Inflammation Flashcards
Dystrophic and metastatic calcification
Dystrophic is normal serum Calcium in damaged tissue. Atherosclerosis, aortic stenosis (e.g. bicuspid valve). Hypercalcemia or hyperphosphatemia –> deposition of ca in normal tissue, which is “metastatic calcification.”
Hereditary spherocytosis
Cannot see a central area of pallor, then it’s a spherocytes. e.g. absence of spectrin
Ubiquitin
A stress protein. When intermediate filaments are damaged, they are ubiquinated for destruction. MALLORY bodies in fatty change in alcoholic hepatitis (keratin damaged!). Tau protein is ubiquinated neurofibrillary. Lewy body.
Three types of cells
Labile - NEVER in G0, short G0 (e.g. tissues with stem cells - bone marrow, intestine bottom of crypts, skins). Stable cells - G0 phase and needs stimulus to divide (liver, spleen, kidney, SMOOTH muscle). Permanent - can’t get into the cell cycle (striated, cardiac, neurons). With a permanent cell, can’t go through hyperPLASIA. G1 phase is most variable (e.g. proliferative phase of menstrual cycle are more variable). Cancer cells tend to have variable G1 phase.
Glucagon is a phosphorylator
loll
Cyclin-D dependent kinase
Activated by Cyclin D in G1 phase. G1 to S is MOST IMPORTANT checkpoint. Two suppressor genes = Rb (Chromosome 13). Active Cyclin-D dept kinase phosphorylates Rb to allow to get from G1 to S. p53 INACTIVATES that cyclin-d dependent kinase (chromosome 17). HPV inactivates Rb (E7 protein) and p53 (E6 protein). Rb - retinoblastoma.
S phase
4N at this point. G2 phase make tubulin for mitotic spindles (bleomycin). M phase - divides (griseofulvin, MTX, colchicine, paclitaxel - Yew tree) G0 or go into G1.
Growth alterations
Atrophy - decreased in tissue MASS. Cell decreases in size. Less mitochondria than normal. e.g. Increased pressure (hydronephrosis). e.g. brain atrophy - AD, atherosclerosis.. Hypopituitary –> adrenal gland (fasciculata - cortisol and reticularis - sex hormones; but glomerulosa is OK b/c aldo NOT stimulated by ACTH release). CF in Pancreas has blocked exocrine ducts –> back pressure -> atrophy. Renal vascular stenosis -> atrophic kidney -> increased renin.
Hypertrophy
Increase in size NOT NUMBER. Cardiac muscle hypertrophy - block is before the G2, the cells have 4N?.
Hyperplasia
Increase in NUMBER of cells. (Endometrial hyperplasia). However, prostate hyperplasia does NOT go into prostate cancer. All the other ones predispose to cancer. ALL HORMONE-stimulated GLANDS undergo hyperplasia.
Gravid uterus
Hypertrophy AND hyperplasia. 50:50
Psoriasis
Hyperplasia. Excess of stratum corneum. MTX works.
Metaplasia
Replaces one cell type to another. e.g. Barrett’s esophagus (glandular stroma where should be squamous epithelium)
Two parasites that produce cancer
Clonorchis sinesis - cholangiocarcinoma. Shistosoma hemtobium: transitional epithelium -> squamous metaplasia in the bladder
Actinic keratosis –>
Squamous cell carcinoma
Rubor, calor, tumor
HISTAMINE-mediated. Tumor from inc. permeability (venule) -> exudate.
Dolor
Bradykinin - activated by XII, increases vessel permeability and edema; and cough. Bradykinin is degraded by ACE. (Angioedema complication of ACEi). PGE2.
Directed chemotaxis
C5a, LTB4, (IL-8)
Opsonization
IgG, C3b; Neutrophils must have receptors for these opsonins.
Chronic inflammation
Macrophage/monocyte
Oxygen-dependent Myeloperoxidase system
Mol O2 (NADPH oxidase in cell membranes of neutrophils and monocytes but NOT macrophages w/ NADPH - HMP shunt, G6Pd, glutathione) –> superoxide. This respiratory burst measured by radiation detectors (nitro blue tetrazolium). NBT is a dye that goes into test tube. Free radical oxygen will cause a BLUE color. Superoxide dimutase –> peroxide. MPO (Myeloperoxidase from red granules in Neutrophils and Monocytes): peroxide + Cl- –> BLEACH. Macrophages lose this system.
G6Pd deficiency
Susceptible to infection b/c low MPO system function –> hemolysis
Chronic Granulomatous Disease
X-linked recessive. Missing NADPH oxidase + respiratory burst. Don’t have superoxide, peroxide. HAVE MPO + Cl. If some bacteria makes peroxide that stays (Catalase NEG) —> system available. They can’t kill Staph (Coagulase AND Catalase +). But CAN kill Strep.
