Pathoma Ch. 1-2 Basics Flashcards
Conjunctival –> stratified keratinizing squamous
Vitamin A deficiency –> Keratomalacia (metaplasia)
Pieces of bone in muscle after trauma
Myositis ossificans (metaplasia)
Streak ovary in Turners…type of tissue failure
Hypoplasia
Cyanosis w/ chocolate-colored blood
PaO2 and SaO2
Causes?
Tx?
Methemoglobinemia (Fe2+ –> Fe3+)
SaO2 low
Oxidant stress (sulfa drugs, nitrates) Newborns
IV methylene blue (Fe3+ reducing agent)
Pre-eclampsia…see what on biopsy of placental BVs?
Fibrinoid necrosis (via the HTN)
Fibrinoid necrosis…classic examples
Vasculitis, Malignant hypertension
Cellular injury, DNA damage, etc —> apoptosis…
What protein/gene is down-regulated to allow for apoptosis? What happens?
BCL-2 decreases –> cytochrome C can leak out of mitochondria and activate caspases
Caspases activate what?
Proteases and endonucleases
Negative selection of T cells in thymus is via what?
Fas-FasL –> apoptosis
CD95
Fas receptor on target cells for apoptosis
How does a T cell kill a cell? (2)
- Via perforins and granzyme (pores –> caspase activation)
2. Via Fas-FasL
Cytochrome C oxidase
Complex 4 in ETC (final step)
3 free radicals and the enzymes that destroy them
- Superoxide (O2-) - Superoxide dismutase
- Hydrogen peroxide - Catalase
- Hydroxyl (OH-) - glutathione peroxidase
Oxygen-dependent killing in neutrophils (2)
- NADPH oxidase (O2 to O2-)
2. Myeloperoxidase (O2- to H2O2)
Mechanism of damage in hemochromatosis and wilsons
How to prevent this normally?
Metals –> free radical damage (Fenton reaction)
Metal carrier proteins (transferrin, ceruloplasmin)
Mechanism of damage in acetaminophen damage
P450 metabolism –> free radicals –> hepatic necrosis
How do free radicals cause damage?
Peroxidation of lipids
Oxidation of DNA and proteins
Dry cleaning industry –> fatty change in liver…cause and pathway?
Carbon tetrachloride –> P450 –> CCl3 (free radicals) –> cell injury/swelling of RER –> decreased protein (apolipoprotein) synthesis –> fatty change
Continued rise in cardiac enzymes after MI treatment w/ tPA
Free radical damage (reperfusion injury)
2 steps of T-cell selection in thymus
- Positive selection (EFFECTIVE self-binding)
2. Negative selection (TOO MUCH self-binding)
All amyloid has what 2 shared features?
- Beta-pleated sheet
2. Congo red stain and apple-green birefringence
Mediterranean ancestry
Episodes of fever + appendicitis/arthritis/MI SYMPTOMS
Congo red staining within tissue
Familial pattern
Cause?
Amyloid type?
Familial Mediterranean Fever
Neutrophil dysfunction
SAA (Secondary amyloidosis)
Systemic amyloidosis…2 types
- Primary (AL - Ig light chains) - plasma cell dyscrasias
2. Secondary (AA - SAA) - chronic inflammation
Nephrotic syndrome
Restrictive cardiomyopathy/arrhythmia
Tongue enlargement, malabsorption, HSM
Secondary amyloidosis
6 types of localized amyloidosis
- Senile cardiac amyloidosis (normal transthyretin)
- Familial amyloid cardiomyopathy (mutated transthyretin – restrictive cardiomyopathy)
- Type 2 DM (amylin –> islets)
- Alzheimers (A-beta from APP –> brain)
- Dialysis (beta-2 microglobulin –> joints)
- Medullary thyroid carcinoma (calcitonin)
Anaphylatoxins…function?
C3a and C5a – activate mast cells –> histamine release
PGI2, PGD2, PGE2
LTC4, LTD4, LTE4
Histamine
PGs = vasodilation, permeability
LTDs = vasoconstriction, bronchospasm, vascular permeability
Vasodilation, permeability
C3b
C5a
Opsonin for phagocytosis
Neutrophil chemoattractant
Classical activation of complement
IgM or IgG on antigen –> C1 activation
“GM makes CLASSIC cars”
Hageman factor…fxns?
Factor XII – when exposed to COLLAGEN…
- Activates intrinsic clotting cascade
- Activates complement
- Activates kinin system (bradykinin)
Bradykinin…fxns?
Vasodilation and permeability (w/ histamine)
Pain (w/ PGE2)
Redness and warmth…mediators?
Bradykinin, histamine, and PGs
Swelling…mediators?
