines.
Tx: Stem cell transplant
X-linked agammaglobulinemia
Defect.
infections
(Bruton Tyrosine Kinase)
bacterial infections (decreased opsonins like IgG), enterovirus (IgA), GIARDIA (IgA)
Note: presents after 6 mo old.
Common variable immunodeficiency
Low levels of immunoglobulin because of either B or Th1
IgA deficiency
associated with celiac
Hyper IgM
Mutated CD40 or CD40L
Wiskott Aldrich
What is the triad and the inheritance pattern?
Triad of Thrombocytopenia, eczema, Recurrent infections.
X-linked
c5-c9 defiency
Neisseria infection
C1 inhibitor deficiency
Hereditary angioedema, periorbital edema
What are the antiapoptotic signals?
Bcl-2 and Bclx
What are the proapoptotic signals?
Bak, Bax, Bim
What cytokines to macrophages produce?
IL-1, IL6, IL8, IL12, TNFalpha
What cytokines to T cells produce?
IL2, IL3
What cytokines do TH1 cells produce?
INF
What cytokines do TH2 cells produce?
IL4, IL5, IL10
Where are the stem cells of bowel?
Mucosal crypts
Keloid has what type of collage?
Type III collagen excess.
What surface markers do regulatory T cells express?
What can mutations of these manifest as?
CD4+ (associated with MS, TIDM)
CD25+ which is IL-2R
Fox P3 (Immune dysfuction polyendocrinopathy, enteropathy, xlinked IPEX)
AIRE gene significance and defect?
Autoimmune polyendocrine syndrome.
Triad of hypoparathyroidism, adrenal insufficiency, candida infection
What is Leibman Sachs endocarditis
You will see vegetations on boths ides of mitra vale. This is associated with Lupus
What are the three anti-phospholipid antibodies of lupus?
Anti cardiolipin
Lupus anticoagulant
AntiB2 glycoprotein
What cancer does Sjogren’s put you at risk for?
B cell lymphoma
What does CREST stand for?
Calcinosis, Raynaud’s, Esophogeal dysmotility, Sclerodactyly, Telangiectasias
What is Type I collagen in?
Bone
What is Type II collagen in?
Cartilage
What is type III collagen in?
Blood vessels, Granulation tissue
What is type IV collagen in?
Basement membrane
Malignant cells in an amyloid stroma?
Medullary carcinoma of the thyroid
