Exam I (August 15) Review Flashcards
Will albumin increase or decrease during chronic inflammation? Why?
decrease in albumin synthesis and increased hepatic production of fibrinogen, ceruloplasmin, complement components (C3)
How are hepcidin and anemia related?
hepatocytes increase levels of hepcidin during inflammation can cause anemia bc hepcidin decreases absorption of iron in gut (hoping to prevent microbial access to iron)
If a patient presents with leukocytosis and thrombocytosis, what might this indicate? What tests should you run?
During inflammation, healing process begins, growth factors secreted, growth factors stimulate marrow
- increased leukocyte production
- increased platelet production
(leading to possible leukocytosis and thrombocytosis)
indicates inflammation…do CRP test
What would a positive CRP test indicate? Why?
What would a negative CRP test indicate?
In what clinical scenario might a CRP test be falsely elevated?
CRP (Reactive protein) is stimulated by inflammation, is tightly linked to IL-6 levels
so can be used in semi-quantitative fashion for level of inflammation (when normal can exclude significant inflammation)
absent CRP- no chronic inflammation present
Obesity is the one morbidity that can cause a “false” elevation of CRP
What is ESR? Describe the mechanism by which it works. Explain the benefits/disadvantages.
Chronic inflammation causes clinically detectable antibody synthesis expressed as polyclonal increase in IgG
IgG and fibrinogen coat erythrocytes and the red cells then fall more rapidly through a column of plasma-the rate is the ESR.
Rapidly becoming obsolescent because “false elevations” can occur when there is increased IgG present for non inflammatory reason - eg., myeloma, age
How is regeneration related to extracellular matrix?
With regeneration, the connective tissue framework (extracellular matrix) remains in tact and serves and scaffolding for replacement of residual uninjured cells (but have capacity to divide w depends on tissue type; labile, stable, permanent)
ECM is network of interstitial proteins (interstitial matrix or BM)
protein composition: fibrous structural proteins (collagen, elastins)
water hydrated gels (proteogylcans, hyaluronan), adhesive glycoproteins
BM: type IV collagen, laminin, proteoglycan
interstitial matrix: fibrilar collagens, elastin, proteoglycan and hyaluronan
Which growth factor will stimulate the production of epithelial cells and hepatocytes?
TGF alpha
What would a mutation in VEGF lead to?
normal function: angiogenesis, endothelial cell migration and proliferation, increases vascular permeability
mutation: defective angiogenesis and vasculogenesis
VEGF is expressed at low levels in most adult tissues, where are the exceptions?
expressed at higher levels in podocytes in glomerulus and pigment epithelium of retina
A patient on glucocorticoids receives a deep laceration on the arm. How might the drug interact with the healing process?
glucocorticoids are anti-inflammatory, inhibit TGF-beta production
TGF-beta has a role in fibroblast recruitment and angiogenesis, stimulates ECM synthesis
(so glucocorticoids can prod a v abnormal response to healing - need inflammation to start healing process)
A patient fell off her bike earlier in the afternoon and has been waiting in the ER for a few hours. You see her and run some labs. They show low platelet and RBC count. Examining the patients you notice small red dots on their skin. What could this indicate?
Fat and Marrow Emboli develop in patients with severe skeletal injuries
-“Fat Embolism” syndrome is systemic (pulmonary insufficiency, neurologic
-Symptoms, anemia, thrombocytopenia, petechial rash)
Fatal in up to 10% of patients
What are the important mediators for angiogenesis?
VEGF
FGFs, PDGF, TGF-beta
What are pericytes?
a growth factor stimulates pericytes and endothelial cell formation;
pericytes have ability to stimulate endothelial stem cells to proliferate, stimulate the endothelium to mature
What do fibroblasts do? How are they recruited?
synthesize connective tissue proteins
Recruitment, activation driven by many growth factors (PDGF, FGF, TGF−beta)
What is organization?
Definition: Process of transforming granulation tissue into a dense scar
With time blood vessels become less prominent, collagen matures (type III collagen replaced by type I collagen)
Trichrome stain
stains mature (type I) collagen blue
What is the primary mechanism of repair in healing by first intention and second intention?
first intention - epithelial regeneration
second intention- myofibroblasts
What is fibrosis?
Fibrosis refers to excessive deposition of collagen and other ECM components in a tissue
tissues that shouldn’t have scar can become pathologic : lung fibrosis- scar tissue in lung, not normal air exchange between alveoli and blood vessels
Inadequate intake, alcoholism, chronic diarrhea, and inflammatory disease can cause deficiency of what cofactor?
zinc
Total parenteral nutrition can lead to deficiency of what cofactor?
