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What is the function of stellate cells?
produce collagen in the liver
What growth factors inhibits keratinocyte and hepatocyte proliferation?
_______ stimulates matrix metalloproteinases while ______ inhibits MMP
Formation of scar tissue in the brain is called ?
3 types of non-dividing cells?
- skeletal muscle
- cardiac muscle
What is the difference between angioblasts and hemangioblasts?
- Angioblasts--embryonic Hemangioblasts- adult
- endothelial cell precursor endothelial cell precursors
- present in vasculogenesis present in angiogenesis
What are the 2 ways of angiogenesis?
- - branching and extension of pre-existing blood vessels
- - recruitment of endothelial cell progenitors
What stain is used for collagen?
What is the most important fibrinogenic agent?
What are the 3 functions of TGF-beta?
- - Inhibits keratinocytes and Hepatocytes
- - fibrinogen agent
- - Anti-inflammatory
Plasma cell cancer is called what?
Reed-Sternberg cells are cancer cells of what lymphocytes?
Periorbital edema is characteristic of what disease?
How is Nephritic syndrome different from nephrotic syndrome?
- Nephrotic syndrome--- Nephritic Syndrome
- defect in GBM GBM inflammed
- Massive Proteinuria minimal Proteinuria
What is Anasarca?
generalized edema with subcutaneous tissue swelling
What is Lymphedema?
What is the difference between petechiae, purpura, ecchymoses?
- Petechiae--1-2 mm
- Purpura-- >2mm
- Ecchymoses-- >2 cm
Heart Failure cells are seen in what condition?
Chronic congestive left sided heart failure
What are heart failure cells?
macrophages with hemosiderin in the cytoplasm resulting from phagocytosed RBC in the alveoli
What is a nutmeg liver?
Centrilobular necrosis of hepatocytes with surrounding uncongested hepatic tissue
In both congested lung and liver you see macrophages laden with what?
Accumulation of blood in the joints is called?
Petechiae are usually associated with what?
Purpuras are usually associated with what?
What is the difference in terms of iron loss in external and internal hemorrhage?
External Hemorrhage --> iron loss-->Microcytic, Hypochromic anemia
Internal Hemmorrhage --> no iron loss>no anemia
What is hemostasis?
maintenance of blood in fluid state
What is thrombosis?
formation of a thrombus
What are the 3 components of the hemostasis and thrombosis pathways?
- coagulation cascade
What molecule secreted by the endothelium causes transient vasoconstriction?
What 3 molecules actively secreted by the enothelium inhibit platelet activation and aggregation?
- Prostacyclin PGI
- Adenosine Diphosphatase
Platelets bind to vWF in the ECM via what protein?
Platelets bind to other platelets via what protein?
What are the 3 anticoagulant molecules of the endothelium?
- Tissue Factor pathway inhibitor
What is the fibrinolytic agent synthesized by the endothelium?
tissue plasminogen activator t-PA
What are the two cytokines that promote liver regeneration?
After a partial hepatectomy what cells do not play in the regeneration since it is a compensatory growth?
intrahepatic stem or progenitor cels
What cells allow for regeneration?
existing parenchymal cells, not intrahepatic or progenitor cells
In the regenerating liver what are the only cells that may come from bone-marrow derived stem cells?
endothelial and other parenchymal cells
What 2 growth factors are involved in terminating regeneration of the liver?
TGF-beta and activins
What transforming growth factors initiate liver regeneration and stop it?
- TGF-beta---stop it
What genes are involved in initiating the G0 to G1 transition?
AP-1 and c-MYC are activated by what transcription factors?
What are the immediate early genes involved in pushing the cell from G0 to G1 stage?
What organism causes the Plague?
What are the 4 agents classified in category A for bioterrorism?
- small pox
The rubeola virus binds to what receptors?
- CD46--present on all cells
- SLAM--present on cells of immune system
What is responsible for the rash see in measles?
CTL to infected cells with the measles virus
From where is measles antigen taken from for detection?
- nasal exudate
- urinary sediment
What chemokine is necessary to prevent neuroinvasion against west nile?
What is perinatal transmission?
while passing thru the birth canal
What are the modes of transmission of CMV?
What does CMV cause in immunosupressed?
What are the labile or continually dividing cells in the body?
