Cell Differentiation I & II Flashcards
What is replacement?
unable to make cells os same type as those lost. CT types “fill in” the space previously occupied by lost cells
Proliferation is controlled by variety of mediators (GF and inhibitors)
What is regeneration?
make new cells of same type as those lost. Depends on ability of cells to proliferate
Proliferation is controlled by variety of mediators (GF and inhibitors)
Regeneration involves what 2 types of tissues?
Renewing tissues (regeneration - skin & GI)
Compensatory growth (liver & kidney)
Replacement involves what 2 responses?
Wound - wound healing, scar formation
Chronic inflammation - fibrosis
What is labile?
constantly cycling the cell cycle
What is stable?
those cells in Go quiescent - hepatocytes
What are permanent cells?
cardiac myocyte & neurons
What is glioblastoma multiforme? What is the specific signaling pathway?
The malignant of astrocytes. Vascular that can be leaky.
Contrast enhancing mass
The malignant astrocytes produce VEGF in response to hypoxia.
What are examples of tyrosine kinase receptors?
EGF, FGF, VEGF, PDGF, TGF-beta. Found in wound healing
What is systemic sclerosis or scleroderma?
disease of chronic inflammation likely due to autoimmunity
involves widespread damage to small blood vessels
injured endothelium releases PDGF & TGF-beta (both are fibrogenic)
Patients develop progressive interstitial & perivascular fibrosis in skin & multiple organs (can have dyspnea)
sclera - hardening
What is the proposed mechanism for systemic sclerosis?
Immune system activation (effector T & other leuks (B)) create cytokines that injure & narrow blood vessels. Blood vessels then secrete PDGF & TGF-beta which entices fibroblasts to grow –> increases ECM –> fibrosis
What type of signaling do you see with systemic scleraderma?
cytokine signaling.
EPO (GF) & JAK (Janus kinase receptor) –> phosphorylates STAT (signal transducer & activator of transcription) –> gene transcription
Can also lead similar to RTK pathway – GRB2–>SoS–> Ras–> Raf —> MAPKK–> MAPK –> TF of gene transcription
What are examples of cytokine receptors?
Erythropoietin, IFN, IL2-IL4…
What is multiple myeloma?
plasma cell neoplasm - bone marrow disease
Patient can be tired - b/c crowding out other cell types
What increases with multiple myeloma? What can it lead to?
Increase IL6 production by osteoclasts
IL- stimulates the growth of multiple myeloma cells
Multiple myeloma increase bone resorption by osteoclasts
High serum levels of IL6 correlate with poor prognosis
Bone destruction can lead to hypercalcemia
What are the 4 ligand classes of G protein linked signaling? What are examples of each? What is their function?
Small biogenic amines - histamine - capillary dilation, smooth muscle contraction; epinephrine - vasopressor
Peptides - substance P - neurotransmitter; bradykinin - vasodilator
Glycoprotein hormones - parathyroid hormone - Ca homeostasis
Phospholipid signaling molecule - platelet activating factor - immune cell regulation
Known inhibitors of growth signaling include ___
Neurofibromin 1 & 2
TGF-beta
WT-1
Interferon-beta
What are features of neurofibromatosis type 1?
autosomal dominant disorder
1/3000
seen in individuals who inherit 1 mutant allele of NF1 gene
Multiple tumors of peripheral nerves (neurofibromas)
Numerous pigmented skin lesions
Pigmented iris hamartomas
The NF-1 gene product turns ___ off
Ras
ECM can contribute to different diseases
slide 36 - integrins communicate to basal membrane
What are functions of ECM?
provides water, minerals & GF to tissue
determines tissue architecture
basement membrane restricts cancer spread
Successful reconstruction of tissue by regeneration of labile and/or stable cells require preservation of ___
stromal architectural support network – intact basement membrane is critical
Chronic, irreversible injury to hepatocytes can lead to liver disease cirrhosis. Major causes of cirrhosis in the US include
excessive alcohol consumption
Hep B infection
Hep C infection
IV drug abuse
What are the 5 types of cellular adaptations?