Copper
What does Fibronectin do?
binds to cellular integrins and extracellular collagen and attach epidermal basal cells to basement membrane
What part of cell cycle does CDK1 control?
G2 to M
What are the sources and functions for Epidermal Growth Factor (EGF)?
Sources: Activated macrophages, keratinocytes, other cells
Functions: Mitogenic for keratinocytes, fibroblasts; stimulates keratinocyte migration
What are the sources and functions for TGF-alpha?
Sources: Activated macrophages, keratinocytes, other cells
Functions: Stimulates proliferation of hepatocytes, other epithelial cells
What are the sources and functions for VEGF?
Sources: Mesenchymal cells
Functions: Stimulates proliferation of endothelial cells; increases vascular permeability
What are the sources and functions for PDGF?
Sources: Platelets, macrophages, endothelial cells, smooth muscle cells, keratinocytes
Functions: Chemotactic; activates and stimulates proliferation of fibroblasts, endothelial cells; stimulates ECM proteins synthesis
What are the sources and functions for FGF?
Sources: Macrophages, mast cells, endothelial cells, other cells
Functions: Chemotactic, mitogenic for fibrobasts; stimulates angiogenesis,
ECM protein synthesis
What are the sources and functions for TGF-beta?
Sources: Platelets, macrophages, endothelial cells, fibroblasts
Functions: Chemotactic for leukocytes, fibroblasts; stimulates ECM synthesis; suppresses acute inflammation
How do glucocorticoids affect wound healing?
anti-inflammatory, inhibit TGF-beta production (angiogenesis, fibroblast recruitment, collagen synthesis)
collagen deposition is most likely to be deficient when someone on corticosteroid therapy
Describe wound strength after 1 week, 3 months.
1 week- 10% normal (collagen synthesis, collagen modification; cross linking and increasing fiber size)
3 months- 70-80% normal
What does “left shift” mean?
“left shift” means that immature neutrophils are in the blood
lots of immature cells in blood- worry about leukemia
What is mixed tumor? Example?
Single neoplastic clone capable of divergent differentiation
Derived from 1 germ cell layer
More than 1 neoplastic cell type
Example – Salivary Gland
Clone capable of epithelial and myoepithelial differentiation
Pleomorphic adenoma
Neoplastic epithelial cells scattered in neoplastic myxoid stroma
What is the following referred to as when benign or malignant?
Derived from 1 germ cell layer
Salivary glands
(epithelium and myxoid stroma)
Benign: pleomorphic adenoma
Malignant: mixed tumor of salivary gland
What is the following referred to as when benign or malignant?
Derived from more than one germ layer
Gonads:
(arises from totipotential germ cells)
Benign: mature teratoma
Malignant: Immature teratoma, teratocarcinoma
Totipotential germ cells
can differentiate into any cell types found in the human body
Neoplasms originate in gonads, abnormal midline embryonic rests
What would abnormal midline embryonic rests indicate?
Neoplasms originate in gonads
Totipotential germ cells differentiate into any cell types found in human body
Define anaplastic.
Anaplasia is “backward differentiation” loss of the structural and functional differentiation of the cells from which a neoplasm is derived
What is the main inducer and inhibitor of angiogenesis (thinking neoplasia lecture)?
Inducer: VEGF
Inhibitor: Thrombospondin1 (TSP1)
What is HIF-1alpha?
hypoxia inducible factor (HIF-1alpha) transcription factor;
if body going undergoing some hypoxia change, it will release HIF-1alpha which will help promotion of VEGF which will cause angiogenesis
What does the following tumor marker help identify?
AFP
Liver carcinomas
Tumor of yolk sac remnants
Gonadal tumors
What does the following tumor marker help identify?
Carcinoembryonic antigen (CEA)
Colon, Pancreas, Lung, Stomach, Breast
Hematoxylin stain. (H and E)
A basic dye
Stains structures containing acids (e.g. nuclei) blue
hematoxylin (basic so has positive charge and attracts things with a negative charge; things that are blue/purple are nuclei
Eosin stain (H and E)
An acidic dye
Stains structures containing protein (e.g cytoplasm) pink
eosin has negative charge and attracts things with positive charge, cytoplasm is pink bc have lots of RER, mitochondria and lots of proteins there
Would looking at emphysema be better with high or low power?
emphysema -low power
infection- high power (see more on a cellular level)
