Cellular Accumulations/cell Growth, Proliferation, And Adaptation

Front 1

What are two ways that pathologic calcification present as?

What are the differences/.

Back 1

Dystrophic calcification and Metastatic

Dystrophic occurs locally in DAMAGED OR DYING tissue and so Calcium metabolism and serum levels are normal.

In metastatic, the serum calcium levels are elevated and/or there is abnormal calcium metabolism. This elevation in the serum leads to Ca deposition in NORMAL tissue.

Front 2

What do the ff images represent?

In what disease mechanism does this usually occur in? What is the progression of the disease?

Back 2

Dystrophic Calcification with Fat necrosis. Dark blue/purple regions indicate calcium deposits

Acute pancreatitis

Pancreatic enzymes liquefy the membranes of mesentery fat cells, released lipases digest triglycerides from fat cells, released fatty acids combine with calcium

Front 3

What are 4diff mech by which metastatic calcification can occur?

Back 3

1. Inc secretion of PTH which reg. Ca levels
2. Destruction of bone tissue to release Ca. eg. multiple myeloma or bone metastasis
3. Vit D-related disorders
4. Kidney failure

Front 4

What is the most common cause of clinically apparent hypercalcemia

Back 4

Malignancy

Front 5

How do tissues respond to injury

Back 5

-Regenerate
-Replace with fibrosis
-Necrosis

Front 6

What are the categories used to describe cells by proliferative capacity? Give ex. of each

Back 6

Labile - continuously dividing; replace cells being lost constantly. ex. epidermis

Stable - quiescent; usually in Go but may be stimulated to division by rxn to injury going from Go to G1. ex. hepatocytes

Permanent: these cells are done dividing. no regeneration. ex. neuron and cardiac

Front 7

Describe 3 methods of chemical signalling

Give ex.s of each

Back 7

Autocrine: Target sites on the same cell
Paracrine: Target sites on adjacent cells
Endocrine: Target sites on distant cells.


Autocrine: regenerative liver, T-cell lymphocyte maturation
Paracrine: Growth factors and clotting factors.
Endocrine: Hormones

Front 8

What type of cell surface signalling is found in glioblastoma?

What is glioblastoma?

Back 8

RTK signalling

Glioblastoma multiforme is the highest grade glioma (grade 4) tumor and is the most malignant form of astrocytomas. These tumors originate in the brain.

Front 9

What type of cell surface signalling is found in systemic sclerosis/Scleroderma?

Describe scleroderma

Back 9

RTK signalling

Chronic inflammation likely due to autoimmunity, widespread damage to small blood vessels, this leads to release of PDGF and TGF-b --> interstitial and perivascular fibrosis in skin and multiple organs

Front 10

What are STAT proteins?

What type of cell surface signalling are they involved with?

Back 10

STAT - Signal transducer and Activator of Transcription. Cytoplasmic second messengers

They are downstream of cytokine signalling such as erythropoietin (Epo). They activated by JAK (Janus Kinase)

Front 11

What is multiple myeloma?

Decribe the clinical presentation, molecular presentation

Back 11

Multiple myeloma is cancer of the plasma cells in bone marrow.

Clinical presentation: Inc fatigue and weakness, low fxn immune system, chronic back pain

Molecular: IL-6 stimulates it further. MM cell inc bone resorption by osteoclasts, hypercalcemia

Diagnosis: Hypercalcemia

Front 12

Classify the following downstream signalling pathways under RTK, cytokine or G-protein receptors

cAMP, IP3, JAK/STAT, MAP-kinase, DAG, PI3-K

Back 12

RTK - PI3, MAP-K, IP3

G-protein - cAMP

Cytokine - JAK-STAT

Front 13

Classify the ff ligands under the most likely receptor they bind for signalling:

EGF, Epo, IL, histamine, TGF-b, IFN, VEGF,epinephrine, PDGF, bradykinin, PTH, platelet activating factor, G-CSF,

Back 13

RTK: commonly growth factors such as EGF, FGF, VEGF, PDGF, TGF-b

Cytokine: common in hematopoietic cells such Epo, G-CSF, IL, IFN

G-protein: Small biogenic amines such as histamine and epinephrine vasopresser; Peptides such as bradykinin vasodilator, substance; neurotransmitter; Glycoprotein hormones such as PTH; Phospholipid signalling molecule such as platelet activating factor.

Front 14

What aberration in the cell cycle pathway leads to proliferation of cells in the ff?

Glioblastoma multiforme
Systemic sclerosis
Multiple Myeloma

Back 14

Glioblastoma multiforme - RTK signalling (VEGF)
Systemic sclerosis - RTK signalling (PDGF, TGF-b)
Multiple Myeloma - Cytokine signalling (IL 6)

Front 15

Explain the importance of ECM to normal cell growth, proliferation and repair to injury

Back 15

It sequesters molecules such as water and minerals, reservoir of growth factors, substratum for cells to adhere, migrate and proliferate.

The basement membrane is very important as it needs to be intact for regeneration to occur. If not, then fibrosis occurs

Front 16

What do the following have in common?
NF-1, NF-2, TGF-b, WT-1, IF-b

Back 16

Tumor suppressor gene products

Front 17

What is Neurofibromatosis?

What is the molecular basis of the disease?

Back 17

Autosomal dominant disorder; multiple tumors of peripheral nerves, pigmented iris hamartomas

Ras is continually activated because the NF is defective and is not inactivating Ras-GTP to Ras-GDP