USMLE Pathology Flashcards
PaO2 and SaO2 levels in CO poisoning?
PaO2 normal, SaO2 decreased
What cells can only undergo hypertrophy?
Skeletal muscle, heart, neurons
What cellular functions stop working with hypoxia?
Na/K pumps = swelling, Ca pumps = Enzyme activation, Aerobic to anaerobic glycolysis = lactic acidosis, lowers pH
Where is the electron transport chain located?
Inner mitochondrial membrane
What are the three stages of cell death?
Pyknosis (shrinks down), karyorrhexis (nucleus breaks down), karyolysis (broken down)
When do you get a red infarct?
When blood reenters an infarcted area (of loosely connected tissue)
Why is necrosis in the brain liquefactive?
Because microglial cell enzymes destroy everything
What situations do you see liquefactive necrosis in?
Brain ischemia, abscess, pancreatitis
How do you distinguish dystrophic calcification from metastatic calcification?
Dystrophic = normal Ca PO4 in serum, will be elevated in metastatic
What are the three apoptotic pathways?
1) Intrinsic mitochondrial pathway (Bcl2, cytC)
2) Extrinsic receptor-ligant pathway (FasL, TNF)
3) Cytotoxic T cell pathway (perforin, granzymes)
Delayed separation of umbilical cord?
Leukocyte adhesion deficiency
What factors mediate pain?
PGE2 and bradykinin
What factors mediate inflammation
Mast cells, arachidonic acid, TLRs, complement, Hageman’s factor
What are mast cells activated by?
Tissue trauma, C3a, C5a, and cross linking by IgE
What factors are responsible for neutrophil chemotaxis?
LTB4, C5a, IL-8, bacterial products
What is an important example of TLRs in action?
CD14 on macrophages binds LPS on G-ve bacteria to activate NfKB
Features of Chediak Higashi syndrome?
Dysfunctional primary hemostasis Albinism Peripheral neuropathy Infections (pyogenic) Neutropenia Giant granules in leukocytes
Recurrent infections by catalase positive organisms?
Chronic granulomatous disease
How do macrophages continue acute inflamm?
IL-8
How do macrophages initiate resolution and healing?
IL-10, TGF-B
How are CD4 T cells activated?
TCR to MHC II with antigen and B7 to CD28 on T cell
How are CD8 T cells activated
TCR to MHC I with antigen and IL-2 from TH1 CD4+ helper cells
What cytokines are produced by CD4+ Th1 cells?
Helps CD8 T cells
IL-2 - promotes T cell proliferation, IFN-gamma: activates macrophages
What cytokines are produced by CD4+ Th2 cells?
Helps B cells
IL-4 - switch to IgG, IgE
IL-5 eosinophils and switch to IgA
IL-10 inhibits Th1 subtype
How are B cells activated independent of T cells?
BCR binds to antigen and becomes plasma cell expressing IgM, IgD
How are B cells activated by T cells?
B cell presents antigen on MHC II to CD4+ Th2 cells, CD40 on B cell binds CD40L on T cell –> IL4/IL5 for class switching
What are the key cells in granulomas?
Epithelioid histiocytes (surrounded by giant cells and rim of lymphocytes)
How are granulomas activated?
Macrophage presents antigen on MHC II to T helper cell and secretes IL-12 to turn it into TH1 cell. TH1 cell secretes IFN-gamma to turn macrophages into EH cells
What is the cause of DiGeorge syndrome?
Microdeletion 22q11
High yield cause of SCID?
Adenosine deaminase deficiency (builds up in lymphocytes, kills it)
Chronic candida, adrenal failure, hypoparathyroidism. Dx?
Autoimmune polyendocrine syndrome (AIRE deficiency)
What receptors are expressed on Treg cells?
CD4, CD25 (IL2-R), FOXP3
How do Tregs do their work?
Compete with B7 with CTLA4 and release IL-10/TGF-B to shut down MHC II, DC, macrophages, and B7
How does peripheral tolerance work?
Induces anergy if TCR binds MHC II without B7/CD-28 (absent in non-inflammatory states), or self expresses Fas to apoptose
Features of IPEX syndrome?
Immune dysfn, polyendocrinopathy, enteropathy, x-linked
What causes hyper IgM syndrome?
CD40/CD40L mutation = only IgMs produced, susceptible to pyogenic infections
What risks associated with common variable immunodeficiency?
Bacterial, giardia, enterovirus infxns + risk of AI disease/lymphoma
What makes up granulation tissue?
Blood vessels, fibroblasts (for T3 collagen), and myofibroblasts
T1 collagen?
Bone
T2 collagen?
Cartilage
T3 collagen?
Granulation tissue, embryonic tissue, blood vessels
T4 collagen?
Basement membrance
TGF-alpha
Epithelium and fibroblast GF
TGF-beta
Fibroblast GF and anti inflammatory
PDGF
Endothelium, smooth muscle, fibroblast GF
FGF
Angiogenesis and skeletal development
VEGF
Angiogenesis
What kind of collagen is seen in keloid scars?
T3 collagen
Aflatoxins
HCC, in Africa and stored grains
Alkylating agents
Lymphoma, leukemia
Alcohol
SqCC of oropharynx & upper esophagus, HCC, pancreatic cancer
Arsenic
SqCC of skin, lung cancer, angiosarcoma of liver
Nitrosamine
Intestinal type stomach cancer
Vinyl chloride
Angiosarcoma of liver
EBV cancer associations?
Nasopharyngeal cancer, Burkitt lymphoma, CNS in AIDS
HHV 8
Kaposi’s sarcoma in E. European males, AIDS, transplant
HTLV-1
ATLL
Ionizing
AML, CML, Papillary thyroid carcinoma
Ret
Associated with medullary carcinoma of thyroid in MEN2A/2B
PDFG-B overexpression
Astrocytoma
What is ABL responsible for?
9:22 translocation seen in CML and adult B-ALL
What are you at risk of with germline mutation of Rb?
Bilateral retinoblastomas and osteosarcoma