- crypt of the GI
- bone marrow stem cells
- epidermal bulge, sebaceous glands, hair follicle bulge
- corneal stem cells
Where are quiescent cells found in the body?
- parenchymal cells of
- mesenchymal cells--fibroblast
Where are pluripotent stem cells derived from in the zygote?
inner cell mass
Embryonic stem cells are derived from where?
inner cell mass of the zygote
The pluripotent stem cells have what 2 characteristics?
- capacity to generate
- capacity to become any tissue upon induction
After the bone marrow is supressed from irradiation or disease what is the one cell that can reconstitute the whole bone marrow?
HSC can be collected from what 3 areas of the body?
- Bone Marrow
- peripheral cirulation via IL-3---GM-SF
- umbilical cord blood
The mesenchymal bone marrow cells give rise to what cells?
- endothelial precursors
The liver stem cells/progenitor cells are located where?
canals of Hering---between hepatocytes and biliary ductular system
The stem cells located in the canal of Hering give rise to what cells?
Oval cells give rise to what cells?
- stroma--- biliary ductular cells
In contrast to constantly proliferating tissues such as the GI lining, cornea, epidermis or bone marrow the stem cells in the canal of hering of the liver give rise to cells under what condition?
when normal hepatocyte proliferation is blocked
After a partial hepatectomy, regeneration of parenchymal cells would take place from what cells?
division of existing hepatocytes
What are the classicaly non-dividing cells?
- skeletal muscle
- cardiac muscle
Regeneration of skeletal muscle does take place but not from stem cells but from progenitor cells located under the endomysium, the cells are called?
Neuronal stem cells are located in what 2 regions of the brain?
- paraventricular nuclei
- dentate gyrus of the hippocampus
What are the 3 areas of the skin where stem cells are found?
- follicular bulge
- interfollicular stem cells
- sebaceous glands stem cells
When do bulge stems cells divide?
after injury but not during normal homeostasis
Wnt and BMP have what effect on the bulge stem cells?
- Wnt activates stem cells of the bulge
- BMP inhibits stem cell of the bulge
What 2 signalling pathways are important in regulating the activity of the stem cells in the crypts of the small intestine?
- Wnt stimulates
- BMP inhibits
Growth and regeneration of skeletal muscle occurs thru which cells?
What signaling is involved in proliferation of satellite cells?
The limbal stem cells LSC of the cornea are located where?
between conjuctiva and cornea
What growth factor inhibits the Metalloproteinases and keratinocyte proliferation?
Increased fibrosis in conditions such as systemic slerosis(scleroderma), marfans and hypertrophic scars are mediated by increased activity of what growth factor?
What effect does TGF-beta have on the cell cycle?
it inhibits it
What are the 3 functions of TGF beta?
- fibrinogenic agent
- growth inhibitor
What growth factor participates in wound contraction, stimulates fibroblasts, monocytes, smooth muscle cells, angiogenesis?
What are the functions of FGF?
- wound repair
What Growth factor has a role in the development of skeletal muscle, lung maturation and specification of liver from endoderm?
What effect do TGFs have on the proliferation of keratinocytes and hepatocytes?
- TGF alpha---promotes it
- TGF beta--inhibits it
Compensatory regeneration is characteristic of what organ?
What are the 3 growth factors what mediate regeneration after partial hepatectomy?
What hormones act as adjuvants along with TGF alpha, HGF, IL-6 to induce entry into the cell cycle of hepatocytes?
norepinephrine, serotonin, insulin, growth hormone
What are the 7 growth factors that are involved in initiating the cell cycle of the hepatocyte after a partial hepatectomy?
C-FOS and C-JUN---> c-myc, AP-1--->NF-kB, STAT-3, C/EBP
Which growth factor acts as a keratinocyte growth factor?
Defect in type IV collagen results in what syndrome?
hematuria, healing loss, lens sublaxation are symptoms of ?
Defect in collagen type I causes what Ehler's Danlos?
Defect in collagen type III causes what Ehler's Danlos?
What are endothelial cell precursors?
What are hematopoietic/endothelial cell precursors?
What are the steps of angiogenesis ?
- vasodilation via NO or VEGF
- degradation of BM by MMP and plasminogen activat
- recruitment of periendothelial cells--sm muscle
What are the 2 types of angiogenesis?