Histamine, tissue damage
Pain…mediators?
PGE2, bradykinin (sensitize free nerve endings)
Fever…pathway?
Pyrogen (ex. LPS) –> macrophage –> IL-1/TNF –> COX in hypothalamus –> PGE2 –> raised temp set point
Weibel-Palade bodies…fxns?
Via what?
How to remember?
Release vWF and P-selectin
Histamine causes it’s release
W-P = vWf and P-selectin
E-selectin - upregulation signal
TNF, IL-1
Sialyl-Lewis X
Selectin receptor on leukocytes
ICAM and VCAM - upregulation signal
TNF, IL-1
Integrins - upregulation signal
C5a, LTB4 (on leukocytes)
CD18
Integrin deficiency on leukocytes
Pyogenic infections, neutropenia, giant granules in neutrophils, albinism, peripheral neuropathy, mucosal bleeding
Issues?
Chediak-Higashi syndrome
Defective protein trafficking –> impaired phagolysosome, melanin movement, cell granule movement, neurotransmitter movement, platelet granule movement
What is the oxidative burst?
O2 to O2- by neutrophils (via NADPH oxidase)
Catalase positive organisms (5)
Staph, Pseudomonas, Serratia, Nocardia, Aspergillus
NBT test
Catalase converts O2 to O2-
Negative in CGD (colorless/yellow)
Many Candida infections
NBT test turns blue
Respiratory burst intact
MPO deficiency (no HOCl-)
Oxygen-independent killing…mechanisms?
Lysozyme (macrophages)
Major basic protein (eosinophils)
Resolution of inflammation…what happens to neutrophils?
APOPTOSIS
How do macrophages kill?
Lysozyme (oxygen-independent)
4 potential functions of macrophages once they arrive (2-3 days)
- Resolution (IL-10, TGF-beta)
- Continue inflammation (IL-8 –> more neutrophils)
- Abscess (fibrogenic growth factors, cytokines)
- Chronic inflammation (CD4 T cell activation)
5 stimuli for chronic inflammation
- Persistent infection (via macrophages, CD4 cells)
- Virus, mycobacteria, parasites, fungi
- Autoimmune disease
- Foreign material
- Cancers
4 = 28/7
CD4 co-stimulatory = CD28 (T cells) and B7 (APC)
Co-stimulation for CD8-MHC1 interaction
IL-2 (from CD4 T cell)
Macrophages with abundant pink cytoplasm surrounded by giant cells and a rim of lymphocytes
What are the central cells called?
Granuloma
Epithelioid histiocytes
Caseating granuloma…options?
TB, Fungi
Noncaseating granuloma…options? (5)
Foreign body, sarcoidosis, beryllium, Crohn’s disease, cat-scratch disease
Stellate-shaped non-caseating granuloma
Cat-scratch disease
Formation of a granuloma (pathway)
Macrophage (antigen) –> CD4 cell (via MHC2 and IL-12) –> Th1 cell –> IFN-gamma –> macrophage conversion to epithelioid histiocyte and giant cells
Labile cells
Bowel stem cells in MUCOSAL CRYPTS
Skin stem cells in BASAL LAYER
Hematopoietic stem cells (CD34+)
Stabile cells
Hepatocytes
Proximal renal tubules
***Permanent cells
Myocardium
Skeletal muscle
Neurons
When will a SCAR form?
Initial phase of this process?
When the regenerative stem cells are lost or absent
GRANULATION TISSUE (NOT granuloma)
***Granulation tissue…components
Fibroblasts, Capillaries, Type 3 collagen, Myofibroblasts
Main component of scar
What happens to the precursor? What is required?
Type 1 collagen
Collagenase removes type 3 (ZINC COFACTOR)
Patient has a zinc deficiency and gets a deep skin wound. What type of collagen will be present?
Why?
Type 3 (Collagenase cannot remove the type 3 w/o zinc)
***Mediators of tissue regeneration and repair (w/ functions)
TGF-alpha – epithelial and fibroblast GF
TGF-beta – fibroblast GF + inhibits inflammation
PDGF – endothelial, smooth muscle, and fibroblast GF
FGF – angiogenesis
VEGF - angiogenesis
**Primary vs. secondary intention
Primary = wound edges brought together
Secondary = granulation tissue fills defect, myofibroblasts contract the wound (SCAR)
Vitamin C - function
Hydroxylation of proline and lysine (procollagen) – needed for eventual CROSS-LINKING
Copper - function
Lysyl oxidase (CROSS-LINKING lysing and hydroxylysine)
Keloid - made of what?
Most common locations?
Type 3 collagen
Earlobes, Face, Upper Extremities
Hypertrophic scar
Excess scar tissue LOCALIZED TO WOUND