Atrophy, hypertrophy, hyperplasia, metaplasia & dysplasia
What is hyperplasia?
Increase in # of cells as result of proliferation often with inrease in size of tissue/organ
What is metaplasia?
one cell type being replaced by different cell type
What causes hyperplasia?
hormonal stimulation/increased functional demand
may be physiologic
may be compensatory
may be pathologic
Pathological forms of hyperplasia may provide setting for ____
neoplasia
Hyperplasia is found in ____ & ____
endometrial hyperplasia & compensatory hyperplasia in liver
__ signals activate growth response genes
priming.
Gene expression initiates ____. GF promote ___.
cell growth; mitosis
Hormones like ___ may facilitate in compensatory hyperplasia in liver. ___ stop liver cell proliferation
insulin; growth inhibitors
What is a prostate? What pathology is common with prostate?
gland in male productive system - secretions contribute seminal fluid
Hyperplasia
What is hypertrophy?
increase in cell size generally with increase in organ size; don’t have more cells
Hypertrophy & hyperplasia may occur together; however, in non-dividing cells only hypertrophy occur (DNA content of such cells may increase but they don’t undergo mitosis)
What causes hypertrophy?
Increased hormonal stimulation/functional demand
Physiologic (increase in smooth muscle of uterus under hormonal influences of pregnancy)
Pathologic (increase in myocardial volume b/c of elevated systemic vascular P in HT against which heart must pump)
Where is hypertrophy seen?
heart - hypertrophic cardiomyopathy - septal muscle bulges into left ventricular outflow tract
Disarray, extreme hypertrophy & branching of myocytes
Boxcar nucleus demonstrating increased DNA content
What is the mechanism of cardiac hypertrophy?
signals may be mechanical/trophic
myocytes are stimulated to increase synthesis of myofilaments
long-term adaptation can involve change in type of contractile proteins
What is atrophy?
decrease in cell volume due to loss of substance
represents new sate of EQ
What causes atrophy?
decreased workload loss of innervations diminished blood supply inadequate nutrition loss of endocrine stimulation aging local pressure
Color change in aged liver is due to ___
lipofuscin
CF causes what type of cellular adaptation?
atrophy
protein-calorie malnutrition
persistent diarrhea; disruption of normal ion flow eventually leads to pressure atrophy in pancreas
What is metaplasia?
one cell type replaced by another. Progenitor stem cells express new characteristics that are better adapted to altered tissue environment
Most common form - glandular epithelium replaced with squamous epithelium
What are examples of metaplasia?
respiratory epithelium becomes squamous epithelium in airways of smokers
Squamous esophageal epithelial ells replaced with intestinal like columnar cells (Barrett esophagus) - acid reflux - closely monitored - greater risk of carcinoma - 30-40% increase
Barrett esophagus is the single most important risk factor for esophageal ____
adenocarcinoma; 30-40% increased risk for patient with >3cm of Barrett mucosa
Diagnosis - endoscopic evidence of columnar epithelial lining above Gastroesophageal junction & histologic evidence of intestinal metaplasia in biopsy specimen from columnar epithelium
potentially reversible
What is dysplasia?
disordered growth - further loss in control of normal cells groth with possible progression to neoplasia
Marked by changes in nuclei & tissue architecture
Dysplasia is a potentially reversible response to ___ or ___.
chronic injury or stimulation
What are examples of dysplasia?
dysplasia of airway lining epithelium in smokers (usually occurs on background of squamous metaplasia
dysplasia of uterine cervical epithelium w/ HPV infection
Dysplasia often occurs in ___ epithelium
metaplastic
Metaplastic epithelium can be seen WITHOUT dysplasia
Dysplasia can arise WITHOUT going through metaplasia
Dysplasia is measured by __ & ___
low grade & high grade
What is an example of dysplasia?
cervical dysplasia - can see mitotic figures
Cervical dysplasia in Pap smear will show increase in ___
nuclear size; lower amount of cytoplasm by comparison
What is neoplasia?
abnormal proliferation of cells whose growth is uncoordinated with response to host’s needs & generally continues despite removal of stimuli
Implies automonous cellular proliferation, without normal response to control mechanisms