- from existing bv
- fron EPC--endothelial precursor cells
Endothelial precursor cells are important agents of angiogenesis under what conditions?
- vascular implant, tumore, cutaneous wounds
ve-cadherin and VEGF play a role in recruiting what cells?
endothelial precursor cells
What is the difference between healing by primary and secondary intention?
- primary--superficial wound--no scar
- secondary--deep wound--scar formation and wound contraction
What is the purpose of the clot?
- stops bleeding
- provides scaffolding for neutrophils to migrate
What are the 4 components of Granulation tissue?
What are the components of wound healing?
- 1- Clot formation
- 2- Granulation tissue
- 3- Cell proliferation and collagen deposition
- 4- Scar formation
- 5- Wound contraction
- 6- CT remodeling
- 7- Recovery of Tensile Strength
What leukocytes play a crucial role in Tissue repair?
What is the most important fibrinogenic growth factor in tissue repair?
What is the collagen that is first laid down by fibroblasts in granulation tissue?
Type III then Type I
Wound contraction usually occurs in what type of wounds?
What are the 4 components of granulation tissue?
What are the 7 components of wound healing?
- clot formation
- granulation tissue
- cell and collagen proliferation
- scar formation
- wound contraction
- CT remodeling
- recovery of tensile strength
What is wound dehicence?
What is the difference between a keloid and hypertrophic scar?
- hypertrophic scar-excess collagen leads to a raised scar
- keloid---raised scar that goes beyond the boundaries of the wound
What GF is responsible for keloids?
excess granulation tissue which prevents re-epithelialization
What are desmoids?
excessive proliferation of fibroblasts which lie between benign and low grade tumors
What is fibrosis
excess collagen deposition in chronic disease
What cells produce collagen in liver?
What induces the endothelial cells to produce tissue factor/thromboplastin?
How does the endothelium produce anti-platelet effects?
- Adenosine Diphosphatase
How does the endothelium produces anticoagulant effects?
- Heparin- breaks down Clotting factors 9 ,10
- tissue factor inhibitory pathway--breaks down 7
- thrombomodulin activates protein c which breaks down 5 and 8
Increased coagulability seen with age is due to decreased synthesis of what by the endothelium?
Use of oral contraceptives and pregnancy increase the coagulability of blood how?
by increasing synthesis by the liver of prothrombotic molecules or decreasing the synthesis of antithrombotic molecules
Recurrent thromboses, repeated miscarriages, cardiac valve vegetations and thrombocytopenia are symptoms of what?
Anti-phospholipid antibody syndrome
Antiphospholipid antibody syndrome is seen secondary in what condition?
Lines of Zahn--alternating pale and dark streaks signify the thrombus has formed ante or post morten?
What is phlebothrombosis?
Thrombi formed in the arterial or venous end are called red?
venous--because of stasis...more blood can accumulate
Post mortem or ante-mortem thrombi have chicken fat?
What are the 4 fates of thrombus?
- organization and recanalization
What is a mycotic aneurysm?
lodged thrombus becomes infected with bacteria causing an aneurysm
What is Trousseau syndrome?
What is a paradoxical embolism?
thrombi passes thru the atrial or ventricular septal defect into the other side of the heart
Multiple emboli lodged in the pulmonary circulation can lead to what?
pulmonary hypertension and right ventricular failure
How does fat embolism produce anemia, thrombocytopenia?
fat binds RBCs and platelets producing associated anemia and thrombocytopenia
What is a common way of introducing an air embolism?
- obstetric procedures
- chest wall injury
A form of respiratory distress called chokes is caused by what ?
What is caisson disease?
focal necrosis due to persistence of air emboli
What activates complement
- mannose binding lectin
- Microbial surface markers
How do endotoxins trigger DIC?
What metabolic abnormality exacerbates septic shock?
- insulin resistance-
- hyperglycemia inhibits neutrophil action
What are the effects of shock on the adrenals, kidney and lung?
- Adrenal--cortical cell depletion
- kidney--renal tubular necrosis
- lung-diffuse alveolar damage
What is the Ghon complex?
inflmmation of the lung parenchyma and the draining lymph node with TB
Which protein of the anthrax is considered the protective factor?
What is the wool sorter's disease?