MPO deficiency
Have a respiratory burst (normal dye) but can’t make bleach. Autosomal Recessive.
Umbilical cord doesn’t come off.
Integrin (adhesion) molecule defect.
Anaphylotoxins
C3a, C4a, C5a
Nitric oxide
Mostly made in endothelial cells –> vasodilator. Pulm HTN treatment.
IL-1
Pyogen. Stimulates hypthalamus to make prostaglandins which stimulates thermoregulatory center to make fever.
Corticosteroids
Inhibits PLA2. Stops Arachnoid. Stop prostaglandins and leukotrienes. Decrease adhesion molecule synthesis —-> INCREASED neutrophil count (50% of neutrophils are already stuck on endothelium - “demargination.”). Lymphocytoxic - apoptosis via caspases. Eosinophils decreased.
Dipyrimadole
Blocks thromboxane synthase (makes TXA2)
PGE2
Patent ductus. Mucous barrier in stomach. Dysmenorrhea (inc. uterine contractility)
Addison’s disease
NO cortisol. Decreased Neutrophils. Increased eosinophils and lymphocytes.
EM of lymphocyte
All nucleus.
EM plasma cell
Lots of RER = FINGER print. PLASMA cells
Eosinophil
Only inflammatory cell that has crystals in granules. Charcot-Leyden crystals in sputum of asthmatics. IgE Ab connections -> Major Basic Protein for helminthic (Type II hypersensitivity). Purpose of eosinophils in Type I hs is to stop chemical mediators (histamines, etc.)
Histiocyte marker
CD1
Marker for most common leukemia in children
CD10 - ALL.
CD21
EBV - B-cells
Fever
IL-1. PGE2 (made by hypothalamus). RIGHT-shifts O2 curve (increased oxygen) –> Oxygen-dependent MPO system.
Types of inflammation
Suppurative inflammation.
Diptheria
Makes a toxin that leads to damage –> pseudomembrane
Fibrinous inflammation
Inc. vessel permeability. e.g. lupus
Granulation tissue
Fibronectin - adhesion agent, chemotactic agent (dy 3-5). COLLAGEN type III initially (blood vessels). Collegneases break down type III over time. Converts it into type I (Zinc). Max tensile strength = 80% in 3 mo.
Keloid vs hypertrophic scar
Both excess type III collagen deposition. Keloid - blacks, 3rd degree burn –> scar –> squamous cell ca. Also from chronically draining sinus tract –> hyperplasia -> squamous cell carcinoma
Acute vs chronic inflammation
IgM is primary in acute. Most potent activator of complement system in IgM. Pentamer –> boom classical pathway. Pus (exudate). IgG requires two events for complement and doesn’t go beyond C3. 10 days -> isotope switching -> splice out mu heavy chain -> puts in GAMMA heavy chain = IgG. IgG is main in chronic. Monocytes and macrocytes and plasma cells in chronic.
Granuloma formation
Multi-nucleated giant cells. T-IV hypersensitivity (e.g. poison ivy). Alveolar MACROPHAGE holds TB and moves around (lympho-hematogenous spread) and processes that organisms’ antigen. After a week, presents to helper T-cell (Th1 via MHC-II) —> IFN-gamma, macrophage inhibitory factor, IL-2 —> IFN-g is activation for killing by macrophage. Caseous necrosis b/c of lipid. Epithelioid cell = activated macrophage. Fuse –> multi-nucleated giant cells. IL-12 makes memory of Ag experience -> Th1 cell. Often dystrophic calcification. TB stays alive.
Positive PPD
Inject PPD into skin. Langerhans cell = dendritic cell (CD1). Burbick granules. Presents to Th1 w/ memory of previous exposure via MHC-II -> release cytokines –> inflammatory reaction (induration). Older people have less immune response. AIDS patients might not have any + PPD (Can’t make granulomas at all, 5mm +).
Which part of kidney is most specific to ischemia?
Medulla. In nephron, the straight portion of proximal tubule. Second is medullary segment of thick ascending limb (Na-K-2Cl).
Repair cell of lung
Type II pneumocyte - Also makes surfactant
Repair cell of CNS
Astrocyte (stable cell) and can proliferate (gliosis)
ESR
Whole blood into perpendicular cylinder.
Cold agglutunins
IgM antibodies. Agglutination of RBC’s –> Raynaud’s.
Cryoglobulins
Congeal in the plasma —> Raynaud’s. High associated with Hepatitis C.
Acute appendicitis
Absolute neutrophilic leukocytosis. Toxic granulation (More azurophilic granules - MPO’s in here - in neutrophils). Left-shift: means LESS mature neutrophils. Greater than 10% BAND neutrophils.
